Eu research 06 digital mag

EU Research Vol: 2014 Issue 2

SUSTAINABLE DEVELOPMENT

Health, Energy, Technology

HORIZON 2020 BUDGET WARNING

NEW CANCER TREATMENT US researchers on Chemotherapy Alternative

Mรกire Geoghegan-Quinn Progress must be made on Europe-Wide research Follow EU Research on www.twitter.com/EU_RESEARCH

Editor’s No Y ou could say Albert Einstein was our first pop-star scientist.

Early in the 20th century, his two theories of relativity, which proved our perception of the world was far from reality, kicked off his catapult to fame.

When a photograph of the 1919 solar eclipse proved that light could bend, as Einstein predicted, that fame only grew. Few in the general public understood his scientific ideas, but they knew they were witnessing brilliance at work.

Einstein did things his way: Who renounces his country’s citizenship in protest at age 17? Who works six days a week at a patent office while writing four seminal papers that change the field of physics in one year? Who is so sure he’ll win the Nobel that he includes the presumed prize money in negotiations with his estranged wife? Who eschews socks when meeting the president at the White House?

Martin Brodie runs his own media and communications company, after a career in journalism and public relations. After starting his journalist career on the Bristol Evening Post , Martin joined Rolls-Royce plc in Bristol in1980 and held a number of senior communications positions in the defence and civil aerospace businesses before moving to the group’s corporate headquarters in 1991. From then until his retirement in 2009, Martin was responsible for much of the Group’s international communications and was also involved in UK national media relations throughout this period.

His last role was Head of Communications – Europe Middle East and Africa.

His previous roles also included responsibility for engineering and technology, during which he was editor of the first Rolls-Royce environment report, Powering a Better World.

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Consider this: At just 26, Einstein published what are deemed his most important scientific works, establishing that mass, energy, speed and distance are crucial to understanding the universe’s rules. His theories of 1905 are the bedrock of modern physics.

Today, his legacy is evident in everyday life, far outside the labs of physicists — from cell phones and satellite communications to nuclear power plants to medical scanning devices. And Einstein’s superstar status lives on, more than 50 years after his death.

As Einstein once said “If you can’t explain it simply, you don’t understand it well enough”. Throughout this edition of EU Research myself and my team have tried to simply explain what the next generation of researchers and scientists who are following in Einstein’s footsteps are achieving. Who knows, maybe the next superstar is just a few pages away.

Hope you enjoy the issue.

Martin Brodie

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Contents 22 Beat-Health

4 Research News

EU Research’s Richard Davey takes a look at current events in the scientific news

10 HCC Collaborative Research

Jose L. Contreras-Vidal, Hugh Roy and Lillie Cranz Cullen tell us about how incorporating sensory-motor feedback in neuroprosthetic limbs will offer users a greater degree of control and movement

13 HDHL CSA

Dr Pamela Byrne, Professor Hannelore Daniel and Dr Beate Kettlitz of the European led Joint Programming Initiative Healthy Diet for a Healthy Life explain how this initiative will improve our understanding of the complex relationship between diet, exercise and health

16 Direct The IMI-DIRECT project’s work to identify biomarkers in order to define sub-types of the condition could help to improve both diagnosis and treatment of the condition, as project coordinator Dr Hartmut Rütten explains

19 Continuing Development

of PPCM Vaginal Contraceptive Microbicide Mary Frost Weitzel, CEO and President of Yaso Biotech, tells us about her company’s work in developing products that provide protection for women against STDs and prevent unplanned pregnancies

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The strong link between music and movement is used to boost sporting performance and aid the rehabilitation of Parkinson’s patients. The BeatHealth project aims to exploit this close link by creating an intelligent technological architecture, as Professor Benoît Bardy and Professor Simone Dalla Bella explain

26 AmbuLung The AmbuLung project is developing a miniaturised bioartificial lung which will offer an alternative therapy to avoid mechanical ventilation and give the suffering lung time to heal, as Jörg Schneider and Esther Novosel explain

29 Sublima The SUBLIMA project aims to combine time-of-flight PET and MR technology to provide concurrent molecular and anatomical imaging, leading to significant improvements in image quality as well as enabling new possibilities for imaging molecular processes in-vivo, as Dr Dennis Schaart explains

32 National Institute for Health and Clinical Excellence

The UK’s National Institute for Clinical Excellence has drawn up draft guidelines recommending that people at a 10 per cent or higher risk of developing cardiovascular disease should be eligible for treatment with statins, yet the proposal has drawn criticism. We take a look at the issues surrounding the use of the cholesterol-lowering drugs

36 EuroWestNile

West Nile Virus was long considered to be only a minor threat to human health, until a series of outbreaks in the ‘90s. We spoke to Dr Annapaola Rizzoli and Dr Miguel Angel JiménezClavero of the EuroWestNile project about the re-emergence of the virus in Europe and neighbouring countries

39 Pulmostent Endobronchial stenting is a proven therapy in the treatment of lung cancer, yet current stents suffer from some significant drawbacks.

The pioneering researchers at the PulmoStent project are currently developing a new kind of stent based on a combination of stent technologies and tissue engineering, as Professor Stefan Jockenhoevel explains

42 SYNINTER

We speak to Dr Kheya Sengupta, director of the SYNINTER project about her research into cell adhesion and how it could lead to earlier diagnosis of immune deficiency diseases

45 Gasotransmitters ‘Gasotransmitters’, are associated with a number of beneficial biological properties, but they can have adverse effects on health in excess amounts.

The European Network on Gasotransmitters aims to boost the impact of European research in this field, as Professor Andreas Papapetropoulos explains

EU Research

48 Algebraic Geometric

Approaches to Biological Complexity

Researchers need sophisticated mathematical methods to understand how such complex networks process information, as Dr Jeremy Gunawardena, Associate Professor at Harvard Medical School explains

51 Disaster Bioethics Ethical dilemmas frequently arise in the aftermath of natural disasters, yet few resources are specifically available to help guide people on the ground in their decision-making. We spoke to Dr Dónal O’Mathúna, about the Disaster Bioethics project’s work in investigating the types of ethical issues that arise and how people respond

54 Perspect H2O

The world has access to only a finite supply of fossil fuels, making the development of renewable sources of energy a research priority. Photocatalytic systems hold real potential in these terms, say Benjamin Dietzek and Vincent Artero of the PERSPECT H2O COSTAction, who tell us about their research into supramolecular photocatalytic water-splitting

56 The Emergence of

Southern Multinationals and their Impact on Europe Professor Dale Southerton of the ESRC, Defra and Scottish Government funded Sustainable Practices Research Group tells us about their research into how social practices emerge and how they can be changed

59 EUBis There is a growing recognition that the huge amounts of food waste could be a valuable source of important chemicals, an issue that Professor James Clark and his colleagues in the EUBis COST Action network are currently investigating

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62 Mathematical Optimisation

Mathematical optimisation research has not always been coordinated effectively. A new COST Action aims to address this issue by bringing together researchers from different disciplines to exchange results and share information, as Professor Andrea Lodi explains

63 FluMaBack

We spoke to Dr Mitja Mori of the FluMaBack project about their work to improve the design and operation of balance of plant (BoP) components in back up fuel cell systems, which enable stable, secure and efficient operation of the core components, the fuel cells

66 Phototech The PHOTOTECH project is investigating the design and production of biosensors and bioenergy based on photosynthetic activity, work which could have a significant social impact, as Dr Giuseppina Rea explains

69 BETTY

Dr Simon Gay tells us how COST Action IC1201 (BETTY) aims to use behavioural type theory as a basis for new programming languages and software development methods

72 PLEASURE

We spoke to Bianca Pop, dissemination manager of the PLEASURE project about their unique new approach to address this challenge from the processing side instead of using subsitutes or replacers

EDITORIAL Managing Editor Martin Brodie info@euresearcher.com Deputy Editor Patrick Truss patrick@euresearcher.com Deputy Editor Richard Davey rich@euresearcher.com Science Writer Holly Cave www.hollycave.co.uk Acquisitions Editor Elizabeth Sparks info@euresearcher.com PRODUCTION Production Manager Jenny O’Neill jenny@euresearcher.com Production Assistant Tim Smith info@euresearcher.com Art Director Daniel Hall design@euresearcher.com Design Manager David Patten design@euresearcher.com Illustrator Martin Carr mary@twocatsintheyard.co.uk PUBLISHING Managing Director Edward Taberner etaberner@euresearcher.com Scientific Director Dr Peter Taberner info@euresearcher.com Office Manager Janis Beazley info@euresearcher.com Finance Manager Adrian Hawthorne info@euresearcher.com Account Manager Jane Tareen jane@euresearcher.com

EU Research Blazon Publishing and Media Ltd 131 Lydney Road, Bristol, BS10 5JR, United Kingdom T: +44 (0)207 193 9820 F: +44 (0)117 9244 022 E: info@euresearcher.com www.euresearcher.com © Blazon Publishing June 2010

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RESEARCH

NEWS

EU Research’s Richard Davey takes a look at current events in the scientific news

Scotland to be research leader with new ‘sensitised’ robotics centre Creating a new generation of robots that can see, react, learn and adapt to the world around them with minimal or no human control will be the main thrust of a new robotics centre which opens in Edinburgh tomorrow.

Sethu Vijayakumar, Professor of Robotics at Edinburgh University and co-director of the new Edinburgh Centre for Robotics, said the facility will become a hub for robotics in Scotland and help to spawn commercial spin-offs across a wide range of highgrowth sectors from the oil and gas industry to renewable energy, healthcare, assisted living, transport, manufacturing, nuclear, digital media and education. The new centre brings together academics from Edinburgh University’s informatics and engineering departments with Heriot-Watt University’s department of mathematical and computer sciences and department of engineering and physical sciences.

Intended ground breaking work will include developing “intelligent” or “sensitised” robots that can make autonomous decisions themselves and operate in disaster zones where it would be dangerous for human beings - such as the site of the Fukushima nuclear catastrophe in Japan in 2011. Other examples of research to be undertaken by the new centre include developing robots that can carry out underwater surveys of offshore pipelines without being joined to the surface by umbilical cables and giving replacement prosthetic hands - such as those made by the Scottish firm Touch Bionics - a sense of touch. It is estimated that, by 2025, such advanced robotic and autonomous systems in non-military sectors will be worth around £70 billion a year to the global economy.

Both universities have international reputations for their robotics research. Heriot-Watt is well known for its work on subsea robots, which are extensively used in the offshore oil and gas industry.

Edinburgh University enjoys a worldwide reputation for its research on prosthetics, humanoid robots and machine-learning.

Vijayakumar said that, by bringing together 50 researchers from 16 research groups together with more than 30 industrial companies, the multi-disciplinary centre will combine the strengths of both

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universities’ research expertise to create a whole that is larger than the sum of its parts. Last year, robotics was selected by the UK Government as one of the eight most important sectors that will underpin the nation’s industrial strategy. As part of that push the new centre will, said Vijayakumar, provide the robotics sector with highly skilled researchers whose work will help to launch new products, create jobs and boost economic growth.

The new centre has benefited from £5.7 million in funding from the Engineering and Physical Sciences Funding Council which will allow a dozen students per year to embark on doctoral studies with final degrees awarded jointly by both universities. Further support for the centre, worth £9m, will come from commercial sponsors such as Balfour Beatty, BP, Schlumberger, BAE Systems, Honda, Touch Bionics and Network Rail. This will allow students to work in commercial research labs and gain exposure to “real world problems”, Vijayakumar added.

The creation of the joint centre, which will be housed in existing buildings in both universities, follows the allocation of £7.2m of public funding to pay for state-of-the-art hightech equipment for the centre. Some of the equipment has been installed while the purchase of other items, such as a humanoid robot from Nasa, is still being negotiated. “Most of this is not stuff that we can simply get off the shelf - it is highly specialised. unique equipment,” Vijayakumar said. He added that the centre will attract more robotics students to study in Edinburgh as they will be able to attend classes at both universities and have the flexibility to research crossdisciplinary fields not available elsewhere.

Speaking at the launch of a UK strategy to stimulate growth in robotics in the summer, Professor David Lane of Heriot-Watt University - the centre’s other co-director - said the UK must “act quickly” if it doesn’t want to get left behind by countries such as Japan, Korea and the USA. “We need to provide a business environment in the UK that is geared towards helping robotic and autonomous technologies out of the lab and into the marketplace,” he said. “We believe the UK could achieve 10% of the global market share by 2025.”

EU Research

Commissioner urges member states to progress on Europe-wide research area Marie Geoghegan-Quinn has announced it is now up to EU member states to put in reform to necessitate implementation of the European Research Area The European Commission report says that “good progress” has been made to date in setting the foundations to create an environment where researchers and scientific knowledge can flow freely between European countries. But now countries need to do their part and better align their national research efforts with those of the EU, for example, the report says.

increasing competitive project-based funding in some countries and accelerating the pace of change in gender equality in research.

Countries will now put together roadmaps that will outline the next steps that they will take towards implementing the ERA. These will be published by mid2015.

The latest progress report analyses how far along countries are in preparing the ground for a European Research Area. It finds that research organisations and institutions, and funders, show strong support for the creation of ERA. Máire Geoghegan-Quinn, European commissioner for research, innovation and science, said: “We have made good progress on the European Research Area in recent years. It is now up to member states and research organisations to make good on their commitments and put in place the necessary reforms.”

She added: “In particular, national and EU research efforts need to be much more closely aligned if we are to increase impact at EU level.”

Other areas that need more work, according to the report, include

Make sure you vist us on our website www.euresearcher.com. For more information regarding any of your dissemination needs please contact us on info@euresearcher.com

Protein-therapy alternative to Chemotherapy Researchers in the US have shown that an alternative Cancer treatment promising signs in pre-clinical experiments.

As per the latest research findings, a protein therapy may act as an effective and safe alternative treatment option to chemotherapy, currently used treatment process to slow or stop progression of cancer. This experimental therapy has shown significant results in stopping the progression of breast and ovarian cancers in mice. This method acts by disrupting the process that causes the tumor cells to migrate from its original site and spread to various parts of the body through blood. By inhibiting the metastasis of cancer cells, this protein therapy in turn prevents the growth of cancerous cells elsewhere in the body.

Amato Giaccia, co-researcher and a professor at the Stanford University in the US said, ‘ This protein therapy showed effective and non-toxic results in pre-clinical experiments, which are quite promising. This approach could open doors to a new and effective treatment of cancer. The current treatment options of cancer involve chemotherapy that is targeted to slow or stop metastasis, but unfortunately this is not very effective in addition to causing severe side-effects on the patients.

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European Commission support maritime transport to boost maritime research The commission has stated that their investment in shipping can have a direct benefit on maritime research with benefits for other sectors such as climate change and medicine The role of maritime transport in the EU is considerable.

Statistics speak for themselves: almost 90% of the EU external freight trade is seaborne, short sea shipping represents 40% of intra-EU exchanges in terms of ton-kilometers, and over 400 million passengers embark and disembark in European ports every year.

However the sector is also faced with serious challenges. The Costa Concordia disaster in 2012 proved how safety should be a key focus of policy-makers, businesses and engineers over the years to come, while minimizing the environmental impact of maritime transport is high on the EU list of priorities.

EU researchers – notably those supported under FP7 and Horizon 2020 – will have a key role to play in taking on these challenges. But if science can improve maritime transport in the EU, the opposite is also true: our seas and oceans are overflowed with resources that hold potential for a large spectrum of sectors. These include health and medicine, climate change observation, research around biological evolution, energy or even cosmetics. To make the most of this potential, scientists need efficient maritime transport solutions equipped with groundbreaking technologies.

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GOAT-TSE-FREE

Enhancing resistance against TSEs Transmissible spongiform encephalothies, also known as prion diseases, remain a threat to both animal and human health. We spoke to Dr Jan Langeveld of the GOAT-TSE-FREE project about their research into the susceptibility of goats to certain types of TSEs, work which could boost efforts to breed for resistance against the diseases A group of diseases that affect the brain and nervous system of animals and humans, transmissible spongiform encephalothies (TSEs) are a major health concern. The BSE crisis in the UK is perhaps the most prominent example of public health concern around TSEs, but they can also affect other animals as well, an area the GOAT-TSE-FREE project is addressing.

“The project follows up a very large European study which looked into how susceptible goats are to diseases like scrapie and BSE. We are trying to strengthen the scientific basis of our knowledge in this area,” explains Dr Jan Langeveld, the project’s scientific coordinator. The project is also working with goat farmers and breeders to investigate and enhance resistance to these diseases. “Over the last ten years we’ve found that it is possible to breed for resistance to TSEs. You can also breed for resistance to scrapie – which we can find in goats – while we have also looked at resistance to BSE,” continues Dr Langeveld.

Breeding for resistance These different types of TSEs are fairly rare in goats, but the effects of even a single case can be extremely serious. The disease occurs every year in some parts of Southern Europe, and under current rules all the goats in a herd have to be culled if they aren’t resistant, underlining the importance of the research in Dr Langeveld’s international team. “If we can prevent that culling by breeding for resistance then we have gained something. We’ve gained more security for farmers, and also in the food chain,” he points out.

Only one variant form of a specific gene is needed to carry resistance to TSEs. “For this disease you can just breed for one gene. If you find that variant in the population, even in only a small proportion of goats, then you can use these goats to breed for more carriers. The more carriers the lower the disease transmission,” explains Dr Langeveld.

Human Stomach grown from Stem Cells Miniature stomachs – gastric organoids – could help in the study of diseases such as crohns and colitis and could be used in future to repair patients’ stomachs.

Scientists have grown miniature human stomachs from stem cells as a way of studying gastric diseases such as ulcers and stomach cancer and in the future creating tissue to repair patients’ stomachs.

The mini-stomachs are grown in petri dishes from stem cells.

Fully formed, they are the size of a pea and shaped like a rugby ball. They are hollow with an interior lining that is folded into glands and pits like a real stomach.

Crucially, the researchers found that the miniature stomachs, known as gastric organoids, respond to infection very much like ordinary human stomachs.

“There hasn’t been any good way to study human stomach disease before because animals just don’t get the same diseases,” said James Wells, director of the Pluripotent Stem Cell Facility, Cincinnati Children’s Hospital Medical Center, who led the research which is published in Nature.

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(Towards breeding of goats for genetically determined TSEs resistance.)

Dr Jan P. M. Langeveld, Central Veterinary Institute, part of Wageningen UR, Houtribweg 39, 8221RA, Lelystad The Netherlands.

T: +31 (0)320-237217 E: jan.langeveld@wur.nl W: www.goattse.eu W: www.wageningenur.nl/cvi W: http://www.veterinaryresearch.org/ Central Veterinary Institute, part of Stichting Dienst Landbouwkundig Onderzoek (DLO), is registered at the Dutch Chamber of Commerce with number 09098104. The institute is NEN-EN-ISO 9001:2008 certified.

Jan Langeveld, PhD is a prion scientist at Central Veterinary Institute of WageningenUR at Lelystad Netherlands. He is leading this broad European project together with the three DVMs: CVI colleague Lucien van Keulen, Pier Luigi Acutis at IZSTO Torino, and Cristina Acin at UNIZAR Zaragoza.

From left to right: Pier Luigi Acutis, Jan Langeveld, Cristina Acin and Lucien van Keulen.

Chinese Research Funding up for examination Corruption and waste prompt officials to announce that by 2017, the federal science funding programs will be eliminated, replaced by a uniform platform.

According to Nature News, the Chinese government’s announcement of the reforms indicates that wastefulness and mismanagement has led to inefficient use of research funds in the country. Currently, 30 different government departments oversee some 100 competitive grant schemes. The new plan was drafted by the Ministry of Finance and the Ministry of Science and Technology.

The Chinese government spent 236 billion yuan renminbi (about $38.5 billion) in 2013, 60 percent of which was allocated through competitive funding.

They have now announced a plan to reshape federal science funding, including two programs that disburse large grants to researchers on a competitive basis. China’s 863 and 973 programs will be eliminated by 2017, replaced with “independent institutes” that will handle such activities. “China will reform state research fund management, delegating power to independent institutes in a bid to curb academic corruption and sharpen innovation,” according to Xinhua, the staterun newswire, quoted by ScienceInsider. “The government will no longer be in direct charge of research projects.”

EU Research

HORIZON 2020 Budget Warning The European University Association has warned negotiations on the European budget could result in cuts to Horizon 2020 The EUA says it understands that draft budget proposals for 2015 recommend reducing payments for research and innovation. This is out of step with the “political rhetoric” that puts research and development at the heart of Europe’s competitiveness, the EUA said. The council of the EU’s permanent representatives committee agreed its position on the EU commission’s draft 2015 budget in July.

Negotiations between the council, EU parliament and commission on a final version of the budget are due to begin in September.

Any proposed cuts would affect the Horizon 2020 framework programme, the EUA said. Lesley Wilson, secretary general of the EUA, said: “At a time when the European commission has highlighted a sharp increase in the level of competition in the Horizon 2020 funding calls, it is crucial that cuts are not made to the proposed research and innovation budgets. The frequently stated political rhetoric which places emphasis on the central role of research and education in Europe’s future competitiveness must be backed up by commitment and action from the EU institutions.”

MEPs warned earlier this year that the council had a habit of reducing funding for future programmes to pay outstanding bills rolled over from previous years. They added that there was a shortage of funds to meet commission payments due in 2014 and that research projects and the Erasmus + programme may have to wait for money. EU funding has become an increasingly important source of income for many universities in Europe, which raises concerns about this trend, EUA said.

UK minister says research ‘at risk’ from EU data protection laws UK government minister states red tape is holding up vital clinical trials, while new European data protection laws risk preventing medical records being gathered for research George Freeman, who was appointed as the UK’s first life sciences minister last July, said in an interview with The Daily Telegraph that medical advancements such as ‘The 100,000 Genome Project’, which aims to sequence tens of thousands of genomes to map the genetic profile of rare diseases and cancers, are being put at risk by “hostile” European regulation.

Freeman said: “There are a number of areas where the UK and the National Health Service (NHS) is pioneering but EU regulation is in danger of holding back biomedical advances, in regenerative medicine, stem cells, genetics and data.”

The European Commission is considering a range of directives “which would basically risk making Europe, and therefore Britain in Europe, an increasingly unattractive place to do modern medicine and science and that would be a disaster for Britain and NHS patients”, Freeman said. “We need the EU to put in a place a supportive regulatory framework to maximise benefits for patients and taxpayers. This is an area the UK leads and I will be reaching out to the European governments and to the Commission to highlight the work Britain is doing to shape this new landscape.”

Areas that risk being “harmed” by regulation include the UK’s new ‘Care.Data’ scheme, Freeman said. The scheme will see the medical records of all NHS patients transferred to a single central database so they can be accessed by research institutions.

Research funding crisis causes protest rally by European scientists A growing number of scientists throughout Europe, frustrated with inadequate funding for research and a lack of jobs, are banding together to demand that policymakers at national and EU levels take action An open letter outlining their grievances has been published online accompanied by a petition, which as of Friday had been signed by nearly 12,000 scientists.

The letter, drafted by activists from France, Portugal, the UK, Germany, Italy and Greece, states: ‘The national policymakers of an increasing number of member states, along with European leaders, have completely lost touch with the reality of research.

They have chosen to ignore the crucial contribution of a strong research sector to the economy, particularly needed in the countries more severely hit by the economic crisis. Instead, they have imposed drastic budget cuts in research and development

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that make these countries more vulnerable in the mid- and longterm to future economic crises.’

On 26 September, Spanish scientists marched in Madrid demanding reform. Carlos Andradas, professor of mathematics at Complutense University of Madrid, Spain, and president of the Confederation of Spanish Scientific Societies who was one of the organisers of the march stated ‘So far the movement comes mainly from southern European scientists, because we share the situation that our governments are forced by the EU to cut public expenses, and that affects especially our research and development budgets,’ he says. ‘I am sure that scientists from the northern countries will support the initiative.’

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PCFCs’ Proof of Concept Started on the 1 of December 2011, METPROCELL is a 3 year collaborative project funded by the Fuel Cell and Hydrogen Joint Undertaking (FCH JU grant agreement n°277916) where 8 partners work together to develop a new generation of intermediate temperature fuel cells based on the Proton Conducting Fuel Cell technology. Following a complementary approach, METPROCELL aims to develop both anode and metal supported PCFCs by using new electrolytes and electrode materials and implementing conventional as well as new alternative fabrication routes.

Moreover, METPROCELL will bring the proof of concept of these novel PCFCs by the set-up and validation of prototype like stacks in two relevant industrial power systems, namely gas/ micro CHP and APU.

Inset - Lab-scale PCFC

st

METPROCELL has delivered already well performing electrode/electrolyte materials dedicated to an operating temperature range between 550-650°C. Based on an anode supported cell configuration (Ni-BCZY / BCZYYb / BSCF –BCZYYb), maximal power densities of 420 and 532 mW.cm-2 have been demonstrated under lab conditions at 600°C and 650°C, respectively (air electrode: air / fuel electrode: H2 with 3% vol. H2O).

Innovative fabrication routes and materials for METal and anode supported PROton conducting fuel CELLs (METPROCELL) Dr.-Ing. María Parco TECNALIA, Parque Tecnológico de San Sebastián Mikeletegi Pasealekua, 2 E-20009 Donostia - San Sebastián – Gipuzkoa (Spain) maria.parco@tecnalia.com www.tecnalia.com http://www.metprocell.eu

Fracture surface of anode supported PCFC (Ni-BCZY / BCZYYb / BSCF –BCZYYb)

On the journey to the development of well performing metal supported PCFSc, a first milestone has been successfully reached delivering low cost ferritic stainless steels (Iron Chromium steels) porous supports with Thermal Expansion Coefficients (TEC) close to that of the electrolytes (10•10-6 K-1) and improved corrosion resistance under humid H2 at 600°C (oxide thickness below 1 µm after 1000 hours of operation). Additionally, promising results have been achieved towards the development of well-structured electrodes and dense/thin electrolyte layers by means of plasma (APS) and High Velocity Oxy-Fuel (HVOF) spray technologies.

Research partners: TECNALIA RESEARCH & INNOVATION • European Institute for Energy Research • Centre National de la Recherche Scientifique • Technical University of Denmark - DTU Industrial partners : Ceramic Powder Technology AS – (SME) • Marion Technologies – (SME) • TOPSOE FUEL CELL A/S – (Industry) • Höganäs AB –(Industry)

Dr.-Ing. Maria Parco, obtained the doctor degree at the RWTH Aachen.

Project Manager at TECNALIA since 2005. Since 1998, she has been involved in several I+D+I projects related to the thermal spray field.

New prospects for research funding in Middle East North Africa Funding for research and ICT start-uos is greatly increasing in MENA region The MENA region is “home to one of the highest unemployment rates globally” and creating an innovation / startup dynamic is incredibly important. Wamda, a platform to empower entrepreneurs in the Middle East / North Africa (MENA), has published a study on the funding / entrepreneur eco-system in the region.

The very good news is that startup funding is growing in the MENA countries with growth expected to accelerate in coming years. In fact this study, compared to a previous study back in 2009, showed over 3 times the companies receiving investment. The not so good news is there is still a long way to go but then you could say the same of just about any country on the globe.

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The most prominent areas of entrepreneurism is Ecommerce / online, software and then telecom and mobile. So mainly in the digital realm. Interestingly most funded companies are young and run by male entrepreneurs but a good number are founded by females (22%) with 38% having at least one female founder.

While there are very encouraging signs and growth in access to capital the study acknowledges there is much work to be done.

The report states that funders see a need for entrepreneurs needing better strategic planning and financial literacy skills. It was also noted that 70% of the entrepreneurs indicated that finding the right talent was very challenging when building a team. For any follower of the region this has much potential but there is still much work to be done for the MENA countries.

EU Research

Open Letter to Governments outlines the importance of basic research Nearly 5000 scientists have signed the letter, which also warns of a brain drain “from the South to the North and from Europe to beyond.”

Many of the funding and hiring cuts in the southern countries have been done under European pressure to reduce their national deficits, the letter notes. Even in Germany, which has met the European target of spending 3% of its gross domestic product on research, the percentage of scientists working on fixed-term contracts rather than holding permanent positions has risen to as high as 80% at some institutions following the introduction of a new science employment act in 2007.

The economies of Germany and Greece may have little in common.

But scientists in those two countries—and across Europe—believe

Crowd funding to fund Ebola cure Scientists in San Diego experiment with crowd funding to finance research equipment A California-based immunologist leading an international effort to develop new anti-Ebola drugs has raised more than US$100,000 (RM327,400) in online donations to hasten the research, achieving her Internet “crowdfunding” goal in just over two weeks.

The proceeds will be used to purchase a piece of equipment enabling Scripps Research Institute scientists in San Diego to more quickly analyse Ebola antibody samples from survivors of the haemorrhagic fever, according to a spokesperson.

Twenty-five labs in seven countries are providing specimens to Scripps professor Erica Ollmann Saphire, whose consortium helped formulate the experimental ZMapp serum used to treat a number of Ebola-infected patients.

Since March 2014 mostly in the West African countries of Liberia, Sierra Leone and Guinea, there have been 13,703 recorded cases of the disease and there have been over 5,000 officially recorded deaths, although that number is not yet confirmed. Many cases and deaths are unrecorded. The death rate is 70%, although slightly better in treatment centres.

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that their national science systems are facing similar assaults from what they view as wrong-headed government policies.

One positive step that national governments could take to stop that flow, would be to eliminate a country’s investment in public R&D from a calculation of its national deficit. Another accounting change could allow a country that increases its national budget for R&D to proportionately decrease its contribution to European funding schemes.

Structural funds could also be used to curb the brain drain. The open letter is part of a broader movement that includes a 3-week cycling tour around France and a series of meetings at major Italian universities

GM Crops only logical option say leading ecology researchers An Open Letter outlining the benefits and necessities of GM crops undersigned by leading researchers in the field has been published in a number of national newspapers.

More than twenty of Europe’s most prominent plant scientists today signed a joint letter warning that Europe will never meet agricultural targets unless it starts allowing GM crops Ian T. Baldwin, Director of the Max Planck Institute for Chemical Ecology, Jena, Germany )one of the researchers behind the letter) stated that “Plant science has arguably contributed more to the reduction of human suffering than biomedical research, yet compared with the latter it is hugely underfunded worldwide.

Norman Borlaug’s dwarf and rust-resistant varieties of wheat saved many millions from hunger. Basic science performed in Europe is also an efficient way of supporting applied research in poorer countries. “ The open letter concluded “The most pressing global problems – how do deal with environmental change and secure food supply for all – arguably will only be solved with a massively increased worldwide investment in plant research.”

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Natural systems to improve prosthetics Jose L. Contreras-Vidal, Hugh Roy and Lillie Cranz Cullen University Endowed Professor of Electrical & Computer Engineering at the University of Houston, Texas, tell us about how incorporating sensory-motor feedback in neuroprosthetic limbs will offer users a greater degree of control and allow them to replicate the full range of human hand movement and gripping actions The neuroprostheses field

is going through an exciting period, with researchers aiming to develop reliable and intuitive systems that will give users a greater level of control. Based at the University of Houston’s Cullen College of Engineering and the Laboratory for Non-

natural, very intuitive to the user. That means they have to provide feedback to the user about how things are working at the end of the hand. Our project focuses on the feedback aspect of neuroprostheses for reaching and grasping,” he outlines.

Researchers are aiming to improve the

We use surface electromyography (EMG) to measure the electrical activity generated by skeletal muscles of the upper arm or scalp electroencephalography (EEG) to record the amputee’s brain waves. Neural interface algorithms extract the user’s intent from the EMG/EEG signals to generate commands to control the movements of the prosthetic hand in real time invasive Brain-Machine Interface Systems, Dr Jose ‘Pepe’ L. Contreras-Vidal is pioneering research aiming to develop a brain-machine interface to a powered prosthetic hand that users can control with their thoughts as if it were a real hand. “We want systems to be very

reliability and control of prosthetic hands, which are designed for people who have had part of their arm amputated below the elbow. “These prosthetic hands have different types of sensors. For example, they measure the configuration of the hand in space, at all times, or the force

applied to the fingertips in the prosthetic hand,” explains Dr Contreras-Vidal. “To be useful for users, and to help them get better at using the neuroprostheses, we need to find a way to display the sensory information captured by the sensors at the prosthetic limb back to them in a way that is easy to understand and act upon.”

Feedback problem This has historically been a major challenge in the field, as while a great deal of work has been done on getting neural signals to move the prosthetic limb, less attention has been paid to the feedback problem. While movement can now be generated in a prosthetic limb from neural signals recorded at the periphery using the electromyogram (EMG) or centrally using the scalp electroencephalogram (EEG), Dr ContrerasVidal says it’s important to also provide real-time feedback, so that the prosthetic can be adapted to different tasks. “If you don’t have feedback you cannot modulate or affect the way you control the hand. For

(Left) Professor Contreras-Vidal with students Andrew Paek and Harsha Agashe demonstrating the prosthetic hand fitted to amputees.

(Centre) Dr Gene Alford wearing the brain cap. Note that the white traces seen across the picture are typical EEG brainwaves.

The brain wave traces can also be seen over the shirt of the student. (Right) Prosthetic hand worn by amputee Ms Pamela Progule.

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example, most hands have microprocessors, so you could in fact pre-programme some typical hand movements. You can preprogramme a grasp for a bottle, or for a credit card - you can embed those motor programs in the hand and detect intent from the user about which of those two objects they want to grasp,” he explains.

Without feedback, if the object slips from the fingers, or there is an error in the way the hand grasps it, then problems can arise.

“If you don’t have feedback then you can’t correct yourself,” points out Dr ContrerasVidal. “So the hand will complete the task, successfully or not, and there will be no way to change it. But if you utilise feedback on the hand you can correct yourself as you go, and learn from it, which is what you want with a prosthetic hand.”

The question here is how best to send the essential information from the hand back to the user, which will improve their ability to control the prosthetic and grasp different objects. There are several different ways to transmit feedback to the user of the prosthetic hand using non-invasive means. “One is mechanical feedback to an exoskeleton that the user needs to wear, otherwise you cannot map the sensor feedback back to the mechanical effect on the limb. Or you can use small vibrators attached to the surface of the skin – normally these vibrators are embedded within the socket, where the hand is attached to the stump of the amputee,” explains Dr

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Contreras-Vidal. These vibrators will then start to vibrate if a finger on the prosthetic hand touches an object. “That will produce a vibration to the user on their stump, or some part of the limb, that will tell the user; ‘oh, ok, I’m touching this object with my index finger’. That’s with respect to feedback,” continues Dr Contreras-Vidal. “With respect to acquiring the signal for control, we place surface EMG electrodes on different (residual) muscles in the subject to record muscle activity related to the intent. Or we place a scalp EEG cap on their head to record brain activity.”

A prosthetic limb can respond to the intentions of the user through either a combination of brain waves, collected using EEG, or peripherally through residual EMG activity from the amputee’s remaining muscles. Dr Contreras-Vidal and his colleagues are investigating both techniques.

“We’re using both EMG, where we measure electrical activity from the muscles and use those signals to control the prosthetic, and also EEG. In EEG, we measure brain waves from the user and use those to control the prosthetic hand,” he outlines.

The project is also deploying functional near infrared spectroscopy (fNIRS), an optical sensor that measures changes in blood

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At a glance Full Project Title HCC- Medium- Collaborative ResearchImproved Control and Sensory Feedback for Neuroprosthetics Project Objectives The objective is to revolutionize the control and interface of upper limb neuroprosthetics.

The project will lead to a better understanding of the role of sensory feedback (vibrotactile, skin stretch, mechanical) in EEG & EMG-based neural interfaces and will lay the foundation for restoration of sensorymotor function for amputees.

Project Partners Professor Jose L Contreras-Vidal (PI), University of Houston • Associate Professor Marcia O’Malley (PI), Rice University • Associate Professor Brent Gillespie (PI), University of Michigan • Professor Patricia Shewokis (PI), Drexel University Project Funding This project is supported in part by the National Science Foundation Award IIS1219321 Contact Details Audrey Grayson, Director of Communications Cullen College of Engineering E301 Engineering Building 2 University of Houston Houston, TX 77204-4007 A Carnegie-designated Tier One public research university T: +(713) 743-4217 E: aagrayson@uh.edu W: http://www.ee.uh.edu/faculty/ contreras-vidal

Dr Contreras-Vidal

Principal Investigator

Dr. Contreras-Vidal earned his Ph.D. in cognitive and neural systems from Boston University. He held faculty appointments at the University of Maryland-College Park, MD before joining the faculty of the University of Houston as a Professor of Electrical and Computer and Biomedical Engineering and becoming a full affiliate member of The Methodist Hospital Research Institute with appointments in the neurosciences research program and the department of neurosurgery. He directs a neural and rehabilitation engineering research program focusing on non-invasive brain-machine interface systems and neuroprosthetics.

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flow in the brain, to acquire the signals.

“Light is able to penetrate the brain but it cannot go deep – it can only get to the surface of the cortex, but it’s enough to be sensitive to changes in blood flow, in oxygenation/deoxygenation,” explains Dr Contreras-Vidal. “When neurons are active, because a part of the brain is being utilised for a task, then these neurons need to be maintained – a process that requires glucose metabolism, which in turn requires oxygen. Normally there is an onset of blood flow after the onset of electrical activity. The blood arrives to that area to supply oxygen, to maintain the viability of that region in the brain. So we are able to measure that, e.g., the neuron’s oxygen consumption to support proper functioning of cognitive-motor tasks such as controlling a neuroprosthetic.”

Brain and muscle activity These measurements of brain and muscle activity are used to control the hand, building on knowledge of which activity patterns are related to which grasping gestures. The project has analysed these patterns in both healthy people and amputees. “We brought the subjects in and set them up with EMG electrodes, EEG electrodes, or both. Then we interfaced the prosthetic hand and asked them to perform some movements, and saw how those signals in the brain or in the muscle responded to the task,” says Dr Contreras-Vidal. The representation for motor control overlaps with the representation for understanding visual movement; Dr Contreras-Vidal and his colleagues are harnessing this knowledge to gain further detail about the

relationship between hand movement and brain activity. “The amputees can use visual observation together with their motor imagery to do a task. Once that’s been done we can find the mapping between what the hand did and the brain activity,” he outlines. “At that point we are ready to close the loop – that means the brain is now controlling the hand, the hand is receiving the feedback, and the feedback is sent back to the user for error correction and learning.”

The project’s methods can almost be thought of as tools for reverseengineering the brain, in the sense that the more that is known about how the brain works then the better prosthetics can be controlled. While the project’s primary focus is on improving neuroprosthetics for amputees, Dr ContrerasVidal believes their research also holds wider relevance. “We also look at spinal cord injuries, where people still have their hand, but their brain is disconnected from the spinal cord, and therefore their signals cannot reach the hand. We are also thinking about some neural populations like Parkinson’s patients, so I believe findings from the project are applicable to some other clinical populations,” he says. The project’s analysis of the differences between the brains of amputees and healthy people is also highly relevant to our understanding of brain function.

“Our research is not only about improving neuroprostheses, but also about understanding brain circuits and how we can harness more information from those circuits to aid prosthetic control,” says Dr Contreras-Vidal.

The UH team (from left): Mr. Ted Muilenburg (prosthetist), Harsha Agashe (student), Mr. Wilbert Carlile (amputee volunteer donning the EEG brain cap and the prosthetic hand), Prof.

Contreras-Vidal and Andrew Paek (student)

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Unravelling the relationship between diet, exercise and health

The increased incidence of diet- and lifestyle-related diseases is having a negative social and economic impact on many countries. Dr Pamela Byrne, Professor Hannelore Daniel and Dr Beate Kettlitz of the European led Joint Programming Initiative Healthy Diet for a Healthy Life explain how this initiative will improve our understanding of the complex relationship between diet, exercise and health The increased incidence

of diet and lifestyle-related diseases is a major concern across Europe, leading to an intense research focus on the complex relationship between diet, exercise and health. The Joint Programming Initiative (JPI) offers the ideal framework to pursue this type of research, which requires large population studies and controlled trials, as well as a long-term follow-up strategy. “Joint Programming entails a voluntary partnership between Member States (and Associated Countries) of the European Union and beyond and aims to tackle major European societal challenges by combining and coordinating national research programmes and, thereby, making better use of Europe’s public R&D resources,” says Dr Pamela Byrne, Chair of the JPI

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HDHL (Healthy Diet for a Healthy Life). The JPI is working across 23 Member States and associated countries as well as Canada and New Zealand to improve our understanding of how individual, social and environmental determinants influence food and physical activity choices. “Not all Europeans have a healthy diet. This is not only a geographical issue – compare Scotland with Greece – but also a question of the education level, social status and living environment,” according to Professor Daniel, Chair of the Scientific Advisory Board. “However, it is a strength that Europe has this huge diversity in dietary habits and foods – allowing good studies for detailed comparative analysis which can take into account all relevant determinants.”

This diversity is a strength in terms of the variety and volume of data that can be gathered, but that data also needs to be harmonised before it can be analysed.

Professor Daniel says that there are no defined Standard Operating Procedures on how data should be collected. “A specific example is in measuring food intake – in quantitative terms this is a very difficult task, particularly when you consider the huge variety of food items consumed throughout Europe and the wide variability in composition. Standardisation of methodologies and data collection processes is thus a very important issue which will be addressed by the JPI. The European Food Safety Authority is also considering this issue,” she outlines. Food

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companies will of course also modify their products for the particular market they’re operating in, which requires a clear understanding of how these products can positively impact health. This is also taken into account when developing new products. “New foods have to be affordable and to comply with the nutritional, energy and safety needs of consumers, and also with national and supra-national legislation,” points out Dr Kettlitz, Chair of the JPI Stakeholder Advisory Board. “An additional challenge is to develop innovative products and processes within the regulatory ecosystem in a cost-effective and sustainable way. Foods must originate from systems that produce, process, store, package and supply foods in a fully sustainable way. The JPI can provide advice on how things could be done and how a healthy lifestyle could be achieved.”

productivity losses and 22 per cent to the informal care of people with cardiovascular diseases,” says Professor Daniel. There is evidence that lifestyle changes can reduce the risk of people suffering from these and other non-communicable diseases.

“Population studies have shown that up to 80 per cent of cases of coronary heart

Cardiovascular diseases The importance of this research is illustrated by the figures. Cancer and cardiovascular diseases are the leading causes of death in Europe, and they also have a significant economic impact. “The cost of cardiovascular diseases to the EU economy is estimated at €192 billion per year. Of this, 57 per cent is due to direct health care costs, 21 per cent to

disease and up to 90 per cent of cases of type 2 diabetes could potentially be avoided through changing lifestyle factors. Similarly, about one-third of cancers could be avoided by eating healthily, maintaining normal weight and regularly exercising,” according to Professor Daniel.

“Most noncommunicable diseases have diet

(hypercaloric nutrition) and lack of exercise as the most critical determinants involved in the pathogenesis.

Gaining a better understanding of the impact of nutrition and lifestyle across Europe on human health and diseases will help in the challenge to prevent or delay the onset of diet-related chronic diseases. This is one of the research pillars of JPI HDHL. Evidence suggests that being sedentary for large periods of the day may carry a separate risk that is not prevented by short periods of activity, pointing to a pressing need to quantify the impact of physical activity and sedentary behaviour. The JPI aims to combine this work with research on food choice and dietary intake, to gain clearer insights into energy balance and obesity in European populations through the recently launched Joint Action DEDIPAC (Determinants of Diet and Physical Activity). “The first pillar of our strategic research agenda is about trying to understand the most effective ways of improving public health through interventions targeting diet and physical activity. Research will include studies which aim to improve our understanding of the different biological, psychological and socio-cultural factors that impact on health, and how they interact,” outlines Professor Daniel. This research will then

The first pillar of our strategic research agenda is about trying to understand the most effective ways of improving public health through interventions

targeting diet and physical activity

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be used as a basis for the development of interventions aiming to modify the impact of the social, economic, cultural and other factors which affect dietary and physical activity behaviour.

“Interactions with the other research areas are required to develop a full picture of potential determinants. The JPI recently launched a pan-European Joint Action, valued at approximately €17 million, in this area called DEDIPAC. This Joint Action has brought together many of the researchers who are currently working in this area across Europe,” continues Dr Byrne.

Food production The third key pillar of the project’s work is in food production, with the goal of developing healthy, high quality, safe and sustainable foods, building on analysis of their effect on health. Reseachers are also investigating how some foods can be modified to make them healthier; Dr Byrne believes the regulatory ecosystem in Europe poses both challenges and opportunities for the food industry. “Health Claims legislation is one area that can be challenging for the food industry, including small and medium-

sized enterprises, particularly from an innovation perspective,” she says. However, with the creation of Horizon 2020, the new European Research and Innovation Programme, the Commission’s Director Generals are working together to overcome these challenges and provide opportunities to bring new products and processes to the market. “In addition to Health Claims legislation there is also novel food legislation, which allows food companies to bring innovative products onto the market, provided the foods comply with the appropriate food safety standards,” outlines Dr Kettlitz. “However, the European food industry is competitive – at least in some areas – because the foods have a good reputation, are of high quality, and are safe.

As Joint Programming is more than initiating new calls for research, special focus in the implementation plan is given to additional activities such as the alignment of national research programmes and institutional funding; collaborations with related initiatives and third countries; and seeking coherence with Horizon 2020 activities..”

At a glance Full Project Title A Healthy Diet for a Healthy Life (HDHL CSA) Project Objectives Joint programming of research in the field of nutrition, food and health will provide for coordination of national research programmes on the impact of diet and lifestyles on health, contribute significantly to the construction of a fully operational European Research Area on prevention of diet-related diseases and strengthening leadership and competitiveness on the research activities in this field.

Project Partners • Please visit website below for full details Contact Details Project Manager, Jolien Wenink ZonMw P.O. Box 93245 2509 AE Den Haag Den Haag, The Netherlands T: (+31) 070 349 5319 E: jpihdhl@zonmw.nl W: http://www.healthydietforhealthylife.eu

Dr Pamela Byrne (left), Dr Beate Kettlitz (centre) and Prof Hannelore Daniel (right)

Professor Hannelore Daniel holds currently the position of a full Professor of Physiology and Biochemistry of Nutrition and is a director of the Center Institute of Nutrition and Food Research at the Technical University of Munich, Germany.

Her main research interests are metabolic control mechanisms in humans in response to alterations in nutrient supply assessed at the transcriptome, proteome and metabolite levels.

Dr Beate Kettlitz is Director for Food Safety, Science and R & D at FoodDrinkEurope. She studied chemistry at Humboldt University in Berlin before moving into the food industry, where she worked in several regulatory and policy positions before joining FoodDrinkEurope.

Dr Pamela Byrne has 15 years experience working with various public and private sector stakeholders in areas of regulatory, research and innovation policy.

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New insights into type-2 diabetes The incidence of type-2 diabetes continues to rise, and it is set to place a heavy burden on healthcare services across the world. The IMI-DIRECT project’s work to identify biomarkers in order to define sub-types of the condition could help to improve both diagnosis and treatment of the condition, as project coordinator Professor Hartmut Rütten explains The primary means

by which type-2 diabetes is currently diagnosed is through elevated glucose levels. However, the condition can vary widely, and this method of diagnosis does not enable clinicians to tailor treatment to individual cases, according to Professor Hartmut Rütten, the coordinator of the IMI-DIRECT project. “We are currently not able to say; ‘this type-2 diabetes patient should get this medication, and the other should get a different medication’,” he outlines. The project aims to address this by identifying biomarkers which give an insight into the likelihood of responding or non-responding to a certain medication, while researchers also aim to identify those in a pre-diabetic state who are at the highest risk of developing type-2 diabetes. “We are not able to determine whether a pre-diabetic subject will progress to develop the condition soon, or whether

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they will stay in the pre-diabetic state for a longer period of time,” says Professor Rütten.

“Similarly, some patients with type-2 diabetes are on single treatment with metformin, which is first line treatment, for many years. Whereas other patients progress faster, lose control of their glucose levels and need a second form of treatment early.”

Researchers aim to stratify these patients and identify sub-types of type-2 diabetes over the seven-year term of the project, looking at both the initial development of the condition and its progression. Two prospective clinical cohorts have been set up in work package 2, which is led by Professor Paul Franks from Lund University; one following pre-diabetic subjects, and the other looking at patients who already have type-2 diabetes. “We have recruited roughly 2,300 pre-diabetics in the study. We will follow this group for

18 months at first and perform a profound interim analysis, and then later on we will follow them for a further 18 months. We will do extensive phenotyping in order to identify those who are fast progressors from pre-diabetes to type-2 diabetes,” explains Professor Rütten. The second cohort is patients with type-2 diabetes; Professor Franks and his colleagues are monitoring the effectiveness of treatment in this group. “This cohort is being treated with metformin – we are following roughly 850 patients,” he continues. “We are following them initially for 18 months to see who progresses from mono-therapy to needing an additional second line treatment, and as in study one we will follow this group for a further 18 months.

In both studies we have a specific emphasis on the decline in beta-cell function and the progression of the disease.”

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DIRECT Workplan

Prediction model The pre-diabetic group have been recruited according to a risk prediction model based on well-known risk factors like better age, body weight and family history. The goal now is to improve the risk prediction model further. “The aim is to identify additional biomarkers, which will then help us to improve the risk prediction model which we have applied,” outlines

phenotyping of the patients. We’re using MRI and looking on the liver and the pancreas to assess any changes. Then we’re doing glucose or mixed meal tolerance tests to get a better understanding of the beta-cell function. So we’re not just looking at fasting glucose or HbA1c, which reflects glucose control in recent weeks – which is what had been done in most of the studies in the past.”

We have recruited roughly 2,300 pre-diabetics in the study. We will do phenotyping research in order to identify those who are fast progressors from pre-diabetes to type-2 diabetes Professor Rütten. The project is following a broad approach to this work. “A lot has been done in the genetics field, but that’s only made a minimal contribution to risk prediction. We hope that by applying additional ‘omics’ technologies – like proteomics and metabolomics – we can increase the chance of identifying biomarkers, and that this helps us to better predict the risk,” says Professor Rütten.

“We’re also doing a really deep

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This is combined with information on quality of life, food consumption and physical activity, with the aim of getting a detailed picture of the patients. This information is then brought together into a single central data pool, from where all researchers in the consortium can analyse it. “The challenge is to identify the biomarker or biomarker pattern which is the most accurate predictor of risk for the patient,”

explains Professor Rütten. The project’s research also holds real importance to the diagnosis of type-2 diabetes; over half of patients with type-2 diabetes are thought to be unaware that they have the condition, and the consequences can be severe. “Patients who are untreated or whose glucose is not well controlled are at higher risk of developing microvascular or macrovascular complications, such as stroke and myocardial infarction. A classical microvascular complication is diabetic nephropathy, which can be very costly, as in advanced cases dialysis is the only treatment option,” says Professor Rütten.

“Type-2 diabetes really increases the risk of these conditions, and that is the big public health concern. The concern is not simply about blood glucose.”

