Biennial Report ipri. Per indicium ad excellentia. ipri Biennial Report. ipri 2017

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1 12/2016 Creation Africa 07/ th NCID 07/2011 7th NCID 02/2012 World Breast Cancer Report Published 07/2010 First Summer School 07/2010 6th NCID 06/2012 Boyle awarded LLD (honoris causa) 12/2009 MOU U. Dundee 04/2009 Founded 07/ th NCID 06/2011 Epidemiology and Biostatistics Published 07/ th NCID 10/2013 State of Oncology 2013 Published 07/2013 9th NCID 09/2012 Autier PhD Erasmus University 12/2010 Boyle Inducted Hungarian Science Academy 06/2013 Creation of 07/2010 Strathclyde Institute of World Prevention Alliance Founded Global Public Health at 01/2013 Mullie professorship VUB 03/2013 Alcohol: Science, Policy and Public Health Published Biennial Report Per indicium ad excellentia International Prevention Research Institute 95 Cours Lafayette Lyon, France Biennial Report

2 Are we moving too fast? Perhaps we are - going too fast. Perhaps we are driving ahead, leaving too many people behind, quite literally in the dust. Perhaps we are not doing enough for the disenfranchised in low resource countries and for the poorest among us. believes in progress. We believe in providing the best possible evidence for better global health. But we are doubly committed to ensuring that our knowledge be a conduit for better health, not just in privileged quarters, but in the most destitute ones as well. All scientific and policy roads must lead to prevention and better health for all. Biennial Report , International Prevention Research Institute, Lyon, France Contents cannot be copied or otherwise reproduced without express consent of. Printed in France Photographed in Ghana in 2011.

3 Biennial Report: International Prevention Research Institute Contents Contents The International Prevention Research Institute : More than an Acronym, a Commitment Executive Summary Strathclyde Institute of Global Public Health at Guiding Principles Ethics Global Connections New Global Relationships Vietnam National Cancer Hospital National Institute of Oncology of Hungary Poland s Fundacja Promocja Zdrowia Ukraine s RE Kavetsky Institute International Alliance of Patients Organizations The Road to Restrictions on Sunbeds Exposure and Risk: A Thirty Year History PRINCIPAL CONTRIBUTIONS Cancer Breast Cancer Screening Screening for Colorectal Cancer Screening for Cutaneous Melanoma Screening for Prostate Cancer Breast Cancer and Physical Activity Active and Passive Smoking and Risk of Breast Cancer Risk of Cancer in the Rubber Manufacturing Industry Chemotherapeutic Waste Disposal Cancer Scenarios in Scotland Diabetes Diabetes and Pancreas Cancer Retinopathy and Eye Light White Paper on Diabetes Epidemiology Diabetes Treatments and Cancer Risk Diabetes and Physical Activity Diabetes, Diabetes Treatments and Lung Cancer Risk Africa State of Oncology in Africa Cancer is... Attacking Africa - Television Documentary Pathways of Care in Lung Cancer in Africa Education and Training Programmes: A New Initiative UV and Skin Cancer Health and Conflict Health in Conflict and Post-Conflict Environments IMPORTANT CONTRIBUTIONS Multiple Sclerosis Education and Training Vaccination and Infectious Disease Modelling, and Modelling of Other Biomedical Phenomena Nutrition Liver Cancer (Hepatocellular Carcinoma): Curbing the Epidemics Pancreatic cancer: in search of new targets for therapy Guidelines for a Healthier and Longer Life Use of Social Security Databases and Patient Registries Cancer Leadership Cancer Leadership National Cancer Institutes Directors Meetings WPA/ Cancer Control Awards WPA/ Awards for Cancer Control WPA/ Awards for Cancer Control ABOUT US People Senior Faculty Faculty Staff Senior Research Fellows Activity Report Invited Lectures and Talks Publications - Peer Reviewed Publications - Books PhD Examinations, Jurys and Student Supervision Visitors I may dispute, in favour of my chosen road, the road that someone else has taken. I may criticize the workings of his logic... But I must respect the man, if he toils towards the same star. Antoine de Saint-Exupéry

4 - International Prevention Research Institute Overview The International Prevention Research Institute Per indicium ad excellentia T he International Prevention Research Institute () was formally established in April 2009 in France with eight founding members. In March 2010, Services was created and moved into new premises in Ecully. It provides private and public sector organisations with independent authoritative evidence and guidance on critical health risk issues. is an academic, problem-solving institute that works closely with a number of senior figures from different corners of the world on a variety of projects. These have accepted appointments as Senior Research Fellows. The international flavour of activities is reflected in the international nature of the staff: three nationalities in Management, six in Services and thirty among the Senior Research Fellows. The International Prevention Research Institute () comprises two legal entities: Management and Services. The former comprises the initial partners and the latter the salaried staff. Each is run as a not-for-profit with any funds left over at the end of a year used to allow to grow or to fund studies or activities which could not find funding otherwise. The World Prevention Alliance was established as an Association in France under the Loi This is used to facilitate the funding of studies and other activities in lower-resource settings where all funds collected for such activities can be spent directly. For example, the Annual Meeting of National Cancer Institute Directors attracts upwards of 100 Cancer Experts from many countries with the majority of participants from low- or middleincome countries. Travel costs and all local expenses of these participants are covered by the World Prevention Alliance. In June 2013, a formal Memorandum of Agreement was signed between and the University of Strathclyde in Glasgow, Scotland. This established the Strathclyde Institute of Global Public Health at. The aims of this Institute are many but there are several dominant goals. First of all, there is the opening of possibilities for research programmes to be developed between and the University. Strathclyde University has many strengths including in the broad area of Engineering. Developments in Social Engineering have made an enormous contribution to the current state of public health in high-resource countries and the transfer of knowledge to lower-resource settings will almost certainly make a significant contribution to public health. In addition, a Master s and doctoral programme have been created aimed at students from lower-resource countries, allowing the Institute to make a contribution to capacity building in lower-resource countries. In collaboration with colleagues in the University of Strathclyde and King s College London, is a partner in a wide-ranging programme dealing with Health during Conflict and postconflict Public Health. 1

5 - International Prevention Research Institute Overview : More than an Acronym, a Commitment iis for International An international vision is essential if one hopes to be relevant and effective in prevention. This said, we chose to put our first letter in lower case so as not to lose sight of the need for prevention and public health action at local and national levels. Pis for Prevention Ris for Research Prevention of chronic or infectious disease is the most important aspect of Public Health at this time. Prevention is also the cornerstone of s mission. Of course, while it is essential to prevent those diseases which can be prevented, it is also essential to treat those diseases which can be treated and to cure those diseases which can be cured while providing palliation whenever it is needed. Prevention encapsulates a wide spectrum of interventions ranging from primary prevention (avoiding the onset of disease) through secondary prevention (screening and early detection to avoid patients presenting to medical services with advanced disease) and tertiary prevention (appropriate treatment to avoid patients dying from their disease). The application is not only to chronic disease or infectious disease directly, but also to the prevention of risk factors in individuals and populations. Research is another key activity since there are still aspects of chronic disease and lifestyle behaviours which are not understood and hinder prospects for prevention. Research is still needed in many areas. Risk factors exist for approximately one half of all forms of cancer defining the limit of what is theoretically preventable within our current knowledge. How to change the lifestyle behaviours of populations is still a challenge requiring major research activity. Iis also for Institute Institutes aim to be selfless. chose the institutional route to emphasise its intent to make a difference. The partners aimed to undertake research projects that would directly impact prevention and public health, using state of the art epidemiological and biostatistical methodologies. 3

6 - International Prevention Research Institute Overview Executive Summary Increasingly international attention is turning towards a focus on prevention. Prevention ranges over Primary Prevention, to reduce the risk of particular diseases, through Secondary Prevention, identifying chronic diseases early in their natural history when clinical disease may be avoided or the disease identified when it is curable, and Tertiary Prevention, preventing patients with disease from dying from their disease. Successful prevention relies on having secure information about disease determinants, the subset of risk factors whose alteration would lead directly to a reduction in risk, and then working with various sections of society to bring about the necessary changes. It is clear that any unilateral approach to prevention could not be successful. The road that leads from the discovery of a hazard to prevention is usually long and full of obstacles. The path to successful prevention leads through research to build the scientific database on which to build successful prevention programmes in populations. There are many difficulties which still need to be overcome even once the scientific evidence becomes overwhelming. The classical example is of cigarette smoking where the risk of various chronic diseases has been increasingly established since the middle of the twentieth century but decades passed before inroads were made to prevention. The temporal gap between the time when the evidence is available and certain and when the prevention strategy is implemented is still cause for concern. The example of the harmful effects of sunbed use and the history of the road to prevention of melanoma caused by this exposure is outlined in this Report. This report presents the work of the International Prevention Research Institute () in the previous two years of its existence ( ) and outlines the contribution which has made in some thematic areas notably Cancer, Diabetes, Africa, Ultraviolet Light and Skin Cancer and Health during Conflict and post-conflict Public Health. Studies in these themes cover activities conducted in a wide range of settings and all have had an impact on prevention. cannot undertake many of its prevention activities on its own and depends on close cooperation with many other specialist groups. staff are augmented by an international network of Senior Research Fellows who work actively with staff on a variety of projects. The establishment of -Italy, - Africa and -MENA allows deeper focus on regional issues of public health significance. Like itself, these subsidiaries work on a not-for-profit basis. In addition, has close collaborations with a number of leading Institutes including the University of Strathclyde and King s College London; these and other partnerships will be described throughout this Report. Our academic credentials are laid out in our lists of publications as books or in the peer-reviewed scientific literature. We have signed Memorandum of Understanding (MOU)s with the International Alliance of Patients Organizations, National Cancer Institutes (and Ministries of Health) in Vietnam, Hungary and Ukraine and three more countries have agreed to sign in early These agreements cover Cancer Control with a focus on Prevention and we have a partnership with the Prevention Foundation in Poland to help us. Statistics are Patients with the Tears wiped away. To help develop our focus on Cancer Control, we have an agreement ready to sign with the International Association of Patients Organisations. This philosophy comes across very clearly in the State of Oncology in Africa Report and film which we will formally launch on World Cancer Day also has Education as one of its central aims. In conjunction with the University of Dundee, we held a Summer School on Epidemiology and Global Health between 2010 and We developed a textbook on Epidemiology and Biostatistics designed for students attending such a short course and this text has been widely used at other courses, notably in China. In 2013, signed an agreement with the University of Strathclyde to create the Strathclyde Institute of Global Public Health at. As well as having a research focus, it has a teaching focus. Successful and widespread implementation of effective prevention strategies will not only lead to increases in life expectancy but also, and importantly, healthy life expectancy. Prevention recommendations, unfortunately, have been made in silos: Cancer, Cardiovascular Disease, Diabetes, Infectious Disease, etc. To integrate knowledge of prevention strategies over common diseases, has produced evidence-based Guidelines for a Healthier and Longer Life. Developing a stronger focus on prevention should hopefully increase population and legislation awareness about the need for prevention and lead to a more rapid implementation of scientifically-based strategies. Professor Peter Boyle President, The road that leads from the discovery of a hazard to prevention, is usually long and full of obstacles. 5

7 - International Prevention Research Institute Overview 01/2016 ESMO: Boyle, Faculty Coordinator for Cancer Prevention 02/2016 Cancer Prevention, Monaco 04/2016 IAPO, London 04/2016 Diabetes Emerging Stars, Barcelona 06/2016 ASCO, Chicago 06/2016 ADA, New Orleans 07/ th Annual NCID Meeting 10/2016 National Cancer Congress, Vietnam 11/2016 Masterclass, St. Luke s Week, Dublin 11/2016 Boyle: Honorary Fellowship, Royal College of Physicians, Ireland 11/2016 RIVM, Bilthoven 12/2016 Creation of Africa 12/2016 MOU, NOI, Budapest 01/2017 MOU, Ukraine 02/2017 MOU, IAPO IN MEMORIAM 12/2015 UKCTOCS, London 11/2015 ESO, Barcelona 10/2015 Jubilée J-L Touraine 09/2015 ESMO, Vienna 07/ th Annual NCID Meeting 06/2015 Eurasia Course, Moscow 06/2015 ADA, Boston 06/2015 UKCTOCS, London 05/2015 ASCO, Chicago 05/2015 American Urology Mtg., New Orleans 04/2015 Diabetes Global Public Health, Athens 04/2015 Rhode Island Senate Mtg 02/2015 TIC Lecture, Strathclyde U. 01/2015 Mermorial, Nigel Gray 06/2013 Creation of U. of Strathclyde Institute of Global Public Health at 06/2013 Lecture: ASCO, Chicago 06/2013 Autier, Boffetta, Boniol, Boyle and Hainaut Professors at Strathclyde 05/2013 Publication: P53 in the Clinics (Springer 05/2013 Lecture: Israel National Nutrition Week, Tel Aviv 04/2013 Lecture: AACR, Washington DC 03/2013 Alcohol: Science, Policy and Public Health Published 03/2013 Lecture: IADR, Seattle 02/2013 Lecture: Komen Global Breast Summit, Washington DC 01/2013 Lecture: Diabetes Expert Summit, Paris 11/2012 Lecture: The Economist Health Meeting, London 11/2012 Lecture: ASEAN Region Health Ministers Meeting, Jakarta 03/2013 Publication: Alcohol: Science, Policy and Public Health (OUP) 01/2013 Mullie professorship, The Vrije Universiteit Brussel 02/2011 Controversies in Breast Cancer, Muscat 01/2011 Lecture: Diabetes Symposium, Frankfurt 12/2010 Boyle Inducted Hungarian Science Academy 02/2011 Lecture: U. of Indiana, Indianapolis 10/2012 Seminar: Yale University, New Haven 04/2011 Lecture: American Academy of Oral Medicine, Puerto Rico 11/2010 Lecture: Chile National Diabetes, Santiago 09/2012 Lecture: ESMO, Vienna 04/2011 Lecture: Anniversary Hacettepe University, Ankara 09/2010 Expert: Saudi Arabia FDA, Riyadh 09/2012 Lecture: EASD, Berlin 04/2009 Founded 09/2012 Autier PhD Erasmus University 05/2011 Lecture: Mexican National Diabetes, Cancun 09/2010 Lecture: ESSO, Bordeaux 05/2009 Lecture: ASCO, Orlando 06/2011 Epidemiology and Biostatistics Published 09/2010 ASCO Intl Advisory Committee, DC 09/2012 Lecture: American Ass. Clinical Endocrinology, NY 09/2009 Lecture: NCRI, Birmingham 06/2011 Lecture: ASCO, Chicago 08/2010 Lecture: UICC World Congress, Shenzen 07/2012 8th Annual NCID Meeting 11/2009 Lecture: Dasman Diabetes Inst., Kuwait 06/2011 Lecture: American Diabetes Association, San Diego 07/2010 6th NCID 06/2012 Peter Boyle, LLD (honoris causi), University of Dundee 12/2009 MOU U. Dundee 07/2010 First Summer School 07/2011 7th NCID 06/2012 Expert: Food and Drug Administration of Venezuela 04/2010 Lecture: APOCP, Istanbul 07/2011 Seminar: Dublin City University 06/2012 Lecture: American Diabetes Association, Philadelphia 04/2010 Lecture: Physicians of Britain & Ireland 09/2011 Lecture: EASD, Lisbon 06/2012 Lecture: ASCO, Chicago 05/2010 Lecture: Polish National Diabetes, Warsaw 06/2012 Boyle awarded LLD (honoris causa) 10/2011 Lecture: Turkish Association of Endocrinology, Antalya 06/2010 Lecture: EuroCancer, Paris 11/2011 Lecture: Health Ministers Meeting European Council, Poznan 05/2012 Lecture: Association of Breast Surgeons, Bournemouth 07/2010 World Prevention Alliance Founded 11/2011 Lecture: Bulgarian Cancer Congress, Sofia 05/2012 Lecture: German National Diabetes, Stuttgart 01/2012 Lecture: Centre for Excellence in Auto-Antibodies, Derby 04/2012 Lecture: French National Diabetes, Dijon 02/2012 World Breast Cancer Report 04/2012 Lecture: French National Diabetes, Dijon 03/2012 Seminar: Yale U., New Haven 02/2012 World Breast Cancer Report Published Since the publication of s previous Report, Cancer Control has lost four giants who had a close association with. Nigel Gray was a pioneer in Tobacco Control whose special contribution was to organise the integration of the disparate elements of the anti-tobacco movement into the most organic whole that it could be, short of being one big centralised body. Umberto Veronesi was one of the great men of modern Medicine. He was a pioneering surgeon who made many of the great contributions to breast cancer care and treatment, the survival and quality of life of millions of women with breast cancer have benefited from Veronesi s lifetime dedication and work. Marvin Zelen pioneered the development of the Biostatistics of Randomised Clinical Trials and built up the Department of Biostatistics of Harvard School of Public Health into a world leader. Sandor Eckhardt made an outstanding contribution not only to Oncology in his native Hungary, but also globally through his work with the UICC which emerged under his leadership as a global powerhouse. The work of this trio has had a major impact on reducing the numbers of cases of cancer and improving patients survival and quality of life. Their contribution was immense. May they Rest in Peace. 06/2013 NIDDK-NIH-FDA, Bethesda 09/2014 ESMO: Boyle, Lifetime Achievement Award 06/2013 Lecture: ADA, Chicago 07/ th Annual NCID Meeting 07/2013 9th NCID 05/2014 Lecture: Tongji Medical College, Wuhan 07/2013 9th Annual NCID Meeting 04/2014 Lecture: ASEAN Health Ministers, Kuala Lumpur 07/2013 Additional premises in Ecully 03/2014 Lecture: ESMO Lung Cancer, Geneva 09/2013 Lecture: EASD, Barcelona 03/2014 Seminar: U. of Strathclyde, Glasgow 09/2013 Lecture: ECCO, Amsterdam 03/2014 Lecture: European Breast Cancer Congress, Glasgow 10/2013 Publication: State of Oncology /2014 Lecture: Swiss National Diabetes Day, Zurich 10/2013 State of Oncology 2013 Published 03/2014 Lecture: BioBridges, Florence 10/2013 Lecture: European Health Forum, Bad Gastein 02/2014 Lecture: Intl Cancer Congress, Madrid 10/2013 Lecture: U. of Pennsylvania, Philadelphia 02/2014 Lecture: ICACT, Paris 11/2013 John A Rock Visiting Professor, Louisiana State U., New Orleans 01/2014 Lecture: Royal College of Physicians of England, London 11/2013 Elected Member of Academia Europaea 12/2013 Pasterk leaves, becomes Admin. Dir., BBMRI-ERIC U. of Graz 11/2013 Lecture: World Cancer Leaders, Cape Town

8 - International Prevention Research Institute Overview Strathclyde Institute of Global Public Health at Research into Causes Worldwide Useful Learning Evidence-Based Founded in 2009 with the broad goal of contributing to the improvement of health in populations worldwide, the International Prevention Research Institute () aims to increase prospects for prevention through training, education, prevention research and research into causes worldwide with a focus on low and lower-middle income countries. In order to help further these aims, in June 2013, the International Prevention Research Institute signed an agreement with the University of Strathclyde, established in Glasgow, Scotland, to create the Strathclyde Institute of Global Public Health at. Institute of Global Public Health Training The University of Strathclyde was established in 1796 as the place of useful learning and this remains the mission today: to combine academic excellence with social and economic relevance. In 2012, the University of Strathclyde was awarded the title University of the Year 2012 by The Times Higher Educational Supplement and in 2013 was awarded Innovative University of As the place of useful learning the University is committed to the advancement of society through the pursuit of excellence in research, education and knowledge exchange, and through creative engagement with partner organisations at local, national and international levels and through teaching and research, the University aims to contribute to the development and quality of life of Glasgow (where it is situated), Scotland and the United Kingdom and the international community. The Institute of Global Public Health aims to be unique in its evidence-based approach to practical global Public Health problems. The Institute would have the potential to act as (1) a focal point for activities of other Departments and Faculties (e.g. Engineering, Law, Social Sciences and Pharmacology and Pharmacy) of the University of Strathclyde in establishing international programmes; and (2) a centre where other Universities, Research Institutes, Governments and NGOs could come together on specific research and intervention projects. The project developed should bring mutual added value to both the University of Strathclyde and the International Prevention Research Institute (). Peter Boyle was the inaugural Director of the Institute and became co-director when Sir Harry Burns, former Chief Medical Officer for Scotland, joined the Institute. As well as Professor Boyle and Professor Burns, Philippe Autier, Mathieu Boniol and Pierre Hainaut from were appointed as Professors within the University of Strathclyde. The joint efforts of the International Prevention Research Institute and the University of Strathclyde should see the development and growth of an Institute which, through programmes of research, training and education, would make a difference to the health of the world. In this regard, a Master s programme and a doctoral programme have been launched aimed at students from lower-resource regions focusing on the theory and practical aspects of Public Health in those regions of the world. The model for the future of Health and Public Health research will increasingly focus around public-private initiatives and funding. This will be a strategic axis for continual development. Prevention Research Focus on Lower and Middle Income Countries 9

9 - International Prevention Research Institute Overview Guiding Principles Ethics guiding principles are: Independence Transparency Integrity Impartiality, and Timing. All scientific findings are sent for publication in peer-reviewed journals. Specific provisions are made for avoiding any role of public and private sponsors in reporting of scientific findings. recognizes the following documents as additional guidelines: European Commission Recommendation of 11 March 2005 on the European Charter for Researchers and on a Code of Conduct for the Recruitment of Researchers Council of Science Editors White Paper on Promoting Integrity in Scientific Journal Publications International Committee of Medical Journal Editors Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication, February 2006 The ENCePP Code of Conduct, for scientific independence and transparency in the conduct of pharmacoepidemiological and pharmacovigilance studies, May 2010 Moose Guidelines, April 2000 Prisma Guidelines, July 2009 BE PRINCIPLED PEER REVIEWED ADOPT NEUTRALITY ADHERE TO CODE OF CONDUCT ESPOUSE INTEGRITY FOLLOW GUIDELINES BE TRANSPARENT COMPLY DEMAND EVIDENCE All studies is performing are based on scientific excellence and undergo strict ethical review. The ethical review is performed by an International Governance and Ethics Committee. follows all established international ethics recommendations including: International Ethical Guidelines for Biomedical Research Involving Human Subjects, CIOMS 2002 International Ethical Guidelines for Epidemiological Studies, CIOMS 2009 Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine, Council of Europe 1997 Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct The Nuremberg Code, 1949 UNESCO Universal Declaration on the Human Genome and Human Rights, 1997 UNESCO International Declaration on Human Genetic Data, 2003 World Medical Association Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects, 1964 in its last version from 2008 UNESCO Universal Declaration on Bioethics and Human Rights, 2005 believes that all study subjects, no matter their background, have the right to the same level of protection. This is particularly important given the international dimension of all projects, often including countries with less developed ethics guidelines and practices. has established an International Governance and Ethics Committee to have all research studies which involve human subjects or data reviewed. Our Committee Members come from around the world: Mr David Byrne, Chairman (Ireland) Professor Clement Adebamowo (Nigeria) Dr Kazem Behbehani (Kuwait) Ambassador Mireille Guigaz (France) Lord Mackay of Clashfern (United Kingdom) Dr Edith Olah (Hungary) Professor Luis Pinillos Ashton (Peru) Maître Jean Luc Soulier (France) Professor Jean-Louis Touraine (France) Dr Andrzej Wojtyła (Poland) Professor Charles Gillis, Convenor (United Kingdom) The role of this important committee is currently evolving. Its new remit will be reflected soon on the website. 11

10 - International Prevention Research Institute Overview Global Connections It has never been s intention to be everywhere. Ours is not a quest for size and reach. We are therefore grateful that, despite our reserve, collaboration has come our way from the four corners of the Earth. Our staff is international. We have experts that work on a full time basis continents away.our Senior Research Fellows are in the United States but in Oman too. And, visitors from over 100 countries come to the annual National Cancer Institute Directors meeting and other events. Staff, Consultants, Partners Thank you to all, for your support. We are humbled, indebted Senior Research Fellows and doubly motivated to pursue our work. Presentations, Visitors, Meeting Participants 13

11 - International Prevention Research Institute Overview New Global Relationships It is s view that to better fulfil its mission, it is paramount to work with leaders in epidemiology, biostatistics, cancer, diabetes, global public health and other fields of interest for and 2016 were busy years for new, formal relationships. National Institute of Oncology of Hungary The International Prevention Research Institute and the National Institute of Oncology of Hungary have signed an important Memorandum of Understanding. The National Institute of Oncology is the key reference for Hungary s Ministry of Health when making decisions on cancer control policy and strategy. Prof. Boyle signing MOU with Prof. Tran Van Thuan Prof. Miklós Kasler signing MOU with Prof. Boyle Prof. Withold Zatonski signing MOU with Prof. Boyle The International Prevention Research Institute and the National Institute of Oncology, situated in Budapest, share a long-standing commitment to increase capacity in Cancer Prevention. Together, they continue to strive to reduce the burden of cancer both in Hungary and in surrounding countries. Hungary has a long tradition in medical research which stretches back many decades. Even in difficult times, the tradition of high quality cancer treatment and research has been a feature of Hungarian Medicine. Having collaborated successfully in the past, the parties share a common interest in further strengthening relations and broadening the scope of their collaboration and academic activities. Vietnam National Cancer Hospital In 2016, The International Prevention Research Institute () signed an important Memorandum of Understanding (MOU) with Vietnam s National Cancer Hospital (Hospital K). The National Cancer Hospital (Hospital K) is the key reference for Vietnam s Ministry of Health when making decisions on cancer control policy and strategy. Hospital K is by far, the country s largest cancer hospital treating up to 5000 patients daily on three different campuses. The participants in this Memorandum of Understanding share a long-standing commitment to increase capacity in Cancer Prevention. Together, they continue to strive to reduce the burden of cancer both in Vietnam and abroad. Having collaborated successfully in the past, the parties share a common interest in further strengthening relations and broadening the scope of their collaboration and academic activities. More specifically, the International Prevention Research Institute and the National Cancer Hospital (K Hospital) will work together to develop training opportunities and to implement multiple Cancer Prevention, and Cancer Control, activities in Vietnam More specifically, The International Prevention Research Institute and the National Institute of Oncology of Hungary will work together to develop training opportunities and to implement multiple Cancer Prevention, and Cancer Control activities in Hungary. Both parties will work with other Cancer Institutes world-wide to examine the effectiveness of treatments in the general population of cancer patients. Poland s Fundacja Promocja Zdrowia The International Prevention Research Institute () and the Fundacja Promocja Zdrowia (Health Promotion Foundation HPF) of Poland, represented by its President Professor Witold A. Zatonski have signed a Memorandum of Understanding to collaborate on a range of concrete actions. These two European-based organizations with a long-standing commitment to Prevention both in Europe and worldwide, have come together to further enhance each other s capacity. Activities outlined in the MOU include training opportunities for Polish professionals in Prevention Research and Policy, the open exchange of advanced information and knowledge in disease prevention, provision of teaching materials to Polish professionals, the organisation of joint scientific events and others including joint fundraising efforts to further the aspirations of the joint effort. After years of working alongside the world renowned anti-tobacco advocate Professor Zatonski, this MOU represents an opportunity to escalate our efforts in a more formal setting; I believe that our partnership will lead to quantifiable improvements in Prevention Research and Policy, says Professor Boyle. He adds, It is also an honour to be working with an organization whose Honorary President is his Eminence Kazimierz Cardinal Nycz. Professor Zatonski concurs adding, I believe that the Health Promotion Foundation of Poland, will benefit greatly from s incomparable experience and impact in Global Public Health and Prevention in particular. 15

12 - International Prevention Research Institute Overview Ukraine s RE Kavetsky Institute The International Prevention Research Institute, represented by its President, Professor Peter Boyle, concluded discussions and signed an important Memorandum of Understanding with the RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the National Academy of Science of Ukraine, represented by Academician Vasyl F. Chekhun, Director of the Institute., and RE Kavetsky Institute, situated in Kyiv, share a long-standing commitment to increase capacity in Cancer Prevention. and RE Kavetsky Institute will work together to develop training opportunities and to implement multiple Cancer Prevention, and Cancer Control, activities in Ukraine. RE Kavetsky Institute was established under the Ministry of Health of the Ukrainian SSR in July The founder and first director of the Institute was Rostislav E. Kavetsky, Member of the Academy of Sciences of the Ukrainian SSR. Today, the Institute is a strong academic center with considerable material and human resources and more than 50 years of experience. Research fellows of the Institute have been awarded 18 State Prizes in Science and Technology, 19 laureates of personal prizes of eminent scientists of the NAS of Ukraine, eight titles of Honoured Workers of Ukraine, and one title of Honoured Doctor of Ukraine. The Institute s research interests include the study of the Environment and Cancer looking at the effects of potentially carcinogenic environmental factors (chemical carcinogens, ionizing and non-ionizing radiation) on the molecular and cellular processes of carcinogenesis and development of the agents that can modify them. There are also substantial programmes in Translational Medicine looking at innovations in diagnosis and treatment and in Personalised Medicine. Believe that a further shore is reachable from here. Seamus Heaney International Alliance of Patients Organizations, represented by its President, Professor Peter Boyle, concluded discussions and signed an important Memorandum of Understanding with the International Alliance of Patients Organizations (IAPO), represented by the Chair of the Board, Jolanta Bilińska. The role of patients organisations is morphing rapidly from its initial lobbying focus to a much more involved and proactive role in matters such as clinical trial design and advocacy in the design of healthcare organisation and delivery. IAPO activity is focused on promoting patient-centric healthcare. IAPO achieves this by being the global voice for all who suffer from any disease, disability, illness, impairment or syndrome, and by being the focal point for patients organisations worldwide. IAPO s unique global alliance is committed to improving the lives of patients beyond borders. IAPO nurtures relationships with members, partners and all those involved in healthcare, and builds dialogue with global decision-makers to promote patient-centric healthcare. There are currently 276 Member Organisations in IAPO, representing 71 countries and 51 disease areas. will work with IAPO in strengthening its research portfolio and providing the evidence-based information necessary in the current environment. will also benefit from having access to the patient s voice in planning and executing its own research in a wide variety of disease areas including cancer, diabetes and multiple sclerosis. 17

13 - International Prevention Research Institute Sunbeds The Road to Restrictions on Sunbeds Exposure and Risk: A Thirty Year History In the closing years of the 1980s, realizing that melanoma incidence in Europe was increasing and that there had been no substantial progress in treatments, some members of the EORTC Melanoma Group met in the office of Ferdy Lejeune in Brussels to discuss possibilities of melanoma prevention. Two options were at stake at this moment: a cohort study of individuals with dysplastic atypical naevi, to determine whether this was a melanoma precursor or a marker of risk, and an epidemiological study addressing the risk of use of psoralens (a known mutagen and carcinogen) as tanning accelerators in sunscreens and the risk eventually associated with artificial ultraviolet tanning. Concern about a possible role of sunbed exposure in the development of cutaneous melanoma arose in the last years of the 1980s. In those years, the UVA portion of the UV spectrum was deemed to be an innocent wavelength, while the UVB represented the carcinogenic fraction of the solar spectrum reaching the earth ground. Because the UV spectrum of sunbed devices consisted mainly of UVA, this exposure was considered as not being involved in skin carcinogenic processes. However, two case-control studies in England and Canada pointed out that a relationship between exposure to sunlamps and sunbeds might exist. In addition, a survey in Brussels showed that melanoma patients were greater users of artificial ultraviolet sources than the general population, and that the incidence of melanoma in different geographical areas in Belgium increased proportional to the percentage of people using tanning devices (Autier et al, 1991). In the following months, Peter Boyle convened a meeting at the International Agency for Research on Cancer to discuss the possibility of introducing a multi-national study of melanoma into the SEARCH Programme, which he directed. Invitees included EORTC Melanoma Group members (Stéphane Carrel, Jean-Pierre Césarini, Jean-François Doré, and Ferdy Lejeune,) together with melanoma epidemiologists (Bruce K Armstrong, Mark Elwood, Rick Gallagher, Ole Moller-Jensen and Calum Muir). It was agreed to abandon the idea of a cohort of dysplastic nevi since its pathological definition was not unanimous, and to concentrate on a case-control study of melanoma risk factors which had only been investigated in Scotland and Denmark and not elsewhere in Europe. Consequently in 1991, with the help of a grant from the Europe against Cancer programme, a multicentre case-control study was launched in Belgium, France and Germany. This case-control-study was incredibly productive, demonstrating that exposure to sunlamps or sunbeds starting 10 years before diagnosis was associated with an increased risk of melanoma for at least 10 hours of accumulated exposure, the risk being higher for subjects who experienced skin-burn due to sunlamps or sunbeds, and for those who exposed their skin for tanning purposes (Autier et al, 1994; Autier et al, 1995). The study also showed that sunscreens prepared with psoralen were a direct melanoma risk factor which subsequently resulted in their ban by the European Commission. Because of this finding, the company manufacturing the psoralen sunscreen sued Philippe Autier for dissemination of unscientific information, leading to a trial that the company eventually lost. Norway and Sweden were among the first countries to implement national regulations for indoor tanning devices, in 1982 and 1983, respectively. And in 1997, France was the first country to regulate access to commercial use of sunbeds, limiting UVB to 1.5% of the emitted UV, banning unstaffed machines and prohibiting use by minors <18 years. A further EORTC case control study, investigating the association between sunbed use and cutaneous melanoma in adults and conducted between 1999 and 2001 in Belgium, France, The Netherlands, Sweden and the United Kingdom failed to demonstrate an association: overall adjusted odds ratio (OR) associated with ever sunbed use was 0.90 (95% CI: 0.71, 1.14) (Bataille et al, 2005). This 19

14 - International Prevention Research Institute Sunbeds publication is frequently cited by the proponents of sunbed use as a large European study showing the safety of sunbed exposure while deliberately ignoring the companion article (de Vries et al, 2005) demonstrating that, probably due to increased public awareness, cases may have under-reported their sun exposure and, most likely, their sunbed exposure. In addition, high percentages of sunbed use among controls indicated possible recruitment bias: eligible controls who were sunbed users were probably more likely to accept the invitation to participate than non-users, possibly due to a feeling of guilt or worry about their habits. Such selective participation may have strongly influenced the risk estimates of sunbed use in this study. The concern that there may be an association between exposure to artificial UV radiation and skin cancer was reactivated in when the 10th Report on Carcinogens published by the National Toxicology Program in the USA classified UVA radiation as a Known Carcinogen to Humans. The concern was fuelled by the evidence that the tanning industry used biased arguments for promoting exposure to artificial UV sources (Autier, 2004), and expended much efforts for convincing public health authorities that professionally supervised artificial UV tanning was safer than sun tanning (Autier et al, 2011b). In spring 2004, irritated by a press release from the tanning industry falsely citing a WHO fact sheet on sunbeds and advocating artificial tanning as a preparation to summer sun exposure, the NGO Sécurité Solaire wrote to the French President Jacques Chirac to ask him to ban such advertisements. Subsequently, in October 2004, the French Ministry of Health contacted the Director of the International Agency for Research on Cancer (IARC), Dr Peter Boyle, raising a particular concern about the continuous increase in incidence of melanoma in France and in the world, and requested IARC to investigate the possibility of re-evaluating the carcinogenic risk associated with UV radiation, particularly concerning artificial UV sources and the use of indoor tanning facilities. Since the last IARC Monograph on UV radiation in 1992, a large number of epidemiological and experimental studies had been conducted on the risks associated with exposure to UV radiation. In response IARC Director Peter Boyle convened in June 2005 a small working group (Philippe Autier, Mathieu Boniol, Jean-François Doré, Sara Gandini, Adele Green, Julia Newton-Bishop, Martin A Weinstock, Johan Westerdahl, and Stephen D Walter) that conducted an extensive literature analysis and a meta-analysis. Based on 19 studies (18 case-control studies, of which 9 were population based, and one prospective study) that included 7,355 melanoma cases and 11,275 controls from case-control studies and 106,378 cohort members, the group concluded that ever-use of sunbeds was associated with an increase in melanoma risk (RR=1.15 (95% CI: 1.00, 1.31)), more especially when exposure started before 30 years of age (RR=1.75 (95%CI: 1.35, 2.26)) (IARC, 2006). The strong association between sunbed exposure starting at an early age and melanoma prompted public health warnings recommending to ban the access to sunbeds to subjects less than 18 years of age (Autier et al, 2008). It is worthy of note that, a few years later, a new meta-analysis conducted by the same group and based on 27 studies, fully confirmed these results (Boniol et al, 2012). These works encouraged many European countries and states in Australia, the USA and in Canada to put an age restriction on the access to artificial suntan parlours. In 2006, the Scientific Committee on Consumer Products (SCCP) from the European Commission issued an Opinion on Biological effects of ultraviolet radiation relevant to health with particular reference to sunbeds for cosmetic purposes, of which the conclusion was SCCP is of the opinion that the use of UVR tanning devices to achieve and maintain cosmetic tanning, whether by UVB and/or UVA, is likely to increase the risk of malignant melanoma of the skin and possibly ocular melanoma. In addition, SCCP proposed to limit erythemally weighted irradiance of sunbeds to 0.3 W/m2, i.e. 11 standard erythema doses (SED) per hour, equivalent to tropical sun, which the WHO terms extreme exposure (SCCP, 2006). In June 2009, IARC re-evaluated the carcinogenicity of solar and ultraviolet radiation. And based on the available data, and more especially on the IARC (2005) meta-analysis, the working group concluded that there is sufficient evidence in humans for the carcinogenicity of the use of UV-emitting tanning devices. UV-emitting tanning devices cause cutaneous malignant melanoma and ocular melanoma. Use of UV-emitting tanning devices is carcinogenic to humans (Group 1) (IARC, 2012). Shortly after IARC classification of sunbeds as a Group 1 carcinogen, Brazil issued a total ban on commercial tanning facilities. This ban was followed by bans in Australia and now, all Australian States have banned commercial tanning facilities. Since the IARC classification of sunbeds, several major studies confirmed the carcinogenicity of sunbed exposure. Among these, the analysis of an epidemic of melanoma in Iceland could relate the sharp increase in incidence of melanoma on the trunk among women younger than 50 years to the development of indoor tanning facilities in the Reykjavik area (Hery et al, 2010). Another analysis of a previously published case-control study, but excluding those who had reported burns from indoor tanning use, investigated the interaction between sunbed use and sunburns from outdoor solar radiation and the risk of melanoma. Significantly increased risk was found for melanoma across all sunburn categories, the highest risk being found for those who reported zero lifetime sunburns (OR=3.87 (95% CI: 1.68, 8.91)) (Vogel et al, 2014). An accumulation of other epidemiological data has documented the likelihood that the UVA is involved in carcinogenic processes taking place in the skin (Autier et al, 2011a). More recently, following a request from the European Commission, the Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) reviewed recent evidence to update the 2006 SCCP Opinion on the Biological effects of ultraviolet radiation relevant to health, with particular reference to sunbeds for cosmetic purposes. The public consultation on the preliminary opinion raised nearly 1,000 comments, in majority from sunbed industry representatives and sunbed associations. In its final opinion, SCHEER concluded that that there is strong evidence that exposure to UVR, including that emitted by sunbeds, causes cutaneous melanoma and squamous cell carcinoma at all ages and that the risk for cancer is higher when the first exposure takes place in younger ages. There is also moderate evidence that exposure to UVR, including that emitted by sunbeds, also increases the risk of basal cell carcinoma and ocular melanoma, and added that there is no safe limit for exposure to UV radiation from sunbeds (SCHEER, 2016). The carcinogenicity of sunbed exposure should no longer be a matter of debate. Sunbed exposure represents a major public health concern. Its contribution to skin cancer incidence is far from being negligible: it has been estimated that In Europe, 3,438 (5.4%) of 63,942 new cases of melanoma diagnosed each year are attributable to sunbed use, women representing most of this burden (Boniol et al, 2012), and the risk concentrates in the population that started sunbed use before the age of In addition, sunbed exposure is associated with early onset melanoma. It required thirty years of research and analysis, including legal action against researchers, to lead to the current situation where the carcinogenic effects of sunbeds are established and that steps are taken to legislate against their use and thereby leading to reduce the risk of melanoma in the population. The road between identification of a hazard and its prevention can be long and can contain many obstacles which need to be overcome. Autier P. Perspectives in melanoma prevention: the case of sunbeds. Eur J Cancer. 2004;40(16): Autier P, Boyle P. Artificial ultraviolet sources and skin cancers: rationale for restricting access to sunbed use before 18 years of age. Nat Clin Pract Oncol. 2008;5(4): Autier P, Dore JF, Eggermont AM, Coebergh JW. Epidemiological evidence that UVA radiation is involved in the genesis of cutaneous melanoma. Curr Opin Oncol. 2011a;23(2): Autier P, Joarlette M, Lejeune F, Lienard D, Andre J, Achten G. Cutaneous malignant melanoma and exposure to sunlamps and sunbeds: a descriptive study in Belgium. Melanoma Res. 1991;1(1): Autier P, Dore JF, Breitbart E, Greinert R, Pasterk M, Boniol M. The indoor tanning industry s double game. Lancet. 2011b;377(9774): Autier P, Dore JF, Schifflers E, Cesarini JP, Bollaerts A, Koelmel KF, et al. Melanoma and use of sunscreens: an Eortc case-control study in Germany, Belgium and France. The EORTC Melanoma Cooperative Group. Int J Cancer. 1995;61(6): Bataille V, Boniol M, De Vries E, Severi G, Brandberg Y, Sasieni P, et al. A multicentre epidemiological study on sunbed use and cutaneous melanoma in Europe. Eur J Cancer. 2005;41(14): Boniol M, Autier P, Boyle P, Gandini S. Cutaneous melanoma attributable to sunbed use: systematic review and meta-analysis. BMJ. 2012;345:e4757. de Vries E, Boniol M, Severi G, Eggermont AM, Autier P, Bataille V, et al. Public awareness about risk factors could pose problems for case-control studies: the example of sunbed use and cutaneous melanoma. Eur J Cancer. 2005;41(14): Hery C, Tryggvadottir L, Sigurdsson T, Olafsdottir E, Sigurgeirsson B, Jonasson JG, et al. A melanoma epidemic in Iceland: possible influence of sunbed use. Am J Epidemiol. 2010;172(7): IARC. Radiation. IARC Monogr Eval Carcinog Risks Hum. 2012;100(Pt D): IARC working group. Exposure to artificial UV radiation and skin cancer. Lyon, France: SCCP. Request for a scientific opinion: Biological effects of ultraviolet radiation relevant to health with particular reference to sun beds for cosmetic purposes. Scientific committee on consumer products (SCCP), SCHEER. Opinion on Biological effects of ultraviolet radiation relevant to health with particular reference to sunbeds for cosmetic purposes. Brussels, Belgium: Scientific Committee on Health, Environmental and Emerging Risks Vogel RI, Ahmed RL, Nelson HH, Berwick M, Weinstock MA, Lazovich D. Exposure to indoor tanning without burning and melanoma risk by sunburn history. J Natl Cancer Inst. 2014;106(7). 21

15 - International Prevention Research Institute Principal Contributions PRINCIPAL CONTRIBUTIONS The International Prevention Research Institute was established to bring about change. From day one, we have never been satisfied with doing the least. Our goal is to be exhaustive, continuously. To this end, we self-fund projects that we believe, can help steer global public health in a better direction. What follows in the coming pages are a series of major contributions made by in tandem with our partners and sometimes on our own. We believe that the road to better health is evidence; when it comes to people s health, getting to the destination quickly, efficiently but also accurately, saves lives for many and improves quality-of-life for the living. 23

16 - International Prevention Research Institute Principal Contributions Cancer Breast Cancer Screening Screening impacts cancer mortality through decreasing the number of advanced cancers with poor prognosis, while patient management impacts cancer mortality through decreasing the fatality of cancers. The effectiveness of cancer screening is the ability of a screening method to reduce cancer mortality by reducing the incidence of advanced cancers in populations. Breast cancer mortality is declining in most high income countries since around Dramatic mortality declines of 30 to 45% over 20 to 25 years have been observed in more than twenty European and North American countries (Autier et al, 2010), updated in abstract No P by Pizot et al presented at the San Antonio Breast Cancer Symposium (SABCS) 2016). The continuous improvements in the management of breast cancer patients are playing a major role in these mortality reductions (Park et al, 2015). In contrast, the impact of mammography screening on mortality reductions seems to be limited, while at the same time this screening has led to the detection of many small cancers or of lesions (e.g., the in situ cancers ) of unknown clinical significance, that would never had presented a hazard to a women s health in her lifetime (i.e., overdiagnosis). These gloomy conclusions on mammography screening were reached by studies that have shown no or modest decline in the incidence of advanced cancers, including that of de novo metastatic (stage 4) cancers at diagnosis in populations where mammography screening is widespread for long periods (Autier et al, 2012a; Autier et al, 2011b; Autier et al, 2014). These findings are in contradiction with the well-known fact that effective cancer screening impacts cancer mortality through decreasing the number of advanced cancers with poor prognosis. Additional studies found that breast cancer mortality reductions are similar in areas with early introduction and high penetration of screening than in area with late introduction and low penetration of screening (Autier et al, 2011a; Autier et al, 2012b). The conclusions of s studies have been largely confirmed by similar studies done by other groups in Europe and in North America (Bleyer, 2011; Bleyer et al, 2012; de Glas et al, 2014; Harding et al, 2015). 30% In randomised trials on cancer screening, the reduction of the risk of cancer death reported in articles (the observed reduction) should be similar to the risk of cancer death predicted on the basis of the reduction of the numbers of advanced cancers. 1 The absence of similarity in the three breast screening trials diplayed in the figure indicates a probability of biases in the trial conduct and analysis (after Autier et al (2016)) % reduction of risk of breast cancer death 25% 20% 15% 10% 5% 28% 2% 27% 11% 21% 10% 0 HIP Two-county UK Age 1 *Three trials on breast screening reported data allowing the calculation of predicted risk reduction Observed reduction in the risk of breast cancer death Predicted reduction in the risk of breast cancer death 25

17 - International Prevention Research Institute Principal Contributions Mammography screening programmes have been implemented in most high income countries when six randomised trials, and especially the four trials conducted in Sweden, showed that periodic breast screening of women 40 to 74 years of age could reduce the risk of breast cancer death by about 20 to 25% (Independent UK Panel on Breast Cancer Screening, 2012). The contradiction between results of the randomised trials and of population studies led scientists to re-appraise the Swedish mammography trials. Our research conducted in 2013 to 2016 has demonstrated that the design and statistical analysis of the breast screening randomised trials were different than that of all trials on screening for cancers other than breast cancer (Autier et al, 2015). scientists found compelling indications that these trials overestimated reductions in breast cancer mortality associated with screening (see figure), in part because of the statistical analyses themselves, in part because of improved management and underreporting of breast cancer as the underlying cause of death in screening groups (Autier et al, 2016). It was also found that if the Swedish trials had published some crucial results as other randomised trials on screening for non-breast cancers, the imperfections of Swedish trials would have been more apparent. The Greater New-York Health Insurance Plan (HIP) trial was the first randomised study suggesting the efficacy of breast screening. However, the re-appraisal found that results of the HIP trial are biased because of the underreporting of breast cancer cases and deaths that occurred in women who did not participate to screening (Autier et al, 2016). Finally, the re-appraisal also examined the UK Age trial which was conducted among women 39 to 41 years of age at randomisation. It was found that after 17 years of follow-up, the UK Age trial showed no benefit of mammography screening starting at age 39-41, while overdiagnosis was considerable (Autier, 2015). The more treatments are efficient, the greater the number of women need to be screened for preventing one breast cancer death, and the more overdiagnosis caused by screening, and the greater the number of women with overdiagnosed breast cancer for one breast cancer death prevented with screening. These relationships deteriorate with decreasing effectiveness of screening (After Autier (2016b)) Number of women to screen Number of women to be screened to prevent one breast cancer death Number of women with overdiagnosis Number of women with overdiagnosis to prevent one breast cancer death with screening 0% 25% 50% 0% 25% 50% As a consequence, the number of women needed to screen for preventing one breast cancer death increases with treatment potency (see figure). Moreover, the imbalance between screening effectiveness and overdiagnosis augments with the potency of treatments. Because there is a fairly great chance that in many countries, dying from breast cancer will become increasingly uncommon, the possible role of mammography screening in breast cancer mortality reductions will become increasingly marginal, while the harms will remain the same. In conclusion, if the implementation of screening programmes has undoubtedly contributed to increase breast awareness and the quality of health services to breast cancer patients, there remains an urgent need to direct research efforts on alternative technologies for breast cancer screening, i.e., a test which is really able to early detect cancers before they progress to an advanced stage that is difficult to treat and with minimal harm in terms of over-diagnosis. Also, for preserving an acceptable harm-benefit balance, screening should be targeted to women at high risk of breast cancer death. Autier P. Breast cancer: Doubtful health benefit of screening from 40 years of age. Nat Rev Clin Oncol. 2015;12(10): Autier P. Efficient Treatments Reduce the Cost-Efficiency of Breast Cancer Screening. Ann Intern Med. 2016a. Autier P. Efficient Treatments Reduce the Cost-Efficiency of Breast Cancer Screening. Ann Intern Med. 2016b;164(4): Autier P, Boniol M. The incidence of advanced breast cancer in the West Midlands, United Kingdom. Eur J Cancer Prev. 2012a;21(3): Autier P, Pizot C, Boniol M. Stable incidence of advanced breast cancer argues against screening effectiveness. BMJ. 2014;349(nov25 10):g6358. Autier P, Boniol M, Gavin A, Vatten LJ. Breast cancer mortality in neighbouring European countries with different levels of screening but similar access to treatment: trend analysis of WHO mortality database. BMJ. 2011a;343:d4411. Autier P, Koechlin A, Smans M, Vatten L, Boniol M. Mammography screening and breast cancer mortality in Sweden. J Natl Cancer Inst. 2012b;104(14): Autier P, Boniol M, Smans M, Sullivan R, Boyle P. Statistical analyses in Swedish randomised trials on mammography screening and in other randomised trials on cancer screening: a systematic review. J R Soc Med. 2015;108(11): Autier P, Boniol M, Smans M, Sullivan R, Boyle P. Observed and Predicted Risk of Breast Cancer Death in Randomized Trials on Breast Cancer Screening. PLoS One. 2016;11(4):e Autier P, Boniol M, La Vecchia C, Vatten L, Gavin A, Hery C, et al. Disparities in breast cancer mortality trends between 30 European countries: retrospective trend analysis of WHO mortality database. BMJ. 2010;341:c3620. Autier P, Boniol M, Middleton R, Dore JF, Hery C, Zheng T, et al. Advanced breast cancer incidence following population-based mammographic screening. Ann Oncol. 2011b;22(8): Biller-Andorno N, Juni P. Abolishing mammography screening programs? A view from the Swiss Medical Board. N Engl J Med. 2014;370(21): Birnbaum J, Gadi VK, Markowitz E, Etzioni R. The Effect of Treatment Advances on the Mortality Results of Breast Cancer Screening Trials: A Microsimulation Model. Ann Intern Med Bleyer A. US breast cancer mortality is consistent with European data. BMJ. 2011;343:d5630. Bleyer A, Welch HG. Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med. 2012;367(21): de Glas NA, de Craen AJ, Bastiaannet E, Op t Land EG, Kiderlen M, van de Water W, et al. Effect of implementation of the mass breast cancer screening programme in older women in the Netherlands: population based study. Bmj. 2014;349:g5410. Fletcher SW. Breast cancer screening: a 35-year perspective. Epidemiol Rev. 2011;33(1): Harding C, Pompei F, Burmistrov D, Welch HG, Abebe R, Wilson R. Breast Cancer Screening, Incidence, and Mortality Across US Counties. JAMA Intern Med Independent UK Panel on Breast Cancer Screening. The benefits and harms of breast cancer screening: an independent review. Lancet. 2012;380(9855): Jatoi I. The impact of advances in treatment on the efficacy of mammography screening. Prev Med. 2011;53(3): Park JH, Anderson WF, Gail MH. Improvements in US Breast Cancer Survival and Proportion Explained by Tumor Size and Estrogen-Receptor Status. J Clin Oncol. 2015;33(26): USPSTF. Screening for testicular cancer: U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern Med. 2011;154(7): % Mortality reduction due to breast cancer patient management % Overdiagnosis 20% Mortality reduction with screening mammography 10% Mortality reduction with screening mammography 20% Mortality reduction with screening mammography 10% Mortality reduction with screening mammography A recurring question is whether the advent of effective therapies and the improvement in performances of all relevant medical, radiotherapy and surgical disciplines after 1990 has affected the effectiveness of screening mammography (Biller-Andorno et al, 2014; Fletcher, 2011; Jatoi, 2011). As a matter of fact, the high effectiveness of cis-platinum based therapies on testis cancer, even when already metastatic, has rendered obsolete the few attempts made to promote screening for this cancer (USPSTF, 2011). On the basis of studies that have estimated how the availability of efficient adjuvant and chemo treatments has changed reductions in risks of breast cancer death reported by randomized trials on breast screening (Birnbaum et al, 2016), we have documented that increasingly efficient patient management reduces the number of screen-prevented breast cancer deaths (Autier, 2016a). 27

18 - International Prevention Research Institute Principal Contributions Screening for Colorectal Cancer Colorectal cancer is a major public health issue in most western countries. Colorectal cancer is the second most commonly diagnosed cancer in the world and has poor prognosis when metastasised to lymph nodes or distant organs. After lung cancer, it is the most common cause of cancer death Changes in CRC mortality* from 1989 to 2010 is highly variable across European countries (after Ait Ouakrim et al (2015)) Men - % Change % -40% -30% -20% Malta Hungary ( 89-09) Slovenia Slovakia Latvia Portugal Ukraine Russian Federation ( 89-09) Belarus ( 89-09) Bulgraia Spain Greece ( 89-09) Estonia Lithuania Poland Croatia Macedonia ( 91-10) Romania -10% 0 10% Austria Switzerland ( 89-07) Germany Czech Republic France ( 89-09) Luxembourg ( 89-09) UK UK, England and Wales Ireland ( 89-09) Belgium Norway Finland UK, Northern Ireland Italy ( 89-09) Denmark ( 89-07) EU27 ( 89-09) Sweden UK, Scotland The Netherlands Iceland ( 89-09) USA 20% 30% -50% -40% -30% 40% 50% 60% 70% 80% 90% 100% -50% -40% -30% -20% -10% 0 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% -50% -40% -30% in Europe. In 2012, it was estimated that 241,600 European men were diagnosed with colorectal cancer, and that 113,200 men died from the disease. For European women, 205,200 cases of colorectal cancer and 101,500 related deaths were recorded that year. -20% Women - % Change % 0 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Austria Germany Czech Republic UK Luxembourg ( 89-09) Switzerland ( 89-07) Ireland ( 89-09) France ( 89-09) UK, Northern Ireland UK, England and Wales Belgium UK, Scotland EU27 ( 89-09) Finland Italy ( 89-09) Iceland ( 89-09) Hungary ( 89-09) Denmark ( 89-09) Malta Portugal Slovakia ( 92-10) The Netherlands Slovenia Estonia -20% Sweden Norway Spain Belarus ( 89-09) Ukraine Bulgaria Latvia Greece ( 89-09) Lithuania Poland Russian Federation ( 89-09) Croatia Macedonia ( 91-10) Romania USA -10% 0 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% In collaboration with the University of Melbourne, we have studied changes in colorectal cancer mortality in European countries (Ait Ouakrim et al, 2015). Since 1989, many European countries have undergone changes in the prevalence of risk factors for colorectal cancer such as obesity and alcohol intake, participation to screening programmes, and access to specialised care and effective treatments. As a result, colorectal cancer mortality is falling in an increasing number of mainly Nordic, and Western European countries, presumably because of favourable changes in risk factors, access to screening, less late presentation when metastases have already spread in distant organs (e.g., in the liver), the development of therapies with increased efficiency and more generally, better management of patients. For the sake of comparison, the mortality change in the USA is displayed in the figure. In Central, Eastern and Southern European countries, colorectal cancer mortality is still on the rise, sometimes markedly like in Romania, Croatia and Poland. These unfavourable trends are essentially due to poor dietary patterns, high alcohol consumption, late stage at cancer diagnosis, reflecting low awareness and absence of screening, and limited availability of effective therapies. The persistent greater colorectal cancer mortality in men than in women suggest that differences in risk factors play a major role, because women tend to be more health aware and to adopt healthier behaviours, while participation to screening tends to be similar in both sexes. Screening methods for early detection of the colorectal cancer are gradually improving. The old guaiac-based faecal occult blood test (gfobt) is progressively replaced by the immunology-based FOBT (ifobt) which is more sensitive and can detect adenomatous polyps. The most efficient screening methods are those based on the endoscopic examination of the distal colon (sigmoidoscopy) and of the entire colon (colonoscopy). The ifobt and endoscopic methods lead to the removal of polyps from which most colorectal cancer arise. This iterative polypectomy leads on its turn to a decrease in both the incidence and mortality of this cancer. The role of screening can be illustrated by the comparison of mortality trends in countries having similar socio-economic status and access to modern therapies (see figure below). In Austria and Germany, endoscopic screening has been widely promoted in the 2000s, while colorectal cancer screening is in pilot phases in the Netherlands and in Sweden. Surveys using a same methodology for inquiring about past exposure to endoscopic examinations of the large bowel have shown examination rates two to three times higher in Austria and Germany than in the Netherlands and Sweden ( Reductions in colorectal cancer mortality are more pronounced in the former than in the latter countries (see figure below). Because of the many similarities between the four countries, such difference can hardly be explained by changes on the influence of factors other than screening. Proportions of men and of women aged 50 or more who reported at least one endoscopic examination of the large bowel over the last 10 years and reductions in colorectal cancer mortality from 2009 to 2011 in selected European countries with similar access to high quality health care % reduction in CRC mortality 60% 50% 40% 30% 20% 10% 0 Men: 23% or more Women: 23% or more Men: 10% or less Women: 10% or less Austria Germany The Netherlands Sweden Ait Ouakrim D, Pizot C, Boniol M, Malvezzi M, Boniol M, Negri E, et al. Trends in colorectal cancer mortality in Europe: retrospective analysis of the WHO mortality database. BMJ. 2015;351:h

19 - International Prevention Research Institute Principal Contributions Screening for Cutaneous Melanoma Cutaneous melanoma is the most deadly form of skin cancer. It is known that subjects harbouring many melanocytic naevi (or moles) are at higher risk of melanoma. It has thus been proposed that subjects with skin nevi should have their skin periodically examined for the identification of pigmented spots that could evolve into life-threatening melanoma. The ability of regular skin screening to reduce one s chance to die from a melanoma has never been tested in an experimental design. The conduct of a community-based randomised trial on skin screening has been attempted in Queensland, Australia, that part of the world where the highest risk of melanoma is observed among light-skinned subjects (Aitken et al, 2002). However the trial did not succeed in recruiting sufficient numbers of subjects to reach a conclusion on the public health value of screening for melanoma. Aitken JF, Elwood JM, Lowe JB, Firman DW, Balanda KP, Ring IT. A randomised trial of population screening for melanoma. J Med Screen. 2002;9(1):33-7. Boniol M, Autier P, Gandini S. Melanoma mortality following skin cancer screening in Germany. BMJ Open. 2015;5(9):e Breitbart EW, Waldmann A, Nolte S, Capellaro M, Greinert R, Volkmer B, et al. Systematic skin cancer screening in Northern Germany. J Am Acad Dermatol. 2012;66(2): Force USPST. Screening for skin cancer: Us preventive services task force recommendation statement. JAMA. 2016;316(4): Katalinic A, Waldmann A, Weinstock MA, Geller AC, Eisemann N, Greinert R, et al. Does skin cancer screening save lives?: an observational study comparing trends in melanoma mortality in regions with and without screening. Cancer. 2012;118(21): Wolff T, Tai E, Miller T. Screening for skin cancer: an update of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;150(3): In 2003, an intervention study on skin screening was conducted in Northern Germany (Breitbart et al, 2012; Katalinic et al, 2012). The intervention consisted of total body skin examinations of adults performed by general practitioners and by dermatologists. Despite a low participation rate of 20%, investigators reported a dramatic reduction in the mortality due to melanoma starting around screening initiation and lasting for a few years. These results prompted considerable interest and public health agencies were invited to consider new recommendations more favourable to skin screening. In particular, the US Preventive Services Task Force (USPSTF) was asked to reconsider its review of 2009 in which it was concluded that the evidence on the health benefits of skin cancer screening was insufficient for issuing a recommendation (Wolff et al, 2009). In 2014, performed a detailed analysis of the mortality statistics related to melanoma in Germany. When the analysis was confined to areas where the screening intervention took place, it was found that in recent years, the melanoma mortality had returned to rates prevailing before screening (see figure) (Boniol et al, 2015a). Thus there was a fairly high chance that the apparent transient decline in melanoma mortality was spurious and due to the misreporting of causes of death by doctors who had also been involved in the skin screening intervention. The research served as a reference for the USPSTF to justify the absence of change of conclusions reached in the review of 2009 (Force, 2016). Melanoma mortality/100, First pilot project SCREEN project Screened area (SH) Germany Men Women Trend in cutaneous melanoma mortality in the screened area Schleswig Holstein (SH) as compared with the whole of Germany. Data from the Federal Statistical Office ( de) as of 15 December 2014 and from GEKID as of 10 December Box=period of SCREEN project (Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany) (July 2003 June 2004). 31

20 - International Prevention Research Institute Principal Contributions Screening for Prostate Cancer The use of the serum prostate specific antigen (PSA) concentration for prostate cancer early detection is not recommended, and most public health agencies recommend against the use of PSA testing for mass screening purposes. The main reason for these recommendations is the considerable amount of harm associated with screening, due to the overtreatment of many prostate cancers that would have remained asymptomatic during lifetime (i.e., overdiagnosed cancers). The harms consist mainly of incontinence and in erectile dysfunction. The harms due to overdiagnosis is a high price to pay for an uncertain number of prostate cancer deaths avoided. The recommendations have generally been directed to occasional or PSA testing in men free of prostate symptom. The case of periodic PSA testing with monitoring of PSA levels was not really addressed by most recommendations. According to some studies, raising PSA levels over time could indicate the presence of a fast growing prostate cancer, in other words, of a cancer that would deserve radical therapy with minimal risk of overdiagnosis. Distribution of the percentage variation of prostatespecific antigen level between the first and the second measurement in the PLCO study. The blue curve is a kernel density estimation with bandwidth = 0.6. PLCO, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; PSA, prostate-specific antigen. The carried out an analysis of the risk of prostate cancer according to changes in serum PSA concentrations over time using the data form the large randomised trials in the USA called the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial (Andriole et al, 2009). The analysis found that timevariations in PSA concentrations followed 30% 25% 20% 15% 10% 5% 0-100% -80% -60% -40% a quasi-normal distribution without evidence of extreme changes that would represent the signature of the presence of a fast growing prostate cancer (see figure) (Boniol et al, 2015). Statistical analyses further showed that if raising levels over time could predict the diagnosis of a prostate cancer, there was no relationship with the aggressiveness (i.e., the Gleason score) of the prostate cancer. Hence, rising PSA concentrations are not helpful for determining whether a men is developing a potentially life-threatening prostate cancer. -20% 0 20% 40% Curve: Kernel (c=0.6) Percentage variation of PSA level 60% 80% 100% 120% 140% 160% 180% 200% Andriole GL, Crawford ED, Grubb RL, 3rd, Buys SS, Chia D, Church TR, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360(13): Boniol M, Autier P, Perrin P, Boyle P. Variation of Prostate-specific Antigen Value in Men and Risk of High-grade Prostate Cancer: Analysis of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Study. Urology. 2015;85(5):

21 - International Prevention Research Institute Principal Contributions Breast Cancer and Physical Activity Observational studies have shown that physical activity could reduce the risk of breast cancer and the use of hormone replacement therapy (HRT) increases the risk of breast cancer. The objective our study was to quantify the association between physical activity and breast cancer and to investigate the influence of HRT use and other risk factors on this association. Results from stratified meta-analyses of breast cancer risk and physical activity A systematic literature search and quantitative analysis was conducted and reported following PRISMA guidelines regarding meta-analysis of observational studies. Eligible articles for this study had to: (i) report data on incident cases of breast cancer or on breast cancer deaths; (ii) report measurement of physical activity, being occupational and/or non-occupational, and using any metrics to quantify physical activity; (iii) have a prospective design. Articles with prevalent cases of breast cancer were excluded. A meta-analysis was undertaken using a random effects model to investigate the association between physical activity and breast cancer risk. As physical activity assessment and reporting of results were very heterogeneous across studies, breast cancer risk associated with the highest level of physical activity was compared with the lowest level of physical activity. Heterogeneity between studies was evaluated by the I² statistics and publication bias was assessed with Begg test, Egger test and Macaskill test. Sensitivity analyses were carried out and stratified meta-analyses considering several confounding factors were performed. A dose-response analysis, using a non-parametric approach, was also conducted with studies reporting physical activity either in hours/week or in MET-h/week (Metabolic equivalent of task). Thirty eight studies were included in our analysis representing 4,124,275 women of which 116,304 were diagnosed with a breast cancer during the study period. The summary relative risk (SRR) for breast cancer in the highest vs. the lowest category of physical activity was 0.88 (95% CI: 0.85, 0.90) with 29% of heterogeneity and no strong evidence of publication bias. The stratified analyses revealed that physical activity decreased the risk of breast cancer by about 12% irrespective of the place of residence, type of physical activity, adiposity, menopausal status, and the hormone receptor status of tumours (see figure). Nevertheless, the decreased risk was more pronounced in women with low BMI (SRR=0.84 (95% CI: )), women with ER-/PR- phenotype (SRR=0.80 (95% CI: 0.69, 0.92)) and women who never used HRT (SRR=0.78 (95% CI: 0.70, 0.87)). Studies conducted before 1989 reported greater decreases in breast cancer risk than studies conducted after 1989 (SRR=0.80 (95% CI: 0.72, 0.90)) and SRR=0.89 (95% CI: 0.86, 0.92), respectively) that could be partly explained by the less prevalent use of HRT before Dose-response analyses were performed with the 18 studies that reported physical activity either in MET-h/week or in hours per week. Significant dose-response relationships were found (p < ) between amounts of physical activity and breast cancer risk irrespective of the metric used indicating steady reductions in risk with increasing physical activity, without evidence for a threshold. For example, a physically inactive women engaging in at least 150 min per week of vigorous physical activity would reduce their lifetime risk of breast cancer by 9%, a reduction that might be two times greater in women who never used HRT. This meta-analysis demonstrates three important findings. Firstly, increased levels of physical activity lead to reductions in the risk of breast cancer irrespective of the type of physical activity, place of residence, adiposity, menopausal status, and the hormone receptor status of tumours. Secondly, breast cancer risk seems to decline with increasing physical activity, without a threshold effect. Thirdly, women who ever used HRT had no reduction of breast cancer risk associated with physical activity which raises the hypothesis that HRT use would cancel out the preventive effect of physical activity against breast cancer. Pizot C, Boniol M, Mullie P, Koechlin A, Boniol M, Boyle P, et al. Physical activity, hormone replacement therapy and breast cancer risk: A meta-analysis of prospective studies. Eur J Cancer. 2016;52: This study indicates that avoidance of sedentary behaviours and promotion of physical activity may contribute to control the increase in breast cancer burden taking place in most populations over the world. The time is ripe for organising large population randomised trials that will better inform on the feasibility of policies encouraging physical activity to prevent breast cancer occurrence. On the other hand, other lifestyle risk factors such as alcohol drinking that are known to be associated with an increased risk of breast cancer should also be considered in strategies aiming at preventing breast cancer (Pizot et al, 2016). 35

22 - International Prevention Research Institute Principal Contributions Active and Passive Smoking and Risk of Breast Cancer Observational studies on active or passive smoking and breast cancer, as well as metaanalyses and reviews have reached a wide range of conclusions, from a lack of association to suggestion of a causal association. In order to provide up-to-date quantitative estimates of the association between active and passive smoking, and the risk of breast cancer, a systematic review and meta-analysis of case-control and cohort studies published until March 2015 were conducted. A total of 86 prospective and case-control studies were included in 4 main meta-analyses estimating the risk of incident invasive breast cancer in ever/current/former smokers compared to never smokers, and in never active but passive smokers compared to women never exposed. Active smoking: Results of meta-analyses were indicative of statistically significant moderate increased risks of breast cancer associated with ever, current and former active tobacco smoking (between 8% and 13% increased risk) (see table). The results of the dose-response analysis indicated that with every additional year of smoking the relative risk of breast cancer incidence is multiplied by (see figure). As a consequence, the risk of breast cancer in women who smoke during 10, 20 or 30 years is increased by 5, 10, and 16%, respectively. The likelihood of an association is further supported by the quasi absence of heterogeneity in results of prospective studies and by the stability of results across different subgroups, notably in pre-menopausal and post-menopausal women, after adjustment for alcohol consumption, and when passive smokers were excluded from the referent group. Summary of meta-analyses results, stratified by studies design and types of exposures Meta-analysis Number of studies Studies design Total number of cases Summary relative risk Confidence interval Heterogeneity I 2 Active smoking exposure and breast cancer risk Ever active smoking 71 P & R 125, , % Ever active smoking 27 P 68, , % Ever active smoking 44 R 56, , % Current active 49 P & R 103, , % smoking Current active 27 P 63, , % smoking Current active 22 R 40, , % smoking Former active 49 P & R 103, , % smoking Former active 27 P 62, , % smoking Former active smoking 22 R 40, , % Passive smoking exposure and breast cancer risk Ever passive smoking 31 P & R 34, , % Ever passive smoking 11 P 18, , % Ever passive smoking 20 R 16, , % P = prospective design and R = retrospective design Passive smoking: Exposure to environmental tobacco smoke also seems associated with a moderately increased risk of breast cancer (between 7% and 30%). However, results for passive smoking are more delicate to interpret because of the difficulty to assess exposure to second-hand smoking exposures, and of the relatively small number of available studies. Robustness of results: The heterogeneity of results between studies was more manifest for retrospective designs, with zero to low heterogeneity among results from prospective studies. The summary relative risk estimates have remained remarkably stable over time, and the accumulation of studies has steadily reduced the variance of estimated risks. Results were robust across stratified analyses and leave-one-out sensitivity analysis did not identify any one study that strongly influenced the results. There was little to no evidence of publication bias. As time passes, the evidence accumulates for considering that active tobacco smoking is associated with a modest, but real increase in the risk of breast cancer. The consistency of findings, the low heterogeneity of results of prospective studies, the dose-response found in prospective studies, the permanent higher risk since the first studies done on the topic, and the absence of influence of major confounders on associations are all indicating that the relationship would be causal. For passive smoking also, the evidence for a modest but real association with breast cancer strengthens with the accumulation of data. In this respect, public health policies should inform women about the risk of breast cancer associated with both active and passive smoking. (Macacu et al, 2016). 37

23 - International Prevention Research Institute Principal Contributions Relative risk of breast cancer incidence in function of the duration of ever actively smoking (in years) among 12 studies with prospective designs. The colour of the points indicates the original study, and the size of the points is inversely proportional to the variance of the RR estimate given in this study. The linear regression trend line is drawn in black, using the summary slope estimate b = 1.005, and the dotted lines represent the 95 % confidence interval of the slope estimate Risk of Cancer in the Rubber Manufacturing Industry Working in the rubber manufacturing industry was classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC 1982, 1987, 2012). This evaluation was mainly based on workers first employed in the first half of the XX th century. Many technological and occupational changes have occurred in this industry since the 1960s and yet little data is available for more recently employed workers. The mortality and cancer incidence of rubber industry workers first employed after 1975 was studied in five European countries. In a second part, a meta-analysis on the risk of cancers in the rubber manufacturing industry was conducted RR 1.0 Study AlDelaimy2004 Bjerkaas2013 Catsburg2014 Catsburg2015 Cox2011 Gram2005 Land2014 Luo2011 Manjer2004 Olson2005 Reynolds2004 Xue2011 Subjects were recruited in five European countries (Germany, Italy, Poland, Sweden and the United Kingdom), if they had at least one year of employment in the rubber manufacturing industry and were first employed on or after 01/01/1975. Workers were followed-up to 2012 for mortality (all countries) and cancer incidence (Sweden and the UK). Mortality and cancer incidence were compared with those observed in the general population using age-, gender-, country- and period-specific standardised mortality/incidence ratios (SMRs/SIRs). SMRs were computed for all-cause mortality, cardiovascular mortality, respiratory mortality and major cancer sites. SIRs were computed for major cancer sites only. Heterogeneity analyses were conducted type of industry (tyres; general rubber goods/grg; mixed), and duration of employment. In total, 38,457 subjects (77% men) contributing 949,370 person-years and 2,275 deaths were included in the mortality study (Boniol et al, 2016). No statistically significant increased risk of any cause of mortality was observed (see table), including for bladder cancer. Significantly reduced risks were found for lung cancer, all forms of cancers and all-cause mortality. Risks were lower in the tyre industry than in the general rubber goods industry. For example the SMRs for all forms of cancers were 0.68 (95% CI: 0.60, 0.76); 0.74 (95% CI: 0.61, 0.88) and 1.03 (95% CI: 0.91, 1.18) for workers employed in the tyre, mixed and GRG industries, respectively. Analysis of all-cause mortality by duration of employment revealed decreasing SMRs with increasing duration of employment Duration smoking (years) Al-Delaimy WK, Cho E, Chen WY, Colditz G, Willet WC. A prospective study of smoking and risk of breast cancer in young adult women. Cancer Epidemiol Biomarkers Prev. 2004;13(3): Bjerkaas E, Parajuli R, Weiderpass E, Engeland A, Maskarinec G, Selmer R, et al. Smoking duration before first childbirth: an emerging risk factor for breast cancer? Results from 302,865 Norwegian women. Cancer Causes Control. 2013;24(7): Catsburg C, Kirsh VA, Soskolne CL, Kreiger N, Rohan TE. Active cigarette smoking and the risk of breast cancer: a cohort study. Cancer Epidemiol. 2014;38(4): Catsburg C, Miller AB, Rohan TE. Active cigarette smoking and risk of breast cancer. Int J Cancer. 2015;136(9): Cox DG, Dostal L, Hunter DJ, Le Marchand L, Hoover R, Ziegler RG, et al. N-acetyltransferase 2 polymorphisms, tobacco smoking, and breast cancer risk in the breast and prostate cancer cohort consortium. Am J Epidemiol. 2011;174(11): Gram IT, Braaten T, Terry PD, Sasco AJ, Adami HO, Lund E, et al. Breast cancer risk among women who start smoking as teenagers. Cancer Epidemiol Biomarkers Prev. 2005;14(1):61-6. Land SR, Liu Q, Wickerham DL, Costantino JP, Ganz PA. Cigarette smoking, physical activity, and alcohol consumption as predictors of cancer incidence among women at high risk of breast cancer in the NSABP P-1 trial. Cancer Epidemiol Biomarkers Prev. 2014;23(5): Luo J, Margolis KL, Wactawski-Wende J, Horn K, Messina C, Stefanick ML, et al. Association of active and passive smoking with risk of breast cancer among postmenopausal women: a prospective cohort study. BMJ. 2011;342:d1016. Macacu A, Autier P, Boniol M, Boyle P. Active and passive smoking and risk of breast cancer: a meta-analysis. Breast Cancer Res Treat. 2015;154(2): Manjer J, Johansson R, Lenner P. Smoking is associated with postmenopausal breast cancer in women with high levels of estrogens. Int J Cancer. 2004;112(2): Olson JE, Vachon CM, Vierkant RA, Sweeney C, Limburg PJ, Cerhan JR, et al. Prepregnancy exposure to cigarette smoking and subsequent risk of postmenopausal breast cancer. Mayo Clin Proc. 2005;80(11): Reynolds P, Hurley S, Goldberg DE, Anton-Culver H, Bernstein L, Deapen D, et al. Active Smoking, Household Passive Smoking, and Breast Cancer: Evidence From the California Teachers Study. JNCI Journal of the National Cancer Institute. 2004;96(1): Xue F, Willett WC, Rosner BA, Hankinson SE, Michels KB. Cigarette smoking and the incidence of breast cancer. Arch Intern Med. 2011;171(2): The analysis of cancer incidence was restricted to Sweden and the United Kingdom, for which complete data were available (Boniol et al, 2017b). In total, 16,026 individuals (397,975 person-years) were included in the analysis, and 846 cancer cases (excluding non-melanoma skin) were recorded. No statistically significant risk of cancer of any site was observed (see table). Significantly reduced risks were identified for lung cancer, all forms of cancer (excluding skin), non-hodgkin s lymphoma and prostate cancer. Overall, results were similar to those observed for mortality. The cohort study of rubber manufacturing industry workers was contextualised by conducting a global meta-analysis on the risk of cancer in the rubber manufacturing industry (Boniol et al, 2017a). Observational studies reporting a risk estimate of cancer in this population were systematically searched. Summary relative risks (SRRs) were computed for each cancer site with at least four risk estimates. A sensitivity analysis was conducted by restricting the study to workers first employed on or after 01/01/1960. The literature search identified 46 cohort and 59 case-control studies. Summary relative risks by cancer site are described in the figure. An increased risk was found for bladder cancer (SRR=1.36 (95% CI: (1.18, 1.57))), leukaemia (1.29 (95% CI: 1.11, 1.52)), lymphatic/haematopoietic system (1.16 (95% CI: 1.02, 1.31)), and larynx cancer (1.46 (95% CI: 1.10, 1.94)). There was a borderline significant increased risk of lung cancer (1.08 (95% CI: 0.99, 1.17)). SRRs were not statistically significantly increased nor decreased for all other cancer sites. In stratified analyses, risks of cancer were no longer increased for workers employed after 1960, including for cancer sites that showed a statistically significant increased risk when all studies were considered. Risk of bladder cancer, lung cancer, larynx cancer and leukaemia were increased among workers in the rubber manufacturing industry. However, elevated risks were no longer seen among workers first employed after The cohort study of workers employed in the European rubber manufacturing industry since 1975 found no increased risk of cancer incidence or cancer mortality. As these cohorts are relatively young, continued surveillance is required for confirming the absence of long-term risk. In addition, confirmation from other cohorts would be useful. 39

24 - International Prevention Research Institute Principal Contributions Results of meta-analyses on occupational exposure to rubber manufacturing industry and risk of cancer, results presented for each cancer site. All* 0.97 [ 0.92, 1.02 ] Bladder* 1.36 [ 1.18, 1.57 ] Lung* 1.08 [ 0.99, 1.17 ] Stomach 1.06 [ 0.95, 1.17 ] Leukaemia* 1.29 [ 1.11, 1.52 ] Hodgkin's disease 1.30 [ 0.78, 2.16 ] Non Hodgkin's Lymphoma 0.98 [ 0.77, 1.24 ] Multiple Myeloma 1.05 [ 0.82, 1.35 ] Lymphatic and haematopoeitic system NOS 1.16 [ 1.02, 1.31 ] Gallbladder* 1.91 [ 0.97, 3.77 ] Liver 0.96 [ 0.79, 1.17 ] Bone and connective tissue 1.41 [ 0.62, 3.22 ] Brain and central nervous system 1.05 [ 0.88, 1.25 ] Head and Neck* 1.12 [ 0.89, 1.42 ] Oesophagus* 1.10 [ 0.83, 1.44 ] Colon 1.03 [ 0.93, 1.14 ] Rectum 1.05 [ 0.93, 1.18 ] Colorectum 1.01 [ 0.95, 1.07 ] Digestive system NOS 1.00 [ 0.93, 1.06 ] Larynx* 1.46 [ 1.10, 1.94 ] Pleura/mesothelioma* 2.11 [ 0.42, ] Melanoma 0.76 [ 0.44, 1.30 ] Non Melanoma skin 0.85 [ 0.63, 1.13 ] Pancreas 0.96 [ 0.87, 1.05 ] Kidney 0.98 [ 0.83, 1.15 ] Thyroid 2.03 [ 0.80, 5.15 ] Prostate 0.94 [ 0.83, 1.07 ] Testis 0.59 [ 0.18, 2.00 ] Other Male Genital 0.92 [ 0.69, 1.23 ] Breast 0.93 [ 0.74, 1.18 ] Body of uterus* 1.04 [ 0.20, 5.36 ] Cervix 0.77 [ 0.40, 1.45 ] Ovary 0.89 [ 0.60, 1.30 ] SRR with 95% CI *: statistically significant heterogeneity between studies Observed deaths and standardised mortality ratios (SMRs) among 38,457 workers first employed in the European rubber manufacturing industry since 1975, by gender. Statistically significant associations are in bold. Men Women Combined Cause of deaths Observed SMR (95% CI:) Observed SMR (95% CI:) Observed SMR (95% CI:) Primary outcomes Bladder cancer (0.49, 1.52) (0.06, 2.29) (0.46, 1.38) Lung cancer (0.68, 0.94) (0.61, 1.35) (0.70, 0.94) Secondary outcomes All cancers (0.74, 0.88) (0.72, 0.97) (0.76, 0.87) Stomach cancer (0.84, 1.56) (0.61, 2.46) (0.88, 1.53) Leukaemia (0.58, 1.63) (0.14, 4.02) (0.53, 1.35) Non-Hodgkin s (0.40, 1.37) (0.28, 2.57) (0.47, 1.34) lymphoma Multiple myeloma (0.81, 2.98) (0.56, 5.11) (0.89, 2.68) Exploratory outcomes** All causes of death 2, (0.71, 0.89)* (0.78, 0.94) (0.73, 0.89)* Cardiovascular (0.71, 0.90) (0.61, 0.90) (0.70, 0.89) diseases Respiratory (0.72, 1.19) (0.38, 1.42) (0.71, 1.13) diseases excluding pneumonia Brain and central (0.66, 1.39) (0.46, 2.14) (0.69, 1.34) nervous system cancer Colorectal cancer (0.44, 0.86) (0.71, 1.91) (0.55, 0.94) Kidney cancer (0.49, 1.38) (0.51, 1.32) Larynx cancer (0.69, 2.04) (0.65, 1.93) Liver cancer (0.40, 1.31) (0.40, 1.20) Melanoma (0.45, 1.71) (0.36, 1.28) Oesophagus (0.57, 1.41) (0.54, 1.30) Oral cavity and (0.62, 1.53) (0.59, 1.43) pharynx Pancreas cancer (0.64, 1.36) (0.70, 2.44) (0.72, 1.35) Prostate cancer (0.52, 1.21) Breast cancer (0.60, 1.23) - - Cervical cancer (0.74, 2.10) - - Ovarian cancer (0.38; 1.40) - - * Significant heterogeneity between the five countries (p<0.05). ** Results of exploratory analysis with less than five deaths observed were not reported. 41

25 - International Prevention Research Institute Principal Contributions Observed cases and standardised incidence ratios (SIRs) among 16,026 workers first employed in the European rubber manufacturing industry since 1975, by country. Statistically significant associations are in bold. Sweden (N=7,424; PY=174,767) United Kingdom (N=8,602; PY=223,208) Combined (N=16,026; PY=397,975) Cancer sites Observed SIR (95% CI:) Observed SIR (95% CI:) Observed SIR (95% CI:) Primary outcomes Bladder (0.73, 1.72) (0.42, 1.02) (0.61, 1.28) Lung (0.63, 1.34) (0.53, 0.94) (0.59, 0.93) Secondary outcomes All cancers combined (0.81, 0.99) (0.69, 0.85) (0.74, 0.92)* (except skin) Stomach (0.37, 1.71) (0.55, 1.57) (0.61, 1.43) Leukaemia (0.09, 0.88) (0.54, 1.58) (0.48, 1.28) Non-Hodgkin s (0.31, 1.18) (0.41, 1.08) (0.45, 1.00) lymphoma Multiple myeloma (<0.01, 1.04) (0.45, 2.05) (0.44, 1.91) Exploratory outcomes** Brain and central (0.50, 1.49) (0.31, 1.20) (0.52, 1.21) nervous system Colon, rectum and (0.78, 1.41) (0.39, 0.75) (0.49, 1.22)* anus Kidney (0.43, 1.55) (0.49, 1.39) (0.57, 1.29) Larynx (0.37, 1.87) (0.49, 1.96) Melanoma (0.92, 1.78) (0.22, 0.75) (0.37, 1.70)* Oesophagus (0.45, 1.37) (0.51, 1.39) Oral cavity and (0.63, 2.02) (0.56, 1.44) (0.71, 1.48) pharynx Pancreas (0.38, 1.74) (0.33, 1.37) (0.47, 1.34) Prostate (0.63, 1.02) (0.54, 0.94) (0.64, 0.92) Testis (0.67, 2.16) (0.32, 1.04) (0.53, 1.45) Breast (0.60, 1.08) (0.67, 1.29) (0.73, 1.13) Endometrial (0.25, 1.50) (0.32, 2.33) (0.42, 1.58) Ovary (0.52, 2.16) (0.50, 2.54) (0.69, 2.02) * Significant heterogeneity between the two countries (p<0.05). ** Results of exploratory analyses with less than five cases observed were not reported. Disclosure: The study was partially funded by an unrestricted research grant from the European Tyre and Rubber Manufacturers Association (ETRMA) and was conducted and reported in full independence from the sponsor. Boniol M, Koechlin A, Boyle P. Meta-analysis of occupational exposures in the rubber-manufacturing industry and risk of cancer. Int J Epidemiol. 2017a;(submitted). Boniol M, Koechlin A, Sorahan T, Jakobsson K, Boyle P. Cancer incidence in cohorts of workers in the rubber manufacturing industry first employed since 1975 in the UK and Sweden. Occup Environ Med. 2017b;(in press). Boniol M, Koechlin A, Swiatkowska B, Sorahan T, Wellmann J, Taeger D, et al. Cancer mortality in cohorts of workers in the European rubber manufacturing industry first employed since Ann Oncol. 2016;27(5): IARC. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol 28: The Rubber Industry. Lyon, France: International Agency for Research on Cancer; IARC. The rubber industry. Overall Evaluations of Carcinogenicity: an Updating of IARC Monographs, Volumes 1 to 42, Suppl 7. IARC Monographs on the Evaluation of the Carcinogenic Risks to Humans. Lyon, France: International Agency for Research on Cancer; p IARC. Occupational exposures in the rubber-manufacturing industry. Chemical Agents and Related Occupations. IARC Monographs on Evaluation of Carcinogenic Risks to Humans. 100F. Lyon, France: International Agency for Research on Cancer; p Chemotherapeutic Waste Disposal Remarkable efforts continue to be made to identify human carcinogens which are causes of cancer in men and women. Once such causes have been identified, steps can be taken to avoid the exposure of populations wherever possible. An important topic in protecting cancer patients, carers and potentially the general public from exposure to cancer causing chemicals relates to the excretions of patients who are receiving chemotherapy. Some of these excretions, whether in sweat, urine, vomit or faeces contain identified carcinogens and little attention has been given to such exposures. Chemotherapy drugs have been proven to cause second primary neoplasms in patients receiving them and once this had been identified, steps were initially introduced to avoid exposure to medical personnel in the preparation and delivery of these compounds. Many drugs are used to treat cancer and over 20 chemotherapy drugs, including widely used agents such as cyclophosphamide, doxorubicin, 5-FU and etoposide, cause patients receiving them to excrete identified human carcinogens in vomit, sweat, urine or faeces. With the cancer burden increasing with the ageing of the population and the increasing tendency to give patients chemotherapy as out-patients, the potential for increasing numbers of individuals to be exposed to carcinogens in excreted material is increasing also. It is of considerable concern that systems for the collection of this carcinogenic waste outside the hospital environment are to the largest extent unavailable. Guidelines have been prepared for hospitals, oncology doctors and nurses and cancer drug producers to avoid or minimise their exposure to these carcinogenic risks. When patients are sent home following treatment, advice is given to restrict use to one specified toilet to the patient or, if not possible, to flush twice. This will reduce the exposure to patients and their carers but will not eliminate the potential exposure. In addition, it could be foreseen that there are circumstances in which failure to deal with this source of carcinogens could lead to wider exposure in communities. Every step needs to be taken to reduce exposure to all known cancer causing agents. It is essential to pay more attention to the protection of care givers and the environment. Many types of chemotherapy excrete identified human carcinogens in the hours and days following treatment (e.g. adriamycin), in sweat, faeces, urine or vomit exposing care-givers to these dangerous chemicals. In hospital there are special procedures for dealing with such hazardous waste but these do not exist in the home environment. General advice such as restrict use of one toilet to the cancer patient or flush twice do not solve the problem. Apart from posing a threat to care givers and family members, these hazardous chemicals enter into our sewage systems and general environment and have been doing so on a daily basis for several decades. Preventing these chemicals from posing a threat to care givers and entering our waterways and water supply must be an issue of paramount importance. The medical profession, the insurance industry, the pharmaceutical companies and politicians must join forces to fight this cause of human suffering on all fronts. 43

26 - International Prevention Research Institute Principal Contributions Cancer Scenarios in Scotland In 2001, NHS Scotland published a report on Cancer Scenarios, designed as an aid to planning cancer services in Scotland in the next decade (Scottish Executive Health Department, 2001). The authors made predictions of how incidence and mortality rates for 19 cancers would change in the following years. Fifteen years after the publication of that report, observed incidence and mortality data have become available, and an assessment of the predictions made previously was timely. Ratio of predicted over observed incidence and mortality age standardised rates, for 17 cancer sites in men, for 4 time periods. Cancer sites are listed in increasing order of number of observed new cases for the period Observed incidence and mortality data for each of the cancers concerned were downloaded from ISD Scotland (Information Services Division) website. Observed absolute numbers of new cancer cases and deaths, as well as age-standardised incidence and mortality rates were compared to predicted ones. Incidence rates in men were mostly underestimated, with colorectal and kidney cancers being accurately predicted. Similar results were observed for mortality rates in men: most cancers were underestimated, with head and neck cancers, oesophageal and stomach cancers being accurately predicted (see top figure). Incidence rates in women were mostly underestimated, with colorectal, breast and ovarian cancers being accurately predicted. The accuracy of mortality rates predictions in women was cancer site-dependent; for some cancers mortality rates were underestimated, while for others overestimated, with oesophageal and stomach cancer mortality being accurately predicted (see bottom figure). Ratio of predicted over observed incidence and mortality age standardised rates, for 19 cancer sites in women, for 4 time periods. Cancer sites are listed in increasing order of number of observed new cases for the period A large relative deviation from one of the ratio predicted/observed, could mean a small variation in terms of absolute numbers, for cancers with a low number of cases and deaths. Reversely, a small deviation from 1 of the ratio predicted/observed could mean a large variation in terms of absolute numbers, for cases with high numbers of cases and deaths. For three cancer sites non-hodgkin s lymphoma, Hodgkin s lymphoma, and leukaemia in adults assessment of the accuracy of the predictions was not feasible, due to important discrepancies between the predicted and observed databases for the observed period of , which was used as control. Bladder cancer assessment was also hindered, by coding changes implemented after the projections were made. These coding changes led to a reclassification of invasive bladder cancers, and an artificial reduction of the incidence of bladder cancer. The accuracy of the projected incidence and mortality rates was variable across cancers and genders, and it was generally poorer for predictions further in time (as is to be expected with future projections models). However, an important point to keep in mind is that projections can indicate possible future outcomes for current trends and how these may potentially be influenced by policies and interventions. By having sufficient notice and knowledge, these outcomes can be influenced through actions meant for improvement, so that even if originally projected outcomes are not realised, the projections purpose can be considered fulfilled if they have led to changing an undesirable outcome. The Cancer Scenarios project in Scotland has helped better orient Scotland s cancer plan and has led to continued projections, evaluations and updates. Scottish Executive Health Department. Cancer Scenarios: An aid to planning cancer services in Scotland in the next decade. Executive. ETS;

27 - International Prevention Research Institute Principal Contributions Diabetes Diabetes is sneaking up on the world, one step at a time. While policymakers have been paying attention to communicable diseases and, at best, cancer, diabetes has been steadily invading populations both in developed and developing countries. Indeed, Diabetes is poised to become the world s leading chronic disease. In light of this, has increased its commitment to providing the evidence and guidance required to spur effective actions and policies. Diabetes and Pancreas Cancer Pancreas cancer is the 12th most common type of cancer in the world with men being more affected than women. Disparities in pancreas cancer incidence prevail around the world with developed countries more affected than developing countries. Pancreas cancer is a poor prognosis cancer with a 5-year survival rate below 10% that is mostly explained by the advanced stage at diagnosis and the older age of patients which represents an obstacle to surgery. Moreover, there is a lack of primary prevention that would act on modifiable risk factors and no early detection through a screening of people at risk for this cancer. Thereby, there is an important need to know the aetiology of pancreas cancer to improve the current situation. Recent meta-analyses suggested that primary prevention should focus on modifiable risk factors such as smoking, alcohol consumption and adiposity. Moreover, other meta-analyses suggested higher surveillance of people with a family history of pancreas cancer or with a history of gallbladder diseases as well as the eradication of HBV and HCV infections in Asian and African countries in order to control the burden of pancreas cancer. The association between diabetes, pancreatitis and pancreatic cancer has been long studied and several studies suggested that diabetes and pancreatitis would be the strongest risk factors of pancreas cancer. If these relations are true, early diagnosis of pancreas cancer could be made through the screening of diabetic people and people with a history of pancreatitis. In order to clarify the association between diabetes and its medication, pancreatitis and the risk of pancreas cancer, a series of systematic reviews and meta-analyses were undertaken. Regarding diabetes and the risk of pancreas cancer, 64 cohort studies were included in our meta-analysis and the summary relative risk (SRR) of pancreas cancer in patients with diabetes was 1.94 (95% CI: 1.77, 2.12) with a large degree of heterogeneity between studies (I 2 =97%, p<0.01) and some evidence of publication bias. When the effect modification by duration of diabetes was investigated, a higher increased risk was observed in studies with the shortest history of diabetes and lower risk was observed in studies with a longer duration of diabetes but the association remained statistically significant with a SRR of 1.36 (95% CI: 1.19, 1.55) for more than ten years of diabetes duration (Batabyal et al, 2014). This result suggests that diabetes could be the initial presentation of pancreas cancer. Regarding pancreatitis and the risk of pancreas cancer, 29 cohort studies were included in our meta-analysis on all forms of pancreatitis and the SRR of pancreas cancer in patients with a history of pancreatitis was 9.72 (95% CI: 6.01, 15.73) with a large degree of heterogeneity between studies (I²=93%, p<0.0001) and no evidence of publication bias. The restriction of the analysis to acute or unspecified pancreatitis gave a lower effect with a SRR of 5.15 (95% CI: 4.13, 6.41) while the restriction to chronic pancreatitis gave a stronger association with a SRR of (95% CI: 5.19, 26.26) with still large degree of heterogeneity in both sub-analyses. Moreover, several studies reported a higher risk within the first year of diagnosis of acute pancreatitis and suggested that acute pancreatitis could be an initial presentation of pancreas cancer. As diabetes and pancreatitis are both strong risk factors for pancreas cancer, a meta-analysis of the risk of pancreatitis among diabetic patients was performed. Eight independent observational studies were selected for the analysis and a statistically significant 2-fold increased risk of pancreatitis was found in patient with diabetes (SRR=1.94 (95% CI: 1.61, 2.35), with a large amount of heterogeneity between studies (I²=93%, p<0.01) and no evidence of publication bias. 47

