The effect of metformin on reducing symptom duration among outpatient adults with COVID-19 has not been studied. To assess metformin compared with placebo for symptom resolution during acute infection with SARS-CoV-2. The Accelerating COVID-19 Therapeutic Interventions and Vaccines platform evaluated repurposed medications for mild to moderate COVID-19. Between September 19, 2023, and May 1, 2024, participants 30 years or older with confirmed SARS-CoV-2 infection and 2 or more COVID-19 symptoms for 7 days or less were included at 90 US sites. Participants were randomized to receive metformin (titrated to 1500 mg, daily) or placebo for 14 days. The primary outcome was time to sustained recovery (3 consecutive days without COVID-19 symptoms) within 28 days of receiving the study drug. Secondary outcomes included time to clinic visit, emergency department (ED) visit, hospitalization, or death. Safety events of interest were hypoglycemia and lactic acidosis. Among 2991 participants who were randomized and received study drug, the median age was 47 (IQR, 38-58) years; 1895 (63.4%) were female, 25 (0.8%) were American Indian of Alaska Native, 77 (2.6%) were Asian, 350 (11.7%) were Black, African American, or African, 1392 (46.5%) identified as Hispanic or Latino, 8 (0.3%) were Native Hawaiian or other Pacific Islander, 2395 (80.1%) were White, and 2044 (68.3%) reported 2 or more doses of a SARS-CoV-2 vaccine. Among 1443 (48.2%) participants who received metformin and 1548 (51.8%) who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio, 0.96; 95% credible interval [CrI], 0.89-1.03; P for efficacy = .11). The median time to sustained recovery was 9 days (95% CI, 9-10) for metformin and 10 days (95% CI, 9-10) for placebo. No deaths were reported; 103 participants reported clinic visits, ED visits, or hospitalization: 54 in the metformin group and 49 in the placebo group (hazard ratio, 1.25; 95% CrI, 0.82-1.78; P for efficacy = .13). Overall, 35 (1.2%) reported ED visits or hospitalization (1.1% in the metformin and 1.3% in the placebo group). Seven participants who received metformin and 3 who received placebo experienced a serious adverse event over 180 days. There were 4 episodes of participant-reported hypoglycemia in the placebo group and 2 in the metformin group. In this randomized clinical trial, metformin was not shown to shorten the time to symptom resolution in low-risk adults with COVID-19. The median days to symptom resolution was numerically but not significantly lower for metformin. Safety was not a limitation in the study population. ClinicalTrials.gov Identifier: NCT04885530
The pressure response of bulk and two−dimensional (2D) MoS2 crystals (monolayer, bilayer, and many–layered), directly transferred to the diamond surface of the diamond anvil cell (DAC) used for high−pressure application, is examined by means of Raman and photoluminescence (PL) spectroscopy. For the high–pressure experiments of 2D MoS2, the Daphne 7474 oil and the 4:1 methanol–ethanol mixture are alternatively used as pressure-transmitting media (PTM), while the former is also used as PTM in the case of bulk MoS2. Characteristic differences are observed in the pressure evolution of the Raman spectral profile and the pressure coefficients of the peak frequencies between the bulk and the 2D MoS2 crystals of various thicknesses, which also depend on the PTM used. These observations, along with the pressure evolution of the PL spectrum of 2D MoS2, are ascribed to the different stress conditions in each case (hydrostatic vs. uniaxial compression perpendicular to the MoS2 layers), the adhesion of the 2D MoS2 crystals on the diamond anvil, as well as the nature of the particular PTM used and its interaction with the studied system.
Non-jetted AGN exhibit hard X-ray emission with a power law spectrum above ∼2 keV, which is thought to be produced through Comptonization of soft photons by electrons and positrons (pairs) in the vicinity of the black hole. The origin and composition of this plasma source, known as the corona, is a matter open for debate. Our study focuses on the role of relativistic protons accelerated in black-hole magnetospheric current sheets in the neutrino production of AGN coronae. We present a model that has two free parameters, namely the proton plasma magnetization σ_ p, which controls the peak energy of the neutrino spectrum, and the Eddington ratio λ_ Edd (defined as the ratio between X-ray luminosity L_ X and Eddington luminosity L_ Edd), which controls the amount of energy transferred to secondary particles. Furthermore, we combine our coronal model with an AGN population in order to provide a prediction for the diffuse neutrino flux measured on Earth. We compare our results with the observational data by IceCube and we find a satisfactory agreement on both the flux value and the slope of the neutrino distribution when we assume a σ_ p value of 10^5 for all the sources in our sample.
An ATCA processor was designed to instrument the first layer of the CMS Barrel Muon Trigger. The processor receives and processes DT and RPC data and produces muon track segments. Furthermore, it provides readout for the DT detector. The ATCA processor is based on a Xilinx XCVU13P FPGA, receives data via 10 Gbps optical links and transmits track segments via 25 Gbps optical links. The processor is instrumented with a Zynq Ultrascale+ SoM connected with an SSD which provides the necessary resources for enhanced monitoring and control information. The design of the board as well as results on its performance are presented.
ImportanceThe effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain.ObjectiveTo assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19.Design, Setting, and ParticipantsThe ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19. Between August 25, 2022, and January 20, 2023, a total of 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were 30 years or older with confirmed SARS-CoV-2 infection and at least 2 acute COVID-19 symptoms for 7 days or less.InterventionsParticipants were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days (n = 601), or placebo (n = 607).Main Outcomes and MeasuresThe primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID-19 clinical progression scale score; and difference in mean time unwell. Follow-up occurred through day 28.ResultsAmong 1208 participants who were randomized and received the study drug, the median (IQR) age was 50 (40-60) years, 65.8% were women, 45.5% identified as Hispanic/Latino, and 76.8% reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40]). Additionally, unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported. Thirty-five participants reported health care use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy = .86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo) but no deaths.Conclusions and RelevanceAmong outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms.Trial RegistrationClinicalTrials.gov Identifier: NCT04885530
