Environmental Health Perspectives

Wildfire smoke poses a growing health risk worldwide, yet the magnitude and temporal evolution of mortality after episodic exposure remain poorly resolved, limiting burden assessment. Using monthly county-level wildfire PM2.5 and mortality data from the United State, we exploit episodic exposure contrasts to deconvolve overlapping mortality responses and recover the impulse-response function. The excess mortality response peaks approximately three years after an exposure pulse and subsides by five years. We estimate 1.7 (95% uncertainty interval: 1.1-2.3) million smoke-associated deaths during 2011-2023, approximately ten times estimates using long-term ambient PM2.5 mortality relative risks. Circulatory and respiratory diseases contribute comparably and dominate this burden. Responses are markedly greater among adults [≥]65 years; during the COVID-19 pandemic, population-wide cumulative responses are significantly higher over at least the first seven months after exposure. Reducing wildfire smoke exposure can thus yield substantial health benefits over multiple years, particularly when population vulnerability is heightened.

Total serum perfluorooctane sulfonate (PFOS) concentration and its isomer composition describe different aspects of internal exposure, but their respective associations with depressive symptoms remain uncertain. We examined adults aged 18-25 years in NHANES August 2021-August 2023 using survey-weighted models of the Patient Health Questionnaire-9 (PHQ-9). Total measured PFOS was the sum of linear PFOS and pooled monomethyl-branched PFOS; composition was their log-ratio. The analytic cohort included 169 participants, with 147 complete cases for core adjustment. Median total PFOS was 1.70 ng/mL, the median linear fraction was 72.2%, and the weighted prevalence of PHQ-9 [≥]10 was 22.6%. In the joint adjusted model, a doubling of total PFOS at fixed composition corresponded to -0.49 PHQ-9 points (95% CI, -1.65 to 0.68); a doubling of the linear-to-branched ratio at fixed total corresponded to 0.21 points (-1.94 to 2.36). Algebraic rescaling across the reported interquartile ranges yielded differences of -0.58 points (-1.95 to 0.81) for total PFOS and 0.13 points (-1.16 to 1.41) for composition. The inverse continuous-score association weakened with adjustment, whereas the screening odds ratio primarily lost precision. Excluding three observations with an isomer below detection shifted both joint coefficients. The data therefore do not establish an independent composition association or equivalent isomer effects. Experimental evidence supports candidate oxidative, inflammatory, and synaptic pathways, but differential protein binding and elimination prevent a serum composition ratio from being interpreted directly as brain dose or toxicity. Larger longitudinal analyses with isomer-resolved exposure and toxicokinetic measurements are needed to test these pathways.

Researchers must often rely on observational data to draw conclusions about the causal relationship between an exposure and an outcome. This is common in environmental epidemiology research, where the assignment to an exposure can be unethical or impossible. Consider a setting in which we seek to estimate excess mortality during heat waves, but are unable to randomize individuals to moderate or extreme heat. We propose to follow a causal framework for non-randomized time series that uses what we call historical time series matching to construct hypothetical randomized experiments, in which background covariates are balanced. We applied this framework and assessed the following causal question: Are daily mortality counts among elderly Americans higher during hot versus warm summer time periods? We addressed this causal question by drawing frequentist, Fisherian, and Bayesian inferences for five American cities. We estimated the average treatment effect of heat on three-day mortality with 95% Fisherian intervals to be 0.5 [-3.6, 4.4] deaths in Pittsburgh, 3.7 [0.7, 6.6] deaths in Seattle, 12.5 [6.1, 18.9] deaths in Chicago, 8.5 [1.4, 15.6] deaths in Los Angeles, and 20.3 [11.2, 29.5] deaths in New York.

Biodiversity is globally threatened by chemical pollution, yet toxicity data remain unavailable for millions of species and tens of thousands of chemicals, severely limiting our ability to assess ecological impacts. Here we present TRIDENT-2, a multimodal artificial intelligence model for predicting chemical toxicity across evolutionarily diverse eukaryotic species. Trained on 560,780 toxicity assays spanning 82,775 chemicals, 6,793 species, and multiple exposure scenarios, TRIDENT-2 accurately predicts toxicity across Eukaryota with an average median absolute error ranging from 1.76 to 3.80. By jointly learning from chemical, biological, and experimental information, it remains accurate across broad chemical and taxonomic distances, allowing for toxicity assessment for species and chemicals beyond the current experimental evidence. Our findings demonstrate that artificial intelligence can help overcome longstanding data limitations in ecotoxicology, paving the way for improved decision-making and reducing chemical impacts on biodiversity and ecosystems.

Background: Chronic arsenic exposure in drinking water causes skin lesions and cancers and raises infant, cardiovascular and all-cause mortality in Bangladesh. National surveys tested source water in 2012-13, 2019 and 2025 with different kits, so the trend is uncertain. Objectives: We estimated how arsenic in source water changed after laboratory adjustment of 2012-13 readings, and how many people remained exposed. We also assessed whether districts high in earlier surveys held most people exposed in 2025. Methods: We analysed 11,624 households in three Multiple Indicator Cluster Surveys. We counted arsenic strictly above 10 and 50 parts per billion (ppb). Results: Estimates reproduced published 2019 and 2025 tables. After laboratory adjustment of 2012-13, the share above 10 ppb fell from 24.0% to 14.4% (adjusted ratio 0.61, sampling 95% CI 0.55 to 0.67; 0.69 with interview month). Above 50 ppb it fell from 10.9% to 8.6% (0.80, 0.69 to 0.93; 0.93 with month). Most of the fall at 10 ppb occurred within source types. Without false positives, it would vanish only if later kits detected 61% of sources above 10 ppb. About 26 million people used such water in 2025 (kit scenarios 23 to 32 million). The 25 districts high in 2012-13 and 2019 held 39% of the population but 72% of those exposed (bootstrap 95% interval 60 to 76). Clustering was evident, but no district was a significant hotspot. Conclusions: Arsenic above 10 ppb was lower in 2025 than in 2012-13, but the size of the fall depends on unverified later kits. Change at 50 ppb and since 2019 was unclear after month adjustment. One household in seven exceeded the WHO guideline in 2025. Districts found high earlier held most exposed people, supporting prioritised well testing there alongside broader surveillance. Future surveys need one kit with a laboratory cross-check.

Per- and polyfluoroalkyl substances (PFAS) are present throughout the environment due to decades of use in many commercial products and industrial processes. These molecules contain a hydrophobic fluorocarbon tail and a functional headgroup (typically a carboxylic or sulfonic acid) that allows hydrophilic interactions with the surrounding environment. These properties make them inherently resistant to degradation, difficult to track through the environment, readily bioaccumulative, and likely to impact human health. Through collaboration with town officials, multiple meetings with local sustainability committee members and school officials, and direct contact with individual homeowners, we conducted community-driven sampling of PFAS in well water from 105 houses in Tremont, ME, a rural coastal town that relies on private wells for drinking water. The rate of PFAS detection for one or more analytes across all wells (N=105) was 69%. Of all wells tested, 16 (15%) exceeded the current public drinking water standard in Maine (20 ng/L for 6 PFAS), and an additional 17 (totaling 31% of all wells tested) exceeded Maine's newly adopted public drinking water standards for the state (based on EPA 2024 standards). Because private wells are unregulated, homeowners may use these results as a guide for taking action to maintain safe drinking water. Both hierarchical cluster analyses and pairwise Spearman's rank correlation of PFAS test results revealed similar profiles in households near and far from one another. Along with the absence of obvious, large-scale potential point sources of PFAS contamination, these findings support septic systems as the primary source of PFAS contamination in drinking water across this town. The community-driven approach to the sampling effort has enabled information sharing on the importance of water filtration options, discussion of long-term pollution abatement strategies for individual households and the town, and focused efforts for future well water testing and PFAS mitigation.

Long-term PM2.5 exposure is associated with increased mortality and is usually represented by annual mean concentration, which does not capture how concentrations are distributed across days. We tested whether the prespecified PM2.5 magnitude-rank index (PMRI), a summary of within-year daily concentration structure, improves mortality prediction beyond the annual mean. Daily modeled PM2.5 estimates were linked to age-adjusted mortality rates for 27,289 county-years from 3,064 U.S. counties during 2003-2011. PMRI is the largest k for which at least k days reached k micrograms per cubic meter. County-grouped 10-fold cross-validation compared models with annual mean alone versus annual mean plus PMRI, with additional geographic, temporal, cause-specific, and specification analyses. Annual mean PM2.5 had the highest standalone predictive performance. Adding PMRI increased county-held-out R-squared from 0.0802 to 0.1391 (increase in R-squared = 0.0589; 95% CI, 0.0499-0.0677) and reduced RMSE and MAE. Improvement persisted across geographic and temporal validations and all six cause-specific mortality outcomes. Within-year PM2.5 exposure structure therefore contains reproducible mortality-predictive information not captured by annual mean concentration.

Human metabolism converts inorganic arsenic to the pentavalent methylated species MMA(V) and DMA(V), the forms most people excrete, and the forms long read as the end of a detoxification pathway. Whether a transporter sets how much of these metabolites reaches the genome has not been tested in a mammalian cell. We expressed human AQP3, AQP7, AQP9 or AQP10 in HEK293T and MRC5-SV40 cells and measured gamma-H2AX by flow cytometry across dose series of As(V), MMA(V) and DMA(V), pairing every aquaporin with a GFP-Tubulin control and an untransfected mock acquired in the same replicate. As(V) was inactive in HEK293T cells and only weakly active in MRC5-SV40 cells to 20 micromolar, and both methylated species damaged DNA only in the millimolar range, DMA(V) being the more potent of the two in both cell lines. Against that weak baseline, AQP9 and AQP10 raised DMA(V)-induced gamma-H2AX in HEK293T cells by roughly 17 percentage points over the matched control, more than doubling the damage the same exposure produced in control cells, whereas AQP3 and AQP7 changed it not at all. AQP9 alone remained active with MMA(V). The ranking held in MRC5-SV40 fibroblasts at one-sixth the size, and within single wells the damage rose with the amount of AQP9 a cell carried while the control was flat. Aquaglyceroporins therefore discriminate among arsenic species, and AQP9 and AQP10 turn a weakly genotoxic metabolite into a substantially more genotoxic one.

Background: In coastal Bangladesh, saline drinking water has been linked to raised blood pressure. The 2025 Multiple Indicator Cluster Survey (MICS) measured electrical conductivity (EC), a salinity indicator, in source water, but its report gave no population counts or district estimates. Objectives: To estimate how many people live in households whose tested source has high EC, and to describe patterns by place, household characteristics, source type and arsenic. Methods. EC was measured in source water of 6,040 households in 64 districts, February to June. In 14.5% of households the tested source was not the main drinking-water source. Primary outcomes were EC above 1,500 and 3,000 microsiemen/cm, survey risk classes that are not health-based standards. Estimates were survey weighted; comparisons were observational. Results: EC exceeded 1,500 microsiemen/cm in 5.3% of households (95% CI 4.7 to 5.9), about 9.0 million people, including 1.8 million above 3,000 microsiemen/cm. Coastal-zone districts held 26% of households but 70% of those above 1,500 microsiemen/cm. Shares varied little by wealth or in households with young children or pregnant women. Nationally, deep tube wells more often had high EC because most are coastal. In the coastal zone, deep and shallow wells had similar shares (16.1% and 17.9%). After district adjustment, EC was about 18% lower in deep wells (geometric mean ratio 0.82, 0.73 to 0.92). Within upazilas (restricted sample) it was 0.93 (0.80 to 1.07). Arsenic above 10 ppb was more common where EC was high, but this link weakened after district adjustment. Conclusions: Millions of people live in households whose tested source has high EC, mostly in coastal and south-central districts. Deep wells had modestly lower EC after geographic adjustment, but the difference shrank within upazilas and depended on the handling of implausibly low readings. The findings support measuring EC alongside arsenic, with documented meter calibration.

Current insecticide toxicology still lacks an integrated understanding of how lethal and sublethal exposure shape organismal performance across biologically and environmentally relevant contexts. In particular, insecticide susceptibility may vary with physiological state, environmental conditions, and recent exposure history, factors that are only partially captured by standardized toxicity assessments. Here, using Drosophila melanogaster, we systematically compared responses to three insecticides with distinct modes of action - acetamiprid, chlorantraniliprole, and deltamethrin - across developmental stages, sexes, adult ages, and ambient temperatures. Insecticide sensitivity varied substantially across these conditions, with temperature modulating toxicity in a compound-dependent manner. Notably, deltamethrin caused substantial lethality at concentrations more than 10,000-fold below approved field application rates. Beyond these context-dependent differences in acute toxicity, sublethal pre-exposure to each insecticide rapidly reduced lethality during a subsequent challenge with the same compound, with increased tolerance already detectable after 24 h. Importantly, these exposure conditions that enhanced insecticide tolerance were associated with reduced resistance to environmental challenges, including heat and nutrient starvation, revealing a potential trade-off in organismal stress resilience. Acetamiprid exposure further altered reproductive performance in a concentration-dependent manner, with higher exposure reducing egg production while increasing developmental success among the resulting offspring, such that the number of offspring reaching adulthood remained largely unchanged. Together, these findings demonstrate that insecticide susceptibility is highly context dependent and can be rapidly modified by recent exposure history. We identify short-term, compound-specific, and potentially costly tolerance as an underappreciated consequence of insecticide exposure and highlight the importance of incorporating biological context, environmental conditions, and sublethal exposure history into pesticide risk assessment.

Cadmium (Cd) is an emerging environmental risk factor for cognitive decline and Alzheimer's disease, and few interventions limit its effects on the brain. Akkermansia muciniphila, a human gut commensal, is neuroprotective through mechanisms that remain unclear. Building on our finding that A. muciniphila prevented Cd-induced memory deficits without reducing brain Cd burden (Wang et al., 2026a), we tested whether it reprograms Cd-disrupted hippocampal RNA regulation. Male C57BL/6J mice received A. muciniphila (1x10^9 CFU, oral gavage, 5 days/week) before and throughout 9 weeks of 3 mg/L CdCl2 exposure; hippocampi were analyzed by RNA-seq, m6A epitranscriptomic profiling, and rMATS-based alternative-splicing analysis. Cd disrupted hippocampal neuropeptide signaling, neuronal excitability, and synaptic plasticity. Co-exposure with A. muciniphila reversed signatures enriched for Nrf2-centered cytoprotective signaling and opposed m6A and splicing changes across more than a thousand genes, largely without changes in total mRNA abundance. Restored events converged on machinery governing local translation, calcium-dependent plasticity, and synaptic transmission. Projected onto predicted protein structures, most introduced a premature termination codon predicted to trigger nonsense-mediated decay or edited short loop and linker segments rather than rebuilding folded domains, regulation largely invisible to gene-level expression analysis. Among these, paired events amplifying semaphorin-plexin signaling, an axis linked to oligodendrocyte injury and memory consolidation, were reversed. These findings identify restoration of hippocampal transcript fate and splice-isoform selection as a mechanism potentially underlying A. muciniphila-mediated protection against Cd neurotoxicity, and establish post-transcriptional RNA regulation as a gut-brain target for mitigating environmentally driven neurotoxicity.

Introduction: Pesticide exposure has been associated with poorer mental health, yet little is known about whether seasonal fluctuations in agricultural pesticide use are associated with cyclical changes in mood among people living in agricultural communities. We evaluated associations between 10 peak and off-peak pesticide spray seasons and ecological momentary assessment (EMA)-derived mood in a floricultural region in Ecuador. Methods: 496 participants completed repeated EMA surveys across 10 assessment administrations over 2.5 years (2022-2024), including one single-assessment administration and nine 10-day bursts (Nobservations=14,332). Mood outcomes included negative affect (sadness, anxiety, stress, anger, tiredness, difficulty concentrating; overall mean=2.79, Standard Deviation [SD]=1.32), positive affect (happiness, motivation; overall mean=4.21, SD=1.60), and behavioral dysregulation (aggression and impulsivity, overall mean=1.86, SD=1.29). Generalized linear mixed models estimated pooled, between-person and within-person associations between peak pesticide spray seasons and mood, adjusting for demographic and longitudinal factors Effect modification by sex, floricultural occupation, and cohabitation with a floricultural worker was assessed. Results: Peak spray seasons were associated with higher negative affect ({beta}=0.11 [0.06, 0.16]) and behavioral dysregulation ({beta}=0.10 [0.05, 0.15]) but not positive affect ({beta}=0.01 [-0.05, 0.07]). Associations were driven by within-person changes. Sex modified associations with negative affect, which were stronger in males than females. Floricultural occupation modified associations, with poorer mood, greater behavioral dysregulation and lower positive affect among floricultural workers than non-workers. Discussion: Peak pesticide spray seasons were associated with worsening of negative affect and behavioral dysregulation. EMA may provide a sensitive approach for detecting short-term neurobehavioral changes associated with seasonal pesticide exposure.

Background: Observational studies have linked air pollution to otitis media, but confounding and reverse causation preclude causal inference. We used two-sample Mendelian randomization (MR) to assess genetic causal effects of six air pollutants on non-suppurative otitis media, represented by otitis media with effusion (OME). Methods: Exposure GWAS for PM2.5, PM2.5 absorbance, PM2.5-10, PM10, NO2 and NOx were obtained from UK Biobank (MRC-IEU), and the outcome was FinnGen R13 H8_NONSUPPNAS (12,397 cases, 464,237 controls). Inverse-variance weighting was primary, with MR-Egger, weighted median and mode, MR-PRESSO, leave-one-out and Steiger analyses, reverse MR and exploratory multivariable MR (MVMR). Asthma, allergic rhinitis and chronic rhinosinusitis served as positive controls, and three suppurative otitis media phenotypes served as negative controls. Results: After false-discovery-rate correction, none of the six pollutants was significantly associated with OME; the sole nominal signal was PM10 (OR=1.555, 95% CI 0.947-2.553, P=0.081), which reversed with the 88-SNP pooled set (OR=0.64, 0.24-1.69, P=0.365). At 80% power, minimum detectable ORs ranged widely from 1.69 to 32.09; only PM2.5-10 and PM10 had values near 2, so moderate effects (OR 1.2-1.5) cannot be excluded. Confirmatory positive controls using phenotype-specific instruments were strongly positive, whereas negative-control outcomes showed no associations (all FDR>0.85). Every nominal reverse-MR signal had a significant MR-Egger intercept (the PM2.5 absorbance signal also showed significant heterogeneity and MR-PRESSO tests), indicating horizontal pleiotropy rather than reverse causation. MVMR was exploratory only, as conditional F statistics were below 10. Conclusions: We found no evidence for large-effect genetic causal associations between the six air pollutants and OME. These null findings argue against large, lifetime-average causal effects, and the associations reported in observational studies may instead reflect residual confounding, shared comorbidity or differences in exposure windows.

Environmental exposure involves pollutant mixtures. Building on evidence that individual bisphenols alter zebrafish larval physiology and transcriptomic profiles at ng/L concentrations, we assessed the effects of specific mixtures of BPS, BPF, and BPAF without (M1) or with (M2) BPA. Experimentally, M1 and M2 induced 4.16% and 6.54% mortality in zebrafish larvae, despite the concentration addition model predicting no toxicity. Both mixtures reduced swimming-locomotor activities. These behaviors were accompanied by organ-level functional defects, as in vivo optical mapping revealed bradycardia and increased high-frequency (30-80 Hz) brain oscillations for both mixtures, while M2 additionally altered low-frequency (0.2-4 Hz) brain activity. The neurophysiological changes were accompanied by neurovascular remodeling, with in vivo two-photon microscopy revealing decreased vascular length and branching. Finally, transcriptomic analysis revealed common M1- and M2-induced alterations linked to pathways of vascular function, neuronal communication, and metabolism. M2 altered additional pathways of cardiac and neuronal signaling, consistent with the reported organ-physiology effects. We discuss the environmental relevance of mixture exposures and assess whether BPA intensifies mixture-induced responses.

Background: Non-optimal air temperature increases the risk of preterm birth, but how temperature-related risks may translate into future population burden remains uncertain. We aimed to estimate the association between temperature and preterm birth in Sweden and assess how preterm birth burden may change under plausible future temperature conditions. Methods: We conducted a nationwide population-based cohort study of singleton births in Sweden from 1973 to 2018. Weekly mean temperature was assigned at the parish level according to maternal residence. Cox proportional hazards models with a distributed lag nonlinear model were used to estimate nonlinear and delayed associations between temperature and preterm birth. The estimated exposure response relationship and baseline hazards were then incorporated into an individual-based microsimulation of gestational progression under projected temperatures for 2025 to 2055. Future projections were examined across multiple climate models under SSP1-2.6 and SSP3-7.0 scenarios. Outcomes included the annual number and cumulative incidence of preterm births and the temperature-attributable fraction. Results: Among 4,338,825 singleton births, 211,397 (4.9%) were preterm. Temperature preterm birth associations were modest overall. The clearest increase in hazard was observed following exposure to very low temperatures, particularly -10C at short lags. Higher temperatures showed no clear increase in risk. From 2025 to 2055, the annual cumulative incidence of preterm birth and the temperature-attributable fraction was expected to remain broadly stable, with limited differences between emissions scenarios. In contrast, the absolute number of preterm births was expected to over the projection period, primarily reflecting increases in the projected number of pregnancies rather than substantial changes in temperature-associated risk. Conclusions: Very low temperatures were associated with a modest short-term increase in preterm birth risk in Sweden, hot temperatures showed little evidence of increased risk. Applying these associations to future climate conditions suggested limited changes in preterm birth incidence or the proportion attributable to temperature through 2055. However, the absolute burden of preterm birth may increase as the population at risk grows. This highlights the importance of considering demographic change alongside climate projections when assessing future maternal and neonatal health burden.

Coal-fired power plants remain a major source of fine particulate matter (PM2.5) exposure and mortality in the United States. Announced retirement dates mark when those burdens are expected to end, but rising electricity demand, partly from data centers supporting cloud computing and artificial intelligence, has led utilities and regulators to revisit them. Of 50 coal plants scheduled in January 2024 to retire before 2035, 20 had later or removed dates by January 2026. Projecting coal PM2.5 and mortality among Medicare beneficiaries from the 20 plants for 2026-2035, we estimate the revised schedule would result in 1,256 additional deaths (1,136 to 1,376), raising mortality to 3.1 times the original burden. Eighteen plants operate in balancing authorities with hyperscale data-center demand, and federal orders and utility filings supporting several plants' operation cited data-center growth. Retirement schedules are revised faster than health consequences are assessed, and those delays carry a measurable mortality cost.

Wildfire smoke exposure is increasing across the U.S., but the long-term neurological effects of smoke-specific fine particulate matter (PM2.5) and its carbonaceous components remain uncertain. Using Medicare data from 2002 through 2019, we examined incident Alzheimer's disease (AD) and Alzheimer's disease and related dementias (ADRD) among 39,678,630 fee-for-service Medicare beneficiaries followed from 2005 through 2019. We identified 3,501,414 incident AD cases over 258.5 million person-years and 8,377,416 incident ADRD cases over 248.6 million person-years. We linked the cohort with annual, high-resolution estimates of smoke and non-smoke PM2.5 mass and carbonaceous components (elemental and organic carbon) and fitted stratified Cox proportional hazards models. Per 1 g/m3 increase, smoke PM2.5 was associated with incident AD (hazard ratio [HR], 1.015, 95% confidence interval [CI], 1.005-1.026) and ADRD (1.029 [1.024-1.035]). Smoke carbonaceous fraction was also associated with AD (1.063 [1.042-1.085]) and ADRD (1.090 [1.077-1.103]). Within the ADRD endpoint, smoke-related associations exceeded their corresponding non-smoke associations on a per-unit-mass basis. Per interquartile range, associations were smaller for smoke PM2.5 (AD, 1.005 [1.002-1.008]; ADRD, 1.009 [1.008-1.011]) than for non-smoke PM2.5 (AD, 1.086 [1.079-1.094]; ADRD, 1.048 [1.043-1.053]). Associations varied across geographic, racial, socioeconomic, and clinical subgroups. Long-term wildfire smoke exposure, particularly its carbonaceous fraction, was associated with higher incidence of AD and ADRD among older U.S. adults. The associations correspond to 2,284 and 11,142 incident cases per year of AD and ADRD attributable to smoke PM2.5 among older Medicare beneficiaries, with the carbonaceous fraction accounting for most of this burden. These findings support the use of source-resolved and composition-specific smoke metrics in dementia research and wildfire-smoke health-impact assessments.

