Variation of organic carbon and nitrate with river flow within an oceanic regime in a rural area and potential impacts for drinking water production

International audienceOver the last two decades, climate change has become a major environmental and public health concern due to the increase of the mean temperature on the Earth and its consequences on extreme meteorological events such as floods and droughts. These events induce very low or very high river flows that may impair surface water quality, and therefore result in potential health impacts when used for drinking water production. The present study aims at assessing the impact of hydrologic regime on surface water quality with a particular emphasis on total organic carbon (TOC) and nitrate. Water quality data from three French rivers acquired over a 27 years period, from January 1983 to December 2009, show the influence of extreme flows. Variation in TOC and nitrate concentrations showed opposite patterns for the whole range of flow rate (from less than 10% up to more than 100% of the mean flow). Regarding fluxes, TOC increased continuously with flow rate while nitrate was stable for very high discharges. The C/N ratio expressed from TOC and nitrate concentrations showed high values for extreme flows and particularly for very low flow rates, generally in summer, where nitrate is assimilated by biomass. Considering TOC and nitrate fluxes, it is confirmed that the worst situations were encountered for very high flow rates, namely for TOC exportation during surface runoff which was related to heavy rains or floods. These findings are of great importance with regard to the adaptation for drinking water treatment in facing extreme hydrological conditions, of which the frequency is increasing with climate change

BBADIS-16-507-R1 1 Integrative network analysis reveals time-dependent molecular events underlying left ventricular remodeling in post-myocardial infarction patients

International audienceTo elucidate the time-resolved molecular events underlying the LV remodeling (LVR) process, we developed a large-scale network model that integrates the 24 molecular variables (plasma proteins and non-coding RNAs) collected in the REVE-2 study at four time points (baseline, 1month, 3months and 1year) after MI. The REVE-2 network model was built by extending the set of REVE-2 variables with their mechanistic context based on known molecular interactions (1310 nodes and 8639 edges). Changes in the molecular variables between the group of patients with high LVR (>20%) and low LVR (<20%) were used to identify active network modules within the clusters associated with progression of LVR, enabling assessment of time-resolved molecular changes. Although the majority of molecular changes occur at the baseline, two network modules specifically show an increasing number of active molecules throughout the post-MI follow up: one involved in muscle filament sliding, containing the major troponin forms and tropomyosin proteins, and the other associated with extracellular matrix disassembly, including matrix metalloproteinases, tissue inhibitors of metalloproteinases and laminin proteins. For the first time, integrative network analysis of molecular variables collected in REVE-2 patients with known molecular interactions allows insight into time-dependent mechanisms associated with LVR following MI, linking specific processes with LV structure alteration. In addition, the REVE-2 network model provides a shortlist of prioritized putative novel biomarker candidates for detection of LVR after MI event associated with a high risk of heart failure and is a valuable resource for further hypothesis generation

Étude pilote de l’entretien motivationnel chez des personnes condamnées pour conduite avec facultés affaiblies

