European Heart Journal (2014) 35, 2497–2503 doi:10.1093/eurheartj/ehu289 Profile: Frans Van de Werf, MD, PhD, FESC, FACC, FAHA Frans Van de Werf is Emeritus Professor of Cardiology at the University of Leuven, Belgium. His work on thrombolytic therapy for myocardial infarction ushered in a new era in patient management and outcomes. Leuven University Medical School 2009 Born in Mechelen, Belgium, Van de Werf’s early ambition was to become a civil engineer and he might have succeeded if his secondary school had provided mathematics at a higher level. Possibly influenced by an uncle who was a surgeon, he opted for medicine and enrolled at medical school in the University of Leuven in 1966 with no particular preconceptions or aspirations. During his undergraduate years at Leuven—which he says was and is the best medical school in Belgium—he worked through the different medical specialities with equal interest and graduated as one of the best students in his year. His strong academic record gave him the pick of specialities and he opted for cardiology, which was at that time attracting the brightest and the best. At the suggestion of his professor he applied for a grant from the Belgian National Fund for Research to study cardiology. He started work on what would later become his PhD into the origins of the third heart sound. At that time Leuven had an international reputation for mechanocardiography and phonocardiography and, although they became obsolete later, they were used by Van de Werf along with catheterizations and echo-Doppler examinations to demonstrate something unique in diastolic function concerning the reversal of the transmitral pressure gradient in early and late diastole. To the young postgraduate’s delight and enduring pride his findings were published in both Circulation and the Journal of Clinical Investigation. He later switched focus and is now widely recognized as an expert, if not a pioneer, in fibrinolytic therapy and the treatment of acute MI. He concedes that hard work has been a big part of his success, but he also believes being in the right place, at the right time with the right people has helped. He considers himself fortunate in having worked at the same institution as prominent researcher De´sire´ Collen, who discovered the properties of tissue plasminogen activator (t-PA). Van de Werf believes that during the late 1980s a lot of different threads came together to facilitate his research progress such as the work on streptokinase by the likes of Peter Rentrop in Hanover. He says: ‘After I saw the data presented at a conference organised by Rentrop in Hanover in the late 1980s, there was no doubt in my mind about it’. Van de Werf resolutely translated his bench work with De´sire´ Collen’s new agent alteplase t-PA to the bedside and used t-PA to treat the first patient in the world at the university hospital in Leuven. Manufacture of t-PA by recombinant DNA technology was swiftly taken up and introduced into treatment regimens. Studies culminated in the GUSTO 1 trial in which 40 000 patients with MI demonstrated that t-PA was superior to streptokinase. Later studies by Van de Werf on slightly modified t-PA (TNK-t-PA) would demonstrate that it is equivalent to t-PA and also that it can be given as a single dose, thus making it convenient for treating patients in the ambulance. In the late 1980s, it became accepted that mechanical recanalization of the coronary artery with a balloon and stenting was superior to lytic therapy and this is now considered to be the best reperfusion therapy. Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: [email protected]. Downloaded from by guest on October 15, 2014 Frans Van de Werf 2498 CardioPulse A very recent development surrounds the difficulty of a time delay in being able to offer primary PCI to patients with MI. Given that PCI needs to be performed within a maximum delay of 90–120 min after first medical contact, treating patients with lytic therapy while they are en route to a PCI hospital seems to be a good compromise if primary PCI cannot be delivered within this time window. According to Van de Werf, the recent STREAM trial has shown the benefits of this strategy. Future studies should, he believes, centre on adjunctive antithrombotic therapy and how beneficial the new anti-platelet agents are when they are given together with a lytic agent. A second proposal involves testing a lower or half dose of a lytic agent in elderly patients to reduce the risk of intra-cranial haemorrhage. The STREAM trial showed how a reduced dose of tenecteplase appeared to be sufficient in elderly patients to open the coronary artery and possibly reduce the risk of an intra-cranial haemorrhage. He is a fellow of the American College of Cardiology and the European Society of Cardiology, and has served on many major national and international committees and boards. He has been a visiting fellow at institutions of excellence around the world. His publications exceed 600 and he has served on numerous editorial boards including the New England Journal of Medicine and Circulation. He was editor-in-chief of the European Heart Journal between 2003 and 2009. Van de Werf’s work has been formally recognized at home and abroad, but aside from the plaudits, he takes great satisfaction from the fact that the results of his work are one of the success stories of modern medicine. He is keen for that story to continue and has recently announced a number of special scholarships supported by money set aside from clinical trials to provide funding for two or three research fellowships into cardiovascular medicine. Dr Frans Van de Werf has received research grants and honoraria from several companies involved in the development of lytic and antithrombotic agents for acute coronary syndromes. Hubert Pouleur No one doubts that clinicians and drug companies are locked in a complex embrace, but Dr Hubert G. Pouleur, MD, PhD, vice-president and cardiovascular disease area expert, Pfizer, Inc., New York City, is someone who understands the issue more than most Jobs for cardiologists in the pharmaceutical industry do not get much higher than this. Dr Hubert G. Pouleur, MD, PhD, is vice-president and cardiovascular disease area expert for Pfizer, Inc., based in New York, USA. As such, he chairs a committee responsible for reviewing and technically endorsing what are called the ‘development and life cycle’ plans of all products produced by the company for the treatment of cardiovascular disease. He and his colleagues therefore make decisions on projects that thousands of investigators in Europe and elsewhere are working on, from the earliest ‘proof of concept’ through to licensing. His routine work also includes the evaluation of risk and safety management plans and technical assessments of major investment decisions—often for billions of dollars-being made by the company. It is a far cry from the time, 20 years ago, when he was pursuing a successful academiccareer inBelgium.Thiswasat the medical school ofthe Catholic University of Leuven, Leuven, a relatively small city, but supercharged with intellectual vitality and a commercial and governmental life that reflects its close proximity to Brussels. Here, he followed a conventional path, from MD to a full professorship in his early 40s. He ran a research team of 10, and was the principal investigator of the NIH-sponsored trial SOLVD, but already there were signs of another path. Although his academic life was based in Leuven, he had spent a year as an NIH Fogarty Fellow at the University of California at San Diego, where he worked on the haemodynamics of heart failure with Dr John Ross Jr.—famed for trans-septal catheterization. And during his last 5 years in Leuven he worked part-time with the UK arm of a US-headquartered pharmaceutical company, trialling ranolazine and providing clinical advice for the approval of nicardipine. He recalls: ‘During my time in Leuven I got to know most of the big players in the cardiovascular field. I was always trying to attract Fellows from elsewhere – my goal was to have a Japanese Fellow, because I knew I was competing with US universities and I was very proud eventually to get one, from the University of Kyoto! I was getting offers from pharmaceutical companies and one day when I was fishing with a friend he suggested I take a job as a Distinguished Clinical Scientist at Syntex Pharmaceuticals, Maidenhead, UK – even though I was neither distinguished nor a scientist! I used to fly out and back one day a week’. ‘It helped me to make the transition from academia to industry. It’s not easy for some academics – their expectations are too high. They believe the pharmaceutical industry is a kind of academia with bigger resources and often want to do things not aligned with what management wants! You need both basic and applied research, but obviously Downloaded from by guest on October 15, 2014 How to cross the border between academia and the pharmaceutical industry 2499 CardioPulse Centre for Therapeutic Innovation, Boston Lab, Centre for Therapeutic Innovation, Boston in industry there is much more applied research and you need to prioritise. Here at Pfizer we have set up the Centres for Therapeutic Innovation scheme which attempts to bridge the two’. ‘Club 30’: twenty-year anniversary ‘Club 30’ of the Polish Cardiac Society continues the extraordinary and successful idea of Prof. Leszek Ceremuz˙yn´ski Leszek Ceremuz˙yn´ski How it began . . . To change the world for the better, you need to be a perceptive observer, a charismatic visionary and, above all, like and respect the people who appear on your road. Such a person was Prof. Leszek Ceremuz˙yn´ski, an experienced cardiologist, an internationally recognized scientist and a remarkable organizer. Although