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

High-throughput analysis of bulk and contact conductance of polymer layers on electrodes

An approach for high-throughput analysis of bulk and contact conductance of polymer layers is described and evaluated. The approach, based on s24-technique (simultaneous two- and four-point conductance measurements), was realized as a high-throughput method and applied for investigation of conductive polymers on an array of interdigital platinum electrodes. Several examples demonstrate distinctive influence of combinatorially varied conditions of polymer synthesis (polymerization charge, content of copolymers) as well as chemical treatment of the synthesized polymers in bulk and contact resistance of metal/polymer/metal systems. The developed high-throughput s24-technique can be widely applied to material research for investigation of bulk and contact electrical properties

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Evidence of a J/ψΛJ/\psi\Lambda structure and observation of excited Ξ−\Xi^- states in the Ξb−→J/ψΛK−\Xi^-_b \to J/\psi\Lambda K^- decay

First evidence of a structure in the $J/\psi{\Lambda}$ invariant mass distribution is obtained from an amplitude analysis of $\Xi_b^-{\rightarrow}J/\psi{\Lambda}K^-$ decays. The observed structure is consistent with being due to a charmonium pentaquark with strangeness with a significance of $3.1\sigma$ including systematic uncertainties and look-elsewhere effect. Its mass and width are determined to be $4458.8\pm2.9^{+4.7}_{-1.1}$ MeV and $17.3\pm6.5^{+8.0}_{-5.7}$ MeV, respectively, where the quoted uncertainties are statistical and systematic. The structure is also consistent with being due to two resonances. In addition, the narrow excited $\Xi^-$ states, $\Xi(1690)^-$ and $\Xi(1820)^-$, are seen for the first time in a $\Xi^-_b$ decay, and their masses and widths are measured with improved precision. The analysis is performed using $pp$ collision data corresponding to a total integrated luminosity of 9 fb$^{-1}$, collected with the LHCb experiment at centre-of-mass energies of 7, 8 and 13 TeV

Branching Fraction Measurements of the Rare Bs0→ϕμ+μ−B^0_s\rightarrow\phi\mu^+\mu^- and Bs0→f2′(1525)μ+μ−B^0_s\rightarrow f_2^\prime(1525)\mu^+\mu^- Decays

The branching fraction of the rare $B^0_s\rightarrow\phi\mu^+\mu^-$ decay is measured using data collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV, corresponding to integrated luminosities of 1, 2, and 6 fb$^{-1}$, respectively. The branching fraction is reported in intervals of q$^2$, the square of the dimuon invariant mass. In the q$^2$ region between 1.1 and 6.0 GeV$^2$/c$^4$, the measurement is found to lie 3.6 standard deviations below a standard model prediction based on a combination of light cone sum rule and lattice QCD calculations. In addition, the first observation of the rare $B^0_s\rightarrow f_2^\prime(1525)\mu^+\mu^-$ decay is reported with a statistical significance of 9 standard deviations and its branching fraction is determined

Study of coherent J/ψJ/\psi production in lead-lead collisions at sNN \sqrt{{\mathrm{s}}_{\mathrm{NN}}} = 5 TeV

International audienceCoherent production of J/ψ mesons is studied in ultraperipheral lead-lead collisions at a nucleon-nucleon centre-of-mass energy of 5 TeV, using a data sample collected by the LHCb experiment corresponding to an integrated luminosity of about 10 μb$^{−1}$. The J/ψ mesons are reconstructed in the dimuon final state and are required to have transverse momentum below 1 GeV. The cross-section within the rapidity range of 2.0 < y < 4.5 is measured to be 4.45 ± 0.24 ± 0.18 ± 0.58 mb, where the first uncertainty is statistical, the second systematic and the third originates from the luminosity determination. The cross-section is also measured in J/ψ rapidity intervals. The results are compared to predictions from phenomenological models.[graphic not available: see fulltext

Searches for 25 rare and forbidden decays of D+D^{+} and Ds+ {D}_s^{+} mesons

International audienceA search is performed for rare and forbidden charm decays of the form ${D}_{(s)}^{+}\to {h}^{\pm }{\mathrm{\ell}}^{+}{\mathrm{\ell}}^{\left(\prime \right)\mp }$, where h$^{±}$ is a pion or kaon and ℓ$^{(′)±}$ is an electron or muon. The measurements are performed using proton-proton collision data, corresponding to an integrated luminosity of 1.6 fb$^{−1}$, collected by the LHCb experiment in 2016. No evidence is observed for the 25 decay modes that are investigated and 90 % confidence level limits on the branching fractions are set between 1.4 × 10$^{−8}$ and 6.4 × 10$^{−6}$. In most cases, these results represent an improvement on existing limits by one to two orders of magnitude.[graphic not available: see fulltext

Observation of New Resonances Decaying to J/ψK+J/\psi K^++ and J/ψϕJ/\psi \phi

International audienceThe first observation of exotic states with a new quark content cc¯us¯ decaying to the J/ψK+ final state is reported with high significance from an amplitude analysis of the B+→J/ψϕK+ decay. The analysis is carried out using proton-proton collision data corresponding to a total integrated luminosity of 9  fb-1 collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV. The most significant state, Zcs(4000)+, has a mass of 4003±6-14+4  MeV, a width of 131±15±26  MeV, and spin parity JP=1+, where the quoted uncertainties are statistical and systematic, respectively. A new 1+  X(4685) state decaying to the J/ψϕ final state is also observed with high significance. In addition, the four previously reported J/ψϕ states are confirmed and two more exotic states, Zcs(4220)+ and X(4630), are observed with significance exceeding 5 standard deviations