The figures underline the scale of the issue. It was estimated in 2010 that there were around 285 million patients with type-2 diabetes across the world, which Professor Rütten says is set to place a heavy burden on healthcare systems. “We are currently seeing an epidemic of type-2 diabetes. There’s a good chance that in 1020 years time we will see high numbers of

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At a glance Full Project Title Innovative Medicines Initiative: DIabetes REsearCh on patient straTification (DIRECT) Project Objectives The overarching aims of the consortium are to identify biomarkers that address current bottlenecks in diabetes drug development and to develop a stratified medicines approach to the treatment of type 2 diabetes with either existing or novel therapies. The identification and validation of important biomarkers for glycaemic deterioration and treatment response may be used to predict and monitor the effect of therapeutic interventions in subtypes of diabetes with different pathophysiology.

Project Funding The project “DIabetes REseraCh on patient straTification (DIRECT)” has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n° 115317, resources of which are composed of financial contribution from European Union`s Seventh Framework programme (FP7/2007-2013) and EFPIA companies´ in kind contribution.

Project Partners The DIRECT team is coordinated by Sanofi, Eli Lilly and the University of Dundee together with 3 additional pharma partners and 20 academic institutions.

See website for full details.

Contact Details Professor Hartmut Rütten Sanofi Aventis Group, Division of Diabetes, Germany, T: +49 69 305 13547 E: hartmut.ruetten@sanofi.com W: www.direct-diabetes.org/

people coming to health systems with complications,” he warns. The project’s work to monitor the effectiveness of treatment interventions takes on real importance in these terms. “It is quite natural in drug treatment that some patients do not respond to certain drugs as well as others. In workpackage 3 led by Professor Ewan Pearson we look at the responses to classical treatment,” outlines Professor Rütten. “Roughly 10-15 percent of patients are non-responders to metformin, which is the first line therapy, while there are also non-responders to sulphonylureas and GLP-1 receptor agonist.

We want to improve our understanding of the underlying causes behind this, to identify those patients who are responders or non-responders, so that patients get the best therapy.”

Short-term effects The focus in this research is the shortterm effects of the treatment, as it is quickly apparent whether a patient is responding. Currently physicians have to use their intuition and clinical acumen when prescribing drugs; the project aims to help tailor treatment to the needs of each individual patient.

“The hope is that in future we can identify which patient should get which drug by analysis of biomarkers. So we can give patients drugs that we know they will respond to,” explains Professor Rütten. The project’s work could also have implications for the

pharmaceutical sector in the search for new drugs to treat type-2 diabetes. “The inclusion criteria for drug trials is determined by elevated HbA1c and a certain BMI index. If we can identify those patients who are progressing fast then we could use those patients in clinical studies to make them more predictive in terms of not only efficacy, but maybe also in terms of safety,” continues Professor Rütten. “It would help us to reduce the costs of development if we are able to identify or segment specific parts of the patient population.”

The first step is rigorous analysis of the two cohorts. So far 2,300 pre-diabetics have been recruited, along with roughly 850 diabetic patients, a strong foundation for the project’s research agenda. “At the beginning of next year we will have the ‘omics’ data on all baseline samples in order to see maybe the first evidence of differences between patients. By the end of 2016 we will reach the first milestone, where we will see who are the progressors and who are the non-progressors. Hopefully then we will be able to identify biomarkers, which predict progression or non-progression of the disease,” outlines Professor Rütten. The second step will be to validate the biomarkers, then assess whether they are predictive. “That’s something we want to do in the second step, probably in two or three years from now. As this is a seven year project, this will ensure that we are also able to perform the validation study,” says Professor Rütten.

Professor Hartmut Rütten

Professor Hartmut Rütten has been working for Sanofi-Aventis in different positions since 1996, where he has worked for many years as head of the Cardiovascular Research Department. Since 2010 he has been head of Translational Medicine at the R&D Diabetes Division. He received his degree in medicine from the University of Cologne. Besides a medical doctorate, he holds a PhD in Philosophy from the University of Oxford Brookes.

He has also held a professorship at the University of Frankfurt since 2013.

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US company aims to develop female contraceptive While men can buy condoms to protect themselves against STDs and prevent unplanned pregnancies, there is a huge market need for an inexpensive, over-the-counter product that will do the same for women. Mary Frost Weitzel, CEO and President of Yaso Biotech, tells us about her company’s work in developing products that provide protection for women Condoms provide protection for men against sexually transmitted diseases (STDs) and unintended pregnancy, but as yet there is no similarly safe, inexpensive and protective product available to women (with perhaps the exception of the female condom). With approximately 330 million new cases of STDs and 84 million unplanned pregnancies a year, there is vast potential for such a product, which American biotechnology company Yaso Biotech aims to tap into. “Our objective is to develop and launch a contraceptive vaginal microbicide, a multi-purpose technology. It’s a topical drug product that is applied vaginally prior to intercourse, and it protects women – and men – from a variety of STDs, as well as unintended pregnancy,” says Mary Frost Weitzel, the company’s CEO and President. If it is to be widely adopted this microbicide must not

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only be effective in protecting women, but also pleasant to use. “Our vision is an inexpensive multi-purpose product that has widespread adoption because it is pleasant to use. It’s important that it’s pleasant to use as well as provide protection from both unwanted pregnancy and infection because people may logically wish to protect themselves, but emotional and sensual needs trump logic,” continues Frost Weitzel.

Anionic polymer The active element of the drug is a polymer called PPCM, an attachment and fusion inhibitor which prevents a virus from attaching and fusing to the host cell. The drug, an entirely new chemical entity, is synthesized from mandelic acid by a relatively simple process. The structure, use and synthetic method are the subject

of a patent and a new PCT patent application. Researchers studying an earlier version of the drug called SAMMA have found that it interferes with the binding of envelope glycoprotein 120 (GP120), which is found in HIV, and has been shown to work with both CD4+ T-cells and macrophages. “It’s been successful in preventing infection by all clades of HIV that have been tested to date – clade b HIV is particularly significant because it is the dominant form in Europe, the Americas, Japan, Thailand, and Australia,” says Frost Weitzel. Studies have shown that the drug also prevents herpes in a mouse model. Researchers believe that it interferes with binding to any heparan-sulfate binding site on a host cell, suggesting it could be effective against a broad range of infections. “For instance; human papilloma virus could

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How the HSV virus infects a human cell

How PPCM protects you from HSV infection

also be inhibited from attachment and fusion,” outlines Frost Weitzel. “PPCM is highly charged. We believe that the mechanism itself is probably charge dependent.”

This high charge may also be the reason that PPCM is contraceptive. PPCM inhibits hyaluronidase, an enzyme necessary for sperm penetration of the ova, and also induces premature shedding of the acrosome – a cap-like structure on the head of the sperm which is necessary for fertilization. “Interestingly enough, the sperm remain motile and survive – yet without the acrosome they can no longer fertilize an egg. We consider the survival of the sperm yet another indicator of PPCM’s safety,” says Frost Weitzel.

“Surfactant-based contraceptives, such as nonoxynol-9, work by attacking lipids and destroying cells, damaging vaginal tissue as well as killing sperm. Our drug does not damage epithelial cells (vaginal, cervical or penile) or sperm.”

Safety is of course a primary concern, and researchers at Yaso Biotech are working on animal safety studies to assess the impact of the drug. “We first want to know if the drug is generating any tissue inflammation that actually promotes infections in humans. In rabbit vaginal irritation studies there was no noticeable inflammation, redness, or irritation above placebo levels,” says Frost Weitzel.

However, sex itself can be disruptive. The mechanical ‘injury’ alone generates an inflammatory response and the presence of

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semen can raise pH in the vagina, which can reduce a woman’s natural ability to prevent infection. “Normally the vagina has a slightly acidic pH which supports resident protective bacteria. PH goes up after the introduction of semen, and natural protective flora, including Lactobacilli, and other natural defenses, such as secretory leukocyte protease inhibitor (SLPI), can be reduced after intercourse,” points out Frost Weitzel. “That’s always been a dilemma for researchers – what’s your baseline in terms of safety? It should be; what’s the condition of the vagina immediately after intercourse and are we making it worse or better with our drug?”

Yaso Biotechnology is currently being funded by the National Institutes of Health (NIH) under a Small Business Innovation Research (SBIR) Phase II grant 2 R44 AI084225-02. Specifically, the National Institute of Allergy, and Infectious Diseases (NIAID) is the leading institute researching vaginal microbicides against HIV and other sexually transmitted diseases and have been supportive of the company’s research. Frost Weitzel says the company is now keen to complete required Preclinical Studies, which include genetic mutagenicity, oral and IV toxicity, long term dosing studies, and

Our objective is to develop and launch a contraceptive vaginal microbicide. It’s a topical drug product that is applied vaginally prior to intercourse, and it protects

women – and men – from a variety of STDs, as well as unintended pregnancy In laboratory studies, PPCM does not affect levels of SLPI, and neither does it increase the activity of proinflammatory cytokines. “This is important because a number of other leading sulfonated anionic polymers which have been studied for HIV protection, do reduce the activity of SLPI,” says Frost Weitzel. “Our research suggests that PPCM in fact does not cause any damage beyond what would be expected from a placebo gel – which is minimal.”

reproductive toxicity, so that they may start human safety studies and pursue further research on vaginal flora. “Based on what we’ve observed and the development in this field, we’re extremely confident that our Investigational New Drug (IND) application will be accepted

by FDA,” she explains. “Once we have secured our IND, we will be allowed to begin human safety studies under the auspices of the U.S. Federal Drug Administration (FDA).”

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Sustainable business model Vaginal microbicides are not a new concept. Scientists have been working on microbicides since the mid-1990s in an effort to find a woman-controlled prophylactic to prevent sexually transmitted HIV, which at the time was infecting millions annually in Africa.

People were just not willing to use condoms and the epidemic was felling those most important to society – the mothers. Predecessor organizations, such as the Gates Foundation, the National Institutes of Health and CONRAD, paved the way scientifically and clinically for Yaso but also showed the company how expensive and difficult it is to develop an HIV-prevention product. A vaginal microbicide against HIV would continue to be supported by foundations, NGOs and governments. Their work continues today but Yaso is following a different path to market.

Yaso is developing a product that will prevent infection by herpes simplex (HSV), Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT), as well as unplanned pregnancy. “We seek these indications because these infections are much more prevalent than HIV in industrialized countries. Developing a prophylactic for these diseases will allow us to develop a sustainable commercial enterprise which in turn will allow us to work with non-profits to help women in underdeveloped economies – even within developed countries,” says Frost Weitzel.

“Also, there is a strong co-factor between ulcerative infections, such as HSV and HIV acquisition. That is, a person with HSV is much more susceptible to infection with HIV. If we prevent infection by HSV we may help reduce HIV infection rates as well.”

“This is not to say Yaso has abandoned all hope of seeking an HIV claim. However, the expense of pursuing this claim, coupled with the sobering study results of the previous HIV prevention trials, convinces us we would be wise to combine PPCM with another drug that works against infection with a different mechanism of action,” continues Frost Weitzel. A combination product should theoretically reduce infection rates yet further because more of the virus is neutralized in different ways. “We need to be much further along in development – at least Phase II clinical trials – before we will feel it is wise to attempt a combination of PPCM with, say, a reverse transcriptase

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inhibitor to demonstrate HIV prevention.

HIV prevention trials are large, expensive and long,” says Frost Weitzel.

Another important aspect of the company’s research is consumer acceptance. “This product is used during sex. If it is too messy, too drying, irritating, or smells bad – people just won’t use it and it will fail. If a product interferes with pleasure or romance, adoption will be low,” says Frost Weitzel.

Sales of personal lubricants have been growing at double digits for over a decade now, so people can enjoy products that enhance love making; the challenge is to formulate it properly. Frost Weitzel says it’s also important to consider the prevailing cultural attitudes in this area.

“A great deal of this is about people’s willingness to be inconvenienced during sex.

Condoms have obvious disadvantages. They can be difficult to put on, and one or both partners can often feel them. In addition, using condoms can bring up issues about trust and love,” she points out.

Men may feel that a female partner who wishes him to use a condom doesn’t trust him. Unfortunately, studies have found that men in areas with a high incidence of STDs are often reluctant to wear condoms, despite the well-publicized risks of infection. It can also be difficult to persuade young people who want to appear ‘cool’ and fearless to use personal protection. The marketing of PPCM therefore has to focus on the pleasure, the power, and the freedom that it offers to women, rather than the scientific aspects.

“We are hoping that this product will be a pleasant part of love-making for both partners. But, most importantly, it will allow women an option to protect themselves without negotiation if need be.

We plan to introduce it in different product forms over time because that is what the market demands,” continues Frost Weitzel.

These forms include an aqueous gel, an ovule and a thin film.

Yaso has contracted researchers at the Albert Einstein College of Medicine who are currently testing the effectiveness of these different product forms in mice.

“The drug seems to release from the matrix properly. We must make sure that the excipients we’re using don’t interfere with efficacy. Then we’ll pick our lead product dosage form for first approval.

That choice will be based on a combination of aesthetics, cost, efficacy and safety,” says Frost Weitzel.

At a glance Full Project Title CONTINUING DEVELOPMENT OF PPCM VAGINAL CONTRACEPTIVE MICROBICIDE Project Objectives Our Mission is to help women make educated decisions about preventing sexually transmitted diseases and family planning, promoting positive behavior and improving their future health and economic prospects.

Project Funding Their current research has been funded by NIH under grant 2R44AI084225-02 Contact Details Project Coordinator, Mary Frost Weitzel Yaso Biotechnology Inc. 8924 E. Pinnacle Peak Rd. St G5-218 Scottsdale AZ 85255 T: +1-480-231-3361 E: mfrost@yasobiotech.com W: www.yasobiotech.com Use of mandelic acid condensation polymer (SAMMA), a new antimicrobial contraceptive agent, for vaginal prophylaxis, Lourens J.D. Zaneveld, D.V.M., Ph.D., Robert A Anderson, Ph.D., Xiao-Hui Diao, M.S., Donald P. Waller, Ph.D., Calvin Chany II, Ph.D., Kenneth Feathergill, M.S., Gustavo Doncel, M.D., Ph.D., Morris D. Cooper, Ph.D., Betsy Herold, M.D.,Fertility and Sterility, Vol. 78, No. 5, November 2002.

Mary Frost Weitzel

Project Coordinator

Mary Frost Weitzel has an MBA from Harvard Business School and 17 years of senior executive experience in the fields of OTC drugs and devices, pharmaceutical research and development as well as women’s reproductive health. In 2005 she co-founded Yaso Biotechnology Inc. to develop a new anti-viral drug, PPCM, as a multi-purpose technology to treat and prevent viral sexually transmitted disease as well as prevent conception.

She has served as PI on two NIH grants and as a grant reviewer for NIH and won the coveted New Venture Prize for Social Enterprise at Harvard Business School in 2013.

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Move to the beat of the music There is a strong link between music and movement, which can be used to both boost sporting performance and aid the rehabilitation of patients with Parkinson’s disease. The BeatHealth project aims to exploit this close link by creating an intelligent technological architecture, as project coordinator Professor Benoît Bardy and scientific manager Professor Simone Dalla Bella explain There is known to be a very strong link between music and movement. Music compels us to move, and as such can be used to both aid rehabilitation and boost sporting performance, areas that the BeatHealth project is exploring. “The ultimate goal of the BeatHealth project is to create an intelligent technological architecture, in the form of a downloadable app delivering rhythmic music to boost or improve movement. The app is connected to sensors and sends data over the cloud. We want the functions of this app to be ‘sciencedriven’, meaning that they exploits the natural link between movement and music in a way that is validated by science,” says Professor Benoît Bardy, the project’s scientific coordinator.

Researchers are investigating why music has these beneficial effects, and how they

can be harnessed. “The usual way to answer this question is to say that music acts as a distractor, from pain or effort.

Secondly, it is thought to be motivational,” explains Professor Bardy. “So it’s motivational to run to music or to walk to music, whether a person is suffering from Parkinson’s disease or is training for an athletic event. However, we believe they are not the only reasons. The main reason is that music acts as a natural synchroniser.”

Biological systems This is a key concept in the BeatHealth project. Professor Bardy says that if music can be used to synchronise the rhythm of different biological systems, such as breathing and running, then a range of potential health applications are opened up. “We say; if this is true, then music can stabilise the way you walk,

and the way you run. So we can exploit this link, which is hard-wired in our neurology, in both performance and rehabilitation,” he explains. The intensity of exercise varies widely though, so it can be difficult to maintain synchronisation between different systems. “Take cycling – when you start cycling uphill you change your frequency and you lose the music,” points out Professor Bardy. “When this happens, then instead of stabilising and acting as a synchroniser between biological systems, the music acts as a de-synchroniser between systems. Instead of stabilising the system it starts unbalancing the system. This is why some runners, cyclists and rowers do not like to listen to music. There is this changing regime all the time during which you either gain or lose synchrony.”

The project aims to overcome this

The current BeatHealth architecture (image by Ghent University).

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challenge by further developing existing technologies – such as the D-Jogger system originally conceived at Ghent University in Belgium, a project partner – which adapt the rhythm of the music to different physiological rhythms, whether an individual is walking, cycling or running. The goal is to maintain constant synchrony, within a certain beats per minute (BPM) range. “You cannot move rapidly from 50 BPM to 200 BPM for example. The system basically has a 10-20 percent signal alignment, in order to maintain the synchrony,” outlines Professor Bardy. In the case of running, the technology detects when the individual’s foot is on the ground, which it uses to align the music to their BPM; the system also gathers and uses other information to maintain synchronisation. “The architecture will gather a limited amount of information on an individual, for example on their physiological status, heart rate and movement dynamics. This information will be used to adapt the music in a specific way in order to maximize walking or running efficiency and hence treat movement disorders,” continues Professor Bardy.

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Parkinson’s disease This research also has significant implications for the treatment of Parkinson’s disease, particularly in improving gait, which is typically slow and unstable, thereby reducing the number of falls and their deleterious consequences such as fractures and hospitalization. Professor Simone Dalla Bella underscores that these gait disorders are very debilitating for the

area though, and studies are ongoing.

“We are interested in understanding the relationship between rhythmic stimulation – such as music – and the pathology of Parkinson’s disease, including the brain mechanisms underlying the beneficial effects of rhythm on movement,” says Professor Dalla Bella. “There are important connections between sensory and motor areas in the brain. So music, by tapping

If music does act as a synchroniser of our biological rhythms then it can stabilise the way we walk or run, and improve movement efficiency. So we can exploit the link between rhythm and movement, which is hard-wired in our neurology, in both performance and rehabilitation. patient. “Patients typically walk slowly, making small steps, and their risk of falling is heightened; in more severe forms of Parkinson’s disease, they have to have people around them to support them,” he explains. Music can be used to stabilise an individual’s walking rhythm, thus increasing mobility, preventing falling and reducing the associated anxiety; this is a complex

into the auditory system in the brain, also activates the motor system. We are interested in this connection between brain regions that are positively affected by music.”

The project is performing clinical studies to look at the effects of the BeatHealth architecture on rehabilitation.

In a first experiment a group of 20 patients have been recruited at the

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Montpellier Academic Hospital, one partner of the BeatHealth consortium, and are undergoing clinical evaluations three days a week, which will give researchers valuable information on the development of the technology. “The patients do these evaluations with the music, either adapted to the frequency of their steps or not. We follow that with a set of questionnaires to get their views on the technology,” outlines Professor Dalla Bella. Many Parkinson’s patients are elderly, and likely to be less comfortable with technology than younger people, so Professor Dalla Bella says it’s important to take their needs into account. “We have to develop a specific technology for the patients that will be different from the technology developed for healthy people. Maybe a tablet for the first group and a smartphone for the second. We are trying to understand the fundamentals of music and movement, in terms of neuroscience, and to see whether the BeatHealth architecture has positive effects,” he continues.

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Beneficial effects These effects are mainly short-term in nature, with the wider goal being to delay the progress of the pathology in Parkinson’s disease patients.

The beneficial effects of music on these patients are fairly well-known, but the BeatHealth project is the first to look at adapting the beat, and researchers will also look at the longitudinal effects of their approach. “The patients are now undergoing the first experiments, and the final part of the project will consist of a six-month evaluation period to see whether the architecture is really improving the way they walk around,” outlines Professor Bardy. Researchers – also including one group from the National University of Maynooth in Ireland and one group from the TECNALIA foundation in Spain – are also looking to improve the architecture further, using the individualized data they have gathered on both runners and Parkinson’s disease patients. “We want to use that data to extract what we call

movement signatures. This is a personalised signature of the way people run, move and walk, in synchrony – or not – with music, which will allow a personalized music-based treatment,” says Professor Bardy.

The project’s more immediate objectives are to bring together the work of the different partners and develop an integrated prototype of the architecture.

This could in future potentially be used on other neurological conditions as well as Parkinson’s disease. “We are rhythmical biological systems, and music is generally rhythmical. So pathologies that have a rhythmic disorder can be aided by music and could potentially be targeted by BeatHealth,” says Professor Bardy. The project is progressing well, and Professors Bardy and Dalla Bella are keen to pursue further research with the team, including the development of more effective long-term strategies for delaying motor and cognitive decline in Parkinson’s disease.

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Q&A EU Researcher: Is the project looking

minutes on a marathon.

So we think the key reason why MP3 players are forbidden in competition is that they improve performance.

In BEAT-HEALTH we are trying to understand the fundamentals of music and movement, in terms of neuroscience, and to assess whether we have positive effects.

at the effects of music on the brain?

Professor Benoît Bardy: We conduct research in the project in order to validate the stabilising effect of music, as a synchroniser between biological systems.

We develop the sensors and we develop the architecture.

The architecture is basically this software, this module that will be available in the app. We send the data collected over the cloud for coaches, doctors, families, social networks, so they can get access to an individual’s degree of synchronisation.

For example a Parkinson’s patient could walk down the street with friends, and then at the end of the day look online and see that they’ve walked 2,000 steps, and 70 percent of them have been synchronised with the music. As a consequence you have been able to walk in a more stable way and for a longer time.

Music can also be beneficial for runners.

Did you know that MP3 players are banned in international competition?

EUR: Those positive effects, would they be halting the progression of Parkinson’s disease?

BB: That’s a good question and we can’t answer it now. The effects we’re looking at are short-term effects, but the pathology has already been declared.

We’re trying to use details to delay or slow down the progress of the pathology, that’s the ultimate goal.

This is not the first time people have conducted research with music on Parkinson’s patients, and looked at the way music stabilises walking. But this is the first time we have taken this adaptive, detailed approach.

EUR: Are they seen almost as

EUR: And you are looking at the

technological doping?

BB: Yes, the IAAF usually say; ‘we consider that technological doping, as it increases performance. The reason is that it distracts from pain and it’s motivational.’

The fact that it’s motivational is not the only reason though. We are pretty sure that when you run in synchrony with the music you run in a much more stable way.

And consequently your running pattern is more efficient.

longtitudinal effect of using music?

BB: Yes, so patients are coming now for the first experiments, and at the end of the project they will be tested for six months. So the final part of the project is a six-month evaluation with the patients, three days a week, to see whether these effects are really improving the way they walk around.

There will also be some retention at the end – so you stop the treatment, they come back a few months later, and we see whether the effect is still there. So that’s to assess the durability of the treatment.

So we are at year 1 now, the final evaluation time will be in two-and-ahalf years time.

EUR: And this could have a big impact on performance?

BB: If you run in synchrony with your favourite BPM, or a kind of modulated BPM, then we think you can gain several

At a glance Full Project Title Health and Wellness on the Beat (BeatHealth) Project Objectives In BeatHealth, we exploit the compelling link between music and movement. We conduct fundamental research to clarify information in music that maximize the beneficial effects on movement kinematics and physiology. In addition, we create an intelligent technological architecture, which deliver embodied, flexible, and efficient rhythmical stimulation adapted to the individual’s skills. The beneficial effects of BeatHealth are evaluated in patients with movement disorders (i.e., Parkinson’s disease), and in healthy citizens of various ages with moderate physical activity.

Project Funding Total €3,83 M / EU funding €2,94 M Project Partners Montpellier 1 University (UM1), France • Ghent University (UGent), Belgium • National University of Ireland, Maynooth (NUIM), Ireland • Fundación TECNALIA Research & Innovation (TECNALIA), Spain • Montpellier Academic Hospital (CHRU), France www.euromov.eu/beathealth/beathealth-partners Contact Details Project Coordinator Benoît G. Bardy T: +33 434 432 661 E: benoit.bardy@univ-montp1.fr W: http://www.euromov.eu/beathealth/

Professor Benoît Bardy (left) Professor Simone Dalla Bella (right)

Benoît Bardy is Professor of Movement Sciences at Montpellier-1 University and a senior member of the Institut Universitaire de France. His research addresses problems of coordination and control of human movements, exploiting virtual and augmented realities, modelling, and simulation techniques. He is the founder and director of EuroMov, a new European research and innovation centre located in Montpellier, France.

Simone Dalla Bella is Professor of Movement Sciences at Montpellier-1 University, a junior member of the Institut Universitaire de France, and an associate member of the International Laboratory of Brain, Music and Sounds Research (BRAMS, Montreal). His research concerns the relations between music, cognition and the brain, and in particular the effects of music on motor behavior (e.g. for the purposes of motor rehabilitation).

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Radical research into a new approach to lung therapy Patients suffering from chronic obstructive pulmonary disease (COPD) are often treated with mechanical ventilation methods. The AmbuLung project is developing a miniaturised bioartificial lung which will offer an alternative therapy to avoid mechanical ventilation and give the suffering lung time to heal, as Jörg Schneider and Esther Novosel explain A debilitating condition in which the lungs are obstructed and airflow restricted, chronic obstructive pulmonary disease affects approximately 5 percent of the global population, and the prevalence is still rising. There is great potential for improvement in the treatment of the disease according to Jörg Schneider, coordinator of the AmbuLung project, an initiative which brings together research partners from across Europe. “The project’s main aim is to develop the first miniaturised wearable ambulatory bioartificial lung for long-term application in an out-patient setting,” he says. The AmbuLung system will be wearable on the patients’ body, and will take over a key function of the lung. “Instead of using the failing lung for gas exchange, providing pressurized oxygen or room air and reducing carbon dioxide like in mechanical ventilation, we take venous blood continously out of the patient’s body and use an artificial lung for gas exchange,” explains Schneider. “It’s more or less an artifical gas exchanger, which mainly removes CO2 from blood and administers oxygen when necessary. By using this

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extra-corporeal artificial device we take over the lung’s gas exchange function.”

These patients will still be able to breathe spontaneously through their lungs and maintain other functions, such as controlling the temperature of their blood,

than the existing one and also the supporting parts like the pump, the power supply and all the other controls will be much smaller than the existing stationary devices, and will be wearable on the patient’s body,” says Schneider. This will

Instead of using the failing lung for gas exchange, providing pressurized oxygen or room air and reducing carbon dioxide like in mechanical ventilation, we take venous blood continously out of the patient’s body and use an artificial lung for gas exchange. It’s more or less an artifical gas exchanger, which mainly removes CO2 from blood and administers oxygen when necessary but the AmbuLung will take over the main part of gas exchange. Similar extracorporeal lung assist devices are already available, but they are still very bulky and immobile and can only be used in intensive care units. By contrast the AmbuLung will be mobile and much smaller. “That’s the main difference with our project. The AmbuLung will be much smaller in every sense – the gas exchanger will be smaller

allow patients a much greater degree of freedom. “The patient will be awake and mobile; instead of being sedated and lying in the ICU bed, they can be mobilised much quicker and their quality of life will improve,” outlines Schneider. “In future they may even be able to move to other places in the hospital, and in time they will also be able to move outside the hospital with this device.”

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Current treatment This treatment with AmbuLung would represent a radical change from current methods of treating chronic obstructive pulmonary disease (COPD). The first choice at the moment is to use noninvasive mechanical ventilation, but if that fails then patients are intubated and put on invasive mechanical ventilation, from which Schneider says it is difficult to recover. “It’s normally very difficult to get patients away from invasive mechanical ventilation back to non-invasive mechanical ventilation, or even to a situation where they don’t need any ventilation at all,” he outlines. There are also several side-effects associated with invasive ventilation. “If you ventilate a failing lung, or a lung with lung disease, then you administer pressurised air to the sick lung, and that may lead to a barotrauma,” continues Schneider. “Also volume trauma and ventilator-induced lung injury in general are common sideeffects of mechanical ventilation. Then there is the danger of infections, injuries of the trachea, and stenosis, as well as other smaller side-effects like disturbance of speaking and swallowing.”

The Ambulung however doesn’t affect the natural function of the lung. Therefore patients who are treated with it won’t need any kind of mechnical ventilation in that specific phase of the therapy, avoiding these side-effects.

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The blood-carrying components of the device are being developed using bio- and hemocompatible materials, which Schneider says is essential in avoiding damage of the patient’s blood during the extra-corporeal treatment.

Biocompatible materials are the default option in medical device technology nowadays. When dealing with blood,

Fluorescence-staining of vital endothelial cells on the AmbuLung surface however, it’s necessary to use materials which are also haemocompatible over the long-term, in addition to their biocompatibility.

This is a much greater challenge, and it’s one the project team is engaged intensively on. All the major components of the device have been designed; now prototypes are

being produced, which will soon be tested to assess their effectiveness. “The next step, which we will probably start in two or three months, will be to test the prototypes in in vivo- studies,” says Schneider.

A key issue will be the durability of the disposable parts of the device, which has been designed to be used for over 60 days.

Current gas exchangers typically last for around 30 days at the most before they have to be exchanged; improving the level of haemocompatibilty, and by extension their durability, depends to a large degree on the surface condition of the gas exchange membrane within the gas exchanger. “Therefore we are going to coat the AmbuLung gas exchanger membranes with endothelial cells, because this is the gold standard – it simulates nature!,” explains project manager Esther Novosel.

By coating the AmbuLung gas exchanger with endothelial cells, the project aims to provide longer lasting support to the lung, aimed first and foremost at COPD patients. The disease is separated into four different stages – Gold I to Gold IV, with Gold I the mildest form and Gold IV the most severe. The device is aimed, first of all, at patients in the severe stages of COPD. “We target

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At a glance Full Project Title AmbuLung (Ambulatory Bioartificial Lung) Project Objectives Novalung’s mission is the development, manufacturing and marketing of innovative medical devices for lung support. These “artificial lungs” operate outside of the patient’s body, overtaking the gasexchange of the failing natural lung.

Project Funding The AmbuLung (Ambulatory Bioartificial Lung) project is being subsidized by the EU with a total of 5.6 Million Euros (project start: 2012).

Project Partners • Novalung GmbH, Heilbronn, Germany / Dr Georg Matheis and Josef Bogenschütz • Fraunhofer Insitute of Interfacial Engineering, Stuttgart ,Germany / Professor Thomas Hirth • The Biological System Engineering Laboratory of the Imperial College London / Professor Dame Julia Polak and Professor Athanasios Mantalaris, PhD • The Università degli studi di Firenze / Professor Massimo Pistolesi, MD Contact Details Project Coordinator, Jörg Schneider Novalung GmbH Im Zukunftspark 1 DE-74076 Heilbronn (Germany) T: +49 7131 27 06 143 E: Joerg.Schneider@novalung.com W: www.novalung.com

Jörg Schneider

Project Coordinator

Before joining Novalung for coordinating the AmbuLung Project Jörg Schneider worked as a freelance consultant in the medical device industry. Prior to this he was the CEO of Resmed Germany, a worldwide leading enterprise in the market of sleep and respiratory medicine. Jörg holds a Dipl.Ing T.U. degree (MS) in biomedical engineering and biokypernetics from the Karlsruhe University of Technology, Germany. He has extensive expertise in successful product launches and interdisciplinary pioneer work to establish new treatment options in the area of pulmonology, cardiology and heart surgery.

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Necessary steps to transform the iLA to a longterm ambulatory lung assist device.

patients with Gold III and Gold IV. These are patients who are frequently hospitalized because of an acute worsening of the disease,” says Schneider. “In one of the next steps we will also target patients in chronic phases of the disease in order to avoid exacerbations.”

The AmbuLung could also be used to treat other lung conditions, including lung injuries, infections like ARDS (acute respiratory distress syndrome) and to support patients waiting for a lung

project’s targets is to reduce the cost of COPD therapy,” explains Schneider. “COPD is actually the fourth most common chronic disease worldwide.”

The disease is thought to affect more than 300 million across the world and the prevalence is still rising, underlining the importance of the project’s research. The ultimate goal is to develop a device that patients can use in their own home, in a way mirroring the evolution of ventricular assist devices (VAD), which were first developed in the ‘80s to support the heart.

The AmbuLung could also be used to treat other lung conditions, including lung injuries, infections like ARDS (acute respiratory distress syndrome) and to support patients waiting for a lung transplant transplant. There is an acute shortage of lung donors at present, and it is not uncommon for patients to pass away while waiting for a transplant; Schneider says the AmbuLung could act as an effective ‘bridge to transplant’ in such circumstances. “The AmbuLung will be an excellent device to overcome the timeperiod until a donor organ is available, as it is designed for long-term use,” he says.

Even if the targeted operation time of 60 days is not sufficient, the gas exchanger can be easily exchanged in the hospital environment when it needs replacing, extending life and reducing the time patients need to spend in hospital, which is one of the major economic drivers behind the project. “Another of the

“Twenty years ago VADs were bulky systems used in the ICU. Nowadays VADs are small, light, and can be worn on the patient’s body. They can be used outside the hospital, when people are at home or travelling for example,” outlines Schneider. The project aims to achieve something similar with the AmbuLung, to reach a point where patients can use the device in their own home, independent of any medical supervision. “How long it will take to get to this stage depends on many factors,” says Schneider. “First of all there’s the financial issue, because such development is not cheap. Then it depends on regulatory issues and the acceptance of the medical community. This is groundbreaking, pioneering work.”

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Improved medical imaging to boost the fight against disease Medical imaging technology is crucial to diagnosing, monitoring and treating disease, now the SUBLIMA project aims to combine time-of-flight PET and MR technology to provide concurrent molecular and anatomical imaging. This work will lead to significant improvements in image quality as well as enable new possibilities for imaging molecular processes in-vivo, as Dr Dennis Schaart explains The

world faces some pressing healthcare concerns, in particularly caring for our ageing population and the increasing incidence of cancer, cardiovascular and neurodegenerative diseases. The big challenge facing health authorities is how to maintain highquality, cost-effective healthcare against this backdrop; Dr Dennis Schaart believes medical imaging technology has an important role to play. “We see medical imaging technology, and molecular imaging technology in particular, as an important contributor to solving the problem,” he says. As partners in the SUBLIMA project, Dr Schaart and his colleagues are working to develop technology for concurrent molecular and anatomical imaging. “There are many different imaging modalities. Many of them visualise anatomy; computed tomography (CT) and magnetic resonance (MR) are well-known examples. That’s quite different from molecular imaging, where you aren’t visualising structures in the body, but rather molecular processes,” he explains. “For example, you can trace a molecule by labelling it with a positron emitter and visualizing it with positron emission tomography (PET).”

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PET detectors The project’s ultimate goal is to fully integrate PET and MR, which will produce higher quality, more detailed images than is currently possible and offer new possibilities for imaging molecular processes in-vivo. While there are many elements to this work, Dr Schaart is

focusing on the instrumentation side, particularly on the PET detectors. “We basically start with the detectors that you need to detect the annihilation photons.

This process involves a number of steps,” he explains. The first step in detecting these 511 keV gamma photons is to absorb them in a scintillator, a type of crystal,

MRI-compatible preclinical PET insert with integrated MRI-RF coil. The black, carbon fiber boxes each contain six fully digital PET detectors.

The white gantry includes water and air cooling distribution rings.

Figure taken from: B. Weissler et al, 2012 IEEE Nuclear Science Symposium and Medical Imaging Conference Record (NSS/MIC), pp. 2113-6 . ©

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Left: 150 mm silicon wafer processed at Fondazione Bruno Kessler.

Right: MRI-compatible PET detector stack without scintillation crystals.

Below: A new type of water-based MRI resonator which is PET-compatible at 7 Tesla. Left: electromagnetic simulations of magnetic field; Centre: a photograph of the resonator; Right: images of the human knee.

which converts the energy of the gamma photons into light. The second step is to convert this tiny flash of light into an electrical signal. “The current technology to do so is the photomultiplier, which employs electron multiplication to get a strong signal” continues Dr Schaart. “It is vacuum tube technology, which is almost a century old and works quite effectively.

However, it doesn’t work in high magnetic fields, so by definition it won’t work inside an MR scanner.”

Researchers in SUBLIMA are developing novel PET detector concepts capable of integrating with MR. MR scanners work on the basis of very high magnetic fields, in order to manipulate the magnetic spins of nuclei in our body. “Based on this principle MR provides an image of anatomy, or even of certain physiological functions. MR is a very versatile technique – depending on the way you manipulate these spins you can do many different things,” says Dr Schaart. The PET detector has to be extremely compact and be able to operate in a high magnetic field if it is to be integrated with MR. Vice versa the quality of the MR images should not be affected by the presence of the PET detectors. This was not previously feasible, but recent technological developments have opened up new possibilities. “One of the most important devices we are developing within our project is the silicon photomultiplier, a new type of photosensor

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which works on very different principles.

It is a solid-state device made of silicon, just like any other chip. So it’s an extremely compact sensor , moreover it has excellent performance characteristics,” explains Dr Schaart.

Actually measuring the relevant information required for image formation is an immensely challenging task nevertheless. Researchers are aiming to measure the times at which the two annihilation photons are absorbed, to a level of precision that allows them to identify the position on the line of response (LOR) where the annihilation –

time information allows you to make higher quality images, so the issue of great importance here is the timing resolution of the detectors. One of the aims of our project is to push the performance of the systems beyond the current capabilities,” he says. “Currently available systems have a timing resolution in the order of 500-600 pico-seconds, which are 10-12 of a second. We have been able to bring this number down to about 100-200 picoseconds. One of our aims is to achieve better and better timing resolution in future, and thereby to achieve better and better images.”

Precise time information allows you to make much cleaner PET images, so the issue of great importance here is the timing resolution of the detectors. One of the aims of our project is to push the performance of the systems beyond the current capabilities effectively where the positron was emitted – took place. “The problem is that these gamma photons travel at the speed of light, so you have to be incredibly fast,” explains Dr Schaart. It is currently not possible to identify the precise position where the annihilation event occurred, but Dr Schaart says they can find the approximate region and are working to improve the technology further. “Precise

Monitoring treatment This will help doctors not only in diagnosing patients, but also in monitoring the progression of disease and the effectiveness of treatment. One can use the tool to assess how a patient is responding to a course of chemotherapy for example, which Dr Schaart says helps doctors tailor treatment more effectively.

“With some of these new, potentially

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At a glance Left: Impression of a 32 mm x 32 mm x 22 mm monolithic scintillator on a digital SiPM array.

Right: Photograph of a 32 mm x 32 mm x 22 mm monolithic scintillator on a digital SiPM array.

The combination of Monte Carlo simulations and time-of-flight (TOF) image reconstruction enables the optimization of system designs based on image quality. These reconstructed images of small artificial lesions (hot spots) in a uniform phantom illustrate the benefit of TOF (600 versus 200 picoseconds time resolution) for a whole body PET/MRI system. high-impact medications, what you may see is that many patients respond positively to the treatment. But in a fraction of the patients there is no response at all – it may depend on their genetic make-up,” he outlines. By combining molecular and anatomical imaging, Dr Schaart says doctors will be able to assess the effectiveness of treatment much quicker. “If you have to rely only on anatomical imaging then you will typically have to wait a few months to see whether it has had any effect. And if there wasn’t a positive response then you will still have the sideeffects.” he says. “In some tumours we are now able to see whether or not the tumour is responding to chemotherapy within two weeks. That allows you to make faster decisions and to manage the disease and the treatment in a much better way.”

The project’s aims are primarily technological, but MR and PET are both very versatile techniques, so there is a range of potential applications. Clearly integrated PET and MR will be an important research tool in for example oncology, neurology, and drug development, but Dr Schaart says that at this point it’s not yet clear where it will be used clinically on a large scale. “It’s a new technique, and we need to see what it will be used for in the future. When PET/ CT was introduced the situation was

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similar,” he outlines. “At first no one knew what to do with it, but today essentially any PET system that is sold is a PET/CT system.” One very important objective for Dr Schaart and his colleagues is to work towards getting these new technological developments into the clinic, although of course manufacturers have an important role to play. “If you want doctors to use a new tool you need to make it exactly right for their needs. For example, we are working very hard to make sure that the operation of the MR subsystem is not compromised by the presence of the PET detectors, which is a challenging task. We need to continue our research to a point where it convinces doctors and biomedical researchers.”

“Interestingly, many of the new technologies we are developing, such as the silicon photomultiplier, also seem to be very suitable for applications outside PET/MR, including PET/CT,” he continues.

“Then I also see clear potential in what we call application-specific devices, where you make dedicated imaging systems targeting specific applications. One example might be dedicated systems for imaging the brain and its functioning in new and better ways than is currently possible. I even foresee applications outside the medical area, such as in particle physics and materials research for example.”

Full Project Title PET/MR combined for maximal efficiency (SUBLIMA) Project Objectives The SUBLIMA project aims at truly simultaneous, fully integrated, solid-state PET/MR technology for concurrent functional and anatomical imaging with unsurpassed image quality. It will combine the extremely sensitive functional imaging possibilities provided by PET with the excellent soft-tissue contrast and complementary functional imaging capabilities of MR. Project Partners • Philips Technologie GmbH, Torsten Solf • Delft University of Technology, Dennis Schaart • Fondazione Bruno Kessler, Claudio Piemonte • University of Heidelberg, Peter Fischer • University of Pennsylvania, Joel Karp • University of Ghent, Stefaan Vandenberghe • Technolution, Paul van Haaren • Ecole Polytechnique Fédérale de Lausanne, Hans Peter Herzig • King’s College London, Paul Marsden • Leiden University Medical Center, Andrew Webb • Micro Systems Engineering GmbH, Joerg Gossler • Philips Electronics Nederland B.V, Rob Smeets • Universitäts Klinikum Aachen, Fabian Kießling Contact Details Torsten Solf Philips Technologie GmbH (Coordinator) X-Ray Imaging Systems Pauwelstrasse 17 D-52074 Aachen, Germany T: +49-172-98 92 012 [1] E: torsten.solf@philips.com W: http://www.sublima-pet-mr.eu/

Torsten Solf

Dr Dennis Schaart

Torsten Solf was born in 1969 in Germany. He studied Biomedical Engineering in Karlsruhe (MS) and University of Michigan. He works for Philips Research since 1999 in Aachen and he is consortium leader of SUBLIMA. Dr. Dennis R. Schaart works at the Radiation Science & Technology department of Delft University of Technology. He is interested in the development of novel instruments for TOF-PET, PET/MRI, particle therapy, and other applications. He is an elected member of the IEEE Nuclear and Medical Imaging Sciences Council, has (co-)authored more than 70 peerreviewed journal papers, and is a frequently invited speaker.

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Statins debate rumbles on The UK’s National Institute for Clinical Excellence has drawn up draft guidelines recommending that people at a 10 per cent or higher risk of developing cardiovascular disease should be eligible for treatment with statins, yet the proposal has drawn criticism. We take a look at the issues surrounding the use of the cholesterol-lowering drugs

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ebate continues about the use of statins, a group of drugs that can help lower the level of low-density lipoproteins (LDL) in the blood. LDL, which is often referred to as ‘bad’ cholesterol due to its role in transporting the content of fat molecules into artery walls, is closely associated with cardiovascular disease, which includes conditions such as coronary heart disease and stroke, making it the focus of a great deal of research attention.

The UK’s National Institute for Clinical Excellence (Nice) has drawn up draft guidelines proposing that anyone with a 10 per cent (or higher) risk of developing cardiovascular disease (CVD) in the next ten years should be eligible for treatment with statins. This recommendation halves the threshold at which people are eligible for preventative treatment, from the previous 20 per cent down to 10 per cent.

There are five main types of statin that can be prescribed to people thought to be at risk of developing cardiovascular disease; atorvastatin, fluvastatin, pravastatin, rosuvastatin and simvastatin, all of which reduce cholesterol levels and hence the risk of CVD. They have been prescribed to otherwise healthy people since 2006, now Nice is extending their use to a wider segment of the population.

Under the new recommendations up to 4.5 million more people, in addition to the existing 13 million, could be eligible for treatment with statins. This comes to around 40 per cent of the population, and Nice believes that the new recommendations will help to prevent up to 28,000 heart attacks and 16,000 strokes a year.

The recommendations have generated controversy however. Some critics argue that it is a case of serious over-prescribing, and suggest that the recommendation has been unduly influenced by the pharmaceutical industry, an allegation firmly rejected by Professor Mark Baker, Director of Clinical Practice at Nice. “Nobody gets into our guidelines group if they have any significant vested interest, particularly a financial interest,” he said.

There is also disagreement over the evidence base used to support the increased use of statins, as well as continued debate over the side-effects of the drugs. While the official NHS advice states that most people tolerate treatment well, it acknowledges that statins can have a number of sideeffects, which include muscle and joint pain, increased hyperglycaemia and problems with the digestive system.

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What is not in doubt is the scale of the issue around cardiovascular disease. CVD is the leading cause of death worldwide, and over 1.6 million men and nearly 1 million women in the UK are affected by chronic heart disease. It is estimated that CVD cost the UK healthcare system £9 billion in 2009, of which around 64 per cent was taken up by the costs of hospital care, while medication accounted for around 23 per cent of the total.

Given these statistics it is unsurprising that CVD is a major research priority. It is not however a single disease but rather a range of conditions, broadly defined as any disease that affects the cardiovascular system.

This includes peripheral arterial disease, vascular diseases of the brain and kidney, and cardiac disease.

A variety of factors are involved in the development of these conditions, with age, gender and blood pressure all known to be important risk factors, while our increasingly sedentary lifestyles further heightens the risk. Scientists and policy-makers are looking for ways to minimise the risk of their occurrence and in the process reduce the heavy burden that CVD places on the NHS. This is set to grow even further over the coming years, due in large part to the rising incidence of obesity, our rapidly aging population and the growing demand for health services. Over 29 per cent of women under the age of 25 are classified as clinically obese, while life expectancy has risen by around ten years since 1950, leading to a rise in the incidence of chronic diseases.

These kinds of statistics only heighten concern about the long-term sustainability of the NHS as it is currently funded, with some people suggesting that prevention of avoidable diseases is the only way to save it from bankruptcy. “Today’s NHS cannot deal with the rising demand, so its survival depends on managing it,” wrote Dr Phillip Lee in the Daily Telegraph.

CVD Prevention

Cardiovascular disease maims and kills people through coronary heart disease, peripheral arterial disease and stroke. Together these kill one in three of us

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Statins could have a significant impact in these terms, helping to prevent CVD in those who are at high risk of developing the disease.

Statins work by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver, and thereby lowering cholesterol levels.

This forms the backdrop for Nice’s decision to extend their use in the wider population, and to allow them to be prescribed for people thought to have a 10 per cent or higher risk of developing CVD. This does not mean statins are instantly prescribed for anybody beyond the threshold – Nice advises GPs to first encourage people to change their diet and take more exercise, but beyond that doctors can use their discretion.

The evidence on their effectiveness is clear, says Dr Jonathan Morrell, in a video on the NHS choices website. “Statins have proved themselves not only to be very effective in lowering cholesterol levels, but we know that by taking them you can reduce your chance of suffering a heart attack or stroke in the future quite considerably,” he says.

Statins critics The Nice proposal has attracted a level of criticism however, with a group of eight eminent doctors, including Sir Richard Thompson, president of the Royal College of Physicians, and Clare Gerada, a previous chair of the Royal College of GPs, signing a letter to Nice and Health Secretary Jeremy Hunt that raises concerns about ‘medicalising’ up to five million currently healthy people.

The doctors also point out that much of the evidence used to support the increased use of statins comes from pharmaceutical company trials, which in many cases have not been put in the public domain, leading to worries about possible biases. “Extensive evidence shows that industryfunded trials systematically produce more favourable outcomes than non

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industry-sponsored ones,” they write.

Other voices have also been raised against increased use of statins, including that of Professor Kim McPherson, who argued that the evidence base was insufficient to justify the Nice advice, while also drawing attention to their side-effects. Drawing on his own experience of using statins, he suggested they had impaired his own mobility and agility, while other patients have experienced digestive problems and memory loss.

These are far from isolated experiences. Dr Kailash Chand, the deputy chairman of the British Medical Association, described his experience after being prescribed statins. “After 6 months I noticed I was having a lack of energy,” he outlined. “My regular exercise was curtailed. I was feeling tired and exhausted.”

The side-effects were such that Dr Chand decided to stop taking statins, and within a few weeks he was feeling much better. His experience correlates closely with the findings of a team of doctors from the University of British Columbia in Canada. Their review found that statins decrease energy and fitness, and also lead to an increase in fatigue and sleep problems.

The data on the side-effects of statins is not conclusive though, as it is extremely difficult to definitively identify the side-effects of a drug, particularly when a patient may be nervous or wary of taking it. Earlier studies have pointed to the existence of the socalled ‘nocebo’ effect, where patients in a trial were prescribed either a statin or a placebo pill, with both reporting exactly the same side-effects.

Ethical dimension There is also an ethical dimension to the debate, with some GPs and the public concerned about putting people on pills before they are actually ill. Statins have now been used for several years to help lower cholesterol levels, while the NHS also advises people on how they can avoid certain diseases.

While we accept the need to vaccinate children against certain

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diseases, and encourage physical exercise among the wider population as a way of maintaining good health, there is still a level of unease about treating people for a condition before any symptoms have manifested themselves.

The NHS was not originally intended to act as promoter of healthier lifestyle choices, but rather as a universal service to provide healthcare to people in times of need. A move towards preventative medicine would represent a significant shift in ethos for the NHS, and also place more responsibility for maintaining health in the hands of individuals, encouraging them to improve their fitness and general wellbeing.

This needs to be set against our knowledge of the close correlation between income and health, and the NHS’ role in protecting the most vulnerable in society. It is well-established that low earners are far more likely to be unhealthy than people on higher wages due to a variety of factors, including stress levels, working environment, and in some cases the quality of their housing.

Nice advice Nice is still standing firm however, arguing that the benefits of statins far outweigh any risks, and that they have already had a significant impact. “Cardiovascular disease maims and kills people through coronary heart disease, peripheral arterial disease and stroke. Together these kill one in three of us,” said Professor Mark Baker, Director of Clinical Practice. “Our proposals are intended to prevent many lives being destroyed.”

“The independent committee of experts found that if a patient and their doctor measure the risk and decide statins are the right choice, the evidence clearly shows there is no credible argument against their safety and clinical use in people with a 10 per cent risk of CVD over 10 years,” outlined Professor Baker.

There is still disagreement about whether they should be prescribed on the widespread scale that is proposed. While the

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majority of experts agree that statins should be prescribed to prevent a second heart attack or stroke, many are still opposed to their more routine use. “If people understood how relatively modest the benefits of statins are, they might be much more conservative about taking them,” argued Dr Tom Perry, of the Canadian research group.

