The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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The biogeochemical significance of gaseous hydrocarbons sorbed to marine sediment

O.: The TriQL.P Browser: Filtering Information using Context-, Content- and Rating-Based Trust Policies

Abstract. The TriQL.P browser is a general purpose RDF browser that supports users in exploring RDF datasets containing information from multiple information sources. Information can be filtered using a wide range of user-definable trust policies. Policies can be based on information context, information content, information or information source ratings, and on the presence or absence of digital signatures. In order to help users understand the filtering decisions, the browser can explain why a piece of information fulfils the selected trust policy. 1 Trust Policies for the Semantic Web The Semantic Web is an open, dynamic network of independent information providers all having different views of the world, different levels of knowledge, and different intentions. Thus, information found on the Semantic Web has to be seen as claims rather than as facts. Before using these claims, the information consumer has to evaluate their trustworthiness and determine the subset which he wants to trust for his specific task

Trauma reloaded: Trauma registry in the era of data science

International audienc

Assessment of coronary artery remodelling by dual-source CT: a head-to-head comparison with intravascular ultrasound

Background: While it is widely assumed that coronary CT angiography permits detection and quantification of ‘positive remodelling’ of coronary atherosclerotic lesions, there is a paucity of data comparing CT with established reference methods. Objective: To assess the accuracy of dual-source CT for detecting positive versus absent or negative coronary artery remodelling of coronary atherosclerotic lesions as compared with intravascular ultrasound (IVUS). Methods: The datasets were evaluated of 38 patients referred for invasive coronary angiography and in whom an IVUS study of one coronary vessel was performed. Coronary CT angiography was performed within 24 h before invasive coronary angiography. Using dual-source CT (Siemens Healthcare, Forchheim, Germany), a contrast-enhanced volume dataset was acquired (120 kV, 400 mA/rot, collimation 2×64×0.6 mm, 60–80 ml contrast agent, intravenous). IVUS was performed using a 40 MHz IVUS catheter (Atlantis, Boston Scientific Corporation, Natick, Massachusetts, USA) and motorised pullback at 0.5 mm/s. 48 corresponding non-calcified and partially calcified plaques within the coronary artery system were identified in both CT and IVUS using bifurcation points as fiducial markers. In CT datasets, multiplanar reconstructions orthogonal to the centre line of the coronary artery were rendered and cross-sectional vessel area was measured at the site of maximal narrowing as well as at a reference segment proximal to the lesion for each of the 48 plaques. The remodelling index (RI) was calculated by dividing the vessel area at the site of maximal narrowing by the area of the reference segment. Corresponding vessel areas and RIs were also determined in IVUS. Results: CT classified 41 plaques as positively remodelled (RI≥1.05) and seven as having either absent or negative remodelling (RI0.9, p<0.0001) than for remodelling indices (r=0.7, p<0.0001) with Bland–Altman analysis showing a systematic overestimation of vessel areas and RI in CT. Interobserver agreement was moderate for CT and IVUS measurements. Receiver operating characteristic curve analysis showed that a RI of 1.1 in CT identified positively remodelled plaques in IVUS with a sensitivity of 83% and a specificity of 78% (area under the curve=0.8, 95% CI 0.7 to 1.0). Using the standard cut-off point of 1.05 to identify positively remodelled plaques in CT resulted in a sensitivity of 100%, and a specificity of 45%. Conclusion: Coronary CT angiography allows analysis of coronary artery remodelling. The degree of positive remodelling is typically overestimated by CT. A threshold of 1.1 for the RI may be optimal to classify plaques as ‘positively remodelled’ in coronary CT angiography

Doubly robust treatment effect estimation with missing attributes

International audienceMissing attributes are ubiquitous in causal inference, as they are in most applied statistical work. In this paper, we consider various sets of assumptions under which causal inference is possible despite missing attributes and discuss corresponding approaches to average treatment effect estimation, including generalized propensity score methods and multiple imputation. Across an extensive simulation study, we show that no single method systematically out-performs others. We find, however, that doubly robust modifications of standard methods for average treatment effect estimation with missing data repeatedly perform better than their non-doubly robust baselines; for example, doubly robust generalized propensity score methods beat inverse-weighting with the generalized propensity score. This finding is reinforced in an analysis of an observations study on the effect on mortality of tranexamic acid administration among patients with traumatic brain injury in the context of critical care management. Here, doubly robust estimators recover confidence intervals that are consistent with evidence from randomized trials, whereas non-doubly robust estimators do not