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    Annual Science Report 2005

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    Annual Science Report 2005

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    Contents 4 RIVM: a research organisation at heart Marc Sprenger Director-General In the spotlight 6 Finding the Eschers in epidemic theories Jacco Wallinga 8 Reaping the profits of what has been sown Bas Bueno de Mesquita 10 Will baby boomers stay healthy longer than their parents? Johan Polder 12 Just a few chemicals are causing most of the problems Dik van de Meent 14 Four thousands steps on a typical workday Wanda Bemelmans & Wanda Vos 16 Tiny particles having large health effects Flemming Cassee RIVM Annual Science Report 2005 18 Fighting microbes without borders Kristin Kremer Contact: Sophie Deleu RIVM Office of Communications 20 The exploding field of medical nanotechnology Sophie.Deleu@rivm.nl Robert Geertsma Text: Peter J. Vermij, Schuttelaar & Partners, The Hague Published by RIVM Publishers Research output Research papers, Books, Chapters & Reports, Printed by OBT, The Hague Doctoral Theses and Professorial Chairs 24 Centre for Infectious Disease Control (RIVM-CIb) RIVM P.O. Box 1 38 Public Health and Health Services (RIVM-V&Z) 3720 BA Bilthoven The Netherlands 44 Nutrition, Medicines and Consumer Safety (RIVM-VGC) telephone: +31 - 30 - 274 91 11 telefax: +31 - 30 - 274 29 71 57 Environmental Risk and Safety (RIVM-MEV)

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    6 7 RIVM: a research organisation at heart Marc Sprenger, Director-General, In 1992, I was a young scientist wondering whether to apply for a But at the same time people should know that RIVM at its core remains a scientific institute. National Institute for Public Our researchers work closely with colleagues across Europe and the rest of the globe. job at the National Institute for Public Health and the Environment Health and the Environment Everything we do meets rigorous scientific standards and our research, which covers the (RIVM) (RIVM). gamut from radiation and toxicology to influenza and obesity, is published in international, peer-reviewed journals. At the time, I mostly thought of RIVM as an institute that produced solid policy reports For our own RIVM staff too, this report has a lot to offer. I hope all our scientists will take the – always reliable, sometimes a bit dense, and, it seemed, not often straight from the front lines opportunity to re-acquaint themselves with the breadth and depth of our common research of science. I confess that I had some doubts about whether such an institute really was the effort. All too often, we are so focused on finishing our own projects that we forget to find out right place for me. what colleagues just down the hall have been up to. What’s more, given our research areas and the fact that we are mostly funded by tax-payers, it’s only fair that society gets the chance That changed, however, when I found out that Daan Kromhout, a nutritional epidemiologist to learn about our research. at RIVM, had published exciting research papers in well-respected international research journals like The Lancet and the American Journal of Epidemiology. It made me realise that I hope RIVM researchers will also take home the message that rigorous science will always RIVM was a place where I would feel right at home; a policy-oriented institute where at the have a place at RIVM and that publishing top-notch papers in peer-reviewed journals is very same time scientists carried out high-quality research. important to us. In fact, I think we should celebrate such successes more frequently. The experience illustrates the importance of showing the world that, besides producing fine and increasingly accessible reports for governments at home and abroad, we also do a lot of excellent research. That message is at the heart of this Annual Science Report. Accomplishments This Annual Science Report reinstates an old tradition at our institute. It demonstrates RIVM’s Workable solutions scientific accomplishments by listing all research papers, books, book chapters, reports and doctoral theses our scientists published in 2005. It highlights a few of those publications, RIVM is a public institute. Society, most notably the Dutch national government, is its main not because they’re the best, but because together they represent the breadth of our client. Our mission is to translate our knowledge and expertise into workable solutions multidisciplinary research. The report also gives some of our scientists a place in the spotlight; for problems our society faces today in the areas of health, nutrition, and environmental it tells us who they are, what they have done and what makes them tick. Like them, we should protection. all explain to others what we are working on more often. We counsel politicians and other policy makers on how to deal with the threat of emerging For young researchers who may wonder about our identity, just as I did many years ago: This infectious diseases like SARS and pandemic flu; we explore how our country can enable its report should convince you that RIVM is, and will remain, a research organisation at heart. I healthcare system to meet the demands of an ageing population and improve public health hope that it’s the kind of institute you, too, would like to join. through prevention; we try to reliably assess the risks to our natural environment, whether it’s from chemicals or radiation. Another part of our work is to disseminate that same expertise to the public at large, using Marc J.W. Sprenger, Ph.D. MD familiar as well as brand new means of communication. For example, we devise practical, Director-General, National Institute for Public Health and the Environment (RIVM), Internet-based information tools such as ‘Kies Beter’, a state-of-the-art website that helps Dutch citizens make better-informed decisions on their personal health and healthcare. We will September 2006, continue to find similarly innovative ways to promote our insights on health, nutrition and the Bilthoven, The Netherlands. environment to the rest of the world.

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    8 Infectious Diseases 9 Finding the Eschers in epidemic advantage is, you don’t have to pay your own airfare,” he smiles. More recently, Wallinga and his colleagues touched another hot-button issue: the threat of a new flu pandemic. This time, while other research groups were predicting a pandemic flu theories virus to spread like wildfire, with every patient infecting up to 17 others, RIVM modellers were early with less dire predictions. Based on historical records, they projected about 1.5 secondary infections from every patient. Again, Wallinga says, by the time they were ready to publish, other researchers had beaten them to the finish line. “We got a footnote in Nature,” he says, After the sudden appearance of SARS, the use of models to “but colleagues know who were among the first. These days we get many requests to join European collaborations.” understand and beat outbreaks of infectious diseases gained Sometimes, the team is more lucky. In 2005, Wallinga’s work on measles bore fruit with a importance. RIVM’s modellers, too, have taken centre stage. paper in PLoS Medicine (see sidebar). “We’ve always published regularly,” Wallinga says, “and it’s nice to see medical journals getting more interested. It’s easier to get papers accepted now, although it’s still a gamble. In the end, publishing is just nice, like a pat on the head. The Jacco Wallings is a biologist first and foremost – but one not repelled by mathematical real kick comes from suddenly spotting order in seemingly chaotic numbers. The rest is just a formulas. He likes to interpret rows of numbers that at first glance seem rather chaotic to find circus in which you have to play along.” the systematic patterns hidden underneath. “At the moment, we’re doing well. In 2003 I was working on my own, now there’s seven of us. As a pre-graduate at Wageningen University, Wallinga modelled the spread of rabies among It’s like the start of an epidemic. Let’s hope it doesn’t die down, as most epidemics eventually foxes. At RIVM, he focuses on human infectious diseases like measles and pandemic flu. After do.” the 2003 outbreak of Severe Acute Respiratory Syndrome (SARS), he sat at the table at the World Health Organisation (WHO) to assess the new virus’s potential threat. “Looking at these series of spikes representing the outbursts of new disease cases, I can’t help Jacco Wallinga, but wonder: what’s going on underneath?” Wallinga says. “What can we do to stop this from Centre for Infectious spreading?” Disease Control Statistical analysis, computer models and mathematical equations play leading roles in (RIVM-CIb) Wallinga’s work. “Yet I get most excited about the biology, not the equations,” he says. Escher drawings The use of computers and mathematical models in biology often generates misunderstandings, Wallinga says. “Frequently people will ask me: ‘We don’t have any data, Vaccination threshold sets the stage for major outbreak could you provide us with a model?’ But without data, I have to tell them, there’s nothing to model.” Measles is a highly infectious, occasionally deadly viral him- or herself but will also prevent 0.61 other cases in Another frequent misconception is that models are either ‘right’ or ‘wrong’, Wallinga says. disease for which a vaccine has been available for decades. a subsequent major outbreak, clearly demonstrating the “A model is a tool one uses to check the validity of a theory about biological mechanisms. In The Netherlands, over 90 percent of the population is public health dimension of measles vaccination. When you try to translate your hypothesis into mathematical equations, inconsistencies will vaccinated. Small subgroups don’t, however, for mostly The authors point out that in The Netherlands, the threshold jump out pretty soon. It is like comparing epidemic theory with the famous drawings of M.C. religious reasons. Unvaccinated members are susceptible was crossed in 2003. Without additional vaccination Escher; while pieces of your theory can be accurate, the full picture may still be impossible. A to imported outbreaks unless they have been in contact efforts, they say, the risk of a major outbreak is real and will mathematical model will quickly bring these errors to light.” with the virus before. Within these subgroups, susceptibility continue to grow. In 2003, when the new, deadly SARS virus started to spread, Wallinga was working on an increases with time after the last major outbreak. The findings may be relevant to all countries with high algorithm to convert timelines of flu cases into epidemiological models. He decided to enter Researchers checked Dutch vaccination records between vaccination rates, as well as countries hoping to attain them the data on SARS cases that WHO put out on its website. 1976 and 2004 and related these to past outbreaks of in the future. Keeping the fraction of susceptible individuals “The outcome shocked us,” Wallinga says. “While WHO was reassuring people by saying SARS measles. They discovered a threshold in susceptibility below the threshold may be the key to averting major wasn’t flu, our model predicted that it was actually worse. Harsh measures would be needed below which chances of a major outbreak are slim. When measles outbreaks. to contain the outbreak. We e-mailed our findings to a British colleague who was stationed more than about 4.3 percent of the population becomes at WHO during the SARS outbreak. It soon became clear that our predictions had been pretty susceptible, however, the risk increases sharply. Wallinga J, Heijne JCM, Kretzschmar M accurate.” Further analysing the data, the authors estimated the A Measles Epidemic Threshold in a Highly Vaccinated In May, when the outbreaks subsided, Wallinga was invited to speak at a WHO conference in benefit of vaccinating each additional child. When Population Geneva. There he discovered other researchers had beaten him by submitting similar findings susceptibility rates are above the threshold, they calculated, PLoS Medicine, Nov 2005, Volume 2, Issue 11, pp. 1152-1157. to Science, one of the world’s premier research journals. Yet people in the modelling field each child that gets the vaccine will not only be protected DOI: 10.1371/journal.pmed.0020316 knew RIVM was up to something. Speaking invitations kept popping up in his mailbox – in 2005 Wallinga addressed conferences in, for instance, Palm Springs (US) and Singapore. “The

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    10 Nutrition & Health 11 Reaping the profits of what has been been meticulously kept ever since. For the RIVM cohorts, half of the samples are stored at the Bilthoven campus, while backups are kept in Lyon. “Right now there is a boom in research papers based on questionnaires, which mostly generate weak epidemiological associations,” sown says Bueno de Mesquita. “In the coming years I expect a strong upsurge in papers based on biochemical and genetic markers found in those biological samples.” Such studies could eventually help assign risks to individual people and their personal lifestyle decisions. “Last week I took part in a teleconference on pancreatic cancer with the US National Cancer In the early 1990s, RIVM joined international cohort studies on Institute,” he adds. “They will analyse genes in samples taken from large international cohorts, including EPIC. Genomics will increasingly be integrated in epidemiological research. After lifestyle habits and chronic diseases like cancer. In 2005, an interim that there will be proteomics, where we will be looking at patterns of proteins in the blood, analysis confirmed that high meat consumption is associated with and then metabolomics, focusing on metabolites. And all of that will only make sense when lifestyle factors are also taken into account. So there’s a lot left to be done, and I hope to be an increased risk of colorectal cancer. Over the next few years, able to take part in much of it in my remaining eight years at the institute.” frozen blood samples will shed much more light on such risks. To Bueno de Mesquita, these new research opportunities underscore a key point: RIVM will need to maintain its collection of blood samples for many years to come. “Public investments Bas Bueno de Mesquita started his career as a tropical doctor. For five years, he was stationed in the 1990s have filled this great repository,” he says. “It would be very unfortunate if we in a leprosy hospital in India, at one point delivering basic health care to 40,000 rural would not be able to reap what we have sown.” inhabitants by truck, and later helping local villagers improve the way they cultivate rice and maize. Having seen extreme poverty changed Bueno de Mesquita’s outlook on life, and on the purpose of research into western lifestyles and chronic diseases. “Those people maintained their pride and self-respect while working hard to improve their lives,” he says. “So I reject the idea of low-income groups in rich countries being pitiful and not able to take responsibility. The only dignified way to deal with unhealthy lifestyles is to investigate the risks and then to Bas Bueno de Mesquita, inform people. If alcohol increases a woman’s risk of getting breast cancer, then she should Nutrition, Medicines and have access to that information, since to prevent is so much better than to cure. To that extent Consumer Safety Division governments bear a responsibility, and I hope to contribute to that. But in the end, it’s up to (RIVM-VGC) people to decide themselves.” Eating red meat associated with higher incidence of colorectal cancer Many papers The European Prospective Investigation into Cancer and The analysis showed that, as had been predicted, people Nutrition (EPIC) was initiated in 1992. Supported by the with diets rich in processed and red meat develop colon Bueno de Mesquita’s career took a sharp turn when in 1982, after studying public health at European Commission, the World Health Organisation or rectal cancer more often than those with low intakes Johns Hopkins University in Baltimore (US), he failed to secure a new work permit for India, and the International Agency for Research on Cancer, it of these products. The relationship was consistent across where he was set to start teaching at a university. Wondering whether he should take up his is one of the largest prospective studies ever undertaken culturally diverse countries such as Greece, Spain, and The old job as a physician, he accompanied his former professor in social medicine to a meeting of into the relationships between diet, nutritional status, Netherlands. the International Agency for Research on Cancer (IARC) in Lyon (France). lifestyle, environmental factors and the incidence of cancer The analysis suggests that an average 50-year-old who eats He has been working on cancer and lifestyle ever since. and other chronic diseases. More than 500,000 people in relatively large amounts of red meat has a 1.7% chance of “My work at RIVM basically spanned three large IARC projects,” Bueno de Mesquita says. The ten European countries were questioned and had blood developing colorectal cancer over the next 10 years, while third and biggest study, the European Prospective Investigation into Cancer and Nutrition samples taken at the time of enrolment. Their health status for someone consuming relatively little red and processed (EPIC), will probably keep him busy for the remainder of his career, he adds. Co-ordinating has been monitored ever since. meats, that chance is 1.3%. the largest of two Dutch cohort studies, analysing questionnaires, health records and blood In The Netherlands, more than 40,000 subjects entered samples of close to 23,000 people, and co-authoring papers based on that mountain of data, EPIC between 1993 and 1997, just over half of them through Norat T, Bingham S, Ferrari P, Slimani N, (...), Bueno de Mesquita consumes virtually all his time. RIVM’s MORGEN-EPIC study, co-ordinated by Bas Bueno HB et al. Apart from generating many research papers, international collaborations have another de Mesquita. (The other half enrolled in PROSPECT, a study Meat, Fish, and Colorectal Cancer Risk: The European important advantage, says Bueno de Mesquita: They help prevent the confusion caused by co-ordinated by Petra Peeters at Utrecht University.) Prospective Investigation into Cancer and Nutrition. many separate, smaller and often contradictory epidemiological studies. “Testing hypotheses In June 2005, researchers published an analysis of the Journal of the National Cancer Institute, Vol. 97, No. 12, June 15, in many centres across many countries shows right away whether results are consistent,” he relationships between consumption of processed and red 2005, pp. 906-916. says. Sometimes, he adds, researchers have touted findings to the general public that should meat and fish on the one hand DOI: 10.1093/jnci/dji164 have been replicated first. and the riskof developing colorectal cancer on the other. More solid conclusions may also come from the millions of blood samples currently frozen in liquid nitrogen. They were taken at the time people were enrolled in cohort studies and have

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    12 Health Economics 13 Will baby boomers stay healthy prospects,” he says. Being part of the research community is important if RIVM wants to keep bridging the worlds of science and policy, Polder says. “Most debates these days play out on the international stage, longer than their parents? and new ideas are floated at big conferences. We translate these to policy makers but also strive to participate in the scientific debate ourselves by publishing in peer-reviewed journals. I like writing, and I get a real kick out of seeing our papers printed and used in the field. I think it’s good for RIVM to be seen as a real partner in the academic world.” At the request of the Dutch ministry of Public Health (VWS), Not everyone outside RIVM’s walls is familiar with the institute’s high-quality research, Polder says. “Recently one of my former university colleagues, after a couple of drinks, told me he RIVM’s Centre for Public Health Forecasting publishes a prognosis thought that we don’t do real science at RIVM. I was flabbergasted. It made me think, but he of the country’s future healthcare needs every four years. is wrong. Obviously, we’re not a university. You won’t find people here who keep digging in splendid isolation. Yet we have brilliant scientists for whom RIVM provides a very inspiring Fundamental research helps lay the foundations. environment. And I myself have published one of my best papers while at this institute.” Johan Polder was trained as an economist. Unlike most of his college peers, he says, he was never attracted by courses in business administration, accountancy, or fiscal regulation. Macro-economic and institutional questions excite him much more. After graduating, he found his calling through his Ph.D. thesis, aptly titled ‘Cost of illness in The Netherlands’. When he was asked in 2002 to join RIVM’s Centre for Public Health Forecasting, Polder says, he asked for two things: full independence from policy makers, and a greater emphasis on scientific rigour. Both wishes were granted. As to the centre’s independence, Polder says, that’s demonstrated by the conclusion, in last year’s Primary Care report (see sidebar) that making patients pay small deductibles for primary care will not really reduce their demand, as many Dutch politicians hoped. The future of primary care in The Netherlands With regard to scientific rigour, Polder says, researchers at the centre are constantly challenging each other to aim for the highest standards. “We ask each other: Did you use the Primary care in The Netherlands is facing rapid changes. primary care. These trends will offset demand reductions Johan Polder, right data and methods? Was your literature search sufficiently comprehensive?” The country’s population ages while new types of care thanks to the prevention of back and neck complaints. Public Health and Health The Centre, Polder says, is built on two pillars. One consists of policy-oriented research, providers are reshaping the field. Also, rising healthcare Rising numbers of part-time practitioners will require more Services Division designed to help policy makers evaluate old policies and design new, more effective ones. The costs prompt the Dutch government to seek regulatory large-scale providers. (RIVM-V&Z) second pillar is fundamental scientific research, aimed at understanding the demographic and changes. Between 2005 and 2020, supply of general practice is epidemiological forces that will shape future healthcare systems. This study, carried out jointly with the Netherlands Institute expected to grow by 11.5%, yet demand will increase by “It is like having two legs,” Polder says; “I would not want to stand on just one of them. for Health Services Research (Nivel), aimed to assess all 13% to 20%. The predicted shortage is less severe than these developments and produce an integrated projection in previous studies because primary care has become of demand, supply and organisation of primary care in more efficient. Efficiency could grow further if more tasks Red Herring theory 2020. It also predicted chances of success for potential are entrusted to assistants and nurse-practitioners, and policy measures. primary mental healthcare is strengthened further. Serious In science, Polder says, he still gets most excited by large-scale economic questions. He is The report concludes that overuse of primary care has shortages of nurses are projected because of sharp rises in fascinated, for instance, by the fact that we don’t really know the effects of ageing populations diminished to a low level in 2005. Attempts to further curb home care. on future healthcare costs. “Will costs rise? If so, to what extent? Will future 70-year-olds unnecessary use will fail unless very high deductibles require as much healthcare as current 70-year-olds? Or is absolute age really not important, as are introduced that cannot be reinsured. The recent Bakker DH de, Polder JJ, Sluijs EM, Treurniet HF (eds) Peter Zweifel’s ‘Red Herring theory’ postulates, while proximity of death is? If that’s true, then restructuring of Dutch health insurance will not significantly Public health forecast for primary care in The Netherlands in healthcare expenses would merely shift, not rise.” affect demand. 2020. Polder has tested the Red Herring hypothesis using Dutch healthcare registries. The theory Curbing demand through increased prevention will only [“Op één lijn - Toekomstverkenning eerstelijnszorg 2020”]. has some merit, he found, but it is not completely right. As is always the case in science, new work short-term. In the long run, prevention will increase Part of series: ‘Public Health Status and Forecasting 2006’ research questions flowed from the analysis. Do different age cohorts have different healthcare demand for primary care, because preventive measures (www.rivm.nl/vtv) demands? Will baby boomers stay healthy longer than their parents did because they enjoyed are often implemented by primary care givers. Moreover, RIVM Report 270751009/2005 greater prosperity? If so, what does that mean for the future costs of healthcare? “I’m writing a prevention causes further ageing which in turn will lead to ISBN 9031346195 research proposal to further look into those exact questions,” Polder says. a higher prevalence of chronic disorders like asthma and www.rivm.nl/bibliotheek/rapporten/270751009.pdf At this point, Polder says, it would be classified as fundamental research, supported by RIVM’s diabetes and to more injuries, all increasing demand for strategic research program and carried out in co-operation with universities such as Tilburg and Rotterdam. “Yet it could become very relevant for the 2010 edition of our policy-oriented