Many UK doctors take a different view though, and are keen to ensure that the continued controversy does not lead to people deciding on a different course of treatment. Professor Sir Rory Collins, a Professor of Medicine and Epidemiology at Oxford University, oversaw the analysis of study data on statins, and says the drugs are extremely safe. “I don’t want people to be misinformed about statins,” he says.

The British Medical Journal (BMJ) itself published two papers in 2013 which made mistakes on the extent of side-effects from statins, yet both are still in the public domain. Both authors argued that the side-effects of statins meant it was not always appropriate to prescribe them to low-risk patients, but have since withdrawn their statements on the frequency of side-effects.

This is integral to the continued debate over whether statins should be prescribed to patients not thought to be at a high risk of developing CVD. The efficacy of the drugs is not in doubt, but the way in which they should be used remains hotly contested, while it could also be argued that prescribing statins to low-risk patients removes their reponsibility for managing their own health, which is the professed goal of much health policy.

While welcoming the debate over the use of statins, Professor Collins is keen to ensure that decisions are based on accurate information. “I think it is perfectly reasonable that people decide not to take a statin or a doctor decides not to recommend it, but I think people should be able to make an informed choice,” he says.

Sir Andrew Dillon Chief Executive, National Institute for Health and Clinical Excellence

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Understanding the epidemiology of West Nile Virus

First identified in Uganda in 1937, West Nile Virus was long considered to be only a minor threat to human health, until a series of outbreaks in the ‘90s prompted a renewed research focus. We spoke to Dr Annapaola Rizzoli and Dr Miguel Angel Jiménez-Clavero of the EuroWestNile project about the re-emergence of the virus in Europe and neighbouring countries For many years West Nile Virus was not thought to be a major threat to human health, but in the ‘90s there was a series of outbreaks and the virus spread beyond Europe and the Mediterranean, reaching the Americas in 1999, where it has since caused more than 1,500 deaths. Concern over the threat has stimulated a renewed research focus on the virus, as illustrated by the work of the EuroWestNile project.

“The major scope of the project is to improve our understanding of the drivers behind the re-emergence of West Nile Virus (WNV) and provide new diagnostic and surveillance tools. We aim to characterise the ecology of WNV in Europe, and to better understand the interaction between environment, reservoir hosts and vectors in each of the regions where the virus is emerging,” says Dr Annapaola Rizzoli, the project’s scientific coordinator. In Europe and neighbouring countries, the virus is more actively circulating in four main areas; the Mediterranean basin, Central Europe, the Caucasus and the Middle East.

“The ecology of the virus is likely to be different in Europe. We don’t have big outbreaks, apart from in some areas,” continues Dr Rizzoli. “For example, in certain south-eastern European countries, such as Greece, or in countries belonging to the Russian federation, the number of cases reported each year is quite high compared to what we are observing in Spain or Southern France, where the virus has also been detected.”

The virus itself is a generalist pathogen, part of the flavivirus family of viruses. Its

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genome is comprised of ribonucleic acid (RNA), and this fact confers a high variability on the virus at the genomic level, which has allowed the virus to evolve, giving rise to several different genetic variants. “These variants can differ not only at the antigenic level, which is the way the immune system recognises these viruses, but also in a number of other characteristics. For instance the host range – the range of species that can act as a host for the virus – can vary, and maybe there are also some variations regarding the virulence of the virus for a given species.

These genetic variations provide the basis

identified both lineage 1 and lineage 2 in co-circulation.” The different lineages can now be rapidly distinguished thanks to the development of new prototypes of WNV diagnostic Nucleic Acid Tests (NAT) and antibody assays obtained within the Eurowestnile project.

Generalist pathogen The ecology of the virus is extremely complex however. WNV was first identified in Uganda in 1937, and it is thought that the various lineages have been circulating between Europe and Africa for quite a long time. “According to

The major scope of the project is to improve our understanding of the drivers behind the re-emergence of West Nile Virus. We aim to characterise the epidemiology of West Nile Virus in Europe, and to better understand the interaction between environment, host and vector in each of the regions where the virus is emerging for the evolution of each of the types of this virus,” says Dr Miguel Angel JiménezClavero, an expert on virus genomics and pathogenicity. So far eight genetic lineages of WNV have been identified (and some more are still in study), of which the two most common circulating in Europe are lineages 1 and 2. “It’s very interesting to note that different lineages can circulate within the same country, which is what is happening in northern Italy,” says Dr Rizzoli. “The Padana valley (or Po Valley) is one of the areas most affected by WNV in western Europe – our colleagues have

the most recent phylogenetic analysis we can identify two major processes of emergence; one is following periodical reintroduction of new variants from Africa to Europe and the Middle East. The basic ecology is that the virus is spread through birds and it is introduced in new areas where, if the mosquito population is competent and the density is sufficiently high it starts an amplification phase,” outlines Dr Rizzoli. It has also been demonstrated that the variants of the virus which have already established themselves can persist long after they

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were initially introduced and periodically re-emerge. “The viruses induce chronic infection in some species, like certain types of birds for example, and can also be transmitted between wildlife and humans in the absence of reintroduction. The virus is able to persist also in mosquitoes,” explains Dr Rizzoli. “There is also new evidence that infected overwintering mosquitoes can survive during Winter and then start a new transmission cycle in the following season. So this combination of continuous re-introduction, as well as persistent and endemic circulation phases and then new scale events, characterises the complex ecology of WNV in Europe.”

The virus can vary widely in the severity of the disease, with researchers observing a significant gradient between East and West. Dr Rizzoli and her colleagues are also looking into the underlying causes behind these regional disparities. “We aim to understand why, for example, the number of cases is so high in certain countries and not in others . If you look at the European Centre for Disease Prevention and Control website you can see how this spatial variation in incidence is significant in certain cases.” The project is collecting data on the different variants of the virus from all the participating countries, part of the wider goal of developing an integrated European research capacity on the virus.

“Our goal is also to develop a biobank of the WNV lineages and strains, which are collected within the participating countries,” outlines Dr Rizzoli. “We are also working to develop animal models to understand pathogenicity. We aim to study the immune response to these viruses, to develop new diagnostic tests to detect its infection, and to identify the best available treatments using these animal models.

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Above: Researchers working with West Nile virus at CISA facility under biosecurity level 3 with enhanced measures to avoid exposure to biological risks.

Below: Participants of the EuroWestNile project during the second annual meeting held in Madrid in 2013.

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At a glance

Animal models

Full Project Title European West Nile collaborative research project Project Funding funded by EC under the theme HEALTH.2010.2.3.3-3.

Project Partners • Instituto de Salud Carlos III (ISCIII) • Agencia Estatal Consejo Superior de Investigaciones Científicas (CSIC) • Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA) • Vircell S.L. (VIRCELL) • Inmunología y Genética Aplicada, S.A. (INGENASA). [Spain] • Veterinaermedizinische Universitaet Wien (Vetmeduni Vienna). [Austria] • Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’environnement et du Travail (ANSES) • Institut Pasteur (IP) in Paris. [France] • Central Virology Laboratory (CVL). Israel • Istituto Zooprofilattico Sperimentale della Lombardia ed Emilia Romagna (IZSLER) • Istituto Superiore di Sanità (ISS) • Istituto Zooprofilattico Sperimentale delle Venezie (IZSV) • Fondazione Edmund Mach (FEM). Italy • Central Research Institute of Epidemiology (CRIE).

Russia • Institut Pasteur de Dakar (IPD). [Senegal] • Institute of Vertebrate Biology Academic of Science of the Czech Republic (IVB) [Czech Republic] Contact Details Dr Annapaola Rizzoli Head of the Animal Ecology Research Group Research and Innovation Centre Fondazione Edmund Mach San Michele all’Adige (TN), Italy T: +39 0 461615433 E: annapaola.rizzoli@fmach.it W: www.eurowestnile.org

The main animal model being used is mice while researchers are also using birds, as WNV is propagated in a cycle between mosquitoes and certain species of wild birds. The main means of transmitting the virus is through mosquito bites. “Certain species of wild birds act as a reservoir host for the virus. This is the way the virus remains in nature. But sometimes this cycle spills over, and affects other species – for instance mammals. Horses and humans are particularly susceptible to the disease” explains Dr Jimenez-Clavero. This is well illustrated by recent WNV epidemics as far afield as Russia and the Americas, so the project is also working to provide new tools to mitigate the impact of the virus. “The

Dr Miguel Angel Jiménez-Clavero (left) Dr Annapaola Rizzoli (right)

Annapaola Rizzoli is a wildlife veterinarian and her major scientific interest and expertise is in the field of parasitology, wildlife diseases ecology, epidemiology and risk assessment of emerging vector-borne and zoonotic diseases.

She is the Coordinator of the Eurowestnile project, WP leader in EDENext project (www. edenext.eu [1]) and Coordinator of a new Laboratory of Excellence in Epidemiology and Modelling (LExEM) funded by the autonomous province of Trento (www.lexem.eu [2]).

Miguel Angel Jimenez-Clavero is a virologist and researcher working at the High Biosecurity Facility of CISA-INIA, equipped with a work environment in high bio-containment levels. His current areas of interest cover molecular epidemiology and viral evolution studies, diagnosis and surveillance of viral diseases with high dispersal ability and/or special virulence.

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environmental conditions and combining it with satellite information to develop risk models. “Several studies have shown how a vector population can better survive and develop in a warmer climate, but this also depends on precipitation regimes,” continues Dr Rizzoli. “Extreme weather events can have a big impact – it has been shown for example that heatwaves may favour the transmission of WNV. The viruses also have the ability to evolve and mutate, and this is what’s happening.”

This adaptability further complicates the goal of improving treatment of WNV. There is currently no effective vaccine against WNV for humans (a vaccine for horse is available), and while the project’s primary focus is on generating new knowledge on

We also aim to develop new animal models to study the immune response to these viruses, to develop new diagnostic tests to detect its infection, and to identify the best available treatments best approach for protecting public health is to know when the virus can spill over and which conditions can enhance transmission,” outlines Dr Rizzoli. “ In humans there is no vaccine available, hence to prevent WNV disease the most effective way is to reduce the numbers of mosquito bites. So education, and risk communication to vulnerable communities are all important, along with integrated strategies aimed at suppressing mosquito density in certain places.”

Researchers are collecting data in all the countries where the virus has emerged and are working to identify these early predictors of the risk of WNV infection. This is a complex task, as many factors are involved in the re-emergence of WNV. “Climate change for example is among the several factors affecting the emergence of vectorborne diseases. In wetter, warmer climates mosquitoes can reproduce more quickly,” says Dr Rizzoli. The project is monitoring the dynamics of mosquitoes in these variable

the virus, Dr Jiménez-Clavero says their work can help in the search for improved treatment and disease prevention. “One of the good things about our animal models is that they can be used to test new drugs and vaccines against the virus–and our contribution is to provide better animal models for testing new treatments,” he outlines. While this is clearly an important research goal the project is also looking at fundamental issues around the virus, including the behaviour of mosquitoes. “The virus selects and adapts to different species of mosquitoes in the same way it adapts to different hosts. Some species of mosquitoes, especially locally, can act as better vectors than others,” explains Dr Jiménez-Clavero.

“This is very important in limiting the spread of the virus at the local levels. So it will be important to accurately define which mosquitoes are involved in each location, which may be helpful to choose better ways to control these mosquitoes.”

Participants of the EuroWestNile project during a visit to a field work area in Doñana National Park, Spain.

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PulmoStent project takes aim at lung cancer Endobronchial stenting is a proven therapy in the treatment of lung cancer, yet current stents suffer from some significant drawbacks. The pioneering researchers at the PulmoStent project are currently developing a new kind of stent based on a combination of stent technologies and tissue engineering, as Professor Stefan Jockenhoevel explains The incidence of lung cancer continues to rise with around 1.35 million new cases diagnosed each year, and it remains the most common form of cancer in the world. Stents are used in treatment to widen airways, yet Professor Stefan Jockenhoevel says current models have some significant drawbacks, preventing their use as a routine treatment. “One of the problems with current stents is that they have open-pore structures. That means that the tumour can grow again into the lumen through the pores of the stent structure,” he explains. Based at Aachen University in Germany, Professor Jockenhoevel is the coordinator of the PulmoStent project, which aims to develop a new kind of stent to treat lung cancer. “The current state-of-the-art is to cover these stents – mostly with just a

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silicon film, which acts as a barrier for the tumour, preventing the tumour ingrowth through the gap between the stent struts,” he continues.

This helps prevent tumour in-growth, but it also negatively affects the role of

this is a good basis for all kinds of bacteria to grow and disperse in the whole lung.

This is a major problem in treatment with airway stents,” outlines Professor Jockenhoevel. The project is working to resolve these problems by developing an

On the luminal side we bring in the patients’ own respiratory epithelium, which can grow on the luminal side, so the complete function of the airway is

reconstructed within this stent the respiratory epithelium, which lines the respiratory tract and helps remove mucus from the lung. If the respiratory epithelium is not able to remove mucus then this can lead to occlusion of the stent, which can have serious consequences. “The patient is vulnerable to pneumonia, furthermore

endobronchial stent based on a combination of stent technologies and tissue engineering. “We’re building a new stent device using a porous material, which also contains specific anti-tumour drugs to prevent tumour in-growth,” says Professor Jockenhoevel. “On the luminal

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side we bring in the patients’ own respiratory epithelium, which can grow on the luminal side, so the complete function of the airway is reconstructed within this stent.”

Respiratory epithelium The first step in this is cultivating the patients’ own cells to help provide a functional respiratory epithelium on the luminal side of the stent. Researchers in the project take cells from the nose,

stent is designed to be used on patients with a life expectancy of six months to a year, enabling patients to enjoy their later months and also reducing the burden on health services. “We hope the stent will help to reduce complications and the time a patient will need to spend in hospital, which is also very important from a socio-economic perspective. Patients can really do something with the last months of their life,” stresses Professor Jockenhoevel.

We’re building up a new stent device using a porous material, which also contains specific anti-tumour drugs to prevent tumour in-growth. On the luminal side we bring in patients’ own respiratory epithelium cultivate them and then transfer them to the stent. “A part of the stent can be produced classically, like a normal medicinal product. We can introduce the cells to the lumen at a later point, shortly before implantation,” outlines Professor Jockenhoevel. This addresses two important points: preventing the growth of the tumour and also keeping the airway open, which Professor Jockenhoevel says helps improve the patients’ quality of life significantly. “If you use the classical silicon-coated stent then the patient goes to the clinic quite regularly.

They might need a bronchoscopy just to suck the mucus out of the lung, which is not very pleasant,” he outlines. “It really affects quality of life, and ultimately it’s also lifethreatening, as the patient might get pneumonia.”

This is an important point in the treatment of lung cancer, as the disease can be extremely debilitating, particularly in the latter stages. The

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The stent itself is quite durable, so Professor Jockenhoevel believes it could also be used in other applications.

“It could be used in some paediatric applications, for example where there is a malformation of the airway tract, or after a burn injury, where there is socalled inhalation trauma. It could also be used to treat tracheomalacia, which affects the structure and health of the trachea,” he says.

Jockenhoevel says it’s also possible to modify its shape. “Currently we are concentrating on making a tubular stent, but we could also make a Y-shaped one,” he outlines. “The airway system has a lot of side branches, which get progressively smaller. We could potentially make stents with up to three arms, so that the stent can fit into different parts of the anatomical structure.”

Researchers plan to test the technology in sheep within the next few months to assess the proof-of-concept and the overall effectiveness of the stent.

Professor Jockenhoevel expects that the tests will provide important information about the effectiveness of the stent. “We can see if the anchorage of the stent is good, for example, and to assess safety and whether the stent materials affect the surrounding healthy tissue. So you can really see if it performs well or not, which is the aim of the trial,” he says.

Researchers are already looking towards clinical trials in patients, while Professor Jockenhoevel and his colleagues are also investigating the wider potential of the stent. “Our next steps are the implementation of

Platform technology The stent itself is a platform technology, so different types of cells can be put on the luminal side, a point which further illustrates its wider potential. The project has investigated putting cells from the esophagus on the stent to treat esophagus tumours; however, Professor Jockenhoevel says their primary focus is on lung cancer.

“We have already taken steps towards pre-clinical trials with lung cancer,” he says. The stent can be used on both the trachea and the bronchi, while Professor

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PulmoStent as a specific aspect of the so-called Biostent. This is a platform technology stent which can also be used for cardiovascular, urogenital i.e. applications,” he explains.

The initial aim is to prove the stent can be applied as a means of treating atherosclerosis, a disease which affects arterial blood vessels. Professor Jockenhoevel believes that improved stent technology could have a significant impact on the treatment of the disease. “There’s a huge need for improved stent technology in the treatment of atherosclerosis, specifically with regard to small blood vessels – for example in the carotid artery, which brings blood to the brain,” he explains. “We want to investigate the use of viable stents in treating this disease and to bring this approach to clinical trials. We are doing this in parallel to our work in PulmoStent, and it belongs on the same platform technology which we have patented.”

At a glance Full Project Title Development & Evaluation of a Viable Stent Device for the Treatment of Broncho Tracheal Cancer (PulmoStent) Project Objectives The aim of the project is to develop a viable endotracheal stent (syn. PulmoStent) for the treatment of broncho-tracheal cancer diseases. The concept is based on the combination of stent technologies with the principles of tissue engineering.

Project Funding Funding (Requested EC contribution) €3,167,699.00 Project Partners Universities: (Coordinator) University Hospital Aachen (UKAachen), Dept. of Applied Medical Engineering, Dept. of Internal Medicine, Germany • National University of Ireland, Galway (NUIG), Dept. of Mechanical and Biomedical Engineering, Ireland • RWTH Aachen University, Institut für Textiltechnik (RWTH-ITA), Germany • Utrecht University (UU), Dept. of Pharmaceutics, Netherlands. SMEs: Epithelix SÀRL, Switzerland • 3T GmbH, Germany • Vysera Biomedical Limited, Ireland Contact Details Project Coordinator, Professor Stefan Jockenhoevel University Hospital Aachen (UKAachen) Dept. of Tissue Engineering & Textile Implants, Institute of Applied Medical Engineering Helmholtz Institute Aachen Pauwelsstr. 20; 52074 Aachen; Germany T: +49 241 80 23402 F: +49 241 80 82102 E: jockenhoevel@hia.rwth-aachen.de W: http://www.ame.hia.rwth-aachen.de/

Professor Stefan Jockenhoevel

Project Coordinator

Professor Stefan Jockenhoevel has a crossfaculty bridging professorship between the Institute for Textile Technology (Faculty of Mechanical Engineering) and the AME-Helmholtz Institute for Biomedical Engineering (Faculty of Medicine) at the RWTH Aachen University.

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Understanding the dynamics of the immune system Cell adhesion is a fundamental biological process which has significant implications for how the immune system responds to foreign bacteria or viruses. We spoke to Dr Kheya Sengupta, director of the SYNINTER project about her research into cell adhesion and how it could lead to earlier diagnosis of immune deficiency diseases The environment governing

cell behaviour is enormously complex, with a wide variety of factors affecting the way they interact with their environment and adhere to different surfaces. This is an area of great interest to Doctor Kheya Sengupta, the Director of the SYNINTER project. “The project is really at the interface of materials science and biophysics. My general area of interest is cell adhesion,” she outlines. The project aims to design innovative substrates and detection techniques to understand the dynamics and spatial organisation of the immunological synapse, which is formed at the interface between a T-lymphocyte and an antigen-presenting cell; research into cell adhesion is a crucial element in this work. “Cells adapt their stiffness according to the surface on which they are

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located. So if the substrate is hard then the cells also become hard, whereas if the substrate is soft then the cells are also soft,” says Dr Sengupta.

T-lymphocyte cells The mechanism by which cells sense their environment is not very well understood however, an issue the project is working to address. Dr Sengupta and her colleagues are looking in particular at T-lymphocytes, cells which are responsible for recognising foreign molecules in the body.

“These T-lymphocytes cells have receptors on their surface – these are antibody-like proteins. These proteins are able to recognise antigens, which are fragments of protein – or other substances – that are found in the body,” she explains. These

cells are able to recognise fragments of protein from invading bacteria or viruses and to initiate a response, while they also play a role in the aftermath of an attack.

“Their job afterwards is to have a memory of this attack, which is why vaccines target these T-lymphocyte cells,” continues Dr Sengupta. “T-lymphocytes are able to recognise antigen-presenting cells through their T-Cell Surface Receptor (TCR).”

These T-lymphocytes are even able to recognise processes that are activated by only a very few molecules – out of the millions in our bodies – and to respond accordingly. This response is thought to be related to the way T-cells reorganise the proteins of their membrane. “An important question is: what are the underlying physical interactions which

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Left Image: The surface of T-cells are covered with T-cell receptors (TCR), that recognize foreign antigens. The TCR are habitually present in the form of single molecules or random clusters. Using our patterned substrates, we were able to direct the position of these clusters (imaged by Total Internal Reflection Fluorescence microscopy in the inset).

We put ordered dots of an antibody against the TCR-complex (anti-CD3, seen in red on the main image) on glass.

When T-cells interact with this surface, they organize their TCR in such a way that the TCR clusters (cyan) co-localize with the antibody dots.

Image taken by: Dr. Fuwei Pi.

enable these molecules to re-organise on the membrane of the cell?” says Dr Sengupta. In order to address this question researchers have to image the process; it is not currently possible to do this in vivo, so rather than look at cellcell interaction, many researchers instead take a T-cell and put it on a glass slide. “They put the relevant molecules

closely mimics the physiological environment, while Dr Sengupta and her colleagues are also looking at the clustering of the proteins. “Another aspect which was not previously captured in research was the fact that the proteins on antigen-presenting cells are not only mobile but also structured, in the sense that they are often presented

Cells adapt their stiffness according to the surface on which they are located. So if the substrate is hard then the cells also become hard, whereas if the substrate is soft then the cells are also soft of the antigen-presenting cell – namely the antigen itself and one adhesion molecule – and put them on a glass slide,” explains Dr Sengupta. “Just throwing these two proteins on a glass slide does not replicate the physiological environment though.”

The project is following a different approach however, using silicone with a calibrated stiffness and replacing the glass slide with a substrate. This more

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in the form of clusters,” she explains.

Mimicking these clusters is a key part of the project’s research agenda. “This kind of patterning has been done before, but not in the context of T-cells. It has been shown that clustering is important in tissue cells, that it impacts on cell adhesion. Researchers varied the sizes of these clusters and showed that if it is below a certain critical size then the cells fail to adhere. This is really a

fundamental point about cell adhesion,” says Dr Sengupta.

Researchers in the project aim to perform similar studies on T-lymphocytes, yet conventional techniques are not well-suited to this purpose. The current protocol used for presenting nano- patterned substrates to cells is based on using gold nano-dots, which is not compatible with certain types of optical microscopy, a set of techniques used to magnify images of small samples. “For instance, you can’t use total internal reflection fluorescence microscopy – an advanced microscopy technique – with gold nano-dots,” explains Dr Sengupta. The project is developing substrates which are compatible with optical microscopy, enabling Dr Sengupta to analyse proteins in depth. “I’m replacing the gold nanodots with nano-dots of organic molecules, on which I put the relevant protein, supported by a lipid bilayer,” she continues. “So I put antigens in the form of dots, and I showed for the first time that the T-cell receptors on the T-cell surface co-localise with the antigen.”

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At a glance

Immune deficiency diseases

Full Project Title Smart interrogation of the immune synapse by nano-patterned and soft 3D substrates (SYNINTER)

This research holds real importance to our understanding of the immune deficiency diseases that arise from faulty cell adhesion.

Leukocyte adhesion deficiency (LAD), a rare disorder which can result in recurring infections, is an important example. “What happens in this case is that the adhesion molecules are present but they’re nonfunctional. At the moment, the way we detect diseases is mostly based on biochemistry – we detect whether the proteins are present or not,” says Dr Sengupta. These types of tests do not show whether a protein is nonfunctional; one potential way to address this is to challenge the cell with different kinds of patterns and force it to reveal its deficiency.

“If the environment is challenging, then fully-functional cells are probably going to overcome these challenges and do their jobs, whereas the slightly deficient cells would fail. This would be a way to diagnose any kind of disease where the structure of the immune synapse is affected at an early stage,” outlines Dr Sengupta.

Project Objectives We aim to design innovative substrates and suitable detection techniques to understand better the dynamics and spatial organization found in the immunological synapse, with the ultimate goal of developing new diagnostic tools for sensitive detection of immune deficiency diseases that arise from faulty adhesion.

Project Funding Funding is from ERC, supported by CNRS (Centre national de la recherche scientifique) and AMU (Aix Marseille Université).

Project Collaborators Laurent Limozin, Laboratoire Adhésion & Inflammation - CNRS/INSERM/AMU and Anne Charrier (CINaM, CNRS/AMU) Post-docs working on the project: Dr. Fuwei Pi and Dr. Astrid Wahl.

Contact Details Project Coordinator, Dr Kheya Sengupta CINaM, Campus de Luminy Case 913, 13288 Marseille Cedex 9 T: +33 6603 02862 E: sengputa@cinam.univ-mrs.fr W: http://cordis.europa.eu/project/ rcn/106787_en.html

Many people with LAD are actually unaware that they are suffering from the disease, as certain progenitor cells still function. However, it does leave people very vulnerable to infection. “They fall ill often but they don’t know why, and doctors don’t know why, because they seem to have all the proteins necessary,” says Dr Sengupta. The ultimate goal is to develop a technique capable of identifying these non-functioning cells, and hence to diagnose conditions like LAD at an earlier stage, but for the moment Dr Sengupta’s research is focused on more immediate objectives. “A lot of our work in future will be focused on quantifying the cell images which come in. We are already collaborating with biologists, but I would like to ask biologists to make genetically engineered cells which mimic the deficiencies that we find in diseases like LAD,” she says.

“Therefore, I would know whether or not a cell is diseased or defective in this particular way, and this will be a way to test my system.”

The SYNINTER team

Dr Kheya Sengupta

Project Coordinator

Kheya Sengupta did her PhD in India on liquid-crystalline phases of phospholipids.

In 2001 she moved to the laboratory of Erich Sackmann in Munich where she studied bio-mimetic systems. In 2004 she moved to Philadelphia, and worked on cell adhesion and mechanics. In 2005 she moved back to Germany, where she continued her work on adhesion of cells and cell models. In 2007 she moved to Marseilles as a researcher at CNRS, the National Scientific Research Council of France. She works at the Marseille Interdisciplinary Centre for Nano-Sciences.

Her current interests include adhesion and mechanics of cells and cell mimetic models, and the interaction of such soft systems with nano-scale objects.

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A family of endogenously produced gaseous molecules, ‘gasotransmitters’, are associated with a number of beneficial biological properties, but they can have adverse effects on health in excess amounts. The European Network on Gasotransmitters aims to boost the impact of European research in this field, as Professor Andreas Papapetropoulos explains

Boosting the impact of Gasotransmitter research A family of endogenously produced gaseous molecules, ‘gasotransmitters’, play important roles in many human organs and tissues, including the heart and the blood vessels, the immune system and the nervous system. The three principal gasotransmitters are nitric oxide (NO), carbon monoxide (CO) and hydrogen sulphide (H 2S). “A common feature linking NO, CO and H 2S is that they are produced by human cells in small amounts, but are associated with considerable toxicity when present in high concentrations. High concentrations might be the result of uncontrolled endogenous production or exposure to high exogenous levels,” explains Professor Andreas Papapetropoulos, the coordinator of the European Network on Gasotransmitters (ENOG). www.euresearcher.com

The prototype gasotransmitter is NO, which was described in 1980 as endothelium derived relaxing factor (EDRF). While a fair amount of information is available on NO, less is known about CO and H 2S, an issue that Professor Papapetropoulos and his colleagues are working to address. “We’re trying to employ some of the paradigms used to understand the biological actions of NO in order to unravel the properties of the newer gasotransmitters (i.e. CO, H 2S),” he continues. “We have already learnt a lot about CO and H 2S over the past decade. The true challenge though is to harness the therapeutic potential of the newer gasotransmitters, once we understand more about how they work in our bodies.”

The network is working to boost the

quality, competitiveness and impact of European biomedical research in this area. Bringing together scientists from 24 European countries, the network aims to facilitate research on gasotransmitters by encouraging researchers to share their reagents, tools, knowledge and ideas. Another important aspect of the network is to provide financial support for mobility of young and early stage researchers between member laboratories. ENOG members have already published several joint publications as a result of their common work within the network.

Working groups NO and H 2S are derived from amino acids and CO is produced through the breakdown of iron-containing structures

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(C. Szabo, Gaseotransmitters: New Frontiers for Translational Science. Sci. Transl. Med. 2, 59ps54 (2010).)

Credit: C. Bickel/Science Translational Medicine. called haem, while Professor Papapetropoulos says they are also quite different in their reactivity. “H 2S is more promiscuous – it reacts with more biological molecules than NO, and then CO has fewer targets than the other two,” he explains. The project is investigating key issues around gasotransmitters, including their abundance in different cells of the body, how their production is controlled and what happens when their production becomes deregulated. A number of beneficial biological properties are associated with gasotransmitters, which researchers are trying to exploit.

“Gasotransmitters inhibit programmed cell death (or apoptosis). They also dilate blood vessels, protect the heart, exert anti-inflammatory properties under most conditions and are neuro-protective,” outlines Professor Papapetropoulos.

To answer the scientific questions on gasotransmitters, the action is divided into four working groups, covering different aspects of gasotransmitter chemistry and biology. This encompasses

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both fundamental research into their roles in the body, as well as more applied work.

“One of the working groups is studying the production of the gasotransmitters and the signalling pathways they trigger, while another is looking at their role in physiology and in the initiation and progression of disease,” says Professor Papapetropoulos. “A third group is looking

Translational problems and opportunities It has become apparent that gasotransmitters are found in almost every tissue in the body. “This widespread distribution tells us they are important for many functions, but also makes it difficult to selectively inhibit gasotransmitters in one part of the body without interfering with normal

Gasotransmitters inhibit programmed cell death (or apoptosis). They also dilate blood vessels, protect the heart, exert anti-inflammatory properties under most conditions and are neuro-protective at making new chemical entities, potentially new drugs (or lead compounds that will lead to drugs), that will either boost or inhibit the production or action of gasotransmitters, depending on whether they are in shortage or surplus in the disease studied. A fourth group employs these agents in different disease models, to see if they are effective.”

physiological processes in another,” Professor Papapetropoulos points out.

Two forms of constitutive (expressed at all times) NO synthase (the enzyme that produces NO in the body) have been identified – one that is known to be primarily expressed in the endothelium, which lines all our blood vessels, and one in nerves. “We don’t currently have good

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At a glance selective inhibitors that can differentiate between the two types of NOS. If one could come up with novel drugs that can inhibit only the neuronal NO, we might have a new candidate drug to use in strokes,” says Professor Papapetropoulos.

Inhibiting neuronal NOS has been shown to be advantageous in treating strokes. However, whilst the NO that comes from the endothelial NO synthase is beneficial, you clearly need a compound to selectively inhibit one form of NOS and not the other. “It is equally difficult to selectively target an organ with a deficiency in a gasotransmitter without affecting the function of other tissues,” says Professor Papapetropoulos.

In spite of these difficulties, there are clinically used drugs that work by modifying gasotransmitter levels. For example, nitroglycerin (NTG) has been used since 1867 to treat angina pectoris: it

Effective collaboration is essential to building on this kind of fundamental knowledge and developing new drugs, a complex process that calls for a wide range of expertise. “You need biochemists to produce and characterize the enzymes that generate or respond to gasotransmittrers, structural biologists to define the 3 dimensional structures of the enzymes, and medicinal chemists to design the chemicals that would affect the function of the enzymes by targeting their active sites.”

“Then, once the novel chemicals have been synthesized, you need pharmacologists to test the compounds for their efficacy. If need be, compounds undergo several rounds of optimisation,” outlines Professor Papapetropoulos. “On the other hand, molecular biologists and geneticists make crucial contributions by generating model organisms that lack

The true challenge though is to harness the therapeutic potential of the newer gasotransmitters, once we understand more about how they work in our bodies is effective against this condition because of the NO it generates. Physicians had used NTG for over 100 years, without knowing exactly how it worked.

It is thus not surprising that the scientists that described the mode of action of NTG were awarded the Nobel Prize for Physiology/Medicine in 1998.

More recently, drugs that target the ‘receptor’ for NO (soluble guanylyl cyclase) received marketing authorisation approval for pulmonary hypertension; interestingly they activate the ‘NO-receptor’ without releasing NO. The research performed within the ENOG is currently pre-clinical in nature, with researchers aiming to identify diseases which could be treated by either supplementing or inhibiting gasotransmitter production. “H 2S for example shows great promise for cardioprotection and gastrointestinal protection. Ultimately the hope is to translate these findings into therapeutic gain,” explains Professor Papapetropoulos.

“Interestingly, we have found some drugs, for example zofenopril, that are currently in clinical use and produce H 2S. It remains to be determined what percentage of the beneficial effects of the drug are gasotransmitter-related.”

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the expression of gasotransmitterrelated enzymes, or overexpress them.

Then physiologists characterize the phenotype of these animals generated.

This latter approach can give valuable information about the types of diseases that would benefit from gasotransmitter treatments, so you can study which diseases they are involved in. It is exactly this multidisciplinary approach we are trying to take to get answers within our network.”

There is great scope for further research, so while the current COST action will end in 2015, Professor Papapetropoulos and his colleagues are looking to continue their work in this area. Plans are already in place to apply for further funding (particularly to procure Horizon 2020 funding from the EU) and establish wider collaborative projects. “We are already in contact with other societies and scientists throughout the world that work with NO and H2S. European scientists will have a very prominent position in the new networks formed,” says Professor Papapetropoulos.

“We also aim to establish partnerships with SMEs and biotech companies that are interested in developing chemicals, therapeutic agents and detection reagents for gasotrasnmitters.”

Full Project Title Gasotransmitters Project Objectives The objective of our network is to collate scattered knowledge, resources and expertise on NO, CO and H2S in Europe and to drive research in order to better understand gasotransmitter biology so that the therapeutic potential of gasotransmitters can be harnessed.

We aim to disseminate innovation, boost collaborations and increase the European competitiveness in this field of research.

Project Funding European Science Foundation Project Partners 170 members from 24 European countries. http://www.cost.eu/domains_actions/ bmbs/Actions/BM1005 Contact Details Project Coordinator, Andreas Papapetropoulos, B.Pharm, Ph.D., F.A.H.A., FBPharmacolS Professor of Pharmacology Drug Discovery & Pharmacology Group Department of Pharmaceutical Chemistry Faculty of Pharmacy University of Athens Athens 15771 Greece T: +30 210 727 4786 E: apapapet@pharm.uoa.gr W: http://www.gasotransmitters.eu/ W: http://en.pharm.uoa.gr/

Andreas Papapetropoulos, B.Pharm, Ph.D.

Project Coordinator

Andreas Papapetropoulos (BPharm, PhD, FAHA, FBPharmacolS) is Professor of Pharmacology at the Faculty of Pharmacy of the University of Athens and Affiliated Investigator at the Biomedical Research Foundation of the Academy of Athens. He is board certified in Pharmacy, member of several scientific journal editorial boards and European Medicines Agency expert.

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Molecular networks are subject to many interactions between components, while the components themselves can exist in multiple states. Researchers need sophisticated mathematical methods to understand how such complex networks process information, as Dr Jeremy Gunawardena, Associate Professor at Harvard Medical School explains

Making sense of molecular networks The complexity of molecular

networks is a challenge for biology researchers, who need sophisticated new mathematical methods to track how these networks process information and make decisions.

This is an area of long-standing interest to Dr Jeremy Gunawardena, coordinator of the Algebraic Geometric Approaches to Biological Complexity project. “This project is trying to exploit some methods from pure mathematics which have not been used in biology at the molecular level before. We think these methods have some very powerful features that allow us to rise above molecular complexity,” he says.

Based at Harvard Medical School in the US, Dr Gunawardena and his colleagues are now using these ideas, which have their roots in a discipline called algebraic geometry, to get a sense of the capabilities of very complicated networks. “We’re really trying to get a functional understanding of the network of molecular interactions. The underlying complexity has two forms,” he outlines. “One is that there are a lot of interactions between the components. The other issue is that the components themselves can exist in multiple states. So you have the complexity of the components themselves, as well as the complexity of the interactions through which the components talk to each other.”

Chemical signals The molecular networks within cells can be stimulated by external chemical signals, such as growth factors or hormones that are typically conveyed around the body in blood or within tissues. These signals impinge on molecules in the membrane of the cell, the receptor molecules. “These

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receptor molecules become activated, and they instigate a process of signal transduction inside the cell. They recruit various molecular components, and they undertake various forms of processing on that signal until the cell decides what to do as a result of seeing that signal. Signal transduction networks are typical of the systems we look at,” explains Dr Gunawardena. The signal might be a cue for the cell to begin to divide and proliferate, or to go down a differentiation pathway and become a particular type of cell. “These signal transduction networks could participate in decision-making in early development,” continues Dr Gunawardena.

“Once the organism has actually been constructed and reached adulthood then evolution is very good at re-using these mechanims, so that the same signal transduction networks can implement the organism’s normal physiological responses.

They can also become deranged when the organism falls ill, which is why understanding their functionality can help us develop more effective therapies.”

There are multiple layers of complexity within these networks, with various signals, mechanisms and events affecting the way they are structured. The project is mainly focusing on the protein level, at which there is a particularly high level of complexity. “Once a gene has been turned on, once a protein has been expressed and is present in the cell, evolution has found ways to actually modify the structure of the protein,” explains Dr Gunawardena.

These modifications can occur with different chemical groups. “Pretty much any protein in any cell in your body is continuously being subjected to this post-

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Everyone who tries to study biology these days comes up against the problem of molecular complexity. We believe that algebraic geometry offers us a mathematical language which can help us rise above that complexity and thereby complement the insights

which come from experimental studies

translational modification, as it’s called.

So, even though that protein came from a single gene, and one might think; ‘ok we’ve got a single gene, we’ve got a single protein’ – in practice that protein could be in millions of modification states,” points out Dr Gunawardena. “We’re talking about just one protein here, and we have this huge network of proteins, all of which are interacting and different modification states of one protein may behave differently to other modification states of the protein. We’re particularly interested in these kinds of protein-level complexities that come from post-translational modification.”

Mathematical methods Researchers are using mathematical methods to distil some of the underlying principles behind this complexity. These methods are potentially very powerful, because of the way in which chemistry works. “Once you describe biochemistry in mathematical terms and try to explain how biochemical reactions work, they give rise to polynomial equations. These equations are sums of many terms, each of which looks like a product of the key variables,” explains Dr Gunawardena.

From a mathematical point of view algebraic geometry can be thought of as the mathematical study of polynomial systems; Dr Gunawardena believes that combining these methods with biochemical understanding could yield important results. “There’s often a lot of accumulated knowledge about some aspects of the complexity that we see, and a lot of experimental evidence for instance about the number of modification states that a particular protein would have, as well as knowledge about the reactions through which other proteins control and regulate those modifications,” he says.

“We often start from knowledge of the network of reactions that is outlined in the literature, that’s typically our starting point. We try to use mathematics to distil predictions from that, which we can then test experimentally.”

The systems inside cells tend to have a lot of moving parts but only certain things can be measured experimentally.

Researchers have discovered that it is possible to focus on a small number of components, and by doing so gain wider insights. “We could say; ‘we’re particularly interested in these components, because we think these are the key regulators,’”

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At a glance Full Project Title Algebraic Geometric Approaches to Biological Complexity Project Objectives My research group studies information processing in mammalian cells using a combination of experimental, mathematical and computational approaches. We are particularly interested in exploiting new methods from pure mathematics to distill biological principles from the new molecular understanding that has emerged from the Human Genome and other genome projects.

Contact Details Project Coordinator, Jeremy Gunawardena Associate Professor, Virtual Cell Program Department of Systems Biology Harvard Medical School 200 Longwood Avenue Boston, MA 02115, USA T: +1 617 432 4839 E: jeremy@hms.harvard.edu W: http://sysbio.med.harvard.edu/ faculty/gunawardena/

explains Dr Gunawardena. The question here is whether it’s possible to eliminate all the background complexity, and just focus on the key components of interest; Dr Gunawardena says algebraic geometry provides methods for doing this in a systematic way. “It may be that there isn’t an equation between the components that we’ve selected, because there’s more complexity that we didn’t appreciate,” he

relatively small systems because the current algorithms are slow and computationally expensive. However, Dr Gunawardena says it’s often the case that researchers can still get by with restricting attention to a simpler class of equations.

“We’re interested in developing more powerful computational tools, computational algorithms which are much faster, but which only tell us about certain

The components themselves can exist in multiple states.

So you have the complexity of the components, as well as the complexity of the interactions through

which they talk to each other says. “But what we can do is try to work out the equations, and if we fail then that gives us a hint as to what other things we might want to include, until finally we’ve got a small set of things that include the components we’re interested in, as well as those we possibly hadn’t appreciated previously. We’ve got an equation on just those things, and now we can go and test that. We don’t have to measure everything in the network, we just have to look at those particular components.”

These methods could in principle be applied to virtually any system, but in practice they only work efficiently for

kinds of equations, which are good enough for the problem at hand” he outlines.

“Everyone who tries to study biology these days comes up against the problem of molecular complexity. We believe that algebraic geometry offers us a mathematical language which can help us rise above that complexity and thereby complement the insights which come from experimental studies. It can help us to look at very complicated molecular and cellular machines and identify the principles on which they work.”

Jeremy Gunawardena

Project Coordinator

Jeremy Gunawardena is a pure mathematician by training. He held academic appointments at the University of Chicago and Trinity College, Cambridge before joining Hewlett-Packard (HP) Research. He became HP’s Director of Basic Research in Europe before returning to academic life as Associate Professor at Harvard Medical School’s Department of Systems Biology.

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Queuing for basic supplies after Typhoon Haiyan in the Philippines.

Photograph by Paul Stevens.

Ethics and Disasters Ethical dilemmas frequently arise in the aftermath of natural disasters, yet few resources are specifically available to help guide people on the ground in their decision-making. We spoke to Dr Dónal O’Mathúna, Chair of COST Action IS1201 about the Disaster Bioethics project’s work in investigating the types of ethical issues that arise and how people respond The

scale of natural disasters sometimes overwhelms local resources.

Unable to deal with the massive medical and humanitarian task, authorities sometimes ask for international assistance. However, both local and international teams face major ethical issues in disaster response, an area which forms the primary focus of the Disaster Bioethics COST Action. “Our focus is on those situations where large numbers of people are affected in a very severe way, leading to serious medical and humanitarian needs. We’re looking at the types of ethical issues that then arise, and how we can provide resources to help people respond to ethical dilemmas,” says Dr Dónal O’Mathúna, the Chair of the Action. www.euresearcher.com

The project arose out of a realisation that people on the ground after disasters face many challenges, including ethical dilemmas. “After the Tsunami of 2004 a lot of decisions needed to be made for which evidence was lacking. Such decisions were further complicated by their ethical dimensions, especially how to decide who to treat when you can’t treat everyone due to a lack of resources,” says Dr O’Mathúna. “Similarly, after the Haiti earthquake there were many questions about how best to treat crush injuries.

Was amputation always the right course of action? Such decisions have an ethical component, as well as requiring research evidence. In response to such questions, more research was called for, but conducting research during disasters raises even more ethical questions.”

Natural disasters The primary focus of the project is on natural disasters, but Dr O’Mathúna says these can’t always be neatly separated from those in which human activities have played a part. For example, the damage from Hurricane Katrina was intensified by years of poor planning and a poorly coordinated response. Similarly, ethical issues arise in refugee camps whether people have been displaced by conflict or natural events. The importance of humanitarian responses is clear, but Dr O’Mathúna says a more evidence-based approach is needed. “Today there’s a much greater emphasis on finding ways to collect data during a disaster that helps future responders. With the calls for data collection, outcome evaluation, needs assessment, and other research, ethical

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guidelines for disaster research are also needed,” he outlines.

The priority in disaster response remains with the immediate medical and humanitarian issues, yet Dr O’Mathúna believes it is also important to gather evidence to inform future responses. The COST project is looking at the ethical aspects of disaster research and response.

“Our project is examining the ethical aspects of responding to disaster victims, helping to ensure that the people who are injured have their dignity upheld as much as possible, and that they are involved in ethical decision-making as much as is practically feasible given the conditions,” says Dr O’Mathúna. “There are ethical issues for the doctors and nurses who go into these situations.”

Highly trained medical and healthcare staff sometimes find that they’re unable to act according to their normal ethical standards in a disaster setting. This creates what’s called ‘moral distress’, feelings of anxiety and distress about how they are making those decisions – or being prevented from doing what they believe is right. “We’re developing training tools that will help responders prepare, so that they will be aware of the types of issues that they may have to face when they get out into these settings,” outlines Dr O’Mathúna.

“These ethical dilemmas are still going to be difficult to handle in and of themselves,

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but at least we can help prepare people a little better to face those decisions.”

The nature of these decisions will vary according to the exact circumstances people face. If responders travel to a nation with very different values to their own there may also be cultural differences, which Dr O’Mathúna says must at least be acknowledged as part of an ethical response. “There may be significant

a situation completely different to anything they’ve experienced before, which reinforces the importance of preparation. “Some of the NGOs [nongovernmental organisations] that we have talked to have noted that up to half of the responders they train for such missions will not go on a second one,” says Dr O’Mathúna. “In many cases that’s because of the ethical dilemmas that they’ve had to

Our project is examining

the ethical aspects of responding to disaster victims, helping to ensure that the people who are injured have their dignity upheld as much as possible, and that they are involved in ethical decision-making as much as is practically feasible given the conditions differences regarding who makes medical decisions in different cultures,” he points out. “If it’s the way things are done in another culture then that person needs to be prepared to think those issues through, and to have a way of processing them.

They may even need to decide ahead of time whether they are willing to work according to somebody else’s ethical values in certain situations.”

These types of situations can occur where there is quite a broad-based international response to a disaster. In many cases these responders are entering

face - they feel like those were so overwhelming that they never want to be part of another response team again.” That can be a great loss of experience and training resources to the organisations.

Effective training is crucial to preparing people well, and also to ensuring that they have skills relevant to the situations they’re going to face. There is often intense publicity around natural disasters and people understandably want to help, but aid should be targeted at actual needs, which has not always been the case in the past.

“People have arrived from other countries

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unable to speak the language, not really trained for the needs that are there, not understanding the way things work elsewhere, or the resources that already exist,” outlines Dr O’Mathúna. “We need to realise that just because we want to help, it doesn’t mean that people need the sort of help that we might think they do.”

Ethical dimensions There is a need for clear direction in these circumstances, for people to think about what is really needed, and about how public goodwill can be directed most effectively.

These types of decisions have clear ethical dimensions, says Dr O’Mathúna. “How can we ensure the just and fair allocation of resources when they get out to these places?

How can policies be put in place to ensure that the donations go to those who really need the help?” he outlines. This may be particularly difficult in conflict situations.

“Some organisations have a clear policy of being neutral, and of taking care of everybody. But there are other organisations who decide that this will cause other problems,” says Dr O’Mathúna.

These kinds of issues are enormously complex, and there are no easy answers.

However, Dr O’Mathúna hopes that the project will give responders clearer guidelines and practical training tools to help make ethical decisions. “We’re bringing together doctors, practitioners, responders,

and various organisations who are involved in the field. We’re bringing them together with ethicists from academic backgrounds and other international organisations to look at the issues, to have the people with field experience describe the practical, ethical dilemmas they face,” he says. “They have been saying to us; ‘we need help to think these issues through. What really are the kind of ethical values that we need to highlight and prioritise?’”

The project aims to develop guidelines, policy proposals and training materials out of this research that could be used to help prepare responders. Ethical theory has historically been directed mainly towards finding ideal solutions in ideal settings, but a disaster setting is far from ideal; Dr O’Mathúna says it is important to take this into account. “Decision-making processes need to be appropriate for these non-ideal settings,” he outlines. The project also aims to build collaborative teams that will pursue funding for specific disaster bioethics research projects, which Dr O’Mathúna hopes will lead to a new generation of researchers trained in both ethics and humanitarian work. “They would be able to get involved in disaster response and policy-making organisations. With both humanitarian experience and training in ethics, they would be able to help various organisations address the ethical dilemmas that their members face,” he says.

Photographs taken in the aftermath of Typhoon Haiyan.

Photographer Paul Stevens.

At a glance Full Project Title Disaster Bioethics: addressing ethical issues triggered by disasters Project Objectives The primary objective of COST Action IS1201 is to build an interdisciplinary network of scholars, relief agencies and policy-makers that will stimulate scholarly discussion on disaster bioethics and contribute to improved ethical decision-making for disasters by identifying ethical issues in disaster preparation and response, proposing guidelines, and developing training materials and other ethics resources.

Project Partners The Action has partners from 28 countries that participate in COST, primarily European countries. The Action has collaborative links with other researchers in Canada, USA, New Zealand and Kenya.

Project Funding Funding is provided for the Action from COST, an intergovernmental framework for European Cooperation in Science and Technology (funding period: 2012-2016).

Contact Details Chair of the Action, Dónal O‘Mathúna, PhD Senior Lecturer, Dublin City University, Ireland E: donal.omathuna@dcu.ie Science Officers Individuals, Societies, Cultures and Health (ISCH), COST Office E: valentina.vignoli@cost.eu E: rossella.magli@cost.eu W: www.DisasterBioethics.eu

Dónal O‘Mathúna

Dónal O’Mathúna, PhD is Chair of COST Action IS1201: Disaster Bioethics. He is Senior Lecturer in Ethics, Decision-Making & Evidence in the School of Nursing & Human Sciences, Dublin City University, Ireland and Visiting Professor at the European Master in Disaster Medicine. He co-edited Disaster Bioethics: Normative Issues when Nothing is Normal (Springer, 2014).

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Harnessing the potential of photocatalytic systems

The world has access to only a finite supply of fossil fuels, making the development of renewable sources of energy a research priority. Photocatalytic systems hold real potential in these terms, say Benjamin Dietzek and Vincent Artero of the PERSPECT H2O COSTAction, who tell us about their research into supramolecular photocatalytic water-splitting Renewable energy is widely recognised as a research priority, with scientists investigating new generation methods that could potentially reduce our dependence on fossil fuels. Photocatalytic systems, which work by harvesting sunlight and split water to produce molecular oxygen and hydrogen, hold real potential in this regard says Benjamin Dietzek, the Chair of the PERSPECT H2O COST-Action. “The Action focuses in particular on supramolecular photocatalytic water splitting. This is where arguably the greatest breakthroughs in sustainable hydrogen-production are expected, as molecular design enables the tuning of molecular function towards optimal elementary processes,” he outlines. “We face many scientific

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challenges in this work, which are being adressed in the Action through a coherent, structured approach to research.”

This work holds real importance to our economic future, particularly in the context of continued concern about conventional sources of energy, in terms of both their environmental impact and their long-term sustainability. Energy is of course crucial to many areas of economic activity, and while new techniques have been developed to tap into previously inaccessible sources of gas and oil, the world has only a finite stock of fossil fuels, reinforcing the potential importance of renewable energy. “The development of novel approaches towards hydrogen as a solar fuel (e.g. produced from solar energy and water) and

researching the infrastructure, which it will have to be associated with - e.g. a hydrogen-based economy - is naturally of the utmost importance to ensuring sustainable economic growth,” says Benjamin Dietzek.

The Action brings together partners from across Europe, with the shared goal of developing a fundamental understanding of the function which determines light-induced elementary reactions in supramolecular photocatalytic water splitting, and to realize novel supramolecular photocatalysts for water catalysts. Collaboration is essential in pursuing these kinds of ambitious research objectives which bring together scientists from different disciplines; Dr Dietzek says the structure of the Action enables and

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encourages researchers to share important findings. “COST is the ideal tool to tackle these challenging tasks as it allows us to establish a pan-European research network dedicated to such an important and technologically challenging scientific goal,” he enthuses.

Functional materials The Action aims to develop functional materials and ultimately integrate them into functioning photocatalytic devices, which it is hoped will produce a sustainable source of renewable energy.

A sound understanding of a variety of processes critical to water splitting is crucial to this goal, hence the Action’s work also includes exploratory research into the fundamental structure of supramolecular architectures. “Within the Action researchers are investigating all the elements of supramolecular architectures that are required for artificial photosynthesis,” explains Vincent Artero. “This includes antenna systems, where we aim to enhance the absorption of visible light and ensure efficient energy transfer to a primary reaction center where charges are generated.”

Rau, Professor Leticia González, Professor Antonin Vlcek and Dr. Elizabeth Gibbson.

One of the key issues being addressed in these working groups is the stabilization of the catalytic centres, which are essential to the long-term operation of catalytic systems. Researchers will generate ligand frameworks to stabilise the highly oxidized metal centres. These frameworks will be inert towards being oxidized or reduced by the metal centre during catalytic turn-over.

Researchers are also working to optimize molecular structures, including investigations into whether it is possible to design artifical structures which are capable of coherent energy transfer, a process which was recently discovered in natural light-harvesting systems.

Sven Rau, the coordinator of the working group concerned, says this research will bring some important benefits.

“Optimized catalysts will not generate ‘more energy’ in the sense that the reactions they catalyse are determined by the chemistry and associated thermodynamics. However, optimized catalysts will optimize the yield of solar to chemical energy conversion and/or will increase the number of reactions

The Action focuses in particular on supramolecular photocatalytic water splitting. This is where arguably the greatest breakthroughs in sustainable hydrogen-production are expected The turnover of the catalyst, namely the amount of hydrogen and oxygen generated over a certain time-period, will directly affect the power of the targeted photocatalytic device. The Action is therefore working to design optimized antenna systems. “This requires that the photocatalyst itself is very efficient in generating the reaction products. To this extent the Action works with a certain set of catalyst lead structures, which have been established by Action members, and also investigates ways to improve their function,” says Benjamin Dietzek. “At the same time we are also targeting novel lead structures for water oxidation and proton reduction catalysts.”

This broad research agenda requires a range of expertise, hence the Action brings together scientists from a range of fields in four different working groups, which are coordinated by Professor Sven

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taking place in a given time interval,” he explains.

As scientists learn more about these fundamental aspects of water-splitting and catalysis, the research focus in future is likely to shift towards more applied, technological topics and the development of novel supramolecular photocatalysts. This research could have a significant economic impact, yet supramolecular photocatalytic water splitting is still some way from practical application and there is still a great deal to learn about the topic. This is an area of great interest to Vincent Artero, who intends to pursue further research in this area which he hopes will pay long-term dividends. “We will seek further financial support from both the EU and national funding agencies that will allow us to carry on this exciting European research project,” he says.

At a glance Full Project Title Supramolecular photocatalytic water splitting (PERSPECT-H2O) Project Objectives PERSPECT-H2O wants to develop a fundamental understanding of the function determining light-induced elementary reactions in supramolecular photocatalytic water splitting and to realize novel supramolecular photocatalysts for water splitting.

Project Partners PERSPECT-H2O integrates leading European groups and national research centers, focusing on a central theme of contemporary research in homogeneous photocatalysis and integration of supramolecular photocatalysts towards the construction of functional materials.

Contact Details Project Coordinator, Benjamin Dietzek Institute for Physical Chemistry Friedrich Schiller University Jena Helmholtzweg 4 07743 Jena T: +49 3641 206332 E: benjamin.dietzek@uni-jena.de W: www.perspect-h2o.eu

Dr Benjamin Dietzek (left) Dr Vincent Artero (right)

The scientific work of Dr Benjamin Dietzek addresses the application of femtosecond timeresolved spectroscopy and non-linear microspectroscopy in biophotonics and material photonics. Different experimental techniques are combined in order to characterize the lightinduced charge transfer steps in novel artificial light collecting molecules.

Vincent Artero, from the Life Science Division of CEA in Grenoble, develops research projects in bioinspired chemistry for H2 applications and artificial photosynthesis. He’s particularly interested in the development of molecularbased (photo)electrode materials.

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Tracking the FDI flows

The established patterns of foreign direct investment have started to change over recent decades, with outward investment from the emerging world growing at a rapid pace and an increasing number of southern multi-nationals investing in advanced economies. Professor Louis Brennan tells us about his research into the extent of the phenomenon, the factors driving it, and its likely impact Foreign direct investment (FDI) has historically been directed between northern, developed economies, or from developed economies into emerging nations. However, the established patterns of FDI have started to change over recent decades, an area of great interest to Professor Louis Brennan.“Some decades ago you started to see south-south flows, where firms from developing and emerging economies started to invest, typically in neighbouring, comparable economies. In the ‘90s we then started to see a new pattern emerging, of investment by companies from less mature economies into advanced countries.

This phenomenon, although of very small magnitude initially, has accelerated quite substantially over the past decade,” he says. Based at Trinity College, Dublin, Professor Brennan is the coordinator of a project looking at this trend. “We look at the extent of the phenomenon, the factors

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driving it, and we also seek to evaluate the impact of it,” he outlines.

Some of these companies are from southern hemisphere nations such as Brazil and South Africa, but the project’s scope is not limited solely to enterprises from south of the equator. Southern multinationals are broadly defined within the project as those companies from outside the established triad of North America, pre-accession Europe and Japan. “So the term ‘southern multi-national’ is not exclusive to the southern hemisphere at all,” explains Professor Brennan. The project aims to compare these multinationals across a broad range of criteria.

“How do Brazilian multi-nationals compare to Chinese multi-nationals? How do Indian multi-nationals compare to Chinese multi-nationals?” outlines Professor Brennan. “We are looking to compare them in terms of their country of origin and also issues like the different

sectors in which they operate, the nature of the ownership structure of the company, and their mode of entry into the European market.”

Southern multi-nationals The figures underline the growing economic influence of these southern multi-national companies. Somewhere in the region of 30 percent of outward FDI is now from the non-traditional, nonadvanced countries of the world, a proportion that is set to rise further in future. “That investment is growing at a faster pace than investment from the developed countries. So it’s an increasing phenomenon, and it’s an increasingly significant phenomenon,” says Professor Brennan. These emerging multi-nationals are targeting quite a diverse range of economies, with the recent financial crisis having left many businesses and nations in need of capital. “We’ve seen many

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examples in recent years of investment coming into Europe, particularly the distressed economies of Europe, as there are some good buying opportunities available. Companies and countries are in need of capital, and these southern multinationals are able to acquire distressed assets at attractive valuations,” explains Professor Brennan.

These multi-nationals vary widely in structure. While a large share of Chinese investments tend to be by state owned enterprises, and the state plays a similarly central role in many Russian companies, Professor Brennan says Indian companies tend to more family-controlled type conglomerates.

“There’s less state involvement in these types of companies.

There’s a variety, but the role of the state, in general, is much greater in these companies than you would observe in the case of multi-nationals from developed economies,” he outlines. These investments can be used almost as a way to exert influence; there have been examples of this recently in the relationship between Russia and some of its neighbours. “Some companies have adopted policies which reflect the interests of the state and its foreign policy priorities,” acknowledges Professor Brennan. “The most overt examples of multi-nationals from emerging

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economies serving state interests have been those of Russia.”

The project is also looking at the impact of these investments and how these southern multi-nationals fare in Europe when they enter the market. Researchers don’t have much data to make this assessment, as growing investment from southern multi-nationals is a relatively recent phenomenon, but Professor Brennan says they have still been able to identify some general trends. “The companies that are more internationalised

advanced world generally. They have to overcome differences in terms of the institutional environment and cultural differences more generally,” says Professor Brennan.

These companies may also have very different management and organisational practices to those in more developed economies. “These companies are coming in to advanced economies because they want to accelerate their own development.

They want to move up the value chain, they want to acquire know-how, they want to

These companies are coming in to advanced economies because they want to accelerate their own development.

They want to move up the value chain, they want to acquire know-how, they want to acquire technology, they want to acquire assets prior to their entry into Europe tend to be more successful than those who have little international experience prior to entering the European market,” he outlines. The global economy today is much more integrated than it was in the past, yet companies still face challenges when they enter new markets. “These challenges are greater for companies coming from the emerging world into Europe and the

acquire technology, they want to acquire assets,” explains Professor Brennan. This can then be used to strengthen the company’s position in their own domestic market. “In the case of Chinese companies, it’s very much related to playing a role in terms of China’s own domestic development.

These companies can acquire know-how and technology, then deploy that back in the Chinese market to improve their

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At a glance Full Project Title The Emergence of Southern Multinationals and their Impact on Europe Project Objectives The main objectives of this Action are to develop an enhanced capacity for scholarly analysis of the emergence of Southern Multinationals to establish and test empirically their impact on Europe and its stakeholders; to assess existing EU wide and country policies in relation to this phenomenon and make policy recommendations.

Project Partners Belgium • Bosnia and Herzegovina • Croatia • Denmark • Finland • France • Germany • Hungary • Iceland • Ireland • Israel • Italy • Netherlands • Norway • Poland • Portugal • Romania • Serbia • Slovenia • Spain • Sweden • Switzerland • Turkey • United Kingdom • American University of Cairo, Egypt • Institute of World Economy and International Relations, Russian Federation Project Funding This is a COST ACTION funded grant http://w3.cost.esf.org/index. php?id=233&action_number=IS0905 Contact Details Project Coordinator, Louis Brennan School of Business, Trinity College, Dublin 2 Dublin Ireland T: +35318961993 E: brennaml@tcd.ie W: http://www.cost.eu/domains_actions/ isch/Actions/IS0905 Brennan, L. (ed.) “The Emergence of Southern Multinationals and their Impact on Europe”, Palgrave Macmillan, 2011.

Hay, Francoise, Milelli, Christian and Yunnan Shi, “The Impact of the Global Financial Crisis on the Presence of Chinese and Indian fFirms in Europe”, Sussex Academic Press, 2012.

domestic operations,” continues Professor Brennan. The knowledge and capabilities acquired in advanced markets can be very valuable to companies looking to develop and grow in their own domestic market.

Chinese market The Chinese market is developing very rapidly and competition is intense, yet the stage of development varies widely between sectors. Relatively few Chinese companies currently offer high-value, advanced products or services to their customers, so they can differentiate themselves by acquiring expertise and assets from other markets. “Companies can gain an advantage not only against other domestic players, but also against any foreign competition,” says Professor Brennan. This hints at a relationship between levels of FDI and the strength of the domestic market, which changes as an economy matures and develops. “Inward FDI tends to happen through the early and medium stages of the development of an economy. As an economy develops, you then see the beginning of outward FDI taking place,” outlines Professor Brennan.

As an economy moves towards a more advanced stage of development, there is more or less an equal balance between the volume of inward and outward FDI. Investment from the emerging economies into the developed economies is progressing at a rapid rate, which Professor Brennan believes is a symptom of a wider trend. “The world is re-balancing – we’re seeing a shift eastwards in the world’s economic centre of gravity. Economic

power is growing in the developing world.

This phenomenon of companies from emerging economies investing in the developed economies is a striking and very significant example of that rebalancing of power,” he says. “We anticipate that these companies will start to compete directly against established companies in developed markets. Up until now we’ve seen western companies competing against domestic companies in emerging markets. But we’re going to see more and more companies from emerging economies position themselves in advanced markets.”

This trend has been accelerating in recent years, yet Europe lags behind the US in terms of collecting data. This is an issue which Professor Brennan believes needs to be addressed. “If you don’t have data on the phenomenon, then you’re at a loss in terms of informing policy and policy responses to it,” he points out.

While many established economies are keen to attract FDI, these southern multinationals come from a very different institutional environment, which raises a number of issues. “We feel that the European Parliament should become much more active in the field of investment policies. In particular to safeguard the core pillars of the European social model in terms of issues like labour rights and the environment,” stresses Professor Brennan. “There’s a need to make sure that the core pillars of the European social model are protected, and that multinationals coming into Europe adhere to these pillars.”

Nolke, Andreas, “State Capitalism 3.0: Emerging Markets Multinational Corporations and Home Government Support”, Palgrave Macmillan, forthcoming.

Dr Louis Brennan

Project Coordinator

Dr Louis Brennan is a Fellow of Trinity College and Professor within the School of Business at Trinity College, Dublin. He previously served as Director of the Institute for International Integration Studies at Trinity College. His most recent books have been The Business of Space – The Next Frontier of International Competition co-authored with Alessandra Vecchi and Enacting Globalization: Multidisciplinary Perspectives on International Integration.

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EU Research

Getting the valu€ out of food waste

Vast amounts of food waste are generated across the world every year, which creates huge social, environmental and economic problems. There is a growing recognition that this food waste could be a valuable source of important chemicals, an issue that Professor James Clark and his colleagues in the EUBis COST Action network are currently investigating The UN estimates

that around 1.3 billion tonnes of edible food is wasted across the supply chain every year, which creates huge social, environmental and economic problems. Utilising food waste as a resource could help address these problems, believes Professor James Clark, the Chair of the EUBis COST Action. “We wanted to look at the international dimension, recognising that food waste valorisation is an area of increasing interest worldwide,” he says. The action brings together researchers from a range of fields to investigate the waste that occurs at each stage of the food supply chain. “Obviously crops are grown in a field, which are then harvested and stored.

They’re then transported to at least one processing factory, which processes the crop and generates a product. It’s then packaged and distributed – probably to a warehouse and then on to a supermarket, for example. So we’re looking at the waste that occurs in each of those stages,” explains Professor Clark.

There is a growing recognition that this waste could be a valuable resource of important chemicals. Every food type contains certain common primary metabolites, of which cellulose is the most prominent example. “Cellulose is a natural polymer, which can have value in its own

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right, or it can be used to make other chemicals,” explains Professor Clark.

Cellulose can be broken down to make sugars, which Professor Clark says are

he outlines. “Now, following that route there are certain types of chemicals that can be made from many different types of food waste. One of the most prominent at the moment is bio-ethanol, which is very well known. So some companies are making bio-ethanol, mostly as a fuel.

Then several companies are making biosuccinic acid from a variety of food types.”

Platform molecules These chemicals are a common feature of

Microwave technology is a versatile option for turning food waste into chemicals, materials and fuels very interesting chemicals. “They can be used to get higher value chemicals. So you can convert cellulose into sugar, then sugar can be converted into chemicals,”

today’s commercial landscape, with something like 100,000 different molecules used in a wide variety of consumer products across the European Union. Platform molecules, which play a key role in the ongoing development of new molecules, are crucial to meeting commercial demand for effective chemicals, so Professor Clark says the COST action’s work follows two directions. “We have the streams of chemicals which are naturally present in food waste – a nice example is limonene from orange peel. These are chemicals that are waiting to be used, that nature provides automatically.

That’s one set of chemicals,” he explains.

“Then we have the chemicals we can make by processing the major components of food waste, in particular

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cellulose. They then become another bunch of chemicals that become intermediates – platforms – for making even more chemicals.”

The action aims to get high value chemicals out of these food waste streams, bringing international researchers together to produce commercially viable chemical commodities. This research is very much inter-disciplinary in scope, and could have significant commercial value. “Most of our chemical industry is based on using oil to make molecules, which then go into everything from plastics to pharmaceuticals,” points out Professor Clark. Food waste could be an alternative source of these molecules, helping both conserve existing resources and improve waste management. “Food waste is full of molecules. If we can take the molecules directly out of these different types of food waste, then that could save an awful lot of oil processing and a lot of oil. We could get the molecules by a different route,” continues Professor Clark. “For example, wheat straw is full of surface chemicals. We can extract the molecules and use them for various applications.”

Researchers are using green, sustainable technologies for this purpose, focusing on the extraction and production of highvalue chemicals. While it is possible to get low-value chemicals from food waste at a localised level, through composting or anaerobic digestion (AD), the action is working on a larger scale, hence logistics is an important consideration. “We tend to think more about where there is already a

to take that to the next stage – to try it out on a pilot scale and actually work with much larger quanities,” says Professor Clark.

Greener molecules With somewhere in the region of 100 million tonnes of oranges grown a year worldwide, this technology has enormous potential. Professor Clark says it is also

If we can take the molecules directly out of these different types of food waste, then that could save an awful lot of oil processing and a lot of oil Food waste is full of molecules.

large volume of food waste - that means food processing companies and growers,” says Professor Clark. The project is working with the commercial sector to extract valuable molecules from several types of food waste, including used coffee grounds and citrus peel. “We have technology that allows us to get the valuable chemicals out of the peel. We’ve now got an agreement with a big company

possible to extract important chemicals from other types of citrus fruit, which are quite chemically similar to oranges. “We can achieve this without interfering at all with the production of the food. So we’re simply taking the stuff that we don’t want from the food and using that to make valuable chemicals,” he outlines. Using food waste in this way represents a significant shift for major processing

Some of the EUBis team

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companies. “We’re talking about new supply chains here; about companies who are willing to work with us on valorising their current waste streams, companies who are willing to work on the technologies to actually get these chemicals from the waste streams, and also companies who are interested in the greener, more sustainable molecules coming out of these supply chains,” says Professor Clark.

This holds real importance in the context of increasingly stringent legislation on the way certain chemicals are produced, while there is also growing pressure from consumers on companies to limit their impact on the environment.

Together, these factors are leading big users of chemicals to look towards new production methods. “A good example would be Procter & Gamble, who announced recently that they wanted 50 percent of the raw materials they use in making their products to be either biobased, or sourced from recycled materials,” says Professor Clark.

Companies are also under pressure to send less material to landfill, which Professor Clark believes is the worst option in terms of resource utilisation.

“Once the resource has gone to landfill it’s difficult to think about getting it back again, for any type of waste. So that’s the worst option,” he explains. “Composting gives you a little bit of value again back into the land, while AD gives you some value back in terms of energy.”

The highest value products are derived from chemical valorisation, underlining the wider importance of the action’s work.

Professor Clark and his colleagues are working with both small and large food companies to widen the impact of their research. “We’re trying to demonstrate to them what’s possible in terms of what we can do with their food waste,” he says.

This represents a significant shift from the conventional business model, yet Professor Clark says some companies do see it as an investment in their future.

“Companies are actively working with us to plan future bio-refineries that would take things like food supply chain waste and other types of bio-waste – such as forestry waste and paper waste,” he continues. “Some companies believe this is a way to both guarantee their own supply lines and also open up some new business opportunities.”

At a glance Full Project Title Food waste valorisation for sustainable chemical, materials and fuels (EUBis) Project Objectives ‘The objective of this project is to provide an integrated alternative renewable source of carbon for the production of industrially relevant bio-derived chemicals, fuels and materials via the exploration of novel and advanced routes for food supply chain waste valorisation’.

Project Funding Funded by COST (European Cooperation in Science and Technology): COST is supported by the EU RTD Framework Programme Contact Details Project Coordinator, Professor James Clark Green Chemistry Training, Education & Networks Assistant Green Chemistry Centre of Excellence, University of York, Heslington, York, United Kingdom YO10 5DD T: +44 1904 322559 E: james.clark@york.ac.uk W: www.greenchemistry.net W: costeubis.org Pfaltzgraff, L.A., Macquarrie, D.J. & Clark, J.H. (2014). The potential of microwave technology for the recovery, synthesis and manufacturing of chemicals from bio-wastes. Catal. Today, available online 9th January 2014.

Lin, C.S.K., Pfaltzgraff, L.A., Herrero-Davila, L., Mubofu, E.B.,Abderrahim, S., Clark, J.H., Koutinas, A., Kopsahelis,N., Stamatelatou, K., Dickson, F., Thankappan, S., Mohamed, Z., Brocklesby, R. & Luque, R. (2013).

Professor James Clark

Project Coordinator

Many types of food waste offer opportunities to extract valuable chemicals.

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Professor James Clark is Director of the Green Chemistry Centre of Excellence (GCCE) and of the Biorenewables Development Centre (BDC). James has been at the forefront of green chemistry worldwide for about 20 years. He has won numerous awards including the RSC Environment Prize, the SCI Chemistry for Industry award, the RSC John Jeyes and SCI Environment medals.

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Models to meet modern energy challenges Mathematical optimisation has long been central to decision making in the energy sector, but research has not always been coordinated effectively. A new COST Action aims to address this issue by bringing together researchers from different disciplines to exchange results and share information, as Professor Andrea Lodi explains The increasing size and complexity of Energy Production and Distribution (EP&D) networks is heightening the need for sophisticated systems which support operational, regulatory and design decisions. This has long been a focus of research, yet much of it was historically done independently by different research communities; Professor Andrea Lodi is the coordinator of a COST action which aims to coordinate interdisciplinary research. “The focus of the project is on providing appropriate means to the different research communities interested in Decision Support Systems (DSS) and EP&D to effectively exchange results,” he outlines.

Collecting the right data, both historical and current, is a key step towards the optimisation of EP&D networks. Data from sources like sensors and mobile tools helps researchers define the real problems that need to be solved and ensure their work is targeted at practical needs. “In addition, data must be made available to the scientific community, so as to boost research and development,” says Professor Lodi. “The

Mathematical Optimization in the Decision Support Systems for Efficient and Robust Energy Networks (COST Action TD1207) Professor Andrea Lodi DEI, University of Bologna, Italy E: andrea.lodi@unibo.it http://www.energy-opt.eu/

Professor Lodi believes data must be made available to the scientific community, while close interaction will allow the Action to take energy consumption into account as a key factor in decision making.

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tight interaction with industrial partners and Domain Experts allows the Action to take energy consumption into account as a key factor for decision making.”

Decision Support Systems This research encompasses virtually all aspects of EP&D, bringing together communities of experts in mathematics, computer science and engineering.

Professor Lodi and his colleagues across these disciplines are exchanging results in a highly novel way. “We aim to exploit the often-overlooked fact that the construction of the mathematical models underlying a DSS entails the need to ‘distill’ information about the actual application, thus overcoming the (sometimes conflicting) views of the many different experts that study the different aspects of a complex problem,” he explains.

The action is also considering renewable sources of energy, which bring enormous opportunities in terms of effective utilization and design.

However, coordinating these different energy sources introduces even more challenges from an optimization perspective.

“Environmental issues are hotly debated nowadays, and are central to the Action.

Renewable sources are fundamental for the sustainability of EP&D, but their integration in the current production mix is extremely challenging due to several factors, among which is their uncertainty.

This requires novel approaches involving many different skills that need to be developed and honed,” says Professor Lodi.

There is no specific mathematical technique that in isolation can tackle the current challenges facing the energy sector, underlining the importance of continued research and collaboration in this area. The Action is committed to sharing its findings and this will form a key part of the future agenda. “The goal is to build a Wiki Page for EP&D containing all the material collected and developed during the Action in terms of data, models, algorithms, software implementations and publications, which should be able to survive the end of the Action and assume a central role in further developments of the wider area,” continues Professor Lodi.

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Improving the operation of Balance of Plant components

There is significant scope to improve the durability, efficiency and cost-effectiveness of fuel cell systems.We spoke to Dr Mitja Mori of the FluMaBack project about their work to improve the design and operation of balance of plant (BoP) components in back up fuel cell systems, which enable stable, secure and efficient operation of the core components, the fuel cells The

development of sustainable, environmentally friendly sources of energy is a global research priority.

However, while a great deal of attention has been focused on developing new technologies, there is also significant potential to improve BoP components and achieve the optimal operation of fuel cell

components available. But they were either too robust, too expensive or not the most appropriate with respect to the operation of the overall fuel cell system,” continues Dr Mori. “The focus now is on improving existing BoP components and developing new ones. At the end, we will integrate them into a backup fuel cell system and

The operational stage of a backup fuel cell system is when the greatest environmental impact occurs, so the hydrogen production technology and performance characteristics of BoP components, and of the overall system, are the most important considerations systems, an area being addressed by the FluMaBack project. “The general aim of the project is to improve the performance, life time and cost of balance of plant (BoP) components for backup fuel cell systems,” says Dr Mitja Mori, the project’s dissemination coordinator.

The project brings together partners from across the EU to develop various BoP components, including the air blower, humidifier, heat exchanger and hydrogen recirculation pump. “The project partners had some previous versions of BoP

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Researchers in the project aim to improve the reliability of these BoP components, and also to reduce production costs, simplify manufacturing and extend their lifetime. This has involved both modifying existing components and developing new ones. “The hydrogen blower and air humidifier were developed from scratch, so both are completely new products. The air-blower was modified because the fuel cell is a very specific component – this was essential to meeting the requirements of the fuel cell – while the heat exchangers were also modified and one of them was removed from the system,” outlines Dr Mori.

aim to prove that these BoP components – and the overall system – are more efficient, less expensive, last longer and meet all required performance criteria.”

Air humidifier with hollow semi-permeable fibres

Hydrogen recirculation pump

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Above: Balance of plant components developed under the FluMaBack project.

