FORT: una herramienta de regresión borrosa

El uso de las técnicas de regresión sobre las observaciones experimentales ha permitido el estudio de numerosos fenómenos en diversos campos de la ciencia, y muy especialmente en las ciencias sociales. Dichas técnicas requieren de un número suficiente de observaciones “precisas”, exactas y fiables. Sin embargo, no siempre es posible obtener el conjunto de observaciones necesario, o éstas contienen algún tipo de imperfección en los datos, debido a la imprecisión o vaguedad de los mismos. En cualquier caso, con suficientes datos o no, con imperfecciones o no, los modelos obtenidos deberían proveer de capacidades predictivas y descriptivas [JCr02]. Las actuales herramientas, o las más fácilmente accesibles, tienen limitado el uso de modelos y difícilmente usan las técnicas de la teoría de conjuntos borrosos. Se propone en este trabajo una herramienta abierta de regresión que admita el uso de cualquier modelo de curva independientemente de su naturaleza. Además, esta herramienta permitirá el uso de diferentes formas de borrosidad y por su diseño permitiría cualquier modelo propuesto por el usuario si éste prevee que éstos tienen características que sean suficientemente predictivas y descriptivas. Esta primera aproximación de una herramienta abierta de regresión se realiza un estudio sobre diferentes modelos paramétricos simbólicos, usados comúnmente en la práctica en disciplinas tan heterogéneas como pueden ser la Ingeniería del Software, la Economía o en cualquier campo en donde puedan aparecer imprecisiones en la información. [ABSTRACT] The use of regression techniques in experimental observations has led to the study of numerous phenomena in various fields of science, especially in social science. These techniques require a sufficient number of “precise”, exact and reliable observations. However, it is not always possible to obtain all the necessary group of observations or these have some failings, as a result of inexact or vague data. Nevertheless, having more or less data, with or without failings, the obtained paradigms should provide predictive and descriptive capacities. The current tools or those more accessible have limited paradigm application and hardly use the techniques relating the fuzzy sets theory. In this first approach to an open regression tool, a study has been carried out of the different parametric, symbolic paradigms, commonly used in the practice of such diverse disciplines as Software Engineering, Economy or any other field where information imprecision can appear

Experience sampling methods for the personalised prediction of mental health problems in Spanish university students: protocol for a survey-based observational study within the PROMES-U project

IntroductionThere is a high prevalence of mental health problems among university students. Better prediction and treatment access for this population is needed. In recent years, short-term dynamic factors, which can be assessed using experience sampling methods (ESM), have presented promising results for predicting mental health problems.Methods and analysisUndergraduate students from five public universities in Spain are recruited to participate in two web-based surveys (at baseline and at 12-month follow-up). A subgroup of baseline participants is recruited through quota sampling to participate in a 15-day ESM study. The baseline survey collects information regarding distal risk factors, while the ESM study collects short-term dynamic factors such as affect, company or environment. Risk factors will be identified at an individual and population level using logistic regressions and population attributable risk proportions, respectively. Machine learning techniques will be used to develop predictive models for mental health problems. Dynamic structural equation modelling and multilevel mixed-effects models will be considered to develop a series of explanatory models for the occurrence of mental health problems.Ethics and disseminationThe project complies with national and international regulations, including the Declaration of Helsinki and the Code of Ethics, and has been approved by the IRB Parc de Salut Mar (2020/9198/I) and corresponding IRBs of all participating universities. All respondents are given information regarding access mental health services within their university and region. Individuals with positive responses on suicide items receive a specific alert with indications for consulting with a health professional. Participants are asked to provide informed consent separately for the web-based surveys and for the ESM study. Dissemination of results will include peer-reviewed scientific articles and participation in scientific congresses, reports with recommendations for universities’ mental health policy makers, as well as a well-balanced communication strategy to the general public

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field