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Iran has a longstanding challenge in supplying water during prolonged drought periods. This has drawn considerable attention towards the dam industry over the past four decades, leading to the study, construction and operation of several large dams. These dams played a critical role in controlling the massive floods of 2019 and 2020, among others. Nevertheless, due to the increased intensity and frequency of extreme events because of climate change, the downstream regions of these large storage dams still face significant damages. This is mainly attributed to the insufficient dredging of rivers and tributaries, lack of rule curve and operation guideline for some storage dams, inaccurate prediction of flood volume, violation of land-use and water management action plans, promotion of industries with high water need, and floodplain encroachment. In this study, we aim to evaluate the performance of several large dams in the Karkheh and Karoon river basin, located in southwestern Iran, in managing the floods took place in the aforementioned periods. We also discuss the challenges and the lessons learned, with suggestions for improving the flood management in the country.

Background: Investigations into long-term fine particulate matter (PM 2.5 ) exposure's impact on nonaccidental and cardiovascular (CVD) deaths primarily involve nonrepresentative adult populations at concentrations above the new Environmental Protection Agency annual PM 2.5 standard., Methods: Using generalized linear models, we studied PM 2.5 exposure on rates of five mortality outcomes (all nonaccidental, CVD, myocardial infarction, stroke, and congestive heart failure) in 12 US states from 2000 to 2016. We aggregated predicted annual PM 2.5 exposures from a validated ensemble exposure model, ambient temperature from Daymet predictions, and mortality rates to all census tract-years within the states. We obtained covariates from the decennial Census and the American Community Surveys and assessed effect measure modification by race and education with stratification., Results: For each 1-µg/m 3 increase in annual PM 2.5 , we found positive associations with all five mortality outcomes: all nonaccidental (1.08%; 95% confidence interval [CI]: 0.96%, 1.20%), all CVD (1.27%; 95% CI: 1.14%, 1.41%), myocardial infarction (1.89%; 95% CI: 1.67%, 2.11%), stroke (1.08%; 95% CI: 0.87%, 1.30%), and congestive heart failure (2.20%; 95% CI: 1.97%, 2.44%). Positive associations persisted at <8 µg/m 3 PM 2.5 levels and among populations with only under 65. In our study, race, but not education, modifies associations. High-educated Black had a 2.90% larger increased risk of CVD mortality (95% CI: 2.42%, 3.39%) compared with low-educated non-Black., Conclusion: Long-term PM 2.5 exposure is associated with nonaccidental and CVD mortality in 12 states, below the new Environmental Protection Agency standard, for both low PM 2.5 regions and the general population. Vulnerability to CVD mortality persists among Black individuals regardless of education level., Competing Interests: Disclosure: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Mechanistic studies of the effects of environmental risk factors have been exploring the potential role of microRNA(miRNAs) as a possible pathway to clinical disease. In this study we examine whether levels of toenail metals are associated with changes in extracellular miRNA(ex-miRNA) expression., Methods: We used data derived from the Normative Aging Study from 1996 to 2014 to conduct our analyses. We looked at associations between measured toenail metals: arsenic, cadmium, lead, manganese, and mercury and 282 ex-miRNAs in this population using canonical correlation analyses (CCAs) and longitudinal median regression. We adjusted for covariates such as age, education, body mass index, drinking and smoking behaviors, diabetes, and where available, seafood consumption. The p-values obtained from regression analyses were corrected for multiple comparisons. Ex-miRNAs identified to be associated with toenail metal levels were further examined using pathway analyses., Results: Our dataset included 937 observations from 589 men with an average age of 72.9 years at baseline. Both our correlation and regression analyses identified lead and cadmium as exposures most strongly associated with ex-miRNA expression. Numerous ex-miRNAs were identified as being associated with toenail metal levels. miR-27b-3p, in particular, was found to have high correlation with the first canonical dimension in the CCA and was significantly associated with cadmium in the regression analysis. Pathway analyses revealed messenger RNA (mRNA) targets for the ex-miRNAs that were associated with a number of clinical disorders including cancer, cardiovascular disease, and neurological disorders, etc. CONCLUSION: Toenail metals were associated with changes in ex-miRNA levels in both correlational and regression analyses. The ex-miRNAs identified can be linked to a variety of clinical disorders. Further studies are required to validate these findings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Joel Schwartz and Andrea Baccarelli reports financial support was provided by National Institute of Environmental Health Sciences. Feiby Nassan reports a relationship with Novo Nordisk Inc that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Earlier studies have revealed microRNAs (miRNAs) as potential biomarkers for neurological conditions, however, such evidence on psychiatric outcomes is limited. We utilized the Normative Aging Study (NAS) cohort to investigate the associations between extracellular miRNAs (ex-miRNA) and psychiatric symptoms among a group of older male adults, along with the targeted genes and biological pathways. We studied 569 participants with miRNA profile primarily measured in extracellular vesicles isolated from plasma, and psychiatric symptoms reported over 1996-2014 with repeated measures. Global and dimension scales of psychiatric symptoms were measured via the administration of Brief Symptom Inventory (BSI) per visit covering nine aspects of psychiatric health, such as anxiety, depression, hostility, psychoticism, etc. Ex-miRNAs were profiled using small RNA sequencing. Associations of expression of 395 ex-miRNAs (present in >70% samples) with current mental status were assessed using single-miRNA as well as Least Absolute Shrinkage and Selection Operator (LASSO)-based multi-miRNAs linear mixed effects models adjusting for key demographic and behavioral factors. Biological functions were explored using pathway analyses. We identified ex-miRNAs associated with each BSI scale. In particular, hsa-miR-320d was consistently identified for two global scales. Similar overlapping miRNAs across global and dimension scores included hsa-miR-379-3p, hsa-miR-1976, hsa-miR-151a-5p, hsa-miR-151b, hsa-miR-144-3p, etc. Top KEGG pathways for identified miRNAs included p53 signaling, Hippo signaling, FoxO signaling, protein processing in endoplasmic reticulum and several pathways related with cancer and neurological diseases. This study provided early evidence supporting the associations between extracellular miRNAs and psychiatric conditions. MiRNAs may serve as biomarkers of subclinical psychiatric illness in older adults., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Growing evidence suggests that long-term air pollution exposure is a risk factor for cardiovascular mortality and morbidity. However, few studies have investigated air pollution below current regulatory limits, and causal evidence is limited. We use a double negative control approach to examine the association between long-term exposure to air pollution at low concentration and cardiovascular hospitalizations among US Medicare beneficiaries aged ≥65 years between 2000 and 2016. The expected values of the negative outcome control (preceding-year hospitalizations) regressed on exposure and negative exposure control (subsequent-year exposure) are treated as a surrogate for omitted confounders. With analyses separately restricted to low-pollution areas (PM 2.5  < 9 μg/m³, NO 2  < 75.2 µg/m 3 [40 ppb], warm-season O 3  < 88.2 μg/m 3 [45 ppb]), we observed positive associations of the three pollutants with hospitalization rates of stroke, heart failure, and atrial fibrillation and flutter. The associations generally persisted in demographic subgroups. Stricter national air quality standards should be considered., (© 2024. The Author(s).)

Background: The relationship between long-term exposure to PM 2.5 and mortality is well-established; however, the role of individual species is less understood., Objectives: In this study, we assess the overall effect of long-term exposure to PM 2.5 as a mixture of species and identify the most harmful of those species while controlling for the others., Methods: We looked at changes in mortality among Medicare participants 65 years of age or older from 2000 to 2018 in response to changes in annual levels of 15 PM 2.5 components, namely: organic carbon, elemental carbon, nickel, lead, zinc, sulfate, potassium, vanadium, nitrate, silicon, copper, iron, ammonium, calcium, and bromine. Data on exposure were derived from high-resolution, spatio-temporal models which were then aggregated to ZIP code. We used the rate of deaths in each ZIP code per year as the outcome of interest. Covariates included demographic, temperature, socioeconomic, and access-to-care variables. We used a mixtures approach, a weighted quantile sum, to analyze the joint effects of PM 2.5 species on mortality. We further looked at the effects of the components when PM 2.5 mass levels were at concentrations below 8 μg/m 3 , and effect modification by sex, race, Medicaid status, and Census division., Results: We found that for each decile increase in the levels of the PM 2.5 mixture, the rate of all-cause mortality increased by 1.4% (95% CI: 1.3%-1.4%), the rate of cardiovascular mortality increased by 2.1% (95% CI: 2.0%-2.2%), and the rate of respiratory mortality increased by 1.7% (95% CI: 1.5%-1.9%). These effects estimates remained significant and slightly higher when we restricted to lower concentrations. The highest weights for harmful effects were due to organic carbon, nickel, zinc, sulfate, and vanadium., Conclusions: Long-term exposure to PM 2.5 species, as a mixture, increased the risk of all-cause, cardiovascular, and respiratory mortality., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joel D Schwartz reports financial support was provided by National Institute of Environmental Health Sciences. Joel D Schwartz reports a relationship with US Department of Justice that includes: paid expert testimony. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To estimate exposure-response associations between chronic exposure to fine particulate matter (PM 2.5 ) and risks of the first hospital admission for major cardiovascular disease (CVD) subtypes., Design: Population based cohort study., Setting: Contiguous US., Participants: 59 761 494 Medicare fee-for-service beneficiaries aged ≥65 years during 2000-16. Calibrated PM 2.5 predictions were linked to each participant's residential zip code as proxy exposure measurements., Main Outcome Measures: Risk of the first hospital admission during follow-up for ischemic heart disease, cerebrovascular disease, heart failure, cardiomyopathy, arrhythmia, valvular heart disease, thoracic and abdominal aortic aneurysms, or a composite of these CVD subtypes. A causal framework robust against confounding bias and bias arising from errors in exposure measurements was developed for exposure-response estimations., Results: Three year average PM 2.5 exposure was associated with increased relative risks of first hospital admissions for ischemic heart disease, cerebrovascular disease, heart failure, cardiomyopathy, arrhythmia, and thoracic and abdominal aortic aneurysms. For composite CVD, the exposure-response curve showed monotonically increased risk associated with PM 2.5 : compared with exposures ≤5 µg/m 3 (the World Health Organization air quality guideline), the relative risk at exposures between 9 and 10 µg/m 3 , which encompassed the US national average of 9.7 µg/m 3 during the study period, was 1.29 (95% confidence interval 1.28 to 1.30). On an absolute scale, the risk of hospital admission for composite CVD increased from 2.59% with exposures ≤5 µg/m 3 to 3.35% at exposures between 9 and 10 µg/m 3 . The effects persisted for at least three years after exposure to PM 2.5 . Age, education, accessibility to healthcare, and neighborhood deprivation level appeared to modify susceptibility to PM 2.5 ., Conclusions: The findings of this study suggest that no safe threshold exists for the chronic effect of PM 2.5 on overall cardiovascular health. Substantial benefits could be attained through adherence to the WHO air quality guideline., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Institutes of Health (NIH) and Alfred P Sloan Foundation for the submitted work. FD reports funding from NIH and Alfred P Sloan Foundation; JDS reports funding from NIH. All other authors declare no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite strong evidence of the association of fine particulate matter (PM 2.5 ) exposure with an increased risk of lung cancer mortality, few studies had investigated associations of multiple pollutants simultaneously, or with incidence, or using causal methods. Disparities were also understudied., Objectives: We investigated long-term effects of PM 2.5 , nitrogen dioxide (NO 2 ), warm-season ozone, and particle radioactivity (PR) exposures on lung cancer incidence in a nationwide cohort., Methods: We conducted a cohort study with Medicare beneficiaries (aged ≥ 65 years) continuously enrolled in the fee-for-service program in the contiguous US from 2001 to 2016. Air pollution exposure was averaged across three years and assigned based on ZIP code of residence. We fitted Cox proportional hazards models to estimate the hazard ratio (HR) for lung cancer incidence, adjusted for individual- and neighborhood-level confounders. As a sensitivity analysis, we evaluated the causal relationships using inverse probability weights. We further assessed effect modifications by individual- and neighborhood-level covariates., Results: We identified 166,860 lung cancer cases of 12,429,951 studied beneficiaries. In the multi-pollutant model, PM 2.5 and NO 2 exposures were statistically significantly associated with increased lung cancer incidence, while PR was marginally significantly associated. Specifically, the HR was 1.008 (95% confidence interval [CI]: 1.005, 1.011) per 1-μg/m 3 increase in PM 2.5 , 1.013 (95% CI: 1.012, 1.013) per 1-ppb increase in NO 2 , and 1.005 (0.999, 1.012) per 1-mBq/m 3 increase in PR. At low exposure levels, all pollutants were associated with increased lung cancer incidence. Men, older individuals, Blacks, and residents of low-income neighborhoods experienced larger effects of PM 2.5 and PR., Discussion: Long-term PM 2.5 , NO 2 , and PR exposures were independently associated with increased lung cancer incidence among the national elderly population. Low-exposure analysis indicated that current national standards for PM 2.5 and NO 2 were not restrictive enough to protect public health, underscoring the need for more stringent air quality regulations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Oil spill is the main cause of marine pollution in the waterbodies with rich oil resources. In this study, we developed and compared the performance of variable-complexity machine-learning models to detect oil spill origin, extent, and movement over large scales. To this end, we trained Support Vector Machine (SVM), Random Forest (RF), and Convolutional Neural Network (CNN) models by using the statistical, geometrical, and textural features of Sentinel-1 SAR data. Our results in the Persian Gulf showed that CNN is superior to RF and SVM classifiers in oil spill detection, as evidenced by the testing accuracy of 95.8 %, 86.0 %, and 78.9 %, respectively. The results suggested utilizing both ascending and descending orbit pass directions to track the movement of oil spill and the underlying transport rate. The proposed methodology enables the detection of probable leaking tankers and platforms, which aids in identifying other sources of oil pollution than tankers and platforms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Epidemiologic evidence on the relationships between air pollution and the risks of primary cancers other than lung cancer remained largely lacking. We aimed to examine associations of 10-year exposures to fine particulate matter (PM 2.5 ) and nitrogen dioxide (NO 2 ) with risks of breast, prostate, colorectal, and endometrial cancers., Methods: For each cancer, we constructed a separate cohort among the national Medicare beneficiaries during 2000 to 2016. We simultaneously examined the additive associations of six exposures, namely, moving average exposures to PM 2.5 and NO 2 over the year of diagnosis and previous 2 years, previous 3 to 5 years, and previous 6 to 10 years, with the risk of first cancer diagnosis after 10 years of follow-up, during which there was no cancer diagnosis., Results: The cohorts included 2.2 to 6.5 million subjects for different cancers. Exposures to PM 2.5 and NO 2 were associated with increased risks of colorectal and prostate cancers but were not associated with endometrial cancer risk. NO 2 was associated with a decreased risk of breast cancer, while the association for PM 2.5 remained inconclusive. At exposure levels below the newly updated World Health Organization Air Quality Guideline, we observed substantially larger associations between most exposures and the risks of all cancers, which were translated to hundreds to thousands new cancer cases per year within the cohort per unit increase in each exposure., Conclusions: These findings suggested substantial cancer burden was associated with exposures to PM 2.5 and NO 2 , emphasizing the urgent need for strategies to mitigate air pollution levels., Competing Interests: The authors declare that they have no they have no conflicts of interest with regard to the content of this report. This work was supported by the National Institutes of Health grants R01ES032418 and P30ES000002. The Medicare data are available upon request to the Centers for Medicare and Medicaid Services. The grid-level PM2.5 data are available at https://doi.org/10.7927/0rvr-4538. The grid-level NO2 data are available at https://doi.org/10.7927/f8eh-5864. The ZIP code-level PM2.5 and NO2 are available at https://doi.org/10.7927/9yp5-hz11. Other covariate data are publicly available with sources described in the article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Background: The molecular effects of intermediate and long-term exposure to air pollution and temperature, such as those on extracellular microRNA (ex-miRNA) are not well understood but may have clinical consequences., Objectives: To assess the association between exposure to ambient air pollution and temperature and ex-miRNA profiles., Methods: Our study population consisted of 734 participants in the Normative Aging Study (NAS) between 1999 and 2015. We used high-resolution models to estimate four-week, eight-week, twelve-week, six-month, and one-year moving averages of PM 2.5 , O 3 , NO 2 , and ambient temperature based on geo-coded residential addresses. The outcome of interest was the extracellular microRNA (ex-miRNA) profile of each participant over time. We used a longitudinal quantile regression approach to estimate the association between the exposures and each ex-miRNA. Results were corrected for multiple comparisons and ex-miRNAs that were still significantly associated with the exposures were further analyzed using KEGG pathway analysis and Ingenuity Pathway Analysis., Results: We found 151 significant associations between levels of PM 2.5 , O 3 , NO 2 , and ambient temperature and 82 unique ex-miRNAs across multiple quantiles. Most of the significant results were associations with intermediate-term exposure to O 3 , long-term exposure to PM 2.5 , and both intermediate and long-term exposure to ambient temperature. The exposures were most often associated with the 75th and 90th percentile of the outcomes. Pathway analyses of significant ex-miRNAs revealed their involvement in biological pathways involving cell function and communication as well as clinical diseases such as cardiovascular disease, respiratory disease, and neurological disease., Conclusion: Our results show that intermediate and long-term exposure to all our exposures of interest were associated with changes in the ex-miRNA profile of study participants. Further studies on environmental risk factors and ex-miRNAs are warranted., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joel D Schwartz reports financial support was provided by National Institute of Environmental Health Sciences by grant R01ES027747. Joel D Schwartz reports a relationship with US Department of Justice that includes: paid expert testimony. Feiby L. Nassan is a current employee and a shareholder of Biogen, Cambridge, MA. The original work on this study at Harvard T. H. Chan School of Public Health (HSPH), however, pre-dated the current employment. This manuscript does not mention any Biogen products or any of the disease states that Biogen is actively doing research in (to the coauthor's knowledge)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Seasonal temperature variability remains understudied and may be modified by climate change. Most temperature-mortality studies examine short-term exposures using time-series data. These studies are limited by regional adaptation, short-term mortality displacement, and an inability to observe longer-term relationships in temperature and mortality. Seasonal temperature and cohort analyses allow the long-term effects of regional climatic change on mortality to be analyzed., Objectives: We aimed to carry out one of the first investigations of seasonal temperature variability and mortality across the contiguous United States. We also investigated factors that modify this association. Using adapted quasi-experimental methods, we hoped to account for unobserved confounding and to investigate regional adaptation and acclimatization at the ZIP code level., Methods: We examined the mean and standard deviation (SD) of daily temperature in the warm (April-September) and cold (October-March) season in the Medicare cohort from 2000 to 2016. This cohort comprised 622,427,230 y of person-time in all adults over the age of 65 y from 2000 to 2016. We used daily mean temperature obtained from gridMET to develop yearly seasonal temperature variables for each ZIP code. We used an adapted difference-in-difference approach model with a three-tiered clustering approach and meta-analysis to observe the relationship between temperature variability and mortality within ZIP codes. Effect modification was assessed with stratified analyses by race and population density., Results: For every 1°C increase in the SD of warm and cold season temperature, the mortality rate increased by 1.54% [95% confidence interval (CI): 0.73%, 2.15%] and 0.69% (95% CI: 0.22%, 1.15%) respectively. We did not see significant effects for seasonal mean temperatures. Participants who were classified by Medicare into an "other" race group had smaller effects than those classified as White for Cold and Cold SD and areas with lower population density had larger effects for Warm SD., Discussion: Warm and cold season temperature variability were significantly associated with increased mortality rates in U.S. individuals over the age of 65 y, even after controlling for seasonal temperature averages. Warm and cold season mean temperatures showed null effects on mortality. Cold SD had a larger effect size for those who were in the racial subgroup other, whereas Warm SD was more harmful for those living in lower population density areas. This study adds to the growing calls for urgent climate mitigation and environmental health adaptation and resiliency. https://doi.org/10.1289/EHP11588.

Background: While the health effects of air pollution and temperature are widely studied, the molecular effects are poorly understood. Extracellular microRNAs (ex-miRNAs) have the potential to serve as diagnostic or prognostic biomarkers and/or to act as intercellular signaling molecules that mediate the effects of environmental exposures on health outcomes., Methods: We examined the relationship between short-term exposure to air pollution and ambient temperature and the ex-miRNA profiles of participants in the Normative Aging Study (NAS) from 1999 to 2015. Our exposures were defined as same-day, two-day, three-day, one-week, two-week, and three-week moving averages of PM 2.5 , NO 2 , O 3 , and temperature which were derived from high-resolution spatio-temporal models. The ex-miRNA profiles of the subjects were obtained during follow-up visits. We analyzed the data using a longitudinal quantile regression model adjusted for individual covariates, batch effects, and time trends. We adjusted for multiple comparisons using a false discovery rate (FDR) correction. Ex-miRNAs that were significantly associated with exposures were further investigated using pathway analyses., Results: We found that all the examined exposures were associated with changes in ex-miRNA profiles in our study, particularly PM 2.5 which was responsible for most of the statistically significant results. We found 110 statistically significant exposure-outcome relationships that revealed associations with the levels of 52 unique ex-miRNAs. Pathway analyses showed these ex-miRNAs have been linked to target mRNAs, genes, and biological mechanisms that could affect virtually every organ system, and as such may be linked to multiple clinical disease presentations such as cardiovascular disease, respiratory disease, and neurological disease., Conclusions: Air pollution and temperature exposures were significantly associated with alterations in the ex-miRNA profiles of NAS subjects with possible biological consequences., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr. Feiby L. Nassan is a current employee and a shareholder of Biogen, Cambridge, MA. The original work on this study at Harvard T. H. Chan School of Public Health (HSPH), however, pre-dated the current employment. This manuscript does not mention any Biogen products or any of the disease states that Biogen is actively doing research in (to the coauthor’s knowledge). Dr. Joel D. Schwartz has appeared as an expert witness on behalf of the US Department of Justice in cases involving violations of the Clean Air Act.]., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background & Aim: Numerous studies have linked air pollution with cardiovascular diseases. Fewer studies examined the associations at low concentration levels or assessed potential modifiers. Some investigations only examined hospitalizations, which can miss incident cases. This study aims to address these gaps through a nationwide cohort study of Medicare enrollees., Methods: Our study cohort comprise all Medicare enrollees (≥65 years old) continuously enrolled in the fee-for-service program and both Medicare part A and B across the contiguous U.S. from 2000 to 2016. We examined the associations of population-weighted ZIP code-level annual average PM 2.5 , NO 2 , and warm-season O 3 (May-October), with the first diagnoses of atrial fibrillation (AF), congestive heart failure (CHF), and stroke. We fit multi-pollutant Cox proportional hazards models adjusted for individual demographic characteristics and area-level covariates. We further examined these associations at low pollutant concentration levels and the potential effect modifications by race/ethnicity and comorbidities (diabetes, hypertension, hyperlipidemia)., Results: Elevated PM 2.5 and NO 2 levels were associated with increased incidence of AF, CHF, and stroke. For each 1 μg/m 3 increase in annual PM 2.5 , hazard ratios (HRs) were 1.0059 (95%CI: 1.0054-1.0064), 1.0260 (95%CI: 1.0256-1.0264), and 1.0279 (95%CI: 1.0274-1.0284), respectively. For each1 ppb increase in annual NO 2 , HRs are 1.0057 (95%CI: 1.0056-1.0059), 1.0112 (95%CI: 1.0110-1.0113), and 1.0095 (95%CI: 1.0093-1.0096), respectively. For warm-season O 3 , each 1 ppb increase was associated with increased incidence of CHF (HR=1.0035, 95%CI: 1.0033-1.0037) and stroke (HR=1.0026, 95%CI: 1.0023-1.0028). Larger magnitudes of HRs were observed when restricted to pollutants levels lower than NAAQS standards. Generally higher risks were observed for Black people and diabetics., Conclusions: Long-term exposure to PM 2.5 , NO 2 , and warm-season O 3 were associated with increased incidence of cardiovascular diseases, even at low pollutant concentration levels. Black people and people with diabetes were found to be vulnerable populations., Competing Interests: Declaration of Competing Interest I have read the journal's policy and the authors of this manuscript have the following competing interests: Joel Schwartz has been an expert witness for the US Department of Justice in cases involving Clean Air Act violations., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Few studies have simultaneously examined the effect of long-term exposure to air pollution and ambient temperature on the rate of hospital admissions with cardiovascular and respiratory disease using causal inference methods., Methods: We used a variation of a difference-in-difference (DID) approach to assess the effects of long-term exposure to warm-season temperature, cold-season temperature, NO 2 , O 3 , and PM 2.5 on the rate of hospital admissions for cardiovascular disease (CVD), myocardial infarction (MI), ischemic stroke, and respiratory diseases from 2001 to 2016 among Medicare beneficiaries who use fee-for-service programs. We computed the rate of admissions by zip code and year. Covariates included demographic and socioeconomic variables which were obtained from the decennial Census, the American Community Survey, the Behavioral Risk Factor Surveillance System, and the Dartmouth Health Atlas. As a secondary analysis, we restricted the analysis to zip code-years that had exposure to low concentrations of our pollutants., Results: PM 2.5 was associated with a significant increase in the absolute rate of annual admissions with cardiovascular disease by 47.71 admissions (95 % CI: 41.25-56.05) per 100,000 person-years, myocardial infarction by 7.44 admissions (95 % CI: 5.53-9.63) per 100,000 person-years, and 18.58 respiratory admissions (95 % CI: 12.42-23.72) for each one μg/m 3 increase in two-year average levels. O 3 significantly increased the rates of all the studied outcomes. NO 2 was associated with a decreased rate of admissions with MI by 0.83 admissions (95 % CI: 0.10-1.55) per 100,000 person-years but increased rate of admissions for respiratory disease by 3.16 admissions (95 % CI: 1.34-5.24) per 100,000 person-years. Warmer cold-season temperature was associated with a decreased admissions rate for all outcomes., Conclusion: Air pollutants, particularly PM 2.5 and O 3 , increased the rate of hospital admissions with cardiovascular and respiratory disease among the elderly, while higher cold-season temperatures decreased the rate of admissions with these conditions., Competing Interests: Declaration of competing interest Dr. Joel D. Schwartz has appeared as an expert witness on behalf of the US Department of Justice in cases involving violations of the Clean Air Act., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Numerous studies have documented PM 2.5 's links with adverse health outcomes. Comparatively fewer studies have evaluated specific PM 2.5 components. The lack of exposure measurements and high correlation among different PM 2.5 components are two limitations., Methods: We applied a novel exposure prediction model to obtain annual Census tract-level concentrations of 15 PM 2.5 components (Zn, V, Si, Pb, Ni, K, Fe, Cu, Ca, Br, SO 4 2- , NO 3 - , NH 4 + , OC, EC) in Massachusetts from 2000 to 2015, to which we matched geocoded deaths. All non-accidental mortality, cardiovascular mortality, and respiratory mortality were examined for the population aged 18 or over. Weighted quantile sum (WQS) regression models were used to examine the cumulative associations between PM 2.5 components mixture and outcomes and each component's contributions to the cumulative associations. We have fit WQS models on 15 PM 2.5 components and a priori identified source groups (heavy fuel oil combustion, biomass burning, crustal matter, non-tailpipe traffic source, tailpipe traffic source, secondary particles from power plants, secondary particles from agriculture, unclear source) for the 15 PM 2.5 components. Total PM 2.5 mass analysis and single component associations were also conducted through quasi-Poisson regression models., Results: Positive cumulative associations between the components mixture and all three outcomes were observed from the WQS models. Components with large contribution to the cumulative associations included K, OC, and Fe. Biomass burning, traffic emissions, and secondary particles from power plants were identified as important source contributing to the cumulative associations. Mortality rate ratios for cardiovascular mortality were of greater magnitude than all non-accidental mortality and respiratory mortality, which is also observed in cumulative associations estimated from WQS, total PM 2.5 mass analysis, and single component associations., Conclusion: We have found positive associations between the mixture of 15 PM 2.5 components and all non-accidental mortality, cardiovascular mortality, and respiratory mortality. Among these components, Fe, K, and OC have been identified as having important contribution to the cumulative associations. The WQS results also suggests potential source effects from biomass burning, traffic emissions, and secondary particles from power plants., (© 2022. The Author(s).)

The COVID-19 containment response policies (CRPs) had a major impact on air quality (AQ). These CRPs have been time-varying and location-specific. So far, despite having numerous studies on the effect of COVID-19 lockdown on AQ, a knowledge gap remains on the association between stringency of CRPs and AQ changes across the world, regions, nations, and cities. Here, we show that globally across 1851 cities (each more than 300 000 people) in 149 countries, after controlling for the impacts of relevant covariates (e.g., meteorology), Sentinel-5P satellite-observed nitrogen dioxide (NO 2 ) levels decreased by 4.9% (95% CI: 2.2, 7.6%) during lockdowns following stringent CRPs compared to pre-CRPs. The NO 2 levels did not change significantly during moderate CRPs and even increased during mild CRPs by 2.3% (95% CI: 0.7, 4.0%), which was 6.8% (95% CI: 2.0, 12.0%) across Europe and Central Asia, possibly due to population avoidance of public transportation in favor of private transportation. Among 1768 cities implementing stringent CRPs, we observed the most NO 2 reduction in more populated and polluted cities. Our results demonstrate that AQ improved when and where stringent COVID-19 CRPs were implemented, changed less under moderate CRPs, and even deteriorated under mild CRPs. These changes were location-, region-, and CRP-specific.

Mounting epidemiological evidence has documented the associations between long-term exposure to multiple air pollutants and increased mortality. There is a pressing need to determine whether risks persist at low concentrations including below current national standards. Air pollution levels have decreased in the United States, and better understanding of the health effects of low-level air pollution is essential for the amendment of National Ambient Air Quality Standards (NAAQS). A nationwide, population-based, open cohort study was conducted to estimate the association between long-term exposure to low-level PM 2.5 , NO 2 , O 3 , and all-cause mortality. The study population included all Medicare enrollees (ages 65 years or older) in the contiguous U.S. from 2001 to 2017. We further defined three low-exposure subcohorts comprised of Medicare enrollees who were always exposed to low-level PM 2.5 (annual mean ≤12-μg/m 3 ), NO 2 (annual mean ≤53-ppb), and O 3 (warm-season mean ≤50-ppb), respectively, over the study period. Of the 68.7-million Medicare enrollees, 33.1% (22.8-million, mean age 75.9 years), 93.8% (64.5-million, mean age 76.2 years), and 65.0% (44.7-million, mean age 75.6 years) were always exposed to low-level annual PM 2.5 , annual NO 2 , and warm-season O 3 over the study period, respectively. Among the low-exposure cohorts, a 10-μg/m 3 increase in PM 2.5 , 10-ppb increase in NO 2 , and 10-ppb increase in warm-season O 3 , were, respectively, associated with an increase in mortality rate ranging between 10 and 13%, 2 and 4%, and 12 and 14% in single-pollutant models, and between 6 and 8%, 1 and 3%, and 9 and 11% in tripollutant models, using three statistical approaches. There was strong evidence of linearity in concentration-response relationships for PM 2.5 and NO 2 at levels below the current NAAQS, suggesting that no safe threshold exists for health-harmful pollution levels. For O 3 , the concentration-response relationship shows an increasingly positive association at levels above 40-ppb. In conclusion, exposure to low levels of PM 2.5 , NO 2 , and warm-season O 3 was associated with an increased risk of all-cause mortality.

Background: Little is known about the associations between ambient environmental exposures and the risk of acute episodes of psychiatric disorders. We aimed to estimate the link between short-term exposure to atmospheric pollutants, temperature, and acute psychiatric hospital admissions in adults aged 65 years and older in the USA., Methods: For this study, we included all people (aged ≥65 years) enrolled in the Medicare programme in the USA who had an emergency or urgent hospital admission for a psychiatric disorder recorded between Jan 31, 2000, and Dec 31, 2016. We applied a case-crossover design to study the associations between short-term exposure to air pollution (fine particulate matter [PM 2·5 ], ozone, and nitrogen dioxide [NO 2 ]), ambient temperature, and the risk of acute hospital admissions for depression, schizophrenia, and bipolar disorder in this population. The percentage change in the risk of hospital admission and annual absolute risk differences were estimated., Findings: For each 5°C increase in short-term exposure to cold season temperature, the relative risk of acute hospital admission increased by 3·66% (95% CI 3·06-4·26) for depression, by 3·03% (2·04-4·02) for schizophrenia, and by 3·52% (2·38-4·68) for bipolar disorder in the US Medicare population. Increased short-term exposure to PM 2·5 and NO 2 was also associated with a significant increase in the risk of acute hospital admissions for psychiatric disorders. Each 5 μg/m 3 increase in PM 2·5 was associated with an increase in hospital admission rates of 0·62% (95% CI 0·23-1·02) for depression, 0·77% (0·11-1·44) for schizophrenia, and 1·19% (0·49-1·90) for bipolar disorder; each 5 parts per billion (ppb) increase in NO 2 , meanwhile, was linked to an increase in hospital admission rates of 0·35% (95% CI 0·03-0·66) for depression and 0·64% (0·20-1·08) for schizophrenia. No such associations were found with warm season temperature., Interpretation: In the US Medicare population, short-term exposure to elevated concentrations of PM 2·5 and NO 2 and cold season ambient temperature were significantly associated with an increased risk of hospital admissions for psychiatric disorders. Considering the increasing burden of psychiatric disorders in the US population, these findings suggest that intervening on air pollution and ambient temperature levels through stricter environmental regulations or climate mitigation could help ease the psychiatric health-care burden., Funding: US National Institute of Environmental Health Sciences, US Environmental Protection Agency, and US National Institute on Aging., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Environmental risk factors for psychiatric health are poorly identified. We examined the association between air pollution and psychiatric symptoms, which are often precursors to the development of psychiatric disorders., Methods: This study included 570 participants in the US Veterans Administration (VA) Normative Aging Study and 1,114 visits (defined as an onsite follow-up at the VA with physical examination and questionnaires) from 2000-2014 with information on the Brief Symptom Inventory (BSI) to assess their psychiatric symptom levels. Differences in the three BSI global measures (Global Severity Index - GSI, Positive Symptom Distress Index - PSDI and Positive Symptom Total - PST) were reported per interquartile (IQR) increase of residential address-specific air pollutants levels (fine particulate matter - PM 2.5 , ozone - O 3 , nitrogen dioxide - NO 2 ) at averages of 1 week, 4 weeks, 8 weeks and 1 year prior to the visit using generalized additive mixed effects models. We also evaluated modification by neighborhood factors., Results: On average, among the NAS sample (average age, 72.4 yrs. (standard deviation: 6.7 yrs.)), an IQR increase in 1- and 4- week averages of NO 2 before visit was associated with a PSDI T score (indicator for psychiatric symptom intensity) increase of 1.60 (95% Confidence Interval (CI): 0.31, 2.89), 1.71 (95% CI: 0.18, 3.23), respectively. Similarly, for each IQR increase in 1- and 4-week averages of ozone before visit, PSDI T-score increased by 1.66 (95% CI: 0.68, 2.65), and 1.36 (95% CI: 0.23, 2.49), respectively. Stronger associations were observed for ozone and PSDI in low house value and low household income areas. No associations were found for PM 2.5 ., Conclusions: Exposure to gaseous air pollutants was associated with higher intensity of psychiatric symptoms among a cohort of older men, particularly in communities with lower socio-economic or housing conditions., Competing Interests: Conflicts of Interest None declared.

Background Long-term air pollution exposure is a significant risk factor for inpatient hospital admissions in the general population. However, we lack information on whether long-term air pollution exposure is a risk factor for hospital readmissions, particularly in individuals with elevated readmission rates. Methods and Results We determined the number of readmissions and total hospital visits (outpatient visits+emergency room visits+inpatient admissions) for 20 920 individuals with heart failure. We used quasi-Poisson regression models to associate annual average fine particulate matter at the date of heart failure diagnosis with the number of hospital visits and 30-day readmissions. We used inverse probability weights to balance the distribution of confounders and adjust for the competing risk of death. Models were adjusted for age, race, sex, smoking status, urbanicity, year of diagnosis, short-term fine particulate matter exposure, comorbid disease, and socioeconomic status. A 1-µg/m 3 increase in fine particulate matter was associated with a 9.31% increase (95% CI, 7.85%-10.8%) in total hospital visits, a 4.35% increase (95% CI, 1.12%-7.68%) in inpatient admissions, and a 14.2% increase (95% CI, 8.41%-20.2%) in 30-day readmissions. Associations were robust to different modeling approaches. Conclusions These results highlight the potential for air pollution to play a role in hospital use, particularly hospital visits and readmissions. Given the elevated frequency of hospitalizations and readmissions among patients with heart failure, these results also represent an important insight into modifiable environmental risk factors that may improve outcomes and reduce hospital use among patients with heart failure.

Background: Studies examining the nonfatal health outcomes of exposure to air pollution have been limited by the number of pollutants studied and focus on short-term exposures., Methods: We examined the relationship between long-term exposure to fine particulate matter with an aerodynamic diameter <2.5 micrometers (PM 2.5 ), NO 2 , and tropospheric ozone and hospital admissions for 4 cardiovascular and respiratory outcomes (myocardial infarction, ischemic stroke, atrial fibrillation and flutter, and pneumonia) among the Medicare population of the United States. We used a doubly robust method for our statistical analysis, which relies on both inverse probability weighting and adjustment in the outcome model to account for confounding. The results from this regression are on an additive scale. We further looked at this relationship at lower pollutant concentrations, which are consistent with typical exposure levels in the United States, and among potentially susceptible subgroups., Results: Long-term exposure to fine PM 2.5 was associated with an increased risk of all outcomes with the highest effect seen for stroke with a 0.0091% (95% CI, 0.0086-0.0097) increase in the risk of stroke for each 1-µg/m 3 increase in annual levels. This translated to 2536 (95% CI, 2383-2691) cases of hospital admissions with ischemic stroke per year, which can be attributed to each 1-unit increase in fine particulate matter levels among the study population. NO 2 was associated with an increase in the risk of admission with stroke by 0.00059% (95% CI, 0.00039-0.00075) and atrial fibrillation by 0.00129% (95% CI, 0.00114-0.00148) per ppb and tropospheric ozone was associated with an increase in the risk of admission with pneumonia by 0.00413% (95% CI, 0.00376-0.00447) per parts per billion. At lower concentrations, all pollutants were consistently associated with an increased risk for all our studied outcomes., Conclusions: Long-term exposure to air pollutants poses a significant risk to cardiovascular and respiratory health among the elderly population in the United States, with the greatest increase in the association per unit of exposure occurring at lower concentrations.

Background: Accumulating evidence links fine particulate matter (PM 2·5 ) to premature mortality, cardiovascular disease, and respiratory disease. However, less is known about the influence of PM 2·5 on neurological disorders. We aimed to investigate the effect of long-term PM 2·5 exposure on development of Parkinson's disease or Alzheimer's disease and related dementias., Methods: We did a longitudinal cohort study in which we constructed a population-based nationwide open cohort including all fee-for-service Medicare beneficiaries (aged ≥65 years) in the contiguous United States (2000-16) with no exclusions. We assigned PM 2·5 postal code (ie, ZIP code) concentrations based on mean annual predictions from a high-resolution model. To accommodate our very large dataset, we applied Cox-equivalent Poisson models with parallel computing to estimate hazard ratios (HRs) for first hospital admission for Parkinson's disease or Alzheimer's disease and related dementias, adjusting for potential confounders in the health models., Findings: Between Jan 1, 2000, and Dec 31, 2016, of 63 038 019 individuals who were aged 65 years or older during the study period, we identified 1·0 million cases of Parkinson's disease and 3·4 million cases of Alzheimer's disease and related dementias based on primary and secondary diagnosis billing codes. For each 5 μg/m 3 increase in annual PM 2·5 concentrations, the HR was 1·13 (95% CI 1·12-1·14) for first hospital admission for Parkinson's disease and 1·13 (1·12-1·14) for first hospital admission for Alzheimer's disease and related dementias. For both outcomes, there was strong evidence of linearity at PM 2·5 concentrations less than 16 μg/m 3 (95th percentile of the PM 2·5 distribution), followed by a plateaued association with increasingly larger confidence bands., Interpretation: We provide evidence that exposure to annual mean PM 2·5 in the USA is significantly associated with an increased hazard of first hospital admission with Parkinson's disease and Alzheimer's disease and related dementias. For the ageing American population, improving air quality to reduce PM 2·5 concentrations to less than current national standards could yield substantial health benefits by reducing the burden of neurological disorders., Funding: The Health Effects Institute, The National Institute of Environmental Health Sciences, The National Institute on Aging, and the HERCULES Center., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

We examined the association between average annual fine particulate matter (PM 2.5 ) and ozone and first hospital admissions of Medicare participants for stroke, chronic obstructive pulmonary disease (COPD), pneumonia, myocardial infarction (MI), lung cancer, and heart failure (HF). Annual average PM 2.5 and ozone levels were estimated using high-resolution spatio-temporal models. We fit a marginal structural Cox proportional hazards model, using stabilized inverse probability weights (IPWs) to account for the competing risk of death and confounding. Analyses were then repeated after restricting to exposure levels below the current U.S. standards. The results showed that PM 2.5 was significantly associated with an increased hazard of admissions for all studied outcomes; the highest observed being a 6.1% (95% CI: 5.9%-6.2%) increase in the hazard of admissions with pneumonia for each μg/m 3 increase in particulate levels. Ozone was also significantly associated with an increase in the risk of first hospital admissions of all outcomes. The hazard of pneumonia increased by 3.0% (95% CI: 2.9%-3.1%) for each ppb increase in the ozone level. Our results reveal a need to regulate long-term ozone exposure, and that associations persist below current PM 2.5 standards., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Natural and synthetic anion receptors are extensively employed, but the structures of their bound complexes are difficult to determine in the liquid phase. Infrared spectroscopy is used in this work to characterize the solution structures of bound anion receptors for the first time, and surprisingly only two of three hydroxyl groups of the neutral aliphatic triols are found to directly interact with Cl(–). The binding constants of these triols with zero to three CF3 groups were measured in a polar environment, and KCD3CN(Cl(–)) = 1.1 × 10(6) M(–1) for the tris(trifluoromethyl) derivative. This is a remarkably large value, and high selectivity with respect to interfering anions such as, Br(–), NO3(–) and NCS(–) is also displayed. The effects of the third “noninteracting” hydroxyl groups on the structures and binding constants were also explored, and surprisingly they are as large or larger than the OH substituents that hydrogen bond to Cl(–). That is, a remote hydroxyl group can play a larger role in binding than two OH substituents that directly interact with an anionic center.