Social perspective taking is associated with self-reported prosocial behavior and regional cortical thickness across adolescence

Basic perspective taking and mentalising abilities develop in childhood, but recent studies indicate that the use of social perspective taking to guide decisions and actions has a prolonged development that continues throughout adolescence. Here, we aimed to replicate this research and investigate the hypotheses that individual differences in social perspective taking in adolescence are associated with real-life prosocial and antisocial behavior and differences in brain structure. We employed an experimental approach and a large cross-sectional sample (n=293) of participants aged 7-26 years old to assess age-related improvement in social perspective taking usage during performance of a version of the Director task. In subsamples, we then tested how individual differences in social perspective taking were related to self-reported prosocial behavior and peer relationship problems on the Strengths and Difficulties Questionnaire (SDQ) (n=184) and to magnetic resonance imaging (MRI) measures of regional cortical thickness and surface area (n=226). The pattern of results in the Director task replicated previous findings by demonstrating continued improvement in use of social perspective taking across adolescence. The study also showed that better social perspective taking usage is associated with more self-reported prosocial behavior, as well as to thinner cerebral cortex in regions in the left hemisphere encompassing parts of the caudal middle frontal and precentral gyri and lateral parietal regions. These associations were observed independently of age, and might partly reflect individual developmental variability. The relevance of cortical development was additionally supported by indirect effects of age on social perspective taking usage via cortical thickness

Magnetic Interactions and Transport in (Ga,Cr)As

The magnetic, transport, and structural properties of (Ga,Cr)As are reported. Zincblende Ga$_{1-x}$Cr$_{x}$As was grown by low-temperature molecular beam epitaxy (MBE). At low concentrations, x$\sim$0.1, the materials exhibit unusual magnetic properties associated with the random magnetism of the alloy. At low temperatures the magnetization M(B) increases rapidly with increasing field due to the alignment of ferromagnetic units (polarons or clusters) having large dipole moments of order 10-10$^2$$\mu_B$. A standard model of superparamagnetism is inadequate for describing both the field and temperature dependence of the magnetization M(B,T). In order to explain M(B) at low temperatures we employ a distributed magnetic moment (DMM) model in which polarons or clusters of ions have a distribution of moments. It is also found that the magnetic susceptibility increases for decreasing temperature but saturates below T=4 K. The inverse susceptibility follows a linear-T Curie-Weiss law and extrapolates to a magnetic transition temperature $\theta$=10 K. In magnetotransport measurements, a room temperature resistivity of $\rho$=0.1 $\Omega$cm and a hole concentration of $\sim10^{20}$ cm$^{-3}$ are found, indicating that Cr can also act as a acceptor similar to Mn. The resistivity increases rapidly for decreasing temperature below room temperature, and becomes strongly insulating at low temperatures. The conductivity follows exp[-(T$_1$/T)$^{1/2}$] over a large range of conductivity, possible evidence of tunneling between polarons or clusters.Comment: To appear in PRB 15 Mar 200

Image Quality Assessment Using Spatial Frequency Component

Image quality assessment (IQA) is a crucial technique in perceptual image/video coding, because it is not only a ruler for performance evaluation of coding algorithms but also a metric for ratio-distortion optimization in coding. In this paper, inspired by the fact that distortions of both global and local information influence the perceptual image quality, we propose a novel IQA method that inspects these information in the spatial frequency components of the image. The distortion of the global information mostly existing in low spatial frequency is measured by a rectified mean absolute difference metric, and the distortion of the local information mostly existing in high spatial frequency is measured by SSIM. These two measurements are combined using a newly proposed abruptness weighting that describes the uniformity of the residual image. Experimental results on LIVE database show that the proposed metric outperforms the SSIM and achieves performance competitive with the state-of-the-art metrics. ? 2009 Springer-Verlag Berlin Heidelberg.EI

TiViPE Simulation of a Cortical Crossing Cell Model

Abstract. Many cells in cat and monkey visual cortex (area V1 and area 17) respond to gratings and bar patterns of different orientation between center and surround [18]. It has been shown that these cells respond on average 3.3 times stronger to a crossing pattern than to a single bar [16]. In this paper a computational model for a group of neurons that respond solely to crossing patterns is proposed, and has been implemented in visual programming environment TiViPE [10]. Simulations show that the operator responds very accurately to crossing patterns that have an angular difference between 2 bars of 40 degrees or more, the operator responds appropriately to bar widths that are bound by 50 to 200 percent of the preferred bar width and is insensitive to non-uniform illumination conditions, which appear to be consistent with the experimental results.

Genome-Wide and Abdominal MRI-Imaging Data Provides Evidence that a Genetically Determined Favourable Adiposity Phenotype is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease and Hypertension

Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such “favourable adiposity” alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined magnetic resonance imaging (MRI) data with genome-wide association studies (GWAS) of body fat % and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity, but a favourable metabolic profile. Consistent with previous studies, individuals carrying more “favourable adiposity” alleles had higher body fat % and higher BMI, but lower risk of type 2 diabetes, heart disease and hypertension. These individuals also had higher subcutaneous fat, but lower liver fat and lower visceral-to-subcutaneous adipose tissue ratio. Individual alleles associated with higher body fat % but lower liver fat and lower risk of type 2 diabetes included those in PPARG, GRB14 and IRS1, whilst the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified “favourable adiposity” alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglyceride in metabolically low risk depots.Diabetes UK RD Lawrence fellowship, European Research Council, Wellcome Trust and Royal Society grant, European Regional Development Fund, Medical Research Council, German Federal Ministry of Education and Research, German Research Foundation, Innovative Medicines Initiative Joint Undertaking, European Union's Seventh Framework Programme, Dutch Science Organisation, Scottish Government Health Directorates, Scottish Funding Council and Medical Research Council UK and the Wellcome Trust

New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475,000 Individuals

Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association. Methods and Results - Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, ≈475 000), and the other in the subset of individuals of European descent (≈423 000). Twenty-one SNVs were genome-wide significant (P<5×10-8) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant. Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research