• Principles and methods to assess the risk of immunotoxicity assocated with exposure to nanomaterials.

      Bonner, J; Lopez, YIC; Fadeel, B; Halappanavar, S; Kanno, J; Ng, KW; Savolainen, K; van Loveren, H; Yu, IJ; Park, M; et al. (2019-10-22)
    • Priorities for improving chemicals management in the WHO European Region-stakeholders' views.

      Vincenten, Joanne A; Zastenskaya, Irina; Schröder-Bäck, Peter; Jarosinska, Dorota Iwona (2020-05-08)
    • Prioritisation of food-borne parasites in Europe, 2016.

      Bouwknegt, Martijn; Devleesschauwer, Brecht; Graham, Heather; Robertson, Lucy J; van der Giessen, Joke Wb; The Euro-Fbp Workshop Participants (2018-03)
      Background and aimsPriority setting is a challenging task for public health professionals. To support health professionals with this and in following a recommendation from the Food and Agriculture Organization of the United Nations (FAO) and World Health Organization (WHO), 35 European parasitologists attended a workshop from 8-12 February 2016 to rank food-borne parasites (FBP) in terms of their importance for Europe and regions within Europe.Methods:Countries were divided into European regions according to those used by the European Society of Clinical Microbiology and Infectious Diseases. We used the same multicriteria decision analysis approach as the FAO/WHO, for comparison of results, and a modified version, for better regional representation. Twenty-five FBP were scored in subgroups, using predefined decision rules.Results:At the European level,Echinococcus multilocularisranked first, followed byToxoplasma gondiiandTrichinella spiralis. At the regional level,E. multilocularisranked highest in Northern and Eastern Europe,E. granulosusin South-Western and South-Eastern Europe, andT. gondiiin Western Europe. Anisakidae, ranking 17th globally, appeared in each European region's top 10. In contrast,Taenia solium, ranked highest globally but 10th for Europe.Conclusions:FBP of importance in Europe differ from those of importance globally, requiring targeted surveillance systems, intervention measures, and preparedness planning that differ across the world and across Europe.
    • Pro-inflammatory responses to PM 0.25 from airport and urban traffic emissions

      He, Rui-Wen; Shirmohammadi, Farimah; Gerlofs-Nijland, Miriam E.; Sioutas, Constantinos; Cassee, Flemming R. (2018-11)
    • Probabilistic approach for assessing cancer risk due to benzo[a]pyrene in barbecued meat: Informing advice for population groups.

      Jakobsen, Lea Sletting; Georgiadis, Stylianos; Nielsen, Bo Friis; Bokkers, Bas G H; Boriani, Elena; Duedahl-Olesen, Lene; Hald, Tine; Nauta, Maarten J; Stockmarr, Anders; Pires, Sara M (2018-01-01)
      Consumption of meat prepared by barbecuing is associated with risk of cancer due to formation of carcinogenic compounds including benzo[a]pyrene (BaP). Assessment of a population's risk of disease and people's individual probability of disease given specific consumer attributes may direct food safety strategies to where impact on public health is largest. The aim of this study was to propose a model that estimates the risk of cancer caused by exposure to BaP from barbecued meat in Denmark, and to estimate the probability of developing cancer in subgroups of the population given different barbecuing frequencies. We developed probabilistic models applying two dimensional Monte Carlo simulation to take into account the variation in exposure given age and sex and in the individuals' sensitivity to develop cancer after exposure to BaP, and the uncertainty in the dose response model. We used the Danish dietary consumption survey, monitoring data of chemical concentrations, data on consumer behavior of frequency of barbecuing, and animal dose response data. We estimated an average extra lifetime risk of cancer due to BaP from barbecued meat of 6.8 × 10-5 (95% uncertainty interval 2.6 × 10-7 - 7.0 × 10-4) in the Danish population. This corresponds to approximately one to 4,074 extra cancer cases over a lifetime, reflecting wide uncertainty. The impact per barbecuing event on the risk of cancer for men and women of low body weight was higher compared to higher bodyweight. However, the difference due to sex and bodyweight between subgroups are dwarfed by the uncertainty. This study proposes a model that can be applied to other substances and routes of exposure, and allows for deriving the change in risk following a specific change in behaviour. The presented methodology can serve as a valuable tool for risk management, allowing for the formulation of behaviour advice targeted to specific sub-groups in the population.
    • A probabilistic approach to assess antibiotic resistance development risks in environmental compartments and its application to an intensive aquaculture production scenario.

      Rico, Andreu; Jacobs, Rianne; Van den Brink, Paul J; Tello, Alfredo (2017-12)
      Estimating antibiotic pollution and antibiotic resistance development risks in environmental compartments is important to design management strategies that advance our stewardship of antibiotics. In this study we propose a modelling approach to estimate the risk of antibiotic resistance development in environmental compartments and demonstrate its application in aquaculture production systems. We modelled exposure concentrations for 12 antibiotics used in Vietnamese Pangasius catfish production using the ERA-AQUA model. Minimum selective concentration (MSC) distributions that characterize the selective pressure of antibiotics on bacterial communities were derived from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) Minimum Inhibitory Concentration dataset. The antibiotic resistance development risk (RDR) for each antibiotic was calculated as the probability that the antibiotic exposure distribution exceeds the MSC distribution representing the bacterial community. RDRs in pond sediments were nearly 100% for all antibiotics. Median RDR values in pond water were high for the majority of the antibiotics, with rifampicin, levofloxacin and ampicillin having highest values. In the effluent mixing area, RDRs were low for most antibiotics, with the exception of amoxicillin, ampicillin and trimethoprim, which presented moderate risks, and rifampicin and levofloxacin, which presented high risks. The RDR provides an efficient means to benchmark multiple antibiotics and treatment regimes in the initial phase of a risk assessment with regards to their potential to develop resistance in different environmental compartments, and can be used to derive resistance threshold concentrations.
    • Probabilistic derivation of the interspecies assessment factor for skin sensitization.

      Bil, W; Schuur, A G; Ezendam, J; Bokkers, B G H (2017-08)
      An interspecies sensitization assessment factor (SAF) is used in the quantitative risk assessment (QRA) for skin sensitization when a murine-based NESIL (No Expected Sensitization Induction Level) is taken as point of departure. Several studies showed that, on average, the murine sensitization threshold is in good correspondence with that determined in humans. However, on an individual level, the murine and human sensitization thresholds may differ considerably. In this study, the interspecies SAF was quantified by using a probabilistic approach, to be able to take these cases into account. As expected, the geometric means of the probability distributions of murine and human sensitization threshold ratios were close to one, but taking the 95 th percentile of these distributions resulted in an interspecies SAF of 15. By using this value, one is sure that with 95% probability, the sensitization threshold determined in mice does not underestimate the human threshold. It can be concluded that a murine-based NESIL requires the use of an interspecies SAF (of 15) in the QRA for skin sensitization, to correct for the differences between mice and humans. This empirically derived interspecies SAF contributes to refinement of the risk assessment methodology.
    • Probabilistic dietary exposure assessment taking into account variability in both amount and frequency of consumption.

      Slob, Wout (2006-07-01)
      Probabilistic dietary exposure assessments that are fully based on Monte Carlo sampling from the raw intake data may not be appropriate. This paper shows that the data should first be analysed by using a statistical model that is able to take the various dimensions of food consumption patterns into account. A (parametric) model is discussed that takes into account the interindividual variation in (daily) consumption frequencies, as well as in amounts consumed. Further, the model can be used to include covariates, such as age, sex, or other individual attributes. Some illustrative examples show how this model may be used to estimate the probability of exceeding an (acute or chronic) exposure limit. These results are compared with the results based on directly counting the fraction of observed intakes exceeding the limit value. This comparison shows that the latter method is not adequate, in particular for the acute exposure situation. A two-step approach for probabilistic (acute) exposure assessment is proposed: first analyse the consumption data by a (parametric) statistical model as discussed in this paper, and then use Monte Carlo techniques for combining the variation in concentrations with the variation in consumption (by sampling from the statistical model). This approach results in an estimate of the fraction of the population as a function of the fraction of days at which the exposure limit is exceeded by the individual.
    • Probabilistic dietary risk assessment of triazole and dithiocarbamate fungicides for the Brazilian population.

      Jardim, Andreia Nunes Oliveira; Mello, Denise Carvalho; Brito, Alessandra Page; van der Voet, Hilko; Boon, Polly E; Caldas, Eloisa Dutra (2018-05-04)
      Residue data for triazoles (TR) and dithiocarbamates (DT) in 30,786 samples of 30 foods were obtained from mainly two national monitoring programs, and consumption data from a national survey conducted among persons aged 10 years or older About 16% of the samples contained TR, mainly grape (53.5%), and 16.2% contained DT, mainly apple (59.3%). Flusilazole was the index compound for the acute effects of TR for women of child-bearing-age (cranium-facial malformation and skeletal variation), cyproconazole for the chronic effects of TR (hepatoxicity), and ethylene-bis-dithitiocarbamates (EBDC) for DT (thyroid toxicity). Exposures were estimated using the Monte Carlo Risk Assessment software. Different models were tested, and a Model-Then-Add approach was found to best estimate the chronic exposures to DT and TR. At the 99.9th percentile (P99.9), the cumulative acute TR intakes accounted for up to 0.5% of the flusilazole ARfD, mainly from beans and rice consumption. The chronic TR and DT intakes accounted for 1 and 6.7% of the respective index compound ADIs, with beans and rice accounting for most of the TR intake (∼70%), and apple for about 51-56% of the DT intake. The estimated risks from the exposure to TR and DT indicate no health concern for the Brazilian population.
    • Probabilistic inversion for chicken processing lines

      Cooke, Roger M; Nauta, Maarten; Havelaar, Arie H; Fels, Ine van der (Elsevier, 2006-01-25)
      We discuss an application of probabilistic inversion techniques to a model of campylobacter transmission in chicken processing lines. Such techniques are indicated when we wish to quantify a model which is new and perhaps unfamiliar to the expert community. In this case there are no measurements for estimating model parameters, and experts are typically unable to give a considered judgment. In such cases, experts are asked to quantify their uncertainty regarding variables which can be predicted by the model. The experts’ distributions (after combination) are then pulled back onto the parameter space of the model, a process termed “probabilistic inversion”. This study illustrates two such techniques, iterative proportional fitting (IPF) and PARmeter fitting for uncertain models (PARFUM). In addition, we illustrate how expert judgement on predicted observable quantities in combination with probabilistic inversion may be used for model validation and/or model criticism.
    • Probing the limits of predictability: data assimilation of chaotic dynamics in complex food webs.

      Massoud, Elias C; Huisman, Jef; Benincà, Elisa; Dietze, Michael C; Bouten, Willem; Vrugt, Jasper A (2018-01)
      The daunting complexity of ecosystems has led ecologists to use mathematical modelling to gain understanding of ecological relationships, processes and dynamics. In pursuit of mathematical tractability, these models use simplified descriptions of key patterns, processes and relationships observed in nature. In contrast, ecological data are often complex, scale-dependent, space-time correlated, and governed by nonlinear relations between organisms and their environment. This disparity in complexity between ecosystem models and data has created a large gap in ecology between model and data-driven approaches. Here, we explore data assimilation (DA) with the Ensemble Kalman filter to fuse a two-predator-two-prey model with abundance data from a 2600+ day experiment of a plankton community. We analyse how frequently we must assimilate measured abundances to predict accurately population dynamics, and benchmark our population model's forecast horizon against a simple null model. Results demonstrate that DA enhances the predictability and forecast horizon of complex community dynamics.
    • Probiotics: immunomodulation and evaluation of safety and efficacy.

      Ezendam, Janine; Loveren, Henk van (2006-01-01)
      The intake of probiotics has been associated with beneficial effects on the immune system, such as improved disease resistance and diminished risk of allergies. This review gives an overview of the immunomodulatory effects of probiotics investigated with in vitro assays, experimental animal models, and clinical trials, and explores possible mechanisms underlying the immunomodulatory effects. Immunomodulation, however, is not always beneficial and might induce detrimental effects; therefore, a scheme is proposed for benefit-risk assessment of immunomodulation by probiotics. Within this scheme, expert judgment based on data derived from a panel of in vitro assays, animal models, and clinical trials should lead to conclusions on efficacy and safety aspects of probiotics.
    • The problem of resistance in Mycobacterium tuberculosis may be underestimated in Africa.

      B Cadmus, Simeon I; Falodun, Olutayo I; Fagade, Oba E; Murphy, Robert; Taiwo, Babafemi; Van Soolingen, Dick (2018-06-25)
      The true burden of tuberculosis (TB) and particularly multidrug-resistant (MDR) TB in Sub-Saharan Africa has remained underestimated.
    • Proficiency Testing of Virus Diagnostics Based on Bioinformatics Analysis of Simulated High-Throughput Sequencing Data Sets.

      Brinkmann, Annika; Andrusch, Andreas; Belka, Ariane; Wylezich, Claudia; Höper, Dirk; Pohlmann, Anne; Nordahl Petersen, Thomas; Lucas, Pierrick; Blanchard, Yannick; Papa, Anna; et al. (2019-08-01)
      Quality management and independent assessment of high-throughput sequencing-based virus diagnostics have not yet been established as a mandatory approach for ensuring comparable results. The sensitivity and specificity of viral high-throughput sequence data analysis are highly affected by bioinformatics processing using publicly available and custom tools and databases and thus differ widely between individuals and institutions. Here we present the results of the COMPARE [Collaborative Management Platform for Detection and Analyses of (Re-)emerging and Foodborne Outbreaks in Europe] in silico virus proficiency test. An artificial, simulated in silico data set of Illumina HiSeq sequences was provided to 13 different European institutes for bioinformatics analysis to identify viral pathogens in high-throughput sequence data. Comparison of the participants' analyses shows that the use of different tools, programs, and databases for bioinformatics analyses can impact the correct identification of viral sequences from a simple data set. The identification of slightly mutated and highly divergent virus genomes has been shown to be most challenging. Furthermore, the interpretation of the results, together with a fictitious case report, by the participants showed that in addition to the bioinformatics analysis, the virological evaluation of the results can be important in clinical settings. External quality assessment and proficiency testing should become an important part of validating high-throughput sequencing-based virus diagnostics and could improve the harmonization, comparability, and reproducibility of results. There is a need for the establishment of international proficiency testing, like that established for conventional laboratory tests such as PCR, for bioinformatics pipelines and the interpretation of such results.
    • A progesterone-brown fat axis is involved in regulating fetal growth.

      McIlvride, Saraid; Mushtaq, Aleena; Papacleovoulou, Georgia; Hurling, Chloe; Steel, Jennifer; Jansen, Eugène; Abu-Hayyeh, Shadi; Williamson, Catherine (2017-09-06)
      Pregnancy is associated with profound maternal metabolic changes, necessary for the growth and development of the fetus, mediated by reproductive signals acting on metabolic organs. However, the role of brown adipose tissue (BAT) in regulating gestational metabolism is unknown. We show that BAT phenotype is lost in murine pregnancy, while there is a gain of white adipose tissue (WAT)-like features. This is characterised by reduced thermogenic capacity and mitochondrial content, accompanied by increased levels of markers of WAT and lipid accumulation. Surgical ablation of BAT prior to conception caused maternal and fetal hyperlipidemia, and consequently larger fetuses. We show that BAT phenotype is altered from day 5 of gestation, implicating early pregnancy factors, which was confirmed by reduced expression of BAT markers in progesterone challenged oophorectomised mice. Moreover, in vitro data using primary BAT cultures show a direct impact of progesterone on expression of Ucp1. These data demonstrate that progesterone mediates a phenotypic change in BAT, which contributes to the gestational metabolic environment, and thus overall fetal size.
    • Programme of the Community Network of Reference Laboratories for Human Influenza to improve Influenza Surveillance in Europe.

      Meijer, Adam; Brown, Caroline; Hungnes, Olav; Schweiger, Brunhilde; Valette, Martine; Werf, Sylvie van der; Zambon, Maria (2006-11-10)
      All laboratories participating in the Community Network of Reference Laboratories for Human Influenza in Europe (CNRL) co-ordinated by the European Influenza Surveillance Scheme (EISS) should be able to perform a range of influenza diagnostics. This includes direct detection, culture, typing, subtyping and strain characterisation of influenza viruses, diagnostic serology and the creation of archives for clinical specimens and virus isolates. To improve the capacity and quality of the laboratories of the CNRL and to increase the consistency in performance among all 25 European Union countries plus Norway, Romania, and Switzerland, five task groups were set up in February 2005. These task groups developed work programmes in the areas of virus isolation, antibodies, molecular virology, quality control assessment and antiviral susceptibility testing. This report outlines the programmes and the results achieved in the first half-year of operation of the task groups. The action plans are challenging and it is expected that these efforts will lead to considerable improvements in the performance of the laboratories and in the standardisation of methods employed in Europe with regard to routine influenza surveillance and early warning for emerging viruses.
    • Projections of the Healthcare Costs and Disease Burden due to Hepatitis C Infection under Different Treatment Policies in Malaysia, 2018-2040.

      McDonald, Scott A; Azzeri, Amirah; Shabaruddin, Fatiha Hana; Dahlui, Maznah; Tan, Soek S; Kamarulzaman, Adeeba; Mohamed, Rosmawati (2018-08-25)
      The World Health Organisation (WHO) has set ambitious goals to reduce the global disease burden associated with, and eventually eliminate, viral hepatitis.