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La gouvernance, idée et concept dont l'utilisation s'est répandue d'une manière étendue au début de la décennie 90 de la part des organisations internationales, comme méthodologie afin de réaliser le développement de la sociabilité dans les pays développés suite à l'incapacité des administration. Comme, elle jouit d'une grande importance pareillement pour les pays développés et les pays en vois de développement afin d'y réaliser les ambitions des citoyens en offrant une croissance globale et durable. L'engagement pour appliquer les principes de gouvernance, constitue des supports fondamentaux pour le dévelo-ppement des entreprises et leurs exigences de divulgation, de transparence et d'égalité entre les actionnaires soutenir les décisions des investisseurs concernant les investissements. Cependant la différence du contenu dans l'application et les priorités des systèmes comptables d'un pays à un autre pays et devant l'étendue et la globalisation du commerce, de l'investissement et de l'échange commercial entre les différents pays, fait que des efforts ont commencé se regrouper pour mettre des fondements et règles pour la fonction comptable, d’où sont né ce qu'on appelle par normes comptables internationales, ont pour objectif l'unification des principes comptables au niveau international afin d'offrir une base unique pour la lecture des états financières des différentes entreprises dans le monde.

International audience; BackgroundHIV-related stigma diminishes the quality of life of affected patients. Little is known about perceived and enacted stigma of HIV-infected children in resources-limited settings. We documented the prevalence of perceived stigma and associated factors associated among children on antiretroviral therapy (ART) at a referral hospital in Cambodia.MethodsAfter informed consent, a standardized pre-tested 47-item questionnaire was confidentially administered to consecutive children (7 to 15 years) or their guardians if the child was 18 months to 6 years, during their routine ART visits. The questionnaire explored the sociodemographics of the child and the parents, HIV history, adherence to ART, tolerance of ART and perceived stigma. Associations between perceived stigma and the children¿s characteristics were measured by bivariate and multivariate analyses.ResultsOf 183 children, 101 (55.2%) had lost at least one and 45 (24.6%) both parents; 166 (90.7%) went to school. Of 183 children (female:84, 45.9%, median age 7.0 years, interquartile range: 2.0-9.6), 79 (43.2%) experienced perceived stigma, including rejection by others (26.8%), no invitations to social activities (18.6%) and exclusion from games (14.2%). A total of 43 (23.5 %) children were fearful of their disease and 61 (53.9%) of 113 older than 6 years reported knowledge of their HIV status. Of 136 children over five years and eligible for education, 7 (3.8%) could not go to school due to perceived stigma. Incomplete adherence to ART was reported for 17 (9.2%) children. In multivariate analysis, school attendance (odds ratio [OR]: 3.9; 95% confidence interval [CI]: 2.0-7.9) and income of less than one dollar per person per day (OR: 2.2, 95%CI: 1.1-4.5) were associated with perceived stigma. Conversely, receipt of social support (OR: 0.4, 95% CI 0.2-0.9) was associated with lower risk of perceived stigma.ConclusionPerceived stigma in pediatric ART patients remains a significant issue in Cambodia. Psychological support and interventions should be developed in hospitals, schools, and underprivileged communities to prevent HIV-related stigma for affected children.

Background Aldosterone synthase inhibition provides the potential to attenuate both the mineralocorticoid receptor-dependent and independent actions of aldosterone. In vitro studies with recombinant human enzymes showed LCI699 to be a potent, reversible, competitive inhibitor of aldosterone synthase (Ki = 1.4 ± 0.2 nmol/L in humans) with relative selectivity over 11β-hydroxylase. Methods Hormonal effects of orally administered LCI699 were examined in rat and monkey in vivo models of adrenocorticotropic hormone (ACTH) and angiotensin-II-stimulated aldosterone release, and were compared with the mineralocorticoid receptor antagonist eplerenone in a randomized, placebo-controlled study conducted in 99 healthy human subjects. The effects of LCI699 and eplerenone on cardiac and renal sequelae of aldosterone excess were investigated in a double-transgenic rat (dTG rat) model overexpressing human renin and angiotensinogen. Results Rat and monkey in vivo models of stimulated aldosterone release predicted human dose– and exposure–response relationships, but overestimated the selectivity of LCI699 in humans. In the dTG rat model, LCI699 dose-dependently blocked increases in aldosterone, prevented development of cardiac and renal functional abnormalities independent of blood pressure changes, and prolonged survival. Eplerenone prolonged survival to a similar extent, but was less effective in preventing cardiac and renal damage. In healthy human subjects, LCI699 0.5 mg selectively reduced plasma and 24 h urinary aldosterone by 49 ± 3% and 39 ± 6% respectively (Day 1, mean ± SEM; P

Background Thrombocytopenia is common in the intensive care unit. Potential mechanisms and etiologies behind this phenomenon are multiple and often entangled. We assessed the effect of a systematic approach, using routinely available tests, on the proportion of patients in whom the mechanism (primary objective) and etiology (secondary objective) of thrombocytopenia in a mixed intensive care unit (ICU) could be identified. Methods Before-and-after study of all patients with thrombocytopenia was used. ‘Before’ group had no intervention. New standard operating procedures for thrombocytopenia management were introduced. In the ‘After’ group, bone marrow aspiration; determination of fibrinogen dosage, prothrombin time, factor V, D-dimers; assay of fibrin monomers, ferritin, triglycerides, lactic acid dehydrogenase, aspartate transaminase, alanine aminotransferase, vitamin B12, folates, reticulocytes, haptoglobin, and bilirubin were performed. Results In the Before group (n = 20), the mechanism (central, peripheral, or mixed) was identified in 10 % versus 83% in After group (n = 23) (p p Conclusions Systematic and extensive investigation using routine tests highlights the mechanisms and etiology of thrombocytopenia in most cases.

OBJECTIVE: The best combination of questions to define asthma in epidemiological asthma studies is not known. We summarized the operational definitions of asthma used in prevalence studies and empirically assess how asthma prevalence estimates vary depending on the definition used. METHODS: We searched the Thomson Reuters ISI Web of knowledge and included (1) cross-sectional studies (2) on asthma prevalence (3) conducted in the general population and (4) containing an explicit definition of asthma. The search was limited to the 100 most-cited papers or published since January 2010. For each paper, we recorded the asthma definition used and other variables. Then we applied the definitions to the data of the Portuguese National Asthma survey (INAsma) and of the 2005-2006 National Health and Nutrition Examination Survey (NHANES) computing asthma prevalence estimates for the different definitions. RESULTS: Of 1738 papers retrieved, 117 were included for analysis. Lifetime asthma, diagnosed asthma and current asthma were defined in 8, 12 and 29 different ways, respectively. By applying definitions of current asthma on INAsma and NHANES data, the prevalence ranged between 5.3%-24.4% and 1.1%-17.2%, respectively. CONCLUSIONS: There is considerable heterogeneity in the definitions of asthma used in epidemiological studies leading to highly variable estimates of asthma prevalence. Studies to inform a standardized operational definition are needed. Meanwhile, we propose a set of questions to be reported when defining asthma in epidemiological studies. info:eu-repo/semantics/publishedVersion

Introduction Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) represents the most common hereditary form of cerebral small vessel disease characterized by early-onset stroke and premature dementia. It is caused by mutations in the transmembrane receptor Notch3, which promote the aggregation and accumulation of the Notch3 extracellular domain (Notch3-ECD) within blood vessel walls. This process is believed to mediate the abnormal recruitment and dysregulation of additional factors including extracellular matrix (ECM) proteins resulting in brain vessel dysfunction. Based on recent evidence indicating a role for the transforming growth factor-β (TGF-β) pathway in sporadic and familial small vessel disease we studied fibronectin, fibrillin-1 and latent TGF-β binding protein 1 (LTBP-1), three ECM constituents involved in the regulation of TGF-β bioavailability, in post-mortem brain tissue from CADASIL patients and control subjects. Results Fibronectin and fibrillin-1 were found to be enriched in CADASIL vessels without co-localizing with Notch3-ECD deposits, likely as a result of fibrotic processes secondary to aggregate formation. In contrast, LTBP-1 showed both an accumulation and a striking co-localization with Notch3-ECD deposits suggesting specific recruitment into aggregates. We also detected increased levels of the TGF-β prodomain (also known as latency-associated peptide, LAP) indicating dysregulation of the TGF-β pathway in CADASIL development. In vitro analyses revealed a direct interaction between LTBP-1 and Notch3-ECD and demonstrated a specific co-aggregation of LTBP-1 with mutant Notch3. Conclusion We propose LTBP-1 as a novel component of Notch3-ECD deposits and suggest its involvement in pathological processes triggered by Notch3-ECD aggregation. Electronic supplementary material The online version of this article (doi:10.1186/s40478-014-0096-8) contains supplementary material, which is available to authorized users.

Background Evidence continues to mount concerning the importance of the enteric nervous system (ENS) in controlling numerous intestinal functions in addition to motility and epithelial functions. Nevertheless, little is known concerning the direct participation of the ENS in the inflammatory response of the gut during infectious or inflammatory insults. In the present study we analyzed the ENS response to bacterial lipopolysaccharide, in particular the production of a major proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α). Methods TNF-α expression (measured by qPCR, quantitative Polymerase Chain Reaction) and production (measured by ELISA) were measured in human longitudinal muscle-myenteric plexus (LMMP) and rat ENS primary cultures (rENSpc). They were either treated or not treated with lipopolysaccharide (LPS) in the presence or not of electrical field stimulation (EFS). Activation of extracellular signal-regulated kinase (ERK) and 5’-adenosine monophosphate-activated protein kinase (AMPK) pathways was analyzed by immunocytochemistry and Western blot analysis. Their implications were studied using specific inhibitors (U0126, mitogen-activated protein kinase kinase, MEK, inhibitor and C compound, AMPK inhibitor). We also analyzed toll-like receptor 2 (TLR2) expression and interleukin-6 (IL-6) production after LPS treatment simultaneously with EFS or TNF-α-neutralizing antibody. Results Treatment of human LMMP or rENSpc with LPS induced an increase in TNF-α production. Activation of the ENS by EFS significantly inhibited TNF-α production. This regulation occurred at the transcriptional level. Signaling analyses showed that LPS induced activation of ERK but not AMPK, which was constitutively activated in rENSpc neurons. Both U0126 and C compound almost completely prevented LPS-induced TNF-α production. In the presence of LPS, EFS inhibited the ERK and AMPK pathways. In addition, we demonstrated using TNF-α-neutralizing antibody that LPS-induced TNF-α production increased TLR2 expression and reduced IL-6 production. Conclusions Our results show that LPS induced TNF-α production by enteric neurons through activation of the canonical ERK pathway and also in an AMPK-dependent manner. ENS activation through the inhibition of these pathways decreased TNF-α production, thereby modulating the inflammatory response induced by endotoxin. Electronic supplementary material The online version of this article (doi:10.1186/s12974-014-0202-7) contains supplementary material, which is available to authorized users.

International audience; Background:In primary care surveillance systems based on voluntary participation, biased results may arise fromthe lack of representativeness of the monitored population and uncertainty regarding the population denominator,especially in health systems where patient registration is not required.Methods:Based on the observation of a positive association between number of cases reported and number ofconsultations by the participating general practitioners (GPs), we define several weighted incidence estimatorsusing external information on consultation volume in GPs. These estimators are applied to data reported in aFrench primary care surveillance system based on voluntary GPs (theSentinellesnetwork) for comparison.Results:Depending on hypotheses for weight computations, relative changes in weekly national-level incidenceestimates up to 3% for influenza, 6% for diarrhea, and 11% for varicella were observed. The use of consultation-weightedestimates led to bias reduction in the estimates. At the regional level (NUTS2 level -Nomenclature of Statistical TerritorialUnits Level 2), relative changes were even larger betweenincidence estimates, with changes between -40% and +55%.Using bias-reduced weights decreased variation in incidence between regions and increased spatial autocorrelation.Conclusions:Post-stratification using external administrative data may improve incidence estimates in surveillancesystems based on voluntary participation

Background Last generations of Single Nucleotide Polymorphism (SNP) arrays allow to study copy-number variations in addition to genotyping measures. Results MPAgenomics, standing for multi-patient analysis (MPA) of genomic markers, is an R-package devoted to: (i) efficient segmentation and (ii) selection of genomic markers from multi-patient copy number and SNP data profiles. It provides wrappers from commonly used packages to streamline their repeated (sometimes difficult) manipulation, offering an easy-to-use pipeline for beginners in R. The segmentation of successive multiple profiles (finding losses and gains) is performed with an automatic choice of parameters involved in the wrapped packages. Considering multiple profiles in the same time, MPAgenomics wraps efficient penalized regression methods to select relevant markers associated with a given outcome. Conclusions MPAgenomics provides an easy tool to analyze data from SNP arrays in R. The R-package MPAgenomics is available on CRAN.

Introduction Pain assessment is associated with important outcomes in ICU patients but remains challenging, particularly in non-communicative patients. Use of a reliable tool is paramount to allow any implementation of sedation/analgesia protocols in a multidisciplinary team. This study compared psychometric properties (inter-rater agreement primarily; validity, responsiveness and feasibility secondarily) of three pain scales: Behavioural Pain Scale (BPS/BPS-NI, that is BPS for Non-Intubated patients), Critical Care Pain Observation Tool (CPOT) and Non-verbal Pain Scale (NVPS), the pain tool routinely used in this 16-bed medical ICU. Methods Pain was assessed by at least one of four investigators and one of the 20 bedside nurses before, during and 10 minutes after routine care procedures in non-comatose patients (Richmond Agitation Sedation Scale ≥ -3) who were unable to self-report their pain intensity. The Confusion Assessment Method for the ICU was used to assess delirium. Non-parametric tests were used for statistical analysis. Quantitative data are presented as median (25th to 75th). Results A total of 258 paired assessments of pain were performed in 30 patients (43% lightly sedated, 57% with delirium, 63% mechanically ventilated). All three scales demonstrated good psychometric properties. However, BPS and CPOT exhibited the best inter-rater reliability (weighted-κ 0.81 for BPS and CPOT) and the best internal consistency (Cronbach-α 0.80 for BPS, 0.81 for CPOT), which were higher than for NVPS (weighted-κ 0.71, P

International audience; Whether exertional dyspnoea can be attributed to poor circulatory-muscular conditioning is a difficult clinical issue. Because criteria of poor conditioning such as low oxygen pulse, low ventilatory threshold or high heart rate/oxygen consumption slope can be observed in heart or lung diseases and are not specific to conditioning, we assessed the relationships between physical exercise, conditioning and exertional breathlessness in healthy subjects, in whom the aforementioned criteria can confidently be interpreted as reflecting conditioning. To this end, healthy males with either low (inactive men, n = 31) or high (endurance-trained men, n = 31) physical activity evaluated using the International Physical Activity Questionnaire (IPAQ) underwent spirometry and incremental exercise testing with breathlessness assessment using Borg scale. No significant breathlessness was reported before the ventilatory threshold in the two groups. Peak breathlessness was highly variable, did not differ between the two groups, was not related to any conditioning criterion, but correlated with peak respiratory rate. Nevertheless, endurance-trained subjects reported lower breathlessness at the same ventilation levels in comparison with inactive subjects. Significant but weak associations were observed between isoventilation breathlessness and physical activity indices (Borg at 60 L/min and total IPAQ scores, rho = -0.31, p = 0.020), which were mainly attributable to the vigorous domain of physical activity, as well as with conditioning indices (Borg score at 60 L.min(-1) and peak oxygen pulse or heart rate/oxygen consumption slope, rho = -0.31, p = 0.021 and rho = 0.31, p = 0.020; respectively). In conclusion, our data support a weak relationship between exertional breathlessness and circulatory-muscular conditioning, the later being primarily related to vigorous physical activity.

International audience; Background:The phosphoinositide 3- kinase (PI3K) pathway is involved in the growth of various human cancers,including lymphoid malignancies. However its role in the pathogenesis of follicular lymphoma (FL) has not beenyet described.Methods:To clarify this point, biopsy tissue samples from 38 human FL cases were investigated for PIK3CA somaticmutations in exon 9 and 20 using direct sequencing. The same samples were analyzed using western blotting andimmunohistochemistry to detect expression of AKT, phosphorylated AKT (pAKT), and PTEN proteins. Two cases ofbenign lymphadenitis were used as controls.Results:AKT expression was present in all FL and lymphadenitis cases. 14/38 (37%) FL and 2/2 lymphadenitis casesexpressed pAKT. 9/38 (24%) FL samples showed high level of pAKT, whereas 5/38 (13%) FL cases and 2/2 benignlymphadenitis samples expressed low level of pAKT. PTEN expression was observed in 30/38 (79%) FL and 2/2benign lymphadenitis cases, whereas 8/38 (21%) FL cases showed loss of PTEN expression. 3 cases with positivepAKT did not express PTEN. PIK3CA mutations were not detected in any sample.Conclusions:These data suggest that the PI3K/AKT signaling pathway could be activated in a subset of FL cases,due to either AKT phosphorylation or PTEN downregulation, in the absence of PIK3CA mutations.

Background Hand synergies have been extensively studied over the last few decades. Objectives of such research are numerous. In neuroscience, the aim is to improve the understanding of motor control and its ability to reduce the control dimensionality. In applied research fields like robotics the aim is to build biomimetic hand structures, or in prosthetics to design more performant underactuated replacement hands. Nevertheless, most of the synergy schemes identified to this day have been obtained from grasping experiments performed with one single (generally dominant) hand to objects placed in a given position and orientation in space. Aiming at identifying more generic synergies, we conducted similar experiments on postural synergy identification during bimanual manipulation of various objects in order to avoid the factors due to the extrinsic spatial position of the objects. Methods Ten healthy naive subjects were asked to perform a selected “grasp-give-receive” task with both hands using 9 objects. Subjects were wearing Cyberglove Ⓒ on both hands, allowing a measurement of the joint posture (15 degrees of freedom) of each hand. Postural synergies were then evaluated through Principal Component Analysis (PCA). Matches between the identified Principal Components and the human hand joints were analyzed thanks to the correlation matrix. Finally, statistical analysis was performed on the data in order to evaluate the effect of some specific variables on the hand synergies: object shape, hand side (i.e., laterality) and role (giving or receiving hand). Results Results on PCs are consistent with previous literature showing that a few principal components might be sufficient to describe a large variety of different grasps. Nevertheless some simple and strong correlations between PCs and clearly identified sets of hand joints were obtained in this study. In addition, these groupings of DoF corresponds to well-defined anatomo-functional finger joints according to muscle groups. Moreover, despite our protocol encouraging symmetric grasping, some right-left side differences were observed. Conclusion The set of identified synergies presented here should be more representative of hand synergies in general since they are based on both hands motion. Preliminary results, that should be deepened, also highlight the influence of hand dominance and side. Thanks to their strong correlation with anatomo-functional joints, these synergies could therefore be used to design underactuated robotics hands.

International audience; Background:Natural Language Processing (NLP) has been shown effective to analyze the content of radiologyreports and identify diagnosis or patient characteristics. We evaluate the combination of NLP and machine learningto detect thromboembolic disease diagnosis and incidental clinically relevant findings from angiography andvenography reports written in French. We model thromboembolic diagnosis and incidental findings as a set of concepts,modalities and relations between concepts that can be used as features by a supervised machine learning algorithm. Acorpus of 573 radiology reports was de-identified and manually annotated with the support of NLP tools by a physicianfor relevant concepts, modalities and relations. A machine learning classifier was trained on the dataset interpreted by aphysician for diagnosis of deep-vein thrombosis, pulmonary embolism and clinically relevant incidental findings. Decisionmodels accounted for the imbalanced nature of the data and exploited the structure of the reports.Results:The best model achieved an F measure of 0.98 for pulmonary embolism identification, 1.00 for deep veinthrombosis, and 0.80 for incidental clinically relevant findings. The use of concepts, modalities and relations improvedperformances in all cases.Conclusions:This study demonstrates the benefits of developing an automated method to identify medical concepts,modality and relations from radiology reports in French. An end-to-end automatic system for annotationand classification which could be applied to other radiology reports databases would be valuable for epidemiologicalsurveillance, performance monitoring, and accreditation in French hospitals.

International audience; Background:To date, few studies have investigated serum vitamin D status in patients with inherited ichthyosis.The aim of this study was to determine the prevalence of vitamin D deficiency (defined as serum level

International audience; F17 fimbriae are produced by pathogenic Escherichia coli involved in diarrhea and septicemia outbreaks in calves and lambs. These proteins result from the expression of four different clustered genes, namely f17A, f17D, f17C and f17G, encoding a pilin protein, a periplasmic protein, an anchor protein and an adhesin protein, respectively. Several variants of f17A and f17G genes have been reported and found genetically associated with typical virulence factors of bovine pathogenic E. coli strains. In this study, a new F17e-A variant, closely related to F17b-A, was identified from a collection of 58 E. coli isolates from diarrheic calves in Iran. While highly prevalent in Iranian F17-producing clinical isolates from calves, this variant was rare among E. coli from a French healthy adult bovine population, suggesting a possible association with virulence. The f17Ae gene was also found in the genome of the Shiga-like toxin variant Stx1d–producing bovine E. coli strain MHI813, and belonged to a gene cluster also encoding a new F17-G3 variant, which greatly differed from F17-G1 and F17-G2. This gene cluster was located on a pathogenicity island integrated in the tRNA pheV gene. The gene coding for a third new F17f-A variant corresponding to a combination of F17c-A and F17d-A was also identified on the pVir68 plasmid in the bovine pathogenic E. coli strain 6.0900. In conclusion, we identified three new F17-A and F17-G variants in cattle E. coli, which may also have significant impact on the development of new diagnostics and vaccination tools.

Background DNA methylation is associated with aberrant gene expression in cancer, and has been shown to correlate with therapeutic response and disease prognosis in some types of cancer. We sought to investigate the biological significance of DNA methylation in lung cancer. Results We integrated the gene expression profiles and data of gene promoter methylation for a large panel of non-small cell lung cancer cell lines, and identified 578 candidate genes with expression levels that were inversely correlated to the degree of DNA methylation. We found these candidate genes to be differentially methylated in normal lung tissue versus non-small cell lung cancer tumors, and segregated by histologic and tumor subtypes. We used gene set enrichment analysis of the genes ranked by the degree of correlation between gene expression and DNA methylation to identify gene sets involved in cellular migration and metastasis. Our unsupervised hierarchical clustering of the candidate genes segregated cell lines according to the epithelial-to-mesenchymal transition phenotype. Genes related to the epithelial-to-mesenchymal transition, such as AXL, ESRP1, HoxB4, and SPINT1/2, were among the nearly 20% of the candidate genes that were differentially methylated between epithelial and mesenchymal cells. Greater numbers of genes were methylated in the mesenchymal cells and their expressions were upregulated by 5-azacytidine treatment. Methylation of the candidate genes was associated with erlotinib resistance in wild-type EGFR cell lines. The expression profiles of the candidate genes were associated with 8-week disease control in patients with wild-type EGFR who had unresectable non-small cell lung cancer treated with erlotinib, but not in patients treated with sorafenib. Conclusions Our results demonstrate that the underlying biology of genes regulated by DNA methylation may have predictive value in lung cancer that can be exploited therapeutically. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-1079) contains supplementary material, which is available to authorized users.

International audience; Background:A prospective study was conducted to evaluate the impact of an educational reproductive healthprogram on medical student peer educators and the secondary school pupils whom they taught.Methods:The Marseille School of Medicine and ten public secondary schools participated in the study. Medicalstudents were recruited and trained as peer educators to promote sexual health in the secondary schools. Themedical students and secondary school pupils were evaluated before and after education program. The mainoutcome measure was the sexual health knowledge score on a 20-item questionnaire (maximum score 20).Results:A total of 3350 students attended the peer-led course conducted by 107 medical students. The medicalstudents’score increased significantly before and after the course (from 15.2 ± 1.8 to 18.3 ± 0.9; p < 0.001). Theknowledge score of the pupils increased (from 7.8 ± 4 to 13.5 ± 4.4; p < 0.001). The girls’score was significantlyhigher than the boys’score after the course, but not before (14.5 ± 3.3 vs 12.5 ± 4.6; p < 0.001). Prior to the course,the score among the female medical students was significantly higher than that of the males. The overall know-ledge increase was not significantly different between medical students and secondary school pupils (mean 3.1 ± 1and 5.7 ± 4 respectively; p > 0.05).Conclusions:The program was effective in increasing the knowledge of medical students as well as secondaryschool pupils. Male sexual health knowledge should be reinforced.

Background Teaching of medication prescribing is a specific challenge in general practice curriculum. The aim of this study was to identify and rank the competencies required for prescribing medication for general practice residents in France. Methods Qualitative consensus study using the nominal group technique. We invited different stakeholders of the general practice curriculum and medication use in primary care to a series of meetings. The nominal group technique allowed for the quick development of a list of consensual and ranked answers to the following question: “At the end of their general practice curriculum, in terms of medication prescribing, what should residents be able to do?”. Results Four meetings were held that involved a total of 31 participants, enabling the creation of a final list of 29 ranked items, grouped in 4 domains. The four domains identified were ‘pharmacology’, ‘regulatory standards’, ‘therapeutics’, and ‘communication (both with patients and healthcare professionals)’. Overall, the five items the most highly valued across the four meetings were: ‘write a legible and understandable prescription’, ‘identify specific populations’, ‘prescribe the doses and durations following the indication’, ‘explain a lack of medication prescription to the patient’, ‘decline inappropriate medication request’. The ‘communication skills’ domain was the domain with the highest number of items (10 items), and with the most highly-valued items. Conclusion The study results suggest a need for developing general practice residents’ communication skills regarding medication prescribing.

Background Prostate cancer is the second leading cause of male cancer death in developed countries. Although the role of angiogenesis in its progression is well established, the efficacy of anti-angiogenic therapy is not clearly proved. Whether this could depend on differential responses between tumor and normal endothelial cells has not been tested. Methods We isolated and characterized three lines of endothelial cells from prostate cancer and we tested the effect of Sunitinib and Sorafenib, and the combined treatment with the anti-androgen Casodex, on their angiogenic functions. Results Endothelial cells isolated from prostate tumors showed angiogenic properties and expression of androgen and vascular endothelial cell growth factor receptors. Sunitinib affected their proliferation, survival and motility while Sorafenib only showed a minor effect. At variance, Sunitinib and Sorafenib showed similar cytotoxic and anti-angiogenic effects on normal endothelial cells. Sorafenib and Sunitinib inhibited vascular endothelial cell growth factor receptor2 phosphorylation of prostate cancer endothelial cells, while they differentially modulated Akt phosphorylation as no inhibitory effect of Sorafenib was observed on Akt activation. The combined treatment of Casodex reverted the observed resistance to Sorafenib both on cell viability and on Akt activation, whereas it did not modify the response to Sunitinib. Conclusions Our study demonstrates a resistant behavior of endothelial cells isolated from prostate cancer to Sorafenib, but not Sunitinib. Moreover, it shows the benefit of a multi-target therapy combining anti-angiogenic and anti-hormonal drugs to overcome resistance. Electronic supplementary material The online version of this article (doi:10.1186/1471-2407-14-939) contains supplementary material, which is available to authorized users.

Background Gemcitabine/Cisplatin (Gem/CDDP) combination has demonstrated a clear survival advantage over gemcitabine alone and has become a new standard in advanced Biliary Tract Carcinoma (aBTC). However, Gemcitabine/Oxaliplatin (GEMOX) combination and Gemcitabine/Carboplatin (Gem/Carb) combination regimens have shown efficacy in phase II trials and there is no comparative study between different platinum salts. We assessed the efficacy and safety of different platinum-based chemotherapies at first line in aBTC patients. We also analysed the second-line chemotherapy. Methods Sixty-four consecutive patients with aBTC diagnosed between 1998 and 2010 were included for analysis. At first line chemotherapy, 44 patients received one day GEMOX regimen (gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 Day 1, every 2 weeks), and 20 patients received Gem/Carb regimen (gemcitabine at 1000 mg/m2 Days 1 and 8 with carboplatin delivered according to an area-under-the-curve (AUC) 5 at day 1, every 3 weeks). At second line, a total of 16 patients received a fluoropyrimidine-based chemotherapy. Results With GEMOX regimen, median progression-free survival (PFS) was 3.7 months (95%CI, 2.4 to 5) and median overall survival (OS) was 10.5 months (95%CI, 6.4 to14.7). The main toxicity was peripheral neuropathy (20% grade 2 and 7% grade 3). Grade 3/4 haematological toxicities were rare. With Gem/Carb regimen, PFS was 2.5 months (95%CI, 2.1 to 3.7) and OS was 4.8 months (95%CI, 3.7 to 5.8). The main grade 3/4 toxicities were haematological: anaemia (45%), thrombocytopenia (45%), and neutropenia (40%). At second-line, fluoropyrimidine-based chemotherapy was feasible in only a fourth of the patients. The median OS was 5.3 months (95%CI, 4.1 to 6.6), and median PFS was 4.0 months (95%CI, 2.6 to 5.5). Conclusions One day GEMOX regimen has a favourable toxicity profile and could be an alternative to standard Gem/CDDP regimen, in particular in unfit patients for CDDP. At second-line, selective patients may benefit from fluoropyrimidine-based chemotherapy.

International audience; Background:Little is known about the prevalence of intimate partner violence (IPV) and its associated factorsamong adolescents and younger women.Methods:This study analyzed data from nine countries of the WHO Multi-country Study on Women’s Health andDomestic Violence against Women, a population based survey conducted in ten countries between 2000 and 2004.Results:The lifetime prevalence of IPV ranged from 19 to 66 percent among women aged 15 to 24, with mostsites reporting prevalence above 50 percent. Factors significantly associated with IPV across most sites includedwitnessing violence against the mother, partner’s heavy drinking and involvement in fights, women’s experience ofunwanted first sex, frequent quarrels and partner’s controlling behavior. Adolescent and young women face asubstantially higher risk of experiencing IPV than older women.Conclusion:Adolescence and early adulthood is an important period in laying the foundation for healthy andstable relationships, and women’s health and well-being overall. Ensuring that adolescents and young women enjoyrelationships free of violence is an important investment in their future.

Background The frequency of antidepressant (ADs) prescription is high, with general practitioners (GPs) responsible for about 80% of the prescriptions. Some studies considered prescriptions meet DSM criteria, while others stress inadequate use. The importance of biological and psychosocial determinants of GP prescription behaviour remains little explored. We aimed to describe the importance of these biological and psychosocial determinants and their weight in the daily practice of GPs. Methods During a week chosen at random, 28 GPs collected the AD prescriptions made within the previous six months, regardless of the reason for the patient contact. Bio psychosocial and AD treatment characteristics were recorded for all patients. In a random sample of 50 patients, patient characteristics were assessed via a structured face-to-face interview with the GP. Results The frequency of AD prescription was 8.90% [3.94 -17.02]. The GPs initiated 65.6% [60.1-70.8] of the prescriptions. The rate of AD prescription for non-psychiatric conditions was 18%. Patients had from 1 to 9 conditions, showing a high level of multi-morbidity. There was a strong influence of past medical history and contextual problems, such as work related problems. Conclusion AD prescription is related to complex contextual situations and multi-morbid patients. GPs use a bio psycho social approach, rather than a purely biological assessment. Awareness of these influences could improve prescription by GPs.

Background In Huntington’s disease (HD), the ratio between normal and mutant Huntingtin (polyQ-hHtt) is crucial in the onset and progression of the disease. As a result, addition of normal Htt was shown to improve polyQ-hHtt-induced defects. Therefore, we recently identified, within human Htt, a 23aa peptide (P42) that prevents aggregation and polyQ-hHtt-induced phenotypes in HD Drosophila model. In this report, we evaluated the therapeutic potential of P42 in a mammalian model of the disease, R6/2 mice. Results To this end, we developed an original strategy for P42 delivery, combining the properties of the cell penetrating peptide TAT from HIV with a nanostructure-based drug delivery system (Aonys® technology), to form a water-in-oil microemulsion (referred to as NP42T) allowing non-invasive per mucosal buccal/rectal administration of P42. Using MALDI Imaging Mass Spectrometry, we verified the correct targeting of NP42T into the brain, after per mucosal administration. We then evaluated the effects of NP42T in R6/2 mice. We found that P42 (and/or derivatives) are delivered into the brain and target most of the cells, including the neurons of the striatum. Buccal/rectal daily administrations of NP42T microemulsion allowed a clear improvement of behavioural HD-associated defects (foot-clasping, rotarod and body weights), and of several histological markers (aggregation, astrogliosis or ventricular areas) recorded on brain sections. Conclusions These data demonstrate that NP42T presents an unprecedented protective effect, and highlight a new therapeutic strategy for HD, associating an efficient peptide with a powerful delivery technology. Electronic supplementary material The online version of this article (doi:10.1186/s40478-014-0086-x) contains supplementary material, which is available to authorized users.

International audience; Background:The aims of the study were (i) to investigate the relationship between elite marathon race times andage in 1-year intervals by using the world single age records in marathon running from 5 to 93 years and (ii)toevaluate the sex difference in elite marathon running performance with advancing age.Methods:World single age records in marathon running in 1-year intervals for women and men were analysedregarding changes across age for both men and women using linear and non-linear regression analyses for eachage for women and men.Results:The relationship between elite marathon race time and age was non-linear (i.e.polynomial regression 4thdegree) for women and men. The curve was U-shaped where performance improved from 5 to ~20 years. From5 years to ~15 years, boys and girls performed very similar. Between ~20 and ~35 years, performance was quitelinear, but started to decrease at the age of ~35 years in a curvilinear manner with increasing age in both womenand men. The sex difference increased non-linearly (i.e.polynomial regression 7thdegree) from 5 to ~20 years,remained unchanged at ~20 min from ~20 to ~50 years and increased thereafter. The sex difference was lowest(7.5%, 10.5 min) at the age of 49 years.Conclusion:Elite marathon race times improved from 5 to ~20 years, remained linear between ~20 and ~35 years,and started to increase at the age of ~35 years in a curvilinear manner with increasing age in both women andmen. The sex difference in elite marathon race time increased non-linearly and was lowest at the age of ~49 years.