University of São Paulo

About: University of São Paulo is a education organization based out in São Paulo, Brazil. It is known for research contribution in the topics: Population & Context (language use). The organization has 136513 authors who have published 272320 publications receiving 5127869 citations. The organization is also known as: USP & Universidade de São Paulo.

Genetic mechanisms of critical illness in Covid-19.

Abstract: Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10−8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10−8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10−12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10−8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte–macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice. A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Regional Climate Modeling for the Developing World: The ICTP RegCM3 and RegCNET

Abstract: Regional climate models are important research tools available to scientists around the world, including in economically developing nations (EDNs). The Earth Systems Physics (ESP) group of the Abdus Salam International Centre for Theoretical Physics (ICTP) maintains and distributes a state-of-the-science regional climate model called the ICTP Regional Climate Model version 3 (RegCM3), which is currently being used by a large research community for a diverse range of climate-related studies. The RegCM3 is the central, but not only, tool of the ICTP-maintained Regional Climate Research Network (RegCNET) aimed at creating south–south and north–south scientific interactions on the topic of climate and associated impacts research and modeling. In this paper, RegCNET, RegCM3, and illustrative results from RegCM3 benchmark simulations applied over south Asia, Africa, and South America are presented. It is shown that RegCM3 performs reasonably well over these regions and is therefore useful for climate studies in...

IAHS Decade on Predictions in Ungauged Basins (PUB), 2003–2012: Shaping an exciting future for the hydrological sciences

Abstract: Drainage basins in many parts of the world are ungauged or poorly gauged, and in some cases existing measurement networks are declining. The problem is compounded by the impacts of human-induced changes to the land surface and climate, occur-ring at the local, regional and global scales. Predictions of ungauged or poorly gauged basins under these conditions are highly uncertain. The IAHS Decade on Predictions in Ungauged Basins, or PUB, is a new initiative launched by the International Association of Hydrological Sciences (IAHS), aimed at formulating and implementing appropriate science programmes to engage and energize the scientific community, in a coordinated manner, towards achieving major advances in the capacity to make predictions in ungauged basins. The PUB scientific programme focuses on the estimation of predictive uncertainty, and its subsequent reduction, as its central theme. A general hydrological prediction system contains three components: (a) a model that describes the key processes of interest, (b) a set of parameters that represent those landscape properties that govern critical processes, and (c) appropriate meteorological inputs (where needed) that drive the basin response. Each of these three components of the prediction system, is either not known at all, or at best known imperfectly, due to the inherent multi-scale space-time heterogeneity of the hydrological system, especially in ungauged basins. PUB will therefore include a set of targeted scientific programmes that attempt to make inferences about climatic inputs, parameters and model structures from available but inadequate data and process knowledge, at the basin of interest and/or from other similar basins, with robust measures of the uncertainties involved, and their impacts on predictive uncertainty. Through generation of improved understanding, and methods for the efficient quantification of the underlying multi-scale heterogeneity of the basin and its response, PUB will inexorably lead to new, innovative methods for hydrological predictions in ungauged basins in different parts of the world, combined with significant reductions of predictive uncertainty. In this way, PUB will demonstrate the value of data, as well as provide the information needed to make predictions in ungauged basins, and assist in capacity building in the use of new technologies. This paper presents a summary of the science and implementation plan of PUB, with a call to the hydrological community to participate actively in the realization of these goals.

Reference values for lung function tests. II. Maximal respiratory pressures and voluntary ventilation

Abstract: The strength of the respiratory muscles can be evaluated from static measurements (maximal inspiratory and expiratory pressures, MIP and MEP) or inferred from dynamic maneuvers (maximal voluntary ventilation, MVV). Although these data could be suitable for a number of clinical and research applications, no previous studies have provided reference values for such tests using a healthy, randomly selected sample of the adult Brazilian population. With this main purpose, we prospectively evaluated 100 non-smoking subjects (50 males and 50 females), 20 to 80 years old, selected from more than 8,000 individuals. Gender-specific linear prediction equations for MIP, MEP and MVV were developed by multiple regression analysis: age and, secondarily, anthropometric measurements explained up to 56% of the variability of the dependent variables. The most cited previous studies using either Caucasian or non-Caucasian samples systematically underestimated the observed values of MIP (P < 0.05). Interestingly, the self-reported level of regular physical activity and maximum aerobic power correlates strongly with both respiratory and peripheral muscular strength (knee extensor peak torque) (P < 0.01). Our results, therefore, provide a new frame of reference to evaluate the normalcy of some useful indexes of respiratory muscle strength in Brazilian males and females aged 20 to 80.

A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis.

Abstract: Motor neuron diseases (MNDs) are a group of neurodegenerative disorders with involvement of upper and/or lower motor neurons, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), progressive bulbar palsy, and primary lateral sclerosis. Recently, we have mapped a new locus for an atypical form of ALS/MND (atypical amyotrophic lateral sclerosis [ALS8]) at 20q13.3 in a large white Brazilian family. Here, we report the finding of a novel missense mutation in the vesicle-associated membrane protein/synaptobrevin-associated membrane protein B (VAPB) gene in patients from this family. Subsequently, the same mutation was identified in patients from six additional kindreds but with different clinical courses, such as ALS8, late-onset SMA, and typical severe ALS with rapid progression. Although it was not possible to link all these families, haplotype analysis suggests a founder effect. Members of the vesicle-associated proteins are intracellular membrane proteins that can associate with microtubules and that have been shown to have a function in membrane transport. These data suggest that clinically variable MNDs may be caused by a dysfunction in intracellular membrane trafficking.