33 research outputs found

    Fact sheet: Systematic reviews and the quality of evidence

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    Systematic reviews as a means of assessing the quality of evidence in scientific studie

    On the Biological Plausibility of Artificial Metaplasticity

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    The training algorithm studied in this paper is inspired by the biological metaplasticity property of neurons. Tested on different multidisciplinary applications, it achieves a more efficient training and improves Artificial Neural Network Performance. The algorithm has been recently proposed for Artificial Neural Networks in general, although for the purpose of discussing its biological plausibility, a Multilayer Perceptron has been used. During the training phase, the artificial metaplasticity multilayer perceptron could be considered a new probabilistic version of the presynaptic rule, as during the training phase the algorithm assigns higher values for updating the weights in the less probable activations than in the ones with higher probabilit

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    Controlling picolitre droplet impact dynamics by tailoring the solid subsurface

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    The oscillatory dynamics of picolitre water droplets following impact onto a range of hydrophobic surfaces is found to be influenced by the underlayer stiffness and thickness. The relative contributions of surface functionality versus subsurface hardness have been decoupled by utilising plasmachemical surface functionalisation and underlayer crosslinking respectively. Higher oscillation frequencies are measured for softer and thicker films, which correlates to a larger surface deformation around the liquid droplet contact line
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