Unconditional care in academic emergency departments

Recent news stories have explicitly stated that patients with symptoms of COVID-19 were "turned away" from emergency departments. This commentary addresses these serious allegations, with an attempt to provide the perspective of academic emergency departments (EDs) around the Nation. The overarching point we wish to make is that academic EDs never deny emergency care to any person

Ectopic Lymphoid Structures Support Ongoing Production of Class-Switched Autoantibodies in Rheumatoid Synovium

Costantino Pitzalis and colleagues show that lymphoid structures in synovial tissue of patients with rheumatoid arthritis support production of anti-citrullinated peptide antibodies, which continues following transplantation into SCID mice

Measuring outcome differences associated with STEMI screening and diagnostic performance: a multicentred retrospective cohort study protocol

Introduction: Advances in ST-segment elevation myocardial infarction (STEMI) management have involved improving the clinical processes connecting patients with timely emergency cardiovascular care. Screening upon emergency department (ED) arrival for an early ECG to diagnose STEMI, however, is not optimal for all patients. In addition, the degree to which timely screening and diagnosis are associated with improved time to intervention and postpercutaneous coronary intervention outcomes, under more contemporary practice conditions, is not known. Methods: We present the methods for a retrospective multicentre cohort study anticipated to include 1220 patients across seven EDs to (1) evaluate the relationship between timely screening and diagnosis with treatment and postintervention clinical outcomes; (2) introduce novel measures for cross-facility performance comparisons of screening and diagnostic care team performance including: door-to-screening, door-to-diagnosis and door-to-catheterisation laboratory arrival times and (3) describe the use of electronic health record data in tandem with an existing disease registry. Ethics and dissemination The completion of this study will provide critical feedback on the quality of screening and diagnostic performance within the contemporary STEMI care pathway that can be used to (1) improve emergency care delivery for patients with STEMI presenting to the ED, (2) present novel metrics for the comparison of screening and diagnostic care and (3) inform the development of screening and diagnostic support tools that could be translated to other care environments. We will disseminate our results via publication and quality performance data sharing with each site. Institutional ethics review approval was received prior to study initiation

IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases

International audienceB lymphocytes have critical roles as positive and negative regulators of immunity. Their inhibitory function has been associated primarily with interleukin 10 (IL-10) because B-cell-derived IL-10 can protect against autoimmune disease and increase susceptibility to pathogens. Here we identify IL-35-producing B cells as key players in the negative regulation of immunity. Mice in which only B cells did not express IL-35 lost their ability to recover from the T-cell-mediated demyelinating autoimmune disease experimental autoimmune encephalomyelitis (EAE). In contrast, these mice displayed a markedly improved resistance to infection with the intracellular bacterial pathogen Salmonella enterica serovar Typhimurium as shown by their superior containment of the bacterial growth and their prolonged survival after primary infection, and upon secondary challenge, compared to control mice. The increased immunity found in mice lacking IL-35 production by B cells was associated with a higher activation of macrophages and inflammatory T cells, as well as an increased function of B cells as antigen-presenting cells (APCs). During Salmonella infection, IL-35- and IL-10-producing B cells corresponded to two largely distinct sets of surface-IgM(+)CD138(hi)TACI(+)CXCR4(+)CD1d(int)Tim1(int) plasma cells expressing the transcription factor Blimp1 (also known as Prdm1). During EAE, CD138(+) plasma cells were also the main source of B-cell-derived IL-35 and IL-10. Collectively, our data show the importance of IL-35-producing B cells in regulation of immunity and highlight IL-35 production by B cells as a potential therapeutic target for autoimmune and infectious diseases. This study reveals the central role of activated B cells, particularly plasma cells, and their production of cytokines in the regulation of immune responses in health and disease

In vitro nuclear interactome of the HIV-1 Tat protein

<p>Abstract</p> <p>Background</p> <p>One facet of the complexity underlying the biology of HIV-1 resides not only in its limited number of viral proteins, but in the extensive repertoire of cellular proteins they interact with and their higher-order assembly. HIV-1 encodes the regulatory protein Tat (86–101aa), which is essential for HIV-1 replication and primarily orchestrates HIV-1 provirus transcriptional regulation. Previous studies have demonstrated that Tat function is highly dependent on specific interactions with a range of cellular proteins. However they can only partially account for the intricate molecular mechanisms underlying the dynamics of proviral gene expression. To obtain a comprehensive nuclear interaction map of Tat in T-cells, we have designed a proteomic strategy based on affinity chromatography coupled with mass spectrometry.</p> <p>Results</p> <p>Our approach resulted in the identification of a total of 183 candidates as Tat nuclear partners, 90% of which have not been previously characterised. Subsequently we applied <it>in silico </it>analysis, to validate and characterise our dataset which revealed that the Tat nuclear interactome exhibits unique signature(s). First, motif composition analysis highlighted that our dataset is enriched for domains mediating protein, RNA and DNA interactions, and helicase and ATPase activities. Secondly, functional classification and network reconstruction clearly depicted Tat as a polyvalent protein adaptor and positioned Tat at the nexus of a densely interconnected interaction network involved in a range of biological processes which included gene expression regulation, RNA biogenesis, chromatin structure, chromosome organisation, DNA replication and nuclear architecture.</p> <p>Conclusion</p> <p>We have completed the <it>in vitro </it>Tat nuclear interactome and have highlighted its modular network properties and particularly those involved in the coordination of gene expression by Tat. Ultimately, the highly specialised set of molecular interactions identified will provide a framework to further advance our understanding of the mechanisms of HIV-1 proviral gene silencing and activation.</p

Advances in photonic quantum sensing

Quantum sensing has become a mature and broad field. It is generally related with the idea of using quantum resources to boost the performance of a number of practical tasks, including the radar-like detection of faint objects, the readout of information from optical memories or fragile physical systems, and the optical resolution of extremely close point-like sources. Here we first focus on the basic tools behind quantum sensing, discussing the most recent and general formulations for the problems of quantum parameter estimation and hypothesis testing. With this basic background in our hands, we then review emerging applications of quantum sensing in the photonic regime both from a theoretical and experimental point of view. Besides the state-of-the-art, we also discuss open problems and potential next steps.Comment: Review in press on Nature Photonics. This is a preliminary version to be updated after publication. Both manuscript and reference list will be expande

Access to In-Network Emergency Physicians and Emergency Departments Within Federally Qualified Health Plans in 2015

INTRODUCTION: Under regulations established by the Affordable Care Act, insurance plans must meet minimum standards in order to be sold through the federal Marketplace. These standards to become a qualified health plan (QHP) include maintaining a provider network sufficient to assure access to services. However, the complexity of emergency physician (EP) employment practices – in which the EPs frequently serve as independent contractors of emergency departments, independently establish insurance contracts, etc… – and regulations governing insurance repayment may hinder the application of network adequacy standards to emergency medicine. As such, we hypothesized the existence of QHPs without in-network access to EPs. The objective is to identify whether there are QHPs without in-network access to EPs using information available through the federal Marketplace and publicly available provider directories. RESULTS: In a national sample of Marketplace plans, we found that one in five provider networks lacks identifiable in-network EPs. QHPs lacking EPs spanned nearly half (44%) of the 34 states using the federal Marketplace. CONCLUSION: Our data suggest that the present regulatory framework governing network adequacy is not generalizable to emergency care, representing a missed opportunity to protect patient access to in-network physicians. These findings and the current regulations governing insurance payment to EPs dis-incentivize the creation of adequate physician networks, incentivize the practice of balance billing, and shift the cost burden to patients

Access to In-Network Emergency Physicians and Emergency Departments Within Federally Qualified Health Plans in 2015

Introduction: Under regulations established by the Affordable Care Act, insurance plans must meet minimum standards in order to be sold through the federal Marketplace. These standards to become a qualified health plan (QHP) include maintaining a provider network sufficient to assure access to services. However, the complexity of emergency physician (EP) employment practices – in which the EPs frequently serve as independent contractors of emergency departments, independently establish insurance contracts, etc… – and regulations governing insurance repayment may hinder the application of network adequacy standards to emergency medicine. As such, we hypothesized the existence of QHPs without in-network access to EPs. The objective is to identify whether there are QHPs without in-network access to EPs using information available through the federal Marketplace and publicly available provider directories.Results: In a national sample of Marketplace plans, we found that one in five provider networks lacks identifiable in-network EPs. QHPs lacking EPs spanned nearly half (44%) of the 34 states using the federal Marketplace.Conclusion: Our data suggest that the present regulatory framework governing network adequacy is not generalizable to emergency care, representing a missed opportunity to protect patient access to in-network physicians. These findings and the current regulations governing insurance payment to EPs dis-incentivize the creation of adequate physician networks, incentivize the practice of balance billing, and shift the cost burden to patients