• Identification and ranking of environmental threats with ecosystem vulnerability distributions.

      Zijp, Michiel C; Huijbregts, Mark A J; Schipper, Aafke M; Mulder, Christian; Posthuma, Leo (2017-08-24)
      Responses of ecosystems to human-induced stress vary in space and time, because both stressors and ecosystem vulnerabilities vary in space and time. Presently, ecosystem impact assessments mainly take into account variation in stressors, without considering variation in ecosystem vulnerability. We developed a method to address ecosystem vulnerability variation by quantifying ecosystem vulnerability distributions (EVDs) based on monitoring data of local species compositions and environmental conditions. The method incorporates spatial variation of both abiotic and biotic variables to quantify variation in responses among species and ecosystems. We show that EVDs can be derived based on a selection of locations, existing monitoring data and a selected impact boundary, and can be used in stressor identification and ranking for a region. A case study on Ohio's freshwater ecosystems, with freshwater fish as target species group, showed that physical habitat impairment and nutrient loads ranked highest as current stressors, with species losses higher than 5% for at least 6% of the locations. EVDs complement existing approaches of stressor assessment and management, which typically account only for variability in stressors, by accounting for variation in the vulnerability of the responding ecosystems.
    • Identification of atopic dermatitis subgroups in children from 2 longitudinal birth cohorts.

      Paternoster, Lavinia; Savenije, Olga E M; Heron, Jon; Evans, David M; Vonk, Judith M; Brunekreef, Bert; Wijga, Alet H; Henderson, A John; Koppelman, Gerard H; Brown, Sara J (2018-03)
      Atopic dermatitis (AD) is a prevalent disease with variable natural history. Longitudinal birth cohort studies provide an opportunity to define subgroups on the basis of disease trajectories, which may represent different genetic and environmental pathomechanisms.
    • Identification of data-driven Dutch dietary patterns that benefit the environment and are healthy

      Biesbroek, Sander; Monique Verschuren, W. M.; van der Schouw, Yvonne T.; Sluijs, Ivonne; Boer, Jolanda M. A.; Temme, Elisabeth H. M. (2018-02-16)
    • Identification of differences in health impact modelling of salt reduction.

      Hendriksen, Marieke A H; Geleijnse, Johanna M; van Raaij, Joop M A; Cappuccio, Francesco P; Cobiac, Linda C; Scarborough, Peter; Nusselder, Wilma J; Jaccard, Abbygail; Boshuizen, Hendriek C (2017)
      We examined whether specific input data and assumptions explain outcome differences in otherwise comparable health impact assessment models. Seven population health models estimating the impact of salt reduction on morbidity and mortality in western populations were compared on four sets of key features, their underlying assumptions and input data. Next, assumptions and input data were varied one by one in a default approach (the DYNAMO-HIA model) to examine how it influences the estimated health impact. Major differences in outcome were related to the size and shape of the dose-response relation between salt and blood pressure and blood pressure and disease. Modifying the effect sizes in the salt to health association resulted in the largest change in health impact estimates (33% lower), whereas other changes had less influence. Differences in health impact assessment model structure and input data may affect the health impact estimate. Therefore, clearly defined assumptions and transparent reporting for different models is crucial. However, the estimated impact of salt reduction was substantial in all of the models used, emphasizing the need for public health actions.
    • Identification of naturally processed mumps virus epitopes by mass spectrometry: Confirmation of multiple CD8+ T cell responses in mumps patients.

      de Wit, Jelle; Emmelot, Maarten E; Meiring, Hugo; van Gaans-van den Brink, Jacqueline A M; van Els, Cécile A C M; Kaaijk, Patricia (2019-09-27)
    • Identification of Requirements for Computer-Supported Matching of Food Consumption Data with Food Composition Data.

      Koroušić Seljak, Barbara; Korošec, Peter; Eftimov, Tome; Ocke, Marga; van der Laan, Jan; Roe, Mark; Berry, Rachel; Crispim, Sandra Patricia; Turrini, Aida; Krems, Carolin; et al. (2018-03-30)
      This paper identifies the requirements for computer-supported food matching, in order to address not only national and European but also international current related needs and represents an integrated research contribution of the FP7 EuroDISH project. The available classification and coding systems and the specific problems of food matching are summarized and a new concept for food matching based on optimization methods and machine-based learning is proposed. To illustrate and test this concept, a study has been conducted in four European countries (i.e., Germany, The Netherlands, Italy and the UK) using different classification and coding systems. This real case study enabled us to evaluate the new food matching concept and provide further recommendations for future work. In the first stage of the study, we prepared subsets of food consumption data described and classified using different systems, that had already been manually matched with national food composition data. Once the food matching algorithm was trained using this data, testing was performed on another subset of food consumption data. Experts from different countries validated food matching between consumption and composition data by selecting best matches from the options given by the matching algorithm without seeing the result of the previously made manual match. The evaluation of study results stressed the importance of the role and quality of the food composition database as compared to the selected classification and/or coding systems and the need to continue compiling national food composition data as eating habits and national dishes still vary between countries. Although some countries managed to collect extensive sets of food consumption data, these cannot be easily matched with food composition data if either food consumption or food composition data are not properly classified and described using any classification and coding systems. The study also showed that the level of human expertise played an important role, at least in the training stage. Both sets of data require continuous development to improve their quality in dietary assessment.
    • Identification of TUB as a novel candidate gene influencing body weight in humans.

      Shiri-Sverdlov, Ronit; Custers, Anne; Vliet-Ostaptchouk, Jana V van; Gorp, Patrick J J van; Lindsey, Patrick J; Tilburg, Jonathan H O van; Zhernakova, Sasha; Feskens, Edith J M; A, Daphne L van der; Dollé, Martijn E T; et al. (2006-02-01)
      Previously, we identified a locus on 11p influencing obesity in families with type 2 diabetes. Based on mouse studies, we selected TUB as a functional candidate gene and performed association studies to determine whether this controls obesity. We analyzed the genotypes of 13 single nucleotide polymorphisms (SNPs) around TUB in 492 unrelated type 2 diabetic patients with known BMI values. One SNP (rs1528133) was found to have a significant effect on BMI (1.54 kg/m(2), P = 0.006). This association was confirmed in a population enriched for type 2 diabetes, using 750 individuals who were not selected for type 2 diabetes. Two SNPs in linkage disequilibrium with rs1528133 and mapping to the 3' end of TUB, rs2272382, and rs2272383 also affected BMI by 1.3 kg/m2 (P = 0.016 and P = 0.010, respectively). Combined analysis confirmed this association (P = 0.005 and P = 0.002, respectively). Moreover, comparing 349 obese subjects (BMI >30 kg/m(2)) from the combined cohort with 289 normal subjects (BMI <25 kg/m(2)) revealed that the protective alleles have a lower frequency in obese subjects (odds ratio 1.32 [95% CI 1.04-1.67], P = 0.022). Altogether, data from the tubby mouse as well as these data suggest that TUB could be an important factor in controlling the central regulation of body weight in humans.
    • Identifying and correcting epigenetics measurements for systematic sources of variation.

      Perrier, Flavie; Novoloaca, Alexei; Ambatipudi, Srikant; Baglietto, Laura; Ghantous, Akram; Perduca, Vittorio; Barrdahl, Myrto; Harlid, Sophia; Ong, Ken K; Cardona, Alexia; et al. (2018)
      Methylation measures quantified by microarray techniques can be affected by systematic variation due to the technical processing of samples, which may compromise the accuracy of the measurement process and contribute to bias the estimate of the association under investigation. The quantification of the contribution of the systematic source of variation is challenging in datasets characterized by hundreds of thousands of features.In this study, we introduce a method previously developed for the analysis of metabolomics data to evaluate the performance of existing normalizing techniques to correct for unwanted variation. Illumina Infinium HumanMethylation450K was used to acquire methylation levels in over 421,000 CpG sites for 902 study participants of a case-control study on breast cancer nested within the EPIC cohort. The principal component partial R-square (PC-PR2) analysis was used to identify and quantify the variability attributable to potential systematic sources of variation. Three correcting techniques, namely ComBat, surrogate variables analysis (SVA) and a linear regression model to compute residuals were applied. The impact of each correcting method on the association between smoking status and DNA methylation levels was evaluated, and results were compared with findings from a large meta-analysis.
    • Identifying germ cell mutagens using OECD test guideline 488 (transgenic rodent somatic and germ cell gene mutation assays) and integration with somatic cell testing

      Marchetti, Francesco; Aardema, Marilyn J.; Beevers, Carol; van Benthem, Jan; Godschalk, Roger; Williams, Andrew; Yauk, Carole L.; Young, Robert; Douglas, George R. (2018-08)
    • Identifying the source of food-borne disease outbreaks: An application of Bayesian variable selection.

      Jacobs, Rianne; Lesaffre, Emmanuel; Teunis, Peter Fm; Höhle, Michael; van de Kassteele, Jan (2017-01-01)
      Early identification of contaminated food products is crucial in reducing health burdens of food-borne disease outbreaks. Analytic case-control studies are primarily used in this identification stage by comparing exposures in cases and controls using logistic regression. Standard epidemiological analysis practice is not formally defined and the combination of currently applied methods is subject to issues such as response misclassification, missing values, multiple testing problems and small sample estimation problems resulting in biased and possibly misleading results. In this paper, we develop a formal Bayesian variable selection method to account for misclassified responses and missing covariates, which are common complications in food-borne outbreak investigations. We illustrate the implementation and performance of our method on a Salmonella Thompson outbreak in the Netherlands in 2012. Our method is shown to perform better than the standard logistic regression approach with respect to earlier identification of contaminated food products. It also allows relatively easy implementation of otherwise complex methodological issues.
    • IL-18 reduces ultraviolet radiation-induced DNA damage and thereby affects photoimmunosuppression.

      Schwarz, Agatha; Maeda, Akira; Ständer, Sonja; Steeg, Harry van; Schwarz, Thomas (2006-03-01)
      UV-induced DNA damage has been recognized as the major molecular trigger for photoimmunosuppression. IL-12 prevents UV-induced immunosuppression via its recently discovered capacity to reduce DNA damage presumably via induction of DNA repair. Because IL-18 shares some biological activities with IL-12 we studied the effect of IL-18 on UV-induced DNA damage and immunosuppression. IL-18 reduced UV-induced apoptosis of keratinocytes and supported long-term cell survival on UV exposure. Injection of IL-18 into mice that were exposed to UV radiation significantly lowered the number of apoptotic keratinocytes. Accordingly, radiation immunohistochemistry revealed reduced amounts of DNA damage in epidermal cells upon injection of IL-18. These effects were not observed in DNA repair-deficient (XpaKO) mice, indicating that IL-18 like IL-12 reduces DNA damage via DNA repair. UV-mediated suppression of the induction of contact hypersensitivity, which is known to be primarily triggered by DNA damage, was prevented upon injection of IL-18 before UV exposure in wild-type but not in XpaKO mice. In contrast to IL-12, IL-18 was not able either in wild-type or in XpaKO mice to break UV-induced immunotolerance that is mediated via regulatory T cells rather than in a DNA damage-dependent fashion. This result indicates that IL-12 is still unique in its capacity to restore immune responses because of its effect on regulatory T cells. Together, these data identify IL-18 as a further cytokine that exhibits the capacity to affect DNA repair. Though being primarily a proinflammatory cytokine through this capacity, IL-18 can also foster an immune response that is suppressed by UV radiation.
    • Immune response-eliciting exposure to Campylobacter vastly exceeds the incidence of clinically overt campylobacteriosis but is associated with similar risk factors: A nationwide serosurvey in the Netherlands.

      Monge, Susana; Teunis, Peter; Friesema, Ingrid; Franz, Eelco; Ang, Wim; van Pelt, Wilfrid; Mughini-Gras, Lapo (2018-05-07)
      We aimed to estimate population-level exposure to Campylobacter and associated risk factors, using three approaches for serological data analysis.
    • Immune Responses After 2 Versus 3 Doses of HPV Vaccination up to 4½ Years After Vaccination: An Observational Study Among Dutch Routinely Vaccinated Girls.

      Donken, Robine; Schurink-Van't Klooster, Tessa M; Schepp, Rutger M; van der Klis, Fiona R M; Knol, Mirjam J; Meijer, Chris J L M; de Melker, Hester E (2017-02-01)
      In 2014 the Netherlands switched from 3 to 2 doses for routine vaccination with the prophylactic bivalent human papillomavirus (HPV) vaccine. The current study explored whether antibody responses are noninferior after 2 versus 3 doses in girls.
    • Immunity against measles, mumps, rubella, varicella, diphtheria, tetanus, polio, hepatitis A and hepatitis B among adult asylum seekers in the Netherlands, 2016.

      Freidl, Gudrun S; Tostmann, Alma; Curvers, Moud; Ruijs, Wilhelmina L M; Smits, Gaby; Schepp, Rutger; Duizer, Erwin; Boland, Greet; de Melker, Hester; van der Klis, Fiona R M; et al. (2018-02-14)
      Asylum seekers are a vulnerable population for contracting infectious diseases. Outbreaks occur among children and adults. In the Netherlands, asylum seeker children are offered vaccination according to the National Immunization Program. Little is known about protection against vaccine-preventable diseases (VPD) in adult asylum seekers. In this 2016 study, we assessed the immunity of adult asylum seekers against nine VPD to identify groups that might benefit from additional vaccinations. We invited asylum seekers from Syria, Iran, Iraq, Afghanistan, Eritrea and Ethiopia to participate in a serosurvey. Participants provided informed consent and a blood sample, and completed a questionnaire. We measured prevalence of protective antibodies to measles, mumps, rubella, varicella, diphtheria, tetanus, polio type 1-3 and hepatitis A and B, stratified them by country of origin and age groups. The median age of the 622 participants was 28 years (interquartile range: 23-35), 81% were male and 48% originated from Syria. Overall, seroprotection was 88% for measles (range between countries: 83-93%), 91% for mumps (81-95%), 94% for rubella (84-98%), 96% for varicella (92-98%), 82% for diphtheria (65-88%), 98% for tetanus (86-100%), 91% (88-94%) for polio type 1, 95% (90-98%) for polio type 2, 82% (76-86%) for polio type 3, 84% (54-100%) for hepatitis A and 27% for hepatitis B (anti-HBs; 8-42%). Our results indicate insufficient protection against certain VPD in some subgroups. For all countries except Eritrea, measles seroprotection was below the 95% threshold required for elimination. Measles seroprevalence was lowest among adults younger than 25 years. In comparison, seroprevalence in the Dutch general population was 96% in 2006/07. The results of this study can help prioritizing vaccination of susceptible subgroups of adult asylum seekers, in general and in outbreak situations.
    • Immunodominance in T cell responses elicited against different domains of detoxified pneumolysin PlyD1

      van Westen, Els; Poelen, Martien C. M.; van den Dobbelsteen, Germie P. J. M.; Oloo, Eliud O.; Ochs, Martina M.; Rots, Nynke Y.; van Els, Cecile A. C. M. (2018-03-06)
    • Immunogenicity of Influenza Vaccines: Evidence for Differential Effect of Secondary Vaccination on Humoral and Cellular Immunity.

      Rosendahl Huber, Sietske K; Hendriks, Marion; Jacobi, Ronald H J; van de Kassteele, Jan; Mandersloot-Oskam, Jolanda C; van Boxtel, Renée A J; Wensing, Anne M J; Rots, Nynke Y; Luytjes, Willem; van Beek, Josine (2018-01-01)
      While currently used influenza vaccines are designed to induce neutralizing antibodies, little is known on T cell responses induced by these vaccines. The 2009 pandemic provided us with the opportunity to evaluate the immune response to vaccination in a unique setting. We evaluated both antibody and T cell responses in a cohort of public health care workers (18-52 years) during two consecutive influenza seasons from 2009 to 2011 and compared the MF59-adjuvanted pandemic vaccine with the unadjuvanted seasonal subunit vaccine that included the pandemic strain [The study was registered in the Netherlands Trial Register (NTR2070)]. Antibody responses were determined in serum by a hemagglutination inhibition assay. Vaccine-specific T cell responses were evaluated by detecting IFN-γ producing peripheral blood mononuclear cells using whole influenza virus or vaccine-specific peptide pools as stimulating antigens. Mixed effects regression models were used to correct the data for influenza-specific pre-existing immunity due to previous infections or vaccinations and for age and sex. We show that one dose of the pandemic vaccine induced antibody responses sufficient for providing seroprotection and that the vaccine induced T cell responses. A second dose further increased antibody responses but not T cell responses. Nonetheless, both could be boosted by the seasonal vaccine in the subsequent season. Furthermore, we show that the seasonal vaccine alone is capable of inducing vaccine-specific T cell responses, despite the fact that the vaccine did not contain an adjuvant. In addition, residual antibody levels remained detectable for over 15 months, while T cell levels in the blood had contracted to baseline levels by that time. Hereby, we show that pandemic as well as seasonal vaccines induce both humoral and cellular responses, however, with a different profile of induction and waning, which has its implications for future vaccine design.
    • Immunogenicity, effectiveness, and safety of measles vaccination in infants younger than 9 months: a systematic review and meta-analysis.

      Nic Lochlainn, Laura M; de Gier, Brechje; van der Maas, Nicoline; Strebel, Peter M; Goodman, Tracey; van Binnendijk, Rob S; de Melker, Hester E; Hahné, Susan J M (2019-11-01)
      Our search identified 1156 studies, of which 1071 were screened for eligibility. 351 were eligible for full-text screening, and data from 56 studies that met all inclusion criteria were used for analysis. The proportion of infants who seroconverted increased from 50% (95% CI 29-71) for those vaccinated with MCV1 at 4 months of age to 85% (69-97) for those were vaccinated at 8 months. The pooled geometric mean titre ratio for infants aged 4-8 months vaccinated with MCV1 compared with infants vaccinated with MCV1 at age 9 months or older was 0·46 (95% CI 0·33-0·66; I2=99·9%, p<0·0001). Only one study reported on avidity and suggested that there was lower avidity and a shorter duration of immunity following MCV1 administration at 6 months of age than at 9 months of age (p=0·0016) or 12 months of age (p<0·001). No effect of age at MCV1 administration on cellular immunity was found. One study reported that vaccine efficacy against laboratory-confirmed measles virus infection was 94% (95% CI 74-98) in infants vaccinated with MCV1 at 4·5 months of age. The pooled vaccine effectiveness of MCV1 in infants younger than 9 months against measles was 58% (95% CI 9-80; I2=84·9%, p<0·0001). The pooled vaccine effectiveness estimate from within-study comparisons of infants younger than 9 months vaccinated with MCV1 were 51% (95% CI -44 to 83; I2=92·3%, p<0·0001), and for those aged 9 months and older at vaccination it was 83% (76-88; I2=93·8%, p<0·0001). No differences in the risk of adverse events after MCV1 administration were found between infants younger than 9 months and those aged 9 months of older. Overall, the quality of evidence ranged from moderate to very low.
    • Immunoglobulin A deficiency in children, an undervalued clinical issue.

      Koenen, M H Mischa; van Montfrans, J M Joris; Sanders, E A M Elisabeth; Bogaert, D Debby; Verhagen, L M Lilly (2019-12-01)
    • The immunomodulatory effects of measles-mumps-rubella (MMR) vaccination on persistence of heterologous vaccine responses.

      Zimmermann, Petra; Perrett, Kirsten P; van der Klis, Fiona R M; Curtis, Nigel (2019-02-21)
      It is proposed that measles-containing vaccines (MCV) have immunomodulatory effects which include a reduction in all-cause childhood mortality. The antibody response to heterologous vaccines provides a means to explore these immunomodulatory effects. This is the first study to investigate the influence of measles-mumps-rubella (MMR) vaccine on the persistence of antibodies to a broad range of heterologous infant vaccinations given in the first year of life. In total, 319 children were included in the study. All infants received routine vaccinations at 6 weeks, 4 and 6 months of age. At 12 months of age, 212 children were vaccinated with measles-mumps-rubella (MMR) and Haemophilus influenzae type b-meningococcus C (Hib-MenC) vaccine while the remaining 99 children had not yet received this vaccine. In the MMR/Hib-MenC-vaccinated group, blood was taken 28 ± 14 days after receiving these vaccines. Antibodies against diphtheria, tetanus, pertussis (pertussis toxin, filamentous haemagglutinin, pertactin), poliomyelitis (type 1, 2, 3) and 13 pneumococcal serotypes were measured. Geometric mean antibody concentrations (GMC) and seroprotection rates were compared between MMR/MenC-Hib-vaccinated and MMR/MenC-Hib-naïve participants. In the final analysis, 311 children were included. Seroprotection rates were lower in MMR/Hib-MenC-vaccinated children against pertussis toxin and pneumococcus serotype 19A. After adjustment for pre-specified factors, MMR/Hib-MenC-vaccinated infants had significantly higher antibody concentrations against tetanus (likely explained by a boosting effect of the carrier protein, a tetanus toxoid), while for the other vaccine antigens there was no difference in antibody concentrations between the two groups. This article is protected by copyright. All rights reserved.