Rare Genetic Variation in 135 Families With Family History Suggestive of X-Linked Intellectual Disability.

Families with multiple male children with intellectual disability (ID) are usually suspected of having disease due to a X-linked mode of inheritance and genetic studies focus on analysis of segregating variants in X-linked genes. However, the genetic cause of ID remains elusive in approximately 50% of affected individuals. Here, we report the analysis of next-generation sequencing data in 274 affected individuals from 135 families with a family history suggestive of X-linked ID. Genetic diagnoses were obtained for 19% (25/135) of the families, and 24% (33/135) had a variant of uncertain significance. In 12% of cases (16/135), the variants were not shared within the family, suggesting genetic heterogeneity and phenocopies are frequent. Of all the families with reportable variants (43%, 58/135), we observed that 55% (32/58) were in X-linked genes, but 38% (22/58) were in autosomal genes, while the remaining 7% (4/58) had multiple variants in genes with different modes on inheritance. This study highlights that in families with multiple affected males, X linkage should not be assumed, and both individuals should be considered, as different genetic etiologies are common in apparent familial cases

Information content of pre-earnings disclosures made by analysts.

Motivated by conflicting research on the complimentary and substitutive association between analysts’ information and earnings, we aim to investigate the association between these competing information sources. We found no substitutive association, even with analysts’ uncertainty during the pre-disclosure period. Investors take into account both when revising their trading decisions

Effects of spiral of silence and message civility on modes of opinion expression on Facebook

This study investigates aspects of Spiral of Silence theory and message civility in the social networking site, Facebook. Facebook was chosen as it is the most popular social networking site globally, has features which allow opinion expression in a sequential format, and requires its users to engage in opinion expression with their personal profiles, making anonymity difficult. These features make opinion expression on Facebook similar to some aspects of offline opinion expression. In addition, Facebook also allows users to indicate support for a post through the ‘like’ and ‘share’ buttons. Dubbed “click speech”, they can be considered new forms of opinion expression that represent a rising trend in social media. The effects of the Spiral of Silence — in particular, fear of isolation and opinion congruence — along with message civility were studied using a 2 x 2 between-subject experiment. A web-based survey format was used to examine the influence of these factors on participants’ likelihood to like, comment on or share the link in Facebook, as well as comment offline in subsequent conversations. 502 undergraduates between 21 - 26 years of age were recruited and randomly assigned to one of four experimental conditions. Results indicate that fear of isolation increased the likelihood of commenting on Facebook posts. Also, a civil climate increased the likelihood of liking comments on Facebook posts. Findings suggest that “click-speech” could be considered a form of opinion expression and could be compared to other forms of online opinion expression. Keywords: Facebook, Spiral of Silence, fear of isolation, opinion congruence, civilityBachelor of Communication Studie

Understanding the effect of transverse vibration on hollow fiber membranes for submerged forward osmosis processes

External concentration polarization (ECP) remains a pervasive challenge for submerged forward osmosis (FO) systems, as it critically reduces the water flux of membranes. In this study, we propose to use transverse vibration on hollow fiber membranes to effectively reduce the ECP and increase the FO water flux performance. The effects of different vibrating amplitude and frequency were investigated. Also, the vibration effect was evaluated under different draw solution concentrations, membrane orientations and draw solute types. Our results show increased water flux with increasing vibrating intensity (i.e., amplitude and frequency) while maintaining a constant specific reverse solute flux (Js/Jw). At the highest amplitude (1.2 cm) and frequency (3 Hz) used, the mass transfer coefficient is increased from 0.7 × 10−5 m s−1 (at no vibration) to 1.8 × 10−5 m s−1, which falls within the optimal flux range as determined from our FO modelling results. The increment in mass transfer coefficient is found to be closely related to the improved hydrodynamic conditions due to vibration, and less dependent on the membrane orientation and draw solution concentration. In addition, both modelling and experimental results show that maintaining a reasonably high mass transfer coefficient is especially important for FO process with severe ECP conditions, such as when dilutive ECP is present (i.e., active-layer-facing-feed-solution orientation) or when a high water flux is applied (usually in the active-layer-facing-draw-solution orientation). However, the severe ECP arising from large draw solutes (e.g., larger sized polymer with low diffusivity and high viscosity) might not gain greater benefits from the vibration or improved hydrodynamic conditions.Economic Development Board (EDB)The authors would like to acknowledge funding support from the Economic Development Board (EDB) of Singapore

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease

Polymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC4

Purpose: The evidence of a relation between folate intake and one-carbon metabolism (OCM) with pancreatic cancer (PanCa) is inconsistent. In this study, the association between genes and single-nucleotide polymorphisms (SNPs) related to OCM and PanCa was assessed. Methods: Using biochemical knowledge of the OCM pathway, we identified thirty-seven genes and 834 SNPs to examine in association with PanCa. Our study included 1,408 cases and 1,463 controls nested within twelve cohorts (PanScan). The ten SNPs and five genes with lowest p values (<0.02) were followed up in 2,323 cases and 2,340 controls from eight case-control studies (PanC4) that participated in PanScan2. The correlation of SNPs with metabolite levels was assessed for 649 controls from the European Prospective Investigation into Cancer and Nutrition. Results: When both stages were combined, we observed suggestive associations with PanCa for rs10887710 (MAT1A) (OR 1.13, 95 %CI 1.04-1.23), rs1552462 (SYT9) (OR 1.27, 95 %CI 1.02-1.59), and rs7074891 (CUBN) (OR 1.91, 95 %CI 1.12-3.26). After correcting for multiple comparisons, no significant associations were observed in either the first or second stage. The three suggested SNPs showed no correlations with one-carbon biomarkers. Conclusions: This is the largest genetic study to date to examine the relation between germline variations in OCM-related genes polymorphisms and the risk of PanCa. Suggestive evidence for an association between polymorphisms and PanCa was observed among the cohort-nested studies, but this did not replicate in the case-control studies. Our results do not strongly support the hypothesis that genes related to OCM play a role in pancreatic carcinogenesis