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    14 Environmental Toxicology 15 Just a few chemicals are causing looking back, I should have known it all along,” he says. “To my mind, the message to governments is clear: Instead of regulating 10,000 chemicals, we should probably focus our efforts on quickly identifying the 500 most important ones.” most of the problems Understandably, Van de Meent says, his clients are not overly interested in basic research questions like these; they have to work with the regulation as it has been enacted, and mathematical simulations usually don’t solve their problems. As a result, it can be difficult for RIVM scientists to find the time to finish such research. That’s why Van de Meent relishes his Environmental risk assessment often means dealing with many collaboration with Radboud University Nijmegen, where he has been a part-time professor since 2002. “I laid the groundwork for this research during my sabbatical in Osnabrück, uncertainties; we know very little about the tens of thousands of Germany,” he says, “but it was thanks to Jasper Harbers, a graduate student from Nijmegen, chemicals floating around. How to make the best use of what we that we could finish this paper quickly. And it got published in Environmental Science and Technology – the highest-impact journal in the field.” do know? Dik van de Meent was trained in organic geochemistry at the University of Delft. Even as a student, he was curious about the environmental impact of man-made chemicals, whose number was rapidly growing. As an ‘environmental chemist’ at the university, Van de Meent tried to understand the behaviour of chemicals in the environment. To assess their long- range effects he helped build mathematical models in which chemicals moved between soil, freshwater, groundwater and the atmosphere. Van de Meent’s early work landed him a job as an environmental toxicologist at the Dutch National Institute for Drinking-water Supply (Rijksinstituut voor Drinkwatervoorziening), which merged into RIVM in 1984. Van de Meent has fond memories of those early days. Working in a small institute, he says, often meant counselling policy makers very directly. He remembers being called into the office of Hans Könemann, who in the early 1980s headed the department of chemical substances at the Ministry of Public Housing, Spatial Planning and the Environment (VROM) and would later Finding the needles in a chemical haystack join RIVM. Könemann had a problem: A new law would oblige companies to report their new chemicals, after which the government had to quickly assess their environmental impact. He In Europe, more than 103,000 man-made chemicals are these uncertainties in a computer, however, they were able Dik van de Meent, had no idea yet how to handle those reports. registered at the European Chemicals Bureau. Most of them to estimate the overall toxic pressure much more reliably. Environment and Safety “I remember telling him: ‘One fool can ask more questions than seven wise men can answer’,” are currently exempt from regulation since they were on the The researchers went on to study the impact of the Pareto Division says Van de Meent . “Afterwards, my boss had to save me from trouble.” market when rules were introduced. Extensive toxicological Principle, according to which 20 percent of any group will (RIVM-MEV) For Van de Meent, the meeting became a turning point. “Könemann said: ‘You can stay up data is available for only a small fraction, so worries remain typically cause 80 percent of the effect. Statistically, they in your ivory tower dealing with many scientific uncertainties, or you can come down and about the thousands of chemicals about which we know very found, 83 percent of the chemicals can be expected to help me build a system that works.’ With those words he converted me. We may not yet know little. contribute only negligibly (less than 0.1 percent) to the everything about a situation, but that shouldn’t keep us from using what we do know. If only The European Commission has proposed new legislation overall toxic pressure, while the remaining 17 percent will be nanograms of a compound are likely to be in the water, while grams are needed for toxic for Registration, Evaluation and Authorisation of Chemicals ‘possibly relevant’. effects, then it’s not a priority for regulation. In a way, that meeting ultimately led to the paper (REACH), which could come into effect as early as 2007. Such calculations, the authors suggest, could lead to more we finished in 2005” (see sidebar). Industries would have to document the toxic effects of about cost-efficient ways to monitor and regulate the release of 10,000 chemicals, both old and new. chemicals. Rather than spread research and regulation Setting priorities Van de Meent and his colleagues collected data on 343 efforts evenly over all chemicals, governments could try to high-production chemicals reaching North Sea ecosystems. pinpoint the small number of compounds that have the most Over the past decades, many thousands of new chemicals have been introduced into the They calculated th e so-called ‘toxic pressure’ of all those profound environmental effect. environment. Regulating them all to prevent harm is still a huge challenge, since very chemicals combined, and then tried to estimate the little is known about most of them. “The million dollar questions are how to quantify the individual contribution of each one based on production Harbers JV, Huijbregts MJ, Posthuma L, Meent D Van de environmental risk of all those chemicals together and to help governments set the right volumes, emission rates, chemical structure, persistence, Estimating the Impact of High-Production-Volume Chemicals on priorities.” bio-reactivity, and so on. Remote Ecosystems by Toxic Pressure Calculation For Van de Meent the big surprise came when he found that, at least mathematically, a tiny Getting reliable estimates for individual compounds proved Environmental Science & Technology, Vol. 40, No 5, pp. 1573-1580 fraction of all chemicals is probably responsible for most of the environmental risk. “Our impossible because of the many uncertainties. By modelling DOI: 10.1021/es051633m simulations suggest that 95 percent of the toxicity comes from just 5 percent of all chemical compounds. We just don’t know yet which ones. That really opened my eyes, although,

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    16 Health & Prevention 17 Four thousands steps on a typical aided lifestyle counselling. She’s also considering writing a proposal to use blood samples from one of RIVM’s cohort studies to find bio-markers that can predict obese people’s risk of developing cardiovascular disease. workday Meanwhile, both are still riding the wave of their successful cost-effectiveness study. “We scored points internationally,” Bemelmans says. “It has become easier to give workshops and presentations, and I’ve been invited to a working group at the World Health Organisation.” The researchers have submitted adapted versions of the report to several peer-reviewed To combat rising overweight and a growing lack of exercise among journals. Says Vos: “As researchers, we also have a personal reputation to uphold. We liked putting out a colourful RIVM report, but publishing in the New England Journal of Medicine its citizens, the Dutch government wants to promote physical wouldn’t harm either.” activity. A large-scale intervention program could bring significant health gains at reasonable costs, researchers have found. Wanda Bemelmans and Wanda Vos are often called ‘the two Wandas’. They both studied nutrition at Wageningen University; they both bike to work from Zeist, a residential town six kilometres south of the RIVM campus; and upon arrival, they walk up to adjacent offices. To the outside world, such similarities can be confusing – especially because both ended up doing research for the same report. “Some people got lost looking for the right Wanda, but since we’re next-door neighbours, that was easy to clear up,” both Wandas say. Wanda Vos was a dietician when she joined RIVM in 1997. She became a researcher and earned her Ph.D. degree in 2004 after studying the health aspects of physical exercise. Wanda Bemelmans joined RIVM in 2002 after finishing her doctoral thesis on lifestyle-counselling for high-risk patients. Together, they proved to be the perfect couple to co-ordinate a comprehensive, first-time study into the costs and feasible health gains of a national campaign promoting exercise. Exercise plan would save lives at moderate cost Shocked As part of a strategy to combat rising obesity and cost approximately € 94 million per year or € 6 per capita. overweight, the Dutch Ministry of Health, Welfare and Sport Meeting the plan’s objectives would prevent tens of Researching the blessings of exercise and training has made them more conscious of their (VWS) plans to launch a National Action Plan for Sport thousands of cases of cardiovascular disease, diabetes and own behaviour, the Wandas say, and made them realise how difficult it is to meet the Dutch and Physical Activity. The authors set out to give the plan cancer over the next twenty years, which would save many Wanda Vos and Standard for Healthy Exercise: More than 30 minutes of moderate exercise at least five days a scientific underpinnings and to calculate the cost-benefit lives. Every life year gained, the authors calculated, would Wanda Bemelmans, week. Bemelmans frequently takes weekend hikes, she says, but that isn’t enough. Vos used ratio in euros per life year gained. cost somewhere between € 6,000 and € 6,500. Added Public Health and to visit the health club twice a week, but hasn’t picked up the routine after returning from Comprehensive research of the literature and an inventory quality-adjusted life years (QALY) would cost between € Health Services Division maternity leave. She also used to do ballroom dancing, but that habit has waned, too. of expert opinions and experiences from local programs 5,600 and € 6,100 – amounts well within generally accepted (RIVM-V&Z) “For a long time, I thought I was easily getting my 10,000 steps a day,” says Bemelmans. produced key factors and conditions determining the boundaries for health interventions, they conclude. “When I finally used a step counter, I was quite shocked to learn that I barely reached 4,000. chances of success. Any plan should use an integrated It’s disappointing to realise how little exercise you get on a typical workday.” approach and secure support and operational assistance Wendel-Vos GCW, Ooijendijk WTM, Baal PHM van, Storm I, Luckily for both, they still have their 20-minute bicycle commute. “Thanks to that, I’m still of all relevant stakeholders, the authors conclude. Groups Vijgen SMC, Jans M, Hopman-Rock M, Schuit AJ, Wit GA de, complying with the norm,” says Bemelmans. that can be targeted selectively should be identified and Bemelmans WJE While both really enjoy doing scientific research, combining the work with other scientific research should be part of the plan. Cost-effectiveness and health gains in realising policy commitments can be challenging, they say. In recent years, they have sensed a tendency to Based on analyses of two Dutch pilot projects, the ambitions for physical activity and overweight: underpinning move towards performing meta-analyses and compiling research published by others. “In authors defined feasible objectives of a National Action the National Action Plan for Sport and Physical Activity. the long run, that could harm our capacity to do high-quality research,” says Bemelmans. Plan. After five years, they say, such a plan could reduce [Kosteneffectiviteit en gezondheidswinst van behalen Gathering your own data makes it a lot easier to publish papers and establish a scientific the prevalence of inactive individuals (currently at beleidsdoelen bewegen en overgewicht - Onderbouwing reputation, adds Vos. about 8%) by one or two percentage points, and the Nationaal Actieplan Sport en Bewegen] Both researchers are brimming with plans for new research projects. Vos, fresh from maternity prevalence of overweight (currently at about 47%) by RIVM report 260701001/2005 leave, is contemplating a study into how social environment affects exercise behaviour, a one to three percentage points. Implementation would http://www.rivm.nl/bibliotheek/rapporten/260701001.pdf subject also topping international research agendas. Bemelmans has secured funding from the Netherlands Organisation for Scientific Research (ZonMw) to study the efficacy of computer-

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    18 Environmental Health 19 Tiny particles having large health preferences on which journal we publish in, as long as our peers and the public can find our papers,” he says. Being involved in experimental and field research is essential for RIVM, Cassee says, although effects policy questions will always be the starting point. Luckily, he says, his main client, the Ministry for Housing, Spatial Planning and the Environment (VROM), agrees that broader research has a place within its assignments. More fundamental research, Cassee says, is funded by RIVM’s own strategic research fund (SOR) and sources outside. Much confusion arose in 2005 when new, EU-mandated limits for Even those two sources cannot answer all the needs of an ambitious research group. That’s not a bad thing, Cassee says. “Our limited capacity has forced us to collaborate with colleagues peak concentrations of particulate matter went into force. Refining abroad. Thanks to that, we now have strong partnerships with all the important players in the such standards and understanding the health effects of small field – in Europe, the US and Japan.” Having seen examples world-wide, Cassee likes the set-up of the US EPA. “EPA has a strong particles in ambient air will take many years of research. research programme on air pollution. What’s more, EPA also funds external research, enabling it to influence science agendas elsewhere,” he says. Cassee helped EPA review joint research programs of US universities and institutes. “I’d love to set up similar projects with universities Flemming Cassee was trained as a biologist and earned his Ph.D. at Utrecht University after and TNO in our own country,” he says. studying the health effects of inhaling aldehydes. Following a few years at the Dutch institute The next few years Cassee hopes to clear up how particulate matter produces health effects. for applied research (TNO) in Zeist, he moved to RIVM in Bilthoven, also close to Utrecht, in “Thus far we’ve done mostly association studies in which all particle types and sizes were 1995. added up,” he says. “We have learned a lot about the complexity of particulate matter, but for Cassee now heads RIVM’s section of Toxic Effects of Air Pollution, where he still does inhalation more source-oriented abatement strategies we need to know what goes on underneath. Do research. Part of that work is done in RIVM’s unique mobile lab, a trailer in which human particles enter the body only through the lungs, or can they also enter through nasal passages? volunteers can be exposed to various concentrations of particulate matter in air sampled at Which type causes which health effect? What’s the role of particles smaller than one hundred remote high-risk locations such as highway roadsides. nanometres, which currently are not regulated at all? Are peak exposures very important or In 2005, Cassee found himself in the eye of a political storm after the implementation of new should we focus on long-term exposures? Those are the questions that really get us excited.” EU rules on maximum levels of particulate matter. Overall levels in the Netherlands had fallen for many years and still continued to decline. But to the public at large, the introduction of lower limits for peak loads suggested they were rapidly rising instead. The new measures caused many major building projects to be put on hold, leading to intense legal and political wrangling and a flurry of media reports. Ultimately, the Dutch government decided to take Hypertensive rats can be models for susceptible humans sea salt particles, blown in from the North Sea, out of the equation – a pragmatic solution that isn’t necessarily evidence-based, Cassee notes. The health consequences of airborne particulate matter Air taken from a road tunnel was injected directly into the In an attempt to stem the confusion, Cassee, together with the Netherlands Environmental are of major concern because epidemiological studies trachea of the rats at various concentrations. For this breed Assessment Agency, authored a comprehensive report, entitled ‘A closer look at particulate have shown effects at concentrations often observed in of rats, the optimal testing dose lies between three and ten matter’ (Fijn stof nader bekeken). ambient air. Increased concentrations of particulate matter milligrams of particulate matter per kilogram body weight, Halfway 2006, the political dust has mostly settled. What’s left are the many news clippings have been linked to increased hospital admissions, visits the researchers found. Necropsies to check for health effects covering Cassee’s office walls. to emergency rooms, and even premature deaths. Health are best performed 24 hours after exposure. Among the Flemming Cassee, effects have also been observed in animal research and health effects seen were pulmonary inflammation, oxidative Environment and Safety inhalation studies using human volunteers. Not only the stress and, possibly, changes in blood circulation. Division Peer-reviewed respiratory tract is affected; cardiovascular disease, too, Spontaneously hypertensive rats are good models for (RIVM-MEV) appears to be an important consequence of exposure to assessing possible health effects of particulate matter in When Cassee arrived at RIVM, he says, reports used to be his department’s main outlet particulate matter. humans, the researchers conclude. – papers in peer-reviewed journals were published only occasionally. Cassee has worked Much research will be needed, however, to understand hard to turn that situation around. Today, he says, his department produces as few reports as these relationships and to compare the effects of ambient Gerlofs-Nijland ME, Boere AJF, Leseman DLAC, Dormans JAMA, possible. “In general, gray literature, including reports, is no longer cited in reviews by the US air at different locations. Sandström T, Salonen RO, Bree L van, Cassee FR. Environmental Protection Agency (EPA) or the World Health Organisation,” he says. “Our work This study, part of two multi-centre EU-funded research Effects of particulate matter on the pulmonary and vascular has to be peer-reviewed.” projects, aimed to determine which dose should be used in system: time course in spontaneously hypertensive rats Cassee doesn’t regret the transition. Writing reports is often time-consuming because many animal testing and how long after exposure necropsies on Particle and Fibre Toxicology 2005, 2:2, 24 March 2005. people like to have their say, he says, while research papers only need the consent of co- the animals should be performed. The study used rats prone www.particleandfibretoxicology.com/content/2/1/2 authors and, if the subject is politically sensitive, his boss. What’s more, he adds, reports don’t to hypertension to guarantee that effects are picked up, and DOI:10.1186/1743-8977-2-2 show up on PubMed, an international, web-based database for life-science-related papers. to simulate susceptible humans. Cassee has published papers in highly respected journals in the field of toxicology, aerosol research, epidemiology and environmental exposure. “Personally, however, I don’t have strong

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    20 Infectious Diseases 21 Fighting microbes without borders many previous studies focused on Europe and Asia, Kremer plans to do more testing on strains emerging in Africa and South-America. (She’s already looking forward to the meetings abroad.) Another advantage of the collaboration project is that there’s an emphasis on fundamental A world-wide epidemic of tuberculosis is raging, and strains of the research, leading to many opportunties to publish in peer-reviewed journals. “To me, that’s very important,” Kremer says. “Apart from one yearly report on the state of TB in The microbe that are resistant to drugs and a widely Netherlands, these days we try to publish in international journals. That way, everyone can used vaccine are emerging. Recognising these strains is the first read what we’ve done. And yes, I prefer to publish in high-impact journals; I think every researcher should aim for a paper in Science or Nature. But of course it usually doesn’t work step in understanding the epidemic–and ultimately defeating it. that way. We just had a paper published in Emerging Infectious Diseases, which was great, although I confess we had tried The Lancet first.” Next on Kremer and Van Soolingen’s list: applying for a grant from RIVM’s strategic research Kirsten Kremer used to dream about leaving her country and going to Ethiopia, to fight fund to have the genomes of about twenty TB strains fully sequenced. That, too, could prove poverty and tropical diseases where they occur. But the plan fell through; instead Kremer now invaluable for the development of a new, improved, and affordable vaccine, which many contributes to the fight from the RIVM campus in Bilthoven. From 2000 to 2003, she managed scientists agree is the world’s best hope to halt TB in poor countries. Says Kremer: “I really an international effort to find the best way to identify separate strains of Mycobacterium hope I will be able to contribute to that.” tuberculosis, the causative agent of TB, a disease that kills nearly two million people world- wide annually. Thanks in part to Kremer’s research, there now is a new standard test for discriminating between different M. tuberculosis strains; it produces reliable results in less than a day, rather than several weeks. What’s more, thanks to these tests researchers are now homing in on why some tuberculosis strains evade the current TB vaccine more easily than others. Such knowledge could help researchers find new, better vaccines. Genetic fingerprinting Kristin Kremer’s career path at RIVM was unusual. She didn’t start out as a researcher; in Beijing strain may be evading TB drugs and vaccines 1993, after graduating from the Institute for Life Sciences and Chemistry, she became a lab technician at RIVM’s Diagnostic Laboratory for Infectious Diseases and Perinatal Screening. Although tuberculosis (TB) has all but disappeared in rich Kremer then checked 49 studies world-wide for the There, she performed genetic fingerprinting techniques. countries, the disease is still raging world-wide. The World occurence of the so-called M. tuberculosis Beijing strain, Thanks in part to her being fluent in English, Kremer quickly found her way into international Health Organisation (WHO) estimates that one-third of first described in Beijing in 1995 but found all over the collaboration projects. In 2000, the lab initiated a new research project funded by the the world’s population is infected with Mycobacterium world since then. The strain is now dominant in Southeast European Commission (EC), and Kremer’s boss, Dick van Soolingen, co-ordinated the tuberculosis, TB’s causative agent. Many of them, especially Asia and some parts of Russia, while in Western Europe its contributions from 32 participating labs. Kremer became the project’s manager, a perfect those who are also carrying HIV, will eventually become ill. impact is still small but growing. position for setting up research for a Ph.D. thesis. In 2004, according to WHO figures, 9 million people got sick Finally, Kremer and colleagues applied the best And as it turned out, the project also gave her ample opportunity to fulfill her desire to spend and 1.7 million died of TB, with death rates highest in Africa fingerprinting techniques to analyse two subtypes within time abroad. “I enjoy being in touch with people all over the world,” Kremer says. “Our lab has and Southeast-Asia. the Beijing strain. Only one of these, dubbed the ‘typical a good reputation, and people ask me all sorts of questions about genetic fingerprinting. It’s Hampering the battle against the bacillus is the appearance Beijing strain’, proved to be associated with vaccine and Kristin Kremer, great to be able to help them out quickly.” of strains that have become resistant to either anti- drug resistance. It was also more prominent in younger Centre for Infectious She loves doing research, but it often has to be combined with other assignments, Kremer says. TB drugs or Bacille Calmette-Guerin (BCG), a partially patients. The findings add weight to the theory that the Disease Control Recently, for instance, she has taken over a few management tasks; she’s also filling in for a effective vaccine used in many countries. Learning how Beijing strain is the microbe’s adaptive response to the (RIVM-CIb) colleague who coordinates the diagnostic analysis of Mycobacterium samples, which routinely to quickly and reliably distinguish TB strains is important current generation of TB drugs and vaccines. come in at a rate of about 1,500 per year. “Diagnostic testing always comes first,” Kremer says. for understanding the epidemic and devising new control And she doesn’t regret it; it’s nice to work on real patients, people with names and histories, strategies. Kremer K once in a while. As part of a European research project Kremer worked with Genetic markers for Mycobacterium tuberculosis; Besides, the daily routine can also spawn new research. “In 1997, for example, we 30 other labs to compare 21 DNA fingerprinting tests. All characterisation and spread of the Beijing genotype characterised a new Mycobacterium species from a two-year-old Somalian patient.” labs characterised 131 unmarked isolates, 62 of which were (Ph.D. thesis) After earning her Ph.D. in 2005, Kremer quickly moved on to new international research doubles. Two tests topped the list with equal reproducibility ISBN 90901955521 projects. RIVM will co-ordinate a new EC-funded project called TB-ADAPT, in which eleven and discriminatory power, the researchers found. labs will take a very close look at genetic variation among M. tuberculosis strains. The goal: to find specific spots in the genome that affect resistance against vaccines or drugs. Because

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    22 Medical Technology 23 The exploding field of medical important for RIVM’s ability to stay in touch with the principal scientists in the field. “If you do research yourself, you are better able to assess the importance and quality of other people’s work, even if it’s in a neighbouring field,” he says. “At conferences, people approach you nanotechnology differently if you present your own data.” He cites the example of Wim de Jong, his co-author and RIVM colleague, who is well known internationally because of his experimental work. RIVM’s unique position as a public health institute that actively participates in research programs has benefited policy clients, says Geertsma. For instance, when he represents the Triggered by developments in science, RIVM set out to take stock Dutch government in European Union committees, strong ties with research have helped put The Netherlands on a par with bigger member states like France, Germany, and the UK. “In of the potential health risks of emerging nanotechnologies. 2004, the Dutch government used our scientific input to place emerging medical technologies Researchers at the institute are preparing to extend their own high on the agenda in Europe,” he says. “Subsequently, the European Commission asked The Netherlands to chair a working group on the topic.” work in the budding field. Many more chances for in-depth research may be just around the corner. Researchers from several RIVM departments have joined hands to set up a Nanotechnology Safety Centre. Funded by internal as well as external sources, they plan to collaborate extensively with Robert Geertsma was trained in organic chemistry – back at the University of Twente, he research partners outside. considered switching to courses in medical materials but decided against it. Yet at RIVM he ended up at the Medical Technology Section, and he now is a senior author of two comprehensive reports on medical applications of nanotechnology. The irony isn’t lost on him, but Geertsma says he’s hardly the only one who ended up switching to nanotechnology. He cites the example of David Reinhoudt, his university mentor, who now chairs the board of NanoNed, a Dutch research and development initiative dedicated to nanotechnology. A few years ago, Geertsma approached the Ministry of Health, Welfare and Sport (VWS) with the idea of identifying potential health risks of this emerging technology. His international More data on nano-particles’ toxic effects needed contacts told him a lot was happening, Geertsma says, and the government agreed it was time to take stock of developments and start thinking about potential problems. Nanotechnology is the design, characterisation, production Still, not much is known about nanomaterials’ potential The results of the study, written jointly with Boris Roszek and Wim de Jong, surprised him, says and application of structures, devices and systems by toxic effects, the second report says. Free-floating particles Geertsma. “Nanotechnology has already developed further and more widely than I had ever controlling the shape and size of materials at the nanometre in the nanometre range in particular warrant research, since imagined,” he says. “That is also the key message in these reports: the technology is booming scale. (One nanometre is one-millionth of a millimetre.) very small particles tend to be much more reactive than and in medicine it’s already being applied today. We urgently need more toxicology research In two reports, published simultaneously in 2005, RIVM bigger ones with the same chemical composition. Therefore, because, apart from the fact that nano-particles can be highly reactive, we don’t really know presented an overview of current and future medical relying on existing toxicological data will not be sufficient. very much about the risks.” applications of the technology as well as an assessment of Special attention should be given to drug-delivery systems its risks for human health. that release nano-particles or nano-tubes inside the body. In medicine, the first report says, the impact of Regulatory guidance at European levels is recommended, as Dig deeper nanotechnology will be profound, ranging from diagnostics is further research into nanotoxicology. to therapy and tools for prevention. Some types of On a scale ranging from policy advisor to bench scientist, Geertsma describes himself as nanotechnology are already in use, for instance in surgery, somewhere in the middle. His lab experience dates back to his university years, which ended medical imaging, and tissue engineering. Examples in 1994. At RIVM, his main clients are policy departments at the health ministry and the Dutch include nano-structured surgical blades and suture needles Roszek B, Jong WH de, Geertsma RE Health Care Inspectorate (IGZ), both of which are focused more on ‘desk research’ than on reinforced with stainless-steel. Other applications are found Nanotechnology in medical applications - State of the art in experimental studies. in contrast-enhancing agents for magnetic resonance materials and devices Robert Geertsma, For their investigation of the state of the art and the risks of nanotechnology, Geertsma and imaging, bone replacements, wound dressings, anti- RIVM Report 265001001/2005 Nutrition, Medicines and colleagues researched the scientific literature, examined company websites and attended microbial textiles, in-vitro molecular diagnostic chips, www.rivm.nl/bibliotheek/rapporten/265001001.pdf Consumer Safety Division scientific conferences. The study resulted in two reports, both of which made his clients happy. micro-cantilevers, and micro-needles. In the next few years, (RIVM-VGC)) They’re now used internationally to summarise the issues in the budding field. many other applications will hit the market, in particular in Jong WH de, Roszek B, Geertsma RE Yet Geertsma himself would have liked the opportunity to delve just a little bit deeper, and surgery, cancer diagnosis, cancer therapy, bio-detection of Nanotechnology in medical applications - Possible risks for redraft the reports into full-blown research papers that could have been submitted to peer- disease markers, molecular imaging, implant technology, human health reviewed journals. Finding the time to do that, however, isn’t easy, he says. In recent years, tissue engineering, and devices for drug, protein, gene, or RIVM Report 265001002/2005 Geertsma says, it has become more difficult to convince policy makers at the health ministry radionuclide delivery. www.rivm.nl/bibliotheek/rapporten/265001002.pdf that RIVM researchers sometimes need to dig deeper than the policy question at hand. Being intimately involved with the research itself, Geertsma says, will nevertheless be

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    Research Output

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    26 Research output | Centre for Infectious Disease Control 27 Research output Berk PA, Jonge R de, Zwietering MH, Abee T, Kieboom J Acid resistance variability among isolates of Salmonella enterica serovar Typhimurium DT104. Brussee JE, Smit HA, Brunekreef B, Jongste JC de Author’s reply to: Exhaled nitric oxide in 4-year-old children: relationship with asthma and atopy [Letter to the Centre for Infectious Disease Control J Appl Microbiol 2005; 99(4):859-66 editor]. Eur Resp J 2005; 26(2):359-60 CIb Bogaert D, Veenhoven RH, Sluijter M, Wannet WJ, Rijkers GT, Mitchell TJ, Clarke SC, Goessens WH, Schilder AG, Sanders Buijtels PCAM, Petit PLC, Verbrugh HA, Belkim A van, EA, Groot R de, Hermans PW Soolingen D van Molecular epidemiology of pneumococcal colonization Isolation of nontuberculous mycobacteria in Zambia: in response to pneumococcal conjugate vaccination in eight case reports. Research Papers (International, 143) children with recurrent acute otitis media. J Clin Microbiol 2005; 42(12):6020-6 J Clin Microbiol 2005; 43(1):74-83 Abbink F, Buisman AM, Doornbos G, Woldman J, Kimman TG, Backendorf C, Wit J de, Oosten M van, Stout GJ, Mitchell Caro V, Njamkepo E, Amersfoorth SCM van, Mooi FR, Advani Conyn-van Spaendonck MAE JR, Borgstein AM, Horst GT van der, Gruijl FR de, Brouwer Boot R, Berg L van den, Lith HA van, Veenema JL A, Hallander HO, He Q, Mertsola J, Riffelmann M, A Poliovirus-specific memory immunity in seronegative elderly people does not protect against virus excretion J Infect Dis 2005; 191(6):990-9 B J, Mullenders LHF, Hoeijmakers JHJ Repair characteristics and differentiation propensity of long-term cultures of epidermal keratinocytes derived Rat strains differ in antibody response to natural Haemophilus species infection. Laboratory Animals 2005; 39(4):413-20 C Vahrenholz C, Konig CHW von, Guiso N Pulsed-field gel electrophoresis analysis of Bordetella pertussis populations in various European countries with from normal and NER-deficient mice. different vaccine policies. Amersfoorth SCM van, Schouls LM, Heide HGJ van der, Advani DNA Repair 2005; 4(11):1325-36 Boot R, Hinz KH Microbes Infection 2005; 7(7-8):976-82 A, Hallander HO, Bondeson K, Konig CHW von, Antigenic relationship of avian strains of three Bordetella Riffelmann M, Vahrenholz C, Guiso N, Caro V, Njamkepo Bakker-Woudenberg IAJM, Vianen W van, Soolingen D van, species determined by ELISA. Chacon-Salinas R, Serafin-Lopez J, Ramos-Payan R, Mendez- E, He Q, Mertsola J, Mooi FR Verbrugh HA, Agtmael MA van Vet Rec 2005; 157(15):447-8 Aragon P, Hernandez-Pando R, Van Soolingen D, Flores- Analysis of Bordetella pertussis populations in European Antimycobacterial agents differ with respect to their Romo L, Estrada-Parra S, Estrada-Garcia I countries with different vaccination policies. bacteriostatic versus bactericidal activities in relation to Borgdorff MW, Werf MJ van der, Haas PEW de, Kremer K, Differential pattern of cytokine expression by J Clin Microbiol 2005; 43(6):2837-43 time of exposure, mycobacterial growth phase, and their Soolingen D van macrophages infected in vitro with different use in combination. Tuberculosis elimination in the Netherlands. Mycobacterium tuberculosis genotypes. Apetroaie C, Andersson MA, Sproer C, Tsitko I, Shaheen R, Antimicrob Agents Chemother 2005; 49(6):2387-98 Emerg Infect Dis 2005; 11(4):597-602 Clin Exp Immunol 2005; 140(3):443-9 Jaaskelainen EL, Wijnands LM, Heikkila R, Salkinoja- Salonen MS Banus HA, Kranen HJ van, Mooi FR, Hoebee B, Nagelkerke NJ, Borgen K, Loo I van, Koedijk F, Laar M van de Deutekom H van, Supply P, Haas PEW de, Willery E, Hoijng Cereulide-producing strains of Bacillus cereus show Demant P, Kimman TG Increase of gonococcal quinolone resistance in the SP, Locht C, Coutinho RA, Soolingen D van diversity. Arch Microbiol 2005; 184(3)141-51 Genetic control of Bordetella pertussis infection: identification of susceptibility loci using recombinant congenic strains of mice. Netherlands from 2002-2004. Eurosurveillance Weekly 2005; 10(11) D Molecular typing of Mycobacterium tuberculosis by mycobacterial interspersed repetitive unit-variable- number tandem repeat analysis, a more accurate method Arend SM, Haas P de, Leyten E, Rosenkrands I, Rigouts L, Infect Immun 2005; 73(2):741-7 Boshuizen JA, Reimerink JHJ, Korteland-van Male AM, Ham for identifying epidemiological links between patients Andersen P, Mijs W, Dissel JT van, Soolingen D van VJJ van, Bouma J, Gerwig GJ, Koopmans MPG, Buller HA, with tuberculosis ESAT-6 and CFP-10 in clinical versus environmental Barwolff S, Grundmann H, Schwab F, Tami A, Behnke M, Dekker J, Einerhand AWC J Clin Microbiol 2005; 43(9):4473-9 isolates of Mycobacterium kansasii. Geffers C, Halle E, Gobel UB, Schiller R, Jonas D, Klare Homeostatis and functional of goblet cells during J Infect Dis 2005; 191:1301-10 I, Weist K, Witte W, Dinger E, Beilecke K, Ruden H, rotavirus infection in mice. Diavatopoulos DA, Cummings CA, Schouls LM, Brinig MM, Gastmeier P Virology 2005; 337(2):210-21 Relman DA, Mooi FR Asten L van, Zangerle R, Aguado IH, Boufassa F, Broers B, Incidence of transmission of pathogens in intensive care Bordetella pertussis, the causative agent of whooping Brettle RP, Robertson JR, McMenamin J, Coutinho RA, units. Results of the SIR 3 study. Bosman A, Meijer A, Koopmans M cough, evolved from a distinct, human-associated lineage Prins M Anaesthesist 2005; 54(6):560-6 Final analysis of Netherlands avian influenza outbreaks of B. bronchiseptica Do HIV disease progression and HAART response vary reveals much higher levels of transmission to humans Plos Pathogens 2005; 1(4):e45 among injecting drug users in Europe? Berg H van den, Lodder W, Poel W van der, Vennema H, Roda than previously thought. Eur J Epidemiol 2005; 20(9):795-804 Husman AM de Eurosurveillance Weekly 2005; 10(1) Diaz R, Crespo FM, Herrera S, Sevy-Court J, Marrero A, Genetic diversity of noroviruses in raw and treated sewage Soolingen D van Avoort HGAM van der water. Boven M van, Mooi FR, Schellekens JFP, Melker H de, Laboratory cross-contamination of Mycobacterium P3 ELISA unfairly managed Res Microbiol 2005; 156(4):532-40 Kretzschmar M tuberculosis during preparation of smears. Quarterly update WHO Polio Labnetwork 2005; XI-1:3 Pathogen adaptation under imperfect vaccination: Internet J Third World Med 2005; 2(2) implications for pertussis. Proc R Soc B 2005; 272(1572):1617-24

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    28 Research output | Centre for Infectious Disease Control 29 Diederen BMW, Jong CMA de, Aarts I, Peeters MF, Gageldonk- Gazouli M, Ikonomopoulos J, Koundourakis A, Bartos M, Grundmann H, Baerwolff S, Tami A, Behnke M, Schwab Kam KM, Yip CW, Tse LW, Wong KL, Lam TK, Kremer K, Au Lafeber AB van, Wilbrink B, Zee A van der Pavlik I, Overduin P, Kremer K, Gorgoulis V, Kittas C F, Geffers C, Halle E, Gobel UB, Schiller R, Jonas D, Klare I, BK, Soolingen D van D No evidence of Legionella infection in general practice patients presenting with acute respiratory infections in The Netherlands Characterization of Mycobacterium tuberculosis complex isolates from Greek patients with sarcoidosis by Spoligotyping Weist K, Witte W, Beck-Beilecke K, Schumacher M, Ruden H, Gastmeier P How many infections are caused by patient-to-patient K Utility of mycobacterial interspersed repetitive unit typing for differentiating multidrug-resistant Mycobacterium tuberculosis isolates of the Beijing family Clin Microbiol Infection 2005; 11(5):410-2 J Clin Microbiol 2005; 43(9):4858-61 transmission in intensive care units? J Clin Microbiol 2005; 43(1):306-13 Crit Care Med 2005; 33(5):946-51 Duijkeren E van, Wolfhagen MJHM, Heck MEOC, Wannet Geubbels ELPE, Wille JC, Nagelkerke NJD, Vandenbroucke- Kamp HJ van der, Oudshoorn CG, Elvers BH, Baarle M van, WJB Grauls CMJE, Grobbee DE, Boer AS de Grundmann H, Goossens H Otten BJ, Wit JM, Verkerk PH Transmission of a Panton-Valentine leucocidin-positive, Hospital-related determinants for surgical-site infection Report of working group 1: public health challenges Cutoff levels of 17-alpha-hydroxyprogesterone in neonatal methicillin-resistant Staphylococcus aureus strain following hip arthroplasty Clin Microbiol Infect 2005; 11(Suppl 1):36-40 screening for congenital adrenal hyperplasia should be between humans and a dog Infect Control Hosp Epidemiol 2005; 26(5):435-41 based on gestational age rather than on birth weight J Clin Microbiol 2005; 43(12):6209-11 Hahne S, Macey J, Tipples G, Varughese P, King A, Binnendijk J Clin Endocrinol Metab 2005; 90(7):3904-7 Giessen JWB van der, Fonville M, Briels I, Pozio E R van, Ruijs H, Steenbergen J van, Timen A, Loon AM van, Duizer E, Koopmans M Efficacy of ethanol-based hand rubs [Letter to the editor] J Hosp Infect 2005; 61(4):362-3 Phylogenetic analysis of encapsulated and non- encapsulated Trichinella species by studying the 5S rDNA tandemly repeated intergenic region H Melker H de Rubella outbreak in an unvaccinated religious community in the Netherlands spreads to Canada Kasteren MEE van, Mannien J, Kullberg BJ, Boer AS de, Nagelkerke NJ, Ridderhof M, Wille JC, Gyssens IC Quality improvement of surgical prophylaxis in Dutch Vet Parasitol 2005; 132(1-2):51-5 Eurosurveillance Weekly 2005; 10(5) hospitals: evaluation of a multi-site intervention by time Duynhoven YT van, Jager CM de, Kortbeek LM, Vennema H, series analysis Koopmans MP, Leusden F van, Poel WH van der, Broek MJ Gooskens J, Neeling AJ de, Willems RJ, Wout JW van ‘t, Hahne S, Ward M, Abbink F, Binnendijk R van, Ruijs H, J Antimicrob Chemother 2005; 56(6):1094-102 van den, eXplosie Project Team Kuijper EJ Steenbergen J van, Timen A, Melker H de A one-year intensified study of outbreaks of gastroenteritis Streptococcal toxic shock syndrome by an iMLS resistant M Large ongoing rubella outbreak in religious community in Kerkhof M, Wijga A, Smit HA, Jongste JC, Aalberse RC, in The Netherlands type 77 Streptococcus pyogenes in the Netherlands the Netherlands since september 2004 Brunekreef B, Gerritsen J, Postma DS, PIAMA Study Group Epidemiol Infect 2005; 133(1):9-21 Scand J Infect Dis 2005; 37(2):85-9 Eurosurveillance Monthly 2005; 10(1-3):53 The effect of prenatal exposure on total IgE at birth and sensitization at twelve months and four years of age: The Fischer ARH, Jong AEI de, Jonge R de, Frewer LJ, Nauta MJ Gori A, Bandera A, Marchetti G, Esposti AD, Catozzi L, Nardi Hak E, Schonbeck Y, Melker H de, Essen GA van, Sanders EAM PIAMA study Improving food safety in the domestic environment: the GP, Gazzola L, Ferrario G, Embden JDA van, Soolingen D Negative attitude of highly educated parents and health Pediatr Allergy Immunol 2005; 16(1):10-8 F need for a transdisciplinary approach Risk Analysis 2005; 25(3):503-17 van, Moroni M, Franzetti F Spoligotyping and mycobacterium tuberculosis Emerg Infect Dis 2005; 11(8):1242-8 care workers towards future vaccinations in the Dutch childhood vaccination program Vaccine 2005; 23(24):3103-7 Kivi M, Pelt W van, Notermans D, Giessen A van de, Wannet W, Bosman A Flint JA, Duynhoven YT van, Angulo FJ, DeLong SM, Braun P, Large outbreak of Salmonella Typhimurium DT104, the Kirk M, Scallan E, et.al. Griethuysen A van, Loo I van, Belkum A van, Vandenbroucke- Havelaar AH, Garssen J, Takumi K, Koedam M, Ritmeester W, Netherlands, september-november 2005 Estimating the burden of acute gastroenteritis, foodborne Grauls C, Wannet W, Keulen P van, Kluytmans J Foneyne L de la, Bousema T, Vos JG Eurosurveillance Weekly 2005; 10(no 12) disease, and pathogens commonly transmitted by food: an Loss of the mecA gene during storage of methicillin- Intraspecies variability in the dose-response relationship international review resistant Staphylococcus aureus strains for Salmonella Enteritidis associated with genetic Koopmans M Clin Infect Dis 2005; 41(5):698-704 J Clin Microbiol 2005; 43(3):1361-5 differences in cellular immune response Outbreaks of viral gastroenteritis: what’s new in 2004? J Food Prot 2005; 67(9):2008-15 Curr Opin Infect Dis 2005; 18(4):295-9 Foppen JW, Mporokoso A, Schijven JF Grode L, Seiler P, Baumann S, Hess J, Brinkmann V, Eddine Determining straining of Escherichia coli from AN, Mann P, Goosmann C, Bandermann S, Smith D, Heide R van der, Koopmans MPG, Shekary N, Houwers DJ, Koopmans M breakthrough curves Bancroft GJ, Reyrat JM, Soolingen D van, Raupach B, Duynhoven YTHP van, Poel WHM van der Food-borne norovirus outbreaks: a nuisance of more than J Contam Hydrol 2005; 76(3-4):191-210 Kausmann SHE Molecular characterizations of human and animal group a that? Increased vaccine efficacy against tuberculosis of rotaviruses in The Netherlands Wiener Klin Wochenschr 2005; 117(23-24):789-91 Gageldonk-Lafeber AB, Heijnen MLA, Bartelds AIM, Peters MF, recombinant Mycobacterium bovis bacille Calmette- J Clin Microbiol 2005; 43(2):669-75 Plas SM van der, Wilbrink B Guerin mutants that secrete listeriolysin Koster B, Borgen K, Meijer H, Plas S van der, Kuyvenhoven V G A case-control study of acute respiratory tract infection in general practice patients in the Netherlands Clin Infect Dis 2005; 41(4):490-7 J Clin Invest 2005; 115(9):2472-9 Grotenberg GM, Witte MD, Hoof PA van, Spalburg E, Reiss P, Hijnen M, Gageldonk PG, Berbers GA, Woerkom T van, Mooi FR The Bordetella pertussis virulence factor P.69 pertactin Large scale contact tracing after a case of open tuberculosis in a supermarket, the Netherlands, January- February Noort D, Neeling AJ de, Koert U, Marel GA van der, retains its immunological properties after overproduction Eurosurveillance Weekly 2005; 10(2) Overkleeft HS, Overhand M in Escherichia coli Synthesis and biological evaluation of gramicidin S dimers Protein Expr Purif 2005; 41(1):106-12 Org Biomol Chem 2005; 3(2):233-8

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    30 Research output | Centre for Infectious Disease Control 31 Kovats RS, Edwards SJ, Charron D, Cowden J, D’Souza R, Ebi Langermans JAM, Doherty TM, Vervenne RAW, Laan T Mooijman KA, Ghameshlou Z, Bahar M, Jofre J, Havelaar AH Pedoby RG, Gay NJ, Giammanco A, Baron S, Schellekens J, KL, Gauci C, Gerner-Smidt P, Hajat S, Hales S, Hernandez van der, Lyashchenko K, Greenwald R, Agger EM, Aagaard Enumeration of bacteriophages in water by different Tischer A, Olander RM, Andrews NJ, Edmunds WJ, Lecoeur K Pezzi G, Kriz B, Kutsar K, McKeown P, Mellou K, Menne B, O’Brien S, Pelt W van, Schmid H Climate variability and campylobacter infection: an C, Weiler H, Soolingen D van, Dalemans W, Thomas AW, Andersen P Protection of macaques against Mycobacterium laboratories of the European Union in two interlaboratory comparison studies J Virol Methods 2005; 127(1):60-8 H, Levy-Bruhl D, Maple PA, Melker H de, Nardone A, Rota MC, Salmaso S, Conyn-van Spaendonck MA, Swidsinksi S, Miller E international study tuberculosis infection by a subunit vaccine based on a The seroepidemiology of Bordetella pertussis infection in Int J Biometeorol 2005; 49(4):207-14 fusion protein of antigen 85B and ESAT-6 Morcillo N, Giulio B de, Chirico C, Kuriger A, Dolmann A, Western Europe Vaccine 2005; 23(21):2740-50 Alito A, Zumarraga M, Soolingen D van, Kremer K, Cataldi Epidemiol Infect 2005; 133(1):159-71 Kremer K, Arnold C, Cataldi A, Gutierrez C, Haas WH, A Panaiotow S, Skuce RA, Supply P, Zanden AGM van der, Lanting CI, Tijn DA van, Loeber G, Vulsma T, Vijlder JJM de, First description of Mycobacterium tuberculosis Beijing Pinelli E, Withagen C, Fonville M, Verlaan A, Dormans J, Soolingen D van Verkerk PH genotype in Argentina Loveren H van, Maizels RM, Giessen J van der Discriminatory power and reproducibility of novel DNA Clinical effectiveness and cost-effectiveness of the use of Rev Argent Microbiol 2005; 37:92-5 Persistent airway hyper-responsiveness and inflammation typing methods for Mycobacterium tuberculosis complex the thyroxine/thyroxine-binding globulin ratio to detect in Toxocara canis-infected BALB/c mice strains congenital hypothyroidism of thyroidal and central origin Morre SA, Spaargaren J, Fennema JSA, Vries HJC de, Coutinho Clin Exp Allergy 2005; 35(6):826-32 J Clin Microbiol 2005; 43(11):5628-38 in a neonatal screening program FA, Pena AS Pediatrics 2005; 116(1):168-73 Real-time polymerase chain reaction to diagnose Poel WHM van der, Heide RV van der, Bakker D, Looff M de, Kremer K, Kam Yan Au B, Chi Wai Yip P, Skuce R, Supply P, lymphogranuloma venereum [Letter to the editor] Jong J de, Manen N van, Gaasenbeck CPH, Borgsteede FHM Man Kam K, Soolingen D van Li WM, Wang SM, Li CY, Liu YH, Shen GM, Zhang XX, Niu TG, Emer Infect Dis 2005; 11(8):1311-2 Attempt to detect evidence for tick-borne encephalitis Use of variable-number tandem-repeat typing to Gao Q, Soolingen D van, Kremer K, Duanmu HJ virus in ticks and mammalian wildlife in The Netherlands differentiate Mycobacterium tuberculosis Beijing family Molecular epidemiology of Mycobacterium tuberculosis in Mostowy S, Inwald J, Gordon S, Martin C, Warren R, Kremer Vector Borne Zoonotic Dis 2005; 5(1):58-64 isolates from Hong Kong and comparison with IS6110 China: a nationwide random survey in 2000 K, Cousins D, Behr MA restriction fragment length polymorphism typing and Int J Tuberc Lung Dis 2005; 9(12):1314-9 Revisiting the evolution of Mycobacterium bovis Poel WHM van der, Heide R van der, Verstraten ERAM, spoligotyping J Bacteriol 2005; 187(18):6386-95 Takumi K, Lina PHC, Kramps JA J Clin Microbiol 2005; 43(1):314-20 Lodder WJ, Roda Husman AM de European bat lyssavirus, the Netherlands Presence of noroviruses and other enteric viruses in Nauta MJ Emer Infect Dis 2005; 11(12):1854-9 Kummeling I, Thijs C, Penders J, Snijders BEP, Stelma F, sewage and surface waters in The Netherlands Microbiological risk assessment models for partitioning Reimerink J, Koopmans M, Dagnelie PC, Huber M, Jansen MCJF, Bie R de, Brandt PA van den Appl Environm Microbiol 2005; 71(3):1453-61 N and mixing during food handling Int J Food Microbiol 2005; 100(1-3):311-22 Reisig F, Kremer K, Amthor B, Soolingen D van, Haas WH Fast ligation-mediated PCR, a fast and reliable method Etiology of atopy in infancy: the KOALA Birth Cohort Study Pediatric Allergy Immunol 2005; 16(8):679-84 Lodder-Verschoor F, Roda Husman AM de, Berg HHJL van den, Stein A, Pelt-Heerschap HML van, Poel WHM van der Year-round screening of noncommercial and commercial Nauta MJ, Havelaar AH A process risk model for Campylobacter in poultry R for IS6110-based typing of Mycobacterium tuberculosis complex J Clin Microbiol 2005; 43(11):5622-7 Kurepina N, Likhoshvay E, Shaskina E, Mathema B, Kremer K, oysters for the presence of human pathogenic viruses Acta Horticulturae 2005; 674:392-402 Soolingen D van, Bifani P, Kreiswirth BN J Food Prot 2005; 68(9):1853-9 Reniers G, Araya T, Schaap A, Kumie A, Kebede D, Nagelkerke Targeted hybridization of IS6110 fingerprints identifies Nys S, Tjhie JHT, Bartelds AIM, Heijnen MLA, Peeters MF, N, Coutinho R, Sanders EJ the W-Beijing mycobacterium tuberculosis strains among Loots MA, Jong MD de, Soolingen D van, Wetsteyn JC, Faber Stobberingh EE Monitoring cause-specific adult mortality in developing clinical isolates WR Erythromycin resistance in the commensal throat flora of countries: a comparison of data sources for Addis Ababa J Clin Microbiol 2005; 43(5):2148-54 Chronic leg ulcer caused by Mycobacterium patients visiting the general practitioner: a reservoir for and its implications for policy and research immunogenum resistance genes for potential pathogenic bacteria Social Sci Med 2005; 61(9):1952-7 Laar MJW van de, Fenton KA, Ison C, on behalf of the ESSTI J Travel Med 2005; 12(6):347-9 Int J Antimicrob Agents 2005; 26(2):133-7 network Reuter G, Krisztalovics K, Vennema H, Koopmans MP, Szucs G L Update on the European lymphogranuloma venereum epidemic among men who have sex with men Mangen MJJ, Havelaar AH, Bernsen RAJAM, Koningsvels R van, Wit GA de Pebody RG, Gay NJ, Giammanco A, Baron S, Schellekens J, Tischer A, Olander RM, Andrews NJ, Edmunds WJ, Lecoeur Evidence of the etiological predominance of norovirus in gastroenteritis outbreaks-emerging new-variant and Eurosurveillance Monthly 2005; 10(4-6):134 Landeweert R, Leeflang P, Smit E, Kuyper T M The costs of human Campylobacter infections and sequelae in the Netherlands: a DALY and cost-of-illness approach P H, Levy-Bruhl D, Maple PAC, Melker H de, Nardone A, Rota MA, Salmaso S, Conyn-van Spaendonck MAE, Swidsinski S, Miller E recombinant noroviruses in Hungary J Med Virol 2005; 75(4):598-607 Diversity of an ectomycorrhizal fungal community studied Acta Agricult Scand C 2005; 2:35-51 The seroepidemiology of Bordetella pertussis infection in Robinson DA, Kearns AM, Holmes A, Morrison D, Grundmann by a root tip and total soil DNA approach Western Europe H, Edwards G, O’Brien F, Tenover FC, McDougal LK, Monk Mycorrhiza 2005; 15(1):1-6 Meijer A, Valette M, Manuguerra JC, Perez-Brena P, Paget J, J Clin Microbiol 2005; 43(3):1220-7 AB, Enright MC Brown C, Velden K van der Re-emergence of early pandemic Staphylococcus aureus Implementation of the community network of reference as a community-acquired meticillin-resistant clone laboratories for human influenza in Europe Lancet 2005; 365(9466):1256-8 J Clin Vir 2005; 32(2):87-96

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    32 Research output | Centre for Infectious Disease Control 33 Rockx B, Baric RS, Grijs I de, Duizer E, Koopmans MPG Santibanez S, Niewiesk S, Heider A, Schneider-Schaulies Schouten JM, Graat EAM, Frankena K, Giessen AW van de, Takumi K, Garssen J, Jonge R de, Jong W de, Havelaar W Characterization of the homo- en heterotypic immune J, Berbers GAM, Zimmermann A, Halenius A, Wolbert A, Zwaluw WK van der, Jong MCM de Release kinetics and cell trafficking in relation to bacterial R responses after natural norovirus infection J Med Virol 2005; 77(3):439-46 Deitemeier I, Tischer A, Hengel H Probing neutralizing-antibody responses against emerging measles viruses (MVs): immune selection of MV A longitudinal study of Escherichia coli O157 in cattle of a Dutch dairy farm and in the farm environment Vet Microbiol 2005; 107(3-4):193-204 T growth explain the time course of blood neutrophils and monocytes during primary Salmonella infection Int Immunol 2005; 17(1):85-93 Rockx BH, Bogers WM, Heeney JL, Amerongen JL van, by H protein-specific antibodies? Koopmans MP J Gen Virol 2005; 86(2):365-74 Semret M, Alexander DC, Turenne CY, Haas P de, Overduin P, Takumi K, Giessen J van der Experimental norovirus infections in non-human primates Soolingen D van, Cousins D, Behr MA Transmission dynamics of Echinococcus multilocularis; its J Med Virol 2005; 75(2):313-20 Schellekens J, Konig CH von, Gardner P Genomic polymorphisms for Mycobacterium avium subsp. reproduction number, persistence in an area of low rodent Pertussis sources of infection and routes of transmission in paratuberculosis diagnostics prevalence, and effectiveness of control Rockx BHG, Vennema H, Hoebe CJPA, Duizer E, Koopmans the vaccination era J Clin Microbiol 2005; 43(8):3704-12 Parasitology 2005; 131(1):133-40 MPG Pediatr Infect Dis J 2005; 24(5 Suppl):19-24 Association of histo-blood group antigens and Skraber S, Italiaander R, Lodder WJ, Roda Husman AM de Teunis P, Brandhof W van den, Nauta M, Wagenaar J, Kerkhof susceptibility to norovirus infections Schets FM, During M, Italiaander R, Heijnen L, Rutjes SA, Noroviruses in archival samples H van den, Pelt W van J Infect Dis 2005; 191(5):749-54 Zwaluw WK van der, Roda Husman AM de Emerg Infect Dis 2005; 11(3):489-91 A reconsideration of the Campylobacter dose-response Escherichia coli O157:H7 in drinking water from private relation Rodriquez-Lazaro D, D’Agostino M, Herrewegh A, Pla M, Cook water supplies in the Netherlands Skraber S, Schijven J, Gantzer C, Roda Husman AM de Epidemiol Infect 2005; 133(4):583-92 N, Ikonomopoulos J Water Res 2005; 39(18):4485-93 Pathogenic viruses in drinking-water biofilms: a public Real-time PCR-based methods for detection of health risk? Teunis PFM, Lodder WJ, Heisterkamp SH, Roda Husman AM Mycobacterium avium subsp. paratuberculosis in water Schets FM, Engels GB, During M, Roda Husman AM de Biofilms 2005; 2:1-13 de and milk Detection of infectious Cryptosporidium Oocysts by Mixed plaques: Statistical evidence how plaque assays may Int J Food Microbiol 2005; 101(1):93-104 cell culture immunofluorescence assay: applicability to Spaargaren J, Fennema HSA, Morre SA, Vries HJC de, underestimate virus concentrations environmental samples Coutinho RA Water Res 2005; 39(17):4240-50 Rutjes SA, Italiaander R, Berg HHJL van den, Lodder WJ, Roda Appl Environ Microbiol 2005; 71(11):6793-8 New lymphogranuloma venereum chlamydia trachomatis Husman AM de variant, Amsterdam Tiemersma EW, Monnet DL, Bruinsma N, Skov R, Monenn Isolation and detection of enterovirus RNA from large- Schets FM, Roda Husman AM de Emerg Inf Dis 2005; 11(7):1090-2 JCM, Grundmann H volume water samples by using the nucliSens miniMAG Health complaints linked to surface water recreation in Staphylococcus aureus bacteremia, Europe [Letter to the system and real-time nucleic acid sequence-based the Netherlands, 2000-2003 Spaargaren J, Schachter J, Moncada J, Vries HJC de, Fennema editor] amplification Eurosurveillance Weekly 2005; 10(3) HSA, Pena AS, Coutinho RA, Morre SA Emerg Inf Dis 2005; 11(11):1798-9 Appl Environ Microbiol 2005; 71(7):3734-40 Slow epidemic of lymphogranuloma venereum L2b strain Schijven JF, Roda Husman AM de Emerg Inf Dis 2005; 11(11):1787-8 Trotter C, Samuelsson S, Perrocheau A, Greeff S de, Melker H Ry van Beest Holle M de, Meijer A, Koopmans M, Jager CM Effect of climate changes on waterborne disease in The de, Heuberger S, Ramsay M de, Kamp EEHM van de, Wilbrink B, Conyn-van Netherlands Steenbergen J van, Debast S, Kregten E van, Berg R van den, Ascertainment of meningococcal disease in Europe Spaendonck MAE, Bosman A Water Sci Technol 2005; 51(5):79-87 Notermans D, Kuijper E Eurosurveillance Monthly 2005; 10(10-12)247 Human-to-human transmission of avian influenza a/H7N7, Isolation of Clostridium difficile ribotype O27, toxinotype The Netherlands, 2003 Schouls LM, Ende A van der, Pol I van de, Schot C, Spanjaard III in the Netherlands after increase in C.difficile- Tsolaki AG, Ganeux S, Pym AS, Goguet de la Salmoniere YOL, Eurosurveillance Monthly 2005; 10(12) L, Vauterin P, Wilderbeek D, Witteveen S associated diarrhoea Kreiswirth BN, Soolingen D van, Small PM Increase in genetic diversity of Haemophilus influenzae Eurosurveillance Weekly 2005; 10(7) Genomic deletions classify the Beijing/W strains as a Samper S, Iglesias MJ, Rabanaque MJ, Gomez LI, Lafoz MC, serotype b (Hib) strains after introduction of Hib distinct genetic lineage of mycobacterium tuberculosis Jimenez MS, Ortega A, Leczano MA, Soolingen D van, vaccination in the Netherlands Stout GJ, Oosten M van, Acherrat FZ, Wit J de, Vermeij WP, J Clin Microbiol 2005; 43(7):3185-91 S Martin C, the Spanish Working Group on MDR-TB Systematic molecular characterization of multidrug- resistant Mycobacterium tuberculosis complex isolates J Clin Microbiol 2005; 43(6):2741-9 Schouten JM, Giessen AW van de, Frankena K, Jong MCM de, Mullenders LHF, Gruijl FR de, Backendorf C Selective DNA damage responses in murine Xpa, Xpc and Csb keratinocyte cultures Veen Y van der, Hahne S, Ruijs H, Binnendijk R van, Timen A, Loon A van, Melker H de from Spain J Clin Microbiol 2005; 43(3):1220-7 Graat EAM Escherichia coli O157 prevalence in Dutch poultry, pig finishing and veal herds and risk factors in Dutch veal DNA repair 2005; 4(11):1337-44 Surikova OV, Voitech DS, Kuzmicheva G, Tatkov SI, Mokrousov V Rubella outbreak in an unvaccinated religious community in the Netherlands leads to cases of congenital rubella syndrome herds IV, Narvskaya OV, Rot MA, Soolingen D van, Filipenko ML Eurosurveillance Monthly 2005; 10(10-12):274 Prev Vet Med 2005; 70(1-2):1-15 Efficient differentiation of Mycobacterium tuberculosis strains of the W-Beijing family from Russia using highly Veldhuijzen IK, Smits LJ, Laar MJ van de polymorphic VNTR loci The importance of imported infections in maintaining Eur J Epidemiol 2005; 20(11):963-74 hepatitis B in The Netherlands Epidemiol Infect 2005; 133(1):113-9

