Gene expression profile predicts outcome after anthracycline-based adjuvant chemotherapy in early breast cancer

International audiencePrognosis of early beast cancer is heterogeneous. Today, no histoclinical or biological factor predictive for clinical outcome after adjuvant anthracycline-based chemotherapy (CT) has been validated and introduced in routine use. Using DNA microarrays, we searched for a gene expression signature associated with metastatic relapse after adjuvant anthracycline-based CT without taxane. We profiled a multicentric series of 595 breast cancers including 498 treated with such adjuvant CT. The identification of the prognostic signature was done using a metagene-based supervised approach in a learning set of 323 patients. The signature was then tested on an independent validation set comprising 175 similarly treated patients, 128 of them from the PACS01 prospective clinical trial. We identified a 3-metagene predictor of metastatic relapse in the learning set, and confirmed its independent prognostic impact in the validation set. In multivariate analysis, the predictor outperformed the individual current prognostic factors, as well as the Nottingham Prognostic Index-based classifier, both in the learning and the validation sets, and added independent prognostic information. Among the patients treated with adjuvant anthracycline-based CT, with a median follow-up of 68 months, the 5-year metastasis-free survival was 82% in the "good-prognosis" group and 56% in the "poor-prognosis" group. Our predictor refines the prediction of metastasis-free survival after adjuvant anthracycline-based CT and might help tailoring adjuvant CT regimens

(Table 1) Chemical composition and bulk densities of dolerites from ODP Hole 504B lower dikes

Chemical interactions between seawater and the oceanic crust have been widely investigated during recent years. However, most of these studies concern the uppermost volcanic part of the crust. The contribution of the underlying sheeted dike complex to the global budget of the oceans is inferred solely from some ophiolite studies and from the 500-m high-level dike section of DSDP/ODP 504B which was drilled in 1981. Hole 504B is the only place where a continuous and long (1260 m) section in the sheeted dike complex has been cored, and it is now regarded as a reference section for the upper oceanic crust. Many petrological and chemical data from these dolerites are available, including the relative proportions of veins, extensively altered adjacent rocks, and less altered 'host-rocks'. For these three reasons, considering the entire dike section penetrated by Hole 504B is a unique chance to study chemical fluxes related to hydrothermal alteration of this part of the oceanic crust. The calculation of any chemical flux implies knowledge of the chemical composition of the fresh precursor (protolith). Previously, mean compositions of glasses (=P1a) or basalts from the Hole 504B volcanics have been used as protoliths. In this paper, we calculate and discuss the use of various protoliths based on dolerites from Hole 504B. We show that the most adequate and realistic protolith is the mean of individual protoliths that we calculated from the acquisition, by automatic mode, of about 1000 microprobe analyses in each thin-section of dolerite from the Hole 504B lower dikes. Consequently, PFm is further used to calculate chemical fluxes in the dike section of Hole 504B. The chemical compositions of the host-rocks adjacent to alteration halos tend to converge to that of PFm with depth, except for Fe2O3t and TiO2. Because the volume percent of alteration halos increases with depth, the total fluxes related to these halos increase with depth. This explains why the mean flux (host-rocks+halos+veins) of the upper dikes is roughly similar to the mean flux of the lower dikes. During the alteration of the entire Hole 504B dike section, the dolerites gained relatively large quantities of Fe2O3t (+4.0 g/100 cm**3) and released much SiO2 (-6.8 g/100 cm**3), CaO (-5.8 g/100 cm**3), and TiO2 (1.6 g/100 cm**3), and minor Al2O3 (-0.7 g/100 cm**3) and MgO (-0.7 g/100 cm**3). We show the importance of the choice of the protolith in the calculation of chemical budget, particularly for elements showing low flux values. In Hole 504B, the Mg uptake by the volcanics during low temperature alteration added to the Mg release by the dikes gives a net flux of -0.07x10**14 g/year. We propose that part of the Mg uptake by the oceanic crust, which is necessary to compensate the rivers input (-1.33x10**14 g/year), occurs in the underlying gabbros and/or in sections which are altered such as Trinity and Troodos ophiolites. Compared with ophiolites, fluxes calculated for elements other than Mg for the entire crust are generally similar (in tendency, if not in absolute value) to that we obtained from Hole 504B

ANALYSE « GÉOLOGIQUE » DES DÉPÔTS MINIERS ET INDUSTRIELS DU BASSIN MINIER DE PROVENCE LE TERRIL SAINT PIERRE

International audienc

Multiscale tomography of buried magnetic structures: its use in the localization and characterization of archaeological structures

International audienceWe have previously developed a method for characterizing and localizing 'homogeneous' buried sources, from the measure of potential anomalies at a fixed height above ground (magnetic, electric and gravity). This method is based on potential theory and uses the properties of the Poisson kernel (real by definition) and the continuous wavelet theory. Here, we relax the assumption on sources and introduce a method that we call the 'multiscale tomography'. Our approach is based on the harmonic extension of the observed magnetic field to produce a complex source by use of a complex Poisson kernel solution of the Laplace equation for complex potential field. A phase and modulus are defined. We show that the phase provides additional information on the total magnetic inclination and the structure of sources, while the modulus allows us to characterize its spatial location, depth and 'effective degree'. This method is compared to the 'complex dipolar tomography', extension of the Patella method that we previously developed. We applied both methods and a classical electrical resistivity tomography to detect and localize buried archaeological structures like antique ovens from magnetic measurements on the Fox-Amphoux site (France). The estimates are then compared with the results of excavations

Subsurface electrical imaging of anisotropic formations affected by a slow active reverse fault (Trévaresse thrust), Provence, France

In seismic hazard assessment studies, near-surface geophysical prospecting is increasingly used to help in identifying active faults and to constrain seismic deformation parameters (fault offset, recurrence...). In the current study, electrical tomography was used (1) to locate the Trevaresse slow reverse fault (Provence, SE France), the source of the most important seismic event recorded in the 20th century in France and (2) to test electrical tomography's ability to detect faults and tectonic deformation in a complex geological environment. Our study is supported by a detailed geologic and geomorphic field study. In the investigated area, where the geology is made of a succession of folded marl and limestone layers, electrical images are strongly influenced by electrical macro-anisotropy which plays a critical role in this survey, depending on the investigation scale. When resolution (i.e. the smallest target that can be resolved) is larger than the layer thickness (at depth and/or for large electrode spacing), inversion is unable to retrieve the real structure. To successfully interpret these electrical images, in terms of tectonically induced dip variations, we constrain field data interpretation by comparing measured and inverted electrical data with synthetic modelling results and geological data. The synthetic models were hypothetical coarse geological structures determined on the basis of geological/ geomorphologic information (e.g. outcropping layers). For shallow depths, when the resolution is smaller or equal to the anisotropy scale, an electrical tomogram yields straightforward interpretation of the subsurface structure. Coupled with numerical modelling, electrical results successfully helped in positioning a trench for fault characterization. (c) 2007 Elsevier B.V. All rights reserved

ANALYSE « GÉOLOGIQUE » DES DÉPÔTS MINIERS ET INDUSTRIELS DU BASSIN MINIER DE PROVENCE LE TERRIL SAINT PIERRE

International audienc

Origin of groundwater salinity and hydrogeochemical processes in a confined coastal aquifer: Case of the Rhone delta (Southern France)

The Rhône delta, South of France (Camargue, 750 km2) is a coastal saline wetland located along the Mediterranean Sea. The confined aquifer of this delta shows high values of electrical conductivity rising from the north (4 mS/cm) to the shoreline (58 mS/cm). This work aims to identify the origin of groundwater salinity and the geochemical processes occurring in this coastal confined aquifer according to the degree of salinity. A natural tracing approach is considered using monthly sampling in 8 piezometers for chemical and isotopic analyses (18O, 2H, 13CTDIC). Ionic and isotopic ratios demonstrate that strong salinities are due to a simple mixing between Mediterranean seawater and freshwater; seawater contribution reaches up to 98% at 8 km from the shoreline. Seawater intrusion induces a particular groundwater chemistry which varies with the degree of seawater contribution: (1) In the less saline part of the aquifer (seawater contribution 20%), the intrusion induces SO4 reduction which is confirmed by highly depleted δ13CTDIC values (up to −19‰). The δ13CTDIC also reveals that methanogenesis processes may occur in the most reductive part of the aquifer. Due to SO4 reduction, the intrusion induces a shift in carbonate equilibrium leading to supersaturation with respect to dolomite and/or magnesian calcite. Thus carbonate precipitation may occur in the area strongly influenced by seawater

First-in-human Study to Evaluate a Single Injection of KiOmedine®CM-Chitosan for Treating Symptomatic Knee Osteoarthritis

