Multilocus genetic models of handedness closely resemble single-locus models in explaining family data and are compatible with genome-wide association studies.

Right- and left-handedness run in families, show greater concordance in monozygotic than dizygotic twins, and are well described by single-locus Mendelian models. Here we summarize a large genome-wide association study (GWAS) that finds no significant associations with handedness and is consistent with a meta-analysis of GWASs. The GWAS had 99% power to detect a single locus using the conventional criterion of P < 5 × 10(-8) for the single locus models of McManus and Annett. The strong conclusion is that handedness is not controlled by a single genetic locus. A consideration of the genetic architecture of height, primary ciliary dyskinesia, and intelligence suggests that handedness inheritance can be explained by a multilocus variant of the McManus DC model, classical effects on family and twins being barely distinguishable from the single locus model. Based on the ENGAGE meta-analysis of GWASs, we estimate at least 40 loci are involved in determining handedness

A Distinct Three-Factor Structure of Restricted and Repetitive Behaviors in an Epidemiologically Sound Sample of Preschool-Age Children with Autism Spectrum Disorder

Prior studies investigating restricted and repetitive behavior (RRB) subtypes within autism spectrum disorder (ASD) have found varied factor structures for symptom groupings, in part, due to variation in symptom measurement and broad sample age ranges. This study examined RRBs among 827 preschool-age children, ages 35 to 71 months, through an exploratory factor analysis of RRB items from the Autism Diagnostic Interview-Revised (ADI-R) collected through the Study to Explore Early Development. The factor structures of RRBs among children with confirmed ASD versus those with non-autism developmental concerns were qualitatively compared. Correlations between RRB factors and participant characteristics were examined in the ASD group. Three conceptually well-defined factors characterized as repetitive sensorimotor behaviors (RSMB), insistence on sameness (IS), and a novel stereotyped speech (SPEECH) factor emerged for the ASD group only. Distinct factors were supported by different clinical correlates. Findings have implications for improving differential diagnosis and understanding of ASD symptomatology in this age range

Maternal Pre-pregnancy Body Mass Index and Gestational Weight Gain in Relation to Autism Spectrum Disorder and other Developmental Disorders in Offspring

Most prior studies examining maternal pre-pregnancy body mass index (BMI) in relation to offspring autism spectrum disorders (ASD) have reported an association, though findings are not uniform and few have also examined gestational weight gain (GWG). Therefore, we examined both in the Study to Explore Early Development, a multi-site case–control study of children born in 2003–2006. Children identified from clinics, schools, and birth certificates were enrolled at ages 2–5 year and using standardized developmental evaluations, classified as: ASD, other developmental delays (DD), or population-based controls. Maternal height, weight, and GWG were self-reported during the telephone interview. Three primary weight risk factors were examined: (a) Pre-pregnancy BMI, classified as underweight to obese, (b) GWG continuous and categorized as quintiles, and (c) Institute of Medicine clinical weight-gain recommendations. Odds ratios adjusted (AOR) for sociodemographic and prenatal factors were calculated among term singletons, comparing the ASD (n = 540) or DD (n = 720) groups to the control group (n = 776). The AOR of ASD and maternal obesity was 1.37 (95%CI 0.98–1.92). Associations with higher GWG were stronger (Quintile5 vs. Quintile3 AOR = 1.58, 95%CI 1.08–2.31), and particularly so among overweight/obese women (AOR = 1.90, 95%CI 0.98–3.68). DD was associated with maternal overweight and obesity (obesity AOR = 1.48, 95%CI 1.08–2.02), but not with total GWG or clinical recommendations. High maternal BMI and GWG are risk factors for other pregnancy and child outcomes, and our results suggest they may also represent modifiable risk factors for neurodevelopmental outcomes. Autism Res 2019, 12: 316–327 © 2018 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary: In a large, national study, we found that children with autism were more likely than unaffected children to have mothers with higher weight gain during pregnancy; risk of autism may be even stronger if mothers were also overweight before pregnancy. Children with other developmental delays were more likely to have mothers who were overweight or obese before pregnancy, but not who gained more weight during pregnancy. Overweight and weight gain may represent factors that could be modified

Many Young Children with Autism Who Use Psychotropic Medication Do Not Receive Behavior Therapy: A Multisite Case-Control Study

Objectives: To explore how many pre-school aged children with autism spectrum disorder (ASD) used psychotropic medication, child and geographic factors associated with psychotropic medication use, and how many children who used psychotropic medication did or did not ever receive behavior therapy. Study design: Children 2-5 years of age were enrolled from 2012 to 2016 in a multisite case-control study designed to investigate the development and risk factors of ASD. Children with a positive ASD screen or ASD diagnosis upon enrollment were asked to complete a comprehensive evaluation to determine ASD status and developmental level. Caregivers completed a Services and Treatments Questionnaire and multiple self-administered questionnaires to determine child use of psychotropic medication, ever receipt of behavior therapy, and presence of co-occurring symptoms. Results: There were 763 children who were classified as ASD and had data collected on the Services and Treatments Questionnaire. Of those, 62 (8.1%) used psychotropic medication to treat behavioral symptoms and 28 (3.7%) were ≤3 years of age when medication was first started. Attention problems (aOR, 7.65; 95% CI, 3.41-16.1; P < .001) and study site (aOR, 2.62; 95% CI, 1.04-6.56; P = .04) were significantly associated with psychotropic medication use after controlling for maternal race/ethnicity. More than one-half (59.7%) of those who used psychotropic medication did not ever receive behavior therapy. Conclusions: Many preschool-aged children with ASD who use psychotropic medication do not receive behavior therapy. Pediatricians are an important resource for children and families and can help facilitate behavioral treatment for children with ASD and other disorders

Demographic and Operational Factors Predicting Study Completion in a Multisite Case-Control Study of Preschool Children

Participant attrition can limit inferences drawn from study results and inflate research costs. We examined factors associated with completion of the Study to Explore Early Development (2007-2011), a multiple-component, case-control study of risk factors for autism spectrum disorder in preschoolers, conducted in California, Colorado, Georgia, Maryland, North Carolina, and Pennsylvania. Participants (n = 3,769) were asked to complete phone interviews, questionnaires, an in-person evaluation, and biologic sampling. We examined whether participant demographic and administrative factors predicted completion using mixed-effects logistic regression models. Completion of individual key study components was generally 70% or higher. However, 58% of families completed all per-protocol data elements (defined a priori as key study components). Per-protocol completion differed according to mother's age, race, educational level, driving distance to clinic, number of contact attempts to enroll, and number of telephone numbers provided (all P < 0.05). Case status was not associated with completion, despite additional data collection for case-confirmation. Analysis of a subset that completed an early interview revealed no differences in completion by household factors of income, primary language spoken, number of adults, or number of children with chronic conditions. Differences in completion by race and education were notable and need to be carefully considered in developing future recruitment and completion strategies

A Phenotype of Childhood Autism Is Associated with Preexisting Maternal Anxiety and Depression

This study explored whether ASD phenotypes in the child were associated with a history of anxiety or depression in the mother. We hypothesized that an ASD profile in children characterized by mild delays and increased rates of dysregulation would be associated with preexisting maternal anxiety or depression. Participants were 672 preschool children with ASD and their mothers. Children were classified as ASD after a comprehensive developmental evaluation. Mothers reported whether a healthcare provider ever diagnosed them with anxiety or depression before the birth of their child. Four child ASD phenotypes were derived from latent class analysis: Mild Language Delay with Cognitive Rigidity (Type 1), Significant Developmental Delay with Repetitive Motor Behaviors (Type 2), General Developmental Delay (Type 3), and Mild Language and Motor Delay with Dysregulation (i.e., aggression, anxiety, depression, emotional reactivity, inattention, somatic complaints, and sleep problems) (Type 4). Type 2 ASD served as the referent category in statistical analyses. Results showed that 22.6% of mothers reported a diagnosis of anxiety or depression before the birth of their child. Maternal anxiety or depression was associated with 2.7 times the odds (95% confidence interval: 1.4, 5.3) of Type 4 or Dysregulated ASD in the child; maternal anxiety and depression was associated with 4.4 times the odds (95% confidence interval: 1.4, 14.0) of Type 4 or Dysregulated ASD in the child. Our findings suggest an association between Dysregulated ASD in the child and anxiety and depression in the mother. These findings can enhance screening methods and inform future research efforts

