Forgotten Antibiotics: An Inventory in Europe, the United States, Canada, and Australia

In view of the alarming spread of antimicrobial resistance in the absence of new antibiotics, this study aimed at assessing the availability of potentially useful older antibiotics. A survey was performed in 38 countries among experts including hospital pharmacists, microbiologists, and infectious disease specialists in Europe, the United States, Canada, and Australia. An international expert panel selected systemic antibacterial drugs for their potential to treat infections caused by resistant bacteria or their unique value for specific criteria. Twenty-two of the 33 selected antibiotics were available in fewer than 20 of 38 countries. Economic motives were the major cause for discontinuation of marketing of these antibiotics. Fourteen of 33 antibiotics are potentially active against either resistant Gram-positive or Gram-negative bacteria. Urgent measures are then needed to ensure better availability of these antibiotics on a global scal

JAK2 V617F Constitutive Activation Requires JH2 Residue F595: A Pseudokinase Domain Target for Specific Inhibitors

The JAK2 V617F mutation present in over 95% of Polycythemia Vera patients and in 50% of Essential Thrombocythemia and Primary Myelofibrosis patients renders the kinase constitutively active. In the absence of a three-dimensional structure for the full-length protein, the mechanism of activation of JAK2 V617F has remained elusive. In this study, we used functional mutagenesis to investigate the involvement of the JH2 αC helix in the constitutive activation of JAK2 V617F. We show that residue F595, located in the middle of the αC helix of JH2, is indispensable for the constitutive activity of JAK2 V617F. Mutation of F595 to Ala, Lys, Val or Ile significantly decreases the constitutive activity of JAK2 V617F, but F595W and F595Y are able to restore it, implying an aromaticity requirement at position 595. Substitution of F595 to Ala was also able to decrease the constitutive activity of two other JAK2 mutants, T875N and R683G, as well as JAK2 K539L, albeit to a lower extent. In contrast, the F595 mutants are activated by erythropoietin-bound EpoR. We also explored the relationship between the dimeric conformation of EpoR and several JAK2 mutants. Since residue F595 is crucial to the constitutive activation of JAK2 V617F but not to initiation of JAK2 activation by cytokines, we suggest that small molecules that target the region around this residue might specifically block oncogenic JAK2 and spare JAK2 wild-type

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Exploration of physical activity within a community: Representations and habits of the citizens

Au moins 60% de la population mondiale ne pratique pas le niveau quotidien d’activité physique (AP) recommandé pour qu’en découle des avantages sur la santé. Face à cette problématique, le modèle écologique de promotion de l’AP révèle les différents leviers d’actions qui inciteront chaque citoyen à s’engager dans un style de vie plus actif au sein de leur communauté (Sallis et al., 2005). Ce modèle reconnait l’influence des représentations, habitudes et comportements des individus à l’égard de l’AP qui, en tant que déterminants modifiables, devraient être une des cibles des actions de promotion de l’AP dans chaque communauté (Kahn et al., 2002). Notre étude s’inscrit dans un projet visant à promouvoir l’activité physique au sein d’une commune de la région liégeoise. Elle porte plus spécifiquement sur l’identification des habitudes des habitants en matière d’activité physique et sur la notoriété des activités existantes. Un questionnaire a été complété par 141 personnes. Il portait sur certaines caractéristiques sociodémographiques, sur la pratique d’activité physique (IPAQ) et sur les initiatives proposées par la communauté. Par ailleurs, un entretien semi-structuré avec les individus les moins actifs de l’échantillon (n = 21) a été réalisé afin d‘affiner les données disponibles. Les principaux résultats montrent que 52% des habitants interrogés au sein de cette commune n’atteignent pas les recommandations actuelles en matière d’AP. En moyenne, ils ont connaissance de la présence de 1,48 organisation sportive dans leur communauté. Le sexe, l’âge et la saison influencent les résultats obtenus. Les personnes interviewées ont montré une méconnaissance des principaux concepts en rapport avec l’AP. La discussion des résultats met en avant la nécessité d’intervenir auprès de certains publics cible (femmes, ainés) mais également de changer les représentations des habitants quant à l’AP (bienfaits, recommandations, etc.) et d’améliorer la notoriété des opportunités de pratique par une communication mieux adaptée

Remote scientific visualization of progressive 3D meshes with X3D

International audienceThis paper presents a framework, integrated into the X3D file format, for the streaming of 3D content in the context of remote scientific visualization; a progressive mesh compression method is proposed that can handle 3D objects associated with attributes like colors, while producing high quality intermediate Levels Of Detail (LOD). Efficient adaptation mechanisms are also proposed so as to optimize the LOD management of the 3D scene according to different constraints like the network bandwidth, the device graphic capability, the display resolution and the user preferences. Experiments demonstrate the efficiency of our approach in scientific visualization scenarii