COVID-19 Vaccine Uptake Among Residents and Staff Members of Assisted Living and Residential Care Communities-Pharmacy Partnership for Long-Term Care Program, December 2020-April 2021

OBJECTIVES: In December 2020, CDC launched the Pharmacy Partnership for Long-Term Care Program to facilitate COVID-19 vaccination of residents and staff in long-term care facilities (LTCFs), including assisted living (AL) and other residential care (RC) communities. We aimed to assess vaccine uptake in these communities and identify characteristics that might impact uptake. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: AL/RC communities in the Pharmacy Partnership for Long-Term Care Program that had ≥1 on-site vaccination clinic during December 18, 2020-April 21, 2021. METHODS: We estimated uptake using the cumulative number of doses of COVID-19 vaccine administered and normalizing by the number of AL/RC community beds. We estimated the percentage of residents vaccinated in 3 states using AL census counts. We linked community vaccine administration data with county-level social vulnerability index (SVI) measures to calculate median vaccine uptake by SVI tertile. RESULTS: In AL communities, a median of 67 residents [interquartile range (IQR): 48-90] and 32 staff members (IQR: 15-60) per 100 beds received a first dose of COVID-19 vaccine at the first on-site clinic; in RC, a median of 8 residents (IQR: 5-10) and 5 staff members (IQR: 2-12) per 10 beds received a first dose. Among 3 states with available AL resident census data, median resident first-dose uptake at the first clinic was 93% (IQR: 85-108) in Connecticut, 85% in Georgia (IQR: 70-102), and 78% (IQR: 56-91) in Tennessee. Among both residents and staff, cumulative first-dose vaccine uptake increased with increasing social vulnerability related to housing type and transportation. CONCLUSIONS AND IMPLICATIONS: COVID-19 vaccination of residents and staff in LTCFs is a public health priority. On-site clinics may help to increase vaccine uptake, particularly when transportation may be a barrier. Ensuring steady access to COVID-19 vaccine in LTCFs following the conclusion of the Pharmacy Partnership is critical to maintaining high vaccination coverage among residents and staff

Between Pixels And Play: The Role of the Photograph in Videogame Nostalgias

The histories of videogames are so often contained with nostalgia for the screen, for the arcade, console, computer or game box design, and for the experience of playing itself. Various amateur photographs now archived on Flickr allow us to remember beyond the stereotypical, albeit iconic, imagery of Pac-Man and Space Invaders. The essence of play becomes captured in the photograph as a “collective memory” and “reflective nostalgia” for the places, times and actions inherent in the histories of the early 1970s and 1980s videogame era. It is through debating the so-often implied “reconstructed nostalgias” offered by videogame companies to consumers in their remakes of classic game titles that this paper explores “reflective nostalgia” of videogames by examining the role of photographs taken during the act of playing these games. In doing so it reframes 1980s videogame nostalgias beyond the “mediated space” of the screen, and moves instead towards the “play space” as another way of keeping these histories alive

Anaesthetic Impairment of Immune Function Is Mediated via GABAA Receptors

GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A) receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients.We demonstrate, using RT-PCR, that monocytes express GABA(A) receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A) receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A) receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin.Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem

Exome-wide association study to identify rare variants influencing COVID-19 outcomes : Results from the Host Genetics Initiative

Publisher Copyright: Copyright: © 2022 Butler-Laporte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.Peer reviewe

Solid-phase arsenic speciation in aquifer sediments: A micro-X-ray absorption spectroscopy approach for quantifying trace-level speciation

Arsenic (As) is a geogenic contaminant affecting groundwater in geologically diverse systems globally. Arsenic release from aquifer sediments to groundwater is favored when biogeochemical conditions, especially oxidation-reduction (redox) potential, in aquifers fluctuate. The specific objective of this research is to identify the solid-phase sources and geochemical mechanisms of release of As in aquifers of the Des Moines Lobe glacial advance. The overarching concept is that conditions present at the aquifer-aquitard interfaces promote a suite of geochemical reactions leading to mineral alteration and release of As to groundwater. A microprobe X-ray absorption spectroscopy (μXAS) approach is developed and applied to rotosonic drill core samples to identify the solid-phase speciation of As in aquifer, aquitard, and aquifer-aquitard interface sediments. This approach addresses the low solid-phase As concentrations, as well as the fine-scale physical and chemical heterogeneity of the sediments. The spectroscopy data are analyzed using novel cosine-distance and correlation-distance hierarchical clustering for Fe 1s and As 1s μXAS datasets. The solid-phase Fe and As speciation is then interpreted using sediment and well-water chemical data to propose solid-phase As reservoirs and release mechanisms. The results confirm that in two of the three locations studied, the glacial sediment forming the aquitard is the source of As to the aquifer sediments. The results are consistent with three different As release mechanisms: (1) desorption from Fe (oxyhydr)oxides, (2) reductive dissolution of Fe (oxyhydr)oxides, and (3) oxidative dissolution of Fe sulfides. The findings confirm that glacial sediments at the interface between aquifer and aquitard are geochemically active zones for As. The diversity of As release mechanisms is consistent with the geographic heterogeneity observed in the distribution of elevated-As wells

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

Widespread genomic influences on phenotype in Dravet syndrome, a ‘monogenic’ condition

Dravet syndrome is an archetypal rare severe epilepsy, considered “monogenic”, typically caused by loss-of-function SCN1A variants. Despite a recognisable core phenotype, its marked phenotypic heterogeneity is incompletely explained by differences in the causal SCN1A variant or clinical factors. In 34 adults with SCN1A-related Dravet syndrome, we show additional genomic variation beyond SCN1A contributes to phenotype and its diversity, with an excess of rare variants in epilepsy-related genes as a set and examples of blended phenotypes, including one individual with an ultra-rare DEPDC5 variant and focal cortical dysplasia. Polygenic risk scores for intelligence are lower, and for longevity, higher, in Dravet syndrome than in epilepsy controls. The causal, major-effect, SCN1A variant may need to act against a broadly compromised genomic background to generate the full Dravet syndrome phenotype, whilst genomic resilience may help to ameliorate the risk of premature mortality in adult Dravet syndrome survivors

Use of whole genome sequencing to determine genetic basis of suspected mitochondrial disorders: cohort study

Funder: University of Cambridge; FundRef: http://dx.doi.org/10.13039/501100000735Funder: Alzheimer's Society; FundRef: http://dx.doi.org/10.13039/501100000320Funder: Leverhulme Trust; FundRef: http://dx.doi.org/10.13039/501100000275Funder: National Institute for Health Research; FundRef: http://dx.doi.org/10.13039/501100000272Funder: Department of Health; FundRef: http://dx.doi.org/10.13039/501100000276Funder: Evelyn Trust; FundRef: http://dx.doi.org/10.13039/501100004282Funder: Wellcome Trust; FundRef: http://dx.doi.org/10.13039/100004440Funder: Medical Research Council; FundRef: http://dx.doi.org/10.13039/501100000265Abstract: Objective: To determine whether whole genome sequencing can be used to define the molecular basis of suspected mitochondrial disease. Design: Cohort study. Setting: National Health Service, England, including secondary and tertiary care. Participants: 345 patients with suspected mitochondrial disorders recruited to the 100 000 Genomes Project in England between 2015 and 2018. Intervention: Short read whole genome sequencing was performed. Nuclear variants were prioritised on the basis of gene panels chosen according to phenotypes, ClinVar pathogenic/likely pathogenic variants, and the top 10 prioritised variants from Exomiser. Mitochondrial DNA variants were called using an in-house pipeline and compared with a list of pathogenic variants. Copy number variants and short tandem repeats for 13 neurological disorders were also analysed. American College of Medical Genetics guidelines were followed for classification of variants. Main outcome measure: Definite or probable genetic diagnosis. Results: A definite or probable genetic diagnosis was identified in 98/319 (31%) families, with an additional 6 (2%) possible diagnoses. Fourteen of the diagnoses (4% of the 319 families) explained only part of the clinical features. A total of 95 different genes were implicated. Of 104 families given a diagnosis, 39 (38%) had a mitochondrial diagnosis and 65 (63%) had a non-mitochondrial diagnosis. Conclusion: Whole genome sequencing is a useful diagnostic test in patients with suspected mitochondrial disorders, yielding a diagnosis in a further 31% after exclusion of common causes. Most diagnoses were non-mitochondrial disorders and included developmental disorders with intellectual disability, epileptic encephalopathies, other metabolic disorders, cardiomyopathies, and leukodystrophies. These would have been missed if a targeted approach was taken, and some have specific treatments