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    34 Research output | Centre for Infectious Disease Control 35 Versteegh FGA, Mertens PLJM, Melker HE de, Roord JJ, Wallinga J, Heijne JCM, Kretzschmar M Xiridou M, Kretzschmar M, Geskus R Zeijl JH van, Bakkers J, Wilbrink B, Melchers WJG, Mullaart Schellekens JFP, Teunis PFM A measles epidemic threshold in a highly vaccinated Competition of pathogen strains leading to infection with RA, Galama JMD V Age-specific long-term course of IgG antibodies to pertussis toxin after symptomatic infection with Bordetella pertussis population Plos Genetics 2005; 2(11):e316 X variable infectivity and the effect of treatment Math Biosci 2005; 197(2):153-72 Influenza-associated encephalopathy: no evidence for neuroinvasion by influenza virus nor for reactivation of human herpesvirus 6 or 7 Epidemiol Infect 2005; 133(4):737-48 Wannet WJB, Spalburg E, Heck MEOC, Pluister GN, Zee A van der, Heck M, Sterks M, Harpal A, Spalburg E, Clin Infect Dis 2005; 40(3):483-5 Tiemersma E, Willems RJL, Huijsdens XW, Neeling AJ de, Kazobagora L, Wannet W Versteegh FGA, Weverling GJ, Peeters MF, Wilbrink B, Veenstra-van Schie MTM, Leeuwen-Gerritsen JM van, Mooi-Kokenberg EANM, Schellekens JFP, Roord JJ Etienne J Emergence of virulent methicillin-resistant staphylococcus aureus strains carrying panton-valentine leucocidin genes Z Recognition of SCCmec types according to typing pattern determined by multienzyme multiplex PCR-amplified fragment length polymorphism analysis of methicillin- Zouza FA de, Declerck S, Smit E, Kowalchuk GA Morphological, ontogenetic and molecular characterization of Scutellospora reticulata Community-acquired pathogens associated with in the Netherlands resistant Staphylococcus aureus (Glomeromycota) prolonged coughing in children: a prospective cohort J Clin Microbiol 2005; 43(7):3341-5 J Clin Microbiol 2005; 43(12):6042-7 Mycol Res 2005; 109(6):697-706 study Clin Microbiol Infect 2005; 11(10):801-7 Ward M, Brandsema P, Straten E van, Bosman A Electronic reporting improves timeliness and Viebahn M, Doornbos R, Wernars K, Loon LC van, Smit E, completeness of infectious disease notification, The Bakker PAHM Netherlands, 2003 Ascomycete communities in the rhizosphere of field- Eurosurveillance Monthly 2005; 10(1-3):27-30 Research Papers (Dutch, 59) grown wheat are not affected by introductions of genetically modified Pseudomonas putida WCS358r Welte R, Postma M, Leidl R, Kretzschmar M Avoort HGAM van der Environ Microbiol 2005; 7(11):1775-85 Costs and effects of chlamydial screening: dynamic versus Polio in 2004: de dynamiek van een verdoemd virus Duizer E, Kroneman A, Vennema H, Duijnhoven Y van, Viebahn M, Veenman C, Wernars K, Loon LC van, Smit E, Bakker PAHM static modeling Sex Transm Dis 2005; 32(8):474-83 A Infectieziekten Bulletin 2005; 16(2):46-8 Beaujean DJMA, Tiemersma EW, Neeling AJ de, Wannet WJB Koopmans M Veel uitbraken van gastro-enteritis door norovirus veroorzaakt door een nieuwe GGII.4-variant Assessment of differences in ascomycete communities in Wensing AMJ, Vijver DA van de, Angarano G, Coul EL op de, Nationale MRSA-surveillance nieuwe stijl: de resultaten na Infectieziekten Bulletin 2005; 16(2):59-61 the rhizospere of field-grown wheat and potato FEMS Microbiol Ecol 2005; 53:245-53 et al. Prevalence of drug-resistant HIV-1 variants in untreated individuals in Europe: implications for clinical B een half jaar Infectieziekten Bulletin 2005; 16(4):113-6 Duizer E, Morroy G, Wijk P van, Timen A, Koopmans M Inactivatie van calicivirussesn: maatregelen in geval van Vlaminckx BJM, Pelt W van, Schouls LM, Silfhout A van, management Bijkerk P een norovirusbesmetting Mascini EM, Elzenaar CP, Fernandes T, Bosman A, J Infect Dis 2005; 192(6):958-66 Risicobeheersing van Campylocbacter-infecties via Infectieziekten Bulletin 2005; 16(2):61-3 Schellekens JFP kuikenvlees in Nederland Long-term surveillance of invasive group A streptococcal Widdowson MA, Rockx B, Schepp R, Poel WHM van der, Vinje Infectieziekten Bulletin 2005; 16(7):237-40 Duynhoven YTHP van, Jager CM de, Heuvelink AE, Zwaluw disease in The Netherlands, 1994-2003 J, Duynhoven YT van, Koopmans MP WK van der, Maas HME, Pelt W van, Wannet WJB Clin Microbiol Infect 2005; 11(3):226-31 Detection of serum antibodies to bovine norovirus Boer IM de, Duynhoven YTHP van H9e stond het met de Shiga toxineproducerende in veterinarians and the general population in the Meldingen van voedselgerelateerde infecties en explosies Escherichia coli O157 in Nederland in 2004? Vlaminckx BJM, Pelt W van, Schellekens JFP Netherlands Infectieziekten Bulletin 2005; 16(10):377-83 Infectieziekten Bulletin 2005; 16(9):336-42 Epidemiological considerations following long-term J Med Virol 2005; 76(1):119-28 surveillance of invasive group A streptococcal disease in Boot R, Berg L van de, Vlemminx M Fuijkschot J, Pasman JW, Kortbeek LM, Verrips A, Willemsen the Netherlands, 1992-2003 Wijngaard C van den, Asten L van, Rockx B van, Pelt W van, Serologisch onderzoek van wilde Rattus rattus en R. MAAP Clin Microbiol Infect 2005; 11(7):564-8 Vrese M de, Rautenberg P, Laue C, Koopmans M, Herremens Godeke G, Koopmans M Syndromic approach to West Nile virus: the Netherlands 2002-2003 norvegicus Biotechniek 2005; 44:120-3 F Neurocysticercose: een importziekte om aan te denken Tijdschr Neur Neurochir 2005; 106:3-8 T, Schrezenmeir J Morb Mortal Weekly Report 2005; 54(Suppl):205 Coul ELM op de, Laar MJW van de Greeff SC de, Hahne SJM, Melker HE de Probiotic bacteria stimulate virus-specific neutralizing Stijging in meldingen acute hepatitis C door LGV- Rijksvaccinatieprogramma nog altijd zeer effectief antibodies following a booster polio vaccination Eur J Nutr 2005; 44(7):406-13 Willems RJL, Top J, Santen M van, Robinson A, Coque TM, Baquero F, Grundmann H, Bonten MJM Global spread of vancomycin-resistant Enterococcus C uitbraak? Infectieziekten Bulletin 2005; 16(6):206-9 G Infectieziekten Bulletin 2005; 16(7):235-7 Greeff SC de, Schellekens JFP, Mooi FR, Melker HE de Waar K, Herremans MMPT, Vennema H, Koopmans MPG, faecium from distinct nosocomial genetic complex Dijkstra F, Plas SM van der, Meijer A, Wilbrink B, Jong JC de, Effect van vaccinatie tegen kinkhoest op de incidentie van Benne CA Emer Infect Dis 2005; 11(6):821-8 Bartelds AIM kinkhoest in Nederland, 1996-2003 W Hepatitis E is a cause of unexplained hepatitis in the Netherlands J Clin Virol 2005; 33(2):145-9 D Surveillance van respiratoire infectieziekten in 2004/2005 Infectieziekten Bulletin 2005; 16(6):198-205 Ned Tijdschr Geneeskd 2005; 149(17):937-43

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    36 Research output | Centre for Infectious Disease Control 37 Hahne S, Ruijs H, Abbink F, Binnendijk R van, Melker H de Koedijk F, Veen M van, Laar M van de Mylius S Schets FM, Roda Husman AM de Rubella-epidemie in Nederland Mogelijkheden voor internationale samenwerking bij de Interventiedilemma’s bij grieppaniek Gezondheidsklachten in relatie tot recreatie in H Infectieziekten Bulletin 2005; 16(2):42 Hahne SJM, Abbink F, Binnendijk RS van, Ruijs WLM, bestrijding van LGV in Europa Infectieziekten Bulletin 2005; 16(5):153-5 Infectieziekten Bulletin 2005; 16(2):49-50 Neeling AJ de, Verbrugh HA oppervlaktewater in de zomer van 2004 Infectieziekten Bulletin 2005; 16(10):372-7 Steenbergen JE van, Melker HE de Koedijk FDH, Coul ELM op de, Laar MJW van de Gebruik van antibiotica in Nederland het laagste van Schets FM, Vries JMC de, Lierop GS van, Lodder WJ, Rubella-epidemie in Nederland in 2004-2005: alertheid op congenitaal rubellasyndroom vereist Ned Tijdschr Geneeskd 2005; 149(21):1174-8 Aangifte acute hepatitis B in 2003. Aandeel van heteroseksuelen neemt toe Infectieziekten Bulletin 2005; 16(1):15-7 N Europa Infectieziekten Bulletin 2005; 16(6):191-2 Duynhoven YTHP van, Roda Husman AM de Twee explosies van zwemmersjeuk in de zomer van 2004 Infectieziekten Bulletin 2005; 16(4):130-5 Notermans DW, Pelt W van, Kivi M, Giessen AW van de, Heijnen ML, Waldhober Q Koedijk FDH, Doul ELM op de, Laar MJW van de Wannet WJB, Bosman A Spanjaard L, Hof S van den, Melker HE de, Vermeer-de Bondt Overzicht van kiemsurveillance die voor de openbare Chronische hepatitis B infecties in Nederland: een Sterke toename van infecties met Salmonella serotype PE, Ende A van der, Rijkers GT gezondheidszorg van belang is overzicht van 2001-2003 Typhimurium DT104 in Nederland Toename van het aantal invasieve infecties door Infectieziekten Bulletin 2005; 16(10):360-3 Infectieziekten Bulletin 2005; 16(1):18-22 Ned Tijdschr Geneeskd 2005; 149(53):2992-4 Haemophilus influenzae type b Ned Tijdschr Geneeskd 2005; 149(49):2738-42 Heuvelink AE, Ripping M, Duynhoven YTHP van Kooi TII van der, Hofs S van den, Wille JC Oosten M van Zo rauw hadden ze het niet gegeten, maar wel gedronken. Surveillance van beademing-gerelateerde pneumonieen Extra hepatits-B-vaccinatie voor baby’s van draagsters Timen A, Vliet JA van, Koopmans MPG, Steenbergen JE van, Escherichia coli O157 en/of Campylobacter Infectieziekten Bulletin 2005; 16(8):268-9 binnen PREZIES Tijdschr Hyg Infectiepreventie 2005; 24(1):7-9 O Infectieziekten Bulletin 2005; 16(10):364 Oosten M van, Boer AS de T Coutinho RA Vogelgriep H5N1 in Europa: vooralsnog gering gezondheidsrisico voor Nederland Hof S van den Koopmans MPG BMR-vaccinatie en autisme Ned Tijdschr Geneeskd 2005; 149(46):2547-9 Uitspraak Raad van State van belang voor vrijwillige Poxviridae en de volksgezondheid Infectieziekten Bulletin 2005; 16(5):171-4 surveillancesystemen Infectieziekten Bulletin 2005; 16(3):94-5 Timmermans R, Boot R, Reubsaet FAG Infectieziekten Bulletin 2005; 16(1):10-1 Pelt W van, Wannet WJM, Giessen AW van de, Mevius DJ, Microbiologische verrassingen in sentinels en fosterdieren Kuijper EJ, Debast SB, Kregten E van, Vaessen N, Notermans Koopmans MPG, Duynhoven YTHP van Biotechniek 2005; 44:195-7 Jacobs PHA, Gageldonk-Lafeber AB van, Jager CM de, Bruin JP J Legionella-besmetting op een vakantiepark Infectieziekten Bulletin 2005; 16(7):257-9 DW, Broek PJ van den Clostridium difficile ribotype O27, toxinotype III in Nederland P Trends in gastro-enteritis van 1996 tot en met 2004 Infectieziekten Bulletin 2005; 16(7):250-6 Vliet JA van MRSA in de openbare gezondheidszorg Jong A de Ned Tijdschr Geneeskd 2005; 149(38):2087-9 Rahamat-Langendoen JC, Vliet JA van, Suijkerbuijk AWM Signalering van bedreigingen door infectieziekten V Infectieziekten Bulletin 2005; 16(1):9-10 Hygiënisch koken voorkomt infecties Voedingsmiddelentechnologie 2005; 38(1/2):9 Laar MWJ van de SOA nemen opnieuw toe: voorlopige cijfers 2004 R in Nederland in 2002 en 2003 door het wekelijkse signaleringsoverleg Vliet JA van, Warris-Versteegen AA De naoorlogse geschiedenis van Yersinia enterocolitica in Jong JC de, Rimmelzwaan GF, Bartelds AIM, Meijer A, Fouchier RAM, Osterhaus ADME L Infectieziekten Bulletin 2005; 16(4):116-7 Loo IHM van, Spaargaren J, Laar MJW van de Ned Tijdschr Geneeskd 2005; 149(40):2238-42 Ruijs WLM, Morroy G Nederland Infectieziekten Bulletin 2005; 16(7):265-6 Het influenzaseizoen 2004/’05 in Nederland met de Resistentie van gonokokken in Nederland; resultaten van Ervaringen van GGD-artsen met influenza in verpleeg- en Vries G de, Altena R van, Soolingen D van, Broekmans JF, Hest grootste epidemie van de laatste 5 jaar, door virusvariant een enquete bij medisch-microbiologische laboratoria verzorgingshuizen in het influenzaseizoen 2004-2005 NAH van A/California, en de vaccinsamenstelling voor het seizoen Ned Tijdschr Geneeskd 2005; 149(22):1217-22 Infectieziekten Bulletin 2005; 16(7):242 Een uitbraak van multiresistente tuberculose uit Oost- 2005/’06 Europa in Nederland Ned Tijdschr Geneeskd 2005; 149(42):2355-61 Medema GJ, Roda Husman AM de Sande MAB van der, Ruijs WLM, Cools HJM, Meijer A, Plas SM Ned Tijdschr Geneeskd 2005; 149(35):1921-4 Inspectierichtlijn voor analyse microbiologische veiligheid van der K Kate LP ten, Loeber JG, Knijf P de, Bovenberg JA Trends in onze genen: hielprikkaarten bewaren voor M drinkwater H2O 2005; 38(2):9-11 S Toepassing van antivirale middelen bij influenza-uitbraken in verpleeghuizen in het Ward M, Prins JM, Bruynesteijn van Coppenraet L, Lindeboom J, Kuijper EJ, Sande MAB van der onderzoek op lichaamsmateriaal Medisch Contact 2005; 60(4):1767-9 Morroy G, Wijkmans C, Duizer E Norovirusuitbraak op een internationale jamboree influenzaseizoen 2004-2005 Infectieziekten Bulletin 2005; 16(7):240-2 W Een cluster van kinderen met chronische lympadenitis en M. haemophilum Infectieziekten Bulletin 2005; 16(10):358-9 Koedijk F, Coul ELM op de, Laar MWJ van de Infectieziekten Bulletin 2005; 16(2):57-9 Sande MAB van der, Ruijs WLM, Meijer A, Cools HJM, Plas SM Aangifte acute hepatitis B in 2004. Aandeel mannen van der, Morroy G Warris-Versteegen AA, Vliet JA van neemt toe Mulder J, Giessen J van der Influenza uitbraken in verpleeghuizen 2004-2005. Wat De naoorlogse geschiedenis van salmonellose anders dan Infectieziekten Bulletin 2005; 16(8):296-8 Hoe oud is deze vos zijn de consequenties voor het komende griepseizoen? (para)tyfus in Nederland Zoogdier 2005; 16(1):3-7 Tijdschr Verpleeghuisgeneeskd 2005; 30:22-5 Infectieziekten Bulletin 2005; 16(5):176-9

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    38 Research output | Centre for Infectious Disease Control 39 Wijngaard CC van den, Asten L van, Vliet JA van, Pelt W van, Zeeuw AE van de, Wille JC, Hof S van den Pinelli E, Kortbeek LM, Giessen JWB van der Steenbergen JE van, Dalen PJ van Koopmans M Aandachtspunten bij het starten en onderhouden van Toxocara Structuur van de infectieziektebestrijding W Syndroomsurveillance om uitbraken van ongebruikelijke infectieziekten vroegtijdig te signaleren Ned Tijdschr Geneeskd 2005; 149(40):2243-5 surveillance van ziekenhuisinfecties binnen het PREZIES netwerk. Praktische punten naar aanleiding van de ontvangst van de surveillanceresultaten (fase 3) In: Cox FEG, Wakelin D, Gillespie SH, Despommier DD, eds. Parasitology. Topley & Wilson’s microbiology and microbial infections. 10th ed. In: Helsloot I, Steenbergen JE van, eds. Infectieziektenbestrijding. Studies naar organisatie en praktijkwerking. Tijdschr Hyg Infectiepreventie 2005; 24(3):55-7 London: Hodder Arnold, 2005;750-6 Den Haag: Boom Juridische Uitgevers, 2005;109-36 Wille J, Hof S van den Openbaarheid geen doel op zicht. Rechterlijke uitspraak Zeeuw AE van de, Wille JC, Hof S van den Polderman AM, Giessen JWB van de Timen A, Wijngaarden JK van beschermt vrijwillig surveillanceproject Aandachtspunten bij het starten en onderhouden van Medische parasitologie: handleiding bij de De leerpunten van SARS Medisch Contact 2005; 60(10):399-401 Zeeuw AE van de, Wille JC, Hof S van den surveillance van ziekenhuisinfecties binnen het PREZIES netwerk. Praktische punten bij kwaliteitsverbeterende activiteiten (fase 4) laboratoriumdiagnostiek. 4e dr. Arnhem: Syntax Media, 2005 T In: Helsloot I, Steenbergen JE van, eds. Infectieziektenbestrijding. Studies naar organisatie en praktijkwerking. Aandachtspunten bij het starten en onderhouden van Tijdschr Hyg Infectiepreventie 2005; 24(6):125-8 Schets FM, Roda Husman AM de, Havelaar AH Den Haag: Boom Juridische Uitgevers, 2005 Z surveillance van ziekenhuisinfecties binnen het PREZIES netwerk. Praktische punten tijdens de uitvoering van de surveillance (fase 2) S Water analysis: microbiological In: Worsfold PJ, Townshend A, Poole CF, eds. Encyclopedia of analytical science. 2nd ed. Tijdschr Hyg Infectiepreventie 2005; 24(2):27-32 Oxford: Elsevier, 2005;336-44 Steenbergen J van, Everdingen J van, eds Waar zouden we zijn zonder infecties? Essays over infectieziekten ter gelegenheid van 10 jaar LCI Alphen aan den Rijn, Belvedere-Medidact, 2005 Books, Chapters & Reports Bosman A, Vliet JA van Kerkhof JHTC van de, Steenbergen JE van Surveillance en signalering van infectieziekten Introductie in de infectieziektebestrijding B In: Helsloot I, Steenbergen JE van, eds. Infectieziektenbestrijding. Studies naar organisatie en praktijkwerking. K In: Helsloot I, Steenbergen JE van, eds. Infectieziektenbestrijding. Studies naar organisatie en praktijkwerking. Doctoral Theses Den Haag: Boom Juridische Uitgevers, 2005;85-107 Den Haag: Boom Juridische Uitgevers, 2005;19-48 Kremer K Genetic markers for Mycobacterium tuberculosis: Conyn-van Spaendonck MAE, Haperen VR van Kennis vergaren, vermeerderen en verspreiden Kimman TG, Hoebee B Relevance of genetic background in respiratory tract K characterization and spread of the Beijing genotype Amsterdam: Universiteit van Amsterdam, 2005. C In: Helsloot I, Steenbergen JE van, eds. Infectieziektenbestrijding. Studies naar organisatie en praktijkwerking. infections In: Kimpen J, Ramilo O, eds. The microbe-host interface in respiratory Den Haag: Boom Juridische Uitgevers, 2005;221-39 tract infections. Norfolk: Horizon Bioscience, 2005;1-30 Everdingen J van, Steenbergen J van Pieterman R, Steenbergen J van, Everdingen J van Professorial Chairs Leven op aarde: de mens als macrobe Maximale veiligheid? Fantomen van voorzorg bij E In: Steenbergen J van, Everdingen J van, eds. Waar zouden we zijn zonder infecties? Essays over infectieziekten ter P infectieziekten In: Steenbergen J van, Everdingen J van, eds. Waar zouden Coutinho RA Professor of Epidemiology and Infectious Disease control Koopmans MPG Professor of Viral infections in the gastrointestinal tract gelegenheid van 10 jaar LCI. Alphen aan den Rijn, Belvedere-Medidact, 2005:17-24 we zijn zonder infecties? Essays over infectieziekten ter gelegenheid van 10 jaar LCI. Alphen aan den Rijn, Belvedere-Medidact, 2005:189-204 C University of Amsterdam Gründmann H K Erasmus University, Rotterdam, Mooi FR Helsloot I, Steenbergen JE van, eds Professor of Epidemiology of microbial diseases Professor of Molecular Microbiology H Infectieziektebestrijding. Studies naar organisatie en praktijkwerking. Den Haag: Boom Juridische Uitgevers, 2005 Pinelli E Medische parasitologie In: Polderman AM, Giessen JWB van de. Medische G University of Groningen M Utrecht University parasitologie: handleiding bij de laboratoriumdiagnostiek. 4e dr. Arnhem: Syntax Media, 2005

