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Studies characterizing associations between phenols, phthalates and thyroid hormones during pregnancy produce inconsistent results. This divergence may be partly attributable to false positives due to multiple comparison testing of large numbers of chemicals, and measurement error as studies rely on small numbers of biospecimens despite high intra-individual variability in urinary chemical metabolite concentrations.This study employsA two-tiered approach was implemented:The ToxCast/Tox21 screening reduced the chemical set from 16 to 13 and the associated number of statistical comparisons by 19%. Parabens were negatively associated with free triiodothyronine (T3) and the T3/T4 (total thyroxine) ratio. Monobenzyl phthalate was positively associated with total T4 and negatively with the T3/T4 ratio. Effect modification by iodine status was detected for several compounds (among themFor these chemicals, screening for compounds with an increased likelihood for thyroid-related effects and relying on repeated urine samples to assess exposures improved the overall performance of multichemical analyses of thyroid disruption. This approach may improve future evaluations of human data for the thyroid pathway with implication for fetal health and may serve as a model for evaluating other toxicity outcomes. https://doi.org/10.1289/EHP10239.

International audience; Background and objectives: Studies focusing on the neurodevelopmental effects of phthalates seldom consider exposure during infancy, a critical period for brain development. Most rely on parent-completed questionnaires to assess child neurodevelopment, which may be subject to reporting error. We studied the associations between prenatal and infancy exposure to phthalates and objective measures of neurodevelopment at the age of two. Methods: We relied on 151 mother-child pairs from the SEPAGES mother-child cohort. Women were asked to collect three spot urine samples per day over seven consecutive days during the second (median: 18.0 gestational weeks) and third (median: 34.2 gestational weeks) trimesters of pregnancy. They then collected one urine sample per day over seven consecutive days from their infants around the age of 12 months. Metabolites of phthalates and non-phthalate plasticizers were measured in within-subject and within-period pools of repeated urine samples. Eye tracking tasks were performed at two years allowing to compute four indicators linked with cognitive development and visual behavior: mean fixation duration, novelty preference, percent time spent looking at the eyes and mean reaction time. Results: Pre-natal exposure to monobenzyl phthalate at the second and third trimesters was associated with shorter fixation durations. In models allowing for interaction with child sex, these associations were only observed among girls. Exposure to di(2-ethylhexyl) phthalate at the third but not the second trimester was associated with increased time spent looking at a novel face and eyes. We observed faster reaction times and decreased time spent looking at the eyes in a face recognition task, with increased post-natal exposure to monoethyl, mono-iso-butyl and mono-n-butyl phthalates. Discussion: Relying on improved exposure assessment, we highlighted associations of pre-and post-natal exposure to phthalates with indicators derived from eye tracking tasks, mainly in girls. Some of these indicators have been affected in individuals with neurodevelopmental disorders.

Contact tracing is an evidence-based intervention to control many communicable diseases, including COVID-19. Before the COVID-19 pandemic, contact tracing in Michigan focused on HIV, sexually transmitted infections, and tuberculosis, and it was conducted by state and local health department staff. Within 2 weeks of the first reported COVID-19 cases in Michigan in March 2020, the existing public health workforce was overwhelmed by the need for contact tracing and daily symptom monitoring. This case study narrates the development of a staffing plan that included volunteers and contractual staff to conduct centralized contact tracing in a home-rule state (ie, a state in which local health departments have full authority and autonomy under public health code to conduct the functions necessary to prevent disease, including contact tracing). This case study details various training, workforce management, and technology tools that were used. During the study period (May 2020–June 2021), contact tracers called 432 218 contacts and 269 439 were successfully reached, 48 134 of whom reported developing symptoms. The most important lesson learned was the need for more automated processes to improve efficiency in processing volunteer applicants, training, and scheduling. Nonetheless, the centralized workforce was successful, was flexible, and met the changing demands in Michigan.

Recent glaciations in northwestern Russia completely covered the Barents Sea during four glacial advances. At the peaks of those glacial advances, there were no nearshore macrofauna. Consequently, colonization by species that now inhabit present-day nearshore waters must have occurred since the habitat became available and hospitable, less than 15 ka. We analyzed microsatellite data from Eleginus nawaga (Gadiformes: Gadidae) collected from Khaipudyrskaya Bay in the southeastern Barents Sea with coalescent-based models to estimate the times and effective population sizes that existed before and after major historical demographic changes. Colonization of E. nawaga, which could only follow establishment of a lower trophic-level food web, provides an indicator of the for that timing. The results of the analyses were consistent with two major demographic events. After an initial founding event from a small number of individuals before ~ 140 ka, the population grew to an effective size of about 2700 individuals. Subsequently, probably as the ice receded after the Last Glacial Maximum, it plateaued at ~ 26,000 about 3000 years ago. Colonization likely came from eastern populations following the Saalian Period, after which there was little nearshore ice to the East of the Kara Sea.

This article examines how respondents understood items in the Spanish versions of the Short-Form 36 (SF-36v2). Cognitive interviews of the SF-36 were conducted in 2 phases with 46 Spanish speakers living in the United States. Roughly one-third (17/46) of respondents had difficulty understanding the Role Emotional items upon their initial reading, and almost half (21/46) provided examples that were inconsistent with the intended meaning of the items. The findings of this study underscore the importance of conducting cognitive testing to ensure conceptual equivalence of any instrument regardless of how well validated it appears to be.

ImportanceLittle is known about long-term associations of early-life exposure to extreme temperatures with child health and lung function.ObjectivesTo investigate the association of prenatal and postnatal heat or cold exposure with newborn lung function and identify windows of susceptibility.Design, Setting, and ParticipantsThis population-based cohort study (SEPAGES) recruited pregnant women in France between July 8, 2014, and July 24, 2017. Data on temperature exposure, lung function, and covariates were available from 343 mother-child dyads. Data analysis was performed from January 1, 2021, to December 31, 2021.ExposuresMean, SD, minimum, and maximum temperatures at the mother-child’s residence, estimated using a state-of-the-art spatiotemporally resolved model.Main Outcomes and MeasuresOutcome measures were tidal breathing analysis and nitrogen multiple-breath washout test measured at 2 months of age. Adjusted associations between both long-term (35 gestational weeks and first 4 weeks after delivery) and short-term (7 days before lung function test) exposure to ambient temperature and newborn lung function were analyzed using distributed lag nonlinear models.ResultsA total of 343 mother-child pairs were included in the analyses (median [IQR] maternal age at conception, 32 [30.0-35.2] years; 183 [53%] male newborns). A total of 246 mothers and/or fathers (72%) held at least a master’s degree. Among the 160 female newborns (47%), long-term heat exposure (95th vs 50th percentile of mean temperature) was associated with decreased functional residual capacity (−39.7 mL; 95% CI, −68.6 to −10.7 mL for 24 °C vs 12 °C at gestational weeks 20-35 and weeks 0-4 after delivery) and increased respiratory rate (28.0/min; 95% CI, 4.2-51.9/min for 24 °C vs 12 °C at gestational weeks 14-35 and weeks 0-1 after delivery). Long-term cold exposure (5th vs 50th percentile of mean temperature) was associated with lower functional residual capacity (−21.9 mL; 95% CI, −42.4 to −1.3 mL for 1 °C vs 12 °C at gestational weeks 15-29), lower tidal volume (−23.8 mL; 95% CI, −43.1 to −4.4 mL for 1 °C vs 12 °C at gestational weeks 14-35 and weeks 0-4 after delivery), and increased respiratory rate (45.5/min; 95% CI, 10.1-81.0/min for 1 °C vs 12 °C at gestational weeks 6-35 and weeks 0-1 after delivery) in female newborns as well. No consistent association was observed for male newborns or short-term exposure to cold or heat.Conclusions and RelevanceIn this cohort study, long-term heat and cold exposure from the second trimester until 4 weeks after birth was associated with newborn lung volumes, especially among female newborns.

Background Ambient temperature, particularly heat, is increasingly acknowledged as a trigger for preterm delivery but study designs have been limited and results mixed. We aimed to comprehensively evaluate the association between ambient temperature throughout pregnancy and preterm delivery. Methods We estimated daily temperature throughout pregnancy using a cutting-edge spatiotemporal model for 5347 live singleton births from three prospective cohorts in France, 2002–2018. We performed Cox regression (survival analysis) with distributed lags to evaluate time-varying associations with preterm birth simultaneously controlling for exposure during the first 26 weeks and last 30 days of pregnancy. We examined weekly mean, daytime, night-time and variability of temperature, and heatwaves accounting for adaptation to location and season. Results Preterm birth risk was higher following cold (5th vs 50th percentile of mean temperature) 7–9 weeks after conception [relative risk (RR): 1.3, 95% CI: 1.0–1.6 for 2°C vs 11.6°C] and 10–4 days before delivery (RR: 1.6, 95% CI: 1.1–2.1 for 1.2°C vs 12.1°C). Night-time heat (95th vs 50th percentile of minimum temperature; 15.7°C vs 7.4°C) increased risk when exposure occurred within 5 weeks of conception (RR: 2.0, 95% CI: 1.05–3.8) or 20–26 weeks after conception (RR: 2.9, 95% CI: 1.2–6.8). Overall and daytime heat (high mean and maximum temperature) showed consistent effects. We found no clear associations with temperature variability or heatwave indicators, suggesting they may be less relevant for preterm birth. Conclusions In a temperate climate, night-time heat and chronic and acute cold exposures were associated with increased risk of preterm birth. These results suggest night-time heat as a relevant indicator. In the context of rising temperatures and more frequent weather hazards, these results should inform public health policies to reduce the growing burden of preterm births.

The first cluster of SARS-CoV-2 cases with lineage B.1.1.7 in the state of Michigan was identified through intensive university-led surveillance sampling and targeted sequencing. A collaborative investigation and response was conducted by the local and state health departments, and the campus and athletic medicine COVID-19 response teams, using S-gene target failure screening and rapid genomic sequencing to inform containment strategies. A total of 50 cases of B.1.1.7-lineage SARS-CoV-2 were identified in this outbreak, which was due to three coincident introductions of B.1.1.7-lineage SARS-CoV-2, all of which were genetically distinct from lineages which later circulated in the broader community. This investigation demonstrates the successful implementation of a genomically-informed outbreak response which can be extended to university campuses and other settings at high risk for rapid emergence of new variants.