Background: Single-injection viscosupplementation is currently performed with cross-linked hyaluronan (e.g. Durolane®) for treating symptomatic knee osteoarthritis. Objective: This first-in-human study evaluated the safety and performance of single-injection treatment with non-crosslinked KiOmedine®CM-Chitosan. Methods: Patients with painful knee osteoarthritis were randomly assigned to the KiOmedine®CM-Chitosan (n=63) or Durolane® (n=32) group. Patients were blinded to treatment and followed up for 26 weeks. Durolane® was used as scientific control to ensure the validity of the study and reliability of results. No direct comparison was performed between the two groups. The primary objective was defined as an intra-group effect size of 0.8 at 13 weeks post-injection compared to baseline on WOMAC-A (pain). Secondary outcomes included self-reported knee stiffness and knee function, responder rate, quality-of-life questionnaires, and safety. Results: The primary objective for both the KiOmedine®CM-Chitosan and the Durolane® groups was met: mean pain reduction of 62.5% (effect size 2.08) for the KiOmedine®CM-Chitosan group and 62.4% (effect size 2.28) for the Durolane® group. Secondary performance outcomes showed all clinically relevant treatment effects over 26 weeks for both groups (p<0.05). Treatment-related adverse events were more often reported in the KiOmedine®CM-Chitosan than Durolane® group and were limited to local reactions. No serious treatment-related adverse events were reported. Conclusion: A single intra-articular injection of non-crosslinked KiOmedine®CM-Chitosan is safe and effective for treating symptomatic knee osteoarthritis with a high responder rate. Pain reduction is maintained for 6 months with a high responder rate. The clinical trial registration number: NCT03679208.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Evolution holocène de l’estuaire de la Maye (secteur de Rue, Picardie, France) et implications pour l’occupation humaine

International audienceCette communication présente une reconstitution de l’évolution holocène de la ligne de rivage de l’estuaire de la Maye (dans le secteur de Rue, au Sud du Marquenterre) ainsi que des informations nouvelles sur la configuration de ses ressources et de ses paysages côtiers depuis le moyen-âge. Les données présentées ont été acquises dans le cadre du programme PaleoportRue, soutenu par le Conseil régional de Picardie entre 2011 et 2014, en adoptant une approche géoarchéologique. Des moyens d’investigation de terrain, associant une étude de géophysique (8 profils de tomographie de résistivité électrique) et 8 carottages (par vibro-percussion) réalisés à l’ouest de Rue, ont été mis en œuvre parallèlement à l’exégèse de sources documentaires manuscrites et imprimées (figurées ou non figurées). De nos jours, la ville de Rue est située à environ 7 km du trait de côte, au cœur de la plaine maritime picarde. Cependant, selon différentes sources historiques, elle était lors de son édification à l’époque gallo-romaine, et jusqu’au moyen-âge, l’un des principaux ports maritimes de la côte picarde. Bâtie sur un îlot de galets d’âge pléistocène (localement appelé « foraine »), à l’embouchure de la Maye, Rue devait bénéficier d’un accès direct à la mer et à la rivière pour la pratique de la pêche et le transport des denrées. L’analyse sédimentologique en laboratoire des carottages (mesures de granulométrie LASER et de perte au feu -réalisées au CEREGE- et 20 datations par le radiocarbone) a permis de distinguer quatre unités sédimentaires principales au-dessus des « cailloutis » pléistocènes : i) des dépôts marins datant de la fin du 3e millénaire av. J.-C., ii) une formation tourbeuse qui s’est développée aux 2e et 3e millénaires av. J.-C., iii) des sédiments littoraux qui se sont déposés jusqu’au XIIIe siècle et iv) des remblais modernes. Le croisement des données sédimentologiques, géophysiques et documentaires amène à proposer une évolution originale de l’estuaire de la Maye au cours des 3 derniers millénaires : vers 1000 av. J.-C., la « foraine » de Rue était bordée de vallons marécageux et tourbeux, puis, durant l’Âge du Fer, l’estran était très probablement proche de la « foraine » de Rue. Enfin, durant le Moyen-Âge classique (XIe-XIIIe siècles), le chenal d’écoulement permettant l’accès maritime au port de Rue devait être réduit dans un estuaire ensablé.L’étude des documents issus d’archive apporte des éléments de discussion, notamment sur les ressources locales et les échanges commerciaux. Elle indique par exemple l’exploitation de salines du XIe siècle au XIIIe siècle, dont la localisation précise reste à établir, sans doute sur l’estran