Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Searching for Tensor Currents in the Weak Interaction Using Lithium-8 β\beta Decay

Nuclear physics remains a powerful tool to search for unobserved phenomena by probing the limits of the Standard Model. The electroweak interaction is well-predicted by a pure vector-axial vector structure. However, high-precision measurements of the beta-neutrino correlation coefficient, a$_{\beta\nu}$ in beta decay have long been used as a test for New Physics because of the term’s sensitivity to tensor and scalar currents. The beta decay of $^8$Li is an ideal reaction for probing a$_{\beta\nu}$ due to its high Q-value and delayed alpha emission of the daughter nucleus. By measuring the kinematics of stopped $^8$Li ions in a Paul Trap surrounded with silicon strip detectors backed with plastic scintillators and comparing to simulation, we can set a limit on tensor contributions from a$_{\beta\nu}$. This work represents the analysis of a high-statistics $^8$Li dataset obtained in 2016 to extract a value of a$_{\beta\nu}$. The results indicated a value of $a_{\beta\nu}=-0.3346 \pm -0.0011_{stat} \pm 0.0024_{sys}$ at 1$\sigma$ uncertainty, which is consistent with the Standard Model and is the most stringent tensor current limit yet achieved in the low energy regime

Acute and chronic effects of the incretin enhancer vildagliptin in insulin-resistant rats.

The enzyme dipeptidyl peptidase-IV (DPP-4) inactivates the incretin hormone glucagon-like peptide-1 (GLP-1). Because GLP-1 has therapeutic effects in patients with type 2 diabetes, but its potential is limited by a short half-life, DPP-4 inhibition is a promising approach to diabetes treatment. This study examined acute (single dose) and chronic (once-a-day dosing for 21 days) effects of the DPP-4 inhibitor vildagliptin (0.03-10 mg/kg) on plasma DPP-4 activity, intact GLP-1, glucose, and insulin after an oral glucose load in insulin-resistant Zucker fatty rats and acute effects in mildly insulin-resistant high-fat-fed normal rats. A single oral dose of vildagliptin in Zucker rats produced a rapid and dose-related inhibition of DPP-4: the minimum effective dose (MED) was 0.3 mg/kg. Glucose-induced increases of intact GLP-1 were greatly but similarly enhanced by vildagliptin at doses > or =0.3 mg/kg. Postload glucose excursions decreased, and the insulinogenic index (Deltainsulin/Deltaglucose at 10 min) increased, with an MED of 0.3 mg/kg and a maximally effective dose of 3 mg/kg. The effects of vildagliptin after chronic treatment were nearly identical to those of acute administration, and vildagliptin had no effect on body weight. In fat-fed normal rats, vildagliptin (3 mg/kg) also decreased postload glucose excursions and increased the insulinogenic index, but these effects were smaller than those in Zucker rats. Thus, vildagliptin is an orally effective incretin enhancer with antihyperglycemic activity in insulin-resistant rats and exhibits no tachyphylaxis. GLP-1-mediated augmentation of glucose-induced insulin release seems to make the major contribution to the antidiabetic properties of vildagliptin

X-Ray Energy Deposition Model for Simulating Asteroid Response to a Nuclear Planetary Defense Mitigation Mission

In the event of a potentially catastrophic asteroid impact, with sufficient warning time, deploying a nuclear device remains a powerful option for planetary defense if a kinetic impactor or other means of deflection proves insufficient. Predicting the effectiveness of a potential nuclear deflection or disruption mission depends on accurate multiphysics simulations of the device's X-ray energy deposition into the asteroid and the resulting material ablation. The relevant physics in these simulations span many orders of magnitude, require a variety of different complex physics packages, and are computationally expensive. Having an efficient and accurate way of modeling this system is necessary for exploring a mission's sensitivity to the asteroid's range of physical properties. To expedite future simulations, we present a completed X-ray energy deposition model developed using the radiation-hydrodynamics code Kull that can be used to initiate a nuclear mitigation mission calculation. The model spans a wide variety of possible mission initial conditions: four different asteroid-like materials at a range of porosities, two different source spectra, and a broad range of radiation fluences, source durations, and angles of incidence. Using blowoff momentum as the primary metric, the model-initiated simulation results match the full radiation-hydrodynamics results to within 10%

Reading and Learning to Read, 8th ed.

The new edition of this popular active learning tool continues its comprehensive coverage of philosophies, teaching strategies, and assessment practices that underscore the concepts of evidence-based reading research, the essential components of reading instruction, and data-driven decision making. In this highly popular text, pre-service and in-service teachers are expertly prepared for today\u27s ever-changing literacy classroom. The book\u27s comprehensive approach to teaching reading and writing continues its emphasis on research-based practices, integrating technology, accommodating the needs of diverse and struggling learners, recognizing legislative influences, and standards for reading professionals, while updating readers with new strategies that reflect best-practice reading methodologies. Taking its dedication to struggling learners one step further, the book include features that show teachers how to better understand and use Response to Intervention RTI), what is the role of reading coaches, and how they can assist teachers as they master teaching skills that will help all children succeed.https://engagedscholarship.csuohio.edu/scholbks/1105/thumbnail.jp

Reading and Learning to Read, 8th ed.

The new edition of this popular active learning tool continues its comprehensive coverage of philosophies, teaching strategies, and assessment practices that underscore the concepts of evidence-based reading research, the essential components of reading instruction, and data-driven decision making. In this highly popular text, pre-service and in-service teachers are expertly prepared for today\u27s ever-changing literacy classroom. The book\u27s comprehensive approach to teaching reading and writing continues its emphasis on research-based practices, integrating technology, accommodating the needs of diverse and struggling learners, recognizing legislative influences, and standards for reading professionals, while updating readers with new strategies that reflect best-practice reading methodologies. Taking its dedication to struggling learners one step further, the book include features that show teachers how to better understand and use Response to Intervention RTI), what is the role of reading coaches, and how they can assist teachers as they master teaching skills that will help all children succeed.https://engagedscholarship.csuohio.edu/scholbks/1105/thumbnail.jp

Reading and Learning to Read

https://kent-islandora.s3.us-east-2.amazonaws.com/facultybooks/122/thumbnail.jpgWith a focus on helping elementary reading teachers master teaching skills that will help all children succeed, Revel Reading and Learning to Read includes philosophies, teaching strategies, and assessment practices reflecting and underscoring the concepts of evidence-based reading research and data-driven decision-making. The new 10th Edition is completely up to date; integrates the 2017 ILA Standards and Common Core State Standards (CCSS) initiative throughout the text; features the English Language Arts (ELA) standards respectively as they relate to the content in each chapter; and continues the focus on the applications of technology to literacy instruction, including new coverage of how transliteracies are transforming the way children comprehend and express their understanding of the world.</p