Exposure to per- and polyfluoroalkyl substances and alterations in plasma microRNA profiles in children.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment and can accumulate in humans, leading to adverse health effects. MicroRNAs (miRNAs) are emerging biomarkers that can advance the understanding of the mechanisms of PFAS effects on human health. However, little is known about the associations between PFAS exposures and miRNA alterations in humans. OBJECTIVE: To investigate associations between PFAS concentrations and miRNA levels in children. METHODS: Data from two distinct cohorts were utilized: 176 participants (average age 16.6 years; 75.6% female) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort in the United States, and 64 participants (average age 6.5 years, 39.1% female) from the Rhea study, a mother-child cohort in Greece. PFAS concentrations and miRNA levels were assessed in plasma samples from both studies. Associations between individual PFAS and plasma miRNA levels were examined after adjusting for covariates. Additionally, the cumulative effects of PFAS mixtures were evaluated using an exposure burden score. Ingenuity Pathways Analysis was employed to identify potential disease functions of PFAS-associated miRNAs. RESULTS: Plasma PFAS concentrations were associated with alterations in 476 miRNAs in the Teen-LABs study and 13 miRNAs in the Rhea study (FDR p < 0.1). Specifically, plasma PFAS concentrations were consistently associated with decreased levels of miR-148b-3p and miR-29a-3p in both cohorts. Pathway analysis indicated that PFAS-related miRNAs were linked to numerous chronic disease pathways, including cardiovascular diseases, inflammatory conditions, and carcinogenesis. CONCLUSION: Through miRNA screenings in two independent cohorts, this study identified both known and novel miRNAs associated with PFAS exposure in children. Pathway analysis revealed the involvement of these miRNAs in several cancer and inflammation-related pathways. Further studies are warranted to enhance our understanding of the relationships between PFAS exposure and disease risks, with miRNA emerging as potential biomarkers and/or mediators in these complex pathways.

A Novel Approach to Integrate Human Biomonitoring Data with Model Predicted Dietary Exposures: A Crop Protection Chemical Case Study Using Lambda-Cyhalothrin.

The appropriate use of human biomonitoring data to model population chemical exposures is challenging, especially for rapidly metabolized chemicals, such as agricultural chemicals. The objective of this study is to demonstrate a novel approach integrating model predicted dietary exposures and biomonitoring data to potentially inform regulatory risk assessments. We use lambda-cyhalothrin as a case study, and for the same representative U.S. population in the National Health and Nutrition Examination Survey (NHANES), an integrated exposure and pharmacokinetic model predicted exposures are calibrated to measurements of the urinary metabolite 3-phenoxybenzoic acid (3PBA), using an approximate Bayesian computing (ABC) methodology. We demonstrate that the correlation between modeled urinary 3PBA and the NHANES 3PBA measurements more than doubled as ABC thresholding narrowed the acceptable tolerance range for predicted versus observed urinary measurements. The median predicted urinary concentrations were closer to the median measured value using ABC than using current regulatory Monte Carlo methods.

Potential Effects of Long-Term Exposure to Air Pollution on Dementia: A Longitudinal Analysis in American Indians Aged 55 Years and Older.

(1) Background: American Indians are disproportionately affected by air pollution, an important risk factor for dementia. However, few studies have investigated the effects of air pollution on the risk of dementia among American Indians. (2) Methods: This retrospective cohort study included a total of 26,871 American Indians who were 55+ years old in 2007, with an average follow-up of 3.67 years. County-level average air pollution data were downloaded from land-use regression models. All-cause dementia was identified using ICD-9 diagnostic codes from the Indian Health Service's (IHS) National Data Warehouse and related administrative databases. Cox models were employed to examine the association of air pollution with dementia incidence, adjusting for co-exposures and potential confounders. (3) Results: The average PM2.5 levels in the IHS counties were lower than those in all US counties, while the mean O3 levels in the IHS counties were higher than the US counties. Multivariable Cox regressions revealed a positive association between dementia and county-level O3 with a hazard ratio of 1.24 (95% CI: 1.02-1.50) per 1 ppb standardized O3. PM2.5 and NO2 were not associated with dementia risk after adjusting for all covariates. (4) Conclusions: O3 is associated with a higher risk of dementia among American Indians.

Unmatched spatially stratified controls: A simulation study examining efficiency and precision using spatially-diverse controls and generalized additive models.

Unmatched spatially stratified random sampling (SSRS) of non-cases selects geographically balanced controls by dividing the study area into spatial strata and randomly selecting controls from all non-cases within each stratum. The performance of SSRS control selection was evaluated in a case study spatial analysis of preterm birth in Massachusetts. In a simulation study, we fit generalized additive models using controls selected by SSRS or simple random sample (SRS) designs. We compared mean squared error (MSE), bias, relative efficiency (RE), and statistically significant map results to the model results with all non-cases. SSRS designs had lower average MSE (0.0042-0.0044) and higher RE (77-80%) compared to SRS designs (MSE: 0.0072-0.0073; RE across designs: 71%). SSRS map results were more consistent across simulations, reliably identifying statistically significant areas. SSRS designs improved efficiency by selecting controls that are geographically distributed, particularly from low population density areas, and may be more appropriate for spatial analyses.

Bone lead variability in bone repository skeletal samples measured with portable x-ray fluorescence.

Bone lead serves as a better, more accessible biomarker to many communities experiencing chronic exposure to lead. A new method using low energy x-ray fluorescence in a handheld device (portable XRF) allows us to measure this chronic biomarker in only a few minutes. However, many unknowns remain about this biomarker measured using a new low energy x-ray technique. The low energy of the new method was theorized to measure a slightly different portion of the bone than previous techniques, which could influence measurements at different bone sites and types. We tested how bone measurements varied across five bone sites: mid-tibial shaft, proximal tibia, distal tibia (ankle), ilium, and cranium. We found bone lead measurements are not significantly different between skeletal elements when measured using a portable XRF. On average, bone lead in the repository samples was measured to be 21.6 ± 21.3 µg/g with an XRF detection limit of 2.1 ± 0.5 µg/g. Cumulative lead exposure can be effectively measured using the portable XRF on a variety of bone types, but the tibia should be preferentially measured to compare between studies and individuals.

Per- and polyfluoroalkyl substances in drinking water and hypertensive disorders of pregnancy in the United States during 2013-2015.

Background: Per- and polyfluoroalkyl substances (PFAS) widely exist in the environment and human bodies. Contaminated drinking water is one of the major exposure pathways for humans. Previous studies found weak or moderate associations between PFAS and hypertensive disorders of pregnancy (HDP). Methods: We obtained the number of births and counts of HDP cases for singleton births multiply stratified by county, maternal age, race, education, smoking status, and parity from CDC WONDER, and PFAS water concentrations from EPA UCMR3 data in the United States during 2013-2015. We used binomial regression on the multiply stratified HDP data to produce equal effect estimates and standard errors to those that would be derived from using individual-level data on binary HDP status and demographic covariates in logistic regression. Results: After adjusting for demographic covariates, we found small but statistically significant positive associations between HDP and population-weighted average water concentrations (ng/L) of all four PFAS: Odds ratio (OR) = 1.009, 95% CI = (1.001, 1.016) per IQR increase in perfluorooctanoic acid (PFOA); 1.030, 95% CI = (1.021, 1.040) per IQR increase in perfluorooctane sulfonate (PFOS); 1.008, 95% CI = (1.005, 1.011) per IQR increase in perfluoroheptanoic acid (PFHpA); 1.007, 95% CI = (1.004, 1.010) per IQR increase in perfluorohexane sulfonic acid (PFHxS), and 1.032, 95% CI = (1.022, 1.042) per IQR increase in the sum of four PFAS. Further adjustment for coexposures reversed the effect of PFOA from positive to inverse, and attenuated the effects of PFOS and PFHxS toward the null. After drinking water to serum concentration conversions, our effect estimates for PFOA, PFOS, and PFHxS are similar to previous studies. Conclusions: We found a weak positive association between the PFAS mixture and HDP, although the generalizability is subject to inherent limitations of the public-available datasets.

Arsenic in private well water and birth outcomes in the United States.

BACKGROUND: Prenatal exposure to drinking water with arsenic concentrations >50 µg/L is associated with adverse birth outcomes, with inconclusive evidence for concentrations ≤50 µg/L. In a collaborative effort by public health experts, hydrologists, and geologists, we used published machine learning model estimates to characterize arsenic concentrations in private wells-federally unregulated for drinking water contaminants-and evaluated associations with birth outcomes throughout the conterminous U.S. METHODS: Using several machine learning models, including boosted regression trees (BRT) and random forest classification (RFC), developed from measured groundwater arsenic concentrations of ∼20,000 private wells, we characterized the probability that arsenic concentrations occurred within specific ranges in groundwater. Probabilistic model estimates and private well usage data were linked by county to all live birth certificates from 2016 (n = 3.6 million). We evaluated associations with gestational age and term birth weight using mixed-effects models, adjusted for potential confounders and incorporated random intercepts for spatial clustering. RESULTS: We generally observed inverse associations with term birth weight. For instance, when using BRT estimates, a 10-percentage point increase in the probability that private well arsenic concentrations exceeded 5 µg/L was associated with a -1.83 g (95% CI: -3.30, -0.38) lower term birth weight after adjusting for covariates. Similarly, a 10-percentage point increase in the probability that private well arsenic concentrations exceeded 10 µg/L was associated with a -2.79 g (95% CI: -4.99, -0.58) lower term birth weight. Associations with gestational age were null. CONCLUSION: In this largest epidemiologic study of arsenic and birth outcomes to date, we did not observe associations of modeled arsenic estimates in private wells with gestational age and found modest inverse associations with term birth weight. Study limitations may have obscured true associations, including measurement error stemming from a lack of individual-level information on primary water sources, water arsenic concentrations, and water consumption patterns.

Retrospective exposure reconstruction using approximate Bayesian computation: A case study on perfluorooctanoic acid and preeclampsia.

BACKGROUND: In environmental epidemiology, measurements of toxicants in biological samples are often used as individual exposure assignments. It is common to obtain only one or a few exposure biomarkers per person and use those measurements to represent each person's relevant toxicant exposure for a given health outcome, even though most exposure biomarkers can fluctuate over time. When the timing of the exposure reflected by the biomarker measurement is misaligned with disease development especially if it occurs after the disease outcome, results could be subject to reverse causality or exposure measurement error. OBJECTIVE: This study aimed to use an approximate Bayesian computation (ABC) method to improve PFOA exposure estimates and characterize the effects of PFOA on preeclampsia in the C8 Studies. METHODS: Serum PFOA concentrations were measured in blood samples collected during 2005-2006 in West Virginia and Ohio (the C8 Studies), and residential and water use histories and pregnancy outcomes were obtained from self-reports. Our previous results may have been influenced by the choice of methods for characterizing PFOA exposures. Here we use an ABC method to combine measured PFOA serum concentrations and environmentally modeled PFOA concentrations to reconstruct historical PFOA exposures. We also expanded our previous work by assuming more realistic lognormal distributions for key input parameters in the exposure and pharmacokinetic models. RESULTS: Compared to using fixed values of model parameters and Monte Carlo simulations, ABC produced similar Spearman correlations between estimated and measured serum PFOA concentrations, yet substantially reduced the mean squared error by over 50%. Based on ABC, compared to previous studies, we found a similar adjusted odds ratio (AOR) for the association between PFOA and preeclampsia. CONCLUSIONS: Bayesian combination of modeled exposure and measured biomarker concentrations can reduce exposure measurement error compared to modeled exposure.

Predictors of Test Positivity, Mortality, and Seropositivity during the Early Coronavirus Disease Epidemic, Orange County, California, USA.

We conducted a detailed analysis of coronavirus disease in a large population center in southern California, USA (Orange County, population 3.2 million), to determine heterogeneity in risks for infection, test positivity, and death. We used a combination of datasets, including a population-representative seroprevalence survey, to assess the actual burden of disease and testing intensity, test positivity, and mortality. In the first month of the local epidemic (March 2020), case incidence clustered in high-income areas. This pattern quickly shifted, and cases next clustered in much higher rates in the north-central area of the county, which has a lower socioeconomic status. Beginning in April 2020, a concentration of reported cases, test positivity, testing intensity, and seropositivity in a north-central area persisted. At the individual level, several factors (e.g., age, race or ethnicity, and ZIP codes with low educational attainment) strongly affected risk for seropositivity and death.

Critical review on PFOA, kidney cancer, and testicular cancer.

The carcinogenicity of perfluorooctanoic acid (PFOA) has been reviewed previously by several different regulatory agencies and researchers, with contradictory conclusions-especially regarding epidemiological findings on kidney cancer and testicular cancer. In addition, previous dose-response assessments have focused primarily on evidence from animal studies. This critical review summarizes peer reviewed epidemiological studies on PFOA and cancers of the kidneys and testes, using modified Hill's criteria to assess the evidence for causation. We converted exposures to a common scale based on serum PFOA concentrations and applied meta-analysis to estimate the average increase in cancer risk reported by the studies with sufficient information to estimate serum PFOA. Using random effects meta-analysis, we found that the average relative increase in cancer risk per 10 ng/mL increase in serum PFOA for these studies is 16% (95% CI: 3%, 30%) for kidney cancer and 3% (95% CI: 2%, 4%) for testicular cancer. These associations are most likely causal, but results are limited by the small number of studies for testicular cancer, the overlapping study populations for several studies, and the lack of measured or modeled serum PFOA concentrations for several studies.Implications: Our review meta-analysis indicates an average increase in cancer risk per 10 ng/mL increase in serum PFOA for kidney and testicular cancers. These associations are most likely causal, but results are limited by the small number of studies for testicular cancer, the overlapping study populations for several studies, and the lack of measured or modeled serum PFOA concentrations for several studies. The weight of evidence could be even stronger with the addition of future studies conducted in large cohorts.

Estimated seroprevalence of SARS-CoV-2 antibodies among adults in Orange County, California.

Clinic-based estimates of SARS-CoV-2 may considerably underestimate the total number of infections. Access to testing in the US has been heterogeneous and symptoms vary widely in infected persons. Public health surveillance efforts and metrics are therefore hampered by underreporting. We set out to provide a minimally biased estimate of SARS-CoV-2 seroprevalence among adults for a large and diverse county (Orange County, CA, population 3.2 million). We implemented a surveillance study that minimizes response bias by recruiting adults to answer a survey without knowledge of later being offered SARS-CoV-2 test. Several methodologies were used to retrieve a population-representative sample. Participants (n = 2979) visited one of 11 drive-thru test sites from July 10th to August 16th, 2020 (or received an in-home visit) to provide a finger pin-prick sample. We applied a robust SARS-CoV-2 Antigen Microarray technology, which has superior measurement validity relative to FDA-approved tests. Participants include a broad age, gender, racial/ethnic, and income representation. Adjusted seroprevalence of SARS-CoV-2 infection was 11.5% (95% CI: 10.5-12.4%). Formal bias analyses produced similar results. Prevalence was elevated among Hispanics (vs. other non-Hispanic: prevalence ratio [PR] = 1.47, 95% CI 1.22-1.78) and household income < $50,000 (vs. > $100,000: PR = 1.42, 95% CI: 1.14 to 1.79). Results from a diverse population using a highly specific and sensitive microarray indicate a SARS-CoV-2 seroprevalence of ~ 12 percent. This population-based seroprevalence is seven-fold greater than that using official County statistics. In this region, SARS-CoV-2 also disproportionately affects Hispanic and low-income adults.

Shrinkage estimation of long-term water ingestion rates.

BACKGROUND: Water consumption is a necessity for human life, though it also presents an opportunity for exposure to harmful chemicals and toxins. In order to gain a better understanding of the potential levels of chronic exposure, accurate estimates of long-term water consumption are needed. OBJECTIVE: The objective of this study is to estimate long-term water consumption using a nationally representative sample of the US population. METHODS: In this study, we use a random effects model to obtain shrinkage estimates of average daily water consumption for National Health and Nutrition Examination Survey (NHANES) participants from 2005 to 2010, and compare to their empirical 2-day averages. RESULTS: Our results demonstrate that the shrinkage estimates yielded a reduction in estimated mean water consumption. The 95th percentile was reduced from 3292 to 2529 ml/day. In addition, standard deviation of water consumption for this group decreased from 1052 to 688 ml/day. Similar reductions in the mean and variance were observed stratifying by age and race. SIGNIFICANCE: Random effects models may provide a more accurate measure of daily water consumption and could be utilized for future exposure and risk assessments.

Household low pile carpet usage was associated with increased serum PFAS concentrations in 2005-2006.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in the serum of the general US population. Food, drinking water, consumer products, dust, and air have been assessed as PFAS exposure sources for humans. The effects of various types of carpeting on serum PFAS concentrations have been less studied, despite the known use of PFAS in stain-resistant carpet treatments. OBJECTIVE: This study aimed to examine the associations between serum PFAS concentrations and type of residential flooring among the general US population aged 12 years and older using the 2005-2006 National Health and Nutrition Examination Survey (NHANES). METHODS: We used multiple linear regressions adjusted for complex survey design and relevant covariates to analyze the relations between serum PFAS concentrations and type of floor covering (smooth surface, low pile carpet, medium to high pile carpet, and combination of carpet and smooth surface), as well as other potential exposure factors. We used multiple imputation to address missing values. RESULTS: We found significantly higher serum concentrations of perfluorohexane sulfonic acid (PFHxS) and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA) in US residents residing in homes with low pile carpeting compared with those residing in homes with smooth surface. We concluded that among US residents aged 12 years and older residing in homes with low pile carpeting in the home in 2005-2006, on average 24% and 19% of the PFHxS and MeFOSAA body burdens, respectively, could be attributed to carpeting. We found associations between other types of floor covering (medium to high pile carpet, combination of carpet and smooth surface) and some PFAS concentrations compared with the smooth surface, but these results were less consistent and generally not statistically significant. Additionally, a group Wald Chi-squared test showed a significant result for PFOS, indicating different contributions of various types of flooring to PFOS serum concentration. SIGNIFICANCE: Our results are representative of the general US population at the time of the survey, and potentially informative regarding ongoing PFAS exposure from a variety of sources including carpeting.

Per- and polyfluoroalkyl substances in drinking water and birthweight in the US: A county-level study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in the serum of the general US population, and were detected in public water systems serving approximately 16.5 million US residents during 2013-2015. Low birthweight was associated with PFAS exposures in previous studies. METHODS: Birthweights for singleton births during 2013-2015 were obtained from CDC WONDER, multiply stratified by county, maternal age, race, education, smoking status, and parity. PFAS water concentrations were obtained from EPA UCMR3 database and aggregated by county. Multiple regression weighted by inverse variance was used to produce effect estimates equivalent to those that would be obtained from individual-level data on birthweight and confounders. RESULTS: Adjusting for stratification demographic confounders (maternal age, race, education, smoking status, and parity), we found an average change in birthweight of 0.9 g (95% confidence interval [CI] = -0.5, 2.2), -1.3 g (-1.6, -0.9), -3.8 g (-4.9, -2.7), and -3.8 g (-4.3, -3.3) per ng/L increase in the population-weighted average perfluorooctanoic acid, perfluorooctane sulfonate, perfluoroheptanoic acid, and perfluorohexane sulfonic acid in public water supplies by county, respectively. We found an average change in birthweight of -1.0 g (95% CI = -1.2, -0.8) per ng/L increase in the sum of perfluorooctanoic acid, perfluorooctane sulfonate, perfluoroheptanoic acid, and perfluorohexane sulfonic acid concentrations in public water supplies. CONCLUSIONS: The direction and magnitude of association between PFAS and birthweight varied by PFAS chemical in this study. Conclusions are tempered by inherent limitations of the 2 public-use datasets, and by the sensitivity of our results to alternative methods such as mutual adjustment for co-exposures.

Review: Evolution of evidence on PFOA and health following the assessments of the C8 Science Panel.

BACKGROUND: The C8 Science Panel was composed of three epidemiologists charged with studying the possible health effects of PFOA in a highly exposed population in the mid-Ohio Valley. The Panel determined in 2012 there was a 'probable link' (i.e., more probable than not based on the weight of the available scientific evidence) between PFOA and high cholesterol, thyroid disease, kidney and testicular cancer, pregnancy-induced hypertension, and ulcerative colitis. OBJECTIVE: Here, former C8 Science Panel members and collaborators comment on the PFOA literature regarding thyroid disorders, cancer, immune and auto-immune disorders, liver disease, hypercholesterolemia, reproductive outcomes, neurotoxicity, and kidney disease. We also discuss developments regarding fate and transport, and pharmacokinetic models, and discuss causality assessment in cross-sectional associations among low-exposed populations. DISCUSSION: For cancer, the epidemiologic evidence remains supportive but not definitive for kidney and testicular cancers. There is consistent evidence of a positive association between PFOA and cholesterol, but no evidence of an association with heart disease. There is evidence for an association with ulcerative colitis, but not for other auto-immune diseases. There is good evidence that PFOA is associated with immune response, but uneven evidence for an association with infectious disease. The evidence for an association between PFOA and thyroid and kidney disease is suggestive but uneven. There is evidence of an association with liver enzymes, but not with liver disease. There is little evidence of an association with neurotoxicity. Suggested reductions in birthweight may be due to reverse causality and/or confounding. Fate and transport models and pharmacokinetic models remain central to estimating past exposure for new cohorts, but are difficult to develop without good historical data on emissions of PFOA into the environment. CONCLUSION: Overall, the epidemiologic evidence remains limited. For a few outcomes there has been some replication of our earlier findings. More longitudinal research is needed in large populations with large exposure contrasts. Additional cross-sectional studies of low exposed populations may be less informative.

A stratified generalized additive model and permutation test for temporal heterogeneity of smoothed bivariate spatial effects.

Generalized additive models (GAMs) with bivariate smoothers are frequently used to map geographic disease risks in epidemiology studies. A challenge in identifying health disparities has been the lack of intuitive and computationally feasible methods to assess whether the pattern of spatial effects varies over time. In this research, we accommodate time-stratified smoothers into the GAM framework to estimate time-specific spatial risk patterns while borrowing information from confounding effects across time. A backfitting algorithm for model estimation is proposed along with a permutation testing framework for assessing temporal heterogeneity of geospatial risk patterns across two or more time points. Simulation studies show that our proposed permuted mean squared difference (PMSD) test performs well with respect to type I error and power in various settings when compared with existing methods. The proposed model and PMSD test are used geospatial risk patterns of patent ductus arteriosus (PDA) in the state of Massachusetts over 2003-2009. We show that there is variation over time in spatial patterns of PDA risk, adjusting for other known risk factors, suggesting the presence of potential time-varying and space-related risk factors other than the adjusted ones.

Environmental chemical burden in metabolic tissues and systemic biological pathways in adolescent bariatric surgery patients: A pilot untargeted metabolomic approach.

BACKGROUND: Advances in untargeted metabolomic technologies have great potential for insight into adverse metabolic effects underlying exposure to environmental chemicals. However, important challenges need to be addressed, including how biological response corresponds to the environmental chemical burden in different target tissues. AIM: We performed a pilot study using state-of-the-art ultra-high-resolution mass spectrometry (UHRMS) to characterize the burden of lipophilic persistent organic pollutants (POPs) in metabolic tissues and associated alterations in the plasma metabolome. METHODS: We studied 11 adolescents with severe obesity at the time of bariatric surgery. We measured 18 POPs that can act as endocrine and metabolic disruptors (i.e. 2 dioxins, 11 organochlorine compounds [OCs] and 5 polybrominated diphenyl ethers [PBDEs]) in visceral and subcutaneous abdominal adipose tissue (vAT and sAT), and liver samples using gas chromatography with UHRMS. Biological pathways were evaluated by measuring the plasma metabolome using high-resolution metabolomics. Network and pathway enrichment analysis assessed correlations between the tissue-specific burden of three frequently detected POPs (i.e. p,p'-dichlorodiphenyldichloroethene [DDE], hexachlorobenzene [HCB] and PBDE-47) and plasma metabolic pathways. RESULTS: Concentrations of 4 OCs and 3 PBDEs were quantifiable in at least one metabolic tissue for > 80% of participants. All POPs had the highest median concentrations in adipose tissue, especially sAT, except for PBDE-154, which had comparable average concentrations across all tissues. Pathway analysis showed high correlations between tissue-specific POPs and metabolic alterations in pathways of amino acid metabolism, lipid and fatty acid metabolism, and carbohydrate metabolism. CONCLUSIONS: Most of the measured POPs appear to accumulate preferentially in adipose tissue compared to liver. Findings of plasma metabolic pathways potentially associated with tissue-specific POPs concentrations merit further investigation in larger populations.

Assessing the Efficacy of a PhotoVoice-Informed HIV Stigma Training for Health Care Workers.

HIV stigma is a harmful social phenomenon present in United States (US)-based health care settings. This study assessed the efficacy of a participatory PhotoVoice-informed stigma reduction training program focusing on people living with HIV (PLWH) and targeting health care workers. Seventy-three (N = 73) participants were assessed at baseline (T1), within approximately a week of the training (T2), and at a 3-month follow-up (T3) regarding their HIV/AIDS knowledge, attitudes towards PLWH, and observations of enacted HIV stigma. Findings indicated that the training increased knowledge and improved attitudes (ß = 0.56, p < 0.01; ß = 0.58, p < 0.01, respectively) at T2, but these effects diminished at T3 (ß = - 0.03, p > 0.05; ß = - 0.29, p > 0.05, respectively). The training did not, however, have an impact on observations of enacted stigma at T2 (ß = 0.10, p > 0.05) or at T3 (ß = 0.02, p > 0.05). Additional participatory stigma reduction programs that involve diverse groups of health care workers, offer salient study incentives, include time-saving training methods, and comprise a variety of stigma measures, may be particularly beneficial.

Temporal Trends in Per- and Polyfluoroalkyl Substances in Bottlenose Dolphins (Tursiops truncatus) of Indian River Lagoon, Florida and Charleston, South Carolina.

Temporal trends in plasma concentrations of per- and polyfluoroalkyl substances (PFAS) in free-ranging bottlenose dolphins (Tursiops truncatus) inhabiting two geographic areas: Indian River Lagoon, Florida over the years 2003-2015 and the waters surrounding Charleston, South Carolina over 2003-2013, were examined. Nine PFAS met the inclusion criteria for analysis based on percent of values below level of detection and sampling years. Proportionate percentiles parametric quantile regression assuming lognormal distributions was used to estimate the average ratio of PFAS concentrations per year for each chemical. Plasma concentrations decreased over time for perfluorodecanoate (PFDA), perfluorohexane sulfonate (PFHxS), perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluoroundecanoate (PFUnDA) in both locations. Perfluorononanoate (PFNA) decreased with time in Indian River Lagoon dolphins. Perfluorododecanoate (PFDoDA) concentrations significantly increased over time among female Indian River Lagoon dolphins. Regulation and phaseout of specific PFAS groups may have led to the decreasing levels of those PFAS and increasing levels of other replacement PFAS.

Contribution of Geographic Location to Disparities in Ovarian Cancer Treatment.

BACKGROUND: More than 14,000 women in the United States die of ovarian cancer (OC) every year. Disparities in survival have been observed by race and socioeconomic status (SES), and vary spatially even after adjusting for treatment received. This study aimed to determine the impact of geographic location on receiving treatment adherent to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for OC, independent of other predictors. PATIENTS AND METHODS: Women diagnosed with all stages of epithelial OC (1996-2014) were identified through the California Cancer Registry. Generalized additive models, smoothing for residential location, were used to calculate adjusted odds ratios (ORs) and 95% CIs for receiving nonadherent care throughout California. We assessed the impact of distance traveled for care, distance to closest high-quality hospital, race/ethnicity, and SES on receipt of quality care, adjusting for demographic and cancer characteristics and stratifying by disease stage. RESULTS: Of 29,844 patients with OC, 11,419 (38.3%) received guideline-adherent care. ORs for nonadherent care were lower in northern California and higher in Kern and Los Angeles counties. Magnitudes of associations with location varied by stage (OR range, 0.45-2.19). Living farther from a high-quality hospital increased the odds of receiving nonadherent care (OR, 1.18; 95% CI, 1.07-1.29), but travel >32 km to receive care was associated with decreased odds (OR, 0.76; 95% CI, 0.70-0.84). American Indian/other women were more likely to travel greater distances to receive care. Women in the highest SES quintile, those with Medicare insurance, and women of non-Hispanic black race were less likely to travel far. Patients who were Asian/Pacific Islander lived the closest to a high-quality hospital. CONCLUSIONS: Among California women diagnosed with OC, living closer to a high-quality center was associated with receiving adherent care. Non-Hispanic black women were less likely to receive adherent care, and women with lower SES lived farthest from high-quality hospitals. Geographic location in California is an independent predictor of adherence to NCCN Guidelines for OC.