Algorithms for early detection of silent liver fibrosis in the primary care setting - a scoping review

Introduction Fatty liver disease affects almost 30% of the adult population worldwide. Most patients are asymptomatic, and there is not a linear relationship between exposure to risk factors and the risk of developing fibrosis. The combination of a very large, asymptomatic risk population where only a few percent will develop life-threatening liver disease is a growing diagnostic challenge for the health services. Accurate fibrosis assessment in primary care is limited by poor correlation with liver blood tests and low availability of elastography. Non-invasive tests are promising tools, but little is known about their diagnostic accuracy in low-risk populations. Areas covered A scoping review was conducted to identify articles that focused on the current use of biomarkers and algorithms in primary care for the detection of patients with fatty liver disease in need of referral for further work-up. Expert opinion Currently available algorithms for targeted screening for liver fibrosis perform better than the individual routine liver blood tests or liver ultrasonography. However, primary care physicians urgently need algorithms with even higher diagnostic accuracies than what is available today. The main limitation of the existing widely accessible algorithms, such as the FIB-4, is the large number of false-positive tests, resulting in overdiagnosis and futile referrals to secondary care.publishedVersio

How Thioredoxin Dissociates Its Mixed Disulfide

The dissociation mechanism of the thioredoxin (Trx) mixed disulfide complexes is unknown and has been debated for more than twenty years. Specifically, opposing arguments for the activation of the nucleophilic cysteine as a thiolate during the dissociation of the complex have been put forward. As a key model, the complex between Trx and its endogenous substrate, arsenate reductase (ArsC), was used. In this structure, a Cys29Trx-Cys89ArsC intermediate disulfide is formed by the nucleophilic attack of Cys29Trx on the exposed Cys82ArsC-Cys89ArsC in oxidized ArsC. With theoretical reactivity analysis, molecular dynamics simulations, and biochemical complex formation experiments with Cys-mutants, Trx mixed disulfide dissociation was studied. We observed that the conformational changes around the intermediate disulfide bring Cys32Trx in contact with Cys29Trx. Cys32Trx is activated for its nucleophilic attack by hydrogen bonds, and Cys32Trx is found to be more reactive than Cys82ArsC. Additionally, Cys32Trx directs its nucleophilic attack on the more susceptible Cys29Trx and not on Cys89ArsC. This multidisciplinary approach provides fresh insights into a universal thiol/disulfide exchange reaction mechanism that results in reduced substrate and oxidized Trx

La fabrique de la stratégie de '(non-) changement' organisationnel : une approche relationnelle

Accès restreint aux membres de l'Université de Lorraine jusqu'au 2030-01-01The uniqueness of this PhD dissertation is in providing an answer to a reflexive and critical question in the field of change theories in management studies. Is there any organizational and strategic change theory, allowing us to understand its reality in a multidimensional manner and without any scientist, managerial (and more generally ideological) and/or predefined theoretical lenses?For answering this question we have started to think with an epistemological eye on the type of knowledge produced in organization science, by proposing four ideal types of knowledge production. Thus, we have done a critical literature review by classifying the main existing works within the first three ideal-types (namely scholastic, practical, and critical). We have concluded that there exist barely reflexive theories (in the bourdieusien sense) of organizational and strategic change. Multiple causes could generate the current theoretical anemia, which result is a failure to provide a satisfactory reading and understanding of change phenomena. The main causes are the managerialist lenses, streams war in academia which consequence is epistemocentrism and scholastic fallacy, and thus, a disconnection with the field reality, and finally different types of ideology. All these causes are producing either a state of non-change by generating inadequate theories and practices which do not permit to understand and/or catalyze organizational and strategic change. Worst, they contribute to a fallacious knowledge production which could reify the social reality instead of changing it. Indeed, despite the enormous mass of research and practical frameworks on organizational and strategic change, we are still facing total or partial failure in the quasi-totality of organizational and strategic change projects. Then, we try from our critical literature review and our epistemological reflection to explore alternatives to this unfertile situation of the field. One of the alternatives is advancing our change understanding by, precisely, changing radically our vision of what organizational and strategic change could be, and so by innovating heuristically. Consequently, we have adopted a multilevel approach (ontological, epistemological, methodological and theoretical) based on a radical relational approach on reality. This approach has allowed us to consider that the reality is not a substance, and therefore, for understating a phenomenon (here “changing”), we have to consider that it is the result of multiple realities and their relations. Analytically speaking, for proposing a relational theory of change, we have conducted a unique case study, longitudinal, including interviews, secondary data and direct observation (ethnography). This approach has allowed us, without the adoption of predefined theoretical frames, to show that the organizational and strategic change process is hinging on four dimensions mainly (history, dispositions, field and the everyday life), beside the facts that all these dimensions are social supports of change and for having a chance to be successful in the change process is better to initiate it by considering them seriously. Then in the final part of our dissertation we have theorized the three last dimensions by returning to the appropriate literature (historical dimension intrinsically exists within the three other dimensions).This dissertation makes, therefore, four main contributions to the understating and study of change by proposing a new way of considering its reality (ontological), the production of knowledge and its purpose (epistemological), a new approach to study it (methodology) and a new theory of change (theoretical) and strategic changeL’originalité de cette thèse est dans la réponse apportée à une question réflexive, critique et latente dans le champ des théories du changement en management : existerait-il une théorie de changement organisationnel et stratégique nous permettant de comprendre la réalité de ce phénomène de manière multidimensionnelle, non ‘scientiste’ et sans empreinte managérialiste ? Pour répondre à cette question nous commençons par mener une réflexion épistémologique sur le type de connaissances que nous produisons dans les sciences de gestion en proposant quatre idéaux-types. Ensuite, nous menons une analyse critique de la littérature en classant les principaux travaux existant dans les trois premiers idéaux-types (scolastique, pratique et critique) et arrivons à la conclusion qu’il n’existe pas de théories réflexives (dans le sens bourdieusien) du changement organisationnel et stratégique qui nous permettent d’avoir une compréhension moins biaisée de la réalité de ce phénomène. De multiples causes induisent l’anémie des théories actuelles à fournir une lecture satisfaisante du changement qui puisse aller au-delà de la surface (managérialiste), de la guerre des chapelles académiques (épistémocentrisme, déconnexion par rapport à la réalité et erreur scolastique) et croyances naturalisées (idéologies dominantes comme dominées). L’ensemble de ces ‘causes’ produisent plutôt le ‘non-changement’ (la réification) en générant des théories et pratiques inadéquates qui ne permettent pas de comprendre et/ou de catalyser le changement. Pire, elles contribuent à une production de connaissance fallacieuse basée sur de nombreux biais que nous analysons. En effet, malgré la masse impressionnante de recherches sur le changement et de pratiques du changement, la très grande majorité des projets de changement connaissent des échecs patents ou partiels.A partir de ce travail de revue critique et de ce constat, nous tentons d’explorer des alternatives à cette situation inféconde pour la recherche comme pour la pratique du changement. Une alternative possible pour avancer notre compréhension de ce phénomène est de changer radicalement la façon dont nous l’explorons, donc à innover heuristiquement. Nous adoptons donc une démarche multiniveaux (ontologique, épistémologique, méthodologique et théorique) basée sur une approche relationnelle radicale. Cette dernière nous permet de voir le phénomène du changement comme le produit de multiples réalités et de leurs relations. Analytiquement parlant, pour proposer une théorie relationnelle du changement, nous avons mené une étude de cas unique, longitudinale incluant des entretiens, des données secondaires et de l’observation directe (ethnographie). Cette recherche est basée sur une architecture abductive. Cette approche nous a permis, sans l’adoption de cadres théoriques a priori, de mettre en exergue que le changement est principalement dépendant de quatre dimensions (l’histoire, les dispositions, le champ et le quotidien). Pour donner du sens aux résultats empiriques, nous sommes retournés à la théorie en explorant trois de ces dimensions – l’histoire étant intrinsèquement présente dans ces dernières– pour proposer une lecture originale du changement. Nous sommes arrivés à la conclusion que la réussite du changement dépend essentiellement de l’attention portée à son initialisation par le biais des supports sociaux qui matérialisent le (non-)changement. Cette thèse contribue donc de manière singulière aux quatre des cinq dimensions les plus importantes d’un travail de recherche : ontologique, épistémologique, méthodologique et théorique en se basant sur une heuristique innovant

Dynamique moleculaire du methacrylate de methyle et etude par diffusion Raman de sa polymerisation radicalaire

INIST T 74699 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc