10 research outputs found
Recommended from our members
Performance of an MPI-only semiconductor device simulator on a quad socket/quad core InfiniBand platform.
This preliminary study considers the scaling and performance of a finite element (FE) semiconductor device simulator on a capacity cluster with 272 compute nodes based on a homogeneous multicore node architecture utilizing 16 cores. The inter-node communication backbone for this Tri-Lab Linux Capacity Cluster (TLCC) machine is comprised of an InfiniBand interconnect. The nonuniform memory access (NUMA) nodes consist of 2.2 GHz quad socket/quad core AMD Opteron processors. The performance results for this study are obtained with a FE semiconductor device simulation code (Charon) that is based on a fully-coupled Newton-Krylov solver with domain decomposition and multilevel preconditioners. Scaling and multicore performance results are presented for large-scale problems of 100+ million unknowns on up to 4096 cores. A parallel scaling comparison is also presented with the Cray XT3/4 Red Storm capability platform. The results indicate that an MPI-only programming model for utilizing the multicore nodes is reasonably efficient on all 16 cores per compute node. However, the results also indicated that the multilevel preconditioner, which is critical for large-scale capability type simulations, scales better on the Red Storm machine than the TLCC machine
Population pharmacokinetics and pharmacokinetic-pharmacodyamic modeling of antitubercular drugs
Includes abstract.Includes bibliographical references.The pharmacokinetics of rifampicin, isoniazid, pyrazinamide and ethambutol in 78 patients with tuberculosis were described using non-linear mixed effects modeling. Pharmacodynamic data was comprised of weekly sputum liquid culture (using mycobacterial growth indicator tubes) time to detection results from 144 patients during the first 2 months of treatment. The effect of drug exposure on patient outcomes was investigated. To determine the adequacy of ofloxacin drug exposure, the probability of attaining the required area-under-the-curve to minimum inhibitory concentration ratio (AUC/MIC) of ofloxacin was determined in 65 patients on treatment for multidrug resistant tuberculosis. To improve efficiency in the clinical development of new drug regimens, clinical trial simulation was used to determine the optimal study design for a study investigating the efficacy of a new antitubercular drug regimen. The SLCO1B1 rs4149032 polymorphism existed at a high frequency of 0.70 in South Africans and resulted in a 28% decrease in bioavailability of rifampicin. The rifampicin peak concentration was a significant predictor of the 2 month treatment outcomes. A semimechanistic time to event model was developed to analyze days to positivity (time to detection) data. The model was comprised of a biexponential decay model describing bacillary decline in sputum from patients, followed by a logistic model with a lag time for growth of the mycobacteria in liquid culture. For the current 800 mg daily dose of ofloxacin, the probability of attaining an AUC/MIC target ratio of at least 100 was only 0.45. Based on clinical trial simulation, the optimum parallel study design was comprised of 125 study participants in each of 2 arms to achieve a study power of at least 80%. Increasing the study length beyond 42 days reduced study power perhaps due to increased amounts of censored data. Higher doses of rifampicin are required in the majority of South African patients with tuberculosis. A novel pharmacodynamic model of tuberculosis treatment is presented, which can be used for investigation of covariates such as drug exposure. Ofloxacin should be replaced with a more potent fluoroquinolone for treatment of multidrug resistant tuberculosis. Clinical trials should not be unduly long otherwise this may compromise study power