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Jayol A.,University Paris Diderot | Janvier F.,University Paris Diderot | Guillard T.,University Paris Diderot | Guillard T.,Reims Champagne Ardennes University | And 6 more authors.
Journal of Antimicrobial Chemotherapy

Objectives: To determine the genetic location and environment of the qnrA6 gene in Proteus mirabilis PS16 where it was first described and to characterize the quinolone resistance qnrA6 confers. Methods: Transformation experiments and Southern blotting were performed for plasmid and genomic DNA of P. mirabilis PS16 to determine the qnrA6 location. Combinatorial PCRs with primers in qnrA6 and genes usually surrounding qnrA genes were used to determine the genetic environment. The qnrA6 coding region, including or not the promoter region, was cloned into vectors pTOPO and pBR322 and the MICs of six quinolones were measured for transformants of Escherichia coli TOP10 and P. mirabilis ATCC 29906 RifR. Results: QnrA6 was shown to be chromosomally encoded in P. mirabilis PS16 and its genetic environment was 81%-87% similar to that of qnrA2 in the Shewanella algae chromosome. The 5138 bp region up- and downstream of qnrA6 contained an IS10 sequence surrounded by two ISCR1. This resulted in qnrA6 being displaced 1.9 kb from its native promoter but supplied a promoter present in ISCR1. qnrA6 cloned into pTOPO and pBR322 conferred a 4-32-fold increase in fluoroquinolone MICs when expressed in E. coli but only 2-3-fold in P. mirabilis. When including the promoter region, a further increase in resistance was observed in both species, reaching MIC values above clinical breakpoints for only P. mirabilis. Conclusions: QnrA6 is the first chromosomally located qnrA gene described in Enterobacteriaceae. The quinolone resistance conferred by qnrA6 depends on the proximity of an efficient promoter and the host strain where it is expressed. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Source

Blot G.,Paris-Sorbonne University | Saurel P.,Paris-Sorbonne University | Rousseaux F.,Reims Champagne Ardennes University
Proceedings - 2014 International Conference on Control, Decision and Information Technologies, CoDIT 2014

This work relies on connectivism and focuses on the interactions between learners and resources of e-learning materials aiming to discover patterns [13]. The theory of connectivism mainly tells, that knowledge is available through a network of connections. Based on Social Network Analysis, our Time-graph representation uses temporal metrics [12]. Even though longitudinal networks are the most widely used representations of temporal factors, here we considerer time-distribution criterion within a single graph. Path following techniques are not new, but the Time-graph configuration makes it in a specific fashion, that orders resources over a timeline. A resource has not the same impact at the start or at the end of a course. Hence given a specific instant, the Time-graph can inform learners, about important resources. © 2014 IEEE. Source

De Mestier L.,Beaujon University Hospital | De Mestier L.,Reims Champagne Ardennes University | Gaujoux S.,Beaujon Hospital | Gaujoux S.,University Paris Diderot | And 17 more authors.
Annals of Surgery

Background: Management of pancreatic neuroendocrine tumors (PNETs) associated with von Hippel-Lindau disease (VHL) is challenging because of the malignant potential and difficulty in predicting prognosis. Objective: Compare the long-term outcome of resected VHL-PNET and sporadic PNET. Methods: Data of all patients with VHL (n = 23) operated on for nonmetastatic PNET were reviewed. Patient characteristics and recurrence-free survival rates were compared with those in patients operated on for sporadic PNET, matched for tumor size, stage, and Ki-67 index. Results: Patients in both groups had similar demographic characteristics, except that patients with VHL were younger (36 vs 56 years, P < 0.0001). Median tumor size was 30 mm. Median Ki-67 index was 3% and 4% in the VHL and sporadic groups (P = 0.95), respectively, and lymph node metastases were present in 43% and 30% of cases, respectively (P = 0.45). Sixteen (70%) patients with VHL had multiple PNET; lesions less than 15 mm were left in place in 11 patients. Median postoperative follow-up was 107 months (interquartile range, 57-124 months) and 71 months (interquartile range, 58-131 months) in the VHL and control groups, respectively. Median recurrence-free survival could not have been estimated in the VHL group due to the low number of events (hazard ratio, 5.6; 95% confidence interval, 1.4-22.6; P = 0.013). Five patients with VHL died (3 from VHL-related tumors including 1 from PNET), whereas only one control patient died due to unrelated causes. Conclusions: The long-term outcome of resected VHL-PNET is better than that of sporadic PNET. PNET less than 15 mm left in place did not progress. A parenchyma-sparing surgical strategy seems appropriate in patients with VHL-PNET, who may develop more life-threatening tumors of other organs. © 2015 Wolters Kluwer Health, Inc. Source

Raimond E.,Reims Champagne Ardennes University | Ballester M.,University Pierre and Marie Curie | Hudry D.,University of Burgundy | Bendifallah S.,University Pierre and Marie Curie | And 3 more authors.
Gynecologic Oncology

Objective The aim of this study is to assess the impact of sentinel lymph node (SLN) mapping and ultrastaging on the therapeutic management of early-stage endometrial cancer. Methods This retrospective multicenter study covered the period from January 2000 through December 2012 and included 304 women with presumed low- or intermediate-risk endometrial cancer. Node staging, histology results, and the effects of both on therapeutic management were assessed in two groups: those who underwent the SLN mapping and ultrastaging procedure and those treated in accordance with French guidelines. Results The SLN procedure detected metastatic lymph nodes in three times more women than lymphadenectomy did (16.2% versus 5.1%, p = 0.03). Specifically, it found 7 macrometastases (5.1%) and 15 micrometastases (11%); 11 of the latter (8.1%) were detected by serial sectioning and immunohistochemistry (IHC), that is, pathologic ultrastaging. The SLN biopsy false-negative rate was 0% (95% CI: 0-1.6%). This ultrastaging enabled us to modify the adjuvant therapy for half the patients. Women with micrometastases detected by the SLN procedure were treated with external beam radiotherapy (EBRT), while those whose SLN biopsies were negative received vaginal brachytherapy (VBT) or clinical follow-up. SLN biopsies had no impact on recurrence-free survival. Conclusion SLN mapping and ultrastaging improved staging and made it possible to adapt adjuvant therapy to risk of recurrence. © 2014 Elsevier Inc. Source

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