Environmental Health Perspectives

IntroductionDrowning risk begins with water exposure, yet population-water relationships have rarely been quantified at scale using environmental measures. This study explored whether satellite-derived data was associated with subnational drowning mortality and whether associations differed by country income level. MethodsWe linked Global Burden of Disease (GBD 2021) age-standardised drowning mortality rates to satellite-derived exposures for 212 subnational regions across 12 countries (2006-2021; 3,392 region-years). Exposures were extracted via Google Earth Engine and standardised. Gamma-log generalised linear mixed models included region random intercepts and year fixed effects. Income-stratified models were estimated separately. Supplementary models assessed maritime vessel activity. ResultsNear-water population percentage was the strongest correlate of drowning (IRR 1.40; 95% CI 1.33-1.47). Permanent water coverage was protective (IRR 0.80; 0.73-0.88), as were nighttime lights (IRR 0.96; 0.95-0.97) and hot days [≥]30{degrees}C (IRR 0.95; 0.92-0.99). Mean temperature (IRR 1.17; 1.11-1.23) and precipitation (IRR 1.03; 1.01-1.04) were positively associated. Near-water effects were consistent across income strata (LIC 1.25; MIC 1.31; HIC 1.24), while other predictors showed weak or inconsistent within-strata associations. Vessel activity was modestly associated with drowning in Global Fishing Watch models (IRR 1.05; 1.01-1.09) but not in Synthetic Aperture Radar models. DiscussionSatellite-derived indicators can characterise drowning risk at scale, with population proximity to water emerging as a robust cross-context correlate. Protective associations for permanent water suggest landscape configuration may shape risk beyond proximity alone, highlighting geospatial datas value for targeting prevention where surveillance is limited.

Background Ambient air pollution is a leading global health risk and disproportionately affects populations of Low- and Middle-Income Countries (LMICs). In 2021, WHO revised its Air Quality Guidelines (AQG), lowering recommended annual limits for Particulate Matter 2.5 (PM2.5) and Nitrogen Dioxide (NO2). We estimated the potential health and economic impacts of achieving WHO Interim Target 3 (IT3) and AQG concentrations across LMICs. Methods We conducted a health impact assessment across 136 LMICs to quantify one-year changes in all-cause and cause-specific mortality (chronic obstructive pulmonary disease [COPD], ischaemic heart disease [IHD], and stroke) and disease incidence (COPD, dementia, IHD, and stroke) under WHO IT3 and AQG counterfactual scenarios for PM2.5 and NO2. Concentration-response functions were applied at 1km x 1km resolution. Economic welfare impacts of mortality risk reductions were estimated using country-adjusted values of a statistical life (VSL, Int$ PPP-adjusted 2021). Direct medical and productivity-related costs associated with incident cases were estimated using a cost-of-illness (COI) framework. Uncertainty intervals (UI) reflect uncertainty in concentration-response functions. Results Attainment of WHO IT3 and AQG concentrations for PM2.5 was associated with an estimated 16.04% reduction (6.58million, UI: 6.10-7.07million) and 22.97% reduction (9.43million, UI: 8.75-10.11million) in annual deaths, respectively. Corresponding VSL-based estimates of deaths averted were Int$5.5 trillion (7.0% of aggregate LMIC GDP) and Int$8.4 trillion (10.6% of GDP), respectively. For NO2, IT3 and AQG scenarios were associated with estimated reductions of approximately 1.06% (approximately 435,000 deaths, UI: 388,000-483,000) and 2.79% (435,000 deaths; UI: 388,000-483,000), yielding gains of Int$0.6 trillion (0.7% of GDP) and Int$1.5 trillion (1.9% of GDP). Disease-specific mortality reductions were most prominent for IHD and stroke in Asia and Africa. Under the PM2.5 AQG scenario, an estimated 2.82million (1.67-2.97) COPD, 1.10million (0.83-1.37) dementia, 7.3million (6.41-8.19) IHD, and 2.3million (2.19-2.41) stroke cases could be delayed or averted in one year. Associated reductions in direct medical and productivity-related costs were greatest for IHD, COPD, and stroke. NO2-related morbidity reductions were smaller across all outcomes. All estimates represent one-year changes in risk relative to counterfactual exposure and may reflect delayed rather than permanently avoided events. Discussion Achieving both WHO IT3 and AQG values in LMICs could yield substantial reductions in premature mortality and disease incidence, particularly for cardiovascular and respiratory conditions, alongside large, monetised welfare gains from reduced mortality risk. These findings underscore the considerable societal value of air quality improvements and support accelerated action toward meeting WHO guideline levels in regions bearing the highest pollution burden.

