Independent and joint effects of neighborhood-level environmental and socioeconomic exposures on body mass index in early childhood: The environmental influences on child health outcomes (ECHO) cohort.

Past studies support the hypothesis that the prenatal period influences childhood growth. However, few studies explore the joint effects of exposures that occur simultaneously during pregnancy. To explore the feasibility of using mixtures methods with neighborhood-level environmental exposures, we assessed the effects of multiple prenatal exposures on body mass index (BMI) from birth to age 24 months. We used data from two cohorts: Healthy Start (n = 977) and Maternal and Developmental Risks from Environmental and Social Stressors (MADRES; n = 303). BMI was measured at delivery and 6, 12, and 24 months and standardized as z-scores. We included variables for air pollutants, built and natural environments, food access, and neighborhood socioeconomic status (SES). We used two complementary statistical approaches: single-exposure linear regression and quantile-based g-computation. Models were fit separately for each cohort and time point and were adjusted for relevant covariates. Single-exposure models identified negative associations between NO2 and distance to parks and positive associations between low neighborhood SES and BMI z-scores for Healthy Start participants; for MADRES participants, we observed negative associations between O3 and distance to parks and BMI z-scores. G-computations models produced comparable results for each cohort: higher exposures were generally associated with lower BMI, although results were not significant. Results from the g-computation models, which do not require a priori knowledge of the direction of associations, indicated that the direction of associations between mixture components and BMI varied by cohort and time point. Our study highlights challenges in assessing mixtures effects at the neighborhood level and in harmonizing exposure data across cohorts. For example, geospatial data of neighborhood-level exposures may not fully capture the qualities that might influence health behavior. Studies aiming to harmonize geospatial data from different geographical regions should consider contextual factors when operationalizing exposure variables.

Neighborhood Walkability, Historical Redlining, and Childhood Obesity in Denver, Colorado.

Childhood obesity is a precursor to future health complications. In adults, neighborhood walkability is inversely associated with obesity prevalence. Recently, it has been shown that current urban walkability has been influenced by historical discriminatory neighborhood disinvestment. However, the relationship between this systemic racism and obesity has not been extensively studied. The objective of this study was to evaluate the association of neighborhood walkability and redlining, a historical practice of denying home loans to communities of color, with childhood obesity. We evaluated neighborhood walkability and walkable destinations for 250 participants of the Healthy Start cohort, based in the Denver metropolitan region. Eligible participants attended an examination between ages 4 and 8. Walkable destinations and redlining geolocations were determined based on residential addresses, and a weighting system for destination types was developed. Sidewalks and trails in Denver were included in the network analyst tool in ArcMap to calculate the precise walkable environment for each child. We implemented linear regression models to estimate associations between neighborhood characteristics and child body mass index (BMI) z-scores and fat mass percent. There was a significant association between child BMI and redlining (ß: 1.36, 95% CI: 0.106, 2.620). We did not find an association between walkability measures and childhood obesity outcomes. We propose that cities such as Denver pursue built environment policies, such as inclusionary zoning and direct investments in neighborhoods that have been historically neglected, to reduce the childhood health impacts of segregated poverty, and suggest further studies on the influences that redlining and urban built environment factors have on childhood obesity.

Early-life exposure to residential black carbon and childhood cardiometabolic health.

BACKGROUND: Early life exposure to air pollution, such as particulate matter ≤2.5 µm (PM2.5), may be associated with obesity and adverse cardiometabolic health outcomes in childhood. However, the toxicity of PM2.5 varies according to its chemical composition. Black carbon (BC) is a constituent of PM2.5, but few studies have examined its impact on childhood cardiometabolic health. Therefore, we examined relationships between prenatal and early childhood exposure to BC and markers of adiposity and cardiometabolic health in early childhood. METHODS: This study included 578 mother-child pairs enrolled in the Healthy Start study (2009-2014) living in the Denver-metro area. Using a spatiotemporal prediction model, we assessed average residential black carbon levels during pregnancy and in the year prior to the early childhood follow-up visit at approximately 5 years old. We estimated associations between prenatal and early childhood BC and indicators of adiposity and cardiometabolic biomarkers in early childhood (mean 4.8 years; range, 4.0, 8.3), using linear regression. RESULTS: We found higher early childhood BC was associated with higher percent fat mass, fat mass index, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR), and lower leptin and waist circumference at approximately 5 years old, after adjusting for covariates. For example, per interquartile range (IQR) increase in early childhood BC (IQR, 0.49 µg/m3) there was 3.32% higher fat mass (95% CI; 2.05, 4.49). Generally, we did not find consistent evidence of associations between prenatal BC and cardiometabolic health outcomes in early childhood, except for an inverse association between prenatal BC and adiponectin, an adipocyte-secreted hormone typically inversely associated with adiposity. CONCLUSIONS: Higher early childhood, but not in utero, ambient concentrations of black carbon, a component of air pollution, were associated with greater adiposity and altered insulin homeostasis at approximately 5 years old. Future studies should examine whether these changes persist later in life.

