DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Measurement of electroweak WZ boson production and search for new physics in WZ + two jets events in pp collisions at √s=13TeV

A measurement of WZ electroweak (EW) vector boson scattering is presented. The measurement is performed in the leptonic decay modes WZ→ℓνℓ′ℓ′, where ℓ,ℓ′=e,μ. The analysis is based on a data sample of proton-proton collisions at √s=13 TeV at the LHC collected with the CMS detector and corresponding to an integrated luminosity of 35.9 fb−1. The WZ plus two jet production cross section is measured in fiducial regions with enhanced contributions from EW production and found to be consistent with standard model predictions. The EW WZ production in association with two jets is measured with an observed (expected) significance of 2.2 (2.5) standard deviations. Constraints on charged Higgs boson production and on anomalous quartic gauge couplings in terms of dimension-eight effective field theory operators are also presented

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

Synthesis of α,β-Unsaturated Ketones as Chalcone Analogues via a SRN1 Mechanism

An electron-transfer chain reaction between 2-nitropropane anion and α-bromoketones derived from nitrobenzene and nitrothiophene was demonstrated by mechanistic study and a specific convenient synthetic protocol. Thus, 2-bromo-1-(5-nitrothiophen-2-yl)ethanone or 2-bromo-1-(4-nitrophenyl)ethanone were reacted with several cyclic nitronate anions to form α,β-unsaturated ketones via a SRN1 mechanism. This new method can be used to synthesize a wide variety of chalcone analogues

Diagnostic et prise en charge des dyskinésies ciliaires primitives respiratoires

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

Recherche de nouveaux agents pharmacologiques par synthèse et réactivité Srn1[substitution radicalaire nucleophile unimoléculaire] d' alpha-halocétones et par réaction VNS [vicarious nucleophilic substitution of hydrogen] de 5-nitroimidazoles

Ce travail est consacré à la recherche de nouveaux agents pharmacologiques par synthèse et réactivité SRN1 d a-halocétones et par réaction VNS de 5-nitroimidazoles. La première partie décrit la réactivité SRN1 et ses différentes applications. La seconde partie met en évidence les intérêts de l irradiation micro-ondes en synthèse organique. Nous abordons ensuite dans les troisième, quatrième et cinquième parties les études de synthèse et de réactivité d a-halocétones en séries benzénique, thiophénique et pyrrolique. Chaque série a fait l objet d une étude mécanistique SRN1 avec l anion du 2-nitropropane. De nouvelles molécules dérivées d anions nitronates cycliques ont ainsi pu être synthétisées D autres méthodologies, dont l irradiation micro-ondes, ont également été utilisées pour obtenir différentes molécules à potentialités anti-infectieuses et anticancéreuses. Enfin, la sixième partie se consacre à l utilisation de la réaction Vicarious Nucleophilic Substitution of hydrogen en série 5-nitroimidazole pour aboutir à de nouveaux agents antitrichomonas.This work is focused on the research of new pharmacological agents by synthesizing a-haloketones, reacting them through SRN1 reactions and also by proceeding VNS reaction onto 5-nitroimidazoles. The first part describes SRN1 reaction and its different applications. The second part focuses on the advantages of microwave irradiation in organic synthesis. We next study the synthesis of a-haloketones and their reactivity in benzenic, thiophenic and pyrrolic series. For each of them, the SRN1 mechanistic study with 2-nitropropan anion is investigated. New molecules derivated from cyclic nitronate anions have been prepared thanks to this approach. Other methodologies such as microwave irradiation were also used in order to conduct to several molecules with anti-infective and anticancer potential. Finally, we describe VNS reaction in 5-nitroimidazolic series leading to new antitrichomonal agents. Some of anticancer and antiinfective properties of new derivatives have been evaluated.AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Benzodiazépines et assimilés (mise en place d'un programme de lutte contre le mésusage et d'aide au sevrage à l'officine dans le cadre de la loi HPST)

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

Analyse des prescriptions de fluoroquinolones à l'Hôpital de la Conception en 2005

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF