Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe

A combinatorial assessment of AlxCrCuFeNi2 (0 < x < 1.5) complex concentrated alloys: Microstructure, microhardness, and magnetic properties

This article discusses a novel combinatorial approach for assessing composition-microstructure-microhardness-magnetic property relationships, using laser deposited compositionally graded AlxCrCuFeNi2 (0 < x < 1.5) complex concentrated alloys as a candidate system. The composition gradient has been achieved from CrCuFeNi2 to Al1.5CrCuFeNi2 over a length of ∼25 mm, deposited using the laser engineered net shaping process from a blend of elemental powders. With increasing Al content, there was a gradual change from a fcc-based microstructure (including the ordered L12 phase) to a bcc-based microstructure (including the ordered B2 phase), accompanied with an increase in microhardness. Interestingly, with increasing paramagnetic Al content, saturation magnetization as well as coercivity increases and reaches a maximum value when x = 1.3, indicating the tunability of magnetic properties by a paramagnetic element in this alloy system. Such graded alloys are highly attractive candidates for investigating the influence of systematic compositional changes on microstructural evolution and concurrent physical and mechanical properties in complex concentrated alloys or high entropy alloys.NRF (Natl Research Foundation, S’pore

Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: Double blind randomised controlled trial

10.1136/bmj.f3039BMJ (Online)3467911-BMJO