Spin-Charge Separation in the t−Jt-J Model: Magnetic and Transport Anomalies

A real spin-charge separation scheme is found based on a saddle-point state of the $t-J$ model. In the one-dimensional (1D) case, such a saddle-point reproduces the correct asymptotic correlations at the strong-coupling fixed-point of the model. In the two-dimensional (2D) case, the transverse gauge field confining spinon and holon is shown to be gapped at {\em finite doping} so that a spin-charge deconfinement is obtained for its first time in 2D. The gap in the gauge fluctuation disappears at half-filling limit, where a long-range antiferromagnetic order is recovered at zero temperature and spinons become confined. The most interesting features of spin dynamics and transport are exhibited at finite doping where exotic {\em residual} couplings between spin and charge degrees of freedom lead to systematic anomalies with regard to a Fermi-liquid system. In spin dynamics, a commensurate antiferromagnetic fluctuation with a small, doping-dependent energy scale is found, which is characterized in momentum space by a Gaussian peak at ($\pi/a$, $\pi/a$) with a doping-dependent width ($\propto \sqrt{\delta}$, $\delta$ is the doping concentration). This commensurate magnetic fluctuation contributes a non-Korringa behavior for the NMR spin-lattice relaxation rate. There also exits a characteristic temperature scale below which a pseudogap behavior appears in the spin dynamics. Furthermore, an incommensurate magnetic fluctuation is also obtained at a {\em finite} energy regime. In transport, a strong short-range phase interference leads to an effective holon Lagrangian which can give rise to a series of interesting phenomena including linear-$T$ resistivity and $T^2$ Hall-angle. We discuss the striking similarities of these theoretical features with those found in the high-$T_c$ cuprates and give aComment: 70 pages, RevTex, hard copies of 7 figures available upon request; minor revisions in the text and references have been made; To be published in July 1 issue of Phys. Rev. B52, (1995

Overriding water table control on managed peatland greenhouse gas emissions

Global peatlands store more carbon than is naturally present in the atmosphere1,2. However, many peatlands are under pressure from drainage-based agriculture, plantation development and fire, with the equivalent of around 3% of all anthropogenic greenhouse gases emitted from drained peatland3–5. Efforts to curb such emissions are intensifying through the conservation of undrained peatlands and rewetting of drained systems6. Here we report CO2 eddy covariance data from 16 locations and CH4 data from 41 locations in the British Isles, and combine them with published data from sites across all major peatland biomes. We find that the mean annual effective water-table depth (WTDe; that is, the average depth of the aerated peat layer) overrides all other ecosystem- and management-related controls on greenhouse gas fluxes. We estimate that every 10 cm of reduction in WTDe could reduce the net warming impact of CO2 and CH4 emissions (100-year Global Warming Potentials) by at least 3 t CO2e ha-1 yr-1, until WTDe is < 30 cm. Raising water levels further would continue to have a net cooling effect until WTDe is < 10 cm. Our results suggest that greenhouse gas emissions from peatlands drained for agriculture could be greatly reduced without necessarily halting their productive use. Halving WTDe in all drained agricultural peatlands, for example, could reduce emissions by the equivalent of over 1% of global anthropogenic emissions

Cardiovascular safety of celecoxib in acute myocardial infarction patients: a nested case-control study

The objective was to measure the impact of exposure to coxibs and non-steroidal antiinflammatory drugs (NSAID) on morbidity and mortality in older patients with acute myocardial infarction (AMI). A nested case-control study was carried out using an exhaustive population-based cohort of patients aged 66 years and older living in Quebec (Canada) who survived a hospitalization for AMI (ICD-9 410) between 1999 and 2002. The main variables were all-cause and cardiovascular (CV) death, subsequent hospital admission for AMI, and a composite end-point including recurrent AMI or CV death. Conditional logistic regressions were used to estimate the risk of mortality and morbidity. A total of 19,823 patients aged 66 years and older survived hospitalization for AMI in the province of Quebec between 1999 and 2002. After controlling for covariables, the risk of subsequent AMI and the risk of composite end-point were increased by the use of rofecoxib. The risk of subsequent AMI was particularly high for new rofecoxib users (HR 2.47, 95% CI 1.57–3.89). No increased risk was observed for celecoxib users. No increased risk of CV death was observed for patients exposed to coxibs or NSAIDs. Patients newly exposed to NSAIDs were at an increased risk of death (HR 2.22, 95% CI 1.30–3.77) and of composite end-point (HR 2.28, 95% CI 1.35–3.84). Users of rofecoxib and NSAIDs, but not celecoxib, were at an increased risk of recurrent AMI and of composite end-point. Surprisingly, no increased risk of CV death was observed. Further studies are needed to better understand these apparently contradictory results