Dans cette étude pilote contrôlée et randomisée (N = 51), nous avons examiné l’impact d’une intervention brève, l’entretien motivationnel (EM, Motivational Interviewing), comparée à une simple séance d’information comme condition contrôle, chez des personnes condamnées pour conduite avec facultés affaiblies. Les participants devaient avoir un diagnostic actif d’abus ou de dépendance à l’alcool et devaient être recrutés en dehors des programmes officiels de traitement pour conducteurs avec facultés affaiblies de façon à tester l’EM chez des individus qui n’étaient pas nécessairement prêts à changer. Nous avons évalué le pourcentage de jours de forte consommation d’alcool (≥ 6 consommations standards d’alcool par jour), les résultats à l’AUDIT et l’utilisation de services après trois et six mois de suivi. Les résultats indiquent que l’exposition à l’EM a entraîné une réduction significativement plus grande du nombre de jours à forte consommation d’alcool et du nombre de visites à des professionnels de la santé après six mois de suivi. L’ampleur des effets observés est comparable à celle que l’on peut retrouver dans d’autres études employant l’EM avec différentes populations ayant un problème d’alcool. Quoique préliminaires, ces résultats suggèrent que l’emploi de l’EM pourrait être avantageux, même chez des individus qui ne sont pas engagés dans un processus de réhabilitation. Une étude plus approfondie du potentiel de l’EM conduisant directement à une amélioration de la conduite en état d’ébriété est clairement justifiée.A pilot randomized controlled trial (N = 51) investigated the impact of a brief intervention approach : Motivational Interviewing (MI), compared to a simple information session as a control condition, in offenders convicted of driving under the influence (DUI). Participants had a current diagnosis of alcohol abuse or dependence, and were recruited outside of mandated DUI remedial programs, in order to test MI in individuals who were not necessarily prepared to change. We evaluated the percentage of days of significant alcohol consumption (≥ 6 standard drinks a day), AUDIT scores and service utilization at three and six months follow-up. Results indicated that exposure to MI resulted in a significantly greater reduction in the number of days of significant alcohol consumption and fewer visits to health professionals at six months follow-up. Observed effect sizes were comparable to other studies of MI in different populations with alcohol problems. While preliminary, these results suggest that MI for DUI could have benefits, even in individuals who are not involved in a remedial process. A comprehensive study of MI’s potential in more directly improving drinking and driving outcomes is clearly warranted.En este estudio piloto controlado y aleatorio (N = 51), hemos examinado el impacto que produjo una breve intervención, la entrevista de motivación (EM, Motivational Interviewing), en personas condenadas por conducir con facultades debilitadas, comparándola a una simple sesión de información como condición de control. Los participantes debían tener un diagnóstico activo de abuso o de dependencia de alcohol y haber sido reclutados fuera de los programas oficiales de tratamiento para conductores con facultades debilitadas, con el objetivo de probar la entrevista de motivación en individuos que no estaban necesariamente preparados para cambiar. Hemos evaluado el porcentaje de días de fuerte consumo de alcohol (≥ 6 consumos regulares de alcohol por día), los resultados en la verificación y la utilización de los servicios luego de tres y seis meses de seguimiento. Los resultados indican que la exposición a la entrevista de motivación generó una reducción significativamente más importante de días de fuerte consumo de alcohol y de la cantidad de visitas a profesionales de la salud luego de seis meses de seguimiento. La amplitud de los efectos observados es comparable a la que se puede encontrar en otros estudios que emplean la entrevista de motivación con diferentes poblaciones que tienen un problema de alcohol. Si bien preliminares, estos resultados sugieren que el uso de las entrevistas de motivación podría ser ventajoso, incluso con individuos que no están comprometidos en un proceso de rehabilitación. Se justifica ampliamente un estudio más profundo de las posibilidades de la entrevista de motivación como medio para lograr directamente una mejoría en cuando a la conducción de vehículos en estado de ebriedad

DAPAR & ProStaR: software to perform statistical analyses in quantitative discovery proteomics.

UNLABELLED: DAPAR and ProStaR are software tools to perform the statistical analysis of label-free XIC-based quantitative discovery proteomics experiments. DAPAR contains procedures to filter, normalize, impute missing value, aggregate peptide intensities, perform null hypothesis significance tests and select the most likely differentially abundant proteins with a corresponding false discovery rate. ProStaR is a graphical user interface that allows friendly access to the DAPAR functionalities through a web browser. AVAILABILITY AND IMPLEMENTATION: DAPAR and ProStaR are implemented in the R language and are available on the website of the Bioconductor project (http://www.bioconductor.org/). A complete tutorial and a toy dataset are accompanying the packages. CONTACT: [email protected], [email protected], [email protected] (ChloroTypes), ANR-10-INBS-08 (ProFI project, ‘Infrastructures Nationales en Biologie et Sante´’, ‘Investissements d’Avenir’), European Union FP7 program (Prime-XS Project, Contract no. 262067), Prospectom project (Mastodons 2012 CNRS Challenge), Biotechnology and Biological Sciences Research Council (Strategic Longer and Larger Grant ID: BB/L002817/1)This is the final version of the article. It first appeared from Oxford University Press via https://doi.org/10.1093/bioinformatics/btw58

Daptomycin > 6 mg/kg/day as salvage therapy in patients with complex bone and joint infection: cohort study in a regional reference center

Background: Even if daptomycin does not have approval for the treatment of bone and joint infections (BJI), the Infectious Diseases Society of America guidelines propose this antibiotic as alternative therapy for prosthetic joint infection. The recommended dose is 6 mg/kg/d, whereas recent data support the use of higher doses in these patients.Methods: We performed a cohort study including consecutive patients that have received daptomycin >6 mg/kg/d for complex BJI between 2011 and 2013 in a French regional reference center. Factors associated with treatment failure were determined on univariate Cox analysis and Kaplan-Meier curves.Results: Forty-three patients (age, 61 ± 17 years) received a mean dose of 8 ± 0.9 mg/kg/d daptomycin, for a mean 81 ± 59 days (range, 6-303 days). Most had chronic (n = 37, 86 %) implant-associated (n = 37, 86 %) BJI caused by coagulasenegative staphylococci (n = 32, 74 %). A severe adverse event (SAE) occurred in 6 patients (14 %), including 2 cases of eosinophilic pneumonia, concomitant with daptomycin Cmin >24 mg/L. Outcome was favorable in 30 (77 %) of the 39 clinically assessable patients. Predictors for treatment failure were age, non-optimal surgery and daptomycin withdrawal for SAE.Conclusions: Prolonged high-dose daptomycin therapy was effective in patients with complex BJI. However, optimal surgery remains the cornerstone of medico-surgical strategy; and a higher incidence of eosinophilic pneumonia than expected was recorded

