Rapid HIV testing program implementation: lessons from the emergency department

Background: The US Centers for Disease Control and Prevention (CDC) guidelines and the World Health Organization (WHO) both recommend HIV testing in health-care settings. However, neither organization provides prescriptive details regarding how these recommendations should be adapted into clinical practice in an emergency department. Methods: We have implemented an HIV-testing program in the ED of a major academic medical center within the scope of the Universal Screening for HIV Infection in the Emergency Room (USHER) Trial—a randomized clinical trial evaluating the feasibility and cost-effectiveness of HIV screening in this setting. Results and conclusion: Drawing on our collective experiences in establishing programs domestically and internationally, we offer a practical framework of lessons learned so that others poised to embark on such HIV testing programs may benefit from our experiences

Localization and function of the renal calcium-sensing receptor

The ability to monitor changes in the ionic composition of the extracellular environment is a crucial feature that has evolved in all living organisms. The cloning and characterization of the extracellular calcium-sensing receptor (CaSR) from the mammalian parathyroid gland in the early 1990s provided the first description of a cellular, ion-sensing mechanism. This finding demonstrated how cells can detect small, physiological variations in free ionized calcium (Ca 2+) in the extracellular fluid and subsequently evoke an appropriate biological response by altering the secretion of parathyroid hormone (PTH) that acts on PTH receptors expressed in target tissues, including the kidney, intestine, and bone. Aberrant Ca 2+ sensing by the parathyroid glands, as a result of altered CaSR expression or function, is associated with impaired divalent cation homeostasis. CaSR activators that mimic the effects of Ca 2+ (calcimimetics) have been designed to treat hyperparathyroidism, and CaSR antagonists (calcilytics) are in development for the treatment of hypercalciuric disorders. The kidney expresses a CaSR that might directly contribute to the regulation of many aspects of renal function in a PTH-independent manner. This Review discusses the roles of the renal CaSR and the potential impact of pharmacological modulation of the CaSR on renal function

White-gutted soldiers: simplification of the digestive tube for a non-particulate diet in higher Old World termites (Isoptera: Termitidae)

Previous observations have noted that in some species of higher termites the soldier caste lacks pigmented particles in its gut and, instead, is fed worker saliva that imparts a whitish coloration to the abdomen. In order to investigate the occurrence of this trait more thoroughly, we surveyed a broad diversity of termite specimens and taxonomic descriptions from the Old World subfamilies Apicotermitinae, Cubitermitinae, Foraminitermitinae, Macrotermitinae, and Termitinae. We identified 38 genera that have this “white-gutted” soldier (WGS) trait. No termite soldiers from the New World were found to possess a WGS caste. Externally, the WGS is characterized by a uniformly pale abdomen, hyaline gut, and proportionally smaller body-to-head volume ratio compared with their “dark-gutted” soldier (DGS) counterparts found in most termitid genera. The WGS is a fully formed soldier that, unlike soldiers in other higher termite taxa, has a small, narrow, and decompartmentalized digestive tube that lacks particulate food contents. The presumed saliva-nourished WGS have various forms of simplified gut morphologies that have evolved at least six times within the higher termites

ICAR: endoscopic skull‐base surgery

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The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 1: The LBNF and DUNE Projects

This document presents the Conceptual Design Report (CDR) put forward by an international neutrino community to pursue the Deep Underground Neutrino Experiment at the Long-Baseline Neutrino Facility (LBNF/DUNE), a groundbreaking science experiment for long-baseline neutrino oscillation studies and for neutrino astrophysics and nucleon decay searches. The DUNE far detector will be a very large modular liquid argon time-projection chamber (LArTPC) located deep underground, coupled to the LBNF multi-megawatt wide-band neutrino beam. DUNE will also have a high-resolution and high-precision near detector

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report, Volume 4 The DUNE Detectors at LBNF

A description of the proposed detector(s) for DUNE at LBN

Sleep duration, cardiovascular disease, and proinflammatory biomarkers

Michael A Grandner,1,2 Megan R Sands-Lincoln,3 Victoria M Pak,2,4 Sheila N Garland1,5 1Behavioral Sleep Medicine Program, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, PA, USA; 2Center for Sleep and Circadian Neurobiology, University of Pennsylvania, PA, USA; 3Center for Evidence Based Medicine, Elsevier Inc, Philadelphia, PA, USA; 4Division of Sleep Medicine, Perelman School of Medicine, University of Pennsylvania, PA, USA; 5Department of Family Medicine and Community Health, Perelman School of Medicine, University of Pennsylvania, PA, USA Abstract: Habitual sleep duration has been associated with cardiometabolic disease, via several mechanistic pathways, but few have been thoroughly explored. One hypothesis is that short and/or long sleep duration is associated with a proinflammatory state, which could increase risk for cardiovascular and metabolic diseases. This hypothesis has been largely explored in the context of experimental sleep deprivation studies which have attempted to demonstrate changes in proinflammatory markers following acute sleep loss in the laboratory. Despite the controlled environment available in these studies, samples tend to lack generalization to the population at large and acute sleep deprivation may not be a perfect analog for short sleep. To address these limitations, population based studies have explored associations between proinflammatory markers and habitual sleep duration. This review summarizes what is known from experimental and cross-sectional studies about the association between sleep duration, cardiovascular disease, and proinflammatory biomarkers. First, the association between sleep duration with both morbidity and mortality, with a focus on cardiovascular disease, is reviewed. Then, a brief review of the potential role of proinflammatory markers in cardiovascular disease is presented. The majority of this review details specific findings related to specific molecules, including tumor necrosis factor-α, interleukins-1, -6, and -17, C-reactive protein, coagulation molecules, cellular adhesion molecules, and visfatin. Finally, a discussion of the limitations of current studies and future directions is provided. Keywords: sleep duration, inflammation, cardiovascular disease, cytokine