Parity Nonconservation in Neutron Resonances in 133Cs

Spatial parity nonconservation (PNC) has been studied in the compound-nuclear states of 134Cs by measuring the helicity dependence of the neutron total cross section. Transmission measurements on a thick 133Cs target were performed by the time-of-flight method at the Manuel Lujan Neutron Scattering Center with a longitudinally polarized neutron beam in the energy range from 5 to 400 eV. A total of 28 new p-wave resonances were found, their neutron widths determined, and the PNC longitudinal asymmetries of the resonance cross sections measured. The value obtained for the root-mean-square PNC element M=(0.06-0.02+0.25) meV in 133Cs is the smallest among all targets studied. This value corresponds to a weak spreading width Γw=(0.006-0.003+0.154)×10-7 eV

Multicomponent obesity prevention intervention in low-income preschoolers: Primary and subgroup analyses of the NET-works randomized clinical trial, 2012-2017

Objectives. To evaluate a multicomponent obesity prevention intervention among diverse, low-income preschoolers. Methods. Parent-child dyads (n = 534) were randomized to the Now Everybody Together for Amazing and Healthful Kids (NET-Works) intervention or usual care in Minneapolis, MN (2012-2017). The intervention consisted of home visits, parenting classes, and telephone check-ins. The primary outcomes were adjusted 24- and 36-month body mass index (BMI). Results. Compared with usual care, the NET-Works intervention showed no significant difference in BMI change at 24 (-0.12 kg/m2; 95% confidence interval [CI] = -0.44, 0.19) or 36 months (-0.19 kg/m2; 95% CI = -0.64, 0.26). Energy intake was significantly lower in the NET-Works group at 24 (-90 kcal/day; 95% CI = -164, -16) and 36 months (-101 kcal/day; 95% CI = -164, -37). Television viewing was significantly lower in the NET-Works group at 24 (rate ratio = 0.84; 95% CI = 0.75, 0.93) and 36 months (rate ratio = 0.88; 95% CI = 0.78, 0.99). Children with baseline overweight or obesity had lower BMI in the NET-Works group than those in usual care at 36 months (-0.71 kg/m2; 95% CI = -1.30, -0.12). Hispanic children had lower BMI in the NET-Works group than those in usual care at 36 months (-0.59 kg/m2; 95% CI = -1.14, -0.04). Conclusions. In secondary analyses, NET-Works significantly reduced BMI over 3 years among Hispanic children and children with baseline overweight or obesity. Trial Registration: ClinicalTrials.gov Identifier: NCT01606891

Epigenome-wide association of PTSD from heterogeneous cohorts with a common multi-site analysis pipeline

Compelling evidence suggests that epigenetic mechanisms such as DNA methylation play a role in stress regulation and in the etiologic basis of stress related disorders such as Post traumatic Stress Disorder (PTSD). Here we describe the purpose and methods of an international consortium that was developed to study the role of epigenetics in PTSD. Inspired by the approach used in the Psychiatric Genomics Consortium, we brought together investigators representing seven cohorts with a collective sample size of N = 1147 that included detailed information on trauma exposure, PTSD symptoms, and genome-wide DNA methylation data. The objective of this consortium is to increase the analytical sample size by pooling data and combining expertise so that DNA methylation patterns associated with PTSD can be identified. Several quality control and analytical pipelines were evaluated for their control of genomic inflation and technical artifacts with a joint analysis procedure established to derive comparable data over the cohorts for meta-analysis. We propose methods to deal with ancestry population stratification and type I error inflation and discuss the advantages and disadvantages of applying robust error estimates. To evaluate our pipeline, we report results from an epigenome-wide association study (EWAS) of age, which is a well-characterized phenotype with known epigenetic associations. Overall, while EWAS are highly complex and subject to similar challenges as genome-wide association studies (GWAS), we demonstrate that an epigenetic meta-analysis with a relatively modest sample size can be well-powered to identify epigenetic associations. Our pipeline can be used as a framework for consortium efforts for EWAS

Genetic variants affecting bone mineral density and bone mineral content at multiple skeletal sites in Hispanic children

Context: Osteoporosis is a major public health burden with significant economic costs. However, the correlates of bone health in Hispanic children are understudied. Objective: We aimed to identify genetic variants associated with bone mineral density (BMD) and bone mineral content (BMC) at multiple skeletal sites in Hispanic children. Methods: We conducted a cross-sectional genome-wide linkage analysis, genome-wide and exome-wide association analysis of BMD and BMC. The Viva La Familia Study is a family-based cohort with a total of 1030 Hispanic children (4–19 years old at baseline) conducted in Houston, TX. BMD and BMC were measured by Dual-energy X-ray absorptiometry. Results: Significant heritability were observed for BMC and BMD at multiple skeletal sites ranging between 44 and 68% (P < 2.8 × 10− 9). Significant evidence for linkage was found for BMD of pelvis and left leg on chromosome 7p14, lumbar spine on 20q13 and left rib on 6p21, and BMC of pelvis on chromosome 20q12 and total body on 14q22-23 (logarithm of odds score > 3). We found genome-wide significant association between BMC of right arm and rs762920 at PVALB (P = 4.6 × 10− 8), and between pelvis BMD and rs7000615 at PTK2B (P = 7.4 × 10− 8). Exome-wide association analysis revealed novel association of variants at MEGF10 and ABRAXAS2 with left arm and lumber spine BMC, respectively (P < 9 × 10− 7). Conclusions: We identified novel loci associated with BMC and BMD in Hispanic children, with strongest evidence for PTK2B. These findings provide better understanding of bone genetics and shed light on biological mechanisms underlying BMD and BMC variation

Genetic overlap between diagnostic subtypes of ischemic stroke

Background and Purpose: Despite moderate heritability, the phenotypic heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses of diagnostic subtypes with reduced sample sizes. We assessed evidence for a shared genetic basis among the 3 major subtypes: large artery atherosclerosis (LAA), cardioembolism, and small vessel disease (SVD), to inform potential cross-subtype analyses. Methods: Analyses used genome-wide summary data for 12 389 ischemic stroke cases (including 2167 LAA, 2405 cardioembolism, and 1854 SVD) and 62 004 controls from the Metastroke consortium. For 4561 cases and 7094 controls, individual-level genotype data were also available. Genetic correlations between subtypes were estimated using linear mixed models and polygenic profile scores. Meta-analysis of a combined LAA-SVD phenotype (4021 cases and 51 976 controls) was performed to identify shared risk alleles. Results: High genetic correlation was identified between LAA and SVD using linear mixed models (rg=0.96, SE=0.47, P=9×10-4) and profile scores (rg=0.72; 95% confid

The fusion crust of the Winchcombe meteorite: vigorous degassing during atmospheric entry

Introduction: Fusion crusts form during the atmospheric entry heating of meteorites and preserve a record of the conditions that occurred in the last few seconds of their deceleration in the atmosphere [1]. Although fusion crusts are ubiquitous they are rarely characterised and studied because they obscure the primary features of meteorites. Here we report the results of a study of the fusion crust of the Winchcombe CM2 chondrite. The Winchcombe meteorite fell at 21:54 hours on 28 February 2021 in Gloucestershire in the UK and was recovered over the next week. The fall was observed on UKFAll network cameras and recorded by CCTV. The meteoroid had a low entry velocity compared to other observed falls of 13.5 km/s. Study of the fusion crust reveals unique textural features that testify to previously unknown processes related to vigorous degassing of this intensely altered CM2 chondrite. Methods: Six polished blocks of Winchcombe were studied using backscattered electron imaging, elemental mapping, energy dispersive spectroscopy (EDS), electron backscatter diffraction (EBSD) and micro-X-ray fluorescence (XRF). Apparent size distributions and abundances were obtained by threshold analysis using ImageJ. Results: The fusion crust consists of an inner thermally altered substrate and outer melted crust. The altered substrate exhibits unusually abundant dehydration cracks extending up to 5 mm into the meteorite. The crack network encompasses fragments up to 70 µm in diameter (dense rock equivalent) with increasing abundance with decreasing size. Loss of sheet-like habits for phyllosilicates and tochilinite testifies to progressive dehydration towards the exterior. The outer melted crust has a vesicular porphyritic texture with olivine phenocrysts and magnetite in a glassy mesostasis. Grain-size and magnetite abundance increase outwards similar to other CI/CM2 fusion crusts [2]. High Ni (<80 wt%) sulphide-metal droplets occur – often as menisci on vesicles. A magnetite rim occurs on the exterior surface and some vesicles, and include some tabular, rim-parallel magnetite crystals. Unique features in the fusion crust are oscillatory zoned olivine crystals, monolayers of magnetite and silicate warts. Monolayers form chains of magnetite crystals within the mesostasis that have tabular crystals similar to magnetite rims. EBSD data reveals [111] is parallel to the length of tabular crystals and is layer parallel in rims and monolayers. Oscillatory zoned crystals are equant with up to 4 Mg-rich zones. Silicate warts form lenticular features on the surface of the fusion crust and contain dendritic olivine – their compositions are, however, similar to the rest of the crust. Magnetite monolayers lie between warts and the underlying crust. Discussion: The unusualy high abundance of dehydration cracks suggests the tochlinite-rich matrix of the Winchcombe meteorite is particularly sensitive to dehydration, owing to the low decomposition temperature of this mineral (250oC [3]). Mechanical failure of the substrate, in part driven by gas pressure, is likely to inject large abundances of particulates into the meteoroid gas stream. Observations of episodic pulsed plasma in the trail of the fireball may be a phenomena associated with calving of the dehydrated substrate and generate thermal pulses explaining the presence of oscillatory zoning. Other features also are consistent with vigorous degassing. Magnetite monolayers appear to have formed as surface magnetite rims – owing to their similar alignment of tabular crystals. Trapping of surface magneite rims through collapse of melt protrusions is likely to explain how these layers become buried within the crust and is probably driven by perturbation of surface melt by rapid vesicle loss. Finally, silicate warts are likely to be droplets attached to the crust surface. Their dendritic textures suggest higher peak temperatures and strongly suggest they represent droplets removed from other stones in the shower. Warts represent the first discovery of intershower transport of ablation materials, possibly owing to enhanced ablation as a result of vigorous degassing. Implications: The fusion crust of the Winchcombe meteorite illustrates the complexity of processes affecting meteorites during atmospheric flight. Features such as magnetite monolayers and silicate warts have not previously been described, and may be unique to tochlinite-rich CM2 chondrites, which experience vigorous degassing. They may also allow ablation debris to be related to particular types of meteorite, thus providing a distributed record of the meteorite flux. Winchcombe underlines the utility of fusion crust, which should be routinely characterised in addition to meteorite interiors. References: [1] Ramsdohr P. (1967) EPSL 2, 593-598, [2] Genge M. J. & Grady M. M. (1999) MAPS 34 (3).341-356. [3] Fuchs, L. H et al. (1973) Smithsonian Contrib. Earth Sci. 1–3

Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

This paper is dedicated to the memory of Psychiatric Genomics Consortium (PGC) founding member and Bipolar disorder working group co-chair Pamela Sklar. We thank the participants who donated their time, experiences and DNA to this research, and to the clinical and scientific teams that worked with them. We are deeply indebted to the investigators who comprise the PGC. The views expressed are those of the authors and not necessarily those of any funding or regulatory body. Analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org ) hosted by SURFsara, and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu).Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1x10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p < 5x10-8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD.This work was funded in part by the Brain and Behavior Research Foundation, Stanley Medical Research Institute, University of Michigan, Pritzker Neuropsychiatric Disorders Research Fund L.L.C., Marriot Foundation and the Mayo Clinic Center for Individualized Medicine, the NIMH Intramural Research Program; Canadian Institutes of Health Research; the UK Maudsley NHS Foundation Trust, NIHR, NRS, MRC, Wellcome Trust; European Research Council; German Ministry for Education and Research, German Research Foundation IZKF of Münster, Deutsche Forschungsgemeinschaft, ImmunoSensation, the Dr. Lisa-Oehler Foundation, University of Bonn; the Swiss National Science Foundation; French Foundation FondaMental and ANR; Spanish Ministerio de Economía, CIBERSAM, Industria y Competitividad, European Regional Development Fund (ERDF), Generalitat de Catalunya, EU Horizon 2020 Research and Innovation Programme; BBMRI-NL; South-East Norway Regional Health Authority and Mrs. Throne-Holst; Swedish Research Council, Stockholm County Council, Söderström Foundation; Lundbeck Foundation, Aarhus University; Australia NHMRC, NSW Ministry of Health, Janette M O'Neil and Betty C Lynch