Synchronized diffusive-wave spectroscopy: Principle and application to sound propagation in aqueous foams

International audienceWe present an experimental method to measure oscillatory strains in turbidmaterial. Thematerial is illuminatedwith a laser, and the speckle patterns are recorded. The analysis of the deformations of the optical path lengthshows that the speckle patterns are modulated at the strain frequency. By recording those patterns synchronouslywith the strain source, we are able to measure the amplitude and the phase of the strain. This method is testedin the specific case of an aqueous foam where an acoustic wave propagates. The effects of material internaldynamics and heterogeneous deformations are also discussed

Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly.

International audienceThe genetic causes of malformations of cortical development (MCD) remain largely unknown. Here we report the discovery of multiple pathogenic missense mutations in TUBG1, DYNC1H1 and KIF2A, as well as a single germline mosaic mutation in KIF5C, in subjects with MCD. We found a frequent recurrence of mutations in DYNC1H1, implying that this gene is a major locus for unexplained MCD. We further show that the mutations in KIF5C, KIF2A and DYNC1H1 affect ATP hydrolysis, productive protein folding and microtubule binding, respectively. In addition, we show that suppression of mouse Tubg1 expression in vivo interferes with proper neuronal migration, whereas expression of altered γ-tubulin proteins in Saccharomyces cerevisiae disrupts normal microtubule behavior. Our data reinforce the importance of centrosomal and microtubule-related proteins in cortical development and strongly suggest that microtubule-dependent mitotic and postmitotic processes are major contributors to the pathogenesis of MCD

Apprentissage de la pensée informatique : de la formation des enseignant·e·s à la formation de tou·te·s les citoyen·ne·s

National audienceIn recent years, in France, computer learning (under the term of code) has entered the school curriculum, in primary and high school. This learning is also aimed at developing computer thinking to enable students, girls and boys, to start master all aspects of the digital world (science, technology, industry, culture). However, neither teachers, nor parents are trained to teach or educate on these topics. Furthermore, if the educational system progresses progressively towards these objectives, in everyday life and in professional context there is also a need for lifelong training in computer thinking. Large-scale projects on coding initiation are now quite successful in supporting the training of professionals in education on these topics. However, they require an infrastructure of people and important resources to maintain their level of efficiency. In order to further develop the objectives of helping people to demystify IT thinking, we aim to question here the way by which it is possible to conceive a concrete and operational initiative that addresses this issue. A huge challenge: Let's share a proposal here and discuss it.En France au cours de ces dernières années, l’apprentissage de l’informatique (sous le terme d’«​ ​ apprentissage du code​ ​ ») est entré dans les programmes scolaires, en primaire et secondaire. Cet apprentissage vise notamment le développement de la pensée informatique (au sens défini par Wing) afin de permettre aux élèves, filles et garçons, d’acquérir les bases, une étape initiale vers la maîtrise du numérique, sous tous ses aspects (science, technologie, industrie et culture). Cependant, peu d’enseignant·e·s, ou de parents, ont été formé·e·s pour enseigner les sciences du numérique ou éduquer à leurs fondements et leurs usages. De plus, si le système éducatif avance progressivement au niveau de ces objectifs, dans la vie quotidienne et en contexte professionnel, il existe aussi un besoin de formation tout au long de la vie à la pensée informatique. Des projets d’envergure sur l’apprentissage du code sont aujourd’hui forts d’un véritable succès en matière de support à la formation des professionnel·le·s de l’éducation sur ces sujets. Cependant ces projets nécessitent une main d'oeuvre importante tant pour la création de ressources que pour leur actualisation, afin de rester en phase avec les besoins de formation dans un domaine en évolution constante. Dans le but de développer davantage les objectifs de démystification de la pensée informatique vers un large public de citoyens et de citoyennes, nous voulons questionner ici la manière dont il est possible de concevoir une initiative concrète et opérationnelle qui relève ce défi. Partageons ici une proposition et discutons-la. Ce qui est proposé porte un nom : une Université, Citoyenne en Sciences et Culture du Numérique (#UCscN) qui s’inscrit dans la tradition des universités populaires. Il s’agit donc très simplement d’étendre à toutes et tous cette éducation pour penser l’informatique en capitalisant sur l’expérience acquise de Class’Code en formant les professionnel·le·s de l’éducation

Apprentissage de la pensée informatique : de la formation des enseignant·e·s à la formation de tou·te·s les citoyen·ne·s

National audienceIn recent years, in France, computer learning (under the term of code) has entered the school curriculum, in primary and high school. This learning is also aimed at developing computer thinking to enable students, girls and boys, to start master all aspects of the digital world (science, technology, industry, culture). However, neither teachers, nor parents are trained to teach or educate on these topics. Furthermore, if the educational system progresses progressively towards these objectives, in everyday life and in professional context there is also a need for lifelong training in computer thinking. Large-scale projects on coding initiation are now quite successful in supporting the training of professionals in education on these topics. However, they require an infrastructure of people and important resources to maintain their level of efficiency. In order to further develop the objectives of helping people to demystify IT thinking, we aim to question here the way by which it is possible to conceive a concrete and operational initiative that addresses this issue. A huge challenge: Let's share a proposal here and discuss it.En France au cours de ces dernières années, l'apprentissage de l'informatique (sous le terme d'« apprentissage du code ») est entré dans les programmes scolaires, en primaire et secondaire. Cet apprentissage vise notamment le développement de la pensée informatique (au sens défini par Wing) afin de permettre aux élèves, filles et garçons, d'acquérir les bases, une étape initiale vers la maîtrise du numérique, sous tous ses aspects (science, technologie, industrie et culture). Cependant, peu d'enseignant·e·s, ou de parents, ont été formé·e·s pour enseigner les sciences du numérique ou éduquer à leurs fondements et leurs usages. De plus, si le système éducatif avance progressivement au niveau de ces objectifs, dans la vie quotidienne et en contexte professionnel, il existe aussi un besoin de formation tout au long de la vie à la pensée informatique. Des projets d'envergure sur l'apprentissage du code sont aujourd'hui forts d'un véritable succès en matière de support à la formation des professionnel·le·s de l'éducation sur ces sujets. Cependant ces projets nécessitent une main d'oeuvre importante tant pour la création de ressources que pour leur actualisation, afin de rester en phase avec les besoins de formation dans un domaine en évolution constante. Dans le but de développer davantage les objectifs de démystification de la pensée informatique vers un large public de citoyens et de citoyennes, nous voulons questionner ici la manière dont il est possible de concevoir une initiative concrète et opérationnelle qui relève ce défi. Partageons ici une proposition et discutons-la. Ce qui est proposé porte un nom : une Université, Citoyenne en Sciences et Culture du Numérique (#UCscN) qui s'inscrit dans la tradition des universités populaires. Il s'agit donc très simplement d'étendre à toutes et tous cette éducation pour penser l'informatique en capitalisant sur l'expérience acquise de Class'Code en formant les professionnel·le·s de l'éducation

Extending the clinical spectrum of X-linked Tonne-Kalscheuer syndrome (TOKAS):new insights from the fetal perspective

INTRODUCTION: Tonne-Kalscheuer syndrome (TOKAS) is a recessive X-linked multiple congenital anomaly disorder caused by RLIM variations. Of the 41 patients reported, only 7 antenatal cases were described.METHOD: After the antenatal diagnosis of TOKAS by exome analysis in a family followed for over 35 years because of multiple congenital anomalies in five male fetuses, a call for collaboration was made, resulting in a cohort of 11 previously unpublished cases.RESULTS: We present a TOKAS antenatal cohort, describing 11 new cases in 6 French families. We report a high frequency of diaphragmatic hernia (9 of 11), differences in sex development (10 of 11) and various visceral malformations. We report some recurrent dysmorphic features, but also pontocerebellar hypoplasia, pre-auricular skin tags and olfactory bulb abnormalities previously unreported in the literature. Although no clear genotype-phenotype correlation has yet emerged, we show that a recurrent p.(Arg611Cys) variant accounts for 66% of fetal TOKAS cases. We also report two new likely pathogenic variants in RLIM, outside of the two previously known mutational hotspots.CONCLUSION: Overall, we present the first fetal cohort of TOKAS, describe the clinical features that made it a recognisable syndrome at fetopathological examination, and extend the phenotypical spectrum and the known genotype of this rare disorder.</p

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

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/)