Physician documentation of access to firearms in suicidal patients in the emergency department

Introduction: Suicide is the 10th leading cause of death in the United States. An estimated 50% of these deaths are due to firearms. Suicidal ideation (SI) is a common complaint presenting to the emergency department (ED). Despite these facts, provider documentation on access to lethal means is lacking. Our primary aim was to quantify documentation of access to firearms in patients presenting to the ED with a chief complaint of SI.Methods: This was a cross-sectional study of consecutive patients, nearly all of whom presented to an academic, urban ED with SI during July 2014. We collected data from all provider documentation in the electronic health record. Primary outcome assessed was whether the emergency physician (EP) team documented access to firearms. Secondary outcomes included demographic information, preexisting psychiatric diagnoses, and disposition.Results: We reviewed 100 patient charts. The median age of patients was 38 years. The majority of patients had a psychiatric condition. EPs documented access to firearms in only 3% of patient charts.Conclusion: EPs do not adequately document access to firearms in patients with SI. There is a clear need for educational initiatives regarding risk-factor assessment and counseling against lethal means in this patient cohort

Care of bullet-related injuries: A cross-sectional study of instructions and prescriptions provided on discharge from the emergency department

INTRODUCTION: There are more than 80,000 emergency department (ED) visits for non-fatal bullet-related injuries (BRI) per year in the United States. Approximately half of these patients are discharged home from the ED. Our objective in this study was to characterize the discharge instructions, prescriptions, and follow-up plans provided to patients discharged from the ED after BRI. METHODS: This was a single-center, cross-sectional study of the first 100 consecutive patients who presented to an urban, academic, Level I trauma center ED with an acute BRI beginning on January 1, 2020. We queried the electronic health record for patient demographics, insurance status, cause of injury, hospital arrival and discharge timestamps, discharge prescriptions, and documented instructions regarding wound care, pain management, and follow-up plans. We analyzed data using descriptive statistics and chi-square tests. RESULTS: During the study period, 100 patients presented to the ED with an acute firearm injury. Patients were predominantly young (median age 29, interquartile range 23-38 years), male (86%), Black (85%), non-Hispanic (98%), and uninsured (70%). We found that 12% of patients did not receive any type of written wound care instruction, while 37% received discharge paperwork that included instructions to take both an NSAID and acetaminophen. Fifty-one percent of patients received an opioid prescription, with a range from 3-42 tablets (median 10 tablets). The proportion of patients receiving an opioid prescription was significantly higher among White patients (77%) than among Black patients (47%). CONCLUSION: There is variability in prescriptions and instructions provided to survivors of bullet injuries upon ED discharge at our institution. Our data indicates that standardized discharge protocols could improve quality of care and equity in the treatment of patients who have survived a BRI. Current variable quality in discharge planning is an entry point for structural racism and disparity

Counseling on Access to Lethal Means-Emergency Department (CALM-ED): A quality improvement program for firearm injury prevention

INTRODUCTION: Suicide is the 10 METHODS: We conducted this single-center, prospective, quality improvement study (QI) in an urban, academic ED with over 90,000 annual patient visits. The study looked at adult patients who were discharged after presenting to the ED with suicidal crisis. Assessment of access to lethal means was conducted at the bedside, followed by a counseling session regarding safe storage of lethal means and follow-up via telephone call 48-72 hours after ED discharge. We collected data on patient\u27s sociodemographics, psychiatric history, access to lethal means, lethal means storage methods, the patient\u27s specific plans for lethal means storage after discharge, and post-discharge follow-up care. RESULTS: Of 215 eligible patients, 166 voluntarily agreed to participate in CALM-ED, of whom 84 (51%) reported access to lethal means. Following the intervention, 75% of patients described a specific storage plan for their lethal means. Patients with and without access to firearms were equally likely to participate in the follow-up telephone call. CONCLUSION: An ED-based CALM QI intervention is feasible for implementation by non-physician personnel and is well received by patients and families. This intervention has the potential to help saves lives at times of suicide crisis

Requirements for Selection of Conventional and Innate T Lymphocyte Lineages

SummaryMice deficient in the Tec kinase Itk develop a large population of CD8+ T cells with properties, including expression of memory markers, rapid production of cytokines, and dependence on Interleukin-15, resembling NKT and other innate T cell lineages. Like NKT cells, these CD8+ T cells can be selected on hematopoietic cells. We demonstrate that these CD8+ T cell phenotypes resulted from selection on hematopoietic cells—forcing selection on the thymic stroma reduced the number and innate phenotypes of mature Itk-deficient CD8+ T cells. We further show that, similar to NKT cells, selection of innate-type CD8+ T cells in Itk−/− mice required the adaptor SAP. Acquisition of their innate characteristics, however, required CD28. Our results suggest that SAP and Itk reciprocally regulate selection of innate and conventional CD8+ T cells on hematopoietic cells and thymic epithelium, respectively, whereas CD28 regulates development of innate phenotypes resulting from selection on hematopoietic cells

Production and characterization of murine models of classic and intermediate maple syrup urine disease

BACKGROUND: Maple Syrup Urine Disease (MSUD) is an inborn error of metabolism caused by a deficiency of branched-chain keto acid dehydrogenase. MSUD has several clinical phenotypes depending on the degree of enzyme deficiency. Current treatments are not satisfactory and require new approaches to combat this disease. A major hurdle in developing new treatments has been the lack of a suitable animal model. METHODS: To create a murine model of classic MSUD, we used gene targeting and embryonic stem cell technologies to create a mouse line that lacked a functional E2 subunit gene of branched-chain keto acid dehydrogenase. To create a murine model of intermediate MSUD, we used transgenic technology to express a human E2 cDNA on the knockout background. Mice of both models were characterized at the molecular, biochemical, and whole animal levels. RESULTS: By disrupting the E2 subunit gene of branched-chain keto acid dehydrogenase, we created a gene knockout mouse model of classic MSUD. The homozygous knockout mice lacked branched-chain keto acid dehydrogenase activity, E2 immunoreactivity, and had a 3-fold increase in circulating branched-chain amino acids. These metabolic derangements resulted in neonatal lethality. Transgenic expression of a human E2 cDNA in the liver of the E2 knockout animals produced a model of intermediate MSUD. Branched-chain keto acid dehydrogenase activity was 5–6% of normal and was sufficient to allow survival, but was insufficient to normalize circulating branched-chain amino acids levels, which were intermediate between wildtype and the classic MSUD mouse model. CONCLUSION: These mice represent important animal models that closely approximate the phenotype of humans with the classic and intermediate forms of MSUD. These animals provide useful models to further characterize the pathogenesis of MSUD, as well as models to test novel therapeutic strategies, such as gene and cellular therapies, to treat this devastating metabolic disease

CD4 T Cell Immunity Is Critical for the Control of Simian Varicella Virus Infection in a Nonhuman Primate Model of VZV Infection

Primary infection with varicella zoster virus (VZV) results in varicella (more commonly known as chickenpox) after which VZV establishes latency in sensory ganglia. VZV can reactivate to cause herpes zoster (shingles), a debilitating disease that affects one million individuals in the US alone annually. Current vaccines against varicella (Varivax) and herpes zoster (Zostavax) are not 100% efficacious. Specifically, studies have shown that 1 dose of varivax can lead to breakthrough varicella, albeit rarely, in children and a 2-dose regimen is now recommended. Similarly, although Zostavax results in a 50% reduction in HZ cases, a significant number of recipients remain at risk. To design more efficacious vaccines, we need a better understanding of the immune response to VZV. Clinical observations suggest that T cell immunity plays a more critical role in the protection against VZV primary infection and reactivation. However, no studies to date have directly tested this hypothesis due to the scarcity of animal models that recapitulate the immune response to VZV. We have recently shown that SVV infection of rhesus macaques models the hallmarks of primary VZV infection in children. In this study, we used this model to experimentally determine the role of CD4, CD8 and B cell responses in the resolution of primary SVV infection in unvaccinated animals. Data presented in this manuscript show that while CD20 depletion leads to a significant delay and decrease in the antibody response to SVV, loss of B cells does not alter the severity of varicella or the kinetics/magnitude of the T cell response. Loss of CD8 T cells resulted in slightly higher viral loads and prolonged viremia. In contrast, CD4 depletion led to higher viral loads, prolonged viremia and disseminated varicella. CD4 depleted animals also had delayed and reduced antibody and CD8 T cell responses. These results are similar to clinical observations that children with agammaglobulinemia have uncomplicated varicella whereas children with T cell deficiencies are at increased risk of progressive varicella with significant complications. Moreover, our studies indicate that CD4 T cell responses to SVV play a more critical role than antibody or CD8 T cell responses in the control of primary SVV infection and suggest that one potential mechanism for enhancing the efficacy of VZV vaccines is by eliciting robust CD4 T cell responses

Class II Transactivator (CIITA) Enhances Cytoplasmic Processing of HIV-1 Pr55Gag

The Pr55(gag) (Gag) polyprotein of HIV serves as a scaffold for virion assembly and is thus essential for progeny virion budding and maturation. Gag localizes to the plasma membrane (PM) and membranes of late endosomes, allowing for release of infectious virus directly from the cell membrane and/or upon exocytosis. The host factors involved in Gag trafficking to these sites are largely unknown. Upon activation, CD4+ T cells, the primary target of HIV infection, express the class II transcriptional activator (CIITA) and therefore the MHC class II isotype, HLA-DR. Similar to Gag, HLA-DR localizes to the PM and at the membranes of endosomes and specialized vesicular MHC class II compartments (MIICs). In HIV producer cells, transient HLA-DR expression induces intracellular Gag accumulation and impairs virus release.Here we demonstrate that both stable and transient expression of CIITA in HIV producer cells does not induce HLA-DR-associated intracellular retention of Gag, but does increase the infectivity of virions. However, neither of these phenomena is due to recapitulation of the class II antigen presentation pathway or CIITA-mediated transcriptional activation of virus genes. Interestingly, we demonstrate that CIITA, apart from its transcriptional effects, acts cytoplasmically to enhance Pr160(gag-pol) (Gag-Pol) levels and thereby the viral protease and Gag processing, accounting for the increased infectivity of virions from CIITA-expressing cells.This study demonstrates that CIITA enhances HIV Gag processing, and provides the first evidence of a novel, post-transcriptional, cytoplasmic function for a well-known transactivator

Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks

The United States COVID-19 Forecast Hub dataset

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure