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

Functional response of the mirid predators Dicyphus bolivari and Dicyphus errans and their efficacy as biological control agents of Tuta absoluta on tomato

Dicyphus bolivari Lindberg and Dicyphus errans (Wolff) (Hemiptera: Miridae) are naturally widespread in many crops with low-pesticide pressure, where they prey upon several arthropods, including the tomato pinworm Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae). However, their efficacy as biological control agents (BCAs) of this pest needs further investigations. Therefore, in this study the predatory efficacy of D. bolivari and of D. errans on T. absoluta was evaluated on tomato in laboratory and greenhouse trials. Their functional response to different numbers of T. absoluta eggs (up to 350) offered to single females or 5th-instar nymphs for 24 h was assessed in laboratory. Females and nymphs of both predators showed a high voracity and a type II functional response, with an estimated maximum predation rate per day of 189 and 194 eggs for D. bolivari females and nymphs, respectively, and 197 and 179 eggs for D. errans females and nymphs, respectively. The predators showed similar predation rates of T. absoluta eggs on plants in cage trials. However, our greenhouse trial showed that the commonly used Macrolophus pygmaeus (Rambur) (Hemiptera: Miridae), which has a lower individual predation capacity than D. bolivari and D. errans, was more effective in controlling T. absoluta than D. errans and D. bolivari because of its stronger numerical response to densities of T. absoluta and supplemental food than the other two predator species. This shows that long-term greenhouse trials, which include functional and numerical responses to pest densities, are essential to evaluate the efficacy of an omnivorous predator.</p

Brief, Pre-learning Stress Reduces False Memory Production and Enhances True Memory Selectively in Females

Some of the previous research on stress-memory interactions has suggested that stress increases the production of false memories. However, as accumulating work has shown that the effects of stress on learning and memory depend critically on the timing of the stressor, we hypothesized that brief stress administered immediately before learning would reduce, rather than increase, false memory production. In the present study, participants submerged their dominant hand in a bath of ice cold water (stress) or sat quietly (no stress) for 3 min. Then, participants completed a short-term memory task, the Deese-Roediger-McDermott paradigm, in which they were presented with 10 different lists of semantically related words (e.g., candy, sour, sugar) and, after each list, were tested for their memory of presented words (e.g., candy), non-presented unrelated distractor words (e.g., hat), and non-presented semantically related critical lure words (e.g., sweet). Stress, overall, significantly reduced the number of critical lures recalled (i.e., false memory) by participants. In addition, stress enhanced memory for the presented words (i.e., true memory) in female, but not male, participants. These findings reveal that stress does not unequivocally enhance false memory production and that the timing of the stressor is an important variable that could mediate such effects. Such results could have important implications for understanding the dependability of eyewitness accounts of events that are observed following stress

Mathematical Model of Dynamic Work Conditions in the Measuring Chamber of an Air Gauge

The goal of the proposed computational model was to evaluate the dynamical properties of air gauges in order to exploit them in such industrial applications as in-process control, form deviation measurement, dynamical measurement. The model is based on Reynolds equations complemented by the k-&epsilon; turbulence model. The boundary conditions were set in different areas (axis of the chamber, side surfaces, inlet pipeline and outlet cross-section) as Dirichlet's and Neumann's ones. The TDMA method was applied and the efficiency of the calculations was increased due to the "line-by-line" procedure. The proposed model proved to be accurate and useful for non-stationary two-dimensional flow through the air gauge measuring chamber