The JAK1/2 inhibitor ruxolitinib in patients with COVID-19 triggered hyperinflammation: the RuxCoFlam trial

Dysregulated hyperinflammatory response is key in the pathogenesis in patients with severe COVID-19 leading to acute respiratory distress syndrome and multiorgan failure. Whilst immunosuppression has been proven to be effective, potential biological targets and optimal timing of treatment are still conflicting. We sought to evaluate efficacy and safety of the Janus Kinase 1/2 inhibitor ruxolitinib, employing the previously developed COVID-19 Inflammation Score (CIS) in a prospective multicenter open label phase II trial (NCT04338958). Primary objective was reversal of hyperinflammation (CIS reduction of ≥25% at day 7 in ≥20% of patients). In 184 patients with a CIS of ≥10 (median 12) ruxolitinib was commenced at an initial dose of 10 mg twice daily and applied over a median of 14 days (range, 2–31). On day 7, median CIS declined to 6 (range, 1–13); 71% of patients (CI 64–77%) achieved a ≥25% CIS reduction accompanied by a reduction of markers of inflammation. Median cumulative dose was 272.5 mg/d. Treatment was well tolerated without any grade 3–5 adverse events related to ruxolitinib. Forty-four patients (23.9%) died, all without reported association to study drug. In conclusion, ruxolitinib proved to be safe and effective in a cohort of COVID-19 patients with defined hyperinflammation

Hierarchical Reinforcement Learning of Multiple Grasping Strategies with Human Instructions

Grasping is an essential component for robotic manipulation and has been investigated for decades. Prior work on grasping often assumes that a sufficient amount of training data is available for learning and planning robotic grasps. However, since constructing such an exhaustive training dataset is very challenging in practice, it is desirable that a robotic system can autonomously learn and improves its grasping strategy. In this paper, we address this problem using reinforcement learning. Although recent work has presented autonomous data collection through trial and error, such methods are often limited to a single grasp type, e.g., vertical pinch grasp. We present a hierarchical policy search approach for learning multiple grasping strategies. Our framework autonomously constructs a database of grasping motions and point clouds of objects to learn multiple grasping types autonomously. We formulate the problem of selecting the grasp location and grasp policy as a bandit problem, which can be interpreted as a variant of active learning. We applied our reinforcement learning to grasping both rigid and deformable objects. The experimental results show that our framework autonomously learns and improves its performance through trial and error and can grasp previously unseen objects with a high accuracy

Studies of Antibodies to Strains of Influenza Virus in Persons of Different Ages in Sera Collected in a Postepidemic Period

Summary Comparison of antibody content of pre- and postepidemic collections of sera pooled by ages showed an increase in the average antibody level of the population in the postepidemic period. Increase in antibody was most marked in the childhood age range when it was measured with recent A-prime isolates. This correlates with the known high incidence of influenza in childhood. Reinforcement of antibody to older strains, i.e., PR8 and swine virus, was demonstrated in adults. These results were in accordance with the concept that the initial infections of childhood orient the antibody-forming mechanism, so that experience later in life to antigenically similar strains confers progressive reinforcement of the primary antibody, which then characterizes that part of the population throughout life. The findings taken in conjunction with an analysis of antibody content of individual sera collected from consecutive age groups in a post-epidemic period demonstrated that with experience not only is the antibody mechanism oriented by the initial infections of childhood, but that, with experience, antibody reacting with successively prevalent strains is added. This results in a continuing broadening of the antibody spectrum with age which confers the immunity of the older age groups in the population. The analysis of the antibody levels of individual sera showed a few individuals in childhood and adolescence also to have antibody against major antigens of viruses which are no longer prevalent. This indicates that strains with major antigens of older viruses have had a limited circulation in recent years. The age at which antibody against older prototype strains appears and the age range at which antibody is present in greatest amount, as well as the general configuration of patterns of antibody distribution in the population, as shown in this study with pools of human sera and with groups of individual sera, are very similar results to those of the previous study (1). Three independent samples, then, demonstrated the serological recapitulation of the history of the experience with variants of influenza virus.</jats:p

Draft Genome Sequence of <i>Bordetella</i> sp. Strain FB-8, Isolated from a Former Uranium Mining Area in Germany

Here, we present the draft genome sequence of Bordetella sp. strain FB-8, a mixotrophic iron-oxidizing bacterium isolated from creek sediment in the former uranium-mining district of Ronneburg, Germany. To date, iron oxidation has not been reported in Bordetella species, indicating that FB-8 may be an environmentally important Bordetella sp. </jats:p

Additional file 3: of Efficacy of DiaLife, an education program for relatives of adult patients with diabetes – study protocol of a cluster randomized controlled trial

Questionnaire: knowledge about type 2 diabetes (DOCX 32 kb