Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Safety assessment and behavioral effects of Solanum guaraniticum leaf extract in rats

ABSTRACT Solanum guaraniticum is a medicinal plant traditionally used to treat gastric and liver diseases. However, there is no documented evidence corroborating its safety. The present study evaluated the potential toxicity of S. guaraniticum leaf extract after acute administration in rats. Single doses of the extract (1.250, 2.500, and 5.000 mg/kg) were administered by gavage, and the rats were then monitored for 48 h and/or 14 days. Mortality, acute signs of toxicity, and general activity in the open field test were assessed as well as hematological and biochemical parameters, enzymatic activity (δ-aminolevulinate dehydratase and acetylcholinesterase), and oxidative stress parameters (lipid peroxidation level, non-protein thiol content, tissue catalase activity, and serum ferrous reducing power). Phytochemical analysis was also performed by HPLC. The results showed that extract administration produced no deaths (LD50 > 5,000 mg/kg), and no significant adverse effects regarding food consumption, body weight gain, gross pathology, or other parameters. However, the open field tests showed a decrease in spontaneous activity (crossing and rearing) mainly at 48 h after treatment. The results suggest that S. guaraniticum extract is not acutely toxic, but causes alterations in central nervous system activity

經濟學全集「統計學」を讀む

39 pages, 11 captioned figures, 8 tables (5 of them in Appendix A), authors from page 33, submitted to JHEP, figures at http://aliceinfo.cern.ch/ArtSubmission/node/2359 ; see paper for full list of authorsInternational audienceThe measurement of prompt D-meson production as a function of multiplicity in p-Pb collisions at $\sqrt{s_{\rm NN}}=5.02$ TeV with the ALICE detector at the LHC is reported. D$^0$, D$^+$ and D$^{*+}$ mesons are reconstructed via their hadronic decay channels in the centre-of-mass rapidity range $-0.96< y_{\mathrm{cms}}<0.04$ and transverse momentum interval $1<p_{\rm T}<24$ GeV/$c$. The multiplicity dependence of D-meson production is examined by either comparing yields in p-Pb collisions in different event classes, selected based on the multiplicity of produced particles or zero-degree energy, with those in pp collisions, scaled by the number of binary nucleon-nucleon collisions (nuclear modification factor); as well as by evaluating the per-event yields in p-Pb collisions in different multiplicity intervals normalised to the multiplicity-integrated ones (relative yields). The nuclear modification factors for D$^0$, D$^+$ and D$^{*+}$ are consistent with one another. The D-meson nuclear modification factors as a function of the zero-degree energy are consistent with unity within uncertainties in the measured $p_{\rm T}$ regions and event classes. The relative D-meson yields, calculated in various $p_{\rm T}$ intervals, increase as a function of the charged-particle multiplicity. The results are compared with the equivalent pp measurements at $\sqrt{s}=7$ TeV as well as with EPOS~3 calculations

International Nosocomial Infection Control Consortium report, data summary of 50 countries for 2010-2015: Device-associated module

•We report INICC device-associated module data of 50 countries from 2010-2015.•We collected prospective data from 861,284 patients in 703 ICUs for 3,506,562 days.•DA-HAI rates and bacterial resistance were higher in the INICC ICUs than in CDC-NHSN's.•Device utilization ratio in the INICC ICUs was similar to CDC-NHSN's. Background: We report the results of International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2010-December 2015 in 703 intensive care units (ICUs) in Latin America, Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific. Methods: During the 6-year study period, using Centers for Disease Control and Prevention National Healthcare Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DA-HAI), we collected prospective data from 861,284 patients hospitalized in INICC hospital ICUs for an aggregate of 3,506,562 days. Results: Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAI rates were higher in the INICC ICUs: in the INICC medical-surgical ICUs, the pooled rate of central line-associated bloodstream infection, 4.1 per 1,000 central line-days, was nearly 5-fold higher than the 0.8 per 1,000 central line-days reported from comparable US ICUs, the overall rate of ventilator-associated pneumonia was also higher, 13.1 versus 0.9 per 1,000 ventilator-days, as was the rate of catheter-associated urinary tract infection, 5.07 versus 1.7 per 1,000 catheter-days. From blood cultures samples, frequencies of resistance of Pseudomonas isolates to amikacin (29.87% vs 10%) and to imipenem (44.3% vs 26.1%), and of Klebsiella pneumoniae isolates to ceftazidime (73.2% vs 28.8%) and to imipenem (43.27% vs 12.8%) were also higher in the INICC ICUs compared with CDC-NHSN ICUs. Conclusions: Although DA-HAIs in INICC ICU patients continue to be higher than the rates reported in CDC-NSHN ICUs representing the developed world, we have observed a significant trend toward the reduction of DA-HAI rates in INICC ICUs as shown in each international report. It is INICC's main goal to continue facilitating education, training, and basic and cost-effective tools and resources, such as standardized forms and an online platform, to tackle this problem effectively and systematically

Measurement of an excess in the yield of J/psi at very low p(T) in Pb-Pb collisions at root s(NN)=2.76 TeV

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Body mass index and complications following major gastrointestinal surgery: A prospective, international cohort study and meta-analysis

Aim Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a metaanalysis of all available prospective data. Methods This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien–Dindo Grades III–V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. Results This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery formalignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49–2.96, P < 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46–0.75, P < 0.001) compared to normal weight patients. Conclusions In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease