Namilumab or infliximab compared with standard of care in hospitalised patients with COVID-19 (CATALYST): a randomised, multicentre, multi-arm, multistage, open-label, adaptive, phase 2, proof-of-concept trial

BACKGROUND: Dysregulated inflammation is associated with poor outcomes in COVID-19. We aimed to assess the efficacy of namilumab (a granulocyte-macrophage colony stimulating factor inhibitor) and infliximab (a tumour necrosis factor inhibitor) in hospitalised patients with COVID-19, to prioritise agents for phase 3 trials. METHODS: In this randomised, multicentre, multi-arm, multistage, parallel-group, open-label, adaptive, phase 2, proof-of-concept trial (CATALYST), we recruited patients (aged ≥16 years) admitted to hospital with COVID-19 pneumonia and C-reactive protein (CRP) concentrations of 40 mg/L or greater, at nine hospitals in the UK. Participants were randomly assigned with equal probability to usual care or usual care plus a single intravenous dose of namilumab (150 mg) or infliximab (5 mg/kg). Randomisation was stratified by care location within the hospital (ward vs intensive care unit [ICU]). Patients and investigators were not masked to treatment allocation. The primary endpoint was improvement in inflammation, measured by CRP concentration over time, analysed using Bayesian multilevel models. This trial is now complete and is registered with ISRCTN, 40580903. FINDINGS: Between June 15, 2020, and Feb 18, 2021, we screened 299 patients and 146 were enrolled and randomly assigned to usual care (n=54), namilumab (n=57), or infliximab (n=35). For the primary outcome, 45 patients in the usual care group were compared with 52 in the namilumab group, and 29 in the usual care group were compared with 28 in the infliximab group. The probabilities that the interventions were superior to usual care alone in reducing CRP concentration over time were 97% for namilumab and 15% for infliximab; the point estimates for treatment–time interactions were –0·09 (95% CI –0·19 to 0·00) for namilumab and 0·06 (–0·05 to 0·17) for infliximab. 134 adverse events occurred in 30 (55%) of 55 patients in the namilumab group compared with 145 in 29 (54%) of 54 in the usual care group. 102 adverse events occurred in 20 (69%) of 29 patients in the infliximab group compared with 112 in 17 (50%) of 34 in the usual care group. Death occurred in six (11%) patients in the namilumab group compared with ten (19%) in the usual care group, and in four (14%) in the infliximab group compared with five (15%) in the usual care group. INTERPRETATION: Namilumab, but not infliximab, showed proof-of-concept evidence for reduction in inflammation—as measured by CRP concentration—in hospitalised patients with COVID-19 pneumonia. Namilumab should be prioritised for further investigation in COVID-19. FUNDING: Medical Research Council

Following the genes: a framework for animal modeling of psychiatric disorders

The number of individual cases of psychiatric disorders that can be ascribed to identified, rare, single mutations is increasing with great rapidity. Such mutations can be recapitulated in mice to generate animal models with direct etiological validity. Defining the underlying pathogenic mechanisms will require an experimental and theoretical framework to make the links from mutation to altered behavior in an animal or psychopathology in a human. Here, we discuss key elements of such a framework, including cell type-based phenotyping, developmental trajectories, linking circuit properties at micro and macro scales and definition of neurobiological phenotypes that are directly translatable to humans

The Seerah A power perspective

Available from British Library Document Supply Centre-DSC:m00/48294 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Ecological Distribution Patterns of Wild Grasses and Abiotic Factors

Documentation the relative influence of ecological dynamics on species diversity patterns can help us better understand spatial distribution patterns and devise a systematically comprehensive base for carrying out environmental explorations. The current attempt aimed at exploring the distribution patterns, diversity and richness of wild grasses with respect to climatic dynamics in the Gujrat district of Punjab, Pakistan. For this purpose, we applied the randomized sample method and sampled a total of 90 sites across the Gujrat district between 2019 and 2021 to document data on wild grasses and related ecological conditions. After assessment of the significant value index of each grass species with ecological records, we evaluated the data by ordination and cluster analysis. A total of 57 wild grasses from 37 genera were documented from the Gujrat district. The leading genera were Brachiaria, Cenchrus and Setaria, each accounting for 7.02% of all documented species, followed by Aristida and Panicum, each representing 5.76% of the species. Dactyloctenium, Dichanthium, Eragrostis, Polypogon, Poa and Saccharum each accounted for 5.26% of the species, and Digitaria, Pennisetum, Eragrostis, Chrysopogon Poa and Setaria each accounted for 3.51% of the species. Other genera each had a single species. Among all grasses, 75.44% of the species were native and 24.56% species were exotic and introduced to the study area. The leading life forms were therophytes (56.14%), followed by hemicryptophytes (42.11%) and geophytes (1.75%). Microphylls, with a 54.39% share, dominated the leaf size spectra of the wild grasses flora in this research. Other frequent classes included nanophylls (21.05%), macrophylls (19.3%) and leptophylls (5.26%). Flowering phenology of wild grasses showed that mainly species at the flowering phase were recorded during the months of June to August (40.35%) and July to September (19.29%). By applying Ward’s agglomerative clustering method, we classified the ninety transects into four major groups. Ordination analysis showed that different ecological factors had significant (p ≤ 0.002) effects on vegetation relations. The present endeavor provides a basic way to understand the impacts of ecological variables on the structure, diversity, composition and associations of wild grasses, which are helpful to improve the scientific-informed conservation and management measures for the environmental reestablishment of degraded habitat in the studied region