Insights into gene expression profiling of natural resistance to coccidiosis in contrasting chicken lines

Coccidiosis is a parasitic disease with major economic impact, one of whose main causative agents is Eimeria tenella. Chicken breeds display variable natural resistance to this disease. Unravelling the genetic bases of such variations could provide new clues for protection strategies. Transcriptomic experiments were conducted comparing resistant (Fayoumi) and susceptible (Leghorn) lines. Caecum and caecal tonsils were analysed. A global increase in differential gene expression following infection was observed for caecum comparisons, whereas a global decrease following infection was observed for caecal tonsils

Mass Spectrometry-based Absolute Quantification of 20S Proteasome Status for Controlled Ex-vivo Expansion of Human Adipose-derived Mesenchymal Stromal/Stem Cells

International audienceIn Brief 20S proteasomes are very heterogeneous protein complexes involved in many cellular processes. In the present study, we combined an MRM-based assay with the production and purification of entire SILAC labelled pro-teasome to monitor absolute quantities of the different 20S proteasome subtypes in various human cells and tissues. This method applied to adipocyte-derived stem cells (ADSCs) amplified under various conditions highlights an increased expression of immunoproteasome when this type of cell is primed with IFN␥ or amplified in a 20% O 2 environment. Graphical Abstract Highlights • Design of an MRM assay to determine the absolute quantity and stoichiometry of ubiquitous and tissue-specific human 20S proteasome subtypes. • Use of purified isotopically labelled 20S proteasome as internal standard for accurate quantification. • Variation in the expression of immunoproteasome in adipocyte-derived stem cells (ADSCs) grown under different O 2 levels might be causal for change in cells differentiation capacity. • The status of 20S proteasome during ADSCs expansion might constitute an additional relevant quality control parameter to contribute to predict, among other quality markers, their therapeutic capacity

Performance of Small Cluster Surveys and the Clustered LQAS Design to estimate Local-level Vaccination Coverage in Mali

<p>Abstract</p> <p>Background</p> <p>Estimation of vaccination coverage at the local level is essential to identify communities that may require additional support. Cluster surveys can be used in resource-poor settings, when population figures are inaccurate. To be feasible, cluster samples need to be small, without losing robustness of results. The clustered LQAS (CLQAS) approach has been proposed as an alternative, as smaller sample sizes are required.</p> <p>Methods</p> <p>We explored (i) the efficiency of cluster surveys of decreasing sample size through bootstrapping analysis and (ii) the performance of CLQAS under three alternative sampling plans to classify local VC, using data from a survey carried out in Mali after mass vaccination against meningococcal meningitis group A.</p> <p>Results</p> <p>VC estimates provided by a 10 × 15 cluster survey design were reasonably robust. We used them to classify health areas in three categories and guide mop-up activities: i) health areas not requiring supplemental activities; ii) health areas requiring additional vaccination; iii) health areas requiring further evaluation. As sample size decreased (from 10 × 15 to 10 × 3), standard error of VC and ICC estimates were increasingly unstable. Results of CLQAS simulations were not accurate for most health areas, with an overall risk of misclassification greater than 0.25 in one health area out of three. It was greater than 0.50 in one health area out of two under two of the three sampling plans.</p> <p>Conclusions</p> <p>Small sample cluster surveys (10 × 15) are acceptably robust for classification of VC at local level. We do not recommend the CLQAS method as currently formulated for evaluating vaccination programmes.</p

CD95 recruits PLCγ1 to trigger a calcium response promoting Th17 accumulation in inflamed organs of lupus mice

CD95 ligand (CD95L) is expressed by immune cells and triggers apoptotic death. Metalloprotease-cleaved CD95L (cl-CD95L) is released into the bloodstream but does not trigger apoptotic signaling. Hence, the pathophysiological role of cl-CD95L remains unclear. We observed that skin-derived endothelial cells from systemic lupus erythematosus (SLE) patients expressed CD95L, and that after cleavage, cl-CD95L promoted T helper 17 (Th17) lymphocyte transmigration across the endothelial barrier at the expense of T regulatory cells. T cell migration relied on a direct interaction between the CD95 domain called calcium-inducing domain (CID) and the Src homology 3 domain of phospholipase Cγ1. Th17 cells stimulated with cl-CD95L produced sphingosine-1-phosphate (S1P), which promoted endothelial transmigration by activating the S1P receptor 3. We generated a cell-penetrating CID peptide that prevented Th17 cell transmigration and alleviated clinical symptoms in lupus mice. Therefore, neutralizing the CD95 non-apoptotic signaling pathway may be attractive therapeutic approach for SLE treatment