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International audience; La fondation Aralis exerce un triple métier consistant à produire et gérer des logements temporaires dans les métropoles lyonnaise et stéphanoise, et à accompagner socialement les personnes en situations précaires qu’elle loge. Cet organisme est né en 1951-52, en plein contexte colonial, sous le nom de Maison de l’Afrique du Nord (MAN), initialement pour accueillir et loger des travailleurs algériens. À l’occasion des soixante-dix années d’existence d’Aralis, cet ouvrage propose un récit de l’histoire longue et des transformations d’un organisme local de logements. Il montre d’abord comment la gestion coloniale algérienne, rapatriée dans la métropole, a constitué une matrice à disposition pour la MAN. Il décrypte ensuite la façon dont le modèle colonial initial s’est transformé, sous les effets conjoints tant de l’accueil de nouveaux publics que de nouveaux modèles urbains de logements. Il insiste enfin sur la professionnalisation progressive des personnels comme levier permanent de transformations pour inscrire Aralis dans le champ du logement accompagné.

International audience

BACKGROUND MicroRNAs (miRNAs) have been suggested as biomarkers for malignant diseases including hepatocellular carcinoma (HCC). Specifically, hsa-miR-21-5p (miR-21) is among the most frequently deregulated miRNA in cancer. The diagnostic and prognostic value of miR-21 has been demonstrated in HCC tissue, mostly in the Asian population. Although the impact of various factors has been recently reported for circulating hsa-miR-122-5p (miR-122), at present only limited knowledge is available for miR-21. AIM To evaluate the value of miR-21 for the assessment of prognosis in HCC patients and to delineate the influence of clinical and preanalytical factors on miR-21 level in sera. METHODS Patients with confirmed HCC from our European cohort with predominantly alcohol-associated liver damage were included in the study. All subjects were characterized according to their clinical and laboratory work-up and overall survival data were obtained. Quantitative real-time polymerase chain reaction was performed for miR-21 and spiked-in cel-miR-39-3p. The results were compared to previously reported miR-122 data. RESULTS Survival of HCC patients was comparable between patients with low and high serum miR-21 concentration. No association was observed between miR-21 level in sera and Child-Pugh score, Barcelona Clinic Liver Cancer staging system, or etiology of HCC/liver disease. Age, gender, or pretreatment had no association with miR-21 level. A positive correlation was observed between miR-21 and aspartate aminotransferase (r = 0.2854, P = 0.0061), serum miR-122 (r = 0.2624, P = 0.0120), and the International Normalized Ratio (r = 0.2065, P = 0.0496). Negative correlation of miR-21 with serum creatinine (r = -0.2215, P = 0.0348) suggests renal function as a potential influencing factor in miR-21 biogenesis in blood. CONCLUSION The results from this work do not support clinically relevant prognostic value of circulating miR-21 in HCC patients in real-life settings. Following systematic evaluation, we identified renal function and aspartate aminotransferase as potential factors that may affect miR-21 concentration in blood. This knowledge should be considered in future miRNA-based biomarker studies not only for HCC but also for other diseases.

International audience

BACKGROUND There is ongoing search for new noninvasive biomarkers to improve management of patients with hepatocellular carcinoma (HCC). Studies, mostly from the Asian-Pacific region, demonstrated differential expression of liver-specific microRNA-122 (miR-122) in tissue as well as in sera of patients with hepatitis B virus- and hepatitis C virus-induced HCC. AIM To evaluate prognostic value of miR-122 in patients with HCC in a European population and determine potential factors related to alteration of miR-122 in sera. METHODS Patients with confirmed HCC (n = 91) were included in the study over a two-year period. Patients were characterized according to Child-Pugh score, Barcelona clinic liver cancer (BCLC) staging system, etiology of liver disease, laboratory parameters and overall survival. MiR-122 was measured in sera using TaqMan assay normalized to spiked-in cel-miR-39. RESULTS Serum miR-122 quantity was independent of the Child-Pugh score, the BCLC stage or the underlying etiology. Significant positive correlation was found between miR-122 and alanine aminotransferase (P < 0.0001), aspartate aminotransferase (P = 0.0001), alpha-fetoprotein (AFP) (P = 0.0034) and hemoglobin concentration (P = 0.076). Negative correlation was observed between miR-122 level and creatinine concentration (P = 0.0028). AFP, Child-Pugh score and BCLC staging system were associated with survival differences. In overall cohort low miR-122 in sera was only associated with a trend for a better overall survival without reaching statistical significance. Subgroup analysis revealed that low miR-122 was significantly associated with better prognosis in patients with advanced cirrhosis (Child-Pugh class B/C), advanced tumor stage (BCLC B/C/D) and normal AFP (< 7 ng/mL). CONCLUSION Our results strongly support the value of miR-122 as potential biomarker of liver injury and probably prognosis. Nevertheless, the value of miR-122 in prediction of prognosis of HCC patients was limited to certain patients’ subgroups. Since circulating miR-122 may be influenced by impaired renal function, AFP and hemoglobin concentration, those factors need to be considered while interpreting miR-122 level.

The leishmaniases are diseases that affect millions of people across the world, in particular visceral leishmaniasis (VL) which is fatal unless treated. Current standard of care for VL suffers from multiple issues and there is a limited pipeline of new candidate drugs. As such, there is a clear unmet medical need to identify new treatments. This paper describes the optimization of a phenotypic hit against Leishmania donovani, the major causative organism of VL. The key challenges were to balance solubility and metabolic stability while maintaining potency. Herein, strategies to address these shortcomings and enhance efficacy are discussed, culminating in the discovery of preclinical development candidate GSK3186899/DDD853651 (1) for VL.

National audience; This paper aims to evaluate the specific role of volatility and co-volatility risks in the formation of long-term European interest rates over the crisis and post-crisis periods with an active role of the ECB. We propose for that a portfolio choice model with two countries, which generalizes the results of the traditional theory of the term structure of interest rates. Long-term equilibrium rates depend crucially on the covariances between international bond yields anticipated by investors. Positively anticipated covariances amplify the phenomena of fundamentals contagions related to the degradations of public finance debt issuer, while negatively anticipated covariances amplify the phenomena of flight to quality. The econometric approach over the period January 2006 to September 2016 analyses 21 European market pairs in a bivariate GARCH framework. We obtain three important results. 1) The decline of German and French long-term rates very early in the crisis, since March 2011, found a strong support in the reduction in the anticipated covariances towards the peripheral countries, which really amplified the process of flight to quality. 2) The volatility risk premium mechanism on portfolios and bond yields declines sharply during the crisis, and reappears later over the post-OMT period. Everything happens as if the mechanism of international bond portfolio allocation had ceased during the sovereign debt crisis and then reappeared. 3) Acccording to a test a la Forbes and Rigobon [2002], it seems difficult to affirm that QE programmes have led to a significant increase on correlations between bond markets, simply because the correlations were already high before the implementation of QE, particularly since the implementation of the OMT.