Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Technical Report: CSVM Ecosystem

The CSVM format is derived from CSV format and allows the storage of tabular like data with a limited but extensible amount of metadata. This approach could help computer scientists because all information needed to uses subsequently the data is included in the CSVM file and is particularly well suited for handling RAW data in a lot of scientific fields and to be used as a canonical format. The use of CSVM has shown that it greatly facilitates: the data management independently of using databases; the data exchange; the integration of RAW data in dataflows or calculation pipes; the search for best practices in RAW data management. The efficiency of this format is closely related to its plasticity: a generic frame is given for all kind of data and the CSVM parsers don't make any interpretation of data types. This task is done by the application layer, so it is possible to use same format and same parser codes for a lot of purposes. In this document some implementation of CSVM format for ten years and in different laboratories are presented. Some programming examples are also shown: a Python toolkit for using the format, manipulating and querying is available. A first specification of this format (CSVM-1) is now defined, as well as some derivatives such as CSVM dictionaries used for data interchange. CSVM is an Open Format and could be used as a support for Open Data and long term conservation of RAW or unpublished data.Comment: 31 pages including 2p of Anne

Trilingual conversations: a window into multicompetence

A recurrent theme in the literature on trilingual language use is the question of whether there is a specific “trilingual competence.” In this paper we consider this question in the light of codeswitching patterns in two dyadic trilingual conversations between a mother and daughter conducted in (Lebanese) Arabic, French, and English. Quantitative and qualitative analysis of codeswitching in both conversants shows that, despite the fact that both subjects are fluent in all three languages, uses of switching are significantly different for mother and daughter across a number of features, including relative frequency of different switch types, and the incidence of hybrid constructions involving items from two or more languages. The subjects appear to display qualitatively distinct profiles of competence in the trilingual mode. This in turn leads to the conclusion that the facts of trilingual language use are best characterized in terms of “multicompetence” (Cook, 1991). The paper concludes with some further reflections on the uniqueness of trilingual language use (an “old chestnut” in trilingualism research, cf. Klein, 1995)

Quadratic forms and linear algebraic groups

Topics discussed at the workshop Quadratic Forms and Linear Algebraic Groups included besides the algebraic theory of quadratic and Hermitian forms and their Witt groups several aspects of the theory of linear algebraic groups and homogeneous varieties, as well as some arithmetic aspects pertaining to the theory of quadratic forms over function fields over local fields

Proteomic analyses reveal misregulation of LIN28 expression and delayed timing of glial differentiation in human iPS cells with MECP2 loss-of-function.

Rett syndrome (RTT) is a pervasive developmental disorder caused by mutations in MECP2. Complete loss of MECP2 function in males causes congenital encephalopathy, neurodevelopmental arrest, and early lethality. Induced pluripotent stem cell (iPSC) lines from male patients harboring mutations in MECP2, along with control lines from their unaffected fathers, give us an opportunity to identify some of the earliest cellular and molecular changes associated with MECP2 loss-of-function (LOF). We differentiated iPSC-derived neural progenitor cells (NPCs) using retinoic acid (RA) and found that astrocyte differentiation is perturbed in iPSC lines derived from two different patients. Using highly stringent quantitative proteomic analyses, we found that LIN28, a gene important for cell fate regulation and developmental timing, is upregulated in mutant NPCs compared to WT controls. Overexpression of LIN28 protein in control NPCs suppressed astrocyte differentiation and reduced neuronal synapse density, whereas downregulation of LIN28 expression in mutant NPCs partially rescued this synaptic deficiency. These results indicate that the pathophysiology of RTT may be caused in part by misregulation of developmental timing in neural progenitors, and the subsequent consequences of this disruption on neuronal and glial differentiation