10 research outputs found
Compliance with the current recommendations for prescribing antibiotics for paediatric community-acquired pneumonia is improving: data from a prospective study in a French network
Towards frontiers of acyl transfer reaction by nucleophilic enantioselective organocatalysis
Devant lâintĂ©rĂȘt grandissant pour le dĂ©veloppement de stratĂ©gies innovantes applicables Ă la synthĂšse de molĂ©cules complexes, notre groupe sâest orientĂ© vers la construction de motifs prĂ©sents dans un grand nombre de produits biologiquement actifs : les tĂ©trahydropyranes (THP) et les polypropionates. Notre stratĂ©gie, basĂ©e sur la formation diastĂ©rĂ©osĂ©lective de diols mĂ©so primaires, fait intervenir une Ă©tape inĂ©dite de dĂ©symĂ©trisation organocatalysĂ©e par transfert dâacyle asymĂ©trique. Cette approche permet la synthĂšse Ă©nantiosĂ©lective de THP pentasubstituĂ©s qui par la suite peuvent ĂȘtre valorisĂ©s par lâobtention de polypropionates fonctionnalisĂ©s, possĂ©dant quatre centres stĂ©rĂ©ogĂšnes contigus. Par ailleurs, cette nouvelle mĂ©thodologie de dĂ©symĂ©trisation donne accĂšs Ă des motifs cycliques et acycliques comportant plusieurs centres stĂ©rĂ©ogĂšnes quaternaires. Elle constitue, de plus, lâunique exemple de dĂ©symĂ©trisation Ă©nantiosĂ©lective de diols mĂ©so primaires catalysĂ©e par une dialkylaminopyridine chirale. Bien que le transfert dâacyle asymĂ©trique organocatalysĂ© ait Ă©tĂ© trĂšs largement Ă©tudiĂ© depuis la fin des annĂ©es 90, de nombreuses Ă©tudes sont en cours pour accĂ©der Ă des catalyseurs plus sĂ©lectifs et plus nuclĂ©ophiles. InspirĂ© des rĂ©cents travaux de Steglich et Vedejs, notre deuxiĂšme objectif sâest portĂ© sur la synthĂšse Ă©nantiosĂ©lective et modulaire dâune nouvelle famille dâorganocatalyseurs chiraux plus polyvalents dĂ©rivĂ©s de la 1,6-naphtyridine. Leur application, en catalyse nuclĂ©ophile, a pu ĂȘtre Ă©valuĂ©e dans des rĂ©actions de dĂ©doublement cinĂ©tique dâalcools et dans les rĂ©arrangements de Steglich.Alongside metallocatalysis and biocatalysis, organocatalysis has emerged as a complementary and powerful tool that can circumvent limitations associated to the use of metals or enzymes. Because of the growing interest for new innovative methodologies useful for complex molecules synthesis, we get interested in the preparation of versatile building blocks present in many bioactive molecules: tetrahydropyrans (THP) and polypropionates. Based on the diastereoselective formation of primary meso diols, our strategy involves an original organocatalyzed desymmetrization of these compounds by asymmetric acyl transfer. This approach allows the enantioselective synthesis of pentasubstituted THP which were valorized through the synthesis of polypropionates bearing four consecutive stereogenic centers. In addition, this new methodology provides cyclic and acyclic scaffolds with several all carbon quaternary stereogenic centers. It represents the first example in organocatalyzed asymmetric desymmetrization by acyl transfer using a chiral dialkylaminopyridine. Although asymmetric organocatalyzed acyl transfer has been widely studied since the late 90s, several investigations are currently underway to access to new chiral nucleophilic catalysts. Following the recent work of Steglich and Vedejs, we were interested in the development of new chiral organocatalysts derived from 1,6-naphthyridine. Their applications in nucleophilic catalysis have then been evaluated in kinetic resolutions of alcohols and in asymmetric Steglich rearrangements
Le forum de discussion en formation : un espace potentiel dâaccĂšs au rapport quâentretient autrui avec les objets dâapprentissage
This research focuses on the discussion forum, a space for asynchronous communication at distance. Using the discussion forum as part of open and distance learning systems in vocational training, is a growing activity because it is considered as a place offering interesting pedagogical possibilities. Based on the difference between what the designers of these learning systems expect and what can be observed on these forums, we have chosen to approach this social subject from a perspective which is fairly uncommon in other works in this field. Indeed, we focus on the concept of activity and consider contributing to the forum as a situated practice. Our research goal is to identify how the forum constitutes a meditation system which generates activities likely to produce learning. We use professional didactics and mediation theories as a basis for our work. This paper addresses the forum situation, a work situation into which learners are integrated. Thus, the methodological choices are in line with the methods used to analyze situations at work; they establish a distinction between task and activity and during interviews, confront learners with the traces of their activity.In the forum we studied, the learnersâ activity is only mildly consistent with the prescribed tasks. This being said, the forum does seem to be an ideal place to gain access to the way in which others relate to the learning objects. If we take this into consideration it serves as a form of mediation to build, strengthen or re-examine the relationship to learning objects and to control a mutual understanding of them
Coopérer à travers un réseau d'établissements : gouvernance, tensions et controverses
International audienceThe choice of a new form of a network organisation to develop cooperation between the public agricultural schools arose from the will to respond to the social demand in a context of decentralization. One must go beyond the heavy tension between what is established and what is becoming established. This contribution offers a testimony of how the means to "go beyond" are a permanent construction, through the analysis of a few founding controversies of the network âPrĂ©fĂ©rence Formations", reinforced by the social sciences (sociology of translation, social psychology). The current learning of cooperation within this network of schools is a puzzle to the institution and, in parallel, interrogates the schools about their own governance.Le choix d'une nouvelle forme d'organisation en rĂ©seau pour dĂ©velopper la coopĂ©ration entre les Ă©tablissements d'enseignement agricole public est nĂ© de la volontĂ© de mieux rĂ©pondre Ă la demande sociale dans un contexte de dĂ©centralisation. Mais il nĂ©cessite de dĂ©passer la tension forte entre une culture institutionnelle dominante et le caractĂšre fondamentalement instituant du rĂ©seau. Cette contribution propose un tĂ©moignage de la construction permanente des moyens de ce dĂ©passement Ă travers l'analyse de quelques controverses fondatrices du rĂ©seau PrĂ©fĂ©rence Formations, Ă©clairĂ©e par les apports des sciences sociales (sociologie de la traduction, psychologie sociale). L'apprentissage de la coopĂ©ration qui se fait dans le cadre de ce rĂ©seau d'Ă©tablissements intrigue l'institution et interroge parallĂšlement les Ă©tablissements sur leur propre gouvernance
Renforcer les capacités réflexives à des fins de développement professionnel : une grille-repÚres pour la conception de dispositifs pédagogiques
International audienceWhile reflexivity is seen as a not-to-be-missed concept in professional training, references to design pedagogical devices to enhance actorsâ reflective capacities on their professional situations and to foster their professional and personal development are scarce and embedded in a patchwork of theoretical and practical approaches. As designers of such devices in agricultural higher education, our practical experiences, theoretical background and discussions led us to build a model of reflexivity as five intertwined key dimensions. These dimensions deal with aspects of reflexivity that it is possible to work on directly with learners by using appropriate scaffolding methods, which we describe and illustrate in this paper, referring to our teaching experiences. Two dimensions of the model are particularly relevant for people who are not familiar with reflexivity, and sometimes reluctant to practice it.Alors que le concept de rĂ©flexivitĂ© se prĂ©sente comme incontournable en formation professionnelle, les repĂšres pour construire des dispositifs pĂ©dagogiques visant le renforcement des capacitĂ©s rĂ©flexives dâacteurs sur leurs situations professionnelles Ă des fins de dĂ©veloppement professionnel et personnel paraissent, sinon manquants, du moins noyĂ©s dans un foisonnement thĂ©orique et pratique. En tant que concepteurs de tels dispositifs dans le domaine de lâenseignement supĂ©rieur agronomique, nous prĂ©sentons une grille-repĂšres articulant cinq dimensions de la rĂ©flexivitĂ©, forgĂ©e au fil de nos expĂ©riences, de nos Ă©changes et de nos lectures. Ces cinq dimensions renvoient Ă cinq aspects de la rĂ©flexivitĂ© quâil est possible de travailler directement avec des apprenants, en mettant en place un Ă©tayage adaptĂ© que nous caractĂ©risons et illustrons dans lâarticle, en puisant dans nos expĂ©riences de formateurs. Deux dimensions de la grille sont particuliĂšrement pertinentes pour accompagner des publics non familiers avec la rĂ©flexivitĂ©, et parfois rĂ©fractaires aux exercices rĂ©flexifs
Stereocontrol of all-carbon quaternary centers through enantioselective desymmetrization of meso primary diols by organocatalyzed acyl transfer
International audienceThe symmetry breaking of meso primary diols bearing a tetrahydropyran ring was employed, using catalytic asymmetric acyl transfer, to control all-carbon quaternary stereocenters. The planar chiral Fu DMAP catalyst was used in this reaction to reach a high degree of enantioselectivity (up to 97:3 e.r.) through a synergic effect combining a desymmetrization step and a kinetic resolution. Moreover, a beneficial effect was exhibited by C6F6 solvent, yielding the first example of an organocatalyzed asymmetric acyl transfer. The desymmetrized monoesters were then used to obtain, after a straightforward ring opening sequence, complex polyketide building blocks bearing all-carbon quaternary stereocenter
Un entretien pour Ă©valuer des capacitĂ©s Ă partir de situations professionnelles vĂ©cues : un nouveau dĂ©fi pour lâenseignement agricole français
The Ministry of Agriculture in France has recently decided to renovate its technical education diplomas with a so-called "capacity" entry and the implementation of a type of certification assessment involving an interview based on real-life professional situations. How can an interview be designed to serve the certification of skills in vocational training? On which theoretical and technical corpus should it be based ? Being in charge of councelling teachers across this renovation in agricultural education, we have tried to answer these questions by developing an interview approach, which mobilizes both explicitation as defined by Vermersch and the contributions of professional didactics. We then experimented this interview with future agricultural workers in training in order to test its relevance and feasibility. We thus propose in the end an approach composed of two distinct phases during which the type of questions, the language rules, the posture and the intentions of the assessor vary
Highly Enantioselective Acylation of Acyclic Meso 1,3-Diols through Synergistic Isothiourea-Catalyzed Desymmetrization/Chiroablative Kinetic Resolution
International audienceA general and highly efficient organocatalyzed desymmetrization of acyclic meso 1,3-diols through acyl transfer using chiral isothioureas is described. The introduction of Ï-systems in the acyclic substrates provided new opportunities in terms of reactivity, enantioselectivity and synthetic potential. To reach this high level of enantioselectivity (up to er >99:1), the reaction proceeds through a synergistic mechanism involving a desymmetrization reaction and a chiroablative kinetic resolution process. This methodology was used with success as the sole enantioselective catalytic step (developed on a gram scale) to achieve the total synthesis of the antiosteoporotic diarylheptanoid (â)-diospongin A (7 steps)
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