Deepwater Horizon oil spill (DWHOS) responders potentially experienced multiple stressors. We examined associations between DWHOS deployment-related stressor patterns and neurological and endocrine/metabolic conditions among U.S. Coast Guard active duty responders who completed post-deployment surveys (n = 3102). Deployment-related stressor patterns were identified using principal component analysis of self-reported stressors. Neurological and endocrine/metabolic outcomes were classified from military health encounter records. Associations between principal components (PCs) and incident outcomes (2010–2015) were estimated through Cox proportional hazards regression. A five-component solution explained 79.2

INTRODUCTION:ALS is a neurodegenerative disorder with an unknown etiology for 90%-95% of cases. Several environmental and occupational exposures have been investigated although a prospective study examining the association of "ever living/working on a farm" (farming exposure) and insecticide exposure with risk of ALS mortality in women is lacking. METHODS:Within the Women's Health Initiative (WHI), a nested case-control study was conducted among 93,676 women (n = 151 ALS death cases, n = 1,496 matched controls) from the WHI Observational Study. This included a questionnaire about farming and insecticide exposure history 1 year after baseline. Conditional logistic regression models adjusted for education, smoking, and physical activity estimated risk of ALS death. RESULTS:One-third of cases and 21% of controls reported farming exposure. Cases had higher odds of farming exposure than controls (adjusted odds ratio [aOR] = 1.59, 95% CI: 1.09-2.31) and was highest at durations of 15-19 (aOR = 1.81, 95% CI: 1.02-3.21) and ≥20 years (aOR = 2.32, 95% CI: 1.10-4.87) compared to no exposure. Tests for interaction revealed that women with farming and smoking exposure had higher odds of ALS death (aOR = 2.10, 95% CI: 1.26-3.51, p = 0.0045). Little evidence was noted for increased insecticide exposure and ALS mortality risk, although power was limited. CONCLUSION:Among post-menopausal women with 25+ years follow-up, a significant association was noted between farming exposure and risk of ALS death. This increased risk was highest among those who ever smoked. Future studies should include biomarkers of exposure and large cohorts of men and women with occupational and residential histories.

INTRODUCTION:Residential proximity to unconventional natural gas development (UNGD) has been shown to be associated with asthma exacerbations, but there is limited evidence regarding whether exacerbations are associated with a particular distance or phase of well activity. OBJECTIVE:To study the impact of proximity to UNGD activity by well phase and buffer distance. METHODS:We included asthma patients 5-90 years old with a primary diagnosis of asthma and at least one order for medications prescribed for asthma residing in one of eight Southwestern Pennsylvania counties between 2011 and 2020. We matched events (severe exacerbation, emergency department visit, hospitalization) by age group, sex, and year to cohort members without an event of the same or greater severity. The primary exposure measure was an inverse distance-weighted index of UNGD activity up to 10 miles of a patient's residence. We fit a series of adjusted multilevel logistic regression models using tertiles of exposure activity by well phase and buffer distance. RESULTS:Our cohort consisted of 46,676 asthma patients. We found strong evidence for an increased risk specifically during the production phase for all buffer distances examined for all three event types, as based on consistent, statistically significantly elevated odds ratios. Elevations ranged from 2 to 8 times the baseline of no wells within 10 miles of the patient's residence. CONCLUSION:This study provides evidence of increased risk of asthma events with the production phase. This should be considered in determining risk communication and assessment for these vulnerable populations, particularly during the production phase.

The rapid growth of unconventional natural gas development (UNGD), also known as hydraulic fracturing, has raised concerns of potential exposures to hazardous chemicals. Few studies have examined the risk of childhood cancer from exposure to UNGD. A case-control study included 498 children diagnosed with leukemia, lymphoma, central nervous system neoplasms, and malignant bone tumors during the period 2010-2019 identified through the Pennsylvania Cancer Registry. Cases were matched to controls using Pennsylvania birth records. For each subject, a new overall UNGD exposure metric was calculated which incorporates both spatial (proximity) and temporal (duration) aspects of well activity. Conditional logistic regression models were used to estimate the risk of combined and individual cancers by overall UNGD exposure, and well proximity. Children with a higher overall UNGD exposure (3rd/4th quartiles) had an increased risk for the four malignancies combined [OR] 1.69 (95% CI 1.01, 2.82) and 1.79 (95% CI 1.00, 3.19) compared to non-exposed children. Overall, individuals living within 0.5 miles of a UNGD site were 3.94 times (95% CI 1.66, 9.30) more likely to develop a malignancy compared to non-exposed children and the risk of lymphoma within 0.5 miles and 0.5-1 miles was also elevated [ORs of 5.05 (95% CI 1.09, 23.39) and 7.71 (95% CI 1.01, 59.00), respectively] compared to non-exposed. Our study found that overall UNGD cumulative activity as well as a proximity to UNGD wells were associated with an increased risk of childhood lymphoma and overall childhood cancers combined.

Long-term endocrine and metabolic health risks associated with oil spill cleanup exposures are largely unknown, despite the endocrine-disrupting potential of crude oil and oil dispersant constituents. We aimed to investigate risks of longer-term endocrine and metabolic conditions among U.S. Coast Guard (USCG) responders to the Deepwater Horizon (DWH) oil spill. Our study population included all active duty DWH Oil Spill Coast Guard Cohort members (N = 45,224). Self-reported spill exposures were ascertained from post-deployment surveys. Incident endocrine and metabolic outcomes were defined using International Classification of Diseases (9th Revision) diagnostic codes from military health encounter records up to 5.5 years post-DWH. Using Cox proportional hazards regression, we estimated adjusted hazard ratios (aHR) and 95

The Legal Context of Environmental Protection in the United States, W.V. Luneburg Environmental Risk Assessment, I. Hertz-Picciotto Association and Causation in Environmental Epidemiology, N.D. Traven, E.O. Talbott, and E.K. Ishii Statistical Issues in the Design, Analysis, and Interpretation of Environmental Epidemiology Studies, G.M. Marsh Biological Markers of Exposure, M.F. Vine and B.S. Hulka Epidemiologic Aspects of Environmental Hazards to Reproduction, L.E. Sever Risk Factors for Cancer in the Occupational Environment and Relevant Epidemiologic Study Methods, J. Siemiatycki The Epidemiology of Waterborne Disease: The Importance of Drinking Water Disinfection, G.F. Craun Injury, L.S. Robertson Ionizing Radiation, D.J. Strom Electromagnetic Fields and Cancer Risks, G. Theriault Recent Progress in Childhood Lead Exposure, H.L. Needleman Sensitive Subgroups and Normal Variation in Pulmonary Function Response to Air Pollution Episodes, B. Brunekreef, P.L. Kinney, J.H. Ware, D. Dockery, F.E. Speizer, J.D. Spengleer, and B.G. Ferris, Jr. Health Effects from Environmental Noise Exposure, E.O. Talbott and S.J. Thompson Index

OBJECTIVE:Neurotoxic chemicals are suggested in the etiology of amyotrophic lateral sclerosis (ALS). We examined the association of environmental and occupational risk factors including persistent organochlorine pesticides (OCPs) and ALS risk among cases from the Centers for Disease Control and Prevention National ALS Registry and age, sex, and county-matched controls. METHODS:Participants completed a risk factor survey and provided a blood sample for OCP measurement. ALS cases were confirmed through the Registry. Conditional logistic regression assessed associations between ALS and risk factors including OCP levels. RESULTS:243 matched case-control pairs (61.7% male, mean [SD] age = 62.9 [10.1]) were included. Fifteen of the 29 OCPs examined had sufficient detectable levels for analysis. Modest correlations of self-reported years of exposure to residential pesticide mixtures and OCP serum levels were found (p<.001). Moreover, occupational exposure to lead including soldering and welding with lead/metal dust and use of lead paint/gasoline were significantly related to ALS risk (OR = 1.77, 95% CI: 1.11-2.83). Avocational gardening was a significant risk factor for ALS (OR = 1.57, 95% CI: 1.04-2.37). ALS risk increased for each 10 ng/g of α-Endosulfan (OR = 1.42, 95% CI: 1.14-1.77) and oxychlordane (OR = 1.24, 95% CI: 1.01-1.53). Heptachlor (detectable vs. nondetectable) was also associated with ALS risk (OR = 3.57, 95% CI: 1.50-8.52). CONCLUSION:This national case-control study revealed both survey and serum levels of OCPs as risk factors for ALS. Despite the United States banning many OCPs in the 1970s and 1980s, their use abroad and long half-lives continue to exert possible neurotoxic health effects.

