Metabolomic-Based Noninvasive Serum Test to Diagnose Nonalcoholic Steatohepatitis: Results From Discovery and Validation Cohorts

Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease worldwide and includes a broad spectrum of histologic phenotypes, ranging from simple hepatic steatosis or nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). While liver biopsy is the reference gold standard for NAFLD diagnosis and staging, it has limitations due to its sampling variability, invasive nature, and high cost. Thus, there is a need for noninvasive biomarkers that are robust, reliable, and cost effective. In this study, we measured 540 lipids and amino acids in serum samples from biopsy-proven subjects with normal liver (NL), NAFL, and NASH. Using logistic regression analysis, we identified two panels of triglycerides that could first discriminate between NAFLD and NL and second between NASH and NAFL. These noninvasive tests were compared to blinded histology as a reference standard. We performed these tests in an original cohort of 467 patients with NAFLD (90 NL, 246 NAFL, and 131 NASH) that was subsequently validated in a separate cohort of 192 patients (7 NL, 109 NAFL, 76 NASH). The diagnostic performances of the validated tests showed an area under the receiver operating characteristic curve, sensitivity, and specificity of 0.88 +/- 0.05, 0.94, and 0.57, respectively, for the discrimination between NAFLD and NL and 0.79 +/- 0.04, 0.70, and 0.81, respectively, for the discrimination between NASH and NAFL. When the analysis was performed excluding patients with glucose levels >136 mg/dL, the area under the receiver operating characteristic curve for the discrimination between NASH and NAFL increased to 0.81 +/- 0.04 with sensitivity and specificity of 0.73 and 0.80, respectively. Conclusion: The assessed noninvasive lipidomic serum tests distinguish between NAFLD and NL and between NASH and NAFL with high accuracy.Supported by the National Institutes of Health Blueprint for Neuroscience Research (R01AT001576 to S.C.L., J.M.M.), Agencia Estatal de Investigacion of the Ministerio de Economia, Industria y Competitividad (SAF2014-52097R to J.M.M.), CIBER Hepatic and Digestive Diseases and Instituto de Salud Carlos III (PIE14/0003 to J.M.M.), Etorgai 2015-Gobierno Vasco (ER-2015/00015 to R.M., I.M.A., C.A., A.C.), Plan de Promocion de la Innovacion 2015-Diputacion Foral de Bizkaia (6/12/IN/2015/00131 to A.C., C.A.), National Institute of Diabetes and Digestive and Kidney Diseases (RO1DK81410 to A.J.S.), and Czech Ministry of Health (RVO VFN64165 to L.V.)

Les syndicats d’enseignants au xxie siècle

Dans la plupart des pays, la mise en place d’un système scolaire public s’est accom­pagnée de la création de syndicats d’enseignants, qui se sont développés au xxe siècle, au fur et à mesure que l’offre éducative de l’État s’étendait et s’universalisait. Aujourd’hui, les syndicats d’enseignants restent souvent au centre de la discussion sur les changements éducatifs, étant considérés par certains comme un obstacle aux réformes nécessaires, tandis que d’autres voient en eux des défenseurs de valeurs et d’intérêts qui ne sont pas spécifiques aux enseignants, et un bastion de l’éducation publique. S’éloignant de cette logique polarisée, ce nouveau dossier de la Revue internationale d’éducation de Sèvres se propose de cerner, à travers 10 études de cas, les évolutions du syndicalisme enseignant en ce début de xxie siècle. Est-il affaibli, en retrait, ou connaît-il un processus de renouvellement et de recherche de nouvelles formes d’expression qui correspondraient aux transformations éducatives en cours ? À la lecture des articles, on constate une désaffection certaine des enseignants pour leurs syndicats, non seulement dans les pays en développement, marqués par de fortes inégalités sociales dans l’accès à l’éducation, mais aussi dans certains pays développés. Les revendications traditionnelles, en vue de meilleures conditions de travail, de rémunération et de défense des acquis sociaux, ne semblent plus suffire à susciter une adhésion durable. Mais on observe aussi une dynamique nouvelle : dans certains contextes, les syndicats proposent des réformes du système scolaire et du rôle des enseignants. D’autres formes de représentation et d´organisation émergent. Ces changements, encore embryonnaires, permettront-ils, dans les années qui viennent, de donner une nouvelle voix aux enseignants dans les écoles et dans la société ? In most countries, the founding of a state school system went along with the creation of teachers' unions, which developed in the twentieth century as state provision expanded and offered education for all. Teachers' unions tend to remain central to the issue of educational change, being seen by some as an obstacle to necessary reforms, while others see them as defenders of values and interests that are specific to teachers, and as a bastion of public education. Moving away from this polarised logic, the latest dossier of the Revue Internationale d’Education de Sèvres examines 10 case studies to identify changes in teacher unionism at the beginning of the 21st century. Is it weakened and taking a back seat, or is it undergoing a process of renewal and searching for new forms of expression to better fit current educational transformations? The articles highlight a certain disaffection of teachers for their unions, not only in developing countries where access to education is marked by strong social inequalities, but also in certain developed countries. Traditional demands for better working conditions, pay and the defence of existing employment rights no longer seem sufficient to generate lasting support. But a new dynamic is also evident: in some contexts, unions are proposing reforms of the school system and the role of teachers. Other forms of representation and organisation are emerging. Could these changes, still in their infancy, give teachers a new voice in schools and wider society in years to come? En la mayoría de los países, la instauración de un sistema escolar público se ha acompañado de la creación de sindicatos docentes que se han desarrollado a lo largo del siglo XX, conforme se extendía y universalizaba la oferta educativa del Estado. Hoy en día, los sindicatos docentes se mantienen a menudo en el centro de la discusión sobre los cambios educativos, siendo considerados por algunos como un obstáculo para las reformas necesarias mientras que otros ven en ellos unos defensores de los valores y de los interes que no son propios de los docentes, y un bastión de la educación pública. Alejándose de esta lógica polarizada, este nuevo dossier de la Revue internationale d’éducation de Sèvres se propone examinar, a través de unos diez estudios de casos, las evoluciones del sindicalismo docente en este principio del siglo XXI. ¿Se ha debilitado, hecho más discreto o conoce, por lo contrario, un proceso de renovación y de búsqueda de nuevas formas de expresión que correspondrían a las transformaciones educativas en curso? Al leer los artículos del presente número, podemos constatar una desafección creciente de los docentes para con sus sindicatos, no solo en los países en vía de desarrollo, marcados por unas fuertes desigualdades sociales en el acceso a la educación, sino también en algunos países desarrollados. Las reivindicaciones tradicionales para mejorar las condiciones de trabajo, de remuneración y de defensa de los derechos sociales no parecen bastar ahora para suscitar una adhesión duradera. Pero observamos también una dinámica nueva: en algunos contextos, los sindicatos proponen unas reformas del sistema escolar y del papel de los docentes. Otras formas de representación y de organización emergen. ¿Permitirán estos cambios, todavía en ciernes, en los años que vienen, dar una nueva voz a los docentes en las escuelas y en la sociedad

“What’s wrong with the seed?” A comparative examination of an empowering community-centered approach to recovery in community mental health

This cross-sectional group comparison aimed to examine whether personal empowerment, recovery and community integration were associated with the individual's participation in an empowering community-centered model of intervention. Ninety-three participants from an empowering community-centered community mental health organization were compared with a matched group of individuals from standard interventions of four equivalent organizations. Results showed that participants taking advantage of the empowering community-centered approach were more involved in high recovery-oriented programs; and attained higher levels of personal goals and hope, empowerment, and of community integration. An involvement in high recovery-oriented programs (supported employment or independent housing) revealed improved outcomes for the individual. In conclusion, the findings suggested a transformative impact of the empowering community-centered model both at the individual and the program level by altering the resource accessibility and social conditions for people who experience mental illness. The implications of findings for transforming community mental health practice are discussed in detail.Fundação para a Ciência e a Tecnologia (FCT

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88–1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. US National Institutes of Health and Operation Warp Spee