On agnostic post hoc approaches to false positive control

This document is a book chapter which gives a partial survey on post hoc approaches to false positive control

Prise en charge de l'arrêt cardiorespiratoire extrahospitalier : l'importance des premiers maillons

L'arrêt cardiorespiratoire extrahospitalier (ACEH) est un problème complexe, associé à une mortalité importante et ayant un impact profond sur la communauté. Les interventions permettant de renverser ce processus s'articulent autour d'un concept appelé « chaîne de survie » à l'intérieur duquel chaque maillon revêt une importance déterminante sur la progression du traitement. Plusieurs interventions répertoriées dans la littérature démontrent l'existence d'opportunités d'amélioration des issues rencontrées par les victimes d'ACEH, notamment au sein des premiers maillons de la chaîne. Plus spécifiquement, un recours rapide au défibrillateur externe automatisé (DEA) par les premiers témoins est l'intervention associée au nombre de sujets à traiter le plus avantageux pour l'atteinte d'une issue favorable. Au Québec, la formation de base en réanimation cardiorespiratoire (RCR) et l'acquisition d'un DEA sont obligatoires pour les établissements d'enseignement secondaire depuis novembre 2019. Puisque les établissements d'enseignement primaire ne sont pas encore tenus de respecter de telles exigences en matière de formation et d'acquisition de matériel de réanimation, ces sites représentent des secteurs où l'amélioration est possible. Dans le cadre de l'étude au cœur de ce mémoire, les écoles primaires de la région de la Capitale-Nationale ont été sondées pour identifier les principales barrières à l'utilisation efficace et sécuritaire du DEA. La formation inadéquate ou inexistante du personnel des établissements d'enseignement primaire sondés est la principale barrière identifiée (46% des écoles répondantes). Cependant, il est possible de combler ce déficit de formation par l'entremise d'une capsule d'enseignement ciblée. En mesurant les performances des intervenants en milieu scolaire, nous avons démontré une amélioration significative de la qualité de la séquence de défibrillation (passant de 53% à 92%, p < 0,001) et du délai avant le premier choc lors d'un scénario simulant un ACEH (passant de 66 secondes à 47 secondes, p < 0,01). Ces travaux s'inscrivent dans une lignée d'études identifiant des stratégies de consolidation des premiers maillons de la chaîne de survie comme l'éducation citoyenne à la reconnaissance de l'ACEH et à la dispensation de soins immédiats en réanimation et les programmes d'accès public à la défibrillation.Out-of-hospital cardiac arrest (OHCA) is a complex problem associated with significant mortality and profoundly impacts the community. Interventions to reverse this process revolve around the "chain of survival" in which every link is critical to treatment progression. Several interventions listed in the literature demonstrate the existence of opportunities for improving outcomes encountered by OHCA victims, particularly within the first links in the chain. More specifically, it appears that rapid use of an automated external defibrillator (AED) by bystanders is the intervention associated with the most advantageous number needed to treat to achieve a favourable outcome. In the province of Québec, basic training in cardiorespiratory resuscitation (CPR) and acquisition of an AED have been mandatory for high schools since November 2019. However, because the elementary schools are not yet required to meet those obligations regarding training and device acquisition, they represent an area of improvement. In the study presented herein, elementary schools in the Capitale-Nationale region were surveyed to identify the main barriers to the efficient and safe use of the AED. For the elementary schools surveyed, the main barrier identified is staff inadequate or non-existent training (46% of responding schools). However, filling this training gap through a targeted educational module is possible. By measuring the performance of school staff members, we have demonstrated a significant improvement in the quality of the defibrillation sequence (from 53% to 92%, p < 0,001) and the time to first shock during a simulated OHCA scenario (from 66 seconds to 47 seconds, p < 0,01). This work contributes to identifying strategies aiming at consolidating the first links in the chain of survival, such as civic education on the recognition of OHCA and the provision of basic life support, and public access defibrillation programs

Control of Brown Adipose Tissue Glucose and Lipid Metabolism by PPARγ

Brown adipose tissue (BAT) non-shivering thermogenesis impacts energy homeostasis in rodents and humans. Mitochondrial uncoupling protein 1 in brown fat cells produces heat by dissipating the energy generated by fatty acid and glucose oxidation. In addition to thermogenesis and despite its small relative size, sympathetically activated BAT constitutes an important glucose, fatty acid, and triacylglycerol-clearing organ, and such function could potentially be used to alleviate dyslipidemias, hyperglycemia, and insulin resistance. To date, chronic sympathetic innervation and peroxisome proliferator-activated receptor (PPAR) γ activation are the only recognized inducers of BAT recruitment. Here, we review the major differences between these two BAT inducers in the regulation of lipolysis, fatty acid oxidation, lipid uptake and triacylglycerol synthesis, glucose uptake, and de novo lipogenesis. Whereas BAT recruitment through sympathetic drive translates into functional thermogenic activity, PPARγ-mediated recruitment is associated with a reduction in sympathetic activity leading to increased lipid storage in brown adipocytes. The promising therapeutic role of BAT in the treatment of hypertriglyceridemic and hyperglycemic conditions is also discussed

Non-Gaussian Component Analysis using Entropy Methods

Non-Gaussian component analysis (NGCA) is a problem in multidimensional data analysis which, since its formulation in 2006, has attracted considerable attention in statistics and machine learning. In this problem, we have a random variable $X$ in $n$-dimensional Euclidean space. There is an unknown subspace $\Gamma$ of the $n$-dimensional Euclidean space such that the orthogonal projection of $X$ onto $\Gamma$ is standard multidimensional Gaussian and the orthogonal projection of $X$ onto $\Gamma^{\perp}$, the orthogonal complement of $\Gamma$, is non-Gaussian, in the sense that all its one-dimensional marginals are different from the Gaussian in a certain metric defined in terms of moments. The NGCA problem is to approximate the non-Gaussian subspace $\Gamma^{\perp}$ given samples of $X$. Vectors in $\Gamma^{\perp}$ correspond to `interesting' directions, whereas vectors in $\Gamma$ correspond to the directions where data is very noisy. The most interesting applications of the NGCA model is for the case when the magnitude of the noise is comparable to that of the true signal, a setting in which traditional noise reduction techniques such as PCA don't apply directly. NGCA is also related to dimension reduction and to other data analysis problems such as ICA. NGCA-like problems have been studied in statistics for a long time using techniques such as projection pursuit. We give an algorithm that takes polynomial time in the dimension $n$ and has an inverse polynomial dependence on the error parameter measuring the angle distance between the non-Gaussian subspace and the subspace output by the algorithm. Our algorithm is based on relative entropy as the contrast function and fits under the projection pursuit framework. The techniques we develop for analyzing our algorithm maybe of use for other related problems

Recommendations for radiation therapy in oligometastatic prostate cancer:An ESTRO-ACROP Delphi consensus

Background and purpose: Oligometastatic prostate cancer is a new and emerging treatment field with only few prospective randomized studies published so far. Despite the lack of strong level I evidence, metastasis-directed therapies (MDT) are widely used in clinical practice, mainly based on retrospective and small phase 2 studies and with a large difference across centers. Pending results of ongoing prospec-tive randomized trials, there is a clear need for more consistent treatment indications and radiotherapy practices.Material and methods: A European Society for Radiotherapy and Oncology (ESTRO) Guidelines Committee consisting of radiation oncologists' experts in prostate cancer was asked to answer a dedicated question-naire, including 41 questions on the main controversial issues with regard to oligometastatic prostate cancer.Results: The panel achieved consensus on patient selection and routine use of prostate-specific mem-brane antigen positron emission tomography (PSMA PET) imaging as preferred staging and restaging imaging. MDT strategies are recommended in the de novo oligometastatic, oligorecurrent and oligopro-gressive disease setting for nodal, bone and visceral metastases. Radiation therapy doses, volumes and techniques were discussed and commented.Conclusion: These recommendations have the purpose of providing standardization and consensus to optimize the radiotherapy treatment of oligometastatic prostate cancer until mature results of random-ized trials are available.AT would like to acknowledge the support of Cancer Research UK (C33589/A28284 and C7224/A28724) . This project represents independent research supported by the National Institute for Health research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care