Application in general practice of treatment guidelines for patients with dyslipidaemia: The RESPECT study

SummaryBackgroundScreening for and management of dyslipidaemia are crucial in primary and secondary prevention of cardiovascular disease. The impact on general practitioners (GP) of the 2005 French guidelines for hypercholesterolaemia has not been evaluated.AimsTo compare GP's estimation of cardiovascular risk with that from a theoretical calculation; to analyse the consequences of cardiovascular-risk estimation on the threshold of therapeutic intervention and the target low-density lipoprotein cholesterol (LDL-C) concentration; and to analyse patients’ awareness of their hypercholesterolaemia.MethodsThe RESPECT study was a transverse, multicentre, observational survey conducted between March 2006 and February 2007 by 1797 GP in France. Inclusion criteria were adults with primary hypercholesterolaemia who had not taken lipid-lowering drugs within the previous 6 months.ResultsOf the 5627 patients included (60.9% men; mean age±standard deviation 58.2±11.0 years; body mass index 27.2±4.1kg/m2; mean total cholesterol 2.68±0.37g/L; LDL-C 1.79±0.35g/L), 1963 (36.2%) had at least three cardiovascular risk factors. GP identified a high cardiovascular risk level in 40.8%, moderate risk in 45.8% and low risk in 13.4% of patients. These compared with calculated rates of 48, 23 and 29%, respectively (κ concordance 59.4%). For most patients (98.2%), GP defined the therapeutic target based on LDL-C concentration. The target LDL-C was significantly different when cardiovascular risk was estimated by GP versus that calculated theoretically. The higher the estimated risk level, the greater the rate of introduction of lipid-lowering drugs and the shorter the time to the next GP visit. Most patients considered themselves to be well or rather well informed about their cholesterol concentration (91.3%), the causes (64.3%) and consequences of cholesterol-induced diseases (83.7%), and the difference between ‘good’ and ‘bad’ cholesterol (57%). Most (81.5%) patients were aware of the benefits of lipid-lowering drugs on cardiovascular disease prevention; 95.8% considered adequate diet and compliance with pharmacological treatment to be very important.ConclusionRecent French guidelines for hypercholesterolaemia are used widely by GP in practice. They enable correct assessment of overall cardiovascular risk level, have an impact on the therapeutic threshold of intervention by physicians and improve patients’ awareness of the relevance of cholesterol concentration

BioSimulators: a central registry of simulation engines and services for recommending specific tools

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations

Modulating RNA Alignment Using Directional Dynamic Kinks: Application in Determining an Atomic-Resolution Ensemble for a Hairpin using NMR Residual Dipolar Couplings.

International audienceApproaches that combine experimental data and computational molecular dynamics (MD) to determine atomic resolution ensembles of biomolecules require the measurement of abundant experimental data. NMR residual dipolar couplings (RDCs) carry rich dynamics information, however, difficulties in modulating overall alignment of nucleic acids have limited the ability to fully extract this information. We present a strategy for modulating RNA alignment that is based on introducing variable dynamic kinks in terminal helices. With this strategy, we measured seven sets of RDCs in a cUUCGg apical loop and used this rich data set to test the accuracy of an 0.8 μs MD simulation computed using the Amber ff10 force field as well as to determine an atomic resolution ensemble. The MD-generated ensemble quantitatively reproduces the measured RDCs, but selection of a sub-ensemble was required to satisfy the RDCs within error. The largest discrepancies between the RDC-selected and MD-generated ensembles are observed for the most flexible loop residues and backbone angles connecting the loop to the helix, with the RDC-selected ensemble resulting in more uniform dynamics. Comparison of the RDC-selected ensemble with NMR spin relaxation data suggests that the dynamics occurs on the ps-ns time scales as verified by measurements of R1ρ relaxation-dispersion data. The RDC-satisfying ensemble samples many conformations adopted by the hairpin in crystal structures indicating that intrinsic plasticity may play important roles in conformational adaptation. The approach presented here can be applied to test nucleic acid force fields and to characterize dynamics in diverse RNA motifs at atomic resolution

BioSimulators: a central registry of simulation engines and services for recommending specific tools.

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations

BioSimulators: a central registry of simulation engines and services for recommending specific tools

International audienceComputational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations

BioSimulators: a central registry of simulation engines and services for recommending specific tools

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations