BACKGROUND:Early-life temperature exposure, especially during oogenesis, may impact ovarian function later in life. However, the effect of ambient temperature during sensitive developmental windows on ovulation disorders remains unknown. METHODS:We investigate the associations of early-life ambient temperature exposure with incident polycystic ovary syndrome (PCOS) in the Growing Up Today Study II, a United States (US) nationwide prospective cohort. We included females born after 1989 with available outcome and exposure data during the preconception (N = 3265), gestation (N = 3265), and childhood period (N = 3521). Monthly average residential mean temperatures were estimated using the PRISM Climate Group data. We considered exposure windows included preconception (3 months prior to conception), gestational (from conception month to birth), individual trimesters, and childhood (from birth to 1 year before age at menarche). PCOS was identified by self-reported clinical diagnosis. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for PCOS per interquartile range (IQR) increase of mean temperature using Cox models. RESULTS:We identified 234 (7.2%) PCOS cases over the 14.3 ± 4.2 years from age at menarche to 2021. Higher ambient temperatures during the preconception (HR 1.38 per 13.4°C, 95% CI, 0.84-2.27), gestation (HR 1.08 per 6.4°C, 95% CI, 0.74-1.60), and childhood (HR 1.20 per 4.1°C, 95% CI, 0.91-1.59) periods were suggestively associated with higher risk of PCOS. In gestation period, only the first-trimester temperature was associated with higher risks of PCOS (HR 1.75 per 14.4°C, 95% CI, 1.06-2.87). CONCLUSION:Intervention to mitigate heat exposure during pregnancy, especially in the first trimester, may help reduce the risk of PCOS in offspring. Further research is needed to confirm these associations.

Although the menstrual cycle is a vital sign for women’s health, research investigating menstrual cycle length (MCL) trajectories across reproductive life is scarce, often categorizing just two patterns: regular and irregular. We used latent class mixed models (LCMMs) to identify MCL trajectories among 9,332 females enrolled in the Growing Up Today Study, a United States prospective cohort followed from 1996–2023. Participants who self-reported their MCL three or more times were included in the analysis. Additional demographic and health information collected from surveys were included in the descriptive statistics, stratified by trajectory classification. The best fitting LCMM identified four MCL trajectories: “always regular” (94.2% of study population), “early long transition” (2.5%), “late long transition” (3.0%), and “long to short transition” (0.2%). Those classified in the “early long transition” trajectory had a higher proportion of adulthood obesity and polyendocrine metabolic ovarian syndrome (PMOS); “late long transition” individuals had higher proportions of childhood and adulthood obesity, hirsutism, severe acne in adolescence, PMOS, hypothyroidism, hypertension, and endometriosis. The identified MCL trajectories serve as a proof of concept for identifying menstrual irregularity as a signal of disease markers warranting clinical evaluation, though further validation is needed before clinical application.

Background:Living near greenspace is associated with decreased cardiovascular disease (CVD). Greenspace estimates, however, typically represent all types of vegetation using top-down satellite images, which incorporate exposure misclassification and limit policy relevance. Objective:We studied the association between street-view greenspace measures with incident CVD using a large, long-term prospective US cohort of female nurses. Methods:We estimated the percentage of streetscapes composed of visible trees, grass, and other green (plants/flowers/fields) from 350 million street-view images using deep learning models. Estimates were applied to Nurses' Health Study participants (N = 88,788) within 500 m of their residential addresses. We used Cox models to estimate associations from 2000 to 2018 between street-view greenspace measures and risk of incident CVD, assessed through self-report, medical record review, or death certificates, and adjusted for individual- and area-level factors. Results:In adjusted models, higher percentages of visible trees were associated with lower CVD incidence (hazard ratio [HR] per interquartile range [IQR] 0.96 (95% confidence interval 0.93, 1.00]), while higher percentages of visible grass (HR 1.06 [1.02, 1.11]) and other green space types (HR 1.03 [1.01, 1.04]) were associated with higher CVD incidence. We did not observe evidence of effect modification by population density, Census region, air pollution, satellite-based vegetation, or neighborhood socioeconomic status. Findings were robust to adjustment for other spatial and behavioral factors and persisted even after adjustment for traditional satellite-based vegetation indices. Discussion:Specific greenspace types may be protective or harmful for CVD. Aggregating greenspace into a single exposure category limits epidemiological research and potential interventions to increase health-promoting greenspace.

The Health Effects Institute recently completed an extensive research initiative to investigate novel approaches to improve assessment of long-term exposure to outdoor air pollution for health studies in North America and Europe. This overview synthesizes the key results, strengths, and limitations, along with other key research and future research needs. Exposures predicted from the various models, including those accounting for daily mobility patterns and outdoor-indoor infiltration rates, generally resulted in moderately to highly correlated exposure estimates (correlation > 0.7). Health effect estimates associated with the alternative exposures were similar, albeit with some notable differences in the magnitude – but not the direction — of the associations. This research initiative can inform decisions about estimating air pollution exposure in epidemiological studies, as investigators balance concerns about bias, efficiency, and resource needs. Future work is needed to replicate findings in other studies and regions. Other areas of future work include generating representative validation data for long-term exposure estimates, propagating exposure measurement error more fully into health effect estimates and improving understanding of the influence of indoor environments.

Attention-deficit/hyperactivity disorder (ADHD) is associated with social role dysfunction and loneliness. Household dogs and cats may facilitate social interactions and emotional support, but little is known about their associatons with social role function and loneliness among youth with ADHD. In this study, we addressed these associations in 1056 participants from the Growing Up Today Study (GUTS), a cohort of children from the Nurses’ Health Study (NHS)II. ADHD was determined using maternal reports and participants’ self-reports of diagnosis and/or treatment. Pet ownership was assessed during childhood and early adolescence in the 1999 questionnaire, with categories: (1) Dog and cat; (2) Dog but no cat; (3) Cat but no dog; (4) No dog or cat. Outcomes included overall social role functioning (assessed in 2013), quality of interpersonal relationships with mothers (2005) and romantic partners (2010), and loneliness (assessed repeatedly between 2007 and 2016). Overall social role functioning was analyzed using the chi-square test; quality of interpersonal relationships and loneliness were analyzed using generalized mixed models. No significant differences were observed in overall social role functioning across pet categories. Compared to those who had no dog or cat, dog and/or cat owners did not differ in their likelihood of reporting high-quality interpersonal relationships. Similarly, dog and/or cat ownership was not associated with lower likelihood of loneliness compared to those who had no dog or cat. Future studies could examine repeated measures of pet ownership and other aspects of pet ownership, such as emotional attachment, to clarify potential associations with social and psychological outcomes.

Abstract Background Low-risk and favourable-intermediate risk prostate cancer patients are eligible for conservative management. We estimated the probability of conservative management uptake and 10-year rates of curative treatment initiation following conservative management in a prospective cohort of 2,872 health professionals diagnosed with low or favorable-intermediate risk prostate cancer. Methods The study included males with low-risk (grade group 1, stage≤cT2a, prostate-specific antigen (PSA)<10ng/ml) and favourable-intermediate risk (grade group 1, stage cT2b-cT2c or PSA 10-20ng/ml, or grade group 2, stage≤cT2a and PSA<10ng/ml) prostate cancer whom were diagnosed 1986-2019 and were participants in the Health Professionals Follow-up Study. We estimated the variation in conservative management uptake by age and calendar year at diagnosis, prostate cancer risk group, and pre-diagnostic lifestyle using Poisson regression. We estimated 10-year rates of curative treatment initiation in patients that initially received conservative management using Fine and Gray models adjusted for competing risks of lethal progression (prostate cancer death, metastasis, or initiation of hormone therapy) and other-cause death, censoring at December 2022. We assessed the variation in continuation to curative treatment with Cox models. Results The uptake of conservative management was 16% (444/2872). Conservative management was higher in older patients (1 year of additional age - Relative Risk (RR): 1.08, 95% CI: 1.06 - 1.11), in later calendar years (1 additional year - RR: 1.07, 95% CI 1.05 - 1.10)), and in neighborhoods of higher socioeconomic status (1 standard deviation rise - RR: 1.16. 95% CI 1.03 - 1.30). Uptake was lower in favorable-intermediate risk, rather than low-risk, prostate cancer (RR: 0.47. 95% CI 0.35 - 0.61). Among the 444 patients who initially received conservative management, when adjusted for competing risks of lethal progression and other-cause death, the 10-year curative treatment incidence was 22%. Patients were more likely to continue to curative treatment if they were younger at diagnosis (1 year of additional age - Hazard Ratio (HR): 0.96, 95% CI: 0.93 - 0.99) or had healthier post-diagnostic lifestyles (increase of 1 in joint measure of physical activity, BMI, and smoking, scored 0-3 - HR: 1.47, 95% CI 1.01 - 2.15). Conclusion We found age at diagnosis, calendar year at diagnosis, prostate cancer risk group, and neighborhood-level socioeconomic status to affect conservative management uptake, and age at diagnosis and post-diagnostic lifestyle to affect rates of curative treatment initiation following conservative management, in low/favorable-intermediate risk prostate cancer patients. These results could inform the clinical management of low/favorable-intermediate risk prostate cancer. Citation Format: Isaac Allen, Jane Bailey Vaselkiv, Hannah E. Guard, Sinead Flanagan, Hari Iyer, Kevin Kensler, Jaime E. Hart, Mark A. Preston, Andreas Pettersson, Keyan Salari, Edward L. Giovannucci, Adam S. Kibel, Lorelei A. Mucci, Timothy Rebbeck. Uptake of conservative management, and uptake of curative-intent treatment following conservative management, in low and favorable-intermediate risk prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2346.

Individual environmental exposures have been linked to later-life cognition, but their combined effects, particularly on cognitive decline, remain unclear. Using data from 18,462 participants in the Nurses' Health Study cognitive substudy, we assessed the independent and joint associations of long-term exposure to multiple environmental factors with cognitive function and decline, using generalized estimating equations (GEE) and quantile g-computation models, allowing exposures to operate in both protective and harmful directions. Cumulative average exposures to air pollution, seasonal temperature, noise, greenness, light at night (LAN), and neighborhood socioeconomic status (nSES) from 1988 onward were assigned to updated residential addresses. In multiexposure GEE models, each interquartile-range increase in greenness and nSES was associated with 0.026 (95% CI: 0.013, 0.040) and 0.017 (0.005, 0.029) standard-unit increases in cognitive function, respectively. Higher summer temperature was associated with a 0.011 (-0.023, 0.000) standard-unit decrease. Jointly, each quartile increase across all exposures corresponded to a 0.013 (0.001, 0.024) standard-unit higher cognitive score. Higher summer maximum temperature and LAN were associated with faster cognitive decline only in single-exposure models, while no significant joint association with decline was observed. These findings suggest that enhancing protective exposures (greenness, nSES) may help offset the adverse effects of harmful exposures (high temperature, LAN) and support healthier cognitive aging.

Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal and perinatal morbidity, yet modifiable environmental risk factors remain poorly characterized. Prior studies typically have only examined a limited number of exposures and have rarely distinguished HDP subtypes (ie, gestational hypertension, preeclampsia, eclampsia, and chronic hypertension with or without superimposed preeclampsia) or accounted for residential mobility during pregnancy. To address these gaps, we conducted a spatial and contextual exposome study of HDP using linked electronic health records (EHR) and vital statistics data in Florida. We analyzed 686 412 singleton pregnancies conceived between 2013 and 2018, using computable phenotyping to distinguish HDP subtypes. A total of 245 spatial and contextual exposome measures spanning natural, built, and social environments were linked to residential histories from conception through gestational week 19. Using a two-phase double machine learning (DML) framework with exposure-specific, directed acyclic graph-guided confounder adjustment, we conducted discovery and replication analyses, followed by multi-treatment DML to estimate effect sizes. In Phase 1, 26 exposome measures replicated for gestational hypertension and 34 for overall HDP. In Phase 2, 12 measures remained associated with gestational hypertension and 11 with overall HDP, including air toxicants, meteorological factors, ultraviolet radiation, neighborhood crime indicators, environmental noise, and proximity to coastline. No exposures passed multiple-comparison thresholds for preeclampsia or eclampsia. These findings demonstrate that the spatial and contextual exposome contributes to HDP in a subtype-specific manner. Integrating EHR-linked phenotyping, residential mobility, and causal machine-learning methods offers a scalable framework for identifying environmental factors relevant to HDP prevention.

Melatonin regulates circadian rhythms, metabolism, and immunity. Its primary metabolite, 6-sulfatoxymelatonin (aMT6s), is a biomarker linked to cancer risk and metabolic disorders. However, genetic determinants of aMT6s remain poorly understood, with only one prior GWAS limited to an East Asian cohort. We conducted the first multi-ancestry genome-wide association meta-analysis of urinary aMT6s, integrating 11,744 participants from five cohorts: East Asians (Taiwan Biobank), European women (Nurses’ Health Studies), European men (MrOS), and multiethnic participants (MEC). aMT6s was measured from overnight or first-morning urine samples. Association analyses were conducted using both ancestry-aware meta-regression (MR-MEGA) and fixed-effects meta-analysis (METAL). Polygenic risk scores (PRS) were constructed with PRS-CSx and evaluated in phenome-wide analyses in the Mass General Brigham Biobank and UK Biobank. No genome-wide significant loci were identified, and previously reported East Asian signals were not replicated. At suggestive significance, 23 loci emerged, with eight supported by both MR-MEGA and METAL. Several loci showed ancestry-specific heterogeneity, suggesting that genetic associations with urinary aMT6s may vary by population context, although limited power and cohort heterogeneity may also contribute. PRS analyses identified associations with sleep duration and metabolic traits, including type 2 diabetes, but these findings require cautious interpretation. Overall, our results suggest that urinary aMT6s is influenced by a polygenic and potentially population-dependent genetic architecture. This study provides a multi-ancestry framework for investigating melatonin-related biomarkers and highlights the importance of careful interpretation across diverse populations.

Abstract Background /Aims: Research on the link between circadian disruption, particularly from night shiftwork, and colorectal cancer (CRC) has been limited and inconsistent. Few studies have investigated whether other sources of circadian disruption may be associated with CRC or its precursors. One source is solar jetlag that leads to residents in the western vs. eastern part of a time zone to receive less light exposure in the morning and greater light exposure at night, likely suppressing melatonin release and reducing sleep propensity and sleep duration. The objective of this study was to examine the association between solar jetlag and CRC precursors in the United States. Methods: Our study consisted of Nurses’ Health Study (NHS) II participants who received one or more lower endoscopies between 1991-2015. Cases self-reported colorectal polyps in biennial questionnaires and were confirmed by medical record review. As a proxy for solar jetlag, we calculated the distance from the time zone meridian (TZM), based on participant’s geocoded residential address histories, which was modeled as a per 5-degree increase in longitude moving east to west within a time zone. Time-varying multivariable-adjusted logistic regression models for clustered data estimated odds ratios (OR) and 95% confidence intervals (CI). Results: Over a 24-year follow-up period, 72,612 NHSII participants received at least one lower endoscopy; 4,450 conventional adenomas and 4,873 serrated polyps were diagnosed. We found no statistically significant association between distance to TZM and conventional adenomas (OR=1.03; 95% CI=0.99,1.07) or serrated polyps (OR=0.98, 95% CI= 0.95,1.02). Results were similarly null in analyses stratified by age at endoscopy (<50 vs. ≥ 50 years), polyp size, anatomical location, malignant potential, or reason for endoscopy. We observed statistically significant effect modification in which positive associations were observed in the Mountain time zone, among those never engaging in rotating night shift work, areas with higher ultraviolet radiation, and lower latitudes. Conclusions: Although we did not observe an association between distance to TZM and CRC precursors, we found significant effect modification in the association by various covariates determined a priori. These findings require further research into the mechanisms of action and confirmation in other cohorts. Citation Format: Bethsaida Cardona, Trang VoPham, Kyriaki Papantoniou, Eva Schernhammer, Jaime E. Hart, Mingyang Song, Andrew T. Chan. Circadian disruption from time zone position and risk of colorectal cancer precursors in women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6259.

Growing evidence suggests that exposure to fine particulate matter (PM2.5) may accelerate cognitive decline and increase dementia risk, but the roles of individual PM2.5 components, particularly when accounting for exposure measurement error, remain unclear. We followed 12,824 participants in the Nurses' Health Study cognition substudy (2000-2008). One-year average PM2.5 component concentrations preceding each participant's first cognitive assessment were assigned based on residential address. A global cognitive score was calculated as the mean of z-scores from six tests, and individual rates of cognitive decline were estimated using linear mixed models with random intercepts and slopes. Using information on the relationships of personal exposures and nearest-monitor PM2.5 components from a prior validation study, we employed double/debiased machine learning (DML) method to estimate associations between PM2.5 components and cognitive decline while accommodating high-dimensional multi-pollutant exposures and accounting for exposure measurement error. Higher exposure to several PM2.5 components were associated with changes in rates of cognitive decline. In multi-pollutant models without measurement error correction, each doubling of chloride (Cl) concentration was associated with a 0.0003 (95% CI: 0.0000, 0.0005) standard unit slower annual rate of cognitive decline, while each doubling in silicon (Si) was associated with a -0.0025 (95% CI: -0.0050, 0.0000) faster rate of decline. After correction for measurement error, associations generally strengthened: higher bromine (Br), manganese (Mn), and lead (Pb) were significantly associated with faster cognitive decline. In contrast, higher strontium (Sr) and vanadium (V) were associated with slower decline. Our findings suggest that long-term exposure to certain PM2.5 components, and their sources, may be more detrimental to cognitive aging than others, and highlight the critical need to correct for measurement error when assessing the health impacts of PM2.5 and its components. More research is needed to confirm these findings, ideally with access to larger validation studies of component exposures.

BACKGROUND:Sudden cardiac death (SCD) is an important contributor to the global burden of cardiovascular disease. Previous studies have reported an association with extremes in temperature in the hours and days leading up to SCD, but there has been little investigation focusing on the months and year before an SCD event. Therefore, the objective of this study was to investigate the relationship between short-, medium-, and long-term temperature and SCD. METHODS:Temperature predictions using 800-m Parameter-Elevation Regressions on Independent Slopes Model data were used to estimate monthly moving average temperature. Data on temperature were appended to each Nurses' Health Study participant's geocoded residential addresses. SCD cases were determined on the basis of medical record review and next-of-kin reports. Time-varying Cox proportional hazards models were used to assess the association between exposure 1- and 12-month moving averages of temperature and SCD. Individual risk factors, socioeconomic status, and cardiovascular comorbidities were considered as confounders in the final models. RESULTS:Over the follow-up period, there was a total of 428 definite and 36 probable SCD cases among the 118 636 participants. One- and 12-month moving average temperatures were inversely associated with SCD in the basic, risk factor, and fully adjusted models. For example, in the parsimonious individual risk factor model with definite cases only, per interquartile range (15.27 °C for the 1-month moving average temperature, 4.72 °C 12-month moving average temperature) increase in temperature, the hazard ratios for definite SCD were 0.58 (95% CI, 0.44-0.77) for the 1-month and 0.76 (95% CI, 0.66-0.88) for the 12-month moving average. CONCLUSIONS:After controlling for risk factors and cardiovascular morbidities, lower temperatures were associated with SCD. This study demonstrates that short-, medium-, and long-term cold temperature also play an important role in SCD.

BACKGROUND:Over 3.5 million US men are living with prostate cancer (Pica), many with underlying cardiovascular disease (CVD). Fine particulate matter (PM2.5) contributes to higher CVD mortality through inflammation and other mechanisms, and so may increase non-cancer mortality in men with PCa. METHODS:We conducted a retrospective cohort study of 886,876 men diagnosed with PCa between 2000 and 2015 and followed through 2018 across eight state cancer registries. Annual average predictions of five residential PM2.5 component exposures (elemental carbon (EC), organic carbon (OC), nitrate, ammonium (NH4+), sulfate (SO42-)) were obtained from an ensemble-based machine learning model and assigned to geomasked addresses at diagnosis within 50 m (urban) or 1 km (rural). Adjusted hazard ratios (aHR) for associations of components separately and as a mixture with all-cause, PCa, and CVD mortality were estimated from covariate adjusted Cox models. RESULTS:There were 233,898 deaths over 5,836,741 person-years. Per interquartile range (IQR) increase, OC (aHR 1.03 [95 % CI: 1.02-1.04]), NH4+ (aHR 1.02 [1.01-1.03]), and SO42- (aHR 1.11 [1.09-1.13]) were associated with all-cause mortality. CVD mortality was associated with higher EC (aHR: 1.04 [1.02-1.06]), OC (aHR 1.05 [1.03, 1.07]), NH4+ (aHR 1.09 [1.06-1.12]) and SO42- (aHR 1.19 [1.15-1.24]). There were no associations with nitrates or PCa mortality. Per IQR, PM2.5 components mixtures were associated with higher all-cause (aHR 1.03 [1.02-1.04]), PCa (aHR 1.02 [0.99, 1.05]), and CVD mortality (aHR 1.08 [1.05, 1.11]). DISCUSSION:Certain PM2.5 components were associated with higher all-cause and CVD mortality in men with PCa. Studies of air pollution in cancer survivors should consider impacts on non-cancer mortality.

RATIONALE:Short-term ambient air pollution exposure may worsen asthma health. Effects of longer-term air pollution exposures on asthma exacerbations and risk mitigation by dietary factors are unknown. OBJECTIVES:To examine associations between 48-month air pollution exposure and asthma exacerbations and whether a plant-based diet modifies these relationships. METHODS:Women with asthma in the Nurses' Health Study II were followed from 1997 to 2014. We estimated 48-month time-varying average residential ambient fine particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) exposures using nationwide spatiotemporal models. Plant-based diet index (PDI) scores were calculated on the basis of food frequency questionnaires administered every 4 years. Air pollution and diet assessments were repeated measures within individuals, whereas asthma exacerbations in the past year were captured in 1998 and 2014. Average air pollutant exposure was assessed in the 48 months before each outcome assessment year. Single-pollutant and multipollutant logistic regression models with generalized estimating equations to account for repeated measures within participants were used to assess the effects of each air pollutant on asthma exacerbation risk. We also evaluated effect measure modification by PDI scores on the effects of each air pollutant on asthma exacerbation risk using two-way interaction terms. RESULTS:Of 4,326 participants, median 48-month PM2.5, NO2, and O3 concentrations were 13.7 μg/m3, 12.0 ppb, and 25.5 ppb, respectively, from July 1993 to June 1997 and 8.9 μg/m3, 6.6 ppb, and 27.8 ppb, respectively, from July 2009 to June 2013. In adjusted single-pollutant models, greater exposures to both PM2.5 and NO2 were associated with higher odds of asthma exacerbation (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.14-1.80; and OR, 1.25; 95% CI, 1.12-1.38, respectively). In multipollutant models, greater exposure to NO2 was associated with higher odds of asthma exacerbation (OR, 1.23; 95% CI, 1.06-1.42). There were no statistically significant interactions between pollutants and PDI score on asthma exacerbations. CONCLUSIONS:Long-term exposure to ambient NO2 and PM2.5, even at low concentrations, may increase asthma exacerbation risk in women but is not attenuated by a plant-based diet as measured herein. Further research is needed on the long-term effects of inhaled pollutants on asthma health and personal, modifiable strategies to reduce risk.

BACKGROUND:The U.S. Environmental Protection Agency set drinking water Maximum Contaminant Levels (MCLs) for several PFAS in 2024, yet few evaluations of earlier state regulations have been conducted. We evaluated the impact of regulatory actions taken by the New Jersey Department of Environmental Protection (NJDEP) to set PFAS drinking water standards in NJ community water systems (CWS). METHODS:The NJDEP performed statewide testing of CWS PFAS levels in 2006 and 2009-2010, which were supplemented by additional CWS data reported to NJDEP and federal monitoring from 2013 to 2015 using methods including EPA method 537 and 537.1. The NJ Drinking Water Quality Institute formally recommended MCLs to NJDEP for PFNA (13 ng/L) in July 2015, for PFOA (14 ng/L) in March 2017, and PFOS (13 ng/L) in June 2018. Routine CWS monitoring began in 2019, covering the study period of 2006-2025. Quarterly PFOA, PFOS, and PFNA testing results were obtained from 47 CWS with monitoring data before and after the MCL recommendations. Using linear regression, we fit interrupted time series models to estimate the change and trend in PFAS levels following proposed MCLs. RESULTS:We obtained 4,150, 4,086, and 4,053 monitoring results for PFOA, PFOS, and PFNA, respectively. We observed declines in the proportion of PFOA (49.3% v s 14.9%), PFOS (11.6% vs 3.5%), and PFNA (23.6% vs 1.5%) results above the MCL following recommendation of PFAS regulations (chi-squared P < 0.001). There was a 55% (95% CI: 11%, 77%) and 50% (95% CI: 14%, 71%) decline in PFOA and PFNA levels, respectively, following recommendation of MCLs. There were declines in quarterly trend in PFOS (2%, 95% CI: 0%, 5%) and PFNA levels (6%, 95% CI: 2%, 9%). DISCUSSION:Regulated PFAS levels declined following formal recommendation of MCLs to NJDEP. Actions taken toward establishing regulations to limit drinking water PFAS exposures can achieve substantial reductions.

Greenspace exposure in the period surrounding pregnancy may influence autism spectrum disorder (ASD) risk in offspring by reducing risk factors or mitigating effects through various pathways. Current research is limited but suggestive. We explored the association between greenspace exposure during pregnancy and ASD risk, assessing potential periods of susceptibility: 3 months preconception; first, second, and third trimester; and 3 months post-birth. We conducted a nested case-control study within the Nurses’ Health Study II (NHSII), a US prospective cohort followed up biennially. Cases were children of NHSII participants who were maternally reported to have ASD (n = 245). Controls were randomly selected from the full cohort and frequency matched to cases by birth year (n = 1526). Greenspace exposure was assessed using the satellite-based normalized difference vegetation index (NDVI) measured within 270 m and 1230 m radial buffers of the residential address of participants. Temporally matched, time-linked NDVI was used to calculate greenspace exposure for each potential period of susceptibility. Multivariable adjusted logistic regression models were applied to obtain effect estimates. Greenspace exposure during pregnancy was inversely associated with ASD risk when NDVI was measured within a 270 m radial buffer of the residential address. Specifically, an interquartile range (0.144) increase in NDVI during the first trimester decreased the odds of ASD by 25% (odds ratio=0.75, 95% confidence interval: 0.56, 0.99) in a model adjusting for other time periods of exposure. There was no other 3-month exposure period significantly associated with ASD. Adjusting for PM2.5 did not change results. The analysis of NDVI measured within a 1230 m radial buffer showed weaker and inconsistent associations. This study found that greenspace exposure during pregnancy was inversely associated with ASD, with the first trimester being a critical exposure period. Implications for urban and city design provide compelling reasons to increase research in this field. Ours is the first study to report an inverse association between greenspace exposure during pregnancy and autism spectrum disorder risk in offspring that was specific to the first trimester. An interquartile range increase in satellite-based normalized difference vegetation index exposure (0.114) within a 270 m radial buffer of the residential address decreased the odds of ASD by 25% (odds ratio=0.75, 95% confidence interval: 0.56, 0.99). Future research is warranted to confirm these findings in other populations and explore the pathways by which greenspace may mitigate risk. Implications for urban and city design provide compelling reasons to increase research in this field.

Background:Men with prostate cancer (PCa) may be especially vulnerable to per- and polyfluoroalkyl substances (PFAS) exposure due to their endocrine-disrupting and cardiometabolic impacts and cardiotoxicity and immune suppression of treatments. Objective:A pilot study was launched to measure serum and tap water PFAS concentrations in PCa survivors. Methods:Men with PCa were recruited from Rutgers Cancer Institute between February 2025 and March 2026, with ongoing enrollment and follow-up. Eligible men were aged ≥40 years on active surveillance or within 3-12 months of initial definitive treatment. Participants provided blood and residential tap water samples, which were analyzed using mass spectrometry (serum) and modified EPA method 537 (water). Geometric means were used to summarize PFAS concentrations by race and assess serum-tap water correlations. Results:Of 235 eligible patients, 124 (60%) enrolled. Median age was 64 years; 63% were non-Hispanic White, 43% had a Gleason score ≤6. Roughly half of participants provided serum and/or tap water samples. In serum, six PFAS analytes had >80% detection; of these analytes, median concentrations ranged from 0.13 ng/mL (IQR: 0.07-0.20) for PFHpS to 2.55 ng/mL (IQR:1.54-3.82) for nPFOS. Among 74 tap water samples, 9 PFAS analytes had >60% detection; of these, median concentrations of PFNA (0.56 ng/L; IQR: 0.33-0.75), PFOA (3.75 ng/L; IQR: 1.21-5.27), and PFOS (2.29 ng/L; IQR: 0.46-2.89), were below New Jersey Maximum Contaminant Levels. Non-White participants had significantly higher levels of multiple PFAS analytes in both serum and tap water. Serum-tap water correlations were modest (r=0.22-0.41). Significance:The pilot study has demonstrated both the feasibility and importance of studying PFAS exposure pathways as well as potential impacts of PFAS exposure in diverse populations. Impact Statement:This study provides some of the first estimates of PFAS exposure among prostate cancer patients in serum and tap water, showing moderate correlations between tap water and serum concentrations of specific PFAS analytes. These findings can support larger studies to identify environmental exposure sources and evaluate the role of PFAS in prostate cancer progression and outcomes.

Land-based military deployers to Afghanistan and/or Southwest Asia (SWA) encountered exposure to high concentrations of respirable particulate matter (PM) from multiple sources, including desert dust, burn pit smoke, and military occupations. Adverse lung health effects following deployment have been noted, including upper and lower respiratory tract symptoms, asthma, and small airway and other abnormalities on lung biopsy. The American Thoracic Society (ATS) convened a workshop in 2018 to review studies assessing postdeployment respiratory health, describe emerging research, and highlight knowledge gaps. Progress on understanding postdeployment health prompted a second ATS workshop to update current knowledge by (1) reviewing new studies linking exposure assessments to symptoms and/or clinical disease; (2) describing the spectrum of lung pathology reported in previously deployed personnel; (3) evaluating current knowledge of long-term health outcomes after deployment; (4) reviewing data from recent experimental models of deployment-related respiratory diseases (DRRDs); and (5) providing recommendations for future research priorities. Workshop participants agreed that there is substantial evidence linking deployment-related exposures to respiratory symptoms, pulmonary diagnoses, and lung pathology. Knowledge gaps include understanding: (1) the extent and mechanisms through which specific exposures result in impaired pulmonary function, small airways disease, and potentially future chronic pulmonary diseases; (2) the contribution of exposure-related foreign material in the lung to clinical and pathologic findings; and (3) the relationship of pathologic findings to respiratory health, especially those involving small airways.

