• CA19-9 and Apolipoprotein-A2 isoforms as detection markers for pancreatic cancer - a prospective evaluation.

      Honda, K; Katzke, V A; Hüsing, A; Okaya, S; Shoji, H; Onidani, K; Olsen, A; Tjønneland, A; Overvad, K; Weiderpass, E; Vineis, P; Muller, D; Tsilidis, K K; Palli, D; Pala, V; Tumino, R; Naccarati, A; Panico, S; Aleksandrova, K; Boeing, H; Bueno-de-Mesquita, H B; Peeters, P H; Trichopoulou, A; Lagiou, P; Khaw, K-T; Wareham, N J; Travis, R C; Merino, S; Duell, E J; Rodríguez-Barranco, M; Chirlaque, M D; Barricarte, A; Rebours, V; Boutron-Ruault, M-C; Romana Mancini, F; Brennan, P; Scelo, G; Manjer, J; Sund, M; Öhlund, D; Canzian, F; Kaaks, R (2018-09-27)
      Recently, we identified unique processing patterns of apolipoprotein A2 (ApoA2) in patients with pancreatic cancer. This study provides a first prospective evaluation of an ApoA2 isoform ("ApoA2-ATQ/AT"), alone and in combination with carbohydrate antigen 19-9 (CA19-9), as an early detection biomarker for pancreatic cancer. We performed ELISA measurements of CA19-9 and ApoA2-ATQ/AT in 156 patients with pancreatic cancer and 217 matched controls within the European EPIC cohort, using plasma samples collected up to 60 months prior to diagnosis. The detection discrimination statistics were calculated for risk scores by strata of lag-time. For CA19-9, in univariate marker analyses, C-statistics to distinguish future pancreatic cancer patients from cancer-free individuals were 0.80 for plasma taken ≤6 months before diagnosis, and 0.71 for >6-18 months; for ApoA2-ATQ/AT, C-statistics were 0.62, and 0.65, respectively. Joint models based on ApoA2-ATQ/AT plus CA19-9 significantly improved discrimination within >6-18 months (C = 0.74 vs. 0.71 for CA19-9 alone, p = 0.022) and ≤18 months (C = 0.75 vs. 0.74, p = 0.022). At 98% specificity, and for lag times of ≤6, >6-18 or ≤18 months, sensitivities were 57%, 36% and 43% for CA19-9 combined with ApoA2-ATQ/AT, respectively, vs. 50%, 29% and 36% for CA19-9 alone. Compared to CA19-9 alone, the combination of CA19-9 and ApoA2-ATQ/AT may improve detection of pancreatic cancer up to 18 months prior to diagnosis under usual care, and may provide a useful first measure for pancreatic cancer detection prior to imaging. This article is protected by copyright. All rights reserved.
    • Can Transgenic Maize Affect Soil Microbial Communities?

      Mulder, Christian; Wouterse, Marja; Raubuch, Markus; Roelofs, Willem; Rutgers, Michiel (2006-09-29)
      The aim of the experiment was to determine if temporal variations of belowground activity reflect the influence of the Cry1Ab protein from transgenic maize on soil bacteria and, hence, on a regulatory change of the microbial community (ability to metabolize sources belonging to different chemical guilds) and/or a change in numerical abundance of their cells. Litter placement is known for its strong influence on the soil decomposer communities. The effects of the addition of crop residues on respiration and catabolic activities of the bacterial community were examined in microcosm experiments. Four cultivars of Zea mays L. of two different isolines (each one including the conventional crop and its Bacillus thuringiensis cultivar) and one control of bulk soil were included in the experimental design. The growth models suggest a dichotomy between soils amended with either conventional or transgenic maize residues. The Cry1Ab protein appeared to influence the composition of the microbial community. The highly enhanced soil respiration observed during the first 72 h after the addition of Bt-maize residues can be interpreted as being related to the presence of the transgenic crop residues. This result was confirmed by agar plate counting, as the averages of the colony-forming units of soils in conventional treatments were about one-third of those treated with transgenic straw. Furthermore, the addition of Bt-maize appeared to induce increased microbial consumption of carbohydrates in BIOLOG EcoPlates. Three weeks after the addition of maize residues to the soils, no differences between the consumption rate of specific chemical guilds by bacteria in soils amended with transgenic maize and bacteria in soils amended with conventional maize were detectable. Reaped crop residues, comparable to post-harvest maize straw (a common practice in current agriculture), rapidly influence the soil bacterial cells at a functional level. Overall, these data support the existence of short Bt-induced ecological shifts in the microbial communities of croplands' soils.
    • Can universal access be achieved in a voluntary private health insurance market? Dutch private insurers caught between competing logics.

      Vonk, Robert A A; Schut, Frederik T (2018-05-07)
      For almost a century, the Netherlands was marked by a large market for voluntary private health insurance alongside state-regulated social health insurance. Throughout this period, private health insurers tried to safeguard their position within an expanding welfare state. From an institutional logics perspective, we analyze how private health insurers tried to reconcile the tension between a competitive insurance market pressuring for selective underwriting and actuarially fair premiums (the insurance logic), and an upcoming welfare state pressuring for universal access and socially fair premiums (the welfare state logic). Based on primary sources and the extant historiography, we distinguish six periods in which the balance between both logics changed significantly. We identify various strategies employed by private insurers to reconcile the competing logics. Some of these were temporarily successful, but required measures that were incompatible with the idea of free entrepreneurship and consumer choice. We conclude that universal access can only be achieved in a competitive individual private health insurance market if this market is effectively regulated and mandatory cross-subsidies are effectively enforced. The Dutch case demonstrates that achieving universal access in a competitive private health insurance market is institutionally complex and requires broad political and societal support.
    • Can we predict tuberculosis cure? What tools are available?

      Goletti, Delia; Lindestam Arlehamn, Cecilia S; Scriba, Thomas J; Anthony, Richard; Cirillo, Daniela Maria; Alonzi, Tonino; Denkinger, Claudia M; Cobelens, Frank (2018-11)
      Antibiotic treatment of tuberculosis takes ≥6 months, putting a major burden on patients and health systems in large parts of the world. Treatment beyond 2 months is needed to prevent tuberculosis relapse by clearing remaining, drug-tolerant Mycobacterium tuberculosis bacilli. However, the majority of patients treated for only 2-3 months will cure without relapse and do not need prolonged treatment. Assays that can identify these patients at an early stage of treatment may significantly help reduce the treatment burden, while a test to identify those patients who will fail treatment may help target host-directed therapies.In this review we summarise the state of the art with regard to discovery of biomarkers that predict relapse-free cure for pulmonary tuberculosis. Positron emission tomography/computed tomography scanning to measure pulmonary inflammation enhances our understanding of "cure". Several microbiological and immunological markers seem promising; however, they still need a formal validation. In parallel, new research strategies are needed to generate reliable tests.
    • Carbapenemase-producerende enterobacteriën in Nederland : Onopgemerkte versprewiding naar verschillende regio's.

      Leenstra, T; Bosch, T; Vlek, A L; Bonten, M J M; van der Lubben, I M; de Greeff, S C (2017-10-24)
      - Carbapenemase producing Enterobacteriaceae (CPE), including Klebsiella pneumoniae and Escherichia coli, are only sporadically seen in the Netherlands and then mainly in patients who have been transferred from foreign hospitals.- CPE are resistant to virtually all beta-lactam antibiotics, including carbapenems, e.g., meropenem and imipenem. Several genes, e.g., OXA-48, KPC and NDM-1, code for carbapenemase enzymes that deactivate carbapenems.- Control of CPE focuses on timely identification of patients who are infected or are carriers and the application of preventive measures to prevent spread.- Genotypic analysis of CPE isolates submitted to the national CPE surveillance revealed close relationships between 8 NDM-1 positive K. pneumoniae isolates of patients from different parts of the Netherlands and isolates obtained through contact tracing during a known hospital outbreak.- Based on retrospective epidemiological investigation, no shared exposure could be found.- These findings indicate unnoticed spread of CPE in the Netherlands.
    • Cardiovascular Risk Factors Associated With Venous Thromboembolism.

      Gregson, John; Kaptoge, Stephen; Bolton, Thomas; Pennells, Lisa; Willeit, Peter; Burgess, Stephen; Bell, Steven; Sweeting, Michael; Rimm, Eric B; Kabrhel, Christopher; Zöller, Bengt; Assmann, Gerd; Gudnason, Vilmundur; Folsom, Aaron R; Arndt, Volker; Fletcher, Astrid; Norman, Paul E; Nordestgaard, Børge G; Kitamura, Akihiko; Mahmoodi, Bakhtawar K; Whincup, Peter H; Knuiman, Matthew; Salomaa, Veikko; Meisinger, Christa; Koenig, Wolfgang; Kavousi, Maryam; Völzke, Henry; Cooper, Jackie A; Ninomiya, Toshiharu; Casiglia, Edoardo; Rodriguez, Beatriz; Ben-Shlomo, Yoav; Després, Jean-Pierre; Simons, Leon; Barrett-Connor, Elizabeth; Björkelund, Cecilia; Notdurfter, Marlene; Kromhout, Daan; Price, Jackie; Sutherland, Susan E; Sundström, Johan; Kauhanen, Jussi; Gallacher, John; Beulens, Joline W J; Dankner, Rachel; Cooper, Cyrus; Giampaoli, Simona; Deen, Jason F; Gómez de la Cámara, Agustín; Kuller, Lewis H; Rosengren, Annika; Svensson, Peter J; Nagel, Dorothea; Crespo, Carlos J; Brenner, Hermann; Albertorio-Diaz, Juan R; Atkins, Robert; Brunner, Eric J; Shipley, Martin; Njølstad, Inger; Lawlor, Deborah A; van der Schouw, Yvonne T; Selmer, Randi Marie; Trevisan, Maurizio; Verschuren, W M Monique; Greenland, Philip; Wassertheil-Smoller, Sylvia; Lowe, Gordon D O; Wood, Angela M; Butterworth, Adam S; Thompson, Simon G; Danesh, John; Di Angelantonio, Emanuele; Meade, Tom (2019-01-16)
      It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. A panel of several established cardiovascular risk factors.
    • Cardiovascular risk model performance in women with and without hypertensive disorders of pregnancy.

      Dam, Veerle; Onland-Moret, N Charlotte; Verschuren, W M Monique; Boer, Jolanda M A; Benschop, Laura; Franx, Arie; Moons, Karel G M; Boersma, Eric; van der Schouw, Yvonne T (2018-09-12)
      Compare the predictive performance of Framingham Risk Score (FRS), Pooled Cohort Equations (PCEs) and Systematic COronary Risk Evaluation (SCORE) model between women with and without a history of hypertensive disorders of pregnancy (hHDP) and determine the effects of recalibration and refitting on predictive performance.
    • Carry-over of dioxins and PCBs from feed and soil to eggs at low contamination levels-- influence of mycotoxin binders on the carry-over from feed to eggs.

      Hoogenboom, L A P; Kan, C A; Zeilmaker, Marco J; Eijkeren, Jan C H van; Traag, Win A (2006-05-01)
      Laying hens were fed with compound feed containing six different levels of dioxins, dioxin-like PCBs and indicator PCBs for a period of 56 days. This was followed by a period of 56 days on clean feed. Dioxin levels in feed varied from background levels to three times the current EU tolerance limit of 0.75 ng TEQ/kg. At all dose levels a rapid increase was observed in the dioxin levels in eggs. There was a clear linear dose-response relationship between the dioxin levels in eggs and feed. The feed containing 0.4 ng TEQ dioxins per kg resulted in egg levels just above the EU limit of 3 pg TEQ/g fat. Dioxin-like and indicator PCB residues followed a pattern very similar to that of dioxins. Exposure to the highest indicator PCB level of 32 microg/kg resulted in egg levels around 300 ng/g fat. Exposure to dioxins through contaminated soil, mixed at 10% into the feed, resulted in a similar carry-over as from feed. Mycotoxin binders, mixed at 0.5% into the feed, had little effect on the carry-over of dioxins from the feed to the egg. It can be concluded that consumption of feed or soil with even moderate levels of dioxins and dioxin-like PCBs rapidly results in increased levels in eggs. The current EU dioxin limit for feed cannot guarantee egg dioxin levels below the EU-limit.
    • Cascading effects of predator activity on tick-borne disease risk.

      Hofmeester, Tim R; Jansen, Patrick A; Wijnen, Hendrikus J; Coipan, Elena C; Fonville, Manoj; Prins, Herbert H T; Sprong, Hein; van Wieren, Sipke E (2017-07-26)
      Predators and competitors of vertebrates can in theory reduce the density of infected nymphs (DIN)-an often-used measure of tick-borne disease risk-by lowering the density of reservoir-competent hosts and/or the tick burden on reservoir-competent hosts. We investigated this possible indirect effect of predators by comparing data from 20 forest plots across the Netherlands that varied in predator abundance. In each plot, we measured the density of questing Ixodes ricinus nymphs (DON), DIN for three pathogens, rodent density, the tick burden on rodents and the activity of mammalian predators. We analysed whether rodent density and tick burden on rodents were correlated with predator activity, and how rodent density and tick burden predicted DON and DIN for the three pathogens. We found that larval burden on two rodent species decreased with activity of two predator species, while DON and DIN for all three pathogens increased with larval burden on rodents, as predicted. Path analyses supported an indirect negative correlation of activity of both predator species with DON and DIN. Our results suggest that predators can indeed lower the number of ticks feeding on reservoir-competent hosts, which implies that changes in predator abundance may have cascading effects on tick-borne disease risk.
    • Case of seasonal reassortant A(H1N2) influenza virus infection, the Netherlands, March 2018.

      Meijer, Adam; Swaan, Corien M; Voerknecht, Martin; Jusic, Edin; van den Brink, Sharon; Wijsman, Lisa A; Voordouw, Bettie Cg; Donker, Gé A; Sleven, Jacqueline; Dorigo-Zetsma, Wendelien W; Svraka, Sanela; van Boven, Michiel; Haverkate, Manon R; Timen, Aura; van Dissel, Jaap T; Koopmans, Marion Pg; Bestebroer, Theo M; Fouchier, Ron Am (2018-04)
      A seasonal reassortant A(H1N2) influenza virus harbouring genome segments from seasonal influenza viruses A(H1N1)pdm09 (HA and NS) and A(H3N2) (PB2, PB1, PA, NP, NA and M) was identified in March 2018 in a 19-months-old patient with influenza-like illness (ILI) who presented to a general practitioner participating in the routine sentinel surveillance of ILI in the Netherlands. The patient recovered fully. Further epidemiological and virological investigation did not reveal additional cases.
    • Case study: Enschede fireworks disaster: lessons learned.

      van Kamp, I; van der Velden, P; Yzermans, J (2018-11-01)
    • A category approach for reproductive effects of phthalates.

      Fabjan, Evelin; Hulzebos, Etje; Mennes, W; Piersma, Aldert H (2006-10-01)
      In regulatory toxicology, the experimental assessment of reproductive toxicity is one of the most costly endpoints to perform. Categorizing chemicals is an approach that can be used to reduce animal tests in risk assessments of chemicals, for example, via REACH (Registration, Evaluation, and Authorization of Chemicals). The category approach was tested for reproductive toxicity with a group of 10 ortho-phthalate esters, with different side chain lengths. Three ortho-phthalates were used for testing the category. Phthalates with side-chain lengths C4 to C6 that are commonly known to cause reproductive effects were included, as well as the recently discovered mechanism that indicates antiandrogenic effects. The differences in physicochemical properties, absorption rates, and metabolism between the phthalates investigated could not fully explain the difference in reproductive toxicity. It was concluded that phthalates with the alkyl side-chain length from C4 to C6 produce similar severe reproductive effects in experimental animals. It is expected that phthalates included in the tight boundaries of the proposed category would all show severe reproductive effects, especially the antiandrogenic effects. Further testing might not be needed for phthalates within these boundaries. If necessary, limited testing could focus on the critical endpoints. Detailed mechanistic information is needed on phthalates to apply the categories for regulatory toxicology.
    • Cationically modified membranes using covalent layer-by-layer assembly for antiviral applications in drinking water.

      Sinclair TR; Patil A; Raza BG; Reurink D; Hengel SK van den; Rutjes SA; Roda Husman AM de; Roesink HDW; Vos WM de (2019-01-15)
    • CDHR3 gene variation and childhood bronchiolitis.

      Husby, Anders; Pasanen, Anu; Waage, Johannes; Sevelsted, Astrid; Hodemaekers, Hennie; Janssen, Riny; Karjalainen, Minna K; Stokholm, Jakob; Chawes, Bo L; Korppi, Matti; Wennergren, Göran; Heinzmann, Andrea; Bont, Louis; Bisgaard, Hans; Bønnelykke, Klaus (2017-11)
    • Challenges in characterizing the environmental fate and effects of carbon nanotubes and inorganic nanomaterials in aquatic systems

      Laux, Peter; Riebeling, Christian; Booth, Andy M.; Brain, Joseph D.; Brunner, Josephine; Cerrillo, Cristina; Creutzenberg, Otto; Estrela-Lopis, Irina; Gebel, Thomas; Johanson, Gunnar; Jungnickel, Harald; Kock, Heiko; Tentschert, Jutta; Tlili, Ahmed; Schäffer, Andreas; Sips, Adriënne J. A. M.; Yokel, Robert A.; Luch, Andreas; Department of Chemical and Product Safety; Department of Chemical and Product Safety; SINTEF Ocean; Harvard T. H. Chan School of Public Health; Department of Chemical and Product Safety; IK4-Tekniker; Department of Inhalation Toxicology; Institute of Medical Physics & Biophysics; German Federal Institute for Occupational Safety and Health (BAuA); Institute of Environmental Medicine; Department of Chemical and Product Safety; Department of Inhalation Toxicology; Department of Chemical and Product Safety; Department of Environmental Toxicology; Institute for Environmental Research; National Institute for Public Health & the Environment (RIVM); Pharmaceutical Sciences; Department of Chemical and Product Safety (2018)
      Characterization of carbon nanotube dispersions requires measurement of both, concentration and surface area.
    • Changes in (risk) behavior and HPV knowledge among Dutch girls eligible for HPV vaccination: an observational cohort study.

      Donken, Robine; Tami, Adriana; Knol, Mirjam J; Lubbers, Karin; van der Sande, Marianne A B; Nijman, Hans W; Daemen, Toos; Weijmar Schultz, Willibrord C M; de Melker, Hester E (2018-07-05)
      Implementation of human papillomavirus (HPV) vaccination raised concerns that vaccination could lead to riskier sexual behavior. This study explored how possible differences in sexual behavior and HPV knowledge developed over time between HPV-vaccinated and unvaccinated girls.
    • Changes in dietary intake, plasma carotenoids and erythrocyte membrane fatty acids in breast cancer survivors after a lifestyle intervention: results from a single-arm trial.

      Buckland, G; Travier, N; Arribas, L; Del Barco, S; Pernas, S; Zamora, E; Bellet, M; Cirauqui, B; Margelí, M; Muñoz, M; Tusquets, I; Arcusa, A; Javierre, C; Moreno, F; Valverde, Y; Jansen, E; Chajès, V; Castro, C; Agudo, A (2019-01-21)
      The influence of nutrition on breast cancer prognosis is still inconclusive and therefore dietary interventions incorporating dietary biomarkers are needed to confirm compliance with dietary goals and clarify biological mechanisms. The present study assessed whether a lifestyle intervention in breast cancer survivors could affect dietary biomarkers of fruit and vegetables and fatty acids. In this phase II single-arm trial, 37 overweight/obese early stage breast cancer patients completed a 12-week diet and exercise intervention. The intervention involved 1-h weekly diet sessions delivered by a dietician and 75-min bi-weekly physical activity sessions of moderate-to-high intensity led by trained monitors. Before and after the intervention, three 24-h dietary recalls were carried out to calculate nutrient intakes and, in addition, blood samples were taken to measure plasma carotenoids, vitamin E and retinol concentrations and erythrocyte membrane fatty acid (EFA) composition. Wilcoxon signed rank tests were used to assess changes in dietary and biomarkers measurements over the intervention period. After the intervention, there was a significant increase in the intake of dietary carotenoids (+15.1% compared to baseline) but not plasma carotenoids levels (+6.3%). Regarding the EFA levels, we observed a significant decrease in percentage of saturated fatty acids (-1.4%) and n-6 polyunsaturated fatty acids (-2.9%) and an increase in monounsaturated fatty acids (1.7%) and total and long-chain n-3 polyunsaturated fatty acids (by 13.1% and 13.7%, respectively). A favourable decrease in the ratio of long-chain n-6 to n-3 polyunsaturated fatty acids (-9.1%) was also observed. After a short-term diet and exercise intervention in overweight/obese breast cancer survivors, we observed significant changes in dietary nutrients and fatty acid biomarkers, suggesting positive dietary changes that could be relevant for breast cancer prognosis.
    • Changes in Emissions of Ozone-Depleting Substances from China Due to Implementation of the Montreal Protocol.

      Fang, Xuekun; Ravishankara, A R; Velders, Guus J M; Molina, Mario J; Su, Shenshen; Zhang, Jianbo; Hu, Jianxin; Prinn, Ronald G (2018-10-02)
      The ozone layer depletion and its recovery, as well as the climate influence of ozone-depleting substances (ODSs) and their substitutes that influence climate, are of interest to both the scientific community and the public. Here we report on the emissions of ODSs and their substitute from China, which is currently the largest consumer (and emitter) of these substances. We provide, for the first time, comprehensive information on ODSs and replacement hydrofluorocarbon (HFC) emissions in China starting from 1980 based on reported production and usage. We also assess the impacts (and costs) of controls on ODS consumption and emissions on the ozone layer (in terms of CFC-11-equivalent) and climate (in CO2-equivalent). In addition, we show that while China's future ODS emissions are likely to be defined as long as there is full compliance with the Montreal Protocol; its HFC emissions through 2050 are very uncertain. Our findings imply that HFC controls over the next decades that are more stringent than those under the Kigali Amendment to the Montreal Protocol would be beneficial in mitigating global climate change.
    • Changes in LXR signaling influence early-pregnancy lipogenesis and protect against dysregulated fetoplacental lipid homeostasis.

      Nikolova, Vanya; Papacleovoulou, Georgia; Bellafante, Elena; Borges Manna, Luiza; Jansen, Eugene; Baron, Silvère; Abu-Hayyeh, Shadi; Parker, Malcolm; Williamson, Catherine (2017-10-01)
      Human pregnancy is associated with enhanced de novo lipogenesis in the early stages followed by hyperlipidemia during advanced gestation. Liver X receptors (LXRs) are oxysterol-activated nuclear receptors that stimulate de novo lipogenesis and also promote the efflux of cholesterol from extrahepatic tissues followed by its transport back to the liver for biliary excretion. Although LXR is recognized as a master regulator of triglyceride and cholesterol homeostasis, it is unknown whether it facilitates the gestational adaptations in lipid metabolism. To address this question, biochemical profiling, protein quantification, and gene expression studies were used, and gestational metabolic changes in T0901317-treated wild-type mice and Lxrab-/- mutants were investigated. Here, we show that altered LXR signaling contributes to the enhanced lipogenesis in early pregnancy by increasing the expression of hepatic Fas and stearoyl-CoA desaturase 1 (Scd1). Both the pharmacological activation of LXR with T0901317 and the genetic ablation of its two isoforms disrupted the increase in hepatic fatty acid biosynthesis and the development of hypertriglyceridemia during early gestation. We also demonstrate that absence of LXR enhances maternal white adipose tissue lipolysis, causing abnormal accumulation of triglycerides, cholesterol, and free fatty acids in the fetal liver. Together, these data identify LXR as an important factor in early-pregnancy lipogenesis that is also necessary to protect against abnormalities in fetoplacental lipid homeostasis.