The Beat Generation

Program for the tenth annual RISD Cabaret held in the Waterman Building, top floor coinciding with the fiftieth anniversary of the year when Allen Ginsburg, William Burroughs and Jack Kerouac first met and started a movement which changed the face of postwar American and influenced the 1960s as well as the subculture of the \u2770s and \u2780s. Program, poster and tickets designed by Antoinette le Vaillant.https://digitalcommons.risd.edu/liberalarts_cabaret_programs/1012/thumbnail.jp

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Bi-directional Modulation of Somatosensory Mismatch Negativity with Transcranial Direct Current Stimulation: An event Related Potential Study

Appropriate orientation towards potentially salient novel environmental stimuli requires a system capable of detecting change in the sensorium. Mismatch negativity (MMN), an evoked potential calculated by subtracting the response to a standard repeated stimulus and a rare “oddball” stimulus, is proposed as such a change detection mechanism. It is most widely studied in the auditory domain, but here we chose to explore the mechanism of somatosensory MMN, and specifically its dependence on the cerebellum. We recorded event-related potentials (ERPs) evoked in response to auditory and sensory stimuli from 10 healthy subjects before and after anodal, cathodal and sham transcranial direct current stimulation (tDCS) of the right cerebellar hemisphere. There was a significant increase in peak amplitude of somatosensory MMN after anodal tDCS (F((1,9)) = 8.98, P < 0.02, mean difference anodal pre–post: −1.02 μV) and a significant reduction in peak amplitude of somatosensory MMN after cathodal tDCS (F((1,9)) = 7.15, P < 0.03, mean difference cathodal pre–post: 0.65 μV). The amplitude of auditory MMN was unchanged by tDCS. These results reveal the capability of tDCS to cause bidirectional modulation of somatosensory MMN and the dependence of somatosensory MMN on the cerebellum

A Roadmap for the Development and Validation of Event-Related Potential Biomarkers in Schizophrenia Research

New efforts to develop treatments for cognitive dysfunction in mental illnesses would benefit enormously from biomarkers that provide sensitive and reliable measures of the neural events underlying cognition. Here we evaluate the promise of event-related potentials (ERPs) as biomarkers of cognitive dysfunction in schizophrenia. We conclude that ERPs have several desirable properties: (a) they provide a direct measure of electrical activity during neurotransmission; (b) their high temporal resolutions makes it possible to measure neural synchrony and oscillations; (c) they are relatively inexpensive and convenient to record; (d) animal models are readily available for several ERP components; (e) decades of research has established the sensitivity and reliability of ERP measures in psychiatric illnesses; and (f) feasibility of large N (>500) multi-site studies has been demonstrated for key measures. Consequently, ERPs may be useful for identifying endophenotypes and defining treatment targets, for evaluating new compounds in animals and in humans, and for identifying individuals who are good candidates for early interventions or for specific treatments. However, several challenges must be overcome before ERPs gain widespread use as biomarkers in schizophrenia research, and we make several recommendations for the research that is necessary to develop and validate ERP-based biomarkers that can have a real impact on treatment development