L'écrit asynchrone dans un dispositif hybride de simulation globale en contexte universitaire japonais

Our study falls within the field of Didactics of French as a Foreign Language (FFL) and is situated in the area of Technology Mediated Language Learning. It is an action research study that measures the impact on student engagement in a global simulation of a blended learning (BL) environment. We begin by presenting the characteristics of the BL environment, focusing on its asynchronous dimension, materialized through a discussion forum. We then look for indicators of student engagement through the analysis of general participation and interactions in various threads. We show how the affordances of the forum, the nature and scripting of the tasks, and the behavior of the interactants and assessment method tend to influence the quality of engagement. Finally, we compile a list of several indicators of student engagement that could be helpful for designers of BL environment for language learning.Notre étude relève du champ de la Didactique du Français Langue Étrangère (FLE) et se situe dans le domaine de l'Apprentissage des Langues Médiatisé par les Technologies. Il s'agit d'une recherche-action qui mesure l'impact d'un dispositif hybride de simulation globale sur l'engagement d'une classe d'étudiants de 2e année d'une université japonaise. Nous commençons par présenter les caractéristiques du dispositif en focalisant notre attention sur sa dimension asynchrone, matérialisée par un forum de discussion. Nous cherchons ensuite des indicateurs de l'engagement des étudiants par l'analyse de la participation générale et des interactions dans divers fils de discussion. Nous montrons comment les affordances du forum, la nature et la scénarisation des tâches, le comportement des interactants et l'évaluation tendent à influer sur la qualité de l'engagement. Nous compilons enfin dans un tableau les manifestations de l'engagement repérées dans notre dispositif, ce qui sera susceptible d'alimenter la réflexion des concepteurs de dispositifs hybrides.【学術論文

Concerns about the widespread use of rodent models for human risk assessments of endocrine disruptors.

International audienceFetal testis is a major target of endocrine disruptors (EDs). During the last 20 years, we have developed an organotypic culture system that maintains the function of the different fetal testis cell types and have used this approach as a toxicological test to evaluate the effects of various compounds on gametogenesis and steroidogenesis in rat, mouse and human testes. We named this test rat, mouse and human fetal testis assay. With this approach, we compared the effects of six potential EDs ((mono-(2-ethylhexyl) phthalate (MEHP), cadmium, depleted uranium, diethylstilboestrol (DES), bisphenol A (BPA) and metformin) and one signalling molecule (retinoic acid (RA)) on the function of rat, mouse and human fetal testis at a comparable developmental stage. We found that the response is similar in humans and rodents for only one third of our analyses. For instance, RA and MEHP have similar negative effects on gametogenesis in the three species. For another third of our analyses, the threshold efficient concentrations that disturb gametogenesis and/or steroidogenesis differ as a function of the species. For instance, BPA and metformin have similar negative effects on steroidogenesis in human and rodents, but at different threshold doses. For the last third of our analyses, the qualitative response is species specific. For instance, MEHP and DES affect steroidogenesis in rodents, but not in human fetal testis. These species differences raise concerns about the extrapolation of data obtained in rodents to human health risk assessment and highlight the need of rigorous comparisons of the effects in human and rodent models, when assessing ED risk

Robustness and efficacy of an inhibitory consortium against E. coli O26:H11 in raw milk cheeses

International audienceSafety in raw milk cheeses being a major public health issue, the aim of this study was to validate a new bio preservation strategy by evaluating the efficacy of an inhibitory bacterial consortium (Hafnia alvei, Lactobacillus plantarum and Lactococcus lactis) on the growth of E. coli O26:H11 in uncooked pressed cheeses manufactured with different raw milk batches (6 farms, 3 periods). The pathogen was inoculated at very low concentrations (0.5 and 0.05 cfu mL(-1)), close to reality. The inhibitory power of the consortium was determined by culture analyses, and 16S rDNA sequencing of milk batches and cheeses was performed to evaluate the impact of milk microbial composition on the consortium's inhibition capacities. Raw milk batches differed in their fat and protein contents, microbial counts and diversity indices. The consortium's strong inhibitory power and adaptability were confirmed by a reduction of STEC levels (average of 2.8 log cfu g(-1)) in all cheeses, whatever the level of STEC inoculated into the milk. Differences in the growth and inhibition of E. coli in the cheeses depended on the microbial composition of the raw milk batches. Further research using a transcriptomic approach will help to improve understanding of the interactions between the strains

[Renal disorders associated with monoclonal gammopathies: diagnostic and therapeutic progress].

International audienceVarious renal disorders are associated with monoclonal gammopathies, secondary to tissue deposition or precipitation of a monoclonal immunoglobulin (Ig) or a fragment thereof (isolated Ig light chain or heavy chain). They are classified according to the localization of renal lesions, either glomerular or tubular and to the pattern of ultrastructural organization of Ig deposits. Renal disease in monoclonal gammopathies may be isolated, or associated with various systemic symptoms particularly in AL amyloidosis, Randall-type monoclonal Ig deposition disease and monoclonal cryoglobulinemias. Except for myeloma cast nephropathy, which occurs in the setting of high-mass myeloma and is recognized after electrophoretic analysis of proteinuria and AL amyloidosis, which diagnosis is usually made after pathological examination of non-invasive tissue specimens (i.e. abdominal fat or minor salivary glands), a kidney biopsy is required to identify the other types of renal disorders associated with monoclonal gammopathies and to estimate renal prognosis. Renal pathological diagnosis is difficult and relies on careful examination of kidney biopsy samples, by light microscopy, immunofluorescence studies using conjugates specific for Ig light and heavy chains, IgG sub-classes and heavy chain constant domains and by electron microscopy. In some cases, additional studies are required to identify the nature of deposits, such as immuno-electron microscopy or mass spectrometric-based proteomic analysis after laser dissection. In patients with renal disorders related to Ig light chain precipitation or deposition (myeloma cast nephropathy, AL amyloidosis, Randall-type light chain deposition disease), measurement of serum free light chains at baseline and throughout follow-up is mandatory to evaluate clonal response to chemotherapy. A more than or equal to 50% decrease in serum free light chain levels is associated with increased renal and patient survival. In AL amyloidosis, serum levels of markers of cardiac disease (NT-proBNP and troponin) are also closely associated with prognosis. Efficient chemotherapy, tailored to the underlying plasma cell or lymphoproliferative disorder and adapted to renal function, should be promptly introduced, even in the absence of overt malignant haematological disease. Renal prognosis and patient survival (particularly in AL amyloidosis and cast nephropathy) are closely associated with the rapid achievement of an haematological response. The combination of melphalan plus dexamethasone (MDex) is currently used as first-line chemotherapy in systemic AL amyloidosis. Bortezomib-based regimens are commonly employed as first-line treatment in myeloma cast nephropathy and Randall-type monoclonal Ig deposition disease and as second line therapy in AL amyloidosis patients with advanced cardiomyopathy or refractory to previous chemotherapy. Solid organ transplantation (heart and kidney) should be considered in patients with AL amyloidosis or Randall-type monoclonal Ig deposition disease and advanced cardiac or renal failure. Prolonged graft and patient survival may be obtained, providing that recipients do not have other severe organ involvement or symptomatic myeloma and that haematological remission has been achieved with chemotherapy before or after organ transplantation

AL Amyloidosis

<p>Abstract</p> <p>Definition of the disease</p> <p>AL amyloidosis results from extra-cellular deposition of fibril-forming monoclonal immunoglobulin (Ig) light chains (LC) (most commonly of lambda isotype) usually secreted by a small plasma cell clone. Most patients have evidence of isolated monoclonal gammopathy or smoldering myeloma, and the occurrence of AL amyloidosis in patients with symptomatic multiple myeloma or other B-cell lymphoproliferative disorders is unusual. The key event in the development of AL amyloidosis is the change in the secondary or tertiary structure of an abnormal monoclonal LC, which results in instable conformation. This conformational change is responsible for abnormal folding of the LC, rich in β leaves, which assemble into monomers that stack together to form amyloid fibrils.</p> <p>Epidemiology</p> <p>AL amyloidosis is the most common type of systemic amyloidois in developed countries with an estimated incidence of 9 cases/million inhabitant/year. The average age of diagnosed patients is 65 years and less than 10% of patients are under 50.</p> <p>Clinical description</p> <p>The clinical presentation is protean, because of the wide number of tissues or organs that may be affected. The most common presenting symptoms are asthenia and dyspnoea, which are poorly specific and may account for delayed diagnosis. Renal manifestations are the most frequent, affecting two thirds of patients at presentation. They are characterized by heavy proteinuria, with nephrotic syndrome and impaired renal function in half of the patients. Heart involvement, which is present at diagnosis in more than 50% of patients, leading to restrictive cardiopathy, is the most serious complication and engages prognosis.</p> <p>Diagnostic methods</p> <p>The diagnosis relies on pathological examination of an involved site showing Congo red-positive amyloid deposits, with typical apple-green birefringence under polarized light, that stain positive with an anti-LC antibody by immunohistochemistry and/or immunofluorescence. Due to the systemic nature of the disease, non-invasive biopsies such as abdominal fat aspiration should be considered before taking biopsies from involved organs, in order to reduce the risk of bleeding complications.</p> <p>Differential diagnosis</p> <p>Systemic AL amyloidosis should be distinguished from other diseases related to deposition of monoclonal LC, and from other forms of systemic amyloidosis. When pathological studies have failed to identify the nature of amyloid deposits, genetic studies should be performed to diagnose hereditary amyloidosis.</p> <p>Management</p> <p>Treatment of AL amyloidosis is based on chemotherapy, aimed at controlling the underlying plasma clone that produces amyloidogenic LC. The hematological response should be carefully checked by serial measurements of serum free LC. The association of an alkylating agent with high-dose dexamethasone has proven to be effective in two thirds of patients and is considered as the current reference treatment. New agents used in the treatment of multiple myeloma are under investigation and appear to increase hematological response rates. Symptomatic measures and supportive care is necessary in patients with organ failure. Noticeably, usual treatments for cardiac failure (i.e. calcium inhibitors, β-blockers, angiotensin converting enzyme inhibitors) are inefficient or even dangerous in patients with amyloid heart disease, that should be managed using diuretics. Amiodarone and pace maker implantation should be considered in patients with rhythm or conduction abnormalities. In selected cases, heart and kidney transplantation may be associated with prolonged patient and graft survival.</p> <p>Prognosis</p> <p>Survival in AL amyloidosis depends on the spectrum of organ involvement (amyloid heart disease being the main prognosis factor), the severity of individual organs involved and haematological response to treatment.</p

Insight into farmhouse PDO cheese primary production environment to reconcile sanitary control and microbial ecosystems

International audienc

How to design an efficient and robust pipeline for 16S rRNA-gene sequence analysis to improve our understanding on microbial communities?

Voici la composition du Comité d'Organisation (CO) de JOBIM 2015Le Comité Logistique (CL) est présidé par : Philippe LEROY (UMR 1095 INRA/UBP, Unité Génétique, Diversité et Ecophysiologie des Céréales - GDEC, Clermont-Ferrand) Eric PEYRETAILLADE (Université d'Auvergne, Unité EA-CIDAM, Clermont-Ferrand)Trois personnes clefs: Secrétariat JOBIM2015 - Manon MARTINET (LB2MN-EA.CIDAM 4678, Université d'Auvergne) Gestion Administrative - Cathy RESSOT (Direction de la Recherche de l’Innovation et de la valorisation, Université d'Auvergne) Gestion Financière - Isabelle DELPIT (Direction de la Recherche de l’Innovation et de la valorisation, Université d'Auvergne) Le Comité Scientifique (CS) est présidé par : Pierre PEYRET (Université d'Auvergne, Unité EA-CIDAM, Clermont-Ferrand) Jérôme SALSE (MR 1095 INRA/UBP, Unité Génétique, Diversité et Ecophysiologie des Céréales - GDEC, Clermont-Ferrand)Microorganisms are considered one of the most important players involved in different environmental processes and services including nutrient cycling, pollutants attenuation as well as plant, animal and human health. In order to understand the functioning of microbial ecosystems and their impact on ecosystem processes we need to accurately assess their composition and response to environmental constraints. The application of high-throughput sequencing technologies to the study of 16S/18S rRNA-genes has revolutionized the characterization of complex microbial ecosystems. However, although it is now possible to generate hundreds of thousands of sequence reads at low costs, the analysis of the obtained data is still challenging: potential source errors including amplification biases, technical contamination, sequencing artifacts and taxonomical affiliation mistakes can lead to misinterpretations of microbial community diversity. Furthermore, progresses in sequencing technologies produce larger number of sequences at lower cost, but many tools are not scalable and pipelines have to be adapted for huge dataset. With the objective of defining best practices to analyze 16S/18S rRNA-gene sequence data, the Metagenomics, species identification, phylogeny pole of INRA was created to put together experience of biologist, bioinformaticians and statisticians of different laboratories