Abstract Background: Despite treatment advances, the five-year relative survival is 50% for patients with invasive ovarian cancer. Increasing literature demonstrates that distress, depression, and other psychosocial stressors negatively influence survival. Exposure to green spaces - e.g., parks, gardens, forests and street trees - has been associated with lower stress hormone levels and reduced risk of depression. Thus, our objective was to evaluate if greenness exposure, pre-diagnosis, was associated with improved ovarian cancer survival among cases in the Nurses' Health Study (NHS) and NHSII cohorts. Methods: Greenness exposure was assessed seasonally within nearby (270m) and walkable (1230m) distance buffers surrounding NHS and NHSII cohort participants’ residential addresses (updated biennially from 1988 to 2018) using the Normalized Difference Vegetation Index (NDVI; 30m2 resolution)-a satellite-derived indicator of photosynthetic vegetation cover. We used time-varying Cox proportional hazards models to assess cumulative, pre-diagnosis, maximum average NDVI exposure and ovarian cancer specific survival among confirmed cases. Models were adjusted for age and calendar time, US region, population density, and pre-diagnosis factors associated with ovarian cancer survival, including menopause status, family history of breast or ovarian cancer, and parity. Time-varying depression - self-reported antidepressant use or clinician diagnosed depression - was additionally adjusted to evaluate potential mediation of the relationship between greenspace exposure and survival. Results: Analyses included 1,052 women with confirmed ovarian cancer. We observed a suggestive decrease in ovarian cancer mortality risk for a 0.1 unit (10%) increase in cumulative pre-diagnosis 270m NDVI exposure (aHR 0.92; 95% CI 0.79, 1.07) when adjusting for all factors except depression. Adding depression led to a slightly stronger inverse association (aHR 0.90 95% CI 0.76, 1.07), although it did not reach statistical significance. No association was observed for cumulative pre-diagnosis 1230m NDVI exposure. Conclusions: Pre-diagnosis near-residence greenness exposure was suggestively associated with improved survival among ovarian cancer cases. Adjusting for depression status slightly strengthened the inverse association, indicating that the association of greenness with survival is unlikely to be fully explained by depression status; other potential mechanistic pathways (e.g., pollution and temperature reduction, improved sleep quality, physical activity, vitamin D levels and immune function) should be explored. On-going analyses will assess associations by histologic subtype. Future studies are needed to assess the type and quality of nature exposure, including but not limited to green spaces, with risk and survival among patients, with stratification by geographic and ecological regions. Citation Format: Jaileene Pérez-Morales, Hari S. Iyer, Jaime E. Hart, Francine Laden, Laura D. Kubzansky, Joshua M. Moreau, Guillermo Armaiz-Pena, Shelley Tworoger, Charlotte Roscoe. Pre-diagnosis green space exposure and survival in women diagnosed with ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6254.

RATIONALE:Greater ambient air temperatures may have implications for respiratory health. While prior research has primarily examined the associations of air temperature with lung health in the general population, individuals with chronic obstructive pulmonary disease (COPD) may be particularly susceptible. This study aims to assess the associations between air temperature and pulmonary function, as well as biomarkers of inflammation and oxidative stress, in this potentially susceptible population. METHODS:We conducted a study of 166 participants with COPD (either a former or no history of smoking) from eastern Massachusetts, United States, who completed up to 4 visits over 12 months at the VA Boston Healthcare System between 2012 and 2017, yielding 620 observations. Daily mean temperature exposures, at a spatial resolution of 4 × 4 km, were assigned to geocoded home addresses. We used generalized additive mixed models to investigate associations of short-term temperature exposures at 0- to 1-day, 2- to 6-day, 0- to 6-day, and 0- to 13-day moving averages with repeated lung function measurements, blood biomarkers of systemic inflammation (high-sensitivity C-reactive protein [hsCRP], interleukin 6, soluble vascular cell adhesion molecule 1), and urinary biomarkers of oxidative stress (8-hydroxy-2'-deoxyguanosine, malondialdehyde), adjusting for confounders (eg, air conditioner usage and season). We performed mediation analyses to determine if temperature-lung function relationships were mediated by inflammatory or oxidative stress pathways. RESULTS:The population was 97.0% male, mean (SD) age = 72.8 (8.4) years, mean (SD) percent predicted forced expiratory volume in 1 second (FEV1%) = 66.2 (21.8), and mean (SD) temperature = 10.2 °C (10.4 °C). Higher temperature exposures at all moving averages were associated with lower FEV1. For example, per 5 °C increase in temperature at lags of 0 to 1 and 0 to 13 days, FEV1 decreased by (mL, 95% CI) 12.06 (-23.14 to -0.98) and 16.24 (-29.23 to -3.25), respectively. Similarly, higher temperature exposures were associated with lower forced expiratory volume in 1 second/forced vital capacity. There were positive associations between higher temperature across all moving averages and higher hsCRP. For instance, a 5 °C increase in temperature at lags of 0 to 1 days and 0 to 13 days was associated with percent increases in hsCRP of 6.37 (95% CI, 1.05-11.97) and 9.40 (95% CI, 3.02-16.16), respectively. hsCRP did not mediate the temperature-lung function relationship. Associations were similar, adjusting for indoor and outdoor air pollution. No associations were observed with forced vital capacity or other inflammatory or oxidative stress biomarkers. CONCLUSION:Short-term exposures to higher air temperatures were associated with lower lung function and higher hsCRP concentrations among individuals with COPD, suggesting that rising air temperature may be an important determinant of health in this susceptible group.