OBJECTIVES: Obeticholic acid (OCA) is a novel, rationally designed drug targeting the farnesoid X receptor. Efficacy and safety have been demonstrated in POISE, a phase III clinical trial comparing ...OCA regimens to placebo. OCA has been reported to significantly decrease alkaline phosphatase (ALP) and bilirubin compared to placebo thus having the potential to reduce the risk of progressing to end-stage liver disease (ESLD). This analysis evaluated the cost-effectiveness of OCA titration in PBC patients with inadequate response or intolerance to UDCA in France. METHODS: A Markov-model followed a cohort of 10,000 patients over lifetime. The model has two components: the liver disease component defining the PBC risk of progression based on ALP and bilirubin biomarkers; and the clinical endpoint component depicting progression through ESLD, including decompensated cirrhosis, liver transplantations and liver-related mortality. OCA titration (5 to lOmg) in combination with UDCA was compared to UDCA for patients with inadequate response. OCA titration monotherapy was compared to no treatment for patients intolerant to UDCA. Main input parameters were estimated from POISE, the Global PBC Study Group and literature. Direct costs for ESLD and utilities were derived from publications on hepatitis C virus (HCV). RESULTS: OCA titration was shown to be highly effective in preventing ESLD and liver-related mortality, but also more expensive. In patients with inadequate response, the ICER was estimated at €94,284 per quality-adjusted life year (QALY) gained; in patients intolerant to UDCA, the ICER was 682,818/QALY gained. At a willingness-to-pay threshold of €100,000/QALY gained, the probabilities of being cost-effective were 78% and 97%, respectively. These results were robust through deterministic and probabilistic analyses. CONCLUSIONS: From the collective perspective, treatment with OCA titration regimens can improve the health outcomes of PBC patients who currently do not have any alternative therapy and remain a cost-effective use of healthcare resource.
Three different stages of pig antral follicles have been studied in a granulosa-cell transcriptome analysis on nylon microarrays (1152 clones). The data have been generated from seven RNA follicle ...pools and several technical replicates were made. The objective of this paper was to state the feasibility of a transcriptomic protocol for the study of folliculogenesis in the pig. A statistical analysis was chosen, relying on the linear mixed model (LMM) paradigm. Low variability within technical replicates was hence checked with a LMM. Relevant genes that might be involved in the studied process were then selected. For the most significant genes, statistical methods such as principal component analysis and unsupervised hierarchical clustering were applied to assess their relevance, and a random forest analysis proved their predictive value. The selection of genes was consistent with previous studies and also allowed the identification of new genes whose role in pig folliculogenesis will be further investigated.
Aging and obesity induce complex transcriptomic changes in the liver, promoting the development of insulin resistance and type 2 diabetes. In spite of an increasing amount of studies on the role of ...aging and nutrient excess in metabolic disorders, the specific molecular events leading to insulin resistance are still poorly understood.
This study presents a comparative analysis of hepatic gene expression profiles between young adult C57BL/6J mice fed with a low- or a high-fat diet for 1 and 12 months. We evaluated the expression of a defined set of genes implicated in glucose and lipid metabolism as well as key nuclear receptors and their target genes, IGF1 signaling and clock genes.
Aging and short-term high-fat consumption induced insulin resistance, albeit through two distinct processes. Hepatic gene expression changes were more pronounced in the context of aging. We further analyzed expression profiles together with plasma parameters by principal component analysis with regard to diet condition.
Our results suggest that in the liver of C57BL/6J mice, the molecular mechanisms underlying high-fat feeding or aging which mediated insulin resistance were not identical.
Three different stages of pig antral follicles have been studied in a granulosa-cell transcriptome analysis on nylon microarrays (1152 clones). The data have been generated from seven RNA follicle ...pools and several technical replicates were made. The objective of this paper was to state the feasibility of a transcriptomic protocol for the study of folliculogenesis in the pig. A statistical analysis was chosen, relying on the linear mixed model (LMM) paradigm. Low variability within technical replicates was hence checked with a LMM. Relevant genes that might be involved in the studied process were then selected. For the most significant genes, statistical methods such as principal component analysis and unsupervised hierarchical clustering were applied to assess their relevance, and a random forest analysis proved their predictive value. The selection of genes was consistent with previous studies and also allowed the identification of new genes whose role in pig folliculogenesis will be further investigated.
Three different stages of pig antral follicles have been studied in a granulosa-cell transcriptome analysis on nylon microarrays (1152 clones). The data have been generated from seven RNA follicle ...pools and several technical replicates were made. The objective of this paper was to state the feasibility of a transcriptomic protocol for the study of folliculogenesis in the pig. A statistical analysis was chosen, relying on the linear mixed model (LMM) paradigm. Low variability within technical replicates was hence checked with a LMM. Relevant genes that might be involved in the studied process were then selected. For the most significant genes, statistical methods such as principal component analysis and unsupervised hierarchical clustering were applied to assess their relevance, and a random forest analysis proved their predictive value. The selection of genes was consistent with previous studies and also allowed the identification of new genes whose role in pig folliculogenesis will be further investigated.
Cet article traite de l'existence ou non d'un effet de la Peste noire sur l'art du milieu du XIVe siècle. Une profonde mutation artistique consécutive à la Peste avait été régulièrement mise en avant ...par l'historiographie, notamment par un important ouvrage de Millard Meiss publié en 1951. Mais les recherches ultérieures avaient montré que les liens entre le terrible évènement et les mutations de l'art de la fin du Moyen Âge n’avait rien d’évident, et que plusieurs phénomènes lus comme des réactions des artistes à la catastrophe, comme l'émergence d'iconographies macabres ou terrifiantes, préexistaient en fait à l'épidémie. Jérôme Baschet part du cas des Jugements Derniers, dont celui du Camposanto de Pise est antérieur à 1347, avant de revenir sur les différents liens de causalité qui ont pu être inférés entre la Peste et les images : ils montrent qu’ils sont globalement ténus et questionnent la notion d'« art de crise ». Plus largement, il utilise ce cas emblématique pour proposer des éléments de méthodes et un cadre de réflexion sur la relation entre l’art et l’évènement.
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