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

Evaluation of diffusion length and surface‐recombination velocity from a planar‐collector‐geometry electron‐beam‐induced current scan

For performing electron-beam-induced current (EBIC) measurements on sufficiently large samples, the use of a ‘‘planar-collector geometry’’ (i.e., with the collector covering part of the irradiated surface itself) is very attractive. However, the pertinent theoretical EBIC curves for finite surface-recombination velocities s have so far been lacking. This paper presents the complete theoretical expressions for arbitrary values of s and diffusion length L. Simple asymptotic solutions are given for point- and finite-size generation sources. Easy methods are developed to facilitate the application of these solutions in the practical evaluation of L and s from experimental EBIC curves. These methods are applied to experimental data available through the literature

A model for the diffusion and precipitation of antimony in highly doped δ layers in silicon

Antimony δ-doping layers were made by deposition of Sb on monocrystalline Si, followed by the deposition of amorphous Si and a final solid-phase-epitaxy treatment at 620 °C. After post-annealing at temperatures between 625 and 725 °C, Sb precipitates with a diameter of several nm are observed in the δ plane with the aid of transmission electron microscopy. Using channeling Rutherford Backscattering Spectrometry the increase of the precipitated fraction with time was determined from the minimum-yield signal. The results are interpreted using a model for the generation of Sb nuclei which grow subsequently due to lateral diffusion of Sb atoms in the δ plane, followed by incorporation into the nucleus. The generation of the nuclei appears to take place by way of two parallel processes: (i) fast, simultaneous generation of a limited number of nuclei at low-energetic sites in the δ plane, with subsequent diffusion-controlled growth, and (ii) slow, continuous generation of a larger number of nuclei at random sites in the δ plane, with subsequent incorporation-controlled growth. The Sb diffusion at the extremely high concentrations under consideration is very fast and concentration dependent, which can be explained by the model of vacancy-percolation diffusion of Mathiot and Pfister [J. Appl. Phys. 66, 970 (1989)]. The activation energy for incorporation of Sb atoms into liquid precipitates appears to be considerably lower than for incorporation into solid ones

Precipitation of antimony delta-doping layers in Si studied with channeling Rutherford backscattering spectrometry

Antimony 5-doping layers in Si have been prepared using molecular beam epitaxy. First of all, a crystalline buffer layer was deposited at 700°C, followed by Sb deposition from a Knudsen cell. After cooling down to room temperature, amorphous Si was deposited on top and subsequently crystallized using solid phase epitaxy (SPE). The thermal stability of the 8-doping layers was studied in the temperature range of 625-725°C which is only slightly above the SPE temperature. Lateral Sb redistribution was followed by measurement of the Sb minimum yield in channeling Rutherford backscattering spectrometry. An increase in minimum yield was found and was correlated with the formation of precipitates as measured with transmission electron microscopy. The high diffusion coefficients required to explain the observed precipitation are qualitatively in agreement with a diffusion model, based on percolation theory, proposed before for Sb diffusion in heavily doped Si