For non-persistent chemicals such as phthalates, a single spot urine sample only reflects exposure in the past few hours. Collecting repeated urine samples for each participant over windows of sensitivity is expected to improve exposure characterization but has rarely been done. We aimed to rely on within-subject pools of repeated urine samples to assess phthalate exposure during pregnancy and infancy. Women of the French SEPAGES mother-child cohort were asked to collect three urine samples per day over seven consecutive days, twice during their pregnancy (approximatively second (T2) and third (T3) trimesters). For their infants they also collected one sample per day during a week at two (M2) and twelve months (M12). Samples were pooled (within-subject, within-period) prior to phthalate and DINCH metabolite concentrations assessment. Number of pooled samples assayed was 477, 456, 152 and 100 for T2, T3, M2 and M12, respectively. All metabolites were detected in more than 95% of the pooled samples except for the two DINCH metabolites (oh- and oxo-MINCH), MMCHP and oh-MPHP at M2 for which detection frequencies ranged between 64% and 88%. Maternal concentrations of MiBP, MBzP, DEHP metabolites and oxo-MiNP decreased between 2014 and 2017, whereas concentrations of oh-MiNP and the two DINCH metabolites increased (Mann-Kendall p-values, Graphical abstract Image 1, Highlights • Repeated urine samples were collected and pooled within-subject, within period. • Metabolites of phthalates and DINCH were measured in pooled samples. • Frequencies of detection were overall high. • Pregnancy concentrations of MiBP, MBzP, DEHP and oxo-MINP decreased with time. • Pregnancy concentrations of oh-MiNP and DINCH metabolites increased with time., Relying on a recent cohort (2014–2017) with repeated urine samples collected during pregnancy and infancy, we showed that exposure to phthalates and DINCH is still widespread in the general population.

OBJECTIVE Patients with type 2 diabetes are encouraged to lose weight, but excessive weight loss in older adults may be a marker of poor health and subsequent mortality. We examined weight change during the postintervention period of Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) with diabetes support and education (DSE) (control) in overweight/obese individuals with type 2 diabetes and sought to identify predictors of excessive postintervention weight loss and its association with mortality. RESEARCH DESIGN AND METHODS These secondary analyses compared postintervention weight change (year 8 to final visit; median 16 years) in ILI and DSE in 3,999 Look AHEAD participants. Using empirically derived trajectory categories, we compared four subgroups: weight gainers (n = 307), weight stable (n = 1,561), steady losers (n = 1,731), and steep losers (n = 380), on postintervention mortality, demographic variables, and health status at randomization and year 8. RESULTS Postintervention weight change averaged −3.7 ± 9.5%, with greater weight loss in the DSE than the ILI group. The steep weight loss trajectory subgroup lost on average 17.7 ± 6.6%; 30% of steep losers died during postintervention follow-up versus 10–18% in other trajectories (P < 0001). The following variables distinguished steep losers from weight stable: baseline, older, longer diabetes duration, higher BMI, and greater multimorbidity; intervention, randomization to control group and less weight loss in years 1–8; and year 8, higher prevalence of frailty, multimorbidity, and depressive symptoms and lower use of weight control strategies. CONCLUSIONS Steep weight loss postintervention was associated with increased risk of mortality. Older individuals with longer duration of diabetes and multimorbidity should be monitored for excessive unintentional weight loss.

International audience; Background: Within-subject biospecimens pooling can theoretically reduce bias in dose-response functions from biomarker-based studies when exposure assessment suffers from classical-type error. However, collecting many urine voids each day is cumbersome. We evaluated the empirical validity of a within-subject pooling approach and compared several options to avoid sampling each void.Methods: In 16 pregnant women who collected a spot of each urine void over several nonconsecutive weeks, we compared concentrations of 10 phenols in daily, weekly, and pregnancy within-subject pools. We pooled either three or all daily samples. In a simulation study using these data, we quantified bias in dose-response functions when using one to 20 urine samples per subject to assess methylparaben (a compound with moderate within-subject variability) and bisphenol A (high variability) exposures.Results: Correlations between exposure estimates from pools of all and of only three voids per day were above 0.80 for all time windows and compounds, except for benzophenone-3 and triclosan in the daily time window (correlations, 0.57-0.68). With one spot sample to assess pregnancy exposure, correlations were all below 0.74. Using only one biospecimen led to attenuation bias in the dose-response functions of 29% (methylparaben) and 69% (bisphenol A); four samples for methylparaben and 18 for bisphenol A decreased bias to 10%.Conclusions: For nonpersistent chemicals, collecting and pooling three samples per day instead of all daily samples efficiently estimates exposures over a week or more. Collecting around 20 biospecimens can strongly limit attenuation bias for nonpersistent chemicals such as bisphenol A.

The human exposome affects child development and health later in life, but its personal external levels, variability, and correlations are largely unknown. We characterized the personal external exposome of pregnant women and children in eight European cities. Panel studies included 167 pregnant women and 183 children (aged 6-11 years). A personal exposure monitoring kit composed of smartphone, accelerometer, ultraviolet (UV) dosimeter, and two air pollution monitors were used to monitor physical activity (PA), fine particulate matter (PM2.5), black carbon, traffic-related noise, UV-B radiation, and natural outdoor environments (NOE). 77% of women performed the adult recommendation of >= 150 min/week of moderate to vigorous PA (MVPA), while only 3% of children achieved the childhood recommendation of >= 60 min/day MVPA. 11% of women and 17% of children were exposed to daily PM2.5 levels higher than recommended >= 25 mu g/m(3)). Mean exposure to noise ranged from Lden 51.1 dB in Kaunas to Lden 65.2 dB in Barcelona. 4% of women and 23% of children exceeded the recommended maximum of 2 Standard-Erythemal-Dose of UV-B at least once a week. 33% of women and 43% of children never reached the minimum NOE contact recommendation of >= 30 min/week. The variations in air and noise pollution exposure were dominated by between-city variability, while most of the variation observed for NOE contact and PA was between-participants. The correlations between all personal exposures ranged from very low to low (Rho

