Efficient implementation of a component-based joint model

This paper deals with a nonlinear analysis of beam-to-column steel joint. The connection uses an end-plate welded to the steel cross-section of a steel-concrete composite beam and bolted to the column flange. The proposed model developed herein combines the knowledge of prior studies that used the component-based approach, on one hand and the Finite Element algorithmsin plasticity, on second hand. The originality of this work is to efficiently take into account possible gaps between the end-plate and the column flange in case of plastic deformation of some components of the joint during the cyclic loading. The numerical investigation aims topredict the behavior of this type of joint in presence of the gap during the cyclic loading

The efficacy of apremilast in pemphigus: a systematic review of case reports

Pemphigus is a severe autoimmune blistering disorder that significantly affects patients’ quality of life. While corticosteroids and immunosuppressive agents are commonly used, they have substantial side effects, highlighting the need for safer alternatives. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, has shown efficacy in treating other autoimmune diseases and may offer promise for pemphigus. This systematic review evaluated the clinical outcomes, safety, and potential role of apremilast in pemphigus treatment by synthesizing available case reports and series. A literature search was conducted across multiple databases (PubMed, EMBASE, Cochrane, Web of Science, ScienceDirect, and Google Scholar) for case reports and series involving apremilast in pemphigus. Inclusion criteria were a confirmed pemphigus diagnosis and apremilast treatment. Five studies (four case reports and one case series) involving seven patients were included. Apremilast led to significant clinical improvement in four patients, with reductions in disease activity, lesion severity, and symptom scores (Pemphigus Disease Area Index, Autoimmune Bullous Skin Disorder Intensity Score, Visual Analog Scale, and Numerical Rating Score). Increases in regulatory T cells and decreases in anti-desmoglein antibodies were observed. No serious adverse events were reported, although one study noted treatment failure, possibly due to short follow-up or concurrent infections. Apremilast appears to be a promising treatment for therapy-resistant or corticosteroid-intolerant pemphigus patients. Although the evidence is limited, it supports apremilast’s efficacy and favorable safety profile. Further research with larger sample sizes and randomized controlled trials is necessary to confirm these findings

Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses

Background The Solidarity trial among COVID-19 inpatients has previously reported interim mortality analyses for four repurposed antiviral drugs. Lopinavir, hydroxychloroquine, and interferon (IFN)-beta 1a were discontinued for futility but randomisation to remdesivir continued. Here, we report the final results of Solidarity and meta-analyses of mortality in all relevant trials to date.Methods Solidarity enrolled consenting adults (aged >= 18 years) recently hospitalised with, in the view of their doctor, definite COVID-19 and no contraindication to any of the study drugs, regardless of any other patient characteristics. Participants were randomly allocated, in equal proportions between the locally available options, to receive whichever of the four study drugs (lopinavir, hydroxychloroquine, IFN-beta 1a, or remdesivir) were locally available at that time or no study drug (controls). All patients also received the local standard of care. No placebos were given. The protocol specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints were progression to ventilation if not already ventilated, and time-to-discharge from hospital. Final log-rank and Kaplan Meier analyses are presented for remdesivir, and are appended for all four study drugs. Meta-analyses give weighted averages of the mortality findings in this and all other randomised trials of these drugs among hospital inpatients. Solidarity is registered with ISRCTN, ISRCTN83971151, and ClinicalTrials.gov, NCT04315948.Findings Between March 22, 2020, and Jan 29, 2021, 14 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0.6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14 221 patients, including 8275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug although remdesivir was locally available). Compliance was high in both groups. Overall, 602 (14.5%) of 4146 patients assigned to remdesivir died versus 643 (15.6%) of 4129 assigned to control (mortality rate ratio [RR] 0.91 [95% CI 0.82-1.02], p=0.12). Of those already ventilated, 151 (42.1%) of 359 assigned to remdesivir died versus 134 (38.6%) of 347 assigned to control (RR 1.13 [0.89-1.42], p=0.32). Of those not ventilated but on oxygen, 14.6% assigned to remdesivir died versus 16.3% assigned to control (RR 0.87 [0.76-0.99], p=0.03). Of 1730 not on oxygen initially, 2.9% assigned to remdesivir died versus 3.8% assigned to control (RR 0.76 [0.46-1.28], p=0.30). Combining all those not ventilated initially, 11.9% assigned to remdesivir died versus 13.5% assigned to control (RR 0.86 [0.76-0.98], p=0.02) and 14.1% versus 15.7% progressed to ventilation (RR 0.88 [0.77-1.00], p=0.04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19.6% assigned to remdesivir versus 22.5% assigned to control (RR 0.84 [0.75-0.93], p=0.001). Allocation to daily remdesivir infusions (vs open-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomised trials of remdesivir versus no remdesivir yielded similar findings.Interpretation Remdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalised patients, it has a small effect against death or progression to ventilation (or both)

Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses.

BACKGROUND World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.)

Efficient implementation of a component-based joint model

This paper deals with a nonlinear analysis of beam-to-column steel joint. The connection uses an end-plate welded to the steel cross-section of a steel-concrete composite beam and bolted to the column flange. The proposed model developed herein combines the knowledge of prior studies that used the component-based approach, on one hand and the Finite Element algorithmsin plasticity, on second hand. The originality of this work is to efficiently take into account possible gaps between the end-plate and the column flange in case of plastic deformation of some components of the joint during the cyclic loading. The numerical investigation aims topredict the behavior of this type of joint in presence of the gap during the cyclic loading

Manganese orchestrates a metabolic shift leading to the increased bioconversion of glycerol into α-ketoglutarate.

Glycerol is a major by-product of the biodiesel industry and its transformation into value-added products is an ongoing technological challenge. Here we report on the ability of the nutritionally-versatile Pseudomonas fluorescens to synthesize copious amount of α-ketoglutarate (KG) in a glycerol medium supplemented with manganese (Mn). The enhanced production of this keto-acid was mediated by the increased activities of isocitrate dehydrogenase (ICDH)-(NAD)P dependent and aminotransaminases. At stationary phase of growth when the optimal quantity of KG was recorded, these enzymes exhibited maximal activities. Two isoforms of pyruvate carboxylase (PC) that were identified in the Mn-treated cells provided an effective route for the synthesis of oxaloacetate, a metabolite critical in the production of KG. Furthermore, the increased activities of phosphoenol pyruvate carboxylase (PEPC) and pyruvate orthophosphate dikinase (PPDK) ensured the efficacy of this KG-generating metabolic system by supplying pyruvate and ATP from the oxaloacetate synthesized by PC. Mn-exposed whole cells converted 90% of industrial glycerol into KG. This Mn-evoked metabolic network can be optimized into the economic transformation of glycerol into KG

Experimental tests on bolted end-plate connections using thermal insulation layer attached to steel structures

International audienceThis paper deals with the mechanical performances of thermal break for external steel structures (balconies, passageways) attached to a steel facade with external thermal insulation. The proposed solution is composed of a PVC or plywood layers inserted between an end-plate connection and a steel column. Static and cyclic tests are performed on a cantilever beam connected to a steel column by a thermal break in order to investigate the effect of the thermal insulation layer on the rotational stiffness, bending moment resistances and failure modes. These tests highlight on one hand the influence of the thermal insulation and on another hand, the bolt configuration (extended and flush end-plate, stiffeners, RHS or I profile). © SDSS 2019 - International Colloquium on Stability and Ductility of Steel Structures