The COVID-19-wildfire smoke paradox: Reduced risk of all-cause mortality due to wildfire smoke in Colorado during the first year of the COVID-19 pandemic.

BACKGROUND: In 2020, the American West faced two competing challenges: the COVID-19 pandemic and the worst wildfire season on record. Several studies have investigated the impact of wildfire smoke (WFS) on COVID-19 morbidity and mortality, but little is known about how these two public health challenges impact mortality risk for other causes. OBJECTIVES: Using a time-series design, we evaluated how daily risk of mortality due to WFS exposure differed for periods before and during the COVID-19 pandemic. METHODS: Our study included daily data for 11 counties in the Front Range region of Colorado (2010-2020). We assessed WFS exposure using data from the National Oceanic and Atmospheric Administration and used mortality counts from the Colorado Department of Public Health and Environment. We estimated the interaction between WFS and the pandemic (an indicator variable) on mortality risk using generalized additive models adjusted for year, day of week, fine particulate matter, ozone, temperature, and a smoothed term for day of year. RESULTS: WFS impacted the study area on 10% of county-days. We observed a positive association between the presence of WFS and all-cause mortality risk (incidence rate ratio (IRR) = 1.03, 95%CI: 1.01-1.04 for same-day exposures) during the period before the pandemic; however, WFS exposure during the pandemic resulted in decreased risk of all-cause mortality (IRR = 0.90, 95%CI: 0.87-0.93 for same-day exposures). DISCUSSION: We hypothesize that mitigation efforts during the first year of the pandemic, e.g., mask mandates, along with high ambient WFS levels encouraged health behaviors that reduced exposure to WFS and reduced risk of all-cause mortality. Our results suggest a need to examine how associations between WFS and mortality are impacted by pandemic-related factors and that there may be lessons from the pandemic that could be translated into health-protective policies during future wildfire events.

Global rural health disparities in Alzheimer's disease and related dementias: State of the science.

INTRODUCTION: Individuals living in rural communities are at heightened risk for Alzheimer's disease and related dementias (ADRD), which parallels other persistent place-based health disparities. Identifying multiple potentially modifiable risk factors specific to rural areas that contribute to ADRD is an essential first step in understanding the complex interplay between various barriers and facilitators. METHODS: An interdisciplinary, international group of ADRD researchers convened to address the overarching question of: "What can be done to begin minimizing the rural health disparities that contribute uniquely to ADRD?" In this state of the science appraisal, we explore what is known about the biological, behavioral, sociocultural, and environmental influences on ADRD disparities in rural settings. RESULTS: A range of individual, interpersonal, and community factors were identified, including strengths of rural residents in facilitating healthy aging lifestyle interventions. DISCUSSION: A location dynamics model and ADRD-focused future directions are offered for guiding rural practitioners, researchers, and policymakers in mitigating rural disparities. HIGHLIGHTS: Rural residents face heightened Alzheimer's disease and related dementia (ADRD) risks and burdens due to health disparities. Defining the unique rural barriers and facilitators to cognitive health yields insight. The strengths and resilience of rural residents can mitigate ADRD-related challenges. A novel "location dynamics" model guides assessment of rural-specific ADRD issues.

Preliminary investigation of a hypertonic saline nasal rinse as a hygienic intervention in dairy workers.

