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The save deployment of intra-aortic percutaneous mechanical circulatory support devices is highly dependent on the inner aortic diameter. Finding the anatomically and ethically most suitable animal model for performance testing of new pMCS devices remains challenging. For this study, an ovine model using adult ewes of a large framed breed (Swiss White Alpine Sheep) was developed to test safety, reliability, and biocompatibility of catheter-mounted mechanical support devices placed in the descending thoracic aorta. Following the drawback of fluctuating aortic diameter and device malfunction in the first four animals, the model was improved by stenting the following animals with an aortic stent. Stenting the animals with an intra-aortic over the balloon stent was found to standardize the experimental set-up and to avoid early termination of the experiment due to non-device related issues., The International Journal of Artificial Organs, 44 (10), ISSN:0391-3988, ISSN:1724-6040

Previous epidemiologic investigations suggested that maternal thyroid anomalies are a possible causal factor in attention-deficit hyperactivity disorder (ADHD) in progeny, yet clinical trials indicated that levothyroxine treatment was ineffective in preventing neurodevelopmental impairments. We used an Israeli cohort of 385,542 singleton births from 1999–2012 to explore the interrelated roles of maternal thyroid conditions, laboratory gestational thyroid hormone measurements, use of thyroid medications, and offspring ADHD. Analyses were performed using Cox proportional hazards models. Results indicated that maternal hypothyroidism diagnosis was associated with an elevated progeny ADHD hazard (adjusted hazard ratio = 1.14, 95% confidence interval = 1.10, 1.18). However, this association was unmitigated by gestational use of levothyroxine and was unexplained by maternal gestational thyroid hormone levels. Associations with gestational thyrotropin values and hypothyroxinemia were also observed but were robust only in mothers without other records indicative of a thyroid problem. Results indicated that maternal thyroid hypofunction was associated with progeny ADHD but possibly not due to a direct causal relationship. Instead, maternal thyroid hypofunction may serve as a proxy indicator for other factors that affect neurodevelopment through thyroid hormone independent pathways, which are thus unaffected by pharmaceutical treatments for thyroid hypofunction. Factors known to disrupt thyroid functioning should be examined for their independent ADHD-related effects.

BACKGROUND: Residual confounding is a major concern for causal inference in observational studies on air pollution–autism spectrum disorder (ASD) associations. This study is aimed at assessing confounding in these associations using negative control exposures. METHODS: This nested case–control study included all children diagnosed with ASD (detected through 31 December 2016) born during 2007-2012 in Israel and residing in the study area (N= 3,843), and matched controls of the same age (N= 38,430). We assigned individual house-level exposure estimates for each child. We estimated associations using logistic regression models, mutually adjusted for all relevant exposure periods (pre-pregnancy, pregnancy, and postnatal). We assessed residual confounding using post-outcome negative control exposure at age 28-36 months. RESULTS: In mutually adjusted models we observed positive associations with ASD for postnatal exposures to NOx (odds ratio [OR] per interquartile range, 95% confidence interval [CI]: 1.19, 1.02-1.38) and NO(2) (1.20, 1.00-1.43), and gestational exposure to PM(2.5-10) (1.08, 1.01-1.15). The result for the negative control period was 1.04, 0.99-1.10 for PM(2.5,) suggesting some residual confounding, but no associations for PM(2.5-10) (0.98, 0.81-1.18), NOx (1.02, 0.84-1.25) or NO(2) (0.98, 0.81-1.18), suggesting no residual confounding. CONCLUSIONS: Our results further support a hypothesized causal link with ASD that is specific to postnatal exposures to traffic-related pollution.

BACKGROUND AND OBJECTIVE Toenail metal concentrations can be used as an effective biomarker for exposure to environmental toxicants. Typically toenail clippings are measured ex vivo using inductively coupled plasma mass spectrometry (ICP-MS). X-ray fluorescence (XRF) toenail metal measurements done on intact toenails in vivo could be used as an alternative to alleviate some of the disadvantages of ICP-MS. In this study, we assessed the ability to use XRF to measure toenail metal concentrations in real-time without having to clip the toenails (i.e., in vivo) in two occupational settings for exposure assessment of manganese and mercury. MATERIALS AND METHODS The portable XRF method used a 3-min in vivo measurement of toenails prior to clipping and was assessed against ICP-MS measurement of toenail clippings taken immediately after the XRF measurement and work history for a group of welders (n = 16) assessed for manganese exposure and nail salon workers (n = 10) assessed for mercury exposure. RESULTS AND CONCLUSIONS We identified that in vivo XRF metal measurements were able to discern exposure to manganese in welders and mercury in nail salon workers. We identified significant positive correlations between ICP-MS of clippings and in vivo XRF measures of both toenail manganese (R = 0.59, p = 0.02) and mercury (R = 0.74, p

People who experience childhood abuse are at increased risk of mental illness. Twin studies suggest that inherited genetic risk for mental illness may account for some of these associations. Yet, the hypothesis that individuals who have experienced childhood abuse may carry genetic loading for mental illness has never been tested with genetic data. Using polygenic risk scores for six psychiatric disorders—attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BPD), major depressive disorder (MDD), neuroticism, and schizophrenia—we tested whether genetic risk for mental illness was associated with increased risk of experiencing three types of childhood abuse: physical/emotional abuse, physical assault, and sexual abuse, in a cohort of white non-Hispanic women (n = 11,315). ADHD and MDD genetic risk scores were associated with a higher risk of experiencing each type of childhood abuse, while neuroticism, schizophrenia, BPD, and ASD genetic scores were associated with a higher risk of experiencing physical/emotional abuse and physical assault, but not sexual abuse. Sensitivity analyses examining potential bias from the differential recall of childhood trauma, parental socioeconomic status, and population stratification were consistent with the main findings. A one-standard-deviation increase in genetic risk for mental illness was associated with a modestly elevated risk of experiencing childhood abuse (OR range: 1.05–1.19). Therefore, inherited genetic risk may partly account for the association of childhood abuse with mental illness. In addition, future treatments for mental illness will benefit from taking into consideration the co-occurrence of childhood trauma and genetic loading.

We analyzed data on 879,029 children born in 1999-2017 from a large Israeli health fund to evaluate time-trends in incidence of autism spectrum disorder (ASD). This included examining possible effects associated with the adaptation of the DSM-5 criteria for ASD, and the implementation of regulatory changes affecting eligibility for ASD-related stipends and services. ASD cases were ascertained based on electronic medical records review, with complete verification of ASD case status. Results indicated a substantial increase in ASD incidence rate (IR) over time that was overall not appreciably affected by the above changes. Cumulative incidence through age 8 rose from 0.46% (boys: 0.73; girls: 0.18) in 2007 to 1.30% (boys: 2.12; girls: 0.45) in 2018. Age-specific analyzes indicated that the largest increase in IR occurred in toddlers and preschool children, with a more modest increase at older age groups. Results suggest that the rise in early diagnosed ASD does not stem from a downward shift in the distribution of ages at first diagnosis, but rather from early detection of cases not previously diagnosed. Findings highlight the need to expand research aimed at identifying exogenous factors that may underlie the rise in incidence, and to evaluate factors that may contribute to late diagnosis of some cases. Autism Res 2020, 13: 1893-1901. © 2020 International Society for Autism Research and Wiley Periodicals LLC LAY SUMMARY: In an analysis of nearly 900,000 Israeli children born in 1999-2017, we found that the incidence of autism spectrum disorder (ASD) increased significantly over time, especially among toddlers and preschool children but also at older age groups. We additionally observed that changes affecting diagnostic criteria for ASD and eligibility for ASD-related services did not appreciably affect these trends. Results highlight the need to continue research aimed at identifying factors causing this increase and reasons contributing to late diagnosis of some cases.

PURPOSE OF REVIEW: Despite a call for better understanding of the role of environmental pollutant influences on mental health and the tremendous public health burden of mental health, this issue receives far less attention than many other effects of pollutants. Here we summarize the body of literature on non-occupational environmental pollutant exposures and adult depression, anxiety, and suicide—in PubMed, Embase, Web of Science, and PsychINFO through the end of year 2018. RECENT FINDINGS: One hundred twelve articles met our criteria for further review. Of these, we found 88 articles on depression, 33 on anxiety, and 22 on suicide (31 articles covered multiple outcomes). The earliest article was published in 1976, and the most frequent exposure of interest was air pollution (n=33), followed by secondhand smoke (n=20), metals (n=18), noise (n=17), and pesticides (n=10). Other exposures studied less frequently included radiation, magnetic fields, persistent organic pollutants (POPs), volatile organic compounds, solvents, and reactive sulfur compounds. SUMMARY: The current literature, although limited, clearly suggests many kinds of environmental exposures may be risk factors for depression, anxiety, and suicide. For several pollutants, important limitations exist with many of the studies. Gaps in the body of research include a need for more longitudinal, life-course studies, studies that can measure cumulative exposures as well as shorter-term exposures, studies that reduce the possibility of reverse causation, and mechanistic studies focused on neurotoxic exposures.

Background Maternal thyroid dysfunction is suspected of causing adverse neurodevelopmental effects, but current evidence is inconclusive. Epidemiologic investigations generally suggest an association between maternal thyroid dysfunction and neurodevelopment impairments in progeny, but clinical trials of thyroid treatment during pregnancy reported null effects. To better understand these discrepant findings, we evaluated the association between maternal thyroid conditions and autism spectrum disorder (ASD), including examining the role of gestational thyroid-related hormone concentrations and thyroid medications use. Methods Analyses considered 437,222 singleton live births occurring in a large Israeli health fund in 1999-2013, followed through 2016. Thyroid conditions and ASD cases were identified through International Classification of Diseases-9 codes with subsequent validation through review of medical records. Laboratory gestational thyroid hormone measurements were also considered. Results Children of mothers who ever experienced hypothyroidism had a higher risk of ASD compared with children of mothers without hypothyroidism (adjusted odds ratio [aOR] = 1.26, 95% confidence interval [CI] = 1.12, 1.42). The association with hyperthyroidism was less consistent, but elevated in main analyses (aOR = 1.42, 95% CI = 1.04, 1.94). These associations were not explained by maternal gestational thyroid hormones levels nor mitigated by gestational use of thyroid medications. Conclusions Results indicate that maternal thyroid conditions are associated with increased ASD risk in progeny, but suggestively not due to direct effects of thyroid hormones. Instead, factors that influence maternal thyroid function could have etiologic roles in ASD through pathways independent of maternal gestational thyroid hormones and thus be unaffected by medication treatment. Factors known to disrupt thyroid function should be examined for possible involvement in ASD etiology.

Cognitive function at middle age is of particular public health interest, as it strongly predicts later dementia. Children who have experienced abuse subsequently have worse cognitive function than those who have not. However, it remains unclear whether the association of abuse with cognitive function persists into middle age. In 2014–2016, 14,151 women ages 49–69 years who had previously responded to a childhood abuse questionnaire completed a cognitive battery. In models adjusted for childhood socioeconomic status and head trauma, combined physical, emotional, and sexual abuse was associated with lower scores on both Learning/Working Memory (severe abuse, lower scores similar to that observed in women 4.8 years older in our data) and Psychomotor Speed/Attention (severe abuse, lower scores similar to that observed in women to 2.9 years older in our data). Adjustment for adulthood socioeconomic status and health factors (e.g., smoking, hypertension) slightly attenuated associations. In exploratory analyses further adjusted for psychological distress, associations were attenuated. Women exposed versus unexposed to childhood abuse had poorer cognitive function at mid-life. Associations were particularly strong for learning and working memory and were not accounted for by adulthood health factors. Childhood abuse should be investigated as a potential risk factor for cognitive decline and dementia in old age.

BackgroundPrenatal inorganic arsenic (iAs) exposure is associated with pregnancy outcomes. Maternal capabilities of arsenic biotransformation and elimination may influence the susceptibility of arsenic toxicity. Therefore, we examined the determinants of arsenic metabolism of pregnant women in Bangladesh who are exposed to high levels of arsenic.MethodsIn a prospective birth cohort, we followed 1613 pregnant women in Bangladesh and collected urine samples at two prenatal visits: one at 4–16 weeks, and the second at 21–37 weeks of pregnancy. We measured major arsenic species in urine, including iAs (iAs%) and methylated forms. The proportions of each species over the sum of all arsenic species were used as biomarkers of arsenic methylation efficiency. We examined the difference in arsenic methylation using a paired t-test between first and second visits. Using linear regression, we examined determinants of arsenic metabolism, including age, BMI at enrollment, education, financial provider income, arsenic exposure level, and dietary folate and protein intake, adjusted for daily energy intake.ResultsComparing visit 2 to visit 1, iAs% decreased 1.1% (p p 50 μg/g-creatinine) gestational age at measurement was strongly associated with DMA% (β = 0.38, p ConclusionsOur findings indicate that arsenic metabolism and adjusted U-As level increase during pregnancy. We have identified determinants of arsenic methylation efficiency at visit 1.

Zusammenfassung. Aufgrund ihrer zentralen Bedeutung in der Kraftübertagung repräsentiert die Achillessehne in der Sportmedizin eine Prädilektionsstelle akuter sowie degenerativer Verletzungen. Speziell Laufsportarten sind von entsprechenden Pathologien betroffen. Konsekutiv sind eine sportartspezifische Diagnostik sowie Therapieplanung elementar, um eine individualisierte Rehabilitation garantieren zu können. Diesbezüglich gilt es jedoch einige anatomische, diagnostische und therapeutische Besonderheiten der Achillessehne zu beachten. Therapeutisch stehen dabei «in» sowie «out of season» entsprechende Physio- und Stosswellentherapieoptionen im Zentrum. Supportiv können im Einzelfall diverse peritendinöse Infiltrationstechniken evaluiert werden. In diesem Review liegt der Fokus auf der konservativen Therapie von Insertions- und «Midportion»-Tendinopathien der Achillessehne. Auf die nicht-operativen Optionen der Achillessehnenruptur wird ebenfalls eingegangen. Dieser konzise Überblick soll den klinisch tätigen Sportmediziner mit dem relevanten Basiswissen ausstatten.

Background: Former American football players have a higher prevalence of cognitive impairment than that of the US general population. It remains unknown what aspects of playing football are associated with neuropsychiatric outcomes. Hypothesis: It was hypothesized that seasons of professional football, playing position, and experience of concussions were associated with cognition-related quality of life (QOL) and indicators of depression and anxiety. Study Design: Descriptive epidemiology study. Methods: The authors examined whether seasons of professional football, playing position, and experience of concussions, as measured by self-report of 10 symptoms, were associated with cognition-related QOL and indicators of depression and anxiety in a cross-sectional survey conducted 2015 to 2017. Cognition-related QOL was measured by the short form of the Quality of Life in Neurological Disorders: Applied Cognition–General Concerns. The Patient Health Questionnaire–4 measured depression and anxiety symptoms. Of 13,720 eligible men with apparently valid contact information, 3506 players returned a questionnaire at the time of this analysis (response rate = 25.6%). Results: Seasons of professional play (risk ratio [RR] per 5 seasons = 1.19, 95% CI = 1.06-1.34) and playing position were associated with cognition-related QOL. Each 5 seasons of play was associated with 9% increased risk of indicators of depression at borderline statistical significance ( P = .05). When compared with former kickers, punters, and quarterbacks, men who played any other position had a higher risk of poor cognition-related QOL, depression, and anxiety. Concussion symptoms were strongly associated with poor cognition-related QOL (highest concussion quartile, RR = 22.3, P < .001), depression (highest quartile, RR = 6.0, P < .0001), and anxiety (highest quartile, RR = 6.4, P < .0001), even 20 years after last professional play. Conclusion: The data suggest that seasons of play and playing position in the NFL are associated with lasting neuropsychiatric health deficits. Additionally, poor cognition-related QOL, depression, and anxiety appear to be associated with concussion in the long term.

Prepulse inhibition (PPI) is a sensorimotor gating mechanism that reduces interfering influences to the neural processing of incoming stimuli, and is associated with several neurodevelopmental disorders. To date, research on PPI and neurodevelopmental disorders has primarily been in cross-sectional, clinical settings. In this prospective, epidemiologic study, we used a data-driven prediction model to identify socio-demographic predictors of PPI in children and adolescents from Mexico City to inform future etiologic studies evaluating PPI. We conducted variable selection and validation using a modified version of the multiple imputation random lasso (MIRL) variable selection algorithm. MIRL identified six predictors of PPI at a stimulus onset asynchrony of 120 ms or 240 ms. Of those six predictors, maternal education, birthweight, and total breastfeeding months were highlighted as previously unstudied variables associated with enhanced PPI. Our findings highlight the potential value of PPI as an adjunct screening tool for identifying children at risk for neurodevelopmental disorders and underscore the relevance for validation research on this topic.

Background The long-term health consequences of participation in American style football (ASF) are not well understood. Methods We conducted a retrospective cohort study of men who had played in the NFL after 1960. Participants were studied using a standardized self-administered questionnaire designed to determine both the exposure history to ASF and the prevalence of chronic pain, sleep apnea, cardiometabolic disease, and neurocognitive impairment. Logistic regression and negative binomial regression models were used to assess associations between age, ethnicity, body-mass index during professional football career, field position, and football career duration with individual and multiple afflictions. Results In this cohort of former NFL players (n = 3745), approximately one quarter of the eligible former players (27%) reported two or more medical afflictions (chronic pain, cardiometabolic disease, sleep apnea, or neurocognitive impairment). Career duration was significantly associated with an increase in the number of comorbidities. Age, race, and body-mass index were associated with all affliction categories, other than neurocognitive impairment, which was similarly prevalent in middle-aged players and older players. Earlier age when first playing the sport was protective against cardiometabolic affliction. Conclusions Former NFL players report significant combinations of cross-system afflictions. Future work will be required to determine mechanistic underpinnings. However, attention to the whole player, rather than specific organ systems seems critical to improve long-term health outcomes in former ASF professional athletes.

Scheduled to launch in late 2021 the Imaging X-ray Polarimetry Explorer (IXPE) is a Small Explorer Mission designed to open up a new window of investigation -- X-ray polarimetry. The IXPE observatory features 3 identical telescope each consisting of a mirror module assembly with a polarization-sensitive imaging x-ray detector at its focus. An extending beam, deployed on orbit provides the necessary 4 m focal length. The payload sits atop a 3-axis stabilized spacecraft which among other things provides power, attitude determination and control, commanding, and telemetry to the ground. During its 2-year baseline mission, IXPE will conduct precise polarimetry for samples of multiple categories of x-ray sources, with follow-on observations of selected targets. IXPE is a partnership between NASA and the Italian Space Agency (ASI).

BACKGROUND AND AIM: Little is known about the associations between ambient environmental exposures and risk of acute episodes of psychiatric disorders. We aim to estimate the risk of acute psychiat...

Background Long-term exposure to fine particulate matter (PM2.5) has been associated with neurodegenerative diseases, including disease aggravation in Parkinson's disease (PD), but associations with specific PM2.5 components have not been evaluated. Objective To characterize the association between specific PM2.5 components and PD first hospitalization, a surrogate for disease aggravation. Methods We obtained data on hospitalizations from the New York Department of Health Statewide Planning and Research Cooperative System (2000–2014) to calculate annual first PD hospitalization counts in New York State per county. We used well-validated prediction models at 1 km2 resolution to estimate county level population-weighted annual black carbon (BC), organic matter (OM), nitrate, sulfate, sea salt (SS), and soil particle concentrations. We then used a multi-pollutant mixed quasi-Poisson model with county-specific random intercepts to estimate rate ratios (RR) of one-year exposure to each PM2.5 component and PD disease aggravation. We evaluated potential nonlinear exposure–outcome relationships using penalized splines and accounted for potential confounders. Results We observed a total of 197,545 PD first hospitalizations in NYS from 2000 to 2014. The annual average count per county was 212 first hospitalizations. The RR (95% confidence interval) for PD aggravation was 1.06 (1.03, 1.10) per one standard deviation (SD) increase in nitrate concentrations and 1.06 (1.04, 1.09) for the corresponding increase in OM concentrations. We also found a nonlinear inverse association between PD aggravation and BC at concentrations above the 96th percentile. We found a marginal association with SS and no association with sulfate or soil exposure. Conclusion In this study, we detected associations between the PM2.5 components OM and nitrate with PD disease aggravation. Our findings support that PM2.5 adverse effects on PD may vary by particle composition.

Background Fatal police violence in the United States disproportionately affects Black, Native American, and Hispanic people, and for these groups it is a racially oppressive population-level stressor that we hypothesize increases the risk of pregnancy loss. Focusing on core based statical areas (CBSAs) surrounding small and large urban centers, we accordingly tested whether gestational exposure to fatal police violence decreased the number of live births, which is reflective of a rise in lost pregnancies. Methods Our observational study linked microdata for all births (N = 7,709,300) in 520 CBSAs with at least one incident of fatal police violence in 2013–2015 to Fatal Encounters, a database that prospectively identified 2594 police-related fatalities using online media reports and public records. We estimated the association between month-to-month fatal police violence and conceptions resulting in live births using distributed lag quasi-Poisson models with CBSA-level fixed effects, adjusted for seasonality and stratified by maternal race/ethnicity. Findings For each additional police-related fatality that occurred in the first through sixth months of gestation, we observed a 0.14% decrease (95% confidence interval: 0.05%, 0.23%) in the total number of live births within CBSAs, and a 0.29% decrease in births to Black women (95% CI: 0.11%, 0.48%). The association was null for births to White women. Interpretation Our findings suggest fatal police violence may have population-level consequences for pregnancy loss and adds to the evidence regarding the importance of preventing these fatalities. Funding This study was supported in part by NIH grant P30ES00002 to MGW.

Background Diethylstilbestrol (DES) is an endocrine-disrupting pharmaceutical prescribed to pregnant women to prevent pregnancy complications between the 1940s and 1970s. Although DES has been shown in animal studies to have multigenerational effects, only two studies have investigated potential multigenerational effects in humans on preterm birth (PTB), and none on low birthweight (LBW)—major determinants of later life health. Methods Nurses’ Health Study (NHS) II participants (G1; born 1946–64) reported their mothers’ (G0) use of DES while pregnant with them. We used cluster-weighted generalized estimating equations to estimate odds ratios (OR) and 95% confidence intervals (CI) for risk of LBW and PTB among the grandchildren by grandmother use of DES. G1 birthweight and gestational age were considered to explore confounding by indication. Results Among 54 334 G0-G1/grandmother-mother pairs, 973 (1.8%) G0 used DES during pregnancy with G1. Of the 128 275 G2 children, 4369 (3.4%) were LBW and 7976 (6.2%) premature. Grandmother (G0) use of DES during pregnancy was associated with an increased risk of G2 LBW [adjusted OR (aOR) = 3.09; 95% CI: 2.57, 3.72], that was reduced when restricted to term births (aOR = 1.59; 95% CI: 1.08, 2.36). The aOR for PTB was 2.88 (95% CI: 2.46, 3.37). Results were essentially unchanged when G1 birthweight and gestational age were included in the model, as well as after adjusting for other potential intermediate variables, such as G2 pregnancy-related factors. Conclusions Grandmother use of DES during pregnancy is associated with an increased risk of LBW, predominantly through an increased risk of PTB. Results when considering G1 birth outcomes suggest this does not result from confounding by indication.

IXPE, an international collaboration, will conduct x-ray imaging polarimetry for multiple categories of cosmic x-ray sources such as neutron stars, stellar-mass black holes, supernova remnants and active galactic nuclei. The Observatory uses a single science operational mode capturing the x-ray data from the targets. This paper summarizes the IXPE Mission System: Observatory, Launch Segment and Ground System. The IXPE Observatory consists of spacecraft and payload modules built up in parallel to form the Observatory during system integration and test. The payload includes three x-ray telescopes each consisting of a polarization-sensitive, gas pixel x-ray detector, paired with its corresponding grazing incidence mirror module assembly (MMA), x-ray optics set. A deployable boom provides the correct separation (focal length) between the detector units (DU) and MMAs. These payload elements are supported by the IXPE spacecraft which is derived from the BCP-small spacecraft architecture. IXPE is launched to a circular LEO orbit at an altitude of 600 km and an inclination of -0.2 degrees by a Falcon 9 launch vehicle. The ground system consists of three major elements: the ground stations for data receipt and command upload to the Observatory; the Mission Operations Center (MOC) at University of Colorado Laboratory for Atmospheric and Space Physics (CU/LASP); and Science Operations Center (SOC) at NASA Marshall Space Flight Center (MSFC). This paper summarizes the IXPE mission science objectives, updates the Observatory implementation concept including the payload and spacecraft elements, covers the launch segment, ground system and summarizes the mission status since last year's conference including COVID impacts.

Background: Adult-onset neurodegenerative diseases affect millions and negatively impact health care systems worldwide. Evidence suggests that air pollution may contribute to aggravation of neurodegeneration, but studies have been limited. Objective: We examined the potential association between long-term exposure to particulate matter ≤2.5μm in aerodynamic diameter [fine particulate matter (PM2.5)] and disease aggravation in Alzheimer’s (AD) and Parkinson’s (PD) diseases and amyotrophic lateral sclerosis (ALS), using first hospitalization as a surrogate of clinical aggravation. Methods: We used data from the New York Department of Health Statewide Planning and Research Cooperative System (SPARCS 2000–2014) to construct annual county counts of first hospitalizations with a diagnosis of AD, PD, or ALS (total, urbanicity-, sex-, and age-stratified). We used annual PM2.5 concentrations estimated by a prediction model at a 1-km2 resolution, which we aggregated to population-weighted county averages to assign exposure to cases based on county of residence. We used outcome-specific mixed quasi-Poisson models with county-specific random intercepts to estimate rate ratios (RRs) for a 1-y PM2.5 exposure. We allowed for nonlinear exposure–outcome relationships using penalized splines and accounted for potential confounders. Results: We found a positive nonlinear PM2.5–PD association that plateaued above 11 μg/m3 (RR=1.09, 95% CI: 1.04, 1.14 for a PM2.5 increase from 8.1 to 10.4 μg/m3). We also found a linear PM2.5–ALS positive association (RR=1.05, 95% CI: 1.01, 1.09 per 1-μg/m3 PM2.5 increase), and suggestive evidence of an association with AD. We found effect modification by age for PD and ALS with a stronger positive association in patients

BackgroundLead is a ubiquitous toxicant following three compartment kinetics with the longest half-life found in bones. Patella and tibia lead levels-validated measures of cumulative exposure-require specialized X-ray-fluorescence-spectroscopy available only in a few centers worldwide. We developed minimally invasive biomarkers reflecting individual cumulative lead exposure using blood DNA methylation profiles-obtainable via Illumina 450K or IlluminaEPIC bead-chip assays.MethodsWe developed and tested two methylation-based biomarkers from 348 Normative Aging Study (NAS) elderly men. We selected methylation sites with strong associations with bone lead levels via robust regressions analysis and constructed the biomarkers using elastic nets. Results were validated in a NAS subset, reporting specificity, and sensitivity.FindingsParticipants were 73 years old on average (standard deviation, SD = 6), with moderate lead levels of (mean ± SD patella: 27 ± 18 µg/g; tibia:21 ± 13 µg/g). Methylation-based biomarkers for lead in patella and tibia included 59 and 138 DNA methylation sites, respectively. Estimated lead levels were significantly correlated with actual measured values, (r = 0.62 patella, r = 0.59 tibia) and had low mean square error (MSE) (MSE = 0.68 patella, MSE = 0.53 tibia). Means and distributions of the estimated and actual lead levels were not significantly different across patella and tibia bones (p > 0.05). Methylation-based biomarkers discriminated participants highly exposed (>median) to lead with a specificity of 74 and 73% for patella and tibia lead levels, respectively, with 70% sensitivity.InterpretationDNA methylation-based lead biomarkers are novel tools that can be used to reconstruct decades' worth of individual cumulative lead exposure using only blood DNA methylation profiles and may help identify the consequences of cumulative exposure.

BACKGROUND Former American style football players (ASF players) have recognized health concerns associated with prior sport participation. It remains unknown whether categorizations of current health conditions, referred to in this report as afflictions (conceptually framed as neurocognitive, cardiovascular, cardiometabolic, sleep apnea, and chronic pain) are associated with physical and mental function. OBJECTIVE To evaluate the association of afflictions to physical and mental function. It was hypothesized that former National Football League players with any affliction would have worse function compared to unafflicted participants. It was anticipated that multiple afflictions would result in cumulative loss of function. DESIGN Cross-sectional retrospective design. SETTING Academic medical multisite hospital system. PARTICIPANTS A total of 3913 of 15,611 former ASF players who played professionally from 1960 to 2019 (response rate 25%). Assessment of Risk Factors Self-report survey. MAIN OUTCOME MEASURES Each participant completed the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale and Physical Function questionnaires. Responses were used to generate two physical function and one mental function subscale scores. Raw scores were converted to T-scores categorized as impaired (T-score

While chronic neurological effects from concussion have been studied widely, little is known about possible links between concussion and long-term medical and behavioral comorbidities. We performed a retrospective cohort study of 9205 adult patients with concussion, matched to non-concussion controls from a hospital-based electronic medical registry. Patients with comorbidities before the index visit were excluded. Behavioral and medical comorbidities were defined by International Classification of Diseases, Ninth and Tenth Revision codes. Groups were followed for up to 10 years to identify comorbidity incidence after a concussion. Cox proportional hazards models were used to calculate associations between concussion and comorbidities after multi-variable adjustment. Patients with concussion were 57% male (median age: 31; interquartile range [IQR] = 23–48 years) at enrollment with a median follow-up time of 6.1 years (IQR = 4.2–9.1) and well-matched to healthy controls. Most (83%) concussions were evaluated in outpatient settings (5% inpatient). During follow-up, we found significantly higher risks of cardiovascular risks developing including hypertension (hazard ratio [HR] = 1.7, 95% confidence interval [CI]: 1.5–1.9), obesity (HR = 1.7, 95% CI: 1.3–2.0), and diabetes mellitus (HR = 1.8, 95% CI: 1.4–2.3) in the concussion group compared with controls. Similarly, psychiatric and neurological disorders such as depression (HR = 3.0, 95% CI: 2.6–3.5), psychosis (HR = 6.0, 95% CI: 4.2–8.6), stroke (HR = 2.1 95% CI: 1.5–2.9), and epilepsy (HR = 4.4, 95% CI: 3.2–5.9) were higher in the concussion group. Most comorbidities developed less than five years post-concussion. The risks for post-concussion comorbidities were also higher in patients under 40 years old compared with controls. Patients with concussion demonstrated an increased risk of development of medical and behavioral health comorbidities. Prospective studies are warranted to better describe the burden of long-term comorbidities in patients with concussion.

Objectives: Stressful life events, especially relationship events, are frequent in adult life. We investigated the impact of a variety of stressful life events on symptoms of depression, anxiety, and hostility.Methods: We analyzed data from a large prospective cohort study of men (n = 1,437) in the Boston area (assessed in 1985, 1988, and 1991). Main outcomes were measures of depression, anxiety and hostility symptoms. We used the Elders Life Stress Inventory (ELSI) to measure stressful life events in the past 12 months and examine their association with symptoms of depression, anxiety and hostility. First, we analyzed the association of stressful life events with symptom changes; second, we categorized stressful life events into finance/work, health, relationships, loss, living situations events; and third, we estimated the specific association between relationship events and depression, anxiety and hostility symptoms using multilevel models.Results: The most frequent stressful life events were health, relationship, and financial events. Depression, anxiety, and hostility symptoms were relatively stable among men who did not experience these life events. However, those who reported life events in the past 12 months had a greater increase in symptoms of depression (+0.05; 95% CI: 0.01 to 0.10) and of hostility (+0.05; 95% CI: 0.01 to 0.09) than those who did not. Additionally, we found a significant decrease in hostility (−0.05; 95% CI: −0.08 to −0.01) in those experiencing no life events.Conclusion: Relationship events were more important than any other type of events, and were significantly associated with increased depression and hostility in aging men. Although the effects were small, the results point to a need to understand better the impact of relationships on psychopathology in the aging population.

Investigating the joint exposure to several risk factors is becoming a key component of epidemiologic studies. Individuals are exposed to multiple factors, often simultaneously, and evaluating patterns of exposures and high-dimension interactions may allow for a better understanding of health risks at the individual level. When jointly evaluating high-dimensional exposures, common statistical methods should be integrated with machine learning techniques that may better account for complex settings. Among these, Logic regression was developed to investigate a large number of binary exposures as they relate to a given outcome. This method may be of interest in several public health settings, yet has never been presented to an epidemiologic audience. In this paper, we review and discuss Logic regression as a potential tool for epidemiological studies, using an example of occupation history (68 binary exposures of primary occupations) and amyotrophic lateral sclerosis in a population-based Danish cohort. Logic regression identifies predictors that are Boolean combinations of the original (binary) exposures, fully operating within the regression framework of interest (e. g. linear, logistic). Combinations of exposures are graphically presented as Logic trees, and techniques for selecting the best Logic model are available and of high importance. While highlighting several advantages of the method, we also discuss specific drawbacks and practical issues that should be considered when using Logic regression in population-based studies. With this paper, we encourage researchers to explore the use of machine learning techniques when evaluating large-dimensional epidemiologic data, as well as advocate the need of further methodological work in the area.

Background: Ex vivo lung perfusion (EVLP) is a technology that allows the re-evaluation of questionable donor lung before implantation and it has the potential to repair injured donor lungs that are otherwise unsuitable for transplantation. We hypothesized that perfluorocarbon-based oxygen carrier, a novel reconditioning strategy instilled during EVLP would improve graft function. Methods: We utilized perfluorocarbon-based oxygen carrier (PFCOC) during EVLP to recondition and improve lung graft function in a pig model of EVLP and lung transplantation. Lungs were retrieved and stored for 24 h at 4 &deg, C. EVLP was done for 6 h with or without PFCOC. In the transplantation groups, left lung transplantation was done after EVLP with or without PFCOC. Allograft function was assessed by means of pulmonary gas exchange, lung mechanics and vascular pressures, histology and transmission electron microscopy (TEM). Results: In the EVLP only groups, physiological and biochemical markers during the 6-h perfusion period were comparable. However, perfusate lactate potassium levels were lower and ATP levels were higher in the PFCOC group. Radiologic assessment revealed significantly more lung infiltrates in the controls than in the PFCOC group (p = 0.04). In transplantation groups, perfusate glucose consumption was higher in the control group. Lactate levels were significantly lower in the PFCOC group (p = 0.02). Perfusate flavin mononucleotide (FMN) was significantly higher in the controls (p = 0.008). Post-transplant gas exchange was significantly better during the 4-h reperfusion period in the PFCOC group (p = 0.01). Plasma IL-8 and IL-12 levels were significantly lower in the PFCOC group (p = 0.01, p = 0.03, respectively). ATP lung tissue levels at the end of the transplantation were higher and myeloperoxidase (MPO) levels in lung tissue were lower in the PFCOC group compared to the control group. In the PFCOC group, TEM showed better tissue preservation and cellular viability. Conclusion: PFCOC application is safe during EVLP in lungs preserved 24 h at 4 &deg, C. Although this strategy did not significantly affect the EVLP physiology, metabolic markers of the donor quality such as lactate production, glucose consumption, neutrophil infiltration and preservation of mitochondrial function were better in the PFCOC group. Following transplantation, PFCOC resulted in better graft function and TEM showed better tissue preservation, cellular viability and improved gas transport.

Studies of occupational metal exposures and amyotrophic lateral sclerosis (ALS) have focused primarily on known neurotoxicants, including lead, mercury, selenium, and cadmium. However, these exposures are often co-occurring with other lesser studied metals. We conducted a population-based case-control study with the aim of assessing associations between occupational chromium, iron, and nickel exposures and risk of ALS. We identified ALS cases in Denmark from 1982 through 2013 from the Danish National Patient Registry and matched them to 100 controls based on birth year and sex. Cumulative metal exposures were estimated using job exposure matrices applied to occupational history from the Danish Pension Fund. Although mutually adjusted odds of ALS were higher in men with chromium exposures in the third quartile (aOR = 1.24, 95% CI 0.91, 1.69) and fourth quartile (aOR = 1.19, 95% CI: 0.80, 1.76) compared to those with no exposure, differences did not reach statistical significance. We also observed higher odds of ALS in women with nickel exposures in the third quartile (aOR = 2.21, 95% CI: 1.14, 4.28), but not for the fourth quartile (aOR = 0.61, 95% CI: 0.23, 1.64). Our findings do not suggest associations between occupational exposures to these metals and ALS. However, unavoidable non-differential misclassification from the use of JEMs may have masked truly increased risk.

Background/Aims Childhood obesity has become a global epidemic, with 1 in 3 children in the United States affected. The etiology of obesity is multifactorial, including genetic, perinatal, dietary,...

Neurodegenerative disorders, including Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease, are thought to be caused by both genetic and environmental factors. Several metals and metalloids have been identified as neurotoxicants and exposure may occur, for example, via air pollution, contaminated food or drinking water, cigarette smoke, or in occupational settings. Epidemiological evidence of associations between metal exposure and neurodegenerative disorders, however, is scarce. Here we provide an overview of metals that have been suggested to play a role in neurodegeneration. Investigating these associations is challenged by accurate case ascertainment due to complicated diagnosis, multifactorial disease mechanisms, long latency requiring retrospective exposure assessment, and possible reverse causality when comparing cases and controls. Further research on understanding the role of metals in the pathology of neurodegenerative disorders is needed. Future epidemiological studies should be large and high-quality studies to provide the crucial evidence on metal exposures as possible risk factors.

To assess the prevalence of distress and burnout in otolaryngology trainees, including associations with relevant sociodemographic and professional factors, and to compare these results with those of attending otolaryngologists.A cross-sectional survey of trainees and attending physicians.Twelve academic otolaryngology programs.Distress and burnout were measured with the Expanded Physician Well-being Index and the 2-item Maslach Burnout Inventory. The Patient Health Questionnaire-2 and Generalized Anxiety Disorder-2 were used to screen for depressive disorders and anxiety disorders, respectively. Associations with sociodemographic and professional characteristics were assessed.Of the 613 surveys administered to trainees and attending physicians, 340 were completed (56%). Among 154 trainees, distress was present in 49%, professional burnout in 35%, positive depressive disorder screening in 5%, and positive anxiety disorder screening in 16%. In univariable analysis, female gender, hours worked in a typical week (HW), and nights on call in a typical week (NOC) were significantly associated with distress. In multivariable analysis, female gender (odds ratio, 3.91;Otolaryngology trainees experience significant work-place distress (49%) and burnout (35%). Gender, HW, and NOC had the strongest associations with distress and burnout.

To ascertain the prevalence of and associations with distress and professional burnout among academic otolaryngology attending physicians.Cross-sectional survey.Twelve US academic otolaryngology programs.A questionnaire was administered that encompassed sociodemographic and professional features, the Expanded Physician Well-being Index for distress, the 2-item Maslach Burnout Inventory for professional burnout, the Patient Health Questionnaire-2 screen for major depressive disorder, and the Generalized Anxiety Disorder-2 screen for generalized anxiety disorder.The survey response rate was 56% and included 186 attending physicians. The average respondent age was 47 years; 72% were men; 93% were married or partnered; and 86% had children. Distress was present in 40%, professional burnout in 26%, positive depression screening in 8%, and positive anxiety screening in 11%. In a univariable setting, age, hours worked in a typical week, nights on call in a typical week, and years of practice were significantly associated with distress, although in a multivariable setting, only hours worked in a typical week remained significantly associated with a positive Expanded Physician Well-being Index screen (odds ratio for each 10-hour increase, 2.61; 95% CI, 1.73-3.93;Distress or professional burnout occurs in more than a quarter of academic otolaryngology attending physicians, whereas the prevalence of depression or anxiety is approximately 10%. The number of hours worked per week had the strongest association with distress and burnout. These findings may be used to develop and implement programs to promote physician well-being and mitigate professional burnout.

Several meta-analytical attempts to reproduce results of empirical research have failed in recent years, prompting scholars and news media to diagnose a “replication crisis” and voice concerns about science losing public credibility. Others, in contrast, hoped replication efforts could improve public confidence in science. Yet nationally representative evidence backing these concerns or hopes is scarce. We provide such evidence, conducting a secondary analysis of the German “Science Barometer” (“Wissenschaftsbarometer”) survey. We find that most Germans are not aware of the “replication crisis.” In addition, most interpret replication efforts as indicative of scientific quality control and science’s self-correcting nature. However, supporters of the populist right-wing party AfD tend to believe that the “crisis” shows one cannot trust science, perhaps using it as an argument to discredit science. But for the majority of Germans, hopes about reputational benefits of the “replication crisis” for science seem more justified than concerns about detrimental effects.

NASA’s Marshall Space Flight Center (MSFC) maintains an active research program toward the development of high-resolution, lightweight, grazing-incidence x-ray optics to serve the needs of future x-ray astronomy missions such as Lynx. MSFC development efforts include both direct fabrication (diamond turning and deterministic computer-controlled polishing) of mirror shells and replication of mirror shells (from figured, polished mandrels). Both techniques produce full-circumference monolithic (primary + secondary) shells that share the advantages of inherent stability, ease of assembly, and low production cost. However, to achieve high-angular resolution, MSFC is exploring significant technology advances needed to control sources of figure error including fabrication- and coating-induced stresses and mounting-induced distortions.

Purpose Race differences in health are pervasive in the United States. American-style football players are a racially diverse group with social status and other benefits that may reduce health disparities. Whether race disparities in health exist among former professional football players, and whether they differ by era of play, is unknown. Methods We examined the association of self-reported race with health outcomes (e.g., physical and cognitive function, pain, depression and anxiety), among 3,747 participants in the Football Players Health Study, comprised of former National Football League (NFL) players who played since 1960. We conducted analyses stratified by age. Results Black players had increased risk of all five adverse health outcomes versus white players (risk ratio (RR) range=1.36 to 1.89). Native Hawaiians and men of other races had greater risk of all health outcomes except impaired physical functioning, compared with white players (RR range=1.25 to 1.64). No clear patterns were observed by era of play. In general, race disparities were not accounted for by health-related exposures during playing years. Adjustment for current BMI somewhat attenuated associations. Conclusions Social and economic advantages of playing professional football did not appear to equalized race disparities in health.

Frequent maternal use of acetaminophen in pregnancy has been linked to attention-deficit/hyperactivity disorder (ADHD) in children, but concerns regarding uncontrolled confounding remain. In this article, we illustrate use of the negative control exposure (NCE) approach to evaluate uncontrolled confounding bias in observational studies on pregnancy drug safety and explain the causal assumptions behind the method. We conducted an NCE analysis and evaluated the associations between maternal acetaminophen use during different exposure periods and ADHD among 8,856 children born in 1993–2005 to women enrolled in the Nurses’ Health Study II cohort. Information on regular maternal acetaminophen use was collected prospectively in biennial questionnaires. A total of 721 children (8.1%) in the cohort had been diagnosed with ADHD as reported by the mothers. Our NCE analysis suggested that only acetaminophen use at the time of pregnancy was associated with childhood ADHD (odds ratio = 1.34, 95% confidence interval: 1.05, 1.72), and the effect estimates for the 2 NCE periods (about 4 years before and 4 years after the pregnancy) were null. Our findings corroborate those of prior reports suggesting that prenatal acetaminophen exposure may influence neurodevelopment. The lack of an association between acetaminophen use in the pre- and postpregnancy exposure periods and ADHD provides assurance that uncontrolled time-invariant factors do not explain this association.

Background Tampons are used by up to 86% of US women and are a rarely considered potential source of pesticide and metal exposure. Tampons may be of particular concern given the likely higher absorption that occurs in the vagina. Our objective was to examine the potential associations between tampon use and metal concentrations, and biomarkers of inflammation and oxidative stress among healthy women. Methods We used information from a prospective cohort of 259 regularly menstruating women, aged 18–44, followed for two menstrual cycles. Tampon use was assessed using information provided in participant study diaries. Metal concentrations were measured from a blood sample collected at enrollment. Oxidative stress and inflammation biomarker concentrations were determined from blood samples collected at up to 8 clinic visits for each cycle. Linear regression models were used to estimate associations of tampon use with metal exposure, and linear mixed models to estimate associations of tampon use with inflammation and oxidative stress biomarkers at different times during the menstrual cycle. Results We observed non-significantly higher mean levels of mercury for tampon users compared to non-tampon users (exp(β) = 1.25, 95% CI = 0.93, 1.68). We found no evidence of an association between tampon use and inflammation biomarkers. We observed consistently higher isoprostane levels, an oxidative stress biomarker, among tampon users compared to non-tampon users (e.g. exp.(β) = 1.05, 95%CI = 0.96, 1.16, for the average isoprostane during the menstruating week); however, these results were not statistically significant. Conclusions While our results are not statistically significant, we observed suggestive associations between tampon use and elevated levels of mercury and oxidative stress biomarkers. Although our finding should be interpreted in light of our limitations, they indicate that tampons may be a source of exposure to metals and chemicals that have been largely ignored, and any related health effects are an important public health concern. Electronic supplementary material The online version of this article (10.1186/s12940-019-0452-z) contains supplementary material, which is available to authorized users.

ObjectivesPrevious research has indicated links between lead (Pb) exposure and increased risk of neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). In this study, we evaluated the association between occupational Pb exposures and ALS.MethodsALS cases were ascertained through the Danish National Patient Registry from 1982 to 2013 and age and sex-matched to 100 controls. Using complete employment history since 1964 from the Danish Pension Fund, cumulative Pb exposure was estimated for each subject via a Danish job exposure matrix. Associations were evaluated using conditional logistic regression analyses and stratified by sex.ResultsFor men with >50% probability of exposure, there was an increase in odds of ALS for exposures in the 60th percentile or higher during any time 5 years prior to diagnosis (aOR: 1.35; 95% CI 1.04 to 1.76) and 10 years prior to diagnosis (aOR: 1.33; 95% CI 1.03 to 1.72). No significant associations were observed in women, and there were no linear trends seen for Pb exposures for either sex.ConclusionsOur study indicates an association between consistently higher occupational Pb exposures and ALS. These findings support those of previously reported associations between ALS and specific occupations that commonly experience Pb exposure.