Inset Images below: (Top: Air blower, 2nd from the top: Pressure streamlines, 3rd from the top: Fuel cell stack, bottom: UPS system).

The goal is to achieve an operating time of 10,000 hours over the component’s whole lifetime – equivalent to an operational life of 10 years – without any need for additional maintenance. Furthermore, Dr Mori points out that also life cycle assessment is an important element of this work.

“We look at the production or manufacturing process, and calculate the environmental impact of both a single BoP component and of the system overall,” he explains. “So on the one hand we can get clear data on the environmental impacts of single components in comparison to previous versions, and on the other we are able to compare the manufacturing process with the operational phase of the system, where the hydrogen that also has to be produced is used as a fuel.”

LCA assessment Part of the work is life cycle assessment of the system in the manufacturing and operational phases. “It is important to show that hydrogen technologies in backup systems are environmentally sounder and have a lower environmental impact than conventional backup systems,” says Dr Mori. Limiting the environmental impact of production and addressing sustainability issues are key priorities for most companies, a trend that is likely to grow more pronounced in future. “The operational stage of a backup fuel cell system is when the greatest environmental impact occurs, so the hydrogen production technology and performance characteristics of BoP components, and of the overall system, are the most important considerations,” outlines Dr Mori.

Production process This work holds real importance to the operation of fuel cells, potentially improving their efficiency, reliability

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and durability. However, the BoP components must meet the technical requirements of fuel cells if they are to be operational. “You cannot just plug any BoP component into the fuel cell system and expect that it will work perfectly,” stresses Dr Mori. The project is developing and manufacturing BoP components specifically for 3 kilowatt and 6 kilowatt backup fuel cell systems; these components need to meet some exacting requirements. “Fuel cells are very sensitive to impurities. The polymer exchange membrane fuel cell is the heart of this system, and the hydrogen used to power it has to be very clean, 99.999 per cent pure,” says Dr Mori. “Then we also need to consider properties of the hydrogen and air provided for the operation of the fuel cell. The air has to be humidified, because dry air can cause the membrane to dry out. This leads to membrane degradation, which results in reduced power and a shorter lifetime of both the fuel cell and entire system.”

The technology is available today to address these issues and ensure that fuel cells can work more efficiently. A sound understanding of the fluid dynamics phenomena in BoP components is essential in these terms. “If you have a blower that supplies the air or hydrogen to the fuel cell, it should have certain characteristics.

So the volume flow, the efficiency of the blower, should meet specific goals,” explains Dr Mori. The volume flow needs to be within specific boundaries depending on the fuel cell requirements, while Dr Mori says there are also many other issues to consider. “To improve durability, components are usually more robust and thus more material is needed. If in addition more energy is needed, the component will be more expensive. Most criteria in design process preclude each other, which makes this task an even bigger challenge,” he points out.

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Delicate balance A delicate balance needs to be struck between these criteria, and this remains a key priority in development. The performance priorities of the components depends to a degree on the intended application and the likely market; while the project initially focused on emerging markets, Dr Mori says they are now looking more towards Europe and North Africa. “The air blowers and hydrogen blowers are also very useful in various different applications. If the automotive industry decides to use fuel cells very intensively, then the results of our project will be very useful in this area,” he says.

Researchers are currently testing the components and assessing their performance as part of the whole fuel cell system. “A few components will be used in both the 3 kilowatt and 6 kilowatt systems, which is very positive from the cost point of view,” says Dr Mori.

“However, developing BoP components which will fit in both systems is quite a

challenge, as the second system has twice the power and thus requires twice as much air, hydrogen etc.”

The project is testing these components to identify such issues and further improve their performance, with the hydrogen blower proving a particular challenge. A test rig is being built for the hydrogen blower to test its durability. “These blowers are new components. When you are dealing with hydrogen you are always confronted with challenges, because hydrogen is prone to leaking and is not compatible with some common materials used for component body, sealing, lubrication, etc.” explains Dr Mori.

Durability is a research priority for all of the components being developed within the project. “The components should last for 10,000 hours, and that’s without maintenance. But not just the components – the overall system itself should also last for 10,000 hours without maintenance,” stresses Dr Mori. “That is the goal and that’s what we’re working towards.”

At a glance Full Project Title Fluid Management component improvement for Back up fuel cell systems (FluMaBack) Project Objectives The FluMaBack project aims to improve the performance and life time of balance of plant (BoP) components for back up fuel cell systems, and also reduce their cost.

Project Funding Project budget: €4.44 million; Project funding: €2.77 million.

Project Partners • Electro Power Systems: Project Coordinator, Torino, Italy • Tubiflex SPA, Italy • Parco Scientifico e Tecnologico per L’Ambiente - Environment Park Spa, Italy • Institut Jozef Stefan, Slovenia • Fundacion Para el Desarrollo de las Nuevas Tecnologias del Hidrogeno en Aragon, Spain • Nedstack Fuel Cell Technology BV, Netherlands • Onda Spa, Italy • University of Ljubljana, Slovenia • JRC -Joint Research Centre - European Commission, Belgium • Domel d.o.o., Slovenia Contact Details Dissemination Coordinator, Dr Mitja Mori University of Ljubljana Faculty of Mechanical Engineering Aškerčeva 6, SI-1000 Ljubljana, Slovenia T: +386 1 4771 715 E: mitja.mori@fs.uni-lj.si W: http://www.flumaback.eu/ GSM: +386 41 505 003 20th World Hydrogen Energy Conference, Gwangju Metropolitan City, Korea, Jun. 2014 Hannover Messe: Presentation of Domel’s BoP component by FCH JU, 7. - 11. Apr. 2014, Germany Lange Nacht der Forschung, Alpen-Adria_ Universität Klagenfurt Lakeside Science & Technology Park, Apr. 2014, Klagenfurt, Austria.

European Fuel Cell Technology & Applications Piero Lunghi Conference, 11.-13. Dec. 2013

Dr Mitja Mori

Dissemination Coordinator

Contribution of phases in global warming (GW) impact criteria for 3 kW UPS FluMaBack system in - top: manufacturing phase bottom: manufacturing and operation phase (10.000 h) with hydrogen production with electrolysis technology mix.

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Mitja Mori is an Assistant Professor in the Faculty of Mechanical Engineering at the University of Ljubljana. In addition to his teaching work, he has authored or co-authored 35 publications, and is also involved in the professional activities of the Laboratory for Heat and Power.

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Photosynthetic proteins for technological applications Photosynthesis is essential to life on earth, enabling plants and organisms to convert light energy into the chemical energy that fuels their daily activities. The PHOTOTECH project is investigating the design and production of biosensors and bio-energy based on photosynthetic activity, work which could have a significant social impact, as Dr Giuseppina Rea explains Photosynthesis is essential to life on earth. By converting solar energy into chemical energy, it fuels organisms’ daily activities and provides us with the food we eat and the air we breathe, as well as the fuel we burn, says Dr Giuseppina Rea. “Photosynthesis is a highly important biochemical process, which sustains all life on earth. It also provides us with the inspiration to develop new biotechnologies for sustainable life including, among others, the production of biosensors and bio-energy,” she says. Based at the Institute of Crystallography in Rome, Dr Rea is the coordinator of the COST PHOTOTECH project, which is pursuing detailed research into photosynthesis.

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“The main objective of this project is to create a sustainable European network in the field of photosynthesis,” she explains.

“The primary consideration behind the creation of this platform is to attract European scientists to a new scientific and

Photosynthesis-based biosensors A biosensor itself is an integrated device with a bio-sensing element that can interact with compounds from different sources. This property can be harnessed to detect and quantify specific analytes of

By mimicking most of the reactions which occur in photosynthesis, it is possible to get inspiration to construct devices able to detect pollutants and produce energy technological field, which could have a high social impact – the design and production of biosensors and devices for bio-energy based on photosynthetic activity”

interest. “As a consequence of the interaction between the analytes and the bio-sensing element, physical and chemical modification is induced in the bio-sensing element. With the right

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• PSII splits water into electrons and protons upon light absorption.

• The electrons are transferred to the PSII-based half-cell via the outer circuit.

• PSI generates a reductive force and reduces the electron acceptor (MV).

• MV is re-oxi¬dized by molecular oxygen producing water.

recovery of photocurrents Generation of a photoenergy-conversion device by coupling photosystem I and II complexes immobilized in redox hydrogels on individual electrodes.

Angewandte Chemie International Edition 52.52 (2013): 14233-14236. transductor these modifications can be converted into electrical signals,” explains Dr Rea. The strength of these signals is proportional to the concentration of the analyte, meaning it is possible to measure and quantify the analyte of interest. “In this case, it’s a contaminant, a pollutant.

But in another case it could be a molecule of interest in a different research field,” says Dr Rea. Biosensors would be able to recognise pollutants as well as a range of other compounds, so could be applied in a variety of research fields. Dr Rea says that biosensors can be thought of as early warning systems which can detect pollution at specific sites, which can subsequently be analysed in a more precise manner with conventional tools.

“Biosensors can work in situ, as they are a more miniaturised device than the other analytical devices, and can also be operated even by people who don’t have a lot of experience,” she continues.

Dr Rea and her colleagues are working to develop photosynthesis-based biosensors that mimic specific attributes of photosynthetic organisms. “Usually photosynthesis is affected by several pollutants. These pollutants are generated by urbanisation or population increases, as well as industrial and agricultural activities, and can negatively affect human health. So these compounds can interact with the photosynthetic proteins and modify their activity,” she says.

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Researchers can monitor these modifications, convert them into signals, and quantify their levels. “In this way we can produce devices that could potentially be useful both for environmental monitoring and also in addressing certain health issues,” outlines Dr Rea. The field is growing rapidly, in recognition of the wider potential of biosensors, but as yet only a few have been commercialised. “Researchers in the PHOTOTECH team are looking for innovative and scientifically sound solutions to critical issues which are hindering the wider development and use of photosynthesis-based biosensors,” says Dr Rea. “Improving the stability of the bio-sensing elements, while also keeping its functionality when it is integrated in solid-state devices, is essential to delivering robust, reliable, and sensitive biosensor prototypes,” stresses Dr. Rea. The project encompasses a range of research directions and innovations aimed at improving the performance of biosensors.

“We are applying bioinformatics and molecular biology strategies to improve bio-sensing element robustness and/or its specificity and sensitivity. We are also exploring several immobilisation techniques for integrating the advantages of the biological materials that are found in living organisms with the advantages of organic and inorganic materials,” outlines Dr Rea. “Then we are looking to design and fabricate stand-

alone biosensor prototypes, integrating the electronics required for signal processing, and to develop the mechanical structure necessary to host the bio-hybrid components and the sample under test. We are also developing the fluidic architecture necessary to ensure the sensors are automated and easy to use.”

Research breakthroughs This work builds on fundamental research into specific photosynthetic reactions. A comprehensive description of these reactions and their biotechnological applications has recently been reviewed in a collection of papers co-authored by members of PHOTOTECH (1). “One of the main achievements of the project was the collection of bio-sensing elements suitable for integration in solid-state devices. By exploiting protein engineering tools such as in vitro molecular evolution and sitedirected mutagenesis we produced mutants of the green alga Chlamydomonas reinhardtii with enhanced stability and different competence for perception of triazine and urea-types herbicides (2),” says Dr Rea. Researchers are using microalgae whole cells and photocomplexes extracted from purple bacteria or cyanobacteria or plants to develop these biosensors. “The properties of the Photosystem II complex within Chlamydomonas living cells were used to realize amperometric biosensors equipped with a flow injection system to

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At a glance Full Project Title COST Action TD1102. Photosynthetic proteins for technological applications: biosensors and biochips (PHOTOTECH) Project Objectives The objective is to explore, interface and merge the various aspects of the development of photosynthetic proteinsbased bio-devices. The purpose will be the creation of a new research platform by networking researchers and professionals that can combine and integrate diverse disciplines. The main outcome is the co-development of a fully characterized class of bio-organic-inorganic hybrids for biosensors and bio-energy production.

Project Funding PHOTOTECH is funded by COST. COST is Europe’s longest-running intergovernmental framework for cooperation in science and technology funding cooperative scientific projects called ‘COST Actions’.

Contact Details Project Coordinator, Giuseppina Rea, PhD National Research Council of Italy Institute of Crystallography 00015 Monterotondo Scalo, Rome, Italy T: 00 +39 06 90672631 E: giuseppina.rea@ic.cnr.it W: http://www.cost.eu/domains_actions/ cmst/Actions/TD1102; http://www. phototech.eu/

Giuseppina Rea, PhD

Project Coordinator

Giuseppina Rea, PhD, is experienced in plant molecular biotechnologies applied to fundamental research and technological transfer. Research activity focuses on molecular mechanisms and signal networks involved in the light events of photosynthesis and the structure/function/dynamics relationships of the pigment-protein complexes involved in these processes.

The studies aim to produce mutants with improved photosynthetic performance for development of biosensors, life-regenerative supporting system for life in space, and biological farms for nutraceuticals. She has been PI in several international programmes such as SENSBYOSIN (FP7), MULTIBIOPLAT (EUROTRANSBIO), BIOKISPHOTOEVOLUTION (ESA-ASI-NATO).

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detect pesticides in water samples. The cells, entrapped in an alginate gel, were immobilized directly over the surface of a carbon nanotube electrode (3),” explains Dr. Rea. Working with an extracted photosynthetic assembly, “it has been shown that the photocurrent generated by purple bacterial reaction centres (RCs) adhered to gold electrodes can be used as a biosensor to selectively detect potentially harmful triazine herbicides (4),” continues Dr. Rea. “Another recent advance is the

photosynthetic assemblies produce photocurrents, forming the building block of a biological solar cell. RCs from purple bacteria immobilised onto the modified surface of diamond, as well as a bare gold electrode, proved adequate for this purpose.

This approach can be adapted further, as it is possible to artificially synthesize more complex systems. “The feasibility of construction of the first experimental setup serially coupling Photosystem 1-based photocathode and Photosystem 2-based

The primary consideration behind the creation of this platform is to attract European scientists to a new scientific and technological field, which could have a high social impact creation of a bio-nanocomposite material from RCs and conductive metal oxide, ITO, providing a model for new generations of integrated optoelectronic devices (5).”

Research is ongoing also to develop other kind of sensors. “The expertise acquired in the framework of PHOTOTECH allowed the development of a laccasebased biosensor for polyphenols detection exploiting the immobilization laser printing technology (6), and the synthesis of novel dendrimer molecules to detect metal ions (7).”

The project is also looking at using photosynthetic assemblies to produce energy and has developed wellcharacterised devices. “This is the third year of the action, so we are attempting to go beyond the deliverables that were initially proposed,” outlines Dr Rea. Under stimulation with a proper light,

photoanode mimicking the photosynthetic Z-Scheme for biophotovoltaic applications has been successfully proved,” emphasised Dr. Rea. The project is very much interdisciplinary in scope, so has adopted an integrated approach to its work. “We combine aspects of biology, biotechnology, biochemistry and biophysics, polymer chemistry, immobilisation, prototyping, molecular structure and so on. By promoting the project’s results, Dr Rea and her colleagues aim to accelerate the development and adoption of biosensors and biodevices. “We aim to promote the transfer of our fundamental research to technological transfer offices. We will try to convince policy-makers, by disseminating our knowledge, that biosensors are ready to go on the market,” says Dr Rea.

Amperometric detection of herbicides by an algal-based biosensor device.

Sensors and Actuators B: Chemical (2013) 185, 321-330.

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Communication is key to distributed systems Modern life depends on large-scale distributed software systems. The key to making them work is to ensure that their components communicate with each other correctly.

Dr Simon Gay tells us how COST Action IC1201 (BETTY) aims to use behavioural type theory as a basis for new programming languages and software development methods For a long

time data processing was the primary focus in computing development, with isolated machines running their own software systems. However, with modern society growing increasingly dependent on distributed software systems, computing is changing to reflect new priorities. “Most computing now is not based on isolated systems doing data processing. Today we have large networks of communicating systems; things like web applications, online banking and online shopping all make use of distributed computing systems. The key to making distributed computing systems work is to make sure that all the components are communicating with each other correctly,” explains Dr Simon Gay, the coordinator of COST Action IC1201: Behavioural Types for Reliable Large-Scale Software Systems (BETTY). Behavioural type theory, which encompassess a range of concepts, including interfaces, communications protocols and contracts, holds real potential in this area.

“The overall aims of the BETTY project are to continue developing the theory of behavioural types, to try and push behavioural types out into practice, and to make them applicable in practical software development,” continues Dr Gay.

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Many of the standard programming languages in use today were designed with data processing firmly in mind. It was recognised early on in development that the structure of data, or data types, is very important to the effectiveness of a program. “Programmers need to know for example that a person’s address consists of a number of fields, what kind of data is in each field, and what the correct format of that is. Essentially all programming languages have very strong support for these data types. This means that when you’re writing a program, you can write declarations in your program of the data types, the data formats, that you’re working with. Then the programming language system checks that you’re using all parts of the data correctly,” explains Dr Gay. Data types are quite static however, so aren’t well-suited to today’s distributed systems. “Data types describe the structure of data and the relationships between data, but they don’t say anything for example about sequences of operations,” continues Dr Gay. “Most computing now is not about isolated systems processing data, but rather large networks of communicating systems.”

Distributed systems The designer of a distributed system has to consider communication protocols, the sequence and format of messages that are being exchanged between different components.

Current standard programming languages don’t offer effective support for the definition of these communication protocols, says Dr Gay. “Although the programming language may help people get the format of each message correct, it doesn’t help them get the sequence of messages correct, so the programmer often has to test it manually,” he outlines. Programmers have become accustomed to development environments where the system constantly analyses and checks the code that they write, helping them identify errors, but this is not yet available for communication programming. “As soon as you type something on your keyboard which looks like applying an operation to a nonsensical piece of data, you’ll get a little red line under it telling you you’ve done something wrong. So it provides immediate feedback,” says Dr Gay. “At the moment that’s just not available for errors in communication programming.”

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This is an issue which Dr Gay and his colleagues are working to address. The underlying idea behind the project is to think of the communication structures in a distributed system as a type of information, analogous to data types. “We aim to identify all the theories, techniques, tools, programmer support that we like from data types, and then to apply them to behavioural types,” says Dr Gay. A lot of theoretical research has been done on behavioural types, but it is only in the last five years or so that significant progress has been made on putting these ideas into prototype programming languages.

“There are some prototype programming languages in which you can indeed define these behavioural types, use them in programming and get automatic checking.

But these programming languages are either small prototypes or experimental extensions of existing languages – they’re not yet ready for full-scale use by industrial software developers,” continues

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Dr Gay. “Part of our aim is to move closer to a world where these kind of ideas are suitable for use in industrial software development.”

We’re starting to see some work on issues like error handling, but I think we need more of this type of research,” says Dr Gay. One area that he believes warrants further

Today we have large networks of communicating systems; things like web applications, online banking and online shopping all make use of distributed computing systems.

The key to making distributed computing systems work is to make sure that all the components are communicating with each other correctly General approach A lot of work has been done in this area, yet Dr Gay believes one standardised, general approach is required to put these ideas on behavioural types into practice. There are also several other issues to consider before the project’s ideas can be applied practically.

“One thing we need to put these ideas into practice is to look at error recovery and how to handle interaction with components that are outside the nice, perfect design.

exploration is time-outs. “In practical systems, there’s always the possibility that the component you’re trying to talk to has somehow failed, and you can’t wait forever for it to complete your interaction. So usually there’s some notion of a time-out,” points out Dr Gay. “A customer might wait five seconds for a response from the bank for example, and if it doesn’t come then you decide that the bank isn’t operating.”

These types of large, distributed systems

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At a glance Full Project Title COST Action IC1201: Behavioural Types for Reliable Large-Scale Software Systems (BETTY) Project Objectives To use behavioural type theory as the basis for new foundations, programming languages, and software development methods for communication-intensive distributed systems. Behavioural type theory encompasses concepts such as interfaces, communication protocols, contracts, and choreography. As a unifying structural principle it has the potential to transform the theory and practice of distributed software development.

Project Funding €130k - €150k per year over 4 years (October 2012 - October 2016).

Project Partners European Cooperation in Science and Technology (COST) Contact Details Project Coordinator Dr Simon Gay School of Computing Science University of Glasgow Glasgow G12 8QQ, UK T: +44 141 330 6035 E: Simon.Gay@glasgow.ac.uk W: www.behavioural-types.eu

Dr Simon Gay

generally work very well, yet there is still scope for further improvement. One of the working groups within BETTY specifically concerns security, which is a particularly important issue in online banking. “A lot of work is ongoing on techniques for analysing security software, as well as research into integrating security analysis with behavioural type descriptions. We want to encourage more work in that direction, so that a behavioural type communication between the client and the bank should not only talk about the format of the messages that are being exchanged, but also guarantee security properties at certain points,” outlines Dr Gay. The project’s ultimate aim is to help software companies produce reliable, communication-based software more quickly and easily. “Some of the participants in BETTY have their own research projects, some with industrial collaborators. They’re starting to apply behavioural typing ideas, and they’re already starting to see productivity

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benefits,” says Dr Gay. This of course is an important issue for the commercial sector, suggesting that behavioural type theory will have a major part to play in the long-term future of software development. However, Dr Gay says the project will have to consider the techniques that the software industry is currently using if it is to have a wider impact. “The way to do that is to try to develop improvements through existing methodologies. We have the idea of behavioural types, now we want to deploy that in the programming languages people are already working with,” he explains.

This will be an important part of the overall research agenda, both within the original term of the project and beyond.

“We will spend the four-year term of the BETTY project really trying to consolidate the community and setting up new collaborations, which we hope will then continue after the end of the project itself,” says Dr Gay.

Project Coordinator

Dr Simon Gay is a Senior Lecturer in the School of Computing Science at the University of Glasgow, Scotland, where he has been working since 2000.

In addition to chairing COST Action IC1201 (BETTY), he is involved in two research projects funded by the UK EPSRC. Both projects concern structured communication: one for distributed computing systems, and one for manycore microprocessors.

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New strategies are foreseen to reduce fat (saturated and trans-fatty acids), salt (sodium) and sugar (mono- and disaccharides) in food products. We spoke to Bianca Pop, dissemination manager of the PLEASURE project about their unique new approach to address this challenge from the processing side instead of using subsitutes or replacers

When less means more - “reduced-in” food PLEASURE is a research project aiming

at finding solutions to today’s excessive consumption of salt, sugar and saturated fats, by designing different products that have a lower content of these components.

PLEASURE approach is unique, as it is the first attempt of reducing salt, sugar and fat content in food products, from the processing side, by developing innovative processes that will work by optimising the sensorial perception.

The research will lead to novel technologies for the production of several products: pizza and puffing pastry dough, mozzarella-style cheese, Bologna type sausage, cooked ham and dried cured sausage and fruit/vegetables preparations.

In the second step, the concepts used for the mono-food systems will be incorporated into three Ready-to-Eat (RTE) meals: a pizza system, a puffing

pastry with a meat filling and a puffing pastry with a sweet fruit filling.

The technology brings along the possibility to achieve a different dispersion of salt and fat in the food layers, leading to a reduction in the unwanted lipids, salt and sugar (mono- and disaccharides). A focus on the sensorial perception of the sugars, fats and salts is planned, as consumer acceptance is fundamental.

For the salt reduction, a combined approach that includes both replacers and methods that feature the enhancement of the saltiness perception are used. A reduction of 30 % of the salt content for cooked sausage Bologna style and cooked

PLEASURE (Novel Processing approaches for the development of food products Low in fAt, Salt and sUgar) The PLEASURE project aims at developing innovative processes and/or implementing novel technologies to allow the development and production of food products with low content of fat (saturated and trans-fatty acids), as well as salt and sugar.

Dipl. Ing. Bianca Pop Pleasure Dissemination Manager SC TRITECC SRL, Cosminului Str.8, 400642 ClujNapoca, Romania T: +40 364 80 14 58 E: bpop@tritecc.ro W: www.tritecc.ro BIANCA POP, senior project manager, has an engineering degree and vast experience in food quality and safety issues. Ms. Pop has several years of professional experience in managing European projects, being currently responsible as dissemination and communication manager for various FP7 Funded Collaborative Projects.

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Above: Masticator Below: Cutting Process

ham has been developed by using HPP treatment and / or the use of phosphates.

Similar progress has been obtained with pizza dough by implementing salty micro domains in the dough to enhance saltiness perception while reducing the overall salt content.

Fibres, natural ferments and enzymes are used for the substitution of fats, with the aim of redesigning the microstructures of the products to optimise taste and other properties. The total saturated fat content will be reduced by replacing fats with vegetable oils.

A mozzarella-style cheese both for direct consumption and for use in pizza products with a low content of sodium and fat will be designed. High pressure homogenisation and enzyme technologies are used to modulate taste and texture and to enhance the flavour intensity.

In addition to a successful screening and optimization procedure, novel process equipment had been developed and adapted to high viscous products like fruit purees or tomato paste. Within the process developed, the whole sucrose and glucose present in the fruit preparations had successfully been removed.

PLEASURE is an ambitious project that will have a major impact on developing and manufacturing of traditional and processed food from different European countries.

PLEASURE outcomes intend to bring about the scientific bricks which will permit to develop optimized strategies of salt, sugar and lipids reduction in particular in the case of assembled solid foods, namely RTE meals. The results described above and more will be shared to academia and industry in an international conference that will be held in association with the Health and Food Days (JAS - Journées Aliments & Santé) in La Rochelle, France during 18-19 June 2014. Coffee breaks and lunch break will be used as opportunities to taste and compare different products based on process approach for salt-sugar and lipid reduction concepts. For more information please visit: http://www.pleasure-fp7.com/

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