123 research outputs found
Critique de la DĂ©claration universelle des Droits de lâhomme
Peut-on critiquer la DĂ©claration universelle des Droits de lâhomme (DUDH) ? On peut lĂ©gitimement se poser la question quand on Ă©coute le concert de louanges quâon adresse habituellement Ă cette cĂ©lĂšbre rĂ©solution, votĂ©e par lâAssemblĂ©e gĂ©nĂ©rale de lâOrganisation des Nations unies (ONU) le 10 dĂ©cembre 1948. Selon RenĂ© Cassin, qui en est lâun des principaux inspirateurs, « quelque chose de nouveau est entrĂ© avec elle dans le monde : elle est le premier document de valeur Ă©thique adoptĂ© par lâen..
Les atteintes aux droits fondamentaux par lâĂ©tat de siĂšge et lâĂ©tat dâurgence
« Danton venait de se lever ; il avait vivement reculĂ© sa chaise.â Ăcoutez, cria-t-il. Il nây a quâune urgence, la RĂ©publique en danger. Je ne connais quâune chose, dĂ©livrer la France de lâennemi. Pour cela tous les moyens sont bons. ». Ces propos, rapportĂ©s par Victor Hugo, montrent que lâidĂ©e que lâurgence justifie la mise Ă lâĂ©cart de la lĂ©galitĂ© ordinaire ne date pas dâhier. Elle remonte au moins Ă la Convention. La nouveautĂ©, câest que lâurgence sâest banalisĂ©e depuis la seconde moitiĂ© d..
Le droit de lâenfant au respect de son « intĂ©rĂȘt supĂ©rieur ». Critique rĂ©publicaine de la dĂ©rive individualiste du droit civil français
La famille est officiellement prĂ©sentĂ©e comme lâ« un des piliers » des sociĂ©tĂ©s occidentales. Il sâagit pourtant dâun pilier bien fragile, dont les assises ont Ă©tĂ© profondĂ©ment Ă©branlĂ©es par lâĂ©volution des mĆurs. Face Ă ce constat, difficilement niable, la France a rĂ©agi en adaptant son droit aux nouvelles aspirations des citoyens. Elle a donc entrepris de « rĂ©nover le droit de la famille » . Mais elle semble peiner dans la tĂąche quâelle sâest fixĂ©e de reconstruire celui-ci sur des « repĂšres..
Effets dâune supplĂ©mentation en iode et sĂ©lĂ©nium de la vache gestante sur les statuts en oligo-Ă©lĂ©ments et immunitaire du veau nouveau-nĂ©
Le sĂ©lĂ©nium est un anti-oxydant qui intervient dans la constitution des sĂ©lĂ©noenzymes (glutathion peroxydases, GSH-Px) et qui contrĂŽle lâactivation des neutrophiles, macrophages et des lymphocytes B. En synergie avec les iodures, il participe Ă©galement Ă la rĂ©gulation de la fonction thyroĂŻdienne. Etant donnĂ© lâefficacitĂ© du transfert transplacentaire de ces 2 oligo-Ă©lĂ©ments, lâobjectif de cette Ă©tude Ă©tait dâĂ©valuer le bĂ©nĂ©fice dâune supplĂ©mentation en iode et sĂ©lĂ©nium pendant la pĂ©riode du prĂ©partum chez les veaux nouveau-nĂ©s. Au total, 12 vaches gestantes issues dâun Ă©levage allaitant de la Haute-Vienne ont Ă©tĂ© rĂ©parties en 2 lots : un lot tĂ©moin de 5 vaches (lot A) et un lot de 7 vaches (lot B) supplĂ©mentĂ©es par voie orale par du sĂ©lĂ©nite de sodium (400 mg) et de lâiodure de calcium (1 200 mg) 20 Ă 35 jours avant la date prĂ©vue du part. Les activitĂ©s de la GSH-Px Ă©rythrocytaire (GSH-Pxe) et les concentrations plasmatiques en iode inorganique et en T4 totales ont Ă©tĂ© mesurĂ©es avant le traitement (J0) et le jour du vĂȘlage chez les femelles gestantes ainsi que chez les veaux Ă la naissance et 24 h-36 h aprĂšs. Chez ces derniers, la protĂ©inĂ©mie et les concentrations plasmatiques en IgG ont aussi Ă©tĂ© dĂ©terminĂ©es. MalgrĂ© une situation de double carence en sĂ©lĂ©nium et en iode caractĂ©risĂ©e par des activitĂ©s GSH-Pxe et des concentrations plasmatiques en iode inorganique faibles conduisant Ă une hypothyroĂŻdie sub-clinique chez 8 femelles gestantes, la supplĂ©mentation a permis dâamĂ©liorer le statut sĂ©lĂ©nique et de maintenir la fonction thyroĂŻdienne au vĂȘlage chez les mĂšres. Chez les veaux, bien quâaucune diffĂ©rence significative nâait pu ĂȘtre obtenue entre les 2 lots, les activitĂ©s de GSH-Px Ă la naissance et 24 h-36 h aprĂšs ainsi que le statut immunitaire des veaux de 1 jour (reflĂ©tĂ© par la protĂ©inĂ©mie et la concentration plasmatique en IgG) ont Ă©tĂ© positivement corrĂ©lĂ©es avec le statut sĂ©lĂ©nique des mĂšres au vĂȘlage. Ces rĂ©sultats suggĂšrent que lâadministration de sĂ©lĂ©nium et dâiode en prĂ©partum chez la vache allaitante peut augmenter les dĂ©fenses immunitaires des veaux en amĂ©liorant le statut sĂ©lĂ©nique maternel
Evaluation of the dystrophin carboxy-terminal domain for micro-dystrophin gene therapy in cardiac and skeletal muscles in the DMDmdx rat model
Duchenne muscular dystrophy (DMD) is a muscle wasting disorder caused by mutations in the gene encoding dystrophin. Gene therapy using micro-dystrophin (MD) transgenes and recombinant adeno-associated virus (rAAV) vectors hold great promise. To overcome the limited packaging capacity of rAAV vectors, most MD do not include dystrophin carboxy-terminal (CT) domain. Yet, the CT domain is known to recruit α1- and ÎČ1-syntrophins and α-dystrobrevin, a part of the dystrophin-associated protein complex (DAPC), which is a signaling and structural mediator of muscle cells. In this study, we explored the impact of inclusion of the dystrophin CT domain on ÎR4-23/ÎCT MD (MD1), in DMDmdx rats, which allows for relevant evaluations at muscular and cardiac levels. We showed by LC-MS/MS that MD1 expression is sufficient to restore the interactions at a physiological level of most DAPC partners in skeletal and cardiac muscles, and that inclusion of the CT domain increases the recruitment of some DAPC partners at supra-physiological levels. In parallel, we demonstrated that inclusion of the CT domain does not improve MD1 therapeutic efficacy on DMD muscle and cardiac pathologies. Our work highlights new evidences of the therapeutic potential of MD1 and strengthens the relevance of this candidate for gene therapy of DMD
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 â„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/)
A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing
Purpose
Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the âClinVar low-hanging fruitâ reanalysis, reasons for the failure of previous analyses, and lessons learned.
Methods
Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted.
Results
We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency).
Conclusion
The âClinVar low-hanging fruitâ analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock
9. La Fonction publique territoriale en 1991
Lebreton Gilles. 9. La Fonction publique territoriale en 1991. In: Annuaire des collectivités locales. Tome 12, 1992. pp. 397-411
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