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Infectious diseases are caused by pathogenic micro-organisms which can be bacteria, viruses, parasites or fungi. The diseases can be spread through many different routes, either directly or indirectly. Military personnel are at high risk of contracting infections, in particular vector-borne and zoonotic infections, during overseas deployments, where they may be exposed to endemic or emerging infections to which they do not have immunity. Additionally, overcrowded settings with poor sanitation are high risks for disease. Genomics is having a transformational impact on medicine. It is enabling advances in accurate diagnosis of infectious disease, development of effective and targeted treatment strategies and opportunities to assess pathogenicity. Further, it supports the detection, surveillance of infectious diseases, the development and assessment of vaccines, as well as the assessment and prediction of anti-microbial resistance. These capabilities are all key military needs to protect personnel in this inter-connected world. The advances in sequencing technologies have resulted in an explosion of genomic data. However, making sense of genomic data requires advances in computational analysis technologies together with crossdisciplinary scientific approaches, skill sets and people. There are extensive reference databases of genomic data. One such open access database is PubMLST.org: it contains well curated genomes for more than 100 microbial species and genera integrated with provenance and phenotype information. All levels of sequence data, from single gene sequences up to and including complete, finished genomes can be accessed on this platform. This data is, however, both large and complex and intractable to analyse and understand using traditional analysis tools. This paper will discuss the challenges of analysing such genomic data for bacterial infections and consider the application of bioinformatics tools and techniques to analyse and communicate microbial genomic data in healthcare.

How can we assess the quality of an analytical deliberative decision support procedure in environmental health practice? Objectifying quality criteria is difficult for several reasons. Opening up evaluation to a diversity of critics is one approach to take into account different actor perspectives and complexity. We describe how social scientists organized extended peer evaluation of a participatory multi-criteria procedure that was applied in Flemish environmental health practice. International peer review was combined with local extended peer evaluation. Social scientists collaborated closely with natural scientists and policy representatives in designing several evaluative activities and in interpreting the results.We discuss how these different perspectives came to reach conclusions, with a special focus on methodological decision-making. A process of learning by doing and negotiating, finding a methodological path amidst practicalities, complexity and ambition.

Abstract
Background
PFAS are persistent, bioaccumulative compounds repelling water, oil and stains which are widely used. There is mounting evidence linking exposure to a range of adverse health outcomes including renal, hepatic, immunotoxic, reproductive, endocrine disrupting and carcinogenic effects. PFAS possibly also induce neurobehavioral and developmental effects. Within Flanders Environment and Health Studies (FLEHS) internal exposure to PFAS and relevant health effects are assessed since 2008.

Results
Adolescents 14–15 y (2010–2011) living in an industrially contaminated area (without known PFAS contamination) and adults 50–65 y (2014) randomly sampled from the general Flemish population using a stratified clustered multi-stage design, were recruited. For the adolescents perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were measured in serum, for the adults PFOS, PFOA, perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA) and perfluorobutane sulfonate (PFBS). In adolescents the Neurobehavioral Evaluation System (NES3) computerized battery of tests developed to study the neurological effects of an exposure to environmental agents was applied. The adults did the Stroop test, the NES3 Continuous Performance Test and the NES3 Digit Span Test. In adolescents sleepiness, masculinity and femininity were assessed via the Epworth Sleepiness Scale and Personal Attributes Questionnaires, respectively. In adolescents PFOA was associated with significantly increased somnolence, and PFOS with a significant inverse association with boys' femininity and with girls' masculinity. In adolescents, PFAS were also associated with a marginal decrease in sustained attention (PFOS) and cognitive performance (PFOA) and a significant decrease in short-term memory (PFOS). However, in older adults PFOS was associated with a significant increase in the capacity to pay attention and PFHxS with a significant increase in sustained attention.

Conclusion
Our observations point to neurobehavioral and cognitive effects of PFAS. The neurobehavioral effects might in part result from the changes in sex hormone levels that have been reported to be associated with internal exposure to PFAS. Interestingly, whereas in relation to cognition some adverse effects were recorded for adolescents, for elderly persons our observations rather suggest possible weak positive effects with respect to cognition. Our observations might be in line with the view that PFAS have many, sometimes contrasting health effects.

Abstract
Background
The successive FLEHS campaigns assess internal exposure to pollutants and associated early biological and health effects in participants of different age groups.

Materials and methods
Mother–newborn pairs (N = 220 in 2008–2009, age 18–42 years; N = 269 in 2013–2014, age 18–44 years), 197 adolescents 14–15 years (2010–2011), 201 adults 20–40 years (2008–2009) and 205 adults 50–65 years (2014) were recruited. For the various groups of subjects different sets of PFAS were assessed. Perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorobutane sulfonate (PFBS) were determined in cord plasma and peripheral serum as these were the PFAS compounds for which we had access to high quality measurements and which were expected to be present in the highest concentrations. Participants filled out a questionnaire based on the European Community Respiratory Health Survey questionnaire on asthma and allergy. In these cross-sectional studies associations were assessed using stepwise multiple logistic regression, with confounders (including smoking and familial occurrence of the disease) and potential covariates selected on the basis of experience in our previous studies and a literature search. Forest plots of odds ratios summarize the associations between the various PFAS on the one hand and the different immune outcomes on the other hand.

Results
For several self-reported immune system-related diseases inverse associations with PFAS serum concentrations were observed. These inverse associations were more pronounced in mothers and adults than in adolescents. A significant inverse association was observed in adults and mothers (for mothers based on measurements on cord plasma) between PFNA, PFOS, and PFHxS and asthma (for mothers also for PFOA), in mothers between PFHxS, PFNA and PFOS and allergic rhinitis, in mothers and adults between PFHxS and PFOS and some forms of allergy (for mothers also for PFOA), in adults between PFOA and eczema, and in adolescents between PFOS and systemic allergy.

Conclusion
Internal exposure to PFAS was associated with changes in immunological processes consistent with what has been reported in the literature. Whereas these changes were observed in many publications to be associated with adverse health effects, our findings suggest that they can also lead to inverse associations with certain immune system-related diseases.

Because of their dirt-, water- and oil-repelling properties, per- and polyfluoroalkyl substances (PFASs) are frequently used in a broad variety of consumer products. They have been detected in human samples worldwide. In Flanders, Belgium, the Flemish Environment and Health Studies (FLEHS) measured the levels of five PFAS biomarkers in four different age groups of the Flemish population and identified determinants of variability in exposure. Cord plasma or peripheric serum samples and questionnaire data were available for 220 mother-newborn pairs (2008-2009), 269 mother-newborn pairs (2013-2014), 199 adolescents (14-15 years old, 2010), 201 adults (20-40 years old, 2008-2009) and 205 adults (50-65 years old, 2014). Measured levels of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) in Flanders are in the middle or low range compared to concentrations reported in other Western countries. Levels of perfluorobutanesulfonic acid (PFBS) were below the quantification limit in 98%-100% of the samples. Despite decreasing levels in time for PFOS and PFOA, 77% of the adults (2014) had serum levels exceeding HBM-I values of 5 mu/L for PFOS and 2 mu g/L for PFOA. Beside age, sex, fish consumption, parity and breastfeeding, the multiple regression models identified additionally consumption of offal and locally grown food, and use of cosmetics as possible exposures and menstruation as a possible route of elimination. Better knowledge on determinants of exposure is essential to lower PFASs exposure. ; This paper is based on research conducted within the framework of the Flemish Centre of Expertise on Environment and Health, funded by the Environment, Nature and Energy Department of the Flemish government, the Department of Public Health and the Department of Science of the Flemish government. The views expressed herein are those of the authors and are not necessarily endorsed by the Flemish government. ; Colles, A (reprint author), VITO Hlth, Boeretang 200, B-2400 Mol, Belgium. ann.colles@vito.be

The ubiquitous use of organophosphate flame retardants and plasticizers (PFRs) in a variety of consumer products has led to widespread human exposure. Since certain PFRs are developmental and carcinogenic toxicants, detailed exposure assessments are essential to investigate the risk associated with environmental exposure levels. However, such data are still lacking for European countries. In this study, concentrations of thirteen PFR metabolites were measured in urine samples from 600 adolescents from Flanders, Belgium. 1-Hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP), diphenyl phosphate (DPHP), bis(1,3-dichloro-isopropyl) phosphate (BDCIPP), 2-hydroxyethyl bis(2-butoxyethyl) phosphate (BBOEHEP), 2-ethylhexyl phenyl phosphate (EHPHP) and 2-ethyl-5-hydroxyhexyl diphenyl phosphate (5-HO-EHDPHP) were frequently detected (>83%) in all participants. Comparisons with study populations from outside the EU showed that urinary levels of DPHP, BDCIPP and BCIPHIPP were generally within the same range. Only exposure to 2-ethylhexyl diphenyl phosphate (EHDPHP) was presumably higher in Flemish adolescents. However, determinants analysis through multivariate regression analyses did not reveal significant predictors that may explain this finding. Significantly higher levels of BDCIPP were observed in participants with new decorations at home, while adolescents with highly educated parents had higher levels of BBOEHEP and BDCIPP. Furthermore, multiple PFR metabolite concentrations followed a seasonal pattern. Estimated daily intakes (EDIs) were calculated from the internal dose by including fractions of urinary excretion (FUE) estimated in in vitro metabolism studies. EDIs ranged from 6.3 ng/kg bw/day for TBOEP to 567.7 ng/kg bw/day for EHDPHP, which were well below the available oral reference doses for all investigated PFRs. This suggests that the associated risk is low at present. This is the first report on internal exposure to seven commonly used PFRs in a European population. ; We thank the participating adolescents and their families. Without their effort this study would not have been possible. We also thank J. Bombeke for his assistance during the sample preparation. This paper is based on research conducted within the framework of the Flemish Center of Expertise on Environment and Health (FLEHS 2016-2020), funded by the Government of Flanders, Department of Environment & Spatial Development. The views expressed herein are those of the author (s) and are not necessarily endorsed by the government of Flanders. The Flemish Environment and Health Study was commissioned, financed and steered by the Ministry of the Flemish Community (Department of Environment) (grant ID: Steunpunt Milieu & Gezondheid), including the partial funding of the Ph.D. of Michiel Bastiaensen. Celine Gys acknowledges the funding of a PhD fellowship from Research Foundation Flanders (project G0E5216N).

Human biomonitoring (HBM) monitors levels of environmental pollutants in human samples, which often is a topic of concern for residents near industrially contaminated sites (ICSs). Around an ICS area in Menen (Belgium), including a (former) municipal waste incinerator and a metal recovery plant, increasing environmental concentrations of dioxins and polychlorinated biphenyls (PCBs) were observed, causing growing concern among residents and authorities. The local community succeeded in convincing the responsible authorities to investigate the problem and offer research funding. Persistent organic pollutants (POPs) were measured in two consecutive HBM studies (2002-2006 and 2010-2011), in the context of the Flemish Environment and Health Study (FLEHS), as well as in soil and locally produced food. Meanwhile, local authorities discouraged consumption of locally produced food in a delineated area of higher exposure risk. Ultimately, HBM and environmental data enabled tailored dietary recommendations. This article demonstrates the usefulness of HBM in documenting the body burdens of residents near the ICS, identifying exposure routes, evaluating remediating actions and providing information for tailored policy strategies aiding to further exposure reduction. It also highlights the role of the local stakeholders as an example of community-based participatory research and how such an approach can create societal support for research and policy. ; Funding: The HBM studies were conducted within the framework of the Flemish Center of Expertise on Environment and Health (FLEHS 2002–2006 and 2007–2011), funded by the Flemish Government, Department of Environment & Spatial Development, Flemish Planning Bureau for the Environment and Spatial Development (formally: Department of Environment, Nature & Energy); Department of Economics, Science and Innovation and the Flemish Agency for Care and Health. The scienceto-policy process of the HBM results was funded by the Department of Environment & Spatial Development, Flemish Planning Bureau for the Environment and Spatial Development (formally: Department of Environment, Nature & Energy) and the Flemish Agency for Care and Health. The egg study was funded by the Government of Flanders, Department of Environment & Spatial Development, Flemish Planning Bureau for the Environment and Spatial Development (formally: Department of Environment, Nature & Energy); the Flemish Agency for Care and Health and the Flanders Environment Agency. The views expressed herein are those of the author(s) and are not necessarily endorsed by the Flemish Government. Acknowledgments: The authors wish to express their gratitude to the participants of the studies for their cooperation and to the study nurses and study fieldworkers for their contribution to the study. We also thank the SGS laboratory for collection and analysis of the egg samples and Josworld for designing the leaflet on dietary recommendations for consumption of home-produced eggs.

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants of public health concern. Multiple biological mechanisms have been hypothesized to contribute to PAHs-associated adverse health effects. Little is known about the impact of PAHs on endocrine stress and inflammation in adolescence. We examined 393 Flemish adolescents (14-15 years) cross-sectionally, measured urinary concentrations of hydroxylated naphthalene, fluorene, phenanthrene and pyrene metabolites, and calculated the sum of all measured metabolites. We determined hair cortisol concentration (HCC) as endocrine stress biomarker, leucocyte counts and neutrophil-lymphocyte ratio (NLR) in peripheral blood as inflammatory biomarkers, and urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) concentration as oxidative stress biomarker. Exposure-response associations were analyzed by multiple regression, adjusted for a priori selected covariates. A doubling of 1-hydroxypyrene concentration was associated with a factor of 1.13 (95% CI: 1.03, 1.24) increase in HCC and a factor of 1.07 (95% CI: 1.02, 1.13) increase in 8-oxodG. Doublings of 2- and 3-hydroxyphenanthrene concentrations were associated with a factor of 1.08 (95% CI: 1.02, 1.14) and 1.06 (95% CI: 1.00, 1.12) increase in 8-oxodG, respectively. Doubling of 2-hydroxyphenanthrene and of the sum of 2- and 3-hydroxyfluorene was associated with, respectively, a factor of 1.08 (95% CI: 1.02, 1.14) and 1.06 (95% CI: 1.01, 1.13) increase in NLR. Our results indicate the glucocorticoid pathway as a potential target for PAH exposure in adolescents and suggest oxidative stress, endocrine stress, and inflammation in adolescence as underlying mechanisms and early markers for PAH-related adverse health effects. ; Government of Flanders, Department of Environment & Spatial Development; Flemish Center of Expertise on Environment and Health

Background: Exposure to air pollution and traffic noise are associated with adverse health outcomes in adolescents. Chronic endocrine stress and systemic inflammation have been hypothesized to underlie the adverse health effects. Simultaneous assessment of inflammation and chronic endocrine stress in epidemiological studies is lacking. The aim of the study was to investigate biomarkers of chronic endocrine stress and inflammation in relation to long-term residential exposure to air pollution and traffic noise in adolescents. Methods: In Flemish adolescents (14-15 years), we determined hair cortisol concentration (HCC) as a chronic stress biomarker in 3-cm scalp-near hair sections (n = 395), and leucocyte and leucocyte subtype counts (neutrophils, monocytes, lymphocytes) as inflammatory biomarkers in peripheral blood (n = 385). Daily particulate matter (PM2.5, PM10), nitrogen dioxide (NO2) and black carbon (BC) concentrations were modelled at the residential address and averaged over 3-month and 1-year periods prior to sampling. Residential traffic noise level was estimated and classified in 5 dB intervals. Sex-specific associations between residential exposures and effect biomarkers were studied using linear regression models, adjusted for a priori selected covariates. Results: In boys, HCC increased with a factor 1.30 (95% CI: 1.10, 1.54) for an increase in 1-year mean NO2 from the 25th to 75th percentile (p75/p25), after adjustment for age, BMI, personal and neighborhood socioeconomic status. The corresponding estimate for PM10 was 1.24 (95% CI: 1.02, 1.51). Total leucocyte count in boys, adjusted for the aforementioned covariates and recent health complaints, was positively associated with PM2.5, PM10, NO2 and BC. In particular, the neutrophil count increased with a factor 1.11 (95% CI: 1.03, 1.19) for a (p75/p25)-factor increase in 1-year mean BC, corresponding estimates for PM2.5, PM10 and NO2 were 1.10 (95% CI: 1.01, 1.19), 1.10 (95% CI: 1.01, 1.20) and 1.08 (95% CI: 1.00, 1.16). Lymphocyte count increased with a factor 1.05 (95% CI: 1.01, 1.10) for a (p75/p25)-factor increase in 1-year mean NO2. Similar results were observed for 3-month mean exposures. Results were robust to adjustment for recent air pollution exposure. In girls, air pollutants were not associated with HCC or differential leucocyte count. Residential traffic noise level was not associated with HCC or leucocyte counts in boys nor girls. Conclusions: Long-term residential exposure to air pollutants was positively associated with chronic endocrine stress and inflammation in adolescent boys, not in girls. This study may contribute to a better understanding of the early pathophysiological changes that may underlie adverse health effects of air pollution exposure in adolescents. ; Government of Flanders, Department of Environment & Spatial Development; PhD fellowship at the University of Antwerp; VITO - Flemish Center of Expertise on Environment and Health

Chronic biological stress may adversely affect adolescents' physical and mental health, but insight in the personal and environmental factors that determine chronic stress is limited. We measured 3-month cumulative hair cortisol concentration (HCC) in 419 adolescents, participating in the Flemish Environment and Health Study. Adolescents' health and lifestyle characteristics, household and neighborhood socio-economic status as well as neighborhood urbanicity were assessed as potential determinants of HCC, using multiple linear regression models. We additionally explored heterogeneity of our results by sex. HCC were significantly higher in boys from densely populated neighborhoods, the association was not significant in girls. Accordingly, boys living outside cities had significantly lower HCC than boys, living in cities. HCC was significantly lower in adolescents with an optimal vitality, a measure of a positive mental health status. In adolescent girls, menarcheal status (pre-/postmenarche) was a significant determinant of HCC. Our findings are the first to suggest that residential urbanicity may have an impact on chronic biological stress in a general population of adolescent boys. ; This paper is based on research conducted within the framework of the Flemish Center of Expertise on Environment and Health (FLEHS 2016-2020), funded by the Government of Flanders, Department of Environment & Spatial Development. VV was supported by a PhD fellowship at the University of Antwerp and VITO, funded by the Flemish Center of Expertise on Environment and Health. We thank the adolescents and their families who participated in FLEHS IV. Without their effort, this study would not have been possible. We thank the field workers from the Provincial Institute of Hygiene and VITO for the sample and data collection.

BACKGROUND: the mixed and complex nature of industrially contaminated sites (ICSs) leads to heterogeneity in exposure and health risk of residents living nearby. Health, environment, and social aspects are strongly interconnected in ICSs, and local communities are often concerned about potential health impact and needs for remediation. The use of human biomonitoring (HBM) for impact assessment of environmental exposure is increasing in Europe. The COST Action IS1408 on Industrially Contaminated Sites and Health Network (ICSHNet) decided to reflect on the potential and limitations of HBM to assess exposure and early health effects associated with living near ICSs. OBJECTIVES: to discuss challenges and lessons learned for addressing environmental health impact near ICSs with HBM in order to identify needs and priorities for HBM guidelines in European ICSs. METHODS: based on the experience of the ICSHNet research team, six case studies from different European regions that applied HBM at ICSs were selected. The case studies were systematically compared distinguishing four phases: the preparatory phase; study design; study results; the impact of the results at scientific, societal, and political levels. RESULTS: all six case studies identified opportunities and challenges for applying HBM in ICS studies. A smart choice of (a combination of) sample matrices for biomarker analysis produced information about relevant time-windows of ex posure, which matched with the activities of the ICSs. Combining biomarkers of exposure with biomarkers of (early) biological effects, data from questionnaires or environmental data enabled fine-tuning of the results and allowed for more targeted remediating actions aimed to reduce exposure. Open and transparent communication of study results with contextual information and involvement of local stakehold ers throughout the study helped to build confidence in the study results, gained support for remediating actions, and facilitated sharing of responsibilities. Using HBM in these ICS studies helped in setting priorities in policy actions and in further research. Limitations were the size of the study population, difficulties in recruiting vulnerable target populations, availability of validated biomarkers, and coping with exposure to mixtures of chemicals. CONCLUSIONS: based on the identified positive experiences and challenges, the paper concludes with formulating recommendations for a European protocol and guidance document for HBM in ICS. This could advance the use of HBM in local environmental health policy development and evaluation of exposure levels, and promote coordination and collaboration between researchers and risk managers.

Co-authors: Glória Isidro, Henriqueta Louro, Maria João Silva (INSA) ; The current deliverable describes the process of revision of the first list of indicators (published in June 2017 as D6.1.) and presents the indicator leaflets ((see attachment 1) that link key results of HBM4EU to the objectives of the project as laid down in the description of action. These indicator leaflets already contain a lot of results on the revised list of indicators, and give very valuable information on the progress of HBM4EU in relation to the specific goals of the project. Combining the information from these leaflets in the frame of expected impacts will allow us to put forward conclusions towards impact and sustainability of HBM4EU. As such, this restructured list answers to the main comments on the first list of indicators from the task 6.5 partners, the Management Board, the Governing Board and the EU Policy Board, in concretu to: • Drastically reduce the number of indicators from 48 indicators (including 9 internal indicators) on the first list to 28 indicators on the revised list without losing essential information. Moreover by bundling related indicators we now have 22 indicator leaflets (and 1 overview leaflet); • Make the relationship between the indicators and the goals of HBM4EU more clear by structuring the list of indicators according to the overarching objectives and specific goals; • Use the indicators to say something about the impact of the HBM4EU project: the indicator leaflets were used to give input for the impact section of the periodic technical reporting 2018 to describe the progress made for the 5 expected impacts of HBM4EU. This exercise will be continued and ameliorated in the 2019 periodic technical reporting as more indicator leaflets will be available compared to 2018; • Link the indicators with the work on sustainability of HBM in Europe: the indicators were presented at the sustainability workshop in Paris. Participants indicated that they think the leaflets will be useful for institutional discussions, national hub meetings, meetings with policy makers and other meetings and that they would like to use them as soon as they are available. The added value of having indicators of success, is to monitor the implementation and achieved impact of HBM4EU. This will allow for a more efficient tracking of achieved goals. This deliverable will help to further optimize and revise the first set of indicators to monitor the implementation of the HBM4EU and the achieved impact. The indicators of success are written in a clear language, they are concise and capture the main achievements in the list of indicators that has been agreed amongst the partners. Therefore, they can be easily used by all partners across the consortium, the EU Policy Board and our HBM4EU ambassador Thomas Jackl. ; HORIZON2020 Programme Contract No. 733032 HBM4EU ; info:eu-repo/semantics/publishedVersion