A national cross-sectional study among drug-users in France: epidemiology of HCV and highlight on practical and statistical aspects of the design

<p>Abstract</p> <p>Background</p> <p>Epidemiology of HCV infection among drug users (DUs) has been widely studied. Prevalence and sociobehavioural data among DUs are therefore available in most countries but no study has taken into account in the sampling weights one important aspect of the way of life of DUs, namely that they can use one or more specialized services during the study period. In 2004–2005, we conducted a national seroepidemiologic survey of DUs, based on a random sampling design using the Generalised Weight Share Method (GWSM) and on blood testing.</p> <p>Methods</p> <p>A cross-sectional multicenter survey was done among DUs having injected or snorted drugs at least once in their life. We conducted a two stage random survey of DUs selected to represent the diversity of drug use. The fact that DUs can use more than one structure during the study period has an impact on their inclusion probabilities. To calculate a correct sampling weight, we used the GWSM. A sociobehavioral questionnaire was administered by interviewers. Selected DUs were asked to self-collect a fingerprick blood sample on blotting paper.</p> <p>Results</p> <p>Of all DUs selected, 1462 (75%) accepted to participate. HCV seroprevalence was 59.8% [95% CI: 50.7–68.3]. Of DUs under 30 years, 28% were HCV seropositive. Of HCV-infected DUs, 27% were unaware of their status. In the month prior to interview, 13% of DUs shared a syringe, 38% other injection parapharnelia and 81% shared a crack pipe. In multivariate analysis, factors independently associated with HCV seropositivity were age over 30, HIV seropositivity, having ever injected drugs, opiate substitution treatment (OST), crack use, and precarious housing.</p> <p>Conclusion</p> <p>This is the first time that blood testing combined to GWSM is applied to a DUs population, which improve the estimate of HCV prevalence. HCV seroprevalence is high, indeed by the youngest DUs. And a large proportion of DUs are not aware of their status. Our multivariate analysis identifies risk factors such as crack consumption and unstable housing.</p

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Reflexions sur la dynamique d'une population de tetras-lyre Tetrao tetrix L. des Alpes francaises

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

A comparative analysis between recreational and commercial fisheries of whitefish (Coregonus lavaretus) in Lake Annecy

International audienceCommercial and recreational fishing play an important role in lake ecosystems or local populations, contributing to socio-economic development in many countries. However, conflicts can arise due to shared exploitation of coregonid species, such as whitefish (Coregonus lavaretus), by professionals and anglers. The aim of this study is to assess the differences in catch levels, fishing efforts, seasonal variabilities and their relationship with environmental factors between commercial and recreational whitefish fisheries in Lake Annecy, where conflicts have occurred before a change in fishing regulations and could potentially reappear. Fishing data were obtained from annual fishing diaries of anglers and from obligatory declaration data by professionals. Stakeholders collaboration has enabled the re-establishment of an annual fishery monitoring programme since 2015, providing valuable additional data. The results indicate that the differences in catches mainly explained by environmental conditions, fishing effort, and differential use of techniques. Professional fishers, using a combination of two types of fishing gears (pelagic and benthic), showed greater fishing efficiency throughout the season. In contrast, recreational fishing displayed greater variability in whitefish catches due to variations in fishing effort and due to techniques employed which is more effective in the first part of the fishery season. This study provides valuable quantitative data for understanding the annual and seasonal dynamics of whitefish fisheries in Lake Annecy. The results enable fisheries managers to better understand catches fluctuations; will help to establish resource management criteria and to mitigate potential conflicts between commercial and recreational fisheries. These insights contribute to more effective fisheries management and resource preservation

Short-term response to the North Atlantic Oscillation but no long-term effects of climate change on the reproductive success of an alpine bird

International audienceDeciphering the effects of climatic conditions on population dynamics is of major importance in understanding how organisms are likely to be affected by climate changes. Using data from broad-scale annual censuses between 1990 and 2007, we show that winter and summer North Atlantic Oscillations affect several breeding success indicators of the Black Grouse () in the French Alps. We did not find any trend in hen counts or breeding indexes over the study period. Surprisingly for a bird specialised in cold climates, we show that Black Grouse optimise their reproductive output for positive values of the winter NAO corresponding to the average NAO index of the last 30 years. Extreme NAO values lead to lower breeding success, indicating that the grouse may be more able to track trends in climate than an increase in the frequency of extreme years. Our result show that, at least from a short-term perspective, Black Grouse productivity is not threatened by a trend towards warmer climatic conditions in the Alps, but may be affected by an increased frequency of extreme years. We advocate the use of the NAO as a climate proxy rather than using heavily noised and biased local climate descriptors in studies focusing on the global response to climate over a large spatial scale

Effects in cancer cells of the recombinant L-Methionine gamma-lyase from Brevibacterium aurantiacum. Encapsulation in human erythrocytes for sustained L-methionine elimination.

International audienceMethionine deprivation induces growth arrest and death of cancer cells. To eliminate L-methionine we produced, purified, and characterized the recombinant pyridoxal 59-phosphate (PLP)-dependent L-methionine g-lyase (MGL) BL929 from the cheese-ripening Brevibacterium aurantiacum. Transformation of an Escherichia coli strain with the gene BL929 from B. aurantiacum optimized for E. coli expression led to production of the MGL-BL929. Elimination of L-methionine and cytotoxicity in vitro were assessed, and methylation-sensitive epigenetics was explored for changes resulting from exposure of cancer cells to the enzyme. A bioreactor was built by encapsulation of the protein in human erythrocytes to achieve sustained elimination of L-methionine in extracellular fluids. Catalysis was limited to alpha, gamma-elimination of L-methionine and L-homocysteine. The enzyme had no activity on other sulfur-containing amino acids. Enzyme activity decreased in presence of serum albumin or plasma resulting from reduction of PLP availability. Elimination of L-methionine induced cytotoxicity on a vast panel of human cancer cell lines and spared normal cells. Exposure of colorectal carcinoma cells to the MGL-BL929 reduced methylCpG levels of hypermethylated gene promoters including that of CDKN2A, whose mRNA expression was increased, together with a decrease in global histone H3 dimethyl lysine 9. The MGL-erythrocyte bioreactor durably preserves enzyme activity in vitro and strongly eliminates L-methionine from medium