Comparison of accuracy of fibrosis degree classifications by liver biopsy and non-invasive tests in chronic hepatitis C

<p>Abstract</p> <p>Background</p> <p>Non-invasive tests have been constructed and evaluated mainly for binary diagnoses such as significant fibrosis. Recently, detailed fibrosis classifications for several non-invasive tests have been developed, but their accuracy has not been thoroughly evaluated in comparison to liver biopsy, especially in clinical practice and for Fibroscan. Therefore, the main aim of the present study was to evaluate the accuracy of detailed fibrosis classifications available for non-invasive tests and liver biopsy. The secondary aim was to validate these accuracies in independent populations.</p> <p>Methods</p> <p>Four HCV populations provided 2,068 patients with liver biopsy, four different pathologist skill-levels and non-invasive tests. Results were expressed as percentages of correctly classified patients.</p> <p>Results</p> <p>In population #1 including 205 patients and comparing liver biopsy (reference: consensus reading by two experts) and blood tests, Metavir fibrosis (F_M) stage accuracy was 64.4% in local pathologists vs. 82.2% (p < 10^-3) in single expert pathologist. Significant discrepancy (≥ 2F_Mvs reference histological result) rates were: Fibrotest: 17.2%, FibroMeter^2G: 5.6%, local pathologists: 4.9%, FibroMeter^3G: 0.5%, expert pathologist: 0% (p < 10^-3). In population #2 including 1,056 patients and comparing blood tests, the discrepancy scores, taking into account the error magnitude, of detailed fibrosis classification were significantly different between FibroMeter^2G(0.30 ± 0.55) and FibroMeter^3G(0.14 ± 0.37, p < 10^-3) or Fibrotest (0.84 ± 0.80, p < 10^-3). In population #3 (and #4) including 458 (359) patients and comparing blood tests and Fibroscan, accuracies of detailed fibrosis classification were, respectively: Fibrotest: 42.5% (33.5%), Fibroscan: 64.9% (50.7%), FibroMeter^2G: 68.7% (68.2%), FibroMeter^3G: 77.1% (83.4%), p < 10^-3(p < 10^-3). Significant discrepancy (≥ 2 F_M) rates were, respectively: Fibrotest: 21.3% (22.2%), Fibroscan: 12.9% (12.3%), FibroMeter^2G: 5.7% (6.0%), FibroMeter^3G: 0.9% (0.9%), p < 10^-3(p < 10^-3).</p> <p>Conclusions</p> <p>The accuracy in detailed fibrosis classification of the best-performing blood test outperforms liver biopsy read by a local pathologist, i.e., in clinical practice; however, the classification precision is apparently lesser. This detailed classification accuracy is much lower than that of significant fibrosis with Fibroscan and even Fibrotest but higher with FibroMeter^3G. FibroMeter classification accuracy was significantly higher than those of other non-invasive tests. Finally, for hepatitis C evaluation in clinical practice, fibrosis degree can be evaluated using an accurate blood test.</p

N° 22 — GENDREAU-MASSALOUX Michèle. Recteur des académies d'Orléans-Tours (1981-1984) et de Paris (1989-1998)

Gendreau-Massaloux Michèle, Stern Marie, Gallois Joëlle, Mignaval Pierre. N° 22 — GENDREAU-MASSALOUX Michèle. Recteur des académies d'Orléans-Tours (1981-1984) et de Paris (1989-1998). In: Témoins et acteurs des politiques de l'éducation depuis la Libération. Tome 5 - Inventaire de cinquante entretiens. La fonction rectorale. Paris : Institut national de recherche pédagogique, 2008. pp. 79-80. (Témoins et acteurs des politiques de l'éducation, 1

N° 22 — GENDREAU-MASSALOUX Michèle. Recteur des académies d'Orléans-Tours (1981-1984) et de Paris (1989-1998)

Gendreau-Massaloux Michèle, Stern Marie, Gallois Joëlle, Mignaval Pierre. N° 22 — GENDREAU-MASSALOUX Michèle. Recteur des académies d'Orléans-Tours (1981-1984) et de Paris (1989-1998). In: Témoins et acteurs des politiques de l'éducation depuis la Libération. Tome 5 - Inventaire de cinquante entretiens. La fonction rectorale. Paris : Institut national de recherche pédagogique, 2008. pp. 79-80. (Témoins et acteurs des politiques de l'éducation, 1

Oblivious and Semi-Oblivious Boundedness for Existential Rules

International audienceWe study the notion of boundedness in the contextof positive existential rules, that is, whether thereexists an upper bound to the depth of the chase pro-cedure, that is independent from the initial instance.By focussing our attention on the oblivious and thesemi-oblivious chase variants, we give a character-ization of boundedness in terms of FO-rewritabilityand chase termination. We show that it is decidableto recognize if a set of rules is bounded for several classes and outline the complexity of the problem

Quick and efficient approach to develop genomic resources in orphan species: Application in Lavandula angustifolia.

Next-Generation Sequencing (NGS) technologies, by reducing the cost and increasing the throughput of sequencing, have opened doors to generate genomic data in a range of previously poorly studied species. In this study, we propose a method for the rapid development of a large-scale molecular resources for orphan species. We studied as an example the true lavender (Lavandula angustifolia Mill.), a perennial sub-shrub plant native from the Mediterranean region and whose essential oil have numerous applications in cosmetics, pharmaceuticals, and alternative medicines. The heterozygous clone "Maillette" was used as a reference for DNA and RNA sequencing. We first built a reference Unigene, compound of coding sequences, thanks to de novo RNA-seq assembly. Then, we reconstructed the complete genes sequences (with introns and exons) using an Unigene-guided DNA-seq assembly approach. This aimed to maximize the possibilities of finding polymorphism between genetically close individuals despite the lack of a reference genome. Finally, we used these resources for SNP mining within a collection of 16 commercial lavender clones and tested the SNP within the scope of a genetic distance analysis. We obtained a cleaned reference of 8, 030 functionally in silico annotated genes. We found 359K polymorphic sites and observed a high SNP frequency (mean of 1 SNP per 90 bp) and a high level of heterozygosity (more than 60% of heterozygous SNP per genotype). On overall, we found similar genetic distances between pairs of clones, which is probably related to the out-crossing nature of the species and the restricted area of cultivation. The proposed method is transferable to other orphan species, requires little bioinformatics resources and can be realized within a year. This is also the first reported large-scale SNP development on Lavandula angustifolia. All the genomics resources developed herein are publicly available and provide a rich pool of molecular resources to explore and exploit lavender genetic diversity in breeding programs

Optimization and robustness of blood tests for liver fibrosis and cirrhosis.

International audienceOBJECTIVES: To optimize the performance and feasibility of fibrosis blood tests and evaluate their robustness. DESIGN AND METHODS: The derivation population included 1056 HCV patients with liver biopsy and blood markers. Validation populations included 984 patients with various viral hepatitis causes, and Fibroscan and/or liver biopsy and/or blood markers. RESULTS: The bootstrap method validated the markers of the original FibroMeter(2G), but not those of Fibrotest and Hepascore, and provided a hyaluronate-free FibroMeter(3G). AUROCs for significant fibrosis were: FibroMeter(2G): 0.853 vs. FibroMeter(3G): 0.851, p=0.489. Compared to FibroMeter(2G), FibroMeter(3G) had a significantly higher patient rate with predictive values ≥90% for significant fibrosis. Accuracy for fibrosis stage classification was: Fibrotest: 37.9%, FibroMeter(2G): 74.9%, and FibroMeter(3G): 86.9% (p<10(-3)). CONCLUSION: The bootstrap method validated FibroMeter(2G) and provided a cheaper and more feasible hyaluronate-free FibroMeter(3G) with comparable performance. Compared to binary diagnosis, fibrosis stage classification increased discrimination, with an increased accuracy to 87% for FibroMeter(3G)

Prime Editing in the model plant Physcomitrium patens and its potential in the tetraploid potato

International audienceSince its discovery and first applications for genome editing in plants, the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technology has revolutionized plant research and precision crop breeding. Although the classical CRISPR-Cas9 system is a highly efficient tool for disruptive targeted mutagenesis, this system is mostly inefficient for the introduction of precise and predictable nucleotide substitutions. Recently, Prime Editing technology has been developed, allowing the simultaneous generation of nucleotide transitions and transversions but also short defined indels. In this study, we report on the successful use of Prime Editing in two plants of interest: the plant model Physcomitrium patens and the tetraploid and highly heterozygous potato (Solanum tuberosum). In both cases editing rates were lower than with other CRISPR-Cas9 based techniques, but we were able to successfully introduce nucleotide transversions into targeted genes, a unique feature of Prime Editing. Additionally, the analysis of potential off-target mutation sites in P. patens suggested very high targeting fidelity in this organism. The present work paves the way for the use Prime Editing in Physcomitrium patens and potato, however highlighting the limitations that need to be overcome for more efficient precision plant breeding