Evaluating Arguments From the Reaction of the Audience

In studying how lay people evaluate arguments, psychologists have typically focused on logical form and content. This emphasis has masked an important yet underappreciated aspect of everyday argument evaluation: social cues to argument strength. Here we focus on the ways in which observers evaluate arguments by the reaction they evoke in an audience. This type of evaluation is likely to occur either when people are not privy to the content of the arguments or when they are not expert enough to appropriately evaluate it. Four experiments explore cues that participants might take into account in evaluating arguments from the reaction of the audience. They demonstrate that participants can use audience motivation, expertise, and size as clues to argument quality. By contrast we find no evidence that participants take audience diversity into account

Analysis of Thyroid Response Element Activity during Retinal Development

Thyroid hormone (TH) signaling components are expressed during retinal development in dynamic spatial and temporal patterns. To probe the competence of retinal cells to mount a transcriptional response to TH, reporters that included thyroid response elements (TREs) were introduced into developing retinal tissue. The TREs were placed upstream of a minimal TATA-box and two reporter genes, green fluorescent protein (GFP) and human placental alkaline phosphatase (PLAP). Six of the seven tested TREs were first tested in vitro where they were shown to drive TH-dependent expression. However, when introduced into the developing retina, the TREs reported in different cell types in both a TH-dependent and TH-independent manner, as well as revealed specific spatial patterns in their expression. The role of the known thyroid receptors (TR), TRα and TRβ, was probed using shRNAs, which were co-electroporated into the retina with the TREs. Some TREs were positively activated by TR+TH in the developing outer nuclear layer (ONL), where photoreceptors reside, as well as in the outer neuroblastic layer (ONBL) where cycling progenitor cells are located. Other TREs were actively repressed by TR+TH in cells of the ONBL. These data demonstrate that non-TRs can activate some TREs in a spatially regulated manner, whereas other TREs respond only to the known TRs, which also read out activity in a spatially regulated manner. The transcriptional response to even simple TREs provides a starting point for understanding the regulation of genes by TH, and highlights the complexity of transcriptional regulation within developing tissue

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A new stress sensor and risk factor for suicide: The T allele of the functional genetic variant in the GABRA6 gene

© 2017 The Author(s). Low GABA transmission has been reported in suicide, and GABRA6 rs3219151 T allele has been associated with greater physiological and endocrine stress response in previous studies. Although environmental stress also plays a role in suicide, the possible role of this allele has not been investigated in this respect. In our present study effect of rs3219151 of GABRA6 gene in interaction with recent negative life events on lifetime and current depression, current anxiety, as well as lifetime suicide were investigated using regression models in a white European general sample of 2283 subjects. Post hoc measures for phenotypes related to suicide risk were also tested for association with rs3219151 in interaction with environmental stress. No main effect of the GABRA6 rs3219151 was detected, but in those exposed to recent negative life events GABRA6 T allele increased current anxiety and depression as well as specific elements of suicide risk including suicidal and death-related thoughts, hopelessness, restlessness and agitation, insomnia and impulsiveness as measured by the STOP task. Our data indicate that stress-associated suicide risk is elevated in carriers of the GABRA6 rs3219151 T allele with several independent markers and predictors of suicidal behaviours converging to this increased risk

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Making General Internal Medicine Research Relevant to the Older Patient with Multiple Chronic Comorbidities

General Internal Medicine research evolves in response to the needs of the patients to whom we provide care. Currently, many studies exclude older adults who deeply affect the clinical care of this population. With the number of older adults increasing, creating research protocols that include older adults with multiple chronic comorbidities is imperative. Through funding from the Association of Specialty Physicians, a working group of aging-responsive researchers from the Society of General Internal Medicine was convened to tackle this issue. The goal of this article is threefold: 1) to shed light on the current exclusion of older adults in research; 2) to identify and propose research protocol solutions for overcoming barriers to including older adults in research; and 3) to provide suggestions for research funding. The extent to which these recommendations can create change depends greatly on our researcher colleagues. By embracing these challenges, we hope that the care provided to older adults with multiple chronic conditions will no longer be extrapolated, but become evidence-based

Effects of randomizing second eyes in a trial to evaluate preoperative medical testing for cataract surgery

The statistical and practical implications of including second eye surgeries were examined in a clinical trial designed to evaluate the impact of routine preoperative testing prior to cataract surgery on major medical events occurring within seven days following surgery. In order to detect a 0.8% difference in the rates of rare major medical events between the tested and untested groups, 20,000 surgeries must be randomized. About 30% of cataract operations were estimated to be done on second eyes of patients already included in the cohort. Different options for dealing with second eye surgeries were: (1) exclusion of all second eye surgeries, (2) inclusion of second eye surgeries only if the first eye is not enrolled, (3) inclusion of first and second eyes but randomization of patients rather than eyes, and (4) inclusion of first and second eyes but randomization of surgeries rather than patients. The final decision was to exclude second eye surgeries done within 28 days of first eye surgeries, but to rerandomize all other second eye surgeries. Differences in event rates between treatment groups can be estimated using Generalized Estimating Equations, and the association between outcomes of first and second eye operations estimated with pairwise odds ratios. An anticipated small positive correlation is likely to have minimal impact on statistical power and effective sample size