Enhancing discovery of genetic variants for posttraumatic stress disorder through integration of quantitative phenotypes and trauma exposure information

BACKGROUND: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). METHODS: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. RESULTS: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. CONCLUSIONS: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods

Extended magic phase in twisted graphene multilayers

Theoretical and experimental studies have verified the existence of ``magic angles'' in twisted bilayer graphene, where the twist between layers gives rise to flat bands and consequently highly correlated phases. Narrow bands can also exist in multilayers with alternating twist angles, and recent theoretical work suggests that they can also be found in trilayers with twist angles between neighboring layers in the same direction. We show here that flat bands exist in a variety of multilayers where the ratio between twist angles is close to coprime integers. We generalize previous analyses, and, using the chiral limit for interlayer coupling, give examples of many combinations of twist angles in stacks made up of three and four layers which lead to flat bands. The technique we use can be extended to systems with many layers. Our results suggest that flat bands can exist in graphene multilayers with angle disorder, that is, narrow samples of turbostatic graphite.Comment: Main text: 4 pages, 4 figures -- Supplementary Material: 15 pages, 13 figure

Multi-Disciplinary Hands-On Desktop Learning Modules and Modern Pedagogies

Our team’s research focuses on fundamental problems in undergraduate education in terms of how to expand use of well researched, yet still “new”, teaching pedagogies of ‘sensing’ or ‘hands-on’, ‘active’ and ‘problem-based learning’ within engineering courses. It is now widely accepted that traditional lectures ARE NOT best for students – yet that is what the community almost universally does. To address this issue we are developing new Desktop Learning Modules (DLMs) that contain miniaturized processes with a uniquely expandable electronic system to contend with known sensor systems/removable cartridges, as well as, unknown expansions to the project. We have shown that miniaturized mimics of industrial-scale equipment produce process data that agree with correlations developed for large-scale equipment. We are now adapting concepts shown efficacious in a single chemical engineering course to a variety of engineering classes within civil, mechanical, bio- and electrical engineering. Some examples of new hands-on learning applications in chemical engineering include a boiler / condenser and evaporative and shell & tube heat exchangers. In bioengineering, we are developing prognostic devices for separating Prostate Cancer Tumor Cells (PCTCs) from blood, sensing for the presence of PCTCs, a thermoregulation simulated limb cartridge for studying kinematics of heat flow and heat distribution in human extremities, and immunoaffinity neuron-like ion selective electrodes. In civil engineering, the DLMs illustrate open channel flow units and a solar powered Rankine cycle is underway in mechanical engineering. We are implementing DLMs along with team learning pedagogy. In this paper we will present technical aspects surrounding development of a large number of new learning cartridges. While the assessment strategies being developed are broadly applicable we will just present one instance, with the civil engineering cartridge, of the identification of misconceptions and experimental design for assessing the impact of the DLM on learning. The assessment includes a pre- and post-test assessment to determine improvement in understanding basic concepts and persistence and/or repair of misconceptions

Hippocampal Functional Dynamics Are Clinically Implicated in Autoimmune Encephalitis With Faciobrachial Dystonic Seizures

This is the first study to investigate functional brain activity in patients affected by autoimmune encephalitis with faciobrancial dystonic seizures (FBDS). Multimodal 3T MRI scans, including structural neuroimaging (T1-weighted, diffusion weighted) and functional neuroimaging (scene-encoding task known to activate hippocampal regions), were performed. This case series analysis included eight patients treated for autoimmune encephalitis with FBDS, scanned during the convalescent phase of their condition (median 1.1 years post-onset), and eight healthy volunteers. Compared to controls, 50% of patients showed abnormal hippocampal activity during scene-encoding relative to familiar scene-viewing. Higher peak FBDS frequency was significantly related to lower hippocampal activity during scene-encoding (p = 0.02), though not to markers of hippocampal microstructure (mean diffusivity, p = 0.3) or atrophy (normalized volume, p = 0.4). During scene-encoding, stronger within-medial temporal lobe (MTL) functional connectivity correlated with poorer Addenbrooke's Cognitive Examination-Revised memory score (p = 0.03). These findings suggest that in autoimmune encephalitis, frequent seizures may have a long-term impact on hippocampal activity, beyond that of structural damage. These observations also suggest a potential approach to determine on-going MTL performance in this condition to guide long-term management and future clinical trials