28 - International Prevention Research Institute Principal Contributions As diabetes is associated with a 2-fold increased risk of pancreatitis and pancreas cancer, one would say that these increased risk are driven by anti-diabetic treatments (ADT), therefore this hypothesis was investigated in several meta-analyses. Based on published meta-analyses, Sulphonylureas and insulin treatments appeared to significantly increase the risk of pancreas cancer. Sulphonylureas were significantly associated with a 70% (SRR=1.70 (95% CI: 1.27, 2.28)) (Singh et al, 2013) increased risk of pancreas cancer in observational studies but this result was no longer significant in randomized controlled trials (RCTs). The effect of insulin seems to be stronger as meta-analyses reported a significant 2.5 fold increased risk of pancreatic cancer (SRR=2.66 (95% CI: 2.07, 3.43)) (Bosetti et al, 2014). However, when the analysis was stratified by duration of use, the association was stronger for a shorter insulin use (<5y) but declined with increasing duration of use and became not significant after 10y of use. Retinopathy and Eye Light Diabetic Retinopathy (DR) is a complication of Diabetes Mellitus, which affects the eye. As one of the major causes of visual impairment in the world it is a major Public Health challenge. Any patient with diabetes is at risk, regardless of the type of Diabetes (I or II). On average, more than 25% of patients with Diabetes will develop DR. The International Diabetes Federation (IDF) states that the number of people living with diabetes is expected to rise from 415 million (2015) to 642 million by 2040 (+ 54%) if no urgent action is taken (International Diabetes Federation, 2015). Inversely, Metformin seems to reduce the risk of pancreas cancer but most of the results remained statistically non-significant. Regarding Thiazolidinediones, no association with pancreas cancer was found neither in observational studies nor in RCTs. Diabetic Retinopathy results from damage to the small blood vessels of the retina (i.e. the fundus of the eye) through changes in the blood flow. Generally, Retinopathy has no symptoms until it is advanced because damage to the blood vessels is the direct cause of blindness but its consequence around the macula, the seeing part of the eye. Concerns have been raised on the potential association between incretin-related therapies and the risk of developing pancreatitis, which could result in an increased risk of pancreas cancer. Hence, meta-analyses were undertaken in order to assess the risk of pancreatitis and pancreatic cancer associated with the use of incretins compared to the use of other anti-diabetics treatment. Based on 19 observational studies, a borderline significant increased risk of pancreatitis (SRR=1.31 (95% CI: 1.01, 1.70)) was observed in users of incretins compared to non-users with a large amount of heterogeneity (I 2 =89%, p-value<0.05) and some evidence of publication bias. However, this association was no longer significant when the analysis was conducted by type of incretins (e.g. GLP-1RAs and DPP-4 inhibitors). Pancreas cancer risk was investigated in nine prospective studies and the SRR in incretin users was 1.23 (95% CI: 0.88, 1.73) with significant heterogeneity between studies (I 2 =81%, p-value<0.0001) and no indication of publication bias. As mentioned earlier, new-onset of diabetes may be a manifestation of early pancreas cancer, and this can potentially confound an association between anti-diabetic treatments and pancreas cancer. Thereby, these results must be interpreted with caution and long term RCTs with large sample size especially design to detect long term outcomes should be needed for establishing causality. Lesions of Diabetic Retinopathy and anatomy of the eye in a colour fundus image The only way to prevent people with diabetes from becoming blind is with regular screening of their eye fundus, consisting of an examination of their eye fundus and a visual assessment test. Direct ophthalmoscope or digital colour photographs of the retina are the methods used for first line screening (see figure). Then, a severity grade is given by trained staff. In case of a severe stage, the patient must be referred to an ophthalmologist for further examination and treatment. Good glucose, blood pressure and cholesterol control can also reduce the risk of developing sight-threatening complications. Optic Disk Hard Exudates Macula Haemorrhage + Cotton wool spot Microaneurysm In this study, we demonstrated that early diagnosis of pancreas cancer through screening of diabetic people or people with a history of pancreatitis may be an important advancement in the control of pancreas cancer. However, further studies are need to clarify if diabetes and pancreatitis are consequences or causes of pancreas cancer. Remote screening programmes fo patients with Diabetes have been in existence for some years in countries such as in Wales where every diabetic patients over the age of 12 is registered in the Diabetic Eye Screening Service for Wales (DESW) programme. For every patient four images of the retina (two per eye) are taken and sent to the screening service where graders give them a severity mark and decide if the patient must be referred to an ophthalmologist. Batabyal P, Vander Hoorn S, Christophi C, Nikfarjam M. Association of diabetes mellitus and pancreatic adenocarcinoma: a meta-analysis of 88 studies. Ann Surg Oncol. 2014;21(7): Bosetti C, Rosato V, Li D, Silverman D, Petersen GM, Bracci PM, et al. Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium. Ann Oncol. 2014;25(10): Singh S, Singh PP, Singh AG, Murad MH, McWilliams RR, Chari ST. Anti-diabetic medications and risk of pancreatic cancer in patients with diabetes mellitus: a systematic review and meta-analysis. Am J Gastroenterol. 2013;108(4):510-9; quiz 20. As the grading is based on eye fundus images, their quality is essential. However, a significant number of images can have strong contrast variation (due to the geometry of the eye or the acquisitions conditions). This can be a limiting factor for the diagnosis of the disease. Currently to address this problem, graders have to manually adjust their contrast. We have initiated a research project to improve diagnosis of Diabetic Retinopathy. First of all, it is necessary to standardize contrast across the entire image. A fully automatic method, based on image processing, evens the contrast of dark and bright elements across the entire image. This method is much more powerful than the state of the art methods used now for grey scale images. Our method has been tested on more than 2000 images acquired from different screening services and taken under different conditions both in high- and low-income countries. Some images were bright, while others were dark. For all images, the contrast has been enhanced for lesions such as micro-aneurysms and the vascular structures (see figure below). The lesions are now easier to detect by graders. The results obtained are very promising. Our method will vastly improve the diagnosis of Diabetic Retinopathy and other lesions in colour eye fundus images. Indeed, the lesions become far more evident in comparison of the original image. Importantly, our method is fully automated and can easily be integrated in the screening system. 49

29 - International Prevention Research Institute Principal Contributions Comparison between original and enhanced images acquired both in good and in harsh conditions Original image acquired in optimal conditions Enhanced image White Paper on Diabetes Epidemiology We have put together an updated review of the research done on the most relevant topics related to diabetes mellitus, awaiting publication as the White Paper on the Epidemiology of Diabetes. Diabetes is a collection of disorders characterised by hyperglycaemia and glucose intolerance, due to either lack of insulin in the body, or to the body s inefficient way of using it. Morbidity and mortality from diabetes arise from a large list of complications associated with diabetes and they represent a large burden to the public health sector. Burden of Diabetes Original image acquired in harsh conditions Enhanced image Type 1 diabetics represent about 5% of the diabetic population, while type 2 diabetes mellitus (T2DM) represents the grand majority with 90% to 95% of diabetics. The incidence and prevalence estimates were found to be highly heterogeneous. The global prevalence of both forms of diabetes mellitus (DM) combined varied approximately between 5% and 11% on average, between regions. A higher prevalence of DM among older populations and in urbanized areas was observed. A large proportion of people living with diabetes mellitus remains undiagnosed, especially in low and middle income countries. Evidence points to an increasing trend of T2DM among children and adolescents. In 2012, an estimated 1.5 million deaths were directly caused by diabetes (T1DM and T2DM combined), more than 80% of which occurred in low- and middle-income countries. Aetiology of diabetes: Type 1 diabetes has a strong genetic component, although other risk factors have been identified such as Enterovirus infection and Non-Hispanic White ethnicity. No difference in T1DM risk was observed by gender and the evidence regarding the association between physical activity and nutrition and T1DM has been inconsistent so far. Well established risk factors that are known to increase the risk of T2DM are family history of diabetes, increasing age, obesity, ethnicity and low socio-economic status. Healthy dietary patterns and all types of physical activity were found to be protective factors for T2DM, while unhealthy dietary patterns, sedentary time and smoking significantly increased the risk of T2DM. Among potential risk factors, depression, vitamin D status, and sleep disorders all increased significantly the risk of T2DM. Epidemiology of Complications from Diabetes Eye Light - Eye fundus colour images enhancement service for Diabetic Retinopathy diagnosis ( has received funding from the European Union s Horizon 2020 research and innovation programme under grant agreement No Guillaume Noyel,, has been coordinator of the project. An abstract and a poster were presented at the World Diabetes Conference 2015 of the International Diabetes Federation: (Noyel et al, 2015b). Other conference papers in image processing have been presented: (Noyel et al, 2015a, 2016). International Diabetes Federation. IDF Diabetes Atlas. International Diabetes Federation,, Noyel G, Jourlin M. Asplünd s metric defined in the logarithmic image processing (LIP) framework for colour and multivariate images. IEEE International Conference on Image Processing; Quebec City: IEEE; 2015a. p Noyel G, Jourlin M, editors. Spatio-colour Asplünd s metric and Logarithmic Image Processing for Colour Images (LIPC). CIARP XXI IberoAmerican Congress on Pattern Recognition; ; Lima, Peru. Noyel G, Jourlin M, Thomas R, Bhakta G, Crowder A, Owens D, et al. Contrast enhancement of eye fundus images. IDF 2015; Vancouver2015b. The main complications under review were acute complications hypoglycaemia and ketoacidosis and microvascular, long-term complications - neuropathy (nerve damage), retinopathy (eye damage) and nephropathy (kidney damage). Risk factors identified for hypoglycaemia were duration of diabetes (for T1DM) and older age and duration of insulin treatment (for T2DM). Diabetic ketoacidosis (DKA) is mostly seen in T1DM patients. In children, at T1DM diagnosis, the prevalence of DKA varies between 12.8% in Sweden and 80% in the United Arab Emirates. DKA at diagnosis of T2DM varies between 5% and 25%. Main causes of DKA recurrences are (usually preventable) insulin treatment interruptions. The risk of developing diabetic neuropathy and retinopathy (DR) increases with longer duration of diabetes. Diabetic peripheral neuropathy was generally more prevalent in T2DM than in T1DM patients. The prevalence of DR was estimated to be higher in T1DM than in T2DM patients (77.3% vs 25.2%). Diabetic nephropathy (DN) affects ~20-40% of diabetic patients. Microvascular long-term complications can be prevented and delayed through early detection and good glycaemic, blood tension and lipids control. Diabetes and Risk of Cancer The relative risks of diabetic patients compared to non-diabetics were two fold or higher for cancers of the endometrium, liver and pancreas. Prostate cancer appeared to be less present in diabetic men. Lung and thyroid cancer did not seem to be associated with 51

30 - International Prevention Research Institute Principal Contributions diabetes. Bladder cancer, breast cancer, colorectal, gallbladder and biliary tract cancer, gastric cancer, and renal cancer were more present in diabetics than in non-diabetics, but the evidence was inconclusive. Overall studies showed a substantial risk of bias and high heterogeneity among results, representing a major limitation in the interpretation of the results. Diabetes and Risk of Cardiovascular Disease Diabetes is an established risk factor for cardiovascular disease. For all outcomes considered (cardiovascular mortality, coronary heart disease and stroke), the risk associated with diabetes was approximately doubled in type 2 diabetic patients, and multiplied by eight in type 1 diabetic patients. The risk of cardiovascular diseases was more marked among women than among men, and also in younger subjects and in non-smokers. Diabetes and other disorders: Evidence indicated that patients with diabetes had a higher risk of an episode of acute pancreatitis, of tuberculosis, of dementia and of depression. Gestational Diabetes Mellitus Gestational diabetes mellitus is a condition in which women without previously diagnosed diabetes develop glucose intolerance and insulin resistance during pregnancy. It usually occurs in the third trimester of pregnancy, and disappears after the baby is delivered. Prevalence of GDM varied globally between ~2% and ~10% using older diagnostic criteria, and between ~10% and ~30% using recent diagnostic criteria. There are a series of non-modifiable risk factors which are associated with GDM: increasing gestational age, history of previous GDM, family history of DM, hypertension, history of macrosomic pregnancies, history of poor obstetric outcomes, increasing body height, as well as modifiable risk factors such as: overweight and obesity, weight gain during pregnancy and higher intake of fat. Gestational diabetes is associated with perinatal and neonatal complications such as macrosomia and preeclampsia. Women who had GDM have an increased risk of developing T2DM after delivery. However, results should be interpreted with care given the highly heterogeneous nature of the diagnostic criteria, both for gestational diabetes and for the complications. In addition, the variation in research protocols and in the gestational care among countries, and in time, limit even more the comparability and interpretation of studies of GDM. This White Paper on the state of the knowledge on the epidemiology of diabetes mellitus has provided up-to-date estimates of the current global burden of diabetes and its complications, has reviewed the evidence on the potential associations between diabetes and other diseases and identified areas where further research is still needed. Bota M, Pizot C, Koechlin A, Dragomir M, Macacu A, Franchi M, Valentini F, Coppens K, Noyel G, d Onofrio A and Boyle P. White paper. Epidemiology of diabetes. Technical Report 2015, International Prevention Research Institute, Lyon, France (2015) Diabetes Treatments and Cancer Risk While T1DM patients need lifelong insulin therapy, patients with T2DM advance in a progressive way, which usually starts from a prediabetic state characterised by hyperinsulinaemia to diabetes itself which is characterised by constant insulin resistance and a progressive reduction in insulin secretion. This results in an increase in disease severity, which is then followed by an increase in the use of hypoglycemic therapy. The selection of an appropriate decision on the type of therapy is under continuous discussion between patients and their doctors, based on risks and benefits specific to each patient. When diet and physical activity are no longer enough to control the hyperglycemia, patients need to start taking anti-diabetic medications (ADM), which are various and act at different levels of the glycemic pathway. In order to quantify and have an overview of the available data on the possible associations between the use of treatments for diabetes and a potential excess risk of cancer in diabetic patients, an online literature search was carried out in PubMed (January 1966-July 2015) for all meta-analyses and pooled analyses evaluating the association between diabetic treatments (metformin, sulfonylureas (SU), thiazolidinedione (TZD), incretins or insulin) and the risk of cancer. Complementary manual searches were done on the references of relevant publications. Metformin is often the therapy of choice for the first line treatment. Its primary mode of action is by re ducing hepatic glucose output, therefore reducing the blood levels of circulating glucose and insulin. Although the underlying mechanisms are not known, results from a growing number of observational studies suggest that metformin would reduce the risk of developing cancer. From Gandini et al (2014) 25 cohort studies, 16 case-control studies, 6 randomized trials 65,504 cases of cancer, 1,177,857 subjects SRR for cancer incidence: 0.69 (95% CI: 0.52, 0.90) SRR for cancer mortality: 0.66 (95% CI: 0.54, 0.81) SRR for cancer incidence from randomized clinical trials: 0.95 (95% CI: 0.69, 1.30) Metformin appears to reduce the risk of cancer, but this needs to be verified by randomized clinical trials Sulfonylureas are another type of therapy for diabetes; they act by stimulating beta cells of the pancreas to produce insulin. From Wu et al (2015) SRR all studies: 1.20 (95% CI: 1.13, 1.27) SRR RCT: 0.91 (95% CI: 0.81, 1.02) Among studies, results were very heterogeneous, and not conclusive Thiazolidinediones are an insulin-sensitising class of drugs; to date, two drugs from this class are available: pioglitazone and rosiglitazone. Some suspicion of an associated increased risk of bladder cancer has been raised by a number of population based studies. There is strong evidence for an association between Thiazolidinedione (TZD) use and risk of bladder cancer and more precisely for Pioglitazone use: From Bosetti et al (2013) 6,068 cases and 2,151,031 participants SRR for TZD: 1.13 (95% CI: 1.05, 1.23) SRR for Pioglitazone: 1.20 (95% CI: 1.07, 1.34) SRR for Rosiglitazone: 1.08 (95% CI: 0.95, 1.23) Regarding other cancer sites or all cancer combined, no association was found between TZD use and cancer risk. 53

31 - International Prevention Research Institute Principal Contributions The incretin based therapies act by improving glucose-dependent insulin secretion. Two types of drugs are available on the market: glucagon-like peptide 1 receptor agonists (GLP1 RA) and dipeptidyl-peptidase-4 inhibitors (DPP-4). The recent arrival on the market of these drugs makes it impossible to report their potential association with cancer. Consequently, data on this subject is scarce, conflicting and of poor quality. Further studies are need in order to establish causality between incretin based therapies and risk of cancer. Insulin is required by all T1DM patients and many of the late stages T2DM patients. It is available in a wide variety of formulations: long acting, medium acting, and short acting. Concerns for an increased risk of cancer among diabetic patients using insulin have been raised in the recent past. However, none of the concerns have been validated by epidemiological studies free of bias and confounding. Insulin therapy may increase the risk of several cancer compared with other antidiabetic medication: SRR for colorectal cancer: 1.69 (95% CI: 1.25, 227) (Bu et al, 2014) SRR for pancreatic cancer: 2.66 (95% CI: 2.07, 3.43) (Bosetti et al, 2014) SRR for hepatocellular cancer: 2.61 (95% CI: 1.46, 4.65) (Singh et al, 2013) SRR for lung cancer: 1.23 (95% CI: 1.10, 1.35) (Wu et al, 2014) SRR for all cancer: 1.21 (95% CI: 1.08, 1.36) (Wu et al, 2015) An increased risk was also suggested for stomach, kidney and respiratory cancers SRR for cancer incidence failed significance when the analyses were restricted to cohort studies or RCT hence there is a need of new studies (RCT and/or cohorts) to clarify the situation. reporting a change in FBG or HbA1c were considered eligible. Both studies not reporting a physical activity contrast between groups and those including differential co-interventions (e.g. diet, medication, etc.) between study groups were excluded. Mixed-effects random models were used to compute the change of FBG (mg/dl) and HbA1c (%) associated with an increase of 100 minutes of physical activity per week, allowing the inclusion of more than two exposure groups per study and therefore, accounting for inter- and intra- study variability. When possible, i.e. when convergence of the model was met, a random effect was employed on both intercept and slope of each study (random model); in the contrary case, a random effect on slope and a fixed-effect of intercept was computed (fixed intercept model). Heterogeneity across studies was assessed with the ratio of the standard error of fixed intercept and random models, reflecting the amount of heterogeneity explained by inter-study variability. Publication bias was evaluated by means of visual inspection of funnel plots and with the Macaskill test. Stratified analyses were carried out according to several population or intervention characteristics. Conjointly, meta-regressions were computed to test if these characteristics interacted significantly with changes in FBG and HbA1c associated with physical activity. Sensitivity analysis were performed according to publication year, study size, outcome data completeness and existence of a co-intervention, etc. A total of 125 independent studies were included in the meta-analysis. For FBG, based on 105 studies, an increase of 100 minutes of physical activity per week was associated with an average change of -2.75mg/dl of FBG (95%CI -3.96, -1.55) (see figure), with high heterogeneity (83.5%). When the analysis was restricted to type 2 diabetes and prediabetes subjects (56 studies), the average change in FBG was significantly higher, respectively mg/dl (95% CI: -7.42, -2.01). Bosetti C, Rosato V, Buniato D, Zambon A, La Vecchia C, Corrao G. Cancer risk for patients using thiazolidinediones for type 2 diabetes: a meta-analysis. Oncologist. 2013;18(2): Bosetti C, Rosato V, Li D, Silverman D, Petersen GM, Bracci PM, et al. Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium. Ann Oncol. 2014;25(10): Bu WJ, Song L, Zhao DY, Guo B, Liu J. Insulin therapy and the risk of colorectal cancer in patients with type 2 diabetes: a meta-analysis of observational studies. Br J Clin Pharmacol. 2014;78(2): Gandini S, Puntoni M, Heckman-Stoddard BM, Dunn BK, Ford L, DeCensi A, et al. Metformin and Cancer Risk and Mortality: A Systematic Review and Meta-analysis Taking into Account Biases and Confounders. Cancer Prev Res (Phila). 2014;7(9): Singh S, Singh PP, Singh AG, Murad MH, Sanchez W. Anti-diabetic medications and the risk of hepatocellular cancer: a systematic review and meta-analysis. Am J Gastroenterol. 2013;108(6):881-91; quiz 92. Wu L, Zhu J, Prokop LJ, Murad MH. Pharmacologic Therapy of Diabetes and Overall Cancer Risk and Mortality: A Meta-Analysis of 265 Studies. Sci Rep. 2015;5: Wu Y, Liu HB, Shi XF, Song Y. Conventional hypoglycaemic agents and the risk of lung cancer in patients with diabetes: a meta-analysis. PLoS One. 2014;9(6):e Based on 76 studies reporting data on HbA1c, each additional 100 minutes of physical activity per week were associated with an average change of -0.14% of HbA1c (95% CI: -0.18, -0.09) (see figure). High heterogeneity (73%) between studies was observed and the inspection of funnel plot and the Macaskill test suggested publication bias (p<0.001): smaller studies seemed to be published more often when reporting positive results. Similarly to FBG, when restricting the analysis on type 2 diabetes and prediabetes subjects (60 studies), the decrease in HbA1c was significantly higher, respectively-0.16% (95% CI: -0.21, -0.11). For both FBG and HbA1c, pooled estimates did not vary when the analysis was stratified by gender, study duration, age or BMI, and heterogeneity remained high in all sub-group analyses. Also, most sensitivity analyses did not alter the results; however, differences in pooled estimates were observed when stratifying by study size. Slightly higher decreases were observed in larger studies (>40 subjects) for FBG, and in smaller studies for HbA1c, but meta-regressions showed no statistically significant difference (see table). Diabetes and Physical Activity Cohort studies suggest a positive impact of physical activity in decreasing the risk of diabetes (Ekelund et al, 2012; Grontved et al, 2014; Laaksonen et al, 2005; Weinstein et al, 2004). Also, some intervention studies report decreases in main diabetes markers (fasting blood glucose and glycated haemoglobin) with increasing physical activity level (Balducci et al, 2010; Nishijima et al, 2007; Sigal et al, 2014). However, the roles of the type and intensity of physical activity remain unclear. The aim of this study was to quantitatively evaluate the role of physical activity on changes in fasting blood glucose (FBG) and glycated haemoglobin (HbA1c) in different populations, including people with type 2 diabetes and pre-diabetes. The associations between physical activity and decreases of FBG and HbA1c were independent of the type, duration or intensity of physical activity. Nevertheless, slightly larger reductions for both FBG and HbA1c were observed in interventions with supervised physical activity when compared to unsupervised interventions. This difference was however not statistically significant for FBG (p=0.20 test for interaction), while it was for HbA1c (p=0.01 test for interaction). The observation of a constant impact of physical activity on FBG and HbA1c irrespective of the type and intensity of the intervention increases prospects for prevention. For diabetics encountering several barriers to the practice of physical activity, these results are encouraging, suggesting that as long as the duration of physical activity is maintained, tailored interventions taking into account age, health condition and potential discomfort would still be proven effective. Increased physical activity should be, therefore, recommended strongly as an adjunct to any anti-diabetes therapy. A systematic literature search and quantitative meta-analysis was conducted and reported following PRISMA guidelines for metaanalyses of interventional studies. Randomized trials of physical activity interventions with more than 1 week of follow-up and 55

32 - International Prevention Research Institute Principal Contributions Forest plot of the association between physical activity and change in fasting blood glucose Forest plot of the association between physical activity and change in fasting blood glucose Study Almenning2015 Kerling2015 Kim2015 Mendham2015 Motahari Tabari2015 Vasconcellos2015 Vinetti2015 Zou2015 Arciero2014 Geliebter2014 Herzig2014 Kanaya2014 Mitranun2014 Sigal2014 Sousa2014 Fritz2013 Grieco2013 Trussardi Fayh2013 McCormack2013 Ortega2013 Racil2013 Venojarvi2013 Choi2012 Dobrosielski2012 Kim2012 Lee2012a Lee2012b Nordby2012 Oliveira2012 Snel2012 Straznicky2012 Sung2012 Andrews2011 Belli2011 Dhooge2011 Drapeau2011 Ferrer Garcia2011 Friedenreich2011 Kurban2011 Mason2011 Wu2011 Arikawa2010 Desch2010 Ibanez2010 Kadoglou2010a Kadoglou2010b Koo2010 Ku2010 Morton2010 Negri2010 Okada2010 Plotnikoff2010 Sartor2010 Wycherley2010 Yavari2010 Burtscher2009 Davis2009 Hordern2009 Shah2009 Shenoy2009 Brun2008 Davison2008 Gordon2008 Lambers2008 Sixt2008 Winnick2008 Wycherley2008 Zhang2008 Middlebrooke2006 Orr2006 Shaibi2006 Wagner2006 Weiss2006 Bjorgaas2005 Dunstan2005 Frank2005 Giannopoulou2005 ODonovan2005 Stewart2005 Thomas2005 Ross2004 Baldi2003 Castaneda2002 Janssen2002 Kang2002 Boudou2000 Dunstan1998 Dunstan1997 Torjesen1997 Raz1994 Vanninen1992 Huttunen1989 Verity1989 Ronnemaa1986 Wallberg1986 Landt1985 Campaigne1984 Besnier2015 Kacerovsky Bielesz2012 Lucotti2011 Praet2008 Ahmadizad2007 Lindgarde2007 DiPietro2006 Cauza2005a Mean FBG change Change with 95% CI 0.4 [ 0.1, 0.7 ] 0.0 [ 0.5, 0.5 ] 0.1 [ 0.4, 0.2 ] 0.2 [ 0.7, 0.3 ] 0.5 [ 1.3, 0.2 ] 0.3 [ 0.7, 0.0 ] 0.3 [ 0.9, 0.4 ] 0.4 [ 0.8, 0.1 ] 0.5 [ 0.7, 0.2 ] 0.3 [ 0.7, 0.1 ] 0.2 [ 0.7, 0.2 ] 0.5 [ 1.3, 0.2 ] 0.3 [ 1.3, 0.6 ] 0.0 [ 0.1, 0.2 ] 0.5 [ 1.2, 0.2 ] 0.0 [ 0.1, 0.2 ] 0.0 [ 0.3, 0.3 ] 0.1 [ 0.3, 0.5 ] 0.1 [ 0.3, 0.2 ] 0.1 [ 0.3, 0.1 ] 0.0 [ 0.4, 0.3 ] 0.1 [ 0.3, 0.5 ] 0.2 [ 0.6, 0.2 ] 0.0 [ 0.5, 0.4 ] 0.5 [ 0.9, 0.2 ] 0.5 [ 0.9, 0.0 ] 0.0 [ 0.1, 0.2 ] 0.0 [ 0.2, 0.2 ] 0.4 [ 1.1, 0.3 ] 1.2 [ 1.9, 0.5 ] 0.2 [ 0.6, 0.2 ] 0.5 [ 1.2, 0.2 ] 0.2 [ 0.1, 0.5 ] 0.3 [ 1.1, 0.4 ] 0.3 [ 1.2, 0.7 ] 0.2 [ 0.1, 0.5 ] 0.6 [ 1.2, 0.1 ] 0.0 [ 0.2, 0.2 ] 0.4 [ 1.1, 0.3 ] 0.0 [ 0.2, 0.1 ] 0.2 [ 0.1, 0.5 ] 0.3 [ 1.1, 0.6 ] 0.0 [ 0.2, 0.3 ] 0.1 [ 0.7, 0.5 ] 0.7 [ 1.2, 0.1 ] 0.9 [ 1.3, 0.5 ] 0.1 [ 0.1, 0.3 ] 0.0 [ 0.5, 0.4 ] 0.3 [ 1.1, 0.5 ] 0.5 [ 1.3, 0.2 ] 0.2 [ 0.3, 0.7 ] 0.0 [ 0.6, 0.7 ] 0.2 [ 0.9, 0.5 ] 0.7 [ 1.4, 0.0 ] 1.0 [ 1.5, 0.5 ] 0.1 [ 0.3, 0.5 ] 0.1 [ 0.5, 0.2 ] 0.0 [ 0.4, 0.4 ] 0.1 [ 0.3, 0.1 ] 2.1 [ 2.7, 1.4 ] 0.2 [ 1.2, 0.7 ] 0.2 [ 0.2, 0.5 ] 2.0 [ 2.6, 1.3 ] 0.8 [ 1.7, 0.1 ] 0.0 [ 0.4, 0.3 ] 0.1 [ 0.3, 0.4 ] 0.8 [ 1.5, 0.1 ] 0.7 [ 1.3, 0.0 ] 0.1 [ 1.0, 0.7 ] 0.1 [ 0.8, 0.9 ] 0.1 [ 0.4, 0.5 ] 0.2 [ 1.0, 0.6 ] 0.0 [ 0.2, 0.2 ] 0.5 [ 1.1, 0.0 ] 0.1 [ 0.8, 0.7 ] 0.0 [ 0.8, 0.7 ] 1.0 [ 1.4, 0.6 ] 0.2 [ 0.7, 0.2 ] 0.0 [ 0.2, 0.1 ] 0.2 [ 0.5, 0.1 ] 0.0 [ 0.2, 0.2 ] 0.3 [ 1.2, 0.5 ] 0.4 [ 1.2, 0.3 ] 0.0 [ 0.4, 0.3 ] 0.0 [ 0.3, 0.2 ] 0.0 [ 0.8, 0.8 ] 0.2 [ 1.0, 0.6 ] 1.5 [ 1.8, 1.1 ] 0.1 [ 0.2, 0.0 ] 0.5 [ 1.2, 0.2 ] 0.3 [ 0.9, 0.3 ] 0.2 [ 1.2, 0.7 ] 0.2 [ 1.0, 0.6 ] 0.4 [ 1.2, 0.4 ] 0.3 [ 1.1, 0.6 ] 0.1 [ 0.1, 0.4 ] 0.3 [ 1.3, 0.6 ] 0.1 [ 0.5, 0.3 ] 0.0 [ 0.8, 0.7 ] 0.7 [ 1.3, 0.1 ] 0.2 [ 0.8, 0.5 ] 0.0 [ 0.7, 0.6 ] 0.6 [ 1.1, 0.0 ] 0.0 [ 0.4, 0.4 ] 0.8 [ 1.6, 0.0 ] 0.28 [ 0.40, 0.15 ] Study Mendham2015 Natesan2015 Park2015 Tomas Carus2015 Vinetti2015 Zou2015 Kanaya2014 Mitranun2014 Sigal2014 Sousa2014 Fritz2013 Venojarvi2013 Choi2012 Dobrosielski2012 Gibbs2012 Nordby2012 Oliveira2012 Snel2012 Sung2012 Tunar2012 Andrews2011 Belli2011 D'hooge2011 Ferrer Garcia2011 Kurban2011 Church2010 Kadoglou2010a Kadoglou2010b Koo2010 Ku2010 Morton2010 Negri2010 Okada2010 Plotnikoff2010 Salem2010 Wycherley2010 Yavari2010 Arora2009 Hordern2009 Leehey2009 Loimaala2009 Shenoy2009 Brun2008 Cheung2008 KrouselWood2008 Lambers2008 Sixt2008 Tsang2008 Wycherley2008 Nishijima2007 Sigal2007 Middlebrooke2006 Wagner2006 Bjorgaas2005 Dunstan2005 Giannopoulou2005 Thomas2005 VanRooijen2004 Baldi2003 Cuff2003 Castaneda2002 Boudou2000 Dunstan1998 Raz1994 Vanninen1992 Huttunen1989 Verity1989 Ronnemaa1986 Wallberg1986 Landt1985 Campaigne1984 Besnier2015 Kacerovsky Bielesz2012 Lucotti2011 Praet2008 Cauza2005a Mean HbA1c change Change with 95% CI 0.2 [ 0.3, 0.0 ] 0.2 [ 0.3, 0.0 ] 0.2 [ 0.4, 0.0 ] 0.3 [ 0.4, 0.1 ] 0.2 [ 0.3, 0.0 ] 0.1 [ 0.2, 0.1 ] 0.1 [ 0.2, 0.1 ] 0.1 [ 0.4, 0.1 ] 0.0 [ 0.1, 0.1 ] 0.2 [ 0.4, 0.0 ] 0.0 [ 0.1, 0.0 ] 0.1 [ 0.2, 0.1 ] 0.1 [ 0.2, 0.1 ] 0.2 [ 0.3, 0.0 ] 0.2 [ 0.4, 0.0 ] 0.1 [ 0.2, 0.0 ] 0.1 [ 0.3, 0.1 ] 0.2 [ 0.4, 0.0 ] 0.2 [ 0.4, 0.0 ] 0.1 [ 0.3, 0.1 ] 0.0 [ 0.1, 0.1 ] 0.2 [ 0.4, 0.0 ] 0.1 [ 0.4, 0.1 ] 0.1 [ 0.3, 0.0 ] 0.2 [ 0.4, 0.0 ] 0.1 [ 0.3, 0.0 ] 0.2 [ 0.3, 0.1 ] 0.3 [ 0.4, 0.1 ] 0.0 [ 0.1, 0.0 ] 0.1 [ 0.3, 0.0 ] 0.1 [ 0.3, 0.1 ] 0.1 [ 0.3, 0.0 ] 0.2 [ 0.3, 0.0 ] 0.1 [ 0.3, 0.1 ] 0.3 [ 0.5, 0.2 ] 0.1 [ 0.3, 0.1 ] 0.3 [ 0.4, 0.1 ] 0.2 [ 0.5, 0.0 ] 0.1 [ 0.2, 0.1 ] 0.1 [ 0.3, 0.1 ] 0.2 [ 0.4, 0.0 ] 0.2 [ 0.4, 0.0 ] 0.1 [ 0.4, 0.1 ] 0.0 [ 0.2, 0.2 ] 0.1 [ 0.4, 0.1 ] 0.1 [ 0.4, 0.1 ] 0.0 [ 0.1, 0.1 ] 0.1 [ 0.3, 0.0 ] 0.2 [ 0.4, 0.0 ] 0.0 [ 0.1, 0.0 ] 0.3 [ 0.4, 0.2 ] 0.1 [ 0.3, 0.1 ] 0.1 [ 0.3, 0.1 ] 0.2 [ 0.4, 0.0 ] 0.1 [ 0.3, 0.1 ] 0.2 [ 0.4, 0.0 ] 0.0 [ 0.1, 0.1 ] 0.1 [ 0.3, 0.1 ] 0.1 [ 0.4, 0.1 ] 0.1 [ 0.2, 0.1 ] 0.2 [ 0.4, 0.0 ] 0.2 [ 0.4, 0.0 ] 0.1 [ 0.3, 0.1 ] 0.2 [ 0.4, 0.1 ] 0.2 [ 0.4, 0.0 ] 0.1 [ 0.3, 0.1 ] 0.1 [ 0.3, 0.1 ] 0.2 [ 0.4, 0.0 ] 0.1 [ 0.3, 0.1 ] 0.1 [ 0.4, 0.1 ] 0.2 [ 0.4, 0.1 ] 0.0 [ 0.2, 0.1 ] 0.1 [ 0.3, 0.1 ] 0.2 [ 0.4, 0.1 ] 0.1 [ 0.3, 0.1 ] 0.1 [ 0.4, 0.1 ] 0.14 [ 0.18, 0.09 ] Change in FBG(mg/dl) per 10 minutes per week of physical activity Change in HbA1c(%) per 100 minutes per week of physical activity 57

33 - International Prevention Research Institute Principal Contributions Changes in fasting blood glucose (FBG) and glycated haemoglobin (HbA1c) per 100 minutes of physical activity per week Change in FBG (mg/dl) Change in HbA1c (%) Analysis Nb. of studies (arms) Physical activity (per 100mn/week) (95% CI:) Nb. of studies (arms) Physical activity (per 100mn/week) (95% CI:) Main analysis 105 (257) (-3.96, -1.55) 76 (184) (-0.18, -0.09) Stratified analysis by : Gender: Men* 12 (30) (-1.24, 0.46) 10 (24) (-0.34, -0.04) Women* 25 (62) (-4.76, -0.19) 12 (29) (-0.08; -0.01) Both genders 69 (165) (-5.40, -1.70) 55 (131) (-0.20, -0.10) Study duration: <20 weeks 69 (169) (-4.56, -1.31) 50 (119) (-0.17, -0.07) >20 weeks* 36 (88) (-4.94, 0.78) 26 (65) (-0.22, -0.06) Age: Children* 12 (29) 0.36 (-0.79, 1.51) 7 (17) (-0.53, 0.07) Adults 93 (228) 3.05 (-4.44, -1.65) 69 (167) (-0.17, -0.09) BMI: Normal weight* 8 (17) (-8.40, 2.08) 5 (11) (-0.05; 0.05) Overweight 36 (89) (-5.08; -0.30) 23 (54) (-0.12; -0.03) Obese 56 (137) (-2.76, -0.54) 43 (105) (-0.21, -0.09) Patients type: All Diabetic and prediabetic 61 (143) (-7.29, -2.32) 67 (159) (-0.22, -0.12) T2DM and prediabetic 56 (133) (-7.42, -2.01) 60 (144) (-0.21, -0.11) T1DM* 5 (10) 1.36 (-0.66, 3.37) 7 (15) (-0.61, 0.24) Other* 44 (114) (-1.28, 0.70) 9 (25) (-0.09; -0.01) Physical activity type: Aerobic (AE)** 51 (122) (-4.28, -0.97) 28 (63) (-0.31; -0.13) Resistance(RT)* 20 (42) (-4.05, 1.58) 14 (30) (-0.28; 0.08) Combined AE and RT*** 14 (30) (-4.56, -0.53) 19 (39) (-0.32, -0.15) Walking** 16 (34) (-11.48; -0.36) 14 (34) (-0.30, -0.07) Other** 9 (18) (-13.88, -1.88) 8 (16) (-0.14, 0.07) Diabetes, Diabetes Treatments and Lung Cancer Risk Lung cancer is such a common disease that even a small, real increase in risk associated with diabetes would represent a significant problem for Public Health. The association between diabetes and a (higher) risk of developing lung cancer requires to be clarified. A series of meta-analyses were conducted to investigate associations with diabetes and diabetes treatments and lung cancer risk. A total of 37 risk estimates of lung cancer risk among diabetic patients are available from 35 studies. The Summary Relative Risk (SRR) from the meta-analysis of all studies was SRR=1.04 (95% CI: 0.96, 1.12). This indicates that there is no significant increase in risk of lung cancer among patients with diabetes compared to a comparable group without diabetes (see figure below). However, there was a great deal of heterogeneity indicating the potential impact of small studies on the overall result. Risk of lung cancer in patients with diabetes *Main model did not converge for both outcomes; results are presented for the same model, where the intercept was fixed ** Main model did not converge for HbA1c; results are presented for the same model, where the intercept was fixed *** Main model did not converge for FBG; results are presented for the same model, where the intercept was fixed Other: patients not reported as diabetic, e.g. healthy Other types of physical activity e.g. Tai chi, yoga, football, etc. Balducci S, Zanuso S, Nicolucci A, De Feo P, Cavallo S, Cardelli P, et al. Effect of an intensive exercise intervention strategy on modifiable cardiovascular risk factors in subjects with type 2 diabetes mellitus: a randomized controlled trial: the Italian Diabetes and Exercise Study (IDES). Arch Intern Med. 2010;170(20): Ekelund U, Palla L, Brage S, Franks PW, Peters T, Balkau B, et al. Physical activity reduces the risk of incident type 2 diabetes in general and in abdominally lean and obese men and women: the EPIC-InterAct Study. Diabetologia. 2012;55(7): Grontved A, Pan A, Mekary RA, Stampfer M, Willett WC, Manson JE, et al. Muscle-strengthening and conditioning activities and risk of type 2 diabetes: a prospective study in two cohorts of US women. PLoS Med. 2014;11(1):e Laaksonen DE, Lindstrom J, Lakka TA, Eriksson JG, Niskanen L, Wikstrom K, et al. Physical activity in the prevention of type 2 diabetes: the Finnish diabetes prevention study. Diabetes. 2005;54(1): Nishijima H, Satake K, Igarashi K, Morita N, Kanazawa N, Okita K. Effects of exercise in overweight Japanese with multiple cardiovascular risk factors. Med Sci Sports Exerc. 2007;39(6): Sigal RJ, Alberga AS, Goldfield GS, Prud homme D, Hadjiyannakis S, Gougeon R, et al. Effects of aerobic training, resistance training, or both on percentage body fat and cardiometabolic risk markers in obese adolescents: the healthy eating aerobic and resistance training in youth randomized clinical trial. JAMA Pediatr. 2014;168(11): Weinstein AR, Sesso HD, Lee IM, Cook NR, Manson JE, Buring JE, et al. Relationship of physical activity vs body mass index with type 2 diabetes in women. JAMA. 2004;292(10): Heterogeneity analyses revealed no significant difference between studies that adjusted for smoking status of participants (SRR = 0.98 (95% CI: 0.90, 1.06) based on 15 risk estimates) and studies that did not adjust for smoking (1.08 (95% CI: 0.95, 1.24)) based on 17 risk estimates). Similarly, geographical region where the studies were conducted had little impact on the summary relative risk. The SRR and 95% CI: were 1.02 (95% CI: 0.89, 1.18), 1.01 (95% CI: 0.88, 1.17) and 1.10 (95% CI: 0.93, 1.31) in North America, Europe and Asia, respectively (see table). 59

34 - International Prevention Research Institute Principal Contributions Stratified analyses according to smoking status and geographical region Risk of lung cancer in diabetic patients treated with non-glargine insulin (blue), insulin glargine (red) and all insulins combined (black) Number of estimates SRR 95% CI: I 2 All Studies (0.97, 1.12) 96% Studies adjusting for Smoking (0.90, 1.06) 70% Studies not adjusting for (0.97, 1.20) 98% smoking Studies conducted in North (0.89, 1.18) 59% America Studies conducted in Europe (0.89, 1.14) 95% Studies conducted in Asia (0.96, 1.27) 66% In total 15 risk estimates were found on the risk of lung cancer in insulin users; six for thiazolidinediones (TZDs) and nine for metformin (see table below). There was a borderline increased risk of lung cancer in insulin-treated diabetic patients as compared to other treated diabetic patients (SRR=1.16 (95% CI: 1.00, 1.36)). This increased risk was limited to non-glargine users: based on five risk estimates, the SRR was 1.37 (95% CI: 0.96, 1.94) with strong heterogeneity (I² = 81%). The risk of lung cancer in insulin glargine users was close to unity: SRR=1.04 (95% CI: 0.91, 1.19) based on ten studies (see figure). There was a statistically significant decreased risk of lung cancer in patients treated with TZD: SRR=0.67 (95% CI: 0.51, 0.87). However, as only six studies were found, more detailed analyses were not possible. From nine studies, there was no increased or decreased risk of lung cancer among metformin users. The summary relative risk was 0.91 (95% CI: 0.77, 1.06) with large heterogeneity (I² = 72%). Stratified analyses of lung cancer risk in diabetes patients according to treatment therapy Number of estimates SRR 95% CI: I 2 All Insulins: all studies (1.00, 1.36) 64% All Insulins: observational (0.98, 1.37) 69% Non-glargine insulins (0.96, 1.94) 81% Glargine: all studies (0.91, 1.19) 0% Glargine: observational (0.88, 1.18) 0% Thiazolidinediones (0.51, 0.87) 55% Metformin (0.77, 1.06) 72% In conclusion, the risk of lung cancer is not increased among patients with diabetes compared to non-diabetic subjects. Among diabetic patients, those prescribed with glargine did not have an increased risk of lung cancer although users of other insulins had a non-significant increased risk. Users of TZD had a decreased risk of lung cancer while there was no significant protection conferred by using metformin. Koechlin A, Boyle P. Diabetes, Diabetes Treatments, and Lung Cancer Risk. American Diabetes Association; New Orleans, United States of America 2016a. Koechlin A, Boyle P. Lung cancer risk, diabetes and diabetes treatments. American Society of Clinical ONcology; Chicago, United States of America 2016b. This work was selected for a poster presentation at the American Diabetes Association s (ADA) 76th Scientific sessions in June, 2016 (Koechlin et al, 2016a) and at the American Society of Clinical Oncology (ASCO) annual meeting (Koechlin et al, 2016b). 61

35 Africa - International Prevention Research Institute Principal Contributions Africa fatigue: the belief that Africa must help itself and that Africa is no longer a continent in need. The first is true, the second is false. Yes, Africa can, and is, helping itself, but Africa is still in need of international support and collaboration. Let us not take another wrong turn; let us continue to accompany Africa, especially in matters of public health. We do. 63

36 - International Prevention Research Institute Principal Contributions State of Oncology in Africa The State of Oncology in Africa 2015 is a unique report about cancer in Africa, written by health professionals working in Africa or international colleagues working closely with Africa. Overall, it paints a depressing and deplorable picture of the current situation. It demonstrates how too many patients do not seek, or cannot access, professional medical advice. Those who do, do so when the cancer is at an advanced stage when cure is no longer possible. Africa suffers from a lack of oncologists from all disciplines, oncology nurses and the other necessary health professionals and technicians to support their work. There is a lack of treatments and treatment centres. Most countries do not have any radiotherapy equipment or access to opioid drugs for palliative care and pain control. The situation is bound to get worse as the population grows and ages and cancer risk factors imported from highresource countries add to the local risk factors with infections still top of the list. CALL TO ACTION This is a Call to Action to African governments, foreign governments, ODA funders of health such as the World Bank and international NGOs to rise to the challenge of Cancer in Africa with specific, coordinated actions. The cancer situation in Africa is critical. Global Society cannot, once again, react too slowly to an African health crisis. Over the next decades, cancer will cause Africans to suffer and die in much greater numbers than today. Yet there is hope. Those professionals who do care for Africa s cancer patients are doing a magnificent job, frequently in desperate circumstances: they deserve our full respect and admiration. There is hope from the success of high-quality, sustainable collaborations but, unfortunately, it is not enough. Significantly, such extraordinary examples rely on international charitable donations rather than governmental funding or structural funds from official development assistance (ODA). There is a wide variety of statistics available regarding cancer in Africa although most are estimates. However, statistics are patients with the tears wiped away. It is bad to have cancer and worse to have cancer if you are poor and disconnected from the public health system. Radical solutions to improve the situation in Africa and other poor countries are urgently needed: the status quo is not an appropriate. New models are needed to cope with and improve this situation. It is impossible to avoid the conclusion that there is an urgent need for major increases in domestic public funding of cancer care, the recognition that cancer care should be part of ODA and better Private-Public Partnerships, involving a number of sources from different areas, to make the necessary progress with the briefest delay. These partnerships need the commitment of the wide span of industries involved in the technology for diagnosis and treatment. It needs the commitment and engagement of Governments and Non-Governmental Organisations to be effective. Effective will be measured against the Right of every patient with cancer to have the most appropriate treatment and care for their disease. The International Covenant on Economic Social and Cultural Rights (ICESCR) was voted by the United Nations General Assembly in 1966 and came into force in This multilateral treaty provides that State Parties to the Covenant recognize the right of everyone to the enjoyment of the highest attainable standard of physical and mental health. Article 12.2 contains important determinants of the right to health such as prevention and treatment of diseases essential for the enjoyment of the right. There are 164 parties to the treaty. Why has it not been effective in dealing with the cancer problem in Africa? Why has it not been invoked? It is essential to move from a passive position to an active voice. We can turn our heads and walk away from this situation (as we often do,) and betray all those dedicated clinicians, nurses and other personnel grasping with the overwhelming problem of cancer on the Continent. Or, we can do something. As with cancers everywhere, African cancers deserve to be prevented, to be treated, to be cured and to be palliated. If we do not do it now, starting immediately, it will be too late and Africa s cancer crisis will continue to spiral out of control. 1 The International Covenant on Economic Social and Cultural Rights (ICESCR) should be invoked as the basis for action. This multilateral treaty provides that State Parties to the Covenant recognize the right of everyone to the enjoyment of the highest attainable standard of physical and mental health. Article 12.2 contains important determinants of the right to health such as prevention and treatment of diseases essential for the enjoyment of the right. 2 There is a need to train more oncologists and health professionals in cancer care and provide the necessary infrastructure which is urgently needed to identify and treat patients. More general and specialist surgical capacity is critical as are concomitant enhancements in imaging and pathology. 3 The drugs and equipment necessary to treat patients with cancer must be made available. We need to deliver, install and maintain adequate numbers of resource appropriate Radiotherapy machines. It should be the right of cancer patients, no matter where they are to have access to the appropriate treatment of their disease. 4 Opioids must be available for controlling the pain of patients with terminal cancers (and other diseases). International Agencies should make this a priority activity and come to agreements with Governments of countries where these are not available. 5 Since half of cancer in Africa is currently caused by chronic infection, relevant infection control and vaccination programmes must be funded and implemented continent-wide. 6 Information and education campaigns to wipe out stigma and misinformation must be conceived and disseminated. 7 Making Universal Health Coverage globally available and strengthening health systems is critical for improving cancer care. This is also a critical area for the corporate and social responsibility agendas for the private industries including all trans-african corporations. 8 High quality cancer institutions, all over the world, should establish collaboration ventures with cancer centres and institutes in every African country, as well as with public health services. 9 Finally, international philanthropy is vital to help fund these efforts. 65

37 - International Prevention Research Institute Principal Contributions I don t want to leave you. Jovia Cancer is... Attacking Africa - Television Documentary Why would an internationally recognized epidemiology and biostatistics institute decide to produce a film? If it did choose to produce a film, wouldn t a film on its core competence make more sense? Wouldn t it be reasonable to produce, say, a series of interviews of specialists simply commenting on data analysis? Why would it step into the realm of advocacy? In late 2014 and throughout 2015, Peter Boyle, Cemil Alyanak and several experts and co-authors, were working on the State of Oncology in Africa Report. The data was irrefutable, Cancer in Africa was a clear and present danger that was being ignored by both international public health organizations, governments and aid agencies, and most African governments. But if the data was so clear, why wasn t more being done? The report, they felt, would speak to the urgency of the problem. It would make the case for developing appropriate prevention, treatment, care and palliation policies. How could one argue with these numbers: over half of African countries have no radiotherapy units and/or outlaw the use of opiodes to treat pain? But would the Report succeed in elevating the crisis to an emotionally committed level? Would they manage to incite policymakers to act swiftly? Plainly, would policymakers be sufficiently swayed by the data alone, to invest now in a disease that will peak in ten or twenty years? Thus came about the idea of a film that would, first and foremost, bring the suffering to the forefront. It would fearlessly shine a light on all that was missing from the fight against cancer in Africa. It would use interviews, images and data. It would not give anyone a pass, ensuring that the message was clear: Cancer is... Attacking Africa! But the film would not stop there. It would not allow itself to be cornered into darkness. It would also shine a bright light on the amazing efforts of medical professionals working tirelessly in clinics, hospitals and even in people s homes throughout Africa. It would show the efforts of an organization in Uganda dedicated to home-based care for the terminally ill. It would give us the tour of a Hospital in Kenya that dares to aspire to the standards of a developed country. It would take us to Senegal where despite inhumane conditions in some of the care facilities, the staff press on providing chemotherapy in tiny over-crowded rooms and radiotherapy with a single Cobalt unit which is more often broken than working. The result has been the film: Cancer is... Attacking Africa. It was entirely produced by faculty, senior research fellows, staff and consultants. The film was funded both by and by an unrestricted grant from Pfizer, Inc. who entirely respected their commitment to have zero influence on the film whatsoever. The film has been edited into two versions, a 22-minute synopsis and the full length 59-minute version. Starting in 2017 they will be shown widely on African television stations, on the internet and in congresses and on campuses worldwide. plans to produce future films to further leverage the data that overwhelming demonstrates that Global Public Health, though substantially funded, often lacks the aggressive and selfless policy-making that is our Human Right. The film was produced by Professor Peter Boyle and Dr. Cemil Alyanak, entirely filmed and edited by Alyanak and guided by the on-the-ground expertise of African cancer authority Professor Twalib Ngoma. See Cancer is... Attacking Africa, and other videos, at: Finally, without hesitation, the hero of the film is a young woman, Jovia, born and raised in Kampala, who alone, without parents, without a husband who had left her years back, burdened by the care of a daughter and a younger brother, had to face both the scourge of HIV/AIDS and cancer of the cervix. She was interviewed three weeks before she passed, weak and destitute, yet still full of the life and hope of a 29-year old. RIP Jovia. 67

38 - International Prevention Research Institute Principal Contributions Pathways of Care in Lung Cancer in Africa Lung cancer is the commonest cancer worldwide, and while most new lung cancer cases were reported in less developed regions (58%), low incidence rates were estimated for Africa (7.7 and 2.6 per 100,000 in men, and women, respectively) (Ferlay et al, 2015). These numbers are best guess estimates of the lung cancer situation in Africa, because very little accurate data is available from African countries. Most countries lack nationwide cancer registries, and have no reliable source of mortality data (Ferlay et al, 2015; Joubert et al, 2012). In most African settings, due to the low awareness of cancer, and the lack of, or inadequate screening services, patients are diagnosed with cancers at advanced stages of the disease, when therapeutic solutions, where available, are likely less effective (Nanguzgambo et al, 2011). In many cases they are not diagnosed at all. African regions have high prevalence of tuberculosis (WHO, 2016) and high prevalence of HIV (UNAIDS, 2016), both of which have been shown to increase the risk of lung cancer (Sigel et al, 2012; Yu et al, 2011). All of these elements lead to the hypothesis that lung cancer in Africa is an under-estimated problem, poised to escalate in the near future. In order to start developing a programme tackling the issues of lung cancer in Africa, a consultative two day meeting was held in Johannesburg, at the beginning of November 2016, to discuss components of a multi-country protocol, in Swaziland, Lesotho, Tanzania, Kenya and South Africa. Representatives presented the state of lung cancer in each country, and the common themes that emerged were: general lack of awareness (even among health-care workers), lack of oncology personnel and equipment, lack of data, delays in diagnosis as well as late stage diagnosis implying very poor survival outcomes for patients. The meeting identified key areas where a programme to progress lung cancer in Africa should focus: education, training and increasing awareness, data collection systems, earlier diagnosis. The program is in its infancy, with a grant application expected beginning The programme s main objective is to help advance the case of lung cancer in Africa, through several concerted steps. Clearly Identify Pathways of Lung Cancer Care Understanding Pathways of Care is a basic requirement which, once understood, can impact on determining where issues of Access could be optimally introduced to the process of care with optimal effect. This information is unknown at present and may well vary between countries, regions and cultural groups. It is essential information to have in order to build a programme. Investigate the Relationship Between Tuberculosis and Lung Cancer in High Risk Groups Tuberculosis and lung cancer share many symptoms and clinical signs (Fontenelle et al, 1970), and it is very likely that cases of lung cancer are misdiagnosed as tuberculosis (TB), at least initially. Through the use of a recently developed blood test for lung cancer (Jett et al, 2014; Lam et al, 2011), EarlyCDT-Lung, high risk patients or patients with suspected lung cancer, will benefit from earlier diagnosis. In addition, there is an important research question in evaluating the use of this test in the differential diagnosis of tuberculosis and lung cancer. Partnerships will be developed in order to engage relevant stakeholders and have their support and collaboration. Collaboration will be sought with research institutions, ministries, government-international partners, private sector, NGOs, and civil society. The scope of the programme is two-fold. On one hand, answer crucial questions about misdiagnosis of lung cancer due to TB, the pathways of care of lung cancer, and potential differential diagnosis of lung cancer and tuberculosis. On the other hand, move a step further towards progressing lung cancer in sub-saharan Africa, by increasing awareness of cancer in general, and of lung cancer in particular, educating health-care workers on signs and diagnosis of lung cancer, and achieving earlier diagnosis, which will in turn lead to improved survival. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN Int J Cancer. 2015;136(5):E Fontenelle LJ, Campbell D. Coexisting bronchogenic carcinoma and pulmonary tuberculosis. Ann Thorac Surg. 1970;9(5): Jett JR, Peek LJ, Fredericks L, Jewell W, Pingleton WW, Robertson JF. Audit of the autoantibody test, EarlyCDT(R)-lung, in 1600 patients: an evaluation of its performance in routine clinical practice. Lung Cancer. 2014;83(1):51-5. Joubert J, Rao C, Bradshaw D, Dorrington RE, Vos T, Lopez AD. Characteristics, availability and uses of vital registration and other mortality data sources in post-democracy South Africa. Glob Health Action. 2012;5:1-19. Lam S, Boyle P, Healey GF, Maddison P, Peek L, Murray A, et al. EarlyCDT-Lung: an immunobiomarker test as an aid to early detection of lung cancer. Cancer Prev Res (Phila). 2011;4(7): Nanguzgambo AB, Aubeelack K, von Groote-Bidlingmaier F, Hattingh SM, Louw M, Koegelenberg CF, et al. Radiologic features, staging, and operability of primary lung cancer in the Western cape, South Africa: a 1-year retrospective study. J Thorac Oncol. 2011;6(2): Sigel K, Wisnivesky J, Gordon K, Dubrow R, Justice A, Brown ST, et al. HIV as an independent risk factor for incident lung cancer. AIDS. 2012;26(8): UNAIDS. Fact sheet. Global HIV statistics WHO. Global tuberculosis report Yu YH, Liao CC, Hsu WH, Chen HJ, Liao WC, Muo CH, et al. Increased lung cancer risk among patients with pulmonary tuberculosis: a population cohort study. J Thorac Oncol. 2011;6(1):32-7. Strengthen Hospital-Based Registries Hospital-based registries have direct access to key clinical information such as disease stage, pathology, treatment and follow-up information to calculate survival. Some regions/countries already have started implementing cancer registries, while others would welcome the opportunity to do so. An important part of the programme will focus on strengthening those registries already in place and on starting up new registries where there are none. Achieve Earlier Diagnosis Having earlier diagnosis, and gradually down-staging lung cancer cases (e.g. no longer diagnosing a cancer at stage IV, but at stage III) would be an important step towards improving lung cancer outcomes for African patients. In order to achieve earlier diagnosis, there is a need for education, training, and raising awareness. Part of the project will focus on education and training of healthcare workers and community workers on signs and symptoms of lung cancer, as well as lung cancer care and support. Awareness of cancer in general, and of lung cancer in particular, at the community level would be increased through the use of tailored messages, which would be previously adapted and validated in the communities for which they are intended. 69

39 - International Prevention Research Institute Principal Contributions Education and Training Programmes: A New Initiative Development of learning resources for partnership with a consortium of Universities Since its inception has been committed to developing appropriate education and training programmes for low and middle income countries (LMIC). An early initiative established a summer school ( ) for Public Health and Epidemiology in collaboration with the University of Dundee (Course directors Prof. Peter Boyle, Prof Irene Leigh VP Dundee and Prof Margaret Smith Dean of Nursing). This was very successful: many students were sponsored to attend and over 100 applicants wished to attend the third course. Subsequently a Dundee University on-line learning Master s programme in Global Health was launched in 2012, which enrolled some alumni from summer schools and has grown in strength since that time (through the School of Nursing, which also graduates nurses around the world via an on-line and blended learning undergraduate degree). Additionally the Strathclyde institute of Global Public Health has been launched (co Director Sir Harry Burns, previous CMO Scotland), with the intention of initiating Master s programmes including appropriate technology for bioengineering and to perform research in epidemiology and public health policy. Masters programmes in the UK welcome students from LMIC but extremely high international fees make this route available to the few candidates from LMIC who can obtain international sponsorship. There is a need to develop in-country educational resources and programmes, which can be made available to a consortium of Universities, who both accredit the programme and provide in-country learning facilities. With the development of. Africa and other international partnerships, the academic infrastructure of makes possible an integrated framework for such programmatic approaches. Therefore, existing educational material for modules on biostatistics and epidemiology will be converted into an on-line learning resource. This is enabled by a fellowship from the British Association of Dermatologists to for Prof Irene Leigh to coordinate this project. Other modules, which follow, could include modules on Public Health, Infectious Diseases and Non-Communicable Diseases. This project has been greeted enthusiastically by both staff and potential educational collaborators. As Prof. Irene Leigh is a dermatologist, some of the Fellowship will be concerned with Skin cancer in Africa (see chapter on Skin cancer in publication The State of Oncology in Africa ). Skin cancers are a huge and increasing health burden globally equal to the total of all other cancers combined, and they are associated with substantial morbidity, mortality and costs to healthcare providers. Although predominantly in Western populations, this appears to be a problem also in Sub-Saharan Africa particularly in genetically predisposed patients such as those suffering from albinism, xeroderma pigmentosum or those with HIV. There is little information concerning the size of this problem. Irene will spend some of her Fellowship time at the Regional Dermatology Training School on Moshi, North Tanzania, where a centre for the care for local albinos has been in place for many years. She will also develop on line learning resources for Dermatology in Africa and investigate the possibilities of new research activity in Moshi. She will also be seeking support for a World Skin Cancer Report. is committed to developing education and training programmes. 71

40 - International Prevention Research Institute Principal Contributions UV and Skin Cancer Prevention of Ultraviolet (UV) exposure and skin cancer is an important activity of. Between 2015/2016, several research activities were conducted on primary, secondary and tertiary prevention of skin cancer. Those regarding secondary prevention of skin cancer are reported in a broader chapter on cancer screening (See the Cancer Chapter). The activities on primary prevention focused on the application of knowledge and competence acquired at on the assessment of population UV exposure through the success of the European project Eurosun conducted between 2010 and From this project, methods were developed for estimating, from satellite images, ground exposure to UV radiation and individual chronic exposure to UV (see figure below). Map of the daily average UV irradiation (in J/ cm2) in Europe for the month of June, averaged over the period From this expertise, new projects were conducted on UV exposure and risk of non-skin diseases. For instance, another project, UVPro, focused on occupational UV exposure in France. Past studies conducted by senior researchers have suggested there was sufficient evidence to consider sunbed use to increase the risk of cutaneous melanoma (Boniol et al, 2012). The exposure to this risk factor fits particularly well with the role of intense UV exposure in childhood for the initiation of melanoma in adulthood. Between 2015/2016, original studies were conducted to better understand the aetiology of cutaneous melanoma, and more particularly the risk factors associated with melanoma mortality. Lastly, research activities were conducted on new candidate factors to be considered as melanoma prognostic factors such as UV exposure, vitamin D level and nevi count. Safe tanning is simply a myth. UV exposure and risk of non-skin disease Ocular Disease From a collaboration between Cecile Delcourt (University of Bordeaux, France) and Mathieu Boniol (, Lyon), a study on the association between residential ultraviolet exposure and risk of cataract and age-related macular degeneration (AMD) was conducted within the Alienor Study (Delcourt 73

41 - International Prevention Research Institute Principal Contributions et al., 2014). The Alienor Study was a population-based study of 963 residents of Bordeaux (France), aged 73 years or older, who underwent an eye examination, including intraocular pressure (IOP), central corneal thickness (CCT), and biomechanical properties of the cornea measurements using the Ocular Response Analyser. Early and late AMD was classified from retinal colour photographs. Cataract extraction was defined as absence of the natural lens at slit-lamp. Individual residential UV exposure was estimated from Eurosun satellite data. This study showed that highly exposed subjects (higher quartile of ambient UV) were at increased risk for cataract extraction (odds ratio [OR]=1.53 (95% confidence interval [CI]: 1.04, 2.26); P = 0.03) and of early AMD (OR=1.59 (95% CI: 1.04, 2.44); P = 0.03), compared to subjects in the intermediate quartiles. Mean corneal hysteresis (CH), corneal resistance factor (CRF), and CCT were 9.4 ± 1.9, 9.8 ± 1.9 mm Hg, and ± 36.8 μm, respectively (Schweitzer et al, 2016). In the multivariate analysis, CH and CRF values were significantly lower in subjects having higher ambient UV exposure (-0.50 (95% CI: -0.88, -0.12)); P < 0.01; and (95% CI: -0.78, -0.13); P < 0.05, respectively). Central corneal thickness was not significantly associated with ambient UV exposure. This study further confirmed the increased risk for cataract extraction in subjects exposed to high ambient UVR and also suggested a risk of early AMD; encouraging the use of UV exposure information when assessing progression of ocular diseases. It also showed that biomechanical properties of the cornea were modified by metabolic and lifetime environmental factors, especially UV exposure. However, the process through which these factors may influence onset and progression of ocular diseases or IOP measurements needs further investigation. Haematological Malignancies A consortium of three institutes coordinated by Jean-Francois Doré (Inserm, Lyon), Jacqueline Clavel (Inserm, Paris) and Mathieu Boniol (, Lyon) joined their expertise in an ANSES funded project named HelmeUV investigating the role of UV radiation exposure and risk of childhood haematological malignancies (CHM) in France (Coste et al, 2015). These studies suggested that higher residential UV exposure may be positively associated with a higher incidence of PBC-ALL in early childhood independently of known and suspected risk factors. The critical time window of exposure could also be prenatal and further investigations are required. ELFE Cohort A childhood cohort of 18,000 children recruited in a representative sample and followed from birth to adulthood (current age: 5 years) is currently ongoing in France. The study involved research projects since its inception; and is participating in the assessment of individual UV exposure of children at different time during the follow-up. Methodology was developed to link individual place of residence and main holidays locations to Eurosun database; in addition, different metrics of sun exposure were constructed from past experience in conducting observational studies on UV exposure. The study is currently ongoing and data analysis will be possible in the coming years. Several markers could be investigated: early UV exposure and impact on children development, on allergies, on infectious disease, or on early biomarkers of cancer such as nevi development. Occupational UV Exposure Outdoor workers are potentially at risk of high UV exposures during their occupations both as the cumulative amount of UV received and by the intensity of exposures. Some countries, such as Germany, have recently considered occupational outdoor jobs as eligible for compensation in case of UV related diseases caused by such activities. A European directive was prepared to promote the legal framework for increasing protections of outdoor workers from UV exposures. However, only scarce data exists on UV exposure assessments and these come from measurements conducted in highly selected group of workers such as shipmen. Very few studies actually exist on broader, population-based, estimation of occupational exposure to UV, and aside of expert opinions, no study ever evaluated who can be considered as exposed outdoor. This project conducted two complementary investigations, one ecological linking Eurosun UV data to the French National Registry of Childhood Haematological Malignancies, and the other observational by including individual UV exposure to ESCALE and ESTELLE studies, two nationwide case-control studies conducted in and , respectively. Residential UV exposures at diagnosis were estimated using the Eurosun database by linkage to one of the 36,326 Communes with mainland France. The annual daily average UV exposure of the children ranged from 85.5 to J/cm2. The French national registry identified 9,082 cases of acute leukaemia and 3,563 cases of lymphoma diagnosed before the age of 15 years from 1990 to The incidence of CHM was calculated by Commune, year, age and gender and expressed as the standardized incidence ratio (SIR). UV data from 1988 to 2007 were extracted from the Eurosun database. For each additional 25 J/ cm2 of UV exposure, there was a significant increase in precursor B-cell acute lymphoblastic leukaemia (PBC-ALL) in children of less than 5 years old (SIR 1.18 (95% CI: 1.10, 1.27)). Further analysis of PBC-ALL in young children suggested a better fit of models with a threshold, with the risk increasing above 100 J/cm2, for which the SIR was 1.24 (95% CI: 1.14, 1.36) for a 25 J/cm2 increase. The results remained stable when analyses were stratified by deprivation index or degree of urbanization of the Communes. When analysing the association between CHM and UV exposure in the two case-control studies, and adjusting for confounding factors (breastfeeding, birth order, early infections, day-care, parental use of home pesticides during pregnancy, pre-conception paternal smoking, exposure to road traffic, to garage and petrol stations), residential exposure to UV was associated with PBC-ALL (OR=1.30 (1.16, 1.45)) for the 3 highest deciles of exposure (UV>105.5 J/cm²) compared to the others (UV J/cm²), which was similar to the ecological association. 75

42 - International Prevention Research Institute Principal Contributions The UVPro project was an ANSES funded project coordinated by four institutions represented by David Vernez (IST Lausanne), Jean-Francois Doré (Inserm, Lyon), Jean-Luc Bulliard (University Hospital, Lausanne) and Mathieu Boniol (, Lyon). The aim of this project was to investigate the level of UV exposure of outdoor workers in France and estimate their level of exposure accounting for postures adopted in different occupations. Occupational UV Exposure in French Outdoor Workers The first part of UVPro consisted in evaluating the jobs that could be considered as exposed to occupational UV in France. A random survey was conducted in 2012 in individuals aged 25 to 69 years for which the median daily standard erythemal UV dose (SED) was estimated from exposure time and place and matched to Eurosun satellite UV data. A total of 889 individuals were exposed to solar UV with highest doses observed among gardeners (1.19 SED), construction workers (1.13 SED), agricultural workers (0.95 SED), and culture/art/social science workers (0.92 SED). Information and communication technology, industry, and transport workers were highly exposed (>0.70 SED). Significant factors associated with high occupational UV exposure were sex (P < ), phototype (P = ), and taking lunch outdoors (P < ). This study established a ranking of occupations, including unexpected occupations, according to various classifications (ISCO, ISIC and grouping of jobs under broader categories) that could be used to estimate the burden of occupational exposure in France and be reproduced in other countries (Boniol et al, 2015b). The yearly median exposure of the outdoor worker population ranged from 77 kj/m2 to 116 kj/m2, and road workers, building workers, and gardeners were the most exposed. This whole project developed the necessary tools and demonstrated the possibility to evaluate the level of occupational UV exposure as well as their distribution by anatomical body part in a broader population. Melanoma aetiology Sunbed Use as an Additive Risk of Melanoma Sunbed use is a risk factor for cutaneous melanoma (Boniol et al, 2012), and their use were classified as carcinogenic to humans by the International Agency for Research on Cancer. researchers were involved between 2015 and 2016 in several scientific publications that were used to confirm the opinion of major health agencies. The task of getting a clear opinion is more and more impaired by intrusive and delusive activities of the indoor tanning industry (Autier et al, 2011). General Model to Predict Individual Exposure to Solar UV Measured daily ambient doses over the year 2012 In parallel of the estimation of occupational UV exposure at a population level, specific modelling was developed with a 3D numeric model (SimUVEx) to compute UV exposure ratios (ER) for various body sites and postures (Vernez et al, 2015a) (see figure). From the 3D numeric model, a regression was developed to define ER predictors and showed good agreement with simulated data (r2=0.988). In addition, relative errors were relatively small from +20% to -10% in daily doses predictions, and on average only 2.4% (-0.03% to 5.4%) in yearly dose predictions. These ER will be very helpful for future research to estimate anatomical exposure of outdoor workers based only on ambient UV data and postural cadastre. Anatomical UV Exposure in French Outdoor Workers Among gaps in knowledge, some authors argued that the risk of melanoma associated with sunbed use was restricted to skin sensitive population and that sunbeds could be safely used by the majority of the population. This statement is in theory not plausible from previously published observational studies which already adjusted for skin sensitivity. Nevertheless, the publication of a reanalysis of a large case-control study in USA closed this debate (Vogel et al, 2014). This study provided another demonstration that the risk associated with sunbed use was not limited to skin-sensitive populations; it also showed increased risk even in those not having experienced sunburns in their lifetimes. In addition, we further re-analysed the reported risk estimates and further proposed that the risk of melanoma associated with sunbed use could act in an additive relationship rather than the classical multiplicative model (Boniol et al, 2015a). As a consequence, the overall population impact of sunbed use could be even greater than anticipated. By combining both approaches estimation of UV exposure at population level, and modelling of anatomical estimation of UV exposure based on ambient UV anatomical exposure was assessed (Vernez et al, 2015b). 77

43 - International Prevention Research Institute Principal Contributions Changing Mortality as a Marker of Change in Melanoma Aetiology To better understand the aetiology of cutaneous melanoma, a study was conducted on long time-trends of cutaneous melanoma mortality by major countries throughout the globe (Autier et al, 2015). Using the World Health Organisation (WHO) mortality database, age-period-cohort models were fitted for seven regions with lightskinned populations. The analysis showed that cohort effects better explained changes in melanoma mortality over time than period effects with an increased risk in successive generations from 1875 until a peak year. Peak years were for subjects born in in Oceania, in North America, in Northern Europe, in the United Kingdom (UK) and Ireland, 1948 in Western Europe and 1957 in Central Europe (see figure). After peak years, lifetime risk of melanoma death gradually decreased in successive generations and risks of subjects born in were back to risk levels observed for subjects born before In Southern Europe, birth years with highest lifetime risk of melanoma death have not yet been attained. As time passes, melanoma deaths will steadily rarefy in younger age groups and concentrate in older age groups, and ptentially fade away after Cumulative lifetime risk of melanoma death in regions according to year of birth relative to the risk in men and women born around 1935 Independently from screening or treatment, over next decades, death from melanoma is likely to become an increasingly rare event. The temporary epidemic of fatal melanoma was most probably due to excessive UV-exposure of children that prevailed in , and mortality decreases would be due to progressive reductions in UV-exposure of children over the last decades. Prognostic factors of melanoma The search for new prognostic factors of melanoma remains an important research topic with increasing questions on the potential role of Vitamin D supplementation of melanoma patients. Without clear evidence of any beneficial impact of vitamin D supplement use in melanoma patient, this appears as a more and more frequent practice and even becomes a standard in some countries (NICE, 2015). Our research evaluated association between sun exposure, vitamin D level and other phenotypic markers as prognostic factors of cutaneous melanoma. A simple question is whether UV exposure is a potential prognostic factor. Most guidelines recommend to dermatologists to encourage decrease exposure to UV of melanoma patients. This recommendation is pragmatically justified by the increased risk of secondary melanoma following the diagnosis of a primary tumour. But this practice has never received a systematic scientific evaluation. With raising concerns on vitamin deficiencies, some melanoma patients receive a vitamin D supplementation to compensate for their supposed decreased sun exposure, should they follow dermatologist s recommendations. First 25(OH)D3 measurements performed within 180 days after diagnosis on melanoma patients participating to MelanCohort A) before and B) after standardization on age, sex, body mass index, and month of blood sampling. The line corresponds to the Loess curve (locally weighted scatterplot smoothing) fitted to 25(OH)D3 measurements and date of blood sampling, and the corresponding 95% confidence limits. This Loess curve was estimated for display purpose only. UV exposure Eurosun s UV data were linked by Cristina Fortes (Istituto Dermopatico dell Immacolata, IDI, Rome, Italy) and Mathieu Boniol (, Lyon) to the hospital registry of cutaneous melanoma of IDI Rome. With data from 972 primary cutaneous melanoma cases, prognostic factor of UV exposure was assessed (Fortes et al, 2016). First, no protective effect was found for UVB or individual sun exposure variables on melanoma mortality. However, an increased risk of mortality was found among patients with cutaneous melanoma located on the lower limbs and in the highest decile of UVB exposure ( J/cm) after controlling for sex, age and Breslow thickness (relative risk: 4.78 (95% confidence interval: 1.30, 17.5)). The increased risk of mortality for the highest decile of UVB was also confirmed in the subsample after controlling for sex, age, education, use of sun lamps, pigmentary characteristics and diet. These results suggested no protective effect of sun exposure for melanoma mortality but suggested increased risks for melanomas located on the lower limbs. Studies on UV exposure before and after diagnosis do not yet allow to derive a firm conclusion on the positive or negative role of sun exposure on melanoma prognosis. Further studies, in particular randomised trials, would be required to conclude on the need to maintain or reduce sun exposure after the diagnosis of cutaneous melanoma. 79

44 - International Prevention Research Institute Principal Contributions Vitamin D From initially published studies and research hypothesis, it was suggested that a low level of circulating vitamin D at diagnosis could be associated with a low prognosis of melanoma. To better understand the potential role of vitamin D level of melanoma patients, a collaboration was developed between Philippe Saiag (Université de Versailles St-Quentin, Boulogne-Billancourt, France) and Mathieu Boniol (, Lyon) and resulted in a research project funded by the French National Agency on Cancer (INCA). Prognostic value of 25-hydroxyvitamin D3 levels at diagnosis was assessed in 1,171 melanoma patients locate in Paris area and followed prospectively (Saiag et al, 2015) (see figure). While 25(OH)D3 levels at diagnosis were inversely correlated with prognostic factors such as AJCC stage (P <.001 Kruskal-Wallis), Breslow s thickness (P <.001 Spearman correlation), and ulceration (P <.001 Kruskal-Wallis), these were not associated with the risk of relapse. However, changes in 25(OH)D3 levels during follow-up were associated with worse prognosis: With a third quartile Q3 of average change per year (-0.30 to 4.60 nmol/l/y) used as reference, hazard ratios for the first, second, and fourth quarters were 1.94 (95% confidence interval [CI]: 1.36, 2.76), 1.23 (95% CI: 0.85, 1.78), and 1.61 (95% CI: 1.14, 2.28), respectively. Autier P, Koechlin A, Boniol M. The forthcoming inexorable decline of cutaneous melanoma mortality in light-skinned populations. Eur J Cancer. 2015;51(7): Autier P, Doré JF, Breitbart E, Greinert R, Pasterk M, Boniol M. The indoor tanning industry s double game. The Lancet. 2011;377(9774): Boniol M, Autier P, Boyle P, Gandini S. Cutaneous melanoma attributable to sunbed use: systematic review and meta-analysis. BMJ. 2012;345:e4757. Boniol M, Dore JF, Greinert R, Gandini S, Cesarini JP, Securite S, et al. Re: Exposure to indoor tanning without burning and melanoma risk by sunburn history. J Natl Cancer Inst. 2015a;107(5):djv102-djv02. Boniol M, Koechlin A, Boniol M, Valentini F, Chignol MC, Dore JF, et al. Occupational UV exposure in French outdoor workers. J Occup Environ Med. 2015b;57(3): Coste A, Goujon S, Boniol M, Marquant F, Faure L, Dore JF, et al. Residential exposure to solar ultraviolet radiation and incidence of childhood hematological malignancies in France. Cancer Causes Control. 2015;26(9): Delcourt C, Cougnard-Gregoire A, Boniol M, Carriere I, Dore JF, Delyfer MN, et al. Lifetime exposure to ambient ultraviolet radiation and the risk for cataract extraction and age-related macular degeneration: the Alienor Study. Invest Ophthalmol Vis Sci. 2014;55(11): Fortes C, Mastroeni S, Bonamigo R, Mannooranparampil T, Marino C, Michelozzi P, et al. Can ultraviolet radiation act as a survival enhancer for cutaneous melanoma? Eur J Cancer Prev. 2016;25(1): Newton-Bishop JA, Beswick S, Randerson-Moor J, Chang YM, Affleck P, Elliott F, et al. Serum 25-hydroxyvitamin D3 levels are associated with breslow thickness at presentation and survival from melanoma. J Clin Oncol. 2009;27(32): NICE. Melanoma: assessment and management Saiag P, Aegerter P, Vitoux D, Lebbe C, Wolkenstein P, Dupin N, et al. Prognostic Value of 25-hydroxyvitamin D3 Levels at Diagnosis and During Follow-up in Melanoma Patients. J Natl Cancer Inst. 2015;107(12):djv264. Schweitzer C, Korobelnik JF, Boniol M, Cougnard-Gregoire A, Le Goff M, Malet F, et al. Associations of Biomechanical Properties of the Cornea With Environmental and Metabolic Factors in an Elderly Population: The ALIENOR Study. Invest Ophthalmol Vis Sci. 2016;57(4): Vernez D, Milon A, Vuilleumier L, Bulliard JL, Koechlin A, Boniol M, et al. A general model to predict individual exposure to solar UV by using ambient irradiance data. J Expo Sci Environ Epidemiol. 2015a;25(1): Vernez D, Koechlin A, Milon A, Boniol M, Valentini F, Chignol MC, et al. Anatomical UV Exposure in French Outdoor Workers. J Occup Environ Med. 2015b;57(11): Vogel RI, Ahmed RL, Nelson HH, Berwick M, Weinstock MA, Lazovich D. Exposure to indoor tanning without burning and melanoma risk by sunburn history. J Natl Cancer Inst. 2014;106(7). Figure 5: Hazard ratio (HR) of risk of relapse by yearly trend in 25(OH)D3 during follow-up of melanoma patients participating to MelanCohort adjusting on age, sex, body mass index, American Joint Committee on Cancer stage, and baseline 25(OH)D3 level. The reference category is -0.5 to 0.5 nmol/l/year. Gray vertical lines correspond to quartile of the distribution of the yearly trend in 25(OH)D3. CI = confidence interval. This study showed that, contrary to published data from Newton-Bishop (Newton-Bishop et al, 2009), 25(OH)D3 level as diagnosis was not an independent prognostic factor of melanoma as long as the statistical analysis of data properly accounted for major prognostic factors, in particular Breslow s thickness (see figure). In addition, this study showed that variation of 25(OH)D3 during follow-up was an independent melanoma prognostic marker. Further studies should investigate how much other modulators of 25(OH)D3 levels, such as inflammation, could explain such association. 81

45 - International Prevention Research Institute Principal Contributions Health and Conflict Health in Conflict and Post-Conflict Environments The preservation of Health during conflict and preparing and implementing post-conflict Public Health is a major and neglected challenge for global public health. Particularly in the case of the latter (the transition from violence to security, stability and, eventually, legitimate functioning government), is not simply a matter of economic and fiscal policy, and donor support. It requires radically different, contextually sensitive understanding of the political economy of health in conflict, the bio-political aspects of health and deep knowledge of how any particular conflict effects the socio-cultural dynamics of populations from refugees, to internally displaced people and those remaining in the conflict environment, as well as host and neighbouring countries. The International Prevention Research Institute, The Strathclyde Institute of Global Public Health@i-PRI and the World Prevention Alliance, have developed a programme of activities in this area with their partners from the Conflict and Health Research Group, King s Centre for Global Health, King s College London and the Department of Bioengineering at the University of Strathclyde in Glasgow, Scotland. Led by Richard Sullivan (King s College London) this collaboration brings high-level expertise in a number of key domains to focus on this under-researched are of global health. The following sections outline recent work to give a clearer idea of what such collaborations are capable of doing. Battlefield Medicine The link between military and civilian medicine has deep historical roots (Chatfield-Ball et al, 2015). In high-income countries each successive conflict that the military engages in affords the opportunity to contribute improvements in trauma care, many of which are translated into civilian healthcare systems. The wars of the last decade in Iraq and Afghanistan have changed the nature of injuries seen on the battlefield leading to further trauma management innovation. Lessons learned in these hostile environments have guided many developments in trauma care in high-income countries resulting in improved casualty outcomes and a lower mortality rate; an objective shared by the civilian and military trauma doctrine. On the other hand, trauma management is a neglected epidemic in low- and middle-income countries, both in civilian and conflict settings. Trauma is responsible for more global deaths annually than HIV, malaria and tuberculosis combined, but receives a fraction of the attention and funding. Death from accidental or non-accidental injury has fast become the leading cause of death in young people in low middle-income countries. 83

46 - International Prevention Research Institute Principal Contributions One of the greatest challenges to implementing any sort of trauma intervention in a resource-poor setting is the inadequacies in the health system in which it is set. Weak health systems and poor public funding test both the feasibility and the sustainability of trauma care development. With trauma constituting such a significant portion of mortality and economic impact, and with many simple cost-effective solutions being pioneered in the military setting in high-income countries, this area should be one of the most active research areas for cost-effective health investment and knowledge transfer. The battlefield has been a key area for innovations in trauma care and throughout the great wars of the last two centuries, military and civilian trauma care have evolved synergistically. According to the Global Burden of Disease, trauma is now responsible for five million deaths each year. High-income countries have made great strides in reducing trauma related mortality figures but low middle-income countries have been left behind with high traumarelated fatality rates, primarily in the younger population. Much of the progress high-income countries have made in managing trauma rests on advances developed in their armed forces. This analysis looks at the recent advances in high-income military trauma systems and the potential transferability of those developments to the civilian health systems particularly in low middle-income countries. It also evaluates some potential lifesaving trauma management techniques, proven effective in the military, and the barriers preventing these from being implemented in civilian settings. (Chatfield-Ball et al, 2015). Explosive Remnants of War During the Great War of , an estimated one tonne of explosives was fired for every square metre of territory on the Western front and clearance continued for decades after the conflict ended (Connolly, 1998). In the Ypres Salient, an estimated 300 million projectiles that the British and the Germans forces fired at each other during World War I were duds (i.e. failed to explode): most of them have not been recovered and in 2013, 160 tonnes of munitions, from bullets to 15 inch naval gun shells, were unearthed from the areas around Ypres (Hall, 2013). The French Département du Déminage (Department of Mine Clearance) recovers about 900 tons of unexploded munitions every year. Since 1945, over 600 French clearers have died handling unexploded munitions. Over 20 members of Belgian Explosive Ordnance Disposal (DOVO) have died disposing of First World War munitions since the unit was formed in Civilian deaths are also common. In the area around Ypres alone, 260 people have been killed and 535 have been injured by unexploded munitions since the end of the First World War. Shells containing poisonous gas remain viable and will corrode and release their gas content. Long after a conflict has ended, landmine and explosive remnants of war (ERW) contaminated land continues to pose a threat to the health and human rights of the local population. Landmines and ERW kill and maim, causing long term psychological and physical damage to health, and are a social and economic burden on individuals, families, communities and health systems. It has been estimated that, in 2013, there were a total of 3,308 casualties worldwide due to landmines and explosive remnants of war. As many casualties go unreported it is likely that this figure is significantly higher. Although annual casualty numbers have been falling since 1999 the threat of injury and death remains for populations in the fifty-six landmine and ERW contaminated countries also denying arable land for agriculture and contributing in many countries to food insecurity. Landmines and ERW are designed to maim rather than kill which means that the majority of victims survive but are left with debilitating injuries that affect not only their own physical and mental health but impacts upon their families and the local community. The World Health Organisation (WHO) estimates that 650 million people worldwide are disabled. This equates to approximately 10% of the world s population. Of those people, 80% currently live in low income countries (LICs) that are often at various stages of economic development depending on active conflict or post conflict state. The World Health Survey carried out in 2004 found, across 59 countries, the prevalence rate of disability in the adult population to be 15.6%, from 11.8% in High Income Countries to 18% in LICs. LIC s account for 84% of the world s population and 90% of the total disease burden. However, fewer than 3% of persons with disabilities in LIC s have access to required rehabilitation services. Without access to the rehabilitation they require, those with disability may become entrenched in a cycle of poverty. The WHO estimates that amongst the disabled people living in LIC s the need for prostheses will have risen to 30 million by The need for orthotic intervention is thought to be even higher, but remains underreported as requirements are not as visible as are those of prosthetics. The estimated 30 million low-income amputees worldwide have limited access to qualitative prosthetic care. This is the reason why researchers from the University of Strathclyde (Department of Bioengineering), and members of Dutch-based social enterprise organisation ProPortion initiated the concept of the leg bank. The aim of LegBank is to increase the access to affordable, high quality prosthetic service provision for people in low- and up-coming economies. 85

47 - International Prevention Research Institute Principal Contributions Initially in post conflict countries and with the intention to scaling up other countries. LegBank has developed an innovative device with a service model to reach low-incomes amputees and increase access to high quality prosthetics. The device, developed by researchers from Strathclyde University and design engineers from Reggs, known as Majicast, is a handsfree casting device used for manufacturing lower limb prosthetic sockets. The socket is the component which connects prostheses securely to patients residual limbs. It is unique for every human being and therefore crucial for pain free walking. Sockets produced with this device, can increase user comfort, stability and fit. This will subsequently result in enhanced quality of life. In addition, the total time and costs for socket production decreases by an estimated 75%. Eradicating Polio in Pakistan (Hussain et al, 2016) Our continuing ability to control and eradicate infectious diseases is predicated on health security. With the world experiecing ever more asymetric conflicts partiuclar involving non state armed groups the impact on public health campagins is becoming more acute. Before the launch of the Global Polio Eradication Initiative (GPEI) in 1988, poliomyelitis paralysed and killed hundreds of thousands of people every year. Polio is highly infectious and horizontal transmission usually occurs via the faeco-oral and oral-oral routes, with faeco-oral transmission contributing to the majority of cases especially in regions with poor hygiene and sanitation. The development of the inactivated poliovirus vaccine (IPV) in 1955, led to a sharp reduction in viral transmission and cases in the USA from approximately 20,000 cases per year in the 1950s to less than 1000 cases by the 1960s. However, the live-attenuated oral poliovirus vaccine (OPV) developed in 1963 remains the major vaccine in the developing world due to its cost-effectiveness, easy oral administration and comparatively better induction of intestinal immunity compared to the IPV. In 2015, four of the six WHO regions were certified as poliofree, leaving Pakistan and Afghanistan as the remaining endemic reservoirs of wild poliovirus. Illiteracy, religious misconceptions, conflict and insecurity in these regions have seriously hampered vaccination efforts and have been directly associated with a rise in wild poliovirus transmission with the potential to unravel the progress made by the GPEI. These fears were realised following an outbreak of 36 cases of polio in Syria and the isolation of wild poliovirus type 1, traced to Pakistan, from sewage samples in Israel towards the end of The successful eradication of wild poliovirus therefore rests on Pakistan s immunisation programme and strategy. Since the launch of the Global Polio Eradication Initiative (GPEI) in 1988 the global incidence of poliomyelitis has fallen by nearly 99 %. From a situation where wild type poliovirus was endemic in 125 countries across five continents, transmission is now limited to regions of just three countries - Pakistan, Afghanistan and Nigeria. A sharp increase in Pakistan s poliomyelitis cases in 2014 prompted the International Health Regulations Emergency Committee to declare the situation a public health emergency of international concern. Global polio eradication hinges on Pakistan s ability to address the religious, political and socioeconomic barriers to immunisation; including discrepancies in vaccine coverage, a poor health infrastructure, and conflict in polio-endemic regions of the country. This analysis provides an overview of the GPEI, focusing on the historical and contemporary challenges facing Pakistan s polio eradication programme and the impact of conflict and insecurity, and sheds light on strategies to combat vaccine hesitancy, engage local communities and build on recent progress towards polio eradication in Pakistan (Hussain et al, 2016). Pakistan s polio eradication campaign is facing a range of challenges due to a poor health infrastructure, managerial and operational deficits and serious inequities in immunisation coverage across the country. Conflict and insecurity have been particularly damaging to polio eradication efforts in recent years, especially in FATA and KP, the main reservoirs of wild poliovirus in the country. Operation Zarb-e-Azb, a military offensive launched in 2014 against militants in FATA, has re-established access to vaccination teams and enabled more intensive SIAs, translating to a significant reduction in reported cases of poliomyelitis in Pakistan s polio eradication effort can capitalize on these gains by addressing the gross inequities in its strategy and infrastructure, help shift perceptions against vaccination through more concerted community engagement and education initiatives, and address vaccine hesitancy using tools such as mass-media campaigns. Strengthening collaborations with influential religious leaders and organisations can also help mitigate the religious and political dimensions of vaccine hesitancy in Pakistan. Addressing these social and systemic deficits is critical to eradicating polio from Pakistan and achieving the GPEI s objectives. Pakistan s polio eradication campaign provides important lessons for the delivery of future global health initiatives in regions in conflict; the role of traditional social and religious norms and their wider diplomatic, security, economic and social repercussions in an era of increasing globalisation should not be underestimated in achieving global health outcomes and fostering broader socioeconomic development. An Assessment of the Barriers to Accessing the Basic Package of Health Services (BPHS) in Afghanistan (Frost et al, 2016) Afghanistan s history is blighted by conflict, a repetitive cycle of externally and internally driven warfare with only brief periods of peace. The decades of conflict decimated much of the social infrastructure including the country s health system. By 2002, Afghanistan had some of the poorest health indicators of any country in the world particularly in the areas of infant, child and maternal 87

48 - International Prevention Research Institute Principal Contributions mortality. In response to these immense health system challenges the Basic Package of Health Services (BPHS) was launched in 2003 followed by the Essential Package of Hospital Services (EPHS) in 2005 by the Ministry of Public Health (MOPH) of the new Afghan interim government with support from international donors and non-governmental organisations (NGOs). With no history of a functioning healthcare system, the creation of the Basic Package of Health Services (BPHS) in 2003 was a response to Afghanistan s dire health needs following decades of war. Its objective was to provide a bare minimum of essential health services, which could be scaled up rapidly through contracting mechanisms with Non-Governmental Organisations (NGOs). Despite the good intentions of the BPHS, not enough has been done to overcome the barriers to accessing its services. This analysis, enabled through a review of the existing literature, identifies and categorises these barriers into the three access dimensions of: acceptability, affordability and availability. As each of these is explored individually, analysis has shown the extent to which these barriers to access are a critical issue, consider the underlying reasons for their existence and evaluate the efforts to overcome these barriers. Understanding these barriers and the policies that have been implemented to address them is critical to the future of health system strengthening in Afghanistan. Surging mobile populations, cheap air travel and increasing international interconnections go hand in hand with the spread of infectious disease. The Role of Open Source, Signals and Image Intelligence Tools in Infectious Disease Outbreak Infectious disease outbreaks SARS, MERS, Ebola have proved to be potent threats to national and international security. Interconnected trade, cheap air travel and increasingly mobile populations, including those as a result of conflicts such as Syria, will continue to make infectious disease outbreaks a significant threat to the global community. This discourse has its roots in the widening of the concept of security that occurred in the 1990 s. Moving away from a primarily inter-state approach, this new conceptualization considered other intra-state and transnational threats as important, including that of disease outbreak. Most previous discussion has focused primarily on whether national intelligence agencies should consider infectious disease as a security risk within their remit of operation, rather than an analysis of their practical techniques for doing so. However, there has been little discussion about how national intelligence agencies would go about this, beyond the occasional unspecific mention of their ability to use clandestine methods to help detect and verify outbreaks. Current conventional surveillance systems for the early detection of epidemics and other diseases fall short of being completely successful. We have explored the ways certain tools and concepts relating to Open Source Intelligence, Signals Intelligence and Image Intelligence from the world of intelligence could and are being applied to infectious disease detection and control as part of global health security. We explored how Open Source Intelligence can be useful due to the ubiquity of internet usage across the world, and analyse some of its previous deployment history in this role at the World Health Organisation. Image Intelligence is evaluated through the potential use of UAV drones, and we look at how they could aid in contact tracing and disease surveillance in areas with a widespread populace and a poor communications infrastructure. Through Signals Intelligence, we explore how the mass collection and analysis of communications data could potentially add to disease surveillance, and balance this against questions of ethicality and cost of use. Our research is not all encompassing by any means and is intended to provide an introductory discussion; it is hoped that this provides a base for future study and possible integration into an effective global surveillance system. Chatfield-Ball C, Boyle P, Autier P, van Wees SH, Sullivan R. Lessons learned from the casualties of war: battlefield medicine and its implication for global trauma care. J R Soc Med. 2015;108(3): Connolly K. Legacies of the Great War United Kingdom: BBC News; Available from: news.bbc.co.uk/2/hi/special_report/1998/10/98/world_war_i/ stm. Frost A, Wilkinson M, Boyle P, Patel P, Sullivan R. An assessment of the barriers to accessing the Basic Package of Health Services (BPHS) in Afghanistan: was the BPHS a success? Global Health. 2016;12(1):71. Hall A. Mustard gas blisters and a daily risk of death: Bravery of soldiers still clearing the iron harvest of World War I shells from beneath Flanders fields.: Associated Newspapers Ltd; Available from: soldiers-tasked-clearing-hundreds-tonnes-deadly-world-war-i-shells-mines-beneath-fields- Flanders.html. Hussain SF, Boyle P, Patel P, Sullivan R. Eradicating polio in Pakistan: an analysis of the challenges and solutions to this security and health issue. Global Health. 2016;12(1):63. 89