Guide pratique à destination des biologistes, bioinformaticiens et statisticiens qui souhaitent s’initier aux analyses métabarcoding: Partage de pratiques et retours d'expérience des membres du pôle métagénomique du PEPI IBIS

National audienceLes méthodes d’analyse métabarcoding (également appelées métagénomique ciblée ou amplicon) sontde plus en plus utilisées pour étudier la diversité des espèces présentes dans un écosystème (micro organismes,plantes, animaux). Le principe consiste à extraire l’ADN d’un échantillon environnemental puis à amplifier par PCR un fragment cible à l’aide d’un couple d’amorces prédéfini. Ces produits PCR, après ajouts de barcodes(oligonucléotides uniques pour chaque échantillon) et adaptateurs de séquençage, sont ensuite séquencés. Après le séquençage, les séquences sont triées par échantillon grâce aux barcodes puis assignées à des taxons par comparaison avec des séquences de référence. Beaucoup de méthodes et outils d’analyse ont été développés pour obtenir une vision la plus précise possible des écosystèmes étudiés. Les techniques de préparation puis d’analyse des échantillons dépendent de l’écosystème, des questions auxquelles on souhaite répondre et de la technologie de séquençage utilisée. Nous proposons des conseils issus de nos expériences, discussions et lectures bibliographiques afin de guider les lecteurs depuis la planification expérimentale jusqu’à l’analyse des données, en détaillant les points de vigilance à chaque étape

Randomized Trial Comparing Double Versus Triple Bortezomib-Based Regimen in Patients With Multiple Myeloma and Acute Kidney Injury Due to Cast Nephropathy

International audiencePURPOSE We report a multicenter controlled trial comparing renal recovery and tolerance profile of doublet versus triplet bortezomib-based regimens in patients with initial myeloma cast nephropathy (CN) and acute kidney injury (AKI) without need for dialysis. METHODS After symptomatic measures and high-dose dexamethasone, patients were randomly assigned to receive bortezomib plus dexamethasone (BD), or BD plus cyclophosphamide (C-BD). In patients with < 50% reduction of serum free light chains (sFLCs) after 3 cycles, chemotherapy was reinforced with either cyclophosphamide (BD group) or thalidomide (C-BD group). RESULTS Ninety-two patients were enrolled in each group. At random assignment, characteristics of the 2 groups were similar, including median age (68 years) and serum creatinine level (305.5 and 273.5 µmol/L in BD and C-BD group, respectively). At 3 months, renal response rate (primary end point) was not different (41 v 47 responders in the BD and C-BD groups, respectively; relative risk [RR], 0.87; P = .46). Very good partial response (free light chain reduction ≥ 90%) or more was achieved in 36 and 47 patients, respectively (RR, 0.76; P = .10). After 1 cycle of chemotherapy, 69 in the BD group and 67 patients in the C-BD group had achieved sFLC level ≤ 500 mg/L. Serious adverse events were recorded in 30 and 40 patients, respectively. At 12 months, 19 patients had died (9 in the BD group v 10 in the C-BD group), including 10 (6 in the BD group and 4 in the C-BD group) from myeloma progression and 3 (0 in the BD group and 3 in the C-BD group) from infection. Within median follow-up of 27 months, 43 and 42 patients switched to new therapy, respectively. Overall, 50 patients (24 in the BD group and 26 in the C-BD group) had died. CONCLUSION This randomized study did not show any benefit of C-BD compared with BD on renal recovery of patients with initial CN not requiring dialysis. Adding cyclophosphamide did not sufficiently improve the efficacy-toxicity balance. Patients with myeloma with AKI are fragile, and indication for doublet or triplet regimen should be adapted to frailty