Value of ultrasonography as a marker of early response to abatacept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results from the APPRAISE study

Objectives: To study the responsiveness of a combined power Doppler and greyscale ultrasound (PDUS) score for assessing synovitis in biologic-naïve patients with rheumatoid arthritis (RA) starting abatacept plus methotrexate (MTX). Methods: In this open-label, multicentre, single-arm study, patients with RA (MTX inadequate responders) received intravenous abatacept (∼10 mg/kg) plus MTX for 24 weeks. A composite PDUS synovitis score, developed by the Outcome Measures in Rheumatology–European League Against Rheumatism (OMERACT–EULAR)-Ultrasound Task Force, was used to evaluate individual joints. The maximal score of each joint was added into a Global OMERACT–EULAR Synovitis Score (GLOESS) for bilateral metacarpophalangeal joints (MCPs) 2–5 (primary objective). The value of GLOESS containing other joint sets was explored, along with clinical efficacy. Results: Eighty-nine patients completed the 24-week treatment period. The earliest PDUS sign of improvement in synovitis was at week 1 (mean change in GLOESS (MCPs 2–5): −0.7 (95% CIs −1.2 to −0.1)), with continuous improvement to week 24. Early improvement was observed in the component scores (power Doppler signal at week 1, synovial hyperplasia at week 2, joint effusion at week 4). Comparable changes were observed for 22 paired joints and minimal joint subsets. Mean Disease Activity Score 28 (C reactive protein) was significantly reduced from weeks 1 to 24, reaching clinical meaningful improvement (change ≥1.2) at week 8. Conclusions: In this first international prospective study, the composite PDUS score is responsive to abatacept. GLOESS demonstrated the rapid onset of action of abatacept, regardless of the number of joints examined. Ultrasound is an objective tool to monitor patients with RA under treatment. Trial registration number: NCT00767325

Selective excitation through multiphonon emission of ZnCdTe quantum dots embedded in Zn-rich ZnCdTe quantum wells

International audienceWe study the energy relaxation of electron-hole pairs in ZnCdTe quantum wells, which is followed by a trapping in self-organized CdTe/ZnTe islands. An optical-phonon emission cascade is observed, giving rise to a selective population of the Cd-rich islands. Using photoluminescence excitation spectroscopy, we determine the energy of the phonons involved in the process. We study also the evolution of the quantum efficiency of the phonon emission process as a function of the photon energy, the number of emitted phonons, and temperature. Moreover, we evidence coupled exciton-phonon states in the quantum dots which explain the trapping of the electron-hole pairs and their recombination

Modélisation de la croissance d'une bulle dans du fromage pendant l'affinage: transport de quantité de mouvement et de matière

International audienceCette présentation orale avait pour objectif de montrer les travaux de l'équipe sur la modélisation de la croissance d'une bulle lors de l'affinage d'un fromage à trou. Elle présente les équations du modèle, les méthodes d'acquisition des paramètres d'entrée

The cell wall lipoprotein CD1687 acts as a DNA binding protein during deoxycholate-induced biofilm formation in Clostridioides difficile

Abstract The ability of bacterial pathogens to establish recurrent and persistent infections is frequently associated with their ability to form biofilms. Clostridioides difficile infections have a high rate of recurrence and relapses and it is hypothesized that biofilms are involved in its pathogenicity and persistence. Biofilm formation by C. difficile is still poorly understood. It has been shown that specific molecules such as deoxycholate (DCA) or metronidazole induce biofilm formation, but the mechanisms involved remain elusive. In this study, we describe the role of the C. difficile lipoprotein CD1687 during DCA-induced biofilm formation. We showed that the expression of CD1687, which is part of an operon within the CD1685-CD1689 gene cluster, is controlled by multiple transcription starting sites and some are induced in response to DCA. Only CD1687 is required for biofilm formation and the overexpression of CD1687 is sufficient to induce biofilm formation. Using RNAseq analysis, we showed that CD1687 affects the expression of transporters and metabolic pathways and we identified several potential binding partners by pull-down assay, including transport-associated extracellular proteins. We then demonstrated that CD1687 is surface exposed in C. difficile, and that this localization is required for DCA-induced biofilm formation. Given this localization and the fact that C. difficile forms eDNA-rich biofilms, we confirmed that CD1687 binds DNA in a non-specific manner. We thus hypothesize that CD1687 is a component of the downstream response to DCA leading to biofilm formation by promoting interaction between the cells and the biofilm matrix by binding eDNA

New Neutron Sensitive Beam Loss Monitor (nBLM)

International audienceThe beam loss detection is of the utmost importance for accelerator safety. At CEA, we are closely collaborating with ESS and DMCS on development of ESS nBLM. The system is based on Micromegas* gaseous detector sensitives to fast neutrons produced when beam particles hit the accelerator materials. This detector has powerful features: reliable neutron detection and fast time response. The nBLM control system provides slow monitoring, fast security based on neutron counting and post mortem data. It is fully handled by EPICS, which drives 3 different subsystems: a Siemens PLC regulates the gas line, a CAEN crate controls low and high voltages, and a MTCA system based on IOxOS boards is in charge of the fast data processing for 16 detectors. The detector signal is digitized by the 250 Ms/s ADC, which is further processed by the firmware developed by DMCS and finally retrieved and sent to EPICS network. For other accelerator projects, we are designing nBLM system close to ESS nBLM one. In order to be able to sustain the full control system, we are developing the firmware and the driver. This paper summarizes CEA’s work on the nBLM control system for the ESS and other accelerators

Space Charge Effects Studies for the ESS Cold Linac Beam Profiler

International audienceFive Ionization Profile Monitors are being built by CEA in the framework of the in-kind contribution agreement signed with ESS. The IPMs will be installed in the Cold Linac where the proton energy range they need to cover extends from 90 MeV to 2 GeV. The ESS fields intensity of 1.10⁺⁰⁹ protons/bunch delivered at a frequency of 352 or 704 MHz, with a duty cycle of 4%, may strongly affect the trajectories of the ionized molecules and electrons created by the passage of the beam through the residual gas. In order to quantify and to develop a correction algorithm for these space charge effects, a code was initiated at ESS and completed at CEA Saclay with the possibility to include real case electric fields calculated with Comsol Multiphysics. A general overview of the code and its preliminary results are presented here

Space Charge Effects Studies for the ESS Cold Linac Beam Profiler

International audienceFive Ionization Profile Monitors are being built by CEA in the framework of the in-kind contribution agreement signed with ESS. The IPMs will be installed in the Cold Linac where the proton energy range they need to cover extends from 90 MeV to 2 GeV. The ESS fields intensity of 1.10⁺⁰⁹ protons/bunch delivered at a frequency of 352 or 704 MHz, with a duty cycle of 4%, may strongly affect the trajectories of the ionized molecules and electrons created by the passage of the beam through the residual gas. In order to quantify and to develop a correction algorithm for these space charge effects, a code was initiated at ESS and completed at CEA Saclay with the possibility to include real case electric fields calculated with Comsol Multiphysics. A general overview of the code and its preliminary results are presented here