Development of a Questionnaire for the Search for Occupational Causes in Patients with Non-Hodgkin Lymphoma: The RHELYPRO Study

Non-Hodgkin lymphoma (NHL), multiple myeloma and chronic lymphocytic leukemia are possibly related to environmental and/or occupational exposure. The primary objective of this study was to develop a questionnaire for screening patients with these blood disorders who might benefit from a specialized consultation for possible recognition of the disease as an occupational disease. The study included 205 subjects (male gender, 67.3%; mean age, 60 years; NHL, 78.5%). The questionnaire performed very satisfactorily in identifying the exposures most frequently retained by experts for their potential involvement in the occurrence of NHL. Its sensitivity and specificity in relation to the final expertise were 96% and 96% for trichloroethylene, 85% and 82% for benzene, 78% and 87% for solvents other than trichloroethylene and dichloromethane, 87% and 95% for pesticides, respectively. Overall, 15% of the subjects were invited to ask National Social Insurance for compensation as occupational disease. These declarations concerned exposure to pesticides (64%), solvents (trichloroethylene: 29%; benzene: 18%; other than chlorinated solvents: 18%) and sometimes multiple exposures. In conclusion, this questionnaire appears as a useful tool to identify NHL patients for a specialized consultation, in order to ask for compensation for occupational disease

TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration

Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) is frequently overexpressed in carcinomas, suggesting a specific role in cancer. Although TRAF4 protein is predominantly found at tight junctions (TJs) in normal mammary epithelial cells (MECs), it accumulates in the cytoplasm of malignant MECs. How TRAF4 is recruited and functions at TJs is unclear. Here we show that TRAF4 possesses a novel phosphoinositide (PIP)-binding domain crucial for its recruitment to TJs. Of interest, this property is shared by the other members of the TRAF protein family. Indeed, the TRAF domain of all TRAF proteins (TRAF1 to TRAF6) is a bona fide PIP-binding domain. Molecular and structural analyses revealed that the TRAF domain of TRAF4 exists as a trimer that binds up to three lipids using basic residues exposed at its surface. Cellular studies indicated that TRAF4 acts as a negative regulator of TJ and increases cell migration. These functions are dependent from its ability to interact with PIPs. Our results suggest that TRAF4 overexpression might contribute to breast cancer progression by destabilizing TJs and favoring cell migration

BeEAM (bendamustine, etoposide, cytarabine, melphalan) prior to autologous stem cell transplant for chemosensitive relapses in patients with follicular lymphoma: a prospective multicentre phase II study in Lymphoma Study Association centres

International audienceNo abstract availabl

Mouvements paysans face à la politique agricole commune et à la mondialisation (1957-2011)

Cette publication s'inscrit dans le cadre du programme de recherche du Centre de Recherches en Histoire Internationale et Atlantique de l'université de Nantes sur l'Histoire des mouvements sociaux dans l'Europe Atlantique. Réfléchissant aux réactions des sociétés civiles de l'ère contemporaine face aux grands événements internationaux de leur temps, ce programme, mené en lien avec les ressources du Centre d'Histoire du Travail (CHT), s'est intéressé à l'histoire des mouvements paysans face aux mutations agricoles conditionnées par la création de la Politique Agricole Commune et face aux changements induits par le développement de l'Organisation Mondiale du Commerce. Outre des mises en perspective larges sur les problématiques de la PAC et de l'OMC, cet ouvrage collectif, issu d'une journée d'études, a cherché à approfondir certains conflits sociaux par la publication d'études scientifiques et monographiques portant sur les régions de l'Ouest, du Sud-Ouest et du monde méditerranéen, de témoignages ou de documents d'archives venant des organisations agricoles (le plan Mansholt, les grèves du lait, les conflits viticoles, les conflits de l'agroalimentaire…)

Scientific workflows for computational reproducibility in the life sciences: Status, challenges and opportunities

International audienceWith the development of new experimental technologies, biologists are faced with an avalanche of data to be computationally analyzed for scientific advancements and discoveries to emerge. Faced with the complexity of analysis pipelines, the large number of computational tools, and the enormous amount of data to manage, there is compelling evidence that many if not most scientific discoveries will not stand the test of time: increasing the reproducibility of computed results is of paramount importance. The objective we set out in this paper is to place scientific workflows in the context of reproducibility. To do so, we define several kinds of repro-ducibility that can be reached when scientific workflows are used to perform experiments. We characterize and define the criteria that need to be catered for by reproducibility-friendly scientific workflow systems, and use such criteria to place several representative and widely used workflow systems and companion tools within such a framework. We also discuss the remaining challenges posed by reproducible scientific workflows in the life sciences. Our study was guided by three use cases from the life science domain involving in silico experiments

Echocardiographic Patterns of Left Ventricular Diastolic Function in Cardiac Amyloidosis: An Updated Evaluation

Aims: Multimodal imaging has allowed cardiac amyloidosis (CA) to be increasingly recognised as a treatable cause of heart failure with preserved ejection fraction, but its prognosis remains poor due to late diagnosis. To assess the left ventricular diastolic function (LVDF) patterns in a large contemporary CA cohort according to the current recommendations and to identify their determinants. Methods and Results: We conducted a monocentric, observational study on a cohort of CA patients from a tertiary CA referral centre. Diastolic function was analysed using standard echocardiography and clinical, laboratory and survival parameters were collected. Four hundred and sixty-four patients with one of the three main type of CA were included: 41% had grade III diastolic dysfunction (restrictive mitral pattern), 25% had grade II diastolic dysfunction, and 25% had grade I diastolic dysfunction; 9% were unclassified. No difference was found between the main CA types. After multivariate analyses, grades II and III were independently associated with dyspnoea, elevated NT-proBNP, cardiac infiltration and systolic dysfunction (global longitudinal strain). Grade I patients had a better prognosis. Conclusions: All LVDF patterns can be observed in CA. One quarter of CA patients have grade I LVDF, reflecting the emergence of earlier stage-related phenotypes with a better prognosis

La domination en question. Des formes et des normes en temps de crise

Objet classique des sciences sociales hérité de la sociologie wébérienne, la domination fait l’objet d’analyses renouvelées alors même que l’érosion des approches marxistes semblait la condamner aux oubliettes de l’historiographie. Tandis que s’animent les débats sur le retour des classes sociales, les travaux sur la construction des genres, les interrogations sur la question raciale, ou encore les discussions autour des notions d’empire et d’impérialisme, viennent aujourd’hui enrichir la réflexion sur l’évolution des rapports sociaux, économiques, politiques et culturels. Dans le droit fil de ces nouvelles approches, ce numéro double de la revue Siècles se propose de considérer, sur la longue durée et à des échelles variées, le dialogue des normes et des formes à l’œuvre dans les rapports de domination. Moments d’observation privilégiés de ces dynamiques, les périodes de remise en cause de celles-ci ont retenu l’attention des contributeurs. La question de la plasticité des systèmes de domination voisinera dès lors avec celle, davantage synchronique, des représentations de la domination en temps de crise. Domination, a classic topic of social sciences derived from Weberian sociology, is the focus of renewed analyses even as the erosion of the Marxist approach seems to condemn it to historiographical oblivion. While debate rages about the re-emergence of questions of social class, work on the construction of gender, questions about the issue of race, and discussion about notions of empire and imperialism, have enriched reflections on social, economic, political, religious, and cultural relations. In line with these recent developments, this double issue of Siècles analyzes, at various levels and over an extended period of time, the dialogue between the norms and the forms, objective or behavioral, lying behind relations of domination. As privileged moments of observation of these dynamics, contributors to this issue have focused on periods during which the notion of domination has been particularly questioned. The issue of the flexibility of systems of domination accompanies in a synchronic fashion the question of representations of domination during times of crisis

Transfusion needs after CAR T-cell therapy for large B-cell lymphoma: predictive factors and outcome. A DESCAR-T study

International audienceChimeric antigen receptor (CAR) T-cells targeting CD19 have been approved for the treatment of relapse/refractory large B-cell lymphoma. Hematotoxicity is the most frequent CAR T-cell-related adverse event. Transfusion support is a surrogate marker of severe cytopenias. Transfusion impacts patients’ quality of life, presents specific toxicities and is known to affect immunity through the so-called transfusion-related immunomodulation, that may impact CAR T-cell efficacy. We analyzed data from 671 patients from the French DESCAR-T registry for whom exhaustive transfusion data were available. Overall, 401 (59.8%) and 378 (56.3%) patients were transfused in the 6-month period before and after CAR T-cell, respectively. The number of transfused patients and the mean number of transfused products increased during the 6-month period before CAR-T, peaked during the first month after infusion (early phase) and decreased over time. Predictive factors for transfusion at the early phase were age > 60 years, ECOG PS ≥2, treatment with axi-cel, pre-CAR T-cell transfusions and CAR-HEMATOTOX score ≥ 2. Predictive factors for late transfusion (between 1 and 6 months after infusion) were pre-CAR T-cell transfusions, CAR-HEMATOTOX score ≥ 2, ICANS ≥ 3 (for red blood cells [RBC] transfusion) and tocilizumab use (for platelets transfusion). Early transfusions and late platelets (but not RBC) transfusions were associated with a shorter progression-free survival and overall survival. Lymphoma-related mortality and non-relapse mortality were both increased in the transfused population. Our data shed light on the mechanisms of early and late cytopenia, and on the potential impact of transfusions on CAR T-cell efficacy and toxicity

Final results of brentuximab vedotin combined with ifosfamide-carboplatin-etoposide in first refractory/relapsed Hodgkin lymphoma: a lymphoma study association phase I/II study.

This phase I/II study assessed the combination of brentuximab vedotin (BV) with ifosfamide-carboplatin-etoposide (ICE) as a second-line therapy in refractory/relapsed (R/R) classical Hodgkin lymphoma (cHL) patients. Phase I study was designed to determine the maximum tolerated dose (MTD) of BV (10 patients) and phase II evaluated the rate of complete metabolic response (CMR) after 2 cycles of BV-ICE (42 patients). There were no dose-limiting toxicities (DLT) during phase I recommending BV 1.8 mg/kg for phase II. Twenty-six patients (61.9%) achieved CMR after 2 cycles of BV-ICE and 37 patients (88%) were transplanted. With a median follow-up of 38 months, the 3-year progression free survival (PFS) and overall survival (OS) rate were 64.3% and 100%, respectively. Hematological toxicities (81%) and infections (21%) were the most frequent adverse event encountered BV-ICE regimen is feasible with manageable toxicities and could be an alternative to other salvage treatments. : ClinicalTrials.gov identifier: NCT02686346