Hepatitis C viral evolution in genotype 1 treatment-naïve and treatment-experienced patients receiving telaprevir-based therapy in clinical trials

Background: In patients with genotype 1 chronic hepatitis C infection, telaprevir (TVR) in combination with peginterferon and ribavirin (PR) significantly increased sustained virologic response (SVR) rates compared with PR alone. However, genotypic changes could be observed in TVR-treated patients who did not achieve an SVR. Methods: Population sequence analysis of the NS3•4A region was performed in patients who did not achieve SVR with TVR-based treatment. Results: Resistant variants were observed after treatment with a telaprevir-based regimen in 12% of treatment-naïve patients (ADVANCE; T12PR arm), 6% of prior relapsers, 24% of prior partial responders, and 51% of prior null responder patients (REALIZE, T12PR48 arms). NS3 protease variants V36M, R155K, and V36M+R155K emerged frequently in patients with genotype 1a and V36A, T54A, and A156S/T in patients with genotype 1b. Lower-level resistance to telaprevir was conferred by V36A/M, T54A/S, R155K/T, and A156S variants; and higher-level resistance to telaprevir was conferred by A156T and V36M+R155K variants. Virologic failure during telaprevir treatment was more common in patients with genotype 1a and in prior PR nonresponder patients and was associated with higher-level telaprevir-resistant variants. Relapse was usually associated with wild-type or lower-level resistant variants. After treatment, viral populations were wild-type with a median time of 10 months for genotype 1a and 3 weeks for genotype 1b patients. Conclusions: A consistent, subtype-dependent resistance profile was observed in patients who did not achieve an SVR with telaprevir-based treatment. The primary role of TVR is to inhibit wild-type virus and variants with lower-levels of resistance to telaprevir. The complementary role of PR is to clear any remaining telaprevir-resistant variants, especially higher-level telaprevir-resistant variants. Resistant variants are detectable in most patients who fail to achieve SVR, but their levels decline over time after treatment

Question answering on web data : the QA evaluation in Quaero

International audienceIn the QA and information retrieval domains, progress has been assessed via evaluation campaigns(Clef, Ntcir, Equer, Trec). In these evaluations, the systems handle independent questions and should provide one answer to each question, extracted from textual data, for both open domain and restricted domain. Quæro is a program promoting research and industrial innovation on technologies for automatic analysis and classification of multimedia and multilingual documents. Among the many research areas concerned by Quæro. The Quaero project organized a series of evaluations of Question Answering on Web Data systems in 2008 and 2009. For each language, English and French the full corpus has a size of around 20Gb for 2.5M documents. We describe the task and corpora, and especially the methodologies used in 2008 to construct the test of question and a new one in the 2009 campaign. Six types of questions were addressed, factual, Non-factual(How, Why, What), List, Boolean. A description of the participating systems and the obtained results is provided. We show the difficulty for a question-answering system to work with complex data and questions

Avidity sequencing of whole genomes from retinal degeneration pedigrees identifies causal variants

Whole genome sequencing has been an effective tool in the discovery of variants that cause rare diseases. In this study, we determined the suitability of a novel avidity sequencing approach for rare disease applications. We built a sample to results workflow, combining this sequencing technology with standard library preparation kits, analysis workflows, and interpretation tools. We applied the workflow to ten pedigrees with inherited retinal degeneration (IRD) phenotype. Candidate variants of interest identified through whole genome sequencing were further evaluated using segregation analysis in the additional family members. Potentially causal variants in known IRD genes were detected in five of the ten cases. These high confidence variants were found in ABCA4, CERKL, MAK, PEX6 and RDH12 genes associated with retinal degeneration, that could be sufficient to cause pathology. Pending confirmatory clinical evaluation, we observed a 50% diagnostic yield, consistent with previously reported outcomes of IRD patient analysis. The study confirms that avidity sequencing is effective in detection of causal variants when used for whole genome sequencing in rare disease applications

Investigation of the Performance of the New Orleans Flood Protection System in Hurricane Katrina on August 29, 2005: Volume 1

This report presents the results of an investigation of the performance of the New Orleans regional flood protection system during and after Hurricane Katrina, which struck the New Orleans region on August 29, 2005. This event resulted in the single most costly catastrophic failure of an engineered system in history. Current damage estimates at the time of this writing are on the order of $100 to$200 billion in the greater New Orleans area, and the official death count in New Orleans and southern Louisiana at the time of this writing stands at 1,293, with an additional 306 deaths in nearby southern Mississippi. An additional approximately 300 people are currently still listed as “missing”; it is expected that some of these missing were temporarily lost in the shuffle of the regional evacuation, but some of these are expected to have been carried out into the swamps and the Gulf of Mexico by the storm’s floodwaters, and some are expected to be recovered in the ongoing sifting through the debris of wrecked homes and businesses, so the current overall regional death count of 1,599 is expected to continue to rise a bit further. More than 450,000 people were initially displaced by this catastrophe, and at the time of this writing more than 200,000 residents of the greater New Orleans metropolitan area continue to be displaced from their homes by the floodwater damages from this storm event. This investigation has targeted three main questions as follow: (1) What happened?, (2) Why?, and (3) What types of changes are necessary to prevent recurrence of a disaster of this scale again in the future? To address these questions, this investigation has involved: (1) an initial field reconnaissance, forensic study and data gathering effort performed quickly after the arrival of Hurricanes Katrina (August 29, 2005) and Rita (September 24, 2005), (2) a review of the history of the regional flood protection system and its development, (3) a review of the challenging regional geology, (4) detailed studies of the events during Hurricanes Katrina and Rita, as well as the causes and mechanisms of the principal failures, (4) studies of the organizational and institutional issues affecting the performance of the flood protection system, (5) observations regarding the emergency repair and ongoing interim levee reconstruction efforts, and (6) development of findings and preliminary recommendations regarding changes that appear warranted in order to prevent recurrence of this type of catastrophe in the future. In the end, it is concluded that many things went wrong with the New Orleans flood protection system during Hurricane Katrina, and that the resulting catastrophe had it roots in three main causes: (1) a major natural disaster (the Hurricane itself), (2) the poor performance of the flood protection system, due to localized engineering failures, questionable judgments, errors, etc. involved in the detailed design, construction, operation and maintenance of the system, and (3) more global “organizational” and institutional problems associated with the governmental and local organizations responsible for the design, construction, operation, maintenance and funding of the overall flood protection system

Description d'une série de 31 cas de PAVM à Stenotrophomonas maltophilia dans le service de réanimation de l'hôpital de Versailles (représentations cliniques, schémas thérapeutiques et évolutions)

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Consommer moins de médicaments et mieux. Un impératif éducationnel et environnemental

La surprescription des médicaments nuit à la qualité de vie et à la sécurité des patients. Elle impacte également le système de santé et l’environnement. Selon le rapport « Décarboner la santé pour soigner durablement » publié par The Shift Project en 2023, les achats de médicaments sont le 1er poste d’émission de gaz à effet de serre (GES) dans le secteur de la santé avec plus de 14.5 millions de tonnes de CO2. Cela représente 29% de la totalité des émissions du secteur. Pour un usage rationnel des médicaments et face aux enjeux liés au développement durable, la déprescription émerge comme une solution. C’est un processus qui vise à identifier et réduire voire arrêter les médicaments surprescrits. Mais elle reste trop peu courante dans la pratique médicale. Dans cet article, nous proposons quelques pistes et leviers d’action pouvant permettre de changer les habitudes des professionnels de santé actuels et futurs en matière de déprescription des médicaments et ainsi promouvoir le concept de soins de santé durables.[Using medications better by using less. An educational and environmental imperative] Overprescription of medications undermines patients’ quality of life and safety. It also impacts the healthcare system and the environment. According to the report “Decarbonizing Health for Better Care” published by The Shift Project in 2023, medication purchases constitute the leading source of greenhouse gas emissions in the healthcare sector, accounting for over 14.5 million tons of CO2 . This represents 29% of the sector’s total emissions. To implement a rational use of medication and in response to sustainable development challenges, deprescribing emerges as a solution. It is a process aimed at identifying, reducing, or even discontinuing overprescribed medications. However, its implementation in routine clinical practice remains limited. In this article, we propose actions and strategies that could foster changes in the habits of current and future healthcare professionals regarding medication deprescribing, thus promoting the concept of sustainable healthcare

Une étude par traitement automatique de la prosodie du français à la frontière des domaines roman et germanique

National audienc