eyes of a hunter eyes of a hunter

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Kate Bellingham: STEM champion and broadcaster on addressing the decline in interest and achievement in STEM education

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Matt Taylor:

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Achim Steiner: UNEP’s Executive Director emphasises the importance of properly addressing climate change

The ESA scientist discusses some of the science to have come from the Rosetta mission

Science & Technology

EYES OF A HUNTER

Is the Eurasian lynx about to return to the UK? Front cover inspired and supported by:

December 2015 • issue 17

Supported by:

In association with:

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FROM SYNTHESIS TO FUNCTION

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he research of the Wickleder group at Giessen University has a strong focus on the synthesis of solid state compounds. Thus, the group has significant expertise in various preparation techniques for solids, including solid state reactions and solvothermal synthesis under harsh conditions. The skillful preparative chemistry is combined with an extensive elucidation of structure-property relations seeking new functions. Applications are seen in the fields of oxide-based compounds (e.g. high k materials), crystalline co-ordination networks, sulfide-based thermoelectrics, and functionalised nanoparticles.

Professor Mathias S Wickleder Inorganic Functional Materials Institute of Inorganic and Analytical Chemistry Justus Liebig University, Giessen, Germany tel: +49 641 99 34100 / 34101 [email protected] http://www.mwickleder.de/

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FOREWORD

Reinhard F Hüttl

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ecember 2013 saw the launch of Horizon 2020. Drawing on lessons learnt from previous instalments of the EU’s framework programmes, the aim here is to further develop the European Union into an Innovation Union. In many European countries today, industry can no longer compete with the availability of cheap labour coming from the emerging economies elsewhere in the world. As such, there is a very clear need to move towards a culture of innovation that will enable Europe to both evolve and compete on the global stage. However, there are of course inherent challenges which must be overcome for this to be a reality, not least the fragmented nature of the EU and its markets. As such, it is now more important than ever for the European Research Area (ERA) to become truly established – and, of course, progress towards this is ongoing.

President Euro-CASE

result of many other important factors, from the ageing demographic to the current migrant crisis. Nevertheless, simultaneous with the necessary handling of these issues moving forwards, innovation must remain a core focus. While there is a sense that Europe is perhaps not as innovation-friendly as it could or indeed should be, the dialogue on the importance of this concept has now become established. This is evident in discussions surrounding the future of Europe’s manufacturing base and reindustrialisation, for instance. Here, there are many obstacles which must be removed in order to prevent a further shift towards what might be called an ‘innovation emergency’. These barriers include issues such as fostering smarter public procurement processes etc., but, in a more general sense, it is clear that a paradigm shift is needed in order to better value the importance of entrepreneurial activity in Europe’s innovation landscape and, indeed, to usher in a cultural change which also values a higher degree of risk taking as a necessary in-road to greater innovation.

Alongside the evolution of the ERA, the European Research Council (ERC) provides a solid foundation on which to build innovative success. Indeed, the ERC’s focus on blue sky thinking has a potential for innovation which is all but impossible to judge or predict, quite simply because it is from such basic research that unexpected developments often emerge, and Within this shift to new cultural perceptions and new innovative practices it is from the unexpected that many, more ‘applied’, technologies and must also come a change in the way ‘failure’ is viewed. In the USA, for instance, an unsuccessful attempt at establishing a start-up company is breakthroughs develop. not seen as a failure; it is instead viewed as part of a learning curve, an In any (current) discussion of the future of European innovation, however, event to be learnt from so as to ensure that the same mistakes are not the financial crisis which has visited such severe effects on many made twice. The same should be true in Europe; we need to be aware member state economies must be highlighted. In this context, it has that a greater degree of risk taking could also mean a greater number become apparent that the EU needs to develop a much stronger and of unsuccessful attempts in various sectors, but that this does not mean more resilient set of ‘innovation ecosystems’ in order to safeguard the that the process is failing – rather, it means that we are learning valuable scientific, technological, and innovative capacities of both individual lessons, from which we will be able to learn and grow, just as the ERA countries and Europe as a whole. There is also, perhaps, an additional and the Innovation Union will also evolve and, together, will thus be able need to change the way in which we approach things in Europe as a to ensure Europe remains at the fore of innovation on the global stage.

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INTRODUCTION

Clifford Holt

Senior Editor

AS

Pan European Networks

each year passes, Europe’s scientific and technological achievements continue to surpass the excellence which has come before, and 2015 is certainly no exception. This year has seen a multitude of discoveries, advances, breakthroughs and new initiatives all driving Europe’s innovation and scientific prowess to greater heights.

Nevertheless, more remains to be done to help those fleeing to Europe. While the Commission has announced it will provide €28m in humanitarian aid to Syrians displaced by the conflict, including some of whom have fled to Jordan, it is clear that the international community must learn to work better together, to co-operatively solve what has rapidly become the worst humanitarian crisis in Europe for decades.

For instance, the LHC at CERN has started its second round of experiments, the scientists at ESA re-established contact with the Philae lander on the surface of Comet 67P/Churyumov-Gerasimenko, with Rosetta going on to expose a daily water-ice cycle, the Graphene Flagship announced ten new projects after the first Joint Transnational Call (JTC) of the Flagship ERA-NET (FLAG-ERA), and robots have been used to produce the first true 3D picture of submarine canyon habitats.

It is thus with both these challenges and successes in mind that I welcome you to the 17th edition of Pan European Networks: Science & Technology, within which you will be presented with a myriad of articles and interviews addressing a plethora of areas and challenges.

Achievements also abound in the policy sphere with the European Commission presenting the Multi Annual implementation Plan (MAP) of the EU Forest Strategy to the European Parliament’s Agriculture Committee, the director general of DG CONNECT addressing the October meeting of the European Parliament’s Committee on Industry, Research and Energy (ITRE) to exchange views on the development of the Digital Single Market, and the Commission releasing official documents for the next Horizon 2020 work programme for 2016-2017. Achievements in science have not been restricted to Europe, with NASA recently announcing the discovery of the strongest evidence yet of flowing water on Mars as well as successfully completing a 50km flyby of Saturn’s moon Enceladus which, it is hoped, will detect molecular hydrogen and so suggest a possibly habitable environment.

Following a foreword by EuroCASE’s Professor Reinhard Hüttl, the Research & Development section includes a special feature on Gender Equality – which, along with our continued coverage of the European Gender Summit, features articles from Kate Bellingham and the Academy of Finland’s Professor Marja Makarow – while in a second special feature on Space, PEN speaks to the European Space Agency’s Dr Matt Taylor about the Rosetta mission and Dr Thomas Reiter about a new ESA astronaut mission to the ISS. The Research & Development section also includes sub-sections on innovation (featuring an interview with Intel’s Professor Martin Curley, the recipient of the 2015 CTO of the Year Award) and materials (including coverage of both the E-MRS’s Fall event in Poland, the Cambridge Graphene Technology Days event in the UK, and an interview with the Graphene Flagship’s Professor Andrea Ferrari), amongst others.

Under the Health umbrella, sections include Public Health (within which PEN reports from EUPHA’s eighth Public Heath Conference in Milan, Italy) and Life Sciences (which, amongst other contributions, includes However, while advances in science and technology continue to progress, interviews with delegates at the sixth EMBO meeting in the UK – Europe faces a serious challenge in the form of the migrant crisis, with Advancing the Life Sciences 2015). Other areas explored here are the very real possibility that this will get much worse before it gets better psychology, imaging, and parasitology. – considering the ongoing conflicts in Syria and the threat posed by ISIS Finally, the Environment & Sustainability section hones in on climate to the international community and, moreover, given the devastating change, featuring an article from the UN’s Achim Steiner, conservation effects that winter will have on these displaced peoples. and reintroduction of wild cats in the UK, and the Arctic. Yet there may be a role for science to play here, too, with the Commission launching the ‘Science4Refugees’ initiative, designed to connect scientific institutions with asylum-seeking and refugee scientists and researchers.

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As ever, I hope you find these pages as interesting and informative a read as I have found in their creation, and, of course, I welcome any comments you may have.

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CONTENTS FOREWORD

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INTRODUCTION

Senior Editor Clifford Holt introduces the latest edition of Pan European Networks: Science & Technology, which focuses on space, gender equality, materials, the life sciences, conservation and climate change

© David Ausserhofer

Professor Reinhard F Hüttl discusses the future of European innovation, including issues such as the fragmentation of Europe’s markets, progress towards the Innovation Union, and the lessons that can be learnt from the USA

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NEWSDESK

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Paneuropeannetworks.com showcases the news stories that have dominated European science and technology in recent months

RESEARCH & DEVELOPMENT

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SPECIAL FEATURE: GENDER EQUALITY 12 PLUGGING THE PIPELINE Kate Bellingham, UK TV presenter, engineer, and champion for girls in science, technology, engineering and mathematics (STEM), discusses her experience in addressing the decline in interest and achievement in STEM education, including a focus on the way in which women remain under-represented in science both in the UK and Europe MASTERING GENDER IN SCIENCE Dr Elizabeth Pollitzer, director of Portia Ltd and co-convenor of the Gender Summits, outlines how this series of events – including the 2015 European instalment, which Pan European Networks attended in Berlin, Germany – have helped to transform discussions of gender in science both in Europe and on the global stage

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A NORDIC GENDER AGENDA Professor Marja Makarow, vice-president of the Academy of Finland (the Finnish Research Council) and Chair of the Board of NordForsk, spoke to Pan European Networks at the seventh European Gender Summit about how gender-related issues are being addressed in the Nordic region

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A STRATEGY FOR DIVERSITY 24 In an interview with Pan European Networks, the BBSRC’s chief executive Professor Jackie Hunter discusses the issue of gender equality in both the UK and Europe – highlighting the importance of role models and sponsorship – and what the research council is doing to ensure gender sensitivity is a part of its approach to research funding INNOVATION PROFILE: Seija Kulkki, from the Aalto University School of Business, revisits RDI design rules

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MAKING THE Euro-CASE Professor Reinhard F Hüttl outlines why a multidisciplinary approach is crucial to the future of European innovation

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PROFILE: The University of Erlangen-Nuremberg discusses inflammation in chronic diseases

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CTOs OF THE YEAR 2015 Pekka Koponen, the founder of Spinverse, elaborates on the CTO of the Year Award, along with comments from this year’s winners

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INNOVATION INSIDE Professor Martin Curley of Intel® speaks to PEN about how the corporation fosters innovation and supports smaller companies, how the European policy landscape is evolving so as to provide a sound legislative structure to support this, and his feelings at being the recipient of the second European CTO of the Year Award

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AN ERA OF INNOVATION European innovation is closely tied to the ERA. Here, PEN also looks at other relevant areas, such as openness and accreditation

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PROFILE: The Faculty of Economic Sciences and Management outlines the programmes, research and projects they offer and undertake

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PROFILE: Inntrion’s Richard Bremer outlines the importance of technology transfer and how it increases the return on research

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SPOTLIGHT: BIOBASED INDUSTRIES 43 BOLSTERING EUROPE’S BIOECONOMY Pan European Networks speaks to the executive director of the Bio-based Industries Consortium, Dr Dirk Carrez, about how the Bio-Based Industries Joint Undertaking (BBI JU) is evolving via a discussion of the calls, the fact that the joint undertaking is now independent from the European Commission, and the developing relationship between policy and industry

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RESEARCH & DEVELOPMENT (continued)

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CARBON CAPTURE A NORWEGIAN RESEARCH STRATEGY Arvid Hallén, the director of the Research Council of Norway, explains how its new main strategy will enable it to promote quality as more than just good research, cultivating breakthrough research that can push the frontiers, not least through large scale programmes in central societal areas PROFILE: Norwegian company 4Subsea use their expertise on flexible pipes to improve integrity management plans, methods and tools

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PROFILE: The University of Bergen talks about how CCUS triggers research for more sustainable energy production

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ENABLING THE CCS FUTURE Theo Mitchell, of the Carbon Capture and Storage Association, provides a snapshot of the state of play in the EU

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PROFILE: The Crown Estate’s Carbon Capture and Storage (CCS) Programme discusses the commercial deployment of CCS

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BLUE ENERGY ADVANCING OCEAN ENERGY As interest in the ocean energy sector continues to mount, Ocean Energy Europe’s Jacopo Moccia speaks to Pan European Networks

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PROFILE: Acadia Tidal Energy Institute are assessing Canada’s tidal energy opportunities

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GRAPHENE GRAPHENE TECHNOLOGY IS HERE The Cambridge Investment Research (CIR) team provide a summary of the 3rd CIR Cambridge Graphene Business Conference

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PROFILE: Max Planck Institute scientists manipulate the electronic properties of SiC-based epitaxial graphene on the atomic scale

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GRAPHENE MEANS BUSINESS, LITERALLY PEN talks to Professor Andrea Ferrari, director of the Cambridge Graphene Centre and Chair of the European Graphene Flagship Executive Board

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PROFILE: The Faculty of Microsystem Electronics and Photonics writes of its history, departments and framework programme participation

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TAKING GRAPHENE TO MARKET PEN spoke to the Rt Hon Lord Alec Broers about some of the issues inherent in the commercialisation of graphene

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A UNIFYING GOAL During Cambridge Graphene Technology Days 2015, the Commission’s Andrew Houghton explained the importance of working together

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PROFILE: The Photon Science Institute and School of Electrical & Electronic Engineering discusses nanostructures for photovoltaics

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BETTER VALUE CIR’s Nick Coutts met with PEN in Cambridge, where he talked about the need for a better value network for graphene

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MATERIALS RESEARCH THE FOURTH INDUSTRIAL REVOLUTION The fourth industrial revolution will require greater support at all levels for innovative materials research

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PROFILE: The Norwegian Centres of Expertise cluster development programme supports innovation and competitiveness in 12 elite clusters

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MATERIALS FOR EUROPE Following the European Materials Research Society’s (E-MRS) Fall Meeting in Warsaw, Poland, Professor Rodrigo Martins – president of the E-MRS’s Senate – spoke to Pan European Networks about the success of the event and the importance of materials research to Europe’s future prosperity

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PROFILE: BioNavis Ltd has developed 20 years of R&D in photonics into products for academia and industry

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INOS’S APPLIED PHOTONIC RESEARCH INOS outlines how the photonic research centre is developing and supplying advanced measurement systems for science and industry

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PROFILE: Max Planck Institute for Polymer Research discusses the new challenges associated with molecular and thin film electronics

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ICT & CYBERSECURITY PUSHING THE CYBERSECURITY AGENDA The European Union Agency for Network and Information Security is at the forefront of cybersecurity, as Steve Purser outlined to PEN

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PROFILE: Silesian University of Technology hosts research that attempts to unravel the unsolved questions of contemporary biology

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ENHANCING WIRELESS COMMUNICATIONS The DIWINE project team outline how the work packages of the initiative come together

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BUILT ENVIRONMENT PROFILE: The Institute for Building Materials writes about the upcoming durability challenges for new reinforced concrete structures

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CONSTRUCTING THE FUTURE PEN reports on the work of the European Construction Technology Platform in driving the growth of the construction sector

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STATISTICS & SOCIETY AN ALTERNATIVE MEASUREMENT The EU statistical office, Eurostat, has been working to better understand wellbeing in the European Union

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RESEARCH & DEVELOPMENT (continued)

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PROFILE: The Montréal Heart Institute works towards putting the ‘person’ back into personalised medicine

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THE Web-COSI EXPERIENCE 118 Donatella Fazio, senior statistician at Istat and co-ordinator of the Web-COSI project, outlines the engagement and exploitation of new technologies for statistics for social innovation by Web2.0 communities, including a discussion of how businesses, governments, young people, and social entrepreneurs all have a role to play 122

SPECIAL FEATURE: SPACE SCIENCE STRAIGHT FROM SPACE The project scientist for the European Space Agency’s Rosetta mission (the first mission ever to orbit a comet’s nucleus and land a probe on its surface), Dr Matt Taylor, met with Pan European Networks at the British Science Festival to discuss some of the science to have come from the mission thus far and the plan to crash land on the comet’s surface

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A SPRINT INTO SPACE Prior to the launch of the iriss mission, which saw ESA astronaut Andreas Mogensen fly to the International Space Station on-board a Russian Soyuz rocket, Dr Thomas Reiter, director for Human Spaceflight Operations at the European Space Agency spoke to Pan European Networks about some of the science the mission would involve

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THE TOURIST/DESTINATION RELATIONSHIP Dr Tatiana Chekalina and the ETOUR research team explain the modelling behind customer-based destination brand equity

PROFILE: Aalto University is empowering students so they can lead the space technology revolution

HEALTH

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PUBLIC HEALTH EUROPEAN HEALTH INFORMATION PEN reports on discussions around the development of a new EU health information system at the EUPHA’s eighth public health conference

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FOODBORNE DISEASES: UNDER-REPORTED? The team at the National Food Institute at the Technical University of Denmark discusses the under-reporting of foodborne diseases

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PUBLIC HEALTH AND POLICY Professor Martin Mckee’s speech at EUPHA’s eighth EPHC raised many important points about the relationship between research and policy

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MEDICAL IMAGING IMAGING IS EVERYTHING Professor Chrit Moonen, president of the European Society for Molecular Imaging (ESMI), speaks to Pan European Networks about advances in areas such as image-guided surgery, as well as issues like standardisation and the argument for the removal of regulatory hurdles

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REFLECTING ON RESPIRATORY HEALTH Professor Jørgen Vestbo, president of the European Respiratory Society, speaks to Pan European Networks about a wide range of respiratory health issues, including deadly strains of influenza and more commonplace respiratory infections, and possible ways they can be addressed

HYBRID IMAGING TECHNOLOGY Pan European Networks looks at powerful neuroimaging techniques such as MRI and MEG, and a new project combining the two

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PROFILE: The BREAKBEN project aims to enable super accurate electromagnetic brain imaging

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NEUROLOGY & MENTAL HEALTH NDGs AND MENTAL HEALTH PEN explores several issues surrounding mental health and neurodegenerative diseases and the work being done to address them

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PROFILE: The Pain Research Group of the University of Porto is taking action against chronic pain

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TELEMEDICINE IN ACUTE STROKE Professor Chiara De Waure, vice-president of the European Public Health Association’s (EUPHA) section on Health Technology Assessment (HTA) met with Pan European Networks at the eighth European Public Health Conference in Milan to discuss telestroke and the challenges involved in its wider implementation

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PROFILE: The Institute of Neurology outlines their work on how to model diseases using stem cells and functional genomics

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PROFILE: The Stroke Centre talks about the many stages of effective stroke treatment and the importance of being organised

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PERSONALISING DEMENTIA CARE Dr Paul De Raeve, president of the European Federation of Nurses Association, highlights key political and research priorities in a discussion of personalised medicine and dementia, and calls for nurses to be made more visible in the ongoing political debate surrounding this in an effort to link these two often separate areas

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HEALTH (continued)

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PROFILE: INCF outlines how Big Data can be used to further our understanding of the human brain

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NUDGE IN THE RIGHT DIRECTION PEN speaks to Ashleigh Woodend about how behavioural economics can be used, for instance, in preventing major depressive disorder

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PROFILE: The University of Bergen’s Mood and Cognitive Function group writes on preventing recurring episodes of depression

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A FOCUS ON PREVENTION Paul Bomke, CEO of Pfalzklinikum, on preventative approaches beyond the healthcare system

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PSYCHOLOGY ENHANCING ORAL LANGUAGE SKILLS Professor James Law explains how a COST Action hopes to address issues in children’s oral language development

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PROFILE: The Stavanger Project – The Learning Child: Gaining better insight in children’s early development by authentic assessment

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THINKING ABOUT HEALTH Health psychology has the potential to tie into new, multidisciplinary and personalised healthcare approaches

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PROFILE: The University of Fribourg’s Department of Psychology explains how clinical neurosciences aid understanding of chronic pain

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LIFE SCIENCES BIOMEDICINE IN THE EU As the EU celebrates 50 years of pharmaceutical legislation, PEN looks at the advances made in, and the importance of, biomedicine

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PROFILE: The Faculty of Pharma, University of Lisbon, outlines its focuses in the areas of drug research and developing medicines

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ADVANCING THE LIFE SCIENCES PEN outlines the sixth EMBO Meeting, which took place in Birmingham, UK, and included the Louis-Jeantet Prize lectures

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PROFILE: The Institute of Human Genetics is searching for new factors involved in genome stability

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PROFILE: The MRC Human Immunology Unit writes about the potential of super-resolution optical microscopy in biomedical research

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THE POLICY DIALOGUE EMBO’s Dr Michele Garfinkel met with PEN to discuss various elements of science policy

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PROFILE: The Bioinspired Molecular Engineering Laboratory explains how smart materials can also come to life

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PROFILE: The Cell Biology Unit at CNRS discusses the dynamics of intracellular organisation, and two lab-developed technologies

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THE RIGHT ENVIRONMENT Director of the Cambridge Institute for Medical Research, Professor Gillian Griffiths, met with Pan European Networks during EMBO’s sixth meeting to discuss some of the areas that the CIMR is exploring, as well as issues such as gender equality in science, the importance of excellence and inclusion, and of creating the right environment PROFILE: The Laboratory for Muscle Plasticity is constantly exploring and researching in their quest to perfect muscle function

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PROFILE: MRC Human Genetics Unit discusses how multidisciplinary approaches aid in understanding our genome and its clinical application

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ACTION ON ELECTROPORATION Professor Damijan Miklavcˇicˇ, chair of the EP4Bio2Med COST TD1104 Action, discusses some of the issues around electroporation

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PROFILE: The Swiss Initiative in Systems Biology writes on how it has united scientists and promoted interdisciplinary research

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THE MOUSE BRAIN PROTEIN ATLAS Jan Mulder and Tove Alm, from the Human Protein Atlas, on the mouse brain as a model for the human brain

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PROFILE: The Universitätsklinikum Erlangen has found a possible explanation as to why the human heart does not regenerate

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USING LIGHT TO SAVE SIGHT Research is helping to develop new medical treatments to save sight, as Dr Simon Pot and Professor Dr Farhad Hafezi write

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PROFILE: The Molecular Systems Physiology group investigate how nutrition and genetic predisposition can affect one’s health

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CANCER FRAMING THE FRAMEWORKS Pan European Networks met the director general of the European Organisation for Research and Treatment of Cancer (EORTC), Dr Denis Lacombe, during the organisation’s course ‘A One-Day Journey through EORTC Activities’ to discuss issues such as pharmacovigilance, clinical trials, and the relevant regulatory frameworks that accompany them

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PROFILE: The Pathology Department at Umeå University, Sweden, searches for new biomarkers and more specific cancer drugs

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PROFILE: The Clinical Cancer Research Center writes about lessons learnt from the past effects of asbestos and how they can aid the future

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THE CANCER-DRINK LINK UEG’s Professor Patrizia Burra discusses the link between alcohol consumption and bowel cancer

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KEY MOLECULAR FACTORS Scientists of the Institute of Cancer Research in Vienna highlight new treatment strategies for liver cancer

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HEALTH (continued)

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MEDICINES MEDICAL PRIORITIES Tackling pain and the issue of toxinology are twin priorities for the medical community, as Pan European Networks details

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PROFILE: Brian Lohse, from the University of Copenhagen, writes that biotechnology is the tool to end the anti-venom crisis

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PROFILE: The Aragon Nanoscience Institute works in the field of nanoscience to constantly improve the treatment of different diseases

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OLD DRUG, NEW HOPES Dr Marcin Kołaczkowski outlines how an old hypnotic drug has become a starting point in the development of innovative antipsychotics

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PARASITOLOGY DISEASE AND PATHOGEN ECOLOGY Dr Helen Hesketh describes some of the research conducted by Dr Bethan Purse and her Disease Ecology group at the NERC Centre for Ecology & Hydrology (CEH), focusing on two areas of disease and pathogen ecology: diseases of veterinary importance transmitted by arthropod vectors and those that are exploited for biological control of insect pests

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PROFILE: The Witold Stefan´ski Institute of Parasitology explains how and why its research focuses on parasites

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ENVIRONMENT & SUSTAINABILITY

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SPECIAL FEATURE: WILD CAT CONSERVATION GOING WILD The chief scientific advisor to the conservation project Wildcat Haven, Dr Paul O’Donoghue, speaks to Pan European Networks about plans to develop a network of protected Scottish wildcat reserves throughout the West Highlands of Scotland, in a bid to save this critically endangered species

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A HAVEN FOR THE LYNX PEN explores the potential UK reintroduction of the Eurasian lynx with the chief scientific advisor of the Lynx UK Trust, Dr Paul O’Donoghue

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POLAR RESEARCH SAVING ANTARCTICA’S OCEAN Dave Walsh, advisor to the Antarctic Ocean Alliance, highlights the need for MPAs in the Antarctic region

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TOWARDS A CONTIGUOUS ARCTIC Professors Jørgen Berge and Paul Renaud and Dr Finlo Cottier discuss international research and education in a contiguous Arctic

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PROFILE: The Centre for Geobiology surveys Arctic seabeds for mining viability and hunts for new animal species

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PROFILE: The Austrian Polar Research Institute addresses misconceptions surrounding the sterility of the cryosphere

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SPECIAL FEATURE: CLIMATE CHANGE TIME FOR GLOBAL ACTION UNEP’s executive director, Achim Steiner, emphasises the importance of properly addressing climate change, including how the Global Goals that emerged from the Sustainable Development Summit, and the much hoped-for agreements that could come out of the COP21 meeting in Paris, will help to ensure a sustainable global future

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PROFILE: Professor Eberhard Fischer, from the University of Koblenz-Landau, writes about monitoring water quality in the tropics

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CLIMATE CONFLICT Professor Paul Rogers speaks to Pan European Networks about how climate change can cause conflict

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PROFILE: SLU’s Dr Chuanxin Sun outlines the need to reduce the methane emissions of rice paddies

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NATURE’S SOLUTIONS Amidst a mounting need to respond to natural hazards, Gorm Dige of the EEA details the role green infrastructure can play

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IN THE FACE OF UNCERTAINTY With the warming global climate having the potential to significantly impact on Europe’s forests, the European Forest Institute’s Dr Marcus Lindner outlines how both practitioners and policy makers must acknowledge the fact that uncertainties are likely to remain and that, as such, decisions must be based on the existing scientific evidence PROFILE: A group of Albert-Ludwigs-University of Freiburg writes about advances in storm damage modelling

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The editor does not necessarily agree with or endorse any of the views or contents of the articles or features within this document. All articles and editorials remain the copyright of the authors, organisations and other relevant authorities by whose kind permission they are reproduced. All information has been checked and is correct at the time of going to press. The publisher will not be responsible for any loss suffered directly or indirectly as a result of the use of or reliance on the information contained herein.

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Please note: All articles marked ‘PROFILE:’ in the Contents are advertising features Front cover designed by Pan European Networks Ltd Front cover inspired by: The Center for Applied Biotechnology and Molecular Medicine Top bar portrait images on the front cover: Matt Taylor © ESA; and Achim Steiner © University of Michigan ISSN 2049-2391 (Print); ISSN 2049-2405 (Online)

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NEWSDESK

THE BIGGEST STORIES IN SCIENCE FROM PANEUROPEANNETWORKS.COM With science considered such a major facet of the European Union’s hopes to develop the world’s leading knowledge economy, it is no surprise that new developments and discoveries are being delivered on an almost daily basis. Some of the most noteworthy events of the last few months include a call by the European Commission to end the gender pay gap – an issue discussed in the Gender Equality section of this publication, the discovery of flowing water on Mars by NASA scientists using an imaging spectrometer on the Mars Reconnaissance Orbiter (MRO), the argument that anti-tobacco campaigns are helping EU citizens to give up smoking, and the testing of a handheld DNA-sequencing device.

The following stories all appeared on our website: www.paneuropeannetworks.com

ANDRIUKAITIS: ANTI-TOBACCO CAMPAIGNS WORKING

celebrate thousands of ex-smokers who shine bright across Europe. I congratulate them all; they are an inspiration to those who are still nti-tobacco campaigns are helping EU struggling to quit.” citizens to give up smoking, according to Andriukaitis added that he would like Health Commissioner Vytenis Andriukaitis. to invite member states and health Speaking in Brussels on the Day of the Ex-Smoker, Andriukaitis said: NGOs to work on a strategic action plan to create more awareness“A rigorous tobacco control policy, supported by awareness-raising raising campaigns as part of a wider disease prevention approach. initiatives such as ‘Ex-smokers are Unstoppable’, is vital for improving He also noted that the implementation of the EU’s updated tobacco directive (2014) is on track in most member states, but said the public health in the EU.” Commission-funded campaigns such as ‘Ex-smokers are Commission is currently discussing with four countries “how their Unstoppable’, which was launched in 2011, and iCoach, a free online implementation could be more effective”. information tool, have already seen great effects: some 36% of iCoach The directive is intended to make smoking less attractive to young users claim to have quit smoking within three months – a saving of people by, for instance, banning cigarette flavourings and including picture warnings on 65% of each cigarette packet. Member states over €262m. “Giving up smoking is an achievement to be proud of, an achievement have until 2016 to implement it. 2 November 2015 which can change your life,” the commissioner continued. “Today we

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COMMISSION MARKS EUROPEAN EQUAL PAY DAY

‘The pay gap between women and men is already unfair, unjustified and unacceptable in the short eading figures at the European Commission term. But in the long term, it accumulates throughout a have called for further action on gender pay woman’s career and results ahead of European Equal Pay Day. in an even more significant 2 November marks the day in the year when women across Europe pension gap, with women’s pensions 39% lower than men’s.’ ‘stop being paid’, while men continue to earn money. With the average The Commission has also published the results of a consultation on hourly wage for women in Europe being 16.3% lower than it is for equality between women and men, confirming that Europeans see the men, campaigners argue that women effectively work 59 days for free gender pay gap as the most urgent inequality to deal with. each year. Looking forward, the statement from the commissioners read: ‘At the Ahead of the day, a joint statement was issued by Commission First current pace, the gender pay gap is declining so slowly that we will Vice-President, Frans Timmermans, Commissioner Marianne Thyssen need to wait another 70 years to achieve equal pay – that’s not one and Commissioner Ve˘ra Jourová: ‘Equality between men and women generation, but two. The pay gap is everyone’s business and everyone is one of the fundamental values of the European Union, but this day stands to gain from its elimination. It’s time to close the gap.’ 30 October 2015 reminds us that it is not one of its fundamental realities.

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MINI DNA SEQUENCER REVEALS SUCCESS handheld DNA-sequencing device developed by Oxford Nanopore has been tested and evaluated by an independent, international consortium co-ordinated by EMBL’s European Bioinformatics Institute (EMBL-EBI).

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The MinION is set to open up new possibilities for using sequencing technology in the field, for example in tracking disease outbreaks, testing packaged food or the trafficking of protected species. The innovative device works by detecting individual DNA bases that pass through a nanopore and, unlike existing sequencing technologies, there are few inherent sensing limits on the length of the DNA sequence that it could read in one go. Mark Akeson of the University of California Santa Cruz, a co-inventor of nanopore sequencing, consultant to Oxford Nanopore, and a MAP participant, said: “The device performs well now,

G7: MOEDAS CHAMPIONS ‘SCIENCE4REFUGEES’ arlos Moedas has highlighted the benefits of the European Commission’s new ‘Science4Refugees’ scheme at a high-level meeting of G7 ministers in Berlin.

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The European Commissioner for Research, Science and Innovation is joining the meeting of science ministers to discuss the contribution of science to solving pressing global challenges. The initiative was launched earlier this week to assist asylum-seeking and refugee scientists and researchers in Europe, and will allow universities and other scientific institutions to voluntarily declare themselves as ‘refugee-welcoming organisations’. The ‘Science4Refugees’ scheme will also allow participating organisations to promote potential positions, internships, training

particularly for viral and bacterial genomes, so you can ship it anywhere and know you’re going to get the same result. “We’re looking at a democratisation of sequencing in the not-so-distant future. That is changing things for people who need to solve critical problems in challenging environments, like tracking Ebola strains during the recent outbreak in West Africa. Another challenging environment is space – the MinION will be the first DNA sequencer tested in space by NASA on the International Space Station.” There are also possibilities for the educational environment. First author Camilla Ip of Oxford University added: “In a few years’ time, people who may be several steps removed from basic genomic research, like teachers in a classroom, could be using this device to teach science in new, exciting ways that have never been possible before.” 16 October 2015

courses or other actions available to asylum-seekers and refugees through the EU’s online ‘EURAXESS – Researchers in Motion portal’. Other topics to be debated at the G7 meeting include strengthening global research efforts on poverty related neglected diseases; improving © European Union global research and digital infrastructures; ocean-related research activities; and developments in clean energy. The topics discussed are a result of the G7 Summit Declaration adopted in June and come at a time when the issue of refugees has been brought into sharp focus as hundreds of thousands have undertaken hazardous journeys in a bid to escape warfare in Syria and North Africa. 9 October 2015

FLOWING WATER DISCOVERED ON MARS

Universe, and now we have convincing science that validates what we’ve long suspected. This is a sing an imaging spectrometer on the Mars significant development, as Reconnaissance Orbiter (MRO), researchers it appears to confirm that have detected signatures of hydrated water – albeit briny – is minerals on slopes where mysterious streaks are flowing today on the surface seen on the Red Planet. © NASA-JPL-University of Mars.” According to NASA, the darkish streaks appear to ebb and flow over The downhill flows, known as ‘recurring slope lineae’, have often been time; they darken and appear to flow down steep slopes during warm described as possibly related to liquid water. The new findings of hydrated seasons, and then fade in cooler seasons. Furthermore, they appear salts on the slopes point to what that relationship maybe to these dark in several locations on Mars when temperatures are above -10°F features, says NASA. The hydrated salts would lower the freezing point (-23°C) whilst disappearing at colder times. of a liquid brine, just as salt on roads here on Earth causes ice and snow Making the announcement, John Grunsfeld, astronaut and associate to melt more rapidly. Scientists say it is likely a shallow subsurface flow, administrator of NASA’s Science Mission Directorate, said: “Our quest with enough water wicking to the surface to explain the darkening. 29 September 2015 on Mars has been to ‘follow the water,’ in our search for life in the

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ENGINEER KATE BELLINGHAM DISCUSSES HER EXPERIENCE IN ADDRESSING THE DECLINE IN INTEREST AND ACHIEVEMENT IN STEM EDUCATION, INCLUDING A FOCUS ON THE WAY IN WHICH WOMEN REMAIN UNDER-REPRESENTED

Plugging the pipeline

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couple of years ago I was asked to speak at a Europe-wide conference on ‘Recruitment in engineering and technology’. I gave my talk the title ‘Collaborate to compete’, with the premise that equipping companies with increasingly-clever (and expensive) ways of attracting the best candidates (or enticing them from another company) was not the solution. The only way to address the shortage of good recruits was actually to grow the talent pool; which shouldn’t be dismissed as ‘someone else’s problem’. The recruiters themselves needed to play a role in increasing the number of STEM-qualified young people and the most effective and efficient way to do that was to collaborate.

Kate Bellingham

In the UK, we have been aware for many years that we had a potential time-bomb on our hands with a shortage of STEM skills and experience.1 From 2008-2011, I had the title of ‘National STEM Careers Co-ordinator’, which involved bringing together many of the stakeholders in careers information and education in an attempt to increase the impact of their work. The role was created as part of the Government School STEM Programme,2 which had 11 different strands; from teacher recruitment and training to curriculum and practical work. Enrichment and enhancement activities were covered, as was the setting-up of a lasting infrastructure, based around our National STEM Centre in York and the regional Science Learning Centres.

The good news is that progress is being made. However, inevitably, the recommendations are that more should be done, particularly in enhancing and scaling-up multistakeholder partnerships.

Gender (im)balance One of the areas picked up by the second paper was the need to reach out and engage marginalised groups, including a call for an ‘evaluation of the impact of efforts to improve the gender balance in STEM studies and STEM activities so as to better understand which methods are really worthwhile’.

The focus was on 11-16-year-olds, and the fact that so many areas were being addressed served to remind us how complex this issue was: there is no silver bullet solution to increasing the uptake and quality of STEM education. It was also clear that the best way to make a difference was collaboration across: a) different curriculum areas; and b) education, industry and government.

In many European countries, women are underrepresented in STEM and we know this is a particular issue in the UK, especially in the physical sciences, engineering, and technology. For several years I have been quoting the report

Leaky pipeline One measure of success was the increase in uptake of STEM subjects post-16.3 The English, Welsh and Northern Irish education system allows some subjects to be dropped at age 14, but the big cut off is at 16, when the choice for most is to work towards ‘A’ levels in three or four subjects, take a focused vocational course, or to become an apprentice.

Looking more broadly across Europe, it is clear that the UK challenges (though perhaps with its own peculiarities due to the education system and idiosyncratic cultural attitudes) are not unique. The 2012 White Paper ‘Science, Technology, Engineering and Mathematics Education – overcoming challenges in Europe’6 and the 2013 follow up ‘Science, Technology, Engineering and Mathematics education in EMEA: advancing the agenda through multistakeholder partnerships’7 show that, while baseline starting points may be different, most European countries have concerns about the low uptake and/or quality of STEM study.

There is no silver bullet solution to increasing the uptake and quality of STEM education

Consequently, this is where many are ‘lost’ from STEM. There are, of course, other holes to plug in the ‘leaky pipeline’ of talent, but post-16 study of STEM is relatively low; hence it being held up as an indicator. It hit the headlines in 2014 that maths was now the most popular ‘A’ level.4 However, only one-fifth of students study maths at all post-16: a far cry from the 85% in Japan reaching the equivalent of an ‘A’ level.5

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looking at why the UK has the lowest percentage of female professional engineers in Europe;8 it always caught people out. It was as if we knew we weren’t doing well, but assumed it was a ‘women-thing’ rather than a ‘UK-thing’. The report compares a number of factors between the UK, Ireland, Italy, and Sweden, including which subjects are compulsory to 14, 16 and 18-year-olds, how much girls enjoyed the subjects and their achievement levels, but also teacher attitudes and careers information, advice and guidance. The UK clearly had a lot of work to do. *Figures are statistically less reliable hence need to be treated with caution

So it was with some trepidation that I looked at the ‘She Figures 2015’ publication.9 However, the UK comes out creditably, with a special mention for the proportion of women researchers in the HE sector. In natural and medical sciences and even in engineering and technology apparently we have at least 40% women, while in engineering and technology, there has been an increase from 19% to 40% between 2005 and 2012. I am wary of jumping to any conclusions, however, my not-very-scientific gut-reaction is that the Athena SWAN Charter has been a major influence. This was established in 2005 to encourage and recognise commitment to advancing the careers of women in STEM (and medicine) employment in higher education and research.

Champion I describe my current role as ‘Championing girls’ opportunities in engineering’. This is much more than just enthusing groups of young women; we also need to influence their influencers, and aim for complete cultural and societal change here in the UK. Clearly, understanding ‘what works’ at a practical level when addressing the genderbalance, is a priority. Last year, a report was published aiming to do just that: ‘Not for people like me? Under-represented groups in science, technology and engineering. A summary of the evidence: the facts, the fiction and what we should do next’ (2014).10 In her introduction, Professor Averil MacDonald acknowledged the depressing fact that many years of activity, energy, and money focused on attracting under-represented groups have made little, if any, impact.

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Proportion of female engineering professionals across the EU states

MacDonald has been working in this area for 30 years herself, as have I, and we know that things need to be done differently. This report is well worth a read as a summary of all the current knowledge, albeit with a UK focus. A couple of things jumped out at me: n A ‘one-off’ event may appear to have an immediate positive effect but is unlikely to have longevity; and n

Competitions may do more harm than good – while they enthuse the winners, there are many girls who would prefer collaborative exploration rather than competitive challenges.

However, the most valuable outcome of MacDonald’s work is ‘People like me’,11 the resource pack for schools which takes a completely new approach to talking to teenage girls about opportunities and careers. The teaching resource starts with their self-identity and personal attributes, and links them to scientific roles, rather than focusing on what you would do as a scientist or engineer, or simply looking at the end-product you would make. The pack was launched at the British Science Festival in September 2015, so it is still early days, but it is exciting that we are taking such innovative strides forward.

Aspirations Self-identity also featured strongly in the work of the King’s College London ASPIRES project which looked at young people’s science and career aspirations age ten to 14.12 It turns out it is not enough to think science is important, or even to be good at it; you need to feel like you’ll fit. And that came across as even more important for girls than boys. In recent years, there has been a surge in organisations putting forward role models in STEM to help young people identify with the scientists and engineers and their jobs and roles. The UK has over 27,000 registered volunteer STEM Ambassadors,13 and groups such as the Stemettes,14 WISE15 and the Women’s Engineering Society16 focus on female role models.

Reality One of my favourites is the grass-roots organisation Science Grrl17 which began in 2012 in the Twitter storm surrounding the video used to launch the EU’s ‘Science: It’s a Girl Thing’ campaign. Science Grrl set out to show the real female face of science in Britain, and are now helping to

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inform STEM policy at a national level as well as running practical local initiatives. Their report ‘Through Both Eyes: The case for a gender lens in STEM’18 moved them from being a group of innovative enthusiasts to centre stage.

teaching and learning, and to provide female role models for younger children. When my children were first at school, I offered to help and was given the chance to listen to individual readers, or to help fundraising with the Parent Teacher Association. As I am quite a confident and proactive person, I asked if I could help with maths, and later to run an after-school STEM club. Both went well; I actually went on to train and work as a secondary school Maths teacher as a result of my experiences. I am sure there are parents, particularly mums, on a career break or working part time, who would be willing to share their STEM expertise but they would not be pushy enough to offer, and the schools are not clear what to ask for.

Another influential factor seen by the ASPIRES project to be key to science aspirations was ‘science capital’ in a child’s home life: family members with science related qualifications, understanding, knowledge (about science and ‘how it works’), interest and social contacts (e.g. knowing someone who works in a science related job). This was borne out by the preparation work for ‘People Like Me’ which showed that parents, and particularly mothers, can be a barrier to girls choosing STEM subjects and careers. The mothers are not wanting to hold their daughters back; they want the reassurance that the girls will be happy in their work. If the parents lack confidence or are not well informed (often through no cause of their own), that can have a profound effect on a girl’s choices. Reaching out to parents is notoriously tricky. The ‘People Like Me’ resource includes lesson plans for working with 11-14-year-old girls, but also a flyer for the parents and an optional additional ‘Mothers and Daughters’ session plan. The Institution of Engineering and Technology (IET) is currently running the ‘Engineer a better world’19 campaign specifically aimed at parents. They are also taking advantage of Naomi Climer, IET President for 2015-16, being the first woman in the role, and getting good mainstream media publicity20 which should appeal to parents. I trained with Naomi as a BBC Engineer, and I am delighted to see her being such a strong role model, and also using her presidential role to speak out for gender equality.

Supporting schools Meanwhile, I am working on a much smaller scale project to reach parents and to encourage women to return to STEM after a careerbreak (another leaky-pipeline spot), to help primary school STEM

In many European countries, women are under-represented in STEM and we know this is a particular issue in the UK, especially in the physical sciences, engineering, and technology

SchoolGateSET21 is an online community for scientists and engineers who are willing to support STEM in their children’s school on an ongoing basis. Initially, the community will provide ideas, advice and informal mentoring, but it could also lead to training opportunities, and to re-establishing lost links with professional science and engineering institutions, who are keen to help people with STEM skills to return to STEM related work. I was wary of setting up something new. When I held the post of National STEM Careers Co-ordinator, I was aware that we had ‘initiative overload’, with so many organisations and companies enthusiastically contacting schools with a variety of offerings. The challenge was to streamline these so that: a) the schools get what is most useful for them; b) the benefit of enrichment and careers engagement goes beyond the ‘low hanging fruit’ of the easy to reach schools; and c) the students get worthwhile inspirational experiences with ongoing positive reinforcement from school and home life. The idea with SchoolGateSET is not to be an additional initiative, but to facilitate connections and make use of an untapped resource.

Tomorrow’s world Creating this kind of online community clearly wasn’t viable when I started out in STEM promotion nearly 30 years ago. When I was presenting the BBC’s weekly science and technology programme ‘Tomorrow’s World’ in the early 90s, most UK viewers only had access to four analogue TV channels. In 1994, I talked

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address the myths that girls just aren’t interested, or it is not for people like them, or you have to be incredibly smart to even bother trying science, or you are either good at maths or you are not. Then we will start to see cultural change. The final statement in the second STEM education paper on EMEA is clearly a call to action: ‘It is clear that there is potential to reverse the decline in interest and achievement in STEM education, if we have the courage and commitment to put in place the measures to address it.’ I would suggest that call is not just to teachers, educationalists, policy advisors, or even the broader stakeholder groups. It should be to the whole of society. References 1

The Supply and Demand for Science, Technology, Engineering and Mathematics Skills in the UK Economy. 2005 http://webarchive.nationalarchives.gov.uk/20130401151715/http://www.education.go v.uk/publications/eOrderingDownload/RR775.pdf

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Background to the STEM Programme and 11 strands. http://www.nationalstemcentre.org.uk/stem-in-context/stem-background

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Overview of A Level results 2014: Campaign for Science and Engineering. http://sciencecampaign.org.uk/?p=14721

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http://www.jcq.org.uk/examination-results/a-levels

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https://www.gov.uk/government/news/new-maths-qualifications-to-boost-numbersstudying-maths-to-age-18

There will always be a role for face-to-face interaction between students and teachers and inspirational STEM Ambassadors, however there are other ways to reach out; to inform, educate, and entertain.

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http://www.ingenious-science.eu/c/document_library/get_file?uuid=3252e85a-125c49c2-a090-eaeb3130737a&groupId=10136

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http://www.ingenious-science.eu/web/guest/second-white-paper-on-stem-education

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An investigation into why the UK has the lowest proportion of female engineers in the EU https://www.nationalstemcentre.org.uk/res/documents/page/1uuftczGmVogqeQoW.pdf

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She Figures website

Competition

10 https://www.wisecampaign.org.uk/resources/2014/11/not-for-people-like-me

‘I’m a Scientist, get me out of here’23 is an imaginative online event which has engaged 600 scientists and over 39,000 teenagers in the UK between 2012 and 2015. It is an ‘X Factor’-style competition between scientists, where the students are the judges, asking the scientists anything they want over fast-paced online text-based live chats, and then voting for their favourite scientist to win a prize of £500 (~€690) to communicate their work with the public. And it would have been unthinkable 20 years ago.

11 https://www.wisecampaign.org.uk/about-us/wise-projects/people-like-me

on Tomorrow’s World about ‘the information superhighway’ and ‘something called the internet’.22 I now show that same YouTube video to school students to show how far we have come in 20 years, and to help them think about preparing for their next 20 years.

Meanwhile the Google Science Fair, Google+, page has nearly three million followers, and instead of watching Tomorrow’s World, my teenage children have played Minecraft and Kerbal Space Programme and watched a wide range of YouTubers, including some talking about science and technology.

We need to do more than simply enthuse groups of young women; we also need to influence their influencers, and aim for complete cultural and societal change here in the UK

12 http://www.kcl.ac.uk/sspp/departments/education/research/aspires/ASPIRES-finalreport-December-2013.pdf 13 http://www.stemnet.org.uk/ambassadors/ 14 http://www.stemettes.org 15 https://www.wisecampaign.org.uk/inspiration/tag/role-models 16 http://www.wes.org.uk/shesanengineer 17 http://sciencegrrl.co.uk 18 http://sciencegrrl.co.uk/assets/SCIENCE-GRRL-Stem-Report_FINAL_WEBLINKS-1.pdf 19 http://www.engineer-a-better-world.org 20 http://www.independent.co.uk/news/people/naomi-climer-first-female-president-ofinstitution-of-engineering-and-technology-vows-to-attract-more-women-into-engineeri ng-10498450.html 21 http://schoolgateset.blogspot.co.uk 22 https://www.youtube.com/watch?v=V8cnP-RtRHU 23 http://imascientist.org.uk

Kate Bellingham

Facilitating change Perhaps one of our biggest challenges is to make talking about (and doing) STEM a more normal everyday thing. Then we will start to

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DR ELIZABETH POLLITZER OUTLINES HOW THE GENDER SUMMITS – INCLUDING THE 2015 EUROPEAN INSTALMENT – HAVE HELPED TO TRANSFORM DISCUSSIONS OF GENDER IN SCIENCE BOTH IN EUROPE AND ON THE GLOBAL STAGE

Mastering gender in science

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hen it was established in 2011, the Gender Summit transformed how gender was discussed in science by involving scientists, gender scholars and policy makers in a joint examination of research evidence demonstrating the influence of biological (sex) and psychosocial (gender) differences in results, and in the quality of outcomes for women and men. The intellectual diversity and scientific and societal relevance of these discussions have expanded with each new Gender Summit. The wide range of topics addressed by nearly 400 speakers so far testify to the richness and complexity of gender as a research issue (the presentations can be seen at www.gender-summit.com).

be more successful in their science career than women. The most agreed-upon answer today is that structural conditions combine with deep seated implicit gender bias (held by both women and men) and together influence how individual merit and the research excellence of women and men scientists are perceived, and how assessment decisions of their work are made. Elizabeth Pollitzer

It would be a mistake to think of Gender Summits as conference events. The scientific discussions have a strong sense of social responsibility and share the purpose of eliminating gender bias from science knowledge and science practice. Furthermore, for many participants – especially those from outside Europe and North America, where different attitudes to gender equality dominate cultures – using science as the context and research evidence as the tool offers safer and more objective grounds from which to advance gender discourse and aspirations for greater gender equality.

15 years after ETAN ‘Gender Summit 7 Europe’ comes 15 years after the publication of the ETAN report, which in 2000 delivered a groundbreaking statistical review of the position of women in science in Europe. The report’s main conclusion that ‘although women constitute half of the undergraduate population there is a continuous drop in the numbers of women at each level’ provoked many studies to seek explanations why men appear to

‘Gender Summit 7 Europe’ comes 15 years after the publication of the ETAN report

Often, the implicit gender bias explanation is readily accepted. References to the possible role played by institutional structures, however, tend to be counteracted by claims that principles of meritocracy and excellence are fully adhered to in organisational processes and practices, and that those with the requisite training, experience, and personal motivation are not hampered in their aspirations to succeed in science careers. This is difficult to accept for many, given the persistence of the ‘leaky pipeline’ phenomenon and that 15 years after ETAN, Europe has 60% of women in undergraduate education and only 20% in top professorial ranks. Is it possible that all the men among the 80% of male professors are as clever, experienced, and motivated to succeed in science careers as all the women among the 20% of female professors? An issue is not just that unequal outcomes in participation elicit a sense of unfairness, but that they also cause science to miss out on the benefits of the gender balancing of teams, such as improved collective intelligence, diversified problem solving styles, more even attitudes to risk, and a broader range of perspectives on problems and solutions. Better news can be taken from the ETAN report’s key recommendation ‘to mainstream gender equality into the […] Framework Programme, and into member state programmes that fund science and technology’. In the last few years, not only has Horizon 2020 adopted gender as a criterion of success, but at the national level several research funders have embedded gender equality and gender dimension conditions within their organisational strategies. Among them are the Research

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Seoul Gender Summit Declaration 1) Collaborate by creating national and regional alliances to enable continued dialogue on common gender problems in science such as criteria of scientific excellence, which are of concern to policy makers, scientists, gender research experts, and stakeholders in science endeavours, including industry and citizens; 2) Ask, to ensure quality of research process, ‘whether, and in what sense, biological sex and gender differences are relevant in the objectives and methodology of the project?’. Evidence demonstrates that the assertion that science is gender neutral is not the case. For instance, when gender is not taken into account, research often results in different health and safety outcomes for women and men; 3) Establish research and innovation protocols, standards, regulatory regimes, as well as binding recommendations in areas where evidence already demonstrates the need to validate results to ensure safety and efficacy for both women and men. Examples include diagnostic biomarkers, stem cell medicine and assistive devices;

State Secretary at the German Federal Ministry of Education and Research, Cornelia QuennetThielen, opened the GS7-Eu, the first European Summit to be held in Germany

Council Norway (RCN), the Swedish Research Council (VR), the German Research Council (DFG), the German Environmental Agency (UBA), and NordForsk, as well as others.

Collaboration through global community 2015 has been a milestone year in the development of the Gender Summit platform. Firstly, two new regions joined its global enlargement: the Gender Summit Africa (April, Cape Town) and the Gender Summit AsiaPacific (August, Seoul). Secondly, the year was marked by the announcements of three major global policy initiatives: the UN’s Sustainable Development Goals, the OECD’s Creating Our Common Future Through Science and Technology agenda, and the African Union Council’s Agenda 2063. In each case, science and technology are presented as holding the key to fulfilling societal aspiration for wellbeing and sustainable economies. But in their current form, these agendas perceive the role of science and technology in a deeply flawed way because they appear to be unaware of the scientific evidence showing widespread gender bias in knowledge and in technologies. These important policy agendas will not deliver the hoped-for improvements unless they question the role of gender. At GS5 Africa, participants recommended that gender research should be mainstreamed into the implementation of the Agenda 2063 goals and other policy initiatives promoted by the

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4) Agree on accepted terminology, schema and models for representing and reporting the role and effects of sex and gender in scientific contexts, for instance when to use the term ‘sex’ and when to use ‘gender’ when explaining study results. There is considerable confusion in the research literature regarding terminology, and this affects the potential for conducting systematic reviews and meta-analytic studies; 5) Create fresh opportunities for developing new markets for science knowledge by advancing gendered innovation ecosystems. Such systems can be constructed by exploiting connections between: 1) gender sensitive research; 2) the different interests and product needs of women and men; and 3) making better use of the available female scientific and creative capital. These may involve, for instance, speech recognition products or devices promoting healthy ageing; 6) Involve more women in innovation value chains – in idea creation, development, and implementation. Evidence shows that: 1) gender balance in a team improves its collective intelligence; 2) in ‘crowdsourcing’ innovation, women outside the formal innovation circles contribute better solutions than others; and 3) when experiments fail, women and men adopt different problem solving strategies; 7) Identify statistics, indicators, and methods for collecting sex-disaggregated data to enable a better understanding of the current situation regarding gender equality in science at institutional, national, and regional levels. Key measures include: 1) gender balance in participation in science education, in research and innovation, and in science-related academic, industrial and related employment; 2) institutional gender equality policies; 3) progression stages in the career pathways of women and men; and 4) applications and success rates in access to research funding; 8) Educate, starting with schools, university students, researchers, managers of research and science communicators about the importance of including gender perspectives in research and innovation. Common sources of resistance to change include implicit and explicit gender bias, and cultural gender stereotypes. Children as young as nine months can distinguish gender roles and by the age of two years have constructed their own gender stereotypes, which reflect those of the society they live in; 9) Judge the individual and scientific quality, and potential, of women and men using clear and fair assessment criteria, monitoring outcomes for signs of gender bias in order to improve the selection process. Evidence shows that bias in the evaluation of merit is common and favours the success of men: in recruitment to research teams and jobs; in career promotion; and in the award of research grants; and 10) Create conditions for the gendered research and innovation principles to be implemented in practice through funding policies and programmes, encouraging cross-disciplinary and cross-sector collaboration, for example between universities, industry and civil society organisations.

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The Nordsforsk panel, headed by Professor Marja Makarow, outlined a strategy for gender equality policy in Nordic countries

This is a demanding task that requires policy makers and science leaders to adopt new perspectives, acquire new expertise, and change their established operating procedures. GS7 Europe examined the impact of policy by showing important examples of the progress made at institutional, national and regional levels, with concrete actions taken by such leading bodies as the League of European Research Universities (LERU), the Welsh and the Swedish Governments, and the ministerial alliance of the Nordic countries, NordForsk.

Closing gaps in scientific understanding Improving the quality of science knowledge by integrating the gender dimension in research content was demonstrated at the summit in the context of biomedical research, involving experimental, post hoc, and meta-analytic methodological approaches. Studies showed how female-male biological distinctions at cell level influence our understanding of their regenerative function. Other studies examined conditions for ensuring the safety of drugs and the different risk factors in cardiovascular diseases experienced by women and men.

Strengthening impact of policy

One of the best examples of achieving cross-cutting impacts was presented by the German Federal Environment Agency (Umweltbundesamt – UBA). After conducting the ‘Gender Relations and Sustainability’ project during 2000-2004, the agency acknowledged that integrating the dimensions of sex and gender creates innovative research that addresses both the environment and the people living in it. This was demonstrated at the summit through the design of the forthcoming German Environmental Survey (GerES). Also in the environmental domain, the study from Women for Climate Change Justice explained the contributions made to gender equality through building gender knowhow in the context of climate change. And, related to this, the role of furthering the knowledge of the consequences of climate change for gender relations, and for (different groups of) women and men – as well as their integration in climate change-related political processes and research.

Gender Summit 7 Europe was opened by Cornelia Quennet-Thielen, State Secretary at the Federal Ministry of Education and Research. The summit was held in Berlin for two reasons: firstly because of Germany’s introduction of the 30% quotas for women in non-executive board positions (‘frauenquote’); and secondly because the annual Falling Walls celebrations provided an opportunity to draw attention to the fact that gender bias in knowledge making creates boundaries that divide quality of research outcomes for women and men in an unequal way, and therefore these ‘walls’ must also fall.

An ethnographic case study from the Technical University Berlin exemplified a physics laboratory located at a university in Germany as having the striking characteristic that among those at the PhD and post-doc levels, women outnumber men. This physics laboratory demonstrates an exceptional assemblage of recruitment, norms and policies of gender equality, work organisation, and professional

African Union Council. To this end, Susan Shabangu, the Minister in the Presidency (of South Africa) responsible for Women, communicated the recommendations proposed at the GS5 Africa to the AU meeting of Ministers in Cape Town, which took place two months after the summit. Similarly, communications were sent from GS6 Asia-Pacific to the secretary-general of the UN, Ban Ki-moon, containing the Seoul Gender Summit Declaration, with the ten principles for mainstreaming gender into research and innovation agreed upon during the summit, and recommendations that gender research should be used to inform the implementation of each Sustainable Development Goal (SDG), and not be restricted to just one. The Seoul Declaration was signed during the summit by the participating institutions and by the participants, and was placed online for the wider community to read and endorse. Following this action, a (first in a series) report will be published before the end of 2015 showing how gender research relates to each SDG. The report is a collaborative effort involving 24 experts who participated as speakers in past Gender Summit events, with further feedback provided during GS7 Europe.

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culture of physics. Studying such clustering of women in male dominated scientific fields helps challenge traditional perspectives on gender and STEM research by deconstructing established gendered notions of STEM fields, such as ‘women don’t like physics’.

analysis of the instruction and evaluation materials revealed the use of gendered language favouring male applicants.

Implementing gender equality promoting measures At the summit, progress in constructing a web portal for quality resources in the field of gender and science, which is being developed by the FP7funded GenPORT project (see: www.genderportal.eu), was reported. It will also include a range of services to help researchers collaborate and access gender expertise. Also showcased was the Robert Bosch Foundation’s AcademiaNet Database, which makes a collection of nearly 2,000 (and growing) CVs of excellent women scientists and engineers, nominated for inclusion by highly respected scientific institutions, available to all those seeking female candidates for decision making roles. Participants benefitted from expert advice on how best to communicate about gender issues in science to reach a wider audience provided by the editor-in-chief of Elsevier’s ‘Connect’, an online platform which offers daily stories for the global science, technology and health communities, reaching over 150,000 readers a month.

The implicit gender bias explanation was analysed in a novel way by a study from the Australian National University. Traditionally, analyses of implicit gender bias tend to focus on psychological factors and on the inequalities occurring within a framework of legitimate decision making characterised by meritocratic values, and they tend to ignore decision making factors connected to wider social fields of meaning. This presents a risk of downplaying the role of social context of knowledge and the associative relationships between the mind and the features of sociopolitical life-world in which scientific communities work, and whose values they may be reproducing in the peer review processes, for example. Several speakers presented studies of implicit gender bias effects. Academic careers increasingly depend on whether the early career researcher has obtained a (prestigious) grant, like the Dutch Veni grant, or the ERC’s starting grant. A study from the Institute of Psychology in the Netherlands presented evidence demonstrating the existence of gender bias in 1) application evaluations and success rates, and 2) language use in instructions and evaluation sheets for personal research grants. Specifically, an applicant’s gender was shown to predict the ‘quality of researcher’, as well as actual success rates. It also showed that gender bias was most prevalent in scientific disciplines with the highest number of applications and with equal gender distribution among the applicants (i.e. life sciences and social sciences). Content

A topical intervention discussed the place of quotas in science examined by a study from EMBO, which considered the use, benefits, and option of using gender quotas to increase the number of women at the highest career levels in academia. The study concluded that ‘quotas require sensitive implementation; moreover, they are not sufficient, further changes in academic settings are necessary to assure that everyone has a fair chance’. The proposed alternative was to use the cascade model, which envisages flexible quotas for female participation at various levels, with quotas calculated according to the percentage of women present at the level immediately below.

Partners, sponsors and supporters GS7 Europe involved three leading organisations in science as partners: Elsevier, Robert Bosch Foundation, and NordForsk; as well as sponsors: KIF, the Swedish Secretariat for Gender Research, and the Elsevier Foundation. Many organisations, including the European Commission through DG Research and Innovation and the European Research Council, made it possible for the excellent collection of speakers to contribute to the programme. Three further regional Gender Summits and one European instalment are already being prepared to take place in the next two years

What’s next? Three further regional Gender Summits and one European instalment are already being prepared to take place in the next two years. They include the Gender Summit North America in Mexico City, April 2016; the Gender Summit Asia-Pacific in Tokyo, May 2017; and the Gender Summit North America in Montreal, November 2017. The European event is planned for November 2016. Regularly updated details can be found at www.gender-summit.com.

Dr Elizabeth Pollitzer Director Portia Ltd UK Co-convenor, Gender Summits [email protected] [email protected] www.portiaweb.org.uk www.gender-summit.com

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PROFESSOR MARJA MAKAROW SPOKE WITH PAN EUROPEAN NETWORKS AT THE SEVENTH EUROPEAN GENDER SUMMIT ABOUT HOW GENDER-RELATED ISSUES ARE BEING ADDRESSED IN THE NORDIC REGION

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course, gender issues are the basic level of diversity. The aim is to raise gender awareness among all Nordic stakeholders.

© Kari Likonen

hen it comes to gender equality, the Nordic region is often held as a beacon of excellence and as a place where issues surrounding gender, in both science and technology and elsewhere, are being addressed. However, in recent years this trend appears to have begun to reverse, with fewer women becoming involved in STEM-related careers, fewer girls and young women studying STEM-related subjects (despite achieving better grades at school than boys), and the number of women on the boards of large companies, in some but not all Nordic countries, being disappointingly low.

Marja Makarow

Marja Makarow, vice-president of the Academy of Finland (the Finnish Research Council), Chair of the Board of NordForsk, the research collaboration platform of the five Nordic countries, and the former vicerector for research and professor of applied biochemistry and molecular biology at the University of Helsinki, delivered a speech at the seventh European Gender Summit (GS7) in Berlin, Germany – attended by Pan European Networks – discussing NordForsk’s policy and activities on promoting gender equality in the Nordic countries.

NordForsk will analyse how men and women perform within its competitive funding calls, and will look to make sure there is no bias by charging the secretariat with the task of reporting once a year to the board about how this has been implemented.

Pan European Networks asked her about this in more detail, as well as about some of the gender equality-related areas in which the Nordic region either excels or requires more attention.

How will NordForsk’s research programme try to identify the reasons behind the negative trend of women in science and technology in Nordic countries? NordForsk adopted a gender policy in 2013, as it is important to lay down these principles. The policy is based on the notion that the gender perspective in research is important for quality. My own view in this regard is that collective intelligence is increased by diversity and, of

Additionally, there are some very simple measures being put into place. Perhaps the most important of which concerns the different assessment and evaluation panels and expert and programme bodies, in that when NordForsk appoints the members, the gender issue is taken into account. Here, the NordForsk policy dictates that at least 40% of the minority gender should be represented in all panels.

One part of NordForsk’s research programme will be the establishment of a Nordic ‘She Figures’ database, which will be curated and updated for research purposes

NordForsk will launch a research programme, tentatively entitled ‘Solving the Nordic Paradox – Gender Gaps in Research and Innovation’. It is based on a report published and developed by the Research Council of Norway, together with NordForsk, on the gender issue in the Nordic countries, which demonstrated that while the Nordic countries are known for being better than average when it comes to the gender balance in academia, the progress we have been making has stagnated and, indeed, may now even be going in the wrong direction. This finding catalysed the launch of the research programme, which was, indeed, one of the report’s recommendations; the programme committee has now been appointed and have begun to put together its basic elements. The research programme will try to find an answer to the question of why the number of women in science and technology in the Nordic countries is now falling. Within the programme committee there are professionals in these issues, and so it has a lot of potential for success.

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One part of the programme will be the establishment of a Nordic ‘She Figures’ database, because of some discrepancies between the figures held by the European Commission and the statistics bureaux in the Nordic countries. The idea here is to not only have accurate numbers, which of course we need for better monitoring, but also to create a research infrastructure in the form of a database which will be curated and updated for research purposes.

In 2012, almost 57% of people who attained a higher education at the tertiary level were women, with Finland and Norway having the highest proportion of both women and men in tertiary education. To what does the Nordic region owe this success, and how does this compare when we think of women attaining qualifications in STEM subjects? That is a very important question and one which necessitates an exploration of the education systems. In Finland, for instance, the school system is totally free and equal to all – there are no ‘elite’ schools or very poor schools –

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The research programme will try to find an answer to the question of why the number of women in science and technology in the Nordic countries is now falling

with access according to where you live. The same is largely true for the other Nordic countries. In a general sense, in Finland girls tend to do better in school than boys; something that many other countries also experience. While the reasons behind this remain unknown, there could be a link to biological development. In Finland this has now resulted in more women than men being accepted to study at university.

How do you feel the gender pay gap in the Nordic region could be better addressed? According to the latest statistics, in Finland women on average earn 20% less than men. This pay gap has also been explored a little further, which has shown that this difference is more pronounced when women are younger, that their earnings become closer to that of their male counterparts when they are aged 40-50, and then the gap increases once again as they get older. One explanation is that women seek employment in positions which aren’t as well paid as those typically populated by men, such as nurses or, particularly in the public sector, low level office jobs. However, this theory does not hold when the education sector is looked at, as this is an area where a very high number of women are employed and which is quite well paid. There may also be the argument that the gender pay gap is something of a hangover from the days when men typically worked and women stayed at home to raise a family. This, however, does not seem applicable to the Nordic countries (though it may well be true elsewhere) because women have been a part of the workforce for a very long time, and the

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percentage of working women here in Finland, for example, is one of the highest in Europe.

On average, some three in ten board members of the largest publicly listed companies are women in the Nordic region, with Iceland and Norway having the largest female share, at 46% and 40% respectively. What more needs to be done to help progress in this area, and do you feel concepts such as quotas work? The figures in Iceland and Norway are very high whereas in Finland the number is much lower (way below 20%). In Norway, the law states that in the private sector there must be a minimum number of women on the boards (and it is quite exceptional for legislation to touch the private sector), which may help to explain their high figures. The last EU justice commissioner, Viviane Reding, wanted this to happen at the EU level but was unsuccessful. In Finland, since the quotas were added to the equality legislation, discussions have taken place around establishing something similar for the private sector, but that has not been accomplished. In Sweden, however, female members of heavyweight companies’ boards have reached a milestone: their number has exceeded the number of male board members whose first name is ‘Anders’. There is a sense that, in this particular situation, quotas are not the ideal solution, and that is because micro-managing the private sector is something that must be handled very delicately. Instead, companies could put into place active policies and they should be made aware that diversity in the board room is as good for collective intelligence as anywhere else. There are, indeed, companies that are very sensitive to this and who have programmes to coach and mentor their promising,

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In Finland girls tend to do better in school than boys

talented young women by ensuring that proactive measures are taken to support them so that they are able to climb the career ladder. This is a laudable measure not least because it challenges the existing culture, and cultural change is at the core of the issue. It is very much a bottom-up approach because companies themselves decide to do this. There may also be structural issues which require attention. That is, in many areas – whether it be business, politics, or research – the way of working (unsociable hours, attendance required at places and events outside of work etc.) doesn’t take into consideration people’s private lives, people who have a family, and this is an automatic barrier for women who, in light of this culture, may not even think about joining the field at all.

When it comes to women in science and technology, how does the Nordic region compare to the rest of the world? In Finland and Iceland 24% of Grade A professors are women, which is more than in the other Nordic countries and the EU average being 20%. This is also the case when we

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begin to look at scientific domains more specifically, with the exception of the ‘bio’ sciences being particularly well-populated with women. Regarding technology, however, the number of women becomes considerably less. This perhaps returns us to the earlier point about the importance of education, in that there are currently not enough young women choosing to study STEM subjects. When it is understood that the STEM-related employment sector is the most rapidly evolving area of the global job market, women stand to become increasingly disadvantaged. We clearly need to attract more girls and women to the STEM subjects and careers, and one way of doing this may be to re-evaluate the definition of subject areas as proposed by universities. That is, there is evidence to suggest that women are interested in ‘living things’ – whether it is an individual human being, animals, health, society, the environment, or Nature, and so on – and less interested in pursuing subjects such as pure mathematics. Indeed, the Technical University of Helsinki in Finland had not seen a rise in the 10% of female students signing up for an IT course, which began with three years of mathematics,

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Diversity in the board room is as good for collective intelligence as anywhere else

despite doing campaigns in schools and promoting the course to female students as much as they could. However, by creating a course entitled ‘Bio-information Technology’, they immediately saw the number of female applicants rise to 70%, despite the fact that the level and duration of mathematics study involved in the course remained exactly the same. It may also be possible to make subjects such as mathematics more attractive to women by demonstrating how this discipline can be applied to areas such as business or society, for instance. Changes such as these could be implemented by universities without cost, and have the potential to have a dramatic effect on how women perceive STEM subjects, and thus their participation within them. A recent study conducted in the USA on STEM-related jobs showed that just 25% of these positions were held by women and that, of course, is unacceptable. Given that the situation in the Nordic region is very similar, it is clear that this is a problem that we share with much of the rest of the world, and perhaps one way forward will be to try to share best practice and discuss the challenges we are experiencing and the ways we can approach them, and it is here that the Gender Summits have a role to play. Professor Marja Makarow Vice-President for Research Academy of Finland +358 (0)29 533 5002 [email protected] http://www.aka.fi

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BBSRC’S CHIEF EXECUTIVE PROFESSOR JACKIE HUNTER DISCUSSES THE ISSUE OF GENDER EQUALITY IN BOTH THE UK AND EUROPE – HIGHLIGHTING THE IMPORTANCE OF ROLE MODELS AND SPONSORSHIP

A strategy for diversity F Professor Jackie Hunter, who joined BBSRC as chief executive in October 2013, has been an outspoken advocate of gender equality throughout her career, and is striving to ensure that the gender question is taken into consideration both within her own research council and beyond.

© BBSRC

unded by the UK Government’s Department for Business, Innovation and Skills (BIS), the Biotechnology and Biological Sciences Research Council (BBSRC) is one of seven that work together as Research Councils UK (RCUK). It has a budget for 2014-2015 of around £509m (~€718.5m) – £459m on research and capital grants and £50m for training and fellowships; and supports around 1,600 scientists and 2,000 research students in universities and institutes across the UK.

Professor Jackie Hunter

In advance of her speech at the Seventh European Gender Summit in Berlin, Germany, in November, Pan European Networks asked her about the issue of gender equality in science in both the UK and Europe, including the importance of role models, and what BBSRC is doing to ensure gender sensitivity.

Horizon 2020 is the first EU R&I framework programme to identify gender as a criterion of success – how would you assess the funding programme as it relates to gender? The Commission has made significant progress on the issue of gender in Horizon 2020 because not only are there specific programmes around gender – such as Science with and for Society – which are very valuable, but there are also explicit questions around gender in the proposals. This means that people are thinking about this issue in a way that they haven’t necessarily done before.

If we don’t get women scientists applying for research funding, and being successful in those applications, then we won’t shift the gender balance at the top because they won’t have the requisite experience for their career progression

Of course, it remains to be seen how successful this is going to be, but this is nevertheless a very promising start and, moreover, some of the funded programmes should now be able to acquire more data, which is crucial. We have found that having accurate and reliable data to drive a dialogue is really important, and we need to achieve this both at the European and member state levels. As such, within Horizon 2020, there is perhaps a need for an evaluation at the halfway point so that we can see where we are, and to look potentially at specific calls for proposals to include the quality of data gathering; because acquiring the data can be a significant amount of work, especially if automated systems aren’t in place (or if they are not fit for purpose). This is something that might need to be incentivised through funding programmes.

Opportunities for advancement in science careers are strongly linked to the demonstration of a good publication record, but also increasingly to success in securing research funding. What actions would you like to see research funders take to ensure objectivity and fairness in the assessment of research excellence? This is very important and when I joined the BBSRC I asked to look at the success rates and application rates by gender, because if we don’t get women scientists applying for research funding, and being successful in those applications, then we won’t shift the gender balance at the top because they won’t have the requisite experience for their career progression. There are thus a number of things which require our attention. First of all, you need to gather the data, and ours has demonstrated that in a number of research councils, my own included, the application rates for women are not always reflective of the eligible principal investigator (PI) population. We have therefore conducted a pilot scheme along with seven universities, within which the focus group

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© Juliacdrd

work has been designed to find out why women are not applying. There are a number of reasons for this, it would seem, and while some of these rest with the universities, some of them are definitely things that funders can work to address.

More women than men go into the biological sciences, and the numbers even remain comparable at the PhD level, but then there is the classic drop off when it gets to reader level and above

application and success rates by gender, which was interesting because they hadn’t seen that in aggregate before.

What particular issues affect female representation and participation in the biotech and biological sciences specifically – how does this field compare to other scientific disciplines?

For instance, at the BBSRC, we ask for a full CV, and that could automatically provide some foundation for bias when you are looking at people with career breaks. This could be solved by asking instead for the applicant’s six major papers, and this is something we are now discussing. At the BBSRC we will be undergoing unconscious bias training for all our assessment panels; another thing we can do – which may or may not be applicable to other funders – is to be more transparent and provide feedback for people who are unsuccessful. We also need to make sure that there is a representative gender balance on panels, even in areas like physics where that might be quite hard to achieve.

It is interesting that more women than men go into the biological sciences, and the numbers even remain comparable at the PhD level, but then there is the classic drop off when it gets to reader level and above. Nevertheless, the biological sciences should perhaps be seen as being better placed to solve this issue because of the relatively high number of women at the beginning of the career path.

Once we have the data we can use it to prompt discussion. At my research council we send a letter to the 30 top institutions that we fund each year. Last year – and this is something that is continuing – this letter contained their

There is a question around role models here, too, and this is also something that the funders and academic institutions can do more about. As a positive example: Cambridge University recently created a publication containing the profiles of the really talented women there, what they are doing, and how they got to where they are. We are thinking

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There are issues around what could be termed ‘sponsorship’, in the sense that the majority of people in senior positions at the moment are male, and if a man is asked to put forward a name for a committee for instance, quite often they will provide a male name. If they are prompted for a woman’s they will be able to provide a perfectly eligible woman, but it is simply not the first name that comes to mind. As such, there needs to be a lot more active sponsorship and challenge to people when they’re asked for names, because unless we get more women being recommended for committees and panels etc., then they won’t have the experience or exposure (or, indeed, confidence) that they need to further their career.

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about doing something similar in the BBSRC. This is important because it demonstrates that women can achieve these positions, that they can also have a family, come from diverse backgrounds, and that they don’t have to behave like a man in order to progress. We also want to highlight the fact that many women in senior positions have worked part-time for portions of their career, but have still been able to achieve success. Until now, perhaps, a pervasive, non-inclusive culture has meant that many women have not felt comfortable telling others that this has been the case, which certainly means that other women have not felt able to request more flexible working, and still more may have avoided this type of career choice entirely. Alongside this, we also need to involve more men in the process because the whole argument is one of diversity; it is not about women becoming more like men or men more like women. It is about everybody having a range of styles which will enable them to be more effective at their work. These are points which are not specific to biology; but there is a sense that the biological sciences and biotechnology areas may be able to start from a better position when it comes to addressing some of these challenges.

What is the BBSRC doing to ensure gender bias and sensitivity is a part of its own work? We have a very clear equality and diversity strategy and, internally, I have also implemented targets. The unconscious bias training that my staff and executive team are undergoing is part of our efforts to make people within the organisation more aware of potential biases. Gender bias is thus high on the agenda.

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We need to involve more men in the process, because the whole argument is one about diversity

We focused very much on gender this year and we want to try to look at diversity more broadly next year as well. When we did focus group work with the universities, we involved people from across the office so as to create a much broader exposure to some of the issues of gender, but we need to include other protected characteristics in future work. For example, self-reporting is an issue that we want to look at. If we look at disability and sexuality characteristics, the level of selfreporting is very low – perhaps because the environment is not conducive to a more inclusive society. A measure of success (for me, at least) will be when we see more selfreporting of these characteristics, because that will indicate that people feel that it is a safe environment in which to do so.

Professor Jackie Hunter Chief Executive Biotechnology and Biological Sciences Research Council (BBSRC) http://www.bbsrc.ac.uk/

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INNOVATION

REVISITING RDI DESIGN RULES Seija Kulkki from the Aalto University School of Business considers the potential reform of research, development and innovation (RDI) design rules

W

hen promoting the revisiting of our perceptions of RDI related to Horizon 2020’s Societal Challenges pillar, we have argued that ongoing digital transformation offers a great opportunity for new dynamism in European societies and economies. Digitalisation may be instrumental in changing the underlying foundations of industries, which may become more human-centric and service-driven, making new sources for growth and job creation through new entrepreneurial spirit and opportunities that could bring about new sources for productivity, efficiency, consequent wealth creation and the wellbeing of humans and Nature. We argue that Europe, through Horizon 2020-related programmes on all levels, has the opportunity to create a globally competitive, new, dominant design of industries for the 21st Century onwards. Our argument relies on four major underlying assumptions. First, the very nature of technology as a phenomenon helps bring us forward; the technology was originally defined as an integrative element between: 1) pure natural sciences and the knowledge of how matter and Nature ‘behave’, and 2) social sciences and humanities with knowledge of how human beings and societies ‘behave’. Until now we have overemphasised the first: the natural science approach with consequent emphasis on productivity gains of economic and industrial activities and organisations. As Porter et al (2011) argue, this has been at the cost of social progress and the wellbeing of humans and Nature. However, since digitalisation as a natural science and industrial efficiency-driven ‘discovery’ is already ‘old’, having evolved since the late 1980s, we may turn our creative minds towards the other part of the formula: humanities and social sciences. However, this leads to a new type of design thinking in RDI related to the integration of natural and social sciences and humanities. We should create designs that benefit both the industrial regime and society. Second, digitalisation isn’t only related to individual products, devices or technologies; it is about shared systems or integrated infrastructures, i.e. how products, technologies, economic and social activities, organisations and institutions can relate through information, communication, knowledge creation and innovation. The phenomenon does not only take place within a factory or a firm, but between them and even more so between all the social and economic activities of societies. This determines even the everyday life conditions of people and Nature. Individual people become part of wider social and economic productive systems. This means new distribution of labour, roles and responsibilities, and consequent sources of productivity and wealth creation. From the view of individual people this is much more than being a consumer. Consequently, we should reassess our device-driven approaches to RDI and develop approaches that are of a more human-centric and systemic view. We have the opportunity to improve the life conditions of human beings and Nature.

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Third, we have learnt that RDI of ICT-based infrastructures often emphasises design rules that integrate industrial activities or technologies; the discussion of industrial internet or device-todevice and machine-to-machine integration of technologies. We argue that the layers of technologies that underlie the services and business models may benefit the design rules of integration derived from human and social behaviour. Human-to-human or social-institutional internet. There are many cases where new digital infrastructures benefit from deep integration that reflects human, user and market behaviour. Today, with social media and crowdsourcing, this would be a natural road to follow. Four, we need to reconsider the role of ‘crowds’ in RDI. They can be equal partners, subjects themselves, even in terms of their expertise, knowledge and capacity to innovate. Even though the level of education and participation in Europe is historically high, we are still influenced by the old attitude that ‘people are masses that do not know’. Hayek (1960) has already challenged that view and promoted collaborative activities for better futures and societies. He has promoted a knowledge society that is done through the knowledgeable and active participation of people with the help of technology, and he discusses the role of people in the societal developments of human rights, democracy and freedom. To conclude; Europe has the opportunity to transform its industrial dynamics towards new dominant design that is more human-centric, systemic and even socioeconomic by nature. This is possible through digitalisation - perhaps for the first time in economic history. One may argue that until now the industries did emerge, evolve and change through introducing new innovative products or technologies that spread, scaled up, and diffused over time through a kind of natural, evolutionary and adaptive processes. Today, we have the opportunity, through wide-scale experimentation, collaboration and ecosystem approach, to make industry or system-level changes. Today, we may transform industries almost consciously. However, this has major impacts of industrial, technology, and innovation policies, as well as on RDI itself.

Professor Seija Kulkki Founding Director of the Center for Knowledge and Innovation Research (CKIR) Aalto University School of Business +358 (0)50 584 9070 [email protected] http://ckir.aalto.fi/en/

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INNOVATION

PRESIDENT OF EURO-CASE PROFESSOR REINHARD F HÜTTL OUTLINES WHY A MULTIDISCIPLINARY APPROACH IS CRUCIAL TO THE FUTURE OF EUROPEAN INNOVATION

Making the Euro-CASE T Pan European Networks asked the organisation’s president, Professor Reinhard F Hüttl, about the importance of bringing the diverse elements of the scientific community together in order to better inform policy and the public, and the role that Euro-CASE can and does play.

© David Ausserhofer

he European Council of Academies of Applied Sciences, Technologies and Engineering (Euro-CASE) is an independent, non-profit organisation of national academies of Engineering, Applied Sciences and Technology from 22 European countries. Its mission is to pursue, encourage and maintain excellence in the fields of engineering, applied sciences and technology, and promote their science for the common good.

Professor Reinhard F Hüttl

It is clear that the transition of Europe’s energy supply can only be successful if we come to a truly European approach. Thus the concept of the energy union is crucial, as we need to ensure a secure, affordable and environmentally friendly European energy system whilst at the same time integrating Europe’s potential for innovation in areas such as storage or smart grids.

How important do you feel it is for the various fields, disciplines and academies to come together in Europe in order to drive progress and innovation? This is really very important. Whenever the opportunity of joining forces on an integrated European level arises, it should be seized upon. And, perhaps more than that, we should be working to make these opportunities become more frequent. This can be achieved via umbrella organisations such as Euro-CASE, which includes a membership of 22 academies, through which we are able to access expertise of around 6,000 top-level scientists, all elected by their peers on the basis of scientific merit. This means they can provide impartial, independent, and balanced advice on technological issues with a clear European dimension to European institutions, national governments, companies, organisations and the general public.

An example of where this is already working is the interdisciplinary collaboration within the context of our Euro-CASE energy platform, which was established in response to the decision by the EU to transform Europe’s energy market. The platform agreed to first elaborate reform options for the European Emission Trading System (EU-ETS), including the discussion about the EU targets and the interaction between different policy fields such as renewables and innovation policy.

Euro-CASE’s energy platform first agreed that it was necessary to elaborate reform options for the European Emission Trading System (EUETS), including the discussion about the EU targets and the interaction between other policy fields

How important was the recent signing of a Memorandum of Understanding (MoU) to strengthen interacademy co-operation in Europe? Many of today’s challenges are cross-cutting and therefore increasingly require the combined expertise from multiple scientific perspectives which academies are well positioned to provide. A clear and united voice of experts from across all scientific disciplines would support the debates about benefits and risks of new technological advances. It would also help policy formulation and contribute, hopefully, to more public confidence in political decisions. The initiative of the academies highlights the potential of independent evidence-based advice for policy making in Europe. Through the MoU, the five academy organisations – Academia Europaea, the panEuropean Academy of Humanities, Letters and Sciences; ALLEA, the European Federation of Academies of Sciences and Humanities; EASAC, the European Academies’ Science

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Advisory Council; Euro-CASE, the European Council of Academies of Applied Sciences, Technologies and Engineering; and FEAM, the Federation of European Academies of Medicine – have declared their intention to collaborate We have seen this collaboration as a necessity, quite simply because science has become more and more multidisciplinary and the great challenges need a multidisciplinary approach. The technical sciences have drawn on expertise from areas such as economics, law, ethics, philosophy, humanities and psychology. As such, it became apparent that policy advice can only be successful if it takes into consideration not only one scientific discipline, but also dwells upon the expertise of other scientific domains. Through the MoU we are able to aggregate many different disciplines and make better use of the knowledge and competencies of more than 100 involved academies in Europe so that political decisions might be based increasingly on multidisciplinary scientific advice.

What are your thoughts on Horizon 2020 – and indeed of the Juncker Commission more generally? H2020 places an increased emphasis on innovation, and although this has been criticised by some parties, I believe that this is a positive development. That is because in Europe – and elsewhere – an increasing amount of taxpayers’ money is being spent on research for specific missions such as climate change mitigation, demographic change, health, security or integrated mobility. Thus, we must be able to demonstrate that this money is being used wisely and that research is resulting in innovative developments which have an impact on our lives – regardless of technological or societal innovation. Advances in science and new technological discoveries are the basis for economic growth in Europe. What we have to do is bring our excellent research results to society and to the market in a better way. I therefore welcome a culture of open innovation, one that involves not only scientists but also has a clear interaction with citizens, societal groups, NGOs and industry. Similarly, Commissioner for Research, Science and Innovation, Carlos Moedas, has made ‘openness’ one of his key topics. I tend to agree with him that ‘open science’ must be ‘open’ in all senses, and therefore include open data as much as

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possible. Science in Europe and Horizon 2020 must also be open to the world: it cannot just be European. Our scientists, engineers and researchers need to co-operate with partners elsewhere in the world. Of course, much of this is already being realised, and research organisations co-operate on a worldwide basis, but it is nevertheless a point which needs to be stressed with regard to future framework programmes for research. Another topic concerning the Commission of Jean-Claude Juncker was, of course, the decision to discontinue the position of a chief scientific advisor, which drew some criticism but led to a new, promising concept of scientific advice in Europe. He asked Commissioner Moedas to come up with a replacement concept. The ‘Scientific Advice Mechanism’ (SAM) was developed in answer to this request and it aims at better addressing the Commission’s need to base their political decisions increasingly on scientific evidence. This also demonstrates that both Juncker and Moedas are aware of the need for independent and unbiased scientific policy advice, and that they support evidence-based decision making. The academies organisation can help in this respect as they do not only join the expertise of highly respected members of the scientific community, but also have a decentralised structure and can provide a national perspective when it comes, for example, to questions about public acceptance of certain technologies.

How do you see the role of Euro-CASE continuing to evolve, and are you on track for your 2020 goal of becoming ‘the voice of European excellence in engineering, applied sciences and technology for the world’? It is important to have an ambitious goal, and ours is certainly ambitious – but one that we will nevertheless strive to achieve. With the new Science Advice Mechanism we aim to ensure a better level of inclusivity and multidisciplinarity and we want to provide joint reports and statements. The five academy networks bring together some 10,000 scientific minds and the goal is to make better use of their joint knowledge and competences. Euro-CASE fully supports this process and will actively contribute to the advancement of this new mechanism. At the same time, Euro-CASE will continue its work and dialogue with stakeholders of technology-related topics such as energy, innovation and the bioeconomy. Especially in Germany, our key strength as an organisation is to bring together science, business and other relevant stakeholders such as NGOs or trade unions and join them around a specific topic. When we think for example about Industry 4.0, digitalisation will not only change the production patterns but also require new competences of the working forces. As such, Euro-CASE aims to further stimulate the European debate around important future topics.

Professor Reinhard F Hüttl President Euro-CASE http://www.euro-case.org/index.php

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REDUCING THE CHRONIC DISEASE BURDEN Chronic inflammatory diseases threaten physical integrity and interfere with the quality of life of millions of people worldwide. New medical concepts aim to reduce the disease burden for patients with such conditions

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nflammation is a central response strategy of the body to react to tissue stress and damage. The human body needs inflammation for defence against intruding micro-organisms and mutated cells, inducing repair of damaged tissue and maintaining immune homeostasis. However, inflammation is a powerful process which can also cause severe tissue damage if it becomes chronic and escapes tight control. Thus, molecular checkpoints that control and reduce the intensity of the inflammatory response have to be postulated. Failure to appropriately stop inflammation leads to chronic diseases such as arthritis, asthma or inflammatory bowel diseases, which in particular involve the inner surfaces of the body. In most of these pathological conditions, the initial trigger for inflammation is long gone while auto-stimulatory loops maintain the chronic inflammatory processes. Approximately 20% of all deaths worldwide are a direct or indirect result of chronic inflammation. The World Health Organization (WHO) announced that it will require new approaches to halt and turn back the growing threat of chronic diseases.1 Various inflammatory disorders start early in life and affect the body over decades, if not for life. In addition, the socioeconomic burden of chronic inflammatory diseases is high, entailing substantial indirect healthcare costs due to sick leave, permanent work disability and early retirement. Furthermore the direct medical costs are also tremendous, given the treatment periods and expensive new anti-inflammatory therapies (e.g. biological agents). Hence, chronic inflammatory diseases increase in their importance for the European healthcare systems. The current therapies for treatment of chronic inflammatory diseases are limited to suppressing the inflammatory process and are usually a life-long undertaking.2 Therapies that re-activate endogenous molecular switches to induce the termination of the inflammatory process are not yet in clinical use. In fact there is a very limited knowledge on the mechanisms of resolution to date, and whether its activation can emerge as a novel strategy to treat chronic inflammatory diseases.

Why resolution fails in chronic inflammatory disease To develop a better understanding of the resolution process of inflammation and its functional failure in chronic inflammatory diseases, the German Research Council (DFG) granted the Collaborative Research Centre (CRC) 1181 ‘Checkpoints for

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resolution of inflammation’ at the University of ErlangenNuremberg, which steps into this gap. The interdisciplinary consortium with 19 scientific subprojects, a central imaging project and an integrated research training group, aims to identify the molecular switches determining the resolution process. The major goals of the researchers are to Professor Dr Georg Schett identify the causes for the dysfunctional resolution process in chronic inflammatory diseases. Furthermore, CRC1181 aims to develop therapeutic strategies to introduce the termination of inflammation and restore immune and tissue homeostasis. Due to the high-level of interdisciplinarity and the strongly clinically anchored focus of the initiative, the DFG recognised a huge potential in CRC1181 for identifying new pathways that could be used to treat inflammation in a sustained way. To maximise the success of this project, researchers in immunology and inflammation in Erlangen co-operate on dedicated, innovative and clearly defined topics with high relevance for human diseases. By generating a better understanding of the resolution of inflammation and developing therapeutic strategies, the scientists aim to reduce both the individual and the socioeconomic burden of chronic inflammatory diseases of the joints, the gut and the lungs. The researchers hypothesise that resolution of inflammation warrants proper molecular control and can be considered an active and highly organised process. They assume that appropriate resolution is disturbed in chronic inflammatory disease, resulting in self-maintenance of inflammation. A physiological reaction of the human body turns into a severe disease. The current state-of-the-art research supports the existence of at least three interlinked molecular switches, which are necessary to contain and finally stop the inflammatory reaction.

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Cytokine switch It is known that inflammation is built on waves of distinct immune cells infiltrating the target tissue and guiding either onset, peak or resolution of inflammation. While the early phases of the inflammatory response are dominated by neutrophils and inflammatory monocytes, later phases are dominated by scavenger cells, like macrophages and eosinophils promoting clearance and resolution of inflammation.3 It is tempting to speculate that effective resolution of inflammation requires a robust switch from pro-inflammatory towards anti-inflammatory cytokine production, which is closely related to the distinct pattern of immune cells orchestrating the different phases of the inflammatory response. Failure to adequately silence or to replace those immune cells, which are responsible for inflammatory cytokine production in the affected tissues, results in a perpetuation of the inflammatory process and tissue destruction. Hence, identifying the cells and molecules accompanying the late resolution stage of inflammation appears to be a key to understanding how inflammation stops and returns to the steadystate condition.

Lymphocyte switch Pro-inflammatory lymphocyte activation is a central step at the interphase between acute inflammatory responses and chronic inflammatory diseases. Sustained lymphocyte activation is responsible for breaking immune tolerance against self, which is an important chronification signal in inflammatory diseases and typically observed in rheumatoid arthritis. On the other hand, an over-activation of cytokine producing lymphocytes is considered an important step in chronic gut and lung inflammation as well. Chronic inflammatory diseases are typically characterised by sustained activation of the adaptive immune system including T and B lymphocytes in the lymph nodes and in the inflammatory lesions. The scientists of CRC1181 hypothesise that the pattern of T cell activation in inflammatory tissues may emerge as a crucial checkpoint controlling either resolution of inflammation or its chronification.4 Also, a tight cross-talk between T lymphocytes and macrophage polarisation and other regulatory innate processes as described above can be envisioned.

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At each of these three steps a series of molecular pathways is operating to ensure appropriate resolution of inflammation. These pathways will be tackled by the scientists of CRC1181 aiming to better understand the process of chronification of inflammation in human arthritis, inflammatory bowel disease and asthma. Furthermore, targeting the crossroads between resolution and chronicity will certainly open new avenues to treat these conditions in an entirely different way, moving the field from suppression of inflammation towards restoring the immune homeostasis. References and further reading 1 Tunstall-Pedoe H. (2005). Preventing Chronic Diseases. A Vital Investment: WHO Global Report. Geneva: World Health Organization: 200. ISBN 92 4 1563001. Also published on http://www.who.int/chp/chronic_disease_report/en/. Int J Epidemiol. 2006. Jul 19. 2 Schett G, Elewaut D, McInnes IB, Dayer JM, Neurath MF. (2013). How Cytokine Networks Fuel Inflammation: Toward a cytokine-based disease taxonomy. Nat Med. 19, 822-824. 3 Uderhardt S, Herrmann M, Oskolkova OV, Aschermann S, Bicker W, Ipseiz N, Sarter K, Frey B, Rothe T, Voll R, Nimmerjahn F, Bochkov VN, Schett G, Krönke G. (2012).12/15-lipoxygenase orchestrates the clearance of apoptotic cells and maintains immunologic tolerance. Immunity. 36:834-46. 4 Finotto S, Neurath MF, Glickman JN, Szabo SJ, Drazen JM, De Sanctis GT, Glimcher LH. (2002). Development of spontaneous airway changes consistent with humans asthma in mice lacking T-Bet. Science. 295;336-338. 5 Schauer C, Janko C, Munoz LE, Zhao Y, Kienhöfer D, Frey B, Lell M, Manger B, Rech J, Nachberger E, Holmdahl R, Krenn V, Harrer T, Jeremic I, Bilyy R, Schett G, Hoffmann MH, Herrmann M. (2014). Aggregated neutrophil extracellular traps acta as cytokine sinks and terminate neutrophil-driven inflammation. Nat Med. 20(5), 511-517. 6 Günther C, Martini E, Wittkopf N, Amann K, Weigmann B, Neumann H, Waldner MJ, Hedrick SM, Tenzer S, Neurath MF, Becker C. (2011). Caspase-8 regulates TNF-alpha-induced epithelial necroptosis and terminal ileitis. Nature. 477:335-9.

Tissue switch Resolution of inflammation requires the controlled removal of immune cells to debunk the inflammatory infiltrate. In addition, resolution of inflammation is accompanied by tissue responses entailing the repair and/or the replacement of damaged tissue.5 Effective resolution therefore has to allow death or evasion of immune cells and promote directed response by resident cells to reconstitute the tissue architecture at the site of former inflammation. These tissue responses do not only have to restore the original tissue architecture, but they may also have intrinsic anti-inflammatory properties.6 How cell death and the reprogramming of resident tissue cells contributes to the resolution of inflammation and induction of repair in the joints, the gut and the lungs will be investigated in the CRC1181 programme.

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Georg Schett MD Professor and Chair Department of Internal Medicine 3, Friedrich Alexander University Erlangen-Nuremberg (FAU) +49 (0)9131 853 9109 [email protected] http://www.medizin3.uk-erlangen.de/en/crc1181/

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PEKKA KOPONEN, FOUNDER OF SPINVERSE, ELABORATES ON THE CTO OF THE YEAR AWARD, ALONG WITH COMMENTS FROM THIS YEAR’S WINNERS

CTOs of the Year 2015

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he European CTO (Chief Technology Officer) of the Year award platform recognises and highlights the importance and impact of technology and innovation in Europe. The award, first launched in Finland, is organised by Spinverse Ltd (innovation consultancy) and EIRMA (European Industry Research and Management Association), and given to the most innovative technology leader of a highly successful European company. Even though CTOs have a crucial role in bringing technology to markets and creating the technology strategy of a company, Spinverse noticed that, unlike many other senior executives such as the CEO, CIO or CFO, nobody was awarding the CTOs. After four years, the award and its publicity has strengthened the role of the CTO in Finland. Spinverse believes in good recognition and success at the European level. The person awarded the CTO of the Year works in a successful, innovative company, is an inspiring leader and a foresighted technology manager. In addition, he or she contributes to the development and sustainability of his or her industry, as well as to society at large. As Robert-Jan Smits, director general of the Directorate-General for

Europe is clearly a powerhouse of innovation, and it is wonderful that an award like this exists to celebrate the dedication, vision, and inspiration that the CTOs across Europe’s diverse industries possess. I am passionate about technological innovation and how we can harness it to impact profound change and improvements to the world. However, innovation doesn’t just happen; it starts with a vision and ends in a product, but it is the detail in between where you find the real engine of innovation; the sleepless nights, the long hours, the inspirational leadership sustained over years, and the unflinching belief that the innovative idea will work in the background of negativity from dissenters who push against novel and new ideas and technology. We live in an incredible time of innovation, but it is still one with huge and frightening problems facing the world, problems such as antimicrobial resistance. This is not a time for us to sit back and wait for change to happen organically; this is a time where we must actively work to combat these issues. With ‘The Internet of Life’™, enabled by our Q-POC device, we hope that we will provide the world with an early warning system for pandemics and a tool to help better steward anti-infectives. I am honoured and humbled to have received this award. It is amazing recognition for the groundbreaking work that comes from the whole QuantuMDx team, they have all worked hard to develop some truly game changing technologies and I’m incredibly proud of what we have achieved so far. It is because of them and the support from our partners and investors that I am able to accept this prestigious award. Jonathan O’Halloran QuantuMDx www.quantumdx.com Research and Innovation (RTO), of the European Commission says: “Europe needs to celebrate those who advance technology and innovate. Initiatives like the ‘CTO of the Year Award’ are very welcome as they lead to role models and further strengthen innovation in Europe.”

The 2014 award The nominations for the year 2014 included excellent candidates representing successful

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companies and industries: from IT start-ups to innovative food producers and world leaders in chemistry and materials. The winners were awarded in two categories, SMEs and large companies. Both the winners, Professor Richard Parker, director of research and technology at Rolls-Royce (see: http://www.paneuropeannetworkspublications. com/ST13/#20), and Dr Gert-Jan Gruter, CTO at Avantium, can be seen as excellent examples of the kind of technology leaders that Europe needs, in all types and sizes of companies. It is a great honour to receive the 2015 CTO of the Year Award, and I feel it is great recognition for the Bright Science community at DSM. DSM is a life and materials sciences company with a unique vision that bright science enables a more sustainable world for both today and for generations to come. That is something I have always believed very strongly in, and if DSM’s achievements under my leadership have demonstrated the importance of innovation for Europe’s future, then it is because I had the good fortune to be part of the right company at the right time. Our efforts have also received valuable support in some great partnerships – we definitely can’t achieve our goals alone. Marcel Wubbolts Royal DSM http://www.dsm.com

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As Gruter explained at the end of his time as the European CTO of the Year: “My CTO of the Year Award was closely related to the development of the YXY technology by Avantium: bringing a new bio-based monomer (FDCA) and polymer (PEF) to the market. We have made a lot of progress towards building the first plant to commercially produce FDCA. We are in the final stage of selecting a site, a feedstock partner, an engineering partner, off-take partners and, last but not least, financial investor partners to start the plant engineering and construction in 2016.” Martin Curley, of Intel Corporation (see http://www.paneuropeannet workspublications.com/ST17/#34), Marcel Wubbolts of Royal DSM, and Jonathan O’Halloran of QuantuMDx are now awarded as European CTOs of the Year 2015. This year’s candidates included numerous excellent nominations, leading the jury to the decision to award two equally brilliant technology leaders in the large company category. All three winners are inspiring leaders who have paid special attention to sustainability and the creation of strong and broad technology collaboration communities. Based on their foresighted technology leadership, Europe has reached the forefront in three very different industries. It is with excitement that we now wait to see what new ideas and innovations their award year will bring.

Pekka Koponen Founder Spinverse www.spinverse.com/ www.ctoeurope.net/

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PROFESSOR MARTIN CURLEY SPOKE TO PEN ABOUT HOW INTEL® FOSTERS INNOVATION, AND HIS FEELINGS AT BEING NAMED THE SECOND EUROPEAN CHIEF TECHNOLOGY OFFICER OF THE YEAR

Innovation inside T he European CTO of the Year Award is presented by the European Industrial Research Management Association and Spinverse, a leader in Nordic innovation consulting. Following the first award last year – to Professor Richard Parker, the director of research and technology at Rolls-Royce plc – the 2015 award was given to Intel’s Professor Martin Curley, Royal DSM’s Marcel Wubbolts and QuantuMDx’s Jonathan O’Halloran. These three individuals were selected after being identified as inspiring leaders who have paid special attention to sustainability and the creation of strong and broad technology collaboration communities.

Professor Martin Curley

In an interview with Pan European Networks, Curley outlined how Intel fosters innovation and supports smaller companies, how the European policy landscape is evolving so as to provide a sound legislative structure to support this, and his feelings at being the recipient of the second of these prestigious awards.

How would you like to see the importance of innovative manufacturing as a key enabler of any technology better highlighted? In terms of bringing innovation to the market, innovative manufacturing is hugely important for a company like Intel, where the manufacturing process is at least as important, if not more important than good product design. That has helped us to achieve a leadership position and so we seek to have a manufacturing process that is one or two steps ahead of our competition. Perhaps predictably, as we innovate our manufacturing processes (for example, moving from 200mm silicon wafers to 300mm), that brings us lots of benefits.

Younger people tend to be digital natives, and so you can bring a product to the market with a lot of digital elements embedded in to it, and you can assume that people will know how to use it

Innovative manufacturing is not just about getting better products or better quality, but about lowering costs and reducing time to market as you innovate. Design for manufacturability is an important concept and is one of the key design constraints that engineers must consider during product design. It is vitally important from a European perspective that we continue to invest in and protect European manufacturing. It is hugely important to develop the knowledge economy; the thought leadership and product design in Europe (and in other places), as well as initiatives like Industry 4.0, which emerged in Germany and is becoming more widely adopted across Europe, are very important to make sure that we continue to have innovation in manufacturing. Indeed, anything that national governments or the European Commission can do to promote and help innovative manufacturing capabilities is really important.

Do you think enough is being done at the national and European levels to bring those areas together and share best practice, whilst also ensuring minimal overlap? In the EU in particular there is a lot going on around smart specialisation, for instance, but there is nevertheless a lot more to do. There is perhaps a growing realisation, especially amongst policy makers, that Europe can’t afford to let its manufacturing base disappear. Five or six years ago that awareness wasn’t there, but now there is a sense that decision makers are aware that manufacturing is vitally important to Europe’s future. This is the necessary first step. There are now some policy efforts to try to strengthen our manufacturing base, and Industry 4.0 is a particularly noteworthy example that deserves a lot of support from stakeholders across Europe. The UK has done a great job in terms of solidifying its technology and manufacturing base, which was a welcome change from what

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appeared to be something of a onedimensional approach focused solely on finance; there has been a kind of rebirth around technology in the UK over the past few years.

How can smaller companies learn from the Intel model? There are often spillover effects when a large company innovates with that innovation going into the marketplace and becoming adopted elsewhere. Traditionally, our ecosystem contains a lot of innovation – not least in manufacturing – but there are nevertheless areas where we require assistance in solving certain problems, and so within that ecosystem we work with other companies, including small start-ups, whom we also help to innovate. The Internet of Things is one of the growth areas in Europe that we are involved in. Having recently hosted a joint event, with Cisco and Deutsche Telekom, a virtual ecosystem was created for 12 start-up companies with very interesting ideas for the Internet of Things. One of these companies has begun to develop a computerised glove that contains sensor technology. This is a small company based in Munich that uses Intel technology in their product. As such, we are helping them to open doors for a technology that could be very important in areas such as manual precision assembly and maintenance.

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You can only measure innovation success when people adopt a product

Last year, the winner of the first CTO of the Year Award, Professor Richard Parker, told me: “Creating technology is not enough; you also have to have the skills to go with it.” What are your thoughts on this, and what role can large innovative companies such as Intel Corporation play? Innovation is all about adoption, and if you create a technology then you have to have an ecosystem or customers sufficiently skilled to use it. One of the key tasks here is if you bring any new product or service to the market, then you have to think about the usability of the product more and more – and also the utility or the usefulness as well as the user experience. Increasingly, the successful companies are those that not only bring great technologies to the market, but those which have really thought out the market adoption strategy in advance. Depending on the product and the market, the level of skill or sophistication of the customer or audience will change. Generation-wise, younger people tend to be digital natives, and so you can bring a product to the market with a lot of digital elements embedded into it, and you can assume that people will know how to use it, whereas perhaps ten or 15 years ago that may not have been the case.

The last time you wrote for Pan European Networks you highlighted how innovation adoption is the hallmark of Innovation 2.0. How do you feel the EU could do more to help facilitate the evolution of customer behaviour in this sense? To return to the idea of innovation adoption, Michael Schrage has a great quote which says that “innovation isn’t innovators innovating, it is customer adopting”. You can only measure innovation success when people adopt a product.

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There is a lot to do when designing a product or service with regard to how well it will be adopted by the consumer, but I don’t necessarily think that the EU has a role to play when it comes to helping to facilitate the evolution of consumer behaviour per se. What the EU can do, however, is improve collaborative funding mechanisms like Horizon 2020 and stimulate the use of living labs, as this is where we get consumers and users involved in the innovation process. In this sense, we have recently seen some success at Intel in the cities of London and Dublin, where we are deploying Internet of Things technologies and working with citizens and users to help co-innovate and imagine the new usage models that can be enabled by these technologies. There has been a significant shift in Horizon 2020 with regard to its predecessor, FP7, which was very much about pure research. In H2020 there is more of a focus on innovation. I sit on the EU CAF CONNECT advisory forum, a digital advisory board to DG CONNECT, and we have been proposing the use of market readiness levels in parallel to technology readiness levels. So, in thinking about the development of new products, it is not just about the maturity of the technology, but also the maturity of the product and everything around it such as the training, usability and the development of the skills required to maintain and sustain the product in the marketplace.

You mentioned how the younger generations are now ‘technologically native’. Do you think more needs to be done in a social sense to familiarise the older generations with new technologies? Increasingly, even some of the older generation – via an osmosis-like process – are adopting new technologies and finding them quite easy to use. Nevertheless, there is certainly a responsibility for all of us to help others less technically-savvy than ourselves to ramp up their skills as the interfaces become simpler and easier to use, and as technology evolves. An example of this would be Intel RealSense™ technology, which has a gesture-based interaction, and which will become more natural. As such, this may be a problem at the moment, and it certainly needs to be addressed, but there is an increasing sense that this is a problem which will dissipate with time.

What are your thoughts on the progress being made towards the Innovation Union? The Innovation Union is a very worthy initiative, and it is essential for the vibrancy of the European Commission that we have this kind of direction. We are collectively making progress; however, like any significant initiative, the short term progress can be seen as unsatisfactory, but when you look at the medium to long term, the progress is in fact quite promising. There have been some very noticeable contributions already, such as the introduction of the European Innovation Scoreboard, whereby country-to-country innovation performance can be compared so as to provide insights that individual countries can use to identify the weak spots in their innovation ecosystems, for instance. Robert-Jan Smits, the director-general of DG RESEARCH, is deeply committed to this and is playing a very important role in ensuring continuity flows from the groundwork made by the previous science commissioner, Máire

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Geoghegan-Quinn, who has now been succeeded by Commissioner Carlos Moedas. Commissioner Moedas has recently discussed areas such as open innovation and open science, arguing that it is important to open up innovation, and so there is a sense that the rhetoric matches the instruments. The new Digital Economy and Society Commissioner Günther H Oettinger has also identified that European companies need to more aggressively adopt digital technologies or risk being left behind. Therefore, the broader picture is certainly a positive one and I am particularly pleased to see that Robert Madelin has now changed roles from the directorgeneral of DG CONNECT to become responsible for cross-cutting innovation in the Commission. The fact that the EU has taken such a senior person to spearhead the efforts around crosscutting innovation is certainly noteworthy.

Finally, to return to your award: what do you think initiatives such as this award can achieve, and what are your thoughts on receiving it? The CTO of the Year Award really helps to promote technology-related careers as a very exciting and viable pathway and helps to highlight the important role of technology and innovation in Europe. It also contributes to a broader effort to try and encourage more students to choose technology, engineering, and science careers, and it is great that this is being done in a European context. I am thrilled to receive the award, but innovation is a team sport and while I am privileged to be the captain of Intel Labs Europe, I accept the award on behalf of the fantastic Intel researchers and the ecosystem players that research and collaborate with us.

Professor Martin Curley Vice-President – Intel Labs Europe Chair – Open Innovation Strategy and Policy Group http://www.intel.eu/content/www/eu/en/ research/intel-labs.html https://sites.google.com/site/openinnovat ionplatform/

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EUROPE’S POWERS FOR INNOVATION ARE CLOSELY TIED TO THE ESTABLISHMENT OF THE ERA. HERE, PEN ALSO LOOKS AT OTHER RELEVANT AREAS, SUCH AS OPENNESS AND ACCREDITATION

An ERA of innovation

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he European Research Area (ERA) – a unified area open to the world in which scientific knowledge, technology and researchers circulate freely – has untold potential to increase the innovative capacity of the research being produced in Europe. With a focus on boosting investment and promoting national competition, common research agendas on grand challenges and infrastructures, facilitating mobility, supporting training and ensuring attractive careers, encouraging gender diversity to foster science excellence and relevance, and optimal circulation, access to and transfer of scientific knowledge, the ERA stands to lead to a significant improvement in Europe’s research performance to promote growth and job creation. The role of the ERA in boosting Europe’s innovation was the subject of a speech delivered by the European Commissioner for Research, Science and Innovation, Carlos Moedas, in Brussels in June 2015. In his address, entitled ‘Open Innovation, Open Science, Open to the World’ delivered at the ‘A new start for Europe: Opening up to an ERA of Innovation’ conference, Moedas explained: “Open innovation is about involving far more actors in the innovation process, from researchers, to entrepreneurs, to users, to governments and civil society. We need open innovation to capitalise on the results of European research and innovation. This means creating the right ecosystems, increasing investment, and bringing more companies and regions into the knowledge economy. I would like to go further and faster towards open innovation.” He added: “I believe we need to do more to create a regulatory environment for innovation to flourish. How do we make sure that legislative processes that take several years can adapt to technologies

European Commissioner for Research, Science and Innovation, Carlos Moedas

More needs to be done to create a regulatory environment for innovation to flourish

that evolve every month? How do we make sure that regulation is based on an innovation principle as well as a precautionary principle? “Second, if we compare the investment levels between the EU and the US, one of the biggest differences in the ecosystem is venture capital. There is far less venture capital in Europe, and venture capital funds do not have the scale or scope to grow companies from early stage to mid-cap and from mid-cap to global players. I would like to address this problem head on through the development of one or several European Fund of Funds that will invest in new generations of great European innovative companies. “Third, we need new actions to get more innovation impact out of Horizon 2020. One way we can do this is to create real synergies with the Structural Funds,” he stated. Fourth, the commissioner pointed to Horizon 2020 as having made a significant step forward in supporting innovation. “I am very proud of this,” he said, “but I also see that Europe does not yet have a world class scheme to support the very best innovations in the way that the

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European Research Council is the global reference for supporting excellent science.”

The key to excellence Moedas continued: “I am convinced that excellent science is the foundation of future prosperity, and that openness is the key to excellence.”

“The future of innovation lies in bringing as many different people, concepts and fields together”

The importance of openness was a topic that the commissioner again highlighted in his speech at the University of Helsinki on 31 August 2015 – the occasion of the university’s 375th Anniversary. Here, in an address entitled ‘The importance of research for the future of Europe’, Moedas said: “It is my opinion that the future of innovation lies in bringing as many different people, concepts and fields together”, adding: “In my eyes, the future lies in open innovation, because openness fuels innovation.” The science commissioner also revealed that open innovation is often found at the intersection of disciplines, rather than from any one single field. He explained: “It comes from how we apply knowledge to the real world around us, together. Such co-operation requires patience and perseverance. Of course, it’s

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much easier to do what we want without consulting anyone else, but with such a blinkered approach, we’d only get so far. To be open means to work in harmony with those who are different from us, who have different opinions from us, and those who see the world differently than us. It takes longer, but it is more effective in the long run: tackling the problems we all face, from all sides, at every opportunity.”

Knowledge base Moedas then provided his audience with an anecdote of a conversation he had with ESA astronaut Luca Parmitano, who had argued that reaching the top of research, science and innovation in Europe is like reaching the top of a tetrahedron – which has four triangular surfaces forming a pyramid, the height of which is directly related to the size of the base, meaning that to get higher, you need a larger base. Moedas explained Parmitano’s point: “If you want to achieve new breakthroughs in science and innovation, you have to increase the size of the knowledge base. Openness is one way to increase the knowledge base, but we also need to invest. We need to invest in universities, we need to invest in innovative companies, and we need to invest in people. “At the European Commission,” he added, “we’re making an historic effort to invest in the things that will give Europe the most opportunities to thrive as an economy, now and in the future. Horizon 2020 is the largest ever European research and innovation programme providing nearly €80bn of public investment in great science, innovative projects, and research careers, but we also need far more private investment. This

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Accreditation Europe is home to many of the world’s top universities and academic and/or scientific institutions – from Oxford and Cambridge in the UK, to Germany’s Max Planck and France’s CNRS. And, as European Commissioner for Research, Science and Innovation, Carlos Moedas has highlighted, while openness is one way to increase Europe’s knowledge base and thus improve Europe’s scientific excellence and innovative potential, we also need to invest: in universities, in innovative companies and in people. Given the fact that Europe plays host to a multitude of excellent universities, accreditation plays a significant role in not only highlighting a particular institution’s importance by lending an element of prestige, but also in attracting the best people – whether they be students or staff. As such, many accreditation organisations operate to bestow accreditation on institutions depending on their areas of speciality. The ENQA (European Association for Quality Assurance in Higher Education) disseminates information, experiences and good practices in the field of quality assurance (QA) in higher education to European QA agencies, public authorities and higher education institutions. The NARIC Network (National Academic Recognition Information Centres) is an initiative of the European Commission created in 1984 to improve academic recognition of diplomas and periods of study in the member states of EU countries, the European Economic Area (EEA) countries and Turkey, for instance. In this way, AACSB International – the Association to Advance Collegiate Schools of Business – is devoted to the advancement of management education. Established in 1916, AACSB International provides its members with a variety of products and services to assist them with the continuous improvement of their business programmes and schools. This includes providing internationally recognised accreditation for undergraduate, masters, and doctoral programmes in business and accounting. According to the organisation’s website, its members range from educational institutions offering business programmes to corporate, non-profit, and public sector organisations that desire to connect with and/or support business education worldwide. However, these members only become accredited if they are able to demonstrate that they can achieve a rigorous set of quality standards. Accreditation thus enables Europe’s academic establishments to not only remain attractive in the competitive education market, but also to widen its horizons and to link with other sectors in order to boost its capacity for innovation. is where there is the big gap, if we compare ourselves to the US or leading economies in Asia.” In light of this, Moedas revealed that the Commission had recently taken a big step forward in addressing this gap through the establishment of the new European Fund for Strategic Investment. He explained: “The European Commission and the European Investment Bank are teaming

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We need to invest in universities, we need to invest in innovative companies, and we need to invest in people

up to support strategic investments worth at least €315bn.”

The definition of unity Having discussed openness to some degree, the science commissioner directed his attention towards the concept of ‘unity’, beginning by quoting Oxford English Dictionary definitions of the word – such as ‘harmony’ and ‘cohesion’, as well as its definition as a mass noun: the ‘state of being joined as a whole’, which he said for him means “the condition of being bound together, as part of something greater”. However, he also expressed his fear that Europe is perhaps beginning to take its unity for granted, and that Europeans no longer notice “how much greater a voice it gives us in the world”. Concluding both his address and the points he had made about unity, Commissioner Moedas remarked: “It is my belief that one of the greatest gifts the academic community can offer to society is to remind us of the importance of co-operation. Co-operation in the tradition of the scholars who entered the very first European universities hundreds of years ago to reveal and share knowledge. Co-operation in an age that offers endless opportunities to collaborate with people all over the world and solve common problems,” and, indeed, it is this openness and this ability – and willingness – to collaborate that are the very cornerstones of the ERA – which embodies the openness discussed by the commissioner.

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PROFILE

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PROGRAMMES AND PROJECTS The Faculty of Economic Sciences and Management outlines the programmes, research and projects they offer and undertake

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he Faculty of Economic Sciences and Management is one of the largest and best equipped at Nicolaus Copernicus University in Toruń, Poland, is a medieval town listed on UNESCO’s World Cultural Heritage List. The Faculty of Economic Sciences and Management was established in 1968. It is the only public school in Poland accredited by the Association to Advance Collegiate Schools of Business (AACSB) programmes. Our faculty offers three levels of teaching programme: bachelor’s, master’s, and doctoral, as well as postgraduate studies and MBA courses. The Executive Master of Business Administration studies is accredited by North Central Association of Colleges and the Association Collegiate Business Schools and Programs (ACBSP). The programme is run by the Nicolaus Copernicus University together with the Dominican University in Chicago.

Internationally oriented The broad scope of our research activities and international education programmes enables us to attract students and teachers from all over Europe and the USA. Every year our teachers and students participate in exchange programmes around the world with one of our university partners, of which there are almost 50. Our faculty also offers a common programme in English for the double degree with the Université d’Angers, France, and Universidad Pablo de Olavide in Sevilla, Spain. Our courses in Business English SEFIC are certified by the London Chamber of Commerce. The Polish-American Center for Leadership and Social Corporate Responsibility and the International Center for Economic Research of Central and Eastern Europe are very active, being important units of the faculty, developing many research projects.

The faculty, as one of the 1,000 best business schools from all over the world, was awarded ‘Three Palms’ by the Eduniversal International Scientific Committee in Paris. In 2015 we organised the international congress of the SPACE association, which gathers business and language schools from many European countries as well as the USA. Since 2014 the faculty has been a part of the international educational research programme, organised and financed by the Spanish banking group Santander. The Faculty of Economic Sciences and Management has many links with business and international organisations. We co-operate with such global companies as: Nestlé, Sharp, PricewaterhouseCoopers, Unilever, EY (previously Ernst & Young) and many Polish stock exchange companies.

The scope of main research projects The Department for Human Resources Management has long specialised in research on enhancing the effectiveness of labour market policies through its systematic evaluation, the use of appropriate procedures for targeting labour market programmes, and the introduction of unemployed profiling procedures, as evidenced by numerous publications devoted to these particular issues. The achievements also include the methodology for measuring the effectiveness of labour market policies developed for the public employment services. The team at the Department for Human Resources Management gained valuable experience in implementing research framework programmes of the European Community, the results of which were deemed very good by the EU Commission. In the field of economics theory, research projects concerning the economic development and institutional order have been developed since 2010. In the field of quantitative methods, the econometric models and tools are developed. The following areas are on special interests: n Primary research (tools and methods): time series modelling and forecasting, co-integrated systems, nonlinear models and nonlinear tests, causality analysis, financial econometrics and analysis of risk, spectral analysis, high frequency data, Bayesian econometrics and spatial econometrics; n

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Applied studies: business cycles and economic growth analysis – international comparisons, dependencies on global financial markets, forecasting in logistics and marketing, modelling of power market, economic and social convergence

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(our partners are VISA Europe and MasterCard), ecological banking and finance. The newest area of our scientific investigations are concentrated on multicultural management projects with partners from Norway, Spain and Finland.

analysis, regional studies, micro-econometrics, GNU Gretl computer package development; and n

Commercial studies: cost index in the road transport sector (2010-2012), training in: ‘Spectral Analysis in Business Cycle Studies’ (2014); and ‘Statistics in Audit’ (2009, 2013, 2014).

The Department of Investment and Real Estate’s research work concentrates on two main pillars directly connected with the pressing economic issues of the present world. The first pillar concerns business internationalisation. Particularly, with regards to international capital flows in the form of Foreign Direct Investment (FDI), including its scale, geographic spread and structure, the potential consequences for the current status and the future development of modern transnational corporations from both developed and developing countries. The second pillar of the studies reflects the problems of investing in the real estate market regarding its specific considerations, risk, financing and property valuation. International and global contexts, as well as the local aspects of the problems investigated, are taken into account in both of the research fields. The Department of the European Integration and Regional Studies conducts educational activities and scientific research in the fields of: economic policy; regional economy development; and international integration. International research projects carried out with partners from Belarus, Lithuania, Latvia, Russia and Ukraine are focused on: n Issues related to the development of the countries and regions of Central and Eastern Europe (CEE), especially transformation and cross-border economic co-operation on the eastern border of the EU; n

The importance of the EU cohesion policy for the competitiveness increases of national and regional economies;

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The role of local governments in managing local and regional development, inclusive growth and meaning of human capital; and

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Smart city theory and practice etc.

The Department of Finance conducts, among other things, scientific research projects in retail payments, electronic banking

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At the faculty there is a strong research stream regarding organisational behaviour. Three projects are currently conducted under the leadership of Professor Aldona Glińska-Neweś. The first project is financed by the Polish National Science Centre; its aim is to identify social phenomena accompanying innovation creation in business and social economy organisations. The research is focused specifically on the social innovations. Among analysed issues particularly, employee interpersonal relationships, role distribution and hierarchical distance are concerned. The project includes multi-methodological approach, i.e. both quantitative and qualitative methods (ethnography, shadowing, and focus group interviews) are adopted. Data collected from 200 companies and 140 social economy enterprises revealed interesting correlations between positive relationships in employee teams and organisation innovativeness. Moreover, categories of innovation teams have been identified on the basis of personal relationships and hierarchical distance dimensions. Further qualitative research steps will allow the team to deepen the knowledge regarding innovation type especially influenced by employee relations as well as specific variables describing those relationships. The second project is multinational and is conducted in co-operation with a French and a Chinese university partner (Université d’Angers and Sun Yat-sen University in Guangzhou). The main purpose of this project is to study emotions as antecedents of employee attitudes in the tourism sector. The third project in this ‘behavioural’ stream is regarding organisational citizenship behaviours and their links with counterproductive work behaviours explained on the ground of the moral licensing theory. The project is conducted in a multinational company and will allow us to study cultural differences in this area.

Professor Jerzy Boehlke Associate Professor Faculty of Economic Sciences & Management Nicolaus Copernicus University +48 (0)56 611 4609 [email protected] https://usosweb.umk.pl/kontroler.php?_action=k atalog2/jednostki/pokazJednostke& kod=1100000000

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MAXIMISING YOUR RETURN Inntrion’s Richard Bremer outlines the importance of technology transfer and how it increases the return on research

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ccording to the EU 2020 strategy, 3% of the EU budget will be invested in research and development. It is generally accepted that investments in research generate economic growth and is of vital importance to turn EU members into competitive knowledge-based economies. However, strengthening global EU competitiveness will not be realised solely through investments in generating new research-based inventions. First, when there is a solid infrastructure for commercialising research, turning inventions into innovations, will we be able to leverage the outcomes of academic research. ‘Technology transfer’ is another term for this process, bringing inventions into licensing agreements, industry collaborations or new ventures. In short, enabling a researcher’s progress to make an impact outside the academic world. Most researchers are indifferent to the process of technology transfer, as their interests and incentives lie in continuous research progress and producing new scientific articles. No matter how scientifically strong a research advancement is, lack of focus on commercial applications will prevent even the most promising project from reaching the private sector. Furthermore, shortage of funding will soon bring any commercial initiative to an end. As a consequence, the technology transfer process is a high risk endeavour, where the number of unknowns will considerably limit the ability to identify early future success stories. The high risk environment explains the general absence of private organisations and venture capital funding. This advocates reinforced governmental funding and best practice dissemination across Europe, sharing experiences and knowledge exchange with international technology transfer organisations. Inntrion is one of a few technology transfer companies in Sweden with the ambition to identify, nurture and invest in technology intensive academic research projects and ventures, thereby reducing time to market for high potential research findings. Together with our partner, Bergenstråhle & Partners, we have developed a process managing risk connected to technology transfer, where an intellectual property readiness assessment interacts with and reinforces market validation efforts. Where the IP readiness assessment focuses on identifying intellectual property with strategic commercial value and potential patent intrusions, our market validation concentrates on interacting with potential customers and stakeholders to gather market feedback

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and ultimately generate paying customers and/or industry collaborations. We believe these two concepts are intertwined and inseparable if developing a successful generic technology transfer model, a conclusion confirmed by several commercialisation projects with researchers at leading universities in Sweden. Richard Bremer Combining IP and market efforts offers a unique possibility to make a multifaceted, early assessment of a project’s potential and rank each one accordingly. As a result, our process will identify vital indicators showing the way for further interventions and will ensure efficient use of limited resources. Our groundwork will unveil risk factors and also identify appropriate measures to manage them. Thereby, the result of this process will improve the attractiveness for entrepreneurs, venture capital and further funding to invest time and capital in research findings with considerable commercial potential. In projects matching our predefined requirements, we add long term commitment to enhance the probability of generating pay-offs after the technology transfer process, including assisting the project with finding an entrepreneur, venture capital and advisory. Successful technology transfer is key to generating growth from European cutting edge research findings and increasing international competitiveness, but it will not occur unless there is a structure for risk reduction and long term involvements. Only then will we be able to achieve improved return on investments in research.

Richard Bremer Founder Inntrion AB +46 (0)73 526 1276 [email protected] http://inntrion.com/

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SPOTLIGHT: BIOBASED INDUSTRIES

PAN EUROPEAN NETWORKS SPOKE TO DR DIRK CARREZ ABOUT CALLS, HOW THE BIO-BASED INDUSTRIES JOINT UNDERTAKING IS EVOLVING, AND THE JU’S INDEPENDENCE FROM THE COMMISSION

Bolstering Europe’s bioeconomy

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he Bio-Based Industries Joint Undertaking (BBI JU) is a public private partnership (PPP), part of the EU’s plan to move its economy to a post-petroleum era. It is expected to help make the EU’s economy more resource-efficient and sustainable, while supporting growth and employment. The JU is dedicated to realising the potential of the European bioeconomy and contributing to a sustainable Circular Economy, by turning biological residues and wastes (from agro-food, forestry and municipal) into greener everyday products, through innovative technologies and biorefineries, which are at the heart of the bioeconomy.

as the development of a common vision and our research agenda.

Dr Dirk Carrez

We developed the Strategic Innovation and Research Agenda (SIRA) in 2013, and we are now working with both the members of the consortium and the Commission to update this so as to take into account what was financed in 2014 and 2015, and what will be included in the call for 2016. We also need to look at other funding programmes to see what has been financed, and at the needs and views of our members, because the number of industry partners in the consortium has more than doubled in the last two years.

€3.7bn will fund the BBI JU between 2014 and 2024, with €975m coming from the European Commission and €2.7bn from its private partner, the Bio-based Industries Consortium (BIC). The BBI JU has remained under the European Commission’s supervision since its formal launch in July 2014. As of October 2015, the BBI JU will function as an independent body, with its own staff and offices, and will be able to manage its own budget and launch its own open calls for proposals, grants and public procurement. Pan European Networks asked the executive director of the Bio-based Industries Consortium, Dr Dirk Carrez, about how the BBI JU has evolved and where the priorities will lie in the future.

What lessons were taken from SusChem when establishing the JU? Perhaps one of the main things we took from SusChem was the elements of the procedure via which we developed the work programme, as well

This vision is important because it brings together the different stakeholders who want to collaborate, and in our case that was even more important because we brought together industrial sectors that, traditionally, had remained separate.

The chemical industry plays a key role because it is central to many of the value chains

We have also become aware that new value chains are being established. To give an example: algae is becoming increasingly important in some areas as feedstock, which is something we hadn’t taken into consideration in the beginning. We are also seeing a heightened interest in combining sectors. This means that instead of having individual value chains – such as those concerning wood, pulp and paper, and so on – they are becoming more connected. For instance, waste from the food industry can be of interest to the chemical industry.

How has the relationship between policy and industry evolved since the beginning of the JU in 2014, and how would you like to see this interaction develop? This is going well. We are working closely with the European Commission on the framework conditions, for instance, which is important because the BBI is one way that we will be able to keep some technological developments in Europe.

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However, more can be done, and we need to address issues such as the facilitation of access to finance, and so we need to ask how the European Investment Bank (EIB) can become more involved, how we can create more visibility, and how we can make a link to the Juncker Plan. The Commission is working hard in this area by, for instance, organising the European Bioeconomy Investment Summit in Brussels.

Algae is becoming increasingly important in some areas as feedstock, which is something we hadn’t taken into consideration in the beginning

We must also work to make the link between the bioeconomy and the Circular Economy, which is something of a hot topic in the political agenda. We are exploring how we can do that by making sure that the Circular Economy does not only focus on the fossil fuels economy but also renewable resources – because we also try to recycle bio-based products, of course. Now that the JU has become independent from the Commission, we have our own staff and budget, but we will continue to work with them on the framework conditions. The relationship with the policy sphere is thus certainly moving in the right direction, and the

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fact that we have a BBI board which includes both members from industry and representatives of different DGs within the Commission – DG Research, DG Agri and DG Growth – is helping to create trust and enabling much more constructive dialogue than we have had in the past.

Amongst the JU’s unique mix of sectors, chemistry plays an important role. Could you expand on this? The chemical industry plays a key role because it is central to many of the value chains; you need the chemical industry to transform the feedstock into a useful chemical product such as a monomer or a polymer for instance. Furthermore, as the nature of these value chains evolves and as increasing overlap between them becomes apparent, new collaborations are also emerging. For instance, as previously mentioned, food waste can provide a supply of cheap feedstock for the chemical industry for certain applications. The chemistry industry therefore plays a key role, not least by linking the different value chains together.

More specifically, the JU has identified that ‘there is a strong, but currently underexploited, potential for valorisation of sugars and lignin streams from wood’. How, then, does the JU hope to be able to address the realisation of new wood-based value chains for the production of chemical building blocks, materials and biofuels? The BBI JU launched its first Call for Proposals in July 2014. All stakeholders (large industries, SMEs, technology providers, academia

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SPOTLIGHT: BIOBASED INDUSTRIES

Europe is setting course for a resource-efficient and sustainable economy – the bioeconomy. The goal is a more innovative, low emissions economy, reconciling demands for sustainable agriculture and fisheries, food security, and the sustainable use of renewable biological resources for industrial purposes, while ensuring biodiversity and environmental protection. According to the European Commission, research and innovation in the bio-based products and processing will provide the means to reduce Europe’s dependency on fossil fuels and contribute to meet its energy and climate change policy targets for 2020. Indeed, the Commission’s website dedicated to the bioeconomy estimates that a shift to biological raw materials and biological processing methods could save up to 2.5 billion tonnes of CO2 equivalents per year by 2030, increasing markets for bio-based raw materials and new consumer products severalfold. The key is to develop new biorefining technologies to sustainably transform renewable natural resources into bio-based products, materials and fuels. This nascent sector is expected to grow rapidly and create new markets and jobs. PPPs thus have a significant role to play when it comes to stimulating additional European research investment, building critical mass by uniting currently fragmented efforts, and ensuring effective and efficient programme management. The BBI Joint Undertaking is designed to implement a programme of research and innovation activities in Europe that will assess the availability of renewable biological resources and the development of new biorefining technologies to sustainably transform these resources into bio-based products, materials and fuels. Those activities should be carried out through collaboration between stakeholders along the entire bio-based value chains, including primary production and processing industries, consumer brands, SMEs, research and technology centres and universities. The nascent sector is expected to grow rapidly and create new markets and jobs, especially in rural and coastal areas. The EU has the industrial, research and renewable resources potential. It is now a matter of deploying it in a sustainable manner to compete in the global bioeconomy race. and RTOs) were encouraged to take part in this new venture and contribute to the deployment of a new and sustainable economy. Ten projects totalling €120m were chosen to boost the EU capacity to stimulate growth and jobs via a more circular, low carbon and sustainable bioeconomy. The seven funded research projects will tackle specific value chain challenges such as sustainability, technology and competitiveness. The two demonstration projects will show the technological and economic viability of biorefinery systems and processes for making chemicals from wood, and for making high value products for detergents, personal care, paints and coatings and composites from sugar beet pulp. The industrial scale flagship project

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will make use of cardoon, an under-utilised oil crop grown on arid and marginal lands, to extract vegetable oils to be further converted into bio-based products (biolubricants, cosmetics and bioplastics). By- and coproducts from the process will also be valorised for energy, feed for animals and added value chemical production. While the results for the 2015 call have yet to be announced, several proposals focused on the new wood-based value chains or on giving added value to those based on forestry, pulp and paper and so on.

Given that the JU is now in its second year, what do you feel have been the biggest achievements thus far, and where do you see your priorities moving forwards? The fact that we have had two calls, coupled with the fact that the BBI JU is now independent, shows that the system is working despite being new. It is also great that we are seeing new sectors becoming interested – the food industry is a good example here, as are the algae-based value chains – and we are witnessing an increased diversification in the kinds of biomass etc. Parallel to that, the enhanced level of collaboration we are experiencing with the Commission means that we are able to boost awareness of the importance of keeping investment in Europe and, as such, are able to underline issues concerning access to finances, and hopefully solve them. A survey being conducted by the EIB is a great example of this. Following on from the flagship and demonstration projects which came from the 2014 call, it is our hope to see more of these coming from the new calls, which will be important for Europe, particularly given the global economic climate and, moreover, because of the competition we are seeing from countries such as China.

Dr Dirk Carrez Executive Director Bio-based Industries Consortium http://biconsortium.eu/

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CARBON CAPTURE

ARVID HALLÉN, DIRECTOR OF THE RESEARCH COUNCIL OF NORWAY, EXPLAINS HOW ITS NEW MAIN STRATEGY WILL ENABLE THE ORGANISATION TO PROMOTE QUALITY AS MORE THAN JUST GOOD RESEARCH

A Norwegian research strategy

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ver the last ten years strategy-oriented efforts have come to play an increasingly important role for the Research Council of Norway. We have designed a set of strategy and policy documents in key areas, implemented a more comprehensive strategic knowledge base in planning and application of funding instruments, and developed arenas for dialogue that have a more targeted strategic focus. We have also sought to promote change through initiatives such as the centre schemes, the large scale programmes in central societal areas, a stronger role vis-à-vis national research infrastructure, and the incorporation of international perspectives as part of the fundamental basis for activities at all levels. The new main strategy takes these developments a step further by explicitly stressing the broader societal mission of the Research Council. Whereas the previous strategy emphasised how we should develop in relation to the quality challenge, the societal challenge, the structural challenge, and the learning challenge in more general terms, the new strategy highlights the need for the research council to enhance its role in relation to the need for greater innovation and sustainability in industry and society at large. This implies that societal challenges must be given a greater role in setting the national research agenda, as well as the agenda for the research council itself.

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Objectives

Arvid Hallén

The strategy has defined a framework of six overall objectives. The first of these represents an aspiration to promote quality as more than just good research and, more specifically, to cultivate breakthrough research that can move the research frontiers. This also involves incorporating breakthrough research as a target in all types of funding instruments, including the thematically-oriented initiatives, as well as amongst all types of research groups. The second objective illustrates that the research council must invest in solving the societal challenges of tomorrow and, in light of this, must encourage greater economic, social, and environmental sustainability. This objective establishes, for the first time, the specific societal challenges on which the council will focus greater effort. Industrial development based on natural resources is one of these areas. The Large-scale Programme for the Optimal Management of Petroleum Resources (PETROMAKS2) will continue to be an important

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North Sea potential PETROMAKS2, the new large scale programme for petroleum, is a continuation of the PETROMAKS programme (2004-2013). It will promote knowledge creation and industrial development to enhance value creation for society by ensuring the development and optimal management of Norwegian petroleum resources within an environmentally sustainable framework. Running from 2013-2022, the programme will provide support for both basic and applied research to generate new expertise and innovations that will lead to: n Reduction of the environmental impact and level of risk related to petroleum activities on the Norwegian continental shelf; funding instrument for activities involving petroleum resources in the future, but activities under the programme must be specifically targeted towards research that promotes the more environmentally friendly, sustainable exploitation of petroleum resources. The next two objectives are linked to innovation and value creation in the private and public sectors. These areas reflect the research council’s clearly stated ambitions regarding the target for research to comprise 3% of GDP, and the role that the private and public sectors will play in this. The objective relating to innovation in the public sector poses some special challenges, as new funding mechanisms for this must be devised.

The Large-scale Programme for the Optimal Management of Petroleum Resources (PETROMAKS2) will continue to be an important funding instrument for activities involving petroleum resources in the future

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Higher recovery rates from new and existing fields;

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More discoveries of oil and gas;

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More environmentally sound and cost-effective drilling and well technology;

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Cost-effective and energy efficient production solutions for the Norwegian continental shelf;

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Improved solutions in the areas of health, safety and the work environment;

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Enhanced petroleum-related industrial development in Norway and abroad; and

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Competence-building and recruitment adapted to the needs of society and the industry.

The objective relating to international co-operation and participation in EU initiatives displays an ambition for Norwegian research to become fully and wholly integrated into the European research market. It is clear that this cannot happen without the help of research council measures across the board.

The programme will support research and technology development for enhancing recovery from fields in production, exploration in immature areas, raising energy efficiency, reducing emissions and research on health and safety (HSE)-related activities. Indeed, research on HSE is an integral component of the PETROMAKS2 programme, and the objective here regarding the HSE initiative for 2012-2016 is to generate new knowledge and promote the development of new solutions that reduce risk by addressing key sectoral challenges in the petroleum industry. This requires close, multidisciplinary co-operation between research players and industry.

The final objective seeks to clarify what it means to be a change agent for Norwegian research, and the specific tasks this will involve.

instruments require effective national measures in order to take advantage of a common European research community.

A unified research council The system of a unified research council, as it is practised in Norway, has been deemed successful in evaluations thus far. This is likely due to a rising need to co-ordinate research policy, a need to employ larger, longer term initiatives, more widespread internationalisation within all types of funding instruments, and a need to further professionalise research administration. A unified research council is better equipped to satisfy these needs in a cohesive fashion. This is not least evident in international efforts, where all types of

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The success of the research councils is also partly due to the fact that change often comes from the outside; the research council can serve as a locomotive for change in the research groups, which may not be able to offer optimal conditions for such changes on their own. The centre schemes are a good example of this.

Arvid Hallén Director General The Research Council of Norway http://www.forskningsradet.no/en/Home_page/1177315753906

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4SUBSEA CORROSION RESEARCH PROJECT Norwegian company 4Subsea uses their expertise on flexible pipes to improve integrity management plans, methods and tools

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Subsea is a Norwegian subsea technology company which focuses on risers and wellhead systems. The company possesses extensive experience and knowledge related to safe operation of flexible pipes. 4Subsea has initiated a research and development (R&D) programme to close critical technology gaps related to long term integrity of flexible pipes. The knowledge gained will be used to develop improved integrity management (IM) plans, methods and tools. The use of flexible pipes has been steadily increasing during the last decades. The need for integrity assessment is therefore on the rise due to: n Ageing of installed pipes; n

Actual safe service life seems to be shorter than the designed service life; and

n

Tail production involving lifetime extension.

The demand for flexible pipe IM is growing in Norway as well as in other areas of the world such as Brazil. Important observations related to integrity assessment of flexible pipes are: n Cost related to the operation of flexible pipes is often higher than expected in the design phase; n

Flexible pipes were originally designed for maintenance-free operation throughout their entire design life, experience shows that maintenance and close follow up are required;

Outer sheath damage and corroded armouring, ref: PSA – Norway, “Un-bonded Flexible Risers – Recent Field Experience and Actions for Increased Robustness”, 2013 n

Failure modes not considered in design has occurred during normal operating, resulting in immediate line shut down, e.g. collapse; and

n

More failures than expected due to operational challenges that are not fully accounted for in the design, e.g. mal-operation, lower robustness than expected and unforeseen incidents.

In most projects, the cost and risk related to replacement and investment make improved IM preferable to replacement. There is a consensus in the industry that there are critical technology gaps and that improved reliability of flexible pipes is required. 4Subsea’s knowledge base for R&D activities include: n 48,000m of flexible pipe has been investigated, most have been dissected, both intact and damaged pipes;

IFE corrosion testing of steel armour wires in flexible pipes

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n

Offshore experience from more than 2,000 annulus tests and vent gas samples;

n

Evaluation of all relevant polymer materials, PVDF, PA11, X-link PE, LDPE and HDPE;

n

Many offshore repairs including with remotely operated vehicles, divers and above sea level; and

n

Projects in Norway, the UK, the Netherlands, and West Africa.

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The programme The primary objective of the FPCM (Flexible Pipes Corrosion Monitoring) project is to provide the industry with tools and services which enable operation of flexible pipes with damaged outer sheaths and reliable prediction of remaining service life: n Development of new and improved ways of assessing structural integrity; and n

Contribute to closing the industry’s technology gaps on the understanding of corrosion mechanisms within flexible pipes with a focus on external sheath breaches.

FPCM is a two-year R&D programme with the following external contributors: n Funding from The Research Council of Norway's petroleum programme PETROMAKS2 enables 4Subsea to execute such a programme; n

Three industrial partners provide part funding, technical input, test samples and verification; and

n

IFE (Institute for Energy Technology): R&D contribution including laboratory testing. IFE has performed research work on internal CO2 and H2S corrosion in oil and gas pipelines for more than 30 years, beginning work on flexible pipes around five years ago.

The synergy of coupling IFE research expertise, 4Subsea’s extensive field experience and three major users of flexibles as partners make the project consortium unique and ensure the best possible basis for success. A breach in the outer sheath is the most common type of flexible pipe damage and the subsequent armour corrosion has resulted in serious accidents including loss of lives. This R&D project addresses reduced strength of the flexible pipe armouring layers in such events. Dramatic corrosion, wear-related pipe failures and near misses have been experienced as a result of outer sheath breaches. However, there are also many examples of outer sheath breaches that have not caused significant corrosion attacks. How to differentiate outer sheath damages that may progress into pipe failure from situations giving moderate or insignificant corrosion is improperly understood by the industry at present. The challenges for the industry are:

1) Reliable detection and location of outer sheath breaches: available methods, as provided by 4Subsea today, are able to identify many types of outer sheath breaches. However, extended capabilities are needed to ensure better detection and location reliability, as well as characterisation of breach sizes; 2) Determination of the imminent and potential severity of detected sheath breaches: n The industry has demonstrated that corrosion of steel armours in water-filled flexible pipe annuli is limited in locations well away from any outer sheath breaches; n

There is a significant knowledge gap on types and locations of sheath breaches that lead to severe corrosion, the corrosion pattern and the potential rate of metal loss; and

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Outer sheath damage and insignificant corrosion of armouring, ref: OMAE2014-24154 n

Some of the relevant corrosion processes have time varying signatures in terms of hydrogen generation and consumption of molecular species that may become very useful for detection of changes caused by outer sheath breaches.

3) Mitigations in terms of repair and monitoring: n 4Subsea provides solutions and services to repair outer sheath breaches today, but far from all breaches can be adequately repaired; n

The industry needs assessment capabilities to determine how soon repairs have to be made and also which outer sheath breaches that can be left without repair; and

n

Flexible pipes with outer sheath breaches require monitoring to verify that no critical corrosion takes place.

The FPCM project will ensure improved knowledge for the industry, methods and tools on flexible pipe IM, giving: n A reduced number of flexible pipe failures and thereby reduced risk for pollution and accidents; and n

Improved IM for flexible pipes and thereby reduced downtime and better planning of maintenance and repair.

Svein Are Løtveit Advisor 4Subsea AS Nesbru, Norway +47 66982700 [email protected] http://www.4subsea.com/

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CARBON CAPTURE UTILISATION AND STORAGE The University of Bergen’s Physics and Technology Department talks about how CCUS triggers research for more sustainable energy production

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lobal energy strategies need to reflect current climate challenges. Huge amounts of energy are needed for future generations, thus it is necessary for existing energy production to be optimised in an environmentally friendly way and for new energy resources to be found. Two aspects of these strategies utilise CO2 as a commodity: CO2 for enhanced oil recovery (EOR) as an enabler of CCUS, and CO2 injection in hydrates; the latter being a win-win situation for CO2 storage with simultaneous natural gas production. A major challenge for these technologies are up-scaling laboratory results to the field scale.

Up-scaling laboratory EOR to on-shore CCUS field pilots Initiatives have recently been launched to perform field pilots to establish large scale laboratories to investigate recovery mechanisms and sweep efficiency at field scale. CO2 for EOR within carbon capture utilisation and storage (CCUS) represents a win-win situation; obtaining significant increased oil production while sequestering CO2. Early CO2 breakthrough and poor sweep efficiency are the main challenges in CO2 EOR, and up-scaling of laboratory EOR to field performance is the ultimate challenge for the oil industry. The objective of performing CO2 foam injections at reservoir scale is to successfully implement efficient mobility control, to improve the micro and macroscopic sweep efficiency in CO2 EOR operations through the use of foam, in heterogeneous and fractured reservoirs; both in onshore and offshore oil fields. An international team of researchers from 11 universities in Norway, France, the Netherlands, UK and USA have started EOR field pilot tests onshore in the USA using hydrocarbon gas-based foam and CO2 foam injection for mobility control in heterogeneous and/or fractured reservoirs. Due to high costs associated with offshore field pilots, negotiations with independent oil companies in Texas and Mississippi have resulted in four agreements of onshore field tests in heterogeneous carbonate and sandstone reservoirs in west Texas and Mississippi, with various types of fractures and heterogeneities. The cost associated with these field tests are only a fraction of the cost for offshore field tests. The CLIMIT Programme of the Norwegian Research Council (NRC) and several oil companies provide funding for the project that includes eight professors, two postdocs, six PhD students and 22 master’s students at the collaborating universities; emphasising researcher mobility and exchange of students. The HC gas and CO2 EOR field tests using foam for mobility control are based on in-kind contributions from the field operators, and in-kind 4D seismic

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techniques from a service company in addition to the cash funding from NRC and participating oil companies.

Mobility control in integrated EOR (IEOR) Fundamental research to determine the physical processes and the optimum boundary conditions for these strategies Professor Arne Graue have been successful partially due to application of complementary, state-of-the-art, in situ fluid saturation measurement techniques in the laboratory. The research results have determined mechanistic fluid dynamics in heterogeneous porous rocks, illustrating the importance of knowing the in situ fluid saturation development to determine the kinetics of fluid flow and the fluid displacement mechanisms. Improved understanding has been obtained by utilising high spatial resolution magnetic resonance imaging (MRI), computerised tomography (CT) scanning and positron emission tomography (PET) to determine fluid saturation development within and around fractures. The results are compared to complementary experiments using nuclear tracer imaging (NTI) in larger scale laboratory models.

Collaborating universities The following universities are collaborating: Rice University, Houston, Texas, University of Texas at Austin, Texas A&M University, Stanford University, Imperial College London, TREFLE Bordeaux, MSU, TU Delft, NTNU, The National IOR Centre of Norway and University of Bergen. Strong interaction with the seven participating oil companies is believed to provide unique research teams and innovative research environments for the participating students.

Project overview The main research activities are: n Special core analysis (SCAL) including micromodel pore size studies at reservoir pressure; n

Up-scaling micromodel results to core plug experiments with in situ saturation imaging;

n

Up-scaling core plug floods to large scale (ft-size) experiments at reservoir pressure with imaging;

n

Up-scaling large scale experiments to numerical grid size simulations;

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n

Up-scaling all results to field scale by performing onshore EOR field pilots;

n

4D seismic by land seismic surveys before, during and after CO2 injection;

n

Obtain advanced reservoir characterisation;

n

Predict reservoir performance by numerical simulations;

n

Perform the field pilots and compare results to the predicted performance; and

n

Improve the numerical tools to match field pilot results.

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Project advantages n

CO2 is commercially available in the USA;

n

The oil industry in Texas has 30 years’ experience in CO2 EOR;

n

Cost associated with onshore field tests is only a fraction of costs for offshore field tests;

n

Short inter-well distances in onshore oil fields yield fast results for sweep and recovery;

n

Foam and mobility control has significant potential for a quantum leap within EOR;

n

Worldwide recognised researchers from 11 reputational institutions; all specialists on mobility control;

n

Focus on up-scaling; the major challenge in obtaining reliable predictive models of oil recovery; and

n

Mobility control may establish next generation CO2 EOR flooding providing potentially less than 10% residual oil in swept zones; establishing a new era in EOR. The total amount of mobile oil that may be produced by this technology is estimated at 137 billion barrels in conventional reservoirs in USA; potentially reducing US-import of crude oil by 30%.

CO2 storage in natural gas hydrates Natural gas hydrates represent an enormous energy potential as the total energy corresponding to natural gas entrapped in hydrate reservoirs might be more than twice the energy of all known energy sources of coal, oil and gas combined worldwide. The abundance and locations of the natural gas hydrate reserves covers all continents. The source of the methane can be either the microbial degradation of organic matter in shallower sediments or deeperseated thermogenic methane accumulations. However, to produce the methane from hydrate accumulations in an economical way is quite a challenge. Of significant importance to the world’s energy need, the fact that hydrates are present in parts of the world where no other similar size of energy reserves are present, provides new strategies for countries and regions with a severe lack of energy resources and in regions with energy poverty. This is particularly relevant in Asia, sub-Saharan Africa and South America. Based on high spatial resolution imaging using MRI, the University of Bergen and ConocoPhillips demonstrated in a collaborative

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effort in the laboratory that exposing hydrates to CO2 spontaneously, without adding energy, produces methane from hydrates while sequestering the CO2. In fact, this is a carbon neutral exchange, as each methane molecule released needs to be replaced by a CO2 molecule. Storage of CO2 in natural gas hydrate reservoirs by replacing the CH4 in the hydrate with CO2 may have some significant attractive potential as this would provide free natural gas and establish a thermodynamically more stable hydrate accumulation. In a joint effort between ConocoPhillips, US DOE and JOGMEC in Japan, a field test injecting CO2 into a hydrate bearing formation in Alaska in 2011-2012 proved this technology on the field scale. Low gas prices in North America due to the shale gas revolution made use of this technology there less economically attractive, however, in Asia, where gas prices are seven to nine times higher, the market for this technology is potent. The above-mentioned innovative technologies are two examples of how collaborative research efforts between universities and industry, supported by governmental funding, may provide more, and new, sustainable energy production for the future.

Professor Arne Graue Department of Physics and Technology, University of Bergen, Norway +47 55 58 27 21 [email protected] http://www.uib.no/en/rg/ptech/62157/upscali ng-co2-foam-eor

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THEO MITCHELL OF THE CCSA DISCUSSES HOW THE NEW EU POLICY FRAMEWORK CAN BEGIN TO DELIVER LONG-AWAITED PROGRESS FOR CARBON CAPTURE AND STORAGE

Enabling the CCS future

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March 2015 came and went without any significant news for the European energy industry. Sure, we had the ‘smart grids for a smart Energy Union’ speech from Energy and Climate Action Commissioner, Miguel Arias Cañete, but for those in the CCS sphere, 31 March 2015 was marked as the date by which the Commission had committed itself to report on the review of the so-called ‘CCS Directive’. It was the date by which we should have known whether the directive was going to be amended, whether its guidance documents were going to be torn up, whether an emissions performance standard was going to be investigated as part of a wide-ranging review of CCSrelated policies. It would mark the end of a nine-month review process undertaken by external consultants on behalf of the Commission.

for a more supportive policy framework for CCS across Europe.

Theo Mitchell

You’ll have gathered by now that the Commission didn’t publish its review report and – at the time of writing this article – it still hasn’t. Delays aside, the CCS Directive review is important for a number of reasons. Not only for the handful of commercial-scale projects currently in development, but also for the wider CCS industry and the plethora of pro-CCS stakeholders that have been repeatedly calling

The White Rose project in the UK will help to capture CO2 emissions linked to energy generation

Within the CCS community we wanted the review to deliver an EU CCS strategy. Something that could provide a focal point for supportive policies at the member state level but without politically-unattractive targets, whether binding or non-binding, or at the EU, or member state level. A strategy would help provide industrial and financial stakeholders with visibility that the EU was serious about CCS, that it had a clear pathway to commercialisation, and that it recognised the significant economic benefits of developing CCS in clustered approaches. It would provide a basis on which to evaluate progress towards deployment in both the 2030 and 2050 horizons. It would re-lay the foundations for an industry that has suffered repeated set-backs since the much-lauded European Council call for 12 commercial-scale CCS projects to be in operation by 2015. Despite the review consultants recommending the development of an EU CCS ‘roadmap’, all indications suggest that the Commission will not develop a new CCS strategy. The review process has, however, arguably led to a more positive positioning of CCS in the context of the wider policy framework. We sit here today with CCS as an integral component of the research and innovation dimension of the Energy Union, an important element of the SET Plan, and with a fair wind (no pun intended) behind the Innovation Fund; a new EU mechanism to support CCS alongside innovative renewable technologies. Go back 12 months or so and things certainly looked a lot less promising: the Commission was less positive; there was an apparent lack of political will at the EU level; and the future of CCS in the 2030 framework

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was viewed with cautious trepidation rather than anticipation.

Moving forwards As welcome as the renewed impetus behind CCS is, without an EU CCS strategy the question remains: how can we deliver costcompetitive CCS within the EU existing policy framework? Even more pertinently perhaps, how can the EU deliver cost-competitive CCS when so many member states wilfully ignore the overwhelming economic and scientific evidence pertaining to its importance? (It is worth reiterating here that the recent IPCC 5th Assessment Report – arguably the most authoritative scientific opinion on climate change – concluded that the costs of achieving climate objectives without CCS could increase by a whopping 138%. Compare that with nuclear: no further nuclear deployment could increase costs by a mere 7%. Just the 131% point difference, then.) Anyway, back to delivery and how the emerging policy framework can enable CCS. Firstly, and most importantly, we need to ensure that the small number of projects nearing completion reach positive conclusions, i.e. that they get built. The ROAD (the Netherlands), Peterhead and White Rose (both UK) projects are all

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CCS offers the potential to enhance climate action

approaching critical decision points in their development cycles and by the middle of next year it is feasible that all three could have taken final investment decisions and be preparing for project construction. These projects not only provide further proof of concept, they would also employ a range of technologies, they would demonstrate a variety of commercial business models, they would collectively abate more than four million tonnes of CO2 per annum, and they would put in place infrastructure that could unlock decarbonisation opportunities for a wide range of industrial emitters that simply have no other option to decarbonise beyond CCS.

Multiple sectors, common infrastructure Part of the reason CCS technology is so valuable in economic and environmental terms is due to its multisectoral benefits. CCS can be used to decarbonise the power sector, industrial sectors (steel, cement, etc.), heating (through the decarbonisation of hydrogen and synthetic natural gas production) and transport, to name just a few applications. But this can only happen if the prerequisite transport and storage infrastructure is developed, and that is neither cheap nor easy to finance. This is the reason that deployment in the power sector is so important. Large power stations can provide the guaranteed ‘anchor load’ of CO2 required to finance infrastructure investments. In the UK, the Contract for Difference Feed-in Tariff regime could effectively secure a guaranteed flow of CO2 through a pipeline over a period of decades. Compare that to an industrial installation such as a steel factory. The operator there not only has a much higher credit risk but operates in a global market, highly vulnerable to changes in commodity prices and the future costs of CO2 emissions. A steel plant operator may have a four to five year investment horizon at best, certainly not suitable for basing the finance of large scale infrastructure on. By developing CCS in the power sector

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not only do we create a valuable source of dispatchable, low carbon electricity, we also enable other emitters to access CCS opportunities associated with their infrastructure. The EU has a track record of delivering positive outcomes for different types of infrastructure and enabling regional co-operation. CCS infrastructure should be viewed similarly. Whether through the Projects of Common Interest regime or the proposed innovation and modernisation funds, EU funding should be used to maximise strategic deployment of CCS and the development of transport and storage infrastructure. This would not only help unlock some of the investment challenges associated with CCS infrastructure, but it could also open up CCS opportunities to member states that are either unable or not inclined to pursue onshore storage. But even if public funding can help develop the necessary infrastructure, who’s going to operate the pipelines and stores when no clear business case exists for doing so? The Zero Emission Fossil Fuel Platform (ZEP) – the European Technology Platform for CCS – has recently suggested the use of EU funding to establish ‘market makers’. A market maker model could derisk infrastructure investments and help kick-start the CO2 storage market. EU funding could then be used to support member states or the private sector to become market makers in the locations that are best suited to CO2 storage and create some early large-scale decarbonisation opportunities.

SSE’s Peterhead Power Station in Aberdeenshire, Scotland, from which Shell proposes to capture 10-15 million tonnes of CO2, over a 10-15-year period, and store it in the depleted Goldeneye reservoir some 100km (62 miles) offshore, under the North Sea

those actions outlined in the national plan put a country on its lowest cost decarbonisation pathway or will it require a step change in activity post-2030? How will industrial sectors be decarbonised without CCS? What are the implications of decisions on jobs, growth and investment? If a member state can credibly answer all of the above without CCS then it should be left to its own devices. (Who determines whether a national plan is credible or not though is another matter entirely, and probably not best-placed in this article.)

How can member states be encouraged to take a more pro-active approach to CCS? The ‘new governance system’ being developed under the Energy Union could provide an important opportunity for doing just that. The system shouldn’t be used to impose CCS on countries that do not have the political will, geographical conditions or public acceptance for the technology; it should be about encouraging member states to take a longer term look at decarbonisation goals. What is needed to decarbonise the whole energy system? How do measures taken to achieve 2030 goals correspond with actions needed by 2050? Will all

In conclusion, political will to persevere with CCS now seems to be at its best since 2009, and by grasping the opportunity to embed CCS into the emerging policy framework the EU is well-placed to create the overarching In the Netherlands, CCS is being explored as a tool to combat climate change

conditions needed for deployment. By pushing for positive outcomes for the early commercial projects and enabling EU funding to support delivery of strategic infrastructure in terms of both capital and operational support, EU institutions can begin to realise the CCS opportunity and move much more positively towards commercialisation. No new policies are needed; it’s just a case of building on what is already in place and maximising the value of EU interventions.

Theo Mitchell The Carbon Capture & Storage Association www.ccsassociation.org

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COMMERCIALISING CCS Dr Ward Goldthorpe and Shabana Ahmad of The Crown Estate’s Carbon Capture and Storage (CCS) Programme discuss the commercial deployment of CCS

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he foremost contemporary challenge for the global community is to manage a transition over the coming decades from an economy characterised by high carbon emissions/low price on carbon pollution to an economy with low carbon emissions/high price on carbon pollution in a socially and environmentally responsible, sustainable way. However, this will not be achieved with conventional market economics and innovation alone because it is constrained in time. It must happen within a limited time if global warming is to be kept to 2°C. And it has to happen within an holistic paradigm of socialised cost because for most decarbonisation activities (and particularly industrial and transport decarbonisation) the private sector cannot make a business case without a contribution from public funding. A realistic and pragmatic global response to climate change will require an acceptance that both developed and developing countries will continue using fossil fuels and producing industrial and transport emissions in the period to 2050, and therefore that the technologies we have at our disposal today should be deployed rapidly to have any chance of mitigating global warming and its consequences. Carbon capture and storage (CCS) is an essential part of the solution for the world to meet its energy, climate and societal goals. In Europe it can help to achieve greenhouse gas emission reduction targets at lower cost while delivering energy security and sustainable industries, with an estimated benefit of €2-4 trillion up to 2050. To realise these benefits actions must now be taken that ensure the right infrastructure is available in time to provide certainty for the inevitable demands of power and industrial emitters, as well as confidence for private sector organisations prepared to deliver the associated services. However, the challenges to deliver this infrastructure can only be overcome by creating new policy frameworks along with finance and business models that appropriately incentivise and address the key risks and funding gaps faced by project developers. Under current market conditions these make any business case uneconomic for private investment.

What is commercially viable CCS? Historically, CCS deployment as a low carbon power generation solution has been seen as a technology challenge rather than a commercial challenge. The reality is that CCS is a technology value chain requiring a combination of facilities and skills which very few individual organisations have. However, each individual technology

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and operating capability has been tried and tested in multiple situations, both onshore and offshore, over the last four decades. In many ways the development of CCS to date has been much like the Apollo Space Programme to put a man on the moon – step by step proving of technology components and operating conditions culminating in the final full system execution. In the end, only when the Apollo 11 team landed safely back on Earth had the full system been tested and missions could become repeatable. We now have the same situation for CCS power generation, with the successful commissioning and operation of the Boundary Dam power station in Saskatchewan, Canada. One often hears that CCS must become ‘commercially viable’ and competitive with renewable power generation technologies. But there is a fundamental difference between the two, because the first integrated power projects are building transport and storage infrastructure that can (and will) be used in a number of different future CCS applications: power, industry, low carbon transport fuels (hydrogen), and low carbon heating. All different sectors of the economy, with different market conditions, trade exposure and different business models. Metrics that only compare if early CCS power projects are competitive with alternatives do not take account of the additional value derived from building infrastructure for the ‘public good’, retention of industries, and job creation in a low carbon economy. Public sector subsidies and the associated policy frameworks that do not take an holistic view across our carbon-based economy are essentially creating barriers to CCS being a viable investment proposition. Making CCS ‘commercially viable’ is not a technology challenge. Complex commercial structures and agreements are required between the various participants in CCS constituent projects. Better and more cost effective equipment, processes and engineering will inevitably lower costs across the CCS chain and deliver economies of scale in clusters and networks. However, the speed of CCS deployment required across the globe to meet climate targets and decarbonise the economy is not going to be delivered through market forces and innovation. It requires a new frame of reference for fiscal support policies and public sector contributions. Because of the additional facilities and operating costs, low carbon fossil fuel power and industrial products will be more expensive than currently existing business as usual alternatives. Hence, without appropriate pricing of carbon dioxide (CO2) as an economic externality, they cannot be competitive in the strictest sense, i.e. cannot be commercially viable. But many renewable

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Table 1

electricity generation technologies are also not viable compared to the business as usual alternatives, and support through subsidies is required to attract private investment in these. It is therefore only really correct to call any technology ‘commercially viable’ if it is compared to others based on a level playing field.

The economics of industrial CCS (ICCS) are different to those in power CCS where international trade is minimal, and where the cost can be passed on to consumers. However, the competitive nature of globally traded industrial products means trade exposed industrial emitters are unable to pass on these additional costs, thus creating a project financing challenge for investment in ICCS.

It is fair and reasonable to expect different technological solutions needed for meeting the world’s climate goals to compete on the basis of either being least cost in terms of subsidies relative to alternatives or being cost effective compared to paying a carbon penalty. Currently CCS projects are unable to overcome the inertia to become commercially viable because there are neither sufficient optimally targeted subsidies allocated through processes that are neutral for technologies at a comparable level of maturity nor are there carbon markets with carbon pricing at a high enough level. The lesson is that CCS can be a commercially viable alternative when policies make it so.

The current absence of sufficiently high carbon prices (regionally and globally) and the lack of a funding mechanism mean that no private company will develop an industrial CCS scheme on its own. Even where CO2 can be captured at a reasonably high purity for low-unit cost in some industrial processes, the low costs do not necessarily mean CCS always makes economic sense. The need for transport links and access to a market for the captured CO2 may still represent significant cost barriers and due to the underlying commodity risk make CCS financing in this area relatively difficult without significant credit enhancement.

The need for an holistic system perspective The current business model paradigm in Europe for power CCS relies on mechanisms that incentivise or penalise emitters (e.g. avoidance of emission penalty, feed in tariff, operational income support) and place the responsibility on emitters to ensure transport and storage infrastructure is developed. This approach has not been successful owing to challenges related to the counterparty risk, the different development timelines and dissimilar investment business cases of the CCS value chain, all combined with long term policy uncertainty.

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Furthermore, in order to create financeable projects, power or industrial capture plant developers are not prepared to take on the value chain integration risk where failures in the performance of the transport and storage operations create liabilities for them. Sharing the burden of such risks could also render their project economics unacceptable, creating financing challenges. The focused development of strategic clusters offers significant commercial feasibility and follow-on advantages over the creation of inefficient isolated and commercially more challenging source to sink projects. The development of anchor hubs and clusters in core EU emitting regions will reduce the barrier to entry for later CCS

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projects, rationalise infrastructure development (thus lowering the cost of later CCS projects), and will act as gateways to CO2 storage for inland member states that require offshore storage. CCS deployment therefore requires an holistic strategic prioritisation due to industrial, social, physical/geological and geographical considerations. Careful planning is needed to develop a CO2 transport and storage network that connects the locations (actual or planned) of major power generation plants and industrial facilities with storage sites. However, for investment in CO2 transport and storage infrastructure to accelerate over the coming decade, a pipeline of potential developments is required, with a continuous funnel of storage resources being explored and appraised. This will allow developers at both ends of the CCS chain to continually bring forward new projects, and also to mitigate against the impact of geological and locational uncertainty. In order for the development of all the different types of projects within the CCS value chain, including CO2 capture, transport and storage to be stimulated, there needs to be confidence within the sector that the complete financial and regulatory framework – within which these projects, clusters and hubs are anticipated to be developed – will offer sufficient visibility and certainty as regards the risks and obligations of developers.

The business case requirements for developers The lack of a consistent political message, backed by moves to incentivise through policy, combined with the absence of visibility of revenues, is inhibiting confidence in the CCS sector because all stakeholders rely on the certainty of revenues (particularly in a project finance model wherein the debt and all other contractual relationships are crystallised on the basis of revenue certainty). Table 1 summarises the key issues that must therefore be appropriately addressed for constituent CO2 capture, transport and geological storage project development to attract investment and create a viable business proposition for investors and developers. Financial risk derives as much from the need for a designed and managed pathway to market for a networked infrastructure comprising different businesses as it does from pure technology risk (the development and evolution of the international LNG industry is a good analogue for the pathway CCS needs to follow in the coming years). There are not many other environmental technologies that comprise a value chain of different businesses – perhaps one good comparison is the collection and disposal of waste that is then used in landfill energy generation. Renewable power generation technologies such as wind and solar are far less complicated when it comes to deployment and business models as they can be built in smaller tranches and are easily connected to an existing grid.

Creating the right policy portfolio The issues identified above highlight the need for innovative new business models and policies that balance the evolving responsibilities of the public and private sectors, contractual relationships and risk allocation among the parties involved in

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CARBON CAPTURE

CCS. These parties would then deliver the investment required in various types of CCS project, including CO2 transport and storage infrastructure development and the establishment of clusters for Europe’s decarbonisation aspirations. A portfolio of policies needs to be proactively managed to help ongoing deployment take place through the economic transition from high to low carbon over decadal timeframes. This will create the line of sight required by the private sector and financial institutions to invest. The two keywords are certainty and stability. The current approaches to revenue models for the CCS value chain create an interdependency that requires de-linking. For the critical investment in storage development (upon which the entire CCS proposition depends), the storage developer must have access to a government pricing mechanism that provides volume guarantees or minimum availability-based payments to ensure that it is not penalised by non-performance of other parts of the CCS chain. This can also facilitate project finance debt lending into the sector and, when also supported by loan guarantees, provides a ‘credit enhancement’ to facilitate investment grade rating of projects that can further reduce the cost of financing. Storage projects in particular will require a special commitment from government to provide a backstop for uninsurable elements, or CCS specific business risk items that are unpalatable for the private sector. To facilitate financing and make CCS constituent projects bankable, government will also need to underwrite the risk of policy and regulation changes through appropriate carve-outs for CCS. This is because, whilst industry may take risk on general change in law/regulation, the retrospective changes to a number of European renewable incentive schemes has created significant sensitivity in the financial community to Change-in-Law risk. Strategic planning and a policy portfolio for enabling infrastructure must be progressed now if Europe as a whole is to retain the optionality of rapid, cost effective CCS deployment post 2030. Understanding that CCS is a low carbon solution for different sectors with different business models can help lead to more holistic, no regrets government policies that support building infrastructure for the public good, retention of industries, and job creation in a low carbon economy whilst simultaneously contributing to a rapid balancing of the global carbon cycle.

Dr Ward Goldthorpe Programme Manager CCS The Crown Estate +44 (0)207 851 5311 [email protected] http://www.thecrownestate.co.uk/

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EUROPE STANDS TO GAIN FROM UTILISING THE OCEAN TO MEET ENERGY NEEDS, AS JACOPO MOCCIA FROM OCEAN ENERGY EUROPE TOLD PEN

Advancing ocean energy A midst the push toward clean and secure energy, interest in the energy potential of European seas is mounting. Indeed, the movement of tides and waves clearly has the potential to be harnessed to meet energy needs. While young compared to the more established renewables such as wind and solar, the ocean energy sector continues to make strides towards proving its renewable energy potential. Jacopo Moccia, policy and operations director at Ocean Energy Europe, spoke with PEN about the developments surrounding the sector. He outlines the prospects for ocean energy as EU decision makers move to boost investment, establish a European energy union, and increase the sustainability and security of European energy.

Reflecting on developments over the course of 2015, what have been the key developments and what is the outlook for the industry today? What we have been seeing this year, and what we will be able to take stock of soon, is the deployment of tidal stream and wave energy projects in real sea conditions. Up until last year there had been the equivalent of about 14MW of a variety of devices in the sea; some small, some large; some were connected to energy distribution networks, and others not. There was a variation in the length of testing, from a matter of a few months, to years. Soon, we will start seeing a significant pick up in the number of machines that have been in the water long enough to show that they are proven; that they have the potential to provide

consistent levels of power, that they are viable concepts; and that we can move forward to the next stage of industry development.

Jacopo Moccia

In 2015-2016, we expect there will be a step change, where the focus moves from R&D types of deployment to something which is starting to look like the beginning of an industry. If this prediction is correct, and if things improve politically and economically over the next couple of years, I think we should be able to see a serious industry rolling out during the course of the next decade, from 2020 onwards. As we have seen, there is a lot of EU research money from Horizon 2020 being awarded to our sector. For 2015, the amount of funding from Horizon 2020 that has been awarded to ocean energy equates to around €41.4m. There is clearly a lot going on, as the activity in the sector has picked up, and there are people who have serious projects that they are taking forward.

The Commission launched its push to establish a European energy union earlier this year. What impact has this had on your work, and what are the implications for ocean energy? Together, the developments happening in the energy sector, alongside international energy politics in recent years, have led to the idea of creating an energy union in Europe; and this push has created a window of opportunity. We know in Europe that we need to go down a new path. Europe needs all the different renewable energy options available. This is not only to meet our power needs; we need to become more sustainable. This is sustainable both in terms of reducing energy imports and environmental impact. The transition towards renewables will require dependency on a number of forms of renewable generation, working together in a complementary fashion. Indeed, wind power is dependent on the wind blowing, and solar

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power is only available during the day, tidal cycles happen regularly twice a day and, although waves are created by the wind, they will carry on activating wave devices even after the wind has died down. There’s a huge amount of complementarity between renewables coming together to meet our energy needs.

Do you feel that support is forthcoming at the EU level, and also at the national level?

For us, there is an opportunity in the ocean energy sector. Whilst there is the political move to go down the renewables path; we need to see new energy technologies arise. Amidst these technologies we clearly feel that ocean energy is the prime mover; the first of the second wave of renewable energy technology.

There is a lot of interest, and certainly some parts of the European Commission are very keen to help promote our industry. There is also a lot of pressure being put on the European Investment Bank (EIB) to develop financial instruments for sectors such as ours that can be made use of beyond the usual grants that one could get from Horizon 2020. More widely, whether there is enough money, and whether the banks are taking enough risk in financing the ocean energy sector; there is clearly a real concern in respect to the question of financing.

Under the right conditions, 30 to 35 years down the line, ocean energy can be the new wind energy, meeting 10% of our energy demand in the EU. The political context is right, in terms of actual individual bits of legislation and the market measures in place, and we are influencing these debates as much as we can. What the industry really needs now is stability in national frameworks, and of course support, as we are still very much in a prototype and demonstration phase and not all the technology is yet in the market. We still very much need to go through some stages of research and

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development, certainly in wave energy, and we need to test some prototypes. The sector requires ‘hours under our belt’ to be able to say this machine works and this machine is bankable. Being not quite there yet, and until we are, we will need backing, including financial support from policy makers.

In regards to the entire energy industry – which is of course pan-European and international – there is a very challenging investment landscape in Europe generally. Institutions have become extremely risk averse in the wake of the financial crisis. Efforts made by the Commission in trying to promote investment in Europe through the Juncker plan, and a new approach by the EIB that is more open to taking on risk, are to be welcomed. Should policy makers push banks such as the EIB to provide green investment opportunities, the industry is clearly poised to take advantage of that and to step up deployment. There is a window of opportunity, there is the political will, but there is a cashflow problem at the moment within the EU and that is affecting us, as well as other industries.

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Turning the tide The European Commission estimates that 0.1% of the energy in ocean waves could be capable of supplying the entire world’s energy requirements five times over. Currently, a number of technologies aimed at harnessing this potential have been investigated and are at different stages of development including tidal and marine energy, wave energy, difference of temperature and salinity energy. The conversion of tidal energy into electricity has been widely investigated and can be compared to the technology used in hydroelectric power plants. In fact, electricity is generated by water flowing into and out of gates and turbines installed along a dam or barrage built across a tidal bay or estuary. More recently, technologies for exploiting wave and currents energy have been developed and tested on a small scale and, for a limited number of cases, on a large scale. On the other hand, technologies relating to the difference of temperature and of salinity are at an early stage of development. With Ocean Thermal Energy Conversion (OTEC), the difference of temperature between cold, deep seawaters and warm, shallow waters creates a thermodynamic cycle, which can be used for producing electricity. In the case of salinity gradients, the difference in salinity between seawater and freshwater creates a pressure difference which can be exploited to extract energy. Today, ocean energy covers around 0.02% of EU energy needs and it is primarily used for electricity production. Ocean energy technologies for electricity generation have progressed at different speeds. Wave energy and tidal/current energy have been actively and increasingly investigated at international level for a number of years, whereas research into OTEC and salinity gradient energy is still in the early stages. Globally installed wave and tidal power arrays will reach a capacity of more than 330 gigawatts (GW) by 2050, according to an International Energy Agency (IEA) forecast. By comparison, the capacity of the much more developed wind energy sector reached the same figure – 336GW – by the end of June 2014. To give this figure some meaning, the Commission explains: together, the world’s wind turbines can generate around 4% of current global electricity demand according to the World Wind Energy Association. Compared to wind energy – and indeed solar power – wave and tidal energy has one big advantage: while it is variable, the energy flows are highly predictable, since tides in particular are very regular. EU-funded researchers are already making considerable advances in these areas, aiming to help industry cut costs and increase reliability with innovative decision making software. When considering the situation at a national level, there are a number of member states that have shown that they’re interested in ocean energy technology, that they’re willing to promote it and are willing to put up space in their seas to develop it. However, the policy framework to support renewables is on and off across Europe.

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In the case of the UK where – from a rhetorical perspective – the government declared the intention to be the world leader in ocean energy; and indeed about 80% of the machines in European waters are in UK waters at the moment. However, the declaration by the government to enact cutbacks in research and development budgets is clearly sending the opposite signal. If this is a political priority for a government, the industry is not going to materialise out of thin air. We need to work together; with industry taking the risk of putting their money on the table, but it has to be matched by governments providing political capital, and banks putting their money on the table, too.

Of course, the challenges in terms of the financing available to the energy sector are clear and evident. Do you feel this puts you in competition with other renewables and fossil fuel-based energy generation over access to resources? Not really; for us the priority is in addressing the risk associated with investment. A developing technology area such as ocean energy obviously carries a certain amount of risk and we’re not actually in competition with any other renewable technologies. If we can prove to the banks that our concepts are viable – either due to the fact we have proven this through testing, or there is a large amount of public backing – then a bank will take it. There is more than enough money in Europe; it’s just that people are scared to invest it. We are not in competition with other technologies, but we’re certainly having very difficult discussions with people over money needed for the sector. Whoever they are – big utilities with clear balance sheet requirements, or banks looking for places to invest money – what they are saying is ‘prove to me that you’re not too risky’. As a sector, we know we’re not, but we haven’t got enough hours on the clock for the bank to feel comfortable investing.

In common with many other parts of the energy sector, engagement with the public over the consequences and implications of ocean energy deployment is key. How do you try to engage with the public and address any concerns over this technology? There are two key aspects. Often the debate around social acceptance revolves around the

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visible impact of infrastructure. Unlike wind turbines that are very clearly visible, ocean energy has been deployed either at water level or underwater, which during these first few years has meant that the projects are simply less visible. However, we need to engage with the public for two reasons. Firstly we need to make everyone aware that this technology exists, that it can work, and that it can take up a significant part of the EU’s power demand over the coming years. At the same time we need to engage with all the other users of the sea and the other actors active in the area; making the case for using space at sea for ocean projects, and acknowledging that there may be an impact. Then we can move to reduce the impact to the best possible extent. More concretely, we have contributed to the Ocean Energy Forum, established by the Commission’s Directorate-General for Maritime Affairs. At present, there is a text of about 20 pages guiding the forum; and there are three main work themes: finance; technology; and environmental consenting. We don’t have a huge amount of data on environmental impacts because we haven’t yet developed large arrays with several turbines or several wave machines in a row. We are already discussing how we can support work in the area, delving down to member state level

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approaches. This is considering what national requirements will need to be taken into account when projects are in the planning process, and when developing the environmental impact assessment. This input has been worked upon alongside other stakeholders, and has been worked into a road map that we are developing as an industry. These challenges of engagement and consideration of environmental impact are a task for everyone. It’s not just a question of saying policy makers must give us money and policy makers must make policies for us. Industry, policy makers and financiers can contribute, with environmental consenting being one such element we are considering. Obviously there will be conflicts in terms of use of sea space, but there may also be disputes over whether or not ocean energy infrastructure is damaging the marine environment. The sooner we start considering this issue, and engaging with other parties, the easier these disputes will be to resolve when we get to the stage where we’re developing projects producing hundreds and hundreds of megawatts of power. The sector will be able to integrate this into impact assessments and be able to prove to everyone and say, ‘we’ve analysed the situation and this particular ocean energy array is more beneficial than it is detrimental’.

Jacopo Moccia Policy & Operations Director Ocean Energy Europe www.oceanenergy-europe.eu

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REDUCING RISK, REDUCING COST The Acadia Tidal Energy Institute is assessing Canada’s tidal energy opportunities

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anada’s best opportunity for developing tidal energy is in Nova Scotia’s upper Bay of Fundy, where the tidal range is the highest in the world and surface current speeds can exceed 6m/s. The responsible harvesting of energy from identified tidal energy sites requires comprehensive examination of the current structures and energy potential; the environmental implications of harvesting energy; and the associated socioeconomic benefits and impacts on communities, fishers and other users. A multidisciplinary team at the Acadia Tidal Energy Institute (ATEI) has been leading research with partners in academia, government, industry and communities in four key areas: hydrodynamic modelling, effects on marine life, finance and sustainable community development.

Quantifying the resource and site assessment Accurately calculating the size of the tidal resource and characterising potential turbine deployment sites are critical to the development of tidal energy. ATEI researchers have developed a suite of hydrodynamic models to simulate the tides and tidal currents throughout the Bay of Fundy. The hydrodynamic models cover both regional and micro-siting scales using high performance computing resources to generate long time simulations. ATEI developed the models through partnerships with the Fundy Ocean Research Centre for Energy (FORCE), Fundy Tidal Inc (FTI) and Dalhousie University to ensure that they are built on

Fig. 1 Nova Scotia and Bay of Fundy showing the location of ATEI at Acadia University and the FORCE and FTI tidal energy development sites

high-resolution bathymetry, and that the simulations are fully validated against all recent measurements of tidal currents. The simulated velocities are analysed using a powerful data analysis tool (PySeidon) that can both convert the simulation data into usable maps of flow characteristics and complete an economic analysis of a project. ATEI has used the numerical simulations to establish both the maximum power potential of the region (>7500 MW) and the practical resource of both the community-scale projects being developed by FTI and the commercial opportunities at FORCE in Minas Passage (Fig. 1). The simulations have been used to design turbine arrays, determine the optimal turbine layout, and estimate annual energy production of the array. ATEI has collaborated with other researchers using computational fluid dynamics (University of New Brunswick, Mavi Innovations) and structural models (Dynamics Systems Analysis) to characterise flow turbulence, model device performance and design moorings and platforms. The ATEI hydrodynamic modelling group has focused on using open source models and data analysis tools that allow for collaboration with other researchers, government regulators, and industry partners on all aspects of tidal energy site assessment.

Assessing risk of turbine-marine life interactions ATEI was founded in 2011 by (from left) Drs John Colton, Shelley MacDougall, Richard Karsten, Anna Redden and Graham Daborn. Meghan Swanburg (not pictured) joined the team in 2013

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Environmental research on marine life in Minas Passage commenced with assessments of the natural use of the FORCE test site (Fig. 1) and is surrounded by several fish species of

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concern. Multi-year acoustic tagging (Vemco technology) and tracking of fish (Fig. 2) and lobsters have identified species specific trends in movements throughout the test site; encounter modelling is underway. ATEI and the Sea Mammal Research Unit (UK) have modelled the spatial and temporal trends in the presence of harbour porpoise based on porpoise click trains detected by passive acoustic sensors (C-POD hydrophones) housed in SUB flotation units. In the coming year, ATEI and partners in Canada and the UK will investigate near-field behaviour of fish and marine mammals near an installed tidal turbine at FORCE. This research will be co-funded by a NS OERAUK Innovate grant. The work will further environmental sensor development and advance software capabilities for the detection of marine life and their behaviour at tidal energy sites.

GIS tool for mapping tidal site data ATEI has partnered with FORCE and TEKMAP Consulting and, with federal and provincial funding, is further developing an interactive web mapping tool to consolidate, visualise and manipulate tidal energy-related data (e.g. power density, bathymetry, hydrophone stations). The mapping tool uses open source software (GeoServer and Heron) to integrate complex spatial information. This enabling initiative is being developed for the emerging tidal energy industry and will be freely available for use by industry, government, researchers, consultants and the broader community.

Fig. 2 C-PODs in SUB housings for detecting harbour porpoise click trains (left); surgery for insertion of a Vemco acoustic tag in a Striped Bass (right) n

Framework for environmental risk assessment and decision making for tidal energy development in Canada;

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Value of delay and implications for government policy;

n

Assessment of the risk of sediment-laden ice to turbines in Minas Passage;

n

Tidal energy resource map for Nova Scotia;

Tidal energy toolkit

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Southwest Nova Scotia resource assessment;

One of ATEI’s initial projects was the development of a tidal energy toolkit to assist communities and businesses in better understanding the opportunities stemming from tidal energy. The toolkit contains a series of modules that describe opportunities and strategies for communities and businesses to become involved in tidal energy development. The modules also provide relevant advice, checklists and links. An addendum to the toolkit, the Tidal Energy Community Engagement Handbook provides a step-by-step guide to community engagement for use by all stakeholders involved in tidal power development.

n

Assessment of the potential of tidal power from Minas Passage;

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Canada’s Marine Renewable Energy Technology Roadmap;

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IEC marine energy standards;

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Educational materials for universities and schools;

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Establishment and hosting of the Fundy Energy Research Network (http://FERN.acadiau.ca); and

n

Hosting of tidal energy workshops and symposia.

ATEI projects and initiatives

Acknowledgements: ATEI thanks numerous project funders, including but not limited to NSERC, NRCan, DFO, Mitacs, ACOA, NS OERA, NS Energy, UK Innovate, FORCE, FTI and both academic and industry partners.

ATEI members have led or contributed to the following reports on or initiatives in marine renewable energy in Canada: n Strategic Environmental Assessments of the Bay of Fundy (2008, updated in 2014); n

Tidal energy toolkit for business and communities;

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Value proposition for tidal energy development in Nova Scotia;

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Assessments of marine mammal, fish and lobster use of the Minas Passage and FORCE test site;

Dr Anna Redden Director Acadia Tidal Energy Institute (ATEI) Acadia University, Wolfville, Nova Scotia, Canada

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Hydrodynamic site assessment of Digby Neck Passages;

+1 (0)902 585 1732

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Pathways of effects models for offshore renewable energy;

n

Community engagement guidelines for tidal energy;

[email protected] http://tidalenergy.acadiau.ca

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THE CAMBRIDGE INVESTMENT RESEARCH (CIR) TEAM PROVIDE A SUMMARY OF THE THIRD CIR CAMBRIDGE GRAPHENE BUSINESS CONFERENCE

Graphene technology is here

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he two days (5 and 6 November) were billed as the Cambridge Graphene Technology Days 2015 (with an ongoing hashtag of #CGD15), with no fewer than six events taking place. The first day saw the second CIR Graphene and Graphene Related Materials (GRM) Masterclass attended by 30 senior corporate executives at the West Cambridge Site, parallel to a graphene technology showcase day and internal meetings held by the Cambridge Graphene Centre (CGC) with partners. Within this showcase the CGC partners’ technologies and CIR exhibitors were together for a very exciting press event with the director of CGC, Professor Andrea Ferrari, on stage with the University of Cambridge ViceChancellor Professor, Sir Leszek Borysiewicz FRS, and David Cardwell, head of Cambridge University’s engineering department. In the evening there was a joint dinner at Madingley Hall for CGC partners and those who had attended the second CIR Graphene Masterclass and those who had arrived to attend the Third CIR Business Conference the following day. 80 delegates attended the dinner, around half each from CGC and CIR. The Third CIR Graphene Business Conference was held on the second day with over one hundred people from business and academia. This followed an inaugural series of events including the CIR Graphene business conference (which was also held in Cambridge, in November 2013) and other CIR Graphene events in May 2014 and February 2015. An excellent audience of delegates enjoyed entertaining presentations,

as well as four panel question and answer sessions and networking opportunities at the exhibition space, where around 40 companies were on show. There were 20 talks throughout the day from academics, dignitaries, business leaders from multi-national companies in space, defence, oil, gas and steel, scale-up materials solutions by providers such as Haydale, and technology developers such as FlexEnable, and further interesting talks from venture capitalists, economists and intellectual property firms. Speakers were highly praised in feedback surveys from CIR conference delegates.

Masterclass During the masterclass, the application projects of large firms and scale-ups were discussed among 30 graphene senior corporate executives with CIR Leader Nick Coutts and colleagues in the context of value network analysis and ‘Routes to Value’. This latter is a

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rigorous strategic method being used by large companies and innovators to ensure that projects are within a process that connects them explicitly with the objective and values of the business, including culture. This is a pioneering method that could help with scaleup gaps, enable large companies to bring in graphene material enhancements and services to add enormous value to the development of application markets.

Following this, the Rt Hon Lord Alec Broers asked whether graphene is the biggest achievement of the 21st Century – comparing it with other areas on the USA’s ‘Grand Challenges’ list, including solar technology; fusion energy; carbon sequestration; nitrogen cycle (whereby the pollution issue here is seen by many as more tangible and urgent than global warming issues); clean water; restoring urban infrastructure; engineering better medicines; enhancing virtual reality (flexible and wearable electronics); preventing nuclear catastrophes; securing cyberspace; personalised learning; and reverse engineering the human brain.

Dr Justin Hayward, director of CIR, said: “I am delighted that Cambridge Investment Research was able to co-organise this set of events with the Cambridge Graphene Centre at this special time for the centre and for graphene, in particular, providing a highly business-focused aspect.”

Sessions In the first session on 6 November, the director of the Cambridge Graphene Centre, Professor Andrea Ferrari, argued that graphene is the future of communication and will become better than silicon by 2024. The vision here is to integrate modulators and photodetectors with graphene. A transceiver prototype with graphene will solve the problem of heat that is insoluble to Moore’s law for data storage and transmissions with current materials.

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heat dissipation and spreading), graphene’s use in a fusion power cell (which could be a solution for completely silent electric aeroplanes), as well as an underlining of the importance of reliability and safety and certification, were also given due consideration. This presentation posited the following as the main issues and R&D directions for aeroplanes: propellers in rotors, energy storage, structures, shielding (objects, RPG, radars, lighting, etc.), optics (lasers, receivers, lenses, and mirrors), displays (wearable electronics, flexible electronics), and ice prevention and de-icing.

The next presentation, by the Institute of Manufacturing’s Professor William O’Neill focused on the ‘manufacturing landscape and drive for impact’, in which he argued that there is a manufacturing economy in the UK and, moreover, that UK manufacturing is of high value. O’Neill also revealed that 85% of research and development finance in the UK comes from manufacturing companies, but that there is a missing connection between lab R&D and alpha level production technologies with large scale manufacturing. Furthermore, he added, while the UK Government invests a lot in R&D, thereby creating great research, “this is just an expense, and we need to add value by delivering technologies through companies” to turn R&D into a return on investment. The keynote speech by Haydale’s CEO, Ray Gibbs, argued that the current market analysis of graphene is wrong and is very hard to predict. He also discussed the significant market for composites, as well as the large markets for graphene materials, but these, he said, are mostly conservative and highly regulated. He therefore underlined the need to look instead (at least initially) to the currently unregulated markets: boats, wind energy, pipes and rails.

Concerning satellites, the main issues and R&D directions were revealed to be: solar arrays (there is a lot of solar radiation to harness; photovoltaic (PV) cover glass could be made thinner and lighter using graphene), multilayer insulation (thermal shield), structures, antenna and mechanisms (higher conductivity needs), shielding, and optics (laser communications). During the second session Dr Samson Patole and Dr Sai Shivareddy of Tata Steel delivered a further keynote on graphene applications on steel for energy storage – an important area given that corrosion is a significant problem for steel, which can enable the large scale implementation of energy storage tech. The speakers outlined the applications of steel in energy storage thus: building integrated PVs (functioning coatings that capture and store thermal energy in phase material on steel for

Industrial challenges For Gibbs, the industrial challenge lies in proving production of graphene materials is repeatable, consistent and cost effective. He called for immediate and better standardisation so as to create “consistent quality and value; and a price good for stakeholders”. The next keynote, delivered by Airbus, focused on issues and opportunities for graphene in the aerospace and defence sectors with the lifecycle costs being highlighted as a particular area for consideration. Areas such as fuel consumption, graphene’s anisotropy (channelling heat,

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buildings); batteries (electroplated steel cans, electrodes and casing); fuel cells (gold plated stainless steel bipolar plates could become cheaper with graphene); and supercapacitors (mostly aluminium and copper but steel for casing). They then turned their attention to the performance improvement required for steel, that is good electrical conductivity; electrochemical stability (corrosion prevention); thermal conductivity (high power devices); and formability and strength (i.e. tribology). Regarding the replacement of gold for coating in LC steel, Patole and Shivareddy argued that the industrial challenges include scaling up – e.g. from pilot line roll-to-roll to large scale graphene coatings – and the ability to coat millions of square metres with tonnes of the material at speeds of up to 100m/min. This, they said, would save billions in fighting corrosion. The presentation by NanoCarbon asked why it is better to transfer graphene in the lab rather than involving third parties and posited that it is safer in terms of intellectual property (IP) (there is no need to share details of applications); is faster (full control), cleaner (full control, no carrier issues), cheaper, and augments learning and optimisation. Cambridge Nanosystems’ presentation explored the transformation of methane into

graphene powder, as well as the use of atmospheric plasma to break difficult and stable molecules like methane, CO2 and other carbon-based molecules. Hydrogen, which also has uses, is a by-product of this process of creating graphene powder, explained Dr Krysztof Koziol.

Revolution The third session included a speech by Novalia’s Dr Kate Stone, who discussed adding interactivity to print and how paper with interactive surfaces could revolutionise the digital world, while OCSiAl’s Will Riches discussed an industrial scale facility for single wall carbon nanotubes (SWCNTs), focusing on touchscreens, paint and coatings, lithium batteries, and polymer composites. Dr Gun-Soo Kim from Standard Graphene (which emerged from Samsung) then spoke about how graphene flakes stand to lead the market before a keynote by FlexEnable’s Dr Paul Cain discussed ‘bringing any surface to life’ – from those which are wearable to those found in the automotive sector. The fourth session included a focus on the intellectual property landscape with regard to graphene by Marks & Clerk’s Mash-Hud Iqbal, who described patent families globally by geography and sector and over time to 2014. Later, BP’s Sheetal Handa delivered a keynote address on the challenges in the oil and gas industry, focusing on sub-sea extraction and the various materials needed; oil pipe transportation and problems with the various materials (sand, oil, water, condensation and welding) in the pipes (i.e. surface interactions); and the idea that applications for 2D materials will mostly be in corrosion resistance, surface treatments, deposits and fouling, self-repairing systems and separations.

Dr J D Hayward MBA G W Smith BA J P Melchiorri BSc Cambridge Investment Research team http://cir-strategy.com/

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TAILORING GRAPHENE’S ELECTRONICS Max Planck Institute scientists in Stuttgart manipulate the electronic properties of SiC based epitaxial graphene on the atomic scale

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raphene, with its unique electronic properties, has matured from a playground for fundamental physics studies to an important material to revolutionise a wide range of applications. The Stuttgart group produces wafer scale graphene on silicon carbide and has developed techniques to engineer the electronic band structure by atomic intercalation and lithographic patterning. With the resulting tailored properties of their graphene, perspective use in electronic devices, spintronics, plasmonics and possibly even superconductivity can be envisioned. Graphene is a newly discovered carbon allotrope consisting of a single layer of carbon atoms arranged in a honeycomb lattice. Its electronic structure is dominated by a linear crossing of conduction and valence bands (the so-called ‘Dirac point’), which causes many unprecedented and peculiar properties of the charge carriers in graphene. Wafer scale graphene can be grown in excellent quality on silicon carbide (SiC) making this material combination an excellent candidate for a technological application. The Stuttgart-based interface analysis group headed by Professor Ulrich Starke is a world-leading entity for producing such graphene layers on SiC. Starke and his collaborators are experts in manipulating the electronic structure of graphene by design, and they command a multitude of methods to precisely analyse the emerging band structure.

Implementation and challenges For the implementation of graphene as a novel electronic material, a major obstacle has been identified in the absence of a gap in its electronic structure, a gap that would be required for digital devices, for example. The opening of such a gap is indeed a major challenge in graphene research. On the other hand, manipulation of the band structure of graphene would open up possibilities for plasmonics, spintronics and even superconductivity. Several

Fig. 1 (left to right) Patterning of SiC, faceting and growth of graphene nanoribbons

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feasible approaches to address and solve these questions, problems and perspectives are being pursued in Starke’s group at the Max Planck Institute (MPI) for Solid State Research in Stuttgart. The lateral constriction of graphene on a nanometre scale is a promising recipe to accomplish the task of inducing a gap. Yet standard lithography techniques to cut structures out of graphene suffer undesired electronic effects, caused by mechanical disturbances such as edge defects, introduced during the etching process. By patterning the SiC wafers in advance, the group can grow the graphene after the cutting process and thus manufacture large arrays of intact graphene nanoribbons so that even large scale integration can be envisioned. Shallow channels regularly spaced on a nanometre scale are milled into the bare wafer material with electron lithography and ion etching techniques. On wafers prepared in this fashion, graphene grows in thin stripes, separated in top mesa, facet and bottom regions, thus representing the separation in periodic nanoribbon arrays (see Fig. 1). The individual electronic features of graphene in the different stripes have clearly been distinguished. Since it is feasible to implement this technique on a wafer scale, structured graphene on SiC substrates has a clear perspective for electronic applications.

Intercalation A second and even more important approach is to introduce foreign atomic species in between graphene and the SiC substrate, so-called ‘intercalation’. This process has developed into a powerful tool to alter the electronic structure of the graphene layers. The foreign atoms are forced to form an atomic layer between SiC and graphene with the effect of decoupling the graphene layer from the substrate (see Fig. 2, top). The possibilities of manipulating the electronic structure of the epitaxial graphene layers on SiC by intercalation appear to be unlimited. The Stuttgart group has demonstrated several examples of this technique. Their hydrogen intercalation process produces quasi-free standing graphene, and has been adopted successfully to wafer scale epitaxial graphene device production by other groups. Quasi-free graphene has also been used by other groups for various fundamental research topics.

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By intercalating various other elements besides hydrogen, the group can manipulate the electronic structure of the graphene layers to adjust the graphene’s physical properties. Strong doping variations can be achieved, as being demonstrated by band structure renditions in the lower panels of Fig. 2. The doping ranges from p-doped with the Dirac point above the Fermi level (lower left image in the case of hydrogen) to moderate or strong n-doping (lower right image in the case of gold). With germanium doping, the scientists in Stuttgart can even create different doping levels and prepare np- and npn-junctions on a spatial nanoscale. With such devices they could demonstrate the equivalency of graphene’s carriers to massless Dirac fermions together with the collaborating group in Hannover, which opens up possibilities for quantum devices. Evidence for Kleintunnelling of graphene electrons was recently published. With extreme high doping, a singularity in the density of states of graphene can be shifted towards the Fermi level, with first indications of superconductivity having been established and published, caused either by the high carrier density alone or by many-body interactions of the graphene carrier system. The strength of many-body interactions in graphene (e.g. between electrons and phonons or plasmons) can be controlled by the intercalation process allowing the tuning of the dielectric constant and promising plasmonic applications. The control of spins by the intercalants and a potential enhancement of spinorbit splitting in the graphene layer opens the path for spintronic devices.

The Interface Analysis Group Having a longstanding experience with silicon carbide surfaces, Starke and his group have been active in graphene research since its discovery in 2004. The group has furnace facilities for the homogeneous growth of epitaxial graphene. Electron spectroscopy and diffraction techniques are used for the characterisation of the graphene and the assessment of the band structure manipulation processes, complemented by regular access to synchrotron beamtimes. In-house nanostructuring facilities are used for the patterning of SiC substrates or graphene layers. The group has an intensive collaboration with the group of Professor Dr Christoph Tegenkamp at the Leibnitz Universität Hannover, Germany.

Fig. 2 (top) Intercalated atomic layer between graphene and the SiC substrate; (bottom) band structure after intercalation of hydrogen (left) and gold (right) S Forti, and U Starke, (2014), Epitaxial graphene on SiC: from carrier density engineering to quasi-free standing graphene by atomic intercalation. J. Phys. D: Appl. Phys. 47, 094013 J Baringhaus, A Stöhr, S Forti, SA Krasnikov, AA Zakharov, U Starke, and C Tegenkamp, (2014). Bipolar gating of epitaxial graphene by intercalation of Ge. Appl. Phys. Lett., 104, 261602 J Baringhaus, A Stöhr, S Forti, U Starke, and C Tegenkamp, (2015). Ballistic bipolar junctions in chemically gated graphene ribbons. Sci. Reports 5, 9955 J Sforzini, L Nemec, T Denig, B Stadtmüller, T-L Lee, C Kumpf, S Soubatch, U Starke, P Rinke, V Blum, FC Bocquet, and FS Tautz, (2015). Approaching Truly Freestanding Graphene: The Structure of Hydrogen-Intercalated Graphene on 6HSiC(0001). Phys. Rev. Lett. 114, 106804 BM Ludbrook, G Levy, P Nigge, M Zonno, M Schneider, DJ Dvorak, CN Veenstra, S Zhdanovich, D Wong, P Dosanjh, C Straßer, A Stöhr, S Forti, CR Ast, U Starke, and A Damascelli, (2015). Evidence for superconductivity in Li-decorated monolayer graphene. Proc. Nat. Acad. Sci. 112, 11795–11799

Key publications: C Riedl, C Coletti, T Iwasaki, AA Zakharov, and U Starke, (2009). Quasi-free standing epitaxial graphene layers on SiC by hydrogen intercalation. Phys. Rev. Lett. 103, 246804 KV Emtsev, AA Zakharov, C Coletti, S Forti, and U Starke, (2011). Ambipolar doping in quasi-free epitaxial graphene on SiC(0001) controlled by Ge intercalation. Phys. Rev. B 84, 125423 I Gierz, JC Petersen, M Mitrano, C Cacho, ICE Turcu, E Springate, A Stöhr, A Köhler, U Starke, and A Cavalleri, (2013). Snapshots of non-equilibrium Dirac carrier distributions in graphene. Nat. Mater. 12, 1119

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Professor Dr Ulrich Starke Group Leader Max Planck Institute for Solid State Research +49 (0)711 689 1345 [email protected] http://www2.fkf.mpg.de/ga/research_index.html

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PROFESSOR ANDREA FERRARI, DIRECTOR OF THE CAMBRIDGE GRAPHENE CENTRE AND CHAIR OF THE EUROPEAN GRAPHENE FLAGSHIP EXECUTIVE BOARD, DISCUSSED SOME OF THE WAYS IN WHICH THE PROJECT HAS EVOLVED

Graphene means business, literally

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he Graphene Flagship is part of the EU’s Future and Emerging Technologies (FET) scheme, which, according to the European Commission, seeks to “turn Europe’s excellent science base into a competitive advantage by uncovering radically new technological possibilities”. Specifically part of the FET flagships, the graphene project aims to develop “a new class of material beyond the era of silicon” and was announced as a winner of a competitive process in 2013. In an interview with Pan European Networks, Professor Andrea Ferrari, director of the Cambridge Graphene Centre and chair of the flagship’s executive board, discussed some of the ways in which the project has evolved and the importance of events such as the Cambridge Graphene Technology Days, which PEN attended, for showcasing how graphene research is already finding applications.

the case in places like China, for instance, where there is much more willingness to take the necessary risks.

Has that always been the case in Europe?

Professor Andrea Ferrari

This is having a significant impact on the European manufacturing base, and we need to be careful that we don’t find ourselves in a situation in which we are lagging behind the rest of the world, because it will be difficult to regain the lost knowhow.

You have highlighted how, as a next step from the EU-funding graphene has received, it is now time for industry to take a lead. Do you feel that the right conditions exist in Europe for that to happen?

In this sense, there is also a need for larger companies to become involved in graphene. How is the flagship working to make this happen?

Yes, everything is coming together in Europe for this to happen.

Are there lessons that Europe can learn from other regions when it comes to the commercialisation and industrialisation of graphene?

There are several large companies involved in the flagship – Nokia, of course, being one of the longest standing, but more recently Bosch, Talga, and the Lego group have joined us as associated members. There is thus a growing number of large and influential companies joining the flagship as we progress.

Yes, but this is not an issue peculiar to graphene. Indeed, unfortunately, European industry has lost a little of its appetite for high risk investment in that those with finances to invest prefer to do this in areas where there is a more positive chance of a higher return, and this has a knock-on effect with regards to Europe’s capacity to innovate. This is certainly not The Commission has made it clear that graphene research should continue to be funded outside of the flagship and, in fact, there are a lot of examples proving that this is happening

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No, and this is evidenced by the way in which some companies in Europe – take IBM, for instance – used to have large research centres some decades ago, but when these companies are looked at now there is a clear shift away from hardware, towards software and services.

Is the same true for smaller companies? Absolutely; we also have many SMEs joining the flagship, as well as start-ups (working on areas such as sensors, for instance). There is a lot of activity going on in this regard.

What progress has been made within Graphene Connect? This is an initiative of the Graphene Flagship to link industry and academia and has already seen some success. In the next phase of the flagship this will be further strengthened. For instance, in February 2016 the flagship will be present at the World Mobile Congress in Barcelona, which will see a gathering of some 100,000 participants, including the major IT

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companies from around the world, so we are certainly raising the bar here.

While you have highlighted the necessity for graphene-related research to also be funded outside of the flagship, the general sense I get from many in the research community is that this is not the case – particularly within H2020. How could this be better addressed? This should absolutely not be the case, and the European Commission has been adamant to that effect. Indeed, if this is happening in some instances, then the fault does not lie with the Commission but with the academic reviewers, who are perhaps unwilling to allocate funding to colleagues who could be perceived as being already sufficiently funded. The Commission has made clear that graphene research should continue to be funded outside of the flagship and, in fact, there are a lot of examples proving that this is happening.

How will the recent FLAG-ERA JTC Call – which has seen the selection of 13 projects in synergy with the Graphene Flagship – help to focus on those areas with lower Technology Readiness Levels (TRLs), and what is the importance of this at this stage of the flagship? The decision to target areas with lower TRLs was made since this was the first call and because of the complexity involved in putting

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The aim of the Cambridge Graphene Technology Days event was to show that, without question, graphene literally means business

this together. That is, FLAG-ERA requires funds to be contributed by all participating countries and, within each country, by all participating funding agencies, which makes it a complicated process from a bureaucratic point of view. In order to make things easier in the first call, it was decided to allow low TRLs research to be funded. This is also important because some countries with low applied research budgets typically have groups producing excellent theory. The FLAG-ERA JTC Call was thus designed to be as inclusive as possible. However, the next call will certainly also target higher TRLs. We need to keep in mind that the overall aim of the flagship is to increase the TRLs across the board.

Why are events such as the Cambridge Graphene Technology Days so important? This event has seen some 50 companies who produce real graphene technology come together – the first time this has happened in the UK. The Cambridge Graphene Technology Days event was not designed to be a ‘conference’; it is a meeting of industry and business rather than academics, and will, through an exhibition, showcase devices, tools and instruments created by utilising graphene, and has demonstrated that investing in basic science creates tangible results in the form of new technology. Our aim is to show that, without question, graphene literally means business.

Professor Andrea Ferrari Chair of the Executive Board European Graphene Flagship www.graphene-flagship.eu

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FACULTY OF MICROSYSTEM ELECTRONICS AND PHOTONICS The Faculty of Microsystem Electronics and Photonics writes of its history, departments and framework programme participation

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he Faculty of Microsystem Electronics and Photonics was established on 1 January 2002, and currently employs 55 academic teachers including ten full professors and nine university professors. There are 44 PhD students while the number of undergraduate and graduate students is about 800. The faculty offers two courses of study: electronics and telecommunication, with two specialisations on the first degree studies (electronics & photonics engineering and digital electronics) and three specialisations on second degree studies (microsystems, optoelectronics & optical waveguide technology, and the English language specialisation electronics, photonics, and microsystems); and mechatronics.

The usable area of the faculty approximately is 7,400m2, including 800m2 of classrooms and over 2,700m2 of laboratories (600m2 of clean rooms). More than half of the faculty’s premises and equipment is no more than eight years old. Every year the staff publish more than 200 papers in scientific journals and conference proceedings, including 50-70 articles indexed on Thomson Reuters Master Journal List. Annually, faculty staff carry out about 30 grants funded by the European institutions (framework programmes), Polish institutions (Ministry of Science and Higher Education, National Centre for Research and Development, National Science Centre) and industry – a list of grants made under framework programmes is appended at the end of this presentation. Based on the above facts, the Polish Committee for Evaluation of Scientific Research Institutions (KEJN), which performs a cyclical, comprehensive assessment of scientific R&D and/or research units according to international standards (scientific and creative achievements, educational potential, material effects and the results of scientific activity), and the Minister of Science and Higher Education awarded the Faculty of Microsystem Electronics and Photonics an ‘A+’ category, the highest in Poland. The faculty’s activity has largely contributed to the fact that today Wrocław is considered as a leading academic centre of so-called ‘highly advanced technologies’ in Poland.

Units within the faculty There are seven scientific units of the faculty: n Division of Microelectronics and Nanotechnology (W12/Z1);

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Division of Vacuum and Plasma Technologies (W12/Z2);

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Division of Micro- and Nanostructures Metrology (W12/Z3);

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Division of Technology and Diagnostics of Microelectronic Structures (W12/Z4);

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Laboratory for Interconnecting and Packaging Electronic Circuits (W12/Z5);

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Division of Microsystems and Photonics (W12/Z6); and

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Division of Micro-engineering and Photovoltaics (W12/Z7).

The Division of Microelectronics and Nanotechnology conducts research in the areas of materials science, nanotechnology, microand nanoelectronics, and optoelectronics. Investigations in this division are concerned with: bandgap engineering; construction and technology of heterostructures based on AIIIBV-N compounds; advanced physicochemical and electrical characterisation of heterostructures (e.g. by means of electron microscopy); atomic force microscopy; X-ray diffraction; impedance spectroscopy and photoluminescence; epitaxial techniques; lithographic techniques; manufacturing of metallic structures; surface passivation; silicon and AIIIBV spatial structuring; and the complex processing of semiconductor structures and devices is developed. Technological characterisation and measuring equipment of this group enable a full investigation cycle from computer simulations, through technology and construction design, to implementation and characterisation of demonstrators made of advanced, nextgeneration semiconductor devices. The main scientific activity of the Division of Vacuum and Plasma Technologies is: the investigation of processes and phenomena occurring during vacuum deposition of thin layers; development and implementation of prototype technologies of thin film deposition; design and fabrication of components for vacuum stands (particularly in various types of magnetron sputtering systems); investigation of field electron emissions as well as charged particle optics and their applications in technological and characterisation equipment technology; laboratory investigation of photovoltaic cells and modules; and long term measurements of photovoltaic modules and systems in natural conditions. The Division of Micro- and Nanostructures Metrology conducts research work aimed at the quantitative and qualitative observation of phenomena occurring on a submicron and nanometer scale. In their research, employees of the department use advanced microscopy close interaction, scanning electron microscopy and focused ion beam microscopy, impedance spectroscopy, X-ray diffraction, optoelectronics and fibre optics. The Division of Technology and Diagnostics of Microelectronic Structures conducts research on: the fabrication of thin-films by means of physical deposition from the gas phase (particularly in magnetron sputtering and electron beam evaporation); the design of functional coatings, including optical coatings; diagnosis and analysis of electrical, optical, structural and functional properties of thin-film materials and structures; analysis of the electrical and optical properties of thin-film materials using numerical modelling; studies of electrical activity of deep doping levels in semiconductor heterostructures (AIIIBV, AIIIN); and low-dimensional structures.

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The main areas of scientific activity of the Laboratory for Interconnecting and Packaging Electronic Circuits include: materials and technologies for the construction of systems and reliable connections in the assembly of electronic equipment (particularly in numerical designing of robust electronic systems); the development of new nanocomposite materials and assembly technologies for effective heat transfer and creation of electrical connections; developing materials and technologies for printed electronics; environmentally friendly design of electronic equipment; numerical prototyping; simulation of reliable electronic systems; and physical reliability testing of electronic equipment. The Division of Microsystems and Photonics conducts research in the areas of: thick-film, as well as low and high temperature cofired ceramics technologies (including ceramic, ceramic-glass and ceramic-polymer microsystems); investigation, design and synthesis of materials (including nanomaterials) for the chemical sensors; measurement and analysis of the properties of planar and fibre photonic devices; and fibre optic network design. The scientific activity of the Division of Micro-engineering and Photovoltaics is focused on: fabrication and characterisation of MEMS- and MOEMS-type silicon, glass and polymer microsystems; multiparametric measurement systems with integrated electronic sensors; miniature medical and biomedical devices using nano- and microengineering techniques; vacuum nano- and microelectronics (e.g. miniaturised vacuum pump for microsystems); development of nano- and microengineering technologies of solid state; standalone photovoltaic systems and their use in the zero energy facilities, including sports and recreational facilities; and long-term studies of so-called ‘green energy installations’.

Research projects realised within EU framework programmes FP5:

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PV-CATAPULT – European collaboration for identification of PV research and markets opportunities, socioeconomics studies, performance assessment and dissemination of PV and PVthermal technology; and

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TASNANO – Tools and technologies for the analysis and synthesis of nanostructures.

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ANGELAB – A new genetic laboratory for non-invasive prenatal diagnosis;

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DOSIMEMS – A passive, wireless MEMS dosimeter for high radiation dose monitoring;

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EDU MEMS – Developing multidomain MEMS models for educational purposes;

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LABONFOIL – Laboratory skin patches and smartcards based on foils and compatible with a smartphone;

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MAC-TFC – MEMS atomic clocks for timing, frequency control and communications;

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MULTILAYER – Rolled multi-material layered 3D shaping technology;

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NANOHEAT – Multidomain platform for integrated more-than-Moore/beyond CMOS systems characterisation and diagnostics;

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NANOTHERM – Innovative nano and micro technologies for advanced thermo and mechanical interfaces;

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NANOTIM – Development, characterisation and reliability of high performance nano thermal interface materials for LED application;

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PARSIMO – Partitioning and modelling of SiP;

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AFRODITE – Advanced facade and roof elements key to large scale building integration of photovoltaic energy;

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PIEZO INSTITUT – European expertise centre for multifunctional and integrated piezoelectric devices;

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MEVIPRO – Innovative thermomechanical prediction and optimisation methods for virtual prototyping of miniaturised packages and assemblies; and

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SE2A – Nanoelectronics for safe, fuel efficient and environment friendly automotive solutions; and

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TACMON2 – Development of a low-cost interactive graphical tactile display as advanced user interface for the visually impaired.

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NANOJOINING – Novel nanocomposite polymers and joining technologies for reliable and efficient assembly of electronic components.

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BIPV-CIS – Improved building integration of PV by using thinfilm modules in CIS technology;

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DAVID – Downscaled assembly of vertically interconnected devices;

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NEPUMUC – New eco-efficient industrial process using microstructured unit components;

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PERFORMANCE - A science based on photovoltaics performance for increased market transparency and customer confidence;

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PRONANO – Technology for the production of massively parallel intelligent cantilever - probe platforms for nanoscale analysis and synthesis;

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Andrzej Dziedzic Dean Faculty of Microsystem Electronics and Photonics Wroclaw University of Technology Wybrzeze Wyspianskiego 27 50-370 Wroclaw, Poland +48 (0)71 320 2594 [email protected] http://www.wemif.pwr.edu.pl

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THE COMMERCIALISATION OF GRAPHENE IS, FOR MANY, THE ENDGAME FOR RESEARCH IN THIS AREA. PEN SPOKE TO THE RT HON LORD ALEC BROERS ABOUT SOME OF THE INHERENT ISSUES

Taking graphene to market

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ncluding a masterclass, press conference, lab tours, expo, and a business conference, the Cambridge Graphene Technology Days 2015 (CGD15) event saw industrial and entrepreneurial growth companies in the graphene and GRM sector brought together with Cambridge University and its new Graphene Centre Building Hub to try to accelerate the value network growth for all who wish to learn about, understand, develop, productise, market, implement and use graphene and graphene-related materials (GRM) and related equipment.

Broers explained that this was a result of the various stakeholders involved in the value chain assuming that the field would evolve on its own, as well as failing to realise that Moore’s law was in fact a reality rather than an exaggeration. What is more, Lord Broers told PEN, it was also widely held at this time that the Japanese owned much of the related industry and that silicon was simply set to become a commodity within that. They were, of course, wrong, and that meant that Europe remained sidelined when it came to the real acceleration of this material and its related technologies.

This is an important effort because while the EU’s attitude towards early creative science has been positive (and, indeed, while the role played by the UK government has also been encouraging), this is perhaps less so when it comes to industrial involvement. When Pan European Networks spoke to The Rt Hon Lord Alec Broers – the former Vice Rector of Cambridge University – at the aforementioned event, he was keen to stress the need for advocacy as soon as possible, because it will simply not be enough to gain ground when it comes to graphene-related research (such as via the potential of the Graphene Flagship) if research results are not commercialised in a timely manner. This, of course, is perhaps similar to the situation that research involving silicon found itself in some decades ago, with steps towards a full realisation of its potential faltering. Indeed, when asked about this, Lord

It is important for those companies already working with graphene to up-scale their procedures, otherwise their sustainability will be questionable

Graphene, not least through the EU’s flagship project, is receiving a significant amount of funding in Europe, and it is hoped that this, coupled with the creation of infrastructure such as the Cambridge Graphene Centre, will enable the creation of viable commercial technologies that can be taken up and spun out into companies. Indeed, this already seems to be happening – as some of the technologies and products being showcased at CGD15 attest. However, it is important for those companies already working in this field to develop the ability to up-scale their procedures. Otherwise, their sustainability will be questionable. While this could perhaps be seen as a question of willpower, for Lord Broers it is more a matter of what he termed courageous investment. Therefore, as far as the Cambridge Graphene Centre is concerned, its ground rules are quite exemplary, focusing as they do on applications rather than on basic science.

Industry and academia Alongside the issue of funding – perhaps even integral to it – lies the importance of the relationship between industry and academia. Asked about this, Lord Broers told PEN that the UK Government is trying very hard to facilitate the relationship via the introduction of

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incentives, and there is a sense that the various research councils understand that. A problem that remains, however, concerns the fact that there are those within academia who were unhappy at reading the word ‘impact’ in the aforementioned ground rules. Despite impact being necessary, this perspective still exists – albeit minimally – and thereby affects industry as people don’t invest or, if they do, they don’t invest enough because they (mistakenly) believe that government finances can take the strain. Industry, then, isn’t reacting in the volume that it should, and this comes down to an issue of risk aversion. Another concern relates to a perceived lack of professionals with an in-depth knowledge of high-tech technical risk in many areas of the UK. This often means that new technologies are purchased, developed and commercialised, in other countries (often outside of Europe). Furthermore, there is apprehension that the UK – perhaps even Europe – has a lack of large companies interested in graphene (although this is not the case in the flagship project, which boasts the involvement of several), while there are too many start-ups populating the sector.

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Graphene, not least through the EU’s flagship project, is receiving a significant amount of funding in Europe

A similar and not unrelated argument posits that it is the middle ground that is lacking, with too few medium sized businesses becoming involved.

Infrastructure As well as the importance of linking industry with academia, Pan European Networks also asked Lord Broers about efforts in the UK to connect facilities and infrastructure (such as the Diamond Light Source, where he had been the chair of the board for several years) with the work taking place on graphene. Within the Diamond Light Source, he said, there is an industrial liaison unit, but this is relatively small in comparison to other areas such as Japan, for instance, where large teams working in this area liaise with multinational companies (like Toshiba) to help industry understand what needs to be done. While the work taking place at the Diamond Light Source is progressing, there is always more to be done when it comes to bringing people together because the situation is fluid and there is always more to do in terms of identifying what areas can be better addressed to ensure Europe remains ahead.

Pre-competitive research Within this falls the idea of pre-competitive research, which involves bringing people together, meaning that a lot of universities form co-operative relationships and so exchange valuable ideas. Things then enter a stage in which significant levels of funding are required and this must be structured in a corporate way that protects intellectual property rights and the research being published, which is often not the case because people keep their ideas under wraps if they aspire to create a

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© geralt

spin-off company. However, publishing can bring benefits as those interested in your research or products and services become aware of them at a global level, particularly now that open access publishing is becoming more widely accepted. For Lord Broers, large successful companies need large scale investment; they need a team of people working together to achieve common goals; intellectual property has to be protected; and they need people to take risks – the example here being the USA, where a competitive environment breeds success. However, this environment can often move beyond the general bounds of competition to something more ruthless, with those investing large sums into risky projects driving them relentlessly in a myopic pursuit of results. While this may be an acceptable – even necessary – approach in some areas, there is a sense that the capacity for this to happen in the UK simply isn’t there, and more amateurish enterprises emerge. In the USA, there is also a tendency for companies to reinvent themselves following failure, which is important in the evolving science and technology-related marketplace. There is an oft quoted saying that of the large American companies that existed at the beginning of the 20th Century only 1% remain; this, however, does not take into account the significant number which re-emerge to take a dominant position (General Motors being a prime example). In Europe, the European Research Area has huge potential to help in the early stages, with industry able to take things from there.

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A perceived lack of professionals with an in-depth knowledge of high-tech technical risk often means that new technologies are purchased, and subsequently developed and commercialised, in other countries often outside of Europe

FET The Graphene Flagship Project was selected in 2013 to receive a total budget of €10bn over the next ten years ahead of several other projects in various different areas. To take one of these: the Guardian Angels for a Smarter Life project (see: http://www.paneuropeannetworks publications.com/st3/#30/ and http://www.pan europeannetworkspublications.com/st7/#116) was designed to take developments in microelectronics, sensors, and communications and apply them to wearable medical instrumentation for general monitoring, as well as for other applications such as fitness. This technology had immediate (health-related) applications and would have built on the advances being made in fields such as medical research and the biomedical sciences as well as electronics and related technologies and, as it was also based in the UK, would have drawn on the country’s strengths in creating and developing small scale sophisticated systems, particularly with regard to the areas of medical and marine electronics. However, despite no applications having been previously (or at least concretely) identified,

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graphene (along with the Human Brain Project) won the European Commission’s Future and Emerging Technologies (FET) competition. So there is a latent sense that this American-type tendency for riskier investment is bleeding through into Europe. It is crucial, however, for Europe to maintain its sophistication and its position at the forefront of science, and as long as those involved hold their nerve and see things through, including the evolution of the necessary infrastructure and related industrial sectors, perhaps the Graphene Flagship Project will enable this.

Lessons learnt Given this plethora of issues, many lessons have now been learnt and Europe is certainly in a better position to move forwards with a relative sense of optimism. However, for Lord Broers there is still a need for European governments to lend an air of enthusiasm to efforts such as the flagship projects in an attempt to further highlight to the taxpayer (because, after all, it is their money being spent) the potential that these initiatives have to change their lives for the better.

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In the USA, a competitive environment breeds success. However, this environment can often also move beyond the general bounds of competition to something more ruthless, with those investing large sums into risky projects driving them relentlessly in a myopic pursuit of results

There are, of course, those who criticise the governmental funding of scientific research. These (sometimes quite influential) people argue that this is a waste of the taxpayer’s money because new technology does not emerge from such a linear model but from advances garnered through the support of pure research. According to Lord Broers, this may sometimes be the case but is certainly not the rule. When it comes to graphene, both pathways have merit and while the question of whether this material is an invention or an evolution remains, for Lord Broers, very few modern technologies have been borne through invention. Rather, they evolve from necessity and, indeed, from past mistakes or, at least, from previously-trodden paths which have resulted in less than ideal solutions to a specific problem but have nevertheless provided the first, tentative steps towards something new and exciting (the development of the first transistor being case in point). With a sustained level of investment – enabled via the FET programme – and the right level of appetite and interest on the part of academia, industry, and government (which certainly appears to exist), graphene’s potential to evolve into a wealth of new technologies will only become more tangible, and perhaps there are lessons here to be learnt by others – that taking a risk is sometimes a necessary first step, but the road to sustainability, and thus value creation, is arduous and requires the input, co-operation and even competition between the various stakeholders if it is to succeed.

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DURING CAMBRIDGE GRAPHENE TECHNOLOGY DAYS 2015, THE COMMISSION’S ANDREW HOUGHTON EXPLAINED THE IMPORTANCE OF WORKING TOGETHER

A unifying goal IN October 2013 the European Commission, under its Seventh Research Framework Programme (FP7), launched two FET Flagship projects: Graphene and The Human Brain Project (HBP). The Commission explained that the flagships are ‘visionary, science-driven, large-scale research initiatives addressing grand Scientific and Technological (S&T) challenges. They are long-term initiatives bringing together excellent research teams across various disciplines, sharing a unifying goal and an ambitious research roadmap on how to achieve it. ‘FET Flagships will establish Europe as the leader in their specific domains and a pole of attraction for international cooperation; they will nurture creativity, flair and talent, attracting the best minds all over the world and creating the skilful multidisciplinary researchers Europe needs. By leading, inspiring and integrating efforts, Flagships become a new partnering model for longterm European collaborative research in the context of the European Research Area (ERA).’ Eventually, it is hoped that the flagships will turn scientific advances into concrete innovation opportunities, growth and jobs, and contribute to addressing some of the major societal challenges Europe is facing. The Commission’s Horizon 2020 website explains: ‘FET Flagships are expected to run for about ten years, with a total budget of around €1bn.

They will bring together a large number of research organisations, including academia, large industry and SMEs. This bold investment cannot be carried out alone by the Commission or any single member state. It requires establishing a close link between related activities at European, national and regional levels and ensuring a mutual reinforcement from the Commission and the member states of the research activities that contribute to the Flagship.’

Funding

The Commission’s Andrew Houghton explained that one reason for having the EU involved in graphene research is that it is integral to ongoing discussions around issues of regulation and legislation

It was this issue of funding which Andrew Houghton, the Commission’s deputy head of the unit concerning the flagships within DG Connect, discussed during the Cambridge Graphene Technology Days event in the UK in November (which Pan European Networks was invited to attend). He explained: “The objective is to run these Flagships for ten years, but getting funding for ten years is almost impossible.” As such, he continued, the stakeholders involved are continuing to look for ways of supporting this work over the long term, an effort which has proved thus far to be a success. Nevertheless, Houghton said, “in order to keep the money coming we need to start showing that the money is having some impact.” This was the main aim of the Cambridge event – to showcase the technologies and products which are already emerging from the graphene-related research taking place in European laboratories. Houghton expanded on this by explaining that while he fully endorsed the need to demonstrate that there is a return on the investment being made in graphene research, “there is a lot to be learnt from working together,” and, indeed, from the

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way that other people “do business”. This, he added, “broadens your mind; it takes you out of your box if you go and see how other people do things. This, to me, is the key role of the flagship.”

Valley of death The translation of research results into commercially viable products is a much focused on problem in Europe – with much promising research falling into the so-called ‘valley of death’ before it ever reaches the market – and Houghton took time in his speech to discuss this. He said: “I think we will find many solutions in Europe as different people come to different solutions, but I personally believe that by working together we can achieve much better than if we all work as 28 separate [member state] entities.” Turning to the environmental and health concerns around materials such as graphene, Houghton explained that the Graphene Flagship “has a whole work package looking at the environmental impact of graphene, as well as the potential and non-potential health aspects.”

Regulation Another reason for having the EU involved, Houghton continued, is that the Commission is integral to ongoing discussions around issues of regulation and how graphene is affected by the REACH legislation – a regulation of the European Union adopted to improve the protection of human health and the environment from the risks that can be posed by chemicals – while enhancing the competitiveness of the EU chemicals industry and promoting alternative methods for the hazard assessment of substances to reduce the number of tests on animals, for example. Houghton explained: “As we go forward towards commercialising graphene, this is one of the key issues alongside standardisation, certification, and so on, that needs to be fixed: we don’t want to walk into the genetically modified crops trap. The flagship can take a lead in this but it’s not something it can do by itself, so I welcome everyone else in the

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As graphene becomes the great success that most believe it will be, people will want to make it themselves, and we have to see it spin out

potential to join in, let’s work together to make sure we can’t have these problems.” Asked by a member of the audience how a co-operative relationship between universities and industry can be maintained once a commercially viable and financially competitive product has been identified, Houghton explained that this will indeed be one of the major challenges for the flagship: “As graphene becomes the great success that we all believe it will be, people will want to go and make it by themselves and we have to see it spin out. This will be a key challenge, and while I don’t know the answers today, I think having the flagship at the beginning where we have to solve all these joint problems is the right way to go. Ultimately people will have to go by themselves.” Thus, as Houghton’s closing remarks suggest, the Graphene Project’s strength, or at least one of them, lies in its ability to bring people together. While the EU’s involvement ensures the legislative and regulatory hurdles are addressed, ultimately, the community will need to find its own way, building on the solid foundations laid by the flagship.

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NANOSTRUCTURES FOR PHOTOVOLTAICS Dr Iain Crowe and Professor Matthew Halsall of the Photon Science Institute at the University of Manchester discuss silicon and germanium nanostructures for photovoltaics

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here is increasing interest in using semiconductor nanostructures in photovoltaic technologies to improve light harvesting and charge carrier collection efficiency. These structures are attractive because their optoelectronic bandgap can be tuned over a wide spectral range, owing to one of the better known consequences of quantum mechanics – via charge localisation – from the ultra-violet through the visible to the nearinfrared, simply by adjusting their physical dimensions. This implies that, at least in principle, such structures can interact (by absorption) over a much wider range of the solar spectrum than any equivalent material in its bulk form. The ability of these nanostructures to interact with and, critically, to influence the optical properties of co-doped rare earth species1,2 adds further functionality. Specifically, energy transfer from silicon nanostructures to erbium has been shown to considerably enhance photo-emission resulting from the internal ƒ-shell transitions of these rare earths. This is an attribute that is also extremely beneficial in other technological application areas,

such as in telecommunications where this could pave the way for miniature optical amplifiers. The nature of the spatial confinement of charge carriers in nanostructures, generally, both strengthens the carrier-carrier interaction and suppresses carrier interactions with lattice vibrations or phonons. The former permits the generation of multiple free carriers from a single absorbed photon, whilst the latter minimises the loss that occurs when carriers relax after absorbing high energy photons. Critically, these exotic structures with length scales on the order of several nanometres can now be fabricated in a highly repeatable manner using a plethora of common laboratory techniques that are increasingly cost effective. Forming layered structures, or super-lattices, of size controlled nanostructures is one way to achieve this increased capture of solar photons to improve the charge generation efficiency. However, generating charge carriers in these nanostructures is one thing, but transporting that generated charge to a junction or terminal in order to realise a current flow is a separate challenge altogether. The conventional wisdom here is that, in order to be able to control the optoelectronic properties of the nanostructures, they must necessarily be electrically isolated from one another, which typically means embedding them in an insulating dielectric – a technique that does not lend itself well to charge transport. Recently, there have been a number of reports of solution processed or colloidal nanocrystal inks that can be integrated with conventional bulk solar cells to boost their otherwise limited performance, particularly at the short wavelength end of the spectrum. The idea being that the larger band-gap nanocrystal layer acts as a photon converter to ‘down-shift’ the energy of incoming photons by re-emission of multiple lower energy photons into the underlying bulk cell to generate additional carriers there whilst mitigating the heat waste that is a normal consequence of absorption of high energy light.

Fig. 1 SSQC process via PL; (a) excess energy of a single absorbed high energy photon in a coupled nanocrystal system is used (b) to generate two lower energy photons (c), adapted after 3

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A similar process, ‘space-separated quantum cutting’ (SSQC), was recently demonstrated in silicon-rich silica containing silicon nanocrystals,3 Fig. 1. The excess energy, generated by the absorption of a high energy photon in a silicon nanocrystal, rather than generating waste heat through phonon assisted relaxation was instead used to excite neighbouring nanocrystals through an efficient, intra-band inverse Auger process resulting in

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Fig. 2 Pulsed DC photocurrent from phosphorus doped silicon nanocrystals of (a-c) increasing size and doping level6

luminescence from both nanocrystals. The same effect was also observed for silicon nanocrystals coupled to erbium, although in this case the emission energy would be too low for efficient capture by an underlying bulk silicon cell. However, if the same effect could be demonstrated in other rare earth species with higher energy electronic transitions, such as Neodymium, then this would be beneficial for harvesting more near-IR solar photons. Recent calculations indicate that such carrier multiplication can also be achieved in germanium nanocrystals,4 and the formation of stable colloids of germanium nanocrystals with H- and Clterminated surfaces, without the use of ligands was also demonstrated.5 This latter aspect is promising because colloidal nanocrystals in such ‘as-cast’ films are not separated by insulating molecules that would otherwise inhibit the charge transport. One can then envisage ink-jet printing of such films directly onto standard solar photovoltaic cells to improve the overall carrier generation and, critically, extraction efficiency. In their own recent work in this area, University of Manchester researchers Dr Iain Crowe and Professor Matthew Halsall, with their collaborator Dr Masashi Ishii from the National Institute for Materials Science (NIMS) in Japan, have studied the optoelectronic properties of phosphorus-doped silicon nanocrystals in thin silica films. They noted that careful control of the silicon nanocrystal size distribution, which is achieved by thermal processing of as-prepared films, also controls the electronic doping levels from the phosphorus. Using a resonant excitation process with pulsed infra-red light from an LED, they have shown that a persistent photocurrent can be achieved in these films,6 Fig. 2, which implies that there is an effective internanocrystal charge transport process, and that this is improved by electron-filling the silicon nanocrystals as a result of the phosphorus doping.

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This is extremely attractive because phosphorus-doped silicon is the industry standard for obtaining n-type emitter layers in bulksilicon solar cell fabrication, the dominant and most established photovoltaic technology in the world with over 90% market share. Given the long term investment in the silicon industry, this share is not likely to be diminished in the near term. On the contrary, silicon-based photovoltaics are certain to be an important green technology for the foreseeable future. Thus the technologies described here, which are essentially add-ons to existing silicon devices, represent one of the best possibilities to improve the efficiency of silicon cells beyond the ShockleyQueisser limit in the short to medium term. References 1 Crowe, Kashtiban et al, J. Appl. Phys., 107, 044316 (2010) 2 Shah, Wojdak et al, J. Luminescence, 132 (12) 3103-3112 (2012) 3 Priolo, Gregorkiewicz et al, Nat. Nanotech., 9, 19-32 (2014) 4 Sevik & Bulutay, PRB. 77, 125414 (2008) 5 Holman & Kortshagen, Nano Lett., 11, 2133 (2011) 6 Ishii, Crowe et al, J. Appl. Phys. 116, (2014)

Iain F Crowe & Matthew P Halsall Photon Science Institute and School of Electrical & Electronic Engineering The University of Manchester +44 (0)161 275 1069 [email protected] http://www.manchester.ac.uk/

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CIR’S NICK COUTTS MET WITH PEN IN CAMBRIDGE, WHERE HE TALKED ABOUT THE NEED FOR A BETTER VALUE NETWORK FOR GRAPHENE

Better value

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ambridge Graphene Technology Days 2015 was held in Cambridge, UK, in November. This event, designed to showcase the translation of graphene into commercially viable, and indeed available, products, saw the bringing together of industry to this end. Cambridge Investment Research (CIR) is a business strategy advisory firm founded in 2002. It specialises in business intelligence, opportunity prioritisation and the route to value through value flows, confidence and options.

applications, can perhaps be better overcome through the development of a better value network for graphene.

What do you feel are the biggest barriers facing the commercialisation of graphenerelated products in the EU?

CIR works to enable its clients to design their innovation and marketing to transform or be transformed by their customers, and also affects Routes to ValueTM, a highly successful method to achieve your business, organisational or wider partnership goals. Nick Coutts has been a CIR Strategy Consultant since 2008. He provides expertise in segmentation, the route to value, service design and opportunity prioritisation. As vice-president of the Global Distribution Channel Strategy for the multinational giant IBM, he was responsible for the development and the effective use of distribution channels for IBM globally, which then contributed to turning this large company around. Pan European Networks met with Coutts at the Cambridge event where he talked about how hurdles facing deployment to the marketplace, often experienced by new graphene-related technologies and

If you have the technology to make graphene products then services in terms of how well that technology has been designed, managed, maintained, and developed determines the value that can be generated from the graphene technology

There are several barriers here, and while they vary from application area to application area, the principal barriers stem from variations in product specifications, which can vary in the same product from the same supplier, and also varies batch-to-batch. What we are lacking is a verification of standards by a third party. Inconsistency in specifications upsets processes and causes delays, and it is clear that the supplier of the material should not be doing self-verification because in many cases they have invested interests. In the UK, the National Physical Laboratory does some work on verification but there is not nearly enough capacity there. The best thing the EU could do would be to get innovation agencies to fund the development of third party independent verification services. This is a question of service desire, however, because the barriers to the adoption and use of graphene are lowered or removed by some services. The innovation agencies could be incredibly active here, and the clusters could be really helpful in providing verification services. They also need to understand that they have to be competent in service design (a core competence).

© OpenClipartVectors

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If you have the technology to make graphene products, then services in terms of how well that technology has been designed, managed, maintained, and developed determines the

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value that can be generated from the graphene technology. This is different to design services, however, and you need to make sure that cost is another independent resource; that you know how to design services that lower the barriers to the adoption and the release of graphene, and verification is only one of these issues.

Are there enough opportunities being seized by spin-offs, and how can this be better enhanced so as to target specific applications? That is an extraordinarily difficult question. The first thing, for me, is that those developing new applications need to link to customers at the earliest possible stage; they must present and develop what customers are prepared to pay for – or what they think the customer might be prepared to pay for. They must also be careful as to which consumer base they choose to engage in the development process, because customers could differ for each application. Some arguments which have featured in the masterclass during today’s event have posited that there is a demand problem, rather than a supply problem; that is, there is a lot of capacity,

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Those developing new applications need to link to customers at the earliest possible stage; they must present and develop what customers are prepared to pay for – or what they think the customer might be prepared to pay for

but people don’t know how to take it up, i.e. the applications for the products that capacity can provide. This is perhaps also relevant to the previous points concerning barriers as it concerns capital expenditure, depreciation, and investment in what are known as ‘legacy systems’ – except here they are more properly referred to as ‘current systems’ (they only become legacy systems after they have been replaced by graphene and alternatives). There is a great inertia in current systems. For instance, if you have heavy investment in one technology and it is working well, the risk lies in moving to a new technology (even if there is potential to save money), because you don’t know how well it will perform. Another risk is that you may want or need to replace the equipment, but it’s still on your books and isn’t fully depreciated, and so you want to wait to make sure this does not affect the balance sheet and profit/loss counts. There is thus a combination of market price and moving from the tried and tested name to an untried and untested risky alternative (as well as the more ‘emotional’ side, whereby senior managers responsible for these decisions, but are perhaps close to retirement, don’t want to make decisions that are going to add risk and delay their retirement). This is indeed something that happens more frequently than some would like to think: there is a natural resistance to moving from the current state to the future state, even if there are compelling arguments for shifting.

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Now that the flagship is beginning to roll out its work in the field of biomedicine, how do you feel the regulatory- and policy-related hurdles will evolve concerning commercial applications? There are two strands here: the usual rational scientific strand and the irrational, emotional response to new technologies. Yes, we have to be cautious, and yes we have to control all new technologies; we will undoubtedly have both positive and negative outcomes, and we may not be able to predict what they might be. Scientists are largely responsible, but maybe there needs to be a European-wide body that provides codes of practice for labs, manufacturers, and supply chains so as to gain a better understanding. I am not an expert in this area but rather in the area of building a value network for graphene where we are identifying the barriers of adoption between all the stakeholders within that value network. Anyone interested in improving smart specialisation should be really interested in understanding the dynamics of the new value networks and how graphene will disrupt existing value networks and, indeed, create new ones.

What role do you see Cambridge Investment Research playing in the graphene landscape moving forwards? We can absolutely help labs and companies identify and prioritise applications and then go and get the evidence to support those working hypotheses. So, instead of gambling resources on assertion and assumption, people are able to choose the applications and prioritise them, and, moreover, they will be able to allocate resources based on evidence rather than ego.

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Anyone interested in improving smart specialisation should be really interested in understanding the dynamics of creating new value networks, and how graphene will disrupt existing ones

In a presentation I gave on smart specialisations some time ago, I discussed the need for a bridge between academia and entrepreneurship; that is, I highlighted that how we take the institutional value created in the laboratory and university and convert it into socioeconomic and environmental value is an absolutely critical process. At the moment, we have lots of activity, but we don’t have process; though, if we are able to develop a well-designed process then the value to society will increase. If we have a poorly-designed process then we constrain the value, and that’s not a good thing. If students have an idea for a graphene application, it is almost completely down to chance whether they have the opportunity to take their project forward: they might win a business prize or a small grant; they might find someone interested in financing them; they might find the right team members and the right competence, but this is completely random, and very often the projects that should go ahead don’t. Students therefore have a choice: do they take a risk and, instead of gaining employment somewhere, go and try to make their application a reality? Or do they go and work for a company which will pay them well for what

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they’ve learnt and studied? At the moment – because of student loans, the cost of living and so many other things – trying to work on their application is not realistic for most students, which is a shame. We have to give them realistic alternatives if we want to increase the rate of bringing an application to market. The value here is not necessarily that we need new products and services based around graphene, but that we actually need employment. We have 750,000 young people unemployed long term, and while this is a loss of tax revenue and a loss of competence development, it is, most importantly, a loss of motivation. An OECD report at the end of 2013 demonstrated that 25% of the young people in Paris, 50% in Madrid, and 60% in Slovakia were unemployed; thus, while youth unemployment is clearly a massive challenge, it was not part of the European debate on how well we innovate.

What do you think the rest of Europe can learn from the UK and from Cambridge in particular when it comes to graphene? The goal of the system is employment, and while the knowledge about graphene – and thus the activities taking place – differ throughout Europe, there is perhaps scope for other areas to learn from the idea that if you have the right environment and the right support then you can create new companies at a much higher rate with a much longer life. Indeed, that is probably the best lesson for other markets in Europe. Most of these things fail not because of the idea, but because of the way in which the idea is executed. Those making the decisions need to ask themselves whether they are running a good process and so are using the right tools and method, have the right sort of competence at the right time. If they are unaware of what competences they need or are unable to access them, then they have an unknown quantity of risk. Competence removes risk, and the great thing about Cambridge is that you can find the competence here. However, they are not all visible; all the resources we need for innovation

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How we take the institutional value created in the laboratory and convert it into socioeconomic and environmental value is an absolutely critical process

are somewhere in the city, the space, people, money, expertise, knowledge and equipment, but you need to know how to find them. We therefore need to transform those resources into services in order to have a managed service platform, and this is the vision I am working on with Markku Markkula, so that cities run innovation as a public service alongside health, education, transport, housing services and emergency services, and alike; because, while I might know where to find a densitometer, for instance, unless I also know the hours of access for when I need specialist help, the cost involved, the capacity of the machine and its availability and so on, then all I know is that the resource exists, which isn’t enough. This proves that the return on that asset depends on the services by which it is made available, and they can’t be achieved without a managed service platform. We therefore need to transform the spaces that are available, the people, the enterprise, the knowledge, finance, equipment and services so that people have a better idea of how things work. Currently, access to these resources is too rigid, but we can change that quite easily, and this is why service design is so important and, indeed, why we have a service design master’s degree available in this area – perhaps the only master’s we will ever need.

Nick Coutts Strategy Consultant Cambridge Investment Research (CIR) http://www.cir-strategy.com/

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THE FOURTH INDUSTRIAL REVOLUTION WILL REQUIRE GREATER SUPPORT AT ALL LEVELS FOR INNOVATIVE MATERIALS RESEARCH

The fourth industrial revolution

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he actual materials used to manufacture industrial products can account for up to 10-15% of the total cost of the product. In Germany, the Federal Ministry of Education and Research (BMBF) believes that about five million people are currently employed in materialsbased industries. To maintain this position, a large funding programme of €100m has been launched to support industries in the country. There is currently no common agreement on the definition of ‘innovation’. It is either related to an economical image (for example, the Organisation for Economic Co-operation and Development’s definition includes a flux of investment money) which cannot be applied to universities as they principally work on inventions; or, on a more political level, innovation is interpreted as the creation of new jobs in a competitive world. It is generally accepted that Europe’s fundamental research is world class, but our ability to transform new knowledge into innovative goods

is grossly inefficient – the so-called ‘Valley of Death’. The consequence of this inability to exploit research outcomes is that European industry accounts for only around 15% of the new high-technology products coming to the market. As such, the question regarding reasons why Europe lags behind other countries still remains. The total hybridisation of the university and industry sectors throughout Europe is required in order to generate a new natural transfer of research findings from academia to start-ups and industry

Year after year, the promoters of successive European framework programmes have promised a significant improvement. However, the lack of success can be simply illustrated by a US newspaper comment about Europe: ‘Billions spent and nothing to show’. For some time now, the E-MRS has been aware of this situation and has worked to gain a proper understanding of the reasons behind it by making comparative investigations of overseas competitors.

Overseas innovation mechanisms In the mid-1980s, the E-MRS – along with its sister materials research societies in the USA, China, Japan and Taiwan – established the International Union of Materials Research Societies (IUMRS), which enabled the organisation of worldwide networking, collaboration and exchanges. Today, IUMRS covers the entire world. Through this friendly collaboration, we have investigated how innovation works overseas, particularly in two major countries: in the USA in the field of photovoltaic; and in China, where we had already been invited to make suggestions for the industries China needs to develop. If CO2 emission is used as a reference point, when the economy’s rapid growth started (around 2005), the specific topics were rare earth elements, magnets for medicine, electronics and aircraft.

Perfect hybridisation Later, a second delegation was invited by the Chinese authorities to analyse innovation in two very different situations: start-ups in a number

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of universities, and large industries employing over 1,000 staff in various cities. In short, it was found that there is a perfect hybridisation between university type research and innovation by companies. It was found that, in large companies, all the directors were technically very competent, often holding scientific doctorates awarded in Europe, and they also acted as professors in the universities. In addition, students can study for a doctorate degree within these institutes/companies. Other university professors act as industrial consultants. New companies can be created and the technical staff at the university can be shareholders with the potential for additional income. The universities are able to select their students from all over the country, and 70% of the young people there are attracted by science and technology.

Education and motivation Essentially, two models were identified: A) Industry financing a new laboratory in a university campus and the ‘clean room’ being shared by the industry and the university; and

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The actual materials used to manufacture industrial products can account for up to 10-15% of the total cost of the product

B) Start-ups can be created and localised within the university, not only by the professors but with participation by the technical staff as shareholders. These start-ups have access to the facilities and equipment under the same conditions as the university staff and students. A representative from the Ministry of Research indicated that start-ups get no public support, but that individuals have to take the risks and the consequences.

What can we learn? It should first be indicated that Europe does not have a unique model for the development of new high-technology-based products. In general, each country has its own model and its own financial structures for technological developments. The following points should be considered: 1) Education for a better social acceptance of innovation The importance of science and technology in education is well recognised and it is essential to engage the next generation. However, today the vast majority of young people in Europe are not really attracted to science. In the USA, to interest young people in the field of materials, an exhibition with games has been developed which travels all over the country. In Europe, the lack of interest is even more serious in the older generation, who tend to largely reject any innovation (EUROSTAT). The mass media should be motivated to arouse interest including the potential gain or loss of employment opportunities for the population. 2) ‘Precautionary principle’ Because of the reluctance to accept the concept of innovation, the political elite, especially in the European Parliament, may be seen to

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apply over-restrictive conditions or inappropriate regulations that seriously restrict new developments. There are numerous examples of this with the Registration, Evaluation, Authorization & Restriction of Chemicals (REACH) perhaps being the most widely known. Furthermore, MEPs voted for the sequestration of CO2 in the ground (CCS), while overseas countries developed new industries for the chemical recycling of CO2, thereby creating new jobs which cannot be delocalised. This could be due to the fact that very few MEPs have any international scientific knowledge. 3) Technical/scientific knowledge of industry leaders Increasingly, the leaders of European industry come from the financial sector and fewer have any practical knowledge of science and technology. Consequently, the correct decisions regarding the development of advanced fields are not taken. The same trend is also developing in the USA. 4) Fragmentation In China, as well as the USA, there is one single RDT space, whereas in Europe each country follows its own development policy. The consequence is that many countries replicate the same research. For example, Germany has launched its own €200m programme on the capture and recycling of CO2 to produce polymers.

Towards a new European innovation policy The model developed by China is extremely successful, and we should take into account most of its characteristics. Europe must adapt to the ‘new’ competition being developed in a globalised world. This will mean that important new decisions are taken by the European

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Instead of investing in CCS, perhaps a better solution would be to develop an ambitious programme to recycle CO2 into a chemical fuel or polymers

authorities as well as by the national policy makers. Furthermore, the following should also be noted: n Definition of a medium and long term strategy for the fourth generation industry: it would be best to have a model defining what the European Commission and each country should develop. The European framework programme, as currently defined, is largely the result of lobbying and is no longer adapted to the real needs of Europe; n

Definition of an energy policy for the longer term: today, it has become very difficult for Europe to compete with shale gas and oil from the USA. Consequently, companies with high energy demands mainly invest in the US – around $75bn (~€66.4bn cf. Bloomberg). Europe has ambitious and very expensive programmes for the extensive use of renewable energy sources, even if Europe is a rather low emitter of CO2 compared to China and the USA. Two problems are yet to be solved: electricity storage and cost per kW/h – the Wp as indicated by the photovoltaics industry is totally irrelevant. In practice, the supply of

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renewable energy has far to go to before it is economically competitive in Europe;

Norwegian innovation In Norway, the ‘Nanotechnology and Advanced Materials (NANO2021)’ programme is the Research Council of Norway’s large scale initiative for research on nanotechnology, microtechnology and advanced materials, and will run from 2012 to 2021. According to the Council, it is a key instrument for following up the Norwegian Government’s national R&D strategy for nanotechnology covering that same period. This identifies three priority areas for publicly-funded R&D activities: basic knowledge development, innovation and commercialisation, and responsible technological development. The NANO2021 programme follows in the footsteps of the Programme on Nanotechnology and New Materials (NANOMAT), which was concluded in 2011, and is designed to bring the national knowledge base in nanotechnology and advanced materials to an even higher international level. New, sustainable technological solutions are needed to meet critical societal challenges and provide a basis for industrial innovation. The NANO2021 programme promotes concentrated, integrated research activities to help to achieve a long term, sustained research effort in the technology area while further enhancing the expertise, quality and capacity obtained in recent years. New knowledge and solutions that would otherwise be difficult to realise will be developed by bringing together long term basic research, applied research and innovation across R&D actors, interest groups, disciplines and subject areas. The Research Council’s website states that the programme uses a wide array of its application types and strategic measures to promote: n The development of basic knowledge relating to priority areas such as energy, the environment, climate impacts, health and medical technology, and use of natural resources. Activities under this pillar of the programme will create a national competency base for solving current and future societal challenges and lay the foundation for tomorrow’s knowledge-based industry; n

n

The development and use of technology through innovation and industry-oriented research activities relating to these priority areas. Activities here are targeted towards tackling current societal challenges and creating new industrial activity in new and existing industries; and Socially responsible technology development: both the development of basic knowledge and the development and use of technology entail ensuring that knowledge and insight are utilised to the benefit of society and the community at large. In all projects, importance will be attached to generating a better understanding of the different impacts of nanomaterials on human health and the ecosystem, and to addressing broad-based ethical and social issues relating to the development, production and application of the technologies, when this is relevant. Activities under this pillar of the programme will provide the knowledge platform needed for responsible, sustainable technology development as well as input for legislation in and regulation of the technology area.

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Total hybridisation of the university and industry sectors throughout Europe: this is required in order to generate a new natural transfer of research findings from academia to start-ups and industry; and

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Do not enforce frequent changes in rules and regulations: this is crucial as such changes are expensive for industry to implement, and make it very difficult for small companies and start-ups to follow as an external expert frequently charges €5,000-€10,000 per day.

The framework programmes The question of whether the priorities for a ‘new industry’ are adequate and clearly defined is an important one. For example, the European Parliament has decided to invest €10bn in CO2 sequestration. However, both the scientific community and the general population do not see it as the best solution. Why not develop an ambitious programme to recycle this pollutant into a chemical fuel or as polymers? Several industrial installations are already under construction in Asia which will generate employment that cannot be delocalised. In Europe only Germany, as stated above, has an adequate research, development and technology programme of €200m in this area. This example also highlights the disconnection between national and European policies. It should also be asked whether the recently launched ‘Vanguard’ programme is adequate. Such programmes should have as a priority the development of competence centres open to all SMEs at a reasonable cost, such as common clean rooms able to develop specific electronic chips, which are available to university students in some countries. Regarding the SME calls found in the framework programmes (FP), we feel that innovation will occur first through start-ups and SMEs. In general, the 15% target for SMEs within the FPs has not been attained, and the recent calls have generated much criticism. It would appear to us that the choice of the so-called ‘experts’ here is inappropriate. Finally, with regard to the following up of projects, in our opinion, the financial follow-up works very well, but the same follow-up does not exist for the technical domain. Because the European Commission pushes for the immediate application of new strategies by industry, the contractors promise roadmaps which cannot be followed in practice. Europe thus has enormous potential to play a significant role in the ‘fourth industrial revolution’, but the current mechanisms are not optimal and a new vision needs to be accompanied by huge changes by European policy and decision makers for this to be realised.

European Materials Research Society (E-MRS) http://www.european-mrs.com/

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ENTREPRENEURIAL ECOSYSTEMS The Norwegian Centres of Expertise (NCE) programme builds innovation platforms and strengthens competitive advantages

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he NCE programme objective is to focus, improve and accelerate the existing development processes within the strongest clusters in the country. With funding over a tenyear period available for each NCE cluster, the programme generates significant results, staking out new directions and moving the Norwegian economy to supplement its oil reliance with innovative clusters and a culture of cross-sectorial collaboration. One of a dozen elite clusters, the Norwegian Centre of Expertise for Micro and Nanotechnology (MNT) is the result of leading electronics firms initiating a dynamic collaboration at the regional college (Buskerud Vestfold University College) and generating support from key governmental partners, including the Industrial Development Corporation in Norway (SIVA), the Research Council of Norway (RCN) and Innovation Norway. The NCE MNT cluster has its base in the Horten region, 90km southwest of Oslo, an area also referred to as the ‘Electronic Coast of Norway’. Here a number of successful companies have carved global leadership positions in markets ranging from healthcare to space and aerospace, from maritime and subsea, to defence, agriculture and environment. The cluster has more than 50 members, from small start-ups to large established companies. The cluster collaborates on technology development, advanced production of ICT systems, microsystems and the usage of micro and nanotechnology in miniature. Integrating smart systems with these technologies provides new functionality for a multitude of products and enables new product development, new business models and increased innovation. There is no one recipe for developing a cluster. At the start of the work on the NCE MNT project, it was important to consider the requests and needs as stated by the industry itself. By communicating with the companies early in the application process, a set of agreed, concrete objectives became the guiding points for the cluster development project. Being part of the cluster should improve the cluster companies’ ability to innovate, and to do this more rapidly and systematically. Cluster collaboration should also increase the ability to identify and adopt to new trends and technologies, to meet and beat shrinking product lifecycles and improve competitiveness in global markets. In 2016, as the end of the ten-year period approaches, the NCE MNT project can report a more than satisfactory performance on the overall objectives of the project to develop a sustainable entrepreneurial ecosystem, a system with shared resources for: 1) Knowledge development; 2) A high tech infrastructure; and 3) An innovation platform for emerging technologies.

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Knowledge development To strengthen relevant education and research programmes, the cluster recruited highly trained experts early on. These experts helped the programmes – and especially the research – to quickly gain industry recognition. Their involvement also led to international bench learning and collaboration with similar environments in Boston, USA, and several European sites. A dedicated EU and H2020 co-ordinator position was created through a NCE MNT initiative, resulting in a number of workshops, projects and a dedicated network for EU oriented initiatives. The NCE MNT project also initiated and contributed to the Norwegian PhD Network on Nanotechnology for Microsystems, established to co-ordinate, integrate, and strengthen PhD programmes in the field of nanotechnology and microsystems in Norway. Drawing on the strengths of the participating institutions, the network facilitates an expansion in scope and depth of the research training in this field nationwide. The NCE MNT cluster played a key role in the Erasmus Mundus Joint International Master in Smart Systems Integration, in a consortium consisting of three reputable European institutions: Heriot-Watt University in Scotland (HW), Buskerud and Vestfold University College in Norway (HBV) and Budapest University of Technology and Economics in Hungary (BME). A direct result of the NCE MNT project includes the Centre for Innovative Ultrasound Solutions for healthcare, maritime, and oil & gas industries (CIUS), formed to join forces and explore synergies between academia and industry using ultrasound technology for different applications. CIUS aims to be a worldleading centre for research and innovation in next generation ultrasound imaging, improving patient care, harvesting of ocean resources, and environmental monitoring. CIUS shall strengthen the innovation culture with emphasis on rapid translation from idea to solutions to facilitate new growth for the industries. It shall be the main educational and knowledge centre for ultrasound technology to ensure the competence and recruitment needed by Norwegian industries, academia, and the healthcare sector.

A high tech infrastructure The second tangible shared resource for the NCE MNT cluster was to build an advanced infrastructure to enable co-location of the cluster resources and partners, unleashing synergies for more and faster innovation speed. In 2011, through the efforts of the NCE MNT cluster, the milestone ‘Vestfold Innovation Park’ was completed, a combined research, development and innovation facility, adjacent to the university campus. The joint resources, expertise, clean rooms and lab facilities located here are key to a number of collaborative development projects involving a number of the cluster partners. Relevant lab and test equipment has been moved to the park to make it available for the use of students,

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Building a globally networked entrepreneurial ecosystem to attract talent, ideas and high tech opportunities

researchers and other partners. A joint equipment fund under development also allows the labs to acquire new tools and machinery. Additionally, a national infrastructure collaboration programme, NorFab, provides access to additional state-of-the-art lab facilities and equipment. The Vestfold Innovation Park also includes a large simulation centre for visualisation, rapid design and product development processes.

An innovation platform for emerging technologies The third key part of the NCE MNT project was the development of an innovation platform that supports and fosters collaboration among creative forces, idea developers, and financial and legal sectors. These participants will not only be present in the centre, but also outside the park, within the regional, national and international networks, while individual cluster members perform specific functions. On behalf of the cluster members, the NCE MNT project also participates actively in key international associations, conferences and cluster meeting places, both as partner and host, building networks and expanding connections to other leading clusters and industries. Technology-based commercialisation requires understanding of technology, marketing, entrepreneurship and leadership. The NCE MNT project set out to create a platform for interaction between tech experts, entrepreneurs and investors. A process of building a comprehensive network that brings in international participants is beginning to show results. The participating companies and entrepreneurs benefit from a strong collaboration culture that provides synergies, supports the initiation of development projects and the execution of innovation processes. Finding and connecting a promising start-up with relevant business partners and experts is often essential. The NCE MNT cluster also assists in the commercialisation of business ideas and the search for external partners. The cluster’s own commercialisation company, MicroTech Innovation, plays an active role as an engine for innovation, along with a number of other

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supporting service providers, ranging from product development, legal services to marketing and staffing, engineering, networking and management for hire. Vestfold Innovation Park is proving to be a place for unleashing synergies, a result of people working together and building connections across disciplines and companies, triggering new ideas, partnerships and collaboration projects. The combination of new start-ups and established cluster companies co-located in the innovation park generates new and highly innovative solutions. This is enabled by the combination of available expertise, clean rooms, labs, incubator and test facilities, as well as prototype development areas and dedicated rooms for pilot production. As the NCE MNT project approaches the end of the ten-year project period, the Electronic Coast companies have developed a sustainable partnership that can outlive the period of public funding offered by the NCE programme. The entrepreneurial ecosystem will remain and continue to develop, generating innovation winners from applied micro- and nanotechnology and smart electronics well into the future.

Roger Dalseg Cluster manager NCE Micro- and Nanotechnology +47 (0)903 65 910 [email protected] http://www.nce-mnt.no/

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PROFESSOR RODRIGO MARTINS – PRESIDENT OF THE E-MRS’S SENATE – SPOKE TO PEN ABOUT THE SUCCESS OF THE EVENT AND THE IMPORTANCE OF MATERIALS RESEARCH TO EUROPE’S FUTURE PROSPERITY

Materials for Europe

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September, the European Materials Research Society (E-MRS) held its annual Fall Meeting in Warsaw, Poland, under the auspices of the European Materials Forum (EMF) which Pan European Networks attended. Here, PEN speaks to Professor Rodrigo Martins, president of the Senate of the E-MRS, Vice-Chair of Energy Materials Industrial Research Initiative (EMIRI), and member of the Advisory Board of Horizon 2020 in DG Research and Innovation (advanced materials, nanotechnology, biotechnology and manufacturing) about the success of the event and the importance of materials research to Europe’s future prosperity.

Commission and the main European stakeholders in the field of materials.

What do you feel are some of the biggest barriers to the wider commercialisation of materialsrelated research in Europe, and how could they be addressed?

How did the E-MRS fall event build on or complement the activities held in Lille earlier in the year? The E-MRS Fall Meeting was really fantastic. The event saw a record number of attendees (over 1,100) and it complemented the Lille meeting by bringing the discussion of new concepts within the so-called ‘Materials Common House’ to the arena of science and technology. Here, for the first time, we were able to bring the interests of the European scientific community in the field of materials into a wider context by bridging the E-MRS and the EUROMAT-2015 meeting (promoted by FEMS) with common events organised between 19-20 September, involving what we called the ‘Materials Weekend’ (the organisation of six tutorial courses and a summer course with more than 200 attendees) and the Materials for Europe workshop: a high level discussion involving the European

The E-MRS Fall Meeting saw a record number of attendees

Most of today’s bottlenecks were discussed by the Director General Clara de la Torre during the workshop referred to above. She highlighted the efforts of the Commission to clearly promote the area of innovation by promoting the creation of the European Innovation Council; the establishment of bridges with structural regional funds by promoting the establishment of common project financing platforms between the Horizon 2020 framework programme and such funds; the establishment of inter-regional programmes tackling common interests as a way to enhance markets and to consolidate key areas of development in Europe where materials can be seen as a cross-cutting enabler; the reinforcement of the consolidation of the Materials Common House; and the role of the different key players in the Alliance for Materials, such as the E-MRS, whose role has been reinforced as a key partner to promote advocacy both in Europe and globally. Concerning the establishment of a new philosophy aiming to promote advanced materials commercialisation, I would like to emphasise the role that the Energy Materials Industrial Research Initiative (EMIRI) will have by acting like a public private partnership (PPP) in a key area of our development.

Do you think the European Commission’s graphene-related activities will help overcome some of these issues? The creative and innovative areas will certainly help to promote a new era of (knowledge-

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Around 2,200 scientists from across Europe gathered in Warsaw in September to debate the key issues connected to materials, including innovation, Horizon 2020 and smart infrastructures. At the ‘Materials for Europe’ event – a part of ‘Materials Weekend’ – on 19 September 2015, more than 70 invited VIP participants discussed with Clara de la Torre, director of the Key Enabling Technologies Directorate in DG Research and Innovation of the European Commission, a strategic view on the latest challenges in the materials field. She focused on the vital role of materials for a highly competitive European industry and explained the Commission’s approaches to coordinating R&I within the framework of the present and future European research programmes and initiatives. Other major topics discussed by academics, industrial materials researchers and politicians in the Polish capital were the innovation policy and the role of materials in this context. In particular, the role of the European Innovation Council to complement the works of the European Research Council was highlighted. The need to follow-up and evaluate projects to ensure that technological breakthroughs relevant to European industry are recognised and market uptake is facilitated was also stressed. Also debated was the need to strengthen the new concept of a Common House of Materials, aimed at discussing and integrating cross-cutting fields where materials are the key requirements for development and progress. Additionally, smart infrastructures and how to potentiate/link them to regional clusters as well as the relationship between Horizon 2020 and the allocated national structural funds, focusing on the various strategies and the policies to be used to gain the maximum benefit, were discussed. ‘Materials for Europe’ was organised by the European Materials Research Society and the Federation of European Materials Societies, under the umbrella of the European Materials Forum and the Alliance for Materials. The event formed an integral part of a Materials Weekend, which brought together the two largest materials conferences ever held in Central Europe, namely the E-MRS Fall Meeting and the FEMS EUROMAT conference; both of which took place at the Warsaw University of Technology. The events aimed to strengthen materials science and engineering in Europe and to increase its visibility as well as demonstrate that the development and implementation of new materials is essential to meet the societal needs associated with energy, health, transport and climate change. In addition to Materials for Europe, the Materials Weekend also included the Warsaw ‘Festival of Science’ as well as tutorial courses on cutting-edge materials developments and a ‘Young Scientists Workshop’.

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based) industrialisation, and this will not only be the case for the graphene platform. Indeed, in Warsaw we organised a graphene-related tutorial which saw the participation of the key players from the Graphene Flagship, including its director, Professor Jari Kinaret – for which we thank the strong contribution of Professor Vincenzo Palermo – which highlighted some areas relevant to this. In addition, the Commission has also been looking for sustainable areas connected to the environment, such as issues surrounding CO2, or novel, low cost and fully recycled multifunctional materials to overall serve the comfort of and to promote a better life for our citizens, such as paper electronics.

One issue we have discussed in the past is the need to bridge the gap between different disciplines. What more do you feel needs to be done here, and what assistance can the E-MRS lend (e.g. Innomatnet etc.)? We have certainly been promoting the issues of multidisciplinarity and interdisciplinarity. For this, another key conclusion we can take is that we increasingly need smart multifunctional materials able to serve a plethora of applications, with emphasis on the key pillars of our development: energy, water, food and health. To close this envelope, we also need to look for novel disruptive concepts connected to the design and production of novel materials, where the area of multifunctional modelling will be a clear key strategic area of our future development. To this end, the E-MRS is heavily involved in promoting the field of materials such as through the STIMULATE project, which is designed to promote the relevancy of materials to the growth of our economy, to the younger generations and European citizens more generally. As usual I say: “No materials, no party.”

Given the success of this year’s E-MRS events, what are your hopes for 2016? I am quite confident of a better and stronger Europe. I am also confident that if we fail to approach research as a way of promoting the conditions required for job creation and the generation of new ideas and concepts – which will go on to be the source of development which will lead Europe to the frontline of science and technology – then we will fail. Research into materials will be key here, and the E-MRS will thus remain at the forefront so as to continue to serve the extraordinary materials community that we have in Europe.

Professor Rodrigo Martins President of Materials Science Department of Faculty of Science and Technology, New University of Lisbon President of the Senate, E-MRS Member of the Advisory Board of Horizon 2020 in DG Research and Innovation (Advanced Materials, Nanotechnology, Biotechnology and Manufacturing) http://www.european-mrs.com/

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WHAT HAPPENS AT THE SURFACE? BioNavis Ltd has developed 20 years of research and development in photonics into products for academia and industry

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ioNavis Ltd is a nine-year-old spin-off from VTT Technical Research Center of Finland that has commercialised 20 years of research and development (R&D) in photonics and biotechnology into contract services and instruments for academia and industry. While Surface Plasmon Resonance (SPR) has been established for more than 20 years in drug discovery, BioNavis has further developed and optimised the technology for material research. Whereas traditional SPR has been developed for label-free protein-protein interaction kinetics measurements, MultiParametric Surface Plasmon Resonance (MP-SPR) measures surface interactions on metals and dielectrics, including cellulose, SiO2, Ag, Pt, ceramics as well as graphene. Apart from kinetics, the MP-SPR can determine thickness and refractive index of thinfilms from a few Ångströms up to microns.

The three application areas of Multi-Parametric Surface Plasmon Resonance are: n Drug development (drug formulation, controlled drug release, drug-cell interaction, nanoparticle targeting, uptake mechanisms, lipid interactions);

Further on, we focus on cases from material sciences.

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Which coating is the best one?

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Biosensor development (assay development for agriculture, food and feed safety, environmental, clinical, border and process control, development of point-of-care biosensors such as electrochemical, SERS, ELISA, fluorescence, nanoparticlebased or printed biosensors); and New materials and coatings (graphene, carbon nanotubes, biobased materials, plasmonic materials, for better antimicrobial coatings, antireflective surfaces, electronics, filter membranes, contact lenses and implants etc.)

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Novel coatings bring better anti-reflective displays, energy efficient solar cells, faster electronics, long-lasting batteries, antimicrobial coatings for energy efficient water transport, selective filters, cell growth promoting substrates or drug-loaded implants for improved healing. Over the years, improved thin-film processing techniques allow thinner and thinner coatings to be produced. On the other hand, techniques that are able to measure thin and ultrathin-films were lagging. Now, MP-SPR can be used to understand the coating process and to fine-tune the functionality, while keeping the overall cost low. The main questions are related to saving expensive material, energy and money as well as coming up with greener solutions for manufacturing. n How to select the best barrier (non-stick/anti-reflective/ moisture) coating?; n

How thin can the nanolayer be and still provide desired functionality?;

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What is the quality of the coating?;

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What is the time needed for my nanoparticles to assemble on the surface?;

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antimicrobial, and drug-loaded functional material that triggers on contact with microbes on implant surfaces. Also, the MP-SPR method has been used to make new antifouling coating materials for the marine environment to prevent algae, bacteria and shellfish attachment. The MP-SPR technology was originally developed specially for material testing in liquid environment. Biocoatings (bioresistant, biocompatible or bioactive) have been experimented on using the BioNavis MP-SPR technology extensively. The technology can characterise both the coating properties (up to microns in thickness, and refractive index) and the desired interactions, swelling or resistance of the coating: n Interaction magnitude and kinetic measurements; n

What are the ideal pH and electric potential conditions for the process?;

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Material properties, thickness, refractive index and swelling;

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Which coating process provides homogeneous coating?; and

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Large variety of substrates;

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How does the layer swell when in contact with gas/moisture/solvent?

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Biocoatings can be anything from solid thin-film coatings to soft hydrogels;

Quality of ultrathin films – Graphene and metal nanolayers

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Water exchange and swelling does not interfere with interaction measurement; and

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Gas, liquid or ambient conditions are possible.

BioNavis has been involved in industrial projects where atomic layer deposition (ALD) and chemical vapour deposition (CVD) were used to produce ultrathin layers of graphene, metals and metal oxides. Resulting nanolayers from 3.5Å (graphene) up to 100nm were studied for their thickness, optical properties and plasmonics. The challenge with graphene and metal nanolayers is that there are no fast and simple methods for analysing the thickness and optical properties. The MP-SPR method is sensitive to metal thickness, roughness and grain structure because these properties affect the plasmonic fingerprint that MP-SPR measures. The method can thus provide information on the quality of the coating (determining refractive index and thickness simultaneously), on dopant effects of metals, as well as to evaluate barrier functionality in different environments such as different buffers, gases or electric potential.

Summary BioNavis Ltd offers contract research and instruments for life sciences, biosensors and materials development. The MP-SPR Navi instruments can be found in laboratories in Europe, Japan, China, USA, Canada, Brazil, Argentina or the Philippines. While the majority of our customers come from academia, the proportion of customers from industry is increasing and we are proud to have some of the Forbes 500 list companies as our partners. BioNavis also offers contract research, where the experiments are always designed in close collaboration with the customer. The research can be anything from small projects over a few days to large projects requiring weeks of work.

Specialty coating characterisation Biological environment raises a challenge for material properties. Products such as implants, contact lenses, food packages and cell substrates need a different kind of tailoring for the application in nanoscale. The repulsion of an implant starts from a nanoscale accumulation of proteins, requiring biocompatible coating. Food packaging needs to keep food fresh, requiring bioresistant antimicrobial properties; and the cell substrate for stem cell growth needs to be bioactive with certain functions to promote the growth of the cells. For industrial development of such coatings, knowing the properties and behaviour of the materials in nanoscale is crucial to understanding the behaviour of the material in bulk. MP-SPR Navi™ instruments have been used extensively in the research of different nanoscale materials; materials such as hydrogels for contact lenses to be both a biocompatible, but

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Dr Johana Kuncová-Kallio CEO Dr Janusz Sadowski Vice-President for R&D EU projects BioNavis Ltd, Finland +358 (0)10 271 5030 [email protected] http://www.bionavis.com/applications/materialscience/

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INOS – THE POLISH STATE-OWNED RESEARCH INSTITUTE – OUTLINES HOW THE PHOTONIC RESEARCH CENTRE IS DEVELOPING AND SUPPLYING ADVANCED MEASUREMENT SYSTEMS FOR SCIENCE AND INDUSTRY

INOS’s applied photonic research

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he Maksymilian Pluta Institute of Applied Optics (INOS) has developed its own expertise in the area of research, industrial and military optical measurement systems applied in different multidisciplinary fields. These include: aircraft and automotive part testing; investigation of new materials, including nanostructures and graphene; measurements of optical parameters (refractive indices, birefringence) of micro-objects; investigation of interaction of high power laser pulses with optical materials; radio frequency (RF) signal detection, analysis and recognition; and application of the RF spectrometry for radio astronomy. Here, three of the institute’s several activities will be presented in detail. The first two concern photonic technologies in the field of materials research, while the third is directed to the application of photonic systems in the field of radio astronomy. All these technologies have been developed at INOS.

VAWI The first material research activity concerns a special type of interferometry technique – the Variable Wavelength Interferometry (VAWI). This innovative research technique utilises INOS patents and has the ability to measure the spectral characteristics of optical parameters (optical retardance, refractive indices and birefringence as well as nonlinear absorption (NLA) and nonlinear refraction (NLR)) of samples with the diameter below 1μm and the thickness of tens of nanometres. However, VAWI systems can also simultaneously measure the spectral characteristics of optical parameters of large samples – with the thickness at the level of 2mm. The VAWI interferometer is a type of non-coherent light interferometer utilising a set of birefractive prisms in the interferometer head. It is worth noting that in the described interferometer system both the object and reference waves propagate through the same path so the interferometer system as a whole is very steady and independent from environmental influence. The system has a mechanism that auto-compensates for errors, resulting in high accuracy measurements (the accuracy of retardation is equal to /500). Such a system can be applied to the measurement of the physical parameters of microstructures, including those with graphene layers, and enables the monitoring of heat transfer through a material covered by a graphene structure. It is also useful for investigations of the modification of material parameters during the material’s interaction with high power laser pulses. Here, the VAWI system utilises the femtosecond (fs) laser to generate the supercontinuum as the light source for the

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interferometer system. The fs fibre laser with a graphene structure allows the INOS team to miniaturise the interferometer illumination system and make it more compact, thereby improving its performance as a whole. The VAWI measurement systems have been delivered to both industrial and research users. Industry has been the driving force in the research area of new photonic materials, especially in the field of photonic integrated circuits which has been growing rapidly during recent years. The interest in searching for a reliable measurement technique had its genesis in finding materials of large and dynamically changing non-linearities. These materials are useful in the integrated microoptics area. The characterisation of non-linear behaviour of optical co-efficients is crucial in production, in particular, to guide the synthesis process of materials. INOS also offers the VAWI systems for applications in the new research areas. Indeed, the unique VAWI techniques can be applied in technological measurement systems as well as optical measurements and the testing of new photonic materials, such as nanostructures including graphene, materials for photonic integrated circuits and photonic structures, composite material technology, chemistry, photochemistry, optics, telecommunication technology, the semiconductor industry, medicine and biomedicine.

VAWI fs Recently, the VAWI technique has a new area of application – it has been found to be of use in the investigation of dynamic changes of the local optical properties of materials in microsamples which undergo the effect of very high power ultrashort laser pulses. In classical interferometry, direct measurements of local

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optical parameters in the presence of a single laser pulse in the investigated area are difficult to perform. Fig. 1 presents the main idea within this technique, the femtosecond laser pulse divides into two pulses. The first penetrates the sample, and when it travels through the investigated material it introduces some changes to the local optical parameters of the sample in the pulse area. The second pulse enters the interferometer, where it creates the sample’s interferogram. If both pulses are synchronised, the interferogram of a sample is made directly during the time when the pulse in the sample is within the interferometer’s field of view. In this way, it is possible to register the pulse exactly when it modifies the sample. This provides the ability to measure local and short term variations of optical parameters. In other words, we can say that ‘we take a snapshot of a light pulse in the matter’. This new technique (VAWI fs) can be applied to investigations of new optical materials with high non-linearities, especially those developed for integrated optics and graphene technologies. A particularly interesting application area for the VAWI fs technique emerges in the investigation of photonic integrated circuits. As long as an integrated circuit is driven by continuous work light sources or even if the light pulses are as short as a picosecond, the circuit works properly according to the

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Fig. 1 The idea of VAWI fs interferograms

design assumptions. However, if light pulses travelling through integrated circuits have a length at the level of tens of fs, some of the integrated circuits can work incorrectly. For example, we can consider the integrated photonic Mach-Zehnder interferometer commonly used as a light modulator. When the arms are not optically balanced, the interference does not occur because the light pulses do not overlap each other at the interferometer exit. As such, the presented technique is a convenient tool for research in the area of micro and nanophotonics.

Laser scanning tomography The second activity in the field of material research concerns the laser scanning tomography (LST) technique. This enables researchers to visualise the structure of defect distribution inside the investigated materials. It utilises the phenomena of laser light scattering on a material’s defects, which become the light scattering centres. This technique has the ability to visualise the defects of the size below the resolving power of light microscopy. In the LST device, a very narrow laser beam (with a diameter of just a few micrometres) is introduced to the sample where the laser light travels through the material in the ‘optical channel’. The scattered light is registered by the charge-coupled device (CCD) camera, perpendicularly to the direction of the illuminating beam. With the high intensity of light in the laser beam even the defects of the size below the light wavelength deliver a detectable signal of scattered light in the CCD camera. The LST has been successfully applied in a semiconductor industry and has helped to tune the technology of semiconductor production. It has also enabled the investigation of such materials as GaP, GaAs, InP, CdTe, quartz and others. INOS developed the compact system based on the LST technology for the Polish industry for GaAs investigations. The LST technology has been extended in a few directions. First one enables us to investigate materials with the large amount of defects strongly scattering the laser light. The institute has developed the system convenient for the research of such materials like opaque ceramics, Si wafers and crystals etc.

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The second extension enables us to investigate materials of low refraction index like glasses, optically clear and transparent laser ceramics and crystals where the defect concentration is rather low, in many samples their size is below the resolution of an imaging objective. Such defects have an important impact on the applicability of such materials. In these types of materials, i.e. an optical channel with a diameter of below a few micrometres, where the light power density can be treated as homogeneous along the channel axis, is much shorter than in the case of semiconductors and may be shorter than the diameter of the CCD camera field of view. This extends the LST scanning time. To obtain a higher channel’s length a special objective has been developed. The LST device has also been adjusted for work with lasers of various wavelengths in the visible range. These enable the researcher to apply standard CCD cameras. This technology was then used in investigations of the laser induced photoluminescence of crystals, and can further evolve toward laser Raman tomography. These new extensions can be utilised for investigations of new materials for high power lasers. The above extensions have enabled us to investigate a very wide palette of materials. Some examples of results are presented in Fig. 2 where one can see the compact LST system, three scans of various GaAs wafers, a scan of Al2O3+ZrO2 ceramics, scan of YAG crystal and a scan of a spinel-glass junction in the laser structure after the thermobonding process –the last two are in pseudocolours. Various defect structures/patterns have been clearly visualised.

Radio astronomy The third area of INOS activity concerns the application of photonic systems in the area of radio astronomy. The institute has been involved in the development of measurement systems for research in the area of spectral analysis of RF signals from radiotelescopes in co-operation with the Torun´Centre for Astronomy, Nicolaus Copernicus University. The spectral analysis is performed over several years but in many cases it is not a real-time process. Some acousto-optic analysers were built before, but they were not applied for investigations of very fast and short term processes. The institute has developed a very high sensitive and fast photonic RF spectrometer for the analysis of the RF radiation from deep space. The spectrometer can analyse signals within the 0.5GHz range with the spectral resolution of 1MHz and with the repetition rate

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Fig. 2 LST system, four scans of various GaAs wafers, a scan of Al2O3+ZrO2 ceramics, and a scan of a YAG crystal

over 100,000 analysing processes per second. The analysis of the RF spectrum is performed in 9μs each. The system utilises the acousto-optic analyser and is equipped with the stable laser source and fast CCD camera. The system has been developed as an extension of our defence technology. These new applications of fast RF spectrometers enable researchers to intercept transient, very short, and almost stochastic phenomena of the RF radiation from space radio sources. Such phenomena are very difficult for detection in real time. The systems will enable the researchers to search space for very short events. It is also convenient for investigations of organic molecules in the Universe. This paper was co-funded by the Polish Operational Program – Innovative Economy (POIG) projects: POIG.01.03.02-14-020/10, POIG.01.03.02-00-055/10.

Jacek Galas, PhD Director Maksymilian Pluta Institute of Applied Optics (INOS) +48 (0)60 443 2844 [email protected] www.inos.pl Dariusz Litwin, PhD Eng Director's Adviser for Multidisciplinary Research Projects Maksymilian Pluta Institute of Applied Optics (INOS) +48 (0)60 556 4546 [email protected]

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MOLECULAR AND THIN FILM CHALLENGES Max Planck Institute for Polymer Research discusses the new challenges associated with molecular and thin film electronics

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he area of molecular and thin film electronics has over the past two decades grown into a tremendously rich, varied and multidisciplinary research field, bringing together scientists with chemical, physical, mathematical, engineering and biological backgrounds. Amongst various types of thin film devices, the Organic Light-Emitting Diode (OLED) is arguably the best known and most successful technology coming forth from this field since practically all smartphones rely on active matrix OLED displays. It must be said, however, that other foreseen applications, such as flexible solar cells and large area OLED lighting, are subject to delayed development. In some cases this is due to lab-to-fab trials attempted too early. Challenges relating to robustness, production yield, reliability, and longevity have perhaps been somewhat underestimated. Nevertheless, the advantages and benefits of thin film (and hence flexible) electronics, with respect to cost reduction and design, have been widely acknowledged and continue to spark new ideas and product concepts such as smart clothing and building-integrated photovoltaics. Interestingly, where some ten years ago such concepts were still almost exclusively considered ‘technology-push’, rapidly advancing automation nowadays ever more prominently puts a societal demand on such future applications, which can only be realised by miniaturised and/or flexible electronics. In view of the above it remains highly important that the thin film electronics field keeps receiving ample attention on an academic level, since many fundamental issues are still to be resolved in making large scale production viable for various applications. In other words, after a decade of research and development into up-scaled fabrication such as roll-to-roll manufacturing, we have learnt that the challenges mentioned above will not be met as long as they are exclusively addressed by research and

development or optimisation efforts taking place outside the academic domain. The Max Planck Institute for Polymer Research has acknowledged this by founding the Molecular Electronics department, headed by Professor Paul WM Blom. The research focuses very much on gaining understanding on a fundamental level, both through modelling and experimentation, addressing not only device performance and endurance but also fabrication-related topics such as film formation dynamics and evaporative drying. Besides, we have introduced (self-) healing concepts that hold great promise to significantly improving yield in an up-scaled production environment. Apart from gaining fundamental understanding to improve performance and fabrication, we are also constantly on the lookout to identify and create new functionalities. One of the most promising and innovative strategies we take here is blending materials with different (opto) electronic properties and controlling their phase behaviour during film casting. Blending has the trivial but significant advantage not to increase the number of fabrication steps during device production: depositing a functional layer consisting of a multi-material blend from a ‘one-pot solution’ is performed within the same effort and timeframe as a film comprising one single functional material. Another innovative effort is to use our expertise in thin film device design to study the interfacing between electronics and physiology, even involving living cells. If you are interested in learning more about thin film and molecular electronics, and/or co-operating with our department, do not hesitate to contact me. We look forward to hearing from you.

Dr Jasper J Michels Group Leader Max Planck Institute for Polymer Research Department of Molecular Electronics +49 (0)6131 379 607 [email protected] http://www.mpip-mainz.mpg.de/molecular_electronics

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STEVE PURSER OF THE EUROPEAN UNION AGENCY FOR NETWORK AND INFORMATION SECURITY ANSWERED PEN’S QUESTIONS ON DIGITAL SECURITY MATTERS IN EUROPE

Pushing the cybersecurity agenda

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Europe becomes ever reliant on digital technology, cybersecurity remains an issue that policy makers at national and European level continue to engage with. From citizens, to businesses, to governments, the issue is a concern for all. The European Union Agency for Network and Information Security (ENISA) is at the forefront of building the strength of network and information security in the EU today. The agency does not act alone; it co-operates with key EU agencies such as Europol, and other national and European bodies engaged with cybersecurity matters.

time and budget, and assisting the executive director in stakeholder relations – Purser is at the heart of activities at ENISA. Here he provides an insight on activities being pursued by the agency, and the challenges ahead.

What are the major cybersecurity trends in Europe at present, and what are the main focuses for the agency? At the agency, our focus is dictated entirely by our stakeholders. In terms of our governance structure, these are represented by two bodies: one is the permanent stakeholder group of industry representatives, the other is the management board who are representatives of EU institutions and member states.

The annual cybersecurity month, held each October, serves as an example of ENISA’s work to promote cybersecurity matters across Europe. With public and private sector partners coming together, each year the size of the coalition involved continues to grow, as does the numbers of countries involved; in 2015 there were 30. It has been so successful in advancing the aim of a more secure Europe that the agency is considering a gradual reduction of the resources it allocates to this activity in order to invest in less developed areas. This is a rational decision, reflecting ENISA’s clear priority of focusing on areas of weakness. Shedding light on matters at present, Steve Purser, ENISA’s Head of Core Operations Department, answers PEN’s questions on developments in cybersecurity. Responsible for three things – working with member states to define the annual work programme, executing that programme within

In recent years, working with the management board, we have defined four strategic objectives, which capture everything we are trying to achieve.

ENISA is at the forefront of promoting cybersecurity in Europe

The first is to develop and maintain a high level of expertise of EU actors for cybersecurity. The second is to assist member states and the Commission in enhancing capacity building, very much a key issue in international cybersecurity. The third is to assist member states and the Commission in developing and implementing the policies needed to meet regulatory requirements. The fourth is to enhance co-operation between the member states of the EU, as well as between all related network and information security (NIS) communities. We have a number of key projects which illustrate the kind of work we do very well. For the last few years we have been working on a document known as the ‘ENISA threat landscape’, where we work together with communities all over the world. While we carry out no threat analysis ourselves, we go throughout the globe collecting as much information as we can, putting it together and consolidating it. We remove the data that people don’t need or don’t agree on; we then promote that which people do agree on and

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tailor it to the needs of stakeholders. This results in a product that represents a global view of the way threats are evolving. Other areas where we have carried out work recently are in cloud security, industrial control systems and SCADA (supervisory control and data acquisition). These are areas where we think we can really add value. However, once we believe other people are working on the subject and they are doing a good job at the European level, we scale back our engagement as we no longer continue to add value. ENISA looks for those things that genuinely need some type of support at European level, to make sure that everyone is rowing the boat in the same direction. And today, for instance, we are at the point that we may soon drop out of working on cloud systems to concentrate on other things, such as smart technologies and the Internet of Things (IoT). We have worked with member states on article 13a of the telecoms directive and article 4 of the ePrivacy directive to make sure that these things were implemented in an industry friendly and economically viable fashion. When the directive was agreed, with the idea that industry has to report serious breaches or data losses, it was largely thought impossible to implement being too costly and largely unviable. Today there is now a working system, producing valuable data, with which people seem to be happy. This has paid back in a short period of time all of the effort put into it. Our largest flagship project is the co-ordination of the CyberEurope exercise, which may well be the biggest cybersecurity exercise in the world. In the exercise, we come together and play out a very sophisticated simulation with real operational teams in environments across Europe, who defend against a simulated cyber attack. While this is what we focus on at the moment, there are some problems, and I will be quite clear about where I think we are not living up to expectations. We are not sufficiently covering new technologies and business models such as the IoT, car-to-car communications, wearable devices, and mobile computing as it continually evolves. This is purely a resource problem. It takes a lot of resources to cover this range of technologies, and at the moment we haven’t been sufficiently persuasive to secure the budget that we need to do this.

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This year has seen Brussels reveal plans to create a Digital Single Market for Europe. What implications does this move have for the work of the agency? Of course, the strategy has only recently come out and at the moment it is a set of ideas, and those ideas will probably evolve. It is a very significant step but the point I would make in terms of implementation is that we are really still on the starting blocks. ENISA is an organisation that concentrates heavily on implementation. While we do engage with policy, I think we are unique in Europe in that we work together with operational communities to translate abstract policy into very concrete things. ENISA contributes to real world solutions; looking for things like good practice and proven methods. We feel the Digital Single Market will become very important, but at the moment we are at the very beginning of the process, and ENISA is not formally involved at this stage. However, it is important to mention that there is an enormous amount of overlap here with a concept that the agency put out previously under the heading of ‘Digital Sovereignty’. In terms of security, this ENISA initiative is closely aligned with what the Commission is looking to achieve with the Digital Single Market. We have commented that current attempts to improve network and information security often don’t achieve an optimal balance between opportunity and risk. There is a tendency to talk about the risk a lot in security circles, but this often misses the opportunity angle there is here. In the past, we have commented that the internal market for security products and services isn’t functioning correctly. I would describe the security market as being a supply/push market. Vendors produce tools such as intrusion detection systems or consolidated logging systems, and this creates a response from customers who are interested in acquiring the tool. This is entirely the wrong way to do things. Firstly, a clear idea of the requirements is needed, then customers ought to be requesting tools to meet these requirements from vendors. Today it is a supply/push market and it is dominated by US companies.

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Further, there is also a problem with knowledge and skills related to cybersecurity. In Europe, such skills are developed and maintained in a rather fragmented manner. Europe needs a more coherent approach for educating citizens and government. This must be aligned with industry needs. Indeed, if you look at certification schemes at the moment they tend to focus on one or two specialised roles within industry (such as the CISO role), whereas there are many other security-related roles to cover.

later, we have a well-established set of standard operating procedures that member states are working towards and improving on. These are very clear and well-defined; people know who to phone in an emergency; and stakeholders understand the mandates of their counterparts in other countries.

Reflecting on the EU cybersecurity strategy, what do you feel this has achieved and what impact has it had on the European cybersecurity community?

In terms of developing industrial and technological resources, ENISA has some very specific tasks. We have been working for some time on standards, co-operating with CEN-CENELEC and ETSI. The way standards are developing are certainly positive in regards to what we are seeking from a policy perspective. We are also very active in supporting the CSCG – CyberSecurity Coordination Group – and we assisted them in their formulation of their white paper for the way forward in standards.

It might not be well known to the general public or even the more specialised public, but it has been a real success. There have been a lot of things achieved within the strategy that are already complete or on their way to completion. Within the section of the strategy on improving cyber resilience, we have definitely helped member states improve their national resilience capabilities. For example, we have worked very closely with them to ensure the national cybersecurity strategies are developing along the same lines so we don’t have fragmentation across Europe. Another example of work in cyber resilience falls upon internet security implications for industrial control systems and SCADA. Here, we carried out a lot of work which had not been done before, and this is now being built upon. SCADA in particular had escaped the radar of cybersecurity for a long time; with industrial control systems, it was never thought that threats could be contractible from the internet. Yet they definitely are, and a lot of progress has been made there. It is essential to reiterate the significance of our pan-European exercises. Before these started in 2010, there was nothing in place. Any reaction to a pan-European event would have been purely best effort. Now, five years

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ENISA was present when Neelie Kroes, the former vice-president at the Commission responsible for the digital agenda, launched the initiative last year; and this was very much a joint effort. At ENISA we work on a continual basis within individual sectors to identify and deepen standards. Further, the Network & Information Security Directive (NID) is an important piece of future legislation, yet it is extremely abstract. Consider article one, that says we are aiming to have a

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very high level of security across Europe and all member states. We have to identify what that means. I think a lot of the work that we have been doing with industry and with standards organisations can be used to make much of the work under the NID much more concrete. There remain things to be done and the big challenge for the future is to make sure that what has been started continues for the next ten years. This will involve monitoring feedback, reinforcement, understanding why things don’t get done and trying to put it right. This is a circular process where we are working on the weak areas of European cybersecurity. ENISA wants to spend more time focusing on things that don’t work and trying to put remedies in place to make sure recommendations that have been put out in the past are followed up.

What role can key institutions play in demonstrating good practice, and sharing case studies across the sector? Essentially, everyone needs to play a role in demonstrating good practice, ENISA plays a special role because it tries to identify good practice in specific areas and make sure these good practices are disseminated, understood and applied. In practice this is a lot more difficult than people think. This remains our biggest input into the cybersecurity environment, but it remains difficult to ensure the flow of information is acted upon. There is too much information facing decision makers in the sector, and those working every day in the environment want to get the job done effectively. They have businesses to run on a day to day basis and find it difficult to determine what is useful information and should be acted upon immediately, and what is less useful. At ENISA we aim to overcome this and share important information.

How important is the EU’s research programme, Horizon 2020, in tackling problems of European cybersecurity? The key message is that there is not enough formal interaction between ENISA and Horizon 2020 (H2020) in particular. As we don’t have any sort of formal role in the programme, we can’t really influence it and, equally, it doesn’t influence us. We can play a much bigger role and can add a lot of value.

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ENISA can help in ensuring that H2020 projects align well with the policy goals of the Union in cybersecurity. Meanwhile, we can play a much bigger part in ensuring that the projects selected can add the most value to the things we are trying to do on a day to day policy basis. That requires ENISA leaders being brought into a decision making committee at the right moment and being able to have a say on cybersecurity matters. Where the projects are concerned, the goal should be that they produce things that generate economic value. Therefore, we should be producing tools or processes and supporting business based on these results. However, while H2020 works to bring together a lot of different people from a lot of different member states to do something, it has historically been proven difficult to take the results of the project forward in terms of commercial products and services once they end. At present, should industry take on the project outcomes and try to use them, there is no support framework for operational exploitation. In other words, when a problem arises, there is often no-one to go back to, with the project members having gone their separate ways. There is the scope to set up a framework to make sure there can be better follow up. It would require working together with universities and EU companies specialised in security to secure a framework for rapid implementation of EU research ideas, and to ensure a feedback mechanism. This would help develop products that work for industry.

Steve Purser Head of Core Operations Department The European Union Agency for Network and Information Security www.enisa.europa.eu

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COMPUTERS MEET BIOLOGY Silesian University of Technology hosts research that attempts to unravel the unsolved questions of contemporary biology

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any of the unsolved questions in contemporary biology require advanced and efficient computational tools in order to have a chance of finding the answer. The bioinformaticians at the Faculty of Automatic Control, Electronics and Computer Science are familiar with these issues as they try to solve such riddles on an everyday basis.

The genome alphabet The study of nucleotide and amino acid sequences contributes to a better understanding of the living organisms and their evolution. The gained knowledge influences the practical approach in such areas as medicine, pharmacology, breeding or crop production. However, the vast amount of genomic and proteomic data, caused by the recent rapid progress in high-throughput sequencing techniques, presents new challenges in the field of storing, processing, and analysing large scale text data (as text is typically used to represent information about genomes and proteomes). The Massively Parallel Computations team is focused on providing biologists and bioinformaticians with effective, fast, and succinct algorithms for manipulation of biological data. Our efforts are aimed at most burning issues in computational biology, including genomic data compression and indexing, sequence comparisons, or phylogeny. In pursuit of best performance, our algorithms are designed to take advantage of the latest achievements in computer technology. They are especially suited for multicore and multiprocessor architectures. Thus, available computational power can be fully utilised, no matter if software is run on a low shelf netbook or a million dollar cluster. Most demanding tasks can be executed on massively parallel devices like graphics processors. Their raw computational power, expressed in floating point operations per second, is ten times larger than that of central processors. Simultaneously, our algorithms are memory efficient. This allows the user to turn his desktop PC into a high

performance computing centre and analyse terabytes of biological data at an impressive rate. Developed techniques are among the most effective solutions to related problems and create new opportunities for high performance analysis of genomic data. For example, QuickProbs, a tool for multiple sequence alignment, handles protein families with several thousand sequences in several minutes at superior accuracy; the Genome Differential Compressor allows 1,000 human genomes to be stored on a single compact disk; and thanks to the Multiple Genome Index a PC equipped with a mere 8GB of RAM is sufficient to search for exact and approximate patterns in such a collection in less than a millisecond.

Mining through the data The Data Mining Laboratory’s research interests comprise statistical and mathematical modelling methods for biomedical study purposes. The group members explore the latest pervading questions arising from high throughput experiments in the fields of genomics, transcriptomics, proteomics and metabolomics. These topics include unravelling biological mysteries through state-of-the-art technology in genome-wide association studies, multiplatform gene expression microarray experiments, proteomic and lipidomic mass spectrometry processing, magnetic resonance imaging, next generation sequencing and more. Among the developed techniques there are a variety of algorithms for feature selection, clustering and classification, as well as pre-processing procedures such as identification and correction of diverse artefacts occurring throughout the measurement process. Furthermore, work is being carried out on the subject of noise filtration techniques for efficient feature extraction. These integrative and combinatory approaches are continually essential for enabling a peek through the keyhole at the structure of intracellular components and reaction networks. Moreover, they allow for the creation of tailored and tuned solutions for biomedical data analysis and inference. The main objective of introducing the established procedures and expanding this domain of science is assisting the discovery of diseases of affluence biomarkers and mechanisms. User friendly applications such as GaMRed for noise modelling and filtration using the decomposition of signal distributions into Gaussian components and NucleoAnnot as a repository search tool are examples of the solutions already available to the research community worldwide.

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although only partly realised, potential for contributing to cancer treatment. This research is considered to be a contribution to a new science called ‘systems biology’, which builds a bridge over the gap between mathematicians and engineers on one side, and biologists and clinicians on the other.

From model to organism

Optimising a trip through the labyrinth The research interests of the System Engineering Group are focused on analysis of cancer dynamics and mathematicallybased synthesis of anticancer therapy. The development of therapy protocols is realised from an engineering point of view as the search for a solution to a specific control optimisation problem. Since, in the case of cancer patients, consecutive measurements providing information about the current state of the disease are not available, the control laws are derived for an open loop structure. Different forms of therapy are incorporated into the models, from chemotherapy and radiotherapy to antiangiogenic therapy, immunotherapy and gene therapy, but the class of the models introduced is broad enough to incorporate other forms of therapy too. The models related to the analysis of cell cycle control proceed to influence the effects on cell population, they then turn into structured models and, finally, signalling pathways involved in carcinogenesis and their influence on therapy outcome.

The Multimodal Interactive Systems Laboratory is a part of the Laboratory of Bioinformatics. Its research interests are focused on the advanced methods and tools which can be used in multimodal simulations for medical problems like virtual and augmented reality, computer games and motion capture systems. Such tools are used for the evaluation of impact on the user and also for analysis of different data (like motion data). Laboratory equipment includes four high quality graphics workstations (MAC Pro) with software such as (Maya, 3D Studio Max, Unity Engine, Zbrush, Photoshop) and virtual reality goggles (Oculus Rift DK2). Our main research concerns motion acquisition, synthesis and analysis tools. GeCONiI teams in co-operation with the Polish-Japanese Academy of Information Technology, where the Human Motion Laboratory with Vicon motion capture system is situated, develops tools for processing motion data such as the Quaternion Lifting Scheme or classification based on Dynamic Time Warping. Based on the real captured data a new quaternion blobby model for automatic determination of joint limits was developed and evaluated. The laboratory also conducts research necessary for the construction of the Inertial Motion Capture Costume for outdoor acquisition and motion analysis. The system operates primarily by determining the orientation rather than position of each sensor. Work is being carried out on algorithms to estimate the orientation based on measurements of IMU sensors.

Some of the most recent results from biomedicine show that the successful treatment of cancer, based on analysis of intracellular processes, might be at hand. Subsequently, solutions to the optimisation problem that arises this way are discussed, not only in strict mathematical terms but also in terms of their applicability. Contrary to existing literature, it does not include therapy as a change of one or more parameters in the model, because this does not allow the development of therapy strategies. The models considered take into account the pharmacokinetics (PK) and pharmacodynamics (PD), cell cycle and phase-specificity of the therapy, drug resistance, angiogenesis and antiangiogenic treatment, immunotherapy, spatial effects and age-structured populations.

The motivation behind this research is the ability to use our tools for medical analysis of motion data and, furthermore, in simulations and entertainment applications (e.g. games), adjustment and evaluation of rehabilitation exercises, and the planning of sports training.

The incorporation of intracellular processes through signalling pathway models is also discussed. Yet another recently developed class of models incorporates the theory of evolutionary games. The team’s contribution in this area is related to modelling new phenomena recently recognised in intracellular communication and signalling, and also to new techniques of spatial game theory modelling including multidimensional and multilayer models. Experience from the areas of control theory and system engineering, and from long term co-operation with molecular biologists and clinicians enables a discussion of biological background and systemic tools in this field, which has a large,

Professor Joanna Polanska Head of the Upper Silesian Centre for Computational Science and Engineering Faculty of Automatic Control, Electronics and Computer Science Silesian University of Technology

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+48 (0)32 237 2144 [email protected] http://www.polsl.pl

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THE DIWINE PROJECT TEAM OUTLINE HOW THE WORK PACKAGES OF THE INITIATIVE COME TOGETHER

Enhancing wireless communications

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IWINE considers wireless communications in a dense relay/node scenario where wireless network coding messages are flooded via dense massively air-interacting nodes in the self-contained cloud while the physical-layer air-interface between the terminals (sources/destinations) and the Cloud is simple and uniform. A complex infrastructure cloud creates an equivalent air-interface to the terminal, which is as simple as possible. Source and destination airinterfaces are completely blind to the Cloud’s network structure. The Cloud has its own self-contained organising and processing capability.

network coding strategy and self-organise without the support of any central co-ordinator. Distributed algorithms have been investigated within the DIWINE project for the estimation of the main parameters that characterise the cloud-network state, such as the timingfrequency offset, the channel/interference state information, and the Cloud network topology. New techniques based on the consensus approach have been investigated where the parameter estimates are computed locally at the nodes and iteratively refined based on peerto-peer information exchange until consensus is reached within the Cloud.

DIWINE WP2 We identified fundamental limits and operational constraints for advanced algorithms in complex scenarios, and this will serve as a reference in the advanced System Level Simulator demonstrations within the DIWINE project. These fundamental limits cover some of the most important issues when implementing and deploying the DIWINE cloud communication solution.

To boost the convergence, especially in cloud scenarios with non-linear or under-determined estimation settings (e.g. for a large number of unknowns and limited local datasets), new schemes with improved tracking capability with respect to the state-of-the-art have been developed, where local estimates are combined, taking into account the different degree of reliability at different nodes.

Such issues include the modulation-coding scheme for the Wireless Butterfly Network (WBN), linear physical-layer network coding (LPNC) in a multilayer relay network, distributed spectrum sensing and synchronisation, the connectivity aspects of wireless multi-hop relay/mesh networks, and the characterisation of confidentiality in terms of secrecy capacity when only statistics of the channel state information are available at the transmitter (CSIT). All these aspects reflect the scenarios that the DIWINE cloud will encounter in practice.

DIWINE WP3 Knowledge of the network state is fundamental in optimising intra-cloud communications and designing efficient resource sharing strategies. Distributed signal processing enables the cloud nodes to estimate, in a fully distributed way, the network-state information needed to set up the

Fig. 1 Examples of distributed networkstate estimation: a) Distributed synchronisation; and b) Distributed interference detection

Methods have been successfully applied to distributed synchronisation by a distributed phase locked loop that dynamically corrects the timing and carrier frequency offset (TO and CFO), based on information extracted from the superimposed signals resulting from the transmitting cloud nodes, as shown in Fig. 1a. Furthermore, in experimental scenarios the cloud nodes can co-operate to acquire information about the surrounding radiopropagation environment (distributed channel estimation), detect the interference pattern caused by co-existing networks (distributed spectrum sensing, see Fig. 1b) or self-learn the Cloud network topology (distributed network localisation). Methods have been tested on real

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effects on the received combined signal constellation, and the NCM design has to carefully respect that. The DIWINE project provides a complex set of WPNC design solutions. In particular it identifies the information-theoretic fundamental limits and achievable rates for the WPNC. It provides design methodology and practically usable NCM schemes for a variety of topologies and channel models, with a particular stress on situations with imperfect sideinformation and channel parameterisation. The resulting performance results show a clear advantage over the classical multi-user technique and even over the classical discrete message network coding.

DIWINE WP5

data, both in smart metering network and critical monitoring and control platforms.

Fig. 2 SMN test bed

DIWINE WP4 Wireless Physical-layer Network Coding (WPNC) is a key component in designing dense wireless communication networks. A major problem of the dense network is the massive interaction of the radio waves from all active nodes, as these signals superpose at the receiver antenna. Traditional techniques try to avoid or minimise the interference by radio resource management. The fundamental principle of WPNC is that, instead of avoiding the interference, it tries to turn the interacting signals into ‘friendly’ signals carrying useful exploitable information. This is achieved by designing Network Coded Modulation (NCM), which is a multi-source co-ordinated coding system respecting the structure of the network and the type of processing at the relays. The relays in the network do not decode or process individual messages of component sources, but they process many-to-one functions of the component messages. This allows a substantial reduction in the processing rates and turns the signal interaction into an advantage. The final destination receives multiple independent forms of the many-toone message function and solves the decoding problem for the desired message.

In order to demonstrate the step-change enhancements provided by the DIWINE paradigm, three demonstrators have been implemented. The first two are hardware test beds showcasing two application cases: future Smart Meter Networks (SMN) and Critical Industrial Monitoring and Control (CIMC) systems. The role of the third demonstrator, the System Level Simulator (SLS), is twofold. Firstly, it serves as a platform for evaluating and demonstrating algorithms whose complexity exceeds the capabilities of the hardware platforms. Secondly, it acts as a bridge between theoretical algorithm development and practical implementation, allowing us to obtain preliminary results of innovative DIWINE algorithms. Future SMNs will be extremely dense and will generally be delay intolerant, e.g. conveying safety critical control messages, and should themselves be energy efficient, especially where mains power is not always available to all nodes. These enhancements, which are achieved by the DIWINE paradigm, are demonstrated by the implementation of two advanced Wireless Physical-layer Network Coding (WPNC) algorithms. They demonstrate energy efficiency, low-delay communications and adaptability through self-organisation. In addition, a consensus-based synchronisation algorithm has been implemented. This is crucial to provide the precise timing required by WPNC, whilst avoiding centralised control. The test bed has been developed using Ettus USRP N210 Software Defined Radio (SDR) devices and is shown in Fig. 2. The physical layer is based on the IEEE802.11a standard.

Fig. 3 CIMC demonstrator

The CIMC test bed (see Fig. 3) has been developed to validate the integration of the DIWINE cloud functions with an industry-standard wireless network implementation. It consists of an existing industrialcompliant wireless system underlaid with a distributed and self-contained network of DIWINE compliant cloud nodes.

The design of the NCM must respect signal and channel characteristics and network structure. Unlike classical point-to-point communications, the relative channel parameterisation has strong non-linear

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Fig. 4 (b)

Fig. 4 (a)

Cloud radio modules are equipped with a dual radio access technology: the first radio supports the WirelessHART standard and is primarily intended to synchronise the network. The second radio supports the DIWINE cloud functions and adopts a proprietary radio interface. A dedicated real-time processor is used to co-ordinate the two parts of the device. The cloud access nodes can thus provide a WirelessHART compliant interface to existing industrial field devices providing them with cloud services and seamless traffic offloading. A co-operative multihop algorithm has also been implemented and tested, which is designed to handle the ‘dynamic publishing’ of data originated from a field device. In the CIMC scenario, dynamic publishing happens when the field device detects some unexpected condition that requires a low-latency reaction. An algorithm to autonomously detect co-channel interference patterns and deliver this information to the host field device has been implemented using distributed consensus based processing. The SLS was employed for the demonstration and evaluation of complex multi-stage networks that employ a type of WPNC known as ‘Hierarchical Decode-and-Forward’ (HDF) for packet forwarding. Packet error probability at the relays is calculated by the SLS based on the current channel conditions, and the SLS is also responsible for emulating packet losses. The throughput versus requested load of the simple three-node

List of all project partners: Technische Universität Dresden (DE) Cˇeské vysoké ucˇení technické v Praze (CZ)

Fig. 4 (a) HDF building block topology; and (b) WPNC versus baseline performance

topology (see Fig. 4 (a)) is shown for different transmit powers on the right of Fig. 4 (b). The HDF results show significant improvement compared to traditional time division based forwarding, which serves as the baseline. By stacking multiple HDF building blocks, complex multistage topologies have also been implemented. The performance of WPNC algorithms in such topologies can be predicted with good accuracy due to the full characterisation of the performance of the basic building blocks. A significant number of publications have been produced in the frame of DIWINE. An overview is provided under http://diwine-project.eu/ public/publications.html including more than 35 magazine/journal/letter publications and 100 conference/workshop papers.

Hrjehor Mark and Pin-Hsun Lin, Technische Universität Dresden, Germany Jan Sýkora, Czech Technical University in Prague, Czech Republic Kostas Ramantas and David Boixade, IQUADRAT Informatica, Spain Stefano Galimberti, Pepperl and Fuchs, Italy

Iquadrat Informatica S.L. (ES) Pepperl+Fuchs Srl (IT) Politecnico di Milano (IT) Consiglio Nazionale delle Ricerche (IT) Toshiba Research Europe Limited (UK) University of Oxford (UK)

Umberto Spagnolini and Monica Nicoli, Politecnico di Milano, Italy David Halls, Toshiba Research Europe Limited – Telecommunications Research Laboratory, UK Stefano Savazzi Consiglio Nazoinale delle Ricerche, Italy

University of York (UK)

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THE DURABILITY CHALLENGE The Institute for Building Materials writes about the upcoming durability challenges for new reinforced concrete structures

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oncrete and reinforced/pre-stressed concrete are and will continue to be the main construction material for civil engineering infrastructure. Much more than in the past this construction technology faces challenges that have been discussed at the International RILEM workshop held at ETH Zürich in Switzerland on 17-18 April 2012.1

For new structures built to expand the civil engineering infrastructure in industrialised and emerging countries, the challenge is to achieve long service life, practical, and costeffective solutions with materials having a reduced environmental footprint. To do this, the cement industry made great efforts in substituting clinker (responsible for a large part of the CO2 emissions) with supplementary cementitious materials (SCM). This substitution is reflected in the decreasing amount of Portland cement (CEM I) and the increase of blended cements (CEM II, CEM III) in Germany (Fig. 1). These modern binder systems containing limestone, fly-ash, burnt oil shale, etc. in a complex blend are being included (and thus allowed) by more and more standardisation bodies such as European Cement Standards EN 197-1 and their national companions. The standards include specifications on the proportions in which they are to be combined, as well as the mechanical, physical and chemical requirements for both the products and their constituents. These blends are suitable for achieving strength similar to Portland cement, and can therefore be used to build concrete structures. From the point of view of the end user (engineer, owner of the structure, society), the final cement-based product – concrete, its strength and especially its durability – is more important. Regarding durability, the European concrete standard EN 206-1 defines exposure classes (a kind of standardised environmental condition) and the (national) requirements for concrete such as water/cement (w/c) ratio, minimum cover depth and minimum cement content. Concrete used on a bridge in the Swiss mountains, for example, is exposed to a severe climate and the use of de-icing salts (exposure condition XD3) and must therefore be of a much higher quality (lower w/c ratio, higher cover depth) compared to concrete used inside a building (XC1). This prescriptive approach is based on a long term history of past experiences. Whereas experience is available with concrete structures made with Portland cement (CEM I), new blended cements with SCM – despite their increasing use – have a much shorter track record. In addition, due to the reduced clinker content, the pH of the pore solution will be lower and questions will therefore arise regarding the corrosion protection of the steel,2 the durability of these new

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Trend of the market share of different cement types in Germany showing the continuous decrease of Portland cement (CEM I)4

structures, and the resistance against carbonation and chlorideinduced corrosion. The further raised question is one of whether the traditional prescriptive approach, with exposure classes and deemed-to-satisfy rules, has to be adapted to the new situation. This would allow a much stronger link between durability-related performance characteristics of the new cements and the properties of concrete. On the other side, more and new test methods will be required, especially regarding the chloride induced reinforcement corrosion.3 References 1 U Angst, RD Hooton, J Marchand, CL Page, RJ Flatt, B Elsener, C Gehlen and J Gulikers, Materials and Corrosion, 63 (2012), No. 12 2 L Bertolini, B Elsener, E Redaelli, P Pedeferri, R Polder, Corrosion of Steel in Concrete – Prevention, Diagnosis, Repair, Wiley-VCH, second edition (2013) 3 U Angst, B Elsener, Chloride threshold values for reinforced concrete – a look back and ahead, in ACI Special Publication, Fall 2015 Convention (November 8-12, 2015), Denver, CO 4 HM Ludwig, Trends bei der Entwicklung CO2 reduzierter Zemente, Die Aktuelle Wochenschau der GDCh – Bauen und Chemie 52/2011

Professor Dr Bernhard Elsener Institute for Building Materials ETH Zürich +41 (0)44 633 2791 [email protected] http://www.ifb.ethz.ch/corrosion/

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THE EUROPEAN CONSTRUCTION TECHNOLOGY PLATFORM IS AIDING THE MEETING OF CHALLENGES IN EUROPEAN CONSTRUCTION, AS PEN DETAILS

Constructing the future

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upporting a competitive and sustainable construction sector is a clear priority for Brussels. Within the EU, the construction and use of buildings accounts for around half of all extracted materials and energy consumption, as well as one-third of water consumption. Meanwhile one-third of all waste in the EU is linked to the building sector. Materials used in construction exceed two billion tonnes per year, rendering it the largest consuming industry in Europe. The flagship initiative being pushed by the European Commission is the public private partnership called the European Construction Technology Platform. The ultimate goal of the ECTP is to aid the enhancement of the construction sector in terms of competitiveness and sustainability, yet it is also assisting construction sector efforts to confront the grand challenges faced by European society today. The programme has singled out clear challenges that it must work to overcome. The reduction of costs and the increase of quality are evident priorities with regards the industrialisation of the construction process; a priority for the ECTP. Such efforts naturally aid the creation of safe and healthy living environments. The efficient use of resources – a clear priority given the efforts being undertaken to establish a Circular Economy in Europe –is at the heart of the ECTP, with it embracing action to reduce the use of energy, materials and other resources in construction and the built environment. Promotion of the sector as innovative and research driven is a further priority.

There is an international aspect to the ECTP with the organisers aware that the platform will aid the competitiveness of the European industry in relation to the United States as well as emerging economies. Meanwhile, the programme has the ambition of contributing to the creation of a common market for construction products and services. Guiding the work of the ECTP are six distinct focus areas: underground construction; quality of life materials; networks; cultural heritage; processes and ICT. Such focus areas help to guide and inform the work of the ECTP, bringing together core stakeholders in order to channel their work towards these areas. Additionally, under the ECTP, the reFINE programme – Research for Future Infrastructure Networks in Europe – is working to tackle challenges associated with major infrastructure, targeting a Europe-wide initiative to develop research efforts linked to major infrastructure projects. As urban areas continue to grow across Europe, the pressures on infrastructure continue to mount. Consequently, the construction sector has a key role to play in addressing these challenges. Indeed, reFINE is proposing and considering the role that underground construction can play in solving them, addressing the lack of space in urban areas, and reducing pollution of air and water. The ageing population is a long term demographic challenge that demands the attention of decision makers from across the policy spectrum. There is no doubt that the construction sector must also address their specific needs. Facing this challenge, the ECTP focus area on Active Ageing and the Built Environment (AABE) is advancing work that defines a strategic research agenda. This will help the sector to utilise innovative processes for the design of integrated and ICT driven, agefriendly environments. According to the ECTP,

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the AABE focus area is providing guidelines for innovation in construction that increase the healthy lifespan of individuals by two to five years. Ultimately, it is hoped that the work of the platform will contribute to an improved built environment for all. Given the ageing populace, due consideration towards the needs of the elderly and disabled populations are being promoted. Importantly, the ECTP is developing work on cross-sectoral innovation in construction, promoting connected and smart environments to support active and healthy ageing; bringing together actors from the construction sector, the health and ageing sectors, and ICT to confront the challenge. Furthermore, the AABE focus area is considering the effectiveness of existing European projects and pilots working in the field; evaluating how their insights on this ageing population challenge can be better understood in construction. At a national level, 14 EU member states, as well as non-EU member Turkey, have national platforms in place. These national platforms, or NTPs – led by industry – are helping to address matters around the built environment, innovation and industry transformation for the

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construction sector in a more local fashion. Bringing together all stakeholders, the platforms seek to confront technological, regulatory and financial blocks in the way of improving the performance and sustainability of the industry. For the ECTP, these national initiatives are understood as being of critical impact, and the platform has worked to co-ordinate the links between the national platforms in Europe today. Indeed the national platforms work with the ECTP towards developing a ‘European Vision 2030’. Through this initiative, a strategic research agenda and roadmaps for research and innovation in the construction sector was conceived. With the backing of industrial stakeholders, and to be initiated in 2030, the vision has helped guide the work and effort of the ECTP. National viewpoints are of course a key source of input. While providing input to the European level, there is also the scope for direct exchange amongst national platforms. This, the ECTP says, provides an opportunity for learning between the national organisations when it comes to best practice, research agendas and national goals. Construction-related research priorities within the national programmes take into account ECTP priorities. The NTPs map national regulations and policies relating to construction, and identify barriers to innovation in the sector that can be addressed at a European level. Furthermore, they work to disseminate knowledge on innovation processes by exchanging national experiences of best practice. More widely, the ECTP works to bring in the involvement of national stakeholders within EurekaBuild, which serves as the umbrella on

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construction within the EUREKA initiative. As an intergovernmental organisation supporting market-driven industrial R&D, bringing together over 40 countries, and promoting involvement within EUREKA, the ECTP is helping to link the construction sector with wider research and development practices in the European region. By adopting a more flexible approach, the ECTP can expand beyond the confines of the EU, ensuring a wider reach of its activities. Simultaneously, the national platforms assist in promoting the work of the ECTP in each national jurisdiction, promoting engagement with the European initiative, and sharing information. Such national platforms also help identify new areas of interest and potential that the ECTP can engage with. While the ECTP continues to develop by taking part in an Horizon 2020 InfoDay on Research PPPs in Brussels on 16 October, the European Commission continues its wider push to enhance the sector. It is clear that job creation and economic growth is at the heart of the Commission’s long term priorities. As a direct example of its work in this area, the Commission has moved to attract young talent into the construction sector by developing a ‘Build Europe with us!’ video programme to promote its attractiveness. Generally, the boosting of energy efficiency in the EU is a strategic priority for Brussels. Brussels has in place the headline goal that buildings will be built or renovated to exceptionally high energy efficiency standards by 2050. In effect, this ambition would see the built environment in Europe approaching an almost energy neutral standard. Indeed, the Commission continues to argue that there is a strong economic, social and competitive rationale for the upscaling of energy efficiency investments in buildings and industry in the EU. Further, the

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investment in energy efficiency is of strategic importance for the EU since it is a “cost effective manner to reduce the EU’s reliance, and expenditure, on energy imports over €400bn a year”, according to the Commission. Analysis this year by the Commission recommends measures such as the creation of energy and cost databases for buildings, and the development of a project rating system to provide a transparent assessment of the technical and financial risks of energy renovation projects for buildings. It has also warned that barriers around the expansion of the green mortgage market should be addressed, and that there should be a review ensuring that current state aid rules do not ‘unnecessarily burden accelerated energy efficiency investments’. There is also, of course, a cultural and historical aspect to the built environment and the ECTP is aiming to ensure the preservation of architectural heritage. With the challenges in place, it is clear that the tools coming forward under the ECTP will continue to help in ensuring the construction sector can achieve sustainable growth in the 21st Century, contributing to long lasting European prosperity.

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AS ATTENTION TOWARDS MEASURING WELLBEING CONTINUES TO MOUNT, EUROSTAT, THE EU STATISTICS OFFICE, HAS BEEN CONDUCTING KEY WORK IN THE ARENA

An alternative measurement

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oday it is widely acknowledged that measures like Gross Domestic Product alone do not show how well (or badly) people and our environment are doing. Hence, when used to evaluate social progress, GDP needs to be complemented by other indicators that measure what matters most for people. At European level this view was summarised in two highly influential documents that were published in 2009: the “GDP and beyond – Measuring progress in a changing world” communication of the European Commission; and the Report of the Commission on the Measurement of Economic Performance and Social Progress co-ordinated by J Stiglitz, A Sen and JP Fitoussi. They made recommendations on how to better measure economic performance, societal wellbeing and sustainability. The European community of official statisticians (called the European Statistical System and comprised of Eurostat and the national statistical institutes) responded to these new policy needs by making proposals on how best to approach these recommendations from a measurement/statistical point of view. A total of 50 specific actions were put forward in a report adopted in 2011, and they were grouped in three main areas: the multidimensional measurement of quality of life; highlighting the household perspective and distributional aspects of income within national accounts aggregates; and environmental sustainability. Regarding the first area, two main fields of action were

decided: building a framework of indicators (mainly based on existing data) for measuring quality of life and collecting new data (especially on subjective wellbeing).

Georgiana Ivan

Measures of wellbeing take a much more rounded approach in assessing how society and the economy are doing

Particularly for the indicators framework, Eurostat worked closely with an expert group comprising representatives of national statistical institutes (many of them coming from countries that had similar initiatives at national level), international organisations and academia. Quality of life is a broader concept than economic production and living standards. It includes the full range of factors that influences what people value in life. In several EU member states people were asked directly what defines a good life and a good society, in order to better know what really matters to them. Their answers were reflected in national wellbeing initiatives, and later on in the European framework through consultations with national experts and the community of users. The set of indicators was developed and organised along 8+1 dimensions which constitute the quality of life framework. Eight of these dimensions concern the capabilities that people should have in order to pursue their selfdefined wellbeing. They include indicators on how people are doing objectively (for example, how long people live) and how they perceive the respective aspect of their life (for example, how they assess their health). The remaining dimension, named ‘overall experience of life’ refers to the personal perception of life in general, and includes overall life satisfaction, the frequency of experiencing positive and negative emotions and whether or not they consider their own life as worthwhile. The new data collected covered mainly the subjective appreciation of life in general, but also of its different aspects (e.g. financial situation, jobs, accommodation, time use and

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social relations) which is usually called ‘wellbeing’. It is meant to complement the objective data on income and living conditions which were already measured quite extensively. It was collected for the first (and so far, only) time in 2013 as an ad hoc module (more detailed data on a specific topic which is not addressed very often) of the European Survey on Income and Living Conditions (EU-SILC). It is an important milestone for official statistics, as data on subjective wellbeing were collected for the first time across all EU member states with the required quality standards. More than 350,000 individuals older than 15 were interviewed in the EU28 member states, plus Switzerland, Iceland, Norway and Serbia (ranging approximately from 2,950 in Iceland and 5,200 in Denmark to 25,500 in Spain).

Life satisfaction in the EU is monitored by Eurostat

Quality of life On 1 June 2015 Eurostat published a statistical book called Quality of life, Facts and Views. The main focus of this publication was on analysing the indicators coming from the

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Subjective Wellbeing module, together with objective living conditions information on the same topic. As Walter Radermacher, director general of Eurostat, stated in the foreword of the publication: “The objective is to shed light on what could impact upon the quality of life, ranging from the educational level, the activity and health status to the family and financial situation.”

A few main findings from this publication are detailed below Europeans are fairly satisfied with their life on the whole. Life satisfaction represents how a respondent evaluates or appraises his or her life taken as a whole. It has a prominent role as it can be regarded as a key indicator of subjective wellbeing. On a scale from 0 (not satisfied at all) to 10 (fully satisfied), nearly 80% of residents aged 16 and over in the European Union rated their overall life satisfaction in 2013 at 6 and higher, with an average (mean) satisfaction of 7.1. In detail, out of every 10 people living in the EU in 2013, 2 rated their satisfaction as 9 or 10 (which is considered high), 6 were moderately satisfied (6-8), while the remaining 2 reported a low life satisfaction (05). The average varied significantly between EU member states. With an overall average of 8, inhabitants in Denmark, Finland and Sweden were the most satisfied, followed by those in the Netherlands and Austria (7.8). At the opposite end of the scale, residents in Bulgaria (4.8) were by far

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Finding satisfaction Europeans are most satisfied with their personal relations and least satisfied with their financial situation and time use. Regarding the different aspects of wellbeing, with an overall average score of 7.8 on a scale from 0 to 10, people in the EU were globally most satisfied with their personal relationships. In contrast, the areas of lowest satisfaction for people living in the EU were their financial situation (an average of 6 among the EU population aged 16 and over) and their time use.

the least satisfied, followed by those in Greece, Cyprus, Hungary and Portugal (all 6.2). People with a low level of education are also more likely to experience low wellbeing; and there are important differences between groups. In the publication the relationship between different wellbeing domains and gender, age, educational level and other relevant categories is assessed systematically, at EU28 level. While women and men are almost equally satisfied, the impact of educational attainment for example is quite important. The most educated almost systematically have a higher assessment of the quality of their life. This is the case partly because education is related to income levels, but the impact of studies is wider than that. The effect of education is strongest regarding satisfaction with the financial situation of the household and lowest regarding satisfaction with time use. Tertiary graduates also had more rewarding social relationships, felt more secure, assessed their health more positively and experienced positive emotions more frequently. This highlights the fact that in many cases there is probably an accumulation of deprivations (or on the contrary, of good situations).

Taking account of the bigger picture The main determinants of life satisfaction are health, income, (good) jobs and social relations. Life satisfaction is a multidimensional concept, and is very much shaped by various factors which lead to different living situations as well as to different expectations and preferences. The health condition appears to be the main determining factor in life satisfaction, ahead of the position on the income scale, situation on the labour market or social relations. The highest average rating of life satisfaction in the EU was to be found among the population reporting a very good health condition (7.9/10, compared to 7.1 for the EU as a whole). The other factors that contribute the most to our wellbeing are the financial situation (an average of 7.5 among the third of the population earning the most at national level), being in full time employment (average of 7.4) and social relations (the average being 7.2 among the population having someone to rely on in case of need as well as among people living in households with dependent children).

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Alternative measures to GDP are providing a more rounded picture of how well people and society are doing

Subjective wellbeing data is important from a social sustainability perspective as low wellbeing is to some extent associated with low trust in institutions (and in particular the political system), which can undermine the democratic foundations of our societies. Trust in institutions, and especially in the political system, was at a very low level in 2013, the mean on a scale from 0 to 10 not exceeding 6 (in Finland, followed by Denmark at 5.9). On the contrary, the lowest means were found in Portugal (1.7), followed by Slovenia, Spain and Greece where it was also lower than 2. Many other interesting insights await the readers of Eurostat’s new Quality of life, Facts and Views publication, and we hope they find it both an enjoyable and a useful read. The book is complemented by an interactive and playful infographic called ‘Quality of life’ that can be found on the Eurostat website. Learning more about various aspects of life in the EU countries can be very fun and easy this way. Given the interest and relevance of quality of life data, Eurostat plans to collect and publish it on a regular basis in the future. So keep an eye on our website if you want to know more about future developments in this field. Georgiana Ivan Eurostat www.ec.europa.eu/eurostat http://ec.europa.eu/eurostat/statisticsexplained/index.php/ Quality_of_life_in_Europe__facts_and_views

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TRUE PERSONALISATION The Montréal Heart Institute works towards putting the ‘person’ back into personalised medicine

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dvances in public health and medicine have contributed to greater longevity, but this has been achieved too often at the price of protracted illness and impoverished quality of life (QoL). Young individuals are increasingly developing conditions (hypertension, diabetes etc.) once thought to be reserved for the ‘elderly’. This coming generation may actually die at a younger age than their parents or grandparents. The burden placed on the healthcare systems to manage these chronic conditions is unparalleled. Current approaches are insufficient to adequately address these multiple and increasingly complex health problems and QoL issues. Revolutionary changes are needed in how we think about and address health and healthcare. There is excitement about ‘personalised medicine’ as the answer to some of these difficulties. However, this work often has a singular focus on a person’s genes to identify the correct and timely medical interventions to optimise treatment success. Such work is indeed very important, but a person, and a person’s health, is far more than the sum of their genes and the correct medical treatment. Environmental, behavioural, and psychological factors as well as the interplay of these with the person’s biology (including their genes) contribute significantly to the behaviours they adopt, whether they remain healthy or not, follow treatment recommendations, and/or how they respond to the illness and its treatment. Health professionals and the general population are still either unaware or sceptical of the importance of psychological factors such as stress and personality traits to health. At policy and clinical levels, these factors receive limited consideration. Yet, up to one-quarter of the population suffers from a diagnosable mental health condition, and even greater numbers suffer from subclinical levels of distress, particularly among those suffering from health problems. The Heart and Mind: research unit in behavioural and complementary medicine, based at the Montréal Heart Institute, and led by Dr Bianca D’Antono, seeks to elucidate some of the psychosocial and psychophysiological determinants and consequences of health and disease, and to apply this knowledge in improving wellbeing. The breadth of research undertaken by this group reflects these multiple goals.

Understanding the psychophysiological pathways to disease Examples from the GAHR I and II studies:

In a prospective study of initially healthy adults aged 19-64 years, Dr D’Antono and her colleagues were interested in examining the associations of psychological factors such as hostile personality, with novel intermediary biological risk factors for coronary artery

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disease (CAD), namely metabolic syndrome and systemic inflammation. Greater hostility (defined by cynical, mistrustful attitudes towards others, anger, and/or aggressive behaviour) in these healthy participants were associated with more disturbances across a cluster of metabolic parameters (abdominal obesity, Dr Bianca D’Antono blood pressure, glucose and lipids). These associations were maintained over the three-year follow-up but were particularly accentuated among older participants. Hostility has been proposed to increase risk for disease via exaggerated and/or prolonged physiological responses to stress. The study did indeed show that responses to a standardised (psychological) stress protocol predicted increased metabolic burden over the three year period, though sex differences were observed. Men, particularly hostile men, who exhibited greater and more prolonged responses of the autonomic nervous system (ANS) to stress, showed an increase in metabolic disturbances over the follow-up. In women, lack of response of the ANS predicted a worse outcome. In a separate study, the group had shown that a blunted ANS response in cardiac surgery patients also predicted more complications during and after surgery. Blunted autonomic response to stress may reflect the impact of chronic stress which may reduce the ability of the person to further adapt to life circumstances. Hostility also predicted elevations in three markers of systemic inflammation. Interestingly, while basal inflammatory activity was particularly elevated in more hostile women and younger individuals, hostile men and older individuals showed the greatest increase in inflammatory activity over the three-year period, and in response to stress. Thus, in healthy individuals, greater hostility was associated with a more atherogenic profile that was independent of lifestyle factors already known to increase risk for CAD. Men and women showed somewhat different profiles that differed and changed over age and time, emphasising the need to consider the unique biological and gender-related realities of individuals across the lifespan.

BEL-AGE An ongoing prospective study in individuals whose health is more compromised is similarly looking at the mechanisms through which childhood trauma, psychological factors, and psychophysiological responses to stress contribute to premature ageing and CAD morbidity/mortality. Metabolic, inflammatory, and autonomic measures in these participants with and without CAD are once again examined to determine whether findings from GAHR and other studies replicate. The association of psychosocial

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Intervening in patients with physical illness In the context of policies of austerity that have gripped Canada and abroad, it becomes imperative to develop creative ways of reaching at-risk individuals.

variables with telomere length and cognitive functioning, other understudied and emerging biological processes of potential import to CAD and ageing more generally, are also investigated. Telomeres cap the end of our chromosomes and are crucial to their integrity. As cells divide, telomeres shorten until they can no longer serve that protective function. This can lead to cell death or the inability of the cell to divide, rendering organisms more vulnerable to disease and accelerating the ageing process. Data from this and other laboratories suggest that psychological factors are associated with shorter telomeres. At the study’s end, with its more than 1,500 participants, BEL-AGE will provide a unique opportunity to examine whether these psychological variables contribute to CAD development, progression, and mortality in part, through more rapid shortening of telomeres, and whether these effects are independent of, moderated by, or mediated by other behavioural (lifestyle), social, environmental or biological processes. Studies such as these have the potential to inform preventive efforts aimed at curbing the toxic effects of psychological burden on premature ageing, efforts that may need to be tailored to reflect individual differences.

Psychological consequences of physical illness Physical illnesses can wreak havoc on a person’s life. The group showed, for example, in a study led by Dr Gilles Dupuis, that a considerable proportion of individuals who experienced a myocardial infarction developed symptoms of post-traumatic syndrome. Patients repeatedly re-experienced the event in their mind over periods of months or years, remaining hyper-vigilant, stressed, and fearful for their health and life. This increased their risk of further events over follow-up. In patients suffering from recurrent syncope (fainting), Dr D’Antono reported considerable psychological distress and psychiatric morbidity that contributed to impoverished quality of life, loss of functioning, and recurrence of syncope. Key issues contributing to a poorer outcome included patients’ beliefs about the nature and consequences of the syncope, their (lack of) confidence about being able to cope with this health problem, as well as their tendency to avoid situations that reminded them of their fainting episodes. These are issues never or rarely addressed by medical professionals. Yet, in a small pilot cognitive-behavioural intervention study that targeted these factors in patients with recurrent syncope, they were able to show dramatic improvements in psychological health, functioning, and syncope recurrence.

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Two pilot studies are currently underway in the Heart and Mind laboratory to evaluate whether two increasingly popular stress management approaches available in the community, yoga and mindfulness meditation, are effective in improving psychological and physical health in individuals suffering from congestive heart failure (yoga) or metabolic syndrome (mindfulness). The latter will specifically examine whether men’s and women’s autonomic responses to psychological stress, whether blunted or hyperreactive, normalise in response to the intervention, and whether these changes are associated with improved metabolic and telomere profiles. Individuals who are diagnosed with life-altering conditions that require extensive changes in lifestyle, at a time when they may be experiencing significant emotional, family, and financial upheaval, frequently have difficulty adhering to treatment recommendations. Most patients do not get the support necessary to navigate all of these difficulties. An ongoing randomised interdisciplinary pan-Canadian investigation, CePPORT, spearheaded by Dr Robert Nolan and in which Dr D’Antono is a co-investigator, has the potential to respond to some of these needs while reducing the gap in terms of reach (to individuals that may not have access to interdisciplinary heart failure clinics). CePPORT is using the web to reach patients with congestive heart failure in the hope of increasing their motivation, confidence, and ability to manage their care, through tailored e-health interventions directed at stress management and key health behaviours.

Challenges There have been dramatic cuts in research funding across the globe, with success rates plummeting. Some politicians have even questioned the usefulness of psychosocial research in health. Yet this research has consistently been of extremely high quality and, more importantly, has shown that addressing the psychosocial concerns of the population can save both costs and lives in the short to long term. Unfortunately, few of these interventions make their way into medical practice. Part of this relates to researchers’ difficulties in rendering their findings accessible to the general population (including politicians and other decision makers).

Dr Bianca D’Antono, PhD Director of “Heart and Mind: research unit in behavioural and complementary medicine” Research Centre Montréal Heart Institute +1 (0)514 376 3330 [email protected] https://www.icm-mhi.org/en/research/labs /clinical-laboratories/heart-and-mind

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DONATELLA FAZIO OUTLINES THE WEB2.0 COMMUNITIES’ ENGAGEMENT AND THE EXPLOITATION OF NEW TECHNOLOGIES FOR STATISTICS FOR SOCIAL INNOVATION

The Web-COSI experience T he theme of the involvement of web communities and the exploitation of new technologies for ‘better statistics’ is dominating the research scene, both in Europe and the wider world. The process capitalises on the two epochal revolutions that are characterising the present phase: the ICT explosion and the ‘beyond GDP’ movement. On one side, Web2.0 applications are profoundly transforming the way information is created and shared and the way in which knowledge is built up within society at large. The process is having an increasing and inexorable impact on statistics: from new ways of collecting data to new ways to disseminate, visualise and recover them.

Donatella Fazio

The powers generated by the ‘new technologies’ and by the ‘beyond GDP movement’ push for a new conscious knowledge towards a social innovation, putting the needs of society as a whole at the centre of the progress, rather than the needs of private individuals.

Communities’ involvement can be achieved both indirectly – by using the ‘liquid data’ available on the web (Big Data, Open Data – supplied by stakeholders and citizens for a variety of reasons) – and directly – through the set-up of collaborative platforms voluntarily nursed by stakeholders and citizens (crowdsourced data). This process serves to enlarge the traditional vision on how to construct and deal with statistics and data, thus opening the dialogue between ‘experts’ and new ‘non-expert’ elements of society. Furthermore, this definitively provides a measure of how the roles of producers and users of information and data can radically change, and how the relationship is moving to bridge the ‘top-down’ and ‘bottom-up’ approaches. On the other side, the ‘beyond GDP’ debate for the definition of new measurements of societal progress in terms of wellbeing and sustainability has grown enormously, creating a critical mass without boundaries at the local, national and international levels. Alongside the

traditional stakeholders, citizens and communities are involved in the discussion; they are willing to lend their voices to the need to go beyond GDP, to narrow the gap between what ‘cold’ economic data says and what people perceive in terms of quality of life related to societal progress and sustainability. The beyond GDP debate (supported by Web2.0) has thus become a global movement, pushing for transforming society.

Web-COSI experience

Web2.0 applications are profoundly transforming the way information is created and shared, and the way in which knowledge is built up within society at large

Against this framework, and amongst the multiple recent actions supported by the EU, stands the experiences drawn from the FP7 Web-COSI project – Web Communities for Statistics for Social Innovation. The project, funded by DG CONNECT, was designed to explore the potential of Web2.0 communities for statistics beyond GDP – and is willing to contribute in an era of data revolution in which “new technologies are leading to an exponential increase in the volume and types of data available, creating unprecedented possibilities for informing and transforming society.”1 The project is based on a four-partner consortium, led by Istat – the Italian National Statistical Institute – in partnership with the Organisation for Economic Co-operation and Development (OECD – www.oecd.org) and alongside Lunaria – the Italian Association for Social Promotion (www.lunaria.org), and i-genius – a social entrepreneur business and enterprise community in the UK (www.i-genius.org). The significant challenge involved in opening up statistics exploiting the internet and interacting with communities means that the consortium interacts with multiple protagonists – traditional stakeholders (national statistical

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institutes (NSIs), academia, international organisations, government agencies) and new stakeholders (civil society organisations, social entrepreneurs, young people, citizens, and communities at large) – to find new solutions to create a better informed society based on a shared knowledge.

Work plan Against this backdrop, the Web-COSI project has conceived a work plan aimed at reaching two main objectives: to foster the understanding and usage of new statistics; and to push for a better integration and complementarity of official and non-official statistics, exploiting the new sources of data available in the net. To reach these goals, the activities carried out in its two-year lifecycle (2014-2015) can be gathered into four groups: n The mapping of the existing digital initiatives for communities’ involvement with statistics beyond GDP and for the exploitation of new technologies to collect ‘better’ data, carried out at local, national and global level; n

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The fostering of the debate and the creation of a critical mass through digital initiatives – blogs, online discussions, webinars, newsletters, target citizens campaigns, data visualisation competitions etc. – and the organisation of face-to-face events (five workshops and four focus groups, and participation in international and national events, networking with other EU and global projects); The fostering of the engagement of young people through the set-up of target initiatives – a European Wikiprogress University Programme and a Youth portal; and The facilitation of communities’ access to statistics, thereby empowering the collection of locally-generated information and data with the development of a Wiki data portal of progress statistics.

The debate generated by Web-COSI is impressive and the conclusions are notable in that they demonstrate a strong potential for a socioeconomic impact and wider societal implications. An exhaustive documentation on the activities carried out and on their results is available on the Web-COSI website (www.webcosi.eu). The engagement of citizens and stakeholders reached by Web-COSI is also extraordinary.

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Web-COSI believes that encouraging communities to share, collaborate, and make use of data and information at both the local and global levels is a winning exercise

There were some 16,000 proactive participants and followers of the activities, and more than 1.5 million people became better informed via social media.

Main results The mapping exercise was conceived as an interactive inventory, and has so far listed 148 notable digital initiatives (focused on beyond GDP data) carried out by more than 111 organisations, including civil society, NSIs, governments and international organisations, interacting with citizens to share information and data, combining top-down and bottomup approaches. The initiatives aim, in various ways and at the global, national, and local levels, to: 1) include people in the development of wellbeing frameworks through online consultation tools and social media; 2) facilitate access to the findings and analysis of data through interactive data visualisation tools; 3) engage people as data interpreters through open data initiatives; and 4) engage people as data producers themselves through technology that allows for crowdsourcing. The dialogue set-up by the project has permitted us to conceptualise the role of the different actors (both old and new) involved so as to search for new and efficient ways of making use of online data interacting with society at large, underlining the points of strength and the open issues of their engagement.

National Statistical Institutes NSIs, the historical producers of official statistics, are now called upon to open the door to a new way of operating so as to be able to take advantage of the liquid data available on the internet generated by a diversity of providers (public and private) as well as that locally generated by crowd sourced platforms. In this direction, NSIs are setting up Web2.0 initiatives to foster an interaction with citizens and to empower statistics via the usage of the internet as a new source of data. They are also moving from fostering the communication and dissemination of statistical information to the exploitation of new ways of collecting data from the internet, evaluating the potential of crowdsourced platforms for a knowledge closer to citizens’ needs. In this sense, the trade-off between

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having more and real-time information and the quality of the statistical information produced is an open issue.

data by governments means more than just putting it on a website; for data to be truly open, it must not only be freely available online, it should also be presented in a format that maximises its potential for re-use. Methodologies to re-use data and the linkage of open data from different sources are ongoing issues that need further attention.

Civil society Civil society (CS) plays a major role in providing data on wellbeing: it complements official statistics whilst covering relevant dimensions and aspects that determine, or have a direct impact on, the quality of life of citizens with adequate, updated, and fit-for-purpose information. Civil society actors involved in the production of statistical information on wellbeing show a broad number of objectives: increasing and ‘democratising’ scientific knowledge; stimulating advocacy for better public policies; pressuring public institutions; engaging citizens; disseminating to the public at large the ‘fundamentals’ (e.g. statistical data, indicators, indexes and so on) to read and understand changes and challenges occurring in our complex societies. The role of CS is crucial at the local level. In this direction, the development of local portals, conceived as data warehouses and tools to enhance the dialogue among all sectors of the locality, must be implemented.

Business The business world is an actor which deals with new sources of data from different perspectives. On the one hand, private ICT companies (Google, Facebook, etc.) can be data providers. On the other, businesses need to know their consumers and their needs in order to understand what to produce and how to produce it. In the first of these perspectives, the setting up of public private partnerships (PPP) is a matter which needs to be investigated. In the second, a close interaction with communities and a careful reading of new measurements of societal progress is an opportunity that should be grasped.

Social entrepreneurs Social entrepreneurship is an emerging and important force for a new economy based on societal progress from a wellbeing perspective. Social entrepreneurs are young users of data but often lack the necessary resources to be able to analyse them at a consistent high level. Greater emphasis should thus be applied to enabling social entrepreneurs to partner with analysts and, indeed, an increased awareness on how to access existing sources of data facilitated by Web2.0 technologies. In this direction, it is important to build up a common language in order to deal with data and information close to the needs of social entrepreneurship.

Academia The academic and research worlds are involved in the exploitation of new technologies, in partnership mainly with NSIs, to study how to use the liquid data available on the internet by testing new techniques (e.g. text mining, text grasping, open data linkage, geo-referenced data) alongside the use of crowdsourced (locally generated) data. Moreover, academia is beginning to complement traditional statistical and economic courses with ones on new ways of dealing with data and information.

International organisations and government International organisations such as the OECD and UNECE push for the usage of integrated (official and non-official) datasets in a wide perspective. The main effort here is to harmonise the processes and the data in order to permit a comparison among the national realities and a ranking system in terms of societal progress. The indicators so constructed demonstrate the matter of inequality among the different areas of the world.

Young People

Governments are working to open the data related to their actions and results in favour of public transparency and participation. The availability of free, accessible, comprehensible, and updated data and information allows citizens to consciously participate in democratic life. Opening up Social entrepreneurship is an emerging and important force for a new economy based on societal progress from a wellbeing perspective

In addition to this, young people also have a fundamental role to play. New generations are particularly eager to be involved in the data and information available, and for which purposes they are willing to contribute to the call for the push for societal progress that ties in to their own expectations for the future. Young people are also the ones who will contribute to the construction of new and better statistics thanks to their proactive efforts in using new skills and technologies. The set-up of new curricula and training courses to learn new skills is therefore another matter that will need to be addressed in the near future.

The communication of data Web-COSI has highlighted the powerful role that the communication of data has to play. Web2.0 technology such as mobile and interactive web platforms allow statistical

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information to be packaged and presented in a way that is much more meaningful for a wider public. Data visualisations can be very appealing, but their importance goes beyond aesthetics: they provide a unique means of highlighting new patterns in statistics and looking at the world in a different way. The visualisation of data usage is thus vitally important in enhancing its understanding and engagement. Storytelling and narrative is similarly needed to foster the understanding and usage of data. This offers a way to help people understand data and to feel that data can provide them with a picture of the reality close to their individual status and, moreover, that it can contribute to change behaviours and actions for both individual and collective growth. In this direction, there is also the necessity to combine quantitative indicators with qualitative ones, and to use comparable data (for instance, by explaining that a certain phenomenon is equal to four tennis courts in size, etc.). Social inclusion through a common knowledge is facilitated by digital technology. In this sense, more effort needs to be made to combat digital exclusion and to build up capacity in marginalised groups (e.g. developing countries, the elderly, the poor, and the low-skilled). A final crucial open issue is the policy use of new statistics, which presents certain difficulties of its own, and the citizen engagement empowered by Web2.0 is essential here. If citizens are educated about the role of statistics in society and policy making and, moreover, of the need to put issues of wellbeing, sustainability, and inequality front and centre, then there will be much greater political incentive for decision makers to enact reform and, indeed, to override entrenched interests opposing those reforms.

Next steps The Web-COSI project has demonstrated that the involvement of web communities for statistics and the exploitation of new technologies to empower the construction, the understanding, and the usage of new statistics (towards an integration of official with non-official statistics) is a significant challenge, but is also an inexorable process which requires new skills, culture, and a radical change of mindset.

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The role played by civil society actors is a valuable lever for the integration of official statistical information on wellbeing produced by public institutions at the local, national or supranational level

© takeyourhealthbackconference

Web-COSI believes that encouraging communities to share, collaborate, and make use of data and information at both the local and global levels is a winning exercise. The creation of a critical mass on the importance of the usage of knowledge (data and information) is the way to build up a society ‘aware and conscious’ of its possibilities (and limits), able to drive individual and collective behaviour alongside policy actions for sustainable societal growth. Web-COSI has experimented with the crucial importance of the partnerships among different sectors of society and can thus argue that only joint efforts by traditional stakeholders and new ones – putting together expert and non-expert forces – can steer the exploitation of all the sources of data and information to create a shared awareness. On 14 October 2015, Web-COSI attended the fifth OECD World Forum on ‘Statistics, Knowledge and Policy: Transforming Policy, Changing Lives’ in Mexico. The forum talk on ‘Opening up wellbeing statistics to new audiences: opportunities and challenges’ was organised to present the Web-COSI experience as an outstanding exercise, supported by the European Commission, in opening-up statistics to new audiences. While the project’s lifecycle formally concluded on 3 December – its final conference at the OECD premises in Paris, France – our work does not end here. The nature of the Web-COSI project means that it is just a starting point, and its main outputs will be implemented in the future to keep the debate alive amongst citizens and stakeholders, and so continue to work jointly towards a real social innovation. The Web-COSI project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 610422. 1 ‘A world that counts,’ by the Independent Expert Advisory Group on a Data Revolution for Sustainable Development (IEAG), chaired by Enrico Giovannini, November 2014 www.undatarevolution.org.

Donatella Fazio Italian National Statistical Institute (Istat) Senior Statistician Head of Unit “R&D project” Web-COSI project co-ordinator [email protected] www.webcosi.eu

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DR TATIANA CHEKALINA AND THE ETOUR RESEARCH TEAM EXPLAIN THE MODELLING BEHIND CUSTOMER-BASED DESTINATION BRAND EQUITY

The tourist/destination relationship

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ourism destinations all over the world, including countries, regions, cities, and even small self-contained locations and resorts, increasingly embrace marketing and branding practices traditionally utilised by businesses. By acting similar to businesses, tourism destinations invest substantial amounts into the design of logos, the development of slogans, the publication of brochures, the creation of sophisticated destination web portals, the organisation of events, and the implementation of a variety of other marketing and branding efforts. As such, tourism destinations need to evaluate their marketing and branding strategies and understand the link between their marketing efforts, and the ability to attract new visitors in order to facilitate repeated visitation and encourage tourists to pay a premium price and spread a positive word-of-mouth message.

Brand equity model The development of a customer-based brand equity model for tourism destinations is an important area of study for Dr Tatiana Chekalina and the ETOUR research team. Customer-based brand equity as the measure of the power of the brand is an important element of marketing and branding practice. Thus, the developed customer-based brand equity model frames the knowledge of the relationships between the tourists and tourism destination brands. The model derives from the field of cognitive psychology and aims to understand the multidimensional brand-related memory structures which exist in tourists’ minds and particularly include destination brand awareness, a variety of destination brand associations related to destination image and quality of destination experience, experienced value and destination loyalty.

However, modelling customer-based brand equity for tourism destinations is a challenging task. First, destinations are very different from businesses since they are geographical places, and these constitute a complex constellation of destination resources, including natural amenities, cultural and historical heritage, tourism infrastructure (e.g. hotels and restaurants), various activities, place atmosphere, service personnel and local inhabitants. Second, destinations cannot be separated from tourists and their physical, emotional, and intellectual involvement into the process of tourism service provision. Most importantly, while destinations can supply a wide range of resources, only a few are actually relevant and utilised by a single individual. Similarly, destination experiences can vary greatly among tourists visiting the same destination. For example, one tourist can find relaxation and tranquility, and another will experience thrill and excitement.

A brand communication message One destination can thus simultaneously attract various tourism segments which have access to a common pool of destination resources. However, the configuration of utilised resources and obtained experiences differs among tourism segments. Consequently, the challenge for destination marketing is to develop a brand communication message, which offers relevant resources, promises desired experiences and reaches the tourist segments that a destination wants to attract. Therefore, the customer-based brand equity model is also a managerial tool, which not only measures the strength of a destination brand and evaluates the success of destination marketing, but also helps destination managers to identify the areas for upgrading their marketing strategies, promotional campaigns and destination product development.

Advancing theories The theoretical outcome of the doctoral thesis monograph presented by Chekalina is new knowledge about how to integrate the tourist into the evaluation of tourism destination brands. The thesis extends existing literature on modelling the tourism destination brand equity, which primarily utilises theoretical and measurement approaches developed for consumer goods, and learns from recent developments in contemporary service-oriented marketing.

© M Lexhagen and T Chekalina

While destinations can supply a wide range of resources, only a few are actually relevant and utilised by a single individual

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The focus of the research by the ETOUR team is on understanding tourism consumption as the core element for evaluation of destination brands, and value co-creation is an underlying logic for the research. The destination vacation is, therefore, exemplified as the process of integration and transformation of both destination resources and tourists’ resources (such as money, time, efforts, emotional and mental involvement). The outcome of this resource integration and transformation constitutes a

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value-in-use, which describes the purpose and the benefit of the vacation at a particular destination. The value-in-use of a tourism destination has many aspects, such as emotional benefits, value of novelty and new knowledge, value of being with family and friends, as well as the symbolic value of visiting a particular destination. A chain of effects is illustrated by the model. First, destination brand awareness is a factor behind tourists’ evaluation of destination resources offered for tourism consumption. In turn, destination resources transform into benefits for the tourists (value-in-use). Similarly, tourists evaluate whether their vacation at the destination was worth the sacrifices they made (e.g. value for money). Finally, evaluation of benefits and sacrifices determines the willingness of tourists to return to the destination and recommend the destination to relatives and friends (destination brand loyalty).

Testing the model Another important research goal is to develop and test the measurement instrument which would serve the purposes of model validation and have substantial managerial relevance for tourism destinations. In her thesis, Chekalina used the example of the Åre (Sweden) mountain destination to test the model for different tourist segments. For instance, in the winter season skiing, service quality, family-friendliness of the destination, tidiness and safety, and interaction with other tourists serve as the main resource inputs which generate emotional value from the tourism destination stay. In the summer season, the configuration of destination resources among different segments is of particular strategic interest for a traditional winter destination. For instance, for the hiking segment Nature is related to hiking as the core segment activity, and Åre village provides the setting for complementary activities. On the contrary, mountain bikers view Nature and the village as one single factor and the setting of their main activity.

© M Lexhagen and T Chekalina

For hiking tourists the value of escape is closely interrelated with relaxation, while for mountain bikers it is combined with the sense of freedom and happiness

The brand relationship studies at ETOUR have been developed in close collaboration with two consecutive projects implemented by the European Tourism Research Institute at Mid Sweden University (ETOUR) and key tourism stakeholders in Åre. First, the EU-financed project ‘Customer-based innovation in tourism’ (2008-2011) focused on developing the frameworks for using the realworld customer-based data for the purpose of marketing and tourism product development. Second, the project ‘Engineering the Knowledge Destination through Customer-based Competence development’ (20112014) financed by the KK-stiftelsen, applied a business intelligence approach to prototypically develop a destination management information system (DMIS-Åre) as a tool to enhance knowledge creation and organisational learning at the tourism destination. The customer perception and experience indicators developed for testing the customerbased brand equity model were fully integrated into the DMIS-Åre system.

The structure of value-in-use is different across the segments. For instance, both hiking and mountain biking tourists seek escape from their daily routine. However, for hiking tourists the value of escape is closely interrelated with relaxation, while for mountain bikers it is combined with the sense of freedom and happiness, while the value of fun and action is another important benefit, which defines the value of the vacation.

Future research

Managerial implications

The other aspect, which has a great potential managerial value, is to introduce the dimension of time and integrate the customer-based brand equity model with customer relationship management systems. As such, obtained customer knowledge can be utilised, for instance, for building a real-time destination recommendation system and optimising the destination experience for tourists.

From a pragmatic perspective, the model can help destinations to set up the structure for tourists’ feedback data and use this data to better understand the unique destination experience for various tourist segments. Furthermore, it can also help them to upgrade their marketing and branding strategies, to identify the drivers behind loyalty towards the destination, and to improve the experience intensive destination offerings showing the core destination recourses leading to the desired destination experiences for tourists. Therefore, findings are targeted towards destination management organisations, tourism industry enterprises, and destinations in general, which aim at increasing the effectiveness of their marketing strategy, optimising the unique value proposition of the destination, and attracting the right segments to the destination.

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The study findings offer various directions for continuing the research. First, the goal is to implement the customer-based brand equity evaluation for destinations with different profiles (e.g. city tourism or culinary tourism), as well as to adjust the model to destinations on different geographical levels such as Sweden as a tourism destination brand.

Dr Tatiana Chekalina ETOUR Research Team http://www.miun.se/en/research/centers-and-institutes/etour

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ESA’S DR MATT TAYLOR MET WITH PEN TO DISCUSS SOME OF THE SCIENCE TO HAVE COME FROM THE ROSETTA MISSION THUS FAR, AND THE PLAN TO CRASH-LAND ON THE SURFACE

Science straight from space

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discuss some of the science to have come from the mission, and the forthcoming plan to crashland Rosetta on the comet’s surface.

Why did you move from the Cluster mission to the Rosetta mission? © ESA

March 2004 the European Space Agency’s Rosetta mission – the first mission ever to orbit a comet’s nucleus and land a probe on its surface – began its circuitous ten-year, 750 million mile trek across the Solar System, crossing the asteroid belt and travelling into deep space, more than five times Earth’s distance from the Sun. Its destination was a periodic comet known as Comet 67P/Churyumov-Gerasimenko and, after rendezvousing in early 2014, Rosetta’s lander, Philae, finally touched down on the surface of the comet in November that year.

Dr Matt Taylor

Despite landing slightly off-target and ‘bouncing’, contact was re-established with the lander, and the science from both the lander and orbiter has been extraordinary – from new theories of surface evolution, to the observation of increased activity during perihelion (when Comet 67P/Churyumov-Gerasimenko made its closest approach to the Sun).

What were the biggest challenges you faced as the project scientist?

Comets are considered the primitive building blocks of the Solar System, and likely helped ‘seed’ the Earth with water, and maybe even life. By studying the nature of the comet’s dust and gas, Rosetta will help scientists learn more about the role of comets in the evolution of the Solar System. Pan European Networks met with the Rosetta mission’s project scientist Matt Taylor during the British Science Festival in September 2015 to The comet reached the closest point to the Sun, or perihelion, along its 6.5-year orbit on 13 August 2015. The comet’s activity, at its peak intensity around perihelion and in the weeks that follow, is clearly visible in the image, including a significant outburst

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There was an opportunity which arose within the Rosetta team, and I was offered the position based on my experience. As the project scientist for Rosetta I am responsible for the science output of the mission, which is essentially the same role as I had held with the Cluster team.

One of my fundamental tasks is to deal with the scientists who want to do particular observations with different instruments but which cannot be done simultaneously. So apart from the challenges inherent in the science of the mission itself, it falls to me to prioritise the science that is to be done, and to make sure that everyone has their fair share of the ability to do the science that they want to do.

During your lecture, you highlighted some of the new discoveries the mission has found – jets emerging from parts of the comet which aren’t being illuminated etc. What do you think have been the biggest surprises thus far? The shape of the comet was perhaps the biggest surprise. The predicted shape (made from ground-based observations) had depicted something which resembled a potato – it is important to note that this was the best possible image we could generate in this way. However, in July 2014 images taken by the scientific camera, OSIRIS, revealed a double-lobed object, and then in August 2014 the ESA

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NavCam shape model revealed the ‘duck’ shape that we are familiar with today. The deuterium to hydrogen ratio found on the comet is also seen by some as a surprise, although others had considered that this could be found. Nevertheless, the fact that Rosetta’s ROSINA instrument measured the water vapour emanating from Comet 67P/ChuryumovGerasimenko and found it to be 5.3 × 10-4, more than three times greater than for Earth’s oceans, is important as the ratio of deuterium to hydrogen in water is a key diagnostic to determining where in the Solar System an object originated and in what proportion asteroids and/or comets contributed to Earth’s oceans. Many of the other things to have come from the mission so far are more ‘great results’ than they are ‘surprises’. In addition to the deuterium to hydrogen measurements we have also measured quantities of molecular nitrogen, which puts into context all the other observations we are making – it tells us that the comet is very old, that it originated in the Kuiper Belt and that it was out there for a long time. This means that we are now able to identify potential formation mechanisms which hint at the comet’s possible origins. And this, of course, can then be added to the

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The lander, Philae, touched down on the surface of the comet in November, 2014

general mix of ideas and theories concerning the evolution of the Solar System more generally. As a plasma physicist, I have been particularly interested in the measurements made by Rosetta and Philae during the probe’s multiple landings which show that the comet’s nucleus is not magnetised, again studying such properties of a comet can provide clues to the role that magnetic fields played in the formation of Solar System bodies almost 4.6 billion years ago.

Did you expect this result? It was one of the measurements that we wanted to make, and we knew that there would be no middle ground – there would either be a magnetic field or there wouldn’t. The result we have obtained again allows us to add this into the general mix of ideas and theories, and thus helps to answer such questions as whether magnetic fields are relevant at particular scales. This result is also significant as it utilises both the lander and the orbiter to take the measurements, and, indeed, we were only able to actually take this measurement because Philae bounced when it landed – we have been able to utilise this ‘accident’ in a positive way to generate science we wouldn’t have been able to do otherwise.

Given Philae’s final location and position, will it still be possible to conduct the science you had planned? The only limitation comes from the Sun and the environment. Philae has essentially been sheltered by its environment, and in a way that has helped as it has remained operational beyond its expected lifetime. When it came out of hibernation before summer we were unable to get a

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persistent and steady communication, meaning we were not able to command any instrument activity.

The Rosetta orbiter heading towards its destination

As we get closer to the comet and hopefully get in to the area where we will get signals again that may enable some more science on the surface. It is important to realise, however, that the orbiter is also doing fantastic science and this is set to continue. The lion’s share of the science was always supposed to come from the orbiter, and one of the constraints we have experienced as a result of the lander coming online is that we have been flying in a certain region around the comet which was not commensurate with some of the observations we wanted to make. This means that we have had to readjust some of our priorities and quite recently we moved to the southern hemisphere to see parts of the comet we had never seen before. That is a balance we have to strike.

The mission generates a number of images a day, but it doesn’t always catch the short lived events. So we have to be lucky, and we are piecing all this together.

Comet 67P/ Churyumov-Gerasimenko around Perihelion

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At the moment, it’s all about the activity we are seeing as a result of perihelion – there is sporadic activity we have never really seen before. All of the teams are working on this and comparing their data in an attempt to piece together the bigger picture.

What preliminary observations of environmental changes etc. were made during perihelion, and what other science do you now hope for? The key thing is that we have actually been able to witness this activity, which is ongoing. We have seen some truly fantastic stuff, such as a jet which actually pushed the solar wind away. This was registered by several of Rosetta’s instruments from their vantage point of 186km away from the comet. They imaged the outburst erupting from the nucleus, witnessed a change in the structure and composition of the gaseous coma environment surrounding Rosetta, and detected increased levels of dust impacts; this outburst had pushed away the solar wind magnetic field from around the nucleus.

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We had expected that such a region, known as a ‘diamagnetic cavity’, would exist a short distance from the comet, a few tens of kilometres. We were having issues navigating close to the comet due to the dusty environment, so we had considered that sampling this region would not be possible. However, there was a massive outburst of material over only a few tens of minutes, which actually pushed that cavity out to where the spacecraft was, and that was a nice result for us around perihelion.

When I spoke to Fred Jansen, Rosetta’s mission manager, in March, discussions on how the mission would end (that is, whether Rosetta would be crash-landed onto the surface of the comet) were ongoing, but this has now been decided, and the mission itself has also been extended. What do you hope will come from this? Yes, the mission has been extended until September 2016, and we will now discuss specifically what we want to do with the remainder of the time we have. The decision to crash Rosetta onto the surface of the comet has also been made, and with that in mind when we are deciding on the science of the mission

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An overview of the scientific instruments onboard Rosetta

we will perhaps risk a little bit more. We will hope to get in to a bound orbit again and get closer and closer to the comet – that’s one of the main things. We are also discussing going to the tail region of the comet to look at the kind of magnetic and plasma interactions that are there and the dust populations and so on – this is one of the things we want to do from a plasma physics perspective, but we have to also take into account the other observations that could be done, and also explore whether this is operationally possible. While I do believe that we could do this, we are constantly learning new things, and we therefore have to change our ideas and modify our expectations as we move forwards, quite simply because this is something that has never been done before. Ultimately, the end of mission scenario is to spiral in and crash onto the surface. There is a scientific driver to this, in that this will enable us to get the highest and best resolution data – not only images but also sampling in situ; getting that close to the comet could mean that we are able find things that we weren’t aware of until now, and would allow us to explore areas such as how the gas accelerates from the nucleus, but we can only do that by taking a risk and by getting as close as possible, which is perhaps acceptable because we are going to crash anyway.

Dr Matt Taylor Rosetta Mission Project Scientist European Space Agency http://www.esa.int/Our_Activities/Space_Science/Rosetta

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DR THOMAS REITER, DIRECTOR FOR HUMAN SPACEFLIGHT OPERATIONS AT ESA, SPOKE TO PAN EUROPEAN NETWORKS ABOUT SOME OF THE SCIENCE THE IRISS MISSION WOULD INVOLVE

A sprint into space IN Mogensen’s iriss mission lasted ten days, during which he devoted his time in space to testing new technologies and improving space operations. His activities included testing a new water-cleaning membrane that mimics Nature, hands-free goggles to help with complex tasks, a tight-fitting suit to alleviate back pain common in astronauts and driving three different rovers on Earth to prepare for missions further out in our Solar System.

biology, and human physiology research, some of which have already been installed. As such, while Mogensen’s mission is only short, it contains a very dense scientific programme.

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September 2015, European Space Agency (ESA) astronaut Andreas Mogensen flew to the International Space Station (ISS) in a Soyuz TMA-18M spacecraft. Launch began at 04:37 GMT (06:37 CEST, 10:37 local time) on 2 September at the Baikonur Cosmodrome in Kazakhstan. After circling the globe for the following two days, the spacecraft docked at 07:39 GMT on 4 September.

Dr Thomas Reiter

All the activities Mogensen will undertake are not designed only for his mission, they are part of the longer term research programmes in various previously established topics and so often compliment this research. However, it is not only an astronaut’s job to undertake scientific research but also to conduct other tasks on the ISS such as the setting up of experiments, maintenance work on the onboard systems and so on. This involves a lot of different systems, and while astronauts learn a lot about them – such as the life support systems, which are quite complex, power distribution, the onboard computer systems and, of course, the various payloads, for example – during their training, when they actually do these activities they need to refer to quite a substantial amount of documentation.

On 12 September Mogensen, Soyuz spacecraft commander Gennady Padalka and Kazakh cosmonaut Aidyn Aimbetov landed in the steppe of Kazakhstan, marking the end of their missions to the ISS. Prior to the launch of the mission, Pan European Networks spoke with ESA’s Director for Human Spaceflight Operations, Dr Thomas Reiter, about some of the activities Mogensen would be undertaking during his time on the ISS, as well as how the iriss mission fits into ESA’s overall vision for manned spaceflight operations moving forwards.

What do you hope to learn from the iriss mission? Every ESA mission to the ISS has a very comprehensive scientific programme prepared for the astronaut. For Andreas Mogensen, this includes various experiments in areas such as technology demonstration, ESA astronaut Andreas Mogensen in space

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What is the significance of the technologies Mogensen will work on during his time in space – such as the augmented goggles?

This can present a significant problem in a zero gravity environment, and so we are looking at ways to help lighten the workload and to enhance efficiency. One such way is through the use of the augmented goggles you mentioned, which Mogensen will test. These goggles provide an augmented reality, providing the wearer with the necessary information to successfully complete a task without the need for the reference documents that are typically required when working on a complex system. A second area Mogensen will explore concerns biology. That is, we know that the zero gravity environment has an interesting effect on some of the functions that are going on in living cells, and Mogensen will perform the Endothelial Cells experiment to look at the mechanism that protects the blood vessels from the circulating

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blood. Interestingly, this thin layer of endothelial cells is very susceptive to gravity, and to understand how this mechanism works is important not only for those spending time in space, and thus zero gravity conditions, but also for people here on Earth who are suffering from age-related diseases, for example.

Can you tell me more about Mogensen’s work with the very first force-feedback-based teleoperation of a rover-based robotic arm system on Earth from the International Space Station? This has two very interesting aspects. First of all, when a robotic automated system on Earth is being controlled from space, it takes time for the signal to travel from the operator to the robot. If this is in Low Earth Orbit (LEO), the delay caused by the signal travel time is usually in the order of a few tenths of a second, but when we think about exploration in the depths of our Solar System, this can extend up to 30 minutes (this was the signal delay time when the Rosetta landing took place in 2014, for instance). Mogensen’s research is looking into so-called ‘delay tolerant networks’, whereby we are working to minimise the effect of the delay on the robotic interaction.

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Following his ten-day mission, Mogensen is greeted back on Earth

Alongside the issue of signal delay, it is also, of course, difficult to operate a robotic arm and/or rover remotely, and one of the most important things here is the inclusion of haptic feedback. During his mission Mogensen will make use of haptic control, providing him with force-feedback to let him feel for himself as the robotic arms encounter resistance. In this way, he can perform dexterous mechanical assembly tasks in the submillimetre range, remote-controlled from space.

Why was iriss chosen to be a sprint mission? Historically, ESA has always undertaken both long and short term missions. Indeed, in the 1990s, short term missions on board the US Shuttle or the Russian Soyuz were more or less the standard, with long term missions being the exception. Today, we want to utilise every possible chance to put astronauts into space, and that is both because we can, as a consequence, have a very comprehensive scientific programme and can complement the research that is already taking place. We will, therefore, enable our astronauts and the whole European Astronaut Corps to acquire operational experience. Mogensen’s mission is important because he will be the flight engineer in the ‘left seat’ of the Soyuz, which is a very responsible and interesting task, and which will mean he can acquire a significant degree of operational experience. The whole Astronaut Corps benefits from the way in which ESA seizes every available opportunity to launch an astronaut into space, and moving forwards we will continue to do so. Because of the way the ISS is operated, these short term missions are a little more seldom than in the past, but there will nevertheless be future opportunities for sprint missions like iriss because despite the brevity of

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such missions there is still a lot of science and operational activities we can undertake through them, and thus a lot to be learnt.

What is the long term development and vision for ESA’s human spaceflight activities? Next year ESA will hold the next ministerial council, during which ESA member states will decide on, amongst other things, the extension of our participation in the ISS programme until 2024. This, as well as our Low Earth Orbit (LEO) activities, is important to the scientific community, who need to know our intentions so that they can continue to plan their research programmes with the knowledge that they will be able to use the ISS or other LEO platforms for a given time. We will also see humans leave LEO and move to larger distances. For instance, ESA is co-operating with NASA to build the service module for the Orion capsule, which will once more take humans to the Moon. A crewless Orion mission is planned to travel around the Moon in 2017, and I personally believe that by the second half of the next decade there is a high likelihood that we will see humans returning to the lunar surface. The longer term vision would then be to build a permanent research post on the Moon, which could then go on to act as something of a stepping stone for a manned mission to Mars. However, a development of this magnitude remains some time away – I would expect at least another 20 years to pass before ESA and its international partners are ready to take on such an endeavour.

How important is the development of such international cooperation when it comes to human spaceflight activities? It is crucial. When we talk about core operations such as spaceflight and specifically exploration and human spaceflight, this always

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Every ESA mission to the ISS has a very comprehensive scientific programme prepared for the astronaut

has two aspects: a functional aspect and a political aspect. The functional aspect refers to the fact that many of the operations and missions – whether current or future – would be very difficult to undertake alone. It simply makes sense for us to share the burden and combine our experience in order to achieve these goals. ESA is an excellent example of how such goals can be achieved if we all pull together; if we pool our resources, industrial capabilities and scientific experience. In addition to the technological and scientific objectives, international collaboration also has a very important meaning in the context of pursuing common goals, and it is here where the political aspect comes in to play. That is, we learn to work with one another beyond the barriers, towards co-operation, that we can perhaps sometimes experience here on Earth.

Dr Thomas Reiter Director for Human Spaceflight Operations European Space Agency (ESA) http://www.esa.int/Our_Activities/Human _Spaceflight

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STUDENT-POWERED REVOLUTION Student-built Aalto-1 nanosatellite from Finland carries miniature technology to space for the first time in in-orbit demonstration

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apid development of technology and improving awareness of global challenges has increased the need for lean and agile space missions, and calls for a new generation of engineers to design them. Miniaturisation of sensor technology and electronics has reduced the weight of a satellite, simultaneously bringing launch prices to within the reach of educational institutions and smaller countries. As a consequence, the field of nanosatellites is increasing with unprecedented speed, as is the number of satellites. Also, Finland has harnessed the nanosatellite boom to take a leap in technology education in order to secure top skills and knowledge for the next generation of space engineers.

A multi-payload mission with high end payloads Finland’s first satellite, the Aalto-1, is one of the most ambitious multi-payload nanosatellite missions ever built. The miniature 4kg satellite is constructed primarily as a student project in extensive collaboration with other Finnish universities and institutions. The satellite carries three high end innovative research devices: an imaging spectrometer built by VTT, a radiation monitor jointly constructed by the Universities of Helsinki and Turku, and an experimental de-orbiting device designed by the Finnish Meteorological Institute. The multistage mission aims for in-orbit demonstrations of all these new technologies for further utilisation in space.

Demonstration of top-quality education A satellite project, performed as a platform for interdisciplinary innovation in the university, involves many engineering disciplines and therefore has provided a convenient environment for co-operation between engineering students from different fields. More than 80 students from various disciplines have taken part in the project over several years. The education experiment has produced dozens of master’s and bachelors’ theses, many conference publications and several scientific publications. The entire student team, but especially quality manager Tuomas Tikka and systems engineer Antti Kestilä, have busy days when making the final tests for the upcoming launch in the beginning of 2016. Kestilä and Tikka, like many project students, are already pursuing doctoral degrees in space technology.

Motivation facilitates learning The satellite project has served as an excellent source of motivation for learning and collaboration. Many students wish to contribute to a real space project and now it is possible. When combining this motivation with project-based teaching and high quality lecture courses, the learning outcome is usually very good or excellent. The CubeSat project concept is also in line with

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Artist’s impression of Aalto-1 satellite

modern university teaching trends, which attempt to integrate all key components of professional expertise with comprehensive learning experiences. The space project has empowered the student team; Aalto University students are already working on three new CubeSat satellite missions. Furthermore, the project alumni established a start-up company for producing an entire constellation of satellites, and this is just a beginning. Completion of the satellite demonstrates the high level of education at Aalto University. The new generation of nanosatellites involve technological developments, the results of which can also be used in other fields. The Aalto University satellite projects ensure that students will continue to work with the right challenges and the latest technology in the future. Designing instruments for use in highly demanding conditions helps us create innovations and teaches us to appreciate build quality.

Jaan Praks Assistant Professor, responsible leader of Aalto-1 satellite project School of Electrical Engineering Aalto University +358 (0)50 420 5847 [email protected] http://aalto-1.aalto.fi

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A PLENARY SESSION AT THE EUPHA’S EIGHTH PUBLIC HEALTH CONFERENCE IN MILAN FOCUSED ON THE DEVELOPMENT OF A NEW EU HEALTH INFORMATION SYSTEM, AS PEN REPORTS

European health information

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Sustainable support

October 2015, Milan played host to the eighth European Public Health Conference, which had been jointly organised by the European Public Health Conference Foundation, the European Public Health Association (EUPHA) and the Österreichische Gesellschaft für Public Health (OEPH).

As such, DG SANTE is working to create sustainable technical support for health information development and research, as well as to contribute to the work of other international institutions who also have activities in this area.

The event, which Pan European Networks attended, aimed to contribute to the improvement of public health in Europe by offering a means for exchanging information and a platform for debate for researchers, policy makers, and practitioners in the field of public health and health services research, as well as public health training and education in Europe.

Schreck continued: “One of the options that our member states are currently exploring is the setting up of a European Research Infrastructure consortium, and this might be a solution that responds particularly well to today’s needs and realities. It will take an entirely bottom-up approach, it is member state-driven, and its costs are mainly borne through contributions in kind by participating organisations.

During the plenary session entitled ‘The New EU Health Information System’, members of the European Commission’s DG SANTE, the Organisation for Economic Co-operation and Development (OECD), Finland’s National Institute for Health and Welfare (THL), and the Commission’s in-house science service, the Joint Research Centre (JRC), came together to discuss the importance of a health information system for the Union and the ongoing work – and challenges involved therein – taking place to this end. Opening the plenary, DG SANTE’s Stefan Schreck, who was acting as the session’s moderator, explained that following on from feedback received from EU member states and organisations, such as the European Centre for Disease Control (ECDC) and the Council of the European Parliament, the need for better EU-level co-ordination on health information became apparent. Furthermore, Schreck explained, from a purely scientific perspective there is no reason why different indicators should exist on the same issue in different member states.

While Europe tends to be quite strong when it comes to the collection of mortality data, it remains relatively weak with regard to data on morbidity

“We also want to support people’s health and health systems in member states according to the specific needs of each country, but such an approach is only possible if the analysis is based on reliable and solid information, and is taken forward in collaboration with member states and the relevant international organisations which are involved in data collection and analysis.” Expanding on this point, Schreck explained that the final system should have three key elements. Firstly, there is a need for better formalisation of EU health indicators in areas other than communicable diseases – he stated that there are currently too many. Then there is a need to develop sustainable technical support for the analysis and reporting back of the information to EU member states, and finally, there is a need for policy support in the form of country-specific analysis and reporting.

OECD The OECD’s Gaetan Lafortune took to the stage after Schreck to deliver a presentation entitled ‘An EU health information system and beyond’. He had chosen this title, he said, as a way of

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highlighting how the OECD is not only working with EU countries but also with many others, both inside and outside of Europe. During his address, Lafortune focused on three main themes, the first of which was that an EU and OECD health information system needed to strike a good balance in providing useful and relevant information on both public health issues and on the healthcare system performance. He added: “Given that this is a public health conference, I will say that the public health part is obviously more important than the health system performance part. But given that most of the money in fact goes to care systems, it is also useful to pay attention to find out how this money is spent, and whether or not it may be being wasted.” Lafortune’s second main message showed how necessary it is to move from basic descriptive data monitoring to providing policy-relevant analysis in response to pressing questions such as what to do with various public health or health system performance problems, and this necessarily involves looking at the cost and benefit of various policy options. His third message was that any EU health information system will need to be based on strong co-operation between countries because

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Gaetan Lafortune from the OECD stressed that any EU health information system will need to be based on strong co-operation between countries because “this is where most of the data will come from”

“this is where most of the data will come from,” as well as on strong cooperation between international organisations. Lafortune added: “We have already started to strengthen our co-operation across international organisations and we are developing joint data questionnaires.” The development of questionnaires began some ten years ago, Lafortune explained to the delegates, with the surveys designed to gather data which could be used in conjunction with that obtained by the WHO on health expenditure and financing. Five years ago this was extended to the collection of data on non-expenditure healthcare statistics and, in 2015, this was extended again to include data on the migration of health workers. He continued: “This is the general framework that we have been using at the OECD for the last ten years, and we have been building on what has been done in countries inside and outside of Europe. It includes a public health component (this is the top part of the framework that looks at the health status of the population and at various non healthcare-related determinants), and a part looking at healthcare system performance. “This framework is also used by DG SANTE,” he said, as well as in the context of the work on health system performance assessment used by DG Employment within the joint assessment framework on health. As such, the framework has a certain amount of flexibility, and there is a wide level of agreement on its importance and usefulness. “If we agree with this framework,” Lafortune continued, “then one of the tasks we face is to look at public health and health system performance and to then try to fill the various parts of this framework with relevant

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comparable data. This is what we are trying to do through our joint efforts with the WHO.” Moving on to data specifics, Lafortune then highlighted how Europe tends to be quite strong when it comes to the collection of mortality data, but remains relatively weak with regard to data on morbidity. Nevertheless, he said, one advantage that Europe has is the establishment of the Healthy Life Years indicator, a European structural indicator calculated by Eurostat that acts as one of the summary measures of population health (known as health expectancies), composite measures of health that combine mortality and morbidity data to represent overall population health on a single indicator.

System performance Progressing to healthcare system performance, Lafortune explained that it is now necessary to collect data on how much countries are spending; that includes total health spending and the allocation of spending between prevention and care, between the different areas of a hospital’s activity, and on pharmaceuticals. This is something that the OECD is already doing but, Lafortune said, there is still the necessity to provide access to the information and this is perhaps a more important policy objective in terms of addressing issues such as financial barriers, geographic barriers (how far people have to go to access services), and access in terms of waiting times for services. To achieve this, Lafortune explained, “we must rely on different sources, whether survey sources or administrative data sources. We also, obviously, need information on quality of care, where we need to know whether care is being delivered in a high quality way, in a safe way, and in a way that provides positive outcomes for patients.” Since the OECD began looking at indicators of care quality some ten years ago, their work now covers quality in primary, acute, cancer, and

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DG SANTE is working to create sustainable technical support for health information development and research

in some aspects of the quality of mental healthcare. Nevertheless, as Lafortune highlighted, there is more to be done, particularly with regard to an increased focus on the quality of care for people with different chronic conditions which, for instance, would include finding out more about the outcomes from interventions such as hip and knee replacement and other conditions associated with ageing. Summing up, Lafortune explained that the OECD will now continue to explore this general framework and try to populate it with relevant and comparable data in order to be able to compare experiences across countries. The development of a new EU health information system is thus a complex task, and one which requires an almost unprecedented level of co-operation between the numerous stakeholders and across Europe’s member states and further afield. While this is certainly not something that will happen overnight, the time it will take will be time well spent, as this system has the potential to significantly help those working in the field of public health both now and in the future and, moreover, to be of huge benefit to Europe’s citizens.

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THE NATIONAL FOOD INSTITUTE AT THE TECHNICAL UNIVERSITY OF DENMARK DISCUSSES THE UNDER-REPORTING OF FOODBORNE DISEASES AND THE BURDEN THIS CAN POSE

Foodborne diseases: under-reported?

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very year, thousands of people suffer from foodborne diseases in Europe. Official statistics suggest that each year over 350,000 people need medical care, are absent from work, or need to attend to children suffering food poisoning (ECDC, 2014).1 While these figures already show that foodborne diseases cause a substantial public health and economic burden, we now recognise that they represent only the tip of the iceberg, and that the real number of cases in the population is largely unknown. The gap between the true number of cases caused by contaminated foods and what is captured by public health surveillance systems can be easily explained: for a case to be identified, the ill person must seek medical care; the doctor must request a sample; the causative pathogen must be identified at a laboratory; and the results must be reported to public health officials. Any failure in this process leads to underdiagnosis and under-reporting.

example liver cancer caused by exposure to a toxin through foods? How can we compare diseases and rank them to define public health priorities?

Harmonised metrics Both international organisations (namely the World Health Organization, through the Global Burden of Disease study)2 and national authorities are interested in answering these questions. For this purpose, harmonised health metrics have been developed to assess the impact of diseases in terms of incidence, severity, duration, and mortality in a population. The most commonly used metric is ‘disability-adjusted life years’ (DALY). A DALY can be understood as the loss of ‘one year of perfect health’, and the disease burden is a measure of the difference between the actual health status due to a foodborne problem and the ideal situation, where all live a long and healthy life without this disease.

So how much do we not know? What is the true burden of foodborne diseases? The National Food Institute at the Technical University of Denmark recently estimated that for every reported case of salmonellosis, seven cases were not reported. This difference is even larger for other bacteria commonly transmitted through foods, such as Campylobacter (one out of 12 cases reported) and VTEC (one out of 31).

So far, only a few countries have embarked on a comprehensive burden of foodborne disease studies. At the National Food Institute, Technical University of Denmark, scientists are working on deriving DALY estimates for a wide range of microbial, chemical and nutritional hazards and risk factors, and will use these to set public health goals, allocate resources, and measure the public health and economic impact of disease.3

Burden

Acknowledging that not all countries have the resources to do so, the WHO will soon publish global and regional estimates of the burden of foodborne diseases.4 The hope is that governments and consumers alike will recognise the true burden of contaminated foods, and support initiatives that can pave the way for a world with safer foods.

And this is the burden caused by foodborne infections, which in most cases result in acute short-term diarrhea, vomiting, and fever, and are therefore easier to identify as food-associated diseases. But what about chronic diseases (such as cancer, or neurological or cardiovascular conditions) caused by exposure to chemicals and unhealthy diets? These diseases can have many causes other than contaminants in the food or diet-related risk factors, and being able to associate exposure to these and their occurrence is challenging enough. How can we measure their impact in the population, and compare them with other foodborne (and non-foodborne) diseases?

Ranking A simple and intuitive way of ranking diseases is based on how often they occur or on the number of deaths that they cause. However, these disease-measures do not provide a full picture of the impact of diseases on human health, because severity and duration of the disease are not taken into account. Let’s look at an example. How can we decide which is a larger public health problem: a very frequent, mild gastroenteritis that typically lasts around seven days, or a rare but severe or life-threating condition, for

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References 1 http://ecdc.europa.eu/en/publications/Publications/AER-2014-VPD-FINAL.pdf 2 http://www.who.int/healthinfo/global_burden_disease/gbd/en/ 3 http://www.food.dtu.dk/english/News/2014/11/The-real-disease-burden-of-foodborneinfections?id=2f65b777-be4e-4109-8503-5c3934b33cba 4 http://www.who.int/foodsafety/areas_work/foodborne-diseases/ferg/en/

Sara Monteiro Piers Senior Researcher Marten Poulsen Head of Research Group National Food Institute Technical University of Denmark www.food.dtu.dk/

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PROFESSOR MARTIN MCKEE’S SPEECH AT EUPHA’S EIGHTH EUROPEAN PUBLIC HEALTH CONFERENCE RAISED MANY IMPORTANT POINTS ABOUT THE RELATIONSHIP BETWEEN RESEARCH AND POLICY, AS PEN DETAILS

Public health and policy

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artin Mckee, a professor of European Public Health at the London School of Hygiene and Tropical Medicine, UK, founding director of the European Centre on Health of Societies in Transition, and research director of the European Observatory on Health Systems and Policies, delivered an extremely interesting and informative presentation during a plenary session entitled ‘Learning from each other: how to transfer best practice across boundaries’ at EUPHA’s eighth European Public Health Conference in Milan, Italy.

However, McKee also pointed out that some of this blame lies at the feet of research funders too, and that “problems lie all the way throughout the process of knowledge transfer”. Building on this point, the professor argued that “a policy that works in one setting may not be easily transferrable to another,” and while there may be many reasons for this, it is firstly necessary that those who make the decisions must first recognise that there is a problem to be solved. “Clearly,” he continued, “we in the public health community have an important role to play in that much of our work involves making the invisible visible. A recent example from our own work has been research documenting the increase of mental illness and suicide associated with austerity policies.

He began his address by explaining that the primary goal for research on health systems and policy is to inform policy and practice, and while Europe’s great diversity – both between and often within countries – is in many ways one of its strengths, this also means that there is not only diversity in the diseases in Europe, but also the policies that have been established to respond to them.

Making it into policy McKee added that while public health events such as EUPHA’s are attended by a diverse range of delegates, who listen to presentations by diverse speakers, and then go on to take the lessons they learn and the ideas they hear to their respective countries and adapt them to their own local circumstances, or propose new ways of doing things, far too often the best research never makes it into policy or practice. There are many reasons for this, he continued. Some of these reasons relate to the research community, who perhaps take too long to complete their investigation, or too long to get their results in to print. There is also the case to be made that much of the published research uses a language that McKee described as “largely impenetrable to anyone who is not inside our discipline”. This also relates to the issue of peer review, with McKee arguing that some reviewers “seem to believe that the quality of a paper should be judged on the obscurity of its vocabulary”.

Far too often even the best research never makes it into policy or practice, and one reason for this may be that researchers take too long to get their results in to print

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“For several years after the beginning of the current economic crisis, discussions among political leaders were dominated almost entirely by how they could protect the enormous sums that had been lent so recklessly by the financial institutions. If there were any discussions at all about the fate of ordinary citizens, it was difficult to find it. But, by assembling the statistics of mortality and data from surveys, we were able to document the massive human cost of austerity.” Referring to a publication that he had co-authored with Johan P Mackenbach, Successes and failures in health policy in Europe, Mckee argued that there have been many policies adopted in different parts of Europe that had been successful in bringing about change. Of even more importance, however, it also showed that some countries, especially the Nordic countries, had been much more successful in adopting such policies. Subsequent work, he said, had gone some way to offer explanations as to why. He said: “We have highlighted the importance of values in society and in particular a belief in the importance of

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investing in the future rather than seeking rewards in the here and now. But even when we have a receptive policy environment, it is important to tailor the new ideas to the context in which they will be implemented.” We need to ask, McKee explained, who will be responsible for making things happen, and so the research looked at various determinants of health and found that in many cases the responsibility lies within many different parts of government, or different tiers of government from the regional to the local to the national. “Do we really always know who is responsible for making a difference?” he asked, and “do we know whether what we are proposing fits with their view of the world? And, if not, what can we do to make sure that it does?” Regarding the politics involved, Mckee posited that here “you will find that effective public health policies are more likely to be implemented in countries that have longer periods of being ruled by left wing governments. And it is not just party politics; politicians are often influenced by personal factors.”

Context When these areas align, the professor argued, they may present a window of opportunity that makes it possible to implement a policy that would be impossible at other times. Sometimes, he continued, this is triggered by something involving a tragedy. As an example, Mckee highlighted how, following the Dunblane massacre in Scotland, UK, in 1996 – whereby a local man entered a school and shot dead a teacher and 16 children – within weeks the British Government had introduced far tighter gun control measures. “That same year,” he added, “another mass shooting with 35 dead this time led the Australian Government to introduce wide ranging gun control. Neither country has had a mass shooting since. Yet these examples remind us of the importance of context – in the USA the continuing toll of deaths in school shootings bizarrely encourages many people to call for guns to be more easily available. “This is an extreme example, but we know that there are many other situations in which the need for a policy is clear, the evidence for a solution has been demonstrated, but the political support is simply lacking.” Turning his attention to the actors and organisations involved in transmitting and

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By assembling the statistics of mortality and data from surveys, the European Observatory on Health Systems and Policies was able to document the massive human cost of austerity

receiving information, McKee stated: “Some organisations are simply not very good at incorporating evidence into policy. A book entitled The Blunders of our Governments analyses a large number of laws adopted by the United Kingdom Parliament by governments of differing political persuasions, all of which had one thing in common – they were disasters. “In many cases, the evidence that they would be disasters was clear from the very beginning, and in others it was not the organisation as such that was at fault but the individual decision maker.” This final point is one that McKee expanded on in detail, arguing that it has now been posited that the hubris of individual politicians has, perhaps predictably, led to numerous political “disasters”.

Corruption “In some cases,” he continued, “there may also be other less visible factors that come into play, where policy makers reach decisions not on the basis of the public interest but rather in pursuit of their own private ones. This may be simple corruption, where bribes are given, but more often it takes the form of the ‘revolving door phenomenon’, whereby powerful corporate interests hold out the prospect of lucrative directorships and consultancies to support the policy makers in their retirement.” According to McKee, tobacco control is a case in point. There is a distinct correlation between the failure to implement comprehensive tobacco control policies and the level of corruption in a country “to the extent that we might actually start looking at tobacco control scores as an indicator of corrupt governments”. It is also remarkable, he said, “that government officials spend large amounts of money with some of the large international consultancy companies only to turn up a few years later working for them. “Corruption has been a problem ever since the invention of money, and possibly even before that, but in a number of countries we are now seeing the emergence of a new but related phenomenon: the neoliberal argument that governments should buy and not make things has led to the hollowing out of the state. Government bureaucracies are under sustained attack, represented as stagnant backwaters resisting innovation. That may have been the case once, and in some cases it may still be, but it is far from an absolute rule.” As interesting and important as all of these points are, their relevance to public health may take some discerning, and so McKee highlighted their applicability thus: “Many governments and even international organisations have cut back radically on their core capacity to generate

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and synthesise evidence. Instead, they contract this work out, often at huge expense, to consultancy companies. Very occasionally, they get something back that is of some use to them, but more often it is simplistic in the extreme, frequently wrong, and riddled with conflicts of interest, as those companies propose courses of action which will advance the interests either of themselves or of their other clients.”

would have agreed with the statement ‘vaccines are risky because they can cause sterilisation’, when in fact the true figure of Nairobians is only 11%.

Complexity The research at the World Bank considered several main sources of bias, the first of which was complexity. Many decisions taken at the bank involve complexity, McKee said, and the researchers cited a seminal study in which some subjects are confronted with a situation in which if they do nothing, one-third of the population will live, but if they act there’s a 33% chance of saving everyone and a 66% chance of saving no-one; while other subjects face a situation in which if nothing is done, two thirds of the population will die. Numerically, of course, the two scenarios are identical, but the research found that those presented with the first of these preferred certainty and avoided the risk of action, while those faced with the second, which was framed in terms of losses, were much more likely to take the chance and act. When this study was replicated at the World Bank, the researchers found that 75% chose certainty when it was framed in terms of gain, and only 34% of those presented with the loss did so – the same as in the original study.

From Mckee’s arguments it would appear – and this was a point that McKee himself underlined in his presentation – that it may be quite easy to catalogue errors and omissions, but incredibly difficult to find the examples of organisations with “the insight and self-confidence to reflect on how they make decisions”.

Cognitive bias The World Bank, he said, is a rare exception here. As researchers preparing the 2015 World Development Report undertook a series of studies among World Bank staff linked, where appropriate, to evidence from surveys and other sources to explore the role of cognitive biases – biases that come into play and that reveal themselves when people are presented with the same evidence but reach very different conclusions. McKee said: “Much of the evidence of cognitive biases comes from the USA, in particular in response to the 2004 presidential election when it became clear that the democratic contender John Kerry, who served with distinction in Vietnam, was being portrayed successfully as a coward, while George W Bush who had avoided service there was being portrayed as a war hero.” Researchers have since established that those from either the Democrat or Republican parties make decisions depending on their preconceived world view; and that even when false statements are corrected by an authoritative source, if the original statement aligns with a person’s prior beliefs, then the correction often reinforces the false belief. Furthermore, when subjects are given the opportunity to look online for information, they seek out the information that agrees with their own point of view. Mckee described how the World Bank was concerned that its staff may be making decisions that perhaps did not reflect reality on the ground. The research conducted for the Development Report, for example, showed that 42% of the staff predicted that most of the poor in Nairobi

Multi-method assessment Gun control is an example of a situation in which the need for a policy is clear, the evidence for a solution has been demonstrated, but the political support is simply lacking

“In our own work,” Mckee continued, “we have developed a framework for the multi-method assessment of health systems in which we try to see these systems through the eyes of those who use them and who deliver them on the front line. What this shows is that the reality is often very different from the official version. “The researchers at the World Bank concluded that for these and for many other reasons it is possible to explain why ‘good people can make bad decisions’ and in this way they inadvertently work against the interest of those they are meant to be helping.”

Successful transfer Looking next at the characteristics of policies that transfer successfully, the professor explained: “To some extent, the factors promoting a successful transfer are intuitive; it is better if the policy is simple and easily understood. Hopefully the one being transferred will be better than the one that is already in place, and it helps if it has already been shown to work elsewhere, but also that it is compatible with existing values and contexts.”

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McKee informed his audience in Milan that there are many possible sources of information – academic journals and policy briefs, for instance – but that “knowledge transfer is primarily a social process, with trusted intermediaries playing a key role. But this causes a problem: who are these intermediaries?” he asked. In light of this question, McKee argued that it is important to look for impartial sources of advice from organisations “that are not pursuing either a narrow political agenda or naked self-interest; we need to be sceptical indeed about so-called ‘think tanks’ and other organisations which are, in reality, lobbyists, even if they pretend not to be. “We must demand total transparency; when they appear on the television or radio it is totally inadequate to simply describe them as free market think tanks and alike. “If we appear with them on interviews or panels we must insist on calling them what they are: tobacco or alcohol or food industry lobbyists, plain and simple. “As researchers, we must develop the emerging body of work on the corporate determinants of health. This involves detailed analysis of the often hidden connections

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There is a distinct correlation between the failure to implement comprehensive tobacco control policies and the level of corruption in a country

between these groups and their corporate sponsors, but we can also use innovative techniques like text mining to expose their influence on laws and policies.”

More to be done Bringing his presentation to a close, the professor said: “We need to do more. We need to ensure that we in the public health community have a seat at the table as trusted advisors who can give an impartial view of the evidence and we also need to expose those who are behind the scenes promoting their own health-damaging interests.” In order to improve the process of translating evidence to policy, McKee argued, the first thing to do is to understand much better the complexity of the influences on policy, which requires a lot of research drawing together disciplines such as psychology, epidemiology, anthropology and political science, and then to “insist on complete transparency, recognising that many of those with a vested interest work very hard to conceal them”. Finally, he said, we need to better understand the cognitive biases that influence decision making, and thereby work to “establish ourselves as trusted sources of evidence, working closely with policy makers and providing them with the evidence that they need in a timely manner”. If, he concluded, this can be done, “then we can finally come together to make the world a better place,” and while this is a significant task, it is not an impossible one, but it will involve the co-operation and collaboration of all relevant stakeholders from across the public health spectrum.

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PROFESSOR JØRGEN VESTBO, PRESIDENT OF THE ERS, SPOKE TO PEN ABOUT A WIDE RANGE OF RESPIRATORY HEALTH ISSUES, INCLUDING DEADLY STRAINS OF INFLUENZA AND MORE COMMONPLACE RESPIRATORY INFECTIONS

Reflecting on respiratory health

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Pan European Networks asked the ERS’s new president, Professor Jørgen Vestbo, for his thoughts on a wide range of issues – from health inequalities, to outbreaks of strains of influenza and to more commonplace infections – and how the society is continuing to work, with science as its foundation, to prevent respiratory diseases across all sections of society.

Lung infections (mostly pneumonia and tuberculosis), lung cancer, and chronic obstructive pulmonary disease (COPD) together accounted for 9.5 million deaths worldwide during 2008, one sixth of the global total. © ERS

he European Respiratory Society (ERS) is an international organisation that brings together physicians, healthcare professionals, scientists and other experts working in respiratory medicine. With a membership representing over 140 countries worldwide, the ERS’s mission is to promote lung health in order to alleviate suffering from disease and drive standards for respiratory medicine globally.

Professor Jørgen Vestbo

Respiratory diseases were the third most common cause of death in the EU28 according to a 2015 Eurostat article. How can such a startling statistic come to be addressed? Respiratory disease is one of the major health challenges of this century. The 2015 Eurostat article you have referred to does indeed reveal that respiratory diseases were the third most common cause of death in the EU28, and this poses a major burden on healthcare budgets, societies and, most importantly, on the people living with chronic lung conditions.

Acute lower respiratory infections are a leading cause of sickness and mortality both in children and adults worldwide

Despite these startling statistics, there is still a general lack of understanding and awareness amongst patients, politicians, and the general public about the range and impact of respiratory disease. The European Respiratory Society is working to change this situation. We are dedicated to promoting scientific research in this field, driving standards in the education of respiratory professionals, and together with the European Lung Foundation (ELF) are advocating to raise awareness of lung disease amongst the public and politicians alike. The ERS and the ELF are committed to the prevention of diseases across all sections of society. The ERS established the ELF with the aim of bringing together patients and the public with respiratory professionals to positively influence lung health. The two organisations work side by side to raise the profile of respiratory diseases across the whole population. This ethos was embedded in the launch of the Healthy Lungs for Life campaign in 2014, which seeks to reduce the number of people suffering from lung disease by raising awareness and knowledge of lung conditions. By focusing on a different theme each year, Healthy Lungs for Life will help prevent lung damage by raising awareness of the key risk factors associated with respiratory disease. We are committed to achieving our goal of alleviating suffering from respiratory disease but we cannot tackle this burden alone. We must work with all stakeholders in respiratory health.

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Socioeconomically disadvantaged populations in low- and middleincome countries are especially vulnerable to the development and exacerbation of respiratory diseases. How can such inequalities come to be addressed, in your opinion (such as through, for instance, a comprehensive and integrated approach taken to address risk factors that span many different policy sectors)? Health inequalities are estimated to cost €1trillion per year, or 9.4% of GDP (Mackenbach, Meerding & Kunst, 2007), placing a huge burden on society. It is well known that social inequality is linked to poor health, and healthcare systems across Europe differ greatly. The gap between the richest and the poorest in society is widening during the economic crisis in Europe and governments are required to make difficult decisions about budgets in times of austerity. Social inequality causes a higher proportion of deaths in respiratory disease than in any other disease. This is true for all age groups, particularly children, and the prevention of respiratory infections could make a major contribution to reducing health inequalities. We need to implement long term strategies to tackle inequalities from birth and prevent a vicious cycle of unequal healthcare throughout generations. Novel approaches are also needed, as the current strategies have mainly benefitted the better educated and affluent parts of the population. This can include targeted messaging to the most vulnerable groups, helping to empower patients to manage their illnesses and be in control of lifestyle factors that could exacerbate diseases. We believe that health should also be considered by all policy makers and the wellbeing of a nation should be a crosssectorial responsibility, from transport to education to agriculture. Ensuring health is prioritised during austerity measures should be of particular importance to the finance departments. Important political decisions and advocacy can change this situation and it is up

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© PhotoLizM

Research efforts are currently focused on the development of a universal vaccine that will give life-long protection against any type of flu, which would represent a major breakthrough

to the scientific community to provide policy makers with evidence-based solutions to tackle this problem.

In addition to chronic respiratory diseases such as COPD etc., influenza and other airborne pathogens can have a significant impact on both populations and healthcare systems. How can these more commonplace issues be better understood and targeted? In our fight against respiratory disease, we must not forget commonplace infections. Acute lower respiratory infections are a leading cause of sickness and mortality both in children and adults worldwide. This includes a number of conditions caused by airborne pathogens, such as acute bronchitis and bronchiolitis, influenza, and pneumonia. The best way to prevent infections is via vaccination. Vaccination against pneumonia and influenza is commonly given to groups who are most at risk, such as the elderly or very young or those with lung disease. There is a need to develop new and more effective vaccines to protect against these infections. Research efforts are currently focused on the development of a universal vaccine that will give lifelong protection against any type of flu, which would represent a major breakthrough. Another key complication in the field of infections is the inappropriate use of antibiotics, which are increasingly losing their effectiveness at treating infections. The bacteria that cause the infections are becoming resistant to antibiotics and this is posing a significant threat to patient safety. This resistance is driven by the overuse of antibiotics and inappropriate prescribing. Drug resistance is becoming an increasing problem in the field of tuberculosis (TB) as multi drug-resistant TB (MDR-TB) is

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currently experiencing a dangerous upsurge across Europe. The ERSWHO Electronic Consilium, launched in 2012, aims to improve the clinical management of difficult-to-treat TB cases. The consilium provides evidence-based clinical advice in an online forum to national consilia or individual practitioners on the management of cases.

harness the power of research during an epidemic to advance medical knowledge in this field and, ultimately, save lives. Effective management of pandemics would also include more open communication between scientific societies and health authorities. These networks are already beginning to work together effectively and can now facilitate the exchange of biological material to help develop interventions. For example, there is evidence to suggest that where we have survivors of a pandemic who have built antibodies to resist the infection, if they share these antibodies with newly infected patients, this could improve treatment.

It is vital that we, as healthcare professionals, ensure we are prescribing antibiotics in the right way and that patients only take antibiotics in the manner they were prescribed. Additionally, new therapeutic strategies that can target drug-resistant bacteria must be developed.

According to the WHO, should avian-human reassortants or mutants such as the highly pathogenic H5N1 strains acquire the capacity to transmit effectively among humans (so if it becomes airborne), the outcome could be disastrous. What can be done to either prevent such outbreaks as that seen in 2009 or ensure effective reactionary strategies are in place should/when they occur?

In the last few years, there has been an increase in the number of new viral respiratory infections, predominantly from zoonotic origins. This crossover – from animals to humans – is resulting in new strains of respiratory tract diseases that are unresponsive to current treatment. Our understanding of the transmission mechanisms is still lacking and this has an important impact on the risk of worldwide pandemics such as SARS, MERSCoV, SIV and H5N1. New therapeutic strategies are needed to tackle the threat of viral respiratory pandemics.

Outbreaks of strains of influenza can be deadly. H5N1 strains have caused large outbreaks in poultry in a number of Asian countries. In addition, other avian subtypes such as H9N2, H7N7, H7N3 and H10N7 have recently caused outbreaks in birds and occasionally human disease in various parts of the world. If mutants of these strains acquire the capacity to transmit among humans, it poses a very serious threat. To overcome and understand this threat, there are several strands of action that we can take to plan for the future. These include new research, drug and vaccine development, an increase in funding and awareness, and improved clinical measures. Over the last ten years, there has been little research directly aimed at improving clinical management or understanding pathogenesis during epidemics. The ERS is a partner in a new European Union-funded project which is aiming to create a European framework to ensure clinical research is built into epidemic responses. The PREPARE project aims to address this problem by ensuring that clinical research studies are implemented in the initial wave of an epidemic and enrol patients across the clinical spectrum to develop high-quality evidence to inform future clinical management strategies. The overall aim of this project is to

It is vital that we, as healthcare professionals, ensure we are prescribing antibiotics in the right way and that patients only take antibiotics in the manner they were prescribed

There needs to be better vaccines and better antivirals available and also drugs that increase our immune response and improve repair mechanisms. This is costly and will require input from governments to encourage drug companies to develop these products and take them through to the market. In the clinical setting, we can also improve infection control measures in hospitals. It is common for pandemics to start at a quiet time in a hospital, perhaps when there is a shortage of staff, for example on a national holiday. Effective infection control measures must be in place 24 hours a day, seven days a week, to help prevent the serious threat of pandemics.

In light of the very varied landscape of challenges presented by respiratory diseases, how do you see the ERS’s work evolving? © Kev Shine

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The ERS is one of the leading independent medical organisations in the world working with

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its members on science, education, and advocacy activities to promote lung health and combat lung disease for today’s society and for future generations. We must constantly change and evolve our strategy to ensure we are best serving the respiratory community and, more importantly, our patients, as the ultimate beneficiaries of the advancement of respiratory science and education. Relationships with third parties are an important element of the work we do – whether that is collaborating with other medical societies through the European Chronic Disease Alliance at the EU level or with the World Health Organization. We will continue to build on these relationships to ensure joined-up working when tackling the challenges we face. In January 2015, the ERS launched a new membership strategy which enables national and regional respiratory societies to offer ERS membership as part of their own membership package. This has helped us build strong partnerships with other societies, widen access

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Over the last ten years, there has been little research directly aimed at improving clinical management or understanding pathogenesis during epidemics

to our own scientific and educational resources, and has helped build a strong network across the globe. Working together with patients is vital and this has been an evolution in the way that healthcare is directed and decided upon. Through the European Lung Foundation we will continue to ensure that patients and healthcare professionals can come together in research, guideline production, and policy to ensure the best care for the future. Our Healthy Lungs for Life campaign will also continue to evolve, addressing the key prevention areas and ensuring we are reaching the global community with important messages about keeping healthy and preventing lung disease. Tobacco control, air quality, and advocacy for health research have been our main focuses in recent years and we have made a lot of progress in these areas. We will now look to the new risk factors that are emerging. For example, the unknown area of e-cigarettes is the subject of an ERS task force at the moment to ensure we can provide public health messages that are evidence-based and reliable.

Professor Jørgen Vestbo President European Respiratory Society (ERS) www.ersnet.org

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• H O R I Z O N 2 0 2 0 P RO J E C T S . C O M • Horizon2020projects.com provides up-to-the-minute, invaluable information regarding the European Commission’s latest and largest ever research and innovation framework programme. Horizon 2020, worth almost €80bn, will shape the future of scientific endeavour in the European Union. Its widened remit, which includes the key pillars of Excellent Science, Industrial Leadership and Societal Challenges, means this framework programme will touch more lives and shape more sectors than any previously. The inclusion of such vital new areas as the Future and Emerging Technologies platform, which will see unprecedented funding for the Human Brain and Graphene projects, will push Europe to the forefront of global science. The sheer vastness of this groundbreaking programme, with its myriad areas of focus and significant resources, demands a need to disseminate the enormous levels of information and scientific results that will be generated. Horizon2020projects.com is a website dedicated to providing that information. No area of Horizon 2020 will be left unexplored as we feature news articles and web interviews on all aspects of the framework programme, with contributors from every sector involved. This website covers comments from scientists at the pinnacle of their profession to the policy makers at the European Commission. There is coverage from individual nations, from key Horizon 2020 events and conferences, and from the rest of the world, to provide the most comprehensive database of tailored information available. Along with its sister site, paneuropeannetworks.com, and the publications PEN: Science & Technology and PEN: Government, Horizon2020projects.com is the best place to view everything you need to be up-to-date and in touch with the European Union’s flagship policy: Horizon 2020.

UK tel: +44 (0)1260 273 802 Brussels tel: +32 (0)249 403 57 email: [email protected]

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ESMI PRESIDENT PROFESSOR CHRIT MOONEN DISCUSSES ADVANCES IN AREAS SUCH AS IMAGE-GUIDED SURGERY, ISSUES SUCH AS STANDARDISATION, AND THE ARGUMENT FOR THE REMOVAL OF REGULATORY HURDLES

Imaging is everything

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he European Society for Molecular Imaging (ESMI) represents an academic community developing and validating imaging technologies and multimodality imaging biomarkers in the life sciences and the use of innovative imaging methods to support basic and clinical research. ESMI aims to position itself between existing organisations representing the basic sciences and the translation of this science into clinical applications in diagnostics and therapy. Professor Chrit Moonen

In an interview with Pan European Networks ESMI’s president Professor Chrit Moonen discusses advances in areas such as image-guided surgery, as well as issues such as standardisation and the argument for the removal of regulatory hurdles.

Furthermore, there are also specific processes which have evolved, and this is true overall in nuclear medicine. The same thing is true with MRI and image-guided therapy, as well as the theranostics field overall which allows for the distribution of macromolecules, say a certain antibody, to be imaged before the antibodydrug combination is administered.

What would you say have been the most significant achievements or advances in molecular imaging in recent years, and where do you think the challenges are going to lie moving forwards? Both the past achievements and the future challenges differ from field to field, but in a general sense molecular imaging has a multimodality approach to looking at processes, and this in itself has led to many achievements and advances. Regarding specific fields, one of the things which really deserves a mention is what is now referred to as ‘image-guided surgery’, which has been quite a breakthrough. Image-guided surgery can exist in multiple forms. For instance, laparoscopy and other minimally invasive surgery methods combine

a ‘camera’ (optical, CT, etc.) and surgery. For ESMI, image-guided surgery is more ‘molecular imaging-guided surgery’, and refers to using molecular markers that help the surgeon discriminate tumour tissue from healthy tissue, for example. There have also been achievements regarding specific instrumentation, especially things like photoacoustic, and combined PET/MRI instrumentation, which is directly relevant to the field of molecular imaging.

Laparoscopy and other minimally invasive surgery methods combine a ‘camera’ (optical, CT, etc.) and surgery

There are thus many different examples, and there have been a significant number of achievements and advancements in molecular imaging and the different subfields.

There is a sense that the future of molecular imaging will necessitate a new generation of specialists who are experts in specific clinical fields, rather than in specific imaging modalities. Does this pose a significant challenge? Yes, that is absolutely true, and this is because in the clinic people tend to become specialists in certain imaging modalities. For instance, if you look generally at radiologists, this is a speciality specifically related to imaging, but their knowledge about the technology itself tends to be fairly limited, whereas in the future the lines between different disciplines and roles will begin to merge. That is not something that is well covered for molecular imaging by any such discipline at the moment, and so there is potential for a significant problem to emerge moving forwards.

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Do you have any thoughts on how that can be addressed? From the specialist’s perspective, it may perhaps fall to the professional societies such as ESMI to organise training courses etc. However, how existing professionals get trained in molecular imaging is a question which has not yet been answered.

While no solution exists for this yet, do you think that the recognition for the necessity of this evolution is already there? Yes, the recognition is there; this is clear from my own work with radiologists both in Europe and further afield. However, it is also necessary to properly bridge the fields of nuclear medicine and radiology, as these are the typical specialists who have to deal with it. The molecular imaging societies do quite a lot here, such as training, but your point is certainly well taken and the success in this area thus far is certainly insufficient.

How existing professionals are trained in molecular imaging is a question which has not yet been answered

What do you feel are the biggest hurdles currently facing imageguided surgery, and do you think that new radiopharmaceuticals able to characterise certain aspects of different tumours will help pave the way to a more personalised medicine? Yes, I think they will, and I also think that this is what we need. With regard to image-guided surgery, we have seen a lot of instrumentation being developed, and that has been quite amazing, but the biggest hurdle now is perhaps the specific contrast agents being able to recognise tumour cells and tumour-related processes – which, of course, are closely related to imaging contrast agents for optical (where we have seen very fast progress recently), nuclear medicine, MRI and so on. Indeed, much depends on how well expressed the target really is, but the progress we have witnessed thus far has been incredible. Within the field of image-guided surgery, there is a lot of research concerned with the agents – and this is also related to the developed of new radiopharmaceuticals – particularly with regard to the amount of contrast agent that you really need. In a general sense, on the one hand there is the argument for lowering the regulatory hurdles

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for such contrast agents, and on the other hand the argument that these regulations are necessary given the fact that you are injecting compounds into the body, and so the finding of an appropriate balance becomes an incredibly important point.

The call for a less bureaucratic regulatory framework regarding radiopharmaceuticals is indeed ongoing. What are your thoughts on that debate, particularly with regard to the issues of safety and public acceptance etc.? There are difference aspects to this debate. In the field of nuclear medicine a lot of effort has been made to lower the hurdles for labelled compounds at very low concentrations, and some of these efforts have seen a degree of success. When attention is turned to a different area such as image-guided surgery – which uses mostly fluorescent dyes – then the required concentrations become rather more substantial and regulatory hurdles correspondingly more significant. However, this brings into play the idea of theranostics in that you can use an active compound to first look at the distribution before administering the treatment. As such, this could serve to enhance acceptance levels, in that it is a more targeted treatment. There is a sense that we should see each field as distinct, in many ways, but in a general sense it is clear that if the regulations are weakened too much and problems emerge then this will set us back. It is therefore important to raise awareness of this issue, and to provide assistance to find an adequate middle ground.

What are your thoughts on the ongoing call for a standardisation of imaging procedures? Standardisation is always a hugely important issue, and it is also one which has been insufficiently addressed. Indeed, if you look at it from the point of view of science project grants, standardisation in imaging is quite simply not one of the ‘sexy’ subjects, and therefore doesn’t tend to receive a lot of money, despite the fact that it is hugely important. But that is the nature of grants, I suppose.

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There has been some progress in this area – such as that being made at the National Cancer Institute in the USA, for example – which is great to see, but it will take a lot of work to see the same level of progress in a wider sense because, currently at least, many scientists are not that interested in it. There is also a need for international collaboration in standardisation, within Europe of course, but also with the USA and Asian countries.

Given these and the many other issues, what role do you see ESMI playing moving forwards? ESMI is important because of its intermodality; it covers all the areas we have discussed, from the contrast agents to the target and also the instrumentation, and it is here where we will continue to play a fundamental role. I would also like to see our role in discussions with the granting agencies in Europe grow stronger, because imaging overall plays such a central role, and this is particularly true of multimodality imaging and molecular imaging. The very special role of imaging is now becoming better recognised in Europe where, at CERN for instance, scientists are working on molecular imaging and imaging instrumentation. Indeed, scientists working in this area at CERN have also taken up an initiative to create a European network in medical imaging, with a special emphasis on multimodality and molecular imaging. The role of ESMI, then, should be an important one as it is positioned in between other imaging societies. Such efforts are important as they will work to give imaging more of a voice in the European landscape and especially European programmes.

Do you have any thoughts on Horizon 2020? In the last call in Horizon 2020 the number of imaging-related topics was quite limited, which was somewhat disappointing as I feel that imaging deserves more attention.

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Within the field of image-guided surgery, there is a lot of research concerned with the agents – and this is also related to the development of new radiopharmaceuticals – particularly with regard to the amount of contrast agent that you really need

As imaging plays such an important role in many major fields, the argument for this increased level of attention is certainly there, and so perhaps it now falls to us to not only react and mobilise our members when such calls appear, but also to perhaps provide more of an advisory voice in the preparation of the calls. Image-guided drug delivery is another area which has seen some interesting advances. This is a subfield in molecular imaging which actually pertains more to the classical drugs and how they are developed towards their specific target. If you look at antibodies and how many barriers they have to cross before they can find their specific target, you realise that there are many ways that crossing such barriers can be improved. We have not even touched on the field of regenerative medicine where molecular imaging has a very important role to play in the tracking and differentiation of stem cells.

Professor Chrit Moonen President European Society for Molecular Imaging (ESMI) [email protected] http://www.e-smi.eu/

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PEN LOOKS AT POWERFUL NEUROIMAGING TECHNIQUES SUCH AS MRI AND MEG, AND A NEW PROJECT COMBINING THE TWO

Hybrid imaging technology

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agnetic Resonance Imaging (MRI) – which uses a circular magnet strong enough to pick up a car to produce detailed images of your internal organs – is used by doctors to see which parts of the brain are active when you perform certain tasks or feel certain emotions and sensations. According to the European Magnetic Resonance Forum, MRI has a wide range of applications in medical diagnosis and over 25,000 scanners are estimated to be in use worldwide. It also has an impact on diagnosis and treatment in many specialties, and since MRI does not use any ionising radiation, its use is generally favoured over computed tomography (CT) scans when either modality could yield the same information.

This research team have established the MEGMRI project in an effort to develop and validate hybrid MEG and MRI technology that will allow simultaneous structural (MRI) and functional (MEG) imaging of the human brain. MEG is a non-invasive 3D functional imaging method with a high temporal resolution compared to other kinds of functional imaging. However, the spatial accuracy of MEG may be compromised when structural imaging is performed separately. This problem will be solved by the dual-modality approach of the MEGMRI hybrid scanner, the project’s website states.

MRI is the investigative tool of choice for neurological cancers as it is more sensitive than CT for small tumours and offers better visualisation of the posterior fossa. The contrast provided between grey and white matter often makes it the optimal choice for many conditions of the central nervous system including demyelinating diseases, dementia, cerebrovascular disease, infectious diseases and epilepsy.

Outstanding precision The new scanner is designed to achieve outstanding precision both in visualising the structure of a patient’s brain and mapping its functions. The ability to produce detailed structural and functional maps in a single imaging session would speed up diagnoses, improve the accuracy of the combined scans and facilitate treatment. It is also hoped that the hybrid scanner will be more affordable than a set of individual MEG and MRI scanners.

MEGMRI project Powerful neuroimaging techniques can map the structure and function of a patient’s brain in great detail. They are crucial for the detection and treatment of many illnesses. Now EU-funded researchers, who built a prototype of an innovative hybrid instrument, have argued that combining two complementary neuroimaging techniques – magnetoencephalography (MEG) and MRI – could provide even better brain scans. Magnetic Resonance Imaging (MRI) is used by doctors to see which parts of the brain are active when you perform certain tasks or feel certain emotions and sensations

Building the prototype involved designing highly advanced sensor technology and harnessing new developments in ultra-low-field MRI. The partners are now fine-tuning and upgrading the device to develop a blueprint that would enable a private sector partner to bring the technology from the lab into hospitals. According to the researchers, the hybrid technology opens up a range of new possibilities. It could, for example, provide neurosurgeons with faster, more detailed information before an operation, or help to detect brain tumours at a very early stage. The team expects the finished instrument to be ready for commercialisation by 2020.

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COMBINED FOR ACCURACY By combining ultra-low-field MRI and MEG with magnetic-field detectors approaching fundamental limits, BREAKBEN aims for super-accurate electromagnetic brain imaging

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rain disorders cause a great deal of suffering and a major economic burden to society; the annual cost in Europe alone has been estimated at €800bn. The goal of the Horizon 2020 Future and Emerging Technologies project BREAKBEN is to dramatically improve the accuracy of magnetoencephalography (MEG) in characterising electrical activity in the brain. This will be done by combining MEG with another powerful electromagnetic imaging technology, magnetic resonance imaging (MRI). By measuring the ultra-weak magnetic fields generated by the brain, MEG can non-invasively inform us about neuronal function. MRI, on the other hand, maps the tissuedependent behaviour of nuclear spins in water molecules, providing accurate structural images. The simultaneous measurement of both MEG and MRI will be key to improving diagnostic information. In BREAKBEN, superconducting SQUID-sensor arrays will be used. The MRI signals are recorded at far weaker magnetic fields than the usual convention, i.e. at about 100 microtesla instead of several tesla. BREAKBEN’s predecessor, the MEGMRI project (2008-2012), indicated that a clinically useful hybrid MEG-MRI system may be possible. The challenge is huge, since the signalto-noise ratio in the MRI measurement must still be improved by a factor of at least 1,000 in circumstances where the relevant magnetic field strengths cover a range from 1 femtotesla to 0.1 tesla or 14 orders of magnitude. The new technology is expected to improve, for example, the mapping of epileptic brain activity. It may also enhance the diagnosis of cancer patients thanks to improved image contrast at ultra-low MRI fields. The MEG-MRI device will also open brain imaging for new patient groups, such as those with metal implants. Cost reductions may be expected thanks to improved workflow and more accurate diagnostics that can shorten hospital stays and optimise treatment. Furthermore, there is hope that the new device can be used to measure the conductivity structure of the brain, which would improve the accuracy of locating brain activity with MEG as well as with EEG. This would also enable further improved accuracy in transcranial magnetic stimulation (TMS) of the brain, a technique also under further development at Aalto University. The co-ordinator of BREAKBEN, Aalto University, together with Elekta, will build the hybrid device. The VTT Technical Research Centre of Finland will develop a new generation of optimised SQUID-sensors. The technology will be used by the BioMag Laboratory of the Helsinki University Hospital in patient trials and by University of Chieti-Pescara in studies of brain connectivity. In a highly ambitious development taking place at

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Physikalisch-Technische Bundesanstalt, Berlin, scientists intend to make another breakthrough by detecting neuronal currents by nuclear magnetic resonance (NMR) techniques, a task often considered nearly impossible but now within reach. Sophisticated ‘phantoms’ will be developed by Ilmenau University of Technology to mimic the properties of the human head and brain in order to allow testing of the sensitivity and accuracy of the developed instruments. References J Olesen et al., The economic cost of brain disorders in Europe, Eur. J. Neurol. 19:155 (2012). R Körber et al., An improved phantom study assessing the feasibility of neuronal current imaging by ultra-low-field NMR, J. Magn. Reson. 237: 182–190 (2013). JO Nieminen et al., Current-density imaging using ultra-low-field MRI with adiabatic pulses, Magn. Reson. Imaging 32:54–59 (2014). PT Vesanen et al., Hybrid ultra-low-field MRI and magnetoencephalography system based on a commercial whole-head neuromagnetometer, Magn. Reson. Med. 69:179 (2013).

Risto Ilmoniemi Academy Professor Department of Neuroscience and Biomedical Engineering Aalto University School of Science +358 (0)50 556 2964 [email protected] https://people.aalto.fi/index.html#risto_ilmoniemi

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PEN EXPLORES SEVERAL ISSUES SURROUNDING MENTAL HEALTH AND NEURODEGENERATIVE DISEASES AND THE WORK BEING DONE TO ADDRESS THEM

NDGs and mental health O ver 600 disorders afflict the nervous system, and the European Commission defines neurodegenerative diseases (NDG) as ‘hereditary and sporadic conditions which are characterised by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral structures of the nervous system. They include diseases such as Alzheimer’s and other dementias, brain cancer, degenerative nerve diseases, encephalitis, epilepsy, genetic brain disorders, head and brain malformations, hydrocephalus, stroke, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), Huntington’s disease, prion diseases, and others.’

correctly folded by using powerful and sophisticated mechanisms to maintain protein homeostasis under adverse conditions. However, with age, the cellular defence systems against misfolded proteins seem to gradually fail, leading to the accumulation of misfolded proteins, with devastating consequences for cells and organisms. Therefore, improving the cells’ ability to deal with misfolded proteins could be useful to reduce and prevent neurodegenerative diseases.’

The framework of health information on neurodegenerative diseases sometimes includes brain diseases, defined as pathologic conditions also affecting the brain (composed of the intracranial components of the central nervous system). This includes (but is not limited to) the cerebral cortex, intracranial white matter, basal ganglia, thalamus, hypothalamus, brain stem, and cerebellum, the Commission’s website dedicated to this area adds.

Research led by Anne Bertolotti at the LMB has identified a novel, selective and safe pharmacological approach to boost a natural cellular defence against misfolded proteins and thus safely preventing protein misfolding diseases in mice.

Misfolded proteins According to the Medical Research Council’s (MRC) Laboratory of Molecular Biology’s (LMB) Neurobiology Division at the University of Cambridge, UK, the deposition of misfolded proteins is a defining feature of many age-dependent human diseases, including the increasingly prevalent neurodegenerative diseases. ‘Why this happens is unclear,’ the LMB says, adding: ‘Cells normally strive to ensure that proteins are

New research at the MRC’s LMB could be a first step towards developing drugs to prevent neurodegenerative diseases

Using cultured cells and mice as a model organism, the research group has found a small molecule named Sephin1 (a selective inhibitor of a holophosphatase), which selectively binds and inhibits PPP1R15A, a regulatory subunit of the protein phosphatase PP1, to safely prolong the benefit of a phosphosignalling pathway and prevent the motor, histological and molecular defects of two otherwise unrelated diseases in mice, Charcot-Marie-Tooth 1B and amyotrophic lateral sclerosis. This small molecule boosts the natural cellular defence systems against damaged proteins and prevents them from accumulating and becoming harmful. This demonstrates that selective inhibition of PPP1R15A can safely prevent two neurodegenerative diseases caused by the misfolding of proteins in mice. It also establishes that phosphatases, up to now thought of as unsuitable drug targets, are targetable, opening up a broad range of possibilities to manipulate cellular functions for potential therapeutic benefits. This research – which was funded by the MRC, the European Research Council, EMBO, the Human Frontier Science Program, the Swiss National Science Foundation, the Italian Ministry

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of Health and NIH – could be a first step towards developing drugs to prevent neurodegenerative diseases.

JPND The EU Joint Programme, Neurodegenerative Disease Research (JPND), is the largest global research initiative aimed at tackling the challenge of neurodegenerative diseases. JPND aims to increase co-ordinated investment between participating countries in research aimed at finding causes, developing cures, and identifying appropriate ways to care for those with neurodegenerative diseases. The ultimate goal of JPND is to find cures for neurodegenerative diseases and to enable early diagnosis for early targeted treatments. However, it does point out that it is not possible to give definitive predictions on how long this might take. In the interim, JPND has identified strategy common research goals through its research that would benefit from joint action between countries in order to accelerate progress on solutions that can alleviate the symptoms and lessen the social and economic impact for patients, families and healthcare systems.

Dementia According to the JPND, amongst the neurodegenerative diseases afflicting the European population – such as Alzheimer’s and Parkinson’s, which it describes as debilitating and largely untreatable conditions that are strongly linked with age – the dementias are responsible for the greatest burden of disease, with Alzheimer’s disease and related disorders affecting over seven million people in Europe. This figure is expected to double every 20 years as the population ages. The JPND website continues: ‘It currently costs approximately €130bn per annum to care for people with dementia across Europe, highlighting age-related neurodegenerative disease as one of the leading medical and societal challenges faced by EU society. Alzheimer’s disease is particularly expensive to manage due to its insidious onset, its everincreasing levels of disability and the length of time over which the condition extends itself. The average duration of this disease is between two and ten years, during which patients will require special care that is a significant burden for both caregivers and for society as a whole.

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‘While large investments have been made in other diseases such as cancer and cardiovascular disease (and we have consequently seen major improvements in treatment and patient outcomes), to date neurodegenerative diseases have not received the same level of funding, despite having a large negative impact on healthy life years.’ As existing treatments for neurodegenerative diseases are very limited, and only treat the symptoms, rather than addressing the cause, and as no new drug treatment for Alzheimer’s disease has been approved in the past five years, the work of the joint programme will be crucial in addressing the burden posed by neurodegenerative diseases moving forwards.

Mental health In addition to – and often alongside – neurodegenerative diseases, mental health issues such as depression also have a significant impact on the health of people across the world. Indeed, the European Depression Association reveals that depression affects 350 million people globally, with direct medical costs associated with managing the condition estimated at some €38bn in the EU alone. Depression is also predicted to become the ‘leading cause of burden by 2030’, according to the organisation. This burden has been highlighted by the WHO in its Comprehensive Mental Health Action Plan 2013–2020, which, the organisation says, ‘focuses international attention on a long-neglected problem and is firmly rooted in the principles of human rights. The action plan calls for changes. It calls for a change in the attitudes that perpetuate stigma and discrimination that have isolated people since ancient times, and it calls for an expansion of services in order to promote greater efficiency in the use of resources.’

World Mental Health Day The issue of stigmatisation was also addressed by the 2015 instalment of World Mental Health Day, which took place on 10 October and which took the theme of ‘Dignity in mental health’. According to the WHO, thousands of people with mental health conditions around the world are deprived of their human rights. As well as being discriminated against, stigmatised and marginalised, they are also subject to emotional and physical abuse in both mental health facilities and the community. Poor quality care due to a lack of qualified health professionals and dilapidated facilities leads to further violations. The WHO is therefore raising awareness of what can be done, and what is being done, to ensure that people with mental health conditions continue to live with dignity, through human rights-oriented policy and law, training of health professionals, respect for informed consent to treatment, inclusion in decision making processes, and public information campaigns. With an ageing population – by 2025 more than 20% of Europeans will be 65 or over, including an incremental growth in the number of over80s – set to further increase incidences of both neurodegenerative diseases and issues concerning mental health, the need for a better understanding of these conditions on the part of the general populace and the concomitant alteration of perceptions is self-evident. Likewise, with new ground being broken into the causes of some neurodegenerative diseases, perhaps new treatment pathways are almost in sight, and with them a reduction in the number of people suffering from these illnesses.

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MOVING AGAINST PAIN The Pain Research Group of the i3S-University of Porto is taking action against chronic pain

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hronic pain is a complex somatic and psychosocial disease that represents a major health problem worldwide. In Europe, 19% of adults suffer from moderate to severe pain. Of those, 34% are in severe pain and 46% in constant pain (Breivik et al., Europ. J. Pain 2006). In Portugal, chronic pain afflicts 37% of the adult population, with total direct (43%) and indirect (57%) annual costs of €4.6bn (2.7% of national GDP) (Azevedo et al., J. Pain 2012). The discovery of new and more potent tools to treat pain is a healthcare priority. Although there is major agreement on that, understanding how chronic pain is generated is essential for the design of therapeutic strategies, data on the neuronal changes that underlie the development of chronic pain and the multiple physical, affective and cognitive conditions associated are scarce. The pain system, while based on a well structured sensory circuitry, brings into play multiple brain centres that, collectively, integrate nociception with other brain functions by adjusting neuronal processing at various levels. Maladaptive changes resulting from particularly intense, long lasting or abnormal pain conditions are believed to lead to malfunctioning of the system with the consequent development of chronic pain. The Pain Research Group at i3S_UPorto is devoted to the understanding of various aspects of chronic pain through a

Alternative promoter regions and neuronal specific regulatory elements of the Prrxl1 gene (From Regadas et al, J. Biol. Chem, 1839, 2013)

multidisciplinary approach, which departs from the neurobiology of the nociceptive system and the plastic changes taking place when chronic pain develops, to the study of specific human pain conditions and their social and economic impact. Following a major contribution to the anatomo-functional characterisation of the nociceptive system, the group is now devoted to the study of the physiopathology of chronic pain. More specifically, we look for chronic pain-induced genetic, neurochemical and electrophysiological changes at the DRG-spinal circuit, the supraspinal pain control circuit and the affectivecognitive circuit. This is accomplished through the engagement of research leaders specialised in each domain and with specific expertise in the appropriate methodological approaches. At the DRG-spinal level, the work develops on two fronts. One team, co-ordinated by Fani Neto, deals with the molecular changes taking place in peripheral neurons upon the establishment of chronic pain. Molecules involved in neuronal damage and repair, such as the neuronal injury markers ATF3 and NPY and the regeneration marker GAP-43, whose expression is increased in both inflammatory and mixed inflammatory/neuropathic pain models, are under focus. The role of the neuronal/glia interplay in these molecular mechanisms is also being investigated, with particular emphasis on diabetic neuropathy, where the expression of the potassium chloride co-transporter is affected, with marked glial activation at the spinal cord.

DRG satellite glial cells are activated in monoarthritic animals (From Nascimento D, Neurosignals 19, 2011)

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The team co-ordinated by Deolinda Lima and Carlos Reguenga looks for putative molecular players at the peripheral and spinal levels through the search for genes involved in development, differentiation and synaptic connectivity of nociceptive DRG and

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spinal neurons, and deregulation of their expression in chronic pain conditions. Developmental studies using expression microarray and ChIP-seq approaches are tracking genes involved in the establishment of the DRG-spinal nociceptive circuitry and, by the use of homemade mutant models, elucidating their role in the differentiation of its various components. In parallel, molecular biology studies investigate transcription and post-translation expression regulating mechanisms. Research on the supraspinal pain control system follows our pivotal results on the occurrence of a brainstem centre, the dorsal reticular nucleus, specifically dedicated to pain facilitation. The main objective is to investigate the role of descending pain facilitation and its interaction with the inhibitory system in the establishment of chronic pain. These studies, co-ordinated by Isaura Tavares, have under focus the aminergic system and its interface with the opioidergic and GABAergic systems. They combine tracing, neurochemical and behaviour approaches with classical pharmacology, gene transfer strategies for neuronal transduction and microdialysis-based neurotransmission evaluation. Among other important findings, it was shown that afferent noradrenergic input into the DRt has pronociceptive effects which, once locally counteracted, result in a potent analgesic action. Although still playing an important role in chronic pain, descending facilitation from the DRt was shown to be endogenously reduced in such condition through an increase in GABAergic inhibition of the spinal afferent trigger. Accordingly, reinforcing DRt activity decrease during chronic pain through spinal administration of GABA receptor agonists has a potent analgesic effect. Studies on affective-cognitive impairment induced by chronic pain and the underlying molecular and circuitry mechanisms are conducted by Vasco Galhardo. Research is based on optogenetic stimulation and multielectrode neurophysiological recording coupled to behavioural evaluation in conscious animals. Circuitry organisation changes supporting pain-induced cognitive defects are being revealed, such as reduced connectivity between the prefrontal cortex and the mediodorsal thalamus in impaired spatial working memory, and reduced dopamine-dependent hippocampal-prefrontal cortex connectivity and dorso-ventral hippocampal connectivity in impaired working memory. As to strategic planning and risk assessment, which is also disrupted in both inflammatory and neuropathic pain conditions, altered prefrontal cortex neuronal activity occurs due to enhancement of amygdala-driven inhibition of medial prefrontal neurons.

Less information is processed in the mPFC– dCA1 circuit after peripheral nerve lesioning (From Cardoso-Cruz H, J. Neurosci. 33, 2013)

The Pain Research Group, as a whole, has recently joined efforts to investigate in detail the noradrenergic and serotoninergic molecular mechanisms that lead to chronic pain by interfering with neurotransmitter and receptor expression at various time points of chronic pain development in inflammatory and neuropathic pain models. With this purpose in mind, the lab is now producing conditional mutants specifically designed to meet questions related to the role of both systems in intra-brain and descending pain control, pain-elicited depression and anxiety and reward encoding during chronic pain. The Pain Research Group also counts on a team dedicated to epidemiological studies addressing the social and economic impact of chronic pain, co-ordinated by José Castro Lopes. Beyond the aforementioned data on chronic pain prevalence in Portugal, there is now evidence that proves Portuguese women are more affected than men, and that lower back pain and other osteoarticular and musculoskeletal diseases are the main contributors to chronic pain in Portugal. It has also been shown that post-surgery pain, reported by 71% of the patients 48 hours after surgery, evolves to chronic pain in 15%.

Deolinda Lima Full Professor, Head of Pain Research Group Faculty of Medicine and i3S Instituto de Investigação e Inovação em Saúde Universidade do Porto +351 (0)22 042 6780 HSV-1-mediated knock down of noradrenaline release in the DRt reduces pain (From Martins et al., Neuropharmacology 71, 2013)

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[email protected] https://sigarra.up.pt/fmup/pt/web_page.Inicial

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EUPHA’S PROFESSOR CHIARA DE WAURE MET WITH PAN EUROPEAN NETWORKS AT THE EIGHTH EUROPEAN PUBLIC HEALTH CONFERENCE IN MILAN TO DISCUSS TELESTROKE AND THE CHALLENGES INVOLVED IN ITS WIDER IMPLEMENTATION

Telemedicine in acute stroke

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elestroke – the employment of telemedicine in the field of stroke care and treatment – involves doctors with advanced training in the nervous system (neurologists) who remotely evaluate people suffering from acute strokes in order to make diagnoses and treatment recommendations to emergency medicine doctors at other sites. This necessarily involves the use of digital video cameras, internet telecommunications, robotic telepresence, smartphones, tablets and other technology.

telestroke, as well as the fact that some of the older generations of healthcare professionals working in this field may not be aware of this necessity – just as they may not be familiar with the new technologies in healthcare which are so integral to its success. Chiara de Waure

Professor Chiara de Waure, vice-president of the European Public Health Association’s (EUPHA) section on Health Technology Assessment (HTA) met with Pan European Networks at the eighth European Public Health Conference in Milan (entitled ‘All for Health – Health for All’) to discuss telestroke and the challenges involved in its wider implementation.

What do you feel are the biggest challenges facing the use of telestroke today? There are perhaps two types of challenge. The first concerns evidence, or the lack of evidence, as to the effectiveness of telestroke. The second is with regard to the importance of multidisciplinary teams involved in Telestroke should not only be viewed as something of benefit to the patient, but also to the emerging body of research surrounding it

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Given the fact that in telestroke many people work together as a team (i.e. a programme manager, clinical co-ordinator, vascular neurologists, neurosurgeons and radiologists at the hub site, and emergency medicine doctors and other staff at the stroke site, as well as radiology technicians, information technology staff, researchers, nurses, nurse practitioners and other staff), what challenges are involved in maintaining a productive multidisciplinary team? Training staff is crucial, and staff could attend courses to familiarise themselves with the importance of this type of approach and the new technologies involved. To ensure that a multidisciplinary team is established and maintained, it is vital to have well-defined clinical pathways, within which everyone involved is aware of their role and responsibilities so that they are able to work in a linear and effective way. Again, this can be related to training in that staff can be trained in leadership, co-ordination, and so on. Indeed, these are elements which have now been incorporated into many university education training programmes, which means that the newer generations of medical doctors, for instance, are coming into the field with not only a knowledge of these areas, but also having come from an educational background where this is the norm.

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Residency is also a very good point at which to train people, because they are already medical doctors by this point, and so they already know all the clinical pathways. They can then go on to become knowledgeable in areas like leadership, co-ordination, and integration. In addition to the doctors involved in telestroke, many of the other professions, such as the nurses, for example, are already being trained in the importance of multidisciplinary working as a part of their education. As such, if clear clinical pathways are defined early on, and everyone is aware of both their own role and the role of the other professionals involved, then the necessary multidisciplinarity demanded by telestroke does not, perhaps, pose too much of a problem. However there is, of course, the issue of scientific language barriers. That is, a medical doctor is unlikely to be well-versed in the technical terminology used by the IT professionals involved in the pathway, and vice versa. As such, it is important to create something of a common vocabulary to ensure the effective communication between disciplines.

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Many healthcare professionals are now being trained in the importance of multidisciplinary working as a part of their education

Telestroke has the potential to enhance patient entry into clinical trials. What are your thoughts on this? This is indeed a great opportunity, and one that we must seize. It is well known, for example, that telestroke allows for patients to be directed to specific centres depending on their status, and so this provides the opportunity for some of them to be entered into a clinical trial. This is crucial from a research point of view because telestroke should not only be viewed as something of benefit to the patient, but also to the emerging body of research surrounding it, and it is only through more research that we will be able to enhance the evidence base, which is fundamental to informing decision makers. This also helps us to establish networks, which is an essential point, particularly when it is understood that some hospitals can often be excluded from research because of their location or because their main mission is different to that of the research centre. By creating a network, however, the researchers are able to access a much wider range of patients for inclusion in clinical trials which is, of course, of benefit for all concerned.

Telestroke also provides an excellent medium for data collection and an unprecedented opportunity for quality assurance. How would you like to see this potential being realised? This is maybe the most significant opportunity for telestroke, although perhaps I am a little biased as I am an epidemiologist, and so I like to collect data. Nevertheless, it is key to be able to look at things such as the recording of procedures and the ability to provide real-time

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communications etc. because this enables the provision of complete patient data. Of course, this will mean that the healthcare professionals involved in the pathway will have to work closely with the IT team very early on to make sure that in the future the data will be accessible and usable. This is vital because when new types of working are established they are usually done so for operational or organisational reasons, and the potential for research down the line can be neglected. There is indeed the potential for this type of research within telestroke because a lot of data is generated, the quality of which can be checked at a later date by, for example, the type of committee that exists for clinical trials, which is in place to evaluate the outcome. The results of this research are also of use to decision makers who have to choose whether or not to invest in telestroke. It is thus paramount to think about this element beforehand so that you can ensure you have the right data, or at least the right way of storing it so as to make it useful.

How do you feel the legal and economic parameters need to be established for telemedicine in the areas of reimbursement, liability, malpractice insurance, licensing, and credentialing? And what are your thoughts on other related issues such as the protection of privacy and confidentiality, informed consent, product liability, and industry standards? This is a very complex issue, and while some areas such as the protection of data already have programmes and initiatives and legislation covering them, they nevertheless remain contentious. To take data protection as just one example: our data – whether it be from our online banking or other personal and valuable details – are stored by a multitude of companies and organisations, and so if this is done without much of an issue on the part of citizens, then the same should be true of the storing of their records and medical information.

If clear clinical pathways are defined early on, and everyone is aware of both their own role and the role of the other professionals involved, then the necessary multidisciplinarity demanded by telestroke does not, perhaps, pose too much of a problem

While some areas such as the protection of data already have programmes, initiatives and legislation covering them, they nevertheless remain contentious

However, there have been instances of people’s data being hacked or stolen from various places online, and so perhaps some of the fears expressed by the public on the storing of their medical data arises from these instances. Data accessibility is a significant issue and while, of course, patient confidentiality has to run tandem to data security, the instruments are there to ensure patient anonymity, and so the perceived problems surrounding data are perhaps not as large as one may first think. From an organisational point of view, it is perhaps time to now look at technology assessment levels. As the vice-president of the EUPHA section on Health Technology Assessment, I believe that this is the best instrument through which to provide answers to these diverse areas because it deals also with organisational, legal, social and economic problems.

Professor Chiara de Waure Università Cattolica del Sacro Cuore Vice-president EUPHA Section on HTA [email protected] http://eupha.org/index.php

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STEM CELLS & FUNCTIONAL GENOMICS The Institute of Neurology outlines their work on how to model neurodegenerative disease using stem cells and functional genomics

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he transformative discovery of induced pluripotent stem cells (iPSCs) less than a decade ago allowed human disease modelling ‘in a dish’. Building on the earlier seminal work of Sir John Gurdon (Cambridge) and Sir Ian Wilmut (Edinburgh), a laboratory led by Shinya Yamanaka discovered a method to generate embryonic-like stem cells from their adult somatic counterparts by using viral transduction of up to four transcription factors. This ‘nuclear re-programming’ allows any nucleated cell to be transformed into stem cells with a remarkable capacity to differentiate into any cell type comprising the human body (termed ‘pluripotency’). This advance has raised tremendous experimental excitement and opportunity including elucidation of initiating pathogenic events in a fully human model system where mutations are conveyed at their pathophysiological levels. In order to truly harness the potential of the iPSC technology in regenerative medicine, robust paradigms to ‘guide’ the differentiation of stem cells into desired region-specific cellular populations are required. Furthermore, cell type-specific functional validation is critical to ensure faithful recapitulation of the requisite developmental instructions that ‘program’ cell fate. To this end, rapid progress is being made with accumulating evidence strongly reinforcing the validity of this approach for resolving underlying disease mechanisms, preclinical drug testing, toxicity screens for different clinically prescribed medications, and potential cellular implantation therapies in the future.

Understanding defects in protein-RNA complexes We study how gene expression is regulated at the level of RNA molecules. Each RNA molecule passes through several regulatory stages, which are controlled by protein-RNA complexes. Mutant RNA-binding proteins and non-coding RNAs are implicated in amyotrophic lateral sclerosis (ALS). We therefore wish to understand how disease-causing mutations affect the composition of protein-RNA complexes and thereby disrupt RNA regulation in a manner that may ultimately cause neurodegeneration. Moreover, we study how protein-RNA complexes participate in the neuronal stress response pathways.This will ultimately permit a mechanistically rationalised

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approach to development of new therapies, which are desperately needed in the arena of neurodegenerative disease.

Our research strategy The human central nervous system has been previously inaccessible to dynamic experimental testing. The advent of iPSCs now permits fundamental insights into both development and disease of different regions of the human nervous system. We study iPSCs derived from patients with monogenetic neurodegenerative conditions, but with particular focus on ALS. We generate enriched populations of iPSC-derived spinal cord motor neurons or glia to discriminate cell autonomous and non-cell autonomous mechanisms of disease. We develop transcriptomic techniques such as UV cross-linking and immunoprecipitation (iCLIP) to examine protein-RNA interactions in iPSCs. This enables us to examine how molecular pathogenic events emerge at specific stages of iPSC differentiation. Through this approach, we aim to identify and discriminate the primary and secondary molecular pathogenic events. This will help to define candidate molecular pathways as targets for small molecule screens.

Rickie Patani, MD PhD Wellcome Trust Clinician Scientist UCL Institute of Neurology +44 (0)2076 794264 [email protected] http://goo.gl/0rz6Xp Jernej Ule, PhD Professor of Molecular Neuroscience UCL Institute of Neurology +44 (0)2031 087462 [email protected] http://www.ulelab.info/

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IMPORTANCE OF ORGANISATION The Stroke Centre talks about the many stages of effective stroke treatment, and the importance of being organised

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troke is a leading cause of death and disability and is associated with high costs.1 Age-adjusted stroke rates have declined in many high income countries, but have risen in low and middle income countries. The stroke incidence increases with age while the elderly population is growing, and effective stroke care is essential. The cornerstone of evidence-based and efficient stroke care is organisation. This applies to collaboration with pre-hospital services within the individual departments, as well as between departments, regions and across sectors. The level of organisation must allow stroke patients to receive relevant investigations within the existing framework, then the best and individualised treatment can be started without wasting time. Patients requiring highly specialised diagnostics and treatment need to be identified anywhere in the system and referred to the relevant specialised departments. Stroke patient care requires a close interdisciplinary cooperation in assessment, treatment and rehabilitation. A well-functioning multidisciplinary organisation requires strong monodisciplinary expertise, monitored quality measurements, the ability to learn from mistakes and to be constantly moving towards improved co-operation.

The patient path The stroke patient path should be seen as a whole, beginning at the pre-hospital phase, where all phases are important. The rehabilitation will soon begin at the hospital and continues at the municipal level. Sector transition from hospital to the municipality implies a risk of discontinuity and must therefore be in focus, with preparation of rehabilitation plans and follow-up by the GP or hospital following clear guidelines. There will be different ways to build the level of organisation when it comes to the individual department and municipality detailed planning, but the overall guidelines, co-operation between sectors, regions and at the national level is important and is described below, as organised in Denmark. The public health system in Denmark is categorised into five regions. In the Danish population, 4,449,881 are 18 years old or above and 10,822 strokes were registered in 2014. Denmark was one of the last countries in Europe to offer IV thrombolytic therapy (IVT) to ischaemic stroke patients. IVT was first offered in all five regions in 2008 but, in return, the level of

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organisation is now so efficient that Denmark is one of the most efficient countries in the world in terms of the number of thrombolysis treatments per capita. The explanation for the quickly achieved success is the organisation of stroke treatment, which was secured in the late 1990s, through the establishment of nationwide stroke units and a mandatory Danish Stroke Registry that monitor quality indicators in the acute phase. The network of stroke units with established guidelines and requirements for the treatment and co-operation could quickly change the visitation of the hyperacute stroke patients to centres with thrombolysis emergency bypassing the local section, while the follow-up treatment could be carried out after thrombolytic therapy via local stroke units. All five regions have at least one IVT centre, of which there are nine in total with three as highly specialised centres – Aarhus, Odense and Rigshospitalet – responsible for the endovascular treatments (EVT). Telecom Thrombolysis is established between thrombolysis centres and co-operating units in some regions, including the Faroe Islands. The numbers and locations of IVT and EVT centres is determined based on geography and population. The staff must have a routine in the reception, assessment and treatment of patients without delay, which requires high patient flow. Simultaneously, however, journey times should be limited and generally not exceed 60 minutes. There are established national clinical guidelines describing the organisation and demands on the quality of treatment (www.sst.dk). A national IVT and EVT advisory group, with participants from all regions, is responsible for updating the guidelines, commenting on the annual report from the Danish Stroke Registry before publication, and meeting regularly to exchange ideas on the improvement of organisation. IVT and EVT centres have an obligation to be active in the development of acute treatment and quickly implement new processes in the ongoing effort to reduce the damage after a stroke.

Prehospital In the hyperacute phase, working directly with the pre-hospital ambulance service is of utmost importance and there is direct contact between the ambulance crews and the specialist on the IVT and EVT centres to ensure optimal visitation. The transport will always be via emergency vehicle, or by helicopter for greater

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distances (i.e. patients from the islands). In the capital region of Copenhagen, we found that on-scene time constituted nearly half of the total alarm-to-door time and is thus a point of focus for improvement.2

Hospital The revised emergency response has had a positive impact on the entire stroke area, with 47% of stroke patients in Denmark admitted within four-and-a-half hours after symptom onset. The major problem is in acute stroke patients recognising (or not recognising) the symptoms. Furthermore, if the patient is disabled they may have difficulty making the emergency call, or are often dependent on others to call for help. The stroke onset time can be difficult to determine, in such instances as patients awaking with symptoms, for example. In 2014, 1,470 ischaemic stroke patients were treated with IVT and 207 with EVT. The national door-to-needle time for IVT was 34 minutes on average (a range of 21-43 minutes), and the median time from stroke onset to IVT centre door was 96 minutes (93-185 minutes). Because of contra-indications or spontaneous remission of symptoms, only about 30% of all received stroke patients receive the treatment within the time window for IVT, but all benefitted from the fast track, resulting in initiation of treatment without delay.

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desirable. The stay on the stroke units is short and, with the brain often affected by the acute injury, much of the information and guidance should be repeated after the acute phase. Complications such as depression, pain, spasticity, seizures or dementia can occur and must also be treated. Data from the Danish Stroke Registry has considerably improved stroke treatment in Denmark. We have learnt that higher quality of care during the early phase of stroke was associated with a lower risk of medical complications and a shorter length of stay in hospital,3,4 and treatment with IVT in patients with ischaemic stroke was associated with improved long term survival.5 The mandatory use of the Danish Stroke Registry has played a crucial role in pushing organisation in the right direction. The performance and quality of each stroke unit is annually compared and published with all staff, leaders of the departments, managers and local politicians held responsible. With this responsibility, actions are taken in order to optimise the stroke patient path for the benefit of all. References 1 Feigin VL et al. Lancet 2014;383(9913):245-254 2 Simonsen SA et al. Scand J Trauma Resusc Emerg Med. 2014 Nov 13;22:65 3 Ingeman A et al. Stroke. 2011;42(1):167-72

The subacute phase

4 Svendsen ML et al. Med Care. 2009;47(5):575-82

It is well known and evidence-based that treatment in stroke units works for all patients regardless of age, gender or severity of the stroke. The pathophysiological assessment must be carried out as soon as possible after admission, and an intensive treatment used to target the most likely cause of the stroke (cardiac embolic stroke, stenosis or dissection of the pre-cerebral arteries and cerebral hypoperfusion) must be initiated. On the first day, the neurologic and circulatory status is monitored systematically to catch the worsening of symptoms and to act on this as soon as it occurs. The interdisciplinary teams work to prevent complications of the disease such as infections or fall episodes, and to start early mobilisation and rehabilitation. The acute diagnostic work-up and treatment on the stroke units are monitored by the Danish Stroke Registry (https://www.sundhed.dk/sundhedsfaglig/kvalitet /kliniske-kvalitetsdatabaser/hjerte-kar-sygdomme/apopleksi-nip/).

5 Schmitz ML et al. Stroke 2014;45(10):3070-2

Discharge

[email protected] https://www.glostruphospital.dk/forskning/forsk ningsomraader/Sider/Enhed-for-KliniskApopleksiforskning.aspx

More than half of the stroke patients are discharged directly from the acute stroke unit, possibly with a rehabilitation plan in hand, which guarantees the continuation of training at the municipal level. Patients with need for in-hospital rehabilitation are transferred to specialised units. It is important to prepare the patient upon discharge and explain the importance of the continued prophylactic actions. A discharge letter should be sent to the patient’s GP. In parallel with the described sectoral transition, offering a follow-up consultation in the hospital is

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Helle K Iversen, MD, DMSci Clinical Research Associate Professor Stroke Centre Rigshospitalet - Glostrup +45 (0)2423 8196

Grethe Andersen, MD, DMSci Professor Danish Stroke Centre Aarhus University Hospital http://www.en.auh.dk/departments/head-andheart-centre/danish-stroke-centre/

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THE EFN’S SECRETARY-GENERAL DR PAUL DE RAEVE CALLS FOR NURSES TO BE MADE MORE VISIBLE IN THE ONGOING POLITICAL DEBATE SURROUNDING PERSONALISED MEDICINE AND DEMENTIA

Personalising dementia care

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cross the world, an estimated 44 million people now live with dementia; this number is set to double by 2030 and triple by 2050.1 Dementia is one of the most debilitating conditions in modern society with huge health, social and financial implications.2 People’s lives, families and communities can be disrupted from the onset of dementia, while dementia is also increasingly considered as one of the leading causes of death among older adults.

The direct financial cost of dementia to the European Union is estimated to be in excess of €130bn a year.3 Tackling the dementia challenge must become a priority for all EU governments if this is to be contained and not spiral out of control in the coming years. Therefore, co-ordination at the European level is paramount if the EU is to respond to this challenge collectively. Governments must continue to develop strategies that deal with dementia holistically, focusing on prevention and risk reduction as well as on the provision of ‘personalised medicine’ for people with dementia and their families.

Socioeconomics From a social and economic rationale, it is necessary to focus on preventive care, helping citizens to have the best chance of remaining free from disease and at the same time improve the care itself, making it more person-centric. Nurses are in the unique and privileged position of having direct access to the daily care needs of people with dementia, and have a key role to play both in managing and preventing this condition. There is substantial evidence indicating that the risk of developing dementia can be modified through a healthier lifestyle, including better control

and detection of hypertension, diabetes, and other cardiovascular risk factors.1

Personalised medicine

Dr Paul De Raeve

Nurses have a key role in public health and prevention in particular due to their unique insight of the patient experience and familiarity with people’s social and family contexts. This enables them to form a comprehensive assessment and discuss targeted interventions with people that can be directly applied to individual circumstances, which is a key principle of ‘personalised medicine’. Any healthcare reform should therefore be about shifting the focus toward delivering personcentric care within sustainable integrated healthcare systems where multidisciplinary teams work in the common endeavour to empower patients in an operational system of continuity of care supported by eHealth.4 Personalised medicine is not only about bringing innovation to medicines and diagnosis systems; it should also be about providing the right healthcare, targeted interventions to prevent diseases, appropriate care at the right time, and building a community that allows individuals to make healthy choices about their own health. Nurses can have direct access to people’s care needs and an in-depth knowledge of the fluctuations of diseases across the care trajectory. They are ideally placed to help not just with the management of dementia, but crucially with its diagnosis. Many people with dementia (40-60%) do not get a timely diagnosis, while for those who are diagnosed, this can be late and by which time clinical signs have progressed and activities involved in daily living, cognition, social ties, and quality of life have already been significantly affected.5 Nurses could therefore become an important

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part in the upscaling of ‘personalised medicine’ towards ‘personalised healthcare’.

Personalised care The future development of ‘personalised care’ necessitates a focus on the education and training of health professionals, not just physicians and researchers. To make personalised ‘medicine’ deployable, continuity of care becomes a key enabler supported by ‘fit for practice’ ICT solutions which operate within the big data approach, which are deployed by a motivated and highly qualified health and social care workforce with the appropriate skills mix to deliver a combined and interactive health and social care system, and which is supported by e- and m-health approaches. E-health services constitute an effective vehicle for managing the current challenges and realising the benefits from a shift towards personalised care as people who suffer from dementia experience the full spectrum of healthcare services due to the nature of the disease, and because it is usually associated with a number of other comorbidities. E-health is an excellent tool to foster education in health and patient empowerment through adequate and remote support from health professionals.6

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Leading the way When upscaling personalised medicine as part of a reform of the health systems throughout the EU, the recognition of nurse-led clinics composed by multi-professional teams are becoming more common and are seen as an effective method for supporting outpatient care after the acute phases of a disease. Sweden was one of the first European countries to create nurse-led clinics for patients with long term conditions such as diabetes and heart failure, but such clinics are now also becoming integrated in many other countries. They are available in Denmark (municipality health clinics are mainly led by nurses and provide prevention and rehabilitation care); in England, Estonia, Finland, France, Sweden and two regions of Spain – Andalucía and Catalonia (LSE, 2009). The Advanced Nurses Practitioner (ANP) therefore has a lot to offer when developing personalised care and especially in relation to people with dementia, as they have knowledge of, and insight into, the entire clinical health and social pathway. The ANP’s high level of experience and expertise, their additional qualifications and skills which enable them to perform tasks such as ordering and interpreting tests and investigations and conducting physical assessments, next to the considerable knowledge of the healthcare system in which they work and its processes,7 supports the upscaling of personalised medicine as described above. Therefore, nurses in advanced roles can enrich the care and treatment of people with dementia by having oversight of the care plan and treatment options for people, helping guide them through the system as necessary; by reviewing people’s progress regularly, and by ensuring they have timely referral to specialist services or diagnostic investigations when these are needed; and by co-ordinating the

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discharge planning process, in collaboration with other professionals, and providing post-discharge follow-up and care co-ordination with community services.

Polypharmacy and comorbidity Furthermore, the long term, complex and comorbid nature of dementia means that people living with this disease often have complex treatment and medication regimes. With polypharmacy being an immediate risk, people with dementia require more intensive reviews of their regimes to ensure these are up-to-date and adequately respond to their needs. Nurses have unparalleled access to people’s health and treatment profiles, and through regular reviews can ensure their medications are fit for purpose and respond to the complexities of individuals. Nurse prescribers have a key function in supporting people with dementia to cope with their sometimes overloaded medication regimes by ensuring the appropriateness and accuracy of prescriptions. They are also able to provide education to people with dementia, as well as their families and carers about medication safety and proper administration, review medications regularly to ensure these fit the needs of the individual, and ensure timely referral when relevant investigations are needed to ensure the safety of prescriptions.

Horizon 2020 While understanding of dementia is increasing, the rate by which the prevalence of dementia rises in Europe outpaces the knowledge generated through research about how to best prevent, treat and respond to this debilitating condition. Horizon 2020 offers unique opportunities to rectify this and to pace up the scale and scope of research on dementia in Europe, particularly through addressing dementia as a societal and health challenge. For example, there is scope for work on understanding the determinants, risk factors and pathways of conditions like dementia, as well as comparing the effectiveness of best practices and health interventions for the older population and exploring e-health approaches to selfmanagement. Personalised medicine utilises research, data, and up-to-the-minute technology to provide better diagnostics and follow-up for citizens than is currently the case. It uses genetic information to discern whether a particular drug or regime will work for a particular patient and assists clinicians in deciding which treatment and care process will be the most effective. Therefore, prompt and decisive action is needed to contain this challenge before it escalates further beyond control. Nurses are the ones best placed to ensure practice, knowledge, and research develop in response to and in conjunction with people’s needs; and that this gets translated and implemented into the daily practice of professionals towards improving the quality of care and life for people living with dementia, as well as their families and carers. To conclude, the realisation of ‘personalised medicine’ needs resources, reforms, appropriate organisation, a high quality nursing workforce, technology, innovation, and, last but not least, political will and dialogue

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with the profession. Therefore, the EFN calls on the Luxembourg and the Netherlands EU presidencies to make nurses visible in the political debate on personalised medicine and dementia, as these are two files which need to be linked. References 1 World Alzheimer Report (2014) Dementia and risk reduction. Alzheimer’s Disease International and Global Observatory for Ageing and Dementia Care, King’s College London 2 World Alzheimer Report (2010) Global economic impact of dementia. Alzheimer’s Disease International 3 European Commission (2009) Communication on a European Initiative on Alzheimer’s disease and other dementias. Brussels, EC 4 EFN (2014), ENS4Care project - eHealth guidelines for nursing and social care. Available at: http://www.ens4care.eu/ 5 Alcove (2013) Timely diagnosis of dementia. Alcove project report 6 Sheikh A, McLean S, Cresswell K (2011). The Impact of eHealth on the Quality and Safety of Healthcare. An updated systematic overview & synthesis of the literature. Final report for the NHS Connecting for Health Evaluation Programme (NHS CFHEP 001). London: Imperial College London 7 http://www.hsj.co.uk/5082712.article#.VPAIxvmsW7o

Dr Paul De Raeve, RN, MSc, MStat, PhD Secretary-General European Federation of Nurses Associations [email protected] http://www.efnweb.eu

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BIG DATA FOR THE BRAIN INCF outlines how Big Data can be used to further our understanding of the human brain

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he global burden of brain diseases is enormous: 36 million people live with dementia, at least 21 million with schizophrenia and 6.3 million with Parkinson’s disease. Leaving aside the devastation of lives and familial impact, the economic cost of dementia alone was estimated in 2010 at $600bn (~€535bn) and is increasing dramatically due to the rapidly ageing world population. The need for better understanding of the brain is urgent. Modern neuroscience has amazing tools at its disposal. We can see the real-time activity of hundreds of thousands of neurons, peer into single synapses and see which genes are active in brain tissue. It’s possible to visualise neurons in a rainbow of colours in a transparent brain. We can direct the release of transmitters with precise light pulses, or image whole structures with sheets of laser light. Investigations range from nanometres to metres, from nanoseconds to minutes, and even hours and years. However, at each scale lies a huge challenge to integrate and compare data from many different methods and sub-disciplines. To truly understand how the brain works and what goes wrong in disease involves the staggering task of meaningfully integrating this information across all scales from genes to behaviour. This is the challenge of neuroinformatics. The challenge can only be met by open science in which data, software and workflows are shared. The academic process often lacks incentives for sharing, resulting in unnecessary duplication of efforts and funding around the world. In 2005 the Global Science Forum of the OECD recognised the need for a concerted global effort to advance the field of neuroinformatics. This led to the founding of the International Neuroinformatics Coordinating Facility (INCF), initially with seven member countries, now 18 members across Europe, North America, Australia and Asia. After a decade of community-based activities, INCF enters its third phase in 2016 at an exciting time for the field: neuroinformatics has emerged from being a discrete specialism and is poised to transform the way neuroscience is conducted. This century marks a shift in the paradigm of investigation in most scientific fields toward novel data-intensive approaches. Neuroscience is no exception: 21st Century brain research is about data. Solutions for data management, storage, sharing and analysis are needed at a scale larger than most labs can easily handle, at least without access to specialised competence not part of a typical neuroscience training path. The plethora of different data formats needs community agreement around standards, tools and interfaces, so that investigators can share tools to handle their data.

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Several large scale brain initiatives have emerged around the globe over the last five years: US BRAIN initiative, Europe’s Human Brain Project, Japan’s Brain/MINDS project and others planned in countries such as China, Korea, Australia and Israel. All promote collaboration around vast amounts of data generated with newly developed methods, and seek ways to integrate and share data nationally and internationally. INCF acts as an international co-ordinator to help these initiatives to ensure that the standards and infrastructure they develop to accomplish their aims are compatible across nations. Modern technology provides enormous opportunities for collaborative research at the global level, enabling scientific advances at a faster rate than ever previously possible. To harness these benefits in neuroscience, international co-ordination of efforts is essential. INCF launches its new phase with a focus on increasing the impact of neuroinformatics in neuroscience through broad community involvement, engagement of neuroscientists, decision makers, publishers and funders, and increasing the scale and impact of training and education. There is an urgent need for neuroinformatics techniques to be included in the training of the next generation of neuroscientists. They will need novel skill sets to enable them to work in a data-intensive field quite different from that which formed their mentors. This generation of scientists will be the ones able to truly harness the power of the ‘Big Data’ era of neuroscience, which will shed light on hitherto unknown paths leading to better understanding of the brain and treatment of disease.

Linda Lanyon INCF Executive Director +46 (0)85 248 6919 [email protected] Malin Sandström INCF Community Engagement Officer +46 (0)85 248 7093 [email protected] http://www.incf.org/

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PEN SPOKE TO ASHLEIGH WOODEND ABOUT HOW BEHAVIOURAL ECONOMICS CAN BE USED IN THE FIELD OF PUBLIC HEALTH BY, FOR INSTANCE, PREVENTING MAJOR DEPRESSIVE DISORDER

Nudge in the right direction

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raditionally, a method of economic analysis that applies psychological insights to human behaviour to explain economic decision making, behavioural economics is, in a broader sense, concerned with the decisions people make on a daily basis, and the consequences of these choices.

behavioural insights present special promise for creating interventions that go along with the grain of human behaviour. Effectively, by making use of behavioural insights in creating interventions and health systems, we are really putting the end user of health services, along with all their biases, first.

It is for this reason, perhaps, that this discipline is increasingly coming to be recognised as having potential for applications in the field of public health, where a person’s decisions – related to lifestyle choices etc. – can have a profound impact on their long term physical and mental wellbeing. At the eighth European Public Health Conference – jointly organised by the European Public Health Conference Foundation, the European Public Health Association (EUPHA) and the Österreichische Gesellschaft für Public Health – in Milan in October 2015, Ashleigh Woodend, from Erasmus University College in the Netherlands, delivered a presentation on the role of behavioural economics in addressing and preventing major depressive disorder. Pan European Networks met with her at the event to discuss this as well as how behavioural economics could fit into public health approaches more generally.

Behavioural economics – and the behavioural sciences more generally – often reveal that people do not act in the way they are expected. How, then, should behavioural economics come to play more of a role in public health issues? It is indeed correct that behavioural insights demonstrate that people are not as rational as traditional economics assumes they are, and so

Behavioural insights demonstrate that people are not as rational as traditional economics assumes they are

As we know, the prevalence of non-communicable diseases is a big health issue in both Europe and much of the world, and behaviours are very important for these types of diseases (as well as of course for infectious diseases). In that sense, behavioural economics and ‘nudges’ – which are adaptations in the way choices are presented to people that directly leverage upon their systematic cognitive biases – certainly have a role to play, because they allow the focus to rest on how we can change people’s behaviour in a way that reflects how they are already behaving; the kind of cost/benefit analysis that they do in their head. Indeed, behavioural economics has huge potential because it provides insights into the rules of thumb that people use on a day to day basis as they make decisions, and these insights can allow us to create smarter interventions.

How would you therefore like to see insights derived from behavioural economics (BE) utilised by policy makers and decision makers? Currently, most policy decisions are based on neoclassical economics, where the individual is seen as purely rational; under this assumption, if you provide people with health information they will make the correct decisions with respect to their health. Of course, that rarely happens, and people make bad decisions despite their knowledge of health risks and advice. There is thus a need for an increased recognition for the behavioural sciences and for behavioural insights to increasingly drive the design of public health interventions.W hat should also be noted here is that just as consumers of

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health services exhibit cognitive biases, so do producers of health services (e.g. doctors and nurses).As such, BE can be used on both sides of the equation to improve health outcomes. That being said, the evidence on the effectiveness of the behavioural sciences in this field is still quite limited. While it is used a lot in the UK by government agencies and the Behavioural Insights Team (BIT), and is becoming more prevalent in the USA, we want to aim for evidence-based policy, and it is therefore important that we don’t jump the gun and assume that a nudge will have a positive impact across the board. The evidence is not there to support that, and any false statements would only cause setbacks. As such, there needs to be a lot more research into how nudges work and whether they work for everyone before we start rolling out interventions en masse.

Issues such as alcohol and substance abuse all tend to be related to the same cognitive biases, one of which is the ‘present bias’, whereby people value the present more than the future and are therefore willing to enjoy now to the detriment of the long term

require trained professionals and are therefore quite expensive. In behavioural economics, however, we are calling for changes in the way that choices are presented to individuals, and this is very low cost in comparison. Therefore, while research is always costly, because of the nature of nudges, overall research into nudges is likely to cost significantly less than other interventions.

Given those various different aspects, how difficult is it going to be to achieve the active participation of a multidisciplinary team? In a general sense, there is a recognition now that we need to be using multidisciplinary research teams anyway, and the field of behavioural economics is a great example of this as it brings together two different fields, namely economics and psychology –although there is perhaps more psychology than economics involved as things currently stand. Nevertheless, there is a distinct sense that people are open to this need for multidisciplinary collaboration, and it will be interesting to see how this continues to evolve.

Is the funding there for that?

There are, of course, many contributing factors when it comes to issues such as mental health – i.e. alcohol and substance (mis)use, physical activity etc. How, then, can behavioural economics help to provide a more cohesive approach?

I think so, not least because of the promise that behavioural economics holds, but also because behavioural interventions, or nudges, are relatively low cost. In the area of depression, for instance, current preventive interventions, to name a few, are cognitive behavioural therapy or interpersonal therapy, both of which

Issues such as alcohol and substance abuse all tend to be related to the same cognitive biases, one of which is the ‘present bias’, whereby people value the present more than the future and are therefore willing to enjoy now to the detriment of the long term. Because behavioural economics looks at the kinds of cognitive biases that are related to a number of behaviours, it is able to tackle a range of health outcomes with the same tools and so does indeed provide a very cohesive approach. When we

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are encouraging people to do physical activity we are not only helping their mental health but also their physical health, and are thus targeting a number of different health outcomes by looking at the same risk factor. When we are talking about mental health issues, something that is of growing importance in developed and developing countries alike, behaviour is fundamental, and so things like physical activity, social interaction, medication adherence, all need to be explored. This means that there is definitely a place for behavioural economics, but more research is needed. In our 2015 commentary paper published in the American Journal of Public Health, we have proposed nudges which could be used for tackling risk factors associated with depression, but they have yet to be tested empirically.

How does your own work/research tie into these areas, and where do you feel future priorities should lie? Currently, there is a need for behavioural economics to extend beyond questions of how much physical activity people are doing on a daily basis and to look at bigger issues such as health system design and poverty, for instance. This presents a challenge, however, because we must also recognise that behavioural insights won’t provide a solution for everything. In the hopes of answering this call to focus on more complex matters, my target is to aim my future research at issues being experienced in developing countries, such as maternal mortality. This will also enable me to explore the role nudges can play in deprived areas, and whether nudges work differently for people of different cultures and socioeconomic status, for instance. This latter goal is of importance given the need to look further into the generalisability of nudges. ‘Nudge’ is a catchall term for tweaks that leverage upon cognitive biases; however, we believe some biases to be more likely to be truly cognitive, such as the anchoring bias, while

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Mental health issues are of growing importance in developed and developing countries alike, and within this an exploration of behaviour is fundamental

others are more socially constructed, such as the present bias. With those biases that are more socially constructed, culture, and other factors, may plausibly impact upon the suitability and effectiveness of nudges. Meanwhile, at the Erasmus University College, we are busy establishing the Rotterdam Centre for Health Promotion, which will serve as a knowledge creator, bank, and distributor with respect to interventions that work for promoting (mental) health and reducing health inequalities. Because of this goal of reducing the health gap, BE holds special promise as it does not rely entirely on health literacy. As such, we also intend to apply behavioural insights to issues that are prevalent in the city, such as diabetes and depression. This, again, will help us to explore the effectiveness and the generalisability of nudges.

Ashleigh Woodend PhD researcher Academic skills co-ordinator Assistant co-ordinator to the EUC Society Oriented Leadership Programme Erasmus University College [email protected] http://www.eur.nl/euc/

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PREVENTING RECURRENCE OF DEPRESSION The University of Bergen’s Mood and Cognitive Function group writes on preventing recurring episodes of depression

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ne of the most serious aspects of Major Depression Disorder (MDD) is the high risk of experiencing recurrent episodes. More than half of those that have been diagnosed with a first episode of depression will suffer from a new episode within two years, and as many as 75% will be diagnosed with recurrent depression within five years after the initial episode. Despite effective treatments for depression today, there is a lack of interventions that aim to prevent relapse and new episodes. Depression is a mood disorder characterised by emotional, biological and cognitive symptoms. Most interventions today target the mood symptoms of the disorder. However, a solid pool of growing evidence shows that an underlying mechanism of the disorder is its associated cognitive aspect. Cognitive deficits such as of memory, attention, and problem solving are commonly reported in the literature, not only during symptomatic phases, but also in a long term perspective in phases of recovery and remission. These problems are also experienced by patients themselves and are often described as impaired cognitive capacity. Patients report that they do not function at the same level as before the depression, which affects work abilities, school performance and everyday life. The long lasting cognitive impairment might represent a risk factor for developing new episodes as it can cause failure to achieve on a premorbid level, and thus lead to negative selfrepresentations and negative rumination. In the Bergen Mood and Cognitive Function group (MCF-group), our focus is to investigate the relationship between factors that can contribute to the high relapse risk in MDD in general, and the contribution of cognitive functioning, emotional information processing and cortisol in particular. Findings indicate that MDD patients show normal performance on most measures of cognitive functioning. However, there is evidence that the patient group is impaired on specific aspects of cognitive functioning, such as inhibition. Inhibition requires higher order functioning to inhibit automatic responses, and impairment is evident in both acute phases of depression and in remission. This function is associated with rumination, which is a core feature of depression. Further, the MCF-group has shown that impaired inhibition in the acute phase predicts relapse during the first year of first episode MDD patients. Thus, it seems that impaired inhibition is a specific

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underlying mechanism representing a risk factor for relapse. Following this, interventions targeting the cognitive mechanisms in order to enhance the cognitive capacity should be explored. One approach to target the cognitive mechanism is through cognitive remediation. CR interventions employ cognitive training to improve or prevent symptoms and optimise everyday functioning and quality of life in an enduring way. This is still a relatively unexplored field in depression and so far no study has aimed to investigate if cognitive training to enhance cognitive capacity in remitted patients will prevent relapse and new episodes in depression. Such a study has been designed and the MCF-group is currently running a pilot in order to investigate feasibility and pinpoint outcome measures as a first step of a randomised controlled trial study.

Åsa Hammar, PhD Group Leader Mood and Cognitive Function Group University of Bergen, Norway +47 (0)5 558 6212 [email protected] http://www.uib.no/en/rg/mcf

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PAUL BOMKE, CEO OF PFALZKLINIKUM, ON PREVENTATIVE APPROACHES BEYOND THE HEALTHCARE SYSTEM

A focus on prevention

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alatinate region braces itself/you: roads to resilience’ is a Palatinate initiative for the promotion of preventive approaches beyond the healthcare system strategies based on prevention to improve the population’s mental health. Nevertheless, prevention programmes constitute less than 7% of the overall health system cost in Germany. With regard to the treatment of mentally ill persons with complex needs, we have now decided to think in a radical new way: our idea is to strengthen resilience on different social levels such as the individual, families, enterprises and communities. The ability to advance personally in times of crisis and not to be broken by these challenging events, to be able to cope well with changes and with the ups and downs of life – this is what is known as resilience. Resilience is of utmost relevance both for individuals and organisations.

Resilience At an individual level – i.e. the strengthening of an individual’s mental resistance – resilience is a key aspect of the services provided by the Pfalzklinikum für Psychiatrie und Neurologie – AdöR (Service Provider for Mental Health). Around 30,000 people are treated and cared for at their 12 locations annually, either as inpatients, in day clinics, or as outpatients. In order to boost their mental health on a long term basis and to counteract any further increase in mental illnesses, the main focus of the efforts has to be on prevention. The preventive fostering of individual resilience will therefore play a central role.

In order to boost mental health on a long term basis and to counteract any further increase in mental illnesses, the main focus has to be on prevention

pathogenetic approaches on which the health system has mainly focused so far). The foremost requirement for this purpose is preliminary, comprehensive communication research aiming at the identification of stigmatising attitudes and their replacement by new relevant information (by means of metaphors, for example). It is only sound knowledge of how communication works, or does not work, that offers the possibility of establishing a broad knowhow of resilience promoting factors and framework conditions amongst citizens.

The results are reflected in a binational project with a similar, newly Above all, however, there is need for action in the fostering of founded initiative (‘Blackpool Better Start’) in Blackpool, UK. organisational resilience. Technological advances, growing market With this concept we also tread new paths when designing the context dynamics, or ageing workforces are just a few examples of megatrends of health communication. that may trigger crisis situations and which are cropping up in organisations such as companies or administrations at an ever more The ‘Palatinate region braces itself/you’ initiative as a socio-ecological rapid pace. Such situations almost invariably call for rapid and and multi-agency approach is aimed at building networks for ‘knowledge mobilisation’, establishing action alliances and learning platforms and comprehensive change to ensure a company’s survival. various projects to be presented using the example of resilience in We also have to think about ways to improve resilience on the level of enterprises and resilience promoting programmes in schools and on the the community, where people live too. These three levels are crucial in community level. establishing a powerful and sustainable prevention strategy.

Salutogenesis For this, we have brought together experts from different institutions in the field of science and practice (sociologists, anthropologists, economists, pedagogues, psychiatrists, communication scientists, ergonomists and so on) in order to promote salutogenesis at community level through the thematic fields of work/school/leisure (instead of

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Paul Bomke CEO Pfalzklinikum Road to Resilience Project www.pfalzklinikum.de

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H O R I Z O N 2 0 2 0 P RO J E C T S : P O RTA L

Horizon 2020 Projects: Portal is the invaluable quarterly digital publication for policy makers, scientists and researchers involved in the EU’s largest ever RDI run on investment programme. The publication features exclusive interviews and articles from top European politicians as well as leading scientists undertaking Horizon 2020-funded research in their fields of expertise. Portal can be accessed via horizon2020projects.com, which offers daily news updates and articles on the latest developments in the framework programme. Published in October 2015, key contributors to the eighth edition of Portal included: l

Lauritz B Holm-Nielsen –The president of EuroScience;

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Elena Bou – KIC InnoEnergy’s innovation director; and

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Andrew Boulton –The past president of the European Association for the Study of Diabetes.

Issue 9 of Portal will be published online in January 2016.

UK tel: +44 (0)1260 273 802 Brussels tel: +32 (0)249 403 57 email: [email protected]

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PROFESSOR JAMES LAW EXPLAINS HOW A COST ACTION HOPES TO ADDRESS ISSUES IN CHILDREN’S ORAL LANGUAGE DEVELOPMENT

Enhancing oral language skills

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ral language (speaking and understanding) is critical to children’s development, affecting the emergence of personal, social and academic skills throughout school and into the workplace. There is evidence for the efficacy and effectiveness of intervention to improve the language skills of these children, but this information is not well disseminated and services are inconsistent across Europe.

COST (European Co-operation in Science and Technology) is a panEuropean intergovernmental framework. Its mission is to enable breakthrough scientific and technological developments leading to new concepts and products and thereby contribute to strengthening Europe’s research and innovation capacities.

Pan European Networks spoke to the Chair of the ‘Enhancing children’s oral language skills across Europe and beyond – a collaboration focusing on interventions for children with difficulties learning their first language’ COST Action, Professor James Law, about how he hopes the Action will enhance the science in the field, improve the effectiveness of services for children with language impairment (LI), and develop a sustainable network of researchers well-placed to answer the key questions in this area.

Could you begin by outlining the issue of LI in Europe today? One of the most important issues from our point of view is how this figures in children’s development. We are interested in oral language, which is essentially a child’s ability to understand and speak to other children and adults, and it is becoming quite clear that there is a large number of children who find this difficult. That is not to say that they are unable to communicate, but that they just do it much less readily than their peers. This makes it very difficult for them to engage with the school

system, for instance, and so they are facing a disadvantage from the outset.

We are interested in oral language, which is essentially a child’s ability to understand and speak to other children and adults, and it is becoming quite clear that there is a large number of children who find this difficult

We estimate that there are some five million children in Europe who fall into this category, and that is using very conservative estimates, hence it is very difficult to say how accurate this actually is because some countries don’t collect any data. With the help of the COST Action we are trying to unify efforts across Europe. We already have 32 countries involved and have received expressions of interest from others, thus enabling us to bring together those who specialise in relevant subjects such as linguistics, psychology, and speech and language pathology.

How important is it to also take into consideration diagnoses such as ADHD?

© Department of Children and Youth Affairs

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Co-morbidity represents a major issue because disorders, such as ADHD (Attention Deficit Hyperactivity Disorder) and autism can occur at the same time; they are not separate disorders. We have psychometric measures that allow us to separate them, of course, but they are nevertheless part of a greater whole. When it comes to child development, there are very few ‘pure’ disorders.

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How do you feel the information regarding the benefits of intervention can be better disseminated, and who would you like to see become better informed? In the UK, there are now numerous agencies and people working in or focused on this area – indeed, the UK Department of Education is also promoting it. As such, in Britain it is a matter of making things more equitable and comprehensive. However, in the case of some of the eastern European countries, the focus needs to be on raising awareness so that people start to think about feasible interventions. Of course, it is necessary to have the right number of practitioners, who are able to provide the services, involved, and that can be one of the more challenging aspects because some countries quite simply don’t have these people. What they do have is a number of academics, but academics do not provide services. This is therefore an interesting situation. Our group includes members who are very theoryorientated, and it is already clear that those who are more concerned with theory don’t tend to be the practitioners; the practitioners are those who actually want to effect change.

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It is crucial for those involved in the Action to have an understanding of how psychology – so all aspects of the child’s development, including things like executive function – link with language development

Is there enough of a bridge between these two sectors, or is that where the COST Action comes in? This is indeed where the COST Action can come to play a role. There have been previous COST Actions in this area – although I was not involved in them – but in one case they had tremendous difficulty reconciling the interests of practitioners and academics. We are making a real effort to try to do this from the start in our Action, and are therefore making practitioners central to our process. This is different to the more traditional approach, within which those more concerned with theory are given the central placement, with practitioners being ‘added on’. We are putting practice first, with theory adding to it.

How much of a role will developmental psychology play in addressing ‘some of the key questions’ in this area (indeed, will other disciplines under the psychology umbrella also be of use?) and how difficult will it be to use knowledge from this field alongside other scientific areas? Developmental psychology is essential, although many developmental psychologists aren’t necessarily interested in change but in ‘capturing’ development; they often have quite a strict view of how much change the environment can actually affect. Nevertheless, we are very open; we don’t ask people which psychological sub-discipline they come from when they join. Indeed, there is a sense that many of the psychologists involved in the COST Action would call themselves ‘developmental’ (although the profession of developmental psychologist doesn’t technically exist). This is very important to the successes we want to achieve because it is crucial for those involved to have an understanding of how psychology – so all aspects of the child’s development, including things like executive

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function – links with language development. Behavioural psychologists are able to do this, while a speech pathologist may be interested in language but may not necessarily have knowledge of the other aspects of development.

In a recent meeting, we have been able to plan further research activities by harnessing the potential of the research activities that are currently ongoing (we don’t fund research ourselves). The aim now is to establish training workshops and short term scientific missions, whereby researchers will be able to move from one centre within the COST Action to another to study for two to three weeks in order to gain specialist knowledge in a particular area.

With reference to other psychological areas it is unlikely, although not impossible, that people working primarily in the field of neuroscience would become involved in the Action. Neuroscientific measurement is unlikely to be accurate enough to measure developmental change as a result of intervention for many years to come. Similarly, while there are many who have an interest in genetics and language development they may be less involved in assessing the extent to which environmental factors such as intervention can affect genetic expression. There is scope to include elements of epigenetics, but this is probably a long way off.

Following on from this, what are your longer term hopes for the Action – and how important is it for this type of initiative to be established in this field?

Given that the COST Action is in its infancy, what will your first steps be? COST Actions begin by establishing working groups which go on to become the focus of the whole thing. People buy into these working groups and then go on to work on particular projects within them. We have one working group on theory, one on service delivery, and one on cultural issues, because we anticipate that the idea of changing the way children do things will be received in different ways depending on different cultural perceptions. For us, the first thing has been to conduct surveys in different countries to find out who works in what ways with children, where they are, and what theoretical frameworks they use, and we are now gathering the feedback from that exercise.

Co-morbidity represents a major issue because disorders, such as ADHD (Attention Deficit Hyperactivity Disorder) and autism can occur at the same time; they are not separate disorders

What we are doing has never been done before, and what is interesting is how quickly people signed up to our COST Action; 32 countries in about six months. That indicates that there is a big demand and interest in what we are trying to do, and, indeed, that there are lots of places around Europe where they don’t have much of an academic infrastructure, but that there are people there who are interested in taking our ideas forward. In terms of my future interests, I would like to see more coherence across Europe. As the boundaries come down, people should be able to move between countries and, moreover, there should be more commonalities between countries in terms of the expectations for these children. Regarding specifics, I would hope that within the next year or so we will have thought about submitting research grant applications to the EU through Horizon 2020 for intervention studies which run across different countries. The question, however, is how to frame that.

Professor James Law Professor of Speech and Language Science Chair ISCH COST Action IS1406 [email protected] http://www.cost.eu/COST_Actions/isch/IS 1406

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AUTHENTIC ASSESSMENT The Stavanger Project - The Learning Child: Gaining better insight in children’s early development by authentic assessment

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he Stavanger Project: The Learning Child is a longitudinal study of more than 1,300 children that aims to investigate toddlers’ and pre-schoolers’ skills in language and mathematics, as well as their social, emotional and motor behaviours. The project also investigates how early development factors relate to the same children’s skills in reading, writing and arithmetic when they reach school age. Additionally, the Stavanger Project seeks to gain knowledge that will contribute to early identification and stimulation of children who may struggle to acquire basic skills. The project will contribute towards increasing the competence of employees at kindergartens and schools when it comes to children’s development. The project holds four assessment points: by observation when the children are toddlers and pre-schoolers, and by standardised tests when the children reach school grades two and five. Although kindergarten attendance is optional in Norway, around 90% of Norwegian children aged one to five attend state-run or private early childhood education and care institutions (ECEC). In the Norwegian ECEC, play and everyday life activities are recognised as the most important educational practice. This stands in contrast to the more academically oriented programmes found in many other countries. Formal training in reading, writing and arithmetic commences when Norwegian children start compulsory schooling at the age of six. The holistic, play oriented nature of Norwegian ECECs has given researchers at the University of Stavanger an opportunity to make authentic assessments of the children’s skills. In order to gain knowledge of the mastery of various skills in children under school

age, previous research has typically used parental reporting or testing undertaken by independent people unfamiliar with the children. In the Stavanger Project, however, skilled ECEC teachers and staff, who know the children well, have used non-obtrusive methods to observe the children’s mastery of these skills in their natural environment – during play and daily activities – over two three-month periods, when the children were two-and-a-half and four-and-a-half years of age.

Findings To date, research findings from the Stavanger Project give new insights on a number of factors concerning early childhood development. So far, new light has been shed on language, mathematical, social and motor skills in toddlers and pre-schoolers. The project also looks at gender differences, multilingualism, and the relations between skills and developmental areas in toddlers and pre-schoolers. The Stavanger Project reveals that there are vast differences in children’s skills in all developmental areas, as early as toddler age. While some toddlers are at the very start of their development, others are at levels expected of children in late pre-school. It is important that the children’s teachers recognise their various skills in order to facilitate learning. This holds particularly true when it comes to detecting risks for weak development. Factors that can be of importance for further development may be found within or across these specific developmental areas.

Mathematical skills and motor skills closely related This article will present two recent studies from the Stavanger Project. The first examines how the level of development in mathematics and motor life skills are related in toddlers, with an emphasis on those with the weakest skills. The results were published in the European Journal of Early Childhood Education1 in June of this year. The study uses data from structured observations of over 1,000 children over a three-month period, starting when the children were two-and-a-half years old. Mathematics is already an important part of play and everyday activities in Norwegian ECEC. However, teachers often find it challenging to determine the children’s mathematical level. Motor skills often seem easier to observe. ECEC staff observed and recorded each child’s mastery of motor skills such as putting on clothes, doing jigsaws, eating with a

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spoon and fork, using scissors, walking around the room without bumping into things, using playground equipment and throwing/catching a ball. The researchers then divided the children into three groups according to their level of motor skills: weak, average and strong. Mathematical skills examined included whether the two-year-olds were able to use their fingers to show their age, if they could use the shape sorter box, play picture lotto, sort toys or objects, demonstrate the difference between big and small, use number words, make patterns and draw a tadpole. Children with good motor skills were more mathematically advanced in all of the areas studied. Those with average motor skills scores also had average scores for mathematical skills. There were big differences in mathematical skill levels between the children with the strongest and weakest motor skills. Most of the children who had weak motor skills also showed poor mathematical skills. This shows that children with weak motor skills should be observed closely for poor mathematical skills. This knowledge will make it easier for teachers to identify and help children who may be at risk of a weak mathematical development. The study does not show causality; only that the level of mathematical proficiency can be reflected in motor skills. More research is required into the significance of motor skills and the early development of mathematical proficiency. The Stavanger Project has data available for further study in this area. It would be particularly interesting to study if poor motor function in two-year-

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olds could be an indicator of slow development in mathematical proficiency when the children reach school age. Though a close relationship between mathematical skills and motor functions exists, ECEC institutions should not focus on just one area and expect that there will be an improvement in the other. The findings reinforce the strength of the holistic approach, which characterises the work of Norwegian kindergartens. It is important to facilitate play-based activities where children can develop in several areas at the same time. Both motor and mathematical skills are essential for children in the here and now, at play and during everyday activities.

Even as two-year-olds, girls are more independent and sociable The second example of recent studies within the Stavanger Project investigates the importance of gender in everyday activities in the kindergarten. The study is published in the June issue of the Early Childhood Educational Journal,2 using the same data as the previous example. In this study, ECEC staff observed the mastery of everyday activities in the children: the extent to which the children took part in games and circle time; how they adapted to meal times and other routines; whether they were able to dress and undress themselves; and whether they mastered eating and drinking without help from adults. It became apparent that girls were more independent than boys in all of the areas studied. Girls mastered

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routines such as changing from one activity to another better than the boys, and were more able to help younger children. The biggest difference between boys and girls was the age at which they were out of nappies and started using the toilet. Over 21% of two-and-a-half year old girls were completely potty trained and out of nappies, compared to just 7.5% of the two-and-a-half year old boys. Up to 68% of the girls had developed an interest in using a potty or toilet compared to 42% of the boys. The girls also scored higher on participation in circle time where singing, games that develop motor skills, and activities involving discussion or narration are important. Such activities require concentration for short periods, as well as the desire and the ability to interact, something that the girls seemed to be better at mastering. To a large extent, social skills and everyday activities are connected with children’s language comprehension, motor skills and self-regulation. Developed language skills in girls may contribute to them being better able to express their needs and desires than boys; children’s language skills may also influence other activities. The differences between boys and girls may be due to both biological expectations as well as different demands and expectations from adults in the children’s environment. Previous studies have shown that girls are more frequently characterised as responsible, co-operative, well behaved, conscientious and diligent. Adults’ behaviour and interaction with children can reflect their own attitudes to gender, thus giving different signals and expectations to boys and girls. The fact that boys tend to run, jump and climb is often seen as good for their development; however, physically active boys are not necessarily better at mastering everyday activities. It is important to provide adequate support for boys, ensuring that they get enjoyment from mastering everyday activities that involve both social and language skills.

Future challenges for the Stavanger Project The Stavanger Project aims to find important knowledge to put into practice in schools and kindergartens, as the two studies also show. Several studies within the project are complete whilst others remain in progress, mainly using data from the first two assessments when the children were toddlers and pre-schoolers.

PSYCHOLOGY

The Stavanger Project – The Learning Child This is a longitudinal study following more than 1,300 children over a period of ten years in Stavanger, Norway. The children were born between 1 July 2005 and 31 December 2007. The aim is to gain increased knowledge on children’s development by investigating the relationship between early developmental areas such as language, mathematics, motor skills and social competency in young children, and the same children’s skills in reading and writing when they reach school age. The project is a collaboration between the Norwegian Centre for Reading Education and Research at the University of Stavanger and Stavanger Municipality; and is multi-institutional, involving researchers from the University of Stavanger’s Reading Centre, Centre for Learning Environment, Department of Early Childhood Education, and Department of Education and Sports Science. The study is conducted in adherence with Norwegian data protection rules and the project’s ethical guidelines assure the children’s anonymity. The Stavanger Project, led by Elin Reikerås, commenced in 2007 and is scheduled to reach completion in 2018. http://lesesenteret.uis.no/research/the-stavanger-project/

As the project proceeds and data from the children at the ages of eight and ten will be made available, new studies will likely lead to even more insight, leaving us with a new and greater understanding of the numerous aspects of children’s development. References 1 Reikerås, E. Moser, T. & Tønnessen, F. E. (2015). Mathematical skills and motor life skills in toddlers: do differences in mathematical skills reflect differences in motor skills? European Early Childhood Education Research Journal, 1-17. doi: 10.1080/1350293X.2015.1062664 2 Meland, A. Kaltvedt, E. & Reikerås, E. (2015). Toddlers Master Everyday Activities in Kindergarten: A Gender Perspective. Early Childhood Education Journal, 1-10. doi: 10.1007/s10643-015-0718-1

Elin Reikerås Project Leader The Stavanger Project: The Learning Child +47 (0)5 183 3451 [email protected] http://lesesenteret.uis.no/research/thestavanger-project/

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AS A NEW AND EVOLVING DISCIPLINE, HEALTH PSYCHOLOGY HAS THE POTENTIAL TO TIE INTO NEW, MULTIDISCIPLINARY AND PERSONALISED HEALTHCARE APPROACHES

Thinking about health

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he National Health Service (NHS) in the UK has described health psychology as a new and rapidly evolving area, defining it as ‘the practice and application of psychological methods to the study of behaviour relevant to health, illness and healthcare’. For example, the NHS website also states that health psychologists may study when and why people seek professional advice about their health, why healthcare professionals do or do not recommend preventative measures, how patients and healthcare professionals interact, how patients adapt to illness, and/or the links between perception, health behaviour, and physical functioning. Health psychologists focus on public health problems, healthcare provisions and responses to illness. These issues may be identified by healthcare agencies (including health service trusts and health authorities), health professionals (such as GPs, nurses and rehabilitation therapists) and organisations and employers outside of national health services.

‘Health psychology’s roots are in the belief that everyone deserves proper medical and psychological care even when daily habits, career, or family life problems contribute to the decrease in physical health and/or psychological wellbeing. The biopsychosocial model views health, wellness and illness as being a result of several different inter-related factors affecting a person’s life from biological characteristics, to behavioural and social conditions (Belloc, N. & Breslow, 1972).’ As the NHS outlines, the breadth of the discipline is far reaching and can involve: n Processes influencing healthcare delivery – investigating the nature and effects of communication between healthcare practitioners and patients. This includes psychological interventions to improve communication, facilitating adherence, and preparing for stressful medical and other procedures; n

Health protective enhancing behaviours – encouraging adoption of behaviours such as exercise, a healthy diet, oral hygiene, health checks/self-examination and attending preventative medical screenings, by using psychological approaches to health problems;

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Health related cognitions – investigating cognitive processes which mediate and determine health and illness behaviours. A range of theoretical models and frameworks are used, not only for explanation and prediction, but also for developing interventions (for example, modifying health beliefs, increasing internal control and/or self-efficacy);

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Psychological aspects of illness – looking at the psychological impact of acute and chronic illness on individuals, families and carers. Psychological interventions may be used to help promote self-management, cope with pain or illness, improve quality of life and reduce disability and handicap; and

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Health risk behaviours – identifying behaviours that may be damaging to a person’s health (smoking, drug abuse, poor diet) and the use of psychological theories and interventions for primary prevention and health-related behaviour change.

Biopsychosocial design According to the Health Psychology of San Diego, ‘the central strategy practiced within health psychology is the biopsychosocial design. The British Health Society explains that health and disease are the effects of a blending of biological, psychological and social factors. Biological determinants consist of genetic conditions and inherited personality traits. Psychological factors are anxiety levels, personality features and lifestyle. Social determinants consist of cultural views, family relationships and support systems.

The central strategy practiced within health psychology is the biopsychosocial design

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With approaches to healthcare becoming more personalised, and with both the health-related research and practices becoming increasingly multidisciplinary, the biopsychosocial design of health psychology means that its heterogeneity has the potential to tie into this evolution very closely, and perhaps provide perspectives and indeed pathways previously unidentified.

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ALL IN YOUR HEAD? The University of Fribourg’s Department of Psychology explains how clinical neurosciences aid understanding of chronic pain

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hronic pain is defined as a pain lasting more than three months, and can be associated with an ongoing illness, it may have been triggered by an initial injury or may have no clear causes. With an estimated prevalence of up to 40%,1 chronic pain is regarded as a major health problem with direct and indirect economic costs estimated at 1.7-5% of the gross national product in western European countries.2 Chronic pain affects people’s wellbeing, their ability to maintain an independent lifestyle, productivity and social relationships. Unsurprisingly, mental disorders, including mood and anxiety disorders, are strongly associated with chronic pain.1 Common examples include chronic lower back pain, post-traumatic pain, osteoarthritis, regional pain syndromes, fibromyalgia and chronic headaches. The mechanisms underlying chronic pain remain largely unknown, and in most cases there is no effective treatment. Because of its complex and subjective nature, pain has received much attention from the neurosciences. With the development of neuroimaging methods, which allow the investigation of neural processes in vivo in the human brain, a large body of research explored how pain information is processed by the central nervous system. These studies identified a so-called ‘pain matrix’ in the brain, i.e. a network of brain regions processing pain information. If the ‘healthy’ pain processing has been largely investigated, there are far fewer neuroimaging studies investigating the neural processing of pain in chronic pain patients. At neural level, chronic pain is characterised by abnormal sensitivity to painful stimuli in the brain and is associated with cellular changes. Our research group, which associates experts of several disciplines from the universities of Fribourg, Bern and Zürich in Switzerland, investigated the role of the dopamine system in pain processing in fibromyalgia patients using neuroimaging methods. Fibromyalgia is a diffuse soft-tissue pain syndrome with unclear pathophysiology that is characterised by strong functional impairment. Because little is known on the causes of fibromyalgia, and because this condition is often accompanied by depressive symptoms, patients are often not taken seriously (“it’s all in your head”) and there is also no efficient treatment for fibromyalgia. It is therefore crucial to understand the underlying processes of fibromyalgia using research methods going beyond the subjective pain reports of the patients. Our results evidenced a disruption of the dopaminergic neurotransmission that was associated with

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changes in the perception of pain in fibromyalgia. Moreover, differences were found between patients with and without depression.3 Together with results from other research groups, our findings indicate that they are specific neural changes in fibromyalgia and therefore that the pain reported by these patients might well be located ‘in their head’. This example shows how clinical neurosciences, i.e. the application of neuroscientific methods to clinical populations, can help understand chronic pain conditions and therefore ameliorate the care and the ‘image’ of these patients. Furthermore, findings from clinical studies in neurosciences can support the development of new, innovative and personalised treatment, which in turn may have a beneficial impact on the economic costs associated with chronic pain conditions in the long term. Whilst we were lucky enough to receive funding for the Swiss Scientific National Foundation for our research, it is more difficult in general to get funding for clinical studies in the field of neurosciences, because patients’ samples are often inhomogeneous and difficult to compare with healthy participants. Even if basic research in neurosciences is important in understanding basic neural mechanisms and allows advances in technology, clinical research is just as important and has direct implications for the health systems and the societal costs related to medical and or mental conditions. 1 Tsang, A., et al., J Pain, 2008. 9(10): p. 883-91. 2 Bergman, S., et al., J Rheumatol, 2001. 28(6): p. 1369-77. 3 Ledermann, K. et al. (2015). Eur J. Neuropsychopharmacology, In Press.

Professor Dr Chantal Martin-Soelch Department of Psychology University of Fribourg Switzerland +41 (0)26 300 7687 [email protected] http://www.unifr.ch/psycho/en

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AS THE EU CELEBRATES 50 YEARS OF PHARMACEUTICAL LEGISLATION, PEN LOOKS AT THE ADVANCES THAT HAVE BEEN MADE AND THE IMPORTANCE OF BIOMEDICINE

Biomedicine in the EU

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September, the EU celebrated 50 years of pharmaceutical legislation. According to the European Commission, much of the impetus behind the adoption of the first law on pharmaceuticals at EU level stemmed from the determination to prevent a recurrence of the thalidomide disaster of the late 1950s to early 1960s, when thousands of babies were born with limb deformities as a result of their mothers taking thalidomide as a sedative during pregnancy. This experience, which shook both public health authorities and the general public, made it clear that to safeguard public health, no medicinal product must ever again be marketed without prior authorisation. Over the past 50 years, a large body of legislation has been developed around this principle, with the progressive harmonisation of requirements for the granting of marketing authorisations and post-marketing monitoring implemented across the entire EU.

products in 2013, with total trade amounting to €156.9bn (EU28) and value of exports reaching more than €107.4bn.” Speaking at the conference organised to celebrate the anniversary, the commissioner also argued that we cannot think about the future without considering the lessons from the past. He said: “The thalidomide disaster will always remind us of the tragic consequences that the absence of an appropriate regulatory framework may have. How many mothers in Europe and elsewhere who took thalidomide in full confidence during their pregnancy have paid the high price of pain? This should never be repeated.

To mark the 50th anniversary of the adoption of the first EU pharmaceutical law, the European Commission held a one-day conference in Brussels on 28 September 2015. The conference reviewed past achievements while focusing on the present and future role of EU pharmaceutical legislation in protecting the health of citizens in the EU and in the world, and in promoting advances in science, innovation and public health.

“Learning from this terrible disaster the founding fathers and mothers of EU pharma legislation agreed on harmonised rules, focusing on a high level of public health protection. The developments over the past fifty years in this sector are a great example of what Europe can achieve, if we work together.”

Challenges Despite the many achievements that have been made, the Commission acknowledges that there are still many challenges ahead. Of course, the different stakeholders see these challenges, but each from different perspectives, and so the conference aimed to bring to the surface these different perspectives in an open and stimulating exchange with representatives from national governments, European institutions, national competent authorities, industry, healthcare professionals, academia and patient groups, with the objective of working towards a shared vision for the future.

In September the EU celebrated 50 years of pharmaceutical legislation

The commissioner also explained that, in what he called “the early years”, trust and collaboration was established between national competent authorities, which thereby ensured

In a statement released on the anniversary, European Commissioner for Health and Food Safety, Vytenis Andriukaitis, said: “European pharmaceutical legislation has, throughout the years, resulted in one of the safest and most advanced systems for monitoring the safety, quality, and efficacy of medicines while at the same time supporting and promoting research and innovation. It is a shining example of the added value the European Union brings into our daily lives. “The EU pharmaceutical sector is one of Europe’s most important economic sectors, employing 1.8% of the total manufacturing workforce. It is also a main employer in R&D terms, employing over 110,000 people. The EU was the world’s biggest trader in medicinal and pharmaceutical

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wait. This makes it even more frustrating when medicinal products that are authorised by the Commission for all of Europe are not available to patients in all member states.”

Transparency and solidarity He therefore highlighted two particular issues: transparency and solidarity. “First, transparency is of course the question of shadow economy, unfair competitions and falsification (directive).

“a common understanding of how to assess, authorise and monitor medicinal products”. “Without this groundwork,” he continued, “later successes such as mutual recognition procedures, the introduction of a centralised approval system and the establishment of the European Medicines Agency would have not been imaginable.”

Progress Of course, progress has since been made, and the Health Commissioner underlined how there now exists a close-knit network of competent authorities in EU member states, as well as the European Medicines Agency (EMA) and the Commission, who all work together to combine their expertise and competences, thereby adding value and avoiding the duplication of efforts. He continued: “The assessment and the authorisation of medicinal products – under centralised procedure – is an inclusive process ensuring shared ownership and trust in the system. “A lot has been done, but we shouldn’t forget the tolling bells. Allergies, reactions to medicines and even clinical death still exist. Therefore we should continue the work on pharmacovigilance and transparency from clinical trials to data registries.” Andriukaitis, of course, is a trained medical doctor, and as such he is able to draw on his knowledge and experience to better fill his role as the European Health Commissioner. Indeed, he informed his auditors at the conference: “I know that patients have very high expectations as regards medical treatments, and call for the speedier translation of scientific progress into accessible and affordable therapies. Nevertheless, they often do not have time to

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Access to ‘innovative medicine’ requires solid clinical evidence to justify public coverage

“On the other hand, transparency also means fair prices. This is a difficult discussion. Patients seem to mistrust the industry claiming that prices are too high and somebody takes a huge profit out of it. The question is – how to create partnerships between pharma industries, member states, healthcare providers and health insurers? How to create mechanisms so that people understand that the profit does not play the main role in the pharma sector? Medicine is not just any type of good; it is a specific good and cannot be created only for profit. “Therefore I truly believe that we need an open debate on medicine pricing because when it is covered by commercial secret, it creates mistrust in the society,” he said. Regarding solidarity, the commissioner added: “Medicines, innovative medicines, and vaccinations cost money. Sometimes they are so expensive that even rich countries cannot afford them because the compensation mechanisms are too weak. “Access to medicine creates a lot of tension in society. Especially because the financing of our healthcare systems is solidarity based. We should know what resources are needed, why they are needed and how they will be compensated. The question is how to find a driving mechanism between solidarity and profit? These questions of transparency and solidarity should be treated in light of Health Technology Assessment.”

Innovative medicines Indeed, as the commissioner highlighted, access to ‘innovative medicine’ requires solid clinical evidence to justify public coverage, and the Health Technology Assessment has proved to be an efficient tool for improving access to innovative technologies, and for providing decision makers with such evidence to support more efficient allocation of funds. He continued: “The Commission and the member states are already co-operating to develop joint assessments of technologies and addressing methodological challenges. Joint forces and expertise will help decision makers to make more informed and faster choices on access to innovative treatments. “Joint forces are also important when we speak about vaccines and long term, stable and functioning platforms for medicines. There is no other way. The joint procurement agreement is a great example of such co-operation.” Andriukaitis concluded this part of his address by briefly mentioning the regulatory environment: “There shouldn’t be an overregulation, but we cannot only regulate when we are in crisis. The right balance should be found so we can create real trust in the system and a long term partnership between the member states and industry.”

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The Norwegian perspective With some 60% of all Norwegian research publications focused on medicine, health and natural sciences, it is clear that biomedicine in the country is coming to the fore. Indeed, a new report published by the Norwegian Research Council (Norges forskningsråd) reveals that the country has seen a significant increase in research funding in recent years, which has served to place Norway in a unique position, as most countries are cutting research funding. The report shows that approximately half of Norway’s business enterprises are qualified to be called innovative companies (most innovation activity takes place in major international industrial companies), placing Norway on an equal footing with the other Nordic countries. Likewise, health and welfare research comprises the largest thematic research area in Norway. Functional genomics research (which is related to and includes elements of biotechnology) will lead to improved health, safer food and a better environment and, according to Norges forskningsråd, Norway has a number of national advantages within biotechnology: extensive health registers for both humans and animals, combined with some of the world’s largest animal and human biobanks. Norwegian aquaculture has used biotechnology for many years to provide consumers with farmed salmon that maintains high health levels without excessive use of antibiotics. Within this area, the Research Council of Norway established the FUGE research programme in 2002 in response to a proposal submitted by a unified Norwegian research community. FUGE is designed to enhance Norwegian research in functional genomics in the following areas: Basic biological research: FUGE will strengthen basic biological research and will help to ensure that Norway emerges as a prominent player in areas of particularly strategic importance or in which it has specialnationaladvantages. Medical research: FUGE will make it possible for Norwegian healthcare services to utilise the new knowledge and products that result from functional genomics, ensuring that Norwegian healthcare remains among the best in the world. Marine research: FUGE will play a role in establishing the knowledge base needed to promote further development of the aquaculture industry and optimal utilisation of Norway’s marine resources. It is also important to facilitate the establishment of a biomarine industrial cluster in Norway. Ethical, environmental and social issues: FUGE will enable Norway to acquire knowledge about the consequences and dilemmas inherent in functional genomics research in order to supplement the public debate, and help to maximise the potential positive impact of such research on society, the environment and the individual. National technology platforms have also been established as the pillars of the FUGE programme. These platforms have national responsibility for developing specific areas of technology and will become technical service centres providing special expertise within the applicable technologies. They provide seminars and meetings for users throughout Norway and conduct international research activities to enhance the development and utilisation of the platform technology.

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Innovative future He then turned his attention to the future of medical innovation by repeating a call he had made numerous times since his appointment as Commissioner for Health: the need to shift from healthcare or treating sickness to disease prevention, wellness, and enhanced performance, as well as innovation and advanced therapies. He explained: “Today there are more and more informed patients who often search for information or exchange views online before and after they visit the doctor. We should take this trend into account and invite people to actively engage in their own health management. “Earlier this year, I visited the eHealth week in Riga. It was fascinating to experience first-hand how innovative developments can empower patients. There is huge potential and I encourage further developments in this area. But it seems to me that we have to work more on preventive technologies to support healthy people. This is why prevention should be our primary concern. “Technological breakthroughs – from sensors providing real-time data on a person’s state of health to the ability to sequence a person’s genome — promise greater visibility over personal health and offer the possibility of earlier diagnosis and hence earlier, more targeted treatment if and when people fall ill.” These technologies will, Andriukaitis added, certainly bring an important shift towards more informed patients taking greater control over their own health. It will also hopefully shift the focus of healthcare to prevention.

Questions Nevertheless, the question remains as to how today’s medicines developers can be provided with a guarantee that healthcare systems can absorb all those innovations, how the political, economic and ethical challenges that this innovation is bringing can be dealt with, and how the obstacles to health infrastructure and business models can be overcome. As commissioner with responsibility for health, Andriukaitis has an overview of ongoing discussions and is also aware of the sensitivities and the need to fully respect each other’s competences. “However,” he said, “that does not mean that we should keep our eyes

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Biological medicines Also attending the event was EuropaBio – the associate of European bio industries – which called on EU policy makers to continue promoting biopharmaceutical innovation, while maintaining high EU standards for the safety and efficacy of medicines. Speaking at the event, Nathalie Moll – EuropaBio’s secretary-general, said: “Europe has clearly come a long way in terms of protecting patient safety and guaranteeing the quality and efficacy of new medicines. We call on the EU drug regulatory network to maintain such high standards in the future while at the same time allowing enough flexibility for the healthcare biotech industry to continue to innovate.”

closed at European level. Instead, we should discuss together how we can perform better. “For the Commission, it is important that through continuous dialogue with member states, academia, industry, civil society and other stakeholders, that we strengthen our analytical capacity and knowledge, to be able to offer EU added value and expertise resulting in the best possible EU co-ordination and effective support.”

Robust system The commissioner concluded his address by highlighting how the last 50 years has seen a great deal being achieved – in terms of medicine development and in terms of the regulatory framework. “Neither science nor the law stood still,” he said. “All in all, a robust system has been established in those five decades – a healthy system. There will be no viable future without promoting health as a sound investment in our people and in our future. “President Juncker recently highlighted the importance of healthcare projects in his State of the Union speech. Some health projects are financed through the €315bn Investment Plan for Europe. Indeed, investment in health is an investment in growth. We need a healthy workforce to tackle today’s challenges and tomorrow’s problems. “Now is a moment to consider the future – a future which is needed in the interest of patients and society. I call pharma to focus more on prevention than cures.”

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EuropaBio called on the EU drug regulatory network to maintain such high standards in the future while at the same time allowing enough flexibility for the healthcare biotech industry to continue to innovate

Robin Evers, Senior Vice-President of Regulatory Affairs, NovoNordisk A/S and chair of the EuropaBio Healthcare Council, added: “We need bold measures to cut red tape, particularly for SMEs, and to streamline patients’ access to new and innovative biotech medicines.” According to EuropaBio, in recent years the healthcare biotechnology industry has led to outstanding medical advances resulting in dramatic improvements to the quality of life of millions of European patients. Only 30 biotech medicines had been authorised in Europe until the entry into force of the centralised approval system in 1995. Since then, and in only 20 years, that number has trebled with approximately 90 applications for marketing authorisation of biotech medicines having been received by the EMA. Biological medicines have become the treatment option for many chronic conditions such as diabetes, anaemia or hepatitis C. They have also become the new standard of care for other diseases such as rheumatoid arthritis or cancer, and represent 50% of all medicines in development. Following on from this, in October the European pharmaceutical industry welcomed the initiative by the European Commission Directorate General for the Internal Market, Industry, Entrepreneurship and SMEs (DG Grow) to host an event on access to biosimilar medicines in Europe. According to the European Federation of Pharmaceutical Industries and Associations (EFPIA), the European Generic and Biosimilar medicines Association (EGA) and EuropaBio, at present, biosimilar medicines represent a small but growing market in the EU, but also harbour a significant potential to increase access to high quality medicines for patients, contribute to the sustainability of healthcare systems, and free up resources for innovative medicines. Effective biosimilar competition is part of the solution to lower healthcare expenditure and to treat more patients. If Europe is able to establish a sustainable market framework to stimulate biosimilar competition, patients, healthcare providers and payers will benefit from an increased choice of available therapies and increased patient access to existing and new therapies, which will help governments to manage their budgets.

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RESEARCH DEVELOPS MEDICINES iMed.ULisboa, Faculty of Pharmacy, University of Lisbon outlines its focuses in the area of drug discovery and development

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he Research Institute for Medicines (iMed.ULisboa) covers the key aspects of pharmaceutical and biotechnological drug research. Particular focus is given to the identification of drug targets and lead substances, from chemicals to biologicals, development of novel biological therapies, such as protein-, gene- and cell-based therapies as well as nanotechnologies, and engagement of drug regulatory affairs. iMed.ULisboa is a multidisciplinary research and innovation unit for life and health sciences funded by the Portuguese Foundation for Science and Technology (FCT) and based at the Faculty of Pharmacy, University of Lisbon. Our mission is to develop novel treatments and benefit human health through top class research. The 2015-20 iMed.ULisboa Strategic Plan takes the theme ‘Research Develops Medicines’, emphasising the impact that top class research has on improving the development of novel therapeutics, thus benefitting human health and societal wellbeing. Our output indicators ensure that our research reflects the dynamics of health needs, namely in areas of ageing and ageing-related diseases such as diabetes, cancer and neurodegeneration, and infection, whilst ensuring co-operation or strong allocation of effort to maximise the national and international impact of this research. In addition, our indicators reflect the needs of others who use our research, in public services and industry, and respond to international research trends. Other research outputs reflect investment in knowledge transfer opportunities that have accelerated the development of promising new technologies and products, as well as investment in infrastructures and training that has been key to improving the productivity of our research.

Capabilities and expertise iMed.ULisboa’s capabilities are built around a network of 15 research groups organised in four programme areas – drug discovery, design, development, and usage – spanning the drug discovery and development spectrum, with an emphasis on innovative, multidisciplinary, and collaborative research to develop medicines. We currently host over 100 PhD researchers and 85 PhD students. Our expertise in drug discovery is focused on integrating cellbased approaches with emerging ‘-omic’ technologies and pathway modelling to identify new targets for the engagement of rational drug design. We use both conventional small molecules and biopharmaceuticals targeting single molecules or complex interacting disease pathway components. Drug design experts focus on in silico screening of chemical libraries and development of bio-inspired, efficient and sustainable synthetic methodologies,

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in addition to biologicals and biotechnology-derived therapeutics such as proteins and non-coding RNAs. Drug development experts concentrate on generating the pharmacological, pharmacokinetic and safety attributes needed to drive molecules into first-in-human studies, through a strategy that integrates new drug delivery systems and non-biological complex drugs, including nanotechnology-based solutions. Finally, our expertise in drug usage is focused in the lifecycle of the product, from regulatory aspects, pharmacovigilance and risk management, to appropriate drug prescription and usage. This strategy will maintain a broadly balanced research portfolio, and at the same time shape it to ensure that research reflects evolution of health needs, namely in areas of ageing and ageingrelated diseases, such as diabetes, cancer, neurodegeneration and infection. Our strategy will additionally ensure co-operation or concentration of efforts to maximise the national and international impact of our research, while reflecting the needs of others who use our research, in public services and in industry, always responding to international research trends. Accelerating the development of promising new technologies and products is key, including investing in knowledge transfer opportunities. The high intensity laboratory, equipment and experimental components of our research are crucial to maintaining the knowledge pipeline and address the scarcity of new drug targets, where academic research and small enterprises may identify novel therapeutic candidates for development and funding. In this regard, collaboration between public and private sectors helps redistribute risk to drive innovation. Moreover, business funding of university research encourages essential links between commerce and academia, orienting research toward topics and ideas that are more likely to create new businesses, products and jobs. Co-operation between the academy and drug companies is likely to become increasingly important in addressing challenges such as cancer, neurodegeneration or infectious diseases by combining products from individual portfolios to create more effective therapies. Our high level of laboratory intensity will continue to make science at iMed.ULisboa even more attractive to academics and industrial investors, fostering new collaborative networks that will ensure competition with similar institutes across the world, especially those in Europe and in emerging markets.

Philosophy and future goals Our philosophy is emphasised and materialised by the increasing number of scientific papers published in international peer-reviewed and high impact journals and with high citation numbers, representing key papers in drug discovery and

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With over 100 integrated PhD researchers a similar number of PhD students are able to develop research projects at iMed.ULisboa, which is an important contribution to a youthful and vigorous atmosphere

development. iMed.ULisboa researchers continue to attract competitive external funds, both from contracts with government bodies and industry research contracts. The European Union funding programmes are a vital source of funding for science and innovation in Portugal, and a large focus has been placed on preparing research at iMed.ULisboa for Horizon 2020 instruments. Building on steady progress, we have set ambitious goals for seeking international research funding that need concerted action for iMed.ULisboa to achieve key targets by 2020. In addition to the scientific activities and examples of knowledge transfer, other indicators and outputs support our vision and objectives for the future. We are involved in an expanding number of networks and synergies locally and at the global level to ensure recognition of iMed.ULisboa’s value and contributions. We integrate key research infrastructures in Portugal and team up with major infrastructures at European level. iMed.ULisboa is also involved in large consortium initiatives for pharmaceutical medicines and drug safety such as the pan-European Education and Training Programmes SafeSciMET and PharmaTrain, funded by the European Innovative Medicines Initiative, bringing together top universities, institutes and the pharmaceutical industry. The FCT PhD Programme in Medicines and Pharmaceutical Innovation (i3DU) has been embraced by iMed.ULisboa, training 19 PhD students in its first year. The i3DU programme is a joint initiative of two reference universities in Portugal, the University of Lisbon and the University of Porto, grouping competences and boosting quality in postgraduate training in co-operation with the pharmaceutical industry. This strong commitment of academia and pharma meets well defined standards for high quality international PhD training, in addition to aligning with the preconised research-innovation-education triangle in Europe. Other successful FCT PhD Programmes are enthusiastically membered by iMed.ULisboa researchers.

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Another fundamental facet of iMed.ULisboa activities is to promote dialogue with the public on science and medicines in general. We have engaged with non-specialist audiences, including public events, school visits, appearances in the media and communicating research to health professionals, patient groups and policy makers in collaboration with scientific societies; the national agency Ciência Viva, among others. Our strategy for the future is built on our unique position and role in contributing to more effective ways for medicines development to succeed, from understanding fundamental questions, with specific life and health issues in mind, to effectively pursuing unrelenting disease problems in today’s society. Acknowledgment: iMed.ULisboa is funded in part by Fundação para a Ciência e a Tecnologia (UID/DTP/04138/2013).

Cecília M P Rodrigues Co-ordinator iMed.ULisboa Faculty of Pharmacy, University of Lisbon Lisbon Portugal +351 (0)21 794 6490 [email protected] http://imed.ulisboa.pt/

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PEN OUTLINES THE SIXTH EMBO MEETING, WHICH TOOK PLACE IN BIRMINGHAM, UK, INCLUDING THE LOUIS-JEANTET PRIZE LECTURES

Advancing the life sciences

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he European Molecular Biology Organization (EMBO) is an organisation of life scientists and a founding member of the Initiative for Science in Europe. According to its website, it has over 1,700 leading researchers who come together to promote excellence in the life sciences. Moreover, its goals are ‘to support talented researchers at all stages of their careers, stimulate the exchange of scientific information, and help build a European research environment where scientists can achieve their best work. ‘EMBO helps young scientists to advance their research, promote their international reputations and ensure their mobility. Courses, workshops, conferences and EMBO Press publications disseminate the latest research and offer training in techniques to maintain high standards of excellence in research practice. EMBO helps to shape science policy by seeking input and feedback from our community and by following closely the trends in science in Europe.’ It also ‘supports talented researchers, selected through impartial evaluation processes, to allow them to do great science. The wide scientific scope across the full range of life science research coupled with the broad geographical reach of more than 1,700 members and associate members – some of the best researchers in Europe and around the world – positions EMBO optimally to serve Europe’s life science community.’

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EMBO aims to define molecular biology in the broadest terms possible, encompassing research on the molecular mechanisms of life at all levels, from single molecules to organisms and ecosystems. To be able to group and retrieve information from a particular area, the EMBO programmes and activities apply a system of 20 broad and non-exclusive categories to their projects, communities and events.

EMBO Meeting The EMBO Meeting is an annual event held in Europe to promote the life sciences and the exchange of scientific results. The meeting encourages scientists to look beyond their own fields, engage with the international scientific community and explore interdisciplinary approaches to research in the life sciences. Participants experience new perspectives on topics that cover the entire range of the life sciences – from studies of molecules and the cell all the way up to investigation of larger, complex biological systems.

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Zechner and Charpentier, in fact, delivered the Louis-Jeantet Prize lectures. According to Sir Paul Nurse – incoming president of the LouisJeantet Foundation – who introduced the speakers, this is a “prize awarded to scientists who carry out outstanding discovery research with the potential for advances in biomedicine and in medical care. It is a significant prize, and it provides resources for the winners to carry out research in areas they think may be of interest in the future.”

EMBO holds that the meeting fosters interactions among the community of life scientists in Europe and beyond, allows scientists from all countries in Europe to hear talks by leading international researchers from all over the world, helps to promote excellence in the life sciences to the widest possible audience, and provides young researchers with access to career opportunities through networking events and other career-related activities.

CRISPR-Cas9 technology Charpentier is a French microbiologist whose pioneering work led to the discovery of the CRISPR-Cas9 technology in 2012. This is considered a revolution in biology and, as a tool for gene editing, it is now widely utilised in research laboratories around the world.

The inaugural EMBO Meeting took place in Amsterdam in 2009. The meeting has subsequently been held in Barcelona, Vienna, Nice, Heidelberg and, jointly with FEBS, in Paris in 2014. The meeting attracts more than 1,000 participants every year, including graduate students, postdoctoral researchers, young investigators and later stage researchers from all areas of the life sciences.

The EMBO Meeting’s website outlines Charpentier’s presentation as describing the origins, mechanisms and applications of the CRISPR-Cas9 technology. It reads: “The RNA-programmable CRISPR-Cas9 system has recently emerged as a transformative technology in biological sciences, allowing rapid and efficient targeted genome editing, chromosomal marking and gene regulation in a large variety of cells and organisms. In this system, the endonuclease Cas9 or catalytically inactive Cas9 variants are programmed with single guide RNAs (sgRNAs) to target sitespecifically any DNA sequence of interest given the presence of a short sequence (Protospacer Adjacent Motif, PAM) juxtaposed to the complementary region between the sgRNA and target DNA. The system is efficient, versatile and easily programmable.

2015 edition In 2015, the sixth EMBO Meeting was held in Birmingham, UK, and was attended by Pan European Networks. In the welcome message to the event, EMBO’s Detlef Weigel (chair of EMBO’s Council) and Maria Leptin (EMBO’s director), said: “The EMBO 2015 Meeting brings together an outstanding line-up of researchers in the life sciences. It is an opportunity to hear about the latest scientific highlights not only from researchers in different disciplines but also from speakers from many countries around the world.”

CRISPR-Cas9 technology, a tool for gene editing, is considered a revolution in biology

“Originally, CRISPR-Cas is an RNA-mediated adaptive immune system that protects bacteria and archaea from invading mobile genetic elements (phages, plasmids). Short crRNA (CRISPR RNA) molecules containing unique genome-targeting spacers commonly guide Cas protein(s) to invading cognate nucleic acids to affect their maintenance. CRISPR-Cas has been classified into three main types and further subtypes. CRISPR-Cas9 originates from the type II CRISPR-Cas system that has evolved unique molecular mechanisms for maturation of crRNAs

Sessions at the event covered areas as diverse as women in science (where Anna Wahl from the Royal Institute of Technology, Sweden, explored the perspectives of gender in academic disciplines) to space (with the European Space Agency’s Dr Matt Taylor delivering a presentation on the Rosetta mission – for which he is the project scientist – as well as options for future missions). Meanwhile, as the welcome message from the conference chairs highlights, in their keynote lectures, Joan Steitz, Peter Walters, Emmanuelle Charpentier, and Rudolf Zechner discussed scientific progress in the study of RNA, memory, gene editing technologies, and lipid metabolism. Meanwhile the three plenary sessions focused on nuclear architecture, pathogens and defence of the biology of stem cells, amongst other topics.

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and targeting of invading DNA, which my laboratory has identified in the human pathogen Streptococcus pyogenes. During the step of crRNA biogenesis, a unique CRISPR-associated RNA (tracrRNA) base pairs with the repeats of precursor-crRNA to form anti-repeat-repeat dual-RNAs that are cleaved by RNase III in the presence of Cas9 (formerly Csn1), generating mature tracrRNA and intermediate forms of crRNAs. “Following a second maturation event, the mature dual-tracrRNA-crRNAs guide the endonuclease Cas9 to cleave cognate target DNA and thereby affect the maintenance of invading genomes. We have shown that the endonuclease Cas9 can be programmed with sgRNAs mimicking the natural dual-tracrRNA-crRNAs to target site-specifically any DNA sequence of interest. I will discuss the biological roles of CRISPR-Cas9, the mechanisms involved, the evolution of type II CRISPR-Cas components in bacteria and the applications of CRISPR-Cas9 as a novel genome engineering technology,” the Charpentier synopsis concludes.

Lipolysis A member of the Austrian Academy of Sciences, Zechner has already received numerous prestigious awards, in particular the Wittgenstein Prize, Austria’s highest scientific award, as well as an Advanced Grant from the European Research Council (ERC). His Louis-Jeantet Prize lecture focused on ‘Lipolysis – more than just the catabolism of fat’. Here, he argued that dysfunctional lipid metabolism is often the underlying cause of obesity, Type 2 diabetes and cardiovascular disease, which continue to grow unabated around the world. In turn, this can lead to accumulations of fats and cholesterol in the liver and heart or on the walls of the arteries, resulting in malfunctions in these organs or tissues. As such, his research has involved the study of the mechanisms governing the metabolism of lipids, specifically focused on lipases, enzymes that degrade fats. According to EMBO, Zechner and his colleagues have found that ‘a new enzyme belonging to this family, adipose triglyceride lipase (ATGL) and its protein co-activator CGI-58,

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Dysfunctional lipid metabolism is often the underlying cause of obesity, Type 2 diabetes and cardiovascular disease

facilitate lipid catabolism in both mice and humans. In other words, these biological molecules play a crucial role in the storage and mobilisation of fats in our body. This discovery revolutionised our understanding of fat turnover. It also offered a mechanistic explanation for the occurrence of rare genetic diseases termed ‘neutral lipid storage diseases’, caused by a deficiency of ATGL or of its protein co-activator. ‘More recently, Rudolf Zechner and his team sought to understand how the breakdown of fat influences cell functions and the pathogenesis of disease. They were able to show a strong correlation between the catabolism of fats and cardiac function. To their surprise, they also discovered that lipid catabolism was involved in the development of cachexia, which takes the form of an uncontrolled and irreversible loss of weight in numerous cancer patients. The Austrian researchers have thus possibly identified a new direction for the treatment of this serious condition.’ The sixth EMBO Meeting was thus incredibly comprehensive and informative, featuring the presentation of groundbreaking research and the award-winning scientists behind them. The 2016 instalment will take place in September in Mannheim, Germany (see: http://www.the-embomeeting.org/), and already looks set to rival its predecessor in scope and content.

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GERM CELLS AND GENOME STABILITY Dr Bernard de Massy’s group is searching for new factors involved in genome stability

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ne of the cellular processes where tight control of the integrity of the genome is of crucial importance is when we transmit our genetic material to the next generation. However, when germ cells differentiate into gametes through a process called meiosis, a specific programme of DNA breakage and repair called ‘meiotic recombination’ is induced. This results in the paradoxical situation whereby the integrity of the genome to be transmitted is highly threatened. How and why this process is programmed is one of our main research interests.

Taking the risk of inducing DNA breaks in the genome The pathway of meiotic recombination is evolutionarily conserved and in most sexually reproducing species defects in meiotic recombination lead to the reduction or loss of fertility. Indeed, meiotic recombination events are required for the proper segregation of chromosomes during meiosis. In addition to its role in segregation, recombination generates new associations of alleles, thereby increasing genetic diversity and thus has long term consequences on genome evolution. At the molecular level, homologous recombination involves cutting, exchanging and ligating DNA strands of homologous DNA sequences. Deleterious consequences on genome stability may ensue if some of those recombination events are processed inaccurately, thus potentially leading to mutations or genome rearrangements. Therefore, meiotic recombination is a double-edged sword, being essential for fertility but facing the challenge to properly control the formation and repair of the many DNA breaks that are generated during this process.

recombination. In particular, we identified a gene, Prdm9, as a master regulator of the localisation of DSBs in the genome of humans and mice (Baudat et al., 2010). This finding revolutionised our concept because a genome-wide control by a single regulator was unexpected, but also because polymorphisms in Prdm9 can lead to genome-wide changes in the distribution of meiotic recombination. Alongside this work, we have developed strategies to evaluate the evolutionary conservation of molecular components participating in the molecular process of meiotic recombination. We addressed this question and were able to identify orthologs in metazoans (including mammals) of two proteins required for the programmed formation of DNA double-strand breaks during meiosis, Mei4 and Rec114, and previously characterised only in S. cerevisiae (Kumar et al. 2010). Our results reinforce our view on the evolutionary conservation of the underlying mechanism, especially as our recent studies further show that the mouse Mei4 and Rec114 proteins share several important properties with those of S. cerevisiae (Kumar et al, 2015). With the identification of major molecular components for meiotic recombination, important questions remain to be addressed if we are to understand their activities, and how they collaborate to achieve the remarkable genome stability and diversity that is transmitted to the next generation through gametes. Other features important for the stability and the dynamic of genomes and epigenomes are also investigated by other teams of the Department of Genome Dynamics of the Institute of Human Genetics providing a unique expertise and multiple interactions.

Regulation and mechanism of meiotic recombination

References

Our group is mainly involved in understanding the molecular mechanisms of meiotic recombination.

Kumar et al. 2010 Genes and Dev

In recent, on the basis of studies in various organisms, several groups have shown that meiotic recombination is initiated by the programmed induction of DNA double strand breaks (DSB). In mouse spermatocytes or oocytes for instance, several hundred DSBs are induced. This represents a tremendous challenge for the integrity of the genome. Several genes have been identified to play key roles in DSB formation and repair, but how these processes are regulated and co-ordinated remains a major challenge in the field.

Searching for key factors involved Our team, by developing complementary strategies and various experimental approaches involving genetics, cellular and molecular biology, biochemistry, genomics and proteomics has identified several novel essential genes for meiotic

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Baudat et al. 2010 Science Kumar et al. 2015 J Cell Sci

Bernard de Massy Group Leader Meiosis and Recombination Group Institute of Human Genetics CNRS Montpellier, France [email protected] http://www.igh.cnrs.fr/

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POTENTIAL OF SUPER-RESOLUTION Super-resolution optical microscopy is a superior tool for investigating living cells, and interdisciplinary efforts are required to proof its full potential in biomedical research

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fficient functioning of the human body involves a multilevel synthesis emerging from collective brain activity to the immune system. Signalling, whether in immune, neuronal, or other cells, is usually controlled by the local redistribution and interactions of a relatively large set of proteins, both on the cell surface and interior.

The spatial scale of these organisational changes ranges from micrometres to single molecular dimensions, i.e. nanometres. In addition, these changes may occur on multiple timescales from micro/milliseconds to minutes/hours. A striking example is the re-organisation of proteins on the cell surface of immune cells, which likely starts within seconds at the molecular scale, is followed within minutes by the re-organisation of receptors into submicrometre-scale protein assemblies (micro-clusters), and after minutes to hours culminates in the formation of a micrometre-scale structure of the so-called ‘immunological synapse’, probably the most essential step during an adaptive immune response.1 Typically, these processes are accompanied or actively driven by collective re-organisations of the immune cells’ interior cytoskeleton, both occurring on macro and microscales over minutes. Similarly during neuronal communication, cellular structures such as axons and synapses have been identified to play a crucial role. They contain key molecules, whose re-organisation is required to maintain and mediate their communication mechanisms.1

Working to understand Understanding the complex interactions of the molecular processes underlying these mechanisms is one of the main objectives of biomedical research. Disorders of these dynamic interplays can lead to disease, but their comprehension to the development of novel therapies. Considering the complexity of, for example, autoimmune diseases or cancer, to-date medical practice demands the most physiological conditions for their research – which can be best matched by studying living species, e.g. live cells and/or organisms. Covering the aforementioned large range of spatial (nanometres to larger than micrometres) and temporal (microseconds to minutes/hours) scales, this necessitates modern observation techniques. Scientifically, it is important that the methods do not influence the biological system during observation. The most suitable tool that can cover all of this is optical far-field fluorescence microscopy, i.e. the use of light-emitting (fluorescent) molecular labels in

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Fig. 1 A) Super-resolution microscopy: Confocal (outer) and superresolution (STED, inner part) images of immunolabelled Titin Z-disk in sarcomers in fixed myofibroblasts. Only the super-resolved image discloses certain details of molecular organisation. B) Trade-offs in optical microscopy: A toolbox of complementary fluorescence-based optical imaging techniques has been developed in order to optimise needs by biomedical applications. The ultimate goal is the development of a microscope technology that fulfils all of these properties

combination with focused light (far-field optics). Fluorescence imaging comprises several characteristics: 1) light hardly influences the system during observations; 2) the use of a lensbased system and focused light allows the observation to take place micro to millimeters away from the given optical element(s), preserving the non-invasiveness and the ability to observe deep inside living cells or organisms; and 3) the fluorescence readout, i.e. the light-induced excitation of emission from a fluorescent molecule (for example, an organic dye or fluorescent protein) labelling a specific protein, achieves the specific and highly sensitive detection of cellular constituents, and thus permits the disclosure of molecular distributions and dynamics.

Limitation Unfortunately, far-field microscopy still has limitations when it comes to temporal and spatial resolution: 1) submillisecond recordings are challenged by the amount of light, and thus the information yield, emitted by the fluorescent labels; 2) minutes to hours-long recordings are limited due to potential phototoxic effects by the light, i.e. light-induced photo-bleaching of the labels and changes or degradation of cells; and 3) the diffraction of light prevents resolving structures at a length-scale below around 200nm. To this end, molecular dynamics and organisations can only be resolved within limited temporal and spatial regimes. A remedy to this might be the use of alternative observation technology. For example, techniques such as electron microscopy, near-field

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microscopy, or atomic-force microscopy can offer spatial resolutions down to molecular scales with the drawback, however, of not being able to investigate the living cell, or only cell surfaces. Consequently, over centuries, a major quest has been pursued to break the limit in spatial resolution of optical far-field microscopy as given by the diffraction of light, nowadays resulting in a whole range of available super-resolution microscopy or nanoscopy techniques.1,2 Approaches such as Structured-Illumination-Microscopy (SIM), 4-Pi, and I5M push diffraction to its very limits, delivering spatial resolutions of down to around 100nm. In contrast, methods such as Stimulated-Emission-Depletion (STED) microscopy, Reversible Saturable Optical (Fluorescence) Transition (RESOLFT) microscopy, (fluorescence) Photoactivated Localisation Microscopy ((f)PALM), (direct) Stochastic Optical Reconstruction Microscopy ((d)STORM), or Ground-State-Depletion (GSD)) microscopy make use of the ability to modulate the fluorescence emission, thereby ensuring that the detected fluorescence signal stems from areas much smaller than the 200nm given by the diffraction limit, i.e. they reach in principle unlimited spatial resolution.1,2 The power of such nanoscopy techniques is highlighted in Fig. 1A, which shows the organisation of cytoskeletal structures in immune cells, indicating that molecular arrangements can be studied inside the intact cell with so far unprecedented spatial resolution. Unfortunately, the increased sensitivity comes at a price:1,2 1) nanoscopy techniques are usually more sensitive to artefacts such as changes introduced by the fluorescent labels; 2) the techniques usually feature less temporal resolution than conventional methods, limiting observations to dynamics slower than seconds to minutes; 3) light-induced effects such as phototoxicity may be increased due to the need of adding light for modulating fluorescence; and 4) the inability to investigate features deep inside cells due to deteriorations (so-called ‘optical aberrations’) when the light passes through several layers of the sample. In cases, users sacrificed spatial resolution and imaged at lower resolution using, e.g. STED or RESOLFT microscopy with lower light powers of the laser modulating the fluorescence emission (these techniques uniquely realise tuning of the resolution through adjusting that laser power), SIM, or even conventional microscopy techniques such as confocal or multiphoton microscopy. On the other hand, the above limitations are approached by input from different disciplines, (bio)chemistry, engineering, and physics:1,2 new labels provide higher photostability and signals as well as improved ways of tagging the molecules of interest; more efficient light sources such as lasers realise optimised ways of exciting and modulating the fluorescence; improved optics such as adaptive optics or light-sheet and multi-spot illumination deliver the light to the sample in a more efficient way and thus minimise aberrations and phototoxicity and maximise acquisition speed; and intelligent data analysis algorithms enhance the content one can extract from an image.

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Another remedy to the above limitations is the combination of nanoscopy techniques with other read-outs, which allows enhancing information contents of the recorded data as done, for example, in spectroscopic-based studies of fast millisecond molecular dynamics using STED-F(L)CS or single-particle tracking PALM (sptPALM), or when combining read-outs such as force, electrophysiology or electron with fluorescence microscopy.

Missed opportunities? In general, the demands of biomedical research are large with applications requiring different aspects of spatial and/or temporal resolution, three-dimensional imaging deep inside the sample, and/or long acquisition times with low phototoxicity (Fig. 1B). The fact that all microscopy approaches are complementary, whether they are diffraction-limited or with nanoscale resolution, promotes research environments with access to various kinds of microscopes and nanoscopes, depending on their suitability for the case in hand. On the other hand, research environments should be strongly interdisciplinary, allowing (bio)chemists, physicists, engineers and biomedical researchers to tightly work together to optimise technology for its use in biomedical research. An ultimate goal would be a microscope that can combine all of the demands set by the users (Fig. 1B). Unfortunately, much advanced technology developed by engineers, physicists, or chemists has not made its way into applications, simply because of missing tight links with biomedical users. The question arises whether we have missed opportunities. Therefore, funding possibilities have to be created, promoting interdisciplinary research environments with access to a broad range of complementary state-of-the-art technology as well as with the chance to test out new approaches. References

1 Hell, SW et al. The 2015 super-resolution microscopy roadmap. J. Phys. D: Appl. Phys. 48, 443001 (2015) 2 Eggeling, C. Willig, KI. Sahl, SJ. & Hell, SW. Lens-based fluorescence nanoscopy. Q Rev Biophys 48, 178–243 (2015).

Marco Fritzsche, PhD Junior Principal Investigator [email protected] Christian Eggeling Professor of Molecular Immunology [email protected] MRC Human Immunology Unit Weatherall Institute of Molecular Medicine, University of Oxford +44 (0)1865 222 167 http://www.nano-immunology.org

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EMBO’S DR MICHELE GARFINKEL MET WITH PEN TO DISCUSS VARIOUS ELEMENTS OF SCIENCE POLICY

The policy dialogue

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5-8 September 2015, EMBO held its sixth ‘EMBO Meeting’ in Birmingham, UK. The conference, held to promote the life sciences and the exchange of scientific results, was designed to encourage scientists to look beyond their own fields, engage with the international scientific community and explore interdisciplinary approaches to research in the life sciences. Participants experienced new perspectives on topics that cover the entire range of the life sciences – from studies of molecules and the cell all the way up to investigation of larger, complex biological systems.

In a general sense, it is very rare for research to be situated in only one country; most projects have collaborators from other countries, even if it is not a requirement to have Europe-wide participation.

Dr Michele S Garfinkel

Pan European Networks travelled to the event to meet with EMBO science policy manager, Dr Michele Garfinkel, to discuss the organisation’s policy programme and other relevant issues such as research integrity, technology assessments, and the importance of enabling scientists themselves to contribute to policy discussions.

Do you feel that excellence and inclusion in evaluating research is an irreconcilable conflict?

What are your thoughts on the ways in which the requirements for researchers to obtain training in research integrity are rapidly evolving in Europe today? First and foremost it is great that, as you say, they are in fact evolving. One of the really big challenges in Europe concerns the uneven development of standards: some countries have quite good standards, while others appear to have none. How those standards should look depends on whether you are thinking of research only within particular countries or from a pan-European perspective.

It is, of course, great if everyone in a collaboration knows what everyone else’s requirements are and, indeed, if they somehow find a way to stick to them. That is not to say, however, that research integrity rules necessarily need to be harmonised at the EU level, but the fact that European bodies are thinking about these issues, are trying to work through them, and are looking at the national level for examples of what might or might not work for Europe is a very positive development.

We are thinking about the practical issues of how to bring research integrity training to our community

From the policy perspective that is a very difficult question, and one which perhaps no-one has the answer to. Many of us have very strong feelings about this issue but, for me at least, there is no real reason to think they are irreconcilable; though there is a sense that we have reached a point where we want to look at that analytically and ask the question in a more rigorous way, looking at trade-offs when trying to incorporate both into research programmes. In any case, we certainly hope that they are not irreconcilable. Everybody can point to an example where this issue was reconciled, but to be able to look at those as a larger group and ask whether there are commonalities, to explore how the successful ones work and how they can be applied (as well as to lay out the benefits given that it takes a lot of effort to reconcile them) is something which remains to be done. Within this, there are many social, cultural, and philosophical issues about how research should be done which will need to be taken into account.

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From the technology policy perspective, there certainly could be innovation benefits, but the fact remains that there simply hasn’t been enough analysis of this debate so as to provide a definitive answer.

It is great to speak with scientists and hear their views on policy and politics

What can you tell me about EMBO’s science policy programme? We are working at the intersection of policy research and policy practice. On the research side, the programme has three major areas that we’re interested in: biotechnology; responsible conduct of research; and scientific publishing. We have a significant focus on scientific publishing because EMBO has several journals. It is very interesting to explore some of the policy issues involved in publishing, such as open access, data issues, research assessments and so on, particularly given the fact that the journals are now under a lot of pressure with regard to issues such as journal impact and what role they should play in research assessments, if any. Alongside this, another area we are working on is related research integrity, whereby we are thinking about the practical issues of how to bring research integrity training to our community, our fellows, our young investigators, and our members, especially in places where this might be lacking. We also want to understand how their training might be done better and more universally. The tools that EMBO has are relatively limited here, however, because we are just at the beginning of developing different types of training. Nevertheless, we are already getting a lot of feedback from our fellows and some of our members about what they would find useful. There is a good deal of work being done by the research integrity community generally which is thinking about which tools are the best, whether a certain online programme works, whether benchside training works, and so on. Again, there are certain things we assume to be true – such as that training is universally good: online training is useful, but benchside training is better – but we don’t actually know those things; they haven’t really been analysed, and so we are now trying things and seeing how they work.

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On the practice side, we are driven to some degree by our community, which includes an elected membership. These are outstanding scientists mostly from Europe and, of course, a key issue for all researchers is money and funding. Just as one example, EMBO, via our director, Maria Leptin, wrote letters to the relevant people in the European Parliament who were dealing with the European financial structure for investment issue. This was not to necessarily criticise its structure or to debate the distribution of funding, but to say that one of the great things about the well-respected ERC system, which EMBO helped to establish, is how rigorously and fairly it reviews the science, and that we would therefore like to see that rigour brought to any funded research, even if it’s not under that particular mechanism. Furthermore, we are a part of the Initiative for Science in Europe, which is a platform of some 17 learned societies who represent a wide variety of research fields in science, social sciences, and humanities, with whom we work on the policy practice side. One such project concerned how open access would affect learned societies, for instance, and from that we were able to distribute a paper to policy makers.

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Given that the life sciences are coming to impact on such a wide range of other areas, how do you see the role of science policies evolving when it comes to issues such as those raised above? In this sense, I see myself as a social scientist (although I’m trained as a biologist) and I think that there is a lot of analytical power in the social science tradition which is of use here. Indeed, the idea is not to get in the way of things happening, but to anticipate and to think about what the world looks like and, moreover, what it would look like with the advent of something new: with a new technology, policy and leader. There is a sense that when it comes to technology assessments we tend to obsess on the new technology and the bad things that can happen, but there is the argument that sometimes doing nothing is worse than doing something. In general, it is perhaps the role of people who think of themselves as being in the broad science policy community to think about these things and to bring together the many stakeholders who would either contribute to these changes or would be affected by them. By bringing together the necessary stakeholders we are able to work through these questions in a structured manner and ask questions such as ‘can you imagine this new technology/this new policy/this new leader? What does the world look like with them, or without them?’. This dialogue is important, because it enables us to elicit different views from different people.

There is a sense that when it comes to technology assessments we tend to obsess on the new technology and the bad things that can happen, but there is the argument that sometimes doing nothing is worse than doing something

exploring the different ways we can do things so that decision makers are aware of their options, are better informed and are thus able to make the right decision for their constituency.

How important is it to discuss policy with scientists, and do events like the one we are at today help with that? While this is quite clearly a scientific conference, we are also trying to bring more policy into EMBO in general. This is a very new programme, and it is great to speak with scientists and hear their views on policy and politics. They have some really good ideas and sometimes all they need is someone relevant with whom they can discuss their thoughts and, of course, if many of the scientists are all highlighting a similar issue then we can explore that further.

Michele S Garfinkel, PhD Manager, Science Policy Programme EMBO www.embo.org/

It is important to note that policy is about expanding options, whereas politics is about narrowing them. Our role is to expand options by

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SMART, LIVING MATERIALS The Bioinspired Molecular Engineering Laboratory explains how smart materials can also come to life

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or just over a decade, a wide variety of dynamic and responsive supramolecular assemblies have been investigated and developed to address biological systems. Since the non-covalent interactions between individual molecular components in such assemblies are similar to the interactions found in living systems, it was possible to integrate chemicallysynthesised and naturally-occurring components to create platforms with interesting bioactive properties. Cells have been occasionally addressed and incorporated in such supramolecular biological systems. However, a broader investigation into the various prospects of combining these two worlds has not yet been reported in a physiologically relevant context. The Bioinspired Molecular Engineering Laboratory of Professor Pascal Jonkheijm attempts to explore the possibilities of developing novel platforms by combining supramolecular chemistry with living bacterial systems and mammalian cells. The biological response at the interface between a biomaterial and the human body is dynamic with changing cellular and molecular players as well as evolving requirements. Moreover, the response is controlled at different length scales, ranging from, for example, keratinocytes migrating into the wound, to collagen fibres guiding the migration process and single proteins that act as chemoattractants. Current biomaterials in clinical applications are static while materials with molecular dynamism would ensure that the interaction between cells and materials is dynamic. Supramolecular chemistry endows upon biomaterials dynamism on a timescale of a millisecond to several hours on length scales ranging from the several hundreds of nanometres to several micrometres. Developing supramolecular systems that display bioactive ligands in a dynamic and responsive manner, with predetermined off-rate kinetics or as molecular gradients to address cells, is one major activity within the laboratory. We also genetically engineer the exterior of cells to display supramolecular binding motifs on them in an attempt to incorporate them as living entities in supramolecular architectures, bio-coatings and biomaterials. When it comes to remedying problems with implant materials, alteration of the top layer of coatings of clinical devices such as stents to include dynamism at the interface of the implant is a simple chemical adjustment with enormous impact on clinical outcome. Our dynamic coating manipulates the endothelial cells in the artery wall so that when they coat the surface of the stent, they prevent the fast-growing smooth muscle cells from proliferating around it. To attach the endothelial cells to the stent’s

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surface we have used dynamic chemistry to create a type of ‘glue’ made from proteins found in the human body. With specially engineered arms, these synthetic proteins can simultaneously grasp the stent and attract endothelial cells. Then, by dynamically addressing the clusters of receptors in the membrane of endothelial cells, we can induce cells to spread themselves over the stent surface until it is completely covered, preventing the blood from clotting in the artery. Our studies provide a glimpse into some of the versatile ways in which supramolecular chemistry and living systems can be combined. The components and concepts investigated can be used interchangeably and also extended towards other fields to develop innumerable other nanotechnology systems. This could essentially allow us to give systems exciting new properties like motility, growth and resistance against external agents. One could imagine that these cells or bacteria can carry within the bloodstream microscopic cargo, like drugs in a microcapsule, and when triggered release this cargo at a particular site, like a cancerous or infected cell. Living cells incorporated in supramolecular materials could possibly also be designed to secrete other components of the material, allowing them to heal the material or make it grow. Several challenges, largely regarding the understanding of these systems, lie ahead. Living systems are extremely difficult to predict and a massive amount of trials and tedious analysis is required to understand the various processes involved. The general outlook gathered from our explorations indicates that a productive future lies ahead for supramolecular biological systems in healthcare applications, and also certainly beyond where the possibilities are limited only by imagination.

Professor Dr Pascal Jonkheijm Laboratory of Bioinspired Molecular Engineering University of Twente +31 (0)53 489 2987 [email protected] http://www.jonkheijm.org/index.html

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DEVELOPING DYNAMICS A team from the Cell Biology Unit at Institut Curie/CNRS discusses the dynamics of intracellular organisation, and two lab-developed technologies

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ur team, localised in the Cell Biology Unit (CNRS UMR144) at the Institut Curie (Paris, France), investigates the dynamics of intracellular organisation, focusing on the study of intracellular trafficking and the investing in the development of original approaches and assays. In particular, two technologies were refined or developed in the lab in the past 15 years.

On the one hand, we applied the recombinant antibody approach to cell biology and the study of cell dynamics.1,2,3 In this frame, we recently developed our own synthetic recombinant antibody library based on a single domain nanobody-like scaffold. We now use this library to answer cell biology questions. We also use our novel library to produce immunological tools to characterise and fight diseases like cancer, infection or hyper-inflammation. On the other hand, we developed a novel assay that allows us to analyse the diversity of the biosynthetic transport pathway and the role of a key compartment of the secretory pathway, the Golgi apparatus.4 We will describe this second aspect of our work here in more detail. The Golgi apparatus resides at the centre of intracellular trafficking, controlling secretory and retrograde routes. It is essential both to ensure housekeeping cellular functions and to sustain highly differentiated ones. Cells indeed use Golgidependent transport to build basic and specialised organelles, to regulate nutrient transport, cellular adhesion and motion, cell-cell contact, or the emission and reception of signals, for example. Any defect of proper Golgi function may thus lead to severe cellular defects and, as a result, to cell death or diseases.5 Golgi organisation, dynamics and function have been studied by many groups for several decades,6 and intensely for more than 40 years. Our knowledge about the mechanisms of Golgi-dependent secretion, the control of anterograde and retrograde intra-Golgi routing, as well as the regulation of the Golgi structure and functions, has dramatically increased but the fine picture is still lacking. The Golgi complex needs to simultaneously fulfil many different essential functions: proper sorting of very diverse cargoes toward specific compartments; segregation of resident and transported proteins and lipids; protein modification by glycosylation or controlled proteolysis; and anterograde transport and retrograde recycling. How very different proteins can be transported inside the same organelle at different speeds and toward various destinations is still an outstanding question, and the underlying mechanisms still poorly understood. For example, are large proteins of similar sizes trafficking together and excluding others? Similarly, are proteins headed for anterograde transport mixing with retrograde cargoes in the Golgi apparatus?

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And more generally, what are the mechanisms responsible for specific sorting and transport? This, of course, has a strong influence on our capacity to draw a comprehensive vision of Golgi-dependent transport routes. In addition, improving our knowledge about the fundamental mechanisms of Golgidependent transport will impact the treatment of certain diseases linked to defective trafficking (e.g. cystic fibrosis, lysosomal diseases, several metabolic and developmental diseases).5,7 Understanding the fundamental rules of Golgi-dependent transport, its diversity and the underlying mechanisms will not only allow us to draw a comprehensive picture of how the dynamics of intracellular transport routes are controlled, but will also help to explain why perturbations may lead to disease. As suggested below, a better comprehension and an improved control of transport routes may additionally lead to the development of original therapeutic options. It is indeed our belief that a deep understanding of the diversity of cellular secretory routes would also be a strong asset to develop original ways to fight many diseases like cancer, neurodegeneration or inflammation because it may help us to perturb the intracellular transport of key factors (e.g. receptors, channels, proteases, chemokines, cytokines, adhesion proteins), hence opening new roads for therapeutic development.

Addressing a central question How to get access to the diversity of Golgi-dependent intersecting routes4,8 has long been a central question. In comparison, knowledge about the complexity of the endocytic pathway has increased dramatically in the past two decades because specific probes, tracing diverse pathways, were developed early. This was instrumental in uncovering alternative routes based on particular lipids, coats, motors or enzymes. Similarly, the nature and the topology of the secretory proteins are diverse. Proteins transported through the Golgi complex are destined to various final compartments like the Golgi apparatus itself, the plasma membrane (including subdomains of the plasma membrane), the extracellular space, the endosomes, lysosomes, etc. These cargoes can be soluble proteins, large aggregates, transmembrane proteins or GPI-anchored proteins. Diversity also exists among transmembrane proteins, some bearing one, others 12 transmembrane domains and travelling as monomeric or multimeric complexes. Such a diversity of cargoes implies that the secretory pathway has to ensure the transport of very different proteins in terms of topology and size. Building a comprehensive model of Golgi dynamics and function thus needs to access and monitor this diversity.

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Fig. 1 Synchronisation of protein transport using the RUSH system. A) Scheme outlining the RUSH system. B) The Golgi enzyme Mannosidase (green) is retained in the endoplasmic Reticulum in the absence of biotin (top). It is transported to the Golgi complex (labelled using an antiGiantin antibody, red) upon addition of biotin (bottom)

Several years ago, our team invested in the development of a versatile system that would allow us to study the full diversity of the secretory pathway. We called it the RUSH assay (Retention Using Selective Hooks, Fig. 1) because it is based on the reversible retention of a reporter protein, fused to a streptavidin binding peptide (SBP) by a selective hook fused to streptavidin.9 Simple addition of biotin, a naturally internalised vitamin, induces fast release of the reporter. Because traffic is controlled and synchronised, this allows us to quantify the transport of the reporter, to analyse the role of regulatory factors or the impact of small molecules, and to compare the transport of different reporters. With this in hand, it is possible to explore several aspects of Golgi-dependent traffic in an unbiased and systematic way, covering multiple scales. We are now using the RUSH assay following several tracks: 1) Using dynamic imaging based on cutting-edge systems (spinning, EMCCD equipped confocal microscope, TIRF or SIM imaging systems), we systematically analyse the diversity of transport using various classes of secretory cargo such as Collagen, Type 1, Type 2, GPI anchors and tetraspan of G-protein couples receptors;

against various cargo, we get a quick access to the relative specificity of the identified molecule. Examples of cargoes studied in this part of our work are receptors and signalling molecules, metalloprotease or virus receptors. By investing in the development of original tools and assays, we thus aim to improve our knowledge about the diversity of secretory routes and their control mechanisms while opening new roads for therapeutic treatment. Our next challenge is to bring the RUSH assay to in vivo usage. Cited References 1 2 3 4 5 6 7 8 9

Nizak, C. et al. Traffic 7, 739-753 (2003). Nizak, C. et al. Science 300, 984-987 (2003). Dimitrov, A. et al. Science 322, 1353-1356 (2008). Boncompain, G. & Perez, F. Histochem Cell Biol 140, 251-260 (2013). Aridor, M & Hannan, LA. Traffic 3, 781-790 (2002). Morré, J D & Mollenhauer, H H. (2009). Aridor, M & Hannan, LA. Traffic 1, 836-851 (2000). Prydz, K. Dick, G. & Tveit, H. (2008). Boncompain, G. et al. Nat Methods 9, 493-498 (2012).

2) Associating the RUSH assay with quantitative proteomics, we start to build a map of the protein landscape faced by cargo at different stages of their intracellular transport; 3) Adapting the RUSH assay to multi-well formats, we use it to screen siRNA libraries by high content screening (HCS) to identify key factors regulating the transport of selected cargoes; and

Dr Franck Perez Dynamics of intracellular organisation CNRS UMR144 - Institut Curie - PSL Research University - Paris - France

4) We also use HCS coupled to the RUSH to screen chemical libraries and identify molecules that more strongly perturb the transport of one cargo involved in the development of human diseases. Because we screen the same chemical libraries

+33 156 246 388

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[email protected] http://umr144.curie.fr/en/team/perez

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CIMR DIRECTOR PROFESSOR GILLIAN GRIFFITHS MET WITH PEN TO DISCUSS SOME OF THE AREAS THAT THE CIMR IS EXPLORING, AS WELL AS ISSUES SUCH AS GENDER EQUALITY

The right environment

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he Cambridge Institute for Medical Research (CIMR) aims to create an inspiring environment in which outstanding scientists can excel. Its state-of-the-art core facilities and support for its researchers helps it to foster new collaborations that spark discoveries about fundamental cellular processes and their relevance in disease.

We would love to be able to capture the final steps when the killer cells release their granules and deliver the lethal hit, but we already know that only one or two of the 50 granules needs to be released to kill the target, and it is difficult to capture that one event.

The CIMR forms a unique partnership between clinical and basic research, aiming to understand the cellular basis of disease. Its strategy is to use cell biology to understand the mechanisms of disease and, conversely, to use genetic disease to reveal crucial mechanisms of cell biology.

Given the fact that imaging is crucial to your work, do you have any hopes for new modalities and perhaps radiopharmaceuticals able to characterise certain aspects of different tumours etc.?

Professor Gillian Griffiths

Pan European Networks met with the CIMR’s director, Professor Gillian Griffiths, during EMBO’s sixth meeting in Birmingham, UK – which itself was aimed at encouraging scientists to look beyond their own fields, engage with the international scientific community and explore interdisciplinary approaches to research in the life sciences – to discuss not only her own research, but also some of the broader issues in science including gender equality and inspiring excellence in science.

What are the biggest challenges when it comes to uncovering the mechanisms controlling secretion from cytotoxic T lymphocytes (CTL) and natural killer (NK) cells? Killer cells of the immune system are exceptionally good at what they do. These cells recognise and destroy virally infected and cancerous cells in our bodies; and they do so with remarkable efficiency and precision. This makes it very challenging to image them as they kill their targets.

Crossing over between fields gives new inspiration, and that is incredibly important. However, this is not something that can be driven artificially

Yes, I do indeed have high hopes for advances of this type. Much of what we have done to date has had to be in vitro because it is just not possible to get the kind of resolution you need in tissues at the moment. My hope therefore would be to achieve really high resolution with low phototoxicity, as this would mean that the cells stay alive, and you would be able to image these events in an organ, for example, when these cells are attacking cancers. Currently, we are able to see the cells, but we can’t see what is going on inside them, and that is, for us, the most fascinating thing – we want to know what is going on inside them and how they work.

Do you feel more needs to be done to bring together different disciplines and those working in different fields – cancer and HIV for instance? Yes, and this is also a very interesting question. Crossing over between fields gives new inspiration, and that is incredibly important. However, this is not something that can be driven artificially; it has got to be nurtured and given a chance to develop, and that is best achieved by allowing curiosity-driven scientists to be able to meet colleagues in different fields. For example, a meeting such as the one hosted by EMBO is great because it provides delegates with the opportunity to hear talks that aren’t

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necessarily directly related to their field, and if someone attends a session that they might not have gone to otherwise, then it makes the whole thing worthwhile. This idea of multidisciplinary working hinges on catching the similarities between systems, and that is one of the things that has really helped my own science. For instance, the similarity we found between the immunological synapse and the primary cilia is now letting us use the information gained from studies on primary cilia to ask whether similar mechanisms are controlling killer cells. This illustrates why I think that it is very important to facilitate cross-disciplinary research. It is important to provide opportunities for scientists from different fields to meet and exchange ideas.

You have also highlighted the importance of clinical collaborations in identifying proteins required for secretion and understanding how these proteins work. How do you approach this? There is a real goldmine at the clinical-basic science interface, and as the director of the Cambridge Institute for Medical Research, I am working to achieve our goal of using that interface to understand the cellular basis of disease. At CIMR we are working to create a very congenial environment in which to support really outstanding scientists (both basic scientists and clinical scientists involved in research at the molecular level) who can interact and spot the links between what the disease is telling them, and what the cell

There is a real goldmine at the clinical-basic science interface

biology is telling them. This happens very readily. If you have the right kind of curiosity-driven scientists and clinicians working alongside each other, remarkable insights emerge. It is important to create the right kind of research environment where talented individuals from these two backgrounds can intermingle and let the research take off.

What are your thoughts on how this type of research is supported at the European level and the role that the EMBL/EMBO plays? One of the most important aspects of EMBO are the big meetings like this where there are lots of different types of science that you wouldn’t normally come across. A T cell (white) killing a target (blue)

In addition, the smaller EMBO workshops are really excellent. They are very congenial and they foster collaborations. They are small and allow a lot of interaction, they allow a lot of people to speak – from students to senior scientists – and they are very inclusive. They were incredibly important for me when I was starting out with my research lab in that they introduced me to a set of colleagues who were really collaborative, and when you are doing work of this type it is important to be able to find a group of people who are very supportive of each other and want the field to move forwards. It is about finding the right scientific community that will really make the research go forward, who are generous and open, and that is the whole ethos of the EMBO meetings and workshops. With regard to EMBL, it is a fantastic place: it has that international buzz and produces first class science, both of which are very important.

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What are your thoughts on the relationship of excellence and inclusion in research? In my opinion it should be the goal of every scientist to do the most thoughtful, high quality research possible, because in the end that is what really matters. One of the enduring lessons that I learnt during my time as a PhD student was to do all research properly, and this has paid enormous dividends throughout my scientific career. And at a meeting like this, it is clear that there are a huge number of scientists following the same path; they are producing excellent research and are taking care to ensure that everything they do is done properly. From that unfolds areas and discoveries that you wouldn’t necessarily have expected. It is one of the joys of being a scientist to know that if you take the time to think about things carefully, and are setting up your experiment properly, you will make observations that could easily be missed if you rush in and cut corners. Excellence is essential in science.

Would you like to comment on the issue of gender equality in science, and how related issues have affected your own career? Throughout my career – at least until recently – gender equality was perhaps an issue I paid less attention to; I simply wanted to be the best scientist I could be. In recent years there has been an increased recognition for the need for gender equality in science, and that has now started to open doors and has made a big difference. The organisers of the EMBO meetings make great efforts to ensure that there is gender equality at all levels.

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In recent years there has been an increased recognition for the need for gender equality in science that has now started to open doors and has made a big difference

A significant issue for women, both those who have undertaken a career in science and otherwise, is motherhood, and in many instances women with children may feel that being a parent and holding their place on the career ladder is more than they can handle, and finding ways to make this possible is something that should be addressed. There are also cultural problems which need to be tackled. For example, clinical environments (such as the one in which I currently work) have a different culture, where it is perhaps more difficult for women, and so that is something that I am trying my best to ameliorate. Perhaps one way to solve some of these issues is to simply include more women; women just do things differently, and including more women will improve things for everyone involved.

Professor Gillian Griffiths Director Cambridge Institute for Medical Research (CIMR) http://www.cimr.cam.ac.uk/ [email protected]

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A QUEST INTO MUSCLE PLASTICITY The Laboratory for Muscle Plasticity is constantly exploring and researching in its quest to perfect muscle function

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oft tissues (muscle, tendon and ligaments) demonstrate a graded capacity to respond to the impact of external stimuli with molecular and cellular adjustments that improve their capacity to withstand the original impact. The diagnostic assessment of the adaptive potential of muscles provides indications on how bottlenecks in the current therapy of musculoskeletal defects can be overcome. The aim being to innovate surgical and rehabilitative approaches to permit the handicapped individual to maximise adaptive stimuli and processes.

Fig. 2 Research approach scheme of the conceptual path of the research strategy of our integrated studies towards improved treatment of the orthopaedic patient

Muscle health is an economic factor

Our research focus

Plasticity is described as the ability of an organism to change its phenotype in response to changes in the environment. This has its place in body homeostasis, especially regarding the implication of skeletal muscle in bodily actions. Through its mechanical actions in locomotion, posture and speech, muscle facilitates interactions with the environment and affects energy expenditure. The reduction of muscles’ functional ability thus develops an important negative impact on our human capacity.

The strategic aim of the Laboratory for Muscle Plasticity at Balgrist University Hospital is to expose the molecular and cellular mechanisms underpinning muscle affections in clinical situations ranging from simple exertion-induced soreness to major musculoskeletal disease of striated muscle, and more so their reversion with rehabilitation. This is done within the goal to identify biological bottlenecks, which opens venues for novel interventions that can halt muscle deconditioning and degeneration. Specific emphasis is put on the myocellular processes of rehabilitative and therapeutic measures after orthopaedic surgery. Towards this end we focus on patient groups which could benefit from an improvement in muscle function. Further, we assess transfer effects on musculoskeletal health and quality of life.

Muscle weakness and associated poor fatigue resistance is a major challenge to modern Western society. It arises due to a reduction in the force-producing capacity of skeletal muscle with prolonged inactivity (disuse), injury or disease. The consequent reduction in strength negatively affects physical fitness and mobility, which lowers the quality of life. Based on epidemiological evidence it is estimated that associated costs accrue to CHF 2,000 (~€1,906) per person per year (Fig. 1). Musculoskeletal health is thus an important financial substrate in Western society.

Research approach and strategy The Laboratory for Muscle Plasticity at Balgrist deploys state-ofthe-art methodology to optimise surgical approaches and rehabilitation based on genetic and physical constitution. The research is embedded in the Orthopaedic Hospital of the University of Zurich. By 2016 it will extend its patient-tailored biomedical research by integrating its activities in the musculoskeletal research centre at Balgrist campus. The following sections highlight active areas and the scientific background of our research towards a personalised approach to musculoskeletal health.

Background

Fig. 1 Healthcare cost in 2011 of the seven major non-transmissive diseases. To the right: focus on affliction of the musculoskeletal system

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Skeletal muscle function relies on shortening of the embedded muscle cells (fibres) and this depends on bioenergetic processes. This results in the capacity for force production, which is dictated by the composition and anatomy of skeletal muscle. This especially implicates the volume content of slow and fast contractile types of myofibrils, mitochondria and capillaries. These cellular variables define the maximal force (strength) and fatigue

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resistance of contraction. Both features are conditioned in a pulsatile manner by muscle use. This occurs because there is a natural degradation of muscle material due to wear and tear of cellular structures. The wasted muscle material must be replaced through the activation of biosynthesis. Mechanical stress with weight-bearing contractions is a potent stimulus for the activation of these synthetic pathways. Energy flux is its most important modulator. The specific conditioning of muscle through physiological factors is amply illustrated by the different outcome of strength-type versus endurance-type sports activities that involve a high load or high repetition number of contractions, respectively. The underlying regulation involves the activation of a molecular programme that is embedded in our genes and which dictates the proteins to be made, i.e. expressed. The study of gene expression allows exposing the mechanistic relationship between the dose and duration of exercise and the resulting effect on muscle function. This knowledge is important to develop rehabilitative interventions or define stimuli that produce a functional outcome. Therapeutic measures based on information of muscle plasticity would thus offer considerable socioeconomic potential for musculoskeletal medicine, but its application in the management of healthcare is underdeveloped today.

PROFILE

condition affecting one in 1,750 individuals each year. Because it renders the function of the affected knees unstable, repair of the damaged soft tissue is strongly indicated. This requires orthopaedic surgery and subsequent physical procedures to support the functional recovery of the reattached ligament and connected muscle as it is weakened due to the prior injury and enhanced catabolism during unloading. Typically this is initiated by resistive types of exercise. The dose-effect relationships for musculoskeletal adaptations with rehabilitation, which define the therapeutic success of orthopaedic surgery, are not well defined. Towards this end we pursue an investigation to define the time course of molecular and cellular adaptations in a major knee extensor muscle with exercise-based rehabilitation subsequent to surgical repair of the ruptured ACL. This study is inspired by our results showing that eccentric types of endurance activity, such as that seen with downhill sports activities (skiing), represent a

Repair mechanisms after rupture of the anterior cruciate ligament As a joint, the knee exerts the important task of translating and potentialising forces being produced in the upper, large thigh muscles via the lever arm of the femoro-patellar articulation. This function is essential to counteract the forces of gravity through the extension of the knee. On the downside, however, the knee joint is exposed to particularly high rates of mechanical stress. This may damage anatomical structures that stabilise the knee joint if the resulting mechanical strain exceeds the typical safety factor for musculoskeletal tissues. This is especially true for the mechanical impact on ligaments that operate in the lateral direction, such as the anterior cruciate ligament (ACL) and medial patella-femoral ligament. Their integrity is challenged by biomechanical vectors that operate in transverse directions to the main movement of the knee joint. This often occurs with intense physical activity in sports and during manual labour and may lead to tendon rupture. This is a relatively frequent

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potent intervention to strengthen the musculotendinous structures that operate on the knee joint. We expect that our study will provide important information as to the quality and effect size of the rehabilitation for the deconditioned muscle and knee function.

Focus on rotator cuff disease The rotator cuff is a complex group of skeletal muscles which facilitate shoulder function. This involves important actions such as internal and external rotation as well as the abduction of the arm. Full or partial tears of rotator cuff tendons are a relatively frequent condition affecting a considerable portion of the population. Ageing-associated factors and injury represent the major cases of the disease. Thereby current numbers indicate that 40% of subjects above 60 years of age demonstrate tears of the rotator cuff. This severely complicates daily activities as it renders the accentuation of the upper extremity in one or more direction hard to impossible. If left untreated, shoulder function is permanently affected because the detached muscle degenerates by shrinkage of muscle cells and their conversion into fat tissue. Eventually this limits kinematics of respective joints, which has the ultimate consequence in the degeneration of the glenohumeral joint. At this point no other option remains than to surgically replace the joint with an expensive endoprosthesis to reinstate limb function. Surgical interventions aimed at repairing the affected shoulder muscle involve the reattachment of the ruptured tendon to the bone via an anchor. Thereby the prevention of adipogenic and atrophic processes in the detached muscle is a priority to warrant optimal surgical repair of the ruptured muscle-tendon unit. Towards improving the therapy of rotator cuff disease, we investigate the time course of molecular and cellular alterations

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in animal models of the ruptured rotator cuff. The aim is to map the mechano-regulated pathobiological process and risk factors of muscle degeneration, which contributes to the healing of muscle-tendon complex. Specific emphasis is put on testing the effectiveness of pharmacological compounds targeting the degradation of structural anchors of the contractile apparatus in muscle fibres. The knowledge is integrated in a clinical trial in which we characterise morphological and genetic biomarkers of the healing response of rotator cuff muscle after surgical repair of the detached tendon. This is motivated by the reported contribution of heritable factors to the healing of the reattached rotator cuff. The aim is to reintegrate the gathered knowledge into personalised surgical approaches and therapies that more efficiently prevent detractions in shoulder muscle function in critical responder groups (Fig. 2).

Professor Martin Flück, PhD Laboratory for Muscle Plasticity University Hospital Balgrist +41 (0)44 386 3791 [email protected] http://www.balgrist.ch/en/Home/Research-andEducation/Orthopaedics/Muskelplastizitaet.aspx

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ILLUMINATING HUMAN GENOME FUNCTION The director of the MRC Human Genetics Unit discusses how multidisciplinary approaches are needed to understand our genome, and to apply that understanding for clinical benefit

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are entering a particularly exciting time for human genetics, with large scale wholegenome sequencing producing data on an unprecedented scale, on the variation in DNA sequence between individuals, between patients and controls, and between normal and tumour cells. At the same time, developments in genome editing, induced pluripotent stem (iPS) cells, microscopy and proteomics are opening up new avenues for the experimental investigation of DNA, RNA, protein, cell, tissue, and organ function. This combination holds the promise of an era of stratified and personalised medicine in which disease is diagnosed, managed and treated based on an understanding of its molecular basis rather than on its superficial symptoms. However, in contrast to the escalating scale of sequence data gathering, studies that address the functional significance of genome variation lag far behind and this is hampering progress in exploiting genomic information in clinical practice. The UK Medical Research Council’s Human Genetics Unit (HGU), at the University of Edinburgh, is at the forefront of addressing this functional deficit. The 28 research groups of the HGU combine exceptional strength and depth in both computational and experimental biology, and aim to drive forward an understanding of the functional and pathogenic significance of human genome variation and of the fundamental mechanisms that underlie human genetic disease and normal biology.

A common language Harnessing ‘Big Data’ from large scale genome sequencing and epigenome profiling requires novel computational and informatics approaches. Each of us is born with about 100 new mutations that were not present in our parent’s genomes. To understand which sequence changes might be deleterious, and which are ‘silent’, computational researchers at the HGU are identifying the

forces that shape both mutation and selection in the human genome and are relating this to information on protein-DNA binding, protein complex formation, genome evolution, and the mechanisms of gene regulation. Too often computational and experimental biologists operate in silos. In 2011 the HGU partnered with the Edinburgh Cancer Research Centre and the Centre for Genomic and Experimental Medicine to form the Institute of Genetics and Molecular Medicine (IGMM) – one of the largest aggregates of human molecular genetics research capacity in the UK. The new IGMM Systems Medicine building accommodates computational and wet-lab scientists in a common open-plan working space that is designed to enhance the computational skills of the latter and the biological knowledge of the former, thereby encouraging the most effective communication between the disciplines.

Biology of the genome The MRC HGU was established in 1956 and quickly became a centre of excellence for studying the variation in chromosome structure in human populations – at the time only possible using microscopy (cytogenetics). Chromosome biology remains a core strength in the modern molecular era and particular interests are: the mechanisms of transcriptional regulation and gene silencing, epigenetic mechanisms and epigenetic dysregulation in cancer, RNA processing pathways, the function of non-coding RNAs and the structure and function of chromosomes.

From genotype to phenotype – the eye, brain and growth The purpose of acquiring whole human genome sequences is to reveal the relationship between genotype and phenotype in defined patient groups and in the population, and to identify the pathogenic consequences of genetic change. This should be at its most straightforward for single gene disorders, but often it is not possible to convincingly demonstrate a deleterious effect of an altered gene sequence. The deep mechanistic insights required to advance these problems will come, not simply from high-throughput global assays, but from clinicians and basic scientists delving deep into specific situations. HGU has particular strengths in the clinical and developmental genetics of paediatric disorders affecting the eye, the brain and growth, and in diseases that affect the function of specific subcellular structures (cilia and centrosomes). Genome editing,

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iPS cells, organoids and increasingly sophisticated fish and mouse models are used to investigate why the mutation of different genes can produce the same disease phenotype, and why different mutations in the same gene can result in different diseases. These studies are revealing the molecular and cellular pathways, the perturbation of which converges to produce a distinct disease state and these are possible targets for therapeutic intervention. In turn, HGU clinical geneticists, and their strong links to the UK National Health Service (NHS) genetic services, have immediate clinical impact by feeding back new findings to families.

Common disease is complex Individually, single gene disorders are rare. The genetics of common human disease is complex – involving the contribution of small effects from many genetic loci. This complexity can be somewhat simplified by using the genetic architecture of relatively isolated populations. Using samples from the Dalmatian islands of Croatia, from the Scottish Islands of Orkney and Shetland, and from the Generation Scotland biobank, HGU scientists – working with other international consortia – have for example revealed the genetic associations linked to many human traits and disease states, including those related to the function of the eyes (short-sight, retinal detachment) and to the excretion of uric acid from the kidney (gout).

The non-coding genome Challenging as it is to analyse DNA sequence variants in protein coding genes, only 2% of the human genome codes for protein. We currently lack the knowledge to understand the functional significance of variation in the vast swathes of the genome that lies outside of genes, however, this is where most of the genetic variation linked to common disease is. The space between genes is populated with DNA that has a regulatory function, either as a source of non-coding RNAs, or as elements ‘enhancers’ that control the precise cell and tissue specific expression of genes that are often quite far – up to one million base pairs – away.

HGU scientists have identified many of these fascinating cases of ‘long range’ gene regulation and are exploring how the threedimensional folding of the genome is involved in these mechanisms. Understanding how sequence variants impact on long range gene regulation requires physiologically relevant, scalable model systems and HGU scientists have developed experimental systems in the zebrafish that can directly compare the regulatory output of sequence variants from the human genome.

Infrastructure and collaboration Science is increasingly reliant on collaboration and on complex technology infrastructure. HGU is an active participant in many projects across the EU including Marie Skłodowska-Curie fellowships and Innovative Training Networks, FP7 and H2020 projects. As well as high computer capacity and other strong core facilities, HGU has a particularly strong reputation in advanced optical imaging. In partnership with Heriot-Watt University, the HGU and IGMM have formed the Edinburgh Super Resolution Imaging Consortium (ESRIC: http://www.esric.org), to bring together the expertise of biomedical and physical scientists and to provide an openly accessible international resource for visualising biological processes from the level of a whole developing organ, down to substructures within the cell and even individual molecules. Light is indeed being thrown on the human genome both to elucidate its complex regulation, so crucial to our normal development and physiology, and to illuminate the causes of dysfunction in disease.

Wendy Bickmore Director MRC Human Genetics Unit IGMM, University of Edinburgh +44 (0)131 651 8570 [email protected] http://www.hgu.mrc.ac.uk

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PROFESSOR DAMIJAN MIKLAVCˇICˇ, CHAIR OF THE EP4BIO2MED COST TD1104 ACTION, DISCUSSES SOME OF THE ISSUES AROUND ELECTROPORATION

Action on electroporation T he exposure of biological cells to a sufficiently strong external electric field results in increased permeability of cell membranes due to electroporation. Since all types of cells (animal, plant and micro-organisms) can be effectively electroporated, without addition of viral or chemical compounds, electroporation is considered to be a universal method and a platform technology. It has become a widely used technology applicable to cancer treatment, gene transfection, food and biomass processing, and microbial inactivation. However, despite significant progress of electroporation-based applications, there is a lack of co-ordination and interdisciplinary exchange of knowledge between researchers from different scientific domains. The European network for development of electroporation-based technologies and treatments (EP4Bio2Med) COST TD1104 Action therefore aims to address this by providing the necessary steps towards EU co-operation in science and technology to foster a basic understanding of electroporation, by improving communication between EU research groups, and by enabling further development of new and existing electroporation-based applications by integrating multidisciplinary research teams, as well as comprehensive training for early career investigators. Pan European Networks asked the chair of the Action, Professor Damijan Miklavcˇ icˇ, for his thoughts on both the Action and the field more generally, including issues such as multidisciplinary working, the need for future research, applications in low-income countries, and support for young researchers.

Where do you feel the largest gaps are in co-ordination and the interdisciplinary exchange of knowledge – i.e. surgeons, medical professionals, academic and other researchers – and what tools need to be developed to rectify this? In any discussion of interdisciplinarity, it is necessary to understand that we are potentially facing a clash between different cultures, and the different languages used by professionals in one discipline may be unintelligible to someone working in another. As such, the first thing we need to do is to develop a common vocabulary, and in order to do that we need to meet with one another, speak to each other, and develop a proper understanding. The development of a level of trust and respect for one another goes hand-in-hand with this. We also need to understand that there is no single view of the same problem or the same topic, because everyone approaches things from a different angle. Indeed, my own background is in electrical engineering, where people think of things in binary terms: something is either correct

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COST (European Co-operation in Science and Technology) is a pan-European intergovernmental framework. Its mission is to enable breakthrough scientific and technological developments leading to new concepts and products and thereby contribute to strengthening Europe’s research and innovation capacities.

or it isn’t, there is no middle ground. This is of course not the same for all scientific disciplines such as the social sciences or various medical fields, for example, where practitioners find it extremely difficult to take time away from their patients in order to attend conferences, webinars, workshops and the like, and so we don’t perhaps get the amount of feedback we would like from that sector. The COST Actions are a great tool for networking and they therefore have the potential to bridge the gap between different disciplines. However, even here the amount of time required may pose a problem for medical practitioners, with, for instance, the training schools we are establishing within the Action being at least three working days long, according to the COST rules.

Many of the more established electroporation techniques – such as applying electroporation for inactivation of micro-organisms, the extraction of biomolecules, even the fast drying of biomass often aims to upscale to the industrial and/or clinical level. How do you hope this can be better achieved? Does it need more support?

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With regard to micro-organisms, or, indeed, anything that relates to food processing, there are, of course, regulations and standards one must adhere to

already being used, their optimisation depended on the power generation technology available at the time. The efficiency of these processes could now be further enhanced as new and improved power generation technologies have since been developed and could be up-scaled to the industrial level. This is not the case with medical treatment because the optimisation was done in vitro and according to preclinical results, especially in cancer treatment by electrochemotherapy.

In what ways do you hope to support young researchers? There are indeed some electroporation applications which are more advanced than others and which may already be used in industry within sectors such as food processing or biotechnology, as well as at the clinical level. The latter of these is slightly different to the others, however, because things take longer to become approved due to strict regulation regarding what can be applied to the patients and under which circumstances. It also requires significant investment to be made in clinical trials which can be difficult to achieve. Of course, the development of technology can be supported with specific instruments such as Horizon 2020 through innovation and research. This was certainly true in clinical use of electroporation, e.g. electrochemotherapy as the result of a recent project in this area has enabled us to develop both a clinical device (FP5 project Cliniporator QLK-1999-00484) – which was then manufactured and is now commercially available – and standard operating procedures (ESOPE QLK-2002-02003).

COST Actions have two instruments which are particularly appropriate for helping young researchers. Training schools are an instrument that we use within the Action, and the other is short term scientific missions (STSM). In our COST Action we have organised (on average) two training schools per year. One of these, the Electroporation-based Technologies and Treatments School, is held in Ljubljana, Slovenia, every November and has been taking place for nearly 15 years (see: www.ebtt.org). In the second year of the COST Action we started the Pulsed Electric Field School in food-related areas (the 2016 edition of this will take place in Dublin, Ireland). These schools include both lectures and hands-on lab work, which is particularly suited to newcomers in the field and young researchers. COST also provides grants to young researchers who attend. The COST Actions are a great tool for networking and they therefore have the potential to bridge the gap between different disciplines

Additionally, we have also organised other schools in Bucharest, Romania, which were targeted at young medical doctors in an effort to disseminate information on electroporation-based treatments such as electrochemotherapy, non-thermal irreversible electroporation and gene therapy.

With regard to micro-organisms or, indeed, anything that relates to food processing, there are, of course, regulations and standards that one must adhere to. For instance, years ago it was widely claimed that food needed to be pasteurised and that pasteurisation could only be achieved through high temperatures, and so electroporation or the inactivation of microorganisms by electroporation did not fall under the definition of this process. Once pasteurisation had been redefined, electroporation applications came to be used. This is a prime example of some of the hurdles which are often experienced when developing a new product or technique. Food processing is also a very good example of a field where there was an immediate need to up-scale to the industrial level with regard to electroporation techniques used for the extraction of molecules from sugar beets, for example. However, while these techniques were

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The STSMs are also useful for young scientists. They can last from five working days to three months and, of course, established professors etc. are unable to take this sort of time away from their own work. Young researchers, on the other hand, are able to go to other labs or companies to learn about new techniques, to do research and experiments they cannot do in their own lab, and this is often the best way to start a new collaboration and to develop stronger ties. This mechanism works very well, and we have had 62 STSMs in the first three years of our COST Action.

Given that electroporation can be successfully used to deal with the world’s most pressing challenges related to health, food, energy and environment, how do you feel the work of the Action ties into emphasis placed on these areas by Horizon 2020? As a researcher I have grown increasingly frustrated by the low success rates of grant applications in Horizon 2020. There is a distinct sense that this is a result of a change in the peer review process as well as other elements, such as a tendency for reviewers to reject applications after they have passed the first stage because, despite not being ‘experts’ in a specific area, they feel there is no need for the development of new or alternative therapies etc. The reviewers are, it seems, under pressure to get rid of as many proposals as fast as possible, and so instead of looking at the positive side of the proposals, they are becoming increasingly focused on the

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There are already researchers and medical doctors looking at the potential of electrochemotherapy or DNA vaccination in low-income countries

negative elements; the moment they find something they are unhappy with they remove the proposal from the application process. It has thus become something of a negative selection process, which is a serious problem for Europe. That is not to say that the best proposals should not be the ones which are successful, but that sometimes some of these proposals simply aren’t making it past the first hurdle for reasons which have nothing to do with their quality or applicability – notwithstanding the argument that there is also a lot of time being spent on proposals which can never be re-applied for. When it comes to the current challenges related to health, food, energy and the environment, electroporation thus has applications, but we are missing the kind of projects which would enable us to develop such platform technologies further. This could be taken up as some kind of flagship initiative or by industry, but industry would have to become stronger if it hoped to successfully address this challenge.

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In oncology, electroporation is a technique especially suitable for low- and middle-income countries, where lack of infrastructure and resources leads to late stage cancer diagnoses. Is socioeconomics something you will take into consideration in the COST Action? Absolutely, and there are already researchers and medical doctors who are looking at the potential electrochemotherapy or DNA vaccination in low-income countries. I was recently invited to serve on one of the World Health Organization’s boards which deals with medical technologies for these countries, particularly radiotherapy, and we found that there is very little space for new treatments because of the existing paradigm in which we try to classify a new treatment as soon as possible rather than allowing it to feed in to, or feed from, other areas. In sociology, this is known as the ‘mainstream effect’: if you are in the mainstream you can publish; if you are out of the mainstream you can’t, and this is often the prime concern for researchers. The problem is similar for the development of new technologies, and it is becoming increasingly clear – at least to me – that we are not as open as we would perhaps like to think where mainstream drugs, for instance, are put forward for candidates in some areas of electroporation rather than non-mainstream drugs, which may not be as effective on their own but when combined with electroporation have enhanced properties. It is therefore about changing the existing mindset. There is also some concern that when papers are being written or read, the author or reader does not have the time to properly describe their procedures or results, and the reader does not have the time to properly analyse the paper. Because of this, some ideas are iterated a couple of times and then simply die out because people don’t catch on.

What are your short and long term aims for the Action, and perhaps beyond? We are now in the final year of the Action, and so will soon begin to put together our final report, but the end results have been in our minds from the very beginning.

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In any discussion of interdisciplinarity, it is necessary to understand that we are potentially facing a clash between different cultures, and the different languages used by professionals in one discipline may be unintelligible to someone working in another

We organised the First World Congress on Electroporation, which gathered together 400 registered participants from 42 countries for four days of discussions and was a great success. We now plan to publish papers in six different peer-reviewed journals from that event. We also have two other things planned that will allow us to sustain this network. Based on the success of the first congress, we will organise a second, this time in Virginia, USA, in two years’ time, and we are looking for partners who might be interested in organising the third world congress as well. We also want to establish an international society that could enable proper communication among researchers working in the field of electroporation through web-based tools, a newsletter, and through the continuation of schools and congresses. A long term goal which will last beyond the COST Action is that we have now signed a contract with Springer to prepare a major reference work called The Handbook of Electroporation (see: http://refworks.springer.com/electroporation). This is a digital book, the first edition of which will be some 1,600-2,000 pages and will serve as a reference source for people working in electroporation as well as for the newcomers and new users. As it will be a digital publication we will be able to upgrade and update it moving forwards, expanding it and producing more volumes. One of the agreements we have with Springer is that the book will be freely accessible to all members of the newlyformed society. Photo sources: Bioelectrics Group of the Pulsed Power Department, Karlsruhe Institute of Technology, Germany; and Faculty of Electrical Engineering, University of Ljubljana, Slovenia.

Professor Damijan Miklavcˇicˇ Chair of the COST TD1104 Action Head of the Laboratory of Biocybernetics University of Ljubljana [email protected] www.electroporation.net http://lbk.fe.uni-lj.si/ www.ebtt.org

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SYSTEMSX.CH The Swiss Initiative in Systems Biology has managed to unite well over 1,000 scientists from 15 partner institutions working on approximately 250 interdisciplinary projects

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date, SystemsX.ch is the largest public research initiative with a focus on one particular field of basic research in Switzerland. The initiative was established in 2007 with the aim of positioning Switzerland among the world leaders in systems biology. To achieve this ambitious goal, SystemsX.ch was formed as a simple partnership that advances systems biology in Switzerland by supporting academic research projects, as well as public private partnerships, educating the next generation of systems biologists and participating in international systems biology programmes. From its humble beginnings as a collaboration between three Swiss universities, the initiative has grown into an unparalleled Switzerland-wide network that has united well over 1,000 scientists from 15 partner institutions working on approximately 250 interdisciplinary projects. “SystemsX.ch is a unique research initiative in Switzerland, stimulating a new scientific approach in biology research. This has required interdisciplinary teams and new infrastructure, propelling molecular life science research forward in Switzerland. I believe this type of research stimulation could serve as a model for new Swiss initiatives in other disciplines where a paradigm shift is required.”

Professor Lucas Pelkmans, University of Zurich, Chairman of the Scientific Executive Board of SystemsX.ch The work of SystemsX.ch as a whole, as well as that of the individual research projects, is overseen by the Swiss National Science Foundation (SNSF). This independent evaluation also ensures that the international competitiveness of the initiative is guaranteed and promoted.

Well-connected in Switzerland and abroad SystemsX.ch not only unites 15 equal partner institutions in Switzerland (see box on page 4), but is also well integrated into international systems biology networks. Particularly in the European Research Area (ERA), SystemsX.ch plays an active role in the promotion of international science projects and the development of research structures in the field of systems biology. For example, SystemsX.ch has been an active partner in the European ERA Systems Biology Applications network (ERASysAPP) since 2013, alongside 15 other partners across 13 European countries.

Systems biology – the big picture Following on the heels of the Human Genome Project, systems biology is seen as the next big step in biological and medical

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research. Systems biologists strive to understand living organisms in their entirety. For this purpose, they examine the composition and dynamics of cellular constituents. However, rather than concentrating on individual components, scientists examine how the different elements interact, from genes to proteins and metabolites. Since systems biology research focuses on the dynamics of biological systems, the mathematical modelling of biological processes plays a central role. With modern technologies such as next generation sequencing, systems biology research generates huge amounts of data. This wealth of data allows the verification of these mathematical models, allowing predictions to be made about the processes and behaviour of the real biological systems.

Interdisciplinarity – the key to success Since the questions formulated in the context of systems biology are multi-layered and complex, they can only be answered through the continuous interplay between analysis in the lab and computer modelling. Systems biology therefore depends on the intensive collaboration between experts from various disciplines such as biology, mathematics, physics, chemistry, computer science, informatics, engineering and medicine. Supporting interdisciplinary research, SystemsX.ch creates the necessary framework for innovative projects as well as successful industry collaborations and start-ups. A research initiative of comparable size, bringing together scientists from fields that had hardly ever worked so closely together, has never before existed in Switzerland. “One of the most important contributions SystemsX.ch has made is the promotion of interdisciplinarity and with it the acceleration of this trend within biological research. This has not only changed the way we approach research questions in our own lab, but is likely to influence research in general, regardless of the specific field.”

Professor Nouria Hernandez, project leader of the RTD Project CycliX, University of Lausanne

Investment in Switzerland as a research hub Systems biology research is costly. It calls for highly developed technological platforms that no individual university or institute can afford. The Swiss Confederation granted SystemsX.ch CHF 120 million (~€110m) for its initiation phase 2008-2012. This enabled the initiative to establish Swiss systems biology research by supporting numerous projects on a matching funds principle: partner institutions are obliged to match any funds they receive with equal amounts from their own resources.

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Large range of research projects SystemsX.ch supports the sustainable establishment of systems biology research in Switzerland with six current project categories. For information on past project categories, see our website: www.systemsx.ch. Research, Technology and Development (RTD) Projects Duration: four years Funding*: CHF 2-8 million Number of projects: 34

Medical Research and Development (MRD) Projects Duration: three years Funding*: CHF 3 million Number of projects: nine

Transfer Projects (TF) Duration: two years with an optional one-year extension Funding*: CHF 300,000 Number of projects: eight

Transition Postdoc Fellowships (TPdF) Duration: two years, with an optional one-year extension Funding*: CHF 300,000 Number of projects: 31

Interdisciplinary PhD (IPhD) Projects Duration: three years, with an optional one-year extension Funding*: CHF 250,000 Number of projects: 87

Special Opportunities Projects Duration: one to two years Funding*: CHF 20,000-200,000 Number of projects: 15

RTDs focus on quantitative biology, integrating a number of different scientific approaches including the most recent developments in theory and modelling. At least two partner institutions and several research groups representing complementary fields contribute to these large scale projects. SyBIT, SystemsX.ch’s bioinformatics project, provides a central service in supporting project groups in coping with their flood of digital data. MRDs are large scale projects in which systems biology approaches are specifically applied to medically or clinically relevant topics. These projects involve a number of interdisciplinary research groups working in at least two different partner institutions.

TFs are collaborations between research groups working in the academic and private sectors (industry, SMEs, hospitals, etc.). The aim of these projects is to promote knowledge transfer between academia and private institutions and to strengthen applied research in systems biology. TPdFs are aimed at expanding young scientists’ basic knowledge in systems biology. Having completed their doctorates, emerging researchers switch to a new area or discipline in order to implement innovative ideas at the interface between classically separate fields.

IPhD Projects serve the purpose of training and encouraging future systems biologists. The main focus of these PhD positions is on collaboration between two different disciplines relevant to systems biology. Young scientists are therefore jointly coached by two supervisors working in different fields. Special Opportunities Projects are projects which do not qualify for other types of funding, but have the potential to contribute significantly to systems biology research in Switzerland. Thanks to this category, SystemsX.ch can flexibly support new projects as well as co-finance novel technologies required for existing ones.

*Approx. funding per project

For the years 2013-2016, the Swiss Confederation has granted an additional CHF 100 million towards the further promotion of systems biology research and the training of young scientists. After this period, SystemsX.ch will come to an end and systems biology will be permanently anchored in the Swiss research community.

Successful promotion of young scientists A sufficient number of suitably trained young scientists are needed to guarantee the long term integration of systems biology into the Swiss research sector. SystemsX.ch recognised this need at an early stage and reacted by taking several measures. These include the Interdisciplinary PhD Projects (IPhD) and the Transition Postdoc Fellowships (TPdF), which are specifically targeted at young, upcoming researchers. In addition, SystemsX.ch organises and finances customised training events for young scientists, mostly in collaboration with partner organisations. These events include retreats, summer schools, and advanced lecture courses.

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“The support I received from SystemsX.ch has made the transition to systems biology much easier for me. Thanks to the opportunities for further training, and my research work within the Transition Postdoc Fellowship, I have gained a deep insight into disciplines which were initially unfamiliar to me. It’s clear to me that I will continue working in the interdisciplinary field of systems biology in the future.”

Dr Roger Geiger, Transition Postdoc Fellow, ETH Zurich and Università della Svizzera italiana (USI)

Shifting to a more medical focus Following on from the initiative’s first phase, in which basic research in systems biology was established, the second phase of SystemsX.ch has seen an increased focus on potential medical applications. With the tenth call for proposals in 2014, the new project category, Medical Research and Development (MRD) Projects, was created. Through these large scale projects in which universities, research institutes and hospitals work together, innovative approaches and technologies for the diagnosis and

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Personalised Precision Medicine (PhosphoNet PPM)

Prostate cancer is the most frequent malignant and third most frequent fatal cancer in men. The scientists involved in the RTD Project PhosphoNet PPM aim to establish a basis for the development of a reliable method to diagnose prostate cancer. Following a positive diagnosis, the researchers want to be able to predict whether the disease will take an aggressive or nonaggressive course. Furthermore, their findings will contribute to improving treatment of patients with hormone therapy-resistant prostate cancer by helping to select optimal individual treatments.

treatment of disease are supported. This ensures that systems biology remains interesting for industry and relevant for society in the long term.

Model for future scientific initiatives Over its lifetime, SystemsX.ch has involved many excellent scientists on all levels and has brought together researchers working in very diverse disciplines. The networking between scientists working in different fields in Swiss universities has increased hugely, as evidenced by the multitude of outstanding scientific publications to come out of these collaborations. Many projects have led to the development of new technologies, as well as spin-offs and start-ups. Additionally, Swiss universities have created new systems biology professorships, showing that the initiative will leave behind a lasting footprint. These successes show that SystemsX.ch can truly serve as a model for future support programmes in the sciences.

Diverse projects – space for innovation The following are just seven examples from almost 250 innovative projects supported by the Swiss Initiative in Systems Biology. Many more can be found at: www.systemsx.ch. Together against malaria (MalarX)

Malaria threatens the health of half the world’s population. Even in Europe, outbreaks of this tropical disease sporadically occur. In order to be able to develop new drugs to combat malaria, it is important to fully understand the interactions between the pathogen and the host organism. In particular, the dormant phase in the liver, characteristic of certain malaria pathogens, is still not fully understood. The interdisciplinary MalarX RTD Project team hopes to shed light on this aspect of the disease. The objective is to develop new therapeutic approaches and to thus contribute to the global eradication of malaria. Principal investigator: Professor Vassily Hatzimanikatis, Laboratory of Computational Systems Biotechnology, EPF Lausanne Participating institutions: EPF Lausanne, University of Bern, University of Geneva Number of research groups: Four

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Principal investigator: Professor Ruedi Aebersold, Institute of Molecular Systems Biology (IMSB), ETH Zurich Participating institutions: ETH Zurich, University of Zurich, Cantonal Hospital of St Gallen, University of Cologne Number of research groups: Eight Looking into the mechanisms of antibiotic resistance (TbX)

In Europe alone, more than 25,000 people die of infections involving resistant bacteria every year. The successful treatment of tuberculosis, a disease which is increasingly present in Europe, is threatened by drug resistance. Within the TbX RTD Project, scientists from various fields are investigating the development and spread of pathogen resistance in tuberculosis. Principal investigator: Professor Sebastien Gagneux, Tuberculosis Research Unit, Swiss Tropical and Public Health Institute, University of Basel Participating institutions: Swiss Tropical and Public Health Institute, University of Basel, ETH Zurich, BioVersys AG, Basel Number of research groups: Eight Learning about forgetting (SynaptiX)

Getting lost on the way home or forgetting a pan on the stove: forgetting as a consequence of old age or disease is a leading cause of care dependency worldwide. Researchers involved in the SynaptiX RTD Project are using fruit flies to investigate the process of forgetting on the level of genes, neurons and involved substances. The knowledge gained may in future contribute to the development of drugs for ailments such as Alzheimer’s disease. Principal investigator: Professor Simon Sprecher, Department of Biology, University of Fribourg Participating institutions: University of Fribourg, University of Bern, University of Nevada Number of research groups: Five From PhD student to entrepreneur (IPhD Project)

Not even in his dreams would the engineer and mathematician Ata Tuna Ciftlik have imagined that during his Interdisciplinary PhD

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SystemsX.ch partner institutions

Project (IPhD), he would manage to develop a device for performing precise and rapid cancer diagnoses at low cost. But that is exactly what he achieved. Within a follow-up project, also supported by SystemsX.ch, Ciftlik tested his innovative device, which has now been patented, under practical conditions in the field of breast cancer diagnostics. In April 2014, he founded Lunaphore, a successful start-up that has secured initial investment of CHF 2 million, and which was recently voted number ten out of the 100 best Swiss start-ups. Former PhD student: Dr Ata Tuna Ciftlik, EPF Lausanne Founder and CEO, Lunaphore technologies From satellite navigation to Petri dishes (TPdF)

Tri Thanh Pham knew all about aeroplanes, aerodynamics, and satellite navigation. However, this young aerospace engineer wanted a stronger link to practical applications and living organisms. That is why in 2012 he seized the opportunity to apply for a SystemsX.ch Transition Postdoc Fellowship (TPdF). Today he works with cells, genes and petri dishes at the Biozentrum in Basel. Among other things, he has developed a method for precisely locating surface measurements of living cells. This innovative achievement was only possible thanks to the extreme interdisciplinarity of his project. Principal investigator: Dr Tri Thanh Pham, University of Basel Host research group: Professor Clemens Cabernard, Biozentrum, University of Basel

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An innovative device for cancer diagnostics (μFluidX)

A win-win situation as good as it gets: as part of the μFluidX transfer project, the pathologists at the University Hospital Zurich are testing an innovative device for cancer diagnostics developed by the IBM research laboratory in Rüschlikon. While the scientists at the university hospital can gain new knowledge in the field of cancer diagnostics by examining tissue samples using this instrument, the developers of the device are able to validate their tool under clinical conditions. This technology and knowledge transfer is part and parcel of a new era in which collaborations between private companies and public research institutions are specifically promoted. In the long run, patients will benefit greatly from such collaborations. Collaboration between: Professor Alex Soltermann, University Hospital Zurich and Dr Govind Kaigala, IBM Research Zurich

Dr Daniel Vonder Mühll Managing Director SystemsX.ch Clausiusstr. 45, CLP D 4 CH – 8092 Zurich +41 (0)44 632 7888 [email protected] http://www.systemsx.ch

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JAN MULDER FROM THE HUMAN PROTEIN ATLAS ON THE MOUSE BRAIN AS A MODEL FOR THE HUMAN BRAIN

The mouse brain protein atlas

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he brain is the most complex organ in the mammalian body. It

The Mouse Brain Atlas

processes sensory information from the external environment;

The tissue-micro array approach used in the Human Protein Atlas (see: www.proteinatlas.org) provides a global map of protein distribution in the human body. One of the sub-atlases, the ‘Tissue Atlas’, currently includes four areas of the human brain: cerebral cortex, hippocampus, lateral ventricle, and cerebellum. Due to the heterogeneous organisation of the brain, with many nuclei and cell-types organised in complex networks, it is difficult to achieve a comprehensive overview in a 1mm tissue sample. Analysis of more human brain samples, including smaller brain nuclei, is desirable in order to generate a more detailed map of protein distribution in the brain. However, due to tissue inaccessibility this is not possible.

produces behaviour, emotions and memories; and autonomously

regulates internal body homeostasis. To fulfil these diverse functions the brain harbours a myriad of neuronal networks, processing information and connecting input and output systems. Over 500 brain regions and subfields can be identified. Within mammalian evolution, the brain has undergone changes that resulted in increased capacities to process information and perform higher cognitive functions in primates and humans. These evolutionary processes mainly involve size expansion, not affecting the basic architecture of the brain and gene-expression in the various cell types that populate the brain. The driving force in evolution is genetic variability passed on from one generation to the next. Many of the mouse proteins have high homology with their human counterpart; this forms the basis of using the mouse brain as a model for the corresponding human brain to explore the expression and distribution of proteins in the various regions and cells. This is the foundation of translational medicine in general and forms the basis of the ‘Mouse Brain Atlas’, which aims to increase knowledge on protein expression and distribution in various brain regions and cells of the mammalian brain.

Fig. 1 The different types of neurological cell classes (ependymal cells, purple), subpopulations (A=astrocytes, blue; M=microglia, brown; N=neuron, green; O=oligodendrocytes, orange), and subcellular locations (axon, dendrite, synapse, and glia endfeet)

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The first version of the Mouse Brain Atlas, launched as part of the Human Protein Atlas database in October 2015, covers all major brain areas and subfields. It currently includes a set of genes that are well known reference genes expressed in the different cell-types that populate the brain, and genes with known or predicted specialised functions not yet studied in relation to brain and brain functions.

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As an alternative, the much smaller mouse brain can provide a complete overview of many regions and cell types, including many currently not available in the Human Protein Atlas. Exploring additional brain regions with specialised functions increases the probability of detecting protein expression and the distribution of genes and proteins currently not detected in the human samples included in the Human Protein Atlas.

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Neurons are the main signalling units in the central nervous system that transmit signals by releasing organic signalling molecules or peptides. This requires cellular specialisation and the expression of proteins necessary for the activity-dependent release of neurotransmitters,

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receptors and transporters. Apart from the neurons, there are a number of cells specialised in supporting neurons and maintaining homeostasis, such as glial cells (astrocytes, microglia, and oligodendrocytes), ependymal cells, and endothelial cells (Fig. 1 shows the different types of cells and cellular interactions in the central nervous system).

Exploring the Mouse Brain Atlas In the Mouse Brain Atlas, a series of mouse brain sections are explored for protein expression and distribution in a large number of brain regions. Our initial aim is to provide information on the overall distribution of proteins in the central nervous system. The size of the mouse brain allows the protein distribution to be visualised in complete coronal cuts of the brain, thereby creating a more complete overview with preserved orientation (see Fig. 2). In turn, this enables the annotation of protein distribution in additional cells (ependymal cells, astrocytes, etc.) and cellular compartments (axon, dendrites, etc.). In addition to the full size images, an online virtual microscope is also available, allowing users to investigate and explore protein distribution in the mouse brain. Relative protein levels in 129 brain regions are determined by measuring relative fluorescence intensity.

Fig. 3 Expression and distribution of the calcium-dependant kinase CAMK2B in the mouse olfactory bulb (OB) and frontal cortex (FrA) (a). In the main olfactory bulb (b) CAMK2B is expressed by neurons and shows immunoreactivity in cell bodies and dendrites. Note the dendrites in the glomerular layer (GL). This is where the olfactory axons enter the brain and make synaptic contacts; each glomerula processes a single odour (c: nuclei; c’: neuron; c’’: overlay of c and c’). CAMK2B is expressed by neurons (green). Nuclei stained blue by DAPI (stains DNA)

neuronal networks involved in processing olfactory information. Note the different levels of green in the layers that form the olfactory bulb (OB). The current version of the Mouse Brain Atlas includes basic functionality and a first set of 88 genes. Future release will include additional genes, additional annotation data (more regions and subfields), and more antibody validation data with each new version of the Human Protein Atlas.

Data integration A lot of research is conducted in animal models, mouse being one of the most common. Integration of human and mouse brain data allows translational aspects of brain proteomics to be explored, for example differences in expression and the distribution of proteins, epitope homology, and antibody specificity and affinity in non-human samples of the mouse brain. The knowledge about similarities and differences in the human and mouse brain is of great importance when using animal models to study human health and disease. The Mouse Brain Atlas is hosted at the Science for Life Laboratory by the KTH Royal Institute of Technology and Karolinska Institute in Stockholm,

The section displayed in Fig. 3 shows the olfactory bulb, the brain area containing the

Sweden. The work is funded by the Knut and Alice Wallenberg foundation Fig. 2 Example of protein distribution of the calcium dependent kinase CAMK2B (green signal) important for calcium signalling in the brain. Analysis of a large series of brain sections containing many brain regions reveals that CAM2K is expressed by many, but not all neurons in the brain

and the Science for Life Strategic and National Infrastructure Funding. References Mulder, J. Wernérus, H. Shi, TJ. Pontén, F. Hober, S. Uhlén, M. & Hökfelt, T. (2007). Systematically generated antibodies against human gene products: High throughput screening on sections from the rat nervous system. Neuroscience, 146(4), 1689–1703. Mulder, J. Björling, E. Jonasson, K. Wernérus, H. Hober, S. Hökfelt, T. & Uhlén, M. (2009). Tissue profiling of the mammalian central nervous system using human antibody-based proteomics. Molecular & Cellular Proteomics: MCP, 8(7), 1612–22.

Jan Mulder, Director Mouse Brain Atlas Tove Alm, Head of Communications HPA Human Protein Atlas Science for Life Laboratory KTH Royal Institute of Technology, Sweden +46 (0)8 524 812 53 [email protected] www.proteinatlas.org

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HEART REGENERATION Scientists at the Friedrich-Alexander-Universität Erlangen-Nürnberg found a possible explanation as to why the human heart does not regenerate

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ardiovascular diseases (CVD) are among the leading causes of death in Europe and worldwide. They present a major socioeconomic burden and their incidence is expected to rise further due to ageing populations in high-income countries and the increasing incidence of cardiac risk factors such as hypertension, obesity, and diabetes in low-income countries. The primary cause of most CVDs is reduced heart function due to the irreversible loss of heart muscle cells, the cardiomyocytes. Consequently, the development of novel strategies to replace lost cardiomyocytes would be of enormous therapeutic value. The group of Professor Felix B Engel at the Friedrich-AlexanderUniversität Erlangen-Nürnberg (Germany) studies ‘induction of cardiomyocyte proliferation’ as a possible strategy to replace lost cardiomyocytes to improve heart function. The research was mainly funded in recent years by the Emerging Fields Initiative (EFI) for ‘Cell Cycle in Disease and Regeneration (CYDER)’ from the Friedrich-Alexander-Universität Erlangen-Nürnberg, the Sofja Kovalevskaja Award from the Alexander von Humboldt Foundation, and grants from the Deutsche Forschungsgemeinschaft (IRTG 1566, PROMISE; EN 453/9-1).

Why study ‘induction of cardiomyocyte proliferation’ as a regenerative strategy? Cardiac regeneration through cardiomyocyte proliferation is potentially achievable for several reasons: 1) adult newt and zebrafish can regenerate their hearts and this occurs via cardiomyocyte proliferation; 2) the foetal mammalian heart grows and can regenerate via cardiomyocyte proliferation; 3) the diseased adult human heart contains a low level of mitotic cardiomyocytes; and 4) low level of cardiomyocyte turnover in the ageing human heart has been reported.1-3

Why does the human heart not regenerate? While the mammalian heart grows through cardiomyocyte proliferation during development, the vast majority of cardiomyocytes stop proliferating shortly after birth. Consequently, the mammalian heart also loses its ability to regenerate.1 For decades, researchers have been trying to induce adult cardiomyocytes to proliferate. Some approaches include overexpression of pro-proliferative genes, stimulation with growth factors or small molecules, and, more recently, micro RNA (miRNA). Many of these approaches efficiently induce proliferation of neonatal cardiomyocytes. Yet, the pro-proliferative effects decrease markedly in adult cardiomyocytes. The underlying reason for this phenomenon is poorly understood. Little emphasis has been put on the causes as to why mammalian cardiomyocytes cease to proliferate, adopting a post-mitotic state. For instance, it remains unclear if factors required for proliferation

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are simply lacking or if factors are expressed that actively maintain cardiomyocytes in a non-proliferative state or whether it is a combination. Meanwhile, it is well known that a large variety of positive cell cycle factors are downregulated in cardiomyocytes during development, while negative regulators are transiently upregulated. Yet, it is poorly understood how all these factors are regulated. In addition, the expression of many of these factors is reversed upon injury without inducing cardiomyocyte proliferation. It is also known that a subset of cardiomyocytes become binucleated (cells undergo mitosis but fail to divide, resulting in cells containing two nuclei) or polyploid (DNA has been replicated without cell division) which might affect their proliferation potential. However, for liver cells (hepatocytes), it has been shown that binucleation as well as polyploidy does not affect proliferation. Other explanations for a decreased proliferation potential of postnatal cardiomyocytes might be the maturation of the contractile apparatus, alterations of the extracellular matrix as well as elevated levels of reactive oxygen species inducing DNA damage. However, there is evidence that an intrinsic timer exists that, independent of these changes, restricts the proliferation potential of mammalian cardiomyocytes. Foetal cardiomyocytes that proliferate in vivo cease to proliferate in vitro after a few cell divisions; even though they have not yet accumulated DNA damage, they are not binucleated or exhibit a highly structured contractile apparatus, not are they affected by extracellular matrix.

What distinguishes a human heart from a zebrafish or newt heart? There are obvious differences between human, newt and zebrafish hearts such as size and the different chamber numbers. Yet it is unclear how the individual cardiomyocytes differ from each other. Morphologically, cardiomyocytes of all three species are rod-shaped containing a highly ordered contractile apparatus. The most obvious difference is that most adult human cardiomyocytes are polyploid or binucleated while adult zebrafish cardiomyocytes are mononucleated and diploid. Yet, it has been shown that newt hearts also contain binucleated cardiomyocytes that can proliferate in vitro. To understand why the adult human heart cannot regenerate, the group of Professor Engel studied the centrosome: a small structure best known for its ability to organise microtubules, e.g. during mitosis to segregate chromosomes. In addition, it is known as the basal body of the primary cilium, a kind of antenna for sensing the environment. Recently, the centrosome has been shown to function as a signalling hub to control cell cycle progression. Thus, alterations of the centrosome might be the cause of the postmitotic state of cardiomyocytes. A centrosome consists of two centrioles that are tightly paired. Engel’s group observed that in

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synthesis (and consequently does not increase the rate of cardiomyocyte renewal) in normal or infarcted adult mouse hearts. Thus, any improvement in cardiac structure and function observed following neuregulin treatment of injured hearts likely occurs independently of overt myocardial regeneration.’ Finally, the expression of the receptor ERBB2, through which NRG1 exhibits its pro-proliferative effect, has this year been described in Nat Cell Biol as ‘significantly downregulated’. These authors observed that ‘Transient induction of caERBB2 following myocardial infarction triggered CM dedifferentiation and proliferation followed by redifferentiation and regeneration’.5 Fig. 1 Postnatal rat cardiomyocyte culture stained for microtubules (red), cardiomyocytes (green), and nuclei (blue)

proliferating foetal cardiomyocytes these centrioles were paired, as expected. However, in postnatal non-proliferating cardiomyocytes the centrioles were un-paired (more than 2μm apart), indicating a defect in centrosome structural integrity. The analysis of centrosome proteins revealed that some were relocalised to the nuclear envelope. Further, microtubules (Fig. red) – functionally – were no longer organised from the centrosome (Fig. non-myocyte) but rather from the nuclear envelope (Fig. green cardiomyocytes). Importantly, induced loss of centrosome integrity in proliferating newborn mammalian cardiomyocytes promoted a post-mitotic state. Finally, the analysis of adult zebrafish and newt cardiomyocytes revealed that they maintained the integrity of their centrosomes. These data suggest that centrosome disassembly is developmentally utilised to achieve the post-mitotic state in mammalian cardiomyocytes and provide a potential explanation for why zebrafish and newts, but not mammals, can regenerate their heart.4 It will become of great importance to demonstrate that the centrosome integrity is required in zebrafish for heart regeneration. Moreover, it will be important to elucidate the mechanisms that control the disintegration of the centrosome and relocalisation of centrosome proteins to the nuclear envelope. Finally, it will be important to understand the physiological relevance of this process.

In conclusion, cardiomyocyte proliferation also appears to be a promising approach due to the recent suggestion of a subpopulation of cardiomyocytes with a higher proliferation potential. However, it appears essential to introduce standards for the evaluation of cardiomyocyte proliferation, more studies need to be independently verified, animal models should be re-evaluated regarding their suitability, and a deeper mechanistic understanding of the post-mitotic state appears to be required. References 1 Leone M, Magadum A, Engel FB. Cardiomyocyte proliferation in cardiac development and regeneration: a guide to methodologies and interpretations. Am J Physiol Heart Circ Physiol. 2015;309(8):H1237-50. 2 Rumyantsev PP. Interrelations of the proliferation and differentiation processes during cardiac myogenesis and regeneration. Int Rev Cytol. 1977;51:186-273. 3 Bergmann O, Zdunek S, Felker A, Salehpour M, Alkass K, Bernard S, Sjostrom SL, Szewczykowska M, Jackowska T, Dos Remedios C, Malm T, Andrä M, Jashari R, Nyengaard JR, Possnert G, Jovinge S, Druid H, Frisén J. Dynamics of Cell Generation and Turnover in the Human Heart. Cell. 2015;161(7):1566-75. 4 Zebrowski DC, Vergarajauregui S, Wu CC, Piatkowski T, Becker R, Leone M, Hirth S, Ricciardi F, Falk N, Giessl A, Just S, Braun T, Weidinger G, Engel FB. Developmental alterations in centrosome integrity contribute to the postmitotic state of mammalian cardiomyocytes. Elife. 2015;4. 5 D’Uva G, Aharonov A, Lauriola M, Kain D, Yahalom-Ronen Y, Carvalho S, Weisinger K, Bassat E, Rajchman D, Yifa O, Lysenko M, Konfino T, Hegesh J, Brenner O, Neeman M, Yarden Y, Leor J, Sarig R, Harvey RP, Tzahor E. ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation. Nat Cell Biol. 2015;17(5):627-38.

A need for standardisation and better technologies Despite several promising publications promoting the idea of ‘heart regeneration through cardiomyocyte proliferation’ the field is highly controversial. Even though it has been shown by numerous researchers that induction of cell cycle activity by several treatments correlates with improved heart function in cardiac injury models, there is so far no evidence of causality. Moreover, there is no study unambiguously demonstrating that induced cell cycle activity results in cardiomyocyte proliferation and tissue growth. Although there are mouse models available to identify in vivo clonal cell growth, most studies still rely on assays that cannot distinguish between proliferation, polyploidisation, and bi/polynucleation.1 A good example for the complexity of the field and the problems in data interpretation is Neuregulin 1 (NRG1). In 2009, it was published in Cell that ‘Injecting NRG1 in adult mice induces cardiomyocyte cell-cycle activity and promotes myocardial regeneration, leading to improved function after myocardial infarction’. In 2014, an article in PLoS One concluded that ‘NRG1β1 treatment does not increase cardiomyocyte DNA

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Professor Dr rer nat Dipl Ing Felix B Engel Universitätsklinikum Erlangen Experimental Renal and Cardiovascular Research Department of Nephropathology Institute of Pathology +49 (0)9131 8543635 [email protected] http://www.nephropathologie.ukerlangen.de/en/ag-engel-exp-renaland-cardiovascular-research/ http://www.efi.uni-erlangen.org/projects/cyder/

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DR SIMON POT AND PROFESSOR DR FARHAD HAFEZI REFLECT ON CUTTING-EDGE RESEARCH THAT IS HELPING TO SAVE SIGHT, THROUGH THE USE OF LIGHT

Using light to save sight

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lthough modern ophthalmology has seen major advances in the past two decades, a number of challenges still remain. We would like to highlight two of them: keratoconus and corneal infection. Keratoconus (KC) is a progressive, degenerative disease in humans characterised by progressive corneal thinning and impaired biomechanics, leading to reduced vision, and ultimately, legal blindness. KC is a disease of the young, and most often affects children and adolescents with an incidence of 1:500 to 1:2,000 in the general population. Until 2002, there was no cure.

Microbial corneal infection, bacterial and fungal, is a leading cause of global blindness in humans, with an estimated six to eight million new cases every year. Little to no access to medical treatment, and increasing resistance to antibiotics make the treatment challenging from a global perspective. Corneal infection is also a major concern in the veterinary field, affecting >10% of eye patients, mostly cats, dogs, and horses. Here, treatment costs and reduced compliance in the face of an intense cornea, and then irradiating the tissue with UV-A light at 365nm. Within topical and systemic treatment often lead to significant loss of vision and just a few minutes, the biomechanical strength of the tissue increases even loss of the eye. by 350%, through the induction of covalent bonds between the amino side chains of the collagen fibres and the proteoglycans of the The common denominator in these two disease complexes is a new extracellular matrix. Since its first application, CXL technology has therapeutic technique called CXL, corneal cross-linking with riboflavin become the standard of care for keratoconus and a number of similar and UV-A light. CXL changes the biomechanical characteristics of the diseases of the cornea in humans. The success rate is more than 95%, cornea, and also has a direct effect on the biology of the tissue. CXL was and complications are rare, when used correctly. In 2004, the first CXL invented in Dresden, Germany, and further developed in Zürich. device was built in Zürich, and for the next four years, the technique was further refined and the spectrum of indications extended. Initial indication: CXL for keratoconus in humans CXL has been used as a treatment modality in humans since 1999. The technique consists of applying riboflavin (vitamin B2) solution onto the

New indication: PACK-CXL for corneal infection in humans Photoactivation of riboflavin had been used in photochemical pathogen inactivation technologies (PCT) for fresh-frozen plasma (FFP) for a number of years. This form of photoactivation enabled donor blood to be treated for various pathogens, such as bacteria and viruses, by inactivating them. The same concept is applied in solar disinfection (SODIS), where water is decontaminated by exposure to intense sunlight over several hours, with the addition of riboflavin. In 2008, we explored the antimicrobial effect of riboflavin photoactivation as a potential application in corneal infection in humans: we conducted a pilot study and treated severe and therapyresistant infectious melting keratitis. Four of the five patients treated showed rapid improvement. The fifth patient needed several weeks

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and continued antibiotic care to improve. We named the new procedure PACK-Crosslinking (photoactivated chromophore for infectious keratitis-crosslinking). In light of these promising results from our pilot study, Makdoumi proposed a non-randomised clinical study to investigate the efficacy of CXL as a first line therapy for treating bacterial keratitis. A total of 16 patients (13 patients with diagnosed corneal ulcer and three patients with corneal infiltrates) without any prior topical or systematic treatment were treated with standard 3mw/cm2 CXL as outlined in the original Dresden protocol. Complete epithelial healing occurred in 15 of 16 patients, and all of them responded with symptom improvement and reduced inflammation although two patients needed supplemental antibiotic therapy. This study suggests that not only might CXL be effective in treating advanced ulcerative infectious keratitis as an adjuvant, but also in treating early-stage bacterial infiltrates as a firstline treatment. Most interestingly, the efficacy of killing multiresistant bacteria (MRSA) is more than 98% with the current treatment parameters, making PACK-CXL a tantalising alternative to antibiotic treatment in the light of increasing antibiotic resistance.

non-inferiority study, using the current standard of care (antimicrobial treatment) as control.

Veterinary application: Experimental and clinical studies both show that current PACK-CXL protocols are more effective against bacterial rather than fungal pathogens. Also, a recent study published by our groups described animal species dependency of PACK-CXL PACK-CXL for corneal infection in veterinary patients PACK-CXL was reported to be successful in >85% of corneal penetration depth into the cornea. Therefore, PACK-CXL protocols infection/ulcer cases in a compilation of the veterinary literature in which need adaptation and customisation to target patient and target micro68 cases were included. Identical results were described in a recent organism species to optimise treatment efficacy. Also, treatment time meta-analysis of PACK-CXL-treated human patients in which 104 cases shortening will be immensely beneficial to veterinary patients by obviating were included. One prospective controlled study examining PACK-CXL the need for general anaesthesia. Therefore, a systematic approach to treatment efficacy in dogs and cats with corneal ulceration confirmed the evaluation of PACK-CXL treatment efficacy and the implementation non-inferiority of PACK-CXL compared to medical treatment and, of PACK-CXL technology in human and veterinary medicine is an important focus of our research. The collaboration between the ELZA importantly, a lack of PACK-CXL treatment related complications. Institute, the Ophthalmology Section of the Vetsuisse Faculty and the How does PACK-CXL work? Laboratory of Ocular Cell Biology at the CABMM is exquisitely suited to PACK-CXL’s antimicrobial therapeutic effect is the result of the effect of answer fundamental scientific and translational lines of questioning UV light interacting with riboflavin as the chromophore. The exact nature involving PACK-CXL. of the underlying mechanisms of action is not fully elucidated yet. We speculate that different mechanisms are responsible: Dr Simon Pot 1) Intercalation of photoactivated riboflavin with the DNA and RNA of the Division of Ophthalmology pathogen, interrupting replication; Equine Department 2) Massive amounts of oxidative stress; and

Vetsuisse Faculty University of Zürich

3) Conformational changes in the three-dimensional structure of the collagen, increasing the tissue’s resistance to enzymatic digestion during infection.

Professor Dr Dr Farhad Hafezi Department of Ophthalmology University of Southern California Los Angeles, California, USA

Outlook

ELZA Institute, Zürich, Switzerland

Human application: We aim at establishing PACK-CXL as a rapid and efficient first-line treatment in infectious keratitis. For this purpose, we focus on shortening the treatment time, and increasing efficacy. Also, we aim at miniaturising the technology, and making it mobile, for use in developing countries. Currently, we are conducting a prospective randomised multicentre trial in 14 countries to investigate PACK-CXL as a sole and first-line treatment in human infectious keratitis. This is a

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Contact: Professor Dr med vet Brigitte von Rechenberg Head of Steering Committee The Competence Center of Applied Biotechnology and Molecular Medicine (CABMM) The University of Zürich

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THE DIET-HEALTH CONNECTION The Molecular Systems Physiology group builds comprehensive models of human cells and human-associated microbes to investigate how nutrition and genetic predisposition can affect one’s health

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ifestyle parameters, such as diet, are recognised as major modulators of human health and have an important contribution to the onset, progression, and severity of various diseases. Dietary components interact directly with the human metabolism as they are absorbed in the small intestine. Moreover, the human gastrointestinal tract is populated by trillions of microbes (microbiota), with the highest microbial density being in the large intestine. In fact, these microbes help us to digest otherwise indigestible nutrients such as complex carbohydrates, thereby providing us with important precursors, such as short chain fatty acids and vitamins. Understanding how the microbes can modulate human health and the role of nutritional composition is an open challenge and a prerequisite for targeted use of pre- and probiotics for prevention and therapy. Finally, the effects of diet and dietary adjustments need to be considered on an individual basis, tailored to one’s genomic context and state of health, i.e. a personalised nutrigenomic approach is required. To address these questions, we use a state-of-the-art computational modelling approach, termed constraint-based modelling (COBRA),1 that has gained increasing importance in systems biology. The comprehensive computational models are assembled in a bottom-up manner from literature and genomic information and describe biochemical transformations occurring in a target organism in a stoichiometric, accurate format. Multiple diverse omics datasets can be integrated and analysed with these models and provide mechanistically-based insight into complex multidimensional datasets. These models can then be used to predict the impact of genetic alterations (e.g. enzyme deficiencies) and of changed environment conditions (e.g. changes in diet composition) on the metabolic state of the target organism.

The human metabolic model The most comprehensive knowledgebase of human metabolism (Fig. 1, Recon 2) was assembled in a community effort based on its predecessor and numerous manually curated metabolic knowledgebases.2 Recon 2 captures more than 7,000 metabolic transformation and transport processes, catalysed by more than 1,700 genes, and over 2,600 unique metabolites. It represents a blueprint for cellular metabolism, distributed over eight cellular compartments. Recon 2 is a knowledgebase as more than 1,500 primary and review literature sources have been considered during its generation. At the same time, Recon 2 can be used as a predictive model for whole-body metabolism, or as a starting point for the generation of cell type and tissue specific metabolic models, through the application of one or more omics data sets. Importantly, hundreds of molecular dietary components are considered in Recon 2 and their effect on human metabolism can be simulated.

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Gut microbiota metabolic models The human gut microbiome can modulate human metabolism. Metagenomics data have provided valuable insights into what microbes live in our gut and where. Now the main open question is: what do these microbes do and how do they influence the host? In a first step towards addressing this question, we have generated the most comprehensive suite of high quality metabolic models for known human gut micro-organisms.4 These microbes belong to 184 species, 83 genera, and 18 taxonomic classes. The metabolic models were validated against literature, ensuring that they captured known metabolic capabilities of gut microbes. These models can be used to study the metabolism of the individual microbes as well as the emerging metabolic characteristics of microbial communities, consisting of a subset or all of these models. For instance, metagenomic data (both 16S rRNA and shotgun sequencing data) can be mapped onto the metabolic models thereby producing personalised microbial community models.

Predicting microbe-microbe interactions Because of the complexity of the gut microbiota composition, it is difficult to determine the metabolic interactions among the individual organisms by experimental methods. One way of determining some of these interactions is using genome-scale metabolic models of individual microbes to help generate hypotheses on the possible metabolite exchanges and effects that can be tested in the laboratory. We are developing computational approaches to investigate the metabolic crosstalk between these microbes and their role within the gut microbial community. To investigate the role of dietary components and microenvironments, typically found in the human gastrointestinal tract, 11 microbes were joined pairwise in all possible combinations.5 A variety of interactions including commensalism, mutualism, and competition, were predicted depending on the nutrient environment. Notably, anoxic conditions promoted mutualistic behaviour in pairs including the lactic acid bacterium L. plantarum. The availability of oxygen abolished these syntrophic interactions, resulting in competition. Recurring cross-feeding patterns between microbes were identified, providing insight into the mechanisms behind the observed microbe-microbe interactions on a molecular level.5

Putting the pieces together: predicting host microbiota interactions So far, a few studies have attempted to predict the metabolic effect of different microbiomes on host metabolism, but they have been mostly limited to topological approaches. To address mechanistic questions with respect to metabolism, more advanced computational analysis tools, such as metabolic models, are required.

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Fig. 1 Map of the human metabolic model with more than 5,000 reactions displayed. The different background colours highlight the various metabolic subsystems. The content of this map can be accessed via http://humanmetabolism.org.

We have developed a scalable computational modelling approach, in which the human metabolic model and a microbial community consisting of eleven microbes were combined.6 The effects of the different microbes on host metabolic functions were systematically explored while simulating four different dietary regimes. A variety of human body fluid metabolites were influenced by microbial presence, including many that have been measured in vivo and found to be affected by the microbiota. The secretion of amino acid derivatives including hormones by the host was increased by up to one hundredfold in the presence of the microbes, in agreement with the role of the microbiota as an additional organ. When comparing two five-member model communities, the more diverse group had a significantly more pronounced effect on host metabolism. The microbes further provided a variety of metabolic products relevant for host health, e.g. energy sources, vitamins, and potentially toxic metabolites. Specific microbes combined with dietary fatty acid supply were able to increase host production of pro-inflammatory leukotrienes, as well as increased production of taurine-containing bile acids.6 This modelling framework represents the human intestinal ecosystem in molecular detail and will be of great value for elucidating the metabolic capabilities of the complex gut ecosystem and its effects on human health. The COBRA approach has great potential for systems medicine due to the scalable nature of the method, i.e. many hundreds of thousands of model variables can be solved simultaneously within a reasonable timeframe and with existing computer resources. Moreover, with the COBRA approach, predictions can still be made when data are incomplete and not all parameter values are known. Omics data generated for healthy and diseased individuals can be mapped onto the host-microbiota model, making this approach well suited for advancing personalised nutrigenomics.

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The human metabolic model, as well as the metabolic models for the gut microbes, can be queried using the Virtual Metabolic Human website http://vmh.uni.lu. References 1 Orth JD, Thiele I, Palsson BO. What is flux balance analysis? Nat Biotechnol. 2010;28(3):245-8. 2 Thiele I, Swainston N, Fleming RM, Hoppe A, Sahoo S, Aurich MK, et al. A community-driven global reconstruction of human metabolism. Nat Biotechnol. 2013;31(5):419-25. 3 Aurich MK, Paglia G, Rolfsson O, Hrafnsdottir S, Magnusdottir M, Stefaniak MM, et al. Prediction of intracellular metabolic states from extracellular metabolomic data. Metabolomics : Official journal of the Metabolomic Society. 2015;11(3):603-19. 4 Magnusdottir S, Heinken A, Bauer E, Ravcheev DA, Fleming RMT, Thiele I. AGORA: a resource of high-quality metabolic reconstructions for 321 diverse gut microbes. submitted. 5 Heinken A, Thiele I. Anoxic Conditions Promote Species-Specific Mutualism between Gut Microbes In Silico. Applied and environmental microbiology. 2015;81(12):4049-61. 6 Heinken A, Thiele I. Systematic prediction of health-relevant human-microbial co-metabolism through a computational framework. Gut Microbes. 2015.

Ines Thiele Principle Investigator of the MSP group University of Luxembourg +352 (0)46 6644 6647 [email protected] http://thielelab.uni.lu

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THE EORTC’S DIRECTOR GENERAL, DR DENIS LACOMBE, DISCUSSES ISSUES SUCH AS PHARMACOVIGILANCE, CLINICAL TRIALS, AND THE RELEVANT REGULATORY FRAMEWORKS THAT ACCOMPANY THEM

Framing the frameworks

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ver 50 years ago, visionary leaders in cancer medicine realised that advancement of patient management requires solid understanding of the disease and biology, vigorous testing of novel treatments, and interdisciplinary collaboration and exchange beyond state boundaries. This remains true today, and is even more important as we move into an era of precision medicine. Platforms for molecular testing are needed to profile each patient’s tumour. Novel tools and imaging methods allow for adequate and early evaluation of the treatment effect. The European Organisation for Research and Treatment of Cancer (EORTC) is well positioned to provide the needed network and infrastructure to advance science and new treatments.

Dr Denis Lacombe

Indeed, the change is not happening fast enough, and because of that there is also a need for us to develop other adaptive strategies which will enable us to overcome these issues presented by the fact that, for instance, industry simply does not have all the necessary expertise or indeed the means to do this kind of new research.

In September 2015, Pan European Networks attended the EORTC’s course ‘A One-Day Journey through EORTC Activities’. Here, during an interview on the sidelines of the event, the organisation’s director general, Dr Denis Lacombe, discussed issues such as pharmacovigilance, clinical trials, and the relevant regulatory frameworks that accompany them.

Given that cancer drugs in First in Human trials are typically administered to oncology patients rather than ‘healthy’ subjects, how do you feel issues such as comorbidity, previous exposure to other treatments and medicines etc. can be better taken into account when it comes to efficacy and so on? We are on the verge of seeing a significant change in the way that this is being approached in Europe today. Of course, in oncology some of the biggest issues arise from the fact that the treatments are toxic and, historically, these treatments have been administered to sick patients, but we now have the means and the methods to begin to do things differently.

The idea here is to be able to create an intelligent trial, and to thus be able to change the scope and design as you progress. However, despite the benefits of taking this approach being highlighted by the EORTC in publications as early as 2013, it takes time for people to change the way they work and for new ideas to be accepted, especially when it comes to clinical trials and the pharmaceutical industry. It is important to keep in mind that this is a highly regulated field, so there is a certain amount of ‘playing it safe’ that slows down change.

The fact that some new clinical trials are smaller in terms of patient numbers, because they target specific patient populations, leave a gap in the safety information being collected

At the EORTC, we have conducted numerous surveys with different stakeholders including industry in an effort to explore and better understand the current and future landscapes. In this sense, conferences such as the one we are attending today also have the potential to aid in opening and furthering the dialogue between the various actors, including both industry and the regulators. As we move

For instance, we know that too many patients experience undue toxicity without also benefitting from the drugs, and we have therefore developed a new concept. That is, traditionally we would begin with a low number of patients, find a dose, and then begin ‘Phase 2’ where we look for activity. Then, if activity is detected, we would begin a large clinical trial, necessitating an increase in resources. While safety comes first, and first human administration needs specific caution, we can now rapidly approach things from an entirely different angle. First, we have to understand the biology of the disease, the mechanism of action, and that requires larger patient groups in the first instance. We have to focus our efforts and available resources on gaining a better understanding of the biology before designing appropriate clinical trials.

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Due to the fact that adverse reactions can sometimes take a long time to emerge, good communication between pre-clinical, medical and pharmacovigilance groups to identify potential safety issues etc. is paramount. How do you feel this can be ensured?

forwards, it is clear that there is an increasing number of companies attending meetings like these, and they come with different types of programmes and ideas. While this enhanced attendance may help the transition towards precision medicine happen faster, the pace of this change nevertheless remains too slow.

What are your thoughts on the argument that targeted therapies may require increased safety surveillance and specific risk management strategies to mitigate target-related adverse reactions? The fact that some new clinical trials are smaller in terms of patient numbers, because they target specific patient populations, can leave a gap in the safety formation being collected as opposed to that garnered from the larger, more traditional trials. What we see happening is that both regulators and industry are trying to build continuous surveillance programmes after a licence has been granted. Indeed, the granting of a licence to bring a product to the market would typically also contain conditions to bring more information later on regarding the safety of the drug. This is a new field that we are trying to develop, and while this is not necessarily original, in that no-one is thinking about conducting large clinical trials when it has already been demonstrated that a small one will suffice, it is clear that drugs need to get to patients, they need treatments, but there have to be programmes attached that provide an element of confidence that the important safety issues have not been overlooked.

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We also have a programme working to cross-match across tumours and to look at the data for guidance in the better monitoring of specific parameters when patients are undergoing oncology treatments

This is indeed the difficulty of the preclinical model: it will never translate into the reality of what you will observe in a human being, simply because the metabolism in an animal is completely different to that of a person. Despite the fact that in many instances a very good model can be developed, this kind of problem remains wholly unpreventable, and it is therefore crucial to have a good strategy in place and to be aware of the importance of monitoring the patient over time. This includes after the drug has been approved, because when the drug is finally administered to a large patient population there is the chance of an emergence of an event that was never even anticipated. At the European level, there is progress being made towards a better continued monitoring of patients because of the possible adverse effects of a medication following its approval, and it is important that this monitoring continues. At the EORTC, we have established a new initiative to explore areas such as this, and those involved use the large databases we have created to investigate the problem of toxicity and to look at the potential occurrence of secondary malignancy as part of outcome research and real life implementation programmes. We also have a programme working to cross-match across tumours and to look at the data for guidance in the better monitoring of specific parameters when patients are undergoing oncology treatments.

From a legislative point of view, do you feel enough is being done to make Europe an attractive place for clinical trials to take place and to support related industries in Europe today? There is a very distinct sense that the European Commission may misunderstand the urgency of the situation, which is both a shame and a significant issue. We have developed a programme to address innovation in the healthcare system based on precision medicine, but this programme was rejected by the Commission, who have decided instead to develop a European Research Network which takes potentially a top-down approach and so essentially may ignore the needs of both the patients and the researchers. We have started an active dialogue over this and we are hopeful that these elements can be taken on board. What we need is a system of agile, rapid mechanism, rather than an archaic system which stands to leave Europe lagging behind the rest of the world.

How, then, are you working with the relevant actors in trying to change how the Commission does business in this area? We need to do some lobbying, and we are also working with DG SANTE to try to address this issue. However, while we will also be voicing our concerns at conferences and events, it appears that the vote has already been cast.

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Do you feel that there are roadblocks that need to be removed when it comes to the regulations which exist in this area? Yes, certainly. The EORTC has been instrumental in the revision of the EU’s Clinical Trials Directive, but what the new and improved version will actually look like remains to be seen. There are many other aspects like ethics committees, access to patients, the way clinical trials are used and so on must also be addressed. Indeed, it is (economically) impossible to open a clinical trial to numerous institutions, and so we need to find another mechanism which enables patients in community hospitals and so on to actually be reached but, currently at least, this is proving to be an impossibility. There are still a lot of things which need to be changed, and it is these kinds of messages that need to be understood at a higher level. There is also a sense that the science is evolving too fast for the regulations. We are now at the stage of immunotherapeutics; tomorrow we will be at another stage; and yet from a regulatory point of view it is almost like we are still at the stage of targeted therapies. What this means is that there is a significant gap between the science being done and the regulations governing it, and while the science is progressing and the patient population in Europe becomes increasingly active (they have certain expectations and are calling for a greater degree of openness and transparency), the existing regulatory frameworks are blocking the evolution.

Do you therefore work with patient organisations to help in this area? We have a lot of initiatives going on at this level, and we remain active in communicating information to patients, as well as in involving them in our processes. We also organise a course for patients every year.

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At the European level, there is progress being made towards a better continued monitoring of patients because of the possible adverse effects of a medication following its approval, and it is important that this monitoring continues

Is it fair to say that you are very concerned about the future for the EU’s innovation framework and whether Europe can retain its leadership? I am indeed unconvinced, and that is why I am fighting for change. But we have to pay attention; we have to put things into a global context. We must also look at the areas which are seeing growth, and we have to look at where industry would predict development, and so on. In addition, we must also convince industry that Europe is the right place for them to come and work, and that is a challenge in itself. The EORTC will also now increasingly look to work with international partners to help further these efforts.

Do you feel that the regulatory framework in which companies operate in, for example, the USA, is much more supportive of their work compared to that which exists in Europe? The discussions are easier in the US with the FDA, and there is a meeting wherein the FDA’s activities are scrutinised and questions concerning why a certain drug was approved (or rejected) etc. are asked. This does not happen in Europe, and there is a very real need for the EMA

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to make its activities transparent and to take the responsibility of taking on our challenges. This does not only concern transparency, however; it is more about engaging in multistakeholder discussions in order to address the challenges head on. We have signs that things are moving in this direction, and we have opened up a dialogue with the EMA to this end. The US system is also much simpler than its European counterpart when it comes to launching a trial, in that there are fewer processes and procedures, which means that it is much more competitive in a world where everybody is looking to start their research as soon as possible. The European regulators need to take action. Otherwise, things will just happen without their involvement. So if they want to have some form of control in these activities, then they have no option but to engage.

Can you highlight some of the EORTC’s priorities as we look towards 2016? Our main activities – in something of a continuance of those we have already started – will involve deploying new innovative programmes. Firstly, this will be in the field of molecular screening and will involve the establishment of new partnerships and looking at issues such as long term toxicity and other safety concerns. We are also the only organisation to have started working with national registries in an effort to understand how patients in real life differ from patients in clinical trials. Indeed, we have now begun a programme addressing the key questions here, and we are also working with the EMA to explore how our infrastructure can better serve the regulators in handling the new datasets that industry will be producing. The EMA has a significant challenge ahead of them because the dogma of the large randomised ‘Phase 3’ trials is vanishing. We are now working with companies which intend to go to the EMA with, first of all, nonrandomised clinical trials which cross diseases – so not necessarily just one tumour – and the challenges for the regulators will be whether to approve a given phase, as well as to identify the benchmark for the disease.

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The European Commission’s website reveals that the most frequently occurring forms of cancer in the EU are colorectal, breast, prostate and lung cancers. In men, lung cancer is the most frequent cause of cancer death, while in women it is breast cancer. In both men and women, colorectal cancer is the second most common cause of cancer death. Although significant advances are being made in the fight against the disease, cancer remains a key public health concern and a tremendous burden on European societies. 2015 is the 30 year anniversary of EU action on cancer. Since 1985, when the heads of state of the countries of the European Community met in Milan and committed themselves to launching the first ‘Europe against Cancer’ programme, actions taken at EU-level have helped to extend and save lives. In a factsheet produced by the Commission for this anniversary, the advances that have been made – and the burden which remains – is made clear. For instance, there were an estimated 1.4 million new cases of cancer in men and 1.2 million in women in the EU in 2012 (most recent data). In the same year, approximately 708,000 men and 555,000 women died from cancer. This makes cancer the most common cause of death in the EU after diseases of the circulatory system. These figures are expected to rise due to Europe’s ageing population; and this is despite the fact that one in three cancers are preventable. The Commission is thus focusing on areas such as addressing the risk factors – with actions including legislation on pesticides, air quality, exposure to carcinogens at work, and the EU tobacco control policy – as well as promoting early screening, all with the aim of reducing cancer incidence by 15% by 2020. This is an ambitious target given the considerable burden posed by cancer – currently and predicted for the future – yet given the advances already made and the focus being placed on this area by the European Commission and others, perhaps it is a target which can be met. Finally, I am happy to report that we have already made a constructive step towards increasing EMA’s involvement, because along with AACR and NCI, they have joined us to host an important conference entitled Innovations and Biomarkers in Cancer Drug Development. This is a landmark event, the first time EMA has ever put its stamp on a conference, and we hope that we will be able to use this meeting as a springboard towards positive change in the development of cancer therapeutics.

Dr Denis Lacombe Director General European Organisation for Research and Treatment of Cancer (EORTC) http://www.eortc.org/

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SEARCHING FOR SPECIFICS The Pathology Department at Umeå University, Sweden, search for new biomarkers and more specific cancer drugs

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he research group led by Professor Maréne Landström at Umeå University, with support from the Knut and Alice Wallenberg Foundation, Swedish Cancer foundation, Umeå University and the Swedish Research Council, study the molecular mechanisms by which transforming growth factor beta (TGFß) causes tumour progression in cancer, with a particular focus on prostate cancer. Intensive research in this field during the last ten years has made it clear that TGFß is one of the most important key factors for aggressive cancer and metastatic disease. Intracellular signals transduced from TGFß is today known to be crucial for the migratory and invasive behaviour of tumour cells, resulting in metastatic disease in several forms of our most common cancers, such as breast and prostate cancer. “It is a bit scary that the tumour cells start to increase their production of TGFß. In normal prostate epithelial cells, TGFß will cause growth inhibition and apoptosis, while in the premalignant stage or in cancer cells, TGFß instead instructs cells to become even more aggressive so that the tumour cells can invade the surrounding tissues and become metastatic. The source of overproduction of TGFß in tumours is an interesting topic for future studies, but is thought to originate from tumour cells and cells in the tumour stroma – which contains a number of different cell types such as blood vessels, muscle cells, fibroblasts and inflammatory cells. It is also likely that TGFß promotes interactions between cancer cells and their surrounding environment in a vicious circle, which is also likely to make the tumour cells even more aggressive,” says Landström.

The international research group, with highly motivated students and postdocs, has found a previously unknown signalling pathway by which TGFß promotes motility and invasiveness of tumour cells. In the cell culture system it is possible to track the specific signals leading to aggressive cancer. “We think that soon we will be able to identify this signalling component in human prostate cancer tissues so that we in the close future can develop molecular methods to identify patients with aggressive disease,” Landström continued. Another important goal for the research group is to search for and validate novel drug targets for patients with hormone-refractory prostate cancer, as we today lack effective treatment strategies for these patients. Unfortunately, this group of patients is expected to increase dramatically on the global level within 10-20 years, due to changes in lifestyle for men in Asia and expected longer lifespan for men in Western society. The research group has mainly focused their studies on prostate cancer. Intriguingly, however, they have found that some common signalling components are of key importance for aggressive behaviour also in other cancer forms, such as lung, breast and renal clear cell carcinoma.

Biomarkers for prostate and kidney cancer As a physician specialised in clinical pathology and a cancer researcher, Landström aims to improve methods for the identification of aggressive prostate cancer in her daily clinical work in order to improve molecular diagnostic tools for personalised medicine for cancer patients. In her research lab, she is searching for the Achilles heel of cancer cells, which means that she is fighting against cancers from two angles: the development of personalised and predictive diagnostic tools, and to find strategies for more effective cancer drugs which can specifically interfere with oncogenic driven TGFß signals. The novel TGFß-driven oncogenic pathway discovered by the research group has identified a number of potentially valuable biomarkers for aggressive cancer, which will now be evaluated in clinical materials in collaboration with Professor Anders Bergh, working at the same department as Professor Landström. The long follow-up time makes it possible to investigate which of the potential novel biomarkers could tell about the prognosis at the

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found to be relevant for prostate cancer, might be relevant for renal cell carcinoma and lung cancer, for example.”

Novel and potential successful drug candidates

Professor Maréne Landström

personal level. In collaboration with Professor Börje Ljungberg, Department of Urology, also at Umeå University, the research group have investigated key components in the oncogenic TGFßsignalling pathway and found that it is possible to identify a subgroup of patients with poor prognosis, using this potential novel biomarker. This potentially useful biomarker correlates with the TGFß-induced transformation of cells giving them the capability to migrate and invade into the stroma through the basal membrane, which is an important barrier and keeps epithelial and stromal cells apart in healthy tissues. Once the tumour cells have invaded into the stroma, they can then transport themselves into the blood or lymph vessels and from there be transported to distant organs or the skeleton, where they give rise to metastasis. At this stage, once tumour cells have invaded the blood stream, cancer can be a deadly disease as it is only localised cancer that can be treated effectively with surgery or radiation.

Validation of a clinically useful biomarker for invasive cancer In 2011, the research group discovered a previously unknown mechanism for oncogenic signals in cancer cells that might make it possible to identify aggressive prostate cancer at an early stage in the disease. An important next goal for Landström and her research group is to evaluate which of the promising biomarkers they have found in their research can be useful as a reliable biomarker, and could also show which cancer cells are aggressive and invasive. She said: “We have here in Umeå a unique opportunity to validate clinically useful biomarkers thanks to researchers who have collected patients’ samples over several decades from people who were both healthy and sick. Therefore we have fantastic material to study. In our local biobank we can investigate if samples from cancer patients already contain a potential marker when they were healthy, before they were diagnosed with cancer. In this way we can investigate whether potential biomarkers identified by us, in the oncogenic signalling pathway that we

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For a long time, it has been generally accepted that TGFß receptors signal from the cell surface. In our research, we surprisingly found it to move into the nucleus where it was able to activate pro-invasive genes that make the cancer cells metastatic. “Intriguingly,” Landström advised, “we also made the original observation that it is only a part of the receptor which enters the nucleus. We are now investigating whether this new knowledge is useful in designing novel strategies to prevent metastatic spreading of tumours which are dependent on this oncogenic pathway driven by TGFß, which is the case for prostate cancer.” In animal studies, the research group now have preliminary and exciting data that supports the fact that they can interfere with the spreading of invasive prostate cells to lymphnodes and distant organs. “We will now need to attract more funding for our research to prove that this treatment can be effective in other forms of cancers. We would also like to investigate further the molecular mechanisms for our novel treatment strategy in vivo and if our treatment strategy could be even more effective in combination with other treatments. “Our project consists of two parts, which are closely related. On one side, we will search for signs of the activated TGFß signal pathway in blood and tissue samples from patients with cancer. On the other side, we are going to investigate which chemical compounds can inhibit oncogenic TGFß signals which drives their metastatic capability, in order to search for potential novel cancer drugs. In this project, we are collaborating with Professor Mikael Elofsson at Umeå University. He has a fantastic and unique chemical library of metabolites, derived from bacterial cells, originating from the Arctic Ocean, for example. This collaboration gives our research yet another fantastic possibility to be successful,” Landström concluded.

Professor Maréne Landström Deputy Head of Pathology Department Umeå University SE-901 87 Umeå Sweden +46 (0)90 785 2458 [email protected] http://www.medbio.umu.se/ominstitutionen/personal/landstrom-marene/

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ASBESTOS: LESSONS LEARNT Lessons of exposure from the old Eternit factory in Aalborg, Denmark, and molecular profiling of mesothelioma can improve prevention, diagnosis and treatment of cancer from exposure to asbestos

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sbestos (Greek: inextinguishable) is the term for a family of naturally occurring minerals that have been used in small scale since ancient times1 (Fig. 1). Industrialisation demanded increased mining and refining in the 20th Century, causing asbestos consumption to peak worldwide at 4.7 million tonnes in 19802 (Fig. 2). In 1960, Wagner et al from South Africa had already linked asbestos to a rare cancer called malignant mesothelioma;3 one of the most lethal cancers that arises in the pleura, the lining of the lungs, in 80% of cases, as well as the peritoneum or the tunica vaginalis testis (Fig. 3). Mesothelioma is relatively chemo and radiation resistant, is usually diagnosed in a late stage, and has a median survival of 12 months with the current state-of-the-art treatment. Importantly, the time from asbestos exposure to cancer development is 20-60 years, and there is no safe lower limit of exposure.1 The role of asbestos was also shown to be a separate carcinogen for the development of lung cancer where combining cigarette smoking and asbestos exposure increased the risk of lung cancer from ten to almost one hundredfold versus non-exposure.4 Asbestos inhalation also induces benign pleural plaques, asbestosis, a pneumoconiosis that may be fatal, and recently was shown to increase the risk of cancer of the throat (pharynx), stomach, colon and ovaries.5 The public health consequences of asbestos are substantial. The WHO reports that 125 million people encounter asbestos in the workplace. In 2004, asbestos-related lung cancer, mesothelioma and asbestosis from occupational exposures resulted in 107,000 deaths and just over 1.5 million Disability Adjusted Life Years (DALY); we know that those figures are also increasing. In addition, several thousands of deaths can be attributed to other

Fig. 1 Bucket-shaped pottery from Telemark, also found in several other areas in Norway, from the Bronze Age to the Roman period (400-575 AD) [1]. They were used for cooking and storage of food, with estimated asbestos content of 65-80% (With permission from Asbjørn Engevik, Bucket-shaped pots: style, chronology and regional diversity in Norway in the late Roman and migration periods, University of Bergen 2007)

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Fig. 2 Trends of asbestos consumption in metric tonnes between 1920 and 2000 based on “Worldwide Asbestos Supply and Consumption Trends from 1900 through 2003” by Robert L Virta2

asbestos-related diseases, as well as to non-occupational exposures to asbestos. Currently, the incidence of the disease is still increasing in most countries, and only in countries in which asbestos control measures were taken during the 1970s, such as Sweden and the United Kingdom, has this levelled off.6 Thus, the worldwide epidemic is in its beginning and in countries that produce and/or use asbestos, such as China, India, Russia, Zambia, Colombia and Kazakhstan, a sharp rise in incidence can be expected.7,8 The cost for the society as a whole, due to human suffering, lost lives and, consequentially, a heavy burden on the healthcare systems in all countries, is substantial. In parallel with asbestos and its increased toll on human life, a novel threat may be on the way as manmade carbon nanofibres could pose a similar danger as indicated in recent in vivo and in vitro studies.1 The city of Aalborg in the North Jutland region of Denmark has hosted two large shipyards and the only Danish asbestos factory, Dansk Eternit-Fabrik A/S, from 1927-1986, which mainly used asbestos of the chrysotile type mined in Cyprus. We examined the incidence of mesothelioma in this geographical area by studying pathology records of the Aalborg University Hospital. More than 500 cases were identified and a thirteenfold increase in mesothelioma, which is still increasing, was registered during the periods of 1970-80 and 2000-10. The calculated national incidence of mesothelioma in 2011 was 2.18/100,000, and more than double, 5.3/100,000, in North Jutland; an international record high incidence showing that the asbestos industry and the chrysotile type asbestos have evidently had a major impact on mesothelioma incidence in northern Denmark.9

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discovery studies for mesothelioma biomarkers of resistance and treatment effects in serum and tumours, in parallel with epidemiological studies. The group collaborates with other universities in Denmark, Norway, Sweden, Greece and China. References 1 Roe OD, Stella GM. Malignant pleural mesothelioma: history, controversy and future of a manmade epidemic. European Respiratory Review: an official journal of the European Respiratory Society 2015;24(135):115-31 doi: 10.1183/09059180.00007014 2 http://pubs.usgs.gov/circ/2006/1298/c1298.pdf.

Fig. 3 Computer tomography of a woman with pleural and mediastinal mesothelioma. This patient was diagnosed at the age of 42. Her asbestos exposure was due to using a hairdryer with asbestos coils for ten years whilst working as a hair dresser. The mesothelioma lesions are seen within the circles (Courtesy of Oluf D Røe). Full case history is published in Røe et al, PloS One 2012, 10.1371/journal.pone.0040521

Occupational exposure to asbestos is the most common cause, but domestic exposure through cohabitation with an asbestos worker and environmental exposure by living in proximity to an asbestos emitting industry have also been acknowledged as risk factors. However, there are still many questions about the mesothelioma in women, which has been regarded as nonasbestos related due to the fact that women rarely worked in the shipyards and asbestos industry. In contrast, we investigated all females diagnosed with mesothelioma and found that almost 80% of the women with a known history had a non-occupational exposure to asbestos either by cohabitation with an asbestos worker or by living in proximity to the Eternit factory (Fig. 3).10 This unique biological repository and high incidence of a relatively rare but lethal manmade disease is now under investigation to understand why some people develop mesothelioma even after a low level of exposure, what we can do to prevent it, and how to treat this more successfully than in the past.

3 Wagner JC, Sleggs CA, Marchand P. Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province. British Journal of Industrial Medicine 1960;17:260-71 4 Barrett JC, Lamb PW, Wiseman RW. Multiple mechanisms for the carcinogenic effects of asbestos and other mineral fibers. Environmental Health Perspectives 1989;81:81-9 5 http://monographs.iarc.fr/ENG/Monographs/vol100C/mono100C-11.pdf. Secondary. 6 Bianchi C, Bianchi T. Malignant mesothelioma: global incidence and relationship with asbestos. Industrial Health 2007;45(3):379-87 7 Gao Z, Hiroshima K, Wu X, et al. Asbestos textile production linked to malignant peritoneal and pleural mesothelioma in women: Analysis of 28 cases in Southeast China. American Journal of Industrial Medicine 2015;58(10):1040-9 doi: 10.1002/ajim.22494 Epub 2015 Jul 6. 8 Joshi TK, Bhuva UB, Katoch P. Asbestos ban in India: challenges ahead. Annals of the New York Academy of Sciences 2006;1076:292-308 doi: 10.1196/annals.1371.072 9 Panou V, Meristoudis, C. , Røe, O.D. Malignant mesothelioma in Aalborg, North Denmark: Pathology reports of the Aalborg University Hospital reveal 562 cases and a 13-fold increase in four decades. Virchows Archives 2014;465 (Suppl 1): http://link.springer.com/article/10.1007/s00428014-1618-2 10 Panou V, Omland, Ø., Meristoudis, C. Hoffmann, L Røe, O.D. Pleural and Peritoneal Malignant Mesothelioma in Women Correlated to Occupational, Domestic and Environmental Asbestos Exposure. Supplement in the Journal of Thoracic Oncology 2015.

A multidisciplinary study group at Aalborg University Hospital and Aalborg University is currently pursuing and implementing

Oluf Dimitri Røe, MD PhD Associate Professor and Consultant Oncologist [email protected] Ursula Falkmer, MD, PhD Professor in Clinical Oncology [email protected]

Fig. 4 Type of asbestos exposure in 45 women with mesothelioma, hospitalised at Aalborg University Hospital between 1992 and 2015. Domestic exposure is defined as exposure through cohabitation with an asbestos worker. Environmental exposure is defined as living in proximity to the Eternit factory before 1986 when it was active10

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Clinical Cancer Research Center Department of Oncology Aalborg University Hospital +45 (0)97 661 411 http://www.aalborguh.rn.dk/Service/English

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THE UEG’S PROFESSOR PATRIZIA BURRA DISCUSSES THE LINK BETWEEN ALCOHOL CONSUMPTION AND BOWEL CANCER

The cancer-drink link IT has been estimated that around one in ten cases of bowel cancer can be linked to alcohol consumption and the risk increases with the more alcohol you drink. Indeed, new research has estimated that bowel cancer risk increases by 21% if you have two or three alcoholic drinks a day (1.5 to six units of alcohol) and by more than 50% if you have four or more drinks a day (six units or more). Even having one alcoholic drink a day (one unit) increases the risk by 7%.

cannot be compared since the methodology to evaluate alcohol consumption is not identical.

Of course, necessitating cultural change is extremely difficult. How do you feel the necessary paradigm shift can be achieved? I believe we need to dedicate time to educate physicians, to inform citizens, and to teach young people. There is still a poor level of knowledge on the effect of alcohol on the body’s organs, and this needs to change.

Alcohol consumption is a major public health concern and Europe has the highest levels of drinkers in the world. The EU currently has the highest alcohol consumption, on average consuming 12.51 litres of pure alcohol per person, more than double the worldwide average.

The WHO has highlighted that highquality screening programmes (FOBT, flexible sigmoidoscopy, colonoscopy and computed tomographic colonography) and sufficient participation could result in a significant mortality reduction. How practical would the rolling out of such programmes be in Europe?

Here, Professor Patrizia Burra – a member of the Public Affairs Committee at United European Gastroenterology (UEG); the EU Policy Councillor for the European Association for the Study of the Liver (EASL); and the head of the Multivisceral Transplant Unit within the Gastroenterology Department at Padova University Hospital, Italy – speaks to Pan European Networks about the link between alcohol consumption and bowel cancer.

Screening programmes are associated with a significant reduction of mortality not only for CRC but also for breast cancer. This reduction is mainly due to an earlier diagnosis. Thus, physicians and general practitioners have to encourage adherence to screening programmes. Secondly, medical associations in Europe have to consider this as a crucial point and to create a larger consensus. Thirdly, health systems in Europe have to improve their programmes to reach similar standards.

Given the increasing evidence linking colorectal cancer (CRC) incidences to alcohol consumption, where would you like to see future research efforts focused? We have to better understand the pathological connection between alcohol and the development of CRC, and to evaluate the presence of other co-factors (such as obesity and diabetes, for instance) which could increase the risk of cancer development. Unfortunately, most of the published studies

ALCOHOL A LCOHOLL AAND ND CCOLORECTAL OLORECTAL CCANCER ANCER

What role will UEG continue to play with regard to the aforementioned issues? STRONG G ASSOCIATION ASSOCIAT BE EEN ALCOHOLIC ALC BETWEEN CCONSUMPTION ONSUMP OF MORE A 1 DRINK PER DAY THAN AND COLORECTAL CANCER

EUROPE DRINKS, EUROPE DRIN , O N AVERAGE, AVERAGE, 550% 0% ON MORE THE M ORE THAN THAN TH E R EST OF OF THE THE WORLD WORLD REST

THE REGULAR CONSUMPTION OF APPROXIMATELY 50G LCOHO OF PURE ALCOHOL INCREASES RISK RISK BY 10-20% B Y 10 -20%

RISK INCREASES BY 21% WITH MODERATE MPT CONSUMPTION (1-4 DPD) ND 550% 0% W ITH H E AND WITH HEAVY CCONSUMPTION ONSUMPTION ((>4 >4 DRINKS) DRINKS)

ONE IN TEN ONE TEN CASES CASES OFF CRC O CRC IS IS LINKED LINKED WITH W ITH ALCOHOL ALCOHOL CCONSUMPTION ONSUMPTION

155 B 155 BILLION ILLION EUROS EUROS SSPENT PENTT AN NUALLY IIN N ANNUALLY EUROPE ASS A RESULT E UROPE A RESULT OF ALCOHOL ALCOHOLL ABUSE ABUSE

Data from United European Gastroenterology Journal: Journal: (1) Farthing M, Roberts S, Samuel D, Williams D, et al, Survey of digestive health across Europe: Final report. Part 1: The burden of gastrointestinal diseases and the organisation and delivery delivery of gastroenterology services across Europe, P,, et al, Survey of digestive health across Europe Europe:: Final report. Part 2: The economic impact and December 2014 2: 539-543 and (2) Anderson P burden of digestive disorders, December 2014 2: 544-546

H GHEST RATES HIGHEST RATES OF OF A LCOHOLL AABUSE BUSE ALCOHOL ECORDED IIN N RECORDED ASTERN EUROPE EUROPE EASTERN

STTATISTICALLLY TTHE STATISTICALLY HE LLOWEST OWEST CONSUMPTION CONSUMPTION OF ALCOHOL ALCOHOLL IN IN EUROPE EUROPE AND MALTA IIN N TTURKEY URKEY A ND M ALTA

The mission of UEG is to improve the prevention and care of digestive diseases in Europe. It will therefore be the lead association in the education of people, the training of young physicians, and the development of higher standards of care across Europe.

Professor Patrizia Burra United European Gastroenterology (UEG) https://www.ueg.eu/

V,, Tramacere V,, et al. Ann Oncol 2011;22:1958–72 Fedirko V Tramacere I, Bagnardi V 2011;22:1958–72

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SCIENTISTS OF THE INSTITUTE OF CANCER RESEARCH IN VIENNA ON NEW TREATMENT STRATEGIES FOR LIVER CANCER

Key molecular factors

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ne of the most aggressive and common forms of liver cancer is hepatocellular carcinoma (HCC). Scientists from the Institute of Cancer Research (ICR) at the Medical University of Vienna, Austria, have identified the receptor AXL as a key factor that causes HCC progression. In addition, it has been discovered that an AXL cleavage product can be used as a diagnostic biomarker. These findings could make a significant difference in HCC therapy. In the Western world, the most common causes of hepatocellular carcinoma (HCC) are metabolic diseases, permanent alcohol abuse, and chronic infections with hepatitis B and C. A team of researchers, led by Professor Wolfgang Mikulits, Head of the Tumour Progression and Metastasis Research Group at the MedUni Vienna’s ICR (Head: Professor Maria Sibilia), and a member of the Comprehensive Cancer Center Vienna (Head: Professor Christoph Zielinski), investigated the role of the AXL receptor tyrosine kinase in the context of HCC as part of a multicentre study.

Promising therapeutic target Transforming growth factor (TGF)-beta is a key regulator of HCC. It is known that at early stages of the disease, it is anti-oncogenic, while at later stages it is pro-oncogenic. Yet, little was known about the mechanisms that turn TGF-beta from having anti-tumorigenic to pro-tumorigenic functions, thus driving HCC progression. Mikulits and his team were able to demonstrate that the presence and activation of AXL leads to a diversion of signalling pathways, enabling the migration and metastasis of liver cancer cells (Fig. 1). As a result, after binding a 14-3-3 adapter protein, AXL is able to influence the extremely important TGF-beta signalling pathway in such a way that it causes the invasion and metastasis of HCC cells. AXL therefore inhibits the anti-oncogenic function of TGF-beta and is thus the crucial factor in the aggressive development of HCC and could be a promising therapeutic target to combat the disease.

Diagnostic tool A large scale multicentre study also revealed a potential diagnostic value for soluble AXL (sAXL), a cleavage product of AXL, in detecting HCC. This sAXL shows significantly increased serum levels in very early stage HCC (BCLC 0), as well as in early stage HCC (BCLC A), as compared to healthy and cirrhotic controls. The high sensitivity (76.9%) and specificity (69.2%) of sAXL in BCLC A exceeds the diagnostic accuracy of the gold standard alpha-fetoprotein. Interestingly, sAXL levels failed to be elevated in primary ovarian, colorectal, and breast carcinomas, as well as in secondary hepatic

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malignancies derived from the colon. Thus, sAXL is specific for HCC and represents a novel biomarker for routine clinical use.

From basic research to clinics The project has been funded by the Austrian Science Fund, FWF P25356, and was supported by the European Union – FP7 Health Research, HEALTH-F4-2008-202047. Therapeutic strategies have been devised in collaboration with Professor Markus PeckRadosavljevic (Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna) to pharmacologically interfere with AXL in clinical trials. A patent for the use of sAXL as a diagnostic biomarker for liver cancer has also been filed by the Medical University of Vienna. Validation studies for the establishment of a diagnostic sAXL tool are ongoing, and the search for partners in the pharmaceutical industry for the worldwide routine clinical use of diagnostic sAXL in HCC is in progress.

Institute for Cancer Research Department of Medicine I Comprehensive Cancer Center Medical University of Vienna http://krebsforschung.meduniwien.ac.at /?L=0

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PEN DETAILS THE ISSUE OF PAIN AND TOXINOLOGY, HIGHLIGHTING THE SITUATION AND THE CHALLENGES IN EUROPE AND AROUND THE WORLD

Medical priorities

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edical science in Europe continues to advance in developing treatments and responses that ensure human health is continually improved. Focusing on matters around pain and toxinology, PEN looks at some of the key dynamics today. Chronic pain – and a necessary response to the problem – is clearly an issue in Europe. Examining the issue is The Painful Truth campaign, which brings together groups in the public, private and third sectors to examine the issue of pain management in Europe. Working to shed light on the dynamics around pain in Europe, the campaign advances efforts to improve how people with chronic pain are diagnosed, enhancing access to innovative and cost effective treatment options.

welfare payments. Chronic pain also has serious consequences for the working life of the sufferer. Those afflicted reported that pain affected their work more than anything else. Whilst some may choose to exit the workplace, for those who remain the negative impact upon their working life is evident. More disturbing is the fact that one in five report that they have lost a job as a result of pain.

Send a message

Across the continent today, it is thought that chronic pain – lasting six months or longer – affects one in five adults. Close to 70% of those suffering from chronic pain do so for more than 12 hours a day despite treatment, and one-third report that they continually suffer pain. The need to address the matter is evident. While, of course, pain presents a terrible and debilitating burden for those suffering, there is a significant wider impact on the families and loved ones also affected. Economically, pain also presents a burden to society, generating costs for European healthcare systems, who are seeking to reduce expenditure. The cost of chronic pain to health systems in the EU is thought to be as high as €300bn, and around 90% of the economic costs of pain are attributed to indirect costs, such as lost productivity, social security and

Innovative pain relief medicines hold much promise

Campaigners stress that the response of healthcare systems needs to improve as regards chronic pain, with patients failing to receive appropriate treatment and support. Amongst health practioners there is a lack of relevant knowledge on how to effectively manage pain, including on the side effects brought about by some treatments. Patients also struggle to fully communicate the degree of pain they are in to their healthcare provider. Moreover, the experience of pain is subjective depending on the individual in question; meaning that communication between patients and providers of treatment requires continued focus. In facing this challenge, patient empowerment is key to informing sufferers of the choices they have over their treatment pathways. According to patient surveys, one-third of patients say they have been poorly informed about new options to manage their pain. The need to act, therefore, is evident as is the need to target the European pain problem with a robust series of cross-sector policy measures, since, according to Pain Alliance Europe (PAE), 40% of people with chronic pain report that it is not adequately controlled. Alongside the chronic pain challenge, there remains a need to respond to pain in the clinical setting. An example of EU support in the arena is the PAIN OUT (Improvement in post-operative PAIN OUTcome) project. The project aims to improve the care of patients with post-operative

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pain in both developed and developing countries. Following surgery, around half of patients will suffer from moderate to severe post-operative pain. A failure to address this pain is not an option given how it damages recovery, raises suffering and places extra burdens on healthcare resources.

Post-operative pain relief is an issue in need of addressing

In February 2015, the MEP Interest Group on Brain, Mind and Pain was launched, with the backing of the European Federation of Neurological Associations (EFNA) and PAE. Over 40 MEPs have backed the launch of the group, ensuring the issue is raised on the EU agenda. Such a move will only help ensure that more EU innovation funding is diverted towards research on the subject, and that healthcare policy better accounts for pain issues.

Throughout the project, patient-reported pain outcomes, alongside clinical data, has been collected in a standardised procedure. The questionnaire used is available in 18 languages and, with over 200 hospitals having taken part in the project, over 300,000 datasets have been collected. The PAIN OUT project continues to aid in the improvement of post-operative pain outcomes by use of a benchmark module that feeds back results, and by the development of an electronic knowledge library that provides easy access to current guidelines. The project will help devise better treatment while feeding into innovation programmes to ensure medicines respond better to the needs of patients.

Launching the group, Marian Harkin, Irish MEP and member of the Group of the Alliance of Liberals and Democrats for Europe, said: “Public awareness, research and funding for these disease areas is not equivalent to the burden and impact. In fact, public research funding for brain disorders equated to only 0.2% of the cost, with the industry investing just a further 0.8%.”

MEP support

Another area of research gaining attention currently is toxinology, the study of which is helping the medical community respond to microbial, plant and animal venoms, poisons and toxins. Particular emphasis

There has been high level backing amongst EU decision makers to push work on pain forward.

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Audrey Craven, the president of the EFNA, also commented: “These long term conditions severely impact quality of life, often leading to considerable disability and sometimes to reduced life expectancy. EFNA and PAE felt more attention was long overdue. A new parliament with many fresh faces was the ideal opportunity to launch the new group. The aim is to encourage research on and access to, innovative treatments, promote prevention and self-management approaches, decrease stigma and work together to improve quality of life for people living with these disabling conditions.”

Venom

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continues to fall on the issue as the consequences of venomous snakebites in areas such as Asia, sub-Saharan Africa and South America. Amongst all venomous animals, snakes lead when it comes to poisonous bites. Naturally this is a particular problem in tropical and rural parts. As developing countries, with their fragile heath systems, struggle to respond, the societal impact of snakebite is magnified. September 2015 proved an opportune time to discuss toxinology matters with the biennial meeting of the International Society of Toxinology (IST). The headline out of the gathering is that the present estimates on the number of snakebite deaths, disability and disabilityadjusted life years (DALYs) lost annually, are twice the present World Health Organization (WHO) and Global Burden of Disease (GBD) estimates. Around five million people around the world suffer from a venomous snakebite each year. However, the IST event heard that the reality is that up to 200,000 people a year are killed by snakebites. Further, it is thought by the IST that venomous snakebites alone account for six million DALYs lost each year. While access to anti-venom is key, so is treatment that can neutralise multiple types of snakebite. Those who suffer, as well as those who treat a snakebite may be unable to identify the species of snake, thus the need for access to a medicine that can treat multiple types of venom is apparent. However, volumes of just such treatments are rapidly dwindling. With the cost of anti-venom treatment being between $250-500 (€225450), the price is often prohibitively expensive during the developing stage. Ensuring a ready supply of affordable anti-venom that can treat a variety of different snakebites is therefore crucial, with researchers urging increased support. While the WHO acknowledge that snakebite is a neglected issue in need of more research activities, the IST has called on international leaders to take a more strident stance on the matter. Indeed, the meeting saw the delegates call on the WHO and governments around the world to reinstate snakebite as a neglected tropical disease (NTD). The association has expressed concern that despite high mortality levels, in

2013 the WHO demoted snakebite from an NTD to a ‘neglected condition’. This meant there was no formal support programme in place. Meanwhile, in 2015, it was dropped altogether, meaning there is no longer staff or expertise allocated to snakebite at the WHO. The IST argues that from a disease burden perspective, it should be ranked in the top three or four diseases, and the WHO ought to have a programme in place to treat and prevent snakebite, ensuring it is reinstated as a leading NTD. Alongside this, a warning that anti-venom stocks are running dangerously low, as well as there being crisis in the quantity and quality of anti-venoms in rural areas, was also issued. Further, there was a warning that where there is anti-venom, too often health staff do not have the training or knowhow to administer it safely or effectively. IST president, Professor Alan Harvey, commented: “Snakebite kills more people than any other NTDs combined, but is almost completely ignored and grossly underestimated. The WHO and governments need to adjust their data and rank snakebite where it belongs, as a very real public health and medical concern, which needs funding, training and focus.” During the course of the event, 400 leaders in the field came together to discuss the subject. It was demonstrated how great improvements could be efficiently made in the treatment and management of snakebite if there is the political will at the national and global levels. To summarise, much modern anti-venom is still being produced using century-old methods. The need for innovation is therefore clear. New research is pointing towards greater understanding of venoms, which will enable the manufacturing of new anti-venoms, but the need for the refocus of attention and resources on the issue of toxinology, and likewise on the issue of chronic pain, is also clear. Globally, great benefits can be achieved not just for patients and health systems, but for entire societies. The excellence to be found in the EU in research and innovation can be turned to more effectively tackling these concerns.

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ANTI-VENOM MORE THAN A LUXURY A professor of the University of Copenhagen writes on how anti-venom should not only be available for the rich

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lthough the snake has been a symbol of medicine and pharmacology, the pharmaceutical industry has forgotten about snakebites. Current technologies used for anti-venom manufacture are without dispute an essential factor in public health, but also present a number of limitations. Anti-venom antibodies are still of animal origin, and hence pose adverse reactions in the human snakebite victims. The majority of components in the anti-venom are horse antibodies, which again could lead to adverse reactions. Anti-venoms are generated from pooling plasma from groups of immunised animals, which inevitably leads to variations throughout batch production. To date, no anti-venom against snakebites has been marketed that was not developed by the traditional animal immunisation and plasma fractionation, not far from the originally proposed methods by Calmette in 1894, the father of anti-venom. Snakebite poisonings represent a public health problem of high impact, especially in rural, impoverished populations of Asia, subSaharan Africa and Latin America. In addition to mortality, these poisonings provoke physical and psychological sequelae in many people, thus affecting thousands of families and communities worldwide, causing much individual and social suffering. It is not just the fisherman or the fieldworker that is bitten and subsequently loses an arm or leg, but the entire family loses the income that is crucial for their sustenance. Parenteral administration of animalderived anti-venoms is still the treatment of choice and hence are on the list of essential drugs of the World Health Organization (WHO). Technological advances within biopharmaceutical development and medicinal chemistry have a responsibility to help pave the way for rational drug design approaches against snake toxins. This could minimise the use of animals and bring forward more effective therapies for snakebite poisonings. There is now an urgent need to explore and develop novel strategies to generate improved anti-venoms and novel toxin inhibitory compounds, especially after the BBC article which referred to Médecins Sans Frontières having said that Fav-Afrique anti-venom production is coming to a halt and stock will run out in 2016. In this context, we need to apply modern medicinal chemistry and biotechnological approaches in the development of new generation snakebite therapies of higher efficacy and safety. Synthetic anti-venom is a possible way out of the problems: it will be shelf stable, highly selective, could be sold for

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a price of $10 (~€8.9), and it would eliminate the cold chain needed with most current anti-venoms. The trend in anti-venom research must also move towards human(ised) antibodies and fragments, which has proven to have better chances to pass clinical trials than biopharmaceuticals due to their high specificity and generally low toxicity. The platform is there now to produce human(ised) antibodies thanks to HUMIRA and others that have paved the way and made it possible. In addition, since most inhibitory peptides are both inexpensive and easy to produce, it is also likely that peptides could in the future be used to treat snakebite envenomings. Supported by venomics and anti-venomics and the vast amount of biotechnologies such as phage display, peptidomimetics, and humanised antibody technologies may soon deliver clinical drug candidates that are not only more efficacious, but also display better properties in terms of half-lives, safety, purity, specific multi-toxin targeting, improved shelf life under harsh conditions, and cost of production and distribution. This is a task which can only be solved by combining many areas of scientific disciplines within academia, governmental and non-governmental funding and knowhow from the biotech industries. This will be discussed in depth in a review article soon to be published by Laustsen et al., From Fangs to Pharmacology from the Lohse Lab.

Brian Lohse Associate Professor Department of Drug Design and Pharmacology Faculty of Health and Medical Sciences University of Copenhagen +45 (0)3533 6658 [email protected] http://drug.ku.dk/research/molecular_and_cellul ar_pharmacology/epidiscovery

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NANOPARTICLES FOR ON-DEMAND DELIVERY Nanomedicine is a fast growing multidisciplinary scientific field that facilitates not only an early diagnosis, but also a selective delivery of bioactive molecules for an improved treatment of different diseases

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anoparticles are materials with dimensions below 100nm. At the nanoscale a given material shows unique properties different from those of its corresponding bulk. For any bulk material the percentage of atoms at the surface is negligible relative to the total number of atoms of the material. Therefore, the properties of the surface atoms are masked by the properties of the bulk. However, at the nanoscale the contribution of the surface atoms plays a significant role, enough to show those unique surface-attributable properties. Quantum confinement in semiconductors, superparamagnetism in magnetic materials and plasmonics in metals are examples of physical phenomena that only occur at the nanoscale.

Applications Some of those distinctive properties attributed to the reduced size have contributed to a plethora of applications in the biomedical field, mainly in therapy and diagnosis. In therapy, controlled, targeted, and triggered drug delivery have been demonstrated thanks to the use of different nanomaterials. In that regard, it is now possible to direct a specific drug or therapeutic moiety to a specific location in the body, sustain its release over time or decide when the transported cargo is released in response to a biochemical or physical internal or external stimuli. In tissue engineering, nanomaterials are used to better support tissue and organ regeneration by directing cell behaviour, controlling the local environment or releasing bioactive agents to speed up the regenerative process. In medical diagnostics nanomaterials are capable of enhancing sensor response time, sensitivity and selectivity for the early detection of many biomarkers compared to the traditional sensors. Nanoparticles are also currently used to image biological processes on the cellular and molecular levels. Furthermore, the resolution and the acquisition times of all the current medical imaging technologies (MRI, PET, CT, etc.) used for diagnosis at the clinical level can be improved with the use of nanomaterials as contrast agents. Nanoparticles can also improve the selectivity and sensitivity of other imaging techniques used in cellular and molecular biology such as fluorescence imaging, dark-field optical microscopy, targeted SERS, optical coherence tomography, multiphoton microscopy etc. paving the way towards their clinical practice.

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Consequently, all those benefits demonstrated by the use of nanoparticles have resulted in several clinical trials involving nanomedicines that are currently underway not only for cancer treatment but also for hypercholesterolemia, diabetes, scar prevention, and so on (Nature Biotech, 30, 471-473, 2012).

A slow road Despite the great potential of nanomaterials and the current advances in nanoparticle synthesis, their transition into the clinic is slow because it remains challenging to produce nanoparticles that are consistent ‘batch-to-batch’. In most cases, the properties that we demand from nanomaterials are critically dependent on their monodispersity, shape, dimensions and surface functionalisation. So, any deviation drives us towards obtaining inconsistent results. Also the achievement of the strictly defined requirements on the characteristics of nanomaterials represents a serious challenge for their large scale production needed for the clinical production. Many of the most sophisticated nanoparticles are currently prepared in time-consuming complex, multistep batch laboratory procedures that are not amenable to large scale production. In fact, there is often a balance between maintaining the ability to control the desired nanoscale features and achieving high throughput. Consequently, the development of new technologies tackling some of these challenges could significantly accelerate the clinical translation of nanomedicines. When using the current discontinuous (batch) reactors in the synthesis of nanoparticles, several drawbacks usually emerge, such as: 1) a heterogeneous distribution of reactants and temperatures in the reactor; 2) insufficient mixing; 3) variations in the physicochemical characteristics of the resulting products for the different batches; 4) their inherent discontinuity; 5) usually, many-labour intensive post-synthesis purification steps are needed; and 6) the synthesis yield is usually low, often producing a few milligrams of material from a long batch process. In order to overcome these disadvantages, microfluidic reactors (e.g. micromechanised micromixers, capillaries, junctions, etc.) have been used in the synthesis of nanoparticles to precisely control reaction temperatures and residence times, rendering, in a continuous way, nanoparticles with narrow particle-size distributions. In microfluidic reactors the small channel dimensions lead to a relatively large surface area-to-volume ratios and increased driving forces for heat and mass transport. Thus,

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compared to conventional batch synthesis, microfluidic systems allow a precise control of the reaction conditions (reaction time, temperature, reactant concentration and stoichiometry). In microreactors a continuous-flow synthesis takes place in the interphase of two mixing laminar streams controlled by molecular diffusion on a molecular level, whereas in batch reactors mixing is accomplished by fast convective processes. The mixing characteristics of microreactors help to reduce or avoid temperature and concentration gradients, decreasing nanoparticle polydispersity and guaranteeing a specific composition and crystalline structure. Thus, microfluidic technologies offer low-cost and easy-to-use platforms for controlling fluid flow. By using the confined and reduced environment that microfluidics provide polydispersity and batch-to-batch variations are avoided. Scaling down reactor dimensions to the sub-millimetre scale therefore provides opportunities for improved size and composition control of nanoparticle synthesis. In addition, complex reactantcontacting schemes that are difficult to achieve in macroscale units can also be realised, and flow patterns can be accurately controlled when using microfluidics.

A group focus Research in our group is focused on the synthesis of nanomaterials in a continuous manner using microfluidics in order to achieve the characteristics required for the nanomaterials used in different biomedical applications. We have developed a strong interest in the preparation of porous and hybrid nanoparticles by controlling their processing and assembly in terms of size, shape, composition, morphology and collective properties. We have synthesised plasmonic, semiconductor, magnetic and polymeric nanoparticles using microfluidic reactors showing an enhanced quality in the resulting materials compared to the traditional batch production. Also, computational fluid dynamics (CFD) are currently used in our group to obtain first a detailed description of the transient fluid flow and the mixing of the reactant streams inside both microfluidic and batch systems considering the chemical reactions involved, and second, to predict the changes over time of the size distribution of nanoparticles due to different phenomena like nucleation, growth, dispersion, dissolution, aggregation, and breakage producing the dispersion. The development of population methods for the numerical solution of the changes in particle size distributions and their recent implementation in commercial software help us in the nanoparticle controlled synthesis and save us experimental work. The qualitative analysis of the flow patterns helps us to identify the mixing phenomena and to corroborate the experimental observations. Our work shows that micromixers can be one of the most efficient devices for continuous production of monodisperse and scalable nanoparticles intended for biomedical applications.

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One of the current projects within the group seeks to demonstrate the use of microfluidics supported by computational fluid dynamics to tailor nanoparticles for on-demand delivery. Our goal is to control nanoparticle synthesis parameters to obtain polymeric nanoparticles with homogeneous particle size distribution loaded with specific drug amounts and produced in a continuous and scalable manner. We plan to produce anaesthetic-loaded nanoparticles for pain management using microfluidic techniques. We are using light-responsive plasmonic and semiconductor nanoparticles to trigger drug release on-demand and reversibly by externally applying near infrared (NIR) light. The use of NIR hyperthermia consists of an increase in the local temperature (41-47°C) by using the heat transmitted by the absorbing nanoparticles upon laser irradiation. Depending on the laser fluency, pulse frequency, wavelength and irradiation time, the amount of drug released from the drug-loaded nanoparticles could potentially be tuned. The combination of those plasmonic nanoparticles with thermally responsible polymers allows developing a reversible drug releasing system which could be switched on or off depending on the need. Not only pain control can benefit from this technology but also other pathologies which need an on demand delivery of drug at a targeted location and specific time such as diabetes, hormonal disorders and so on.

Manuel Arruebo, PhD Associate Professor in Chemical Engineering Aragon Nanoscience Institute University of Zaragoza +34 (0)87 655 4343 [email protected] www.unizar.es/ina

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DR MARCIN KOŁACZKOWSKI FROM JAGIELLONIAN UNIVERSITY IN CRACOW, EXPLAINS HOW AN OLD HYPNOTIC DRUG HAS BECOME A STARTING POINT IN THE DEVELOPMENT OF INNOVATIVE ANTIPSYCHOTICS

Old drug, new hopes IT costs around $800m (~€717m) and takes approximately 15 years to introduce a single drug onto the market. These issues can possibly be decreased by finding new uses for old drugs or by choosing an old drug as a point of entry in the development of novel molecules. Today, the identification of new uses for old drugs has become a science in itself; at least 20 old drugs are currently in diverse stages of the drug discovery process, and a further 24 have been repositioned for new uses.

A new hope Many GABA-ergic drugs such as classical benzodiazepines (diazepam, lorazepam) or more selective positive GABA-A receptor modulators (zolpidem, zaleplon, zopiclone) have been frequently used as additional therapy in several psychiatry units to treat insomnia in patients with psychotic disorders. Interestingly, approximately a third to a half of the patients treated with GABA-ergic drugs experienced a significant improvement; however, whether this was due to sedative and hypnotic effect or to specific antipsychotic influence was difficult to interpret. Recently, our research group has confirmed that among various GABAergic drugs, only zolpidem showed specific antipsychotic properties in animal models of psychosis. Our research revealed that zolpidem has an interesting pharmacological profile and represents an attractive point of entry for the development of innovative antipsychotic drugs. However, zolpidem is a short-acting sleeping pill and has been introduced on the market to induce sleep. It is rapidly metabolised by human liver cytochrome P450 enzymes to its hydroxylated derivatives, which results in a plasma half-life of 2h. Zolpidem is desired from a sleeping disorder point of view due to its short-acting effect; however, it is suboptimal regarding psychosis. Thus, due to its unsuitable pharmacokinetics, it would be rather difficult to reposition zolpidem for the treatment of psychotic diseases such as schizophrenia or bipolar disorder.

Novel analogues As mentioned above, one of the leading strategies in the development of novel biologically active molecules is to start with an old drug. Such an approach allows, for example, for the introduction of crucial drug-like properties to the new compounds. During the course of our research, we created a series of zolpidem analogues in which we made several structural modifications in order to obtain compounds with increased metabolic stability, adjusted to the potential treatment of psychotic disorders. The novel series of zolpidem analogues showed desired antipsychotic properties in animal models of psychosis and is currently being tested by various behavioural tests to

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obtain wider information about the pharmacological profile of the new compounds.

Why new antipsychotics? The first antipsychotic medication, chlorpromazine, was introduced in the 1950s. This was a groundbreaking discovery in the history of modern psychiatry. Both chlorpromazine and other first generation drugs act via monoaminergic receptors, mostly by blocking dopamine D2 receptors. Approximately 20 years later, a second generation of antipsychotics acting through D2 receptors and the serotonin 5-HT2A receptor entered the market. Both classes of antipsychotics were effective in reducing psychotic symptoms; however, they caused numerous side effects such as weight gain, Type II diabetes, hyperlipidemia, QTc interval prolongation, myocarditis, sedation, sexual dysfunction, anticholinergic effect, postural hypotension, and cognitive decline. It is also worth mentioning that those uncomfortable side reactions are the main reasons why patients withdraw from the pharmacological treatment (~30% of all patients). Moreover, up to 40% of patients either fail to respond or respond only partially to the currently available antipsychotics. For the past 50 years, the FDA has approved many novel antipsychotics; however, their mechanism of action was always based on the interaction with monoamine neurotransmitter

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receptors 5-HT2A and D2 receptors. Many clinicians have already highlighted that the development of innovative antipsychotics with a different mechanism of action is crucial in modern psychiatry. Novel zolpidem analogues developed by our group act by positive allosteric modulation of the GABA-A receptor and therefore represent a unique mechanism of action which we believe to be significant in the development of innovative antipsychotic agents.

Who are we? We are a group of medicinal chemists specialising in in silico-supported drug design and discovery, focusing on central nervous system (CNS) disorders, especially psychotic, affective, and cognitive disturbances. We have created a strong network of collaborations with scientific groups to cover a drug discovery process from in silico-supported drug design, through chemical synthesis and broad in vitro screening, to advanced animal models of CNS disorders (for more information, please see www.drug-design.eu). We offer broad in silico studies focused on the design of biologically active compounds, particularly aimed at the CNS. Moreover, we

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It costs around $800m (~€717m) and takes approximately 15 years to introduce a single drug onto the market

offer the opportunity to perform broad radioligand assays at various monoaminergic receptors as well as off-target screening (hERG by automated patch clamp). We have developed various in vivo tests to define the pharmacological profile of future psychiatry drug candidates.

Collaborations We seek for collaborations compatible with our competences to broaden the range of capabilities and create a strong consortium concerning the following: n Synthetic chemists; n

PK studies;

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Brain electrophysiology;

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Brain microdialysis;

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Aged animals;

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Genetic models of neurodegenerative diseases; and

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Intracellular signalling. Marcin Kołaczkowski, PhD Associate Professor Faculty of Pharmacy Jagiellonian University Medical College +48 (0)12 620 5460 [email protected] www.drug-design.eu

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DR HELEN HESKETH DESCRIBES RESEARCH BY THE DISEASE ECOLOGY GROUP AT THE NERC’S CENTRE FOR ECOLOGY & HYDROLOGY

Disease and pathogen ecology

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any pathogens are transmitted between vertebrate hosts (which may include wild and domestic animals and humans) by arthropod vectors such as biting midges, mosquitoes, blackflies and ticks. These arthropods are important as they bridge transmission between hosts. Persistence of such pathogens within animal or human populations is closely linked to the suitability of the environment for these vectors as well as the vertebrate hosts in which a pathogen circulates. Global changes in landscape and climate may influence the interactions between arthropod vectors, the pathogens they carry, and the vertebrate hosts they bite, leading to the emergence or re-emergence of infectious diseases that can have significant medical and/or veterinary impacts.

Dr Helen Hesketh

Data acquired from field experiments are being used to inform mathematical and statistical models that will increase our ability to predict disease distribution and spread patterns and how these may change under current and future environmental conditions.

Identifying and understanding the key drivers of the emergence of arthropod-borne diseases and the severity of their impacts are important issues in designing and implementing better control strategies, for both individual countries and at the European level.

Bluetongue and Schmallenberg diseases There are several recent cases of novel disease incursions within Europe that highlight the current and future major threat posed by vector-borne diseases to veterinary and public health. Two important veterinary examples are the spread of bluetongue virus (BTV) and Schmallenberg virus (SBV), both of which are transmitted between their hosts by certain species of biting midges of the genus Culicoides. Infections with BTV can cause severe disease in sheep and cattle which can lead to huge losses in livestock productions. Schmallenberg virus

causes congenital malformations and abortions of the offspring of sheep, cattle and goats when the mothers are infected during a particular period of pregnancy. Work at the NERC Centre for Ecology & Hydrology (CEH, UK) is focused on understanding how environmental conditions and the availability of different vertebrate host species combine to influence the distribution and population size of the Culicoides vectors and therefore the risk posed to livestock of contracting these diseases.

Understanding midge population dynamics Culicoides species under the microscope – several UK midge species are vectors for bluetongue virus and Schmallenberg disease

The reliance on midge vectors for disease transmission means that disease spread is limited by the distribution and seasonal dynamics of midges at both local and wider geographical scales. These distributions and dynamics are influenced by environmental conditions such as weather and habitat, as well as by midge feeding preferences for different vertebrate hosts. Collaborative research between CEH and the Roslin Institute (Scotland, UK, led by Dr Paul Bessell), funded by the Scottish Government (EPIC – Epidemiology, Population health and Infectious disease Control, see: http://epicscotland.org/), has quantified the influence of temperature on seasonal population patterns of Culicoides midges, and how this may affect the spread of Schmallenberg virus in Scotland. Mathematical models have been combined with statistically estimated patterns of midge seasonal dynamics in different habitats to demonstrate that the potential for SBV spread is highly sensitive to both temperature and the timing of disease introduction. The time window during gestation in which sheep are at risk of birth malformations is relatively narrow, and our

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model can predict periods when high midge abundance and biting present the greatest risk to herds.

Informing control strategies These findings have changed lambing practices in high-risk areas to minimise the chances of infection during pregnancy in sheep. The mathematical models also explored alternative vaccination scenarios and demonstrated that the tactical vaccination of cattle, particularly in high risk areas in southern Scotland, could reduce the overall disease spread. Importantly, given the recent rise in average temperatures experienced in the UK, the model results also demonstrated that at higher than average temperatures, and hence increased transmission potential, the relative impact of vaccination was considerably enhanced. The effectiveness of vaccination was also improved if vectors fed preferentially on cattle rather than sheep, and such preferences are known to significantly affect virus transmission. Culicoides midges generally have a wide host range and feed opportunistically, but some European species have been known to prefer cattle. Understanding the heterogeneous nature of interactions between vectors and host species is therefore essential for creating realistic models to underpin assessments of seasonal and geographical variation in disease risk. These findings are of considerable importance when planning control strategies for Schmallenberg desease and also have important implications for the management of BTV. Critically, this research has highlighted the importance of further empirical research into the environmental determinants and feeding preferences of key midge vector species. Predictive tools such as these may help public health experts and policy makers taking decisions about risk communication, prevention and control measures.

Developing models In other research, partially funded by an EU FP7 project (EDENext, see: http://www.edenext.eu/), CEH has developed a UK data-driven Culicoides mechanistic population model to explore the impact of vector control on seasonal vector abundance. This mechanistic simulation population model for a key midge vector, Culicoides obsoletus, explicitly links environmental variation with life-history processes, such as development time, fecundity and mortality, and predicts the seasonal abundance of the midges.

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Red deer are important wild hosts for midge-borne diseases in Europe

Mechanistic vector dynamics are important because they affect disease seasonality and are, in turn, affected by environmental variability. Building upon this model framework, the group has investigated the efficiency of timing and intensity of vector control. The research showed that with high levels of control the midge populations could be eradicated, whilst low control resulted in only small average annual reductions. An important finding was that there is potential to increase the vector population later in the midge season if early control methods are applied. Decreasing the midge population in spring reduces the density-dependent competition amongst pre-adults, which in turn results in increases in adult midge numbers in autumn. As a consequence, although the control strategy could have a desirable effect on the whole, the increase in peak autumn abundance may have dramatic consequences for the number of new disease cases that could be generated in this warmer period, as well as the prevalence and seasonal persistence of midge-borne diseases. Control efforts should therefore concentrate on reducing the vectors autumn abundance peak, as this will reduce the midge population at both the peak and on average throughout the year and in subsequent years. However, the precise timing is crucial for effective control, particularly if the strategy is used year upon year because late autumn control may increase subsequent late summer populations.

Role of wild deer in disease transmission Importantly, arthropod vectors may feed on wild vertebrates as well as domestic animals, meaning that proximity to wild host species may be a key risk factor for the infection and transmission of diseases in livestock. For example, red deer, roe deer, and fallow deer are known to be important hosts for several midge-borne diseases in Europe, including bluetongue disease. Deer and wild ruminants might influence virus transmission in multiple ways; for example, they may be the preferred hosts for the vectors themselves, and so their presence may strongly influence the size of the vector population. Alternatively, or as well, wild hosts may act as a reservoir for the virus, and without them (even if vectors were present) there would be little or no risk to livestock. In the UK, there are many areas in which wild deer and livestock overlap considerably and CEH is addressing fundamental questions regarding the interactions between

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Research funding The Vmerge project (see: http://www.vmerge.eu/) is funded by the Seventh Framework Programme of the European Commission, and aims to address the risk of emerging viral vector-borne diseases in two main categories of arthropods known to transmit important animal and zoonotic diseases; mosquitoes and Culicoides biting midges. Vmerge intends to establish a continuum between field and experimental research and vector/vector-borne disease surveillance through a logical framework linking innovative diagnostics, prospective surveys in vector populations and their hosts sampled in selected ecosystems. The Vmerge consortium is made of 16 beneficiaries from 12 countries, including five countries from western and northern Africa: Senegal, Mauritania, Morocco, Tunisia and Egypt. It encompasses most European and Mediterranean ecosystems, plus Mauritania and Senegal, making the eco-epidemiological link with Sahelian Africa. Work exploring the use of novel methods for controlling insect pests was funded by the UK Department for Food, Environment and Rural Affairs as project HH3101TX ‘Novel strategies to exploit existing natural infections: synergisms between baculoviruses and other toxins’. The Disease Ecology group supports research in two key science areas within CEH. The Natural Hazards Science Area led by Nick Reynard aims to ‘improve the understanding and prediction of the threats and impacts posed by natural hazards, and the development of management and resilience strategies’. The Ecological Processes and Resilience Science Area led by Alan Watt is concerned with ‘Advancing and applying understanding of ecological and socioecological processes and resilience to the challenges of global environmental change’. Culicoides midges and wild deer, and is developing empirical and modelling studies to better understand how: 1) The distribution and population dynamics of different midge vector species vary across agricultural and natural landscapes in the UK; 2) Whether, and to what extent, different midge vector species bite both deer and livestock, and how these host preferences influence the potential for transmission between wild and domestic host species; and 3) How the distribution and seasonal aggregations of wild deer in the UK influence the potential for midge-borne disease transmission between livestock and wild ruminant herds. Given that landscapes in the UK provide habitats for different vertebrate hosts such as red, roe, and fallow deer and livestock (sheep/cattle), CEH is conducting empirical research to identify how different species of midge are interacting with livestock (sheep) and wild host vertebrates (red and roe deer). The work is focused in Scotland, where significant areas of midge habitat are also home to large populations of both red and roe deer and sheep. A range of techniques are being employed, such as seasonal light trapping to assess the local midge population composition, and molecular

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blood meal analysis to identify the species of wild and domestic vertebrate hosts that engorged midges have fed on. This research is providing critical baseline data on the seasonal distribution and abundance of midges in different habitats, as well as the biting behaviour of different midge vector species that can then be used in predictive models to assess disease transmission risk. Implicit to mitigating for risk of disease in the future is the ability to predict disease distributions and how these may change under current and future environmental conditions. CEH is involved in a collaborative research team on an EU FP7 project entitled Vmerge (see: http://www.vmerge.eu/). This research is developing models to predict the density of wild deer which, when coupled with models of seasonal midge vector abundance, will increase our understanding of how spatial and temporal overlap in host and vector populations influences the risk of future midge-borne disease incursions. Importantly, CEH is contributing hydrological modelling to this project to better understand the impact of droughts and flooding on spatiotemporal risk in disease transmission.

Entomopathogenic disease Other pathogens that occur naturally can attack insects themselves (often referred to as entomopathogens) and research at CEH also considers these diseases. Insects are susceptible to infection with microbial organisms such as bacteria, viruses, fungi and protists. Viruses and bacteria need to be ingested by an actively feeding insect host, whilst fungi can directly penetrate the exoskeleton. Once inside the host these pathogens multiply, often taking over much of the host’s tissues before killing it and releasing new, infectious particles that can be transmitted to new hosts. Over 50 of these pathogens have been developed as microbial pesticides. They are environmentally benign and can be highly host-specific, and are therefore important components of pest management strategies for the control of arthropod pests. Recent EU directives such as Directive 2009/128 ‘Establishing a framework for community action to achieve sustainable use of pesticides’ and the forthcoming directive EC 91/414 to ban many other pesticides mean farmers are increasingly required to reduce their use of broad spectrum chemical pesticides. Microbial biopesticides present a significant alternative that growers are encouraged to incorporate into Integrated Pest

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Management (IPM) alongside conventional pesticides. However, research is needed to expand the range and particularly the reliability of microbial biopesticide products.

Mixed pathogens for pest control The combined use of entomopathogenic micro-organisms with both conventional synthetic pesticides and other applied microorganisms/pathogens maybe a way to synergise efficacy and reduce variability of control. New research at CEH is addressing this through mixed pathogen experimental work in the laboratory and mesocosm experiments, extending them to small scale field trials. The work focuses primarily on a group of viruses called the baculoviruses that specifically infect the caterpillar stages of Lepidoptera (moths and butterflies) and how these viruses interact with other pesticides/microbes. Experimental ‘model’ moth-baculovirus systems have been used extensively to evaluate pathogen transmission dynamics in a controlled way that can inform pathogen-host interactions and disease models. What had been missing is empirical data at the population level describing multiple-pathogen transmission dynamics. This was investigated in a series of field trials where populations of cabbage moths were experimentally manipulated to determine what effect mixing the virus with another pesticide had on pathogen transmission. It was found that the virus transmitted more readily when it was co-applied with a commonly used biopesticide containing the bacterium Bacillus thuringiensis; there was greater mortality of caterpillars due to virus in treatments with both virus and biopesticide, compared to those with only virus applied. Viral infectious propagules released from dead insects can be transmitted to new, uninfected hosts causing a second wave of infection and this is important for sustaining long term control of pest insects. Interestingly, it has been demonstrated that the subsequent second wave of infection was significantly reduced when the biopesticide had been used alongside the virus. This is likely to be due to complex interactions such as changes in spatial distribution of the virus and direct interactions between pathogens within the insect hosts (this has been published in the Journal of Invertebrate Pathology (2015) 132:171-181). Understanding how pathogens can persist and transmit within host populations under these different conditions is

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EC research in neglected infectious diseases Research into neglected infectious diseases (NID) was included in the European Commission’s Seventh Framework Programme (FP7, 20072013) as one of four pillars in infectious diseases research. The aim here was to address research gaps and priority areas for NID through genomic and post-genomic research at the European level, and with the ultimate goal of developing new prophylactics (vaccines), treatments, diagnostics or control tools for neglected infectious diseases. The collaboration between European scientists and scientists in disease endemic countries is highly prioritised, as is the involvement of industry, public private partnerships and non-governmental organisations. Moreover, in December 2014, the EU and Africa doubled research efforts to develop new and better medicines for poverty-related diseases affecting sub-Saharan Africa such as AIDS, tuberculosis, malaria, hookworms and Ebola. Building on the success of the first programme, the second European and Developing Countries Clinical Trials Partnership programme (EDCTP2) was established with a budget of €2bn over ten years, with the EU contributing €683m from Horizon 2020, while around €1.5bn will come from European countries. EDCTP2 heralds a new era of co-operation between Europe and Africa in medical research, with countries from both continents working as equal partners. Carlos Moedas, European Commissioner for Research, Science and Innovation, said at the time: “Infectious diseases like AIDS, Ebola or malaria are a major global threat, but they hit poor communities hardest. The latest Ebola outbreak reminds us that more research is needed to find new medicines and vaccines that will help save millions of lives. Today, Europe and Africa are stepping up their efforts to fight the spread of infectious diseases together. With the investment of €700m from Horizon 2020, the EU will boost research efforts to prevent new epidemics in the future.” essential to evaluating the success of biological control agents in the suppression of pest populations. CEH delivers vital research, from experimental laboratory and field data to predictive models, needed to inform our understanding of host-parasite and vector-borne diseases. This delivers the critical knowledge necessary to both exploit the beneficial effects and mitigate for the detrimental effects of pathogens in the environment both currently and in the future.

Helen Hesketh, Stefanie Schäfer, Susan Withenshaw, Kate Searle, Steven White, Bethan Purse Centre for Ecology & Hydrology [email protected] tweet @WellyHe www.ceh.ac.uk

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PARASITOLOGY

FOCUSING ON THE PARASITE The Witold Stefan´ski Institute of Parasitology explains how and why its research focuses in on parasites

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he Department of Parasitology was created in December 1952 and became the Institute of Parasitology (IP PAS) in 1980. Since 1997, the institute has been located in a modern building in the centre of Warsaw. In 2002, the institute was declared the Centre of Excellence in Parasitology for Central and Eastern Europe by Professor Michał Kleiber, Minister for Science and president of the State Committee for Scientific Research (2002-2007).

Research Currently IP PAS employs 37 scientists: six professors, six associate professors, 13 doctors, eight assistants and four technicians. As a specialist and unique national establishment, the institute conducts interdisciplinary basic research intended to solve important parasitological problems. It addresses the following aspects: 1) Zoological aspects – the biodiversity of parasites in various ecosystems, the parasitic fauna of wild animals (invertebrates, fish, birds, mammals), the morphology of parasites (including their ultrastructure and the study of genomes), the relationship of lifecycles and population biology with various environmental factors, the systematics of certain groups (protozoans, platyhelminthes and nematodes); 2) Physiological aspects of the host-parasite system – the biochemical and physiological conditions needed for the establishment of parasites in hosts, immunology and immunopathology in parasitoses (especially in trichinellosis, neosporosis and echinococcosis); 3) Molecular aspects – the molecular diagnosis of parasitic infection, evaluating the protectivity of recombinant proteins and cDNA vaccines against gastrointestinal helminthes, investigating immune responses of animals vaccinated with ‘naked’ DNA, molecular analysis of parasite diversity; and 4) Epizootiology and control of parasitic diseases – the dynamics of the occurrence of parasites in domestic and wild animals and on pastures under various breeding conditions, the influence of breeding mode on the distribution of parasites, the efficacy of some antiparasitic drugs and parasitic resistance to them.

equipped with all necessary facilities. A room for sterile work, a cooler room and an animal room for small laboratory animals with laminar cabinets and a ventilation system are available. PCR (polymerase chain reaction) is used for a range of DNA analyses, including sequencing, cloning and library generation.

Field stations IP PAS has two field stations outside the city. One, located in Kosewo Górne (225km from Warsaw), currently focuses on controlling parasitic diseases, vertical transmission of parasitic infection and optimisation of deer-breeding conditions (www.kosewopan.pl). The second is located 22km from Warsaw in Łomna Las, and offers the possibility to study the immune response against gastrointestinal nematode infections in goats, sheep and cattle.

Previous involvement in research and training programmes The research group has collaborations with many academic and scientific laboratories. We participated in the European Union’s Fifth and Sixth Framework Programmes.

The future IP PAS welcomes further collaboration to develop pioneering molecules for use in either the prevention or therapeutic treatment of parasitic diseases. We are also interested in co-operation in the area of genetic variability and phylogenetic analysis of pathogens. A strong effort is currently being directed toward the development of an effective vaccine against many parasitosis. All life stages of the parasite express a complex of proteins involved in host invasion, parasite survival and the generation of antibody responses in infected animals. Some of these proteins are suitable for immunodiagnosis and vaccine development. Reproducible sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), two-dimensional electrophoresis (2DE), fluorescent two-dimensional difference gel electrophoresis (2D-DIGE), mass spectrometry and bioinformatics are commonplace in modern parasitological research.

Infrastructure and equipment IP PAS has specialist laboratories for molecular biology, immunology, chemistry and biology. The laboratories are well

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SDS-PAGE and 2DE are used to study and compare the protein profiles of the antigens expressed during the developmental stages of the parasites which are the main subject of research in the institute. The 2D-DIGE is used to establish statistically valid thresholds for assigning qualitative and quantitative differences between antigens corresponding to the different life stages of parasites of interest. The characteristics of protein profiles through the whole lifecycle of parasites will be helpful in understanding host-parasite interactions. 2D immunoblotting is used to verify which of the identified proteins stimulate the immune system of the potential host. Moreover, the use of immunoreactive proteins in recombinant form may provide a new source of diagnostic reagents in Trichinella spp., Neospora caninum, Sarcocystis spp., Fasciola hepatica and Toxoplasma gondii infections. The most common tick species parasitising animals in Poland are Ixodes ricinus and Dermacentor reticulatus. These tick species differ in their distribution, habitats, seasonal activity and host specificity. Ixodes ricinus is the most prevalent and widely distributed, whereas the range of D. reticulatus is limited to eastern and central parts of the country, with several new foci in the middle-west and the west. We intend to describe the role of wild carnivores as an animal reservoir for pathogens of transmissible diseases of human and domestic animals spread by blood-sucking arthropods. This will be done by investigation of the prevalence of wild carnivores such as foxes, badgers and raccoons, infection with bacteria of the genera Rickettsia, Anaplasma, Bartonella and Borrelia, and with protozoans of the genera Babesia and Hepatozoon. We also intend to determine the level of mammal infestation by parasitic arthropods and to use PCR and sequencing methods to determine the molecular characteristics of pathogens. The study of genetic variability and phylogenetic analysis of the pathogens will help to determine the geographic distribution and the origin of isolates.

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PARASITOLOGY

We participate in the Bison Network. We co-operate with international organisations to monitor the status of helminth infections (fasciolosis, ashworthiosis) in both European bison in the wild and those in captivity. We are also interested in parasites of wildlife and breeding cervids, parasite distribution, as well as their morphology, systematics and biology. Our research embraces differential diagnosis of parasite infections and the epidemiology, pathology and treatment of the parasitoses provoked by them. The forest environment, as a source of parasites for humans and animals, is one of the most important problems addressed by the institute. The current topics of research are gastrointestinal nematodes from the family Trichostongylidae, lung nematodes from the family Protostrongylidae and tissue nematodes from the subfamily Onchocercinae. Future research addresses the genetic variability and phylogenetic analysis of pathogens. Based on the occurrence of parafasciolopsosis, elephostrongylosis and ashworthiosis in wild ruminants, the research investigates the possibility of infections being transferred to domestic animals such as cows and sheep, which may use the same pastures as wild animals. Research into parasitic diseases proceeds in wild animals and under farm breeding conditions (Kosewo Górne).

Professor Boz˙ena Moskwa, PhD Head of the Witold Stefan´ski Institute of Parasitology of the Polish Academy of Sciences +48 (0)22 620 6226 [email protected] http://www.ipar.pan.pl/?module=lab&lab=lab33& language=en

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WILDCAT HAVEN’S DR PAUL O’DONOGHUE SPOKE TO PEN ABOUT PLANS TO DEVELOP A NETWORK OF PROTECTED WILDCAT RESERVES THROUGHOUT THE WEST HIGHLANDS OF SCOTLAND

Going wild F

or the last seven years the Wildcat Haven project, working on shoestring budgets from public donations and US grant givers, has rolled out ambitious fieldwork to prevent Scottish wildcats from hybridising into the feral cat gene pool by neutering feral cat populations. Working alongside landowners and local communities, they have delivered almost 500 square miles of threat-free safe haven so far; a desperately needed lifeline for the few Scottish wildcats left in the world.

of hybridisation, so we are well on the way to achieving our overall goal.

Paul O’Donoghue

As their fieldwork team prepares for another tough winter in the remote hills, the organisation has announced expansion plans to accelerate their current work and develop a network of reserves across the West Highlands managed as ideal wildcat habitat. In an interview with Pan European Networks, Dr Paul O’Donoghue, chief scientific advisor to the Wildcat Haven conservation project, discussed some of these efforts and the progress that has been made thus far.

Thus far, we have achieved some amazing things on very low budgets, and now, with an innovative crowd-funded approach supporting land purchases and the expansion of ongoing fieldwork, we hope that the project will eventually come to feed itself, thereby allowing our expansion plans to take place quicker.

What is the main motivation behind introducing the wildcat reserve scheme at this time? Wildcat Haven has achieved a lot in the last five years, and we are now at the point where we have effectively neutered all the feral and pet cats in the Ardnamurchan area. That is, of course, a significant achievement for us, and something we have worked very hard to do. The next exciting phase of the project will be to expand Wildcat Haven, and our long term aim here is ambitious, but nevertheless realistic: we want to create a haven for the Scottish wildcats covering 7,000 square miles of the West Highlands. We have already cleared an area of some 500 square miles

Because we are expanding, a really good way of increasing the speed of this progress is to actually own reserves in strategic places along the west coast of Scotland, and these new reserves can act as hotspots for wildcat conservation. We can establish haven areas around them, working with neighbouring landowners and local communities, and we aim to use the reserves as focal points for the ongoing Wildcat Haven expansion.

There is a sense of a significant overestimation of the number of actual European wildcats

The reason for that urgency is that time is running out for the Scottish wildcats; these animals are without doubt the rarest mammal in Britain, indeed one of the rarest on the planet, and we simply do not have time to hang around. That is why we are looking to expand as quickly as possible; to protect the last remaining wildcats before there are none left to protect.

What is the latest situation regarding their protection? There are probably less than one hundred purebred Scottish wildcats in existence. To give that some context, it makes them 20-30 times rarer than the giant panda. Our approach is that wildcats can, and should, be conserved in the wild where they belong. We do not advocate a captive breeding approach – we have proven that wildcats can be protected in the wild; we have haven areas fully established and we want to expand this.

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Our approach is thus to deal with local landowners and, importantly, to engage local communities. We therefore work with local schools – we get them involved in the project and help them to find out where pet cats and feral cats are in their area, for instance. Community engagement is essential to the success of our project, and with the help of the community we have been able to achieve rapid progress.

The Scottish wildcat is currently classified as an isolated island population of the European wildcat, though there is still considerable debate over whether it should be classed as a distinct subspecies. As a geneticist, what are your thoughts regarding the classification and, given that the European wildcat is not endangered (IUCN Red List – Least Concern), should so much emphasis be placed on the Scottish population? I strongly believe that the Scottish wildcat is wrongly classified, and there is a good reason for that. Hybridisation is widespread on the continent and I think a lot of the cats that are counted as being wildcats are actually hybrids.

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Wildcat Haven wants to create a haven for the Scottish wildcats over 7,000 square miles of the West Highlands

Indeed, there is a sense that there is a significant overestimation of the number of actual European wildcats, and I would predict that if a rigorous assessment of sighted data is carried out, the status of the European wildcats would be reclassified. The Scottish population is without doubt a genetically distinct unit, and that is certainly worthy of conservation merit in its own right.

How accurate, then, is the figure of 35 true wildcats existing in the Scottish Highlands and, following on, is the repopulation of the Scottish wildcat from so small a gene pool viable? This estimate is based on the latest sighted data which comprises some 2,000 records, so it is very comprehensive. The data is also Scotlandwide, so it is about as good as we can get. The Scottish wildcat has been through a very quick population decline, but species that have been through a rapid genetic bottleneck tend to bounce back; because they retain a lot of their genetic diversity they can do so in a relatively healthy state, and we hope that is the same for the Scottish wildcats.

How long will the conservation programmes take before you see an increase in the Scottish wildcat population? We are aiming for a population of 100s, at least 500 over the West Highlands, and we predict that this could be one of the biggest and most ambitious conservation projects ever carried out in Scotland. Wildcat Haven is in it for the long haul – we plan to be working with wildcats for as long as it takes, which will be at least 15-20 years. We

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have set up a haven area of about 500 square miles in some five years with techniques which are becoming increasingly efficient. As such, moving forwards we have a perfect model for wildcat conservation which can be extrapolated and expanded across the whole of the West Highlands. We are only limited by funding; if we had enough money tomorrow to start that process, we have the correct template in place to be able to do so. We know how to do it, and we have proved that it can work; funding is now the only constraint.

What support are you getting from local government and charities in Scotland? The Scottish Government have their own action plan for wildcats. That has been active for six months and will run for a total period of five years. Wildcat Haven welcomes all in situ conservation efforts for the Scottish wildcat, but does not see the need for wildcats to be brought into captivity at this stage.

Are local charities and local councils particularly supportive of your actions? Community councils have been very supportive of us, and different community groups and different community organisations – such as the local Cat Protection League organisations and the Ardnamurchan Women’s Institute. We have knocked on every single house in Ardnamurchan; we believe in engaging every single person in the community, and that involves face-to-face discussions. That is how we find out where every single cat in the area is and thus how we can achieve rapid progress.

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Scottish wildcats are without doubt the rarest mammal in Britain, indeed one of the rarest mammals on the planet

There are hopes of ‘back breeding’ extinct species such as the auroch from primitive breeds of domestic cattle, but this will take decades. Could such an approach be used for the Scottish wildcat? At this stage, all efforts should be focused on protecting wildcats in the wild, and that should continue to be the main focus. There are a range of potential technological assistances which could come to play a role in the future, but I would be concerned if funding was directed towards them at the current time and at the expense of direct fieldwork action. Unless there are safe areas for wildcats to go into and to thrive in, then any other techniques or actions essentially become redundant.

Dr Paul O’Donoghue Chief Scientific Advisor Wildcat Haven https://www.wildcathaven.com/

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PAN EUROPEAN NETWORKS EXPLORES THE POTENTIAL REINTRODUCTION OF THE LYNX TO MAINLAND BRITAIN WITH THE CHIEF SCIENTIFIC ADVISOR OF THE LYNX UK TRUST, DR PAUL O’DONOGHUE

Return of the Lynx

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fter a 1,300 year absence, the UK is set to once again be the home of the Eurasian lynx. The Lynx UK Trust has opened a second national consultation to help further detailed reintroduction plans. It’s anticipated the project could replicate the successes witnessed in continental Europe where the lynx has already made a comeback. Unlike the conservation efforts being undertaken for the Scottish wildcats, the lynx project is purely focused on reintroduction efforts. The wild feline was hunted to the point of extinction from the British Isles around the year 700, a “shocking and very sad situation”, according to Dr Paul O’Donoghue, chief scientific advisor of the Lynx UK Trust, who, in addition to his work on Wildcat Haven, is involved in the project.

respond, the largest ever reply to such a survey, and concluded with the result of 91% of those questioned being in favour of reintroduction. Furthermore, 83% of respondents said they wanted to see the lynx back within the next 12 months.

Paul O’Donoghue

Speaking to Pan European Networks about the reintroduction plans, he detailed a brief history of the relationship between cat and country, and the duty that he sees the UK as now having in restoring this native to its rightful home.

Some of the major reasons for the significant support for the reintroduction of the lynx include the agricultural, conservational and economic benefits it will bring. It’s anticipated that the animal’s deer hunting capabilities will prove particularly valuable to the farming community, whilst tourists are likely to flock to the reintroduction areas in the hope of catching a glimpse of the predator in action. O’Donoghue explained more to PEN. “If you are a crop or dairy farmer, lynx will be your best friend because they will control deer which damage your crops and compete with your cattle for grazing. That costs farmers millions of pounds every year, so lynx would help with that.”

“There is no question that lynx are a full UK species. They were simply removed through persecution – we killed every single lynx and therefore have a moral, and ethical duty, apart from everything else, to bring these animals back and to ensure that they get their rightful place back in the British countryside.”

A farmer’s best friend

Yellowstone effect

Earlier this year, the Lynx UK Trust asked the public for their opinion on bringing back the lynx. The consultation saw over 9,000 people

Alongside the agricultural benefits, the lynx will also assist forest conservation. It is anticipated that the wildcat will help an overburdened environmental landscape and play a part in providing much-needed forest renewal. “There are huge conservation benefits to the entire British countryside,” O’Donoghue said. “To my mind, and the minds of others, the British countryside is dying; it’s effectively being overgrazed by an uncontrolled and burgeoning deer population. If you walk through a woodland now, there is very little evidence of regeneration – if you look at oak woodlands for example, it’s a rarity to see a six or seven year old oak sapling because they are simply eaten.

© Neville Buck

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“There’s now an entirely unnatural age structure in these forests and eventually they will die out

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if regeneration stops, then the old trees will die; there is nothing left to replace them.

saviour of rural communities; they can provide parallel opportunities for economic regeneration.

“Lynx will play a pivotal and crucial role in restoring the balance in the forest – they will promote regeneration and will allow forests to recover.

“Young people are getting jobs in conservation as rangers, as guides, in ecotourism, in accommodation or services. We really think that rural communities will thrive. “It’s not a baseless statement – we have directly seen the enormous positive benefits of lynx for ourselves. So rather than lynx being a problem, people are desperate to get them in their areas because they see the overwhelming economic benefits.”

“That will then do a number of things: it will allow birds and small mammal populations to exist; there will be more forest cover; there will be more habitat, and so we think the knock-on effect to the ecosystem is massive – we call this the kind of ‘Yellowstone effect’, where, when you restore a large carnivore to an ecosystem, biodiversity increases.”

Location, location, location A number of different sites across the UK have been identified as suitable for the reintroduction of the lynx, as O’Donoghue explained. “We have been careful and very diligent in our site selection and we are picking areas that have extensive forest cover, low human population density and high deer density. We want the lynx to have enough habitat, in addition to minimising disturbance – that’s why we picked places like Aberdeenshire in Scotland, Kielder forest and Cumbria in the north of England, as well as Thetford in the east.

Economic driver In addition to agricultural and environmental benefits, the lynx is anticipated to be a key economic lifeline to the UK’s rural areas. With unemployment issues and much-needed economic regeneration, O’Donoghue believes the comeback of lynx could be a “saviour” that local communities have been waiting for.

“All these sites can accommodate lynx comfortably and they will find enough food. The UK will be lynx heaven.” Several other areas of Scotland and England have also been earmarked.

Community engagement

“It’s no secret that some rural communities are struggling,” O’Donoghue commented. “Employment is fairly low, and lynx can be the

The Lynx UK Trust is keen to engage local communities as part of the animal’s reintroduction. Through social media, the project is already attracting vital interest from both local residents and schools keen to see the return of these mammals. O’Donoghue stated: “Using social media, we have a lot of people getting in touch, saying ‘we are so excited’, and ‘when are they coming back?’ “We have had a lot of local schools say ‘Can you come in and speak to our pupils’. That’s really humbling … these people, these children are going to hopefully live with lynx for the rest of their lives, and they are the best stakeholders we can get.”

No harm Unlike some of the world’s big cats, the lynx is not considered a threat to human safety. A key goal of the project will be to emphasise this fact, as well as reassure the local populations that will share their communities with this wild cat. “It’s no secret that there is a perceived risk that lynx are a threat to sheep populations, but it’s only a perceived risk. It’s our job to overcome those perceptions and to re-educate, and that’s something that we are taking very seriously,” O’Donoghue insisted.

© Erwin van Maanen

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“We are dealing with scientists, facts and figures, so it’s our job to present the facts and figures in an objective light and then people will make their own decisions. But we’re confident that when you see the irrefutable evidence that lynx are massive economic drivers, no threat to people

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invited to join the consultation, offer opinions and ask questions of reintroduction plans to provide statutory agencies such as Scottish Natural Heritage and Natural England with a detailed understanding of opinion. The stakeholder consultation will run until the end of 2015 before moving on to consultations at local levels in the areas that trial reintroductions are planned. “We want this to be an open consultative process, and we want to use the stakeholders’ experience and opinion on what they feel are suitable sites,” O’Donoghue said. “Once we select a site in the New Year, we will then carry out a localised consultation that will involve village halls, going into schools, going on the streets, talking to people, using local media. These are the people who are going to be living with the lynx, so we want them to be fully engaged. “After that, it is simply a case of submitting the application. We have already started to draft the application, and that will be submitted next year. We were very hopeful of a positive decision.

© Erwin van Maanen

whatsoever, and no significant risk to sheep farming, the lynx’s reintroduction becomes a complete no-brainer.”

Looking to Europe The reintroduction of the lynx follows similar projects that have taken place in continental Europe, and O’Donoghue explained some of the work that had occurred. “We went to the Harz Mountains in Germany where they have completed a very successful reintroduction; they now call the entire region ‘the kingdom of the lynx’. That’s how much they have bought into the lynx and, as it’s been so successful, they are now planning another huge reintroduction in the south of Germany.” “There have also been very successful reintroductions in France and Scandinavia, with further introductions now planned in Slovenia and Croatia. There’s a huge amount of interest and a resurgence of people wanting lynx back – that’s very good for the species and very good for ecosystem health across Europe,” the chief scientific advisor added.

Moving forward Lynx UK Trust is now embarking on a second national consultation to discuss formally reintroduction for next year. Stakeholders, including landowners, farmers, gamekeepers and conservation groups, have been

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“We think this is, without doubt, the most exciting conservation project ever put forward and developed in the UK. We’re very positive of a successful outcome and we want the whole country to get behind it, support it and to be excited. “To walk through a forest where you know lynx are present will enhance everyone’s lives, it will make the British countryside come alive and we will quickly see the positive benefits to the ecosystem, and that will benefit biodiversity immeasurably.” The UK was once a bastion of the Eurasian lynx, but human activity led to the extermination of this wonderful wild mammal. The UK is now craving the cat’s return, and if successful, the lynx could be roaming through the countryside in the very near future.

Dr Paul O’Donoghue Lynx UK Trust

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DAVE WALSH, ADVISOR TO THE ANTARCTIC OCEAN ALLIANCE, HIGHLIGHTS THE NEED FOR MARINE PROTECTED AREAS IN THE ANTARCTIC REGION

Saving Antarctica’s ocean O ctober 2015 saw 25 governments descend on Hobart, Tasmania, to discuss how to manage and regulate the great Southern Ocean that surrounds Antarctica. The question on everyone’s mind was: would members of the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) finally reach agreement on protecting two vast areas of the marine environment, in the Ross Sea and off the coast of east Antarctica?

strengthening their resilience, and take action for their restoration in order to achieve healthy and productive oceans.

Lifeblood The UN clearly understands that these goals are achievable, and that humanity must strive to reach them by the set deadlines. The oceans are the lifeblood of our planet; covering more than 70% of the Earth’s surface, our oceans feed us, providing livelihoods for millions of people in coastal communities, regulate our weather and other systems, and sequester carbon dioxide.

The answer unfortunately, was “no”. While creation of the marine protected areas failed to get consensus for a fifth time, delegates headed home with a sense that progress was being made, following China’s surprising move of supporting protection of the Ross Sea. CCAMLR desperately needs this kind of impetus and inspired action towards ocean protection; long upheld as a vanguard of marine conservation policy, CCAMLR now trails behind success stories making news elsewhere.

However, we are not treating our oceans with the respect they deserve and need. We are overfishing, causing the rapid depletion of fish populations, and degrading the marine environment and coastal regions through pollution, ocean acidification and climate change. A recent report from the WWF2 found that in just 45 years we have caused half of the wildlife in our oceans to vanish. Not only are our oceans in danger, we are threatening our own future, too.

For example, at the Our Oceans conference in Chile in early October, a number of new, very large marine protected areas (MPAs) were announced, representing an additional 2,473,000 square kilometres of highly protected marine areas. These include huge areas around New Zealand’s Kermadec Islands, and around Chile’s Desventuradas (Unfortunate) and Easter Islands. Following this, in late October, Palau’s president established one of the world’s largest protected areas of ocean in the Pacific island nation’s waters. At the United Nations Sustainable Development Summit in late September, attending countries had signed a new, ambitious and achievable set of targets to protect our oceans by 2020,1 including actions to conserve at least 10% of coastal and marine areas, consistent with national and international law and based on the best available scientific information; and sustainably manage and protect marine and coastal ecosystems to avoid significant adverse impacts, including by

Pristine wilderness

The Southern Ocean makes up roughly 10% of our global ocean, and is home to more than 10,000 unique species, including the commercially targeted Antarctic toothfish.

The wild, icy body of water that encircles Antarctica remains one of the Earth’s last pristine wildernesses, and one of the least-impacted marine environments. Our organisation, the Antarctic Ocean Alliance, campaigns for the protection of this region, which remains untouched (partly due to its relative isolation from human activity). The Southern Ocean makes up roughly 10% of our global ocean, and is home to more than 10,000 unique species, including most of the world’s penguins, whales, seabirds, colossal squid and the commercially targeted Antarctic toothfish.

Marine protected areas Just 1% of the world’s oceans are under strict protection within marine protected areas or reserves; and most of the existing conservation measures lie within territorial waters, not international ones.

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MPAs work by eliminating extractive activities from large areas of the ocean, ensuring that some areas remain undisturbed. This helps populations of fish, marine mammals and birds find nourishment and shelter, to reproduce and replenish their numbers, and to live without disturbance. In addition, healthy marine ecosystems are more resilient to climate change impacts. While creating marine reserves is only one part of dealing with the challenges faced by our planet, it’s a significant one, and an important component of the UN’s ocean goals.

The Southern Ocean is home to most of the world’s penguins

CCAMLR The Commission for the Conservation of Antarctic Marine Living Resources was established in 1982, and is made up of 24 countries, plus the European Union. As part of the Antarctic Treaty System, CCAMLR is tasked with the protection and management of the marine living resources of the vast Southern Ocean. CCAMLR meetings are much like other international fora, where diplomats and NGOs get together to chew over the small print of conservation or geopolitical agreements. Since 2012, however, CCAMLR has been mired in a frustrating impasse, with members bickering over the fine details of Southern Ocean protection, fuelled by national anxieties about fishing rights and complications from various geopolitical issues. A special meeting convened in Bremerhaven in 2013, expressly for the purpose of solving the blockage, failed to have any impact. At the three annual meetings since, proposals were variously blocked by Russia and China. The latter has expressed concerns on how protection would affect its future plans to expand its fisheries. As for Russia, international

conflicts appear to be the most obvious factor, as are ongoing concerns it has regarding the duration of marine protection, along with other technical and scientific aspects of the proposed protection.