Introduction: Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies found in reproductive age women. It is characterized by anovulatory infertility, menstrual dysfunction, and hirsutism. It is thought to be associated with an increased risk of metabolic aberrations, including insulin resistance, hyperinsulinism and type 2 diabetes mellitus (T2D). Due to the racial disparities associated with insulin resistance and T2D, we hypothesized that the prevalence of PCOS like symptoms would be increased on the island of Tobago where women were predominantly of Afro-Caribbean descent. Study Design: A retrospective chart review of 1000 women seen in an obstetrics and gynecological office over a 7-year period was conducted. Inclusion criteria included race, body mass index (BMI)<50, and no diagnosis of a co-morbid endocrinopathy. Of the 1000 women, 884 Afro-Caribbean women were included in the analysis. PCOS diagnosis was made based on clinical signs and symptoms verified on ultrasound. The diagnosis was considered if a patient presented with ≥2 of the following signs and symptoms: infertility after >1yr of unprotected sex; irregular menses with periods >35 d, <21 d or <6/yr; overweight/ obese (BMI>25); hirsutism; and acne. Results: Within the study population, 15.7% of participants had irregular menses, 9.2% had infertility, 4.0% had hirsutism and 0.4% developed acne. The prevalence of PCOS based on clinical diagnoses and ultrasonographic evidence was 19.7%. No statistical difference (p<0.05) was found between the two groups with regards to BMI, age and parity. When stratified by age, differences in infertility were found in the 20-24 and 35-39 year old age groups with rates at 10.5 v 18.9% and 15.4 v. 30.2%, respectively. The incidence of irregular menses also differed among age groups, with PCOS patients reporting significantly higher percentages between 30-50%. Conclusion: PCOS appears to be a common disorder on the island of Tobago with a prevalence of 19.7%. This prevalence is higher than in North American studies but is in line with data excluding biochemical analysis. As PCOS is a heterogeneous disorder with diverse phenotypes and probable ethno-genetic variations, the next step would be to further characterize the characteristics of PCOS in the Tobago population. This includes obtaining a full battery of biochemical profiles of women diagnosed with PCOS-like symptoms and the consideration of gene environment interactions including exposure to endocrine disruptors thought to be involved in the etiology of PCOS.

The worst commercial nuclear accident and the first large-scale voluntary evacuation due to a nuclear event in United States history took place at Three Mile Island (TMI) in 1979. Within a short time, there was a well-recognized impact of the TMI accident by public health officials and academicians upon mental health of nearby residents- particularly pregnant women. Despite long-term and detailed follow-up of this population for cancer outcomes, community concerns continue. Herein, we conduct a scoping and process review of fetal/maternal/child health (MCH) and cancer health outcomes, and consider the findings in light of subsequent accidents. The process evaluation is enhanced by unpublished transcripts of the Pennsylvania Department of Health's (PA DOH) TMI Advisory Panel on Health Research Studies (APHRS), comprised of experts from prominent US research institutions. Research and process strengths included a rapid initial house-to-house health census of over 35,000 individuals, intense medical record reviews, in-person interviews of pregnant women within a 10-mile radius, and coordination of multiple parallel studies by PA DOH with APHRS collaboration. Major limitations include (1) errors in causal inference, (2) limited radiation exposure assessment, (3) failure to include TMI never-exposed groups in risk estimates, (4) exclusion of vulnerable populations, (5) nonindexed/never published investigations, and (6) government-stated need for long-term MCH follow-up that was never conducted. Lingering unaddressed actual and perceived risks were identified as major common themes among TMI, Chernobyl and Fukushima accidents. These findings underscore the need for the establishment of mechanisms to ensure long-term follow-up and preaccident protocols designed to address major health issues with inclusion of vulnerable populations and perceived risks.

BACKGROUND:Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with few risk factors identified and no known cure. Gene-environment interaction is hypothesized especially for sporadic ALS cases (90-95%) which are of unknown etiology. We aimed to investigate risk factors for ALS including exposure to ambient air toxics. METHODS:This population-based case-control study included 267 ALS cases (from the United States [U.S.] Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry National ALS Registry and Biorepository) and 267 age, sex, and county-matched controls identified via a commercial database. Exposure assessment for 34 ambient air toxicants was performed by assigning census tract-level U.S. Environmental Protection Agency (EPA) 2011 National Air Toxics Assessment (NATA) data to participants' residential ZIP codes. Conditional logistic regression was used to compute adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for individual compounds, chemical classes, and overall exposure. Sensitivity analyses using both conditional logistic regression and Bayesian grouped weighted quartile sum (GWQS) models were performed to assess the integrity of findings. RESULTS:Using the 2011 NATA, the highest exposure quartile (Q4) compared to the lowest (Q1) of vinyl chloride (aOR = 6.00, 95% CI: 1.87-19.25), 2,4-dinitrotoluene (aOR = 5.45, 95% CI: 1.53-19.36), cyanide (aOR = 4.34, 95% CI: 1.52-12.43), cadmium (aOR = 3.30, 95% CI: 1.11-9.77), and carbon disulfide (aOR = 2.98, 95% CI: 1.00-8.91) was associated with increased odds of ALS. Residential air selenium showed an inverse association with ALS (second quartile [Q2] vs. Q1: aOR = 0.38, 95% CI: 0.18-0.79). Additionally, residential exposure to organic/chlorinated solvents (Q4 vs Q1: aOR = 2.62, 95% CI: 1.003-6.85) was associated with ALS. CONCLUSIONS:Our findings using the 2011 NATA linked by census tract to residential area provide evidence of increased ALS risk in cases compared to controls for 2,4-dinitrotoluene, vinyl chloride, cyanide, and the organic/chlorinated solvents class. This underscores the importance of ongoing surveillance of potential exposures for at-risk populations.

BackgroundLong-term neurological health risks associated with oil spill cleanup exposures are largely unknown. We aimed to investigate risks of longer-term neurological conditions among U.S. Coast Guard (USCG) responders to the 2010 Deepwater Horizon (DWH) oil spill.MethodsWe used data from active duty members of the DWH Oil Spill Coast Guard Cohort Study (N=45224). Self-reported oil spill exposures were ascertained from post-deployment surveys. Incident neurological outcomes were classified using International Classification of Diseases, 9th Revision, codes from military health encounter records up to 5.5 years post-DWH. We used Cox Proportional Hazards regression to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for various incident neurological diagnoses (2010-2015). Oil spill responder (n=5964) vs. non-responder (n= 39260) comparisons were adjusted for age, sex, and race, while within-responder comparisons were additionally adjusted for smoking.ResultsCompared to those not responding to the spill, spill responders had reduced risks for headache (aHR=0.84, 95% CI: 0.74-0.96), syncope and collapse (aHR=0.74, 95% CI: 0.56-0.97), and disturbance of skin sensation (aHR=0.81, 95% CI: 0.68-0.96). Responders reporting ever (n=1068) vs. never (n=2424) crude oil inhalation exposure were at increased risk for several individual and grouped outcomes related to headaches and migraines (aHR range: 1.39-1.83). Crude oil inhalation exposure was also associated with elevated risks for an inflammatory nerve condition, mononeuritis of upper limb and mononeuritis multiplex (aHR=1.71, 95% CI: 1.04-2.83), and tinnitus (aHR=1.91, 95% CI: 1.23-2.96), a condition defined by ringing in one or both ears. Risk estimates for those neurological conditions were higher in magnitude among responders reporting exposure to both crude oil and oil dispersants than among those reporting crude oil only.ConclusionIn this large study of active duty USCG responders to the DWH disaster, self-reported spill cleanup exposures were associated with elevated risks for longer-term neurological conditions.

To cite: Benatar M, Goutman SA, Staats KA, et al. J Neurol Neurosurg Psychiatry 2023;94:399–402. Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA Neurology, University of Michigan, Ann Arbor, Michigan, USA Staats Life Sciences Consulting, Los Angeles, California, USA Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA ALS Association, Washington, District of Columbia, USA Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King’s College London, London, UK

Cognitive impairment in older adults is a major public concern for Kazakhstan's aging population. We aimed to (1) administer a neuropsychological test battery (NTB) in domains relevant to aging-associated cognitive impairment in a sample of adults aged 60+ without dementia in Almaty, Kazakhstan; (2) investigate the associations between demographic factors and test performance; and (3) provide information on the distribution of NTB scores as preliminary local normative data relevant for this population. A cross-sectional evaluation of 276 participants aged 60+ in Almaty, Kazakhstan, was conducted using cognitive instruments including tests of memory, attention, language, executive functions, visuospatial abilities, and processing speed. Multiple linear regression analyses were used to examine the association of demographic factors with neuropsychological test performance. The results from the regression analysis showed that those who are younger, have more years of education, are women, and are of Russian ethnicity had significantly better performance. The current study illustrated (1) the feasibility of administering the NTB to older adults in the general population in Kazakhstan; (2) the preliminary local normative neuropsychological measures; and (3) their independent associations with age, education, gender, and ethnicity. The findings are a platform for future research on dementia and cognitive impairment in older adults in Kazakhstan.

Background/Aim Evidence demonstrates that coronary artery calcification (CAC) is a biological marker for cardiovascular disease (CVD) risk prediction. Acute cardiovascular effects of temporary and chronic environmental particle exposures sensitive to ≤2.5 micrometers in diameter (here termed “PM2.5”) have been well-studied. However, there is less information on the long-term effects of PM2.5 exposures on the earlier pre-clinical stage of CVD, especially in women (in whom it is also established experience frequent cardiovascular late- and under-diagnoses). This phase of pre-diagnosis pathological activity is classified as subclinical atherosclerosis (SCA) unless and until a patient meets established clinical diagnostic criteria. In this systematic review, we summarize reported associations of long-term PM2.5 and SCA exposure, with investigators placing an emphasis on gender differences in any documented associations. Methods We conducted a comprehensive literature review for articles published from 2007 to 2022 that reported associations of long-term PM2.5 and SCA and evaluated each study with areas of particular focus including study designs, populations at risk, and exposure measures. Results Investigations representing four cohorts yielded equivocal findings related to long-term PM2.5 exposure and CAC. Three cohorts reported positive associations between long-term PM2.5 and CAC development/progression. Two studies supported a strongly positive associations among women or postmenopausal women for PM2.5 on CAC. Studies, however, evaluating PM2.5 exposure associations with carotid intima-media thickness (another biomarker of SCA), reflect increases in both men and women with ↑ PM2.5 levels but reporting no gender differences in PM2.5 exposure and this measure of SCA. Conclusion Our study identifies important gaps in current knowledge synthesis including different methods of PM2.5 estimation and linkage, a lack of consensus of what constitutes long-term air pollution, and the selection of important covariates and intermediate variables. Our aim is to outline best practices going forward in the investigation of PM2.5 long-term exposure and SCA in women

Mortality due to opioid misuse and overdose has increased substantially in the United States over the past two decades. The study objective was to describe the causes of death among persons with opioid-related hospitalizations and examine survival by Hepatitis C virus (HCV) or HIV. Opioid-related hospitalization records in Pennsylvania from 2000 to 2010 were linked to death registry files to assess cause of death, and survival from first hospital discharge date to death date, or December 31, 2010. Accelerated failure time models were used to compare survival between persons with and without HCV or HIV diagnoses. Among the 136,416 individuals with an opioid-related hospitalization, 13.0% died over a median of 56 months of follow-up; the most common causes of death were circulatory diseases (26.4%) and drug overdose (23.5%). There were 27,122 (19.9%) and 3662 (2.7%) persons who had an HCV and HIV diagnosis, respectively. Among patients aged ≥20 years, those with HCV had shorter survival time compared to those without HCV, with discrepancies more pronounced at older ages. Patients with HIV also had shorter survival time (time ratio: 0.29 [95% CI: 0.26, 0.34]) compared to without HIV. These findings show that in a cohort of patients with opioid-related hospitalizations, those with HCV or HIV diagnoses have shorter survival. This has public health implications, providing further evidence that medical providers should educate patients who use opioids about the risks of HCV and HIV infection and focus prevention and treatment to decrease mortality among patients hospitalized for opioid use.

Introduction The acute effects of air pollution and cardiovascular disease (CVD) have been studied, but very few studies have focused on spatiotemporally modeled exposure to air pollutants at the population level. This study aims to examine the short-term association of fine particulate matter (PM2.5), Ozone (O3), Nitrogen Dioxide (NO2) and Sulfur Dioxide (SO2) and CVD emergency room visits (ERV) in Allegheny County for a 13-year period using a case-crossover study design. Aim We sought to estimate the effects of acute exposure to these four pollutants adjusting for temperature on CVD ERV and to compare outcomes in 1999-2005 compared to 2006-2011. Methods Land-use regression was used to model the ground level exposures to PM2.5, O3, NO2 and SO2. CVD ER visits were requested from the local hospitals of the two health networks in Allegheny County, which operate the majority of the ER services. The discharge International Classification of Diseases-9 (ICD-9) codes were used to identify the CVD cases and CVD subgroups. We linked the Zone Improvement Plan (ZIP) code level air pollution data with the patients’ ZIP code (residence) to determine the individual level exposure estimation of both case days and control days. Conditional logistic regression with multi-pollutant and distributed lags of 0-3-days was applied to estimate the effect of acute exposure of these pollutants to CVD ER visits (ERV), adjusting for temperature. Results In the overall analyses, for every interquartile increase of O3 exposure (25.52 ppb), there was a 6.6% (95% CI: 0.8%-12.7%) increase in the odds of an acute myocardial infarction ERV. This was consistent across both time periods. Among women and Black ERV, we observed an association of PM2.5 with acute myocardial infarction, and with ischemic heart disease. Some of these associations persisted in the later years of the study period. The gaseous pollutants (NO2, SO2 and O3) were shown to increase risk of cardiovascular events in both time periods. Conclusion We found an association of PM2.5 and NO2 with CVD ER visits, and this association persisted in the stratified analyses, as well as in the later years with lower exposure levels. The findings suggest that further actions to reduce the pollution level in this area should be taken. Ozone and NO2 were related to increased risk for all CVD, ischemic heart disease (IHD) and acute myocardial infarction (AMI) underscoring the importance of gaseous pollutants and their effect on coronary heart disease (CHD) risk.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no cure. Although the etiology of sporadic ALS is largely unknown, environmental exposures may affect ALS risk. Objective: We investigated relationships between exposure to long-term ambient particulate matter (PM) and gaseous air pollution (AP) and ALS mortality. Methods: Within the Women's Health Initiative (WHI) cohort of 161,808 postmenopausal women aged 50-79 years at baseline (1993-1998), we performed a nested case-control study of 256 ALS deaths and 2486 matched controls with emphasis on PM constituents (PM2.5, PM10, and coarse PM [PM10-2.5]) and gaseous pollutants (NOx, NO2, SO2, and ozone). Time-varying AP exposures estimates were averaged 5, 7.5, and 10 years prior to ALS death using both a GIS-based spatiotemporal generalized additive mixed model and ordinary kriging (empirical and multiple imputation, MI). Conditional logistic regression was used to estimate the relative risk of ALS death. Results: In general, PM2.5 and PM10-related risks were not significantly elevated using either method. However, for PM10-2.5, odds ratios (ORs) were >1.0 for both methods at all time periods using MI and empirical data for PM10-2.5 (coarse) except for 5 and 7.5 years using the kriging method with covariate adjustment. Conclusion: This investigation adds to the body of information on long-term ambient AP exposure and ALS mortality. Specifically, the 2019 US Environmental Protection Agency (EPA) Integrated Science Assessment summarized the neumtoxic effects of PM2.5, PM10, and PM10-2.5. The conclusion was that evidence of an effect of coarse PM is suggestive but the data is presently not sufficient to infer a causal relationship. Further research on AP and ALS is warranted. As time from symptom onset to death in ALS is similar to 2-4 years, earlier AP measures may also be of interest to ALS development. This is the first study of ALS and AP in postmenopausal women controlling for individual-level confounders.