Background: Beaches are popular summertime destinations in Canada. However, they can be affected by specific fecal pollution sources, increasing the risk of recreational water illness. Objectives: This study was conducted to determine the risks of acute gastrointestinal illness (AGI) among Canadian beachgoers and to evaluate the influence of different fecal indicator bacteria (FIB) and other water quality measures on assessing these risks. Methods: In a prospective cohort design, beachgoers were recruited at sites across Canada from 2023 to 2025. Sociodemographic characteristics and exposures were determined through an on-site survey, with a 7-day follow-up survey to determine risks of AGI. Bayesian mixed-effects logistic regression models were fitted to evaluate the effects of an ordinal water contact variable (no contact, minimal contact, body immersion, and swallowed water) on the incident risk of AGI, with an interaction included for water quality indicators. The levels of six FIB and water quality measures were assessed: Escherichia coli, enterococci DNA, three microbial source tracking DNA markers (human HF183/BacR287, human mitochondria, seagull Gull4), and turbidity. Results: A total of 4085 participants were recruited, with 67.6% completing the follow-up survey. The overall incident risk of AGI was 2.6%. Both swallowing water and body immersion increased AGI risks compared to no water contact: median of 20 excess cases (95% Credible Interval [CrI]: 4, 64) and 5 excess cases (95% CrI: 1, 19) of AGI predicted per 1000 beachgoers, respectively. Escherichia coli and seagull DNA marker levels were associated with AGI among those who had water contact, particularly among those who reported swallowing water. Discussion: While the overall burden of AGI due to beach water contact in Canada was low, increased risks are associated with E. coli levels particularly among those who swallow water. This could be related to fecal contamination from seagulls. However, there is substantial uncertainty in the predicted effect sizes.

Background Polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) are combustion-derived pollutants linked to cardiovascular disease. Prior NHANES analyses have evaluated these chemicals individually, failing to capture the correlated co-exposure structures that characterize real-world environmental burden, thereby underscoring the need for application. In this study, we applied an unsupervised machine learning pipeline to urinary biomarker data to identify multi-chemical exposure clusters and quantify their differential cardiovascular risk profiles in a nationally representative US sample. Methods We analyzed 2,979 participants from NHANES between 2017-2018, representing an estimated 36.8 million US adults after complex survey weighting. Twenty-five urinary biomarkers (6 PAH, 19 VOC metabolites) were log-transformed, imputed using Multivariate Imputation by Chained Equations (MICE), and standardized. Uniform Manifold Approximation and Projection (UMAP) was used for dimensionality reduction, followed by Gaussian Mixture Model (GMM) clustering. Survey-weighted prevalence estimates with 95% confidence intervals (CIs) were calculated for hypertension and high total cholesterol within each cluster. Weighted multivariable logistic regression was used to estimate odds ratios (OR) for hypertension, adjusting for age, sex, race/ethnicity, and income. Results Four exposure clusters were identified with a mean assignment probability of 0.948. The High combustion cluster (n=370; estimated 5.1 million US adults) exhibited the highest multi-chemical burden and a weighted hypertension prevalence of 39.3% (95% CI 37.2-41.4%), compared to 28.7% (95% CI 21.9-35.5%) in the Low exposure reference group. After demographic adjustment, High combustion cluster membership was independently associated with 38.4% higher odds of prevalent hypertension (OR 1.38). The prediction model achieved a cross-validated area under the receiver operating characteristic curve (AUC) of 0.849 (SD 0.017). Non-Hispanic Black participants constituted approximately 40% of the High combustion cluster, exceeding their representation in lower-risk clusters. Conclusions Multi-chemical exposome profiling identifies four cardiovascularly distinct subpopulations in the US adult population. Membership in the High combustion exposure cluster was associated with higher odds of prevalent hypertension and disproportionately affected Non-Hispanic Black participants. These findings support the use of multichemical approaches over single-pollutant analyses and highlight the relevance of environmental exposure patterns for making policy and targeted cardiovascular risk stratification.

Colorectal cancer (CRC) is the second leading cause of cancer death globally and the number one cause of cancer death in people under 50 years old. The reasons for the rise of early-onset CRC are unknown, and while anatomically distinct subtypes of CRC have substantial clinical and molecular associations, the etiology of region-specific disease, such as early-onset CRC's enrichment in the distal colon, remains unclear. Understanding regional mutagenesis may identify risk factors for this public health concern and CRC more broadly. To evaluate mutational dynamics across the premalignant colon, we performed whole-genome sequencing of 125 individual colon crypts taken from six standardized regions biopsied during colonoscopy, collected from 11 donors without polyps and 10 with polyps. We observed mutation spectra and accumulation rates consistent with previous whole-organ studies, with greater subclonal mutation capture enabled by experimental design. T>[A,C,G] mutations, which are associated with colibactin genotoxicity from pks+ Escherichia coli, were significantly enriched in the rectum of donors with and without polyps (adjusted p-values < 0.01). Moreover, when comparing findings to crypts from individuals with CRC and sequenced CRC tumors, we observed consistent enrichment of the colibactin-associated mutational signature "ID18" in the rectum in both normal colon crypts and CRC tumors, without significant difference in colibactin-specific single nucleotide variant or insertion-deletion burden in crypts across the three clinical groups (i.e., no polyp, polyp, and CRC). These findings argue against a causal or prognostic role for colibactin in CRC, instead indicating that the proposed association with early-onset disease reflects anatomic specificity rather than cancer-specific clinical relevance.

ObjectivesRising temperatures are a major climate-related hazard for U.S. workers, increasing heat-related illness and a broad range of occupational injuries through indirect pathways often overlooked in economic evaluations. We examined the association between temperature and occupational injury and illness and quantified heat-attributable injuries (including illnesses) and costs in New York State. MethodsWe conducted a time-stratified case-crossover study of 591,257 workers compensation (WC) claims during the warm season (2016-2024). Daily maximum temperature was linked to injury date and county and modeled using natural cubic splines, with effect modification by industry and worker characteristics. ResultsInjury risk increased with temperature, becoming statistically significant at approximately 78{degrees}F. Relative to 65{degrees}F, injury odds increased to 1.06 (95% CI: 1.01-1.10) at 80{degrees}F, 1.12 (1.07-1.18) at 90{degrees}F, and 1.17 (1.11-1.23) at 95{degrees}F. Overall, 5.0% of claims (2,322 annually) were attributable to heat. At temperatures [&ge;]80{degrees}F, an estimated 1,729 excess injuries occurred annually, generating approximately $46 million in WC costs. An estimated $3.2 million to $36.1 million in medical expenditures were associated with incomplete claims, likely borne outside the WC system. ConclusionsThese findings demonstrate substantial economic costs not fully captured within WC and support workplace heat protections as a cost-containment strategy that can reduce health care spending and strengthen workforce resilience.

Background Prenatal exposure to pesticides and psychosocial factors often co-occurs, particularly in low- and middle-income settings, yet their joint effects on epigenetic age acceleration (EAA) in early life remain unknown. We investigated the joint associations of prenatal pesticides metabolites and psychosocial factors on EAA in the first five years of life in the South African Drakenstein Child Health Study. Methods In 643 mothers, we measured 11 urinary pesticide metabolites and seven psychosocial factors during the second trimester of pregnancy. Child DNA methylation was measured in whole blood at ages 1, 3, and 5 years. EAA was estimated using the Horvath, Skin & Blood Horvath (skinHorvath), and Wu epigenetic clocks. Longitudinal associations were estimated using generalized estimating equations, adjusted for confounders. Joint mixture associations were evaluated using weighted quantile sum regression (WQS) and quantile g-computation (QGCOMP). Results The joint prenatal exposure mixture was positively associated with Wu ({beta} per one quintile increase in the mixture [95% CI]: 0.41 years [0.15, 0.80]), skinHorvath (0.11 years [0.06, 0.16]), and Horvath EAA (0.31 years [0.20, 0.46]) over time using WQS. Psychosocial factors, particularly food insecurity, physical interpersonal violence, and stress biomarkers, contributed most to the total mixture effect for all clocks. Pyrethroid metabolites PBA and TDCCA were top pesticide contributors to Wu EAA. Pathway enrichment analyses of clock-specific CpGs revealed distinct biological architectures, with the Wu clock enriched for neurodevelopmental and immune pathways, and metabolic pathways for the Horvath clock. Discussion Joint prenatal exposure to pesticides and psychosocial factors was associated with increased EAA across early childhood, with psychosocial factors contributing the most to the total effect. These findings highlight the importance of assessing chemical and non-chemical stressors jointly and clock-specific biological interpretation in epigenetic aging research.

Military aviation training noise remains understudied despite its widespread impacts across urban, rural, and wilderness areas. The predominance of low-frequency noise and repetitive training can create pervasive noise pollution, yet past research often fails to capture the full range of health and quality-of-life effects. This study analyzed two complaint datasets related to Whidbey Island Naval Air Station noise: U.S. Navy records (2017-2020) and Quiet Skies Over San Juan County data (2021-2023). We analyzed and mapped sentiment intensity from noise complaints relative to modeled annual noise exposure, developed a typology to classify impacts, and modeled the environmental and operational factors influencing complaints. Findings revealed widespread negative sentiment and anger, often beyond the bounds of estimated noise contours, suggesting that annual cumulative noise models inadequately estimate community impacts. Complaints consistently highlighted sleep disturbance, hearing and health concerns, and compromised home environments due to shaking, vibration, and disruption of daily life. Residents also reported significant social, recreational, and work disruptions, along with feelings of fear, helplessness, and concern for children's well-being. The number of complaints were strongly associated with training schedules, with late-night sessions being the strongest predictor. A delayed response pattern suggests residents reach a frustration threshold before filing complaints. Overall, our findings demonstrate persistent negative sentiment and diverse impacts from military aviation noise. Results highlight the need for improved noise metrics, modeling and operational adjustments to mitigate the most disruptive effects.

Prenatal air pollution exposure is associated with childhood asthma, particularly among biological males. The mechanisms remain unclear, but may involve lasting epigenetic changes, such DNA methylation (DNAm), that occur during gestation in response to oxidative stress and inflammation. Higher maternal intake of "protective" micronutrients, like antioxidants, could buffer pollution-induced oxidative stress and inflammation to mitigate potentially adverse DNAm differences contributing to asthma. Using data from 515 CANDLE participants, we examined associations between prenatal NO2, PM2.5, and PM10 and cord blood DNAm, evaluated DNAm mediation of pollution associations with childhood wheeze phenotypes (transient, persistent, and late-onset), and assessed buffering of DNAm by maternal polyunsaturated fatty acid, vitamin C, or folate intake, and overall diet quality measured by the Alternative Healthy Eating Index-Pregnancy (AHEI-P). We identified 19, seven, and five regional DNAm differences associated NO2, PM2.5, and PM10. Mediation analyses suggested a role for HLA-DPA1/DPB1 DNAm in NO2 and PM2.5 associations with transient wheeze. To assess buffering, we fit pollutant-by-diet interaction models, defining buffering as an interaction opposite in sign to the main pollutant effect. One or more micronutrients or AHEI-P attenuated pollutant effects at 16 of 19 NO2-associated DMRs, including HLA-DPA1/DPB1, and all PM2.5- and PM10-associated DMRs. However, attenuation of HLA-DPA1/DPB1 DNAm did not significantly reduce the indirect effect of NO2 on transient wheeze. In sex-stratified analyses, biological males exhibited lower PM2.5-associated DNAm in SERPINB9, a gene linked to lung function. These findings suggest prenatal air pollution alters DNAm, which may contribute to transient wheeze, with some differences partially buffered by maternal diet. Significance StatementPrenatal air pollution exposure contributes to child wheeze and asthma, potentially through the oxidative stress response and subsequent changes to infant DNA methylomes. Here, we used data from the CANDLE cohort to identify cord blood DNAm differences associated with NO2, PM2.5, or PM10. We examined if any alterations mediated the relationship between prenatal air pollution exposures and transient, persistent, or late-onset wheeze at age 4 to 6 years. Some of these DNAm differences appeared to be at least partially buffered by maternal micronutrients and/or overall diet quality.

Wastewater surveillance is increasingly used for antimicrobial resistance (AMR) monitoring in urban environments, but low-resource settings often lack a piped sewerage system. Instead, coprophagous flies--flies that ingest feces--may serve as composite samplers for monitoring fecal wastes present in terrestrial environments. We evaluated whether the class 1 integron-integrase gene intI1 was associated with genetic markers of AMR and fecal source tracking markers (FST) in coprophagous flies collected from latrine entrances and food preparation areas in low-income urban Maputo, Mozambique. We quantified intI1, an enteric 16S rRNA target (for normalization), three FST markers, and 30 ARG targets using qPCR. We normalized concentrations of intI1 and each target to enteric 16S rRNA. We fit linear mixed models with a random intercept for housing compound to estimate within-fly associations between log10 relative abundance of intI1 and log10 relative abundance of each target with and without adjustment for fly taxonomic group, capture location, and standardized fly mass. We also modeled per-fly unique ARG count (i.e., number of ARG targets detected) using Poisson regression. Of 188 flies assayed, 176 passed internal controls; intI1 and enteric 16S rRNA were detected in 95% and 96% of flies, respectively. Higher relative abundance of intI1 was positively associated with ARG and FST targets, with the strongest associations observed for sulfonamide-(sul1: {beta} = 0.87; 95% CI: 0.81, 0.94; sul2: {beta} = 0.81; 95% CI: 0.73, 0.89), tetracycline- (tetA: {beta} = 0.78; 95% CI: 0.70, 0.85; tetB: {beta} = 0.69; 95% CI: 0.60, 0.79), and trimethoprim-related (dfrA17: {beta} = 0.78; 95% CI: 0.70, 0.86) genes. Associations with FST markers were weaker (i.e., human mtDNA: {beta} = 0.46; 95% CI: 0.37, 0.55; human-associated Bacteroides: {beta} = 0.34; 95% CI: 0.25, 0.43). Higher relative abundance of intI1 was also associated with a greater number of ARGs detected: each 10-fold increase in intI1 was associated with an 8% higher expected unique ARG count (aRR=1.08, 95% CI: 1.04-1.12). These findings support the need for further research across different settings exploring intI1 carried by coprophagous flies as a potential standardized screening target for AMR surveillance in unsewered terrestrial environments.

Drowning remains a major global public health challenge, yet how built environment characteristics shape population-level drowning risk remains poorly understood. This study linked satellite-derived built environment data to subnational drowning mortality estimates across 203 regions in 12 countries from 2006-2021. It found that built environment associations with drowning mortality are complex, non-linear, and shaped by development context. Urban extent was strongly protective, while built area near water showed protection overall but increased risk when combined with high population crowding. Almost all drowning mortality variance occurred between regions rather than within regions over time, indicating risk is predominantly determined by place-based characteristics. Income-stratified analyses revealed profound heterogeneity: crowding was protective in low-to middle-income settings but near-null in high-income regions, while waterfront development captured very different realities across contexts. These findings highlight the importance of tailoring drowning prevention strategies to local built environment configurations and development contexts.

Wastewater sequencing is an increasingly valuable tool in tracking the spread of infectious disease agents across space and time in areas of dense human settlement. Among pathogens that can be readily detected by this approach is influenza A, which follows predictable patterns of prevalence through the winter months in North America. Here, we leverage routine surveillance of a municipal wastewater treatment plant in Northern California to describe an atypical, off-season spike in influenza A concentrations that rivals that of the winter respiratory virus season. Drawing upon metagenomic data generated through hybrid-capture sequencing, we assemble and subsequently characterize fragments of divergent influenza genomes that appear to derive predominantly from the avian H16 clade. These strains exhibit close evolutionary relationships to influenza isolated from migratory shorebirds, hinting at potential host species and mechanisms of geographic spread. Analysis of read abundances suggest that these avian strains dominate the pool of influenza circulating during the summer months, when typical human-infecting strains are essentially absent. Together, our results expand the value of wastewater sequencing to encompass sensitive tracking of outbreaks within animals in interface regions where human settlement abuts wildlands, increasing overall pandemic preparedness.

BackgroundDrowning remains a major global public health challenge. This study examined whether the timing and trajectories of urbanisation--beyond the current built environment--are associated with subnational drowning mortality. MethodsWe linked satellite-derived measures of built-environment change (GHSL), population crowding (WorldPop), surface water exposure (JRC Global Surface Water), and infrastructure proxies (VIIRS/DMSP nighttime lights) to GBD 2021 drowning mortality estimates across 203 ADM1 regions in 12 countries (2006-2021; 3,248 region-year observations). Temporal predictors captured recent expansion, development "newness" ([&le;]10-year built share), acceleration/volatility, and a crowdingxgrowth interaction. We screened predictors using LASSO (10-fold cross-validation) and fitted mixed-effects models with region random intercepts. Distributed-lag models tested temporal precedence and development age, and income-stratified models assessed heterogeneity. ResultsAdding temporal predictors improved fit beyond contemporaneous built-environment measures ({Delta}AIC=177; {Delta}BIC=147). In adjusted models, crowdingxgrowth was strongly positively associated with drowning mortality, and a higher share of recent development was associated with higher mortality. Lag models showed a development age gradient: older built environment was most protective. Associations differed by income group, with several key coefficients reversing sign across strata. DiscussionDrowning mortality appears shaped by development histories as well as present-day conditions, with risk concentrated in rapidly changing, dense settings and the newest built environments. Cross-context heterogeneity suggests mechanisms and prevention priorities are unlikely to be uniform. ConclusionsDevelopment timing and trajectories help explain subnational drowning mortality beyond current built form alone. Prevention and planning should prioritise transition-period safety strategies in newly developing and rapidly densifying areas.

Neem-derived biopesticides are increasingly applied in agriculture and have been tested in aquaculture research, yet their effects on non-target aquatic invertebrates remain insufficiently characterized. We evaluated the effect of neem extract on the brine shrimp Artemia franciscana using an integrated ecotoxicological approach combining phenotypic, transcriptomic, and histological analyses. Juvenile A. franciscana exhibited dose-dependent mortality and sublethal abnormalities, with a 24 h median lethal concentration of 292.48 mg/L (95% confidence interval, 257.75- 331.89) for mortality and a median effective concentration of 146.36 mg/L (95% confidence interval, 113.04- 189.50) for the combined endpoint "abnormal + dead". In adults, males showed greater mortality than females after extended exposure. High-throughput RNA sequencing revealed broad treatment-associated differences in transcript abundance, with juveniles displaying downregulation of detoxification enzymes and chitin biosynthesis genes, alongside enrichment of immune- and cuticle-related gene ontologies. Adults showed transcriptional signatures of stress, including upregulation of heat shock proteins and cytoskeletal components, and suppression of genes involved in energy metabolism. Chitin precursor enzymes were selectively downregulated in males, and altered carbohydrate metabolism was observed in females. Histological analyses revealed structural deterioration of the brood sac cuticle and reduced ovarian area in treated females, consistent with transcriptomic evidence of impaired exoskeletal and reproductive processes. Overall, neem exposure was associated with phenotypic, histological, and transcriptomic changes in A. franciscana. These results support the use of combined transcriptomic and histopathological endpoints to characterize responses to plant-derived biopesticides in aquatic arthropods.

Background. Young sexual and gender minorities of color face compound health risks shaped by interlocking systems of racism, cisgenderism, and class inequality. Spatial health research documents that place shapes health, but existing methods cannot specify the mechanisms through which spatial configurations produce different health outcomes for differently positioned people. This gap prevents targeted intervention. ObjectiveTo develop and pilot test the Spatial Intersectionality Health Framework (SIHF), which specifies three mechanisms through which space produces intersectional health inequities: Layered (multiple oppressive systems activating simultaneously), Positional (the same space producing different health pathways by intersectional position), and Conditional (nominally protective spaces carrying hidden costs for specific positions). We also introduce and validate Intersectional Geographically-Explicit Ecological Momentary Assessment (IGEMA) as the methodology operationalizing SIHF across three data levels. MethodsThe GeoSense study enrolled 32 young sexual and gender minorities of color (ages 18-29) in New York City. IGEMA was implemented across three integrated levels: (1) GPS mobility tracking via participants personal smartphones, linked to census tract structural exposure indices across n=19 participants; (2) ecological momentary assessment of intersectional discrimination with multilevel modeling of mood, stress, and sleep outcomes; and (3) map-guided qualitative interviews with SIHF mechanism coding and intercoder reliability assessment across 92 coded records from 18 participants. This study was conducted as the pilot for NIH R01HL169503. ResultsAll three SIHF mechanisms were empirically detectable. A compound structural gendered racism index outperformed every single-axis alternative in predicting daily mood (b=-0.048, p=.001) and stress (b=0.121, p<.001). The Positional mechanism accounted for 71% of coded harm experiences. Intercoder reliability for mechanism assignment reached kappa=0.824 at Stage 2 reconciliation. Daily intersectional discrimination predicted greater sleep disturbance (b=1.308, p=.004). ConclusionsSIHF and IGEMA together provide an empirically testable framework for specifying how space produces intersectional health inequities. Mechanism specification, not spatial location alone, is the condition for designing research and intervention that reaches the source of harm for multiply marginalized populations.

Establishing whether real-world environmental chemical (EC) exposure can induce heritable epigenetic modifications in large, outbred mammals is key to determining long-term developmental impacts of the human exposome. Using an established biosolids-treated pasture (BS) sheep model, we investigated whether gestational exposure to low-level mixtures of EC induced heritable changes in DNA methylation across three generations of sheep. Reduced-representation bisulfite sequencing of liver, blood, and sperm, combined with a structured, lineage-controlled breeding design, revealed widespread but lineage- and sex-specific differentially methylated loci (DML) in F1 offspring, with detectable alterations evident in F2 and F3 descendants. Although most DML were unique to individual sire lineages, or to a single generation, subsets of loci showed repeated involvement across generations and were associated with altered gene expression in F3 descendants. Sperm from F1 males exhibited reduced methylation at numerous loci and, together with seminal plasma, revealed differential expression of several microRNAs. These effects, however, showed limited persistence in F2 males, indicative of intergenerational rather than fully transgenerational persistence. Collectively, these findings demonstrate that complex, low-level chemical exposures can elicit recurrent, sexually dimorphic epigenetic responses in outbred species, but underscore the challenge of disentangling exposure-induced inheritance from genetically regulated methylation variation. Significance StatementEnvironmental chemical (EC) exposures are ubiquitous, yet their capacity to induce heritable epigenetic changes in large, genetically diverse mammals is poorly understood. Using a real-world exposome-based sheep model, we demonstrate that low-level gestational EC exposure leads to sexually-dimorphic and lineage-dependent alterations in DNA methylation that can extend to unexposed descendants. Although genetic ancestry exerts a dominant influence over these responses, repeated alterations at specific loci suggests that environmentally induced epimutations can reoccur across generations in certain genomic contexts.

BackgroundThe rapid growth of the worlds urban population has contributed to the expansion of informal urban settlements in many cities across the world. In these settings, lack of safe sanitation combined with high population density and poverty contributes to heightened health risks for often vulnerable populations. The aim of this study was to evaluate the effect of a shared, onsite sanitation intervention on the nutritional status of children in Maputo, Mozambique. MethodsThe Maputo Sanitation (MapSan) trial was a controlled before-and-after study to evaluate the effect of a shared, onsite sanitation intervention on child health in Maputo, Mozambique. Here, we report the effects on childhood stunting, wasting and underweight, and height-for-age, weight-for-height and weight-for-age z-scores. Children were enrolled aged 1-48 months at baseline and outcomes were measured before and 12 and 24 months after the intervention, with concurrent measurement among children in a comparable control arm. The primary analysis was intention-to-treat. The trial was registered at ClinicalTrials.gov, number NCT02362932. ResultsWe enrolled 757 and 852 children in the intervention and control groups respectively. There was no evidence for an effect of the intervention on any outcome at 12 or 24 months of follow-up except for wasting where there was very weak evidence for an effect (adjusted prevalence ratio: 0.497; 95% CI: 0.22-1.11; p=0.09). In two exploratory analyses - one including only those children born into compounds post-intervention and a second excluding children in control compounds which had independently improved their sanitation facilities during follow-up - we found that stunting increased in the intervention group whilst wasting decreased. ConclusionsThis study contributes to the growing evidence on the role of sanitation in shaping child health outcomes in informal urban settlements. We found no evidence for an effect on stunting and weak evidence for an effect on wasting. More research is needed to understand how sanitation can reduce childhood undernutrition in complex urban environments.

Gene-environment interactions (GEI) contribute to circulating polyunsaturated fatty acid (PUFA) and monounsaturated fatty acid (MUFA) profiles. GEI may partly explain differences in trait variance across genotype groups. To identify GEI for circulating unsaturated fatty acids, we adopted a two-stage strategy. First, we detected quantitative trait loci associated with trait variance (vQTLs). Second, we tested these vQTLs for interaction with fish oil supplements (FOS). We performed genome-wide vQTL screens for 14 plasma PUFA and MUFA phenotypes in a UK Biobank subset of 200,478 participants. At the genome-wide significance threshold (p < 5.0 x 10-8), we identified 172 vQTL-trait pairs across all 14 traits, and 16 of these vQTLs had no marginal genetic effect on the corresponding trait. We found 46 non-overlapping loci across all phenotypes, with an average of 12 vQTLs per trait. Omega-6% and PUFA% had the most independent vQTLs (N = 24) while DHA% and Omega-3% had the least (N = 1 and 2, respectively). For each of the 172 vQTL-trait pairs, we tested the interaction effect of the vQTL with FOS on the corresponding trait. We found six significant interaction signals in DHA, DHA%, Omega-3, Omega-3%, LA, and Omega-6/Omega-3 ratio around the FADS1/2, ZPR1, and SUGP1/TM6SF2 genes. Our results provide a comprehensive resource of vQTLs and gene-FOS interactions shaping the circulating levels of unsaturated fatty acids.

Soil microbes support life on Earth by regulating the availability of nutrients in soils, yet we lack a fundamental, baseline knowledge of which fungi and bacteria are associated with specific soil nitrogen (N) cycling processes across ecosystems. We identified functional and taxonomic groups of fungi and bacteria that are associated with net ammonification and nitrification rates in soils from diverse ecosystems across the United States, including the environmental contexts where these relationships exist. To accomplish this, we co-analyzed soil, microbial, plant, and climatic data from 19 sites across the U.S. National Ecological Observatory Network (NEON). Distinct microbial groups were associated with net ammonification versus nitrification rates, highlighting the need to measure and model these two processes separately. The relative abundance of several microbial groups known for their N-decomposition abilities (i.e., Acidobacteriae, Bacteroidia, Saccharomycetes yeasts, ectomycorrhizal fungi) were positively associated with net ammonification rates across diverse environmental conditions. Meanwhile, pathogenic fungi, copiotrophic bacteria, and bacterial classes containing denitrifying bacteria were positively associated with net nitrification rates in many wet, hot, and high-N environments. These results deepen our understanding of soil microbiome ecology and represent a practical starting point to develop microbial-explicit biogeochemical cycling models at large spatial scales.

The contribution of tree foliage to atmospheric methane (CH4) and nitrous oxide (N2O) fluxes remains a major uncertainty in global GHG budgets. We made repeated in situ measurements of foliar CH4 and N2O fluxes across 25 temperate tree species interplanted at a forest restoration site using high-resolution laser spectroscopy. Tree foliage was consistently a net CH4 sink and a net N2O source in all species. Foliar CH4 oxidation increased by [~]33% in fall relative to spring and was [~]3-fold higher in shade-tolerant than shade-intolerant angiosperm species. Species differences accounted for most of the variability in fluxes, while correlations with soil emissions were comparatively weak. Microbial DNA sequencing revealed that the highest CH4-oxidizing angiosperm species (Tilia americana) harbored abundant Type I methanotrophs, whereas the lowest-oxidizing species (Prunus virginiana) had nearly 100-fold lower methanotroph abundance, with a foliar microbial community dominated by facultative methylotrophs. Global warming potential (GWP) scaling indicates that foliar CH4 uptake overwhelmingly dominates the net climate forcing effect. Our results suggest that the large and predictable differences in foliar CH4 uptake among tree species and associated differences in foliar microbial communities are of importance in understanding and potentially enhancing the global terrestrial CH4 sink.