Livestock workers experience an increased burden of bioaerosol-induced respiratory disease including a high prevalence of rhinosinusitis. Dairy operations generate bioaerosols spanning the inhalable size fraction (0-100 µm) containing bacterial constituents such as endotoxin. Particles with an aerodynamic diameter between 10 and 100 µm are known to deposit in the nasopharyngeal region and likely affect the upper respiratory tract. We evaluated the effectiveness of a hypertonic saline nasal lavage in reducing inflammatory responses in dairy workers from a high-volume dairy operation. Inhalable personal breathing zone samples and pre-/post-shift nasal lavage samples from each participant over five consecutive days were collected. The treatment group (n = 5) received hypertonic saline while the control group (n = 5) received normotonic saline. Personal breathing zone samples were analyzed for particulate concentrations and endotoxin using gravimetric and enzymatic methods, respectively. Pro- and anti-inflammatory cytokines (i.e., IL-8, IL-10, and TNF-α) were measured from nasal lavage samples using a multiplex assay. Inhalable dust concentrations ranged from 0.15 to 1.9 mg/m3. Concentrations of both pro- and anti-inflammatory cytokines, specifically IL-6, IL-8, and IL-10, were significantly higher in the treatment group compared to the control group (p < 0.02, p < 0.04, and p < 0.01, respectively). Further analysis of IL-10 anti-inflammatory indicates a positive association between hypertonic saline administration and IL-10 production. This pilot study demonstrates that hypertonic saline nasal lavages were successful in upregulating anti-inflammatory cytokines to support larger interventional studies.

Environmental risk factors for UV-induced cutaneous neoplasia in horses: A GIS approach.

Objective: Ultraviolet light (UV) is a risk factor for the development of cutaneous neoplasia in many mammalian species. This study evaluated UV exposure as a risk factor of concern for the development of cutaneous neoplasia in equine species due to the significant UV exposure that may accrue over their lifetimes. Animals and samples: Neoplastic biopsy specimens from 3272 horses that were submitted over a 10-year period to the Colorado State University Diagnostic Medicine Center and to the University of Saskatchewan Western College of Veterinary Medicine and Prairie Diagnostic Services were evaluated. Procedure: This retrospective study assessed the spatial relationships between altitude, latitude, longitude, and UV maximum value and the probability of UV-induced cutaneous neoplasia. Results: Cases from areas at high altitude proved to have a higher prevalence of UV-induced cutaneous neoplasia than those from areas at lower elevations. A multivariable regression analysis demonstrated that altitude was the only factor significantly and positively associated with the diagnosis of UV-induced neoplasia. Conclusion and clinical relevance: Evidence of cutaneous neoplasia in horses and environmental factors that influence the degree of UV exposure in a geographic location may aid in diagnosis and suggest preventive measures from UV overexposure.

Facteurs de risque environnementaux des néoplasies cutanées induites par les UV chez le cheval : une approche SIG. Objectif: La lumière ultraviolette (UV) est un facteur de risque pour le développement de néoplasies cutanées chez de nombreuses espèces de mammifères. Cette étude a évalué l'exposition aux UV en tant que facteur de risque préoccupant pour le développement de néoplasies cutanées chez les équidés en raison de l'exposition importante aux UV qui peut s'accumuler au cours de leur vie. Animaux et échantillons: Des échantillons de biopsie néoplasique de 3272 chevaux qui ont été soumis sur une période de 10 ans au Colorado State University Diagnostic Medicine Center et au University of Saskatchewan Western College of Veterinary Medicine and Prairie Diagnostic Services ont été évalués. Procédure: Cette étude rétrospective a évalué les relations spatiales entre l'altitude, la latitude, la longitude et la valeur maximale des UV et la probabilité de néoplasie cutanée induite par les UV. Résultats: Les cas des régions de haute altitude se sont avérés avoir une prévalence plus élevée de néoplasie cutanée induite par les UV que ceux des régions de basse altitude. Une analyse de régression multivariée a démontré que l'altitude était le seul facteur significativement et positivement associé au diagnostic de néoplasie induite par les UV. Conclusion et pertinence clinique: Les preuves de néoplasie cutanée chez les chevaux et les facteurs environnementaux qui influencent le degré d'exposition aux UV dans un lieu géographique peuvent aider au diagnostic et suggérer des mesures préventives contre la surexposition aux UV.(Traduit par Dr Serge Messier).

Prenatal exposure to ambient air pollution and traffic and indicators of adiposity in early childhood: the Healthy Start study.

BACKGROUND: Prenatal exposure to ambient air pollution and traffic have been related to a lower birth weight and may be associated with greater adiposity in childhood. We aimed to examine associations of maternal exposure to ambient air pollution and traffic during pregnancy with indicators of adiposity in early childhood. METHODS: We included 738 participants of the Colorado-based Healthy Start study whose height, weight, waist circumference and/or fat mass were measured at age 4-6 years. We estimated residential exposure to ambient concentrations of fine particulate matter (PM2.5) and ozone (O3) averaged by trimester and throughout pregnancy via inverse distance-weighted interpolation of central site monitoring data. We assessed the distance to the nearest major roadway and traffic density in multiple buffers surrounding the participants' homes. Associations of prenatal exposure to air pollution and traffic with overweight, waist circumference, percent fat mass and fat mass index (FMI) were assessed by logistic and linear regression. RESULTS: Associations of exposure to PM2.5 and O3 at the residential address during pregnancy with percent fat mass and FMI at age 4-6 years were inconsistent across trimesters. For example, second trimester PM2.5 was associated with a higher percent fat mass (adjusted difference 0.70% [95% CI 0.05, 1.35%] per interquartile range (IQR; 1.3 µg/m3) increase), while third trimester PM2.5 was associated with a lower percent fat mass (adjusted difference -1.17% [95% CI -1.84, -0.50%] per IQR (1.3 µg/m3) increase). Residential proximity to a highway during pregnancy was associated with higher odds of being overweight at age 4-6 years. We observed no associations of prenatal exposure to PM2.5 and O3 with overweight and waist circumference. CONCLUSIONS: We found limited evidence of associations of prenatal exposure to ambient PM2.5 and O3 with indicators of adiposity at age 4-6 years. Suggestive relationships between residential proximity to a highway during pregnancy and greater adiposity merit further investigation.

Cows as canaries: The effects of ambient air pollution exposure on milk production and somatic cell count in dairy cows.

Exposure to air pollution, including criteria pollutants such as fine particulate matter (PM2.5) and ozone (O3), has been associated with morbidity and mortality in mammals. As a genetically homogenous population that is closely monitored for health, dairy cattle present a unique opportunity to assess the association between changes in air pollution and mammalian health. Milk yield decreases in the summer if temperature and humidity, measured by the Temperature Humidity Index (THI). As O3 levels increase with warmer temperatures, and summer PM2.5 may increase with wildfire smoke, dairy cows may serve as a useful sentinel species to evaluate subacute markers of inflammation and metabolic output and ambient pollution. Over two years, we assessed summertime O3 and PM2.5 concentrations from local US EPA air quality monitors into an auto-regressive mixed model of the association between THI and daily milk production data and bulk tank somatic cell count (SCC). In unadjusted models, a 10 unit increase THI was associated with 28,700 cells/mL (95% CI: 17,700, 39,690) increase in SCC. After controlling for ambient air pollutants, THI was associated with a 14,500 SCC increase (95% CI: 3,400, 25,680), a 48% decrease in effect compared to the crude model. Further, in fully adjusted models, PM2.5 was associated with a 105,500 cells/mL (95% CI: 90,030, 121,050) increase in SCC. Similar results were found for milk production. Results were amplified when high PM2.5 days (95th percentile of observed values) associated with wildfire smoke were removed from the analyses. Our results support the hypothesis that PM2.5 confounds the relationships between THI and milk yield and somatic cell count. The results of this study can be used to inform strategies for intervention to mitigate these impacts at the dairy level and potentially contribute to a model where production animals can act as air quality sentinels.

Ambient air pollution during pregnancy and DNA methylation in umbilical cord blood, with potential mediation of associations with infant adiposity: The Healthy Start study.

BACKGROUND: Prenatal exposure to ambient air pollution has been associated with adverse offspring health outcomes. Childhood health effects of prenatal exposures may be mediated through changes to DNA methylation detectable at birth. METHODS: Among 429 non-smoking women in a cohort study of mother-infant pairs in Colorado, USA, we estimated associations between prenatal exposure to ambient fine particulate matter (PM2.5) and ozone (O3), and epigenome-wide DNA methylation of umbilical cord blood cells at delivery (2010-2014). We calculated average PM2.5 and O3 in each trimester of pregnancy and the full pregnancy using inverse-distance-weighted interpolation. We fit linear regression models adjusted for potential confounders and cell proportions to estimate associations between air pollutants and methylation at each of 432,943 CpGs. Differentially methylated regions (DMRs) were identified using comb-p. Previously in this cohort, we reported positive associations between 3rd trimester O3 exposure and infant adiposity at 5 months of age. Here, we quantified the potential for mediation of that association by changes in DNA methylation in cord blood. RESULTS: We identified several DMRs for each pollutant and period of pregnancy. The greatest number of significant DMRs were associated with third trimester PM2.5 (21 DMRs). No single CpGs were associated with air pollutants at a false discovery rate <0.05. We found that up to 8% of the effect of 3rd trimester O3 on 5-month adiposity may be mediated by locus-specific methylation changes, but mediation estimates were not statistically significant. CONCLUSIONS: Differentially methylated regions in cord blood were identified in association with maternal exposure to PM2.5 and O3. Genes annotated to the significant sites played roles in cardiometabolic disease, immune function and inflammation, and neurologic disorders. We found limited evidence of mediation by DNA methylation of associations between third trimester O3 exposure and 5-month infant adiposity.

Using non-parametric Bayes shrinkage to assess relationships between multiple environmental and social stressors and neonatal size and body composition in the Healthy Start cohort.

BACKGROUND: Both environmental and social factors have been linked to birth weight and adiposity at birth, but few studies consider the effects of exposure mixtures. Our objective was to identify which components of a mixture of neighborhood-level environmental and social exposures were driving associations with birth weight and adiposity at birth in the Healthy Start cohort. METHODS: Exposures were assessed at the census tract level and included air pollution, built environment characteristics, and socioeconomic status. Prenatal exposures were assigned based on address at enrollment. Birth weight was measured at delivery and adiposity was measured using air displacement plethysmography within three days. We used non-parametric Bayes shrinkage (NPB) to identify exposures that were associated with our outcomes of interest. NPB models were compared to single-predictor linear regression. We also included generalized additive models (GAM) to assess nonlinear relationships. All regression models were adjusted for individual-level covariates, including maternal age, pre-pregnancy BMI, and smoking. RESULTS: Results from NPB models showed most exposures were negatively associated with birth weight, though credible intervals were wide and generally contained zero. However, the NPB model identified an interaction between ozone and temperature on birth weight, and the GAM suggested potential non-linear relationships. For associations between ozone or temperature with birth weight, we observed effect modification by maternal race/ethnicity, where effects were stronger for mothers who identified as a race or ethnicity other than non-Hispanic White. No associations with adiposity at birth were observed. CONCLUSIONS: NPB identified prenatal exposures to ozone and temperature as predictors of birth weight, and mothers who identify as a race or ethnicity other than non-Hispanic White might be disproportionately impacted. However, NPB models may have limited applicability when non-linear effects are present. Future work should consider a two-stage approach where NPB is used to reduce dimensionality and alternative approaches examine non-linear effects.

Association between air pollution and COVID-19 disease severity via Bayesian multinomial logistic regression with partially missing outcomes.

Recent ecological analyses suggest air pollution exposure may increase susceptibility to and severity of coronavirus disease 2019 (COVID-19). Individual-level studies are needed to clarify the relationship between air pollution exposure and COVID-19 outcomes. We conduct an individual-level analysis of long-term exposure to air pollution and weather on peak COVID-19 severity. We develop a Bayesian multinomial logistic regression model with a multiple imputation approach to impute partially missing health outcomes. Our approach is based on the stick-breaking representation of the multinomial distribution, which offers computational advantages, but presents challenges in interpreting regression coefficients. We propose a novel inferential approach to address these challenges. In a simulation study, we demonstrate our method's ability to impute missing outcome data and improve estimation of regression coefficients compared to a complete case analysis. In our analysis of 55,273 COVID-19 cases in Denver, Colorado, increased annual exposure to fine particulate matter in the year prior to the pandemic was associated with increased risk of severe COVID-19 outcomes. We also found COVID-19 disease severity to be associated with interactions between exposures. Our individual-level analysis fills a gap in the literature and helps to elucidate the association between long-term exposure to air pollution and COVID-19 outcomes.

Relationships between social climate and indoor environmental quality and frequently reported health symptoms among teachers and staff in a suburban school district.

Public school teachers represent one of the largest occupational groups in the United States and are vulnerable to job stress and burnout. School social and physical environments may be adversely impacting the health of teachers and other staff, though few studies have explored these relationships. We partnered with a suburban school district in Colorado to assess the association between school environmental quality, social climate, and staff member health. We modeled the number of self-reported frequent health symptoms (experienced at least once a week) using generalized linear models. School-level predictors of interest included: overall social climate scores (unitless), building operations report card (ORC) scores (unitless), and indoor air quality (IAQ) scores (unitless). In total, we had data from 134 staff members from 11 schools in the district. A majority (62%) of our participants were teachers, who reported a greater number of frequent (i.e., at least once a week) health symptoms (mean = 3.2 symptoms experienced at least once per week) compared to staff in other roles (mean = 2.3 symptoms per week). We found that a one standard-deviation (10.5) increase in the overall social climate score was associated with a 0.77-fold (95% CI: 0.60-0.99) change in the number of frequent health symptoms reported. However, this association was attenuated among teachers compared to other staff members. Our results suggested effect modification by social climate on the relationship between IAQ and health, albeit with some uncertainty. For participants with a school climate score below the mean, a one standard-deviation (10.5) increase in IAQ score was associated with a 0.49-fold (95% CI: 0.35-0.70) change in the number of frequently reported symptoms. Overall, our study suggests school climate may be associated with self-reported health symptoms, but that the benefits of improved school climates may not be as strong for teachers compared to other staff. Future work should assess perceived climate at the individual level to assess how staff roles impact how school environments are associated with health outcomes.

Tropical Cyclone Exposures and Risks of Emergency Medicare Hospital Admission for Cardiorespiratory Diseases in 175 Urban United States Counties, 1999-2010.

BACKGROUND: Although injuries experienced during hurricanes and other tropical cyclones have been relatively well-characterized through traditional surveillance, less is known about tropical cyclones' impacts on noninjury morbidity, which can be triggered through pathways that include psychosocial stress or interruption in medical treatment. METHODS: We investigated daily emergency Medicare hospitalizations (1999-2010) in 180 US counties, drawing on an existing cohort of high-population counties. We classified counties as exposed to tropical cyclones when storm-associated peak sustained winds were ≥21 m/s at the county center; secondary analyses considered other wind thresholds and hazards. We matched storm-exposed days to unexposed days by county and seasonality. We estimated change in tropical cyclone-associated hospitalizations over a storm period from 2 days before to 7 days after the storm's closest approach, compared to unexposed days, using generalized linear mixed-effect models. RESULTS: For 1999-2010, 175 study counties had at least one tropical cyclone exposure. Cardiovascular hospitalizations decreased on the storm day, then increased following the storm, while respiratory hospitalizations were elevated throughout the storm period. Over the 10-day storm period, cardiovascular hospitalizations increased 3% (95% confidence interval = 2%, 5%) and respiratory hospitalizations increased 16% (95% confidence interval = 13%, 20%) compared to matched unexposed periods. Relative risks varied across tropical cyclone exposures, with strongest association for the most restrictive wind-based exposure metric. CONCLUSIONS: In this study, tropical cyclone exposures were associated with a short-term increase in cardiorespiratory hospitalization risk among the elderly, based on a multi-year/multi-site investigation of US Medicare beneficiaries ≥65 years.

A Spatiotemporal Prediction Model for Black Carbon in the Denver Metropolitan Area, 2009-2020.

Studies on health effects of air pollution from local sources require exposure assessments that capture spatial and temporal trends. To facilitate intraurban studies in Denver, Colorado, we developed a spatiotemporal prediction model for black carbon (BC). To inform our model, we collected more than 700 weekly BC samples using personal air samplers from 2018 to 2020. The model incorporated spatial and spatiotemporal predictors and smoothed time trends to generate point-level weekly predictions of BC concentrations for the years 2009-2020. Our results indicate that our model reliably predicted weekly BC concentrations across the region during the year in which we collected data. We achieved a 10-fold cross-validation R2 of 0.83 and a root-mean-square error of 0.15 µg/m3 for weekly BC concentrations predicted at our sampling locations. Predicted concentrations displayed expected temporal trends, with the highest concentrations predicted during winter months. Thus, our prediction model improves on typical land use regression models that generally only capture spatial gradients. However, our model is limited by a lack of long-term BC monitoring data for full validation of historical predictions. BC predictions from the weekly spatiotemporal model will be used in traffic-related air pollution exposure-disease associations more precisely than previous models for the region have allowed.