Abstract Background: Rising global temperatures are intensifying exposure to extreme heat, yet access to air conditioning (AC) remains unequal which leaves vulnerable populations without protection against the heat. Household survey data on AC ownership is scarce in low- and middle-income countries limiting the ability to identify areas of cooling gaps. Methods: In this study, we develop a geospatial machine learning framework that integrates household data from the Demographic and Health Surveys (DHS) program with high resolution climatic, socioeconomic and demographic covariates to generate a 5km resolution prediction of AC ownership across low- and middle-income countries in Africa and Asia for the year 2023. Results: The resulting map reveals strong spatial inequalities with high predicted prevalence in wealthier and urban regions, and near zero prevalence across much of Central and West Africa and rural areas. These patterns reflect the adaptation cooling gap where those most exposed to extreme heat are least able to adapt through access to cooling. Conclusion: By producing the first continental-scale, high resolution map of AC ownership, this study lays the foundation for designing and targeting equitable cooling strategies, support heat-health planning particularly in communities most affected and informing sustainable energy policy.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with the potential to disrupt metabolic processes and contribute to carcinogenesis; however, molecular evidence linking alternative and emerging PFAS to ovarian cancer (OC) remains limited. We conducted a biomarker-based case-control study integrating exposureomics with multi-omics profiling. Plasma samples from 128 patients with OC and 128 controls were analyzed for 26 PFAS, untargeted metabolomics, lipidomics, and clinical phenotypes, while urine samples from an additional 100 patients and 100 controls underwent untargeted metabolomic and clinical profiling. Single-compound, burden-based, and mixture models were integrated with PFAS-omics association scans, cross-matrix metabolite prioritization, observational exposure-omics-clinical association-chain analyses, and repeated internal cross-validation. Higher PFAS burdens were consistently associated with OC case status, and DONA, GenX, PFNA, PFPeS, PFUdA, and PFTrDA constituted an OC-prioritized six-PFAS mixture. DONA and GenX exhibited the broadest lipid-related bridging signals, particularly across phospholipids, lysophospholipids, sphingolipids, neutral lipids, and acylcarnitines. Integrated plasma and urine analyses further identified five shared metabolites-elaidic acid, hippuric acid, betaine, corticosterone, and taurocholic acid-that provided incremental and complementary discrimination beyond reference models based on clinical variables and tumor markers in internal cross-validation. Collectively, these findings demonstrate that both alternative and emerging PFAS are associated with a distinct OC-related molecular phenotype involving coordinated lipidomic, metabolomic, and hematologic alterations, while highlighting DONA and GenX as the most prominent exposure-related signals.

Objective Reducing household air pollution exposure during gestation and infancy may have longer-term benefits for child linear growth. We examined whether a liquefied petroleum gas (LPG) cookstove and fuel intervention delivered during gestation and infancy could improve height-for-age Z scores (HAZ) and reduce the risk of stunting at ages 2-5 years in India, Rwanda, and Guatemala. Materials and method The Household Air Pollution Intervention Network (HAPIN) was a randomized controlled trial that enrolled ~3200 pregnant women across Guatemala, India, Peru, and Rwanda. Women in the intervention group received an LPG cookstove and free fuel during pregnancy and until the infant reached 12 months of age. Following the HAPIN trial, we continued following children in Guatemala, India, and Rwanda (N=2169) and measured child height at ages 2, 3, 4, and 5 years (HAPIN 2.0). As prespecified in the study protocol, we used mixed-effects models, as well as linear and log-binomial regression, within the intention to treat (ITT) framework, to evaluate the interventions effect on HAZ and stunting. Subgroup analyses were performed to assess effect modification by child sex, maternal height, and intervention country. Results The intervention reduced gestational exposures to particulate matter (PM2.5: 80.7 vs 117.5 {micro}g/m3), carbon monoxide (CO: 1.3 vs 2.0 ppm), and black carbon (BC: 8.6 vs 12.1 {micro}g/m3) and infancy exposures (PM2.5: 36.9 vs 113.2 {micro}g/m3; CO: 0.60 vs 2.2 ppm). Post-trial PM2.5 exposure were similar between arms: 99.9 vs 98.7 {micro}g/m3. We found no statistically significant effect of the intervention on repeated measures of HAZ ({beta} = -0.06, 95% CI: -0.16, 0.03 p=0.204), annual HAZ, stunting, nor severe stunting at any age during the follow-up. There was no statistically significant effect modification by subgroups. Conclusion Despite substantial reductions in air pollution exposures during the trial, the LPG intervention did not improve growth or reduce stunting risk from ages 2 through 5 years in this multi-country cohort. These findings, consistent with prior results of the lack of effects on growth through 12 months, provide additional evidence that a clean cooking intervention alone may not be sufficient to address childhood stunting in low-resource settings. Future exposure-response analyses will supplement these ITT analyses.