Innovation in Physician Remuneration in France: What Lessons for Canada?

During the past decade, France has experienced two major reforms in remuneration models for general practitioners who work outside public healthcare organizations: Remuneration for Public Health Objectives (Rémunération sur Objectifs de Santé Publique—ROSP) and Experiments with New Models of Remuneration (Expérimentations desNouveaux Modes de Rémunération—ENMR). These two initiatives introduced payments based on performance in the areas of quality of care, organization of services and multidisciplinary practice. In the first model, individual physicians receive incentives for preventive practices, use of generics and improvements in work organization. In the second model, incentives are provided to multi-professional practice groups to foster interdisciplinary collaboration and patient involvement. While French general practitioners accustomed to fee-for-service remuneration were at first reluctant to accept a mixed remuneration model, they eventually came to embrace it. The ROSP has significantly improved targeted areas of practice, although it has had less impact on preventive practices than on use of generics and work organization. The ENMR has helped formalize inter-professional relationships in primary care and has thus contributed to team integration. These "experiments" suggest that a deliberate distinction between changes to individual physician payment and changes to how multi-professional practice groups are paid and practice may be a good starting point when introducing financial incentives to enable benefits and avoid negative consequences

Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals

Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation

Large-scale exome-wide association analysis identifies loci for White Blood Cell Traits and Pleiotropy with Immune-Mediated Diseases

White blood cells play diverse roles in innate and adaptive immunity. Genetic association analyses of phenotypic variation in circulating white blood cell (WBC) counts from large samples of otherwise healthy individuals can provide insights into genes and biologic pathways involved in production, differentiation, or clearance of particular WBC lineages (myeloid, lymphoid) and also potentially inform the genetic basis of autoimmune, allergic, and blood diseases. We performed an exome array-based meta-analysis of total WBC and subtype counts (neutrophils, monocytes, lymphocytes, basophils, and eosinophils) in a multi-ancestry discovery and replication sample of ∼157,622 individuals from 25 studies. We identified 16 common variants (8 of which were coding variants) associated with one or more WBC traits, the majority of which are pleiotropically associated with autoimmune diseases. Based on functional annotation, these loci included genes encoding surface markers of myeloid, lymphoid, or hematopoietic stem cell differentiation (CD69, CD33, CD87), transcription factors regulating lineage specification during hematopoiesis (ASXL1, IRF8, IKZF1, JMJD1C, ETS2-PSMG1), and molecules involved in neutrophil clearance/apoptosis (C10orf54, LTA), adhesion (TNXB), or centrosome and microtubule structure/function (KIF9, TUBD1). Together with recent reports of somatic ASXL1 mutations among individuals with idiopathic cytopenias or clonal hematopoiesis of undetermined significance, the identification of a common regulatory 3 UTR variant of ASXL1 suggests that both germline and somatic ASXL1 mutations contribute to lower blood counts in otherwise asymptomatic individuals. These association results shed light on genetic mechanisms that regulate circulating WBC counts and suggest a prominent shared genetic architecture with inflammatory and autoimmune diseases

Transversal load introduction on sandwich RailwayCarbodies

Sandwich structures made up by foam core and carbon fiber face-sheets are now seen as a promising technical solution for the design of railway carbodies by many railway manufacturers. Despite their numerous advantages over the classical metallic structures, transversal load introduction usually result in high stresses in the core of a sandwich structure. Hence, the fastening of equipment on a sandwich carbody must be studied carefully. The focus of this thesis has been put on the seat fastenings. Several technical solutions were compared. A metallic part, called a C-rail, adhesively bonded on the top of the sandwich panel represents the best solution according to the requirements. The aim of the C-rail is to spread the load and therefore lower the stress concentration in the core. The reaction loads at the seat fastenings, when the seats are loaded according to the European norms, where calculated using finite element (FE) analysis. Guidelines for the design of the C-rail were developed, based on 2D FE models. The focus was put on the reduction of stress concentration in the core. It was shown that an optimal C-rail cross section can be found for a specific sandwich panel. An analytical solution of the residual shear stresses induced by thermal expansion was developed to facilitate the choice of adhesive. It was shown that thick adhesive layers with low shear stiffness have the best strength with respect to temperature changes. Based on the 2D FE model, efficient techniques were derived for the modeling of adhesive layers. The influence of the face-sheet and adhesive modelisation on the stress distribution in the adhesive was studied. For that purpose, several combinations of material properties for the face-sheet and adhesive were investigated. In particular a spring based model of the adhesive was derived in order to include the face-sheet out of plane stiffness. It was shown that the stiffness of the adhesive have a high influence on the stress distribution in the adhesive layer. A 3D model was built up in order to investigate the load cases derived at the fastenings and to validate the qualitative studies based on the 2D models. The choice of the final sandwich panel depends on numerous issues such as sound insulation, dynamic properties or weight.Various sandwich configurations were investigated in order to determine the influence of issues related to equipment fastening on the final choice of sandwich panel. The face-sheet bending stiffness as well as the core stiffness were identified as the key parameters regarding the sandwich panel out of plane strength. The panel configuration obtained by weight optimization of the carbody represents the weakest configuration with respect to out of plane load introduction. Note that the solution proposed fulfilled the requirements for that configuration

Budget Impact Analysis of Heparin-Bonded Polytetrafluoroethylene Grafts (Propaten) against Standard Polytetrafluoroethylene Grafts for below-the-Knee Bypass in Patients with Critical Limb Ischaemia in France

International audienc

Estimation des délais de renouvellement des eaux souterraines des captages prioritaires du bassin Rhône-Méditerranée.Une aide pour orienter les opérations de restauration de la qualité ?

National audienc