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    42 Research output | Public Health and Health Services 43 Hoeymans N, Lindert H van, Westert GP Kremers SP, Visscher TL, Seidell JC van, Mechelen W van, Makinen J, Mertsola J, Mooi FR, Amersfoorth S van, Polder JJ, Meerding WJ, Bonneux L, Maas PJ van der The health status of the Dutch population as assessed by Brug J Arvilommi H, Viljanen MK, Qiushui H A cross-national perspective on cost of illness: a H the EQ-6D Qual Life Res 2005; 14(3):655-63 Cognitive determinants of energy balance-related behaviours: measurement issues Sports Med 2005; 35(11):923-33 M Bordetella pertussis isolates, Finland [Letter to the editor] Emerg Infect Dis 2005; 11(1):183-4 comparison of studies from The Netherlands, Australia, Canada, Germany, United Kingdom, and Sweden Eur J Health Econom 2005; 6(3):223-32 Hoffmann S, Peterbauer A, Schindler S, Fennrich S, Poole Mangen MJJ, Havelaar AH, Bernsen RAJAM, Koningsvels R S, Mistry Y, Montag-Lessing T, Spreitzer I, Loschner B, van Kremers SPJ, Visscher TLS, Brug J, Chin A Paw MJM, Schouten van, Wit GA de Schayck CP van, Smit HA Aalderen M, Bos R, Gommer M, Nibbeling R, Werner- EG, Schuit AJ, Seidell JC, Baak MA van, Mechelen W van, The costs of human Campylobacter infections and The prevalence of asthma in children: a reversing trend Felmayer G, Loitzl P, Jungi T, Brcic M, Brugger P, Frey E, Bowe G, Casado J, Coecke S, de Lange J, Mogster B, Naess LM, Aaberge IS, Wendel A, Hartung T Kemper HCG, Kok FJ, Saris WHM, Kromhout D Netherlands research programme weight gain prevention (NHF-NRG): rationale, objectives and strategies sequelae in the Netherlands: a DALY and cost-of-illness approach Acta Agricult Scand C 2005; 2:35-51 S Eur Respir J 2005; 26(4):647-50 Schellevis FG, Westert GP, Bakker DH de International validation of novel pyrogen tests based on Eur J Clin Nutr 2005; 59(4):498-507 The actual role of general practice in the Dutch health- human monocytoid cells Mantel-Teeuwisse AK, Klungel OH, Schalekamp T, Verschuren care system. Results of the Second Dutch National Survey J Immunol Methods 2005; 298:161-73 Kruijshaar ME, Barendregt J, Vos T, Graaf R de, Spijker J, WMM, Porsius AJ, Boer A de of General Practice Andrew G Suboptimal choices and dosing of statins at start of Med Klin 2005; 100(10):656-61 Hommerson P, Nedeljkovic SI, Klungel OH, Boer A de, Ostojic Lifetime prevalence estimates of major depression: an therapy MC, Grujic MZ, Vojodic NM, Bloemberg BPM, Kromhout D indirect estimation method and a quantification of recall Br J Clin Pharmacol 2005; 60(1):83-9 Schellevis FG, Westert GP, Bakker DH de Cardiovascular drug use and differences in the incidence bias The actual role of general practice in the Dutch health- of cardiovascular mortality in elderly Serbian men Eur J Epidemiol 2005; 20(1):103-11 McKeever TM, Lewis SA, Smit HA, Burney P, Britton JR, care system. Results of the Second Dutch National Survey Pharm World Sci 2005; 27(2):124-8 Cassano PA of General Practice Kruijshaar ME, Hoeymans N, Spijker J, Stouthard MEA, The association of acetaminophen, aspirin, and ibuprofen J Public Health 2005; 13:265-9 Hoogendoorn M, Rutten-van Moelken MPMH, Hoogenveen Essink-bot ML with respiratory disease and lung function RT, Genugten MLL van, Buist AS, Wouters EFM, Feenstra TL Has the burden of depression been overestimated? Am J Respir Crit Care Med 2005; 171(9):966-71 Scher AI, Terwindt GM, Picavet HS, Verschuren WM, Ferrari A dynamic population model of disease progression in Bulletin WHO 2005; 83(6):443-8 MD, Launer LJ COPD Mol GD, Lisdonk EH van de, Smits JPJM, Hoogen JMP van den, Cardiovascular risk factors and migraine: the GEM Eur Respir J 2005; 26(2):223-33 Kruit MC, Launer LJ, Ferrari MD, Buchem MA van Bor JHJ, Westert GP population-based study Infarcts in the posterior circulation territory in migraine. A widening gap in general practice? Socio-economic Neurology 2005; 64(4):614-20 Houben RMA, Leeuw M, Vlaeyen JWS, Goubert L, Picavet HSJ The population-based MRI CAMERA study differences in morbidity between 1975 and 2000 in the Fear of movement/injury in the general population: factor Brain 2005; 128(9):2068-77 Netherlands Severeijns R, Vlaeyen JW, Hout MA van den, Picavet HS structure and psychometric properties of an adapted Public Health 2005; 119(7):616-25 Pain catastrophizing and consequences of musculoskeletal version of the Tampa scale for kinesiophobia Lagoe R, Aspling DL, Westert GP pain: a prospective study in the Dutch community J Behav Med 2005; 28(5):415-24 Current and future developments in managed care in the Nagelkerke N, Smits J, Cessie S le, Houwelingen H van J Pain 2005; 6(2):125-32 Iestra JA, Kromhout D, Schouw YT van der, Grobbee DE, Boshuizen HC, Staveren WA van L United States and implications for Europe Health Res Policy Syst 2005; 3(1):4-15 N Testing goodness-of-fit of the logistic regression model in case-control studies using sample reweighting Stat Med 2005; 24(1):121-30 Slootmaker SM, Chin A Paw MJM, Schuit AJ, Seidell JC, Mechelen W van I Effect size estimates of lifestyle and dietary changes on all-cause mortality in coronary artery disease patients: a systematic review Lagoe R, Westert G Using electronic distribution of health care data to improve community wide care. Bringing HTA into Nam N van, Vries PJ de, Toi L van, Nagelkerke N Malaria control in Vietnam: the Binh Thuan experience Promoting physcical activity using an activity monitor and a tailored web-based advice: design of a randomized controlled trial Circulation 2005; 112(6):924-34 practice. Trop Med Int Health 2005; 10(4):357-65 BMC Public Health 2005; 5:134 Ital J Public Health 2005; 2(2):122 Kassteele J van de, Dekkers ALM, Stein A, Velders GJM Nunn P, Williams B, Floyd K, Dye C, Elzinga G, Raviglione M Smits J, Keij-Deerenberg I, Westert G Model-based geostatistical interpolation of the annual Lagoe RJ, Westert GP, Kendrick K, Morreale G, Mnich S Tuberculosis control in the era of HIV Effects of socio-economic status on mortality:separating K number of ozone exceedance days in the Netherlands Stoch Environ Res Risk Assess 2005; 19(3):173-83 Managing hospital length of stay reduction: a multihospital approach Health Care Management Rev 2005; 30(2):82-92 Nature Rev Immunol 2005; 5(10):819-26 Perenboom RJM, Herten LM van, Boshuizen HC, Bos GAM van the nearby from the farther away Health Econ 2005; 14(6):595-608 Kerkhof M, Wijga A, Smit HA, Jongste JC, Aalberse RC, den Steerenberg PA, Withagen CET, Dalen WJ van, Dormans Brunekreef B, Gerritsen J, Postma DS, PIAMA Study Group The effect of prenatal exposure on total IgE at birth and sensitization at twelve months and four years of age: The Loon AJM van, Tijhuis M, Surtees PG, Ormel J Determinants of smoking status: cross-sectional data on smoking initiation and cessation P Life expectancy without chronic morbidity: trends in gender and socioeconomic disparities Public Health Reports 2005; 120(1):46-54 JAMA, Heisterkamp SH, Loveren H van, Cassee FR Dose dependency of adjuvant activity of particulate matter from five European sites in three seasons in an PIAMA study Eur J Publ Health 2005; 15(3):256-61 ovalbumin-mouse model Pediatr Allergy Immunol 2005; 16(1):10-8 Inhal Toxicol 2005; 17(3):133-45

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    44 Research output | Public Health and Health Services 45 Struijs JN, Genugten MLL van, Evers SMAA, Ament AJHA, Verhaak PFM, Hoeymans N, Garssen AA, Westert GP Leest LATM van, Koek HL, Trijp MJCA van, Bos G, Bots ML, Schoemaker C Baan CA, Bos GAM van den Mental health in the Dutch population and in general Verschuren WMM Als ‘t maar werkt S Modeling the future burden of stroke in the Netherlands. Impact of aging, smoking, and hypertension Stroke 2005; 36(8):1648-55 V practice: 1987-2001 Brit J Gen Pract 2005; 55(519):770-5 Diabetes and hart- en vaatziekten: cijfers en feiten. Deel 2: prevalentie van risicofactoren, mortaliteit en morbiditeit Hart Bulletin 2005; 36(3):83-6 S MGv 2005; 60(9):889-90 Schoemaker C Verstappen SM, Boonen A, Bijlsma JW, Buskens E, Verkleij H, Multidisciplinair en integraal. Vijftig jaar anorexia nervose Teunis P, Brandhof W van den, Nauta M, Wagenaar J, Kerkhof Schenk Y, Albada-Kuipers GA van, Hofman DM, Jacobson Leest LATM van, Koek HL, Trijp MJCA van, Baan CA, Jacobs- in het Maandblad, 1946-1995 H van den, Pelt W van JW, Utrecht Theumatoid Arthritis Cohort Study Group van der Bruggen MAM, Bots ML, Verschuren WMM MGv 2005; 60:1273-81 T A reconsideration of the Campylobacter dose-response relation Epidemiol Infect 2005; 133(4):583-92 Working status among Dutch patients with rheumatoid arthritis: work disability and working conditions Rheumatology 2005; 44(2):202-6 Diabetes en hart- en vaatziekten: cijfers en feiten. Deel 1: prevalentie, incidentie en risicofactoren voor diabetes mellitus Treurniet HF, Berg Jeths A van den, Hollander AEM de Vooruitzien in de volksgezondheid Teunis PFM, Lodder WJ, Heisterkamp SH, Roda Husman AM de Versteegh FGA, Mertens PLJM, Melker HE de, Roord JJ, Schellekens JFP, Teunis PFM Hart Bulletin 2005; 36(2):56-60 Leest LATM van, Trijp MJCA van, Verschuren WMM, Dis SJ van T Tijdschr Gezondheidswetenschappen 2005; 83(7):441-5 Treurniet HF, Hoeymans N, Gijsen R, Poos MJJC Mixed plaques: Statistical evidence how plaque assays may Age-specific long-term course of IgG antibodies to Wetenschappelijke stand van zaken omtrent nieuwe Gezondheid en ziekte in Nederland; het Nationaal Kompas underestimate virus concentrations pertussis toxin after symptomatic infection with risicofactoren voor hart- en vaatziekten. Deel 1: C- Volksgezondheid als informatiebron Water Res 2005; 39(17):4240-50 Bordetella pertussis reactieve proteine en fibrinogeen Ned Tijdschr Geneeskd 2005; 149(5):226-31 Epidemiol Infect 2005; 133(4):737-48 Hart Bulletin 2005; 36(5):146-8 Thai KT, Binh TQ, Giao PT, Phuong HL, Hung Q le, Nam N van, Uiters E, Deville W, Foets M, Westert GP, Verheij RA, Nga TT, Groen J, Nagelkerke N, Vries PJ de Westert GP, Schellevis FG, Bakker DH de, Groenewegen PP, Leest LATM van, Trijp MJCA van, Verschuren WMM, Dis SJ van Groenewegen PP Seroprevalence of dengue antibodies, annual incidence and risk factors among children in southern Vietnam Trop Med Int Health 2005;10(4):379-86 W Bensing JM, Zee J van der Monitoring health inequalities through general practice: the Second Dutch National Survey of General Practice Wetenschappelijke stand van zaken omtrent nieuwe risicofactoren voor hart- en vaatziekten. Deel 2: Lipoproteine-a, homocysteine, chlamydia pneumoniae U Is er samenhang tussen stedelijkheid en etnische verschillen in zorggebruik? Tijdschr Gezondheidswetenschappen 2005; 83(4):205-12 Eur J Public Health 2005; 15(1):59-65 Hart Bulletin 2005; 36(6):171-4 Treurniet HF, Hoeymans N, Gijsen R, Poos MJJC, Oers JAM van, Velden PG van der, Grievink L, Dorresteijn AM, Kamp I van, Thien WMAH Wilk EA van der, Jansen J Oers JAM van, Schrijvers AJP Drogendijk AN, Christiaanse B, Roskam AJ, Marcelissen F, Health status and the challenges for prevention in The Netherlands Public Health 2005; 19(3):159-66 Lifestyle-related risks: are trends in Europe converging? Public Health 2005; 119(1):55-66 O Preventie, je leve(n) lang Tijdschr Gezondheidswetenschappen 2005; 83(3):125 V Olff M, Meewisse M, Gersons BPR, Kleber RJ Psychische klachten en het gebruik van de geestelijke gezondheidszorg na de vuurwerkramp Enschede: een Polder J, Treurniet H, Bakker H de, Sluijs E longitudinaal vergelijkend onderzoek Op een lijn: toekomstverkenning eerstelijnszorg 2020 Tijdschr Psychiatrie 2005; 47(9):571-82 P VGE Bulletin 2005; 22;6-8 Polder JJ Verkleij H, Oers JAM van De toekomst van de eerstelijn Solidariteit als risico Tijdschr Gezondheidswetenschappen 2005; 83(7):393-4 Research Papers (Dutch, 25) Tijdschr Gezondheidswetenschappen 2005; 83(6):319-21 Westert G, Cardol M Achterberg A, Tamsma N Graaf R de, Have M ten, Dorsselaer S van, Schoemaker C, Polder JJ Slapeloosheid becijferd A EUPHIX: inzicht in Europese gezondheid via het web Intermezzo 2006; (6):4-5 G Beekman A, Vollebergh W Verschillen tussen etnische groepen in psychiatrische morbiditeit. Resultaten van Nemesis Een harde lijn Tijdschr Gezondheidswetenschappen 2005; 83(6):317-8 W Huisarts Wet 2005; 48(5):205 Wijga A, Visscher TLS, Bemelmans W Dis SJ van, Leest LATM van, Verschuren WMM MGv 2005; 60(7-8):703-16 Polder JJ Geen stijging meer van overgewicht bij jongeren? 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    46 Research output | Public Health and Health Services 47 Books, Chapters & Reports Lindert H van, Droomers M, Westert GP Polder JJ Tweede nationale studie naar ziekten en verrichtingen in Het leven is een geschenk, maar we krijgen het niet Bemelmans WJE, Mulder I, Hoogenveen RT Horst K van der, Oenema A, Ferreira I, Wendel-Vos W, Giskes de huisartspraktijk. Een kwestie van verschil: verschillen in cadeau: over leeftijd en levensloop en de kosten van de Het risico van roken: epidemiologie K, Brug J zelfgerapporteerde leefstijl, gezondheid en zorggebruik. gezondheidszorg B In: Knol K, Hilvering C, Wagener DJT, Willemsen MC, eds. Tabaksgebruik: gevolgen en bestrijding. Utrecht: Lemma, 2005;91-106 H Potential environmental determinants of selected dietary behaviours in youth In: Brug J, Lenthe F van, eds. Environmental determinants Utrecht: Nederlands Instituut voor onderzoek van de gezondheidszorg NIVEL; Bilthoven: Rijksinstituut voor Volksgezondheid en Milieu RIVM, 2005 In: Wagemakers A, Ubachs-Moust J, Christ L, eds. Tijd van leven, tijd van zorgen. Utrecht: Expertisecentrum LEEFtijd, 2005:148-59 and interventions for physical activity, nutrition and Bruijn GJ de, Kremers S, Wendel-Vos W, Lenthe F van, Brug J smoking: a review. Polder JJ Wendel-Vos W, Droomers M, Kremers S, Brug J, Lenthe F van Environmental interventions for selected dietary Rotterdam: ZonMw, 2005;168-203 Een rookgordijn: over de economische gevolgen van Potential environmental determinants of physical activity behaviours in youth In: Brug J, Lenthe F van, eds. Environmental determinants and interventions for physical activity, nutrition and Huisman M, Lenthe F van, Kremers S, Droomers M, Brug J Environmental interventions on smoking P roken In: Knol K, Hilvering C, Wagener DJT, Willsemsen MC, eds. Tabaksgebruik: gevolgen en bestrijding. W in adults In: Brug J, Lenthe F van, eds. Environmental determinants and interventions for physical activity, nutrition and smoking: a review. In: Brug J, Lenthe F van, eds. Environmental determinants Utrecht: Lemma, 2005;389-403 smoking: a review. Rotterdam: ZonMw, 2005;204-39 and interventions for physical activity, nutrition and Rotterdam: ZonMw, 2005;108-39 smoking: a review. Bruijn GJ de, Kremers S, Wendel-Vos W, Lenthe F van, Brug J Rotterdam: ZonMw, 2005;338-62 Environmental interventions on physical activity in youth In: Brug J, Lenthe F van, eds. Environmental determinants Kremers S, Bruijn GJ de, Wendel-Vos W, Lenthe F van, Brug J and interventions for physical activity, nutrition and Environmental interventions for selected dietary smoking: a review. Rotterdam: ZonMw, 2005;78-107 K behaviours in adults In: Brug J, Lenthe F van, eds. Environmental determinants and interventions for physical activity, nutrition and Doctoral Theses Agyemang CO Brink CL van den Cardol M, Dijk L van, Jong JD de, Bakker DH de, Westert GP smoking: a review. Ethnic variations in blood pressure and hypertension Functional disability in elderly men C Tweede nationale studie naar ziekten en verrichtingen in de huisartspraktijk. Huisartsenzorg: wat doet de poortwachter? Rotterdam: ZonMw, 2005;282-316 Kremers S, Bruijn GJ de, Wendel-Vos W, Lenthe F van, Brug J A Arah O Rotterdam: Erasmus Universiteit, 2005. Proefschrift Amsterdam: Universiteit van Amsterdam, 2005. Proefschrift Utrecht: Nederlands Instituut voor onderzoek van de Environmental interventions on physical activity in adults Performance reexamined: concepts, content and practice Dotinga A gezondheidszorg NIVEL; Bilthoven: Rijksinstituut voor In: Brug J, Lenthe F van, eds. Environmental determinants of measuring health systems performance Drinking in a dry culture. Alcohol use among second Volksgezondheid en Milieu RIVM, 2005 Ferreira I, Horst K van der, Wendel-Vos W, Kremers S Lenthe and interventions for physical activity, nutrition and smoking: a review. Rotterdam: ZonMw, 2005;140-66 Amsterdam: Universiteit van Amsterdam, 2005. Proefschrift D generation Turks and Moroccans: measurements and results Rotterdam: Erasmus Universiteit, 2005. Proefschrift F van, Brug J Bogers RP F Potential environmental determinants of physical activity in youth Lenthe F van, Huisman M, Droomers M, Kremers S, Brug J Potential environmental determinants of smoking B Fruit and vegetable consumption: measurement, determinants andintervention Lambooij MS Promoting cooperation. Studies into the effects of long- In: Brug J, Lenthe F van, eds. Environmental determinants and interventions for physical activity, nutrition and smoking: a review. L In: Brug J, Lenthe F van, eds. Environmental determinants and interventions for physical activity, nutrition and smoking: a review. Maastricht: Universiteit Maastricht, 2005. Proefschrift L term and short-term rewards on cooperation of employees Utrecht: Universiteit Utrecht, 2005. Proefschrift Rotterdam: ZonMw, 2005;32-77 Rotterdam: ZonMw, 2005;318-37 Giskes K, Kamphuis C, Kremers S, Wendel-Vos W, Brug J, Linden MW van der, Westert GP, Bakker DH de, Schellevis FG Lenthe F van Tweede nationale studie naar ziekten en verrichtingen G Potential environmental determinants of selected dietary behaviours in adults In: Brug J, Lenthe F van, eds. Environmental determinants in de huisartspraktijk. Klachten en aandoeningen in de bevolking en in de huisartspraktijk Utrecht: Nederlands Instituut voor onderzoek van de Professorial Chairs and interventions for physical activity, nutrition and gezondheidszorg NIVEL; Bilthoven: Rijksinstituut voor Oers H van Westert G smoking: a review. Volksgezondheid en Milieu RIVM, 2005 Professor of Public Healthcare Professor of Quality of Healthcare Rotterdam: ZonMw, 2005;240-81 O University of Tilburg W University of Tilburg

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    48 Research output | Nutrition, Medecines and Consumer Safety 49 Research output Bezemer ID, Rinaldi S, Dossus L, Gils CH van, Peeters PHM, Noord PAH van, Bueno de Mesquita HB, et.al. C-peptide, IGF-I, sex-steroid hormones and adiposity: Brink CL van den, Picavet HSJ, Bos GAM van den, Giampaoli S, Nissinen A, Kromhout D Duration and intensity of physical activity and disability Nutrition, Medicines and Consumer Safety a cross-sectionalstudy in healthy women within the among European elderly men European Investigation into Cancer and Nutrition (EPIC) Disability & Rehabilitation 2005; 27(6):341-7 VGC Cancer Causes Control 2005; 16(5):561-72 Brink CL van den, Tijhuis M, Bos GAM van den, Giampaoli S, Bingham SA, Norat T, Moskal A, Ferrari P, Slimani N, Bueno de Nissinen A, Kromhout D Mesquita HB, Ocke MC, et.al. The contribution of self-rated health and depressive Is the association with fiber from foods in colorectal symptoms to disability severity as a predictor 0f 10-year Research Papers (International, 136) cancer confounded by folate intake? mortality in European elderly men Cancer Epidemiol Biomarkers Prev 2005; 14(6):1552-6 Am J Public Health 2005; 95(11):2029-34 Airoldi L, Vineis P, Colombi A, Bueno de Mesquita HB, et al. Bamia C, Orfanos P, Ferrari P Bueno de Mesquita HB, Ocke 4-Aminobiphenyl-hemoglobin adducts and risk of MC, et al. Blokland MH, Rossum HJ van, Herbold HA, Sterk SS, Stephany Brouwer C, Abreu RA de, Keizer-Garritsen JJ, Lambooy LHJ, A smoking-related disease in never smokers and former smokers in the European Prospective Investigation into Cancer and Nutrition prospective study B Dietary patterns among older Europeans: the EPIC-elderly study Br J Nutr 2005; 94(1):100-13 RW, Ginkel LA van Metabolism of methyltestosterone, norethandrolone and methylboldenone in a heifer Ament K, Riet PGJH ter, Wering ER van, Trijbels FJM, Veerman AJP, Hoogerbrugge PM, Bokkerink JPM Thiopurine methyltransferase in acute Cancer Epidemiol Biomarkers Prev 2005; 14(9):2118-24 Anal Chim Acta 2005; 529:317-23 lymphoblastic leukaemia: biochemical and molecular Banus HA, Kranen HJ van, Mooi FR, Hoebee B, Nagelkerke NJ, biological aspects Al-Delaimy WK, Ferrari P, Slimani N, Pala V, Johansson I, Demant P, Kimman TG Bokkers BGH, Slob W Eur J Cancer 2005; 41(4):613-23 Nilsson S, Mattison I, Wirfalt E, Galasso R, Palli D, vineis Genetic control of Bordetella pertussis infection: A comparison of ratio distributions based on the NOAEL P, Tumino R, Dorronsoro M, Pera G, Ocke MC, Bueno de identification of susceptibility loci using recombinant and the benchmark approach for subchronic-to-chronic Brouwer C, Vogels-Mentink TM, Keizer-Garritsen JJ, Trijbels Mesquita HB, Overvad K, Chirlaque MD, Trichopoulou congenic strains of mice extrapolation FJM, Bokkerink JPM, Hoogerbrugge PM, Wering ER van, A, Naska A, Tjonneland A, Olsen A, Lund E, Alsaker HER, Infect Immun 2005; 73(2):741-7 Toxicol Sci 2005; 85(2):1033-40 Veerman AJP, Abreu RA de Barricarte A, Kesse E, Boutron-Ruault MC, Clavel-Chapelon Role of 5’-nucleotidase in thiopurine metabolism: enzyme F, Key TJ, Spencer E, Bingham S, Welch AA, Sanchez-Perez Basketter DA, Andersen KE, Liden C, Loveren H van, Boman A, Bos G, Dekker JM, Feskens EJM, Ocke MC, Nijpels G, kinetic profile and association with thio-GMP levels in MJ, Nagel G ; Linseisen J, Quiros JR, Peeters PHM, Gils CH Kimber I, Alanko K, Berggren E Stehouwer CDA, Bouter LM, Heine RJ, Jansen H patients with acute lymphoblastic leukemia during 6- van, Boeing H, Kappel AL van, Steghens JP, Riboli E Evaluation of the skin sensitizing potency of chemicals Interactions of dietary fat intake and the hepatic lipase mercaptopurine treatment Plasma carotenoids as biomarkers of intake of fruits and by using the existing methods and considerations of -480C-->T polymorphism in determining hepatic lipase Clin Chim Acta 2005; 361(1-2):95-103 vegetables: individual-level correlations in the European relevance for elicitation activity: the Hoorn Study Prospective Investigation into Cancer and Nutrition (EPIC) Contact Dermatitis 2005; 52(1):39-43 Am J Clin Nutr 2005; 81(4):911-5 Bruijn ACP de; Drongelen AW van Eur J Clin Nutr 2005; 59(12):1387-96 Beurteilung der Leistung von Krankenhaus- Becker ML, Kallewaard M, Caspers PWJ, Schalekamp T, Bosgra S, Bos PMJ, Vermeire TG, Luit RJ, Slob W Dampfsterilisatoren mit dem europaeischen Helixtest Al-Delaimy WK, Slimani N, Ferrari P, Key T, Johansson Stricker BHC Probabilistic risk characterization: an example with di(2- Zentr Steril 2005; 13(1):17-33 I, Johansson G, Mattisson I, Wirfalt E, Sieri S, Agudo A, Potential determinants of drug-drug interaction ethylhexyl) phthalate Celentano E, Palli D, Secerdote C, Tumino R, Dorronsoro M, associated dispensing in community pharmacies Regul Toxicol Pharmacol 2005; 43(1):104-13 Buijsse B, Feskens EJM, Schlettwein-Gsell D, Ferry M, Kok FJ, Ocke M, Bueno de Mesquita HB, Overvad K, Chirlaque MD, Drug Safety 2005; 28(5):371-8 Kromhout D, Groot LCPGM de Trichopoulou A, Naska A, Tjonneland A, Olsen A, Lund E, Bosgra S, Mennes W, Seinen W Plasma carotene and alpha-tocopherol in relation to 10-y Skeie G, Ardanaz E, Kesse E, Boutron-Ruault MC, Clavel- Berg FA van den, Baken KA, Vermeulen JP, Gremmer ER, Proceedings in uncovering the mechanism behind all-cause and cause-specific mortality in European elderly: Chapelon F, Bingham S, Welch AA, Martinez-Garcia C, Steeg H van, Loveren H van peroxisome proliferator-induced hepatocarcinogenesis the Survey in Europe on Nutrition and the Elderly, a Nagel G, Linseisen J, Quiros JR, Peeters PHM, Gils CH van, Use of the local lymph node assay in assessment of Toxicology 2005; 206(3):309-23 Concerted Action (SENECA) Boeing H, Kappel AL van, Steghens JP, Riboli E immune function Am J Clin Nutr 2005; 82(4):879-86 Plasma carotenoids as biomarkers of intake of fruits and Toxicology 2005; 211(1-2):107-14 Boyes WK, Simmons JE, Eklund C, Benignus VA, Janssen P, vegetables: ecological-level correlations in the European Bushnell PJ Canzian F, McKay JD, Cleveland J, Bueno de Mesquita HB, et Prospective Investigation into Cancer and Nutrition (EPIC) Berg HF, Maraha B, Zee A van der, Gielis SK, Roholl PJM, Applications of dosimetry modeling to assessment of al. Eur J Clin Nutr 2005; 59(12):1397-408 Amsterdam J van, Horst-Graat J van der, Bischoff E, Scheffer GJ, Peeters MF, Kluytmans JAJW Effect of clarithromycin treatment on chlamydia pneumoniae in vascular tissue of patients with coronary neurotoxic risk Environ Toxicol Pharmacol 2005; 19(3):599-605 C Genetic variation in the growth hormone synthesis pathway in relation to circulating insulin-like growth factor-I, insulin-like growth factor binding protein-3, and Steerenberg P, Opperhuizen A, Schouten E artery disease: a randomized, double-blind, placebo- breast cancer risk: results from the European prospective The effect of vitamin E supplementation on serum DHEA controlled trial investigation into cancer and nutrition study and neopterin levels in elderly subjects J Clin Microbiol 2005: 43(3):1325-9 Cancer Epidemiol Biomarkers Prev 2005; 14(10):2316-25 Int J Vitam Nutr Res 2005; 75(5):327-31

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A collaborative study of the European Network of Teratology Information Services Himbergen TM van, Roest M, Graaf J de, Jansen EHJM, Hattori Corpeleijn E, Saris WH, Jansen EH, Roekaerts PM, Feskens EJ, Drongelen AW van, Roszek B van, Tienhoven EA, Geertsma Reprod Toxicol 2005; 19(4):453-8 H, Kastelein JJP, Voorbij HAM, Stalenhoef AFH, Tits LJH van Blaak EE RE, Boumans RT, Kraus JJ Indications that paraoxonase-1 contributes to plasma high Postprandial interleukin-6 release from skeletal muscle in Annex II technical documentation assessed Gennari A, Ban M, Braun A, Casati S, Corsini E, Vandebriel R, density lipoprotein levels in familial hypercholesterolem men with impaired glucose tolerance can be reduced by Med Device Technol 2005; 16(10):21-3 et al. 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    54 Research output | Nutrition, Medecines and Consumer Safety 55 Narbutt J, Lesiak A, Skibinska M, Wozniacka A, Loveren H Oomen JM, Waijers PM, Rossum C van, Hoebee B, Saris WH, Rebel H, Kram N, Westerman A, Banus S, Kranen HJ v, Gruijl Schulz M, Lahmann PH, Boeing H, Hoffmann K, Allen N, Key van, Sysa-Jedrzejowska A, Lewy-Trenda I, Omulecka A, Baak MA van FR de TJA, Bingham S, Bueno de Mesquita HB, et.al. 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Evaluation of pharmaceuticals using a survey of industry practices B Voedingsmiddelentechnologie 2005; 38(26):40-1 Geertsma RE, Hilbers-Modderman ESM N Pharm Weekbl 2005; 140(20):674-7 Nouwen M, Riet-Nales DA van, Norder JA, Lekkerkerker JFF Vandebriel RJ, Och FMM van, Loveren H van J Immunotoxicol 2005; 2:171-80 Toepassing weekmakers geinventariseerd Een gas als geneesmiddel (2) V In vitro assessment of sensitizing activity of low molecular weight compounds Toxicol Appl Pharmacol 2005; 207(Supp 2):142-8 Wijnhoven SWP, Beems RB, Roodbergen M, Berg J van den, Lohman PHM, Diderich K, Horst GTJ van der, Vijg J, G Pharm Weekbl 2005; 140(3):86-90 Ginkel LA van, Ruiter A Pharm Weekbl 2005; 140(28-29):925-7 Tienhoven EAE van, Boer S de Hoeijmakers JHJ, Steeg H van Van veilige voeding tot gezonde voeding. Twintig jaar Resultaten RIVM enquete ‘Infuuspompen’ Verbeeck RK, Junginger HE, Midha KK, Shah VP, Barends DM Biowaiver monographs for immediate release solid oral dosage forms based on biopharmaceutics classificaion Accelerated aging pathology in ad libitum fed Xpd-TTD mice is accompanied by features suggestive of caloric restriction chemisch residuonderzoek binnen het RIVM Voeding Nu 2005; 7(9):25-7 T VIT Journaal 2005; 3(1):5-7 Winkel B te system (BCS) literature data: chloroquine phosphate, DNA Repair 2005; 4(11):1314-24 Kubbinga ME, Riet-Nales DA van, Welink J, Geneesmiddelen tijdens de zwangerschap: vragen en chloroquine sulfate, and chloroquine hydrochloride J Pharm Sci 2005; 94(7):1389-95 Wijnhoven SWP, Zwart E, Speksnijder EN, Beems RB, Olive KP, Tuveson DA, Jonkers J, Schaap MM, Berg J van den, Jacks T, K Lekkerkerker JFF Het gelijk van de patient Pharm Weekbl 2005; 140(30-31):935 W antwoorden Pharm Weekbl 2005; 140(13):443-5 Versantvoort CHM, Oomen AG, Kamp E van der, Rompelberg Steeg H van, Vries A de CJM, sips AJAM Mice expressing a mammary gland-specific R270H Applicability of an in vitro digestion model in assessing mutation in the p53 tumor suppressor gene mimic human the bioaccessibility of mycotoxins from food breast cancer development Food Chem Toxicol 2005; 43(1):31-40 Cancer Res 2005; 65(18):8166-73 Books, Chapters & Reports Verschuur M, Jellema A, Bladbjerg EM, Feskens EJM, Mensink Wisselink HW, Moers APHA, Mars AE, Hoefnagel MHN, Vos RP, Moller L, Vos HL, Maat MPM de WM de, Hugenholtz J Egmond HP van, Jonger MA Jong N de, Meynen E, Brug J, Blekker JG, Ocke MC The plasminogen activator inhibitor-1 (PAI-1) promoter Overproduction of heterologous mannitol 1-phosphatase: Worldwide regulations for mycotoxins in food and feed in Psychological determinants of functional food use: results haplotype is related to PAI-1 plasma concentrations in lean individuals Atherosclerosis 2005; 181(2):275-84 a key factor for engineering mannitol production by Lactococcus lactis Appl Environ Microbiol 2005; 71(3):1507-14 E 2003 (FAO Food and Nutrition Paper 81) Rome: Food and Agriculture Organization of the United Nations, 2005 J of a qualitative study In: Kinger LV, ed. Trends in lifestyle and health research. Nova Science Publishers, 2005 Wolterink A, Kim S, Muusse M, Kim IS, Roholl PJM, Ginkel CG Jong WH de, Jonge R de, Garssen J, Takumi K, Havelaar AH van, Stams AJM, Kengen SWM Egmond HP van, Jonker MA Salmonella assessment of infection risk Dechloromonas hortensis sp. nov. and strain ASK-1, two Worldwide regulations on aflatoxins In: Vohr HW, ed. Encyclopedic reference of novel (per)chlorate-reducing bacteria, and taxonomic In: Abbas HK, ed. Aflatoxin and food safety. immunotoxicology. description of strain GR-1 New York: Taylor & Francis, 2005; 77:94 Berlin: Springer, 2005;573-8 Int J Syst Evol Microbiol 2005; 55:2063-8

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    58 Research output | Nutrition, Medecines and Consumer Safety 59 Kimman TG, Hoebee B Relevance of genetic background in respiratory tract Vleeming W, Schenk E, Opperhuizen A Van tabakszaad naar tabaksrook Research output K infections In: Kimpen J, Ramilo O, eds. The microbe-host interface in respiratory tract infections. In: Knol K, Hilvering C, Wagener DJT, Willsemsen MC, eds. Tabaksgebruik: gevolgen en bestrijding. Utrecht: Lemma, 2005;27-42 Environmental Risk and Safety Norfolk: Horizon Bioscience, 2005;1-30 MEV Vos JG, Laan JW van der, Loveren H van, Albers R, Pieters R Vandebriel RJ Immunotoxicology Toxicogenomics (microarray technology) In: Nijkamp FP, Parnham MJ, eds. Principles of V In: Vohr HW, ed. Encyclopedic reference of immunotoxicology. Berlin: Springer, 2005;651 immunopharmacology, 2nd ed. Basel: Birkhauser Verlag, 2005 Research Papers (International, 79) Bais AF, Kazadzis S, Garane K, Kouremeti N, Grobner J, Bos R, Huijbregts M, Peijnenburg W Blumthaler M, Seckmeyer G, Webb AR, Koskela T, Gorts P, Soil type-specific environmental quality standards for zinc B Schreder J Portable device for characterizing the angular response of UV spectroradiometers in Dutch soil Integr Environ Assessment Manag 2005; 1(3):252-8 Doctoral Theses Appl Opt 2005; 44(33):7136-43 Boumans LJM, Fraters D, Drecht G van Nitrate leaching in agriculture to upper groundwater in Brouwer C Stolker AAM Beck L, Rombke J, Breure AM, Mulder C the sandy regions of the Netherlands during the 1992- Purine enzymes and thiopurine methyltransferase in Determination of veterinary drugs and growth-promoting Considerations for the use of soil ecological classification 1995 period B childhood acute lymphoblastic leukemia Nijmegen: Radboud Universiteit, 2005 S agents in food-producing animals Amsterdam: University of Amsterdam, 2005 and assessment concepts in soil protection Ecotoxicol Environ Saf 2005; 62(2):189-200 Environ Monitoring Assessment 2005; 102(1-3):225-41 Bouwman AF, Drecht G van, Hoek KW van der Berg B van de, Grievink L, Stellato RK, Ijzermans CJ, Lebret E Global and regional surface nitrogen balances in intensive Meijeren CE van Symptoms and related functioning in a traumatized agricultural production systems for the period 1970-2030 Development of an in vitro assay to assess pertussis toxin community Arch Intern Med 2005; 165(20):2402-7 Pedosphere 2005; 15(2):137-55 M in acellular pertussis vaccines Utrecht: Universiteit Utrecht, 2005 Berg B van den, Grievink L, Yzermans J, Lebret E Medically unexplained physical symptoms in the Bouwman AF, Drecht G van, Hoek KW van der Surface N balances and reactive N loss to the environment aftermath of disasters Epidemiol Rev 2005; 27:92-106 from global intensive agricultural production systems for the periode 1970-2030 Bijwaard H, Brugmans MJP, Rispens SM Science in China Ser C Life Sciences 2005; 48(Suppl):1-13 Comment on “Studies of radon-exposed miner cohorts Professorial Chairs using a biologically based model: comparison of current Bouwman AF, Hoek KW van der, Eickhout B, Soenario I Czech and French data with historic data from China and Exploring changes in world ruminant production systems Kromhout D Steeg H van Colorado” by WF. Heidenreich, L. Tomasek, A. Rogel, D. Agricultural Systems 2005; 84(2):121-53 Professor of Public health research Professor of Toxico-genetics Laurier and M. Tirmarche (2004) Radiat Environ Biophys K Wageningen University and Research Centre Loveren H van Leiden University Stephany R 43:247-56 Radiat Environ Biophys 2005; 44(2):149-51 Brack W, Bakker J, Deckere E de, Deerenberg C, Zwart D de, et.al. MODELKEY. Models for assessing and forecasting the Professor of Immuno-toxicology Professor of Food of animal origin Bodar CWM, Pronk MEJ, Sijm DTHM impact of environmental key pollutants on freshwater and L Slob W University of Maastricht Utrecht University Vos J The European Union Risk Assessment on zinc and zinc compounds: the process and the facts Integr Environ Assessment Manag 2005; 1(4):301-19 marine ecosystems and biodiversity Environ Sci Pollut Res 2005; 12(5):252-6 Professor of Toxicology Professor of Toxicological pathology Breure AM S Utrecht University V Utrecht University Boivin MEY, Massieux B, Breure AM, Ende FP van den, Greve GD, Rutgers M, Admiraal W Effects of copper and temperature on aquatic bacterial Soil biodiversity: measurements, indicators, threats and soil functions SoilACE 2005; 83-96 communities Aquatic Toxicol 2005; 71(4):345-56

