The effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain. To assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19. The 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. Participants 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). The 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. Among 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. Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms. ClinicalTrials.gov Identifier: NCT04885530.

Magnetic reconnection is often invoked as a source of high-energy particles, and in relativistic astrophysical systems it is regarded as a prime candidate for powering fast and bright flares. We present a novel analytical model—supported and benchmarked with large-scale three-dimensional kinetic particle-in-cell simulations in electron–positron plasmas—that elucidates the physics governing the generation of power-law energy spectra in relativistic reconnection. Particles with Lorentz factor γ ≳ 3σ (here, σ is the magnetization) gain most of their energy in the inflow region, while meandering between the two sides of the reconnection layer. Their acceleration time is , where η rec ≃ 0.06 is the inflow speed in units of the speed of light and ω c = eB 0/mc is the gyrofrequency in the upstream magnetic field. They leave the region of active energization after t esc, when they get captured by one of the outflowing flux ropes of reconnected plasma. We directly measure t esc in our simulations and find that t esc ∼ t acc for σ ≳ few. This leads to a universal (i.e., σ-independent) power-law spectrum for the particles undergoing active acceleration, and for the overall particle population. Our results help to shed light on the ubiquitous presence of power-law particle and photon spectra in astrophysical nonthermal sources.

Gamma-ray flares of blazars may be accompanied by high-energy neutrinos due to interactions of high-energy cosmic rays in the jet with photons, as suggested by the detection of the high-energy neutrino IceCube-170922A during a major gamma-ray flare from blazar TXS 0506+056 at the ∼3σ significance level. In this work, we present a statistical study of gamma-ray emission from blazars to constrain the contribution of gamma-ray flares to their neutrino output. We construct weekly binned light curves for 145 gamma-ray bright blazars in the Fermi Large Area Telescope Monitored Source List adding TXS 0506+056. We derive the fraction of time spent in the flaring state (flare duty cycle) and the fraction of energy released during each flare from the light curves with a Bayesian blocks algorithm. We find that blazars with lower flare duty cycles and energy fractions are more numerous among our sample. We identify a significant difference in flare duty cycles between blazar subclasses at a significance level of 5%. Then using a general scaling relation for the neutrino and gamma-ray luminosities, with a weighting exponent of γ = 1.0–2.0, normalized to the quiescent gamma-ray or X-ray flux of each blazar, we evaluate the neutrino energy flux of each gamma-ray flare. The gamma-ray flare distribution indicates that blazar neutrino emission may be dominated by flares for γ ≳ 1.5. The neutrino energy fluxes for 1 week and 10 yr bins are compared with the decl.-dependent IceCube sensitivity to constrain the standard neutrino emission models for gamma-ray flares. Finally, we present the upper-limit contribution of blazar gamma-ray flares to the isotropic diffuse neutrino flux.

ABSTRACT For over a century, the identification of high-energy cosmic ray (CR) sources remains an open question. For Galactic CRs with energy up to 1015 eV, supernova remnants (SNRs) have traditionally been thought the main candidate source. However, recent TeV γ-ray observations have questioned the SNR paradigm. Propagating CRs are deflected by the Galactic magnetic field, hence, γ-rays and neutrinos produced via inelastic hadronic interactions are the only means for unveiling the CR sources. In this work, we study the γ-ray and neutrino emission produced by CRs accelerated inside Galactic jets of stellar-mass black holes in X-ray binaries (BHXBs). We calculate the intrinsic neutrino emission of two prototypical BHXBs , Cygnus X–1 and GX 339–4, for which we have high-quality, quasi-simultaneous multiwavelength spectra. Based on these prototypical sources, we discuss the likelihood of the 35 known Galactic BHXBs to be efficient CR accelerators. Moreover, we estimate the potential contribution to the CR spectrum of a viable population of BHXBs that reside in the Galactic plane. When these BHXBs go into outburst, they may accelerate particles up to hundreds of TeV that contribute to the diffuse γ-ray and neutrino spectra while propagating in the Galactic medium. Using HERMES, an open-source code that calculates the hadronic processes along the line of sight, we discuss the contribution of BHXBs to the diffuse γ-ray and neutrino fluxes, and compare these to their intrinsic γ-ray and neutrino emissions. Finally, we discuss the contribution of BHXBs to the observed spectrum of Galactic CRs.

Planetary magnetospheres across our solar system are known to be very efficient accelerators of charged particles. Moreover, the energization processes of magnetotail plasma populations are thought to share similarities among the various magnetospheres. In the present study, we focus on the Jovian magnetosphere, which contains a variety of ion species with different charge states, resulting in a diverse set of acceleration-relevant factors that can be tested. Therefore, we investigate the features of ion acceleration processes in the Jovian magnetosphere, utilizing measurements from the Juno mission. In particular, we use magnetic field data from the MAG instrument, and energetic ion data from the JEDI instrument, in order to investigate the energization of hydrogen (~50 keV to ~1 MeV), oxygen (~170 keV to ~2 MeV) and sulfur (~170 keV to ~4MeV) ions during dipolarization events in Jupiter’s magnetosphere. Here, we present a statistical study of the characteristics of ion acceleration processes in the Jovian magnetotail, such as the maximum energy of each ion species, as well as the Magnetic Local Time (MLT) position and radial distance for each event. Results of our study are a first step towards a comparative analysis of energization processes around dipolarization events in the magnetotails of Earth and Jupiter.

Development of effective, scalable therapeutics for SARS-CoV-2 is a priority. To test the efficacy of combined tixagevimab and cilgavimab monoclonal antibodies for early COVID-19 treatment. Two phase 2 randomized blinded placebo-controlled clinical trials within the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-2/A5401 platform were performed at US ambulatory sites. Nonhospitalized adults 18 years or older within 10 days of positive SARS-CoV-2 test and symptom onset were eligible and were enrolled from February 1 to May 31, 2021. Tixagevimab-cilgavimab, 300 mg (150 mg of each component) given intravenously (IV) or 600 mg (300 mg of each component) given intramuscularly (IM) in the lateral thigh, or pooled placebo. Coprimary outcomes were time to symptom improvement through 28 days; nasopharyngeal SARS-CoV-2 RNA below the lower limit of quantification (LLOQ) on days 3, 7, or 14; and treatment-emergent grade 3 or higher adverse events through 28 days. A total of 229 participants were randomized for the IM study and 119 were randomized for the IV study. The primary modified intention-to-treat population included 223 participants who initiated IM tixagevimab-cilgavimab (n = 106) or placebo treatment (n = 117) (median age, 39 [IQR, 30-48] years; 113 [50.7%] were men) and 114 who initiated IV tixagevimab-cilgavimab (n = 58) or placebo treatment (n = 56) (median age, 44 [IQR, 35-54] years; 67 [58.8%] were women). Enrollment in the IV study was stopped early based on a decision to focus on IM product development. Participants were enrolled at a median of 6 (IQR, 4-7) days from COVID-19 symptom onset. Significant differences in time to symptom improvement were not observed for IM tixagevimab-cilgavimab vs placebo or IV tixagevimab-cilgavimab vs placebo. A greater proportion in the IM tixagevimab-cilgavimab arm (69 of 86 [80.2%]) than placebo (62 of 96 [64.6%]) had nasopharyngeal SARS-CoV-2 RNA below LLOQ at day 7 (adjusted risk ratio, 1.33 [95% CI, 1.12-1.57]) but not days 3 and 14; the joint test across time points favored treatment (P = .003). Differences in the proportion below LLOQ were not observed for IV tixagevimab-cilgavimab vs placebo at any of the specified time points. There were no safety signals with either administration route. In these 2 phase 2 randomized clinical trials, IM or IV tixagevimab-cilgavimab was safe but did not change time to symptom improvement. Antiviral activity was more evident in the larger IM trial. ClinicalTrials.gov Identifier: NCT04518410.

ABSTRACT We present the first results for the dust-scattering rings of GRB 221009A, coined as the gamma-ray bursts (GRBs) of the century, as observed by the Neil Gehrels Swift Observatory. We perform analysis of both time resolved observations and stacked data. The former approach enable us to study the expansion of the most prominent rings, associate their origin with the prompt X-ray emission of the GRB and determine the location of the dust layers. The stacked radial profiles increase the signal-to-noise ratio of the data and allows detection of fainter and overlapping peaks in the angular profile. We find a total of 16 dust concentrations (with hints of even more) that span about 15kpc in depth and could be responsible for the highly structured X-ray angular profiles. By comparing the relative scattered fluxes of the five most prominent rings we show that the layer with the largest amount of dust is located at about 0.44 kpc away from us. We finally compare the location of the dust layers with results from experiments that study the 3D structure of our Galaxy via extinction or CO radio observations, and highlight the complementarity of dust X-ray tomography to these approaches.

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.

The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild to moderate symptomatic COVID-19 is unclear. To evaluate the efficacy of low-dose fluvoxamine (50 mg twice daily) for 10 days compared with placebo for the treatment of mild to moderate COVID-19 in the US. The ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-6) platform randomized clinical trial was designed to test repurposed medications in outpatients with mild to moderate COVID-19. A total of 1288 participants aged 30 years or older with test-confirmed SARS-CoV-2 infection and experiencing 2 or more symptoms of acute COVID-19 for 7 days or less were enrolled between August 6, 2021, and May 27, 2022, at 91 sites in the US. Participants were randomized to receive 50 mg of fluvoxamine twice daily for 10 days or placebo. The primary outcome was time to sustained recovery (defined as the third day of 3 consecutive days without symptoms). There were 7 secondary outcomes, including a composite outcome of hospitalization, urgent care visit, emergency department visit, or death through day 28. Among 1331 participants who were randomized (median age, 47 years [IQR, 38-57 years]; 57% were women; and 67% reported receiving ≥2 doses of a SARS-CoV-2 vaccine), 1288 completed the trial (674 in the fluvoxamine group and 614 in the placebo group). The median time to sustained recovery was 12 days (IQR, 11-14 days) in the fluvoxamine group and 13 days (IQR, 12-13 days) in the placebo group (hazard ratio [HR], 0.96 [95% credible interval, 0.86-1.06], posterior P = .21 for the probability of benefit [determined by an HR >1]). For the composite outcome, 26 participants (3.9%) in the fluvoxamine group were hospitalized, had an urgent care visit, had an emergency department visit, or died compared with 23 participants (3.8%) in the placebo group (HR, 1.1 [95% credible interval, 0.5-1.8], posterior P = .35 for the probability of benefit [determined by an HR <1]). One participant in the fluvoxamine group and 2 participants in the placebo group were hospitalized; no deaths occurred in either group. Adverse events were uncommon in both groups. Among outpatients with mild to moderate COVID-19, treatment with 50 mg of fluvoxamine twice daily for 10 days, compared with placebo, did not improve time to sustained recovery. These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19. ClinicalTrials.gov Identifier: NCT04885530.

Photovoltaic (PV) power production is characterized by high variability due to short-term meteorological effects such as cloud movements. These effects have a significant impact on the incident solar irradiance in PV parks. In order to control PV park performance, researchers have focused on Computer Vision and Deep Learning approaches to perform short-term irradiance forecasting using sky images. Motivated by the task of improving PV park control, the current work introduces the Image Regression Module, which produces irradiance values from sky images using image processing methods and Convolutional Neural Networks (CNNs). With the objective of enhancing the performance of CNN models on the task of irradiance estimation and forecasting, we propose an image processing method based on sun localization. Our findings show that the proposed method can consistently improve the accuracy of irradiance values produced by all the CNN models of our study, reducing the Root Mean Square Error by up to 10.44 W/m2 for the MobileNetV2 model. These findings indicate that future applications which utilize CNNs for irradiance forecasting should identify the position of the sun in the image in order to produce more accurate irradiance values. Moreover, the integration of the proposed models on an edge-oriented Field-Programmable Gate Array (FPGA) towards a smart PV park for the real-time control of PV production emphasizes their advantages.