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

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

Enhancing the non-linear modelling capabilities of MLP neural networks using spread encoding

Two methods for representing data in a multi-layer perceptron (MLP) neural network are described and the resultant ability of networks, trained by the standard back-propagation algorithm, to identify the dynamics of non-linear systems is investigated. One of the data conditioning methods has been widely used in studies of the MLP network and consists of normalising each network input and output variable and applying the normalised data to single network nodes. In the second method, named spread encoding, each network variable is represented as a sliding Gaussian pattern of excitations across several network nodes. The spread encoding technique exhibits similarities with conventional algorithms used in fuzzy logic and a network utilising this method can be considered as a fuzzy-neural type network. Neural networks are configured to represent a non-linear, auto-regressive, exogenous (NARX) input-output model structure and the performance of trained networks is investigated in applications to modelling a real liquid level process unit and a simulation of a highly non-linear chemical process. Results show that using the data normalisation method, a network can provide accurate single-step predictions but is incapable of adequate long-range predictions. In contrast to this, the spread encoding technique significantly enhances the performance of a MLP network model enabling accurate single-step and long-range predictions to be achieved

Características morfológicas de cultivares de soja convencionais e Roundup ReadyTM em função da época e densidade de semeadura Morphologic characteristic of the conventional soybean genotype and Roundup ReadyTM according to the sowing season and seed densities

O trabalho tem como objetivo verificar a influência de diferentes densidades e épocas de semeadura em genótipos convencionais e Roundup ReadyTM (RR), nas características morfológicas de plantas de soja. O experimento foi conduzido em Jari, Rio Grande do Sul (RS). A primeira semeadura foi realizada dentro da época indicada para a cultura (novembro), e a segunda, após a época indicada (janeiro), com as cultivares 'CEP/CD 41', 'CD 201', 'Fundacep 39',' Fundacep 44', 'CD 205', 'BRS 133', 'Fundacep 45', 'A 6001 RG', 'Mágica', 'AL72' e 'A 8100 RG', nas densidades de 250, 400 e 550 mil sementes aptas ha-1, na safra 2005/2006. O delineamento experimental utilizado foi blocos ao acaso, com parcelas subsubdivididas e quatro repetições. Foram avaliados o ciclo das cultivares, a altura de plantas, a altura de inserção do primeiro legume, o número de ramos planta-1 e de ramos m-2, o número de nós na haste principal planta-1 e na haste principal m-2, o rendimento biológico (RB) e o índice de colheita (IC). A semeadura em janeiro ocasiona redução no ciclo da cultura, na altura de plantas, na altura de inserção do primeiro legume, no número de nós planta-1 e de RB e no atraso da semeadura. O aumento da densidade de sementes não proporcionou aumento na estatura de plantas e altura de inserção do primeiro legume, nas cultivares RR. O período do ciclo que é mais afetado com atraso da semeadura é o vegetativo. O IC foi menor na semeadura em novembro; no entanto, o RB foi maior.<br>This paper has the objective to evaluate the influence of seed densities and sowing season in conventional soybean genotype and Roundup ReadyTM (RR), in the morphological characteristic of soybean plant. The experiments were conducted in Jari-RS, Brazil. The first seeding was done within the time prescribed for the crop(November), and the second, after the time indicated (January), with the cultivars 'CEP/CD 41', 'CD 201', 'Fundacep 39', 'Fundacep 44', 'CD 205', 'BRS 133', 'Fundacep 45', 'A 6001 RG', 'Mágica, AL72' and A '8100 RG', at densities of 250, 400 and 550 thousand seed seeds suitable ha-1 in the 2005/2006 harvest. The experiment design was randomized blocks with split plots, with four replications. The cultivars cycle, plant height, height of first pod insertion, number of branches plant-1, branches m-2, nodes' number of the main stem plant-1, nodes main stem m-2, biological yield (RB) and harvest index (IC). Sowing in January causes reduction in the crop cycle, plant height, height of first pod insertion, number of nodes plant-1 and RB and the increase in seed density not increased the height of first pod insertion in RR cultivars. The period cycle that is most affected by the delayed sowing is the vegetative. The IC sowing in November was lower, but the RB was larger

Effect of a Perioperative Intra-Aortic Balloon Pump in High-Risk Cardiac Surgery Patients: A Randomized Clinical Trial

OBJECTIVES: The aim of this study was to evaluate the efficacy of perioperative intra-aortic balloon pump use in high-risk cardiac surgery patients. DESIGN: A single-center randomized controlled trial and a meta-analysis of randomized controlled trials. SETTING: Heart Institute of São Paulo University. PATIENTS: High-risk patients undergoing elective coronary artery bypass surgery. INTERVENTION: Patients were randomized to receive preskin incision intra-aortic balloon pump insertion after anesthesia induction versus no intra-aortic balloon pump use. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite endpoint of 30-day mortality and major morbidity (cardiogenic shock, stroke, acute renal failure, mediastinitis, prolonged mechanical ventilation, and a need for reoperation). A total of 181 patients (mean [SD] age 65.4 [9.4] yr; 32% female) were randomized. The primary outcome was observed in 43 patients (47.8%) in the intra-aortic balloon pump group and 42 patients (46.2%) in the control group (p = 0.46). The median duration of inotrope use (51 hr [interquartile range, 32-94 hr] vs 39 hr [interquartile range, 25-66 hr]; p = 0.007) and the ICU length of stay (5 d [interquartile range, 3-8 d] vs 4 d [interquartile range, 3-6 d]; p = 0.035) were longer in the intra-aortic balloon pump group than in the control group. A meta-analysis of 11 randomized controlled trials confirmed a lack of survival improvement in high-risk cardiac surgery patients with perioperative intra-aortic balloon pump use. CONCLUSIONS: In high-risk patients undergoing cardiac surgery, the perioperative use of an intra-aortic balloon pump did not reduce the occurrence of a composite outcome of 30-day mortality and major complications compared with usual care alone.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Nutritional requirements of energy, protein and macrominerals for maintenance and weight gain of young crossbred Nellore × Holstein bulls on pasture

The objective of this study was to estimate requirements of energy, protein and macrominerals of young Nellore/Holstein crossbreds bulls supplemented on pastures of Brachiaria decumbens Stapf. Thirty-five young bulls, at 8.53±0.18 months of age and with initial body weight of 230.6±6.1 kg were used. Ten animals were slaughtered as reference, in different weight range, and the other animals were slaughtered at the end of the experimental period. For estimate of net energy requirements for weight, a regression equation between log of retained energy (RE) and log of empty body weight gain (EBWG) was constructed. Net requirements of Ca, P, Mg, Na and K were determined by the equation Y' = a.b.Xb-1, in which a and b represent the intercept and the coefficient of equation of prediction of macrominerals in body content, respectively. Requirements of metabolizable energy for maintenance (MEm) were obtained from retained energy in function of metabolizable energy intake (MEI). The requirements of MEm of Nellore/Holstein crossbreds young bulls on pasture was 125 kcal/EBW0.75/day. The efficiency of ME utilization for maintenance (k) of grazing Nellore/Holstein crossbred young mbulls was 0.58 and 0.24 for gain. The total metabolizable protein requirements for an animal with 400 kg and with average daily gain of 1.0 kg, were 638.36 g/day. The dietetic requirements of Ca and P for an animal with 400 kg BW were 0.49 and 0.21% of DM, respectively. Daily metabolizable energy requirement for maintenance of grazing Nellore/Holstein crossbred young bulls was 11.6% greater than the values found for cattle in feedlot in Brazil (112 kcal/kg EBW0.75)