49 - International Prevention Research Institute Important Contributions IMPORTANT CONTRIBUTIONS Multiple Sclerosis Multiple Sclerosis (MS) is a chronic disease which is the most common non-traumatic cause of neurologic disability in young adults. MS-related disability, as it progresses, can be life altering and has a substantial negative impact on quality of life and activities of daily living. Thus, MS is one of major challenges in Global Public Health. Aethiology of Multiple Sclerosis In addition to our key projects, is committed to more broadly investigating and formulating recommendations regarding multiple health issues. The following pages contain some, but not all, of this work. The aetiology of MS remains unclear. It is accepted that auto-reactive lymphocytes, which attack the myelinated axons in the Central Nervous System (CNS) and destroy the myelin and the axons to varying degrees, play an essential role in MS, but the cause of this auto-reactivity and its relapsing-remitting course are unknown (Kalman, 2008). Microbial infections can act as triggers inducing or promoting autoimmunity, resulting in clinical disease manifestations in genetically predisposed individuals. Replication or activation of some infectious agents like Epstein Barr Virus, HSV1 and HSV2, HSV6, and Lyme disease has been observed during MS exacerbations. According to hygiene hypothesis, an increased exposure to infections during childhood confers protection against MS because a heavy burden of microbial or parasitic infections creates a persistent effect on the immune system by shifting from a pro-inflammatory helper Th1 cell profile to an anti-inflammatory Th2 cell profile. The improvements in socioeconomic and lifestyle conditions in many countries during the past century might have eliminated the earlier exposure to infections at young ages and so the protection against autoimmune disorder (Bach, 2002). Other factors have been implicated in the pathogenesis of MS, among which diet, environmental toxins and sunlight, but none of this has been definitively confirmed. Great insights have been acquired recently in factors which vary with latitude like ultraviolet radiation (UVR) and vitamin D. Clinical course of Multiple Sclerosis The clinical course of MS is highly variable and unpredictable. In most patients the disease is characterized initially by episodes of reversible neurological deficits, which are often followed by progressive neurological deterioration over time. The diagnosis is based on the 2010 version of the McDonald criteria which consist of a combination of clinical, imaging and paraclinical tests (ie, CSF, evoked potentials) (McDonald et al, 2001) demonstrating dissemination of central nervous system lesions in both space and time. There is wide consensus among neurologists that patients may be grouped into four major categories based on the course of disease: relapsing remitting (RRMS), primary progressive (PPMS), progressive relapsing (PRMS), secondary progressive (SPMS). 91

50 - International Prevention Research Institute Important Contributions The dynamic evolution of the disease makes possible the conversion from one category to another, for instance from RRMS to SMPS. Because of its unpredictable course a strict and regular clinical follow up of patients is essential. Multiple Sclerosis Epidemiology and Geo-epidemiology The prevalence of MS is approximately 1/1000 (83/100,000 in Europe) and the estimated number of people with Multiple Sclerosis is 2.3 millions in The typical onset is between the ages of 20 and 40 years, and women are affected more frequently than men (approximately 3:1). An increase of the global median prevalence of MS from 30 per 100,000 in 2008 to 33 per 100,000 in 2013 has been observed, mostly owing to increased life expectancy, more diagnostic accuracy, amelioration of socioeconomic structure, and better treatments. The global prevalence of Multiple Sclerosis shows a north south gradient in the northern hemisphere: the prevalence is lower near the equator (<5/100,000) and higher in northern countries (>100/100,000 in North America, Canada and northern Europe); the reverse is observed in the southern hemisphere (Alonso et al, 2008). High prevalence rates are between 45 degrees and 65 degrees north and the observed increased incidence of disease might be due to the reduction of sunlight exposure hours in the Northern countries. It is not clear whether this geographical association is causal. The uneven distribution is influenced by population genetics, interplay between genes and physical environment and socioeconomic structure, including availability of medical facilities (Kurtzke, 1965). Moreover, there is a complex interaction between space and time. Indeed, over the previous 25 years an inversion has been observed of this latitude gradient in Italian regions, Scandinavia and North Atlantic and an attenuation of latitude gradient in Europe and in North America, whereas the latitudinal gradient on the Southern hemisphere remains unchanged. There is evidence that the risk of acquiring MS might be determined at the time of puberty or before with a lengthy latency before symptom onset. Indeed, migrants from high to lower risk areas retain the MS risk of their birth place only if they are more than 15 year old at migration time. Conversely, if they are less than 15 year old they appear to acquire the MS risk of new area. Treatment Several drugs are available to potentially ameliorate the unpredictable course of this disease, the so-called disease modifying therapy (DMTs) comprehensive of: i) the basic therapy, such as Interferon β-1a, β-1b, glatiramer acetate, dimethyl fumarate, teriflunomide; ii) escalation therapy, such as fingolimod, natalizumab, alemtuzumab, mitoxantrone. The indication for therapy depends mainly on the clinical course, disease stage and disease activity. Therapy should be initiated as early as possible with basic therapeutics and monitored clinically with periodic MRI. An ongoing clinical and/or radiological disease activity and/ or relevant side effects, justify the transition from basic to escalation therapy. So far, there are not validated efficacy monitoring protocols or criteria for changing the DMTs for MS, because of: i) the difficulty into distinguishing whether lack of apparent disease activity represents a therapeutic response or the natural history of the disease; ii) the lack of biologic markers that allow one to distinguish treatment responders, partial-responders, and non-responders. The Teriflunomide PASS Study On the 30th August 2013 the European Medicines Agency (EMA) approved the marketing authorisation for Teriflunomide (HMR1726), the active metabolite of Leflunomide used in the treatment of rheumatoid arthritis. Teriflunomide is an immune-modulator agent with both anti proliferative and anti inflammatory activity that has shown to be effective in remitting-relapsing forms of Multiple Sclerosis (MS). The results of two studies of phase III TEMSO (Teriflunomide Multiple Sclerosis Oral) and TOWER (Teriflunomide Oral in people With relapsing remitting multiple sclerosis) showed a significant reduction of annual relapses rate and handicap progression at two years in comparison with placebo. Since 2014 the International Prevention Research Institute has been organising a five-year Post Approval Safety Study (PASS) for Teriflunomide that has been requested by the EMA in order to further evaluate the long-term risks of Teriflunomide (TF). This study called Prospective Cohort Study of Long-Term Safety of Teriflunomide in Multiple Sclerosis Patients in Europe proposed to investigate the incidence of selected safety events and overall safety in patients treated with TF in Europe in real life. The protocol for the study has been developed in collaboration between and the CHMP of the EMA. The study population comprises MS patients from study centres of four countries: Belgium, Denmark, Italy (namely, the region Lumbardy), Norway. All patients are treated with Teriflunomide or with other DMTs. The primary objectives of this PASS study are : i) to characterize the long term safety profile of Teriflunomide by determining the incidence of adverse events of special interest (AESIs) in a real life setting in patients prescribed with Teriflunomide by considering several comparison groups; ii) to evaluate whether the treatment is associated with an increased risk of any of the AESIs compared to other approved DMTs. The AESIs from TF include acute liver injuries, infections, interstitial lung disease and pancreatic effects, notably pancreatitis and other potential risks, serious opportunistic infections including Progressive Multifocal Leukoencephalopathy (PML), malignancies, peripheral neuropathy, and cardiovascular events. The AESIs are associated with the International Statistical Classification of Diseases and Related Health Problems (ICD) codes (version 10) as a support to ensure consistency in the recording of the AESIs. Only adverse events leading to hospital admission will be analysed in this study. Over the two past years different meetings with Principal Investigators (PIs) have been organized, with the purpose of drafting the preliminary aspects and the major elements of the protocol which has been written according to EMA requirements and approved by EMA. In particular, the key actions enacted in this PASS Study are the following: Some national MS registries have been identified through literature search from the results of the MS Barometer 2011 and by enquiring at 33 national MS societies (Flachenecker et al, 2014). All patients have been identified in a pooled analysis of existing National MS registries in Europe. All identified patients are followed by neurologic centres (managing the above registries) at time of MS diagnosis. The centres are used as primary source since they collect routinely on baseline information in the MS Registries: age, gender, disease severity, MS diagnosis, approved therapies for MS, disease status, clinical course, relapses, country, month and year of initiation of the MS therapy. Moreover, the MS Registries also monitor the long-term therapy. We organized site visits with local PIs to consult for a deeper knowledge of their study centres and their National MS registries where patients are enrolled. We made a study to compare the criteria for the diagnosis of MS in each country and to examine the impact of these criteria on the composition of each register. 93

51 - International Prevention Research Institute Important Contributions Before the launch of the study a Pilot Study has been conducted to assess the completeness of patient data in the National MS registries. This has been done by comparing the rosters of each national MS Registry with the corresponding National Prescription Database. This resulted in a population-based databases which will be employed to produce a registry of MS patients for use in the study and to identify exposure to the various therapies, if the National MS Registry is not complete. We also searched patient-related information in other national registries (Death Registers, Cancer Registers, Hospital Discharge Registers). In the northern regions these registers are available and they are linked to National MS registries, covering the entire population in a region included in the Prescription Database. They interconnect as secondary source the information from the several population based registries and link them together by a unique personal and anonymous identity number(passive follow-up). For Belgium and Italy, we have checked the efficiency and reliability of a recorded linkage of different databases. We elaborated a common data collection protocol for use in each selected registry, after circulating among the local Principal Investigators a questionnaire on practical aspects of their registries. The aim is making the pooling of data from all registries feasible both for the retrospective phase (baseline information) and the prospective phase (informations about occurrence of AESIs). We provided study centres also with the organization of data extraction, according to which the baseline informations must be extracted by National MS registries, meanwhile data about AESIs must be extracted passively through linkage of the other registries to National MS registries. We provided the elaboration of a statistical analysis plan containing the variables necessary for to analyse the data of the MS registries database and describing how they are going to be analysed. Al the database necessary for the PASS are created locally in each participating centre and they are not be transferred elsewhere. We checked on reliability of different operating systems (IMED) and of different source codes (INAMI codes) to extract the requested data from the Belgian and Italian registries. Education and Training Education and training in prevention is an essential objective of. As an illustration of the importance of education and training, in particular in low and middle countries, the first book published by in its scientific publication was the textbook on Epidemiology and Biostatistics. Textbook on Epidemiology & Biostatistics It has been used as a reference material since 2010 in the summer school organised by in collaboration with the University of Dundee to train future actors in epidemiology from low and middle income countries. This first book in the scientific publication series is a textbook on Epidemiology and Biostatistics. This book provides an introductory to intermediate level of principles and methods in Epidemiology and Biostatistics. The book is aimed at providing students and junior health workers from all over the world, but especially those from lower-resource settings with clear and concise examples in the subject areas. Epidemiology and Biostatistics. Zheng T, Boffetta P and Boyle P. Scientific Publication 1, Lyon,, 2011, ISBN The high quality of the data recorded by the different National MS registries is allowing the conduct of the study in accordance with the EMA requirements., in cooperation with the participating study centres, will provide the final study report to the EMA. - University of Dundee Summer School on Epidemiology and Global Health The results from this study could be a great challenge for the new category of MS oral agents, since this category of drugs represents an effective improvement of therapy acceptance for many patients refusing injectable treatments. Alonso A, Hernan MA. Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology. 2008;71(2): Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med. 2002;347(12): Flachenecker P, Buckow K, Pugliatti M, Kes VB, Battaglia MA, Boyko A, et al. Multiple sclerosis registries in Europe - results of a systematic survey. Mult Scler. 2014;20(11): Kalman B. Multiple Sclerosis. In: Kalman B, Brannagan TH, editors. Neuroimmunology in Clinical Practice. Malden: Blackwell Publishing Ltd; p Kurtzke JF. Medical facilities and the prevalence of multiple sclerosis. Acta Neurol Scand. 1965;41(5): McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50(1): Between 2010 and 2012, organised jointly with the University of Dundee three consecutive years of a summer school on Epidemiology and Global Health. This summer school targeted health professionals from low- and middle-income countries for which fellowships were provided to encourage participation to these courses. Each year, the programme was organised over three weeks, taught on-campus in Dundee, and provided an introductory course in Epidemiology, Biostatistics and Global Health, with the aim of building a developed understanding in these areas and stimulating quality disease prevention research activities in resourcelimited countries. The programme included several modules such as disease registration; design and analysis of observational studies; causal inference; principles of screening; introduction to biostatistics; analysis of age, period and cohort effect; multivariate analysis; statistical power; contextualising global health; environment and health; improving health outcomes; and reconstruction and capacity building. Over these three years, about a hundred health professionals originated from low and middle income countries were trained. 95

52 - International Prevention Research Institute Important Contributions Master Programme in Global Public Health Training in Systematic Reviews The Strathclyde Institute for Global Public Health is an innovative collaboration in research and education between the University of Strathclyde and the International Prevention Research Institute () in Lyon, France. The partnership established in a curriculum for a two-year full-time Master s programme in Global Public Health. This Master s Programme is a unique, high-level programme that merges the strengths of both institutions. The course was designed in response to the international need to improve global Public Health and to contribute to capacity building necessary for its successful implementation. During the first year, the programme emphasizes the basics in Epidemiology, Biostatistics and Public Health with teaching provided by s professors and internationally renowned leaders in their fields. During the second year the students apply the skills acquired in the first year to global public health issues via a variety of modules such as Provision of Drinking Water, Sanitation, Public Health Law, Civil Engineering, Nutrition and Physical Activity. Math For Public Health (M4PH) In 2015/2016, structured a consortium Math For Public Health (M4PH) setting together practical actors of public health, academia and SMEs. The aim is to create a European Training Network on higher education on new mathematical and statistical models applied to public health ( The objective is to prepare future research leaders, able to conceive multidisciplinary methodological and computational techniques, and to cope them with real public-health data to shape Public Health Policies. Equally important, the early stage scientists will be trained to develop solid communication skills, and they will be exposed to multiple career avenues, at the interface between academic scientific institutes, public health centres and industries. ASSET Summer School Within the activities of the EU-funded project ASSET ( of which is partner, was a key participant, from 21st to 24th September 2015, in the first Summer School on Science in Society related issues in Pandemics, Rome, Italy. The ASSET Summer School aimed at establishing an interactive learning space for researchers and practitioners in the field of Science in Society (SiS) related issues in Pandemics; sharing and exchanging issues related to conducting and communicating research in SiS according to a transdisciplinary perspective, ranging from public health to social science and communication; addressing and critically discussing current discourses on research methodologies and findings as well as on practice-based cases. In 2016, developed a detailed curriculum on training in systematic reviews for researchers and public health officers involved in risk assessment. This was originally planned as a proposal support to fulfil the needs of the European Food safety Authority, and will be further integrated within the new project on online courses (see below). This course consists in a two-week course with 4 major modules: 1. Systematic review and protocol development; 2. Extraction data from studies included in a systematic review, exploring heterogeneity and interpreting the results of a meta-analysis; 3. Appraising reliability of individual studies; 4. Information retrieval techniques. The originality of this curriculum is the use of several case studies built from the experience of s senior researchers and partners involved in this curriculum such as Dan Krewsky (university of Ottawa). Development of Online Courses Since 2016, is working on a new project of online course in epidemiology and global health. Building on past education and training developments, and to enable broader access throughout the world in particular in low and middle income countries, is setting up online course using open source learning platform transferring all the teaching material and experience gathered over past decades by s senior faculty in remotely available resources. These resources will be constantly updated to incorporate new elements in the field of epidemiology such as training in systematic reviews. Vaccination and Infectious Disease Modelling, and Modelling of Other Biomedical Phenomena The prevention of the spread of infectious diseases is one of the major challenges for global public health, and historically was at the root of the birth of Epidemiology. In particular, the introduction of Vaccination is probably the medical development that had the largest impact on public health. An interesting feature of infectious diseases is that their spread can be analysed by means of statistical tools as well as investigated using mathematical models adapted from Statistical Physics models. Indeed, during the past century, synergies between Public Health Sciences, Statistics and Mathematics have resulted in substantial progress in the prevention and control of epidemics and pandemics. Eradication of smallpox late last century was arguably the most important Global Public Health success. In recent decades public health has faced an unexpected enemy: a growing opposition to vaccination for reasons ranging from the spread of uninformed rumours, to philosophical objections to vaccination. Medium and hig income countries are particularly vulnerable to this opposition. PROVA - Pseudo-Rational Objection to Vaccination - is one such rationale. It can be summarized as follows: X disease is now very rare in my country: why should I vaccinate my children or myself? In fact, as per the Internet, vaccines have multiple side effects. Evidence demonstrates that this objection is myopic in that the reason a vaccine-preventable disease is close to eradication is directly due to extensive vaccination programs. PROVA helps us to elucidate two underlying challenges facing Global Public Health s fight against Infectious Disease. First, we live in what sociology calls the Post-Trust-Age (Löfstedt, 2005) in which citizens increasingly distrust all suggestion by public and moral 97

53 - International Prevention Research Institute Important Contributions authorities. Second, the Internet and other media have become formidable rumour mills deprived of scientific foundation. This easy access to rumour vectors has been exploited by increasingly formidable anti-scientific groups who admittedly communicate better than the scientific community. understands that both operational and methodological Public Health Science and Practice have to radically change to win the battle against vaccine-preventable and other infectious diseases; new scientific avenues must be explored if we are to achieve societal change. We are exploring said avenues in collaboration with a network of institutions, in particular within the framework of the SWFS-focused EU project ASSET and the M4PH Training Network. The EU Project ASSET It is increasingly clear that to be effective, Global Public Health in a Post-Trust era, must go beyond the traditional one-way approach, wherein information and decision-making are uni-directional from the top down. The EU plans to overcome misinformation using the paradigm of Science With and for Society as manifested by their research directives in the Horizon 2020 and in the previous FP7 programmes. The key concept of Science With and for Society is that Public Health (and other scientific fields) must not attempt to solve societal challenges single-handedly opting instead for partnerships with, for instance, Civil Society. The ASSET EU project (Action plan in Science in Society in Epidemics and Total Pandemics) is the Mobilisation and Mutual Learning Action Plan (MMLAP), which aims: 1. To address scientific and societal challenges raised by major epidemics, pandemics and associated crisis management using the Science With and for Society paradigm 2. To explore and map Science With and for Society related issues in global pandemics 3. To define and test a participatory and inclusive strategy for success; ASSET combines global Public Health, epidemiological and vaccine research, social and political sciences, gender studies, science communication. has provided substantial guidance to better define the aims and the practices of the Project, both from the operational and the methodological points of view. The project is headed by one of oldest and most important Public Health institutions in Europe, the Istituto Superiore di Sanita (the NIH of Italy), whose consortium members include both academic institutions such as Haifa University and a series of SMEs and Institutions working at the juncture between Science and its Practical Applications to Societal Problems. We observed substantial heterogeneities across Europe as regards vaccine accessibility, the target population, vaccination strategy, non-pharmaceutical infection control measures and respective responsibility of organisms involved in the management of different aspects of the pandemic during the H1N1 crisis. The analysis of risk communication (RC) showed the lack of transparency and coherence of the process and the messages transmitted by authorities. In the field of methodologies a prominent role is assigned to Behavioural Epidemiology. In accordance with our analysis, the expert group recognized that rumours and suspicions regarding adverse effects of vaccines have shaken people s trust in vaccination, contributing to what is known as a post-trust society. The most frequently cited research areas considered as vital for future pandemic preparedness stated by the expert group were: effectiveness of antiviral drugs, technology transfer, mechanism of the emergence of the viruses at the basic level, an epidemiological tool to monitor early detection of outbreaks and trends, standardisation and flexibility of pandemic plans, sociological aspects of vaccination including risk perception, how to improve data sharing, efficiency of social distancing and its impact on the economics, tools for real time evolution of pandemics, and how to optimize the use of mathematical models. Overall, re-building trust in the current post-trust society requires effective RC campaigns that consider the social and cultural heterogeneity of the target population. It is also crucial to exploit and anticipate the role of Social Networks and Internet and integrate their use in communication strategies. RC and PH-related decisions can no more be unidirectional but, to some extent, it ought to be bidirectional. This task has been done in collaboration with Lyonbiopole. Roadmap Responsible and Open, Citizen-Driven Research The aim of this Task of ASSET has been the will design a roadmap towards responsible and open, citizens-driven, research and innovation on PH Sciences in the domains of epidemics and pandemics. Open innovation in pandemic related research requires initial investments because it demands a shift in the traditional, scientist-centered, approach. We reviewed existing experiences of user-driven innovation in the health and pharmaceutical sector. We had to answer to the question to what extent, and according to which conditions, user innovation is possible in the field of GPH research concerning prevention and control of major epidemics and pandemics. Existing initiatives, projects related to the involvement of users in epidemic infectious diseases prevention and response as well as other life sciences SWFS-centered applications were identified. From these listed existing initiatives, a roadmap of recommendations was elaborated (see figure). The central paradigm we adopted is the emerging concept of Public and Patient Involvement in medical and PH scientific research. This task has been done in collaboration with Lyonbiopole. The researchers involved in this project are Dr. Alberto d Onofrio (principal investigator), Ms. Miruna Dragomir, and Dr. Alina Macacu. In the framework of ASSET the International Prevention Research Institute is actively involved in some key tasks. Unsolved Scientific Questions in Pandemics and Epidemics The aim of this ASSET task was to outline within the guidelines of Science in Society - the main unsolved scientific questions regarding epidemics and pandemics, focusing on the H1N pandemic. We complemented our analysis with a questionnaire sent to experts in the field of pandemics and epidemics, and by organizing a focused workshop with a number of EU experts in various scientific fields of Public Health and Sociology. 99

54 - International Prevention Research Institute Important Contributions Graphical Representation of the key points of the proposed Roadmap. An intrinsic limitation of traditional epidemic models is that they are based on a statistical mechanics approach: the contagion is abstracted as a chemical reaction that can or cannot occur upon the random encounter of two particles : the infectious and the susceptible subjects. Building the PPI Rethinking of the research process and pipeline Best Practice Platform and Stakeholder Portal Key Players Groups of patients & their networks EU & national associations of consumers Communication of & Education to PPI Rethinking of the research process and pipeline Neutralise negative side effects Minimize the risks related to a massive PPI in health research Implementation Bidirectionality in public health decisions However useful it may be to describe many epidemic scenarios, this approach misses a critical factor: the above-mentioned behavioural component. Thus, event this theoretical approach fail in correctly describing the recent response to vaccination strategies in case of non-mandatory vaccination. This led in last ten years to the birth of a new branch of epidemiology: the behavioural epidemiology of infectious diseases, aimed at investigating the changes of behaviour of individuals of a population where an infectious disease is spreading, and their impact on the spread itself of the disease. As clearly shown by contributes of the first book ever published on this topic (Manfredi et al, 2013), the behavioural epidemiology is intrinsically multi-disciplinary, requiring the intervention not only of applied mathematics and statistical epidemiology but also of economy, sociology and anthropology. Moreover, this new field has large potentialities to interact with SWFS/SiS, as we recently stressed (Manfredi et al, 2013). A major determinant, negatively influencing the propensity to vaccinate, is the vaccine-related side effects. The propensity to vaccinate is determined by the opposition of two forces: the fear of acquiring the disease, which is related to the perception of its spread, and the fear of suffering vaccine-related adverse events. This tension was modelled by coupling a classical epidemic model with an imitation game dynamic representing the temporal evolution of the average population-level propensity to vaccinate (d Onofrio et al, 2011). However, vaccine awareness campaigns aimed at increasing vaccine propensity can be easily embedded in the model. The resulting model suggests that if the campaign is appropriately intense then it can favour the eradication of the target disease (d Onofrio et al, 2012). The Best Practice Platform (BPP) is a web-based, collection of best, good and promising practices on SIS related issues in GPH concerning prevention of infectious diseases, and control of their spread. This platform will be sided by a Stakeholder Portal, which will provide a gateway for interested stakeholders to register their interest in becoming involved. The Platform and the Portal will synergize in the seeking out and promotion (among researchers, PH institutions, industry etc ) of solutions that are already de-facto or potentially best practices but haven t yet been widely adopted. The work on BPP will result in the development of Guideline for developing the above-outlined Best Practices, which will be part of the platform. These guidelines will be validated through a consensus-building process among stakeholders such as: Organisations, PH institutions, Universities, etc. This in-progress task, leaded by is being done in collaboration with the National Health Institute of Italy and with ZADIG. Behavioural Epidemiology Both vaccine propensity and also the risk of infection depend on behavioural factors often dominated, as above mentioned, by irrational factors. Disease-related risk perception and the consequent changes in the human behaviours impact onto the transmission of the disease, which implies that it can modulate its population dynamics. The increasing qualitative consciousness of this phenomenon and the subsequent start of inflow of related epidemiologic data led in last ten year to a deep rethinking of the mathematical modelling of infectious diseases. These models are not only of intrinsic scientific interest, but they also are useful tools actively employed by national and international public health agencies to decipher epidemic dynamics, and to assess the impact of prevention measures. Recently we applied a classical tool of mathematical economics, Optimal Control, and a somewhat opposite heuristic tool of optimization, Simulated Annealing, to optimally plan these awareness campaigns, by taking into the account the material impossibility of continuously updating the awareness campaign. Our simulations show that the theoretical optimal campaign is far less abstract than believed since it is largely robust (Buonomo et al, 2017a) to large deviations. Moreover, in another work (Buonomo et al, 2017b) we showed that alternating low/large numbers of contacts at risk of infection linked to alternating holidays/school terms can indirectly help awareness campaigns. Namely, we showed that the negative impact of the large number of contacts during the school terms is luckily over-compensated by the decrease of contacts at risk during the holidays. One of most striking phenomena observable in natural, economic and social domains is the so-called abrupt phase transition: the small change of single system parameter can cause a large catastrophic (or hugely beneficial ) effect. The study of this class of phenomena is one of most important aspects of statistical mechanics, and it is at the basis of catastrophe theory. Recently, we proposed a mathematical model (d Onofrio et al, 2017) suggesting that the inclusion of behaviour-dependent vaccine propensity for vaccine-preventable infectious diseases can induce such catastrophic transitions in case of realistic imperfect vaccines (giving non-permanent immunity and partial protection). Notably, it might induce transition from low to very large prevalence in the case where the parameter tuning the fear of vaccine -related side-effects exceeds a threshold, or the parameter tuning the perceived risk of getting the infection decreases below a threshold. We are currently applying phase transition theory to other aspects of the influence of human behaviour on the spread infectious disease. These examples demonstrate that the spread of infectious disease is an ideal object of investigation for methodologies coming from Theoretical Physics. We have illustrated these methods ( exotic for epidemiology as their applications to epidemiology are for physics ) in the book Statistical Physics of Vaccination (Wang et al, 2016), of which contributed the chapters on classical (non-behavioural) and on behavioural modeling. 101

55 - International Prevention Research Institute Important Contributions Modelling of Other Biomedical Phenomena We illustrate here our activity in the modelling of some intra-cellular phenomena that are important to deciphering the pharmacodynamics of key classes of drugs. Classical models of protein dynamics are deterministic. Although useful, deterministic models have shortcomings. Two are very we known: i) the presence of a random disturbance is most often of extra-cellular origin; ii) in last two decades a number of experimental studies have revealed that some proteins are present in very low concentration, which implies a stochastic dynamic due to their low number. However a third major source of randomness is often neglected: genes induce the protein synthesis in a random fashion since they stochastically oscillate between an active and an inactive state. These oscillations, if slow, can induce large stochasticity even in the case where the produced protein is present in very large numbers. In a recent paper (de Franciscis et al, 2016) we fully investigate the effects of interplay between gene stochasticity and noise of extracellular origin, by taking into account that as often is in biology (d Onofrio, 2013) - both these kind of randomness are bounded, i.e. they cannot be approximated by Gaussian variables. Our model suggests that the velocity of gene switching is the determinant of the cellular response to the external noises. We used the paradigm of random gene fluctuations (Puszynski et al, 2014) to explain the experimental dose-response curves of Nutlin, a drug that aims to restore the physiological level of the anti-tumour protein p53 (one of main guardians of the genome, controlling both cell proliferation and differentiation) by inhibiting its key inhibitor Mdm2. The mechanism we found is somewhat universal and does not strictly depend on the complexity of the p53-mdm2 network. Indeed, we obtained qualitatively similar results (Puszynski et al, 2016) for models of drugs acting on very simple linear and non-linear molecular networks. Buonomo B, d Onofrio A, Manfredi P. Public Health Intervention to shape voluntary vaccination: continuous and piecewiese optimal control. (submitted). 2017a. Buonomo B, Carbone G, d Onofrio A. Effect of seasonality on the dynamics of an imitation-based vaccination model with public intervention. Mathematical Biosciences and Engineering (in press). 2017b. d Onofrio A. Bounded Noises in Physics, Biology, and Engineering: Birkhäuser Basel; d Onofrio A, Manfredi P. Bistable endemic states in a Susceptible-Infectious- Susceptible model with behaviour-dependent Vaccination. (submitted) d Onofrio A, Manfredi P, Poletti P. The impact of vaccine side effects on the natural history of immunization programmes: an imitation-game approach. J Theor Biol. 2011;273(1): d Onofrio A, Manfredi P, Poletti P. The interplay of public intervention and private choices in determining the outcome of vaccination programmes. PLoS One. 2012;7(10):e de Franciscis S, Caravagna G, Mauri G, d Onofrio A. Gene switching rate determines response to extrinsic perturbations in the self-activation transcriptional network motif. Scientific Reports. 2016;6: Löfstedt RE. Risk Management in Post-Trust Societies. United Kingdom: Palgrave Macmillan UK; Manfredi P, d Onofrio A. Modeling the interplay between human behavior and the spread of infectious diseases: Springer; Puszynski K, Gandolfi A, d Onofrio A. The pharmacodynamics of the p53-mdm2 targeting drug Nutlin: the role of gene-switching noise. PLoS Comput Biol. 2014;10(12):e Puszynski K, Gandolfi A, d Onofrio A. The role of stochastic gene switching in determining the pharmacodynamics of certain drugs: basic mechanisms. Journal of Pharmacokinetics and Pharmacodynamics. 2016;43(4): Wang Z, Bauch CT, Bhattacharyya S, d Onofrio A, Manfredi P, Perc M, et al. Statistical physics of vaccination. Physics Reports. 2016;664: Nutrition The nutritional research plan focussed on two main research topics, i.e., the relation between nutrition and cancer, and the relation between sugar and health. The aims of both programs are the prevention of chronic diseases: cancer and with obesity associated health problems. Diet, Nutrition and Cancer Project The project aims to produce a report initially focussing on diet, dietary practices, nutrition and cancer and based on findings from meta-analyses and pooled analyses to the largest extent possible. In addition to a series of reports, each section within the report would also be published in a peerreviewed journal. The initial work will concentrate on nutritional risk associated with specific cancers. There are eleven sites of cancer where there are sufficient studies published to arrive at some solid conclusions: colorectal cancer, breast cancer, prostate cancer, oesophageal cancer, lung cancer, oral cancer, kidney cancer, bladder cancer, liver cancer and pancreas cancer. Following completion of the analyses outlined above, the project will continue and develop similar analyses in the fields of cardiovascular disease and diabetes. A first cancer was reported, i.e., colorectal cancer. Colorectal cancer is the third most common cancer in men and the second in women. Significant international variations in the distribution of colorectal cancer have been observed for many years, indicating that nutrition likely play a role in the etiology. We performed a systematic review of meta- and pooled analyses of prospective cohort studies summarizing the evidence between foods and nutrients to colorectal cancer. We found 41 meta-analyses and 6 pooled analyses. In total 48 summary risk estimates (SRE) related high to low food consumption to incidence of colorectal cancer. Eight (17%) estimates were associated with a statistical lower risk of colorectal cancer, eleven (23%) with an increased risk, and 29 (60%) were not significant. Of the 46 SRE relating high to low nutrient intake to incidence of colorectal cancer, two (4%) had an increased risk, nine (20%) a decreased risk, and 35 (76%) were not significant. A progressive shift of 10% of consumption would avoid in total 6.8% of total colorectal cancer, with 3.6% coming from the shift in alcohol 103

56 - International Prevention Research Institute Important Contributions consumption, 1.8% for red meat and 1.6% for processed meat (see Figures). With the exception of consumption of alcohol, meat and dairy, there was no consistent association reported with foodstuffs and nutrients and colorectal cancer risk. Summary risk estimates and 95% confidence intervals from meta- and pooled analyses relating high versus low nutrient intake to colorectal cancer Sugar and Health Our research showed that in prospective studies on sugar-sweetened beverage consumption and body weight, the use of sugar exposure at baseline or of changes in sugar exposure during follow-up, as well as different statistical analysis modalities may end up in different results and conclusions. Basically, as main result, it is the change in total energy intake that was mainly associated with increase in weight. In addition, while on average body weight tended to increase over time, there was a concomitant decrease in sugar-sweetened beverage intake. These two results do not support the hypothesis that obesity would be essentially due to an increase in sugar-sweetened consumption. Rather, adiposity would mainly be the consequence of an imbalance between energy intake and expenditure. Indeed the consumption of sugar-sweetened beverage (and intake of other sugary foods or beverage) plays a role in adiposity due their energy content, but this role is similar to that played by other foods and caloric beverages. The clustering of unhealthy dietary habits and lifestyles with sugar consumption in general suggests the existence of an obesogenic behaviour that is the simultaneous presence of risk factors for obesity and other metabolic disorders in the same individuals. Because of the clustering of sugar consumption with a more unhealthy diet and behaviours, observational studies can hardly disentangle the specific influence that each dietary item or lifestyle may have on outcomes. This obesogenic behaviour implies that acting on a specific factor for preventing or treating weight gain is likely to fail if other factors are left unchanged. For instance, if all efforts are concentrated on the reduction of sugar intake, subjects are likely to adopt compensatory behaviors that will cancel out the benefits expected from reduced sugar intake. In this logic, a reductive single food approach would be poorly effective for preventing adiposity. Summary risk estimates and 95% confidence intervals from meta- and pooled analyses relating high versus low food consumption to colorectal cancer 105

57 - International Prevention Research Institute Important Contributions Liver Cancer (Hepatocellular Carcinoma): Curbing the Epidemics Liver cancer (hepatocellular carcinoma, HCC) is both common and highly lethal in low-resource and emerging countries, in which about 80% of the 800,000 estimated annual case are expected to occur. HCC often develops as the final stage of a complex history of chronic liver disease caused by infectious, metabolic, lifestyle and environmental factors. The geographic distribution of HCC shows a striking ecological correlation with areas of alternating hot-humid seasons, high endemicity for chronic Hepatitis B Virus (HBV) and high dietary contamination by aflatoxins, a group of carcinogenic mycotoxins that contaminates many traditional crops in these regions. As an organ, liver is a powerful ecosystem supporting cancer development: it is rich in nutrient stores, very well supplied in oxygen, has specific immune privileges and is remarkably equipped in detoxifying systems that protect it against cytotoxic drugs. It is therefore extremely difficult to treat unless detected at an early stage and completely removed by surgery. However, in regions of high incidence, the presentation is generally late and advanced, with no manageable treatment option. In sharp contrast with this bleak clinical picture, the main risk factors that cause HCC are, in principle, largely preventable at population level and patients who develop HCC may be accessible for early detection since most of them develop precursor chronic liver disease. However, the patterns of chronic liver diseases in low-resource populations are still largely unexplored and biomarkers and infrastructure is lacking for effective surveillance of these patients, in particular in sub-saharan Africa. potentially treatable stages of the disease is to identify biomarkers for early detection using simple and robust laboratory methods. The current diagnostic biomarker of reference, alpha-fetoprotein, is of limited interest for screening as low levels of AFP are poorly specific for HCC. This has led us to develop an international collaborative effort aimed at discovering and assessing new serum biomarkers tailored for optimal applicability in detecting early HB-related HCC (see figure). Pipeline and strategy for plasma biomarker discovery in hepatocellular carcinoma. First, mini-case/control and case/case comparisons were developed using plasma specimens from healthy HB carriers, patients with cirrhosis and patients with HCC from two distinct regions of high incidence (assembly). Plasma from these subjects were extensively analysed using a deep proteomics pipeline identifying over 2000 low-abundance peptides in each samples (discovery). Peptides distinguishing between HCC and cirrhotic patients in both Gambian and Thai series were selected (mining), and the two strongest hits were validated using simple ELISA-based dosage in over 1100 plasma specimens of cases and controls form different countries (validation) Documenting Chronic Liver Disease Trajectories in Africa There is only limited information on the prevalence of liver fibrosis and liver cirrhosis in the population and in at-risk groups of HB or HC chronic carriers in Sub-Saharan Africa. The 2010 Global Burden of Disease study provides estimates mostly from verbal autopsy given the lack of available vital registration data in most regions. According to this study, cirrhosis mortality varied between 12.9 (Southern Africa) and) and 24.2 (Middle Africa) per 100,000 person years. Due to lack of awareness and of systematic screening, most chronic HB or HC carriers are unaware of their status and are not being followed-up for liver functions and symptoms. To address this question, we have conducted a study in Bamako, Mali, in collaboration with researchers of Centre d Infectiologie Charles Mérieux, Bamako, Service de Gastroentérologie of Hospital Gabriel Touré, Bamako, and Université Catholique de Lyon, France. A total of 276 HB carriers were identified in a cohort of 1466 adult volunteers without diagnosed liver dysfunction. Among these carriers, 32.9% had plasma HBV loads > 104copies/mL, indicative of active viral replication. Furthermore, 35.6% had Fibrotest scores 2, indicative of moderate to severe liver fibrosis (Traore et al, 2015). These results suggest that about one-third of adult HB carriers in this group show signs of active hepatitis and might benefit from anti-hb treatment. Thus, the burden of chronic liver disease (chronic hepatitis, fibrosis, cirrhosis) is under-estimated in sub-saharan Africa. Further studies are currently in progress to investigate the prevalence of HB carriers and chronic liver diseases in other parts of Mali (Timbuktu Region, North Mali, with support of Region Auvergne Rhônes Alpes). New Biomarkers for Early Detection In high resource countries, screening is standard of care for patients at risk (e.g. patients with severe chronic liver disease) in highresource countries, with ultrasonography at 3 6 monthly intervals as the current method of choice. There is no demonstration of the feasibility and efficacy of ultrasonography screening in a low-resource African context. The best option for anticipating diagnosis to Using deep-plasma proteomics, two markers have been identified as performing better than AFP in discriminating cancer against chronic liver disease and cirrhosis, with sensitivities and specificities >90% for HCC associated with HBV (da Costa et al, 2015). These two markers are Osteopontin (OPN) and Latent-TGFbeta Binding Protein 2 (LTBP2), two components of the extracellular matrix of the liver. A recent evaluation of circulating OPN levels in a prospective European cohort revealed that an increase in serum levels of OPN was predictive of HCC up to 2 years ahead of diagnosis. After adjusting for all variables such as AFP and liver enzymes, each 10% increment in OPN levels was associated with a significant increase of developing HCC after 2 years (OR multivariable=1.30 (95%CI: 1.14, 1.48)) (Duarte-Salles et al, 2016). Testing of OPN and LTBP2 can be performed using robust, low cost immunoassays. Therefore, combining these two markers offer attractive characteristics for the screening of HCC in at-risk population groups but their efficacy remains to be evaluated in an African cohort. In another approach, we have used a mass spectrometry methodology initially developed in the field of earth sciences to investigate imbalances in iron and copper isotopes in the plasma and tissues of patients with HCC or cirrhosis from a case-control study in Thailand. These two essential metals are tightly regulated in liver cells, which play a major role in their homeostasis. Our study, published in the Proceedings of the National Academy of Sciences USA (Balter et al, 2015), shows that patients with HCC exhibit a specific isotopic copper signature in the plasma, which may occur as the consequence of perturbed metabolism of these redox-active ions in liver cancer cells. 107

58 - International Prevention Research Institute Important Contributions The Way Forward: 36 steps Against Liver Cancer in Africa In 2008, we proposed a set of 36 measures for reducing the mortality by liver cancer in Africa by the year 2050 (Hainaut et al, 2008). These steps fall into 4 main areas: preventing HB carriage, mitigating aflatoxin exposure, treating HB and HC chronic infections and chronic liver disease, and improving liver cancer detection, diagnosis and therapy. None of these measures on its own will be sufficient to significantly curb the number of death by liver cancer in the next decades. To have a realistic chance of limiting the natural increase in liver cancer cases due to population expansion and ageing, several of these measures need to be combined into an organized and structured action plan for Africa. In 2016, we have reviewed the current status of implementation of each of these measures, highlighting that much remains to be done to fully implement them (Hainaut, 2016). To date, only infant HB vaccination has been rolled out as a structured program, thanks to the efforts of WHO, Unicef and the Gavi Alliance. Since 2014, the vaccine is available in all African countries but population coverage remains insufficient to sustain the hopes of decreasing liver cancer mortality in the next 30 years. Active mitigation of aflatoxin exposure requires a multi-level action plan but passive reduction seems to spontaneously occur through diversification of the diet as African countries move up from low- income towards middle-income status. However, this diversification is likely to take place at different paces in more affluent areas as compared to poorer (mostly rural) areas, which will continue to rely on local production of traditional foodstuff for their subsistence. Since the very few cancer registries operating in West or Middle Africa are mostly based in urban areas, it is possible that we may record in the coming year an apparent decrease in liver cancer incidence rates that might not reflect the burden of the disease in the poorest part of the population. Economic growth and dietary diversification are expected to cause many changes potentially impacting on the incidence rates of liver cancer. On the one hand, better awareness and access to care may improve the prevention and management of chronic liver diseases. On the other hand, a switch towards westernized hypercaloric diet may result in a rapid rise in obesity, metabolic syndromes and diabetes, thus contributing to increase the prevalence of risk factors for liver cancer in both HB carriers and noncarriers, including individuals in whom carriage has been prevented by neonatal vaccination. Monitoring these trends will be essential to sort out positive from negative impacts of these changes. Access to diagnosis, treatment and palliation is dramatically constrained by economic resources. Yet, the trajectory of liver cancer in Africa suggests that a good window of opportunity exists for screening, early detection and early intervention. Achieving this requires developing biomarkers and drugs specifically designed to target the liver cancers in Africa. Indeed, these cancers appear to correspond to specific subgroup of severe liver cancers, different from the most common molecular subtypes occurring in industrialized countries. Another concern is that these biomarkers and drugs should be pitched for usage in low resource contexts and that their efficacy should be demonstrated in clinical trials involving African patients. Balter V, Nogueira da Costa A, Bondanese VP, Jaouen K, Lamboux A, Sangrajrang S, et al. Natural variations of copper and sulfur stable isotopes in blood of hepatocellular carcinoma patients. Proc Natl Acad Sci U S A. 2015;112(4): da Costa AN, Plymoth A, Santos-Silva D, Ortiz-Cuaran S, Camey S, Guilloreau P, et al. Osteopontin and latent-tgf beta binding-protein 2 as potential diagnostic markers for HBV-related hepatocellular carcinoma. Int J Cancer. 2015;136(1): Duarte-Salles T, Misra S, Stepien M, Plymoth A, Muller D, Overvad K, et al. Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population. Cancer Prev Res (Phila). 2016;9(9): Hainaut P. Africa: Liver Cancer. In: Boyle P, Ngomo T, Sullivan R, Ndlovu N, Autier P, Stefan S, Fleming K, and Brawley OW. The State of Oncology in Africa Scientific Publication 4,, Lyon, France (2016). Hainaut P, Boyle P. Curbing the liver cancer epidemic in Africa. Lancet. 2008;371(9610): Traore F, Gormally E, Villar S, Friesen MD, Groopman JD, Vernet G, et al. Molecular characteristics of Hepatitis B and chronic liver disease in a cohort of HB carriers from Bamako, Mali. BMC Infect Dis. 2015;15:180. Pancreatic cancer: in search of new targets for therapy Pancreatic ductal adenocarcinoma (PDAC) is a lethal form of cancer with very few therapeutic options. To date, the causes of pancreatic cancer are not clearly identifies, although a number of risk factors have been identified, such as smoking, obesity, genetics, diabetes, diet, and inactivity. Most cancers are detected at a late, metastatic stage. At the gene level, pancreatic cancer often harbour activating mutations in KRAS2, a critical regulator of intracellular growth signalling cascades involved in growth factor and nutrient sensing, raising the hypothesis that these cancers may be addicted to the activation of this specific pathway. If proven correct, this hypothesis raises hope of a molecular target, which may, in due course, be amenable to drug-based therapy. Indeed, whereas there is currently no effective inhibitor of KRAS2 in the clinics, the use of designer strategies may eventually lead to the development of such drugs in the close future. Despite often harbouring KRAS2 mutations, and despite having invariably poor prognosis, pancreatic cancers show an unpredictable heterogeneity in their growth patterns and initial responses to cytotoxic therapies. In recent years, studies on patterns of genetic alterations using whole genome/exome approaches have identified a large intra- and inter-tumoral heterogeneity in the number and extent of somatic alterations throughout the genome. Thus, a subset of PDAC appears to have highly rearranged genomes and is it possible that these forms may carry a particularly poor prognosis. Research carried out at The Institute of Advanced Studies at the Institute of Advanced Studies in Grenoble in the laboratory of P Hainaut (lead scientist: N Reynoird) have identified an important role of a relatively understudied family of enzymes, the methyltransferases, in regulating the KRAS-dependent signalling cascades in pancreatic cancer cells and in mouse models of pancreatic cancer. Methyltransferases have been the focus intense research, due to their roles in regulating DNA methylation and epigenetic control of gene expression. More recently, the attention has focused on the role of specific sub-families of methyltransferases in regulating the methylation of lysine in proteins, a critical regulatory change affecting histone and chromatin dynamics. Reynoird et al (2016) have shown protein methyltransferases may also control he activity of proteins involved in growth signalling cascades. Specifically, they found that that levels of the lysine methyltransferase SMYD2 were often elevated in PDAC and that genetic and pharmacological inhibition of SMYD2 restricted PDAC cell growth in vitro an in a mouse model of PDAC. This effect appeared to be due to the regulation by SMYD2 of the activity of the stress-response kinase MAPKAPK3 (MK3), a downstream effector of KRAS2. Inhibition of MAPKAPK3 impeded PDAC growth, identifying a new and potentially druggable kinase target in PDAC. Furthermore, inhibition of SMYD2 cooperated with standard chemotherapeutic treatments to reduce the development of experimental PDAC tumors. Overall, these findings underscore a pivotal role for SMYD2 in promoting pancreatic cancer and provide new insights on possible targets for future innovative therapies. Reynoird N, Mazur PK, Stellfeld T, Flores NM, Lofgren SM, Carlson SM, et al. Coordination of stress signals by the lysine methyltransferase SMYD2 promotes pancreatic cancer. Genes Dev. 2016;30(7):

59 - International Prevention Research Institute Important Contributions Guidelines for a Healthier and Longer Life Society is now taking conscious steps in looking for ways to prevent serious disease and to encourage individuals to develop a healthier lifestyle. A Healthy Lifestyle has not been defined and it may never be possible to do so in a generic manner: lifestyle choices are very individual centric. There are lifestyle choices for the individual to take, many of which can lead to a healthier lifestyle. There are also interventions that can be taken to prevent infectious diseases by vaccination and to reduce the impact of several chronic diseases by screening, early detection and delivering appropriate therapy when chances for cure are much higher. An evidence-based Report has been completed and a series of recommendations are made for a healthier lifestyle together with the appropriate scientific support. In this first version, not every possible intervention could be covered but this document will be continually reviewed, enlarged and brought up to date. However, the major issues have been covered. References have been chosen deliberately to demonstrate that knowledge which could be used in formulating prevention strategies has been available for decades and, on many occasions, this has been supplemented with the most up-to-date quantitative summaries. Tobacco use, chiefly cigarette smoking, causes a wide variety of diseases many of which are highly fatal: chronic obstructive pulmonary disease, lung cancer and a wide variety of other forms of cancer, cardiovascular disease and diseases of the gastrointestinal tract, neurological system, eyes and skin. Alcohol use causes a variety of diseases and premature death both resulting from excessive drinking and moderate drinking. In addition to a series of cancers, alcohol consumption is associated with a wide variety of accidents and injuries, frequently during leisure activities. A healthy diet offers protection against cardiovascular disease and, perhaps, cancer (although evidence of this is still lacking). Avoiding underweight, over-weight and obesity is essential for avoiding increased risks of a variety of diseases and conditions. Care is essential in the sun and use of sunbeds should be avoided. Vaccination is important to reduce, even eliminate, many infectious diseases. Continual monitoring of key risk factors for cardiovascular disease and diabetes are also an essential component of a plan for a healthy life. There are active actions that can be taken against serious chronic disease. Screening for Breast Cancer, Cervix Cancer and Colorectal Cancer is strongly recommended. For other forms of cancer, such as ovary, lung, melanoma, prostate and stomach there is no convincing evidence of efficacy at this time. Consideration should be given under medical advice, to prophylactic use of statins and aspirin against cancer and cardiovascular disease. Making the correct lifestyle choices and following the appropriate recommendations outlined in this document, will lead to increases in Healthy Life Expectancy as well as overall Life Expectancy. Not only should subjects live longer but they will do so with a better quality of life. There is more to Health than just the absence of disease. The recommendations here will improve health but will also have a substantial impact on many other aspects of quality of life. Use of Social Security Databases and Patient Registries Social security databases register considerable amounts of information on medications and health services received by individuals. These databases can be linked to patient registries, hospital discharge registries, outpatient registries, pharmacy registries, cancer registries, cause of death registers and so on. Patient registries are complementary to social security databases because they are used for the clinical follow-up of patients with chronic disease. These databases represent immense sources of real world data reflecting the complexity of modern medicine including patient journey in health care systems and consumption of resources. They have the potential to contribute to numerous types of projects, like epidemiological research, effectiveness studies, surveillance of adverse events, sociological approaches, health economics, health service research and so on. Demands for access to these sources of data is increasing because many governments and public health administrations are conscious that sensible use of the available information could lead to better use of resources, avoidance of wastes, identification of poorly efficient health services, improved quality of the health care systems, and ultimately better patient outcome. In addition governments require steadily more real world evidence on the effectiveness and harms associated with health therapies and technologies (i.e., for health technology assessment (HTA)). However, the big data approaches in the health domain face numerous legal and administrative hurdles and nourish a multitude of passionate and complex debates at all levels of the European society, from the citizen to the European institutions. In order to address the concerns of authorities responsible for the social security databases and of health professionals running patient registries, the proposes innovative working procedures that keep the data in owner s computers during the entire study duration. To this end, the has established data handling and analyses procedures that are entirely conducted in the data owner computer system so that no data is transferred to or any other recipient (figure). The procedures are based on the creation of a working database hosted in the data owner computer system in which all data relevant to a specific study are stored. Resolution of anomalous data, variable recodifications, computations, and if needed, linkages with external databases are all performed within this working database. When all data handling procedures are terminated, the variables necessary for statistical analyses are transferred into an analysis database also located in the data owner computer system onto which statistical analysis scripts written by statisticians are applied. The scripts produce the study results as aggregated statistics in tabular format. These aggregated results are transferred to where further analyses can be carried out using meta-analytic techniques. 111

60 Cancer Leadership 2015 La grandeur d un métier est peut être avant tout d unir les hommes... Antoine de St. Exupéry Attendees of the 2015 NCID Meeting held in Lyon, France

61 Cancer Leadership 2016 La grandeur d un métier est peut être avant tout d unir les hommes... Antoine de St. Exupéry Attendees of the 2016 NCID Meeting held in Lyon, France

62 - International Prevention Research Institute Cancer Leadership National Cancer Institutes Directors Meetings The tenth and eleventh meetings of National Cancer Institute Directors (NCID) took place in Lyon in July 2015 and These meetings attract over 150 thought leaders, national cancer institute directors and Ministers of Health from 50 countries at varying levels of income and resource. As requested by participants, the focus on cancer in low resource countries continues to be a focus of these meetings. During our 2015 and 2016 meetings, the /WPA Awards for Contribution to Cancer Control were awarded (see following pages for recipients and details). The 2015 NCID meeting marked the fortieth anniversary of the discovery of the cure of testicular cancer. NCID participants were honored by the presence of and inspiring keynote address by Dr. Larry Einhorn (photograph). Dr Einhorn has been a major figure in Oncology and his discovery of the role of cis-platin in the treatment of disseminated testicular cancer remains one of the key contributions to cancer treatment. NCID plenary sessions cover topics of specific interest to participants. It is a meeting at the highest level designed to facilitate the exchange of ideas between key global cancer control leaders. The first NCID meeting was organized by Professor Peter Boyle in Milan in

63 - International Prevention Research Institute Cancer Leadership WPA/ Cancer Control Awards 2015 WPA/ Awards for Cancer Control On the occasion of the 10th Annual National Cancer Institute Directors Meeting in Lyon (NCID 2015), three outstanding individuals, working in different health areas, were presented with the Professor Peter Boyle, presenting the 2015 WPA/ Awards for Cancer Control to Prof. Einhorn (left), Dr. Merriman (center) and Prof. Kakizoe (right) Thank you World Prevention Alliance / International Prevention Research Institute award in recognition of their contribution to Cancer Control. Dr. Anne Merriman was born in Liverpool and graduated in medicine from University College Dublin in Ireland. Anne subsequently spent 33 years working in Africa (including 10 in Nigeria as a missionary doctor and 20 in Uganda), seven in Southeast Asia, eight in the United Kingdom, and five in Ireland. She introduced palliative care into Singapore in 1985, which became an accepted form of care with the founding of the Hospice Care Association in 1989: this service is still fully functional in Southeast Asia. In 1990, Merriman returned to Africa, initially to Nairobi Hospice, before founding Hospice Africa. She introduced palliative care to Uganda in 1993, by forming an adaptable and affordable model, Hospice Africa Uganda (HAU). In Africa, the largest problem facing palliative care workers involves overcoming the stereotypes and negative connotations associated with morphine. Professor Merriman stresses that if a patient s pain cannot be controlled then holistic care cannot be brought in either. Through here work she has pioneered Palliative Care in Africa. Professor Tadao Kakizoe had a distinguished career as a Urologist focussing on his work in experimental and clinical research on bladder cancer. He made seminal contributions to the development of bladder cancer and to the surgical management of the disease. In 1992, Professor Kakizoe became Director of the National Cancer Center Hospital in Tokyo, Japan and became Director General of the National Cancer Center in When his mandate had been completed, he became President of the Japanese Cancer Society in Professor Lawrence Einhorn is a Distinguished Professor of Medicine at Indiana University School of Medicine and an oncologist of international renown. Dr. Einhorn pioneered the development of the life-saving medical treatment in 1974 for testicular cancer, increasing the cure rate from 10% to 95%. Dr. Einhorn received a B.S. from Indiana University in 1965 and his M.D. from the University of Iowa in He served his internship and residency at IU Medical Center, followed by a fellowship in Haematology/ Oncology at the M.D. Anderson Hospital Tumor Institute in Houston, Texas. He returned to IU Medical Center in 1973 and was named Distinguished Professor of Medicine in He became the first Lance Armstrong Foundation Professor of Oncology in Shortly after his arrival at Indiana University, he tested Cisplatin, a drug which had already failed in a Phase I clinical trial with patients who had various end-stage cancers, including testis cancer. Cisplatin was found to be too toxic, causing severe vomiting, neuropathy, hearing loss and kidney damage in these patients, and it failed to stop the growth and spread of most of the cancers. Dr Einhorn developed a three-drug regimen which had superb results, curing testicular cancer and giving this group of men a near normal life expectancy. Subsequent clinical research directed by Dr. Einhorn established a model for a curable tumor, which has served as the basis of treatment of testicular cancer until the present day. 119

64 - International Prevention Research Institute Cancer Leadership 2016 WPA/ Awards for Cancer Control On the occasion of the 11th Annual National Cancer Institute Directors Meeting (NCID2016), three outstanding individuals working in different areas were presented with the World Prevention Alliance/ International Prevention Research Institute award in recognition of their contribution to Cancer Control. If only the road to fight cancer were as straight and simple... Left to right, Professor Peter Boyle, presenting the 2016 WPA/ Awards for Cancer Control to Mr. Byrne, Professor Loehrer and Professor Zaridze Mr. David Byrne, the former Barrister and Attorney General for Ireland, was appointed European Commissioner for Health and Consumer Protection in 1999 and served until During his term as Commissioner, the European Centre for Disease Control (ECDC) and the European Food Safety Authority (EFSA) were created. Notably, he steered into European law Directive 2001/37/ EC of the European Parliament and of the Council on the approximation of the laws, regulations and administrative provisions of the Member States concerning the manufacture, presentation and sale of tobacco products: this pioneering law against Tobacco paved the way for individual national laws. This was followed-up by his sponsorship of the European Tobacco Advertising Directive (2003/33/EU) which banned all cross border advertising and sponsorship of tobacco products in Europe. Professor Patrick Loehrer is director of the Indiana University Melvin and Bren Simon Cancer Center and the H.H. Gregg Professor of Oncology and associate dean for cancer research at the Indiana University School of Medicine. He is widely recognised as an outstanding clinician and clinical researcher and is a specialist in a variety of forms of cancer. His long-term activity and leadership in developing quality cancer treatment in Eldoret (Kenya) through long term support of AMPATH, which comprises Moi University, Moi Teaching and Referral Hospital and a consortium of North America academic centres led by Indiana University working in partnership with the Government of Kenya. This is an initiative of long standing and has provided high-level education in many aspects of Oncology and quality care where none existed before. Professor David Zaridze was initially a pathologist but re-focussed on Epidemiology during a year spent working with Sir Richard Doll in Oxford, United Kingdom. After a spell at the International Agency for Research on Cancer ( ) he returned to Moscow and in 1987 became Director of the Institute of Carcinogenesis at the N. N. Blokhin Cancer Research Centre. He is currently Deputy Director of the Russian Cancer Research Centre. Professor Zaridze has made a significant contribution to epidemiological research of non-communicable diseases and premature death. He has led a major effort in canсer epidemiology in Russia with his efforts in tobacco and alcohol of particular importance. He has clearly shown the impact of smoking and excessive alcohol drinking on life expectancy and several key diseases including cancer. 121

65 - International Prevention Research Institute About Us ABOUT US People Passion People matter. So too, does their knowledge and rigour. But most of all, it is their passion that drives their work. is known for this passion. We are proud of this, and are committed to growing our organisation not just in numbers, but primarily in the quality of our Senior Faculty, Senior Research Fellows, Faculty and Staff. 123

66 - International Prevention Research Institute About Us People Senior Faculty Peter Boyle PhD DSc FRSE FFPH FRCPSG FRCPE FRCPI FMedSci President Peter Boyle s appointment as President of the International Prevention Research Institute, Lyon, France follows immediately on his tenure as Director of the International Agency for Research on Cancer (IARC/WHO). From he was Director of the Division of Epidemiology and Biostatistics at the Institute of Oncology in Milan, Italy. Prior to that he held posts as Senior Scientist at IARC, Assistant Professor in Epidemiology and Biostatistics at Harvard School of Public Health and the Dana- Farber Cancer Institute (Boston, United States), the West of Scotland Cancer Surveillance Unit (Glasgow, United Kingdom) and the Department of Medicine at Glasgow University. Professor Boyle is the inaugural Director of the University of Strathclyde Institute of Global Public Health at, which is situated in Lyon and Glasgow. He is Professor of Global Public Health at the University of Strathclyde and currently holds Honorary or Visiting Professorships at Glasgow University and Yale University. He is founder and President of the World Prevention Alliance, a nongovernmental organisation committed to prevention research and actions in lower income countries. Peter Boyle s research interests lie in disease prevention and translational research in its broadest sense, from translating cuttingedge scientific discovery into new approaches to treatment to translating information about risk factors into changes in population behaviour. He led the EUROCAN+PLUS project which developed priorities for coordination of cancer research in Europe and was Editor of the World Cancer Report 2008 and the State of Oncology 2013 which highlighted the growing global cancer crisis. The recent publication of State of Oncology in Africa 2015 and the accompanying film Cancer is Attacking Africa, highlight the need for action against chronic disease in low-resource countries. Peter Boyle has previously been a Member of the European Cancer Advisory Board and worked as the scientific advisor to the European Commission on the European Tobacco Contents Directive which was voted into law in He was also responsible for the revisions of the European Code Against Cancer. Peter Boyle has been awarded the Knight s Cross of Order of Merit of the Republic of Poland; Fellowship of the Royal Society of Edinburgh; Honorary Membership in the European Society for Therapeutic Radiology and Oncology (ESTRO), the Hungarian Oncological Association and the Argentine Medical Association; Fellowship of the Royal College of Physicians and Surgeons (Glasgow); Fellowship of the Royal College of Physicians (Edinburgh); Honorary Fellowship of the Royal College of Physicians of Ireland; Fellowship of the Academy of Medical Sciences (United Kingdom); Membership of the European Cancer Academy; Membership of Academia Europea; and Honorary Membership of the Hungarian Academy of Science. He has been awarded honorary doctorates by the Universities of Aberdeen (DSc) and Dundee (LlD). 125

67 - International Prevention Research Institute About Us Philippe Autier Vice-President, Population Research Philippe Autier was born in Brussels, Belgium, and received a Doctor of Medicine degree from the Université Libre de Bruxelles and a diploma in tropical medicine from the Prince Leopold Institute of Tropical Medicine, Antwerp in He started his professional life by joining the humanitarian non-governmental organization Médecins Sans Frontières (MSF), where he helped in Honduras (1985 and 1986), and later in Chad ( ) as the medical coordinator of projects conducted by a team of approximately 50 expatriates and 200 Chadian health workers. In , Philippe Autier was the first head of the medical department of MSF-Belgium. He is one of the founders and a board member of the organisation AEDES that provides Mathieu Boniol Vice-President, Biostatistics Mathieu Boniol was born in Nimes, France, and graduated in Biomathematics and Public Health at the University Lyon 1, France and subsequently obtained a PhD in epidemiology from the Université de Bourgogne, Dijon. expertise in public health to low and middle income countries. In 1990 he received a Fulbright fellowship with a grant from the Frank Boas Foundation to study at Harvard School of Public Health, Boston, Massachusetts, where he was awarded an MPH. In 2011, he received a PhD from the Erasmus University in Rotterdam for his works on the cutaneous melanoma. Philippe Autier has been head of the Prevention and Screening Department of the Jules Bordet Institute in Brussels ( and ), Deputy Director at the European Institute of Oncology in Milano ( ), and Group Head at the International Agency for research on Cancer in Lyon ( ). Philippe Autier is a leading figure in several fields including research on cutaneous melanoma and breast cancer, especially in domains related to the causation, prevention and early detection of these cancers. He is also very involved in the clinical testing of new methods for cancer detection and in health technology assessment. In 2013 he was appointed Professor at Strathclyde University. Philippe Autier is Vice President, Population Research, at the International Prevention Research Institute epidemiological methods and meta-analytic methods. In particular, he has been involved in many analyses of temporal trends and of geographical patterns for exposures and outcomes. Particular areas of expertise are the analysis of cancer registry data on trends in incidence and mortality of diseases, the analysis of exposure distribution and their impact on disease burden, statistical methods in pharmaco-epidemiology, evaluation of cancer screening and the analysis of disease registry data (e.g. linkage between biobanks and medical records) for the evaluation of health programmes or of medical activities. Mathieu Boniol has also contributed to various international collaborative projects involving computation of attributable fraction and to various meta-analyses (melanoma risk, artificial light and skin cancer, vitamin D and cancer). Michel Smans Chief Technology Officer Michel Smans was born in Brussels, Belgium, and received a Masters Degree of Mathematics from the University of Namur. After two years working as Research Assistant to Professor E. Schifflers, he joined the International Agency for Research on Cancer in Lyon and started to transpose advanced mathematical techniques to descriptive epidemiology. He developed the Cancer Mapping Project before moving to the unit of Biostatistics, and later created the IT Support team, expanding its range of activities over the years. Between 2003 and 2009, he held the position of Senior Biostatistician at the International Agency for Research on Cancer in Lyon. He was the coordinator of the EU-funded project EUROSUN. He is a member of the International Task Force on Skin Cancer Screening and Prevention that evaluates the national skin cancer screening in Germany. From 2009 to 2015, he was a member of the board of directors of Euroskin (the European Society of Skin Cancer Prevention) and President of Euroskin between 2011 and In 2013, he was appointed as Professor at Strathclyde University, Glasgow. Mathieu Boniol is Vice-President, Biostatistics at the International Prevention Research Institute, where he supervises a team of statisticians, data managers and other functions. He has published more than 150 scientific articles and has an h-index of 33 (as of January 2017). Michel has held board positions in IT user societies at the French and European level while keeping a strong interest in his original studies in descriptive epidemiology, particularly cancer mapping and Incidence and Mortality Databases. Michel Smans joined the International Prevention Research Institute as Chief Technology Officer in March 2011 with the dual responsibility of ensuring the highest standards of information technology and mathematical excellence for the Institute. His scientific activities mainly deal with etiologic research based on 127

68 - International Prevention Research Institute About Us Irene Leigh Research Director Irene Leigh was born and educated in Liverpool. She obtained her undergraduate medical training and intercalated BSc (Hons) in Anatomy at the London Hospital Medical College and specialised in dermatology at postgraduate level. She spent two years as a lecturer in medicine at the University of Dar es Salaam, Tanzania, before returning to registrar and senior registrar positions in London. In 1983, she was appointed as Consultant Dermatologist to the London Hospital and became Professor of Dermatology in 1992, having completed an MD degree and Professor of Cellular and Molecular Medicine in 1999, when she received a DSc (Med) and was elected as a Fellow of the Academy of Medical Science. She acted as Research Dean ( ) and subsequently Joint Research Director of Barts and the London School of Medicine and Dentistry/NHS Trust. In 2006 Irene Leigh was honoured with an OBE for services to medicine and also became Vice Principal and Head of College of Medicine, Dentistry and Nursing at the University of Dundee and additionally Vice Principal for Research in She stepped down from these roles at the end of 2011 but retains a research professorship at the University of Dundee. She was elected as Fellow of the Royal Society of Edinburgh in She has served on multiple scientific advisory boards in UK and Europe, is currently President of the Rene Touraine Foundation and has held officer positions in UK and European research societies. As past president of the ESDR she organised IID 2013 in Edinburgh, the major investigative dermatology meeting. She has directed the Cancer Research UK Skin Tumour Laboratory since 1983, focusing on research in keratinocyte biology, epithelial differentiation and skin carcinogenesis. This continues as a joint London-Dundee activity identifying genetic changes and molecular mechanisms in squamous cell carcinogenesis in both immunosuppressed and immunocompetent patients. She has also established the genetic basis of multiple genodermatoses, some with sensorineural deafness and cardiomyopathy, which is now leading to research in therapeutic developments through the Dermatology and Genetic Medicine (DGEM) initiative in Dundee. She holds an ERC advanced investigator award to develop preclinical models for testing novel therapies. countries, namely on tumours of the upper-aerodigestive tract (squamous cell carcinoma of the oesophagus in Iran, Kenya, Latin America; lung cancers) and on HepatoCellular Carcinoma (West Africa, Colombia, Egypt, Thailand, China). From 2002 to 2008, he has led the Gambia Hepatitis Intervention Study (GHIS), a large intervention trial aimed at testing the long-term efficacy of newborn HB vaccine against liver cancer in adults in West Africa. Since 2005 he has contributed to developing evidence-based Alberto d Onofrio Research Director Alberto d Onofrio was born in Naples, Italy, graduated in Electrical and Control Engineering at the University of Pisa, Italy and subsequently obtained a PhD in Medical Computer Sciences from the University of Rome- La Sapienza, Italy. Alberto Patrick Mullie Research Director standards for biobanks. Pierre Hainaut is frequently lecturing and giving courses in Post-Graduate programs in different countries and in international summer schools. In 2013 he was appointed as Professor at Strathclyde University. He has written about 375 articles and book chapters and is the editor of several books on molecular epidemiology and on p53. Pierre Hainaut is a Research Director at the International Prevention Research Institute. d Onofrio s main activities are on mathematical epidemiology of infectious diseases, epidemiology of cancer and cancer systems biomedicine. Broadly speaking, he is interested in the effects of nonlinearity and randomness in biological phenomena, from microscopic to population level. He has also contributed to various projects involving computational biology, geographic epidemiology of cancer, and the role of human behavior on the spread of communicable diseases. He has been at the European Institute of Oncology in Milan from 2000 to 2013 starting as Professor Boyle s postdoc fellow and ending as Principal Investigator in Systems Biomedicine. Alberto d Onofrio is a Research Director at the International Prevention Research Institute Pierre Hainaut Research Director Pierre Hainaut was born and educated in Belgium. He obtained an Msc in Science in 1980 and a PhD in Biological Sciences in 1987 from the University of Liège. From 1987 to 1994, he has been held postdoctoral positions in France (INSERM) and in the UK (University of Cambridge, University of York). Most of his laboratory research was focused on molecular genetics, particularly on the tumour suppressor protein p53. He joined IARC as staff scientist in 1995 where he became head of Molecular Carcinogenesis in He is an internationally recognized scientist in the p53 mutation field and hasled the development of the IARC TP53 database. His research has a focus on the molecular pathogenesis of cancers in low- and middle-resource Patrick Mullie was born in Mouscron, Belgium, and graduated in Nutrition and Dietetics at the University College of Leuven and in Epidemiology and Applied Statistics at the University of Maastricht. He subsequently obtained a PhD in Nutritional Epidemiology from the Catholic University of Leuven. Patrick Mullie s main research activities focus on nutritional epidemiology, vitamin D and health, dietary pattern analysis, and e-learning methods for epidemiology. He is involved in many projects in the prevention of adiposity at population level. Those prevention projects are based on the nudging principle, i.e., changing the food environment to making the healthy choice the easiest. For the Belgian Army, he developed survival food packs for extreme conditions, using his past experience as an international guide for arctic exploration in Greenland, Alaska and Siberia. In the past, he was President of the Belgian Association of Dietitians, introducing evidence-based nutrition to the field of dietetics and organizing educational sessions of nutritional 129

69 - International Prevention Research Institute About Us epidemiology, with focus on reading and understanding systematic reviews and meta-analyses. He is affiliated as Professor Systematic Review at the Faculty of Physical Education and Physical Therapy, Free University of Brussels and as Research Director at the Queen Elisabeth Barracks, Belgian Army, Brussels. He is also a lecturer in Nutrition and Epidemiology at the Erasmus University College, Brussels. Guillaume Noyel Research Director Guillaume Noyel was born in Saint-Chamond, France. He obtained a Diplôme d Ingénieur in Electrical Engineering from CPE-Lyon in 2005, and a MSc in Image Processing, from Université Jean Monnet, St Etienne in In 2004, he spent three months engaged in research a the University of Utah, Department of Radiology. In 2005, he spent five months at the Ecole Polytechnique Fédérale de Lausanne, working on colour reproduction. Guillaume received his PhD in Mathematical Morphology from Mines ParisTech in 2008 after having developed morphological methods for multivariate and hyperspectral images, with medical applications for tumour detection. During his PhD he participated in many international conferences and in 2007 was awarded the prize of young stereologist of the International Society of Stereology. He worked as a researcher in image processing at the Michelin Research Centre for six years where he conceived scientific frameworks in texture analysis, image segmentation and 3D image reconstruction with translation for large-scale industrial applications in quality control and 3D imaging. Mireille Guigaz Research Director Mireille Guigaz is a French Ambassador whose main expertise is in Public Health and International Development. She graduated in Law and Political Sciences and completed a PhD in Medical Law and Health Care Economics at the University of Lyon. She also specialised in Hospital Management at the National School of Public Health and attended the National School of Administration. In 2002 she attained an international Masters Degree in Mediation from the Kurt Bösch Institute, Switzerland. Patrick Mullie is a Research Director at the International Prevention Research Institute. He is also member of the Belgian Superior Health Council and of the American Society for Nutrition. He is author of more than ten books about nutrition and more than 40 peer-reviewed publications. Guillaume Noyel has led several scientific joint efforts between industry and public research centres. He joined in 2014 as a Research Director where he developed a programme of research in mathematics and image analysis for public health. He is leading international collaborations with a special focus on Diabetes and retinopathy. He has been published in several journals and has obtained several patents in these fields. Mireille Guigaz has acquired extensive, high-level public health management experience through various assignments in the field. Whilst leading the second public health care region of France, as Regional Director of Health Care and Social Affairs ( ), she held negotiations with over 200 public and private hospitals, setting the path for a five-year strategic regional development scheme. As General Delegate of the National Federation of the twenty comprehensive cancer centres in France (Centres de Lutte Contre le Cancer), she negotiated a new collective labour agreement which is still used as a reference within the global public-private hospital community. From , Mireille Guigaz served as the General Delegate of the Lyon-Auvergne-Rhône-Alpes research cancer hub, working on behalf of the National Cancer Institute (INCA). She was also serving as Chairperson of the Ethics Committee of the International Agency for Research on Cancer (IARC). As Senior Operation Officer for the World Bank from , she started to develop an in-depth knowledge of international development. In 2000 she was nominated as Director of International Development and Technical Cooperation for the Ministry of Foreign Affairs and in 2004 became the first French Ambassador to take charge of the fight against HIV/AIDS, TB and Malaria, working closely with many African countries at both governmental, NGO and community-based levels. From Mireille Guigaz was posted to Rome as Ambassador of France, Permanent Representative to Food and Agriculture Organization (FAO), World Food Programme (WFP) and the Maria Paula Curado Senior Researcher Maria Paula Curado received a Doctor of Medicine degree and a PhD degree from the University of Goias. From 1990 to 2006 she held the position of Director of the Goiania Population-Based Cancer Registry in Brazil. This registry was able to produce data in order to be included by the International Agency for Research on Cancer s (IARC) volume VI-IX of Cancer Incidence in Five Continents. International Fund for Agriculture and Development (IFAD) and participated in the global negotiations, which continue today, to establish a new international commitment to global food security. In December 2011, Mireille Guigaz has been awarded the French National Order of Merit (Commander s class) and in January 2012, she has been appointed again by the French Conseil des Ministres as the French Ambassador for HIV-AIDS, Tuberculosis and Malaria. Maria Paula Curado regularly trained cancer registrars from Portuguese countries in Africa and Brazil. She was one of the Editors of Cancer Incidence in Five Continents volume IX. She was also elected from 2002 to 2006 as Regional Representative for Latin America at the International Association of Cancer Registries (IACR). She joined IARC in 2007 to work within the Cancer Information Group, her main duties being to organize workshops and advisory missions to evaluate and support population-based cancer registries in low- and mediumresources countries as in Africa, Latin America, Caribbean and Asia (Vietnam, India and China). She also has experience in collaborative multicentre studies, including Head and Neck Cancer in Brazil INHANCE and the Concord study with London Hygiene School on survival. She is currently a Senior Researcher at the International Prevention Research Institute with the aim of promoting prevention research in low- and mediumresources countries. 131

70 - International Prevention Research Institute About Us Faculty An organisation is as sustainable as its next generation is capable. Indeed, a successful organization is one that ensures its younger members are constantly challenged and nurtured with new knowledge. is fortunate to have a dedicated junior faculty. They are here for tomorrow but also for today. Their current qualifications and demonstrated achievements place them, we are confident, on par with any other academic institution in our field. The proof of Faculty effectiveness is in the many articles, awards and conference presentations that they regularly produce and receive. All, regularly present papers and posters in prestigious meetings worldwide such as ASCO, ESMO and others. Alina Macacu Alina Macacu was born in Bucharest, Romania. She graduated in 2010 from the National Institute of Applied Sciences (INSA) in Lyon, France, with an engineer s degree and an MSc in Bioinformatics and Modelling. In 2014, she obtained a PhD in Models, Methods and Algorithms in Biology, Health and Environment from the Joseph Fourier University, Grenoble, France, for her work on mathematical modelling of the spread of avian influenza. In 2015, she joined the International Prevention Research Institute as a Research Officer, specialising in Epidemiology and Biostatistics. She has contributed to various projects on topics such as meta-analytic approaches, science with and for society, assessment of models-based predictions, Alice Koechlin and assessment of effects of risk factors, and early detection measures, on cancer incidence and mortality. Alina Macacu s research activities focus on epidemiology of infectious diseases, epidemiology of cancer and mathematical modelling applied to public health, with an interest in projects designed for health improvement in lower-resource settings. Maria Bota Maria Bota was born in Romania. In 2009 she graduated from INSA (National Institute of Applied Sciences) in Lyon, obtaining an engineering diploma (Master in Science and Technology) in Bioinformatics and Modelling. During her studies she undertook several academic and industry-based research internships in international and interdisciplinary environments: IARC (Lyon), Bioinformatics Lab at the University of Leeds, R&D Department of Sanofi Pasteur (Marcy L Etoile), and the Department of Ecology and Evolution of University of Lausanne. In 2010 she joined the team as a Research Officer, specialising in epidemiology and biostatistics applied to a series of public health projects. She took a particular interest in diabetes related projects: postauthorization safety studies for monitoring the long-term safety Cécile Pizot Cécile Pizot was born in Lyon, France. She graduated from INSA Lyon (National Institute of Applied Science) in 2011, obtaining an engineering diploma (Master in Science and Technology) in Bioinformatics and Modelling. During her studies, she undertook several academic and industry-based research internships in multidisciplinary environments including the Bioinformatics and Biostatistics team of IPSOGEN (Marseille) and the Laboratory of Bioinformatics and Integrative Genomic (LBGI) at IGBMC (Strasbourg). In January 2012, Cécile joined the International Prevention Research Institute as a Research of several diabetes drugs and metaanalyses which have been published in peer-reviewed journals and presented during international conferences. In addition, she has coordinated the preparation of a White Paper on the epidemiology of diabetes. In January 2014 she started a PhD in Mathematics and Statistics, focusing on Statistical Issues in the analysis of database studies. Officer, specialised in biostatistics applied to epidemiology and public health. Her main research topics focus on cancer mortality trends especially for breast cancer, physical activity and breast cancer, vitamin D and diabetes, epidemiology and aetiology of pancreas cancer. Alice Koechlin grew up in Saint-Étienne, France, and graduated in Bioinformatics and Modelling at the National Institute of Applied Sciences (INSA) of Lyon in 2010, obtaining an engineering diploma (Master in Science and Technology). She undertook her end of curriculum internships in international and multidisciplinary environments at the International Agency for Research on Cancer and at the Department of Ecology and Evolution of University of Lausanne (Switzerland). Alice Koechlin is a Research Officer at the International Prevention Research Institute. She concurrently conducts a PhD with the University of Strathclyde (Scotland) on statistical methods for meta-analyses in epidemiological studies. She was also involved in research projects focusing on occupational exposures to UV light and to rubber manufacturing industry. Miruna Dragomir Miruna Dragomir was born in Brasov, Romania. After her high school diploma in Romania, she graduated from INSA (National Institute of Applied Sciences) in Lyon, obtaining an engineering degree (Master in Science and Technology) in Bioinformatics and Modelling (2014). During her studies, she undertook several research internships in interdisciplinary and international environments such as BioMerieux and Laboratoire de Biométrie et Biologie évolutive (Lyon). She also worked for two years for a Junior Enterprise (ETIC INSA Technologies), as a Communications Officer and General Secretary, enabling her to hone her communications and organizational skills. She completed her master s degree internship at. She joined as an Assistant Statistician in Since then, she has contributed to projects on various topics including physical activity, vitamin D, diabetes and science with and for civil society, through approaches such as review and meta-analysis of existent published evidence, or analysis and assessment of cancer risk factors. 133

71 - International Prevention Research Institute About Us Francesca Ciaraffa Francesca Ciaraffa was born near Naples. She received a Doctor of Medicine from the Catholic University of Rome in 2002, and a diploma in Neurology in In 2012 she obtained a PhD in Cognitive Neurosciences from the University Pierre et Marie Curie Paris VI and from the Catholic University of Rome to 2013 she worked at National Neurological Institute Carlo Besta in Milan, as part of the experimental research project team Coma. In 2013, joined the National Neurological Institute Mondino in Pavia, department of Neurological Emergencies. Her clinical and research focus is vascular events and other neurological emergencies, on multiple sclerosis, on disorders of consciousness, and on neuropsychology. She is post-doctoral research fellow in Neuro- Epidemiology at IPRI now working on a Prospective Cohort-Study of Long Term Safety of Teriflunomide treatment in Multiple Sclerosis patients in Europe, in collaboration with Multiple Sclerosis Registries of Denmark, Belgium, Swedish, Norway, Italy. Magali Boniol Magali Boniol was born in Lyon, France, and graduated with a Master of Biological System Analysis and Models, from the University Lyon 1 in Following her studies, she worked as Assistant Biostatistician within an association (Audipog) for five years, and then as Assistant of Clinical Research at the Hospices Civils de Lyon. She joined as Assistant Statistician in March Her activities cover several aspects of biomedical research, including literature search for systematic reviews and meta-analysis, data extraction for meta-analysis, analysis of cancer registry data, and other statistical analysis of clinical data. She has been involved in projects on fetal growth restriction, diabetes, breast cancer, and occupational UV exposure. 135

72 - International Prevention Research Institute About Us Staff Kim Coppens Frédérique Delbart Alina Blaj Kim Coppens Kim Coppens was born in St. Agatha-Berchem, Belgium. She graduated from the University College of Ghent, Belgium in 2011 as an Office Manager specialised in translation. During her last year, she studied translation at the Instituto Superior de Contabilidade e Administraçao do Porto, Portugal and undertook an internship at, afterwhich she joined the team as Project Assistant. Since January 2017 she is the Communications Officer. Frédérique Delbart Florence Motais de Narbonne Aida Ben Brahim Nordine Mamoune Frédérique Delbart was born in Lyon. She graduated with a BTS of Executive Assistant at Institut Pitiot, Lyon in Further to her studies, she worked during 21 years in the pharmaceutical industry at Merck Serono Laboratories in Lyon as Executive Assistant. She joined as Personal Assistant to the President in September Alina Blaj Alina Blaj was born in Romania and studied bank finance at Babes Bolyai University at Cluj Napoca in Romania. In 2010 she received a Masters Degree in Management from Lyon 2 University. After working as a financial manager in Lyon for one year, volunteered for V.I.E (Volontariat International en Entreprise) for the French Economic Mission in Bucarest. She is currently studying to become a Chartered Certified Accountant. She joined the team in March 2012 as Accountant. Florence Motais de Narbonne Florence Motais de Narbonne was born in Paris. After her studies she managed teams for several event planning agencies in Lyon and Paris. She worked as Assistant to an orthopaedic surgeon and then as Human Resources Manager Assistant to the Chamber of Commerce and Industry of Rhône-Alpes. She joined in June 2014 as Administrative Assistant. Aïda Ben Brahim Aïda Ben Brahim grew up in Lyon, France. She has a general university studies diploma in Foreign Languages and Civilization. She continued her studies at the Peyrefitte School in Lyon to become a travel agent. Following these studies, she worked in as a travel agent, administrative assistant and switchboard operator. She joined as Receptionist in Nordine Mamoune Nordine Mamoune was born in St. Denis, La Réunion. After his studies and military service he worked as a welder for the nuclear station of Petroplus Raffinage Reichstett, the Centre de Recherche Nucleaire Europeen (Pierrelate) and Superphénix (Creys-Malville). In 1978 he founded Operator Taxis, a taxi business targeting business and corporate accounts. He joined in July 2012 as Driver/Clerical Assistant. 137

73 - International Prevention Research Institute About Us Senior Research Fellows is particularly proud to have attracted such a distinguished panel of Senior Research Fellows. Indeed, to a great degree, our international reach and recognized excellence would not be possible were it not for scientists, academics, policy experts and industry professionals who are able to deliver both accurate evidence-based studies and exceptionally well informed analyses and, when required, recommendations. You will find in our list of Senior Research Fellows scientists at the top of their field of study. You will find academics from the bona fide most exacting academic institutions. You will find ministers of health, university presidents but also a sociologist who has devoted her life to improving the lives of her fellow citizens. Patient advocates are also proud Senior Research Fellows working along side women and men whose body of work lies withing the pharmaceutical industry. From day one, Professor Peter Boyle and his leadership team recognized that, in the words of St. Exupéry, a profession is at its best only because of the women and men who labour in it. Clement Adebamowo Clement Adebamowo, born in Lagos, graduated BM ChB Hons from the University of Jos, Nigeria. He trained in Surgery and Oncology at the University College Hospital Ibadan, Nigeria and at Harvard University where he earned a DSc. He is a Fellow of the West African College of Surgeons and the American College of Surgeons; Director of Office of Strategic Information, Research and Training, Institute of Human Virology, Nigeria; President of the Society of Oncology and Cancer Research of Nigeria; Convener of the Nigerian Research Consortium; Director of the Center for Bioethics, Nigeria; Director of the West African Framework Program on Global Health; and an Associate Professor of Epidemiology, University of Maryland, Baltimore. He is Editor in Chief of Bioethics Online Journal (BeOnline ), Cancer in Africa Online Journal (CIAO ), Associate Editor of Frontiers in Oncology, and Contributing Editor to many other journals. Clement is Honorary Professor, University of Dundee, UK; current Chair of the International Affairs Committee of the American Society of Clinical Oncology; Chairman of the National Health Research Ethics Committee of Nigeria; Member of the Expert Advisory Panel on Clinical Practice Guidelines and Research Methods and Ethics of the World Health Organization (WHO); Country PI of the Partnership for Cohort Development and Training (PaCT); and Nutrition Epidemiology Transition Collaboration (NET). His research interests are noncommunicable diseases epidemiology, AIDS-associated malignancies, and Bioethics. Adil Aljarrah Adil Aljarrah, graduated from the University la-sapienza with honours. He completed his general surgery and breast surgery residency in Scotland obtaining a fellowship in general surgery FRCS (Glasgow) and FRCSI (Ireland). Adil then started intensive research in breast cancer epidemiology at Edinburgh Breast Unit and the University of Edinburgh obtaining a postgraduate MD from Edinburgh University. He then moved to France for further training in breast and reconstructive surgery obtaining an AFSA in breast and reconstructive surgery and microsurgery. After returning to Oman, Adil established the SQUH Breast unit, a unique service in the region. This breast one-stop clinic, introduced multidisciplinary practices to Oman, and the first ever breast reconstruction surgery in Oman. Adil regularly organises international conferences in Oman and is invited worldwide to participate and speak at global health conferences. Adil Aljarrah is also the founder of the Oman Breast Cancer Society (OBCS). Otis W. Brawley Otis Brawley, a graduate of University of Chicago, Pritzker School of Medicine, completed a residency in internal medicine at University Hospitals of Cleveland, Case-Western Reserve University, and a fellowship in medical oncology at the National Cancer Institute. As the chief medical and scientific officer and executive vice president of the American Cancer Society, Otis Brawley, MD, is responsible for promoting the goals of cancer prevention, early detection, and quality treatment through cancer research and education. He currently serves as professor of hematology, medical oncology, medicine and epidemiology at Emory University. He is also a medical consultant to the Cable News Network (CNN). Otis Brawley serves on the Board of Regents of the Uniformed Services University of the Health Sciences. He has served as a member of the Food and Drug Administration Oncologic Drug Advisory Committee, the Centers for Disease Control and Prevention Breast and Cervical Cancer Early Detection and Control Advisory Committee and Chaired the NIH Consensus Panel on the Treatment of Sickle Cell Disease. Among numerous other awards, he was a Georgia Cancer Coalition Scholar and received the Key to St. Bernard Parish for his work in the U.S. Public Health Service in the aftermath of Hurricane Katrina. Paul Burton Paul Burton qualified in Medicine from the University of Leicester in 1983, taking an intercalated BSc in Genetics in As an MRC Training Fellow ( ), he was awarded an MSc in Medical Statistics from the London School of Hygiene (1988). His MD focused on the application of survival models to a variety of complex problems in renal medicine. Paul Burton is a Chartered Statistician (Royal Statistical Society), a member of the Royal College of Physicians (UK), and holds professorships within the Faculties of Public Health in universities both in the UK and Australia. He is on the Specialist Register for Public Health Medicine. In recent years, his research work has increasingly focused on activities that promote and facilitate the construction of major infrastructural research projects in population-based biomedicine. He is a member of the Health Services and Public Health Board at MRC, and the Study Design Expert Group at WT. Naftali Busakhala Dr. Naftali Busakhala is the founder and chairman of the department of Hematology and Oncology at Moi Teaching and Referral Hospital, the teaching hospital for Moi University in Nairobi. Under his leadership, the department has expanded rapidly from about 50 patient visits to over 8000 patient visits per year. Collaborations have been formed with Indiana University, Brown University, University of Massachusetts, and University of Toronto. Dr. Busahkala is now the Co-Director of the Chandaria Cancer and Chronic Diseases Center, in Eldoret Kenya. 139

74 - International Prevention Research Institute About Us Mark Clanton In 2006, Mark Clanton served as Deputy Director of the National Cancer Institute, under NCI Director Andrew von Eschenbach. His duties included providing senior executive oversight of the NCI Cancer Center Core Grant Program. The Director and staff of the Office of Cancer Centers reported to him during this time and he engaged in executive problem solving and senior level sign-off for this program on behalf of the Director of the NCI. Mark currently serves on three cancer center external advisory boards (EAB) including the University of Kansas Cancer Center. He chairs the EAB at the NCI Cancer Center Support Grant (CCSG) designated University of Hawaii Cancer Center and serves as member of the NCI CCSG designed Siteman Cancer Center in St. Louis. Dr. Clanton provides advice and feedback in the public health areas of tobacco control, healthcare disparities, cancer prevention and control as well as general advice on the overall performance of the cancer center against NCI CCSG expectations. Giovanni Corrao Giovanni Corrao became research assistant at the Faculty of Medicine, University of Turin, in In 1988 he was upgraded to Associate Professor at the Faculty of Medicine, University of L Aquila, where he stayed until He is currently Full Professor in Medical Statistics, University of Milano-Bicocca. and the chairman of the Italian College of Medical Statistics Professors. From 2005 to 2009 he was the President of the Italian Society of Medical Statistics and Clinical Epidemiology. From 2009 to 2012 he was the Dean of the Faculty of Statistical Science, University of Milano- Bicocca. He is the founding Editor of the journal Epidemiology, Biostatistics and Public Health. Since 2003 he has been the coordinator of the postgraduate course program in Biostatistics, University of Milano-Bicocca. He currently teaches Medical statistics, Methodology of clinical and epidemiological research and Pharmaco-epidemiology, Biostatistics, and Medical statistics. He is currently the vice-coordinator of the PhD program of Public Health, University of Milano-Bicocca. Prof. Corrao currently carries out his research activity at the Laboratory of Healthcare Research and Pharmaco-epidemiology, Department of Statistics and Quantitative Methods, University of Milano-Bicocca. His main research interest is on methodological issues of clinical research and in the design, analysis and interpretation of statistical models for both observational studies and clinical trials. More recently, he has focused on statistical methods and epidemiological designs in pharmacoepidemiology and outcome research, and on the use of electronic archives in this area. He is currently the coordinator for the University of Milano-Bicocca on 6 collaborative research projects in the field of pharmaco-epidemiology supported from the European, Italian Medicines Agency, and Italian Health Ministry. Jean-François Doré Jean-François Doré, born in 1940 in Fécamp, France, graduated LSc Nat from the Faculty of Sciences, University of Paris, and obtained a Doctorate in Human Biology (Experimental Oncology) from the Faculty of Medicine, University Paris XI. He joined INSERM (French National Institute for Health and Medical Research), and worked in Villejuif (Institute of Cancerology and Immunogenetics) and Lyon (Léon Bérard Cancer Centre) where he was Director of an Immunology and Experimental Oncology INSERM Research Unit. His focus is on human melanoma, exposure to ultraviolet radiation and skin cancer prevention. He was a founding member of the EORTC Melanoma Group. He is a member of the International Task Force on Skin Cancer Screening and Prevention that evaluates the national skin cancer screening in Germany. He is currently President of the Specialized Experts Committee on Physical Agents of the French National Agency for Health Safety. He was awarded the Order of Merit of the French Republic (Knight, 1978). Mark Dumenil Born in London, Mark moved to France in 1981 and directed his career to international healthcare with an interest in introducing medical devices technology that make a difference to patients lives across Europe. With nearly 30 years experience in a variety of international leadership roles at CR Bard Inc., Johnson and Johnson Inc., and CMA Microdialysis AB, Mark has developed strong connections with leading clinical, regulatory and well as market access specialists across Europe. In 1996 Mark joined the Ethicon Division of J&J and was offered a leadership role in developing a new surgical oncology business. This was later merged with urology where he was made Vice President Europe for Oncology and Urology. Today he leads an international healthcare consultancy based in Paris dedicated to introducing successfully promising medical technologies across Europe and lives between France and the UK. Kenneth Fleming Kenneth Fleming is a pathologist with a special expertise in the liver. He graduated from Glasgow University in 1968 and after training posts in Pathology in Glasgow and Oxford, received his DPhil from Oxford University in 1980 and his Fellowship of the Royal College of Pathologists in 1988.He has extensive experience of successful leadership and management in academia with various positions in Oxford and nationally, including appointment as the inaugural Head of the Medical Sciences Division at the University of Oxford from 2000 to He is currently Honorary Consultant in Pathology for the Oxford Radcliffe Hospitals NHS Trust and Associate Head for Academic Affairs of the Oxford Post-Graduate Deanery. In addition, he is leading the development of a MMed in Pathology in Zambia and has developing involvement in fostering increased educational capacity in several east and central African countries. He was made an honorary Fellow of the Royal College of Physicians in 2007 and was appointed the first Director for International Activities of the Royal College of Pathologists in November His main research and clinical interest has been in liver disease and he has over 150 publications in learned journals on aspects of liver pathology and on molecular biology and pathology. Elizabeth Fontham Elizabeth Fontham is the Founding Dean and Professor of Epidemiology Emeritus at Louisiana State University (LSUHSC) School of Public Health and Professor of Pathology in the LSU School of Medicine where she has been on the faculty in the LSUHSC since She also serves as Senior Consultant Epidemiologist to the Louisiana Office of Public Health. Dr. Fontham s major area of research is cancer epidemiology, with an interest in tobacco and nutrition-related cancers and gastric carcinogenesis. She has conducted studies of lung cancer and environmental tobacco smoke, including the largest early study of lung cancer in non-smoking women that provided some of the critical information leading to the classification of second-hand smoke as a human carcinogen. Dr. Fontham has published extensively on stomach cancer and its risk factors, with studies of the high-risk populations in the Andes Mountains of Colombia. Her current research includes the study of innovative approaches to cervical cancer screening in hard to reach women, and studies of the long-term human health effects of the exposures resulting from the Gulf of Mexico Oil Spill. She has served as a member of the NCI Board of Scientific Counselors. She was Treasurer and on the Board of Directors of the American College of Epidemiology of which she is a Fellow. She was a member of the inaugural Editorial Board of Cancer Epidemiology Biomarkers and Prevention as Assistant Editor; Chairman of the Scientific Editorial Board of the North American Association of Central Cancer Registries; and a contributing author for both the Surgeon General s Report and International Agency for Cancer Research Carcinogenesis Monograph series. She is recipient of the Alton Ochsner Award Relating Tobacco and Health, the C.L. Brown Award for Leadership Excellence in Tobacco Prevention; the Leadership and Distinguished Service Award of 141

