109 research outputs found
Non-compartment model to compartment model pharmacokinetics transformation meta-analysis â a multivariate nonlinear mixed model
Background
To fulfill the model based drug development, the very first step is usually a model establishment from published literatures. Pharmacokinetics model is the central piece of model based drug development. This paper proposed an important approach to transform published non-compartment model pharmacokinetics (PK) parameters into compartment model PK parameters. This meta-analysis was performed with a multivariate nonlinear mixed model. A conditional first-order linearization approach was developed for statistical estimation and inference.
Results
Using MDZ as an example, we showed that this approach successfully transformed 6 non-compartment model PK parameters from 10 publications into 5 compartment model PK parameters. In simulation studies, we showed that this multivariate nonlinear mixed model had little relative bias (<1%) in estimating compartment model PK parameters if all non-compartment PK parameters were reported in every study. If there missing non-compartment PK parameters existed in some published literatures, the relative bias of compartment model PK parameter was still small (<3%). The 95% coverage probabilities of these PK parameter estimates were above 85%.
Conclusions
This non-compartment model PK parameter transformation into compartment model meta-analysis approach possesses valid statistical inference. It can be routinely used for model based drug development
Operations of and Future Plans for the Pierre Auger Observatory
Technical reports on operations and features of the Pierre Auger Observatory,
including ongoing and planned enhancements and the status of the future
northern hemisphere portion of the Observatory. Contributions to the 31st
International Cosmic Ray Conference, Lodz, Poland, July 2009.Comment: Contributions to the 31st ICRC, Lodz, Poland, July 200
Measurement of the Depth of Maximum of Extensive Air Showers above 10^18 eV
We describe the measurement of the depth of maximum, Xmax, of the
longitudinal development of air showers induced by cosmic rays. Almost four
thousand events above 10^18 eV observed by the fluorescence detector of the
Pierre Auger Observatory in coincidence with at least one surface detector
station are selected for the analysis. The average shower maximum was found to
evolve with energy at a rate of (106 +35/-21) g/cm^2/decade below 10^(18.24 +/-
0.05) eV and (24 +/- 3) g/cm^2/decade above this energy. The measured
shower-to-shower fluctuations decrease from about 55 to 26 g/cm^2. The
interpretation of these results in terms of the cosmic ray mass composition is
briefly discussed.Comment: Accepted for publication by PR
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