Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Aims: The aims of this study were to compare short-and long-term outcomes for clinical T2N0 oesophageal cancer with analysis of (i) primary surgery (S) versus neoadjuvant therapy plus surgery (NS), (ii) squamous cell carcinoma and adenocarcinoma subsets; and (iii) neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy.Methods: Data were collected from 30 European centres from 2000 to 2010. Among 2944 included patients, 355 patients (12.1%) had cT2N0 disease; 285 (S) and 70 (NS), were compared in terms of short-and long-term outcomes. Propensity score matching analyses were used to compensate for differences in baseline characteristics.Results: No significant differences between the groups were shown in terms of in hospital morbidity and mortality. Nodal disease was observed in 50% of S-group at the time of surgery, with 20% pN2/N3. Utilisation of neoadjuvant therapy was associated with significant tumour downstaging as reflected by increases in pT0, pN0 and pTNM stage 0 disease, this effect was further enhanced with neoadjuvant chemoradiotherapy. After adjustment on propensity score and confounding factors, for all patients and subset analysis of squamous cell and adenocarcinoma, neoadjuvant therapy had no significant effect upon survival or recurrence (overall, loco-regional, distant or mixed) compared to surgery alone. There were no significant differences between neoadjuvant chemotherapy and chemoradiotherapy in short-or long-term outcomes.Conclusion: The results of this study suggest that a surgery alone treatment approach should be recommended as the primary treatment approach for cT2N0 oesophageal cancer despite 50% of patients having nodal disease at the time of surgery.
ISSN: 0959-8049

hal-01666517
https://hal.univ-lorraine.fr/hal-01666517
DOI : 10.1016/j.ejca.2015.11.024

Éditeur(s) : HAL CCSD
Résumé : International audience
Occupational exposure constitutes a common risk factor for lung cancer. We observed molecular alterations in 73% of never-smokers, 35% of men and 8% of women were exposed to at least one occupational carcinogen. We report herein associations between molecular patterns and occupational exposure.BioCAST was a cohort study of lung cancer in never-smokers that reported risk factor exposure and molecular patterns. Occupational exposure was assessed via a validated 71-item questionnaire. Patients were categorised into groups that were unexposed and exposed to polycyclic aromatic hydrocarbons (PAH), asbestos, silica, diesel exhaust fumes (DEF), chrome and paints. Test results were recorded for EGFR, KRAS, HER2, BRAF and PIK3 mutations, and ALK alterations.Overall, 313 out of 384 patients included in BioCAST were analysed. Asbestos-exposed patients displayed a significantly lower rate of EGFR mutations (20% versus 44%, p=0.033), and a higher rate of HER2 mutations (18% versus 4%, p=0.084). ALK alterations were not associated with any occupational carcinogens. The DEF-exposed patients were diagnosed with a BRAF mutation in 25% of all cases. Chrome-exposed patients exhibited enhanced HER2 and PIK3 mutation frequency.Given its minimal effects in the subgroups, we conclude that occupational exposure slightly affects the molecular pattern of lung cancers in never-smokers. In particular, asbestos-exposed patients have a lower chance of EGFR mutations.
European Respiratory Journal

hal-01647080
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647080
DOI : 10.1183/13993003.00716-2017
PUBMED : 29074543

Éditeur(s) : HAL CCSD
Résumé : International audience
BIOEM
Hangzhou, China

hal-01627606
https://hal.archives-ouvertes.fr/hal-01627606

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
: We investigated the in vitro effects of four alkyl-galactofuranoside derivatives, i.e. octyl-β-D-galactofuranoside (1), 6-amino-β-D-galactofuranoside (2), 6-N-acetamido-β-D-galactofuranoside (3), and 6-azido-β-D-galactofuranoside (4) on Leishmania donovani. Their mechanism of action was explored using electron paramagnetic resonance spectroscopy (EPR) and nuclear magnetic resonance (NMR), and ultrastructural alterations by transmission electron microscopy (TEM). Compound 1 showed the most promising effects by inhibiting promastigote growth at IC50 8.96 ± 2.5 μM. All compounds exhibit low toxicity towards human macrophages. Compound 1 had a higher selectivity index than the comparative molecule used, i.e. miltefosine (159.7 versus 37.9, respectively). EPR showed that compound 1 significantly reduced membrane fluidity, compared to control promastigotes and to compound 3. The furanose ring was shown to support this effect since the isomer galactopyranose had no effect on parasite membrane fluidity or growth. NMR showed a direct interaction of all compounds (1>2>3>4) with the promastigote membrane, as well as with octyl-galactopyranose and octanol, providing evidence that the n-octyl chain was primarily involved in the anchoring with the parasite membrane, followed by the putative crucial role of furanose ring in the anti-leishmanial activity. A morphologic analysis of compound 1-treated promastigotes by TEM revealed profound alterations on parasite membrane and organelles, but not with compound 3. Quantification of annexinV binding by flow cytometry confirmed that compound 1 induced apoptosis in >90% promastigotes. The effect of compound 1 was also assessed on intra-macrophagic amastigotes, and showed a reduction in amastigote growth associated with an increase of ROS production, thus validating its promising effect.
ISSN: 0066-4804

hal-00941772
https://hal.archives-ouvertes.fr/hal-00941772
PUBMED : 24468785
DOI : 10.1128/AAC.01350-13

Éditeur(s) : HAL CCSD
Résumé : Poster
International audience
BEMS 2013
Thessalonique, Greece

hal-00926911
https://hal.archives-ouvertes.fr/hal-00926911

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Algorithms issued from the NonLinear Galerkin method have been used in many situations and with different discretizations for the resolution of evolutionary nonlinear equations. The main idea of these methods is to use a splitting of the solution in order to model the equation. According to the splitting of the solution, a splitting of the equation is obtained. The modeling principle is to freeze terms which have a small time variation. In this work we use wavelet discretizations of the 2-D Burgers equations and compare the results with the hierarchical finite elements method. The numerical tests indicate that wavelets give better results than finite elements
ISSN: 0885-7474

hal-00383423
https://hal.archives-ouvertes.fr/hal-00383423
DOI : 10.1007/s10915-004-4806-4

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Because many biological processes related to the dynamics of infectious diseases are caused by complex interactions between the environment, the host(s) and the agent(s), the necessity to address the methodological implications of this inherent complexity has recently emerged in epidemiology. Most epidemiologists now acknowledge that most human infectious diseases are likely to have complex dynamics. However, this knowledge still percolates with difficulty in their statistical "modus operandi". Indeed, for the study of complex systems, the traditional first-line statistical toolbox of epidemiologists (mainly built around the Generalized Linear Model family), despite its undeniable practicality and robustness, has structural limitations deprecating its usefulness. Three major sources of complexity neglected or not taken into account by this first-line statistical toolbox and having deep statistical implications are the multi-level organization of data, the non-linear relationships between variables and the complex interactions between variables. Three promising candidates to incorporate along with traditional tools for a new first-line statistical toolbox more suitable to apprehend these sources of complexity are the generalized linear mixed models, the generalized additive models, and the structural equation models. The aforementioned methodologies have the advantage to be generalizations of GLM models and are relatively easy to implement. Their assimilation and implementation would thus be greatly facilitated for epidemiologists. More globally, this text underlines that an improved use of other methods as such described here compared to traditional ones has to be performed to better understand the complexity challenging epidemiologists every day. This is particularly true in the field of infectious diseases for which major public health challenges will have to be addressed in the coming decades.
ISSN: 1567-1348

inserm-00872354
http://www.hal.inserm.fr/inserm-00872354
http://www.hal.inserm.fr/inserm-00872354/document
http://www.hal.inserm.fr/inserm-00872354/file/main_document.pdf
DOI : 10.1016/j.meegid.2013.09.006

Éditeur(s) : HAL CCSD
Résumé : Poster
International audience
BEMS 2013
Thessalonique, Greece

hal-00926890
https://hal.archives-ouvertes.fr/hal-00926890

Éditeur(s) : HAL CCSD
Résumé : International audience
Comptes rendus de la Physique, sous presse

hal-00923999
https://hal.archives-ouvertes.fr/hal-00923999

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Necroptosis is a programmed cell death pathway that has been shown to be of central pathophysiological relevance in multiple disorders (hepatitis, brain and cardiac ischemia, pancreatitis, viral infection and inflammatory diseases). Necroptosis is driven by two serine threonine kinases, RIPK1 (Receptor Interacting Protein Kinase 1) and RIPK3, and a pseudo-kinase MLKL (Mixed Lineage Kinase domain-Like) associated in a multi-protein complex called necrosome. In order to find new inhibitors for use in human therapy, a chemical library containing highly diverse chemical structures was screened using a cell-based assay. The compound 6E11, a natural product derivative, was characterized as a positive hit. Interestingly, this flavanone compound: inhibits necroptosis induced by death receptors ligands TNF-α (Tumor Necrosis Factor) or TRAIL (TNF-Related Apoptosis-Inducing Ligand); is an extremely selective inhibitor, among kinases, of human RIPK1 enzymatic activity with a nM Kd; has a non-ATP competitive mode of action and a novel putative binding site; is weakly cytotoxic towards human primary blood leukocytes or retinal pigment epithelial cells at effective concentrations; protects human aortic endothelial cells (HAEC) from cold hypoxia/reoxygenation injury more effectively than necrostatin-1 (Nec-1) and Nec-1s. Altogether, these data demonstrate that 6E11 is a novel potent small molecular inhibitor of RIPK1-driven necroptosis.
ISSN: 2045-2322

hal-01616456
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616456
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616456/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616456/file/s41598-017-12788-4.pdf
DOI : 10.1038/s41598-017-12788-4

Éditeur(s) : HAL CCSD
Résumé : Poster
International audience
BEMS 2013
Thessalonique, Greece

hal-00926798
https://hal.archives-ouvertes.fr/hal-00926798

Éditeur(s) : HAL CCSD
Résumé : IPC: C07D 311/60 (2006.01), A61K 31/352 (2006.01), A61P 29/00 (2006.01), A61P 35/00 (2006.01), A61P 37/00 (2006.01), C07D 311/64 (2006.01), C07D 335/06 (2006.01), C07D 407/04 (2006.01), C07D 409/04 (2006.01)
The invention relates to new PI3K/AKT/mTOR inhibitors of formula (I) and their use for the prevention and/or the treatment of a disease selected from the group consisting of: inflammatory diseases, autoimmune diseases, neurodegenerative diseases, cancers, transplant rejection, diseases characterized by a premature aging and tuberous sclerosis.
L'invention concerne de nouveaux inhibiteurs de PI3K/AKT/mTOR, et leur utilisation pour la prévention et/ou le traitement d'une maladie choisie dans le groupe constitué par: des maladies inflammatoires, des maladies auto-immunes, des maladies neurodégénératives, des cancers, un rejet de greffe, des maladies caractérisées par un vieillissement prématuré ou la sclérose tubéreuse.
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139914

Patent N° : WO 2015044229 / EP 2853530
hal-01139914
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139914

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
It has been suggested that prenatal exposure to insecticides adversely affects fetal growth, but the overall results have been inconsistent, partly because of the different exposure sources and exposure assessments used. In the French PELAGIE (Perturbateurs Endocriniens: Étude Longitudinale sur les Anomalies de la Grossesse, l'Infertilité et l'Enfance) mother and child cohort (2002-2006), the authors investigated the association between fetal growth and insecticide exposure (n = 1,213) using an integrated Bayesian latent variable model to include multiple exposure sources: agricultural activities, nonorganic diet, household insecticide use on plants, and household insecticide use against insects. They used a questionnaire to collect information on household use and organic diet, and a national agricultural census provided data on agricultural activities in the women's municipalities of residence. A 0.10-cm decrease in head circumference at birth (95% credibility interval: -0.22, 0.01) was associated with fetal insecticide exposure from agricultural activities in the municipality of residence. Decreases in average birth weight (-27 g; 95% credibility interval: -59, 6) and head circumference (-0.12 cm; 95% credibility interval: -0.26, 0.01) were associated with household insecticide use to treat plants. The present results suggest an inverse association between fetal growth and prenatal insecticide exposure from nearby agricultural activity or household use. Bayesian modeling via latent variables is a natural framework for including multiple sources of exposure to environmental pollutants.
ISSN: 0002-9262

hal-00875979
https://hal.archives-ouvertes.fr/hal-00875979
DOI : 10.1093/aje/kwr422
PUBMED : 22534205

Éditeur(s) : HAL CCSD
Résumé : International audience
This study aims at introducing a method for determining the dielectric properties of lossy materials with high water contents in a millimetre-wave reverberation chamber. Such materials with high water content, e.g. biological tissues can be described by a Debye model. The proposed method consists in fitting the theoretical average absorption cross section to the experiment data resulting from the average absorption cross section measurements. By applying this method on a 4% agar phantom in the 50-65 GHz frequency range, it is demonstrated that the permittivity and conductivity of biological tissues can be determined at millimeter waves using reverberation chamber. The difference between the measured real and imaginary parts and the reference value of the agar phantom is 4.3% and 8%, respectively.
BIOEM 2016
Gand, Belgium

hal-01377570
https://hal.archives-ouvertes.fr/hal-01377570
https://hal.archives-ouvertes.fr/hal-01377570/document
https://hal.archives-ouvertes.fr/hal-01377570/file/bioem%202016_1_final.pdf

Éditeur(s) : HAL CCSD
Résumé : International audience
European Conf. on Antennas and Propagation, EuCAP 2013
Göteborg, Sweden

hal-00924625
https://hal.archives-ouvertes.fr/hal-00924625

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
ISSN: 1932-6203

hal-01114575
https://hal.archives-ouvertes.fr/hal-01114575

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
A thorough phytochemical study of Stereocaulon evolutum was conducted, for the isolation of structurally related atranorin derivatives. Indeed, pilot experiments suggested that atra-norin (1), the main metabolite of this lichen, would interfere with the lifecycle of hepatitis C virus (HCV). Eight compounds, including one reported for the first time (2), were isolated and characterized. Two analogs (5, 6) were also synthesized, to enlarge the panel of atra-norin-related structures. Most of these compounds were active against HCV, with a half-maximal inhibitory concentration of about 10 to 70 µM, with depsides more potent than monoaromatic phenols. The most effective inhibitors (1, 5 and 6) were then added at different steps of the HCV lifecycle. Interestingly, atranorin (1), bearing an aldehyde function at C-3, inhibited only viral entry, whereas the synthetic compounds 5 and 6, bearing a hydroxy-methyl and a methyl function, respectively, at C-3 interfered with viral replication.
ISSN: 1932-6203

hal-01134343
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134343
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134343/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134343/file/Depsides-PloS.pdf
DOI : 10.1371/journal.pone.0120405

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
OBJECTIVE:To identify local meteorological drivers of dengue fever in French Guiana, we applied an original data mining method to the available epidemiological and climatic data. Through this work, we also assessed the contribution of the data mining method to the understanding of factors associated with the dissemination of infectious diseases and their spatiotemporal spread.METHODS:We applied contextual sequential pattern extraction techniques to epidemiological and meteorological data to identify the most significant climatic factors for dengue fever, and we investigated the relevance of the extracted patterns for the early warning of dengue outbreaks in French Guiana.RESULTS:The maximum temperature, minimum relative humidity, global brilliance, and cumulative rainfall were identified as determinants of dengue outbreaks, and the precise intervals of their values and variations were quantified according to the epidemiologic context. The strongest significant correlations were observed between dengue incidence and meteorological drivers after a 4-6-week lag.DISCUSSION:We demonstrated the use of contextual sequential patterns to better understand the determinants of the spatiotemporal spread of dengue fever in French Guiana. Future work should integrate additional variables and explore the notion of neighborhood for extracting sequential patterns.CONCLUSIONS:Dengue fever remains a major public health issue in French Guiana. The development of new methods to identify such specific characteristics becomes crucial in order to better understand and control spatiotemporal transmission.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
ISSN: 1067-5027

lirmm-01379072
https://hal-lirmm.ccsd.cnrs.fr/lirmm-01379072
DOI : 10.1136/amiajnl-2013-002348
PUBMED : 24549761

Éditeur(s) : HAL CCSD Royal Society of Chemistry
Résumé : International audience
ISSN: 2046-2069

hal-01116129
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01116129
DOI : 10.1039/C3RA47255H

Éditeur(s) : HAL CCSD Centers for Disease Control and Prevention
Résumé : International audience
To determine when risk for Buruli ulcer is highest, we examined seasonal patterns in a highly disease-endemic area of Cameroon during 2002-2012. Cases peaked in March, suggesting that risk is highest during the high rainy season. During and after this season, populations should increase protective behaviors, and case detection efforts should be intensified.
ISSN: 1080-6040

Droits : http://creativecommons.org/licenses/by-nc-nd/
hal-01307147
https://hal-amu.archives-ouvertes.fr/hal-01307147
https://hal-amu.archives-ouvertes.fr/hal-01307147/document
https://hal-amu.archives-ouvertes.fr/hal-01307147/file/14-1336.pdf
DOI : 10.3201/eid2108.141336