The PHANGS-JWST Treasury Survey: Star Formation, Feedback, and Dust Physics at High Angular Resolution in Nearby GalaxieS

The PHANGS collaboration has been building a reference data set for the multiscale, multiphase study of star formation and the interstellar medium (ISM) in nearby galaxies. With the successful launch and commissioning of JWST, we can now obtain high-resolution infrared imaging to probe the youngest stellar populations and dust emission on the scales of star clusters and molecular clouds (∼5-50 pc). In Cycle 1, PHANGS is conducting an eight-band imaging survey from 2 to 21 μm of 19 nearby spiral galaxies. Optical integral field spectroscopy, CO(2-1) mapping, and UV-optical imaging for all 19 galaxies have been obtained through large programs with ALMA, VLT-MUSE, and Hubble. PHANGS-JWST enables a full inventory of star formation, accurate measurement of the mass and age of star clusters, identification of the youngest embedded stellar populations, and characterization of the physical state of small dust grains. When combined with Hubble catalogs of ∼10,000 star clusters, MUSE spectroscopic mapping of ∼20,000 H ii regions, and ∼12,000 ALMA-identified molecular clouds, it becomes possible to measure the timescales and efficiencies of the earliest phases of star formation and feedback, build an empirical model of the dependence of small dust grain properties on local ISM conditions, and test our understanding of how dust-reprocessed starlight traces star formation activity, all across a diversity of galactic environments. Here we describe the PHANGS-JWST Treasury survey, present the remarkable imaging obtained in the first few months of science operations, and provide context for the initial results presented in the first series of PHANGS-JWST publications

Experimental Determination of Optimal Conditions for Reactive Coupling of Biodiesel Production With in situ Glycerol Carbonate Formation in a Triglyceride Transesterification Process

This study investigated a reactive coupling to determine the optimal conditions for transesterification of rapeseed oil (RSO) to fatty acid methyl ester (FAME) and glycerol carbonate (GLC) in a one-step process, and at operating conditions which are compatible with current biodiesel industry. The reactive coupling process was studied by transesterification of RSO with various molar ratios of both methanol and dimethyl carbonate (DMC), using triazabicyclodecene (TBD) guanidine catalyst and reaction temperatures of 50–80°C. The optimal reaction conditions obtained, using a Design of Experiments approach, were a 2:1 methanol-to-RSO molar ratio and 3:1 DMC-to-RSO molar ratio at 60°C. The FAME and GLC conversions at the optimal conditions were 98.0 ± 1.5 and 90.1 ± 2.2%, respectively, after 1 h reaction time using the TBD guanidine catalyst. Increase in the DMC-to-RSO molar ratio from 3:1 to 6:1 slightly improved the GLC conversion to 94.1 ± 2.8% after 2 h, but this did not enhance the FAME conversion. Methanol substantially improved both FAME and GLC conversions at 1:1–2:1 methanol-to-RSO molar ratios and enhanced the GLC separation from the reaction mixture. It was observed that higher methanol molar ratios (>3:1) enhanced only FAME yields and resulted in lower GLC conversions due to reaction equilibrium limitations. At a 6:1 methanol-to-RSO molar ratio, 98.4% FAME and 73.3% GLC yields were obtained at 3:1 DMC-to-RSO molar ratio and 60°C. This study demonstrates that formation of low value crude glycerol can be reduced by over 90% compared to conventional biodiesel production, with significant conversion to GLC, a far more valuable product