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    60 Research output | Environmental Risk and Safety 61 Breure AM, Mulder C, Rombke J, Ruf A Gils CH van, Peeters PHM, Bueno de Mesquita HB, Boshuizen Huijbregts MAJ, Geelen LMJ, Hertwich EG, McKone TE, Meent Jaworska J, Nikolova-Jeliazkova N, Aldenberg T Ecological classification and assessment concepts in soil HC, Lahmann PH, Clavel-Chapelon F D van de QSAR applicability domain estimation by projection of the B protection Ecotoxicol Environ Saf 2005; 62(2):211-29 Consumption of vegetables and fruits and risk of breast cancer J Am Med Assoc 2005; 293(2):183-93 A comparison between the multimedia fate and exposure models CalTOX and uniform system for evaluation of substances adapted for life-cycle assessment based on the training set descriptor space: a review Altern Lab Anim 2005; 33(5):445-59 Brinksma EJ, Bracher A, Lolkema DE, Segers AJ, Boyd IS, population intake fraction of toxic pollutants Jong FMW de, Mensink BJWG, Smit EC, Montforts MHMM Bramstedt K, Claude H, Godin-Beekmann S, Hansen G, Grobner J, Schreder J, Kazadzis S, Bais AF, Blumthaler M, Gorts Environ Toxicol Chem 2005; 24(2):486-93 Evaluation of ecotoxicological field studies for Kopp G, Leblanc T, McDermid IS, Meijer YJ, Nakane H, P ; Tax R, Koskela T, Seckmeyer G, Webb AR, Rembges D authorization of plant protection products in Europe Parrish A, Savigny C von, Stebel K, Swart DPJ, Taha G, Piters Traveling reference spectroradiometer for routine Huijbregts MAJ, Rombouts LJA, Ragas AMJ, Meent D van de Human Ecol Risk Assessm 2005; 11(6):1157-76 AJM quality assurance of spectral solar ultraviolet irradiance Human-toxicological effect and damage factors of Geophysical validation of SCIAMACHY Limb Ozone Profiles measurements carcinogenic and noncarcinogenic chemicals for Life Knacker T, Duis K, Ternes T, Fenner K, Escher B, Schmitt H, Atmos Chem Phys Discuss 2005; 5:4893-928 Appl Opt 2005; 44(25):5321-31 Cycle Impact Assessment Rombke J, Garric J, Hutchinson T, Boxall ABA Cassee FR, Boere AJF, Fokkens PHB, Leseman DLAC, Sioutas C, Kooter IM, Dormans JAMA Hanninen OO, Tuomisto JT, Jantunen MJ, Lebret E Characterization of model error in a simulation of fine Integr Environ Assessment Management 2005; 1(3):181- 244 K The EU-project ERAPharm: incentives for the furter development of guidance documents? Environ Sci Pollut Res 2005; 12(2):62-5 C Inhalation of concentrated particulate matter produces pulmonary inflammation and systemic biological effects in compromised rats H particulate matter exposure distributions of the working age population in Helsinki, Finland J Air Waste Manag Assoc 2005; 55(4):446-57 Huijbregts MAJ, Struijs J, Goedkoop M, Heijungs R, Hendriks AJ ; Meent D van de Human population intake fractions and environmental Kok YS, Eleveld H, Schnadt H, Gering F, Gregor J, Bottger H ; Salfeld C, Twenhofel CJW, Reinen HAJM J Toxicol Environ Health 2005; 68(10):773-96 fate factors of toxic pollutants in life cycle impact Comparative study of Dutch and German emergency- Heikens A, Sumarti S, Bergen M van, Widianarko B, Fokkert L, assessment management models for near border nuclear accidents Cleven R, Nur Y, Krystek P, Berg G van den Leeuwen K van, Seinen W Chemosphere 2005; 59(10):1495-504 Radiat Prot Dosim 2005; 113(4):381-91 Monitoring metal speciation in the rivers Meuse and The impact of the hyperacid Ijen Crater Lake: risks of Rhine using DGT excess fluoride to human health Hulzebos E, Sijm D, Traas T, Posthumus R, Maslankiewicz L Kooter IM, Pennings JLA, Opperhuizen A, Cassee FR Water Air Soil Pollut 2005; 165(1-4):249-63 Sci Total Environ 2005; 346(1-3):56-69 Validity and validation of expert (Q)SAR systems Gene expression pattern in spontaneously hypertensive SAR and QSAR Environ Res 2005; 16(4):385-401 rats exposed to urban particulate matter (EHC-93) Dijkema MBA, Grievink L, Stellato RK, Roorda J, Velden PG Heikens A, Widianarko B, Dewi IC, Boer JLM de, Seinen W, Inhal Toxicol 2005; 17:53-65 van der Leeuwen K van Hulzebos E, Walker JD, Gerner I, Schlegel K D Determinants of response in a longitudinal health study following the firework-disaster in Enschede, the Netherlands The impact of the hyperacid Ijen Crater Lake. Part I: concentrations of elements in crops and soil Environ Geochem Health 2005; 27(5-6):409-18 Use of structural alerts to develop rules for indentifying chemicals substances with skin irritation or skin corrosion potential Koster M, Reijnders L, Oost NR van, Peijnenburg WJGM Comparison of the method of diffusive gels in thin films with conventional extraction techniques for evaluating Eur J Epidemiol 2005; 20(10):839-47 QSAR Comb Sci 2005; 24(3):332-42 zinc accumulation in plants and isopods Heikens A, Widianarko B, Dewi IC, Boer JLM de, Seinen W, Environ Pollution 2005; 133:103-16 Fenner K, Scheringer M, Macleod M, Matthies M, McKone T, Leeuwen K van Jager T, Wal L van der, Fleuren RHLJ, Barendregt A, Hermens Strobe M ; Beyer A, Bonnell M, Gall AC le, Klasmeier J, The impact of the hyperacid Ijen Crater Lake. Part II: a JLM Krystek P, Ritsema R F Mackay D, Meent D van de, Pennington D, Scharenberg B, Suzuki N, Wania F Comparing estimates of persistence and long-range total diet study Environ Geochem Health 2005; 27(5-6):475-83 J Bioaccumulation of organic chemicals in contaminated soils: evaluation of bioassays with earthworms Environ Sci Technol 2005; 39(1):293-8 Mercury speciation in thawed out and refrozen fish samples by gas chromatography coupled to inductively coupled plasma mass spectrometry and atomic transport potential among multimedia models Heinrich J, Gehring U, Cyryns J, Hoek G, Fischer P, bellander T fluorescence spectroscopy Environ Sci Technol 2005; 39(7):1932-42 ; Brunekreef B Janssen NAH, Lanki T, Hoek G, Vallius M, Hartog JJ de, Anal Bioanal Chem 2005; 381(2):354-9 Exposure to traffic related air pollutants: self reported Grieken R van, Pekkanen J, Brunekreef B Fraters D, Boumans LJM, Leeuwen TC van, Hoop WD de traffic intensity versus GIS modelled exposure Associations between ambient, personal, and indoor Laak TL ter, Durjava M, Struijs J, Hermens JLM Results of 10 years of monitoring nitrogen in the sandy Occup Environ Med 2005; 62(8):517-23 exposure to fine particulate matter constituents in Dutch Solid phase dosing and sampling technique to determine regions in the Netherlands Water Sci Techn 2005; 51(3-4):239-47 Hendriks AJ, Traas TP, Huijbregts MAJ Critical body residues linked to octanol - water and Finnish panels of cardiovascular patients Occup Environ Med 2005; 62(12):868-77 L partition coefficients of hydrophobic chemicals in complex matrixes Environ Sci Technol 2005; 39(10):3736-42 Gerlofs-Nijland ME, Boere AJF, Leseman DLAC, Dormans partitioning, organism composition, and LC50 QSARs: Jarup L, Dudley ML, Babisch W, Houthuijs D, Swart W, JAMA, Sandstrom T, Salonen RO, Bree L van, Cassee FR meta-analysis and model Pershagen G ; Bluhm G, Katsouyanni K, Velonakis M, Leeuwen HJ van, Tol M van der, Strijp JAG van, Verhoef J, G Effects of particulate matter on the pulmonary and vascular system: time course in spontaneously hypertensive rats Environ Sci Technol 2005; 39(9):3226-36 Cadum E, Vigna-Taglianti F Hypertension and Exposure to Noise near Airports (HYENA): study design and noise exposure assessment Kessel KPM van The role of tumour necrosis factor in the kinetics of lipopolysaccharide-mediated neutrophil priming in whole Particle Fibre Toxicol 2005; 2(2) Environm Health Perspect 2005; 113(1):1473-8 blood Clin Exp Immunol 2005; 140(1):65-72

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    62 Research output | Environmental Risk and Safety 63 Leeuwen HP van, Town RM, Buffle J, Cleven RFMJ, Davison W, Mulder C, Schouten AJ, Hund-Rinke K, Breure AM Rombke J, Breure AM, Mulder C, Rutgers M Vethaak AD, Lahr J, Schrap SM, Belfroid AC, Rijs GBJ, Gerritsen Puy J ; Riemsdijk WH van, Sigg L The use of nematodes in ecological soil classification and Legislation and ecological quality assessment of soil: A ; Boer J de, Bulder AS, Grinwis GCM, Kuiper RV, Legler J, L Dynamic speciation analysis and bioavailability of metals in aquatic systems Environ Sci Technol 2005; 39(22):8545-56 assessment concepts Ecotoxicol Environ Saf 2005; 62(2):278-89 implementation of ecological indication systems in Europe Ecotoxicol Environ Saf 2005; 62(2):201-10 Murk TAJ ; Peijnenburg W, Verhaar HJM, Voogt P de An integrated assessment of estrogenic contamination and biological effects in the aquatic environment of The Mulder C, Wezel AP van, Wijnen HJ van Netherlands Louz D, Bergmans HE, Loos BP, Hoeben RC Embedding soil quality in the planning and management Schmitt H, Haapakangas H, Beelen P van Chemosphere 2005; 59(4):511-24 Cross-species transfer of viruses: implications for the use of of land use Effects of antibiotics on soil microorganisms: time and viral vectors in biomedical research, gene therapy and as live-virus vaccines Int J Biodiv Sci Manag 2005; 1(1):1-8 S nutrients influence pollution-induced community tolerance Walker JD, Gerner I, Hulzebos E, Schlegel K The Skin Irritation Corrosion Rules Estimation Tool J Gene Med 2005; 7(10):1263-74 Luttik R, Mineau P, Roelofs W Mulder C, Wijnen HJ van, Wezel AP van Numerical abundance and biodiversity of below-ground taxocenes along a pH gradient across the Netherlands Soil Biol Biochem 2005; 37:1882-92 Stansfeld SA, Berglund B, Clark C, Lopez-Barrio I, Fischer P ; W (SICRET) QSAR Comb Sci 2005; 24(3):378-84 A review of interspecies toxicity extrapolation in birds and J Biogeogr 2005; 32:1775-90 Ohrstrom E, Haines MM, Head J, Hygge S, Kamp I van, Winding A, Hund-Rinke K, Rutgers M mammals and a proposal for long-term toxicity data Berry BF The use of microorganisms in ecological soil classification Ecotoxicology 2005; 14(8):817-32 Netzeva TI, worth AP, Aldenberg T, Benigni R, Cronin MTI, Aircraft and road traffic noise and children’s cognition and assessment concepts Gramatica P, Jaworska JS, Kahn S, Klopman G, Marchant and health: a cross-national study Ecotoxicol Environ Saf 2005; 62(2):230-48 Meent D van de, Huijbregts MAJ Calculating life-cycle assessmebnt effect factors from N CA, Myatt G ; Nikolova-Jeliazkova N, Patlewicz GY, Perkins R, Roberts DW, Schultz TW, Stanton DT, Sandt JJM van de, Lancet 2005; 365(9475):1942-9 Yoshida S, Muramatsu Y, Peijnenburg WJGM M potential affected fraction-based ecotoxicological response functions Environ Toxicol Chem 2005; 24(6):1573-8 Tong WD, Veith G, Yang CH Current status of methods for defining the applicability domain of (quantitative) structure-activity relationships - Stansfeld SA, Head J, Clark C, Kamp I van, Lopez Barrio I Author’s reply to: Aircraft and road traffic noise and children’s cognietion [Letter to the editor] Y Multi-element analyses of earthworms for radioecology and ecotoxicology Radioprotection 2005: 40(Suppl 1):491-5 the report and recommendations of ECVAM Workshop 52 Lancet 2005; 266:716 Mensinga TT, Sips AJAM, Rompelberg CJM, Twillert K van, ATLA 2005; 33(2):155-73 Zwart D de Meulenbelt J, Top HJ van den, Egmond HP van Steenbergen NTTM, Iaccino F, Winkel M de, Reijnders L, Ecological effects of pesticide use in the Netherlands: Potato glycoalkaloids and adverse effects in humans: an ascending dose study Regul Toxicol Pharmacol 2005; 41(1):66-72 Nieuwlaar E, Waaringa G, Brink C, Vermeulen W Supply curves for eco-efficient environmental improvements using different weighting methods Peijnenburg WJGM Development of a biotic ligand model and a regression model predicting acute copper toxicity to the earthworm Z modeled and observed effects in the Field Ditch Integr Environ Assessment Manag 2005; 1(2):123-34 J Ind Ecol 2005; 9(4):85-96 Apporectodea caliginosa Zwart D de, Posthuma L Meulenbelt J, Vries I de, Leenders MEC Environ Sci Technol 2005; 39:5694-702 Complex mixture toxicity for single and multiple species: Prospectives of poisons information supply in emergency Outer PN de, Slaper H, Tax RB proposed methodologies response planning and service UV radiation in the Netherlands: assessing long-term Steerenberg PA, Withagen CET, Dalen WJ van, Dormans Environ Toxicol Chem 2005; 24(10):2665-76 Medical Review (Przeglad Lekarski) 2005; 62(6):533-7 Mulder C, Aldenberg T, Zwart D de, Wijnen HJ van, Breure O variability and trends in relation to ozone and clouds J Geophys Res 2005; 110:art.no. D02203 JAMA, Heisterkamp SH, Loveren H van, Cassee FR Dose dependency of adjuvant activity of particulate matter from five European sites in three seasons in an AM Peijnenburg W, Groot A de, Jager T, Posthuma L ovalbumin-mouse model Evaluating the impact of pollution on plant-Lepidoptera Short-term ecological risks of depositing contaminated Inhal Toxicol 2005; 17(3):133-45 relationships Environmetrics 2005; 16(4):357-73 P sediment on arable soil Ecotoxicol Environ Saf 2005; 60(1):1-14 Treijtel N, Helvoort H van, Barendregt A, Blaauboer BJ, Eijkeren JC van Mulder C, Cohen JE, Setala H, Bloem J, Breure AM Bacterial traits, organism mass, and numerical abundance in the detrital soil food web of Dutch agricultural Posthumus R, Traas TP, Peijnenburg WJGM, Hulzebos EM External validation of epiwin biodegradation models SAR & QSAR in Env Res 2005; 16(1-2):135-48 T The use of sandwich-cultured rat hepatocytes to determine the intrinsic clearance of compounds with different extraction ratios: 7-ethoxycoumarin and warfarin grasslands Drug Metab Dispos 2005; 33(9):1325-32 Ecol Lett 2005; 8:80-90 Rombke J, Breure AM The ecological classification and assessment of soils Vermeire A, Rikken M, Attias L, Boccardi P, Boeije G, Brooke Mulder C, Dijkstra JB, Setala H Nonparasitic nematoda provide evidence for a linear response of functionally important soil biota to increasing R Ecotoxicol Environ Saf 2005; 62(2):185-6 Rombke J, Breure AM V D ; Bruijn J de, Comber M, Dolan B, Fischer S, Heinemeyer G, Koch V ; Lijzen J, Muller B, Murray-Smith R, Tadeo J European union system for the evaluation of substances: livestock density Status and outlook of ecological soil classification and the second version Naturwissenschaten 2005; 92:314-8 assessment concepts Chemosphere 2005; 59(4):473-85 Ecotoxicol Environ Saf 2005; 62(2):300-8

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    64 Research output | Environmental Risk and Safety 65 Research Papers (Dutch, 9) Smink W, Hoek KW van der, Bannink A, Dijkstra J Vries I de Calculation of methane production from enteric Mercury Breure AM Het nut van biodiversiteit in de diepere ondergrond Rutgers M, Mesman M, Otte PF TRIADE: instrumentarium voor geintegreerde S fermentation in dairy cows Wageningen: Feed Innovation Services, 2005 V In: Brent J, Wallace KL, Burkhart KK, Phillips SD, Donovan JW, eds. B Bodem 2005; (4):152-4 Breure AM ecotoxicologische beoordeling van bodemverontreiniging Leidraad Bodembescherming 2005; afl 62:1170/1-26 Critical care toxicology. Philadelphia: Mosby, 2005;837-43 Bodemecologie in het beleid Smetsers RCM Bodem: 2005; 15(6):219-20 Inschatting van de radiologische situatie na een ongeval Meulenbelt J, Vries I de Toxiciteit van dioxinen door de mens S NVS Nieuws 2005; 30(2):6-14 Vries I, Zoelen GA van, Riel AJHP van, Meulenbelt J Doctoral Theses M Ned Tijdschr Geneeskd 2005; 149(4):168-71 V Absorptieverminderende maatregelen bij de behandeling van vergiftigingen Boivin ME Diversity of microbial communities in metal-polluted Montforts MHMM Validation of the EU environmental risk assessment for Pauw RT, Tijssen TAG, Velde L te, Ponssen H, Fijen JW Een veilig alternatief Ned Tijdschr Geneeskd 2005; 149(53):2964-8 B hetergenous environments Amsterdam: Vrije Universiteit, 2005. veterinary medicines Leiden: Universiteit, 2005. P Pharm Weekbl 2005; 45(11):1421-2 Riedstra D Vries I de, Riel AJHP van, Leenders MEC, Meulenbelt J Actief beleid bij een kind dat een knoopbatterij heeft ingeslikt [Letter to the editor] Meijer YJ Characterization of ozone profile retrieved from satellite Zwart D de Impact of toxicants on species composition of aquatic R Windturbines op veilige afstand? Milieu Magazine 2005; (okt):36-9 Ned Tijdschr Geneeskd 2005; 149(39):2196-7 M measurements Eindhoven: Technische Universiteit, 2005. Z communites: concordance of prediction and field observations Amsterdam: Universiteit van Amsterdam, 2005. Books, Chapters & Reports Professorial Chairs Groenestein CM, Hoek KW van der, Monteny GJ, Oenema O Meulenbelt J Actualisering forfaitaire waarden voor gasvormige Vergiftigingen Meent D van de G N-verliezen uit stallen en mestopslagen van varkens, pluimvee en overige dieren Wageningen: Agrotechnology & Food Innovation, 2005. In: Keeman JN, Schade E, red. Spoedeisende hulp in de huisartspraktijk. Houten: Bohn Stafleu van Loghum, 2005;473-518 M Professor of Environmental Sciences Radboud University Nijmegen Rapport 465 Meulenbelt J, Vries I de Kuikman PJ, Oudendag DA, Smit A, Hoek KW van der Vergiftigingen ROB maatregelen in de landbouw en vermindering van In: Feenstra L, Meinders AE, Schil PEY van, Vandenbroucke K emissies van broeikasgassen. Zichtbaarheid van effecten in de nationale berekening en suggesties ter verbetering van de berekeningssystematiek JP, eds. Codex Medicus. 12e dr. Arnhem: Elsevier, 2005;1231-47 Wageningen: Alterra; Bilthoven: RIVM, 2005 (Alterra Romkens PFAM, Schuur GW, Lijzen JPA, Rietra RPJJ, Dirven- rapport 994; RIVM rapport 680125004) van Breemen EM Meulenbelt J Cadmium R Risico’s van cadmium en lood in moestuinen in de Kempen Wageningen: Alterra, 2005 (Alterra report 1129) M In: Brent J, Wallace KL, Burkhart KK, Phillips SD, Donovan JW, eds. Critical care toxicology. Philadelphia: Mosby, 2005;817-20 Rutgers M, Besten P den Approach to legislation in a global context, the Netherlands perspective-soils and sediments In: Thompson KC, Wadhia K, Loibner A, eds. Environmental toxicity testing. Oxford: Blackwell Publishing, 2005;269-89

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    RIVM National Institute for Public Health and the Environment P.O. Box 1 3720 BA Bilthoven the Netherlands www.rivm.com

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