Early life stages are vulnerable to environmental hazards and present important windows of opportunity for lifelong disease prevention. This makes early life a relevant starting point for exposome studies. The Advancing Tools for Human Early Lifecourse Exposome Research and Translation (ATHLETE) project aims to develop a toolbox of exposome tools and a Europe-wide exposome cohort that will be used to systematically quantify the effects of a wide range of community- and individual-level environmental risk factors on mental, cardiometabolic, and respiratory health outcomes and associated biological pathways, longitudinally from early pregnancy through to adolescence. Exposome tool and data development include as follows: (1) a findable, accessible, interoperable, reusable (FAIR) data infrastructure for early life exposome cohort data, including 16 prospective birth cohorts in 11 European countries; (2) targeted and nontargeted approaches to measure a wide range of environmental exposures (urban, chemical, physical, behavioral, social); (3) advanced statistical and toxicological strategies to analyze complex multidimensional exposome data; (4) estimation of associations between the exposome and early organ development, health trajectories, and biological (metagenomic, metabolomic, epigenetic, aging, and stress) pathways; (5) intervention strategies to improve early life urban and chemical exposomes, co-produced with local communities; and (6) child health impacts and associated costs related to the exposome. Data, tools, and results will be assembled in an openly accessible toolbox, which will provide great opportunities for researchers, policymakers, and other stakeholders, beyond the duration of the project. ATHLETE's results will help to better understand and prevent health damage from environmental exposures and their mixtures from the earliest parts of the life course onward. ISGlobal acknowledges support from the Spanish Ministry of Science, Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S) and support from the Generalitat de Catalunya through the Centres de Recerca de Catalunya Program. We acknowledge collaboration with European projects, specifically: Human Early Life Exposome (HELIX) (FP7 grant agreement number 308333), LifeCycle (H2020 grant agreement number 733206), and Connecting Europe and Canada in personalized health (EUCAN-Connect) (H2020 Grant Agreement number 824989). The Born in Bradford (BiB) cohort is only possible because of the enthusiasm and commitment of the Children and Parents in BiB. We are grateful to all the participants, health professionals, and researchers who have made BiB happen. The BiB cohort is only possible because of the enthusiasm and commitment of the children and parents in BiB. We are grateful to all the participants, health professionals, schools, and researchers who have made BiB happen. BiB has received funding from the Wellcome Trust (101597), a joint grant from the UK Medical Research Council and UK Economic and Social Science Research Council (MR/N024391/1), a British Heart Foundation Clinical Study grant (CS/16/4/32482). The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. We are grateful to all the participating families in Norway who take part in this ongoing cohort study. The Danish National Birth Cohort was established with a significant grant from the Danish National Research Foundation. Additional support was obtained from the Danish Regional Committees, the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Health Foundation, and other minor grants. The Danish National Birth Cohort Biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation. Follow-up of mothers and children have been supported by the Danish Medical Research Council (SSVF 0646, 271-08-0839/06-066023, O602-01042B, 0602-02738B); the Lundbeck Foundation (195/04, R100-A9193); The Innovation Fund Denmark 0603-00294B (09-067124); the Nordea Foundation (02-2013-2014); Aarhus Ideas (AU R9-A959-13-S804); University of Copenhagen Strategic Grant (IFSV 2012); and the Danish Council for Independent Research (DFF—4183-00594 and DFF—4183-00152). The general design of the Generation R Study is made possible by financial support from the Erasmus MC, University Medical Center, Rotterdam, Erasmus University Rotterdam, Netherlands Organization for Health Research and Development (ZonMw), Netherlands Organisation for Scientific Research (NWO), Ministry of Health, Welfare and Sport, and Ministry of Youth and Families. This project received funding from the European Union’s Horizon 2020 research and innovation programme (LIFECYCLE, grant agreement number 733206, 2016; EUCAN-Connect grant agreement number 824989; ATHLETE, grant agreement number 874583). We gratefully acknowledge the contribution of participants, research collaborators, general practitioners, hospitals, midwives, and pharmacies in Rotterdam. The INfancia y Medio Ambiente cohort (INMA) Sababell study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. Fondo Europeo de Desarollo Regional (FEDER) funds; PI12/01890 incl. FEDER funds; CP13/00054 incl. FEDER funds; PI15/00118 incl. FEDER funds; CP16/00128 incl. FEDER funds; PI16/00118 incl. FEDER funds; PI16/00261 incl. FEDER funds; PI17/01340 incl. FEDER funds, PI18/00547 incl. FEDER funds, PI20/01695 incl. FEDER funds), Centro de Investigación Biomédica en Red - Epidemiología y Salud Pública (CIBERESP), Generalitat de Catalunya-Comissió Interdepartamental de Recerca i Innovació Tecnològia 1999SGR 00241, Generalitat de Catalunya-Agencia de Gestión de Ayudas Universitarias y de Investigación (2009 SGR 501, 2014 SGR 822), Fundació La Marató de TV3 (090430), Spanish Ministry of Economy and Competitiveness (SAF2012-32991 incl. FEDER funds), Agence Nationale de Securite Sanitaire de l’Alimentation de l’Environnement et du Travail (1262C0010; EST-2016 RF-21, EST-19 RF-04), and the European Commission (261357, 308333, 603794 and 634453). The INMA Valencia study was supported by grants from Instituto de Salud Carlos III (FIS-FEDER: 13/2032, 13/1944, 14/00891, 16/1288, 17/00663, and 19/1338; Miguel Servet-FSE: CP15/0025 and MSII16/00051, 00051, and MSII20/0006), Alicia Koplowitz Foundation 2017, Generalitat Valenciana (AICO/2020/285), and Spanish Association Against Cancer (AECC) “Seed Ideas” 2019 (IDEAS19098LOPE). INMA Gipuzkoa was funded by grants from Instituto de Salud Carlos III (FIS-PI06/0867, FIS-PI09/00090, FIS-PI13/02187, and FIS-PI18/01142 incl. FEDER funds), CIBERESP, Department of Health of the Basque Government (2005111093, 2009111069, 2013111089, and 2015111065), and the Provincial Government of Gipuzkoa (DFG06/002, DFG08/001, and DFG15/221) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). The Sepages cohort would like to thank the Grenoble University Hospital (CHU-GA) biobank (bb-0033-00069). We thank the Sepages Study group (E. Eyriey, P. Hoffmann, E. Hullo, J. Lepeule, C. Llerena, S. Lyon-Caen, X. Morin, A. Morlot, C. Philippat, I. Pin, J. Quentin, V. Siroux, R. Slama) and the participants of the Suivi de l’Exposition à la Pollution Atmosphérique durant la Grossesse et Effets sur la Santé (SEPAGES) study. We acknowledge support from Auvergne-Rhône-Alpes Région, Soutien aux coopérations universitaires et scientifiques internationales fund to support collaborations between Catalunya and Auvergne-Rhône-Alpes. SEPAGES cohort was supported by the European Research Council (consolidator grant N 311765-E-DOHaD, Principal Investigator [PI], R. Slama), by French National Research Agency (ANR), the ANR (Pregnancy, Air Pollution, Epigenetics and Respiratory health project ANR-12-PDOC-0029-01, PI, J. Lepeule; A Longitudinal Analysis of Effects of Early Life Exposure to Phenols on Health in Humans project, 14-CE21-0007-01, PI, R. Slama; Gut Microbiota in early childhood and Maternal Environmental exposures project, PI, R. Slama; Prenatal Exposure to Tobacco smoking and Air Pollution and Effects on offspring respiratory and neurodevelopmental outcomes ANR 18-CE36-005, PI, J. Lepeule). The Central European Longitudinal Study of Pregnacy and Childhood: The Next Generation (TNG) cohort is supported by the RECETOX research infrastructure (the Ministry of Education, Youth and Sports of the Czech Republic: LM2018121) and the CETOCOEN EXCELLENCE Teaming 2 project of European Union (EU) Horizon 2020 (857560) and the MEYS of the Czech Republic (02.1.01/0.0/0.0/18_ 046/0015975). The Barcelona Life Study Cohort has received funding from European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme under grant agreement number (785994) (Prenatal exposure to urban air pollution and pre and post-natal brain development project) and from the Health Effects Institute (HEI) under Agreement number 4959-RFPA15-1/18-1 (FRONTIER project). Genotyping in the HELIX study was supported by project PI17/01225 (Instituto de Salud Carlos III, co-funded by European Union [European Regional Development Fund], “A way to make Europe”) and the Centro Nacional de Genotipado-CEGEN (PRB2-ISCIII). The Nascita e Infanzia: gli Effetti dell’Ambiente cohort was partially funded by the Compagnia SanPaolo Foundation and the Piedmont Region. The Piccolipiù project was funded by the Italian National Center for Disease Prevention and Control (National Centre for Disease Prevention and Control grants years 2010 and 2014) and by the Italian Ministry of Health (art 12 and 12 bis D.lgs 502/92). The Perturbateurs Endocriniens: Étude Longitudinale sur les Anomalies de la Grossesse, l’Infertilité et l’Enfance study is supported by National Institute of Health and Medical Research and has received multiple funds from the ANR, the French Agency for Food, Environmental and Occupational Health and Safety (ANSES), the Fondation de France, the National Institute for Public Health Surveillance (InVS), the French, Ministry of Labor, the French Ministry of Health, and the French Ministry of Ecology. DataSHIELD is funded under a group of projects that underpin a program of development and application of secure methods for co-analysis, data sharing, and visualization in the Population Health Sciences Institute at Newcastle University (United Kingdom). These include: the “Connected Health Cities project” (North East and North Cumbria) funded by the UK Department of Health (RES/0150/7943/202); the “EUCanConnect project” (European Commission H2020 Flagship Collaboration with Canada); the “58FORWARDS project” (Fostering new Opportunities for Researchers via Wider Access to Research Data and Samples) funded jointly by the Wellcome Trust and the Medical Research Council (108439/Z/15/Z); and the “METADAC project” (Managing Ethico-social, Technical and Administrative issues in Data ACcess) funded jointly by the Medical Research Council, the Wellcome Trust, and the Economic and Social Research Council (MR/N01104X/1 and MR/N01104X/2). We acknowledge the Molecular Genetics Information System team, including Fleur Kelpin, Tommy de Boer, Mariska Slofstra, Connor Stroomberg, Jelmer Veen, Jeroen van Veen, Fernanda de Andrade, Marije van der Geest, Dieuwke Roelofs-Prins, Dennis Hendriksen, Bart Charbon, Joeri van der Velde, Max Postema, Erik Schaberg, Christiaan Hilbrands, Alexander Kellmann, and Luuk Dijkhuis.

Purpose The emerging literature on computer-mediated communication at the study lacks depth in terms of elucidating the consequences of the effects of incivility on employees. This study aims to compare face-to-face incivility with incivility encountered via e-mail on both task performance and performance evaluation. Design/methodology/approach In two experimental studies, the authors test whether exposure to incivility via e-mail reduces individual task performance beyond that of face-to-face incivility and weather exposure to that incivility results in lower performance evaluations for third-parties. Findings The authors show that being exposed to cyber incivility does decrease performance on a subsequent task. The authors also find that exposure to rudeness, both face-to-face and via e-mail, is contagious and results in lower performance evaluation scores for an uninvolved third party. Originality/value This research comprises an empirically grounded study of incivility in the context of e-mail at study, highlights distinctions between it and face-to-face rudeness and reveals the potential risks that cyber incivility poses for employees.

Workforce shortages and market shifts have left many small and medium manufacturers (SMMs) struggling to maintain their operations. Still some SMMs tend not to utilize the workforce development and technical assistance resources available to them. This is particularly true of those in more rural regions where manufacturing is even more essential to the sustained vitality of these economies. This study explores the factors preventing these firms from pursuing and accessing these services. The authors used surveys and interviews to engage manufacturers with fewer than 500 employees in rural Southwestern Virginia and identify factors limiting their participation in these services. Findings indicate constant and consistent outreach to SMMs, regular engagement in social and economic networks, and a diverse array of services tailored to rural SMMs’ needs to play key roles in developing productive partnerships between SMMs and resource providers.

Background Although atopic dermatitis (AD) often starts in early childhood, detailed tissue profiling of early-onset AD in children is lacking, hindering therapeutic development for this patient population with a particularly high unmet need for better treatments. Objective We sought to globally profile the skin of infants with AD compared with that of adults with AD and healthy control subjects. Methods We performed microarray, RT-PCR, and fluorescence microscopy studies in infants and young children ( Results Transcriptomic analyses revealed profound differences between pediatric patients with early-onset versus adult patients with longstanding AD in not only lesional but also nonlesional tissues. Although both patient populations harbored TH2-centered inflammation, pediatric AD also showed significant TH17/TH22 skewing but lacked the TH1 upregulation that characterizes adult AD. Pediatric AD exhibited relatively normal expression of epidermal differentiation and cornification products, which is downregulated in adults with AD. Defects in the lipid barrier (eg, ELOVL fatty acid elongase 3 [ELOVL3] and diacylglycerol o-acyltransferase 2 [DGAT2]) and tight junction regulation (eg, claudins 8 and 23) were evident in both groups. However, some lipid-associated mediators (eg, fatty acyl-CoA reductase 2 and fatty acid 2-hydroxylase) showed preferential downregulation in pediatric AD, and lipid barrier genes (FA2H and DGAT2) showed inverse correlations with transepidermal water loss, a functional measure of the epidermal barrier. Conclusions Skin samples from children and adult patients with AD share lipid metabolism and tight junction alterations, but epidermal differentiation complex defects are only present in adult AD, potentially resulting from chronic immune aberration that is not yet present in early-onset disease.

BACKGROUND: Exposure to certain synthetic phenols is of growing concern, in particular among pregnant women, because of their endocrine disrupting nature. Many phenols are still authorized in personal care products (PCP). We aimed to assess if use of PCPs, by pregnant women could influence their urinary concentrations of synthetic phenols. METHODS: We used a panel design with intense urine sample collection. Eight women completed a diary with exact time and use of PCP in three weeks. We measured the concentrations of phenols (four parabens, bisphenol A and S, two dichlorophenols, triclosan, and benzophenone-3) in 178 urine samples, collected during 7 consecutive days at 3 time points during pregnancy. We characterized PCP use as the total number of PCP applications or as a single PCP use (yes / no) in three time windows (0 to 6, 6 to 12 and 12 to 24 before each urine sample collection). We used adjusted linear and Tobit regressions to assess associations between PCP use and phenol urinary concentrations. RESULTS: The total number of PCP applications was positively associated with ethylparaben, propylparaben and butylparaben concentrations. We observed a peak in urinary concentration of ethylparaben, butylparaben and propylparaben at 2.86, 2.55 and 2.67 hours since last PCP use, respectively and twelve different types of PCPs were positively associated with at least one of these parabens. The bisphenol S concentration increased by 12.4% (95%CI: confidence interval: 5.9; 19.3) for each additional PCP application in the 12 to 24 time window and use of specific PCPs such as anti-stretchmarks cream, facial cleanser and shower gel. Associations varied by time window. CONCLUSION: Our study showed that PCP use was associated with a short-term increase in the urinary concentration of ethylparaben, butylparaben and propylparaben, but not methylparaben. This study also reported a positive association between the use of PCPs and the bisphenol S concentration, a finding that warrants further investigation in cohorts with repeated collection of urine samples and detailed information on PCP use.

