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Background: Air pollution is a recognized risk factor for cardiovascular disease (CVD). Temperature is also linked to CVD, with a primary focus on acute effects. Despite the close relationship between air pollution and temperature, their health effects are often examined separately, potentially overlooking their synergistic effects. Moreover, fewer studies have performed mixture analysis for multiple co-exposures, essential for adjusting confounding effects among them and assessing both cumulative and individual effects., Methods: We obtained hospitalization records for residents of 14 U.S. states, spanning 2000-2016, from the Health Cost and Utilization Project State Inpatient Databases. We used a grouped weighted quantile sum regression, a novel approach for mixture analysis, to simultaneously evaluate cumulative and individual associations of annual exposures to four grouped mixtures: air pollutants (elemental carbon, ammonium, nitrate, organic carbon, sulfate, nitrogen dioxide, ozone), differences between summer and winter temperature means and their long-term averages during the entire study period (i.e., summer and winter temperature mean anomalies), differences between summer and winter temperature standard deviations (SD) and their long-term averages during the entire study period (i.e., summer and winter temperature SD anomalies), and interaction terms between air pollutants and summer and winter temperature mean anomalies. The outcomes are hospitalization rates for four prevalent CVD subtypes: ischemic heart disease, cerebrovascular disease, heart failure, and arrhythmia., Results: Chronic exposure to air pollutant mixtures was associated with increased hospitalization rates for all CVD subtypes, with heart failure being the most susceptible subtype. Sulfate, nitrate, nitrogen dioxide, and organic carbon posed the highest risks. Mixtures of the interaction terms between air pollutants and temperature mean anomalies were associated with increased hospitalization rates for all CVD subtypes., Conclusions: Our findings identified critical pollutants for targeted emission controls and suggested that abnormal temperature changes chronically affected cardiovascular health by interacting with air pollution, not directly., 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 © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In 1987, the United States Environmental Protection Agency recommended installing a mitigation system when the indoor concentration of radon, a well-known carcinogenic radioactive gas, is at or above 148 Bq/m 3 . In response, tens of millions of short-term radon measurements have been conducted in residential buildings over the past three decades either for disclosure or to initially evaluate the need for mitigation. These measurements, however, are currently underutilized to assess population radon exposure in epidemiological studies. Based on two relatively small radon surveys, Lawrence Berkeley National Laboratory developed a state-of-the-art national radon model. However, this model only provides coarse and invariant radon estimations, which limits the ability of epidemiological studies to accurately investigate the health effects of radon, particularly the effects of acute exposure. This study involved obtaining over 2.8 million historical short-term radon measurements from independent laboratories. With the use of these measurements, an innovative spatial random forest (SRF) model was developed based on geological, architectural, socioeconomical, and meteorological predictors. The model was used to estimate monthly community-level radon concentrations for ZIP Code Tabulation Areas (ZCTAs) in the northeastern and midwestern regions of the United States from 2001 to 2020. Via cross-validation, we found that our ZCTA-level predictions were highly correlated with observations. The prediction errors declined quickly as the number of radon measurements in a ZCTA increased. When ≥15 measurements existed, the mean absolute error was 24.6 Bq/m 3 , or 26.5% of the observed concentrations ( R 2 = 0.70). Our study demonstrates the potential of the large amount of historical short-term radon measurements that have been obtained to accurately estimate longitudinal ZCTA-level radon exposures at unprecedented levels of resolutions and accuracy.

Importance: In the United States, Black and Hispanic children have higher rates of asthma and asthma-related morbidity compared with White children and disproportionately reside in communities with economic deprivation., Objective: To determine the extent to which neighborhood-level socioeconomic indicators explain racial and ethnic disparities in childhood wheezing and asthma., Design, Setting, and Participants: The study population comprised children in birth cohorts located throughout the United States that are part of the Children's Respiratory and Environmental Workgroup consortium. Cox proportional hazard models were used to estimate hazard ratios (HRs) of asthma incidence, and logistic regression was used to estimate odds ratios of early and persistent wheeze prevalence accounting for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, and region and decade of birth., Exposures: Neighborhood-level socioeconomic indicators defined by US census tracts calculated as z scores for multiple tract-level variables relative to the US average linked to participants' birth record address and decade of birth. The parent or caregiver reported the child's race and ethnicity., Main Outcomes and Measures: Prevalence of early and persistent childhood wheeze and asthma incidence., Results: Of 5809 children, 46% reported wheezing before age 2 years, and 26% reported persistent wheeze through age 11 years. Asthma prevalence by age 11 years varied by cohort, with an overall median prevalence of 25%. Black children (HR, 1.47; 95% CI, 1.26-1.73) and Hispanic children (HR, 1.29; 95% CI, 1.09-1.53) were at significantly increased risk for asthma incidence compared with White children, with onset occurring earlier in childhood. Children born in tracts with a greater proportion of low-income households, population density, and poverty had increased asthma incidence. Results for early and persistent wheeze were similar. In effect modification analysis, census variables did not significantly modify the association between race and ethnicity and risk for asthma incidence; Black and Hispanic children remained at higher risk for asthma compared with White children across census tracts socioeconomic levels., Conclusions and Relevance: Adjusting for individual-level characteristics, we observed neighborhood socioeconomic disparities in childhood wheeze and asthma. Black and Hispanic children had more asthma in neighborhoods of all income levels. Neighborhood- and individual-level characteristics and their root causes should be considered as sources of respiratory health inequities.

Background: Long-term exposure to air pollution has been linked with an increase in risk of mortality. Whether existing US Environmental Protection Agency standards are sufficient to protect health is unclear. Our study aimed to examine the relationship between exposure to lower concentrations of air pollution and the risk of mortality., Methods: Our nationwide cohort study investigated the effect of annual average exposure to air pollutants on all-cause mortality among Medicare enrolees from the beginning of 2000 to the end of 2016. Patients entered the cohort in the month of January following enrolment and were followed up until the end of the study period in 2016 or death. We restricted our analyses to participants who had only been exposed to lower concentrations of pollutants over the study period, specifically particulate matter less than 2·5 μg/m 3 in diameter (PM 2·5 ) at a concentration of up to 12 μg/m 3 , nitrogen dioxide (NO 2 ) at a concentration of up to 53 parts per billion (ppb), and summer ozone (O 3 ) at concentrations of up to 50 ppb. We adjusted for two types of covariates, which were individual level and postal code-level variables. We used a doubly-robust additive model to estimate the change in risk. We further looked at effect-measure modification by stratification on the basis of demographic and socioeconomic characteristics., Findings: We found an increased risk of mortality with all three pollutants. Each 1 μg/m 3 increase in annual PM 2·5 concentrations increased the absolute annual risk of death by 0·073% (95% CI 0·071-0·076). Each 1 ppb increase in annual NO 2 concentrations increased the annual risk of death by 0·003% (0·003-0·004), and each 1 ppb increase in summer O 3 concentrations increased the annual risk of death by 0·081% (0·080-0·083). This increase translated to approximately 11 540 attributable deaths (95% CI 11 087-11 992) for PM 2·5 , 1176 attributable deaths (998-1353) for NO 2 , and 15 115 attributable deaths (14 896-15 333) for O 3 per year for each unit increase in pollution concentrations. The effects were higher in certain subgroups, including individuals living in areas of low socioeconomic status. Long-term exposure to permissible concentrations of air pollutants increases the risk of mortality., Funding: The US Environmental Protection Agency, National Institute of Environmental Health Services, and Health Effects Institute., Competing Interests: Declaration of interests JDS has appeared as an expert witness on behalf of the US Department of Justice in cases involving violations of the Clean Air Act. FD has received consulting and speaking fees from Johnson and Johnson, Colgate, Sanofi, and Visa, but for research topics that are not related to the one of this Article. All other authors declare no competing interests., (Copyright © 2021 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.)

Importance: Black and Hispanic individuals have an increased risk of intracerebral hemorrhage (ICH) compared with their White counterparts, but no large studies of ICH have been conducted in these disproportionately affected populations., Objective: To examine the prevalence, odds, and population attributable risk (PAR) percentage for established and novel risk factors for ICH, stratified by ICH location and racial/ethnic group., Design, Setting, and Participants: The Ethnic/Racial Variations of Intracerebral Hemorrhage Study was a case-control study of ICH among 3000 Black, Hispanic, and White individuals who experienced spontaneous ICH (1000 cases in each group). Recruitment was conducted between September 2009 and July 2016 at 19 US sites comprising 42 hospitals. Control participants were identified through random digit dialing and were matched to case participants by age (±5 years), sex, race/ethnicity, and geographic area. Data analyses were conducted from January 2019 to May 2020., Main Outcomes and Measures: Case and control participants underwent a standardized interview, physical measurement for body mass index, and genotyping for the ɛ2 and ɛ4 alleles of APOE, the gene encoding apolipoprotein E. Prevalence, multivariable adjusted odds ratio (OR), and PAR percentage were calculated for each risk factor in the entire ICH population and stratified by racial/ethnic group and by lobar or nonlobar location., Results: There were 1000 Black patients (median [interquartile range (IQR)] age, 57 [50-65] years, 425 [42.5%] women), 1000 Hispanic patients (median [IQR] age, 58 [49-69] years; 373 [37.3%] women), and 1000 White patients (median [IQR] age, 71 [59-80] years; 437 [43.7%] women). The mean (SD) age of patients with ICH was significantly lower among Black and Hispanic patients compared with White patients (eg, lobar ICH: Black, 62.2 [15.2] years; Hispanic, 62.5 [15.7] years; White, 71.0 [13.3] years). More than half of all ICH in Black and Hispanic patients was associated with treated or untreated hypertension (PAR for treated hypertension, Black patients: 53.6%; 95% CI, 46.4%-59.8%; Hispanic patients: 46.5%; 95% CI, 40.6%-51.8%; untreated hypertension, Black patients: 45.5%; 95% CI, 39.%-51.1%; Hispanic patients: 42.7%; 95% CI, 37.6%-47.3%). Lack of health insurance also had a disproportionate association with the PAR percentage for ICH in Black and Hispanic patients (Black patients: 21.7%; 95% CI, 17.5%-25.7%; Hispanic patients: 30.2%; 95% CI, 26.1%-34.1%; White patients: 5.8%; 95% CI, 3.3%-8.2%). A high sleep apnea risk score was associated with both lobar (OR, 1.68; 95% CI, 1.36-2.06) and nonlobar (OR, 1.62; 95% CI, 1.37-1.91) ICH, and high cholesterol was inversely associated only with nonlobar ICH (OR, 0.60; 95% CI, 0.52-0.70); both had no interactions with race and ethnicity. In contrast to the association between the ɛ2 and ɛ4 alleles of APOE and ICH in White individuals (eg, presence of APOE ɛ2 allele: OR, 1.84; 95% CI, 1.34-2.52), APOE alleles were not associated with lobar ICH among Black or Hispanic individuals., Conclusions and Relevance: This study found sleep apnea as a novel risk factor for ICH. The results suggest a strong contribution from inadequately treated hypertension and lack of health insurance to the disproportionate burden and earlier onset of ICH in Black and Hispanic populations. These findings emphasize the importance of addressing modifiable risk factors and the social determinants of health to reduce health disparities.

Background: We previously found additive effects of long- and short-term exposures to fine particulate matter (PM 2.5 ), ozone (O 3 ), and nitrogen dioxide (NO 2 ) on all-cause mortality rate using a generalized propensity score (GPS) adjustment approach. The study addressed an important question of how many early deaths were caused by each exposure. However, the study was computationally expensive, did not capture possible interactions and high-order nonlinearities, and omitted potential confounders., Methods: We proposed two new methods and reconducted the analysis using the same cohort of Medicare beneficiaries in Massachusetts during 2000-2012, which consisted of 1.5 million individuals with 3.8 billion person-days of follow-up. The first method, weighted least squares (WLS), leveraged large volume of data by aggregating person-days, which gave equivalent results to the linear probability model (LPM) method in the previous analysis but significantly reduced computational burden. The second method, m-out-of-n random forests (moonRF), implemented scaling random forests that captured all possible interactions and nonlinearities in the GPS model. To minimize confounding bias, we additionally controlled relative humidity and health care utilizations that were not included previously. Further, we performed low-level analysis by restricting to person-days with exposure levels below increasingly stringent thresholds., Results: We found consistent results between LPM/WLS and moonRF: all exposures were positively associated with mortality rate, even at low levels. For long-term PM 2.5 and O 3 , the effect estimates became larger at lower levels. Long-term exposure to PM 2.5 posed the highest risk: 1 μg/m 3 increase in long-term PM 2.5 was associated with 1053 (95% confidence interval [CI]: 984, 1122; based on LPM/WLS methods) or 1058 (95% CI: 988, 1127; based on moonRF method) early deaths each year among the Medicare population in Massachusetts., Conclusions: This study provides more rigorous causal evidence between PM 2.5 , O 3 , and NO 2 exposures and mortality, even at low levels. The largest effect estimate for long-term PM 2.5 suggests that reducing PM 2.5 could gain the most substantial benefits. The consistency between LPM/WLS and moonRF suggests that there were not many interactions and high-order nonlinearities. In the big data context, the proposed methods will be useful for future scientific work in estimating causality on an additive scale.

Importance: Chronic obstructive pulmonary disease (COPD) is a critical public health burden. The neutrophil to lymphocyte ratio (NLR), an inflammation biomarker, has been associated with COPD morbidity and mortality; however, its associations with lung function decline and COPD development are poorly understood., Objective: To explore the associations of NLR with lung function decline and COPD risks., Design, Setting, and Participants: This longitudinal cohort study included white male veterans in the US with more than 30 years of follow-up to investigate the associations of NLR with lung function, COPD, and hypomethylation of cg05575921, the top DNA methylation marker of lung function changes in response to tobacco smoking. This study included 7466 visits from 1549 participants, each examined up to 13 times between 1982 and 2018. A subgroup of 1411 participants without COPD at baseline were selected to analyze the association of NLR with incident COPD. Data were analyzed from September 2019 to January 2020., Exposures: The primary exposure was NLR, which was estimated using automated whole blood cell counts based on a blood sample collected at each visit. The methylation level of cg05575921 was measured in blood DNA from a subgroup of 1228 visits., Main Outcomes and Measures: The outcomes of interest were lung function, measured as forced respiratory volume in the first second (FEV1) in liters, forced vital capacity (FVC) in liters, percentage of FVC exhaled in the first second (FEV1/FVC), and maximal midexpiratory flow rate (MMEF) in liters per minute and COPD status, defined as meeting the Global Initiative for Chronic Obstructive Lung Diseases stage II (or higher) criteria. Both outcomes were measured as each visit., Results: Among 1549 included men (mean [SD] age, 68.3 [9.3] years) with 7466 visits from 1982 to 2018, a 1-unit increase in NLR was associated with statistically significant mean (SE) decreases of 0.021 (0.004) L in FEV1, 0.016 (0.005) L in FVC, 0.290% (0.005) L in FVC, 0.290% (0.065%) in FEV1/FVC, and 3.65 (0.916) L/min MMEF. Changes in NLR up to approximately 10 years were associated with corresponding longitudinal changes in lung function. Furthermore, this increase in NLR was associated with 9% higher odds of COPD (odds ratio, 1.09 [95% CI, 1.03-1.15]) for all visits and 27% higher risk of incident COPD (odds ratio, 1.07 [95% CI, 1.07-1.51]) for participants without COPD at baseline. Additionally, a 1-unit increase in NLR was associated with a mean (SE) decrease of 0.0048 (0.0021 in cg05575921 hypomethylation, which may mediate the adverse association of NLR-related inflammation on lung function., Conclusions and Relevance: These findings suggest that NLR may be a clinically relevant biomarker associated with high risk of lung function impairment and COPD alone or in combination with DNA methylation profiles.

Background: A 'mortality risk score' (MS) based on ten prominent mortality-related cytosine-phosphate-guanine (CpG) sites was previously associated with all-cause mortality, but has not been verified externally. We aimed to validate the association of MS with mortality and to compare MS with three aging biomarkers: telomere length (TL), DNA methylation age (DNAmAge) and phenotypic age (DNAmPhenoAge) to explore whether MS can serve as a reliable measure of biological aging and mortality., Methods: Among 534 males aged 55-85 years from the US Normative Aging Study, the MS, DNAmAge and DNAmPhenoAge were derived from blood DNA methylation profiles from the Illumina HumanMethylation450 BeadChip, and TL was measured by quantitative real-time polymerase chain reaction (qRT-PCR)., Results: A total of 147 participants died during a median follow-up of 9.4 years. The MS showed strong associations with all-cause, cardiovascular disease (CVD) and cancer mortality. After controlling for all potential covariates, participants with high MS (>5 CpG sites with aberrant methylation) had almost 4-fold all-cause mortality (hazard ratio: 3.84, 95% confidence interval: 1.92-7.67) compared with participants with a low MS (0-1 CpG site with aberrant methylation). Similar patterns were observed with respect to CVD and cancer mortality. MS was associated with TL and DNAmPhenoAge acceleration but not with DNAmAge acceleration. Although the MS and DNAmPhenoAge acceleration were independently associated with all-cause mortality, the former exhibited a higher predictive accuracy of mortality than the latter., Conclusions: MS has the potential to be a prominent predictor of mortality that could enhance survival prediction in clinical settings., (© The Author(s) 2019; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Short-term geomagnetic disturbances (GMD) driven by the quasi-periodic 11-year cycle of solar activity have been linked to a broad range of adverse health effects, including cardiovascular diseases (CVD) and total deaths. We conducted a large epidemiological study in 263 U.S. cities to assess the effects of GMD on daily deaths of total, CVD, myocardial infarction (MI), and stroke., Methods: We employed a two-step meta-analysis approach, in which we estimated city-specific and season-stratified mortality risk associated with a GMD parameter (Kp index) in 263 U.S. cities. In addition, sensitivity analysis was performed to assess whether effect modification of particulate matter (PM 2.5 ) in the prior day changed Kp index effects on daily deaths after adjusting for confounders., Results: We found significant association between daily GMD and total, CVD, and MI deaths. The effects were even stronger when we adjusted the models for 24-h PM 2.5 for different seasons. For example, in the winter and fall one standard deviation of z-score Kp index increase was associated with a 0.13 and 0.31% increase in total deaths, respectively (Winter: p = 0.01, 95% CI: 0.02 to 0.24; Fall: p = 0.00001; 95% CI: 0.23 to 0.4), without adjusting for PM 2.5. The effects of GMD on total deaths were also observed in spring and summer in the models without PM 2.5 (p = 0.00001). When the models were adjusted for PM 2.5 the total deaths increased 0.47% in winter (p = 0.00001, 95% CI: 0.3 to 0.65) and by 0.23% in fall (p = 0.001, 95% CI: 0.09 to 0.37). The effects of GMD were also significant associated with MI deaths and CVD. No positive significant association were found between Kp and stroke. The GMD effects on deaths were higher than for 24 h-PM 2.5 alone, especially in spring and fall., Conclusion: Our results suggest that GMD is associated with total, CVD and MI deaths in 263 U. S cities. Increased mortality in the general population during GMD should be further investigated to determine whether those human physiological dynamics driven by variations in solar activity can be related to daily clinical cardiovascular observations.

Objective: To measure sound levels in the aircraft cabin during different phases of flight., Methods: Sound level was measured on 200 flights, representing six aircraft groups using continuous monitors. A linear mixed-effects model with random intercept was used to test for significant differences in mean sound level by aircraft model and across each flight phase as well as by flight phase, airplane type, measurement location and proximity to engine noise., Results: Mean sound levels across all flight phases and aircraft groups ranged from 37.6 to >110 dB(A) with a median of 83.5 dB(A). Significant differences in noise levels were also observed based on proximity to the engines and between aircraft with fuselage- and wing mounted engines. Nine flights (4.5%) exceeded the recommended 8-h TWA exposure limit of 85 dB(A) by the NIOSH and ACGIH approach, three flights (1.5%) exceeded the 8-h TWA action level of 85 dB(A) by the OSHA approach, and none of the flights exceeded the 8-h TWA action level of 90 dB(A) by the OSHA PEL approach., Conclusions: Additional characterization studies, including personal noise dosimetry, are necessary to document accurate occupational exposures in the aircraft cabin environment and identify appropriate response actions. FAA should consider applying the more health-protective NIOSH/ACGIH occupational noise recommendations to the aircraft cabin environment.

Background: Flight attendants are an understudied occupational group, despite undergoing a wide range of adverse job-related exposures, including to known carcinogens. In our study, we aimed to characterize the prevalence of cancer diagnoses among U.S. cabin crew relative to the general population., Methods: In 2014-2015, we surveyed participants of the Harvard Flight Attendant Health Study. We compared the prevalence of their self-reported cancer diagnoses to a contemporaneous cohort in the National Health and Nutrition Examination Survey (NHANES 2013-2014) using age-weighted standardized prevalence ratios (SPRs). We also analyzed associations between job tenure and the prevalence of selected cancers, using logistic regression and adjusting for potential confounders., Results: Compared to NHANES participants with a similar socioeconomic status (n = 2729), flight attendants (n = 5366) had a higher prevalence of every cancer we examined, especially breast cancer, melanoma, and non-melanoma skin cancer among females. SPR for these conditions were 1.51 (95% CI: 1.02, 2.24), 2.27 (95% CI: 1.27, 4.06), and 4.09 (95% CI: 2.70, 6.20), respectively. Job tenure was positively related to non-melanoma skin cancer among females, with borderline associations for melanoma and non-melanoma skin cancers among males. Consistent with previous studies, we observed associations between job tenure and breast cancer among women who had three or more children., Conclusions: We observed higher rates of specific cancers in flight attendants compared the general population, some of which were related to job tenure. Our results should be interpreted in light of self-reported health information and a cross-sectional study design. Future longitudinal studies should evaluate associations between specific exposures and cancers among cabin crew.

Background: Monitoring political and social determinants of delayed or forgone care due to cost is necessary to evaluate efforts to reduce racial and ethnic disparities in access to care. Our objective was to examine the extent to which state Medicaid expansion decisions and personal household income may be associated with individual-level racial and ethnic disparities in delayed or forgone care due to cost, at baseline, before the implementation of the Affordable Care Act., Methods: We used 2012 Behavioral Risk Factor Surveillance System survey data to examine racial and ethnic differences in delayed or forgone care due to cost in states that do and do not plan Medicaid expansion. We examined personal household income as a social factor that could contribute to racial and ethnic disparities in delayed or forgone care., Results: We found that personal income differences were strongly related to disparities in delayed or forgone care in places with and without plans to expand Medicaid. In addition, while delayed or forgone care disparities between non-Hispanic whites and non-Hispanic blacks were lowest in places with plans to expand Medicaid access, disparities between non-Hispanic whites and Hispanics did not differ by state Medicaid expansion plans., Conclusions: As access to insurance improves for diverse groups, health systems must develop innovative strategies to overcome social determinants of health, including income inequities, as barriers to accessing care for Hispanic and non-Hispanic blacks. Additional efforts may be needed to ensure Hispanic groups achieve the benefits of investments in health care access.

Background: Short-term particulate air pollution exposure is associated with reduced heart rate variability (HRV), a risk factor for cardiovascular morbidity and mortality, in many studies. Associations with sub-chronic or long-term exposures, however, have been sparsely investigated. We evaluated the effect of fine particulate matter (PM2.5) and black carbon (BC) exposures on HRV in an elderly cohort: the Normative Aging Study., Methods: We measured power in high frequency (HF) and low frequency (LF), standard deviation of normal-to-normal intervals (SDNN), and the LF:HF ratio among participants from the Greater Boston area. Residential BC exposures for 540 men (1161 study visits, 2000-2011) were estimated using a spatio-temporal land use regression model, and residential PM2.5 exposures for 475 men (992 visits, 2003-2011) were modeled using a hybrid satellite based and land-use model. We evaluated associations between moving averages of sub-chronic (3-84 day) and long-term (1 year) pollutant exposure estimates and HRV parameters using linear mixed models., Results: One-standard deviation increases in sub-chronic, but not long-term, BC were associated with reduced HF, LF, and SDNN and an increased LF:HF ratio (e.g., 28 day BC: -2.3% HF [95% CI:-4.6, -0.02]). Sub-chronic and long-term PM2.5 showed evidence of relations to an increased LF and LF:HF ratio (e.g., 1 year PM: 21.0% LF:HF [8.6, 34.8]), but not to HF or SDNN, though the effect estimates were very imprecise and mostly spanned the null., Conclusions: We observed some evidence of a relation between longer-term BC and PM2.5 exposures and changes in HRV in an elderly cohort. While previous studies focused on short-term air pollution exposures, our results suggest that longer-term exposures may influence cardiac autonomic function.

Background: Few studies have examined the broad health effects of occupational exposures in flight attendants apart from disease-specific morbidity and mortality studies. We describe the health status of flight attendants and compare it to the U.S. population. In addition, we explore whether the prevalence of major health conditions in flight attendants is associated with length of exposure to the aircraft environment using job tenure as a proxy., Methods: We surveyed flight attendants from two domestic U.S. airlines in 2007 and compared the prevalence of their health conditions to contemporaneous cohorts in the National Health and Nutrition Survey (NHANES), 2005-2006 and 2007-2008. We weighted the prevalence of flight attendant conditions to match the age distribution in the NHANES and compared the two populations stratified by gender using the Standardized Prevalence Ratio (SPR). For leading health conditions in flight attendants, we analyzed the association between job tenure and health outcomes in logistic regression models., Results: Compared to the NHANES population (n =5,713), flight attendants (n = 4,011) had about a 3-fold increase in the age-adjusted prevalence of chronic bronchitis despite considerably lower levels of smoking. In addition, the prevalence of cardiac disease in female flight attendants was 3.5 times greater than the general population while their prevalence of hypertension and being overweight was significantly lower. Flight attendants reported 2 to 5.7 times more sleep disorders, depression, and fatigue, than the general population. Female flight attendants reported 34% more reproductive cancers. Health conditions that increased with longer job tenure as a flight attendant were chronic bronchitis, heart disease in females, skin cancer, hearing loss, depression and anxiety, even after adjusting for age, gender, body mass index (BMI), education, and smoking., Conclusions: This study found higher rates of specific diseases in flight attendants than the general population. Longer tenure appears to explain some of the higher disease prevalence. Conclusions are limited by the cross-sectional design and recall bias. Further study is needed to determine the source of risk and to elucidate specific exposure-disease relationships over time.

Objectives: We explored associations between the abolition of Jim Crow laws (i.e., state laws legalizing racial discrimination overturned by the 1964 US Civil Rights Act) and birth cohort trends in infant death rates., Methods: We analyzed 1959 to 2006 US Black and White infant death rates within and across sets of states (polities) with and without Jim Crow laws., Results: Between 1965 and 1969, a unique convergence of Black infant death rates occurred across polities; in 1960 to 1964, the Black infant death rate was 1.19 times higher (95% confidence interval [CI] = 1.18, 1.20) in the Jim Crow polity than in the non-Jim Crow polity, whereas in 1970 to 1974 the rate ratio shrank to and remained at approximately 1 (with the 95% CI including 1) until 2000, when it rose to 1.10 (95% CI = 1.08, 1.12). No such convergence occurred for Black-White differences in infant death rates or for White infants., Conclusions: Our results suggest that abolition of Jim Crow laws affected US Black infant death rates and that valid analysis of societal determinants of health requires appropriate comparison groups.

Background: Geographic variation in traditional cardiovascular disease (CVD) risk factors has been observed among women in the US. It is not known whether state-level variation in cardiovascular inflammation exists or could be explained by traditional clinical risk factors and behavioral lifestyle factors., Methods and Results: We used multilevel linear regression to estimate state-level variation in inflammatory biomarker patterns adjusted for clinical and lifestyle characteristics among 26,029 women free of CVD. Participants derived from the Women's Health Study, a national cohort of healthy middle-aged and older women. Inflammatory biomarker patterns (plasma levels of high-sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (sICAM-1), and fibrinogen) were compared to state-level patterns of traditional CVD risk factors and global risk scores. We found that all three inflammatory biomarkers exhibited significant state-level variation including hsCRP (lowest vs. highest state median 1.3 mg/L vs. 2.7 mg/L, unadjusted random effect estimate 1(st) to 99(th) percentile range for log hsCRP 0.52, p<.001), sICAM-1 (325 ng/ml vs. 366ng/ml, unadjusted random effect estimate 1(st) to 99(th) percentile range 0.44, p<.001), and fibrinogen (322 mg/dL vs. 367 mg/dL, unadjusted random effect estimate 1(st) to 99(th) percentile range 0.41, p = .001). Neither demographic, clinical or lifestyle characteristics explained away state-level effects in biomarker patterns. Southern and Appalachian states (Arkansas, West Virginia) had the highest inflammatory biomarker values. Regional geographic patterns of traditional CVD risk factors and risk scores did not completely overlap with biomarkers of inflammation., Conclusions: There is state-level geographic variation in inflammatory biomarkers among otherwise healthy women that cannot be completely attributed to traditional clinical risk factors or lifestyle characteristics. Future research should aim to identify additional factors that may explain geographic variation in biomarkers of inflammation among healthy women.

Background: An examination of where in the income distribution income is most strongly associated with risk of mortality will provide guidance for identifying the most critical pathways underlying the connections between income and mortality, and may help to inform public health interventions to reduce socioeconomic disparities. Prior studies have suggested stronger associations at the lower end of the income distribution, but these studies did not have detailed categories of income, were unable to exclude individuals whose declining health may affect their income and did not use methods to determine exact threshold points of non-linearity. The purpose of this study is to describe the non-linear risks of all-cause and cause-specific mortality across the income distribution., Methods: We examined potential non-linear risk of mortality by family income level in a population that had not retired early, changed jobs, or changed to part-time work due to health reasons, in order to minimize the effects of illness on income. We used data from the US National Health and Nutrition Examination Survey (1988-1994), among individuals age 18-64 at baseline, with mortality follow-up to the year 2001 (ages 25-77 at the end of follow-up, 106 037 person-years of time at risk). Differential risk of mortality was examined using proportional hazard models with penalized regression splines in order to allow for non-linear associations between mortality risk and income, controlling for age, race/ethnicity, marital status, level of educational attainment and occupational category., Results: We observed significant non-linear risks of all-cause mortality, as well as for certain specific causes of death at different levels of income. Typically, risk of mortality decreased with increasing income levels only among persons whose family income was below the median; above this level, there was little decreasing risk of mortality with higher levels of income. There was also some variation in mortality risk at different levels of income by cause and gender., Conclusion: The majority of the income associated mortality risk in individuals between the ages of 18-77 in the United States is among the population whose family income is below the median (equal to $20,190 in 1991, 3.2 times the poverty level). Efforts to decrease socioeconomic disparities may have the greatest impact if focused on this population.

Background: Understanding the shape of the concentration-response curve for particles is important for public health, and lack of such understanding was recently cited by U.S. Environmental Protection Agency (EPA) as a reason for not tightening the standards. Similarly, the delay between changes in exposure and changes in health is also important in public health decision making. We addressed these issues using an extended follow-up of the Harvard Six Cities Study., Methods: Cox proportional hazards models were fit controlling for smoking, body mass index, and other covariates. Two approaches were used. First, we used penalized splines, which fit a flexible functional form to the concentration response to examine its shape, and chose the degrees of freedom for the curve based on Akaike's information criterion. Because the uncertainties around the resultant curve do not reflect the uncertainty in model choice, we also used model averaging as an alternative approach, where multiple models are fit explicitly and averaged, weighted by their probability of being correct given the data. We examined the lag relationship by model averaging across a range of unconstrained distributed lag models., Results: We found that the concentration-response curve is linear, clearly continuing below the current U.S. standard of 15 microg/m3, and that the effects of changes in exposure on mortality are seen within two years., Conclusions: Reduction in particle concentrations below U.S. EPA standards would increase life expectancy.

We propose a new method for computing power and sample size for linear rank tests of differences between two ordered multinomial populations. The method is flexible in that it is applicable to any general alternative hypothesis and for any choice of rank scores. We show that the method, though asymptotic, closely approximates existing exact methods. At the same time it overcomes the computational limitations of the exact methods. This advantage makes our asymptotic approach more practical for sample size computations at the planning stages of a large study. We illustrate the method with data arising from both proportional and non-proportional odds models in the two ordered multinomial setting.

Background and Purpose: The purpose of the present study was to compare the prevalences of genetic polymorphisms in persons with cryptogenic stroke with those among stroke patients with evidence of large-artery occlusive disease or an unequivocal cardioembolic source (noncryptogenic stroke)., Methods: We compared the prevalences of genetic polymorphisms thought to be related to thrombi formation in young stroke patients with evidence of large-artery occlusive disease or an unequivocal cardioembolic source (noncryptogenic stroke; controls; n=79) with those in young stroke patients without such sources (cryptogenic stroke; cases; n=67). Common variations in the genes encoding factor V, prothrombin, angiotensin I-converting enzyme, 5,10-methylenetetrahydrofolate reductase, endothelial cell nitric oxide synthase, tissue plasminogen activator, plasminogen activator inhibitor-1, and fibrinogen were evaluated. We also compared the allele prevalence of these genes among all stroke patients with those among a large pool of historical controls assayed for these genes., Results: None of these genetic polymorphisms was statistically significantly related to cryptogenic stroke. With respect to a comparison of all ischemic stroke with historical controls, only the prevalence of tissue plasminogen activator D allele among stroke subjects was statistically significantly higher than that of the historical controls (P=0.0014)., Conclusions: These findings generally do not support the hypothesis that genes associated with a prothrombotic state are risk factors among a subgroup of young people with stroke of undetermined cause. Except for the D tissue plasminogen activator allele, the findings also indicated that these genetic factors are unrelated, or only weakly related, to all ischemic stroke.