Thanks to its rich marine life, the Ross Sea remains one of the most intact marine ecosystems on the planet

This year, both Russia and China blocked the east Antarctic proposal, but in an unexpected move, China agreed to a new, larger draft proposal for the Ross Sea, expanding the protected area to 1.5 million km2, following discussions with the United States and New Zealand. This provided a glimmer of hope for the many people who have worked long and hard to make Antarctic marine protection a reality.

Rational use While disagreements were always expected at this meeting, one thing was beyond debate: the creation of large scale MPAs complements CCAMLR’s central objective of conserving Antarctic marine life. In addition, they help to manage the ‘rational use’ of the Southern Ocean. As noted in the Convention on the Conservation of Antarctic Marine Living Resources, which forms the basis for the entire organisation, ‘rational use’ is intended to:3 1) Prevent any harvested population from decreasing to levels so low that it is unable to maintain itself; 2) Maintain and, where necessary, restore the ecological relationships between harvested, dependent and related populations of Antarctic marine living resources; and 3) Prevent or minimise the risk of change to the marine ecosystem based on the best available science.

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The last ocean The Ross Sea MPA proposal (1.25 million km2 before this CCAMLR meeting, now up 1.5m km2 ), put forward by the USA and New Zealand, would protect the oceanic equivalent of Africa’s Great Plains. Thanks to its rich marine life, the Ross Sea remains one of the most intact marine ecosystems on the planet; large populations of its top predators are still present, and it is largely untouched by the ills that plague Earth’s other oceans. In addition, the Ross Sea offers unprecedented opportunities for science and for understanding how large scale, fully functioning ecosystems work and are influenced by climate change and ocean acidification.

East Antarctica The east Antarctic proposal (947,000km2), sponsored jointly by Australia, France, and the European Union, is home to a significant proportion of the Southern Ocean’s penguins, seals, and whales. The eastern Antarctic shelf also contains rare and unusual seafloor and oceanographic features. Scientists are still trying to understand the dynamics between its oceanography and the seafloor environment and to define the species that live there. The region’s unique features, coupled with its biological value to seabirds, seals, and other animals, make the east Antarctic coastal region a prime area for protection. The European Union’s leadership on this proposal is key; quite simply, it ‘wants to see the vulnerable areas around Antarctica better protected in recognition of their global importance’,4 and ‘is committed to the protection of the oceans, domestically and internationally and supports the establishment of MPAs in general and in particular in the convention area of CCAMLR in the Southern Ocean’. While France is a co-proponent, the EU’s participation in CCAMLR gives both CCAMLR and non-CCAMLR European states a voice in pushing for large scale ocean protection.

Erosion of ambition Since they were introduced, both MPA proposals have undergone several compromises, resulting in reductions of the planned protected areas. This October’s increase in the Ross Sea proposal shows a potential new direction for CCAMLR, one that must be maintained, if it is to fulfil its mandate, and to return to its position as the flagship organisation working for marine conservation worldwide. The Antarctic Ocean Alliance (AOA) is calling on CCAMLR nations to immediately designate both MPAs, before any further erosion to their size or duration takes place. AOA believes that CCAMLR countries must overcome the geopolitical hurdles that have stymied past negotiations, and we are calling on CCAMLR’s more recalcitrant members to seize the opportunity to put these two crucial marine protected areas in place, now, and for good. CCAMLR members are no doubt aware of the successful protections afforded to the land of Antarctica. In 1959, at the height of the Cold War, a period of mistrust and rampant paranoia, the world’s most powerful nations, the Soviet Union and the United States, put their differences aside to sign the Antarctic Treaty, thereby protecting the frozen continent in the name of peace and science. Following last year’s meeting, Russia took over the chair of CCAMLR and will continue in the role until November 2016. While diplomatic concerns continue to spoil relations elsewhere, the Antarctic Ocean Alliance is urging Russia to seize this chance to make history while at the helm of CCAMLR as it sails towards a new age of ocean protection.

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The Antarctic Ocean Alliance, a project of the Antarctic and Southern Ocean Coalition (ASOC), is an international coalition of leading environmental and conservation organisations and philanthropists from around the world including ASOC, Blue Marine Foundation (UK), Deepwave (Germany), ECO (NZ), Forest and Bird (NZ), Greenovation Hub (China), Greenpeace, Humane Society International, International Fund for Animal Welfare (IFAW), International Programme on the State of the Ocean (IPSO), Korean Federation for Environmental Movement (KFEM), The Last Ocean, Mission Blue (US), Oceans 5 (US), The Pew Charitable Trusts, and the Whale and Dolphin Conservation Society (WDCS). Associate partners include Oceana, International Polar Foundation, Natural Resources Defense Council (NRDC) and other groups worldwide. For more details, and to get involved, visit www.antarcticocean.org We are also encouraging the EU, France, Australia, New Zealand, the United States and other supporters of the two proposals to remain strong, and to keep their faith in the intrinsic value of protecting the east Antarctic and the Ross Sea. Along with the need to protect the Southern Ocean for its own sake, Antarctica is critical to scientific research, both for the study of how intact marine ecosystems function and for monitoring the impacts of climate change. Fully protected marine reserves are the single most powerful tool that CCAMLR has for fulfilling its mandate to protect the dazzling spectrum of Antarctica’s marine life, and to ensure that the Southern Ocean ecosystem can withstand the impacts of climate change and ocean acidification. References 1 Goal 14: Conserve and sustainably use the oceans, seas and marine resources: http://www.un.org/sustainabledevelopment/oceans/ 2 Living Blue Planet Report http://assets.wwf.org.uk/custom/stories/living_blue_plan et/?_ga=1.19969916.537450017.14422359730 3 Article II of the CCAMLR Convention: https://www.ccamlr.org/en/organisation/camlrconvention-text#II 4 EU to push for establishment of Marine Protected Areas in Antarctica http://ec.europa.eu/information_society/newsroom/cf/ma re/itemdetail.cfm?item_id=11373

Dave Walsh Senior Communications Advisor Antarctic Ocean Alliance www.antarcticocean.org

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PROFESSORS JØRGEN BERGE AND PAUL RENAUD AND DR FINLO COTTIER DISCUSS INTERNATIONAL RESEARCH AND EDUCATION IN A CONTIGUOUS ARCTIC

Towards a contiguous Arctic

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he Arctic is changing. Most dramatic is the changing icescape, with both a reduction in multiyear sea ice and a thinning of the ice cover. Concomitant with these changes, the regional and seasonal characteristics of the Arctic are enhanced. Albeit small, its regions are tightly linked, thus making a year-round and integrated approach crucial for understanding the systems as a whole. With a political landscape that is also changing – the Arctic coastal nations are preparing territorial claims to both the North Pole and the Arctic Ocean sea floor – international co-operation and pan-Arctic perspectives become even more important than before.

Thirdly, but certainly not the least, international co-operation between researchers, and particularly amongst young scientists, has created an important international network that will continue to promote further scientific collaboration and understanding in the future.

Outreach A second pillar of the Mare Incognitum programme has been outreach and communication to society at large. To this end, the recent Polar night exhibition, on display at both Polarmuseet in Tromsø, Norway, and the Anchorage Museum in Alaska, USA, has been our most important product (see: www.uit.no/ressurs/uit/mediebok/Polarnight).

Our ongoing‘Mare Incognitum’ programme includes a multinational team from nations around the Arctic Ocean, throughout Europe, and beyond. The exhibition will also be on display in both the Svalbard Museum In this way, we move beyond the regional approach in attempting to (2016) and at Vitenskapsmuseet in Trondheim, Norway (2017), as well achieve pan-Arctic co-operation and exchange of knowledge, with the as in the USA, in Boston and Washington. ultimate goal of acquiring an holistic view of Arctic marine ecosystems.

Claims of ownership

Marine night One element of Mare Incognitum is the Marine Night project, within which we have recently finished a two-year field campaign aimed specifically at understanding processes during the Polar night in Svalbard. In total, more than 100 students and researchers from more than 15 nations have been involved. The results from these campaigns have been remarkable, refuting the old paradigm of a biological quiescence during the Polar night once and for all. But not only have the results been important, to achieve this we have incorporated significant international training and information exchange.

Education A first pillar of the Mare Incognitum programme is the educational platform, and this includes several elements. Firstly, a new graduate course on ‘Polar night ecology and automated underwater technology’ (UNIS course AB334/834, see: www.unis.no) has been established, which offers a unique insight into how the dark Polar night is best sampled and studied through the use of automated and remotely operated underwater vehicles. It is a blend of the international leading competence on enabling technology from NTNU in Trondheim, Norway, and the pioneering discoveries concerning Polar night biology carried out by our international research team. Approximately 50 students participated on the course during 2014 and 2015 in Ny-Ålesund on Svalbard. Secondly, in concert with this course, 20 MScs, PhDs and postdocs have been sampling material for their theses. These students come from Norway, Poland, Russia, Germany, France, USA, Canada, and the UK, and many have participated through collaboration with the ARCTOS PhD school at UiT The Arctic University of Norway (see: http://www.arctosresearch.net/). The direct results from this are only beginning to be produced, and are expected to increase significantly in the years to come.

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Today, when the Arctic coastal nations have either submitted or are planning to submit their claim of ownership of the seafloor in the Arctic Ocean, we run a risk of losing the opportunity for an holistic, pan-Arctic approach to studying the functioning of the Arctic marine ecosystem. Until now, Mother Nature has provided the most effective barriers to access and knowledge in the Arctic Ocean. But as the Arctic Ocean is opening up through a rapid decline in sea ice, and as enabling technologies allow us to carry out scientific surveys previously unthinkable, it is a realistic prospect that within the next one or two decades we will have a broad and comprehensive understanding of how the Arctic marine ecosystem functions. However, a prerequisite for this is that we do not build political barriers that will only lead to a higher degree of sectorial understanding. In an ocean in which the currents so clearly link all parts of the Arctic together, such barriers would prohibit a fundamental understanding of the contiguous Arctic. Instead, a culture of international collaboration and knowledge exchange, both among scientists and between science and society, is one of the most important tools promoting the integrated understanding and management of the Arctic.

Professor Jørgen Berge Professor Paul Renaud Dr Finlo Cottier Mare Incognitum [email protected] www.mare-incognitum.no/

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ARCTIC SUBSEA SURVEY The Centre for Geobiology surveys Arctic seabeds for mining viability and hunts for new animal species

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he Centre for Geobiology explores active geothermal springs on the Arctic Mid-Ocean Ridge. Research objectives include finding new animal species and examining how mining operations on the seabed will impact the environment.

Subsea mining operations

With the assistance of a new sonar technique, which provides images with more than one hundred times the resolution attained previously, researchers from the Centre for Geobiology (CGB) survey and collect samples from recently discovered volcanic deep sea areas around the island of Jan Mayen. In these areas CGB has identified active geothermal vents at depths of 150 to 2,500 metres below sea level. Researchers are now mapping the unknown animal life and potential mineral deposits found there.

Large amounts of minerals and metals such as iron, copper and zinc are deposited around the geothermal springs. There may also be gold and silver.

“This provides important new knowledge about volcanic and hydrothermal activity. It has also given us new information about the presence of metal deposits in the seabed,” said Professor Rolf Birger Pedersen from CGB.

On their expeditions, the researchers use Bathysaurus, a remotely operated vehicle (ROV) to explore the sea floor in more detail. Among other things, the researchers are interested in identifying metal deposits.

“The geological experiments are part of the EU-financed project Midas. The goal is to gain an understanding of the possible environmental impact of mining operations in the deep seas. Norway has enormous deep water areas with large amounts of resources. Even though we are, first and foremost, conducting basic research, this research may result in commercial operations in the long term,” Pedersen said. Centre for Geobiology n

Centre for Geobiology is a research centre at the University of Bergen (UiB); and

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The centre is funded under the Research Council of Norway’s Centre of Excellence scheme.

Swarming with life on the seabed

The researchers have collected geological and biological samples from the seamounts along Mohns Ridge which is located 80km northeast of Jan Mayen, as well as Kolbeinsey Ridge and the Loki’s Castle vent fields. The largest seamounts are 3,000 metres high. Here we find new, unusual animals including micro-organisms that can survive in extreme temperatures. Such micro-organisms may provide insights into the first life on Earth. “We have discovered over 50 new species in these areas since the centre commenced operations in 2007,” Pedersen said. “We are talking about newly-formed geological landscapes and unique ecosystems. The data and samples we collect provide important, unique information about deep sea biology and geology.”

Reconstructing the origin of species Andreas Hejnol heads the Comparative Developmental Biology of Animals research group at the Sars International Centre for Marine Molecular Biology. They aim to understand animal evolution better.

According to Hejnol, the central question of his ERC funded project is: What is the nature of the molecular and genomic changes that gave rise to the animal diversity we have on this planet? “The proposal aims to reconstruct the evolutionary history of specific embryonic cells of animals, the mesoderm. These embryonic stem cells are present in most animal embryos, including humans,” Hejnol explained. In their work, Hejnol and his team use embryos of ribbon worms, rotifers and other animals. These tiny life forms are all built out of related cell types, making it possible for the researchers to discover ancient genes that may provide answers to the evolution of species in the world’s seas.

Bathysaurus

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“We will reconstruct the ancient evolutionary origin of these cells and identify the changes in the molecular and cellular mechanisms that gave rise to the diversity of these organs in animals,” said Hejnol, whose group make use of cutting-edge technology to achieve their goals.

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Andreas Hejnol

“We aim to use the newest technology in microscopy, computational biology, and comparative genomics to study animals that have never been investigated regarding these questions before,” said Hejnol. “The comparison of the novel data will ultimately elucidate the evolutionary changes that gave rise to the huge diversity of mesodermal organs in animals, including humans.” The project includes leading researchers from Stanford University’s Hopkins Marine Station and the University of Vienna. The group works with marine research centres such as the University of Washington’s Friday Harbor Laboratories and the University of Gothenburg’s Sven Lovén Centre for Marine Sciences.

Nele Meckler

“I work with a new geochemical technique to reconstruct past temperatures, called ‘clumped isotope thermometry’, which has only been developed over the past ten years,” said Meckler, who has already worked with this method for a while, first at the California Institute of Technology, where it was originally developed, and more recently at ETH Zürich. Bjerknes Centre for Climate Research n

Nele Meckler is one of four researchers at the centre to hold a grant from the ERC; and

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The centre was funded under the Research Council of Norway’s Centre of Excellence scheme between 2002 and 2012.

The Sars Centre n

Research centre at the University of Bergen (UiB); and

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Andreas Hejnol holds an ERC Consolidator Grant since February 2015.

How the past informs us about future climate

Geologist Nele Meckler works on reconstruction of past climate conditions.

Meckler’s background is in environmental science and geology, and she specialises in reconstructions of past climate using ocean sediments and cave rocks.

Rolf Birger Pedersen Professor Centre for Geobiology

“I reconstruct past temperatures in the ocean and on land on a variety of timescales, from a few thousand years back to millions of years, to better understand the processes and their connections within our complex climate system. Ultimately, these insights will allow us to make better predictions for future climate change under rising levels of greenhouse gases,” said Meckler, who works at the renowned Bjerknes Centre for Climate Research in Bergen, Norway.

+47 (0)91 330 278

In the project C4T (Climate change across Cenozoic cooling steps reconstructed with Clumped isotope Thermometry), her group will reconstruct changes in ocean temperature and global ice volume during times for which dramatic changes in global climate have been suggested.

[email protected] http://sars.no

For example, the onset of glaciation in Antarctica and in the Northern Hemisphere, which both had enormous consequences for climate worldwide. These changes seem related to large changes in the concentration of atmospheric CO2.

+47 (0)46 586 236

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[email protected] http://uib.no/en/geobio Andreas Hejnol Research Group Leader The Sars Centre +47 (0)93 071 870

Nele Meckler Researcher Bjerknes Centre for Climate Research

[email protected] http://bjerknes.uib.no/en

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LIVING CRYOSPHERE It is truly a misconception that the frozen compartment of the Earth would be a sterile desert

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ce and snow of high altitudes and latitudes have been considered as hostile environments being too harsh for any life form due to extreme low temperatures, low nutrient concentrations, and often high levels of harming radiation. However, according to the writings of Aristotle, the Greek had already found evidence that snow can be a habitat for a special type of unicellular algae which are thriving on the surface of snow packs during late spring presenting a blood red colour. The cryosphere consists of a number of different environments which are all under a certain spell of urgency when considering their persistence on the aspect of climate change. Permafrost, for instance, covers a huge area with a decreasing trend now that the upper layers are prone to melt where they release tonnes of methane. Glaciers, as well as large ice sheets in the Polar regions, also add to the cryospheric ecosystems, as do lake and sea ice, which are crucial for the pelagic food webs due to the provision of valuable nutrients deriving from the ice cover. Overall, each of those habitats are under the umbrella of the atmosphere. For a long time the atmosphere has been seen solely as a transport corridor for inactive spores and dead cells which can possibly be transported from one continent to the other with high altitude cloud systems. New findings, however, prove that even the atmosphere can be addressed as a living space for active metabolising microbes. This fact is interesting when heavy dust storms from the Sahara dislocate a high volume of sand particles that can also harbour potentially pathogenic and still viable cells. The driving factor for life in sub-zero conditions is temperature since the prerequisite for life is liquid water. Specific adaptations enable organisms living in the cryosphere to survive multiple freeze and thaw processes without any cell damage as would be the case with human tissue. Cold adapted organisms such as psychrotrophic and psychrophilic individuals, however, are capable of showing active metabolism and reproduction below freezing point under the premise of having antifreeze proteins. They lower the freezing point of cell water and prevent the build-up of damaging ice needles. In this case, cryophilic life can become encased in ice for long periods with the possibility of remaining viable after thawing, as has been shown with microbial cells retrieved from old ice cores.

Cryosphere communities The communities thriving under those conditions are mainly dominated by microbes. Bacteria, viruses, algae and fungi or some protozoa are found either in brine channels inside the ice or in microscopic veins between ice crystals where elevated salt concentrations lower the freezing point of water to survive.

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Besides microbes, some metazoa can dwell in those unique habitats. Collembola, for instance, are prominent examples of species inhabiting large snow areas. They contain cryoprotectants as well as a dark pigmented surface to avoid any damage deriving from UV-radiation. Tardigrades also show a high level of tolerance against all sorts of environmental stress, not only against cold but heat, desiccation, vacuum or even radioactive radiation. Water bears no bigger than 1.5mm in size are even model organisms for astrobiology. A prime niche for all the above-listed creatures is the supraglacial compartment. The surface of glaciers is subject to short term changes due to daily freeze and thaw cycles. Solar radiation can heat up deposited particles of organic or inorganic origin, which causes those aggregates to melt into the ice where so-called ‘mini lakes’ are created with a sediment layer and an overlying water column. The inoculum with life originates mostly from airborne cells or meltwaters which are transporting uni and multicellular communities into those so-called ‘cryoconite holes’. The name originates from the Swedish polar pioneer Otto Nordenskjöld describing ‘cold dust’ on glacial surfaces. Those cryoconite holes are found worldwide and during summer weeks they harbour extremely active microbial communities producing surprisingly high levels of organic carbon which are made available for adjacent environments.

Increasing temperatures The continuous rise of average temperature influences a number of reactions in the cryosphere. Not only is the extension constantly shrinking in area and thickness, but we can even say that our glaciers are literally becoming greener. With this quote we address the increasing availability of liquid water for active auto and heterotrophic organisms which of course use this fact for increased metabolism and reproduction. As a consequence, glacial surfaces are covered with cells which are equipped with a darker pigmentation as a natural UV-protection. The darker colour provokes a coupling effect to enhanced melting. It is not only that glaciers become biologically more active, but there are also other issues appearing with the ongoing melting. Manmade radionuclides have been deposited in the course of atomic bomb tests, but also via nuclear power plant accidents such as Chernobyl. Those radioactive particles have been stored in glacial ice for a long period of time and are now being released into melt waters in relatively high concentrations. Additionally, glaciers are also crucial economic factors in tourist areas such as the Alps. Skiing slopes on glaciers are not as constant as before and are subject to melt. Hence, hectares of fleece are used to cover up those glacial areas to protect them

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from ablation. This is ethically and ecologically more than questionable since these fabrics contain a chemical called avivage which is water soluble and hazardous to water. To guarantee economic numbers we take pollution of our waters into account – this needs to be seriously scrutinised.

of cold shock (antifreeze) proteins, which are increasingly important and rewarding for biotechnological applications such as the medicine or food industries. With our basic research we hope to contribute to future employments of those unique but highly sensitive environments.

Challenges

As a most enjoyable accompanying task we intend to transfer our knowledge to the younger generation who will soon be in charge of our living space. This we delightfully do within the programme of the Austrian Ministry of Science, Research and Economy, ‘Sparkling Science’.

In order to provide serious models and predictions of biological activity of melting snow and ice, we need high resolution data. However, everyone working in the field under extreme conditions such as in the Arctic or Antarctica knows that even daily routine can become an obstacle. Logistical constraints often impede datasets from attaining sufficient resolution, so the ability to scale up specific environments to a global perspective is restricted due to a lack of manpower to transport the samples. Moreover, the handling of those samples for a sophisticated analysis often implies a manipulation of sensitive organisms which is a mostly irreversible process once completed. Here, the requirement for non-invasive techniques is clearly given and is of pressing urgency. In this case we are currently developing a system called LIFE, Laser Induced Fluorescence Emission, with which photosynthetically active pigments in ice can be detected with a single shot from a laser beam that requires no more sampling, transport or subsequent hands-on analysis. This system finally allows us to provide imperative high resolution in space and time where we can actually lay a virtual grid over cryospheric areas to monitor those environments in terms of their biological potential. This is a rapidly changing process due to ongoing climate change, and could provide us with valuable information about biological loads being released from glacial environments. As mentioned previously, the prerequisite for those communities to establish in the frozen realm is still the possibility of adaptation

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Without flying sparks we cannot move people to think twice about the context of Man and biosphere.

Birgit Sattler & Team Cryo Ao Univ-Professor Dr University of Innsbruck, Austria Institute of Ecology Lakes and Glacier Research Group Austrian Polar Research Institute +43 (0)512 507 51731 [email protected] www.uibk.ac.at/ecology

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UNEP’S EXECUTIVE DIRECTOR, ACHIM STEINER, EMPHASISES THE IMPORTANCE OF PROPERLY ADDRESSING CLIMATE CHANGE

Time for global action T In October in New York, the world witnessed – and was party to – something historic. At the Sustainable Development Summit in advance of the meeting of the UN General Assembly, 193 nations agreed to a sustainable path forward for the planet. Unprecedented in scope and scale, the 2030 Agenda is embodied in 17 goals that encompass the environmental, social and economic aspects of sustainable development. These global goals are not only objectives for the world to aim at; they light a pathway toward a sustainable future for the planet and its people. If this momentous agreement was the only global accord this year, we would call 2015 a turning point for the planet. But, of course, the 21st Conference of Parties in Paris (COP21) is also designed to offer the opportunity to further catalyse global action on climate change. Without directly addressing how to mitigate and adapt to climate change, attempts to achieve the global goals will be seriously compromised. Crucially, addressing climate change is named as an objective in and of itself as Goal 13: Climate Action. Just as importantly, however, the notion of integration means that environmental issues, including climate change, are part of the tripartite approach towards achieving all of the goals. This idea – that none of the goals of sustainability are achievable without addressing environmental, social and economic dimensions concurrently – is fundamental to the 2030 Agenda. Any approach designed to solve these issues in isolation is destined to achieve, at best, only partial, short-lived success. At worst, they undermine our ability to improve in the other two dimensions.

© University of Michigan

he United Nations Environment Programme (UNEP) draws upon the scientific evidence, priorities emerging from global and regional fora, and an assessment of where UNEP can make a transformative difference, to focus its work on seven cross-cutting thematic priorities: climate change, disasters and conflict, ecosystem management, environmental governance, chemicals and waste, resource efficiency and environment under review.

Achim Steiner

From small island states beset by receding shorelines to extreme weather events that exacerbate resource conflict and uproot millions, climate change is eroding the environmental, economic, and social status quo

The notion of universality in the Global Goals is a reflection of our modern world. In 2015, our neighbours are not only in the house or flat next door. They are 5,000 miles away in a drought-ridden desert, or 10,000 miles away on an island in rising seas. What we do in our communities has ripple effects that unbalance the lives of people on the other side of the planet, and vice versa. We need look no further than the issue of climate change to witness these dramatic effects. From small island states beset by receding shorelines to extreme weather events that exacerbate resource conflict and uproot millions, climate change is eroding the environmental, economic, and social status quo. This upheaval is a formidable force and the consequences we feel now are but a taste of the repercussions we will endure if the world is further warmed by two degrees. Shifting weather patterns threaten food production. Ecosystems, the bedrock of our economies and societies, face irreversible changes. As effects such as melting sea ice and glacial retreat accelerate, the overall behaviour of our environment can become violent and unpredictable. If these destabilising outcomes are frightening, the consequences of a world warmed more than 2°C are unthinkable.

Universality Similarly, we cannot achieve global success through unilateral approaches. The global goals apply to all nations – developing and developed – which is reflected in the concept of universality. The conceit that the goals only apply to developing nations is a non-starter. While some goals will naturally apply to certain countries more than others, it is important to recognise that sustainable development is a global ambition. Some countries, including many in Europe, may need to focus more on responsible consumption and production (Goal 12) while others will be focused on simply raising their populations out of poverty (Goal 1). All of these goals apply to all countries in some way.

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SPECIAL FEATURE: CLIMATE CHANGE

The threat we face from climate change, if not headed off now, may be impossible to rein in. That is why COP21 has come at a critical time. We have a unique chance to address the issue of climate change in a decisive and ambitious way. The importance of global collaboration in this task, as with the global goals, cannot be underestimated. Encouragingly, we are already seeing incredible momentum. As of this writing, over 155 parties to the UN Framework Convention on Climate Change (UNFCCC), representing almost 90% of global emissions, have submitted their Intended Nationally Determined Contributions (INDC). This level of commitment bodes well for a universal agreement to emerge from Paris. Nevertheless, serious challenges remain. Ambitious and concrete plans for a quantifiable reduction in emissions will go far to mitigating the effects of climate change. However, while we may be able to prevent the worst-case scenario of more than two degrees of warming with these efforts, the fact remains that the impacts of climate change are already being felt around the world. These effects will necessitate adaptation efforts that will add to the cost of mitigation.

Cost This cost is not insignificant. Climate change is an investment and a financing challenge of unprecedented scale. According to UNEP’s first adaptation report, the global investment required for adaptation to climate change will likely oscillate between US$150-500bn (~€133442bn) per year until 2050. According to the Climate Policy Initiative, some $1.3-1.8 trillion of additional climate finance is needed every year. The current deficit for this financing is large, and is one of the main challenges we will need to address. In 2013, the total amount of public climate finance reached $137bn. Private investment totalled $193bn. While public finance is crucial, it can only provide a portion of the capital required. However, it can act as a stimulus for private finance. Governments can drive demand for green finance with approaches like carbon pricing and incentives for clean energy.

Quiet revolution UNEP has established a number of initiatives that are looking at how to achieve the financing needed both for climate change mitigation and adaptation, and sustainability writ large. We are

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As effects such as melting sea ice and glacial retreat accelerate, the overall behaviour of our environment can become violent and unpredictable

seeing positive signals. UNEP’s Inquiry into the Design of a Sustainable Financial System has uncovered what we term a ‘quiet revolution’. That is, financial actors – from banks and insurance companies to regulators and ministries – are tacking to the winds of change, incorporating sustainability considerations into financial systems across the world. To take one example from Europe: in France, new disclosure requirements on climate change have been introduced for institutional investors as part of the country’s energy transition legislation. This type of change is welcome, and will need to be coupled with a broader shift to a low-carbon, resource-efficient economy if we are to realise our goals for tackling climate change and improving the lot of future generations. Today, 65 countries have embarked on green economy and related strategies. This includes many countries engaged with the Partnership for Action on Green Economy (PAGE) to shift investment and policies towards clean technologies, resource-efficient infrastructure, and well-functioning ecosystems. But most pivotal to the success of international efforts to move forward on climate change and sustainable development will be how principles translate into policy at the international, regional, and national levels. In Europe, there is large potential for continued leadership in moving the world toward a sustainable future with concrete legislation, regulation, and application of sustainable, climate friendly initiatives. The adoption of the 2030 Agenda has demonstrated the ability and potential of international collaboration to set out the pathway to a better future for all. The Paris climate conference represents a second opportunity to ensure a sustainable future where lives and livelihoods around the world are not only safeguarded but also improved.

Achim Steiner Executive Director United Nations Environment Programme (UNEP) http://www.unep.org/

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MONITORING WATER QUALITY Professor Eberhard Fischer from the University of Koblenz-Landau highlights the importance of freshwater algae and bryophytes for monitoring water quality in the tropics

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the working group of Professor Fischer, different organisms are studied, e.g. lichens, fresh water red algae, bryophytes and various flowering plants such as Linderniaceae, gingers or orchids. Here the algae and bryophytes growing in streams and rivers of tropical Africa are addressed.

Freshwater algae and bryophytes – developing a monitoring system for water quality in tropical Africa – the case study of Rwanda Aquatic ecosystems have been subject to anthropogenic impact on a worldwide scale. In rivers, contaminants from agricultural run-off or urban inputs are important in the Northern Hemisphere but also increase in the tropics. Climate change has an impact on aquatic ecosystems as well. For an assessment of these impacts, a biological monitoring is applied. Currently, benthic macroinvertebrates are the most widely used bioindicators, but benthic algae, especially diatoms, are becoming more important. Algae are thus widely used as bioindicators of water quality in Europe. Specially diatom-based indices of water quality, mainly using benthic diatoms, have been developed, but other algal groups, such as freshwater red algae, proved to be valuable indicators for running waters. In Europe, the ecological

Fig. 2 Freshwater red algae (Kumanoa spec.) in a mountain stream

requirements of many diatom species are well known. The European Standard EN 13946 (2003) provides guidance for the sampling and pre-treatment of benthic diatoms from rivers. The majority of bioindication work has been done in Europe and North America, and the diatom-based indices have proved invaluable for water quality biomonitoring in European rivers. Despite an elaborated taxonomic framework, however, new species are discovered regularly within a routine monitoring (e.g. two Navicula species in France and Belgium, cf. Beauger et al. 2015, Phytotaxa 230: 172-182). Recently, these methods have also been applied to South America (Southern Brazil, Lobo et al. 2004, Acta Limnol. Bras. 16: 15-40) and South Africa (e.g. Taylor et al. 2003, Hydrobiologia 592: 455464). However, problems arose when the European-based methods were transferred to Africa, where endemic African taxa are dominant in the samples. It has become clear that the majority of species recorded form a special paleotropical flora with a high percentage of species new to science (see Cocquyt et al. 2014, Phytotaxa 158: 76-84).

Fig. 1 Typical clear stream in Rwanda near the source of the Nile

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This is also true for Rwanda, a small east African country which may serve as a model system for biomonitoring in the tropics. Here, only a few studies on diatoms are available and the knowledge of presumably rich flora is incomplete. The first study was that of Lemmermann (1914, Wissenschaftliche Ergebnisse der Deutschen Zentral-Afrika-Expedition 1907-1908, 2: 92-94),

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who listed 33 taxa in 27 species, mainly from the Rukarara in Nyungwe and Lake Mohasi. A thorough investigation of algae in the rapids of the Rusizi near Bugarama (Kufferath 1957, Acad. Royale Sciences Coloniales Classe des Sciences Naturelles et Medicales Mémoires in-8° Nouvelle série 5, 3: 1-70) at the border of Rwanda, Burundi and the Democratic Republic of Congo, revealed 54 taxa and 51 species of diatoms in 18 genera, with Nitzschia as the most species-rich genus. A total of 11 species are described as new to science and considered as endemic to the Rusizi rapids. An ecological study, including some diatom species, is available for Lake Kivu (Sarmiento et al. 2006, Journal of Plankton Research 28: 815-829). Thus, fewer than 100 species of diatoms are actually known from Rwanda. First results from Rusumo Falls show that at least 30-40 species are present in this locality. The diatom flora is very rich but identification of species is still preliminary. A planned project intends to use diatoms, freshwater red algae and bryophytes to evaluate and subsequently monitor the water quality of streams and rivers in Rwanda. Rwanda is of special hydrological importance as it has a very large diversity of aquatic habitats and harbours one of the sources of the Nile River, which is situated in a mountain rainforest (Nyungwe National Park). In Rwanda there is also the watershed between the Nile and the Congo River on the eastern crest of the Albertine Rift. All streams flowing westward to Lake Kivu end up in Lake Tanganyika and from there in the Congo river system. All streams flowing eastward go to the Akagera-Nile and Lake Victoria, and flow into the Blue Nile. Rwanda has undisturbed sources and clear, unpolluted streams, but also streams and rivers in anthropogenically disturbed landscape mainly polluted by soil erosion. Industrial pollution does not actually play an important role. The aim of the planned study, together with colleagues from Rwanda and Belgium, is to first develop a taxonomic framework by an inventory of the diatom flora in different habitats with emphasis to rivers and streams. Thus, a suite of biomonitoring tools will be introduced that should enable an assessment and subsequent monitoring of benthic diatoms. Other algae suitable for a biomonitoring are freshwater red algae. The advantage of this group is that it is comparatively species poor, but there exist major taxonomic problems. Actually, the taxonomic literature covers mainly Europe, North America, parts of South America (especially Brazil) and Australia. There is also a world monograph of freshwater red algae available (Kumano 2002, Biopress Limited, Bristol). While red algae are regularly used in the biomonitoring of European or North American rivers, there are only few attempts to apply these methods in the tropics. Wanninee et al. (2015) studied the possibility of freshwater red algae as bioindicators for water quality of streams in parts of Thailand (Journal of Agricultural Technology 11: 1349-1358).

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Fig. 3 Riccardia longispica, a typical liverwort of clear streams in rainforests

In Rwanda, like in diatoms, a taxonomic framework has to be developed first. Observations indicate that freshwater red algae of the genera Batrachospermum, Kumanoa and Hildebrandtia are mainly present in the high mountain sources and clear streams. A final plant group successfully used for monitoring water quality, but also for monitoring climate change, is the bryophyte group, e.g. liverworts and mosses (see Frahm 1998, Biologische Arbeitsbücher 57, Quelle & Meyer, Wiesbaden). For Rwanda, the liverworts are already well known (Fischer 2013, Abc taxa 14), but for mosses, a taxonomic framework has yet to be developed. With the development of such a taxonomic framework of benthic diatoms, freshwater red algae and bryophytes for Rwanda, a regular biomonitoring similar to that applied in Europe will enable a continuous monitoring of water quality and of the effects of climate change in a tropical country undergoing numerous ecological changes.

Professor Dr Eberhard Fischer Botany and Biodiversity Department of Biology, Institute for Integrated Natural Sciences University of Koblenz-Landau, Campus Koblenz +49 (0)26 1287 2224 [email protected] https://www.uni-koblenzlandau.de/de/koblenz/fb3/ifin/abteilung-biologie /ag-botanik/mitarbeitende/eberhardfischer/eberhard-fischer

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PROFESSOR PAUL ROGERS SPOKE TO PAN EUROPEAN NETWORKS ABOUT HOW CLIMATE CHANGE CAN CAUSE CONFLICT

Climate conflict

IN

recent months Baroness Joyce Anelay, UK minister of state at the Commonwealth and Foreign Office, has warned that the indirect impacts of global warming, such as deteriorating international security, could be far greater than the direct effects, such as flooding. This is a sentiment that has been echoed by US President Barack Obama – who has called climate change “a serious threat to global security” and heavily criticised climate change deniers. It was against this backdrop that Pan European Networks met with Paul Rogers, Professor of Peace Studies at Bradford University, in the UK, to talk about some of the ways in which the changing climate could come to have an impact on security and what could be done to help.

According to the IPCC, climate change has already begun to hold back wheat and maize yields. What do you feel are the other biggest indicators that climate change is already impacting on food security and how is this driving conflict? In terms of food security, it is perhaps the cereal crops which are showing the most significant impacts so far. In the longer term, however, this is likely to evolve to include a range of other crops as well.

We have to get to grips with the issues surrounding the kind of economic model which has evolved, and which received a significant boost because the defunct Soviet system collapsed and China went mixed economy. That economic system does not now appear to be fit for purpose

As climate change worsens, the indicators are typically evident in the interaction between changes in food production and the ability of people to actually buy food (and thus the price of food). There is currently evidence to suggest that poor grain harvests in China in the early 2000s, which caused a temporary increase in the price of wheat on the world markets, had quite a significant effect in terms of social tensions in many different countries (particularly Egypt). However, whether that particular series of droughts was directly related to climate change is a question which remains. The separate evidence is that extreme weather events are increasing in frequency, and the weather is becoming more variable. This also poses a problem because many of the world’s major food crops have evolved – and, indeed, have been selectively bred – for fairly stable climatic conditions, and those conditions are gradually disappearing. Thus while the effects of climate change on food production are perhaps in the early stages, they are nevertheless being felt, and indeed noticed, and without intervention this trend is only set to worsen.

When it comes to food security, could GM provide an answer – particularly given the fact that, as you have mentioned, many cereal crops have been selectively bred for conditions which seem to be disappearing? It is possible to breed crops in different ways; and while it is perhaps possible to breed a little bit faster with GM in comparison to other methods, the problem with any kind of breeding programme is that you have to do much more thorough testing than many of the big agricultural companies would want to do.

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Some years ago I worked on sugar cane, and the standard length of time that it took to bring a new variety into full production would be between 1012 years, because it had to be tested and re-tested to look at disease and pest resistance, for climatic conditions and so on. However, this degree of testing is crucial, because it means that when the variety becomes available you can have confidence in it.

Whether or not the series of droughts witnessed in the early 2000s were directly related to climate change is a question which remains

There are two things which must be done for this to be achieved, and they are closely related to one another. The first is that the old carbon producers have actually got to decarbonise. They are in absolutely no position to tell other countries to go carbon neutral; unless they do so themselves. If they decarbonise then they will be able to actually encourage other states to develop in different ways. Secondly, the developed nations will also have to provide a great deal of assistance to the emerging ones. Indeed, I would like to see a fair proportion of any international aid programme going towards long term sustainable

Problems emerge where companies have a

development. There are a number of countries that are really trying to push

genuine need to get quick returns, and this can

this, and they have recognised that the developing countries need this aid

mean that corners are cut. As such, when it

in order to make the technical process quicker.

comes to any kind of breeding programme

These are parallel issues and in many ways the latter is almost as

being posited as an ‘answer’ to such questions,

important as the former. However, the thing to remember is the speed at

a cautious approach is needed; you have got

which technology transition is possible – the rate at which mobile phones

to put a much higher premium on the safety of

took off in the West being a case in point.

the variety you produce, otherwise you might find it will collapse or else be much more prone to particular diseases than you expect.

From my own experience in Uganda, some of the major crops – such as maize, bananas and tomatoes – were not native to east Africa, but as soon as the local farmers got to grips with them, and found that they worked,

How do you think the emerging economies of the world can be better guided towards a low carbon, sustainable future?

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they took them on with alacrity. As such, it is clear that peasant conservativism is based on being very cautious about taking anything until you know that it works, and that is because if you are near the margins and it doesn’t work then you are stymied.

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Conflict is an oft-cited reason for famine and displaced populations, and yet may also be a result of such factors. What are your thoughts on the argument that conflict etc. will become much more commonplace moving forwards? The risk of inter-state warfare is probably relatively low, but what one will see is very considerable public anger by people on the margins. The crucial thing that people aren’t getting to grips with is that one of the successes, paradoxically, of the last 40 years has been significant improvements in education and literacy, which means that there are far more young people who now know they are on the margins. One of the two countries across the whole of the Middle East and North Africa, which is seeing more of its young people going to join so-called ‘ISIS’ than any other, is Tunisia, which is actually making a transition to democracy. Tunisia has 130,000 unemployed graduates out of a population of 11 million; its economy is in a mess and, of course, ISIS is deliberately making it worse by damaging the tourist industry because they want more marginalised people as recruits. Years ago, we used to talk about the ‘revolution of rising expectations’ – people at least get richer. Now, it is the ‘revolution of frustrated expectations’ and the risk here is an increase in the number of angry and resentful people, and from there you get the risk of more extreme movements, with the more elite communities often supressing the dissent because it affects their own security.

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Climate change is getting more problematic and is going to require an increasingly rapid rate of transition. It can only be hoped that an absolute catastrophe which finally prompts action can be avoided

Any thoughts on how that can be solved? It is just a huge issue and so there is no single solution. In the broad sense, we have to get to grips with the issues surrounding the kind of economic model which has evolved, and which received a significant boost because the defunct Soviet system collapsed and China went mixed economy. That economic system does not now appear to be fit for purpose. However, the nature of a possible replacement remains elusive. It is doubtful that this would be a return to rigid centrally-planned socialism; it has got to be something different, but, whatever it is, it is clear that the current system is not delivering, and we need to shift from this quite quickly – over the next two decades – while simultaneously addressing the decarbonisation of the developed world and the carbon-neutral sustainable development of the emerging economies. The work of the New Economics Foundation is particularly interesting here because they are trying to tackle the two at the same time by looking at what fiscal measures and what policies can actually speed things up.

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Will limiting rising temperatures to 2°C have any real impact, or have things already gone too far, meaning that priorities must now look to adaptation? I don’t think that we are too late; but it is getting more problematic and the issue is going to require an increasingly rapid rate of transition. What I hope that we avoid are absolute catastrophes which finally prompt action; we need to take action before those catastrophes happen. The other side of the coin, however, is the pace of change which can happen, and is happening in many countries – while Britain is now going backwards under the current government, unfortunately, though that may only be short term.

This U-turn in Britain is indeed a significant change and was a point raised by one of your interlocutors today, who asked whether the UK Government is either unaware of the climate change issue and the effects it can have (so are they ignorant) or are they aware and simply do not want to act. What are your thoughts on this?

As climate change worsens, the indicators are typically evident in the interaction between changes in food production and the ability of people to actually buy food (and thus the price of food)

I think the UK Government are aware that something is happening, and this is perhaps evidenced in the way that the climate change denial community have changed their stance from an outright denial that climate change was even happening, to an acknowledgement that it is, but that it is not a result of human action. This has lent some support to the argument for adaptation, but, of course, if the underlying cause of the change in climate continues to be unknown, then adaptation will have to continue without having any real, long term impact.

The hiatus identified by the IPCC has also been seized upon by climate change deniers, but you have mentioned that this pause is now coming to an end. Can you expand on this?

While the effects of climate change on food production are perhaps in the early stages, they are nevertheless being felt, and indeed noticed, and without intervention this trend is only set to worsen

The detailed data that is now emerging demonstrates that there have been pauses before, and, moreover, that this was never a complete pause – the trend was still up. If it is going up and you take a peak and a trough five years later, it appears to be going down; but that is the difference between an event and a trend, and even during this relative pause the trend has been up. Using this new data, a recently published study has shown that things are now in sync, and that with the oscillation going up and down every five to ten years, if the oscillation goes up at the same time as the trend then the whole thing shows a significant increase (that is one of the reasons why the trend is jagged). Clearly, the trend and the event are now in sync, and in the next five years there is a very real chance that we are going to see a surge, and that may be one of the things which will finally prompt some kind of action.

Professor Paul Rogers Professor of Peace Studies Faculty of Social Sciences University of Bradford http://www.bradford.ac.uk/ssis/staff-profiles/peacestudies/rogers-paul.php

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LOW-METHANE RICE FOR THE PLANET Dr Chuanxin Sun of the Swedish University of Agricultural Sciences at Uppsala discusses the need to reduce the methane emission of rice paddy fields

T

he Earth’s climate has changed dramatically since pre-industrial times due to human activity. The most noticeable change is global warming. Atmospheric methane is the second most important greenhouse gas (GHG) after CO2, as methane’s global warming potential is 25 times that of CO2 in spite of having less content in the atmosphere. It has been reported that the global methane emissions have made a 20% contribution to the warming effects since pre-industrial society. The total global methane emissions are estimated to be about 500-600 million tonnes per year. Among that figure, rice paddy fields are the major anthropogenic source of atmospheric methane emissions, and produce up to 100 million tonnes per year. Yet, there are two potentially dangerous factors of methane-caused global warming that threaten the future of the human race: the first is that the expansion of rice cultivation to meet the escalating demand for food in the coming decades will increase methane emissions from rice paddies; and second, recent reports have indicated that global methane emissions are temperature-dependent. The increasing temperature of the climate will provide ideal conditions for methanogenesis and accelerate methane emissions from different ecosystems, including rice paddies. Therefore, there is an urgent need to curb global methane emissions. Rice agriculture may be the first target for the reduction of methane emissions as it is potentially controllable via sustainable technology.

Paddy rice is important for food security The current human population is around seven billion, and around half eats rice as a staple food. Annual global consumption of rice

per person is around 100kg to 200kg for the rice-consuming population. It is obvious that increasing both rice yield and available land for cultivation is important to meet the accelerating demand for food. Interestingly, a rough calculation indicates that every 100kg rice production will release around 14kg of methane from rice agriculture.

High-starch and low-methane are two important traits in rice breeding, but are difficult to achieve The current methods in reduction of methane emissions in rice agriculture are farming practices, e.g. drainage, that are conditional and non-sustainable. Scientists have suggested that the reduction of methane emissions from paddies can be achieved by breeding high productivity rice. However, it seems very difficult to achieve both of these traits in a rice variety. Many current elite rice varieties with high productivity release a normal amount of, or even more, methane.

A single gene biotech breeding strategy brings dual benefits By employing a single gene of transcription factor from barley that governs sugar metabolism, and source-sink communication to channel carbon allocation in rice plants from below ground to above ground tissues, the international group led by Dr Sun has successfully generated a high-starch, low-methane rice variety called SUSIBA2 rice. Three-year small scale field trials have shown that the rice variety gave rise to around a 10% increase in yield and up to a 90% decrease of methane emissions. Interestingly, the rice variety showed higher methane reduction activity during higher temperatures and higher sugar metabolism. This phenomenon or trait is particularly important in a future climate

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as the predicted higher temperatures would favour this type of rice in cutting methane emissions, which counteracts the challenge of accelerated methane emissions from paddies caused by rising temperatures. The temperature-enhanced trail in SUSIBA2 rice is defined as the ‘snowball effect’, and designed by using the knowledge achieved in the previous research by the same group.

High-starch, low-methane rice research needs future support High-starch, low-methane rice research has received great support from Swedish scientific communities and foundations such as the Swedish University of Agricultural Sciences (SLU), Formas, Sida, and VINNOVA for the programme of Trees and Crops for the Future (TC4F), Lantmännen and Carl Trygger’s Foundation. There are some important remaining scientific issues and questions, however, that need to be addressed, and the project needs continuous support from the Swedish foundations and other financial resources, importantly from the European foundations in the future, in order to solve them. These issues are listed below: 1) SUSIBA2 rice is a GM crop and cannot directly be used by most of the rice cultivating countries. A society-acceptable variety needs to be developed using a similar scientific principle, e.g. the ‘snowball effect’; 2) The long term impact of SUSIBA2 rice on a soil ecosystem needs to be investigated; 3) Assessment of the benefits in food production and methane emission mitigation of cultivating SUSIBA2 rice on a large or farming scale must be undertaken; and

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4) Survey of the ‘snowball effect’ for methane reduction in both Japonica and Indica rice and also in wetland crops. Reference articles for further reading: 1 Su, J., Hu, C., Yan, X., Jin, Y., Chen, Z., Guan, Q., Wang, Y., Zhong, D., Jansson, C., Wang, F., Schnürer, A. & C. Sun. Expression of barley SUSIBA2 transcription factor yields high-starch low-methane rice. Nature 523, 602-606, online, doi:10.1038/nature14673 (2015). 2 Bodelier P.L.E. Bypassing the methane cycle. Nature 523, 534-535 (2015).

Dr Chuanxin Sun Head of Group Department of Plant Biology Uppsala BioCenter, Linnean Centre for Plant Biology Swedish University of Agricultural Sciences (SLU) Uppsala Sweden +46 (0)18 673252 [email protected] http://lcpu.se

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GORM DIGE DETAILS HOW GREEN INFRASTRUCTURE CAN PLAY A CRITICAL ROLE IN RESPONDING TO THE RISING RISK OF NATURAL HAZARDS

Nature’s solutions G reen infrastructure offers attractive solutions to environmental, social and economic issues, and as such needs to be fully integrated across different policy domains. With the European Environment Agency (EEA) recently having published a report on the role of green infrastructure in mitigating the impacts of weather and climate change related natural hazards, here in this interview Gorm Dige, project manager for territorial environment, policy and economic analysis, provides an insight on the importance of Nature-based solutions.

What is green infrastructure and why is it important? The European Commission Communication on Green Infrastructure describes it as a tool for providing ecological, economic and social benefits through Nature-based solutions, for helping to understand the advantages that Nature offers to human society, and for mobilising investments that sustain and enhance these benefits. In other words, it’s a network of Nature, semi-natural areas and green space that delivers ecosystem services, which underpin human wellbeing and quality of life. Green infrastructure can provide multiple functions and benefits on the same spatial area. These functions can be environmental (e.g. conserving biodiversity or adapting to climate change), social (providing water drainage or green space), and economic (supplying jobs and raising property prices). The contrast with grey infrastructure solutions, which typically fulfil single functions such as drainage or transport, makes green infrastructure appealing because it has the potential to tackle several problems simultaneously. Traditional grey infrastructure is still needed, but can often be reinforced with Nature-based solutions. For example, green infrastructure can be used to reduce the amount of storm water runoff entering sewer systems and ultimately lakes, rivers and streams through the natural retention and absorption capabilities of vegetation and soils. Benefits of green infrastructure in such a case could include increased carbon sequestration, improved air quality, urban heat island mitigation, recreational space and additional wildlife habitat. Green

Gorm Dige

areas also contribute to the cultural and historical landscape, giving identity to places, as well as to the scenery of urban and periurban areas where people live and work. Research shows that green infrastructure solutions are less expensive than grey infrastructure, and provide a wide array of co-benefits for local economies, social fabric and the broader environment.

What are the main issues facing the development of green infrastructure? Green infrastructure is relatively new and complex, and there is no widely recognised definition. There is also a lack of quantitative analysis and indicators. As a result, policy makers struggle to integrate green infrastructure into the policy landscape. However, some green infrastructure features go against this trend. For example, ecoducts and natural water management systems, such as green roofs, tend to have clear functions and measures exist to assess their performance. The financial case for green infrastructure can also seem complicated, but, in addition to providing multiple benefits as seen above, it is often cheaper, more robust and sustainable. So instead of defaulting to grey solutions like dikes and pipes for flooding, planners should first look at the benefits of restoring floodplains or wetlands. Finally, green infrastructure is anchored in the EU’s Biodiversity Strategy, but it’s more than just a biodiversity conservation instrument. It can make a significant contribution to the implementation of EU policy objectives concerning regional and rural development, climate change, disaster risk management, agriculture and forestry, and the environment.

What is European policy on green infrastructure and what is being done to tackle the above issues? The EU’s Green Infrastructure Strategy advocates the full integration of green infrastructure into EU policies so that it becomes a standard component of territorial

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development across the EU. The strategy also recognises that green infrastructure can contribute to a range of EU policies whose objectives can be achieved through Naturebased solutions, and places the use of green infrastructure in the context of the Europe 2020 Growth Strategy. In addition, the Biodiversity Strategy aims to ensure that ‘by 2020, ecosystems and their services are maintained and enhanced by establishing green infrastructure and restoring at least 15% of degraded ecosystems’. It also calls on member states to map and assess the state of ecosystems and their services nationally. This work will contribute to the assessment of the economic value of ecosystem services, and promote the integration of these values into EU and national accounting and reporting systems by 2020. Green infrastructure is also recognised elsewhere in the EU policy domain, in particular in the Seventh Environment Action Programme (7EAP), the Regional Policy 2014-2020, the Water Framework Directive, the Nitrates Directive, the Floods Directive, and the EU Strategy on Adaptation to Climate Change. All these initiatives will hopefully lead to improved use of green infrastructure as a policy tool and to practical solutions locally.

How does the EEA contribute to this work? The EEA has engaged in green infrastructure research to support policy makers and the public. In 2011 we published the report ‘Green

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Natural hazards are set to mount with climate change

infrastructure and territorial cohesion’, which underlined the importance of developing tools to detect and measure green infrastructure, and provided input to national and regional priority and target setting. It also fed into the EU’s Communication on Green Infrastructure. The EEA study entitled ‘Spatial analysis of green infrastructure in Europe’ evaluates green infrastructure as an ecological and spatial concept for promoting ecosystem health and resilience, contributing to biodiversity conservation, and benefitting humans by promoting the delivery of ecosystem services such as climate change mitigation, provision of key habitats to biota, and habitat connectivity. ‘Exploring Nature-based solutions – The role of green infrastructure in mitigating the impacts of weather –and climate change-related natural hazards’ is a recently published EEA report that builds on previous reports to demonstrate how green infrastructure contributes to mitigating adverse effects of extreme weather and climate-related events, which are among the most costly and most deadly natural hazards in Europe and globally. The report focuses on certain types of events that will very likely be amplified by ongoing climate change, e.g. landslides, avalanches, floods and storm surges. In addition, the report touches upon the green infrastructure and ecosystem services contributing to global climate regulation. 1 http://www.eea.europa.eu/publications/exploring-nature-based-solutions-2014 Reproduced with kind permission of the European Environment Agency

Gorm Dige Project manager for territorial environment, policy and economic analysis European Environment Agency www.eea.europa.eu

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THE EFI’S DR MARCUS LINDNER OUTLINES HOW PRACTITIONERS AND POLICY MAKERS MUST ACKNOWLEDGE THAT UNCERTAINTIES ARE LIKELY TO REMAIN AND THAT DECISIONS MUST BE BASED ON EXISTING SCIENTIFIC EVIDENCE

In the face of uncertainty

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Climate change will affect all goods and services that forests provide. European forestry is also exposed to rapid changes in societal demands on the forest resources. Both trends challenge the sustainability of the forest-based sector.

How important is it to communicate uncertainty to practitioners and policy makers? © Saku Ruusila

he European Forest Institute (EFI) is an international organisation established by the European states. EFI conducts research and provides policy support on forestrelated issues and facilitates and stimulates forest-related networking while promoting the supply of unbiased and policy relevant information on forests and forestry.

Marcus Lindner

European forests serve multiple functions and provide a broad range of goods and services to society. Increasing societal demand for biodiversity protection and recreational use of forests will in the near future conflict with the increasing demand for wood for material and energy use. Thus there is substantial need for improved decision making and communication support, which will guide future forest resource management and use in Europe. Speaking to Pan European Networks, the head of the EFI’s Sustainability and Climate Change programme, Dr Marcus Lindner, discusses how climate is expected to become more variable with greater risk of extreme weather conditions, and how both practitioners and policy makers must acknowledge the fact that uncertainties are likely to remain and that, as such, decisions must simply be based on the existing scientific evidence.

Foresters have always made their decisions in the face of uncertainty

The major point here is that uncertainties are seen by many as something which can and will be removed and that, moreover, decisions – particularly policy-related decisions – cannot be made until a specific level of certainty has been reached. This is the wrong attitude to take quite simply because there is no reason to believe that we will face any less uncertainty in ten years’ time; there is an inherent uncertainty about what society will do in terms of controlling future emissions (and it is these emissions which are fundamental in any predictions of the future), with there being any number of possible scenarios depending on what economic changes take place as efforts continue to reduce emissions, what political commitments will come from where, and so on. There are also new economies and economic developments to consider, as well as new and emerging technologies which could find applications in relevant areas. Hopefully, within the next ten years we will have some kind of agreement on the world’s emissions as well as, perhaps, a limitation. There is also, of course, progress being made towards limiting climate change to 2°C above pre-industrial levels, but even if we are able to achieve this, there is no way of knowing exactly what the world will be like then, specifically we cannot forecast regional patterns of climate change such as in seasonal precipitation.

© photoshopper

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A starting point should therefore be to properly communicate with those who believe it is better to wait for uncertainties to be explained so as to highlight the fact that we are living in a world that will stay uncertain, and that it is very

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unlikely that, at any time, anyone will be able to say for sure what the future will hold.

That, I’m sure, has its own inherent challenges because – particularly at the policy level – people perhaps tend to rely on a degree of certainty, as something of a precautionary principle, before making any decisions. That is certainly true at the policy level. In terms of forest management, however, foresters have always made their decisions in the face of uncertainty. One hundred years ago, for instance, foresters were unable to predict the future market conditions any more than we are able to do so now, but they nevertheless made decisions on what species to grow and where to establish new plantations and so on, and we are reaping the benefits of those decisions today.

Given these issues and the inherent level of uncertainty, what role do you think science can play? We know what many of the uncertainties are and what this means for the decision making process; we are also able to draw on our 25 years of experience and research on climate change impacts, and so, while the future remains unpredictable, we are able to better explain what we expect to happen under certain assumptions. We know, for example, that, as recently evidenced with Hurricane Patricia, hurricane damages can be expected to increase but, as yet, there has been no solid proof that climate change is having a causative effect, simply because the variability around extreme events is large and it takes time to separate a new trend from the noise of natural variability. Nevertheless, recognising this limitation helps us to better explain the uncertainties. As such, when we look at European forests there are several kinds of scenarios we can discuss from a theoretical perspective. But if I talk to a person on the ground, I know what kind of environmental conditions they live and work in, the forest type they work on, and so on, and this enables me to make much better

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Forests in northern Europe are benefitting from climate change due to the fact that increased temperature extends the growing season and there is sufficient rainfall to sustain productive growth rates

recommendations on the issues they should look at and the possible ways they can deal with the uncertainties. A simple example of this is the fact that many foresters typically plant just one species of tree, the Norway spruce for instance, which they manage on a large scale. This is essentially an exercise in putting all your eggs in one basket, because if an unexpected event such as an insect infestation occurs which only affects this species, or a particularly strong storm or a fire, the forest will be decimated. We are therefore working with foresters to extol the virtues of planting stands of different types of trees.

Climate change may impact forests in ways that are partly opposing. How, then, can adequate adaptation activities be designed and planned? While these conflicting impacts don’t necessarily occur at the same location, there are implications for certain regions. In the north, for instance, we expect to continue to see an increased growth rate – this is certainly true in the boreal forests in northern Sweden and Finland, where the trees are already experiencing much higher growth rates because, in the past, the low temperature had been a limiting factor – and so this is an example of a positive impact of global warming. However, the increasing growth rates and longer growing periods also mean that these forests are more susceptible to the impacts of extreme events because they grow taller and denser, and so a strong storm has the potential to cause a much greater degree of damage, thus negating the positive effects already described. This is even more of an issue when we take into consideration the fact that evidence suggests that we can expect an increase in the number of events of this type in the future. It is therefore important to recognise that while the trees might be growing faster, if you’re a forester in Scandinavia you should perhaps reconsider your thinning schedule, for instance, so that you can ensure you are adapting to the uncertainties of the future and benefitting as much as possible from the changes in growth rates.

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The challenges are different throughout the regions and so foresters need to be more aware that the warming climate will bring with it an increased risk of severe droughts; they need, perhaps, to become more proactive in terms of reducing the risk of storm and fire damage by looking at their management systems. Similarly, while the forests in northern Spain are in the short term still benefitting from climate change due to the fact that increased rainfall is providing the moisture needed for longer growing seasons, this is also causing an increase in biomass in the forests, and if this is not adequately thinned when the region experiences droughts, the effects of forest fires could be devastating.

What role do initiatives such as the MOTIVE project play? The MOTIVE project was the first European project to see these topics studied across different regions and case studies; we studied the same questions in different regions, environments, and socioeconomic conditions. This enabled us to learn by comparing how climate change impacts are likely to occur or are, indeed, already affecting some regions. This is particularly important for the practitioners in the different regions; the practitioners in the north, for instance, need to know what is being done by their more southerly counterparts who are already losing their species (such as those in the regions of Switzerland south of the Alps, or in Catalonia in Spain, for instance). It is similarly important to convey science to both the practitioners and the relevant stakeholders. We also invited some of the stakeholders from different regions to come together and exchange information. In the outcomes of this project, the stakeholders were inspired to see what was happening elsewhere and to learn from the examples of best practice. This exercise provided them

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Foresters perhaps need to become more proactive in terms of reducing the risk of storm and fire damage by looking at their management systems

with a more complete picture of the uncertainties they are facing, as well as of what could occur in their own region in the next decade or two. It really helps to build up capacity to respond to such things, so that is also something we feel that the EFI can assist with. We have member organisations in different regions, we have the contacts and local experts; and, while it is important that these people talk with their decision makers and practitioners, we must also ensure that we are integrating the experience across the whole of Europe, recognising the regional differences and sharing experiences across regions.

As forest-related climate change mitigation policies are highly sensitive to disturbance regimes, what more needs to be done to ensure that they are taken into consideration during the development stage? There seems to be a tendency for climate change mitigation in forestry to focus primarily on maximising the potential of forests as carbon sinks. However, it is important to accompany this with mitigation strategies aiming at the use of forest-based products as these also store

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enter a very dangerous situation. It is therefore important to combine mitigation strategies that rely on carbon sequestration in the forests with strategies that enhance wood product utilisation and enable substituting fossil fuels and materials that have a larger carbon footprint.

Do other disturbance factors, such as pests and insects, also stand to become more frequent due to climate change? That is one of the uncertainties we are experiencing, and we don’t have a response to that as yet. There have been examples of this in other places – the mountain pine beetle has wiped out millions of acres of forest in British Columbia, Canada for instance. Luckily we haven’t had such a situation in Europe – apart from perhaps the outbreak of ash dieback disease, which demonstrated that such incidences can emerge very quickly and seemingly out of nowhere, often with severe consequences.

Amidst these complex issues, what role does the European Forest Institute to play, and how would you like to see research priorities moving forwards? We see ourselves as a knowledge hub and we work to convey scientific knowledge and evidence-based decision support. It is important to have an adequate scientific understanding so as to give meaning to the sometimes conflicting research results which emerge from scientific papers.

© Forest Service Northern Region

carbon and can replace other materials that require a lot more energy and result in much higher greenhouse gas emissions in the production process. Advocating the protection of forests so as to maximise the amount of carbon they can store is the most effective mitigation strategy in the short term. The problem there, however, is that as the forests become denser and taller they will be exposed to exponential increases in disturbances: while you might be storing more carbon, these disturbances – more devastating storm impacts for instance will flatten the forests (a particular risk for older forests in central Europe) – will release that carbon or, at the very least, severely damage the forest. We must therefore understand that if we favour one mitigation policy which increases the disturbance risk over time then we stand to

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The mountain pine beetle has wiped out millions of acres of forest in British Columbia, Canada

That is, while some published results may at first seem to be contradictory in their assessments, when you actually look behind some of the assumptions and the uncertainty in the models, you can explain why they are different; but you need, however, the ability to interpret them in order to give meaning to the science. The evidence-based decision support demands an increasing number of researchers to understand how they can bridge the gap between science and policy in terms of practice, and what kind of interpretations are needed to provide this additional meaning. I have received a lot of positive feedback on our efforts to provide this support on different topics because policy makers can’t possibly be expected to grasp all the implications. We are thus required to better explain why certain things are a certain way, and can also point out what the remaining unknowns are and which areas need additional research.

Dr Marcus Lindner Head of Programme Sustainability and Climate Change European Forest Institute (EFI) [email protected] www.efi.int

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PROFILE

SPECIAL FEATURE: CLIMATE CHANGE

READING THE WIND A group from Albert-Ludwigs-University of Freiburg writes about advances in storm damage modelling

IN

current storm damage research, mapping and reproducing near-surface wind fields associated with destructive storm events is a major challenge. This is mainly because near-surface wind speed is one of the fastest fluctuating atmospheric variables. During storm events, short-time fluctuations of the wind vector, i.e. gusts, are particularly severe and pose a serious threat to ground objects, as well as to life and limb. In central Europe, winter storms that develop around deep low pressure systems cause catastrophic damage to buildings and trees at irregular intervals. In addition to infrequent, catastrophic storm events, less intense storms with frequently recurring maximum gust speed also cause substantial damage to ground objects, i.e. endemic damage. To estimate storm damage risk, local authorities, forest administrations, insurance companies and wind turbine operators require detailed spatiotemporal knowledge about near-surface gust speed fields of storm events.

High-resolution gust speed modelling In recent years, the spatial resolution of gust speed models was often too low for gust speed to be an important predictor variable for empirical storm damage models. A commonly used spatial resolution is 1km: at the University of Freiburg, we therefore developed an empirical gust speed model with a spatial resolution of 50m using boosted regression trees. This resolution is much closer to the typical scale of near-surface gusts than the spatial scale at which previous models simulate gusts. Furthermore, low resolution of gust speed fields implied the use of a rather coarse representation of orography and surface properties like roughness. The combination of coarsely resolved gust speed, orography and surface properties inevitably led to gust speed model performance with potential for improvement. The new gust speed model allows for the estimation of statistical gust speed fields and is also suitable for the simulation of individual catastrophic storm events. It can therefore be applied to problems which require separating the impact of individual catastrophic storm events from the impact of endemic storm events. The flexible model architecture also allows for the combination of catastrophic and endemic storm events without structural modifications. In its current version, the model is based on long term (1979-2013) gust speed data available from the meteorological stations of the German Weather Service.

High-resolution storm damage modelling for forests and landscapes Storm damage formation in forests is subject to complex processes. The factors that are involved in damage formation include weather conditions, orography, human influence, soil conditions and stand conditions. On the basis of the new gust

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Fig. 1

speed model we developed a forest storm damage model for southwest Germany which is based on booking records of the forest administration from the period 1979-2008. The booking records comprise information on the cumulative five-year amount of storm damaged timber. In this same period, the two highimpact storms ‘Wiebke’ (1990) and ‘Lothar’ (1999) hit the forests in the study area. The polyvalent gust speed model outputs allow for the incorporation of the gust speed fields of both exceptional storms, as well as the statistical gust speed field into the storm damage model. The storm damage model outputs are used to produce high-resolution damage maps for return periods up to ten years. Together with knowledge of local experts, the maps allow easy identification of areas prone to storm damage (Fig. 1). Model performance evaluation clearly indicates higher model accuracy compared to the accuracy of storm damage models applied earlier in the study area.

Christopher Jung (MSc) and Dr Dirk Schindler Faculty of Environment and Natural Resources Chair of Environmental Meteorology Albert-Ludwigs-University of Freiburg +49 (0)761 203 3588 [email protected] http://www.meteo.uni-freiburg.de

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Our research group is concerned with the mechanisms of clinical plasticity in skeletal muscle. With animal studies and case-orientated clinical studies we are looking for new approaches to unresolved questions on how muscle function is maintained and re-established in the light of orthopaedic surgery. Current projects include: n Molecular and cellular characterisation of the timescale of changes in the muscles after tendon rupture and repair; n

Human investigation on the influence of genetic factors on muscle plasticity with cardio-rehabilitation;

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Pharmacological intervention to suppress skeletal muscle atrophy and the associated increase in intramuscular fat after tendon tears; and

n

Clinical investigation of the contribution of the muscle phenotype on functional rehabilitation of knee function after surgery. To answer these biological questions, we are using state-of-the-art molecular biology techniques, as well as conventional microanatomy and biochemical methods, on biopsy material taken during operations. In particular, we are focusing on the role of adhesive processes in the muscle fibres in regulating mechanical properties of the stress-modulated phenotype of skeletal muscle.

University Hospital Balgrist Professor Martin Flück, PhD Laboratory for Muscle Plasticity Forchstrasse 340 CH-8008 Zurich, Switzerland

Email: [email protected] Tel: +41 (0) 44 386 3791 Fax: +41 (0) 44 386 3799

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CARBON CAPTURE AND STORAGE

Balancing the Carbon Cycle

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CARBON CAPTURE AND STORAGE:

Balancing the carbon cycle

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arbon Capture and Storage (CCS) has a unique role to play in decarbonising global industrial processes and power generation.There is increasing focus on the necessity to utilise CCS and the International Energy Agency (IEA) has stated that ‘the deployment of Carbon Capture and Storage is critical to global efforts to mitigate climate change and keep global warming below 2°C to pre-industrial levels’.

CCS is a way to address this – CO2 can be removed from the exhaust gases of power stations and industrial plants, transported to a storage site, and pumped more than one kilometre underground into stable geological formations that will keep it there permanently, like the oil and natural gas accumulations of the North Sea and elsewhere in Europe. In fact, CCS is Delivering a low carbon world the only way to dispose of The EU and its member states have recognised that CCS will be the unwanted CO2 that we one of a number of different technological solutions required to produce, and will continue to deliver decarbonisation targets, particularly for industrial produce, from industrial facilities emissions, but efforts to date to move full scale CCS projects such as steelworks, natural gas forward have been less than successful. In order for CCS to fulfil processing, cement and fertiliser its potential and necessary role in decarbonising European plants. CCS in combination with industry, large scale infrastructure for transport and permanent bioenergy (biomass used in storage of CO2 will need to be deployed. For this to take place a electricity and heat production) can number of separate market, investment and co-ordination issues also help to reduce the amount of CO 2 will have to be overcome. already in the atmosphere by producing New metrics are required that effectively value CCS within our ‘negative emissions’. socioeconomic system and which enable governments to CCS is often confused as a power rigorously allocate public funds for decarbonisation options that generation technology, but it is really a suite minimise downside loss (or increased cost) to the economy. Such of many different technologies that are metrics can also help the community relate to and understand combined together through the capture, the reasons why investments in CCS infrastructure are essential transport and storage chain in an analogous to achieving a viable low carbon Europe and the world beyond. way to natural gas or LNG production, transport and utilisation – except in reverse. In this way, CCS What is Carbon Capture and Storage? can be compared to other waste removal activities When fossil fuels are burnt or used in some industrial processes (such as industrial waste and general household CO2 is produced. Because CO2 is considered a major contributor refuse). Industries based on processes for which to global warming, part of the solution to climate change is there is no alternative for decarbonisation will need preventing that CO2 from entering the atmosphere. But we cannot to begin deploying CCS long before 2030 in order for simply turn off the global use of fossil fuels overnight. Europe to meet 2050 emissions targets. Hence, the CO2 Transitioning to a sustainable low carbon world will take many, transport and storage (CTS) infrastructure required for many decades, and our advanced lifestyle will still depend on removing these industrial emissions will be an essential minimum scale that must be built across Europe. industrial activities that produce CO2.

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Energy and climate policy Our energy system is changing. Over the next 15 years there is an expectation that the cost of producing renewable electricity will decrease and its share of supply will increase. But what happens when the wind doesn’t blow and the sun doesn’t shine? And what about other energy forms used for heating and transport? Unfortunately, many renewable energy sources are variable, and that is one of the reasons why governments talk in terms of a portfolio of electricity generation technologies. The variability in electricity production has to be matched by sources that can fill the gap. Currently the best way of doing this on a large scale is to use natural gas-fired turbines that have very fast start-up and shut-down times. Over the coming decades fossil fuel generation capacity will therefore continue to be utilised in order to meet power demand at affordable prices and balance variability in supply from renewable sources. A proportion of this will have to be fitted with CCS to abate emissions.

“Currently, a lack of targeted deployment policies to bridge demonstration efforts with longer term emission reductions initiatives represents the most critical gap in government policy support for CCS globally. The United Kingdom is the only country to date to commence implementing such support.” International Energy Agency, 2014

industrial processes and power plants cost more than conventional ones based on fossil fuels. Across Europe the power station fleet is ageing, and there is a pressing need to build new base-load capacity to ensure the total portfolio delivers affordable and secure electricity. At the same time, however, CO2 emissions from the whole economy need to be reduced. Energy policy therefore has to satisfy the short term needs while avoiding the creation of new emissions for which there is no mitigation solution.

Minimising ‘carbon lock-in’ European governments have taken a ‘middle ground’ on new fossil fuel power stations with a ‘Carbon Capture Ready’ (CCR) policy that essentially requires power stations greater than 300MW generation capacity consented after April 2009 to be capable of retrofitting CCS in the future. A downside to this is the risk that CO2 transport and storage infrastructure is not built in time to enable retrofitting of these unabated power stations so that carbon budgets and climate targets can be met. Because power stations have long operating lives this will lead to carbonlock in.

This should not be considered problematic if common transport and storage infrastructure is seen as synergistic for low carbon industry, bioenergy and power.

The effectiveness of a CCR policy is therefore critically dependent on how realistic the future transport and storage options are. If this infrastructure is not deployed, new-build power stations will eventually lead to residual emissions in the future that will not be abated without prohibitive costs.

The pathway to a low carbon energy system is complicated by a number of factors that together are regularly described as the ‘energy trilemma’. Meeting the three requirements of energy security, affordability and decarbonisation over the next 15-20 years is a complex task. New low carbon technologies,

A key objective of governments’ energy and climate policies should be ensuring carbon lock-in is reduced to the lowest possible level. To effectively manage this risk, governments clearly need to be mindful of the negative impact of slow progress in deployment of CTS infrastructure at scale.

© Aquistore

The Crown Estate | CCS

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Policy drives investment behaviour and benefits

conceptual power or industrial capture projects into reality, offshore storage sites have to be ‘characterised’ and ready to be developed Because carbon (CO2) pollution and the cost of effects of climate – in other words financeable or ‘bankable’. If European and change are not yet priced into all the activities and products of our member state policies are left to focus solely on low carbon economy, we have what economists call an ‘externality’ with the effect or renewable electricity generation, then the all-important that free markets, including all energy forms, do not drive us towards development of CTS infrastructure at scale for use with abating decarbonisation. The UK Government is taking a global lead with its industrial emissions may not be forthcoming. policies to address this externality. In particular, its electricity market reform (EMR) framework is designed to create the transitional Under current regulatory and policy frameworks across Europe, conditions that will result in a properly functioning market for low significant market barriers and market failures exist that discourage carbon electricity in the future. and prevent investment in common CO2 transport infrastructure and However, the electricity sector is only one part of our energy system storage hubs (Fig. 2). Policies at member state and pan-European (Fig. 1, below), with interactions between it and many other energy- levels are not enabling a virtuous cycle of storage appraisal, CTS related activities. Policies operating to decarbonise only one part of infrastructure development, lowering of CCS cost, and construction the system will have spillovers and unintended consequences in of capture plants on power and industry that will deliver a sufficient other parts. Hence decarbonisation of the energy system should be scale of emissions abatement in the required timeframe. This managed holistically to avoid market failures and distortions. outcome also runs the risk that industrial decarbonisation and Furthermore, the private sector does not operate with a system production of low carbon transport fuels in the future will be more perspective of emissions reduction in focus, so its business expensive, and the projected savings to the economy of including models/cases can only ever be as effective as the system-level CCS in the energy system will not be achieved. policies of government. Unless addressed, these barriers and market failures are likely to New policy thinking is urgently required to create the pathway for severely restrict the development of CCS in the coming decade, deployment of CO2 transport and storage infrastructure that can be with a net increase in the cost of decarbonisation across the used for decarbonisation across northern and eastern Europe, and European economy. In the UK the Energy Technologies Institute the western Mediterranean. (ETI) has demonstrated that meeting emissions targets with CCS Developers, investors and financial institutions all need a degree optimally deployed will be cheaper by 1% of GDP (about £30 of certainty to take forward new projects to a final investment billion (~€41.8bn)) per annum by 2050 than if CCS is not utilised. decision (FID) within a low carbon system context. To turn This lower cost includes the benefit of CCS in industry, flexible low

Modern economies are complex 'ecosystems' of energy-related activities and holistic policies are required to manage decarbonisation without creating new market failures and distortions.

Fig. 1

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General CCS Risks

Market Failures By Sector

CCS Market Failure Types

Production and CO2 capture

CO2 emission externalities

Externality: Low priced CO2 emissions

Co-ordination failure

Co-ordination failure Access risk

Imperfect & asymmetric information

Construction & performance risk

Imperfect & asymmetric information on storage

Knowledge creation spill-over

Externally: Capture technology spill-overs

Externally: Exploration spill-overs

Section 2.1.1

Section 2.1.2

Construction & performance risk

Capital market restrictions

Policy perception risk

Public perception risk

CO2 trasport

CO2 storage

Section 2.1.3

Section 2.1.4

Low for non-power sector Medium for power sector Co-ordination failure Volume & development risk

Co-ordination failure Volume risk

Natural monopoly industrial

Natural monopoly of pipeline transport

Natural monopoly of storage hubs

Missing markets

Missing markets CO2 transport

Missing markets CO2 storage

Ability of current regime to address risks/market failures

carbon fuels (for transport and heating), power generation and ‘negative emissions’ using biomass. IEA analysis has shown analogous benefits at a pan-European level. A new socioeconomic paradigm, new metrics and new policy measures are required if infrastructure development is to be encouraged, these benefits realised and climate targets met.

Low

Medium

High

Fig. 2

investment risks, lead times and access to finance/remuneration required to achieve FIDs create a barrier to this happening in practice. We call this market failure a co-ordination failure.

Investment risk is too high

Given time horizons stretching over many decades and the political sensitivity of energy policy, potential storage investors perceive significant risk. The EU CCS Directive (Directive on the geological Market failures Contemporary energy policy is attempting to minimise energy costs storage of carbon dioxide, 2009) effectively requires storage for consumers over the long term while meeting emissions targets operators to carry liabilities for a long time, with potential impacts to over various time periods (carbon budgets). Underpinning this company balance sheets and credit ratings, without clarity about objective is an implied use of CCS on industry, and the critical future income or support mechanisms. This makes overall expected prerequisite for this to eventuate is availability of proven financeable returns difficult to assess. storage sites for capture projects to take FIDs. Given the long lead It is virtually impossible for transport and storage developers to make times for such projects, the consequence of this is that investment an investment case with uncertainty in future demand requirements in storage appraisal and de-risking has to occur ahead of market and uncertain value to investors at the final stage of a value chain demand, but currently there is no market for the disposal of CO2. This disposing of carbon emissions that are currently not fully priced is a classic case of a market failure known as a missing market. through the EU carbon market. No developer can create a business Typically the private sector cannot overcome such a failure, which is case outside a full chain government-backed project. often associated with a ‘public good’ need. The absence of direct public funding support such as capital grants In theory, properly functioning, technology-neutral, market-enabling or capacity payments for transport and storage developers makes frameworks such as the European Trading Scheme or the UK any investment highly speculative and therefore untenable. Hence, Government’s EMR (with a subsidy mechanism known as a Contract without targeted financial incentives for transport and storage for Difference Feed in Tariffs, or CfD FiTs) should provide fossil fuel projects, which are essential public good infrastructure to future-proof power generators with reasons for utilising transport and storage the economy, the pre-FID funding needs for independent storage infrastructure. However, such infrastructure does not yet exist, so the appraisal will not materialise. first CCS power projects have to be built as ‘full chain’ projects. Subsequent expansion of the transport and/or storage infrastructure will then need either further complex full chain contractual/ commercial arrangements between different businesses or independent transport and storage ‘part chain’ projects to be built decoupled from capture projects. But the substantially different

The Crown Estate | CCS

Failure of the market to value the public benefits of CCS

A key characteristic of CCS is that it can create benefits to the economy, consumers and business in the form of ‘avoided costs’. This is a practical and realistic solution to the so-called problem of fossil fuel ‘subsidies’. However, under current policy frameworks there

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Intervention type

Intervention options n n n

Financial incentives

n n n

n

Tax breaks

n

n n

Market creation

n

Direct revenues under carbon penalty frameworks Direct payments under low carbon subsidy frameworks Centralised funding models for transport & storage Capital grants for storage characterisation Purchase guarantee by government Capacity payment by government Cross-sector tax breaks Sector-specific tax breaks (targeting hubs) CO2 storage liability aggregation Options contracts for transport & storage Leasing rounds for options over storage sites Long term storage capacity auctions

Historically, attempts to overcome market failures in infrastructure investment have led to a mixture of public and private participation. Such an approach for CCS transport and storage developers would help to direct funding that creates the right risk-reward profile, and enables the development of coherent long term enduring infrastructure frameworks in which individual projects play a role, but which require national and supranational or regional strategic leadership and decisions, and ensure value for money for the public purse. The table provides some examples of interventions that could comprise a long term infrastructure framework. Some can work at national level and some at supranational level. As discussed, transport and storage stages suffer from being at the ‘downstream’ end of the CCS chain, so mechanisms that provide revenue streams directly to them can greatly improve their development prospects and help to overcome co-ordination failures. Two key components of an effective support framework are fiscal incentives and market creation mechanisms.

The problem of high risk investment in storage appraisal ahead of market demand can be resolved by capital grants and public funding n contributions to ‘market maker’ organisations. Operational support to provide greater certainty on income streams in an emerging market n Public engagement can be achieved through CO2 purchase guarantees or storage programme capacity payments by government. Funding for such payments can Knowledge generation n R&D on CO2 storage come from re-directing government subsidy or carbon-related and monitoring revenue flows rather than relying on the ‘trickle-down’ effect where is no clarity, as to how investors in CCS can share in a portion of this only the power generation/capture plant is remunerated or penalised value, or even how governments can capture the savings to society and the transport and storage operators must await payment from utilisation of their facilities. for wider, longer term decarbonisation that deployment of CCS can deliver. Clearly, to entice investors, the CCS business model needs Lack of a market in the provision of transport and storage services means it is harder for new entrants to value their projects and leads to be an equally attractive investment with other opportunities. to high barriers to market entry. An intervention that is particularly New metrics need to be found that effectively value CCS. The current relevant to this early stage of CCS development is that of creating a approach of valuing CCS simply on the cost of delivering low carbon market for leakage liability insurance (possibly by a similar pooling electricity on a £/MWh basis, or on marginal abatement cost, which arrangement to the nuclear industry) to lower the risks and insurance is then compared to other power generation technologies, is neither costs for storage owners. sufficient nor helpful for driving forward policies or action on CCS requires commercial innovation and infrastructure deployment.

Overcoming the market failures in CCS infrastructure investment

new business structures

There is limited experience in commercially structuring integrated CCS projects and infrastructure with different developers and A long term strategic vision for the development of essential CTS operators, and sector development will involve complex new value infrastructure based on rational and transparent criteria within an chains with novel business structures, risk allocation and holistic energy system context is currently absent from policy counterparty arrangements that can take many years to negotiate. manifestos across Europe. This has the effect of exposing CCS to One key barrier for CCS development is that there is currently no risk important policy risks and decision making biases that damage allocation template which can be readily adapted, so we are starting investment prospects. A change in how to initiate, decide and with a blank canvas on which we need to build a new risk matrix and implement policy in a much more reasoned and holistic way is associated commercial structure. essential if the significant investment by the private sector needed CCS comprises three very different businesses, leading to individual to deploy CCS is to materialise in time to lower total decarbonisation risk profiles that result in dissimilar investment business cases and costs on the pathway to 2050 emissions targets. development timelines – storage has long lead times compared to

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capture, which are much shorter, and transport is sandwiched A key to the success of delivering CCS as an essential component between the two. of the future low carbon system will be avoiding unco-ordinated deployment of full chain ‘demonstration’ power projects over the next Key questions for infrastructure developers are: decade that do little to promote a common transport infrastructure n If I develop a storage site will the capture capacity be built?; or the development of storage hubs that can contribute to economies n Will storage sites be available if I build the pipeline?; and of scale. Such ‘point to point’ CCS projects will suffer economically n Will the CO2 turn up even after I have built my storage site? and will not set up the lower cost options for future use of CCS in The interdependency of capture and storage means that confidence industrial processes, negative emissions applications and low carbon to invest in CO2 storage depends on clarity around the approach to transport fuels. rewarding investment in capture, and at the same time creates access risk for the power plant developer, as they will not build a capture plant without assurances of access to a transport network that can take the CO2 from the power station and deliver it to a storage site. The co-ordination failure for transport and storage leads to volume risk, the result of which is to discourage any speculative oversizing of pipes or speculative appraisal of larger storage sites to allow sharing with future projects.

The option value of CCS Early CCS projects are strategic enablers of lower cost decarbonisation, along with further economic value through job retention and creation, and the reduction of ‘subsidy’ spillovers such as environmental degradation, reduced air quality and human health issues. As such these projects have an option value over the future benefits they create. There is a level of CCS infrastructure capacity that will be unequivocally needed within 15-20 years in order to meet emissions targets and climate goals by the middle of the century. This is not a long time for infrastructure deployment requiring public and private partnerships and commercial, financial and business model innovation. Hence, the sooner we undertake no or low regrets investment in CCS infrastructure that creates the high value options for economy-wide decarbonisation, the more likely we are to lock-in the benefits in a much more cost effective way.

Therefore, additional government interventions are required that address the structural problem of CO 2 transport and storage infrastructure needing a development pathway in parallel to policies that support low carbon power generation or industrial processes. Critically, a distinction needs to be made with renewable power generation projects when formulating policy because, unlike power transmission infrastructure, there is no existing CO2 pipeline network for carbon capture projects to connect to. While individual countries around the North Sea Basin such as the UK, the Netherlands and Norway could create the early to middle stage CO2 transport and storage infrastructure for their own use, it is highly likely that at least some of the CO2 emissions from the major industrial regions of northern and eastern Europe will eventually need to be transported to safe storage sites in the North Sea. Future costs will be minimised if pan-European policies support an emergent smart design that can leverage scale and the legacy pathway for infrastructure deployment followed over the next 10-15 years. CO2 storage represents a realistic option for emissions abatement in low carbon industrial economies. In order to create infrastructure development options with inherent minimal or no regret for investors, the options must be ‘purchased’ by spending money ahead of market demand to generate sufficient understanding of the bankable storage resource and the risks associated with project delivery. At a European scale, existing funding mechanisms such as Horizon 2020 and the Connecting Europe Facility, along with the Strategic Energy Technology Plan, as they relate to CCS, are not currently designed with the intent of creating storage options or to optimise the value of expenditure to ‘buy’ such options within the context of a low carbon system. A portfolio of storage projects with different characteristics and risk profiles is less risky than each project separately. Furthermore, whilst storage potential can be optimised to geological attributes, lowest risk and lowest cost development will require managing a portfolio of storage appraisal options that may change with time.

The way forward

Bespoke, early targeted government investment in CO2 storage Delivering Europe’s aspirations for energy security, decarbon- appraisal combined with mechanisms to provide income support in isation and retention of its industries in a low carbon world means the face of an uncertain emerging market are critical prerequisites that complementary national and pan-European policies should for generating future option value and delivery of choices for private support a clear development pathway for CO2 transport and sector investment in industrial decarbonisation, low carbon fuels, and storage infrastructure. power generation.

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Carbon Capture and Storage (CCS) involves removing CO2 from the exhaust of power plants and industrial processes, transporting it via pipelines or ships, and then pumping it more than a kilometre underground into stable geological formations where it is stored permanently like the oil and natural gas accumulations of the North Sea. CCS is the only known way to decarbonise industries such as steel, cement and fertiliser production.

At the Crown Estate, we focus on the second and third stages of the process, providing leases for the transportation and storage of CO2 in areas of the 12-mile nautical seabed and continental shelf that we manage. Our work includes collaborating with industry and other stakeholders to understand the policies and mechanisms required to create a functioning market for CO2 storage over the next 15 years, how to ensure value for money options are created for deployment of infrastructure, and how to de-risk technical, commercial and legal aspects of permanent CO2 storage. Dr Ward Goldthorpe Programme Manager CCS The Crown Estate +44 (0)207 851 5311 [email protected] www.thecrownestate.co.uk/energy-and-infrastructure/carbon-capture-and-storage/

presents

MUSCLE PLASTICITY FEATURE PRESENTATION

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A quest into muscle plasticity By Professor Dr Martin Flück

University Hospital Balgrist Professor Martin Flück, PhD Laboratory for Muscle Plasticity Forchstrasse 340 CH-8008 Zurich, Switzerland Email: [email protected] Tel: +41 (0) 44 386 3791 Fax: +41 (0) 44 386 3799

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Introductory synopsis Soft tissues (muscle, tendon and ligaments) demonstrate a graded capacity to respond to the impact of external stimuli with molecular and cellular adjustments that improve their capacity to withstand the original impact. The diagnostic assessment of the adaptive potential of muscles provides indications on how bottlenecks in the current therapy of musculoskeletal defects can be overcome. The aim is to provide impetus for innovating surgical and rehabilitative approaches that maximise adaptive stimuli and processes for the handicapped individual. Muscle health is an economic factor

musculoskeletal disease, and more so their reversion with surgery and rehabilitation. This is done within the goal to identify biological bottlenecks, which opens venues for novel interventions that can halt muscle deconditioning and degeneration. Specific emphasis is put on the myocellular processes of rehabilitative and therapeutic measures after orthopaedic surgery. Towards this end we focus on patient groups which could benefit from an improvement in muscle function. Further, we assess transfer effects on musculoskeletal health and quality of life.

Plasticity is described as the ability of an organism to change its phenotype in response to changes in the environment. This has its place in body homeostasis, especially regarding the implication of skeletal muscle in bodily actions. Through its mechanical actions in locomotion, posture and speech, muscle facilitates interactions with the environment and affects energy expenditure. The reduction of muscles’ functional ability thus develops an important negative impact on our human capacity. Muscle weakness and associated poor fatigue resistance is a major challenge to modern western society.1, 2 It arises due to a reduction in the force-producing capacity of skeletal muscle with prolonged unloading due to inactivity (disuse), injury or disease. The consequent reduction in strength negatively affects physical fitness and mobility, which lowers the quality of life. Based on epidemiological evidence it is estimated that associated costs accrue to CHF 2,000 (~€1,906) per person per year (Fig. 1).3 Musculoskeletal health is thus an important financial substrate in western society.

Research approach and strategy The Laboratory for Muscle Plasticity at Balgrist deploys stateof-the-art methodology to optimise surgical approaches and rehabilitation based on genetic and physical constitution. The research is embedded in the Orthopaedic Hospital of the University of Zürich. By 2016 it will extend its patient-tailored biomedical research by integrating its research activities in a new research and development centre at Balgrist campus. The following sections highlight active areas and the scientific background of our research towards a personalised approach to musculoskeletal health.

Our research focus The strategic aim of the Laboratory for Muscle Plasticity at Balgrist University Hospital is to expose the molecular and cellular mechanisms underpinning muscle affections in clinical situations ranging from simple exertion-induced muscle soreness to tendon and ligament injury, and

Background Skeletal muscle function relies on the energy-dependent contraction of the embedded muscle cells (fibres). This is driven by the nerve-induced shortening of the contractile motor (sarcomere) (Fig. 2). This results in the capacity for force production, which is dictated by the composition and anatomy of skeletal muscle as this defines the underlying bioenergetics processes. This especially implicates the volume content of slow and fast contractile types of sarcomeres, mitochondria and capillaries. The interplay of these cellular variables define the maximal force (strength) and fatigue resistance of contraction. Both features are conditioned in a pulsatile manner by muscle use. This occurs because there is a natural degradation of muscle material due to the wear and tear of cellular structures. The wasted muscle material must be replaced through the activation of biosynthesis.

Fig. 1 Healthcare cost in 2011 of the seven major nontransmissive diseases

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A.

C.

B.

D. Fig. 2 Scheme of electrically paced muscle contraction

A) Illustration of the cellular organisation of skeletal muscle. Key elements of the cellular makeup are depicted. Adapted from Scientific American; B) Line graph of the relationship between force production and time after electric activation of fibre contraction. Below the shortening of sarcomeres with contraction is indicated; C) Microscopic image of slow (green) and fast (red) type fibres as detected in a cross-section of a muscle biopsy; D) Different force production and time lag between slow and fast muscle fibres

Repair mechanisms after rupture of the anterior cruciate ligament

Mechanical stress with weight-bearing contractions is a potent stimulus for the activation of these synthetic pathways. Energy flux is its most important modulator. The specific conditioning muscle through physiological factor is amply illustrated by the different outcome of strength-type versus endurance-type sports activities that involve a high load or high repetition number of contractions, respectively (also see Fig. 9).

As a joint, the knee exerts the important task of translating and potentialising forces being produced in the upper, large thigh muscles. This function compromises the lever arm of the femoro-patellar articulation (Fig. 3). Knee function is essential to counteract the forces of gravity through the extension of the knee. On the downside, however, the knee joint is exposed to particularly high rates of mechanical stress. This may damage anatomical structures that stabilise the knee joint if the resulting mechanical strain exceeds the typical safety factor for musculoskeletal tissues.

The underlying regulation involves the activation of a molecular programme that is embedded in our genes and which dictates the proteins to be made, i.e. expressed. The study of gene expression allows exposing the mechanistic relationship between the dose and duration of exercise and the resulting effect on muscle function. This knowledge is important to develop effective rehabilitative interventions that produce a functional outcome. Therapeutic measures based on information of muscle plasticity would thus offer considerable socioeconomic potential for musculoskeletal medicine. The application of this concept in the management of healthcare is underdeveloped today.

This is especially true for ligaments that operate in the lateral direction respective to the main plane of knee movement, such as the anterior cruciate ligament (ACL) and medial patellafemoral ligament (MPFL; Fig. 3). Their integrity is challenged when biomechanical vectors operate in transverse directions to the movement of the knee joint with intense physical activity in sports and during manual labour.

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This may result in the rupture of the challenged soft tissue and is a relatively frequent condition affecting one in 1,750 individuals each year.4 Because the rupture of ligaments renders the function of the affected knees unstable, repair of the damaged soft tissue is strongly indicated. This situation requires orthopaedic surgery followed by physical procedures to support and stimulate functional recovery of the reattached ligament and connected muscle; especially as they are weakened due to the prior injury and enhanced catabolism during unloading. Typically, recovery is initiated by resistive types of exercise. The dose-effect relationships for musculoskeletal adaptations with rehabilitation, which define the therapeutic success of orthopaedic surgery, are not well defined. Towards this end we pursue an investigation to define the time course of molecular and cellular adaptations in a major knee extensor muscle with exercise-based rehabilitation subsequent to surgical repair of the ruptured ACL. This study is inspired by our results showing that eccentric types of endurance activity, such as often seen with downhill sports activities (skiing), represent a potent intervention to strengthen the musculotendinous structures that operate on the knee joint. We expect that our study will provide important information as to the quality and effect size of the rehabilitation for the deconditioned muscle and knee function.

Fig. 3 Anatomy of the knee joint Drawing of relevant structures of the knee joint. The patellafemoral articulation is indicated. MGT: tendon of the medial gastrocnemius muscle; MCL: medial collateral ligament; POL: posterior oblique ligament; VMO: musculus vastus medialis obliquus

actions such as internal and external rotation as well as the abduction of the arm. Full or partial tears of rotator cuff tendons are a relatively frequent condition affecting a considerable portion of the population. Ageing-associated factors and injury represent the major cases of the disease. Thereby current numbers

Focus on rotator cuff disease

indicate that 40% of subjects above 60 years of age

The rotator cuff is a complex group of skeletal muscles which facilitate shoulder function (Fig. 4A). This involves important

demonstrate tears of the rotator cuff. This severely complicates daily activities as it renders the accentuation of

Fig. 4 Fatty atrophy with tears of the rotator cuff A) Drawing of the human rotator cuff with the indication of a rupture of supraspinatus tendon (redrawn from MendMeShop TM ©2011); coronary (B) and sagittal (C, D) images of an MRI scan of the shoulder at different depths of a patient at two time points after a full tear of the supraspinatus muscle tendon. The rate of retraction respective to the site of supraspinatus tendon attachment is indicated with a stippled, red arrow in panel B. Fat tissue (indicated by black arrows) appears in white above the darker contrast of muscle and bony tissue (white arrows); E) Sketch of the surgical procedure used to anchor the torn tendon stump to the bone

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Fig. 5 Degeneration of the rotator cuff after tendon release in a sheep model A) Sketch depicting the location of the infraspinatus muscle, which is targeted for tendon release via osteotomy of the greater tuberosity; B) Computed tomography image visualising the retraction of infraspinatus muscle (based on the detached bone chip) after tendon release; C, D) Microscopic images visualising the increased fat content of infraspinatus muscle in one sheep after 16 weeks of tendon release (D) compared to baseline levels (C). Fat was detected by Oil Red O staining (red) of cross-sections from the bioptic samples. Single muscle fibres can be identified based on the contrast provided by the sarcolemma. Bar indicates 500 micrometres

the upper extremity in one or more direction hard to impossible. If left untreated, shoulder function is permanently affected because the detached muscle degenerates by the shrinkage of muscle cells and their conversion into fat tissue (Fig. 4B-D). Eventually, this limits the kinematics of respective joints, which has the ultimate consequence of the degeneration of the glenohumeral joint. At this point no other option remains than to surgically replace the joint with an expensive endoprosthesis to reinstate limb function. Surgical interventions aimed at repairing the affected shoulder muscle involve the reattachment of the ruptured tendon to the bone via an anchor (Fig. 4E). Thereby the prevention of adipogenic and atrophic processes in the detached muscle is a priority to warrant optimal surgical repair of the ruptured muscletendon unit.

contribution of heritable factors to the healing of the reattached rotator cuff. The aim is to reintegrate the knowledge gathered from our research into personalised surgical approaches and therapies that more efficiently prevent detractions in shoulder muscle function in critical responder groups (Fig. 6).

Maximising the stimulus of rehabilitation It is firmly established that repeated exercise can improve muscle strength and metabolic fitness. It is, however, less appreciated that certain individuals demonstrate a much lower degree of response to matched exercise or demonstrate a handicap to perform at a sufficiently high level to show functional adaptations. A bodily handicap is specifically indicated for patients with cardiovascular disease. Incidentally, these subjects could profit considerably from an improvement in muscle fitness as this counteracts the looming risk of developing Type 2 diabetes and associated systemic consequences. This defect typically consists of the incapacity of the cardiovascular patient to allocate metabolic resources to exercising cardiac and skeletal muscle with an increase in demand.

Towards improving the therapy of rotator cuff disease we investigate the time course of molecular and cellular alterations in animal models of the ruptured rotator cuff (Fig. 5). The aim is to map the mechano-regulated pathobiological process and risk factors of muscle degeneration, which contribute to the healing of the muscle-tendon complex. Specific emphasis is put on testing the effectiveness of pharmacological compounds targeting the degradation of the structural anchors of the contractile apparatus in muscle fibres.

Towards the alleviation of metabolic bottlenecks we have started a clinical investigation in which we test the suitability of special forms of cardiovascular exercise on a soft robotic device (Fig. 7). This tool allows enhancing mechanical loading to exercising muscle at a lower metabolic cost in an individual fashion for both legs. We hope this will potentially boost

The knowledge is integrated into a clinical trial in which we characterise morphological and genetic biomarkers of the healing response of rotator cuff muscle after surgical repair of the detached tendon. This is motivated by the reported

Fig. 6 Research approach general question

Basic

mechanistic concept

specific question

Pre-clinical

Scheme of the conceptual path of the research strategy of our integrated studies towards improved treatment of the orthopaedic patient

improve treatment

test effica

Clinical

test applicability

Treatment

research pipeline

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Fig. 7 Exercise adaptation A) Mechanical and metabolic characteristics of eccentric and concentric forms of exercise; B) Exercise on a soft-robotic device allowing enhanced mechanical loading of exercising muscle in an individual fashion for both legs

understanding exists on how to tailor effective countermeasures to prevent muscle atrophy, especially regarding the use of physiotherapy.5

improvements in muscle power as it allows subjects with lower fitness to perform the training sessions.

Gene therapy to accelerate muscle healing after an Achilles tendon rupture

This is important because the healing period requires time and is often not productively invested. This leads to financial and social impact on the affected individual, who is often months away from work. Towards this goal we have initiated studies to determine the effectiveness of a gene therapeutic approach to halt muscle atrophy. The intervention is directed to boost mechano-sensitive biochemical pathways that control muscle size and muscle force (Fig. 8). The long term goal would be to extend successful approaches into a clinical trial.

Achilles tendons are submitted to forces above sixfold of the body weight. Consequently, injury of the Achilles tendon may occur in consequence of short physical activities that involve a large degree of gravitational loading. The injuries are relatively common, affecting an estimated seven per 100,000 subjects in the general population.5 Rapid reattachment of the tendon stump is a requirement to prevent irreversible degeneration of the ruptured soft tissue and wasting of the concerned muscle due to reduced mechanical impact upon tendon rupture. The concomitant deconditioning of muscle reduces mobility and consequently the quality of life.

Exercise genes that predict the response It is an appreciated fact that considerable variability exists in the population regarding physical strength and endurance as well as their conditioning by training. This has evident implications for rehabilitative interventions aimed at

Despite high quality literature on how to diagnose and treat Achilles tendon rupture surgically, limited mechanistic

Fig. 8 Gene therapy A) Composite figure depicting delivery of the mechano-sensor focal adhesion kinase (FAK) into a lower extremity muscle of a rat. A gene vector is injected into the muscle and uptake is stimulated by electropulsing; B, C) Microscopic visualising the amount of FAK (orange) in muscle fibres of a muscle being injected with a vector that carries the FAK gene or an empty control; D) Consequent effect of forced FAK expression (red) versus empty control (blue) on specific force (in Newton per square metre of the muscle cross-section). Note the higher force in the muscle with forces FAK expression

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Fig. 9 Gene-based personalisation of exercise rehabilitation Composite figure emphasising interaction effects of nature and nurture on the muscle phenotype. Natural constitution and conditioning by environmental stimuli activate a genomic programme that instructs plastic changes of the muscle phenotype. It involves the production of diffusible gene messengers that act as actuators of performance by instructing the making of proteins. Polymorphisms in multiple fitness genes are understood to influence gains in endurance and strength performance by affecting gene expression. ACE, angiotensinconverting enzyme; EPO-R, erythropoietin receptor; HIF-1α, hypoxia-induced factor 1-alpha; MSTN, myostatin; VEGF, vascular endothelial growth factor; PGC-1α, peroxisome proliferatoractivated receptor gamma coactivator 1-alpha

re-establishing musculoskeletal function. In a last, larger research project, we have therefore initiated studies into the mechanism underlying variability in muscle plasticity. In this context, we assess the extent to which muscular adaptations are associated with genomic determinants. We thereby focus on selected gene polymorphisms which affect the muscle phenotype in animals and which encode regulators of muscle plasticity (Fig. 9). The aim being to disentangle the mechanism underlying the responsiveness in healthy subjects to mechanical (i.e. strength-type) and metabolic (i.e. endurance-type) stimuli interventions and to translate this knowledge to the patient.

patient (Fig. 10). Towards this end we call for interactions with academic and industrial partners who are interested in developing our research areas in a joint venture.

References: 1. Booth F W, Chakravarthy M V, Gordon S E, Spangenburg E E (2002): Waging war on physical inactivity: using modern molecular ammunition against an ancient enemy. J Appl Physiol 93(1): 3-30 2. Dean E (2009): Physical therapy in the 21st century (Part I): toward practice informed by epidemiology and the crisis of lifestyle conditions. Physiother Theory Pract 25(5-6): 330-53 3. (2014): Statistical Yearbook of Switzerland, Swiss Federal Statistical Office, NZZ Verlag, ISBN 978-3-03823-874-4 4. Griffin L Y (2008): Noncontact Anterior Cruciate Ligament Injuries: Risk factors and prevention strategies, Journal of the American Academy of Orthopaedic Surgeons

Outlook

8: 141-150

The Laboratory for Muscle Plasticity will continue research in

5. Glazebrook M A (March 2010): New guidelines to address acute Achilles tendon ruptures, AAOS Now (www.aaos.org/news/aaosnow/mar10/research1.asp)

this area at Balgrist campus, which provides a unique combination of dry and wet labs in an open space landscape

Additional information:

that fosters interactions between academic, industrial and

Webpages: http://www.balgrist.ch/en/Home/Research-andEducation/Orthopaedics/Muskelplastizitaet.aspx

medical partners on questions driven by the orthopaedic

Fig. 10 Virtual view of the Balgrist campus. More information is available at www.balgristcampus.ch/en/ for further information consult: https://youtu.be/ooHTAVgZ4I0

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