Background Atopic dermatitis (AD) affects 15% to 25% of children and 4% to 7% of adults. Paradigm-shifting discoveries about AD have been based on adult biomarkers, reflecting decades of disease activity, although 85% of cases begin by 5 years. Blood phenotyping shows only T H 2 skewing in patients with early-onset pediatric AD, but alterations in early pediatric skin lesions are unknown, limiting advancement of targeted therapies. Objective We sought to characterize the early pediatric AD skin phenotype and its differences from pediatric control subjects and adults with AD. Methods Using immunohistochemistry and quantitative real-time PCR, we assessed biopsy specimens from 19 children with AD younger than 5 years within 6 months of disease onset in comparison with adults with AD or psoriasis and pediatric and adult control subjects. Results In lesional skin children showed comparable or greater epidermal hyperplasia (thickness and keratin 16) and cellular infiltration (CD3 + , CD11c + , and FceRI + ) than adults with AD. Similar to adults, strong activation of the T H 2 (IL-13, IL-31, and CCL17) and T H 22 (IL-22 and S100As) axes and some T H 1 skewing (IFN-γ and CXCL10) were present. Children showed significantly higher induction of T H 17-related cytokines and antimicrobials (IL-17A, IL-19, CCL20, LL37, and peptidase inhibitor 3/elafin), T H 9/IL-9, IL-33, and innate markers (IL-8) than adults ( P P Conclusion The skin phenotype of new-onset pediatric AD is substantially different from that of adult AD. Although excess T H 2 activation characterizes both, T H 9 and T H 17 are highly activated at disease initiation. Increases in IL-19 levels might link T H 2 and T H 17 activation.

Background— Interhospital transfer of acute stroke patients is becoming increasingly important as regional stroke systems of care continue to evolve. We describe the characteristics and outcomes of stroke cases transferred to hospitals participating in the Michigan Coverdell Stroke Registry. Methods and Results— Thirty-six hospitals participated in the Michigan registry during 2009 to 2011. Transfer patients were transferred from another hospital either acutely or after admission. Multivariable logistic regression was used to determine predictors of transfer and the independent association between transfer and in-hospital mortality and complications. Of 16 202 acute stroke admissions, 19.1% were transferred. Independent predictors of being transferred included younger age, hemorrhagic stroke, and higher stroke severity, but having a past history of stroke decreased the likelihood of being transferred. Transferred cases had higher in-hospital mortality (12.0% versus 6.4%; P P Conclusions— Transferred patients represent a complex admixture of patient characteristics that result in higher risks of poor outcomes. Our results suggest that it is prudent to account for patient transfer status when comparing hospital outcomes and that stroke registries need to expand their data collection capacity to provide a better understanding of the relative benefits and risks of transferring patients.

In humans, studies based on Developmental Origins of Health and Disease (DOHaD) concept and targeting short half-lived chemicals, including many endocrine disruptors, generally assessed exposures from spot biospecimens. Effects of early-life exposure to atmospheric pollutants were reported, based on outdoor air pollution levels. For both exposure families, exposure misclassification is expected from these designs: for non-persistent chemicals, because a spot biospecimen is unlikely to capture exposure over windows longer than a few days; for air pollutants, because indoor levels are ignored. We developed a couple-child cohort relying on deep phenotyping and extended personal exposure assessment aiming to better characterize the effects of components of the exposome, including air pollutants and non-persistent endocrine disruptors, on child health and development. Pregnant women were included in SEPAGES couple-child cohort (Grenoble area) from 2014 to 2017. Maternal and children exposure to air pollutants was repeatedly assessed by personal monitors. DNA, RNA, serum, plasma, placenta, cord blood, meconium, child and mother stools, living cells, milk, hair and repeated urine samples were collected. A total of 484 pregnant women were recruited, with excellent compliance to the repeated urine sampling protocol (median, 43 urine samples per woman during pregnancy). The main health outcomes are child respiratory health using early objective measures, growth and neurodevelopment. Compared to former studies, the accuracy of assessment of non-persistent exposures is expected to be strongly improved in this new type of birth cohort tailored for the exposome concept, with deep phenotyping and extended exposure characterization. By targeting weaknesses in exposure assessment of the current approaches of cohorts on effects of early life environmental exposures with strong temporal variations, and relying on a rich biobank to provide insight on the underlying biological pathways whereby exposures affect health, this design is expected to provide deeper understanding of the interplay between the Exposome and child development and health.

Craniosynostosis, a condition in which the cranial sutures prematurely fuse, can lead to elevated intracranial pressure and craniofacial abnormalities in young children. Currently surgical intervention is the only therapeutic option for patients with this condition. Craniosynostosis has been associated with a variety of different gene mutations and chromosome anomalies. Here we describe three cases of partial deletion of chromosome 19p. Two of the cases present with syndromic craniosynostosis while one has metopic ridging. A review of the genes involved in the rearrangements between the three cases suggests several gene candidates for craniosynostosis. CALR and DAND5, BMP regulators involved in osteoblast differentiation, and MORG1, a mediator of osteoclast dysregulation may play a role in abnormal cranial vault development. Additionally, CACNA1A, a gene that when mutated is associated with epilepsy and CC2D1A, a gene associated with non-syndromic mental retardation may contribute to additional phenotypic features seen in the patients we describe. In addition, these findings further support the need for genetic testing in cases of syndromic craniosynostosis.

Studies of air pollution effects during pregnancy generally only consider exposure in the outdoor air at the home address. We aimed to compare exposure models differing in their ability to account for the spatial resolution of pollutants, space–time activity and indoor air pollution levels. We recruited 40 pregnant women in the Grenoble urban area, France, who carried a Global Positioning System (GPS) during up to 3 weeks; in a subgroup, indoor measurements of fine particles (PM2.5) were conducted at home (n = 9) and personal exposure to nitrogen dioxide (NO2) was assessed using passive air samplers (n = 10). Outdoor concentrations of NO2, and PM2.5 were estimated from a dispersion model with a fine spatial resolution. Women spent on average 16 h per day at home. Considering only outdoor levels, for estimates at the home address, the correlation between the estimate using the nearest background air monitoring station and the estimate from the dispersion model was high (r = 0.93) for PM2.5 and moderate (r = 0.67) for NO2. The model incorporating clean GPS data was less correlated with the estimate relying on raw GPS data (r = 0.77) than the model ignoring space–time activity (r = 0.93). PM2.5 outdoor levels were not to moderately correlated with estimates from the model incorporating indoor measurements and space–time activity (r = −0.10 to 0.47), while NO2 personal levels were not correlated with outdoor levels (r = −0.42 to 0.03). In this urban area, accounting for space–time activity little influenced exposure estimates; in a subgroup of subjects (n = 9), incorporating indoor pollution levels seemed to strongly modify them. Keywords: Exposure assessment, Air pollutants, Space–time activity, Global Positioning System, Indoor environment, Pregnancy

Objectives. We assessed the burden of systemic lupus erythematosus (SLE) among Arab and Chaldean Americans residing in southeast Michigan. Methods. For those meeting SLE criteria from the Michigan Lupus Epidemiology and Surveillance Registry, we determined Arab or Chaldean ethnicity by links with demographic data from birth certificates and with a database of Arab and Chaldean names. We compared prevalence and incidence of SLE for Arab and Chaldean Americans with estimates for non-Arab and non-Chaldean American Whites and Blacks. Results. We classified 54 individuals with SLE as Arab and Chaldean Americans. The age-adjusted incidence and prevalence estimates for Arab and Chaldean Americans were 7.6 and 62.6 per 100 000, respectively. Arab and Chaldean Americans had a 2.1-fold excess SLE incidence compared with non-Arab and non-Chaldean American Whites. Arab and Chaldean American women had both significantly higher incidence rates (5.0-fold increase) and prevalence estimates (7.4-fold increase) than did Arab and Chaldean American men. Conclusions. Recognizing that Arab and Chaldean Americans experience different disease burdens from Whites is a first step toward earlier diagnosis and designing targeted interventions. Better methods of assigning ethnicity would improve research in this population.

International audience; Background: Toxicology studies have shown adverse effects of developmental exposure to industrial phenols. Evaluation in humans is challenged by potentially marked within-subject variability of phenol biomarkers in pregnant women, which is poorly characterized.Objectives: We aimed to characterize within-day, between-day, and between-week variability of phenol urinary biomarker concentrations during pregnancy.Methods: In eight French pregnant women, we collected all urine voids over a 1-wk period (average, 60 samples per week per woman) at three occasions (15±2, 24±2, and 32±1 gestational weeks) in 2012-2013. Aliquots of each day and of the whole week were pooled within-subject. We assayed concentrations of 10 phenols in these pools, and, for two women, in all spot (unpooled) samples collected during a 1-wk period. We characterized variability using intraclass correlation coefficients (ICCs) with spot samples (within-day variability), daily pools (between-day variability), and weekly pools (between-week variability).Results: For most biomarkers, the within-day variability was high (ICCs between 0.03 and 0.50). The between-day variability, based on samples pooled within each day, was much lower, with ICCs >0.60 except for bisphenol S (0.14, 95% confidence interval [CI]: 0.00, 0.39). The between-week variability differed between compounds, with triclosan and bisphenol S having the lowest ICCs (0.9).Conclusion: During pregnancy, phenol biomarkers showed a strong within-day variability, while the variability between days of a given week was more limited. One biospecimen is not enough to efficiently characterize exposure; collecting biospecimens during a single week may be enough to represent well the whole pregnancy exposure for some but not all phenols. https://doi-org.proxy.insermbiblio.inist.fr/10.1289/EHP1994.

ObjectiveHealthcare workers are highly exposed to various types of disinfectants and cleaning products. Assessment of exposure to these products remains a challenge. We aimed to investigate the feasibility of a method, based on a smartphone application and bar codes, to improve occupational exposure assessment among hospital/cleaning workers in epidemiological studies.MethodsA database of disinfectants and cleaning products used in French hospitals, including their names, bar codes and composition, was developed using several sources: ProdHyBase (a database of disinfectants managed by hospital hygiene experts), and specific regulatory agencies and industrial websites. A smartphone application has been created to scan bar codes of products and fill a short questionnaire. The application was tested in a French hospital. The ease of use and the ability to record information through this new approach were estimated.ResultsThe method was tested in a French hospital (7 units, 14 participants). Through the application, 126 records (one record referred to one product entered by one participant/unit) were registered, majority of which were liquids (55.5%) or sprays (23.8%); 20.6% were used to clean surfaces and 15.9% to clean toilets. Workers used mostly products with alcohol and quaternary ammonium compounds (>90% with weekly use), followed by hypochlorite bleach and hydrogen peroxide (28.6%). For most records, information was available on the name (93.7%) and bar code (77.0%). Information on product compounds was available for all products and recorded in the database.ConclusionThis innovative and easy-to-use method could help to improve the assessment of occupational exposure to disinfectants/cleaning products in epidemiological studies.