Modèles de prévision et prise de décision pour le soutien d’étiage de la Loire

Le bassin de la Loire est caractérisé par une forte variabilité hydrologique naturelle, une grande richesse hydro-écologique et de nombreux usages anthropiques : irrigation, alimentation en eau potable, sports et festivités nautiques, hydroélectricité et refroidissement de quatre centrales nucléaires. Deux ouvrages de retenue, gérés par l’Établissement Public Loire, assurent le soutien d’étiage : Villerest, sur la Loire, et Naussac, sur l’Allier. Leur gestion doit garantir des débits objectifs sur l’Allier et la Loire de manière à concilier ces usages parfois contradictoires, mais en cas de situation critique, telle que l’étiage très sévère de l’été 2003, cette gestion peut être adaptée en associant les usagers sous la présidence du Préfet coordonnateur de bassin au sein d’un comité de gestion. Suite à cet événement, de nouvelles règles de gestion ont été pratiquées pour mieux utiliser les ressources stockées dans les retenues, autour de valeurs de débits objectifs modulables. Afin d’améliorer la gestion de l’étiage, la DIREN Centre, EDF et l’EP Loire ont mis en place une modélisation hydrologique de prévision des débits d’étiage de la Loire à Gien. Ce modèle, opérationnel depuis le printemps 2009 à la DIREN Centre, permet déjà d’évaluer l’efficacité des consignes de gestion dynamique et ouvre des perspectives intéressantes en termes d’aide à la prise de décision pour le soutien d’étiage. Après avoir présenté succinctement le contexte des étiages de la Loire, dans cet article, nous présentons les performances des modèles de simulation et de prévision des étiages, de la simulation des débits à la prévision probabiliste des volumes de déficits. Ensuite, nous présentons l’exemple de l’étiage de 2003 et la manière dont ces prévisions auraient permis d’appréhender et d’anticiper la situation de 2003, aussi bien avec des prévisions probabilistes de débits que de déficits

Human-Derived α1-Antitrypsin is Still Efficacious in Heavily Pretreated Patients with Steroid-Resistant Gastrointestinal Graft-versus-Host Disease

International audienceAlmost one-half of patients developing graft-versus-host disease (GVHD) will not respond to standard first-line steroid treatment. Alpha-1 antitrypsin (AAT) is able to induce tolerance in preclinical models of GVHD. AAT alters the cytokine milieu, promotes a tolerogenic shift of dendritic cells, and skews effector T cells toward regulatory T cells. Gastrointestinal steroid-refractory (SR)-GVHD is a protein-losing enteropathy that might represent the optimal setting in which to use AAT. Here we analyze the outcomes of 16 patients treated with human-derived AAT in advanced-stage gut SR-GVHD, with two-thirds of the patients having failed at least 1 treatment for SR-GVHD. The overall response rate (ORR) was 44%, with a complete response (CR) rate of 27%. Gastrointestinal response was observed in 61% of patients. The median time to best response was 21 days (range, 6 to 26 days). At day 56 after AAT treatment, all CRs were maintained, and the ORR was 39%. The 1-year overall survival was 48% (95% confidence interval, 26% to 74%). Ancillary studies showed that AAT serum levels were in the normal range at the beginning of treatment, whereas fecal loss was elevated. AAT levels consistently rose after exogenous administration, but no correlation was found between serum levels and response. REG3α and IL-33 levels were associated with response while, in contrast to previous reports, regulatory T cells decreased during AAT treatment. This retrospective analysis supports a previous report of AAT as a promising agent in the management of gut SR-GVHD and should prompt its evaluation at an earlier stage

Efficacy of Diabeloop closed‐loop to improve glycaemic control in patients with type 1 diabetes exposed to copious dinners or to sustained physical exercise

International audienc

Long term Immune Reconstitution and infection burden after Mismatched Hematopoietic Stem Cell Transplantation

Mismatched unrelated donor (MMUD) or umbilical cord blood (UCB) can be chosen as alternative donors for allogeneic stem cell transplantation but might be associated with long lasting immune deficiency. Sixty-six patients who underwent a first transplantation from either UCB or 9/10 MMUD (n= 36) and who survived beyond 3 months were evaluated. Immune reconstitution was prospectively assessed at sequential time points after transplantation. NK, B, CD4+ and CD8+T cells and their subsets as well as regulatory T cells (Treg) were studied. Detailed analyses on infections occurring after 3 months were also assessed. The 18-month cumulative incidences of infection-related death were 8 and 3%, and of infections were 72 and 57% after MMUD and UCB transplantation, respectively. Rates of infection per 12 patient-month were roughly 2 overall (1 for bacterial, 0.9 for viral and 0.3 for fungal infections). Memory, naïve CD4+ and CD8+T cells, naïve B cells and Treg cells reconstitution between the 2 sources was roughly similar. Absolute CD4+T cells hardly reached 500 per μL by one year posttransplantation and most B cells were of naïve phenotype. Correlations between immune reconstitution and infection were then performed by multivariate analyses. Low CD4+ and high CD8+T cells absolute counts at 3 months were linked to increased risks of overall and viral (but not bacterial) infections. When assessing for the naïve/memory phenotypes at 3 months among the CD4+ T cell compartment, higher percentages of memory subsets were protective against late infections: central memory CD4+T cells protected against overall and bacterial infections; late effector memory CD4+T cells protected against overall, bacterial and viral infections. At the opposite, high percentage of effector- and late effector-memory subsets at 3 months among the CD8+ T cell compartment predicted higher risks for viral infections. Patients transplanted from alternative donors represent a population with very high risk of infection. Detailed phenotypic analysis of immune reconstitution may help to evaluate infection risk and to adjust infection prophylaxis

Role of DNA Repair Variants and Diagnostic Radiology Exams in Differentiated Thyroid Cancer Risk: A Pooled Analysis of Two Case–Control Studies

International audienceBackground: Given the increased use and diversity of diagnostic procedures, it is important to understand genetic susceptibility to radiation-induced thyroid cancer.Methods: On the basis of self-declared diagnostic radiology examination records in addition to existing literature, we estimated the radiation dose delivered to the thyroid gland from diagnostic procedures during childhood and adulthood in two case-control studies conducted in France. A total of 1,071 differentiated thyroid cancer (DTC) cases and 1,188 controls from the combined studies were genotyped using a custom-made Illumina OncoArray DNA chip. We focused our analysis on variants in genes involved in DNA damage response and repair pathways, representing a total of 5,817 SNPs in 571 genes. We estimated the OR per milli-Gray (OR/mGy) of the radiation dose delivered to the thyroid gland using conditional logistic regression. We then used an unconditional logistic regression model to assess the association between DNA repair gene variants and DTC risk. We performed a meta-analysis of the two studies.Results: The OR/mGy was 1.02 (95% confidence interval, 1.00-1.03). We found significant associations between DTC and rs7164173 in CHD2 (P = 5.79 × 10-5), rs6067822 in NFATc2 (P = 9.26 × 10-5), rs1059394 and rs699517 both in ENOSF1/THYS, rs12702628 in RPA3, and an interaction between rs7068306 in MGMT and thyroid radiation doses (P = 3.40 × 10-4).Conclusions: Our results suggest a role for variants in CDH2, NFATc2, ENOSF1/THYS, RPA3, and MGMT in DTC risk.Impact: CDH2, NFATc2, ENOSF1/THYS, and RPA3 have not previously been shown to be associated with DTC risk

Association results between the five polymorphisms and the risk of developing DTC.

<p>^a Stratified by age and sex.</p><p>^b Stratified by age and sex, and adjusted on BMI, BSA ethnicity, and thyroid radiation dose received before age 15 years.</p><p>^c Multiplicative model of inheritance.</p><p>^d Dominant model of inheritance (combined heterozygotes and rare homozygotes <i>versus</i> common homozygotes).</p><p>^e Recessive model of inheritance (rare homozygotes <i>versus</i> combined heterozygotes and common homozygotes).</p><p>^f S for alleles coding for 12–14 alanines and L for alleles coding for 16–19 alanines.</p><p>Association results between the five polymorphisms and the risk of developing DTC.</p