Exposure to ambient air pollution during pregnancy and inflammatory biomarkers in maternal and umbilical cord blood: The Healthy Start study.

BACKGROUND: Air pollution exposure during pregnancy has been associated with adverse pregnancy and birth outcomes. Inflammation has been proposed as a potential link. We estimated associations between air pollution exposure during pregnancy and inflammatory biomarkers in maternal and cord blood. We evaluated whether maternal inflammation was associated with infant outcomes. METHODS: Among 515 mother-infant dyads in the Healthy Start study (2009-2014), trimester-long, 7- and 30-day average concentrations of particulate matter ≤2.5 µm (PM2.5) and ozone (O3) during pregnancy were estimated, using inverse-distance-weighted interpolation. Inflammatory biomarkers were measured in maternal blood in mid-pregnancy (C-reactive protein [CRP], Interleukin [IL]-6, and tumor necrosis factor-α [TNFα]) and in cord blood at delivery (CRP, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1 [MCP-1], and TNFα). We used linear regression to estimate associations between pollutants and inflammatory biomarkers and maternal inflammatory biomarkers and infant weight and body composition. RESULTS: There were positive associations between PM2.5 during certain exposure periods and maternal IL-6 and TNFα. There were negative associations between recent O3 and maternal CRP, IL-6, and TNFα and positive associations between trimester-long O3 exposure and maternal inflammatory biomarkers, though some 95% confidence intervals included the null. Patterns were inconsistent for associations between PM2.5 and O3 and cord blood inflammatory biomarkers. No consistent associations between maternal inflammatory biomarkers and infant outcomes were identified. CONCLUSIONS: Air pollution exposure during pregnancy may impact maternal inflammation. Further investigations should examine the health consequences for women and infants of elevated inflammatory biomarkers associated with air pollution exposure during pregnancy.

Sociodemographic Characteristics and Physical Activity in Patients with COPD: A 3-Month Cohort Study.

Decreased physical activity (PA) is associated with morbidity and mortality in COPD patients. In this secondary analysis of data from a 12-week longitudinal study, we describe factors associated with PA in COPD. Participants completed the Physical Activity Checklist (PAC) daily for a 7- to 8-day period. PA was measured monthly using the Physical Activity Scale for the Elderly (PASE). At three different time points, daily step count was measured for one week with an Omron HJ-720ITC pedometer. The 35 participants were primarily male (94%) and White (91%), with an average age of 66.5 years and FEV1 44.9% predicted. Common activities reported on the PAC were walking (93%), preparing a meal (89%), and traveling by vehicle (96%). PA measured by both PASE score (p = 0.01) and average daily step count (p = 0.04) decreased during follow-up. In repeated measures multivariable modeling, participants living with others had a higher daily step count (ß = 942 steps, p = 0.01) and better PASE scores (ß = 46.4, p < 0.001). Older age was associated with decreased step count (ß = -77 steps, p < 0.001) whereas White race was associated with lower PASE scores (ß = -55.4, p < 0.001) compared to non-White race. Other demographic factors, quality of life, and medications were not associated with PA. A better understanding of the role of social networks and social support may help develop interventions to improve PA in COPD.

Genome-wide association analysis of canine T zone lymphoma identifies link to hypothyroidism and a shared association with mast-cell tumors.

BACKGROUND: T zone lymphoma (TZL), a histologic variant of peripheral T cell lymphoma, represents about 12% of all canine lymphomas. Golden Retrievers appear predisposed, representing over 40% of TZL cases. Prior research found that asymptomatic aged Golden Retrievers frequently have populations of T zone-like cells (phenotypically identical to TZL) of undetermined significance (TZUS), potentially representing a pre-clinical state. These findings suggest a genetic risk factor for this disease and caused us to investigate potential genes of interest using a genome-wide association study of privately-owned U.S. Golden Retrievers. RESULTS: Dogs were categorized as TZL (n = 95), TZUS (n = 142), or control (n = 101) using flow cytometry and genotyped using the Illumina CanineHD BeadChip. Using a mixed linear model adjusting for population stratification, we found association with genome-wide significance in regions on chromosomes 8 and 14. The chromosome 14 peak included four SNPs (Odds Ratio = 1.18-1.19, p = .3 × 10- 5-5.1 × 10- 5) near three hyaluronidase genes (SPAM1, HYAL4, and HYALP1). Targeted resequencing of this region using a custom sequence capture array identified missense mutations in all three genes; the variant in SPAM1 was predicted to be damaging. These mutations were also associated with risk for mast cell tumors among Golden Retrievers in an unrelated study. The chromosome 8 peak contained 7 SNPs (Odds Ratio = 1.24-1.42, p = 2.7 × 10- 7-7.5 × 10- 5) near genes involved in thyroid hormone regulation (DIO2 and TSHR). A prior study from our laboratory found hypothyroidism is inversely associated with TZL risk. No coding mutations were found with targeted resequencing but identified variants may play a regulatory role for all or some of the genes. CONCLUSIONS: The pathogenesis of canine TZL may be related to hyaluronan breakdown and subsequent production of pro-inflammatory and pro-oncogenic byproducts. The association on chromosome 8 may indicate thyroid hormone is involved in TZL development, consistent with findings from a previous study evaluating epidemiologic risk factors for TZL. Future work is needed to elucidate these mechanisms.

