Marie Lynn Miranda

Brominated flame retardants in placental tissues: associations with infant sex and thyroid hormone endpoints

BackgroundBrominated flame retardants (BFRs) are endocrine disruptors that bioaccumulate in the placenta, but it remains unclear if they disruptxa0tissue thyroid hormone (TH) metabolism. Our primary goal was to investigate associations between placental BFRs, TH levels, Type 3 deiodinase (DIO3) activity and TH sulfotransferase (SULT) activities.MethodsPlacenta samples collected from 95 women who delivered term (>37xa0weeks) infants in Durham, NC, USA (enrolled 2010–2011) were analyzed for polybrominated diphenyl ethers (PBDEs), 2,4,6-tribromophenol (2,4,6-TBP), THs (T4, T3 and rT3), and DIO3 and TH SULT activities.ResultsPBDEs and 2,4,6-TBP were detected in all placenta samples. PBDEs were higher in placental tissues from male infants compared to female infants, with 2,4,6-TBP and BDE-209 levels approximately twice as high. Among male infants, placental BDE-99 and BDE-209 were negatively associated with rT3 placental levels. For female infants, placental BDE-99 and 2,4,6-TBP were positively associated with T3 concentrations. DIO3 activity was also significantly higher in placental tissues from male infants compared to females, while 3,3’-T2 SULT activity was significantly higher in placental tissues from females compared to males. Among males, several PBDE congeners were positively correlated with T3 SULT, while BDE-99 was negatively associated with T3 SULT among females. Associations generally remained after adjustment for potential confounding by maternal age and gestational age at delivery.ConclusionsThese results suggest BFRs accumulatexa0in the placenta and potentially alter TH function in a sex-specific manner, a possible mechanism to explain the sex-dependent impacts of environmental exposure on children’s growth and development. More research is needed to elucidate the effects of BFRs on placenta function during pregnancy, as well as the biological consequences of exposure and thyroid disruption.

Racial isolation and exposure to airborne particulate matter and ozone in understudied US populations: Environmental justice applications of downscaled numerical model output

BACKGROUNDnResearchers and policymakers are increasingly focused on combined exposures to social and environmental stressors, especially given how often these stressors tend to co-locate. Such exposures are equally relevant in urban and rural areas and may accrue disproportionately to particular communities or specific subpopulations.nnnOBJECTIVESnTo estimate relationships between racial isolation (RI), a measure of the extent to which minority racial/ethnic group members are exposed to only one another, and long-term particulate matter with an aerodynamic diameter of <2.5μ (PM2.5) and ozone (O3) levels in urban and nonurban areas of the eastern two-thirds of the US.nnnMETHODSnLong-term (5year average) census tract-level PM2.5 and O3 concentrations were calculated using output from a downscaler model (2002-2006). The downscaler uses a linear regression with additive and multiplicative bias coefficients to relate ambient monitoring data with gridded output from the Community Multi-scale Air Quality (CMAQ) model. A local, spatial measure of RI was calculated at the tract level, and tracts were classified by urbanicity, RI, and geographic region. We examined differences in estimated pollutant exposures by RI, urbanicity, and demographic subgroup (e.g., race/ethnicity, education, socioeconomic status, age), and used linear models to estimate associations between RI and air pollution levels in urban, suburban, and rural tracts.nnnRESULTSnHigh RI tracts (≥80th percentile) had higher average PM2.5 levels in each category of urbanicity compared to low RI tracts (<20th percentile), with the exception of the rural West. Patterns in O3 levels by urbanicity and RI differed by region. Linear models indicated that PM2.5 concentrations were significantly and positively associated with RI. The largest association between PM2.5 and RI was observed in the rural Midwest, where a one quintile increase in RI was associated with a 0.90μg/m(3) (95% confidence interval: 0.83, 0.99μg/m(3)) increase in PM2.5 concentration. Associations between O3 and RI in the Northeast, Midwest and West were positive and highest in suburban and rural tracts, even after controlling for potential confounders such as percentage in poverty.nnnCONCLUSIONnRI is associated with higher 5year estimated PM2.5 concentrations in urban, suburban, and rural census tracts, adding to evidence that segregation is broadly associated with disparate air pollution exposures. Disproportionate burdens to adverse exposures such as air pollution may be a pathway to racial/ethnic disparities in health.

Development of an analytical method to quantify PBDEs, OH-BDEs, HBCDs, 2,4,6-TBP, EH-TBB, and BEH-TEBP in human serum

Polybrominated diphenyl ethers (PBDEs) flame retardants (FRs) were phased-out in the mid-2000s (penta- and octaBDE) and 2013 (decaBDE); however, their hydroxylated metabolites (OH-BDEs) are still commonly detected in human serum. Today, novel FRs such as Firemaster® 550, a mixture that contains two brominated compounds, EH-TBB and BEH-TEBP are used as replacements for PBDEs in some applications, and there is a need to develop a comprehensive analytical method to assess exposure to both legacy PBDEs and novel FRs. This study developed a solid-phase extraction (SPE)-based method to analyze PBDEs, OH-BDEs, 2,4,6-tribromophenol (TBP), hexabromocylcododecane isomers (HBCDs), EH-TBB, and BEH-TEBP in human serum. Briefly, serum proteins were first denatured with formic acid, and then the target analytes were isolated using a SPE column. Finally, the extract was cleaned and fractioned using a silica SPE column. Method performance was assessed by spiking fetal bovine serum with 1–2xa0ng of the target analytes, and method accuracy was quantified by comparison to a serum Standard Reference Material (SRM). The developed method showed good recovery and accuracy for all target analytes with the exception of the very low and very high molecular weight PBDE congeners. Using this method, 43 serum samples collected from the Healthy Pregnancy, Healthy Baby Study (HPHB) cohort in Durham, NC, USA were analyzed for FRs. A novel finding was the ubiquitous detection of 2,4,6-TBP, at levels greater than the individual PBDE congeners. Furthermore, 2,4,6-TBP was positively correlated with PBDEs, suggesting that they may have a similar source of exposure, or that 2,4,6-TBP may result from metabolism of PBDEs in vivo.

Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease

There is a growing literature indicating that genetic variants modify many of the associations between environmental exposures and clinical outcomes, potentially by increasing susceptibility to these exposures. However, genome-scale investigations of these interactions have been rarely performed particularly in the case of air pollution exposures. We performed race-stratified genome-wide gene-environment interaction association studies on European-American (EA, N = 1623) and African-American (AA, N = 554) cohorts to investigate the joint influence of common single nucleotide polymorphisms (SNPs) and residential exposure to traffic (“traffic exposure”)—a recognized vascular disease risk factor—on peripheral arterial disease (PAD). Traffic exposure was estimated via the distance from the primary residence to the nearest major roadway, defined as the nearest limited access highways or major arterial. The rs755249-traffic exposure interaction was associated with PAD at a genome-wide significant level (P = 2.29x10-8) in European-Americans. Rs755249 is located in the 3’ untranslated region of BMP8A, a member of the bone morphogenic protein (BMP) gene family. Further investigation revealed several variants in BMP genes associated with PAD via an interaction with traffic exposure in both the EA and AA cohorts; this included interactions with non-synonymous variants in BMP2, which is regulated by air pollution exposure. The BMP family of genes is linked to vascular growth and calcification and is a novel gene family for the study of PAD pathophysiology. Further investigation of BMP8A using the Genotype Tissue Expression Database revealed multiple variants with nominally significant (P < 0.05) interaction P-values in our EA cohort were significant BMP8A eQTLs in tissue types highlight relevant for PAD such as rs755249 (tibial nerve, eQTL P = 3.6x10-6) and rs1180341 (tibial artery, eQTL P = 5.3x10-6). Together these results reveal a novel gene, and possibly gene family, associated with PAD via an interaction with traffic air pollution exposure. These results also highlight the potential for interactions studies, particularly at the genome scale, to reveal novel biology linking environmental exposures to clinical outcomes.

Access to ophthalmologists in states where optometrists have expanded scope of practice

Importance As the United States considers how to best structure its health care services, specialty care availability is receiving increased focus. This study assesses whether patients lack reasonable access to ophthalmologists in states where optometrists have been granted expanded scope of practice. Objective To determine the estimated travel time (ETT) to the nearest ophthalmologist office for persons residing in states that have expanded scope of practice for optometrists, and to quantify ETT to the nearest ophthalmologist for Medicare beneficiaries who received surgical care from optometrists in those states between 2008 and 2014. Design, Setting, and Participants This study used data from the 2010 US census, a 2016 American Academy of Ophthalmology member database, and a data set of claims data for a random sample of 20% of beneficiaries enrolled in Medicare nationwide from 2008 to 2014 (n=14 063 725). Combining these sources with geographic information systems analysis, the ETT to the nearest ophthalmologist office was calculated for every resident of Kentucky, Oklahoma, and New Mexico. This study also assessed ETT to the nearest ophthalmologist for Medicare beneficiaries in those states who had received surgery from an optometrist from 2008 to 2014. Data analyses were conducted from July 2016 to July 2017. Main Outcomes and Measures The proportion of residents of Kentucky, Oklahoma, and New Mexico who live within an ETT of 10, 30, 45, 60, or 90 minutes of the nearest ophthalmologist office. Results The study included 4 339 367 Kentucky residents, 3 751 351 Oklahoma residents, and 2 059 179 New Mexico residents. Of these, 5 140 547 (50.6%) were female. Racial/ethnic composition included 7 154 847 people (70.5%) who were white, 640 608 (6.3%) who were black, and 1 418 246 (14.0%) who were Hispanic. The mean (SD) age was 37.8 (22.8) years. More than 75% of residents in the 3 states lived within an ETT of 30 minutes to the nearest ophthalmology office, and 94% to 99% of residents lived within an ETT of 60 minutes to the nearest ophthalmology office. Among Medicare beneficiaries who received surgery by optometrists, 58.3%, 51.1%, and 46.9% in Kentucky, Oklahoma, and New Mexico, respectively, lived within an ETT of 30 minutes from the nearest ophthalmologist office. Conclusions and Relevance In the states where optometrists have expanded scope of practice, most residents lived within an ETT of 30 minutes of the nearest ophthalmologist office, as do half of Medicare beneficiaries who received surgical care from optometrists. These results can help inform policy makers when weighing the pros and cons of scope of practice expansion for optometrists.

The Value of Information in Decision‐Analytic Modeling for Malaria Vector Control in East Africa

Decision analysis tools and mathematical modeling are increasingly emphasized in malaria control programs worldwide to improve resource allocation and address ongoing challenges with sustainability. However, such tools require substantial scientific evidence, which is costly to acquire. The value of information (VOI) has been proposed as a metric for gauging the value of reduced model uncertainty. We apply this concept to an evidenced-based Malaria Decision Analysis Support Tool (MDAST) designed for application in East Africa. In developing MDAST, substantial gaps in the scientific evidence base were identified regarding insecticide resistance in malaria vector control and the effectiveness of alternative mosquito control approaches, including larviciding. We identify four entomological parameters in the model (two for insecticide resistance and two for larviciding) that involve high levels of uncertainty and to which outputs in MDAST are sensitive. We estimate and compare a VOI for combinations of these parameters in evaluating three policy alternatives relative to a status quo policy.xa0We find having perfect information on the uncertain parameters could improve program net benefits by up to 5-21%, with the highest VOI associated with jointly eliminating uncertainty about reproductive speed of malaria-transmitting mosquitoes and initial efficacy of larviciding at reducing the emergence of new adult mosquitoes. Future research on parameter uncertainty in decision analysis of malaria control policy should investigate the VOI with respect to other aspects of malaria transmission (such as antimalarial resistance), the costs of reducing uncertainty in these parameters, and the extent to which imperfect information about these parameters can improve payoffs.

A genome-wide trans-ethnic interaction study links the PIGR-FCAMR locus to coronary atherosclerosis via interactions between genetic variants and residential exposure to traffic.

Air pollution is a worldwide contributor to cardiovascular disease mortality and morbidity. Traffic-related air pollution is a widespread environmental exposure and is associated with multiple cardiovascular outcomes such as coronary atherosclerosis, peripheral arterial disease, and myocardial infarction. Despite the recognition of the importance of both genetic and environmental exposures to the pathogenesis of cardiovascular disease, studies of how these two contributors operate jointly are rare. We performed a genome-wide interaction study (GWIS) to examine gene-traffic exposure interactions associated with coronary atherosclerosis. Using race-stratified cohorts of 538 African-Americans (AA) and 1562 European-Americans (EA) from a cardiac catheterization cohort (CATHGEN), we identify gene-by-traffic exposure interactions associated with the number of significantly diseased coronary vessels as a measure of chronic atherosclerosis. We found five suggestive (P<1x10-5) interactions in the AA GWIS, of which two (rs1856746 and rs2791713) replicated in the EA cohort (P < 0.05). Both SNPs are in the PIGR-FCAMR locus and are eQTLs in lymphocytes. The protein products of both PIGR and FCAMR are implicated in inflammatory processes. In the EA GWIS, there were three suggestive interactions; none of these replicated in the AA GWIS. All three were intergenic; the most significant interaction was in a regulatory region associated with SAMSN1, a gene previously associated with atherosclerosis and B cell activation. In conclusion, we have uncovered several novel genes associated with coronary atherosclerosis in individuals chronically exposed to increased ambient concentrations of traffic air pollution. These genes point towards inflammatory pathways that may modify the effects of air pollution on cardiovascular disease risk.

A longitudinal cohort study of malaria exposure and changing serostatus in a malaria endemic area of rural Tanzania

BackgroundMeasurements of anti-malarial antibodies are increasingly used as a proxy of transmission intensity. Most serological surveys are based on the use of cross-sectional data that, when age-stratified, approximates historical patterns of transmission within a population. Comparatively few studies leverage longitudinal data to explicitly relate individual infection events with subsequent antibody responses.MethodsThe occurrence of seroconversion and seroreversion events for two Plasmodium falciparum asexual stage antigens (MSP-1 and AMA-1) was examined using three annual measurements of 691 individuals from a cohort of individuals in a malaria-endemic area of rural east-central Tanzania. Mixed-effect logistic regression models were employed to determine factors associated with changes in serostatus over time.ResultsWhile the expected population-level relationship between seroprevalence and disease incidence was observed, on an individual level the relationship between individual infections and the antibody response was complex. MSP-1 antibody responses were more dynamic in response to the occurrence and resolution of infection events than AMA-1, while the latter was more correlated with consecutive infections. The MSP-1 antibody response to an observed infection seemed to decay faster over time than the corresponding AMA-1 response. Surprisingly, there was no evidence of an age effect on the occurrence of a conversion or reversion event.ConclusionsWhile the population-level results concur with previously published sero-epidemiological surveys, the individual-level results highlight the more complex relationship between detected infections and antibody dynamics than can be analysed using cross-sectional data. The longitudinal analysis of serological data may provide a powerful tool for teasing apart the complex relationship between infection events and the corresponding immune response, thereby improving the ability to rapidly assess the success or failure of malaria control programmes.

Assessing Geographic Variation in Strabismus Diagnosis among Children Enrolled in Medicaid

PURPOSEnTo determine how strabismus diagnosis varies within a given community and across communities among children with Medicaid health insurance.nnnDESIGNnRetrospective cohort analysis.nnnPARTICIPANTSnChildren aged ≤10 years enrolled in Medicaid in Michigan or North Carolina duringxa02009.nnnMETHODSnChildren who met the study inclusion criteria were identified from the Medicaid Analytic Extract database, which includes claims data for all children enrolled in Medicaid throughout the United States. Residential location was determined by the last known 5-digit ZIP code for each child, which was linked to the centroid of a ZIP Code Tabulation Area (ZCTA) for geo-referencing and spatial analyses. International Classification of Diseases, 9th Revision, Clinical Modification billing codes were used to identify children diagnosed with strabismus (code 378.xx). Bayesian hierarchical intrinsic conditional autoregressive spatial probit models were used to determine the risk of a child receiving a strabismus diagnosis in communities throughout Michigan and North Carolina. Maps display communities (ZCTAs) where the 95% credible intervals for the spatial random effects estimates do not cross zero, allowing for identification of locations with increased and decreased strabismus diagnosis risk relative to other communities in the states.nnnMAIN OUTCOME MEASURESnLikelihood of receiving a diagnosis of strabismus.nnnRESULTSnIn 2009, among 519u2009212 eligible children in Michigan, 7535 (1.5%) received ≥1 strabismus diagnosis, and in North Carolina, 5827 of 523u2009886 eligible children (1.1%) were diagnosed with strabismus. In both states, the proportion receiving a strabismus diagnosis among black (0.9% in Michigan; 0.7% in North Carolina) and Hispanic (1.1% in Michigan; 0.8% in North Carolina) children was lower than the proportion for white children (1.8% in Michigan; 1.6% in North Carolina). Children living in poorer communities in both states were less likely to be diagnosed with strabismus independent of their race/ethnicity.nnnCONCLUSIONSnA childs likelihood of being diagnosed with strabismus is associated with characteristics of the residential community where he or she resides. The findings of this study highlight the importance of ensuring that children who live in less affluent communities have access to the necessary services and eye care professionals to properly diagnose and treat them for this condition.

Identifying barriers in the malaria control policymaking process in East Africa: insights from stakeholders and a structured literature review

BackgroundThe complexity of malaria and public health policy responses presents social, financial, cultural, and institutional barriers to policymaking at multiple stages in the policy process. These barriers reduce the effectiveness of health policy in achieving national goals.MethodsWe conducted a structured literature review to characterize malaria policy barriers, and we engaged stakeholders through surveys and workshops in Kenya, Tanzania, and Uganda. We compared common barriers presented in the scientific literature to barriers reported by malaria policy stakeholders.ResultsThe barriers identified in the structured literature review differ from those described in policymaker surveys. The malaria policy literature emphasizes barriers in the implementation stage of policymaking such as those posed by health systems and specific intervention tools. Stakeholder responses placed greater emphasis on the political nature of policymaking, the disconnect between research and policymaking, and the need for better intersectoral collaboration.ConclusionsIdentifying barriers to effective malaria control activities provides opportunities to improve health and other outcomes. Such barriers can occur at multiple stages and scales. Employing a stakeholder - designed decision tool framework has the potential to improve existing policies and ultimately the functioning of malaria related institutions. Furthermore, improved coordination between malaria research and policymaking would improve the quality and efficiency of interventions leading to better population health.