75 - International Prevention Research Institute About Us the American College of Epidemiology; and the Pfizer Award for Excellence in Research, Education and Patient Care. Sara Gandini Sara Gandini has a degree in Statistics (University of Bologna), an MSc in Biometry (University of Reading) and a PhD in Cancer Studies (University of Birmingham). She is a senior investigator in the division of Epidemiology and Biostatistics, at the European Institute of Oncology in Milan (Italy). She has conducted extensive research in cancer epidemiology, including systematic reviews and meta-analyses, with the goal of better understanding cancer aetiology. Her main interest is now melanoma epidemiology and the role of Vitamin D in cancer epidemiology. She is the lead organizer of a multicentre Italian trial on Vitamin D supplementation for melanoma patients. Since 2008 she has been lecturer at the Italian Melanoma Intergroup Master and for statistical courses at the European Institute of Oncology. In December 2011 she was unanimously elected as new President-elect of EuroSkin. Sara Gandini has authored or co-authored over 50 publications and she acts as referee of several international peer reviewed journals, such as JNCI and JCO. In 2008 she received the Bruno Martinetto Award for Research in Chemoprevention. Donato Greco Donato Greco was born in Naples, and graduated in medicine with a specialisation in infectious diseases, public health, epidemiology, and biostatistics. He founded and later directed the National Centre for Epidemiology of the National Institute of Health of Italy, where he served for 32 years. Donato Greco served for four years as Director of the Department of Disease Prevention in the Italian Ministry of Health where he was he led Influenza Pandemic preparedness. As National Epidemiologist at ISS he investigated hundreds of epidemics worldwide including the ECDC response to the 2009 H1N1 pandemic evaluation (May-July 2009). Donato Greco has worked extensively with WHO and the European Center for Disease Control. Today he serves as consultant in communicable diseases surveillance, prevention and risk communication. He has authored more than 150 scientific publications and has been teaching epidemiological methods in Italian universities for many years. Donato Greco has been awarded the Italian Gold Medal for Public Health. André-Robert Grivegnée André-Robert Grivegnée is Head of the Cancer Prevention and Screening Clinic at Jules Bordet Institute in Brussels. As a radiologist, he is Head of the Senology Unit in the same Institution. He is Professor at the Free University of Brussels (Université Libre de Bruxelles). He is involved in Breast Screening Programs in Belgium and at the European Level and is Past-President of the Brussels Program for Breast Cancer Screening. He is administrator of the Association against respiratory diseases (FARES). His Curriculum Vitae includes 102 articles and more than 200 presentations at national and international societies and symposia. He participated in seven European Research projects and is currently involved in a Project on Breast Cancer Risk Evolution. He is an active member of the EORTC Imaging group. He developed a Project of Quality control of Digital Mammography in Breast Cancer Screening which is currently used in several National Screening Programs. Geoffrey Hamilton-Fairley Geoffrey Hamilton-Fairley s entrepreneurial career started in 1982 when he founded a number of companies in the media sector. In 1988 he joined the board of Abingdon as CEO and subsequently became sole owner. Abingdon had a number of quoted and unquoted investments in a variety of sectors; Property, Corporate Finance, Unit Trusts, an ITV franchise (TVS) and a few early technology companies perhaps the most noteworthy being Fortronic which developed the first magnetic strip plastic card swipe technology. In 1998 he launched Premium TV (PTV) securing a contractual joint venture with Eurosport to create British Eurosport. As CEO of PTV Geoffrey Hamilton-Fairley instigated and oversaw the highly complex development of the largest integrated broadband and internet sports broadcasting platform in the world. Over the past ten years Mr Hamilton-Fairley has increasingly focussed his time and energies on the health sector. Geoffrey Hamilton-Fairley has dedicated the past 5 years to the development of Oncimmune Ltd, serving as its Executive Chairman. The company has a unique technology for detecting the immune response to cancer at a very early stage in a cancer s development - up to 4 years before current screening technologies. Peter Johnstone Peter Johnstone was raised in Gresham, Oregon. He graduated from the United States Naval Academy in 1979, completing a Master of Arts degree in Communication from Oklahoma University in 1985 and an MD degree from the Uniformed Services University of the Health Sciences in He completed Residency in Radiation Oncology subsequently at the National Cancer Institute. In December, 2007, Dr. Johnstone was named Chair and William A. Mitchell Professor of Radiation Oncology at Indiana University (IU). He was named President and Chief Executive Officer of the IU proton center in August, 2008, and director of IU cyclotron operations in January, Dr. Johnstone was selected to the ACR Board of Chancellors in 2011, and served as President of the American Radium Society in 2010, and President of the Society for Integrative Oncology in Michel Jourlin Michel Jourlin was born in Saint-Etienne, France, and graduated in Mathematics at the University of Lyon 1. After obtaining his PhD in Pure Mathematics, he turned his research towards Image Processing. His most important contribution is the development of the LIP (Logarithmic Image Processing) Model, which offers a particularly efficient framework for Biomedical and Industrial Image Processing, due to its strong physical and mathematical properties added to its consistency with the Human Visual System. After ten years as Scientific Director of the Engineer School CPE-Lyon, Michel Jourlin is currently Full Professor at the University of Saint- Etienne and develops his research at the CNRS Laboratory Hubert Curien. Dan Krewski Dr. Krewski is Scientific Director of the McLaughlin Centre for Population Health Risk Assessment at the University of Ottawa, and Professor in the School of Epidemiology, Public Health and Preventive Medicine. He holds a Natural Research Council of Canada Research Chair in Risk Science, focusing on risk assessment and management of a wide range of technological and other risk issues. From 2007 to 2012, he served as Associate Scientific Director of PrioNet Canada. Dr Krewski also serves as Chief 143

76 - International Prevention Research Institute About Us Risk Scientist and CEO of Risk Sciences International, a Canadian company established in 2006 in partnership with the U. of Ottawa to help public and private sector clients in understanding, managing, and communicating risk. Prior to 1998, Dr. Krewski held several research and management positions in Health Canada, including as Director of Risk Management and Senior Branch Advisor for Health Risk Assessment. While with Health Canada, Dr. Krewski laid the groundwork for the Departmental Decision-Making Framework for Identifying, Assessing, and Managing Health Risks. Dr. Krewski served as Chair of the National Research Council s Committee on Toxicity Testing and Assessment of Environmental Agents. More recently, Dr. Krewski was closely involved in the US Environmental Protection Agency s NexGen project that proposed a new framework for the next generation of risk science in He also chaired the US Health Effects Institute Diesel Epidemiology Panel evaluating epidemiological evidence on diesel exhaust emissions from a risk assessment perspective. Dr. Krewski is a Fellow of the Society of Risk Analysis and the American Statistical Association, and a lifetime National Affiliate of the US National Academy of Sciences. He currently serves on the Scientific Advisory Committee of the Council of Canadian Academies, which provides science advice to the federal government on a wide range of issues of national and international importance. Carlo La Vecchia Carlo La Vecchia received his medical degree from the University of Milan and a MSc in clinical epidemiology from Oxford University. He is recognized worldwide as a leading authority in cancer aetiology and epidemiology. Presently, he is Professor of Epidemiology at the School of Medicine at the University of Milan. Dr. La Vecchia serves as an editor for numerous clinical and epidemiologic journals. He is among the most renowned and productive epidemiologists in the field with over 1,840 peer-reviewed papers in the literature and is among the most highly cited medical researchers in the world, per ISIHighlyCited.com, the developer and publisher of the Science Citation Index (h index, 125). Dr. La Vecchia is an Adjunct Professor of Medicine at Vanderbilt Medical Center and the Vanderbilt-Ingram Cancer Center. Dr. La Vecchia is a temporary advisor at the World Health Organization in Geneva, and a registered journalist in Milan. He was Adjunct Associate Professor of Epidemiology at Harvard School of Public Health between 1996 and 2001 and Professor of Epidemiology at the University of Lausanne ( ), was Senior Research Fellow at the International Agency for Research on Cancer IARC/WHO between 2006 and 2008, and Head of the Department of Epidemiology at the Mario Negri Institute between 2007 and Dr. La Vecchia s main fields of interest include cancer epidemiology and the risk related to diet, tobacco, oral contraceptive use and occupational or environmental exposure to toxic substances; and analysis of temporal trends and geographical distribution of mortality from cancer, cardiovascular diseases, perinatal and other selected conditions. Bernard Levin Professor Bernard Levin earned his medical degree from the University of the Witwatersrand Medical School in Johannesburg, South Africa. He held academic appointments in the Department of Medicine at the University of Chicago and then served as Chair of the Department of Gastrointestinal Medical Oncology and Digestive Diseases at University of Texas M.D. Anderson Cancer Center until his appointment as Vice President for Cancer Prevention and Population Sciences. He retired from MD Anderson Cancer Center in November 2007 and was appointed as Professor Emeritus. He has served as Chair of the American Cancer Society s National Advisory Task Force on Colorectal Cancer, founding co-chair of the National Colorectal Cancer Roundtable, President of the International Society of Gastrointestinal Carcinogenesis and founding Chair of the World Gastroenterology Organization Foundation whose mission is to raise funds for the training of gastroenterologists in low-resource countries. He was co-editor, with Peter Boyle, of the World Cancer Report published by IARC/WHO in December He currently serves on the editorial board of the Journal of the National Cancer Institute. His research interests include molecular markers for detection of colorectal cancer and better methods for enhancing public awareness of colorectal cancer prevention. His public health interests lie in enhancing medical care in developing countries. Julian Little Julian Little, PhD holds a Canada Research Chair in Human Genome Epidemiology, and is a Professor in (and Chair of) the Department of Epidemiology and Community Medicine at the University of Ottawa. His PhD, from Aberdeen University, was on problems of ascertainment of congenital anomalies. He worked for the EUROCAT Central Registry in Brussels, as a lecturer in epidemiology in Nottingham University, as an epidemiologist in the International Agency for Research on Cancer in Lyon, and as Professor of Epidemiology at Aberdeen University, during which he spent a sabbatical year at the Office of Genomics and Disease Prevention, CDC, Atlanta. His current research includes empirical work on potential biases in genetic association studies, harmonization of biobanks, the potential value of germline genetic profiling in prediction of risk for chronic disease, the potential value of information on family history in predicting risk for chronic disease, potential value of information on HPV and other factors in management of women with low-grade cervical abnormalities, and etiology of cleft lip and palate. Albert Lowenfels Albert Lowenfels has made major contributions in the field of alcohol as a cause of common chronic conditions. Initially trained as a surgeon, he has pursued a second career in gastrointestinal disease epidemiology with a focus on the role of alcohol. His special areas of interest, as represented in more than 200 peer-reviewed publications, include alcohol-related illnesses, epidemiology of pancreatic cancer, and the relation between benign and malignant digestive tract disease. He is currently Professor of Surgery and Professor of Community and Preventive Medicine at New York Medical College. He is also Senior Advisor in the Department Epidemiology and Biostatistics at the European Institute of Oncology in Milan, Consultant in the Department of Community and Preventive Medicine at Weill-Cornell Medical College in Qatar, and External Advisor for a NIH-funded program to detect gene(s) for familial pancreatic cancer (PACGENE). He is a member of the American Gastrointestinal Association, of the American Pancreatic Association, and of the Panc4 Consortium, an international group of investigators associated with case-control studies of pancreatic cancer who have agreed to pool their data for cooperative studies. Melinda Magyari Melinda Magyari, born in Transylvania, obtained her medical degree from the University of Southern Denmark. In 2008 she specialised in neurology and obtained her PhD at the University of Copenhagen in Dr. Magyari is currently the Head of The Danish Multiple Sclerosis Registry and a consulting neurologist at the Danish Multiple Sclerosis Centre, at Copenhagen University Hospital, Rigshospitalet. Dr. Magyari s major research area is in multiple sclerosis epidemiology, with an interest in gender differences in multiple sclerosis. Her current research includes studies on the risk factors, comorbidities and the social consequences of multiple sclerosis and observational studies on treatment effect and safety of disease modifying drugs. She participates extensively in several international multiple sclerosis databases. Donald Mattison Donald Mattison has had a distinguished career in medicine and public health. In 2012 he was concurrently appointed Chief Medical Officer and Senior Vice President of Risk Sciences International and Associate Director of the McLaughlin Centre for Population Health Risk Assessment at the University of Ottawa. In 2013 he was also appointed Medical Advisor to QuarterWatch: Monitoring FDA MedWatch Reports, Institute for Safe Medication Practices. From 2002 to 2012 he was Senior Advisor to the Director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. He has also been the Medical Director of the March of Dimes, Dean of the Graduate School of Public Health at the University of Pittsburgh, Director of Human Risk Assessment at the FDA National Center for Toxicological Research and on the faculty of the University of Arkansas for Medical Sciences, University of Pittsburgh, and Columbia University. During this time, he has also served in the US Public Health Service, with deployments for medical and public health support. In his research, he has led drug development in paediatrics and obstetrics, including safety signal identification and evaluation. He has also led the development of methods in risk assessment for reproductive and developmental endpoints. Currently his research explores approaches to understand drug use, effectiveness, safety and risk-benefit communications, as well as environmental impacts on population health. Dr. Mattison earned a BA (Chemistry and Mathematics) from Augsburg College in Minneapolis, an MS Chemistry from the Massachusetts Institute of Technology and a MD from the College of Physicians and Surgeons, Columbia University. His clinical training in Obstetrics and Gynaecology was at the Sloane Hospital for Women in the Columbia Presbyterian Medical Center in New York. His training in Pharmacology and Toxicology was at the National Institutes of Health, Bethesda, MD. He has published more than 200 peer reviewed articles. In 1997, he was elected a Fellow of the American Association for the Advancement of 145

77 - International Prevention Research Institute About Us Science, in 1999, a Fellow of the New York Academy of Medicine, in 2000 a member of the Institute of Medicine, in 2005 Distinguished Alumni of Augsburg College and in 2009 a Fellow of the Royal Society of Medicine. Jean-Claude Mbanya Jean Claude Mbanya is Professor of Medicine and Endocrinology at the Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Director Biotechnology Center and Coordinator Doctoral School of Life, Health and Environmental Sciences, University of Yaoundé 1 and Adjunct Professor of Medicine, Endocrinology Diabetes, at the University of Technology. He is also Consultant Physician and Director of the National Obesity Centre at the University Teaching Hospital in Yaoundé. He is Past President of the International Diabetes Federation. He initially studied in Cameroon where he obtained his MD and trained at the University of Newcastle upon Tyne where he obtained a PhD and later became a Member of the Royal College of Physicians. He is a Fellow of the Royal College of Physicians, London and Doctor philosophiae honoris causa, University of Oslo. Prof. Mbanya also currently serves on several international scientific and WHO advisory groups, including the Expert Advisory Panel on Chronic Degenerative Diseases and Diabetes and the WHO African Advisory Committee on Health Research and Development. He is a recipient of several international awards. His major interests include diabetes and other noncommunicable diseases epidemiology and prevention, integration of diabetes care in the health care system of developing countries, diabetes complications, obesity and physical activity as risk factors of non-communicable diseases. William R. Miller William R. Miller is an Emeritus Professor at the University of Edinburgh. He completed his BSc and PhD degrees at the University of Leeds before receiving a DSc from the University of Edinburgh. William R. Miller is past Chairman of the Scientific Advisory Board of the Breast Cancer Campaign, past Chairman of the British Breast Group, and was Secretary to the British Association for Cancer Research. He is a member of various editorial boards, including the British Journal of Cancer, New Directions in Endocrine Treatment of Breast Cancer, and The Breast. Miller has published more than 250 articles and made more than 100 presentations at national and international societies and symposia. His research interests include cell biology and tumour endocrinology of breast cancer. He currently organises and runs scientific meetings and editing proceedings - most notably Controversies in Breast Cancer, an annual symposium which is now in its ninth year. Andrew Morris Andrew Morris is the Professor of Diabetic Medicine and Head of Planning and Development in the College of Medicine Dentistry and Nursing at the University of Dundee. He leads a translational research team that focuses on the epidemiological and molecular aetiological basis of diabetes and its complications. He also has a major interest in how managed clinical networks can improve patient care across geographical boundaries. He leads the internationally acclaimed DARTS research study, has published over 170 original papers and has attracted over 20 million in peer reviewed grant funding. He is the principal investigator on many clinical studies of new therapeutics of diabetes as well as genetics of diabetes, including the Wellcome Trust United Kingdom Case Control Collection for Type 2 Diabetes that is recruiting 15,000 individuals. He is also the principal investigator of Generation Scotland, a study of the genetic health in 50,000 Scots. He was awarded the RD Lawrence Award by Diabetes UK in 2003, the Saltire Society Scottish Science Award in 2005 and is a Fellow of the Royal Society of Edinburgh, Scotland s national academy of science and letters. He was appointed by the Minister for Health and Community Care to be Lead Clinician for diabetes in Scotland ( ) and led a national programme of quality improvement in diabetes care. He is also the ehealth Director of NHS Tayside and chairs the Translational Medicine Research Collaboration Steering Group, unique 50 million collaboration between all Medical Schools in Scotland and the pharmaceutical giant Wyeth. Recently he has been appointed as a Chairman of The Wellcome Trust Expert Review Group Genetics, Genomics and Population Research. Paul Ndom Paul Ndom was born in Cameroon and graduated MD from the Faculty of Medicine (CUSS), University of Yaounde. He is Associate Professor of Medicine at the University of Yaounde I, in charge of training in oncology; Head of Medical Oncology Service in Yaounde General Hospital since 1997; President of the NGO SOCHIMIO; Past President of the African Organization for Research and Training in Cancer (AORTIC); Past Director of INCTR in Cameroon; Permanent Secretary of the European and African Congress in Oncology since 2001; Local PI in several research protocols in Yaounde in Kaposi sarcoma, Breast cancer, CML and AIDSrelated malignancies. Alan Nelson Alan Nelson, PhD, is the founder, Chairman and CEO of VisionGate, Inc., founder and Chairman of Nortis, Inc., founder and President of the Predictive Health Analytics Institute (PHAIT), and the former Executive Director of the Biodesign Institute at Arizona State University where he also served as full professor of Bioengineering and of Physics. He holds an appointment as an Associate Member of the Arizona Cancer Center with the University of Arizona. In 2001, he founded VisionGate to develop groundbreaking technology for lung cancer screening using a noninvasive sputum test analyzed on a new device called the Cell-CT, the world s first isotropic-resolution 3D microscope, addressing the world s number one cancer killer. This breakthrough technology has the potential to save tens of millions of lives. Previously, Dr. Nelson was the founder, President and CEO of NeoPath, Inc., a company dedicated to eradicating cervical cancer by inventing and developing the FocalPoint. The technology is now standard of care throughout the world and is credited with saving over 100,000 women s lives. Dr. Nelson was on the tenured faculty at UW where he directed the graduate Medical Imaging Program. Before joining UW, he was an associate professor appointed jointly at MIT and Harvard where he held the W.M. Keck Foundation endowed chair and directed the graduate Radiological Sciences Program. He has decades of senior executive experience in the leadership, management and accountability of large complex programs, using professional project management, and he is certified in quality systems regulations, including ISO-9001 and FDA QSRs and GMP. He brings an in-depth knowledge and experience in translational work and clinical trials for FDA 510(k) and Class III PMA clearances. He is trained in financial accounting, and his companies have passed rigorous government audits with high marks. In the States of Washington and Arizona, Dr. Nelson changed the State Ethics Law and re-wrote the State Intellectual Property Policy, respectively, to facilitate more streamlined and successful technology transfer. Dr. Nelson holds 145 issued patents and has published 120 peer-reviewed papers in the field of biomedical imaging. He received his PhD in Physics/Biophysics from the University of California, Berkeley. He is driven to have impact. Twalib Ngoma Twalib Ngoma is one of Africa s foremost radiation oncologists with special interest in cancer control. He trained at the Christie Hospital in Manchester and Beatson Oncology Centre in Glasgow in the 1980 s and then went back to his home country, Tanzania, where he became the Executive Director of the Ocean Road Cancer Institute. He was also the Director of INCTR s Tanzania office 147

78 - International Prevention Research Institute About Us and a member of the Standing Advisory Group on Nuclear applications (SAGNA) which advises the IAEA Director General on the Agency s activities in the application of nuclear techniques carried out within the programmes of Food and Agriculture, Human Health, Water Resources, Assessment and Management of the Marine and Terrestrial Environments, and Radioisotope Production and Radiation Technology. He has a leading role in Tanzania as the local coordinator and Secretary of the steering committee for the development of a National Cancer Control Strategy and Action Plan. After the selection of Tanzania by the International Atomic Energy Agency to be one of the PACT Model Demonstration Sites for the development of multidisciplinary capacitybuilding projects in cancer control, Twalib Ngoma became a PACT Consultant and National Coordinator. As past President of the African Organization for Research and Training in Africa, he is also addressing the challenges of controlling cancer throughout the continent, where the obstacles posed by limited resources mirror those of his native country. Ibolya Nyulasi Professor Nyulasi is the Head the Department of Nutrition and Dietetics at Alfred Health, Melbourne Australia. Alfred Health is a multi-campus health service that includes a large quaternary teaching hospital with a major trauma, burns services and a 45 bed ICU. It also has a comprehensive cancer program including radiotherapy and bone marrow transplant service. Ibolya is the current President of the Australasian Society of Enteral and Parenteral Nutrition AuSPEN a position she has held in the past and is a life member of the society. She is also member of the ESPEN faculty and holds an Adjunct Associate Professor position in the Department of Medicine at Monash University, Melbourne. In 2016 she was recognised by the European Society for Clinical Nutrition and Metabolism by a Career Achievement Award for her contribution to nutritional sciences and improving the quality of nutritional care of patients. Ibolya started working as an ICU dietitian in the late 1970s at Royal Melbourne Hospital following a period at the Hammersmith hospital in London. She was the Australasian editor of the journal Nutrition from 1998 to She was involved with the development of Monash University Dietetics course which she later led as the course convenor and to the successful accreditation of the new course. In 2003 she was the recipient of grant from the Australia India Council to develop a train the trainer nutrition education program for disease related and maternal child health nutrition in rural India. She chairs The Alfred Hospital small project committee and the Allied Health research committee. Although she heads a clinical department, she has a long-standing interest in research and has published 45 papers in peer reviewed journals in collaboration with researchers across the world. Nyulasi has a major interest in the identification and treatment of malnutrition and the role of nutrition in the care of the critically ill. Christian Partensky Christian Partensky has been Professor of Digestive Surgery at the Claude Bernard University of Lyon since 1977 and Head of the Department of HPB Surgery at the Edouard Herriot Hospital of Lyon since from 1981 to After 2007, he was either concomitantly or sequentially, consultant for surgery, emeritus professor, member of the French High Health Authority Committee for Evaluation of Medical Devices and Medical Technologies, and IARC Senior Visiting Scientist. His main area of interest has been pancreatic cancer. He is a member of the French Academy of Surgery, of the French Association of Surgery, a senior member of the European Surgical Association and fellow of the American College of Surgeons. He was awarded the Order of the French Legion of Honour in Markus Pasterk Markus Pasterk was born in Klagenfurt, Austria and studied Molecular Biology at the University of Vienna, where he received a MSc degree in Early in his career he decided to transition from research to research management. In 2001 Markus Pasterk was promoted Director of the newly created Life Sciences Division within the Austrian Ministry of Science, with responsibilities of research, in particular genomics, biotechnology and medical research. He became the Austrian delegate to the programme committee of the Life Sciences, Genomics and Biotechnology for Health Programme of the 6th EU-Framework Programme. He was also responsible for Austria s international research infrastructure memberships like EMBL and EMBC. He progressed to become the first full-time Deputy Director General for Research in the Ministry of Science in Austria and then to be Scientific Coordinator at the International Agency for Research on Cancer. From the establishment of in April 2009 to December 2013 Markus Pasterk was Chief Operating Officer and Vice President, Science, at the International Prevention Research Institute. In December 2013 he took up the key position of Administrative Director at the new BBMRI-ERIC based in Graz in his native Austria. Paul Perrin Paul Perrin has been Professor of Urology at the University of Lyon since He received his degree in Medicine from the Claude Bernard University in Lyon and his postgraduate training included an internship and residency in Urology at the Hospices Civils University Hospital. He was awarded a fellowship with Roger Barnes in Loma Linda University in California. He was appointed as Dean of the Laennec Medical School and then chaired the Department of International Exchanges Program for students for the Claude Bernard University Lyon 1. He served as Chief of Urology at the Lyon University Hospital from 1986 to 2008 and chaired the Department of Surgery at the Lyon Sud University Hospital from 2005 to He is currently Consultant for surgery to the Claude Bernard University. His main areas of interest are the use of ultrasound in urology, evaluation of outcomes for the treatments of BPH and clinical research in the field of prostate cancer. He is an active member of the French Urologic Association, European Urologic Association and corresponding member of the American Urologic Association. Chris Robertson Chris Robertson is a statistician whose long-term research interests have focussed on the application and development of statistical modelling in epidemiology. Since 2002 he has had a joint appointment as Professor of Public Health Epidemiology in the Department of Mathematics and Statistics at the University of Strathclyde, Glasgow, and also at Heath Protection Scotland (HPS). From 1995 to 2001, he was Head of Biostatistics and Vice Director in Epidemiology and Biostatistics in the European Institute of Oncology, Milano. Prior to that he was a lecturer and senior lecturer in Mathematics and Statistics and Modelling Science at Strathclyde University. Presently his main research is in statistical modelling of infectious diseases and in designing epidemiological studies for disease surveillance systems. He is currently involved with the Ethics Committee and the Data Safety Monitoring Committee of the International Breast Cancer Study Group, and with the West of Scotland Research Ethics Committee. He is also a member of the Scientific Advisory Group for Interdisciplinary Centre for Human and Avian Influenza Research (Edinburg University), and of the Scientific Pandemic Influenza Advisory Committee Subgroup on Modelling for the UK Department of Health. 149

79 - International Prevention Research Institute About Us Hans Joachim Schmoll Prof. HJ Schmoll obtained his medical degree in 1970 from Hanover Medical University. Currently, Prof. Schmoll is the Head of the Division of Hematology and Oncology and Director of the Center for Cell and Gene Therapy, Martin Luther University, Halle, Germany, and Professor of Medicine at Martin Luther University, Germany. He has published over 355 peer review papers with focus on the biology and particular treatment of advanced colon and rectal cancer as well as on germcell cancer. He has been leading author of the first European consensus guideline for germcell cancer in 2004 and of the first international ESMO consensus guideline for diagnosis and treatment of colon and rectal cancer in Pierre Singer Pierre Singer has over 30 years of clinical and academic experience. He was born in France attending medical school at the Louis Pasteur Faculty of Medicine of Strasbourg. Since 1995 he has been the Director of the General Intensive Care Department, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel. Since 2006, Dr. Singer has also been Head of the Institute of Nutrition Research at Rabin Medical Center, Director of the Metabolism Laboratory at the Felsenstein Medical Research Center and Professor of Anesthesia and Intensive Care at the Sackler School of Medicine, Tel Aviv University. Dr. Singer was President of the Israel Society of Intensive Care Medicine ( ), Israel Society for Clinical Nutrition (ISCN) from More recently, Dr. Singer held positions as Chairman of the Department of Anesthesia and Intensive Care, Sackler school of medicine, Tel Aviv University ( ), and Chairman of the European Society for Clinical Nutrition and Metabolism (ESPEN) ( ). He has been appointed as associate editor, section editor or co-editor in various journals such as Intensive Care Medicine, Clinical Nutrition, Clinical Nutrition Experimental, Nutrition or JPEN. From 2002, he has been the Chairman of the Annual Israel Nutrition Week. His research interests center around nutrition and metabolism, sepsis, respiratory disorders technologies. Dr. Singer has supervised more than 50 clinical and academic research theses. He has received numerous awards and grants throughout his career. He is co-author of the teaching modules on Nutrition in the ICU from ESPEN (LLL) and ESICM (PACT) as well as of the ESPEN 2000 Parenteral Nutrition in the ICU guidelines. Dr. Singer has presented over 250 lectures, and had more than 200 invited papers at scientific meetings. He has published more than 125 original articles, 30 review articles, 23 book chapters, and 175 abstracts. He is the editor of a recent book entitled: Nutrition in the ICU: Beyond Physiology. Temple F. Smith Temple Smith graduated with a PhD in Nuclear Physics from University of Colorado. He is a co-developer of the Smith-Waterman sequence alignment algorithm, and was one of the founders of GenBank at Los Alamos. He also founded the Molecular Biology Computer Research Resource at the Dana-Farber Cancer Institute, which later became the BioMolecular Engineering Research Center at the College of Engineering at Boston University. At Boston University he is a professor in the departments of Biomedical Engineering and Pharmacology. He has published nearly two hundred original research journal articles, a dozen review articles and four book chapters. Temple Smith is also a co-founder of Modular Genetics Inc., a gene engineering company. His research is centred on the application of various computer science and mathematical methods for the discovery of the syntactic and semantic patterns in nucleic acid and amino acid sequences, and their evolution. These include the development of new sequence pattern extraction tools (PIMA), multi-domain dissection methods, and protein inverse folding or threading prediction algorithms. Temple Smith has carried out research applications exploiting such methods on problems ranging from the time calibration of HIV and Papilloma viral evolution through the modelling of the 3D structure of the WD repeat protein family and that of the translational GTPases. His current focus is on early evolution, for example, that of a novel family of apoptotic regulatory proteins, the Lifeguard family and the ribosomal proteins. Cristina Stefan Cristina Stefan is the President-Elect of AORTIC (African Organisation for Research and Training in Cancer). She will be President of AORTIC She is also past Vice-President of the South African Medical Research Council where she was responsible for the strategic planning of research (with a special focus on NCDs) as well as education, building up capacity, providing leadership and assuming accountability for the strategic and operational planning of the organisation. A paediatrician by profession, she qualified a few years later as an oncologist, completing a Masters in Epidemiology at York University and a PhD in medical education. She chaired, until 2014, the paediatric haematology oncology unit at Tygerberg Hospital, Stellenbosch University, where she founded the African Cancer Institute. At AORTIC, she is currently the Co-chair of African research, chair of paediatric oncology and chair of African Cancer Economics network. Her activity included the first twinning program in oncology between two African countries, cancer education and research activities, cancer registry as well as contributions to various African National Cancer Control Plans. She serves as an advisor to the Minister of Health in South Africa and various other African committees and groups. Frank Sullivan Frank Sullivan is a medical graduate of Glasgow University. Following clinical training in the West of Scotland, fourteen years as a partner in a practice in Blantyre during which time he completed a PhD and a year s work in the Seychelles, he was appointed to the NHSTayside Chair of Research and Development in General Practice and Primary Care in the University of Dundee. Director of the Scottish School of Primary Care since 2007, he is now also the Director of the Division of Clinical Population Sciences Education in Dundee. Frank Sullivan s research interests lie mainly in health informatics and community based trials, covering the spectrum from recordlinkage of electronic health records to decision support to the evaluation of complex interventions. He has published widely on different types of primary care research notably in the management of long-term conditions such as diabetes and coronary heart disease in the community. He led the Bell s trial which involved more than half of all general medical practices in Scotland whose main paper in the NEJM won the BMA research paper of the year in In the past, Frank Sullivan was Director of the East of Scotland Primary Care Research Network (EastRen) and a member the MRC College of experts and of the Member UK Office for Strategic Co-ordination of Health Research (OSCHR) E-Health Records Board. More recently his work has extended to two large European projects which extract and link primary care and research data. He was a co-author of the BMJ series and book on Health Informatics. Richard Sullivan Richard Sullivan is Director of External Affairs at Kings Health Partners Integrated Cancer Centre and Director of the new KHP Centre for Global OncoPolicy Health, a joint partnership with the European Institute of Oncology. He is also Visiting Professor (Cancer and Public Health) at Universidad Catolica, Santiago de Chile. Richard Sullivan qualified in Medicine at St. Marys Hospital, London. Following training in surgery he undertook a PhD and post-doctoral research in cell signalling at University College London. He then worked in a senior role in the pharmaceutical industry before spending 10 years with Cancer Research UK as their clinical director. Richard serves on multiple international advisory boards, e.g. Charite Comprehensive Cancer Centre Berlin, Irish Clinical Oncology Group, Kings College Marjan Centre for Conflict Conservation, Pfizer Policy Advisory Board and is past UK Director of the Council for Emerging National Security Affairs (CENSA), a Washingtonbased national security think-tank. His current research programmes cover the social and political policy of cancer (OncoPolicy), including e-policy and global public health challenges in 151

80 - International Prevention Research Institute About Us transitional, high-risk conflict areas focusing on DR Congo, Afghanistan and Libya. Robert JS Thomas Robert JS Thomas graduated in Medicine from the University of Melbourne and trained in surgery at the Royal Melbourne Hospital. He commenced surgical practice in Melbourne based at the Royal Melbourne Hospital where he was deeply involved in the teaching of medical students. He then became Professor and Director of Surgical Oncology at the Peter MacCallum Cancer Centre. He was instrumental in the development of the discipline of Surgical Oncology in Australasia and was responsible for the creation of the Surgical Oncology Group within the Royal Australasian College of Surgeons. He now holds the title of Distinguished Fellow within the Division of Surgical Oncology at Peter Mac. His current position is Chief Cancer advisor for the Victorian Government. He is also Chair of the Victorian Cancer Agency with responsibility for the translational research agenda and funding of cancer research in Victoria. Robert Thomas has been heavily involved in the development of cancer reforms within Australia, has been past President of COSA, Chair of the National Committee creating the Colorectal Cancer Guidelines, and was a member of the Ministerial Taskforce on Cancer. He has published over 100 peer reviewed scientific papers and book chapters. He was honoured by the RACS with Excellence in Surgery Award. He is a past Editor-in-Chief of the ANZ Journal of Surgery and has served as Chair of NHMRC panels. He has ongoing research interests in the molecular pathology of gastrointestinal tumours. He has recently been appointed Co-Chairman of The National Cancer Expert Reference Group, a high level group to advise the Federal and State Health Ministers on cancer matters. Jean-Louis Touraine Professor Touraine has been a Professor in Nephrology, Immunology and Transplantation at the Claude Bernard University of Lyon since From 1986 to 2012 he was Head of the Department of Transplantation and Clinical Immunology, Hôpital Edouard Herriot. In the field of immunodeficiency diseases his scientific contributions include the discovery of the Bare Lymphocyte Syndrome, the first successful foetal liver stem cell transplants in humans, the first in utero foetal stem cell transplants into human foetuses, bone marrow and thymic epithelial cell transplants, and other studies and treatments. In the field of renal and pancreatic transplantation he is responsible for new immunosuppressive therapies and prevention of complications. In the field of HIV infection, he completed studies of the mother-to-child transmission and new treatments and gene therapy against HIV in the humanized SCID mouse. In the ethics of transplantation, his work includes foetal development and HIV infection. Finally, in the field of immunology, he has worked on immunological tolerance, T-cell differentiation, role of HLA antigens and antigen recognition by T-cells. Professor Touraine has authored over 1000 scientific papers and 35 scientific books. Since 2007, Professor Touraine is an elected member of the French Parliament (Assemblée Nationale) and a member of The Parliamentary Office for Scientific and Technological Assessment. Ed Trapido Dr. Ed Trapido is Associate Dean for Research at the Louisiana State University School of Public Health, Professor and Wendell Gauthier Chair for Cancer Epidemiology, and the Deputy Director for Population Science in the Stanley S. Scott Cancer Center, and past president of the American College of Epidemiology. He also serves as the lead external evaluator for the International Atomic Energy Agency s and World Health Organization s Program of Action in Cancer Therapy. From , Dr. Trapido was at the U.S National Cancer Institute, as Deputy Director for International Cancer Control in the Office of the NCI Director, and before that, Associate Director of the Epidemiology and Genetics Research Program within NCI s Division of Cancer Control and Population Sciences. Dr. Trapido also co-chaired the Trans-NIH Tobacco and Nicotine Research Interest Group and served as the NCI liaison to the post 9/11 World Trade Center first responders studies. Before 2004, and between , Dr. Trapido was Professor and Vice Chair of the Department of Epidemiology and Public Health at the University of Miami Miller School of Medicine. Dr. Trapido also led the Southeast Regional Cancer Information Service, Florida Cancer Data System (Registry), Early Breast Cancer Detection Program, and the Southeast Comprehensive Cancer Control Coalition. Most of his research has been in tobacco control, cancer prevention and control, health disparities, early detection, and in HIV/AIDS. His recent research includes environmental epidemiology, working on the health effects of the Gulf Oil Spill which occurred in the Gulf of Mexico in April His degrees include an MS in Public Health from the University of North Carolina, and Master s and Doctor of Science degrees in Epidemiology from Harvard Murat Tuncer Murat Tuncer is a specialist in Paediatric Haematology (1991) in Hacettepe University Faculty of Medicine. Between 1997 and 2005, Professor Tuncer was Secretary General of the National Pediatrics Society, an Executive Committee member of International Children s Centre (ICC) ( ), the Union of Middle-Eastern and Mediterranean Pediatric Societies ( ), UNICEF National Committee ( ), Turkish Science Academy Cancer Committee ( ), and a member of the National Cordon Banking Committee ( ). Professor Tuncer currently holds the role of President of the Middle East Cancer Consortium (MECC) (since 2000), and the Asian Pacific Organization for Cancer Prevention (APOCP); he is presently Director of the Cancer Control Department in the Turkish Ministry of Health (since 2000). He has published over 170 international publications, edited 2 international, 4 national textbooks and hundreds of scientific posters in international congresses. Carlos Vallejos Sologuren Dr. Carlos Vallejos Sologuren is principal member of AUNA, one of the most important private healthcare services in Perú. In 1996, he founded the Sociedad Peruana de Oncología Médica, being its first President until In 1998, he was re-elected as President of the Sociedad Peruana de Oncología Médica. He was regional delegate of the Federation Latinoamericana de Sociedades de Cancerología. In 1999, he created ONCOSALUD, the largest private oncological services provider in Perú. One year later, he was elected Principal Investigator of Eastern Cooperative Oncology Group (ECOG), one of the most important scientific organizations in the World. From December 2002 to July 2006, he was the Director General of INEN. In July 2003, he was chosen as Regional Representative of the European Society for Medical Oncology (ESMO) for South America, and became part of the Editorial Committee of the Journal of Oncology. He is the author of the thesis Mieloma Múltiple (1968); and Leucemia Aguda (1987). He participated in more than 169 research projects related to oncology and published more than 60 scientific articles and almost 118 abstracts in several books and magazines. Vallejos Sologuren was Minister of Health of Perú, from July 2006 to December He has received over 46 awards. In 2008, he was elected Vice-President of the Executive Committee of the World Health Organization. In 2010, he was named Director Member of the 153

81 - International Prevention Research Institute About Us International Affairs Committee of the American Society of Clinical Oncology ASCO and became member of International Education Council of Molecular Targeted Therapy of Cancer (MTTC) as chair under ESMO s sponsorship. He returned to the role of Institutional Head of the Instituto Nacional de Enfermedades Neoplásicas (INEN), from February 2008 to January In 2011 he was named President of the Latin American Caribbean Society of Medical Oncology (SLACOM). In May 2012 he was named as Visiting Professor at the Universidad del Salvador in Argentina. Tran Van Thuan Tran Van Thuan was born in Bac Ninh, Vietnam and graduated MD, MSC and PhD from Ha Noi Medical University. He studied at Singapore General Hospital and in 1998, as a clinical fellow, completed a clinical training course on Medical Oncology at Mater Hospital in Sydney and undertook a management course for Cancer Control at the United States National Cancer Institute. Dr. Thuan is affiliated with the American Society of Clinical Oncology (ASCO) and the International Union Against Cancer (UICC). Van Thuan is Associate Professor of Medical Oncology at the National Cancer Hospital of Vietnam. He is Visiting Professor at the Graduate School of Cancer Science and Policy, National Cancer Center of Korea. He is author and co-author of many peer-reviewed scientific publications and books, including 85 articles in oncology. He is a board member of the Vietnam Cancer Society and served as scientific committee co-chair of the annual Vietnam National Cancer Control conference. Dr. Thuan was appointed as Deputy Director of National Cancer Hospital (2007), Director of National Cancer Hospital (2016) and as Director of National Institute for Cancer Control (2010). Dr. Thuan led three state-level research projects, and has been the principal investigator on many international clinical trials conducted in Vietnam. He is member of the advisory council on cancer control of the Government of Vietnam. He also has served on cancer protocol committees for the Ministry of Health. He is a member of the steering group in Health and Medical Sciences of Vietnam United States Joint Committee Meeting. Lars Vatten Lars Vatten was born in Trondheim, Norway, studied Medicine at the University of Tromsø and received a Master of Public Health in 1988 from the University of North Carolina. Two years later the University of Trondheim awarded him a PhD. In 1996, he became chair of Epidemiology at the Norwegian University of Science and Technology, Medical School, a post he still holds. Since 2008 Lars Vatten holds an honorary professorship at Bristol University and is a Visiting Scientist of Harvard School of Public Health since He has a wide research background, with interests covering the epidemiology of various cancers, cardiovascular diseases and diabetes, as well as complications of pregnancy and their consequences for both the mother and child. He has a particular interest in the developmental origin of chronic diseases. Lars Vatten has published more than 200 articles in scientific journals and is co-author of several books. Lars Vatten is a Member of The Norwegian Royal Academy of Sciences and in 2010 received the King Olav V s Prize for Cancer Research. Jim Vaught Jim Vaught spent 14 years at the U.S. National Cancer Institute (NCI), most recently as the Chief of the Biorepositories and Biospecimen Research Branch (BBRB) in the Cancer Diagnosis Program. He earned a BSc in chemistry from the University of Georgia and PhD in biochemistry from the Medical College of Georgia. His additional training and 155

82 - International Prevention Research Institute About Us research at Roswell Park Cancer Institute and the Michigan Cancer Foundation were in the areas of chemical carcinogenesis and drug metabolism. He has been working in the field of biorepository and biospecimen science for over 20 years. In 1999, he was one of the founding members of the International Society for Biological Environmental Repositories (ISBER) and was its second president. He was involved in organizing and writing parts of the first edition of ISBER s Best Practices for Repositories. In 2005, Dr. Vaught joined NCI BBRB and participated in the development of NCI s Best Practices for Biospecimen Resources and the office s other strategic initiatives. Since 2005 he has served as the NIH representative to the Interagency Working Group on Scientific Collections, which was created by the Office of Science and Technology Policy. He serves on several biobank advisory groups including for the Telethon-Italy Genetic Biobank Network; the Stellenbosch University (Cape Town) H3-Africa Governance Advisory Panel; and the Biobanques Network (France) Scientific Board. In addition to ISBER, Dr. Vaught is a member of the American Association for Cancer Research (AACR), the American Society for Pharmacology and Experimental Therapeutics, the European Society for Biopreservation Biobanking and the American Association for Clinical Chemistry. He is the author of nearly 70 peer-reviewed articles and book chapters. From 2006 to 2012 he was Senior Editor for Biospecimens and Biorepositories for the AACR journal Cancer Epidemiology, Biomarkers and Prevention. In 2012 he became Editor-in- Chief of Biopreservation and Biobanking, the official journal of ISBER. In 2013 Dr. Vaught was the recipient of ISBER s award for Outstanding Achievement in Biobanking. Dan Waitzberg Dan Waitzberg is a gastrointestinal surgeon and nutrologist. He received his medical degree from the University of São Paulo (FMUSP) in 1974 and completed his residency in surgery at the Hospital das Clínicas in Dr. Waitzberg obtained his Masters and PhD in surgery from the University of São Paulo, where he also became an Associate Professor from the Department of Gastroenterology in Dr. Waitzberg is the Director of Short Bowel Syndrome Ambulatory, Clinical Director of Nutrition Service, Founder and Director of Nutrology Residence at Hospital das Clinicas, University of São Paulo Medical School. In addition, he has been Director of the Laboratory of Investigation in Metabolism and Nutrition in Digestive Surgery at FMUSP and Founder and Director of GANEP - Nutrição Humana since In GANEP he developed several educational programs in clinical nutrition for the classroom and the internet including the yearly conference Ganepao. He is the Head of the Nutritional Support Team at the Institute of Cancer of the State of Sao Paulo (ICESP) and Hospital Santa Catarina. He is the Scientific Director of the Free Educational Portal of Clinical Nutrition for Health Practitioners since 1991, with 65 thousand registered members. His main research area is clinical and experimental nutrition, with special interest in inflammation, microbiota, molecular biology, and enteral and parenteral therapy, particularly immunonutrition and omega-3 fatty acids, in the context of malnutrition, surgery, obesity and cancer. He is member of several clinical nutrition societies all over the world and serves as a member of several editorial boards and has published over 130 articles in peer-reviewed journals, 120 in non-peer reviewed journals, more than 260 book chapters and 10 books. William Wood William Wood is a graduate of Harvard Medical School. He completed a residency in surgery at the Massachusetts General Hospital and a fellowship in surgical oncology at the National Cancer Institute. He is currently Professor of Surgery at Emory University School of Medicine in the division of Surgical Oncology in the Winship Cancer Institute. He has devoted his research efforts to oncology, first in the immunology of autoantibodies to tumour-associated antigens, then in clinical trials of the multimodality treatment of breast cancer. He has served as Chair of the Cancer and Leukaemia Group B Breast Committee, the Eastern Cooperative Oncology Breast Committee, the NCI Breast Intergroup, and Co-Chair of the NCI Breast Cancer Steering Committee, the Early Breast Cancer Trialists Collaborative Group [Oxford], and BIG-NABCG. He has been a Governor of the American College of Surgeons, a Director of the American Society of Clinical Oncology, and the Christian Medical Association, a member of the Board of Scientific Advisors of the NCI, and President of the Society of Surgical Oncology, the South-eastern Surgical Congress, the Georgia Surgical Association, and the Southern Surgical Association. He has received an honorary doctorate in medicine and surgery from the Universita Politecnica delle Marche, and honorary membership in several colleges and societies. Derek Yach Dr. Derek Yach has focused his career on advancing global health. He is currently the Executive Director of the Vitality Institute. Prior to that he was Senior Vice President of Global Health and Agriculture Policy at PepsiCo where he supported portfolio transformation and led engagement with major international groups as well as new African initiatives at the nexus of agriculture and nutrition. He has headed global health at the Rockefeller Foundation, been a Professor of Global Health at Yale University, and is a former Executive Director for Noncommunicable Diseases and Mental Health of the World Health Organization (WHO). At WHO, Dr. Yach served as cabinet director under Director-General Gro Harlem Brundtland, where he led the development of WHO s Framework Convention on Tobacco Control and the Global Strategy on Diet and Physical Activity. Dr. Yach established the Centre for Epidemiological Research at the South African Medical Research Council. He has authored or co-authored over 200 articles covering the breadth of global health, regularly publishes blog posts, and is cited by the Huffington Post, The New York Times and The Economist. Dr. Yach serves on several advisory boards including those of the Clinton Global Initiative, the New York Academy of Sciences, the NIH s Fogarty International Centre, and the Mass General Global Health Board. He is Chairman of the Board of Cornerstone Capital and sits on the Lancet Commission for Planetary Health. He is also the Chair of the World Economic Forum Global Agenda Council on Ageing. His degrees include an MBChB from the University of Cape Town; BSc (Hons Epi) from the University of Stellenbosch; an MPH from the Johns Hopkins Bloomberg School of Public Health; and a DSc (Honoris Causa) from Georgetown University. Muhammed Aasim Yusuf Muhammed Aasim Yusuf is a gastroenterologist with interest and expertise in therapeutic endoscopy in gastrointestinal cancer. He graduated from the King Edward Medical College, Lahore, in 1986 and trained in internal medicine in Canterbury, and then in Gastroenterology in Birmingham. He received his Membership of the Royal College of Physicians of the UK in 1991, and was elected a Fellow of the Royal College of Physicians of Edinburgh in In 1994, he returned to Pakistan to join the commissioning team at Pakistan s first tertiary care cancer centre, the Shaukat Khanum Memorial Cancer Hospital Research Centre, in Lahore. He became Head of the Department of Internal Medicine in 1999, and was appointed to the position of Medical Director in His main research and clinical interests are in gastrointestinal endoscopy, particularly as applied to cancer care. David Zaridze David Zaridze was born in Tbilisi, Georgia. He is member of Russian Academy of Medical Sciences and Russian Academy of Natural Sciences. He graduated from the Medical Institute in Tbilisi, Georgia (MD). He received a PhD from the Institute of Experimental and Clinical Oncology in Moscow in 1969 and DCc in 1977 from the Cancer Research Centre in Moscow. Initially trained as pathologist, he has pursued a second career in epidemiology of chronic diseases. He worked in Oxford University with Professor Richard Doll in From 1979 to 1985 he was affiliated with International Agency for Research on Cancer in Lyon, France, working in the Unit of Analytical Epidemiology. After returning to Moscow in 1986, he was appointed as Director of the Institute of Carcinogenesis, which is a part of the N. N. Blokhin Russian Cancer Research Centre. Today he is Director of the Department of Epidemiology and Prevention at the Russian Academy of Medical Sciences and he is President of the Russian Cancer Society. David Zaridze was and is still member of several national and international scientific committees, including the European Organization for Cancer Research and the International Agency for Research on Cancer. In December 2011, he received a title of Visiting Professor of Epidemiology of Oxford University. He has authored or co-authored over 200 peer-reviewed publications. Recently he has been appointed as a Deputy Director for Research at his Centre. Tongzhang Zheng Tongzhang Zheng is Professor of Epidemiology (environmental health) at the Yale School of Public Health. He received a D.Sc. from Harvard University in His research interests have been environmental pollution and human health, particularly in cancer epidemiology and aetiology related to environmental hormone disruptors, genetic susceptibility and gene-environmental interaction. His research emphasizes the role of organochlorine compounds (such as PCBs, DDE and other pesticides) in the aetiology of several major cancers in the United States including breast, Non-Hodgkin lymphoma, Hodgkin s diseases, multiple myeloma and testicular cancer. Zheng has considerable experience in conducting epidemiological studies in China. He is the Principal Investigator (PI) for a National Institutes 157

83 - International Prevention Research Institute About Us of Health (NIH) training grant studying air pollution, temperature changes and human health in 6 different cities with different types of air pollution in China. He is also PI for a case-control study of liver cancer in China and serves as Co-Investigator for a case-control study of indoor pollution, gene polymorphisms and risk of lung cancer in Xuanwei County in China. In 2007 he received an Honorary MA from Yale University Kurt Zatloukal Kurt Zatloukal is professor of pathology at the Medical University of Graz with specialisation in molecular pathology, focusing on metabolic and neoplastic diseases, mainly of the liver. He was a member of the Bioethics Commission at the Austrian Federal Chancellery and Austrian representative in the OECD taskforce on biological resource centres and the Roadmap Working Group of the European Strategy Forum on Research Infrastructure. Additionally, he acts as member of the steering committee of the P3G Consortium. In the context of the Austrian Genome Programme (GEN-AU), Kurt Zatloukal is coordinator of the pan- European Biobanking and Biomolecular Resources Research Infrastructure - BBMRI, which is funded by the European Framework Programme 7. This infrastructure aims at providing the technical, ethical, legal, and financial foundation to become a key resource in biomedical sciences, drug development and public health. Witold Zatoński Witold Zatoński, MD, PhD, is a Director and Professor in the Division of Cancer Epidemiology Prevention at Cancer Center Institute of Oncology in Warsaw, Poland. As founder and President of the Health Promotion Foundation, Professor Zatoński has been instrumental in launching numerous health campaigns implemented in Poland and other areas of Eastern Europe. Professor Zatoński has recently completed work on the HEM Closing the Gap project, a complex study examining health inequalities between eastern and western parts of the European Union. At present, Professor Zatoński implements project PONS, aimed at establishing an infrastructure for prospective cohort studies of population health in Poland. Professor Zatoński has been at the forefront of public health and tobacco control in Poland, Eastern Europe, and internationally, for over 35 years. A passionate activist and researcher, he has helped promote policy development through research and dissemination of research evidence and best practice. In 2006 he was awarded the Luther L. Terry award for Distinguished Career by the American Cancer Society. Miri Ziv Miri Ziv is a Medical Sociologist and serves as a consultant for the Israeli medical authorities, providing guidance on issues relating to cancer control. One of her main areas of expertise and interest lies in breast cancer advocacy. Miri is active both locally and abroad. She works towards initiating and implementing national projects, especially around cancer control. She initiated steps that led to the implementation of the National Mammography Screening Program in Israel, Skin Cancer Awareness Month, as well as multiple programs to raise awareness and promote early detection and methods of prevention and new means for rehabilitation. Miri earned a MA degree in Medical Sociology with distinction at the Tel-Aviv University, and completed the study requirements for the PhD. Additionally, she taught Medical Sociology at Tel Aviv University for about a decade. She is a graduate of the Lead Project of the NBCC and of the 92nd St. Y Ford Fellowship Program in New York Developing Community Leaders. Locally, she is a member of: The Israel National Health Committee, the Israel National Council of Oncology, the National Council for Women s Health, the National Council of Health Promotion, and an Executive Board Member of Israel Health Consumers coalition. Internationally, Miri has been serving since 1995 as a National Representative of the European Breast Cancer Coalition Europa Donna (E.D.). From she served at the Executive Board of the European Cancer League (ECL). In July 2006 she was selected to serve on the Executive Board of the Union for International Cancer Control UICC. In August 2008, she was selected for an additional term. The Israeli Association of Public Relations recently awarded Miri as Best CEO in Israel for her innovative and creative activities alongside her profound management skills, as well as the Nurit Kadatzaki-Roz Award from the University of Tel Aviv, for continuing efforts in the fight against cancer. A gold medal of appreciation was awarded to Miri Ziv by the Israeli Society For Clinical Oncology Radiation Therapy. Miri was elected as Global Cancer Ambassador by the American Cancer Society to participate in activities at UN headquarters and was invited to participate in the Israeli delegation to the historic UN General Assembly High-Level meeting on NCDs in September

84 - International Prevention Research Institute About Us Activity Report Invited Lectures and Talks Throughout 2015 and 2016, Senior Faculty and Faculty were very present in meetings worldwide. They were called upon to speak on topics ranging from analysis to policy, from disease - more broadly - to specific topics of interest to scientists, academia and policymakers at the highest level. Many additional talks and lectures are already scheduled for 2017 and Peter Boyle Inquiry into the Nature and Causes of the Health of Nations. University of Strathclyde, Glasgow, United Kingdom, February, 2015 Disposal of Chemotherapeutic Waste. Rhone Island Senate, Providence, Rhode Island, United States of America, April, 2015 Challenges in Disease Prevention and Control. Brown University, Providence, Rhode Island, United States of America, April, 2015 Global Public Health. Athens, Greece, April, 2015 Population-based Strategies to Reduce Mortality from (genito-urinary) Cancers. Moscow, Russia, June, 2015 Transforming Cancer Care Through Big Data. Barcelona, Spain, November, 2015 UKCTOCS: Data Monitoring and Ethics Committee. London, United Kingdom, December, 2015 Identification of Carcinogens. Monte Carlo, Monaco, February, 2016 Inequalities in Cancer Care and Outcome. IAPO, London, United Kingdom, April, 2016 Achieving Cancer Control. National Cancer Institute, Hanoi, Vietnam, October, 2016 Global Public Health. St Luke s Week Masterclass, Dublin, Ireland, October, 2016 Lung Cancer and Smoking. Johannesburg, South Africa, November, 2016 Philippe Autier Presentation at ICACT Congress. Paris, France, 4 5 February 2015 Lecture and Strengthening Links with the University. London, United Kingdom, March 2015 Member of the High Council for Health, Ministry of Health for Sunbed Legislation. Brussels, Belgium, 29 March 1 April 2015 Posters Presentation at ADA Boston, United States of America, 4 9 June Diabetes, diabetes treatments and lung cancer risk. Diabetes, diabetes treatments and lung cancer risk. Diabetes and cancer and impact of therapies: analyses of meta-analyses in Member of the High Council for Health, Ministry of Health for Sunbed Legislation. Brussels, Belgium, September 2015 Posters Presentation at ECCO Vienna, Austria, September Non-tumour risk factors for cutaneous melanoma relapse. The Logic of Cancer Screening Courses for the Eurocan Platform Summer School in Translational Cancer Research. Albufeira, Portugal, October Screening technologies for early detection LEXI Study Mortality in Belgium - Marc Arhyn for Cancer in Africa - Conseil Supérieur de la Santé. Brussels, Belgium, November 2015 Conference on Breast Screening. Paris, France, January 2016 Meeting on Early Detection and Screening of Priority Cancers. Cairo, Egypt, January 2016 Member of the High Council for Health, Ministry of Health for Sunbed Legislation. Brussels, Belgium, 4-6 February

85 - International - Prevention Research Institute 2009 About Us German Cancer Congress. Berlin, Germany, February 2016 Invited by Tata Memorial Center. Mumbai, India, 28 February 4 March 2016 Lixisenatide project/superior Health Council. Brussels, Belgium, 8-12 March 2016 INCA. Paris, France, April Expert testimony for mammography screening Preventing Overdiagnosis Congress. Barcelona, Spain, September Mammography screening effectiveness and overdiagnosis in the Netherlands. Effectiveness of lung cancer screening with low-dose computed tomography: A systematic review and meta-analysis Member of the Jury for WALInnov 2016, Wallonie s Universities Meeting. Brussels, Belgium, 5-12 October 2016 Courses for the Eurocan Platform Summer School in Translational Cancer Research. Albufeira, Portugal, October 2016 General meeting for Episearch at Jules Bordet Institute. Brussels, Belgium, November 2016 Member of the High Council for Health, Ministry of Health for Sunbed Legislation. Brussels, Belgium, 30 November 2 December 2016 Ministry of Health, Cancer Cluster in Fernelmont. Brussels, Belgium, December 2016 Mathieu Boniol Journée Nationale de la Société Française de Photodermatologie. Angers, France, 13 March 2015, Addiction solaire et cabines de bronzage, le point de l épidémiologiste Société Française de Photobiologie. Journées Photoprotection, Paris, France, 4-5 June 2015, Exposition professionnelle aux UVs solaires Table Ronde Société Française de Radioprotection. Paris, France, 1 December 2015, Ultraviolets naturels et artificiels et risque de cancers 3Rd International Conference on UV And Skin Cancer Prevention. Melbourne, Australia, 7-11 December 2015, Monitoring of UV exposure in France children, adults and outdoor workers 3rd International Conference on UV and Skin Cancer Prevention. Melbourne, Australia, 7-11 December 2015, Screening for melanoma: Lessons from the German screening program WHO Intersun Programme. 5th International advisory committee meeting, Bruxelles, Belgium, 1-2 June 2016, Data needed to inform WHO s position regarding sunbeds 20th European Society for Pigment Cell Research (ESPCR) Meeting. Milan, Italy, September 2016, Prognostic value of 25-hydroxyvitamin D3 levels in melanoma patients 20th European Society for Pigment Cell Research (ESPCR) Meeting. Milan, Italy, September 2016, Melanoma mortality worldwide, toward a decreasing burden in the next decades EUROSKIN 8th International Conference 2016 & Annual Scientific Meeting of the Norwegian Society of Photobiology and Photomedicine (NOFFOF). Bergen, Norway, 3-4 November 2016, Recent data on sunbed use and risk of skin cancer targets for future research Invited Talk at the Minisymposium Cancer Modelling: Discreteness and Heterogeneity. ECMTB/SMB 2016: 9th European Conference on Mathematical and Theoretical Biology, and Annual Meeting of The Society for Mathematical Biology, Nottingham, UK, July 11-16, 2016, Tumor heterogeneity: one, none and one hundred thousand Guillaume Noyel Image Processing (ICIP) IEEE International Conference on, Quebec City, QC, Canada, 29 September 2015, Asplünd s metric defined in the logarithmic image processing (LIP) framework for colour and multivariate images. Poster presentation at the Word Diabetes Congress of the International Diabetes Federation. 30 November - 4 December 2015, Vancouver, Canada. Contrast enhancement of eye fundus images. CIARP 2016, 21st IberoAmerican Congress on Pattern Recognition. Lima, Peru, 10 November 2016, Spatio-colour Asplünd s metric and Logarithmic Image Processing for Colour Images (LIPC) Maria Bota Poster Presentations at ADA Boston, United States of America, 4 9 June Diabetes, diabetes treatments and lung cancer risk. Diabetes, diabetes treatments and lung cancer risk. Diabetes and cancer and impact of therapies: analyses of meta-analyses in Poster Presentations at ADA Physical activity and change in fasting glucose and HbA1c in randomised controlled trials. A quantitative meta-analysis. Proxy definition of acute pancreatitis for monitoring the side effects of antidiabetic drugs. Incretin Therapies and Risk of Pancreatitis. Lung cancer risk, diabetes and diabetes treatments. Cecile Pizot Poster Presentations at ASCO Physical activity, hormone replacement therapy and breast cancer risk: a meta-analysis of prospective studies Poster Presentations at San Antonio Breast Cancer Symposium. San Antonio, United States of America December Overview of Breast Cancer Mortality Trends in the World. Alberto d Onofrio Micro and Macro Systems in Life Sciences. Będlewo (Poland), 8-12 June 2015, Mathematical Epidemiology: Going beyond Statistical Mechanics (apparently ). Keynote Invited Speaker at the International Conference Mathematical and Computational Epidemiology of Infectious Diseases The Interplay Between Models and Public Health Policies. Erice (Italy), Ettore Majorana Centre for the Diffusion of Scientific Knowledge, Human Behavior and the Spread of Infectious Diseases: a challenge for modeling Scientific Organization of International Conferences/Workshops. August 30 September 5, 2015 Ettore Majorana Centre for the Diffusion of Scientific Knowledge. Erice (Italy), August 30 September 5, 2015, Mathematical and Computational Epidemiology of Infectious diseases the interplay between models and public health policies 163

86 - International Prevention Research Institute About Us Publications - Peer Reviewed t Mannetje A, Brennan P, Zaridze D, Szeszenia- Dabrowska N, Rudnai P, Lissowska J, et al Welding and lung cancer in Central and Eastern Europe and the United Kingdom. Am J Epidemiol. 2012;175(7): Abedi-Ardekani B, Hainaut P. Cancers of the upper gastro-intestinal tract: a review of somatic mutation distributions. Arch Iran Med. 2014;17(4): Abedi-Ardekani B, Dar NA, Mir MM, Zargar SA, Lone MM, Martel-Planche G, et al Epidermal growth factor receptor (EGFR) mutations and expression in squamous cell carcinoma of the esophagus in central Asia. BMC Cancer. 2012;12:602. Abedi-Ardekani B, Kamangar F, Sotoudeh M, Villar S, Islami F, Aghcheli K, et al Extremely high Tp53 mutation load in esophageal squamous cell carcinoma in Golestan Province, Iran. PLoS One. 2011;6(12):e Aggarwal A, Lewison G, Idir S, Peters M, Aldige C, Boerckel W, et al The state of lung cancer research: a global analysis. J Thorac Oncol Agostini M, Ferro G, Burstyn I, de Vocht F, Portengen L, Olsson A, et al Does a more refined assessment of exposure to bitumen fume and confounders alter risk estimates from a nested case-control study of lung cancer among European asphalt workers? Occup Environ Med. 2013;70(3): Agudo A, Bonet C, Travier N, Gonzalez CA, Vineis P, Bueno-de-Mesquita HB, et al Impact of cigarette smoking on cancer risk in the European prospective investigation into cancer and nutrition study. J Clin Oncol. 2012;30(36): Ait Ouakrim D, Pizot C, Boniol M, Malvezzi M, Boniol M, Negri E, et al Trends in colorectal cancer mortality in Europe: retrospective analysis of the WHO mortality database. BMJ. 2015;351:h4970. Amadou A, Hainaut P, Romieu I. Role of obesity in the risk of breast cancer: lessons from anthropometry. J Oncol. 2013a;2013: Amadou A, Fabre A, Torres-Mejia G, Ortega-Olvera C, Angeles-Llerenas A, McKenzie F, et al Hormonal therapy and risk of breast cancer in mexican women. PLoS One. 2013c;8(11):e Amadou A, Torres Mejia G, Fagherazzi G, Ortega C, Angeles-Llerenas A, Chajes V, et al Anthropometry, silhouette trajectory, and risk of breast cancer in Mexican women. Am J Prev Med. 2014b;46(3 Suppl 1):S Amadou A, Degoul J, Hainaut P, Chajes V, Biessy C, Torres Mejia G, et al Dietary Carbohydrate, Glycemic Index, Glycemic Load, and Breast Cancer Risk Among Mexican Women. Epidemiology. 2015;26(6): Andreotti G, Birmann B, De Roos AJ, Spinelli J, Cozen W, Camp NJ, et al A pooled analysis of alcohol consumption and risk of multiple myeloma in the international multiple myeloma consortium. Cancer Epidemiol Biomarkers Prev. 2013;22(9): Andrews N, McMenamin J, Durnall H, Ellis J, Lackenby A, Robertson C, et al Effectiveness of trivalent seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2012/13 end of season results. Euro Surveill. 2014;19(27):5-13. Ariffin H, Hainaut P, Puzio-Kuter A, Choong SS, Chan AS, Tolkunov D, et al Whole-genome sequencing analysis of phenotypic heterogeneity and anticipation in Li-Fraumeni cancer predisposition syndrome. Proc Natl Acad Sci U S A. 2014;111(43): Aschebrook-Kilfoy B, Ward MH, Zheng T, Holford TR, Boyle P, Leaderer B, et al Dietary nitrate and nitrite intake and non-hodgkin lymphoma survival. Nutr Cancer. 2012;64(3): Aune D, Deneo-Pellegrini H, Ronco AL, Boffetta P, Acosta G, Mendilaharsu M, et al Dietary folate intake and the risk of 11 types of cancer: a case-control study in Uruguay. Ann Oncol. 2011;22(2): Autier P. Breast cancer screening. Eur J Cancer. 2011a;47:S133-S46. Autier P. [Screening for breast cancer: worries about its effectiveness]. Revue du praticien. 2013a;63(10): Autier P. Mammography screening and women with symptomatic breast cancer. Nat Rev Clin Oncol. 2013b;10(9). Autier P. Mammography screening before introduction of the national breast screening programme in Norway. Int J Cancer. 2013c;132(7): Autier P. Breast cancer: Doubtful health benefit of screening from 40 years of age. Nat Rev Clin Oncol. 2015a;12(10): Autier P. Risk factors and biomarkers of life-threatening cancers. Ecancermedicalscience. 2015b;9:596. Autier P. Vitamin D status as a synthetic biomarker of health status. Endocrine. 2016a;51(2): Autier P. Efficient Treatments Reduce the Cost- Efficiency of Breast Cancer Screening. Ann Intern Med. 2016b;164(4): Autier P. Age at cancer diagnosis and interpretation of survival statistics. The Lancet Oncology. 2016c;17(7): Autier P, Boniol M. Caution needed for country-specific cancer survival. The Lancet. 2011a;377(9760): Autier P, Boniol M. Mammography screening and breast cancer mortality--letter. Cancer Epidemiol Biomarkers Prev. 2012a;21(5):869; author reply Autier P, Boniol M. The incidence of advanced breast cancer in the West Midlands, United Kingdom. Eur J Cancer Prev. 2012b;21(3): Autier P, Boniol M. Breast cancer screening: evidence of benefit depends on the method used. BMC Med. 2012c;10:163. Autier P, Boniol M. Effect of screening mammography on breast cancer incidence. N Engl J Med. 2013a;368(7):677. The journey of knowledge is fueled by those who dare to explore, while accepting the outcome without prejudice. Amadou A, Torres-Mejia G, Hainaut P, Romieu I. Breast cancer in Latin America: global burden, patterns, and risk factors. Salud Publica Mex. 2014a;56(5): Amadou A, Ferrari P, Muwonge R, Moskal A, Biessy C, Romieu I, et al Overweight, obesity and risk of premenopausal breast cancer according to ethnicity: a systematic review and dose-response metaanalysis. Obes Rev. 2013b;14(8): Autier P. Frequency, digital technology, and the efficiency of screening mammography. Ann Intern Med. 2011b;155(8): Autier P. Glossary of essential terms used in cancer screening. Eur J Cancer. 2011c;47:S171-S75. Autier P. Risk factors for breast cancer for women aged 40 to 49 years. Ann Intern Med. 2012;157(7):529; author reply 29. Autier P, Boniol M. Pitfalls in using case-control studies for the evaluation of the effectiveness of breast screening programmes. Eur J Cancer Prev. 2013b;22(5): Autier P, Boniol M. RE: Relationship between sunbed use and melanoma risk in a large casecontrol study in the United Kingdom. Int J Cancer. 2013c;132(8):1959. Evidence matters. 165

87 - International Prevention Research Institute About Us Autier P, Boniol M. Response to the letter to the editor sent by J.M. Broeders and S. Moss on our article entitled Pitfalls in using case control studies for the evaluation of the effectiveness of breast screening programmes that appeared in the European Journal of Cancer Prevention, issue of 20 December European Journal of Cancer Prevention. 2014a;23(2): Autier P, Boniol M. Adjunctive ultrasonography for breast cancer screening. The Lancet. 2016a;387(10036):2380. Autier P, Pizot C. Meaningless METS: studying the link between physical activity and health. Bmj. 2016b;354:i4200. Autier P, Boniol M, Dore JF. Is sunscreen use for melanoma prevention valid for all sun exposure circumstances? J Clin Oncol. 2011b;29(14):e425-6; author reply e27. Autier P, Boniol M, Perrin P. Prostate-cancer mortality after PSA screening. N Engl J Med. 2012d;366(23):2230; author reply Autier P, Gandini S, Mullie P. A systematic review: influence of vitamin D supplementation on serum 25-hydroxyvitamin D concentration. J Clin Endocrinol Metab. 2012e;97(8): Autier P, Boniol M, Boyle P. Estimation of amounts of valvular heart disease attributable to benfluorex. Eur Heart J. 2013d;8 nov. Autier P, Boniol M, Boyle P. The benefits and harms of breast cancer screening. Lancet. 2013e;381(9869):800. Autier P, Pizot C, Boniol M. Stable incidence of advanced breast cancer argues against screening effectiveness. BMJ. 2014b;349(nov25 10):g6358. Autier P, Koechlin A, Boniol M. The forthcoming inexorable decline of cutaneous melanoma mortality in light-skinned populations. Eur J Cancer. 2015a;51(7): Autier P, Boniol M, Gavin A, Vatten LJ. Breast cancer mortality in neighbouring European countries with different levels of screening but similar access to treatment: trend analysis of WHO mortality database. BMJ. 2011c;343:d4411. Autier P, Dore JF, Eggermont AM, Coebergh JW. Epidemiological evidence that UVA radiation is involved in the genesis of cutaneous melanoma. Curr Opin Oncol. 2011d;23(2): Autier P, Esserman LJ, Flowers CI, Houssami N. Breast cancer screening: the questions answered. Nat Rev Clin Oncol. 2012f;9(10): Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol. 2014c;2(1): Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health--author s reply. Lancet Diabetes Endocrinol. 2014d;2(4): Autier P, Koechlin A, Smans M, Vatten L, Boniol M. Mammography screening and breast cancer mortality in Sweden. J Natl Cancer Inst. 2012g;104(14): Autier P, Boniol M, Smans M, Sullivan R, Boyle P. Statistical analyses in Swedish randomised trials on mammography screening and in other randomised trials on cancer screening: a systematic review. J R Soc Med. 2015b;108(11): Autier P, Funck-Brentano E, Aegerter P, Boniol M, Saiag P. Re: High nevus counts confer a favorable prognosis in melanoma patients by S ribero and co-workers, published in the International Journal of Cancer, 2015 (online 21 march 2015). Int J Cancer. 2015c;137(12): Autier P, Boniol M, Smans M, Sullivan R, Boyle P. Screening mammography: Authors response to Nystrom and Tabar and colleagues. J R Soc Med. 2015d;108(11): Autier P, Boniol M, Smans M, Sullivan R, Boyle P. Observed and Predicted Risk of Breast Cancer Death in Randomized Trials on Breast Cancer Screening. PLoS One. 2016c;11(4):e Autier P, Boniol M, La Vecchia C, Vatten L, Gavin A, Hery C, et al Disparities in breast cancer mortality trends between 30 European countries: retrospective trend analysis of WHO mortality database. BMJ. 2010a;341:c3620. Autier P, Boniol M, Middleton R, Dore JF, Hery C, Zheng T, et al Advanced breast cancer incidence following population-based mammographic screening. Ann Oncol. 2011e;22(8): Autier P, Koechlin A, Boniol M, Mullie P, Bolli G, Rosenstock J, et al Serum insulin and C-peptide concentration and breast cancer: a meta-analysis. Cancer Causes Control. 2013f;24(5): Autier P, Tryggvadottir L, Sigurdsson T, Olafsdottir E, Sigurgeirsson B, Jonasson JG, et al Autier et al Respond to A Sunbed Epidemic?. Am J Epidemiol. 2010b;172(7): Autier P, Doré JF, Breitbart E, Greinert R, Pasterk M, Boniol M. The indoor tanning industry s double game. Lancet. 2011;377(9774): Azevedo ESG, de Moura L, Curado MP, Gomes Fda S, Otero U, Rezende LF, et al The Fraction of Cancer Attributable to Ways of Life, Infections, Occupation, and Environmental Agents in Brazil in PLoS One. 2016;11(2):e Bagnardi V, Botteri E, Rota M, Pelucchi C, Corrao G, Rehm J, et al Re: light drinking has positive public health consequences. Ann Oncol. 2013a;24(5): Bagnardi V, Rota M, Botteri E, Scotti L, Jenab M, Bellocco R, et al Alcohol consumption and lung cancer risk in never smokers: a meta-analysis. Ann Oncol. 2011;22(12): Bagnardi V, Rota M, Botteri E, Tramacere I, Islami F, Fedirko V, et al Light alcohol drinking and cancer: a meta-analysis. Ann Oncol. 2013b;24(2): Bah E, Carrieri MP, Hainaut P, Bah Y, Nyan O, Taal M. 20-years of population-based cancer registration in hepatitis B and liver cancer prevention in the Gambia, West Africa. PLoS One. 2013;8(9):e Balter V, Nogueira da Costa A, Bondanese VP, Jaouen K, Lamboux A, Sangrajrang S, et al Natural variations of copper and sulfur stable isotopes in blood of hepatocellular carcinoma patients. Proc Natl Acad Sci U S A. 2015;112(4): Barry KH, Zhang Y, Lan Q, Zahm SH, Holford TR, Leaderer B, et al Genetic variation in metabolic genes, occupational solvent exposure, and risk of non-hodgkin lymphoma. Am J Epidemiol. 2011;173(4): Bassig BA, Zheng T, Zhang Y, Berndt SI, Holford TR, Hosgood HD, 3rd, et al Polymorphisms in complement system genes and risk of non- Hodgkin lymphoma. Environ Mol Mutagen. 2012;53(2): Becker N, Schnitzler P, Boffetta P, Brennan P, Foretova L, Maynadie M, et al Hepatitis B virus infection and risk of lymphoma: results of a serological analysis within the European case-control study Epilymph. J Cancer Res Clin Oncol. 2012;138(12): Behrens T, Kendzia B, Treppmann T, Olsson A, Jöckel KH, Gustavsson P, et al Lung cancer risk among bakers, pastry cooks and confectionary makers: the SYNERGY study. Occup Environ Med Bellocco R, Pasquali E, Rota M, Bagnardi V, Tramacere I, Scotti L, et al Alcohol drinking and risk of renal cell carcinoma: results of a meta-analysis. Ann Oncol. 2012;23(9): Berthiller J, Straif K, Agudo A, Ahrens W, Bezerra Dos Santos A, Boccia S, et al Low frequency of cigarette smoking and the risk of head and neck cancer in the INHANCE consortium pooled analysis. Int J Epidemiol Bertuccio P, La Vecchia C, Silverman DT, Petersen GM, Bracci PM, Negri E, et al Reply to Are cohort data on smokeless tobacco use and pancreatic cancer confounded by alcohol use? Ann Oncol. 2011a;22(8): Bertuccio P, La Vecchia C, Silverman DT, Petersen GM, Bracci PM, Negri E, et al Cigar and pipe smoking, smokeless tobacco use and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol. 2011b;22(6): Beverland IJ, Cohen GR, Heal MR, Carder M, Yap C, Robertson C, et al A comparison of short-term and long-term air pollution exposure associations with mortality in two cohorts in Scotland. 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93 - International Prevention Research Institute About Us Smith SJ, Young V, Robertson C, Dancer SJ. Where do hands go? An audit of sequential hand-touch events on a hospital ward. J Hosp Infect. 2012;80(3): Soranna D, Scotti L, Zambon A, Bosetti C, Grassi G, Catapano A, et al Cancer risk associated with use of metformin and sulfonylurea in type 2 diabetes: a meta-analysis. Oncologist. 2012;17(6): Sortino-Rachou AM, Curado MP, Cancela Mde C. Cutaneous melanoma in Latin America: a population-based descriptive study. Cad Saude Publica. 2011;27(3): Speeckaert R, Vermaelen K, van Geel N, Autier P, Lambert J, Haspeslagh M, et al Indoleamine 2,3-dioxygenase, a new prognostic marker in sentinel lymph nodes of melanoma patients. Eur J Cancer. 2012;48(13): Spinosa JP, Riva C, Autier P, Nicot P, Junod B. A Failure Analysis of Invasive Breast Cancer: Most Deaths From Disease Occur in Women Not Regularly Screened. Cancer. 2014;120(18): Stang A, Garbe C, Autier P, Jöckel K-H. 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94 - International Prevention Research Institute About Us Publications - Books Boyle P, Ngoma T, Sullivan R, Ndlovu N, Autier P, Stefan S, Fleming K and Brawley OW. The State of Oncology in Africa Scientific Publication 4,, Lyon, France (2016). Boyle P, Sullivan R, Zielinski C, Brawley OW. The State of Oncology. Lyon, France: International Prevention Research Institute; Boyle P, Gray N, Henningfield J, Seffrin J, Zatoński W. Tobacco: Science, Policy and Public Health - 2nd Edition: Oxford University Press; Boyle P, Boffetta P, Lowenfels AB, Harry Burns OB, Zatonski W, Rehm. J. Alcohol: Science, Policy and Public Health: Oxford University Press; Boyle P, Autier P, Adebamowo C, Anderson BO, Babwe RA, Ashtoon LP, et al World Breast Cancer Report. Lyon, France: International Prevention Research Institute, d Onofrio A, Gandolfi A. Mathematical Oncology 2013: Birkhauser Science; Hainaut P, Olivier M, Wiman KG. p53 in the Clinics: Springer- Verlag New York; Simpson CR, Lone N, Kavanagh K, Ritchie LD, Robertson C, Sheikh A, et al Seasonal Influenza Vaccine Effectiveness (SIVE): an observational retrospective cohort study exploitation of a unique community-based national-linked database to determine the effectiveness of the seasonal trivalent influenza vaccine; p. World Breast Cancer Report 2012 Soliman A, Schottenfeld D, Boffetta. P. Cancer Epidemiology: Low- and Middle-Income Countries and Special Populations: Oxford University Press; p. Zheng T, Boffetta P, Boyle P. Epidemiology and Biostatistics. Lyon, France: International Prevention Research Institute;

95 - International Prevention Research Institute About Us PhD Examinations, Jurys and Student Supervision Under the Supervision of Mathieu Boniol 2016 Brian Køster, PhD Development and validation of scale and questionnaire for evaluation of the UV exposure of the Danes as a scientific tool to reduce the prevalence of skin cancer in Denmark., University of Southern Denmark, Denmark Claudine Backes, PhD (ongoing - half thesis defended in 2016) Solar UV Modelling Anatomical distribution prediction for skin cancer prevention, University of Lausanne, Switzerland Isabelle Hoorens, PhD - Preventive landscape of skin cancer in Belgium. A clinical and health economical analysis., Ghent University, Belgium Referee for the application of Professor Robyn Lucas for a nomination to the Australian Academy of Health and Medical Sciences, Australia (ongoing) 2014 Miruna Dragomir, Master of Engineering Reverse causality in the association between vitamin D and melanoma survival, INSA Lyon, France Francois Bergey, Master of Engineering Modelling biases in epidemiological studies with low risk., INSA Toulouse, France Pascal Caillet, PhD Usage des bases de données de l Assurance Maladie dans la pratique de la pharmacoépidémiologie: exemple des pharmacothérapies de l ostéoporose., Université Claude Bernard, Lyon 1, France 2013 Referee for the application of Dr Robyn Lucas for a promotion at grade of full professor of Australian National University, Australia Isabelle Chaillol, PhD Mesure de l exposition au rayonnement ultraviolet solaire pour les études épidémiologiques., Université Claude Bernard, Lyon 1, France Under the Supervision of Alberto d Onofrio 2014 Dario Domingo, Master of Science in Mathematics Bounded Noises: new theoretical developments, and applications in Pharmacokinetics, University of Pisa, Pisa, Italy. Advisors: Alberto d Onofrio and Prof Franco Flandoli. Francois Bergey, Master of Engineering Modelling biases in epidemiological studies with low risk., INSA Toulouse, France (co=advisor with Prof. M. Boniol) Under the Supervision of Guillaume Noyel European Project Coordinator of the European Project Eye-Light - Eye fundus colour images enhancement service for Diabetic Retinopathy diagnosis ( The project has received funding from the European Union s Horizon 2020 research and innovation programme under grant agreement No Pierre Guilbert, one year. Implementation of fast algorithms for image processing 2016 Sabina Stefan, 6 months intership. Image quality assessment and cataract detection for eye fundus images. Under the Supervision of Maria Bota 2012 Nada Assi, Master of Engineering (6 months internship, co-supervision with Philippe Autier) Evaluating the effectiveness of breast cancer screening in Sweden, INSA Lyon, France Under the Supervision of Alice Koechlin 2015 Matteo Franchi, PhD candidate Meta-analyses of multiple outcomes, University of Milano-Bicocca, Milan, Italy. Visitors 2015 January Maria Trojano, University of Bari Aldo Moro, Bari, Italy Maura Pugliatti, University of Sassari, Sassari, Italy Tomas Olsson, Karolinska Hospital (Solna), Stockholm, Sweden Melinda Magyari, Danish Multiple Sclerosis Center, Copenhagen, Denmark Eva Havrdova, First Medical Faculty Charles University in Prague, Praha, Czech Republic Kjell-Morten Myhr, University of Bergen, Bergen, Norway Stéphanie Tcherny-Lessenot, Sanofi, Chilly-Mazarin, France Stephanie Jurgensen, Genzyme Corporation, Cambridge, Massachussets, United States of America Eva Hatzmann, Genzyme, Naarder, The Netherlands David Byrne, Pathwell, Dublin, Ireland Hans Lehrach, Inst.f. Molekulare Genetik, Berlin, Germany Kurt Zatloukal, Medical University of Graz, Graz, Austria Derek Yach, Vitality Institute, New York, New York, United States of America Twalib Ngoma, Ocean Road Cancer Institute, Dar es Salaam, United Republic of Tanzania Juhaeri Juhaeri, Sanofi, Bridgewater, New Jersey, United States of America Kenneth Fleming, K.Fleming Consultancy Limited, Oxford, United Kingdom February Donato Greco, Roma, Italy David Byrne, Pathwell, Dublin, Ireland March David Owens, Cardiff University School of Medicine, Cardiff, United Kingdom Nadia Ait-Aissa, Sanofi Groupe, Paris, France Catherine Levy, Sanofi, Paris, France 183

96 - International Prevention Research Institute About Us Dan Krewski, University of Ottawa, Ottawa, Ontario, Canada Chris Robertson, University of Strathclyde, Glasgow, Scotland, United Kingdom Donato Greco, Roma, Italy April Evan Lee, Eli Lilly export S.A, Veyrier-Geneva, Switzerland Stéphanie Tcherny-Lessenot, Sanofi, Chilly-Mazarin, France Philippe Truffinet, Sanofi, Chilly-Mazarin, France Eva Havrdova, First Medical Faculty Charles University in Prague, Prague, Czech Republic Melinda Magyari, Danish Multiple Sclerosis Center, Copenhagen, Denmark May Philippe Vanhems, HCL - Groupement Hospitalier Edouard Herriot, Lyon, France June Harry Burns, University of Strathclyde, Glasgow, Scotland, United Kingdom July Twalib Ngoma, Ocean Road Cancer Institute, Dar es Salaam, United Republic of Tanzania August Evi Farazi, University of Nicosi, Nicosia, Cyprus September Evi Farazi, University of Nicosi, Nicosia, Cyprus Donato Greco, Roma, Italy Hugo Fry, Sanofi Pasteur MSD, Lyon, France David Khougazian, Sanofi Pasteur MSD, Lyon, France Andrea Rappagliosi, Sanofi Pasteur MSD, Lyon, France Stephen Lockhart, Sanofi Pasteur MSD, Lyon, France Christelle Saint Sardos, Sanofi Pasteur MSD, Lyon, France Emmanuel Audusseau, Sanofi Pasteur MSD, Paris, France Marc Tiltman, Sanofi Pasteur MSD, Lyon, France Benoît Soubeyrand, Sanofi Pasteur MSD, Lyon, France David Zaridze, Russian N. N. Blokhin Cancer Research Center, Moscow, Russia October Irene Leigh, University of Dundee, London, United Kingdom Fadi El Karak, Saint Joseph University of Beirut, Beirut, Lebanon Hugo Fry, Sanofi Pasteur MSD, Lyon, France Twalib Ngoma,Ocean Road Cancer Institute, Dar es Salaam, United Republic of Tanzania Enrico Pira, University of Turin, Turin, Italy Tom Sorahan, University of Birmingham, Birmingham, United Kindom Carlo la Vecchia, University of Milan, Milan, Italy Jürgen Wellmann, Institute of Epidemiology and Social Medicine University of Muenster, Muenster, Germany Mitra Elahi, HCL - Groupement Hospitalier Edouard Herriot, Lyon, France Robert Thomas, Health Victoria Government, Melbourne, Victoria, Australia Bruno Buonono, Universita degli Studi di Napoli Federico II, Napoli, Italy Witold Zatonski, Health Promotion Foundation, Nadarzyn, Poland Romualdas Gurevicius, Institute of Hygiene,Health Information Center, Linius, Lithuania Donato Greco, Roma, Italy Harry Burns, Glasgow, Scotland, United Kingdom Kjell-Morten Myhr, University of Bergen, Bergen, Norway Pietro Iaffaldano, University of Bari Aldo Moro, Bari, Italy Melinda Magyari, Danish Multiple Sclerosis Center, Copenhagen, Denmark Pierrette Seeldrayers, CHU of Charleroi,Charleroi, Belgium Stéphanie Tcherny-Lessenot, Sanofi, Chilly-Mazarin, France Philippe Truffinet, Sanofi, Chilly-Mazarin, France Robert Thomas, Health Victoria Government, Melbourne, Victoria, Australia Donato Greco, Roma, Italy December Benoît Soubeyrand, Sanofi Pasteur MSD, Lyon, France Guy Courbebaisse, Institut National des Sciences Appliquées, Villeurbanne, France 2016 January Robert Thomas, Health Victoria Government, Melbourne, Victoria, Australia Nyulasi Ibolya, Alfred Hospital, Melbourne, Australia Maria Guilia Marini, Foundation ISTUD, Milan, Italy February Murat Tuncer, Hacettepe University, Sihhiye, Ankara, Turkey March Irene Leigh, University of Dundee, Dundee, Scotland, United Kingdom Michael Lees, Bristol-Myers Squibb, New-York, New-York, United States of America April Christian Partensky, Former Professor of Surgery at Edouard Herriot Hospital, Lyon, France Pietracaprina Massimo, European Institute of Oncology, Milan, Italy Orrechia Robert, European Institute of Oncology, Milan, Italy Jean-Pierre Armand, Institut Claudius Regaud,Toulouse, France Nathalie Schmidely, Bristol-Myers Squibb, New-York, New-York, United States of America May Michel Jourlin, Saint-Etienne, France Christian Partensky, Edouard Herriot Hospital, Lyon, France June Pascal Formizyn, Mines St-Etienne, Saint-Etienne, France Melinda Magyari, Danish Multiple Sclerosis Center, Copenhagen, Denmark July Twalib Ngoma, Ocean Road Cancer Institute, Dar es Salaam, United Republic of Tanzania Trapido Edward, LSU Health Sciences Center, New Orleans, Louisiana, United States of America Otis Brawley, American Cancer Society, Atlanta, Georgia, United States of America Tuncer Murat, Turkish Ministry of Health Sihhiye, Ankara, Turkey Irene Leigh, University of Dundee, London, United Kingdom Masamba Léo, Queen Elizabeth Central Hospital, Blantyr,Malawi Jackson Orem, Uganda Cancer, Institute, Kampala, Uganda Abdelgawad Tamer, Pfizer, New-York, New-York, United States of America Chaudhuri Sarbani, Pfizer, New-York, New-York, United States of America Chavane Léonardo, Jhpiego - Ordem dos Médicos de Moçambique, Maputo, Mozambique 185

97 - International Prevention Research Institute About Us Elkadi Hatem, Pfizer, Dubaï, United Arab Emirates Wamboga Joshua, UAPO, Kampala, Uganda Visagie Atétia, Pfizer, Sandton, South Africa September Robert Thomas, Health Victoria Government, Melbourne, Victoria, Australia Melinda Magyari, Danish Multiple Sclerosis Center, Copenhagen, Denmark Kjell-Morten Myhr, University of Bergen, Bergen, Norway October Cristina Stefan, South African Medical Research Council, Cape Town, South Africa Benoît Soubeyrand, Sanofi Pasteur MSD, Lyon, France November Nguyen Thi Xuyen, former Vice Minister,Vietnam National Cancer Hospital, Hanoi, Vietnam Tran Van Thuan, Vietnam National Cancer Hospital, Hanoi, Vietnam Stefan Cristina, South African Medical Research Council, Cape-Town, South Africa Robert Thomas, Health Victoria Government, Melbourne, Victoria, Australia Stéphanie Tcherny-Lessenot, Sanofi, Chilly-Mazarin, France Pietro Iaffaldano, University of Bari Aldo Moro, Bari, Italy Lorenza Scotti University of Milan-Bicocca, Milan, Italy Pierrette Seeldrayers, CHU of Charleroi, Charleroi, Belgium Philippe Truffinet, Sanofi, Chilly-Mazarin, France Irene Leigh, University of Dundee, Dundee, Scotland, United Kingdom Dinh Viet Chung, Vietnam National Cancer Hospital, Hanoi, Vietnam Dao Van Tu, Vietnam National Cancer Hospital, Hanoi, Vietnam December Virginia Acha,United Kingdom, The Association of the British Pharmaceutical Industry, London, United Kingdom 187

98 In 1995, 500 internally displaced people were forced to relocate from Khorog to Dushanbe, in Tajikistan. It was a long journey with multiple unexpected obstacles including rebels, a storm, washed out roads, hundreds of cows blocking the road, illness and even a child gone missing. Most striking of all was their motivation to move on. They knew they could not turn back. They left so much behind. And yet, the promise of new beginings was enough to give them hope. If we are to overcome our global public health challenges, we must be focussed on moving forward. We must be committed to working together, well above the political or corporate fray. And, we must collectively strive to be truthful in our determination of causes and outcomes by always favoring evidence over conjecture. IDP convoy on the road from Khorog to Dushanbe We cannot promise that we will get to the destination, but what can promise is that we will keep moving forward, along the road to better health, as though we had no choice but to keep going, and because we choose to have faith in better days. Will you join us on the journey? International Prevention Research Institute 95 Cours Lafayette Lyon France info@i-pri.org