Trauma Informed Community Building Evaluation: A Formative Evaluation of the TICB Model and its Implementation in Potrero Hill

This formative evaluation of the TICB model and its implementation in the PTA public housing community was conducted between September 2014 and July 2015 by an evaluation team from the HOPE SF Learning Center. This evaluation was designed to support the further development of the TICB model as well as inform efforts to implement the model in Potrero Terrace and Annex and other communities. This evaluation seeks to examine the implementation and impact of the TICB model at PTA in order to: * Understand the impact of ongoing TICB-informed programming through analysis of outputs and outcomes prioritized by stakeholder partners [see Appendix A]. * Identify facilitators and barriers to implementation of the TICB model in community-building work within PTA and the surrounding Potrero Hill neighborhood. * Inform BRIDGE Housing's work to improve programming, and guide future program priorities and structures. * Generate information to better understand the impact of the financial investment in helping to build community with and between public housing residents and residents of the surrounding neighborhood. * Assess implications for replicability/reproducibility at other public housing communities, including the additional HOPE SF sites, and beyond

Indigenous Evaluation 101 Guidebook

This Guide was developed by Bowman Performance Consulting and Wilder Research as part of our work with the Minnesota Department of Education to conduct an Indigenous Evaluation for Minnesota's Preschool Development Grant. It was developed to help the State of Minnesota, Indigenous organizations, and others to recognize the steps and considerations necessary to design and implement an evaluation that considers Indigenous ways of knowing. It contains concrete tips and tools, and includes links to other resources

The Dust Trail of Comet 67P/Churyumov-Gerasimenko between 2004 and 2006

We report on observations of the dust trail of comet 67P/Churyumov-Gerasimenko (CG) in visible light with the Wide Field Imager at the ESO/MPG 2.2m telescope at 4.7 AU before aphelion, and at 24 micron with the MIPS instrument on board the Spitzer Space Telescope at 5.7 AU both before and after aphelion. The comet did not appear to be active during our observations. Our images probe large dust grains emitted from the comet that have a radiation pressure parameter beta<0.01. We compare our observations with simulated images generated with a dynamical model of the cometary dust and constrain the emission speeds, size distribution, production rate and geometric albedo of the dust. We achieve the best fit to our data with a differential size distribution exponent of -4.1, and emission speeds for a beta=0.01 particle of 25 m/s at perihelion and 2 m/s at 3 AU. The dust production rate in our model is on the order of 1000 kg/s at perihelion and 1 kg/s at 3 AU, and we require a dust geometric albedo between 0.022 and 0.044. The production rates of large (>10 micron) particles required to reproduce the brightness of the trail are sufficient to also account for the coma brightness observed while the comet was inside 3 AU, and we infer that the cross-section in the coma of CG may be dominated by grains of the order of 60-600 micron.Comment: 79 pages, 13 figures, 6 tables. Accepted for publication in Icaru

B cell and/or autoantibody deficiency do not prevent neuropsychiatric disease in murine systemic lupus erythematosus

Background: Neuropsychiatric lupus (NPSLE) can be one of the earliest clinical manifestations in human lupus. However, its mechanisms are not fully understood. In lupus, a compromised blood-brain barrier may allow for the passage of circulating autoantibodies into the brain, where they can induce neuropsychiatric abnormalities including depression-like behavior and cognitive abnormalities. The purpose of this study was to determine the role of B cells and/or autoantibodies in the pathogenesis of murine NPSLE. Methods: We evaluated neuropsychiatric manifestations, brain pathology, and cytokine expression in constitutively (JhD/MRL/lpr) and conditionally (hCD20-DTA/MRL/lpr, inducible by tamoxifen) B cell-depleted mice as compared to MRL/lpr lupus mice. Results: We found that autoantibody levels were negligible (JhD/MRL/lpr) or significantly reduced (hCD20-DTA/MRL/lpr) in the serum and cerebrospinal fluid, respectively. Nevertheless, both JhD/MRL/lpr and hCD20-DTA/MRL/lpr mice showed profound depression-like behavior, which was no different from MRL/lpr mice. Cognitive deficits were also observed in both JhD/MRL/lpr and hCD20-DTA/MRL/lpr mice, similar to those exhibited by MRL/lpr mice. Furthermore, although some differences were dependent on the timing of depletion, central features of NPSLE in the MRL/lpr strain including increased blood-brain barrier permeability, brain cell apoptosis, and upregulated cytokine expression persisted in B cell-deficient and B cell-depleted mice. Conclusions: Our study surprisingly found that B cells and/or autoantibodies are not required for key features of neuropsychiatric disease in murine NPSLE

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

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era