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Linear regression is often used to estimate associations between chemical exposures and neurodevelopment at the mean of the outcome. However, the potential effect of chemicals may be greater among individuals at the 'tails' of outcome distributions. Here, we investigated distributional effects on the associations between gestational phthalate exposure and child Autism Spectrum Disorder (ASD)-related behaviors using quantile regression. We harmonized data from the Early Autism Risk Longitudinal Investigation (EARLI) (n = 140) Study, an enriched-risk cohort of mothers who had a child with ASD, and the Health Outcomes and Measures of the Environment (HOME) Study (n = 276), a general population cohort. We measured concentrations of 9 phthalate metabolites in urine samples collected twice during pregnancy. Caregivers reported children's ASD-related behaviors using the Social Responsiveness Scale (SRS) at age 3-8 years; higher scores indicate more ASD-related behaviors. In EARLI, associations between phthalate concentrations and SRS scores were predominately inverse or null across SRS score quantiles. In HOME, positive associations of mono-n-butyl phthalate, monobenzyl phthalate, mono-isobutyl phthalate, and di-2-ethylhexyl phthalate concentrations with SRS scores increased in strength from the median to 95th percentile of SRS scores. These results suggest associations between phthalate concentrations and SRS scores may be stronger in individuals with higher SRS scores.

Maternal nutrition during gestation has been investigated for its role in child neurodevelopment. However, little is known about the potential impact of gestational caffeine exposure on child autistic behaviors. Here, we assess the relation between maternal caffeine intake during pregnancy and children's behavioral traits related to Autism Spectrum Disorder (ASD). We harmonized data from two pregnancy cohorts, Early Autism Risk Longitudinal Investigation (EARLI) (n = 120), an enriched-risk cohort of mothers who previously had a child with ASD, from Pennsylvania, Maryland, and Northern California (2009-2012), and the Health Outcomes and Measures of the Environment (HOME) Study (n = 269), a general population cohort from Cincinnati, Ohio (2003-2006). Mothers self-reported caffeine intake twice during pregnancy. Caregivers reported child behavioral traits related to ASD using the Social Responsiveness Scale (SRS) when children were aged 3-8 years. Higher scores indicate more ASD-related behaviors. We estimated covariate-adjusted differences in continuous SRS T-scores per interquartile range increase in caffeine intake. Self-reported caffeine intake during pregnancy was positively associated with SRS T-scores among children in EARLI (β: 2.0; 95% CI -0.1, 4.0), but to a lesser extent in HOME (β: 0.6; 95% CI -0.5, 1.6). In HOME, pre-pregnancy body mass index (BMI) modified the association between caffeine intake and SRS T-scores, where more positive associations were observed among women with higher BMIs. Our findings suggest gestational caffeine intake may represent a marker of vulnerability to childhood ASD-related behaviors. Additional studies are warranted to extend these findings.

High quality historical control data, if incorporated, may reduce sample size, trial cost, and duration. A too optimistic use of the data, however, may result in bias under prior-data conflict. Motivated by well-publicized two-arm comparative trials in stroke, we propose a Bayesian design that both adaptively incorporates historical control data and selectively adapt the treatment allocation ratios within an ongoing trial responsively to the relative treatment effects. The proposed design differs from existing designs that borrow from historical controls. As opposed to reducing the number of subjects assigned to the control arm blindly, this design does so adaptively to the relative treatment effects only if evaluation of cumulated current trial data combined with the historical control suggests the superiority of the intervention arm. We used the effective historical sample size approach to quantify borrowed information on the control arm and modified the treatment allocation rules of the doubly adaptive biased coin design to incorporate the quantity. The modified allocation rules were then implemented under the Bayesian framework with commensurate priors addressing prior-data conflict. Trials were also more frequently concluded earlier in line with the underlying truth, reducing trial cost, and duration and yielded parameter estimates with smaller standard errors.

Executive functioning (EF) abilities develop through childhood, but this development can be impacted by various psychosocial environmental influences. Using longitudinal data from the Health Outcome and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort study, we examined if psychosocial environmental factors were significant predictors of EF development. Study participants comprised 271 children and their primary caregivers (98.5% mothers) followed from birth to age 12. We identified four distinct EF developmental trajectory groups comprising a consistently impaired group (13.3%), a descending impairment group (27.7%), an ascending impairment group (9.95%), and a consistently not impaired group (49.1%). Higher levels of maternal ADHD and relational frustration appear to be risk factors for increased EF difficulty over time, while higher family income may serve as a protective factor delaying predisposed EF impairment. Important intervention targets might include teaching positive and effective parenting strategies to mothers whose children are at risk for EF dysfunction. [ABSTRACT FROM AUTHOR]

IntroductionNational data suggest tobacco smoke is positively associated with higher glycated hemoglobin (HbA1c) among adults. Our objective was to examine the association between serum cotinine and HbA1c among adolescents without known diabetes.MethodsWe assessed adolescents 12-19 years old (N = 11550) who participated in the 1999-2012 National Health and Nutrition Examination Survey. We applied sampling weights while performing multiple linear regression analyses.ResultsThe prevalence of serum cotinine indicative of no tobacco smoke exposure (TSE, 3 ng/mL) was 17.9% in our sample. Mean (± standard error) HbA1c in participants with no TSE was 5.16% (±0.01), passive TSE was 5.16% (±0.01), and active TSE was 5.14% (±0.01). No differences in HbA1c were found between TSE groups including sex, age, race/ethnicity, education, income, and physical activity or the fully adjusted model with waist circumference. We found cotinine × sex (p = .01) and cotinine × age (p = .02) interactions. There was an association between cotinine and HbA1c for males but not females. Within males, participants with cotinine ≥3 ng/mL (5.26 ± 0.02) had higher mean HbA1c than those with cotinine 0.05-2.99 ng/mL and

Background: The objective was to determine whether infant neurobehavior measured at five post-gestational weeks could predict social and communicative behavior (SCB) through five and eight years. Methods: Infant neurobehavior was assessed using the Neonatal Intensive Care Unit Network Neurobehavioral Scale, and SCB was measured using the Social Responsiveness Scale (SRS). Adjusted linear regression with generalized estimating equations were employed to estimate the association between infant neurobehavior and SCB. Interaction terms and stratification were used to identify potential effect modification by autism spectrum disorder risk factors. Results: The analyses include n = 214 and n = 227 participants who were examined at 5 weeks and followed to 4/5 and 8 years, respectively. Adjusting for maternal age, race, parity, and education as well as gestational age, only the Neonatal Intensive Care Unit Network Neurobehavioral Scale summary score of "attention" (measured at mean 43.9 gestational weeks) was inversely associated with total SRS T-score through 5 years. However, in analyses stratified by maternal age, the inverse association between "attention" and SCB was significant, but only among offspring of women of advanced maternal age (=35 y); in addition, higher scores of "excitability," "lethargy," and "arousal" were associated with increased total SRS T scores among women of advanced maternal age. The associations were no longer statistically significant at 8 years. Conclusions: Newborns with lower scores on the attention subscale (determined by an ability to localize and track animate and inanimate objects) were more likely to demonstrate deficits in SCB. In addition, infants with increased excitability, lethargy, or increased arousal were more likely to have impaired SCB that persisted through 5 years, but not at 8 years of age. Further work is necessary to identify specific aspects of infant neurobehavior that may affect childhood SCBs.

Context: Most individuals with Turner syndrome (TS) require estrogen for pubertal induction. Current estrogen dosing guidelines are based on expert consensus opinion. Objective: Evaluate whether current international guidelines for estrogen dosing during pubertal induction of individuals with TS result in normal uterine growth. We hypothesized that uterine size in individuals with TS who reached adult estrogen dosing is smaller than in mature females without TS. Methods: Cross-sectional study of patients with TS at the Cincinnati Center for Pediatric and Adult Turner Syndrome Care. Twenty-nine individuals (age 15-26 years) with primary ovarian insufficiency who reached adult estrogen dosing (100 µg of transdermal or 2 mg of oral 17β-estradiol) were included. Comparison of uterine measurements with a published sample of 292 age-appropriate (age 15-20 years) controls without TS. Uterine length, volume, and fundal–cervical ratio (FCR) were measured. Clinical information (karyotype, Tanner staging for breast development, laboratory data) was extracted from an existing institutional patient registry. Results: There was no evidence of compromise of the uterine size/configuration in the TS cohort compared with the controls; in fact, uterine length, mean 7.7 cm (±1.3) vs 7.2 cm (±1.0) (P = .03), and volume, mean 60.6 cm3 (±26.6) vs 50.5 cm3 (±20.5) (P = .02), were both larger in individuals with TS. Conclusion: Current international guidelines for hormone replacement using 17β-estradiol in individuals with TS appear adequate to allow for normal uterine growth by the end of pubertal induction. [ABSTRACT FROM AUTHOR]

Applying Bandura's reciprocal determinism model, differences in math and science experiences influenced by individual, gender, and school variables were investigated within 1,368 elementary students who attended 21 Catholic schools. Math and science were evaluated positively and favored more than other academic subjects. However, advantages were found for boys by lowered math anxiety levels and favoring of math, and for large schools by lowered math anxiety levels and higher student ratings of science. No advantages were found for small schools. However, school poverty rate appeared to have a confounding effect on school size. Discussion is presented pertaining to the specific need to study Catholic school systems regarding student perceptions in light of distinguishing Catholic school factors. (Contains 7 tables.)

AimsEpidemiological studies suggest that sex has a role in the pathogenesis of cardioembolic stroke. Since stroke is a vascular disease, identifying sexually dimorphic gene expression changes in blood leukocytes can inform on sex-specific risk factors, response and outcome biology. We aimed to examine the sexually dimorphic immune response following cardioembolic stroke by studying the differential gene expression in peripheral white blood cells.Methods and resultsBlood samples from patients with cardioembolic stroke were obtained at ≤3 hours (prior to treatment), 5 hours and 24 hours (after treatment) after stroke onset (n = 23; 69 samples) and compared with vascular risk factor controls without symptomatic vascular diseases (n = 23, 23 samples) (ANCOVA, false discovery rate p≤0.05, |fold change| ≥1.2). mRNA levels were measured on whole-genome Affymetrix microarrays. There were more up-regulated than down-regulated genes in both sexes, and females had more differentially expressed genes than males following cardioembolic stroke. Female gene expression was associated with cell death and survival, cell-cell signaling and inflammation. Male gene expression was associated with cellular assembly, organization and compromise. Immune response pathways were over represented at ≤3, 5 and 24 h after stroke in female subjects but only at 24 h in males. Neutrophil-specific genes were differentially expressed at 3, 5 and 24 h in females but only at 5 h and 24 h in males.ConclusionsThere are sexually dimorphic immune cell expression profiles following cardioembolic stroke. Future studies are needed to confirm the findings using qRT-PCR in an independent cohort, to determine how they relate to risk and outcome, and to compare to other causes of ischemic stroke.

ObjectiveHemorrhagic transformation (HT) is a major complication of ischemic stroke that worsens outcomes and increases mortality. Disruption of the blood-brain barrier is a central feature of HT pathogenesis, and leukocytes may contribute to this process. We sought to determine whether ischemic strokes that develop HT have differences in RNA expression in blood within 3 hours of stroke onset prior to treatment with thrombolytic therapy.MethodsStroke patient blood samples were obtained prior to treatment with thrombolysis, and leukocyte RNA was assessed by microarray analysis. Strokes that developed HT (n = 11) were compared to strokes without HT (n = 33) and controls (n = 14). Genes were identified (corrected p