Prenatal Exposure to Tobacco and Offspring Neurocognitive Development in the Healthy Start Study.

OBJECTIVE: To explore the associations between prenatal exposure to tobacco and neurocognitive development, in the absence of prematurity or low birth weight. STUDY DESIGN: We followed mother-child pairs within Healthy Start through 6 years of age. Children were born at ≥37 weeks of gestation with a birth weight of ≥2500 g. Parents completed the Third Edition Ages and Stages Questionnaire (n = 246) and children completed a subset of the National Institutes of Health Toolbox Cognition Battery (n = 200). The Ages and Stages Questionnaire domains were dichotomized as fail/monitor and pass. Maternal urinary cotinine was measured at approximately 27 weeks of gestation. Separate logistic regression models estimated associations between prenatal exposure to tobacco (cotinine below vs above the limit of detection) and the Ages and Stages Questionnaire domains. Separate linear regression models estimated associations between prenatal exposure to tobacco and fully corrected T-scores for inhibitory control, cognitive flexibility, and receptive language, as assessed by the National Institutes of Health Toolbox. A priori covariates included sex, maternal age, maternal education, daily caloric intake during pregnancy, race/ethnicity, household income, maternal psychiatric disorders, and, in secondary models, postnatal exposure to tobacco. RESULTS: Compared with unexposed offspring, exposed offspring were more likely to receive a fail/monitor score for fine motor skills (OR, 3.9; 95% CI, 1.5-10.3) and decreased inhibitory control (B: -3.0; 95% CI, -6.1 to -0.7). After adjusting for postnatal exposure, only the association with fine motor skills persisted. CONCLUSIONS: Prenatal and postnatal exposures to tobacco may influence neurocognitive development, in the absence of preterm delivery or low birth weight. Increased developmental screening may be warranted for exposed children.

Community-wide Mortality Rates in Beijing, China, During the July 2012 Flood Compared with Unexposed Periods.

BACKGROUND: On 21-22 July 2012, Beijing, China, suffered its heaviest rainfall in 60 years. Two studies have estimated the fatality toll of this disaster using a traditional surveillance approach. However, traditional surveillance can miss disaster-related deaths, including a substantial number of deaths from natural causes triggered by disaster exposure. Here, we investigated community-wide mortality risk during this flood compared with rates in unexposed reference periods. METHODS: We compared community-wide mortality rates on the peak flood day and the four following days to seasonally matched nonflood days in previous years (2008-2011), controlling for potential confounders, to estimate the relative risks (RRs) of daily mortality among Beijing residents associated with this flood. RESULTS: On 21 July 2012, the flood-associated RRs were 1.34 (95% confidence interval = 1.11, 1.61) for all-cause, 1.37 (1.01, 1.85) for circulatory, and 4.40 (2.98, 6.51) for accidental mortality, compared with unexposed periods. We observed no evidence of increased risk of respiratory mortality. For the flood period of 21-22 July 2012, we estimated a total of 79 excess deaths among Beijing residents; by contrast, only 34 deaths were reported among Beijing residents in a study using a traditional surveillance approach. CONCLUSIONS: To our knowledge, this is the first study analyzing community-wide changes in mortality rates during the 2012 flood in Beijing and one of the first to do so for any major flood worldwide. This study offers critical evidence on flood-related health impacts, as urban flooding is expected to become more frequent and severe in China.