at the time he was an established professor of cardiology, he was fully aware of the problems that young, talented and ambitious cardiologists in training experienced during the 1990s in Poland. He recognized the need for a forum for the most promising young cardiologists to meet informally and socially. They would share the Downloaded from by guest on October 15, 2014 Dr Pouleur finally made the jump to industry in 1993, when he went to work for Pfizer, Inc., in New York and Groton, CT. Here, he put his clinical expertise to use, notably in a team that recommended the licensing of atorvastatin. After 3 years, his experience grew (with the job title vice-president, Cardiovascular and Metabolics, Clinical Development and Life Cycle Management) in the quasi-academic setting of the Pharmaceutical Research Institute of the Bristol Myers Squibb Co, Princeton, NJ. He recruited MDs and clinical scientists to build up a team of .115 people involved in the filing and approval of a number of new drugs and also worked on a portfolio of products that brought in ‘more than $4 billion in sales’. In 2001, he was head-hunted back to Pfizer, where he became senior medical director, with worldwide responsibilities for cardiovascular, metabolic and endocrine products. His career with Pfizer took off, with promotions to senior executive positions involved with major policy decisions. The sheer variety of his work, and the challenges it presented, were indeed a far cry from academia. Therapeutically, it ranged over COX-2 inhibitors, cannabinoid receptor antagonist and the new oral anticoagulant apixaban, as well as the disappointing, ill-fated cholesterylester transfer protein inhibitor torcetrapib. Part of Dr Pouleur’s job is to keep in close contact with university departments in the cardiovascular area—not for commercial reasons, but to discuss new ideas. Looking ahead to the next 5 years, he said: ‘It’s been particularly rewarding to see the advent of statins – from a series of trials, not only by Pfizer, but by others, which have changed the guidelines for managing risk factors in ischaemic heart disease and created a return estimated at $1.3 trillion in value to the world community! And it seems that the lower the cholesterol the greater the benefit’. ‘Over the next 5 years we will see the introduction of monoclonal PCSK9 inhibitors – the question is, does an even lower cholesterol level, say, LDL cholesterol of 20 mg/dL, lower risk even more and is it safe? The PCSK9 inhibitors, such as bococizumab [the proposed generic name for RN316 (PF-04950615)] now in Phase III trials should help to answer this. I also think that the novel oral anticoagulants (NOACs) will be used more and more. Not that warfarin will disappear - it is an extremely effective drug, but, unlike NOACs, it affects many coagulation factors besides prothrombin, and even with good control of the INR there are complications, particularly intracranial bleeding’. ‘Other areas where new treatments will be required – though I’m not sure they will happen in 5 years – include tackling the huge burden of diabetes and better treatments for congestive heart failure. Although we realize that heart failure is a syndrome, not a single disease, we are short of targets. Also, in coronary heart disease, inflammation may be a culprit, though many drugs that reduce inflammation systemically don’t reduce cardiovascular events and may increase them. So, I think we still need a much better understanding of the inflammatory process in atherosclerosis, otherwise we keep ‘shooting in the dark’!’ If nothing else, Dr Pouleur’s career demonstrates the complexity and variety of tasks that any cardiologist entering the pharmaceutical industry must expect to embrace. And, in an era of shrinking grant allocations, he believes that he and his colleagues are well placed to make good the social responsibility that was once only attributed to the prerogative of governments and other major funding bodies. 2500 CardioPulse common problems of the younger generation, which in turn would facilitate future professional cooperation, including clinical and scientific networking. He used to say that friendships established in youth would enable people to cooperate harmoniously when they become mature professors. As the then president of the Polish Cardiac Society, Leszek Ceremuz˙yn´ski convinced the Board to establish a new section ‘The Club 30’. In January 1994 he delegated Krzysztof Narkiewicz to organize the inaugural meeting which took place on 16 September 1994, just 20 years ago! Strict rules of membership Traditional symbols Membership is very prestigious in the cardiology community in Poland. There are currently 85 active and 102 inactive (over 40 years old) members. Members are recognized by their wearing a club badge (the shape of a small red heart with the number 30 on it) designed by Prof. Ceremuz˙yn´ski (Figure 1A). All new members of ‘Club 30’ are solemnly incorporated to the community during the opening ceremony of the annual International Congress of the PCS, and receive such club badges (Figure 2). There is also a sculpture as the symbol of the presidency of ‘Club 30’ which passes on to subsequent presidents (Figure 1B), former presidents receiving a small copy as a souvenir. There is also a captain’s hat and a ring belonging to the current president of ‘Club 30’, which are transferred to succeeding presidents (Figure 1C and D). Figure 1 Traditional symbols of ‘Club30’: (A) Club badge, (B) Presidential sculpture, (C) Captain’s hat, (D) Ring used by the president. Courtesy of K. J. Filipiak & E. A. Jankowska. Club mission ‘Club 30’ organizes its own sessions during the annual International Congress of the PCS. Traditionally, one session is structured around difficult cases and an associated panel discussion [in 2013, two representatives of the Cardiologists of Tomorrow (COT) Nucleus of the ESC participated in such a session], another is a very concise and lively summary of the news from the annual ESC Congress (in 2013, the title was ‘Best from Amsterdam’). In recent years, ‘Club 30’ has also co-organized sessions during several conferences of the working groups of the PCS (e.g. in the field of preventive cardiology, heart failure and arrhythmias). One of the aims of the ‘Club 30’ is the promotion and facilitation of research activities at the highest level among its members. Every year ‘Club 30’ presents an award named after Prof. Ceremuz˙yn´ski for an original paper published by a member, as the first author in a journal with the highest impact factor. It is worthy of note that winning papers have been published by members of ‘Club 30’ in top cardiology journals, e.g. JAMA, Circulation, EHJ. In its scientific stream, ‘Club 30’ launched the multicentre CAPS-LOCK-HF (Complex Assessment of Psychological Status LOCated in Heart Failure) study, co-ordinated by Ewa A. Jankowska and Agnieszka Rydlewska from Wroclaw, where 11 participating centres recruited 758 patients with systolic heart failure in only a few months (joint papers to be published in due course). Members of ‘Club 30’ undertake several measures to involve medical students into activities of the PCS, particularly in research projects. Several sessions during the medical students’ conferences were organized under the honorary auspices of ‘Club 30’. During the International Congresses of the PCS in 2011 and 2013, ‘Club 30’ co-organized the original papers competition of students. In 2013, the competition took place in English due to the international jury with the involvement of the members of the ‘Club 30’ Board, and members of the ESC COT Nucleus were invited. Importantly, a few candidates had already joined ‘Club 30’ while they were still medical students! Traditionally, an important element of ‘Club 30’ activities are the annual spring general meetings which take place in attractive tourist Figure 2 Incorporation of new members into ‘Club 30’ at XVII International Congress of the Polish Cardiac Society, 2013 in Wroclaw (courtesy CASUS-BTL). Figure 3 The nine presidents of ‘Club 30’ of the Polish Cardiac Society 1994–2015. Courtesy of K. J. Filipiak & E. A. Jankowska. Downloaded from by guest on October 15, 2014 ‘Club 30’ did not aim to include all young cardiologists in training. Ceremuz˙yn´ski’s idea was for an elite forum for future eminent Polish cardiologists. To become a member of ‘Club 30’, a young candidate had to prove that he/she was sufficiently talented, passionate, and energetic to join this section. A candidate had to be a member of the Polish Cardiac Society (PCS), ,40 years old (hence the name ‘Club 30’) and be the first author of an abstract presented during the ESC, AHA, or ACC Congresses initially. Subsequently, the second criterion became stricter and changed to the first authorship of an original scientific paper published in a journal with an impact factor. The published thesis had to be defended during the spring meeting of the club and be accepted by the community by vote. To date, there have been nine Presidents of ‘Club 30’ coming from different cardiology centres in Poland (Figure 3). 2501 CardioPulse areas of Poland. Members spend an unforgettable weekend there together with their families. During these weekend meetings, candidates present their papers, there are scientific discussions, but also these are opportunities to get to know each other better within ‘Club 30’ and socialize during sports, games, singing, and dancing. Similarly, members of ‘Club 30’ organize their meeting during the International Congresses of the PCS and during the annual congresses of the ESC. Achievements of its members What is ‘Club 30’ today? ‘Club 30’ is a unique young community in the cardiology world. Although it has strict formal rules and obligations related to the status of the section in the PCS, ‘Club 30’ is first of all a group of friends supporting each other. The meetings have a formal scientific programme and stormy discussions. Although ‘Club 30’ is maturing and has now reached its 20 year anniversary, paradoxically its members are not ageing in their minds. The founder of ‘Club 30’, Prof. Ceremuz˙yn´ski wrote on the 15th anniversary of ‘Club 30’ ‘. . . Club 30 is a teenager today. It is a great age. It has the inexhaustible force to move mountains, is full of aroused curiosity which continues to increase and overflows with ambition and youthful idealism . . .’ A tragic car accident in 2009 ended his work. We have remained faithful to his dreams and ideals. Downloaded from by guest on October 15, 2014 The members of ‘Club 30’ have started to shape the contemporary face of Polish cardiology and significantly contribute to Polish achievements and activities within the ESC. They are gradually becoming the leaders in diverse areas of Polish cardiology, becoming involved in various clinical, scientific, social, and political activities. Waldemar Banasiak was the first president of the PCS who originated from ‘Club 30’. Currently, four members of the PCS Board have their roots in ‘Club 30’. The previous and current editor-in-chiefs of ‘Kardiologia Polska’, respectively, Piotr Kułakowski and Krzysztof J. Filipiak, are also the members of ‘Club 30’. The same is with the previous and current chairmen of the Congress Programme Committee of the PCS, namely Piotr Ponikowski and Dariusz Dudek, respectively. Members of ‘Club 30’ have contributed and still contribute to the activities of the ESC. Piotr Ponikowski is the ESC Councillor (2012–14) and former president of the HFA (2010–12). Dariusz Dudek is a member of EAPCI Board and Tomasz Zdrojewski was a member of the EACPR Board. Three of them have been or are members of the Congress Programme Committee of the ESC. It is worthy of note that Krzysztof Narkiewicz was the president of the friendly society, namely European Society of Hypertension (2009–11). Some of them work actively within working groups of valvular heart disease, e-cardiology, cardiovascular pharmacology, myocardial function, atherosclerosis, and vascular biology, and are involved in the ESC Guidelines committee. Members of ‘Club 30’ have actively contributed to the development of the COT initiative since its inception. 2502 CardioPulse Country of the month initiative of EACPR: Germany The structure of health care in Germany reported by the National Cardiovascular Disease Prevention Coordinators, Prof. Helmut Gohlke and Prof. Ulrich Keil Helmut K. H. Gohlke, MD FESC FACC, Cardiologist, Associate Professor, University of Freiburg Ulrich Keil, MD PhD EFESC, Professor Emeritus, Department of Epidemiology and Social Medicine, University of Mu¨nster Continued Lifestyle and risk factors Overall (%) Men (%) Women (%) ................................................................................ Health care Germany has a compulsory health insurance system in which every person residing in Germany is covered for diagnosis and treatment of diseases and cardiac rehabilitation (CR). About 0.2% of the population has no health insurance. The general health care and consultation is managed by physicians—general practitioner and specialists—in private practice. Both can refer patients to the appropriate hospital as deemed necessary. In 2011 there were 380 physicians per 100 000 inhabitants (OECD average: 320) working in the health-care system; about half of these were in private practice.1 Hypertension (.140/ 90 mmHg) (age ≥65) 55 54 57 Type 2 diabetes Salt intake/day 6.6 6.7 9g 6.5 6.5 g Alcohol consumption 27 g/day Risky alcohol consumption (highest % in the 19– 28 years group) 33 22 AUDIT Ca ≥5/4 points for males/females (alcohol use disorders identification test) 45 32 a Alcohol use disorders identification test.3 Main actors and prevention methods Risk factors Lifestyle and prevalence of risk factors in Germany2 Lifestyle and risk factors Overall (%) Men (%) Women (%) ................................................................................ Smoking 30 Overweight (BMI 25– ,30) 36 34 44 26 29 Obesity (BMI ≥30) 16 16 16 Continued There is no detectable governmental strategy for cardiovascular prevention. Preventive activities are supported by non-governmental organizations (NGOs): the German Heart Foundation (GHF), a patient organization with 80 000 members; the German Cardiac Society; the German Society of Cardiovascular Prevention and Rehabilitation; with respect to smoking by a Task Force Non Smoking and Pulmonary and Cancer Societies. There are preventive checkups by general practitioners: At the age of 35, there is a cardio check-up evaluating risk factors. Downloaded from by guest on October 15, 2014 ‘At the time of the unification of Germany in 1990, life expectancy in the East was considerably lower than in the West. Since 1990 the German East-West mortality difference narrowed rapidly, particularly for women aged 50– 64, for whom the mortality in the East declined below that of the West in 2000. This East-West mortality cross-over for German women is attributable to smoking: When smoking-attributable deaths are removed, the mortality cross-over vanishes’. (Adapted from key messages of the article ‘Reversing East-West mortality difference among German women, and the role of smoking’ by M. Myrskyla¨ and R. Scholz, Int J Epidemiology 2013; 42: 549– 558.) 2503 CardioPulse Prevention activities The GHF publishes short brochures for lay people summarizing the preventive recommendations regarding nutrition, cholesterol, exercise, and general lifestyle but also secondary pharmacological prevention. Each year in November the GHF launches a national educational campaign with one specific topic: cardiovascular risk factors, prevention and early recognition of myocardial infarction (MI) or symptoms of heart failure, of valvular heart diseases or of rhythm disturbances, in particular atrial fibrillation with its associated risks. More than 1200 seminars are offered in November throughout the country by local hospitals, rehabilitation clinics and local physicians—usually cardiologists. The campaigns are also supported by regional and national news media reaching some 40 million people. The GHF also promotes physical activity in schools for 8–10year-old children by running the project ‘Skipping Hearts’: workshops to teach rope skipping and local competitions are organized by GHF’s instructors. So far, ‘Skipping Hearts’ has reached .3200 schools (exceeding 150 000 students). The ‘Task Force Non Smoking’4 represents 11 medical societies (cardiac, pulmonary, cancer, addiction, general prevention, physicians’ associations) in Germany, dealing with the consequences of smoking; the Task Force tries to improve non-smokers’ rights by lobbying for better legislation. 25 –40% in a phase III CR programme.5,6 If the patient is already retired, CR will be paid for by the health insurance. Aims for the future † Risk factor counselling has to be reimbursed by insurance companies. † Risk stratification by a scoring system should become part of the check-up at 35 years of age. † Smoking bans have to be extended; restriction of advertising—as outlined in the FCTC (WHO Framework Convention on Tobacco Control)—has to be implemented. † The implementation of the new EU-Tobacco Products Directive has to be observed and supported or demanded. † Fruit and vegetable consumption should be increased; trans-fatty acids (TFAs) should be labelled as such and consumption reduced. For example, in Austria and Denmark TFAs are banned from industrial products. † Obesity and reduced physical activity in children are increasing problems for society. Both inactivity and overweight are associated and should be approached by political, societal, educational, and medical means. Cardiac rehabilitation References Since 1974, phase II CR after MI and cardiac surgery and for a number of other indications (listed in the table) is guaranteed by law.5 Traditionally, a 3-week course of CR takes place in a residential setting with emphasis on exercise training, risk factors, and secondary prevention. In recent years, however, ambulatory CR has become a wellestablished alternative method if the quality criteria of the residential setting are met. Cardiac rehabilitation is paid for by the retirement funds with the proven assumption that early CR improves the return to work rate, delays premature retirement and is cost-effective from the perspective of the retirement fund. About 50 –60% of qualifying patients participate in a phase II and 1. Information about Germany in relation to other OECD Countries. http://www.oecdbetterlifeindex.org/countries/germany (2 September 2014). 2. Gesundheitsberichterstattung des Bundes [Reports on the health care system in Germany put together by the state]. http://www.gbe-bund.de/gbe10/pkg_isgbe5. prc_isgbe?p_uid=gastd&p_aid=&p_sprache=D (2 September 2014). 3. Saitz R. Unhealthy alcohol use. N Engl J Med 2005;352:596 –607. 4. [Access to Task Force Non Smoking/Aktionsbu¨ndnis Nichtrauchen]. http://www. abnr.de/index.php?article_id=1 (2 September 2014). 5. Karoff M, Held K, Bjarnason-Wehrens B. Cardiac Rehabilitation I Germany. Eur J Prevent Cardiol 2007;14:18–27. 6. Bjarnason-Wehrens B, McGee H, Zwisler A-D, Piepoli MF, Benzer W, Schmid J-P, Dendale P, Pogosova N-GV, Zdrenghea D, Niebauer J, Mendes M. Cardiac rehabilitation in Europe: results from the European Cardiac Rehabilitation Inventory Survey. Eur J Prevent Cardiol 2010;17;410 – 418. CardioPulse contact: Andros Tofield, Managing Editor. Email: [email protected] Downloaded from by guest on October 15, 2014 Andros Tofield
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