اشترك بالحزمة الذهبية واحصل على وصول غير محدود شمرا أكاديميا
تسجيل مستخدم جديدTwo General Methods for Population Pharmacokinetic Modeling: Non-Parametric Adaptive Grid and Non-Parametric Bayesian
129
0
0.0
(
0
)
اسأل ChatGPT حول البحث
ﻻ يوجد ملخص باللغة العربية
Population pharmacokinetic (PK) modeling methods can be statistically classified as either parametric or nonparametric (NP). Each classification can be divided into maximum likelihood (ML) or Bayesian (B) approaches. In this paper we discuss the nonparametric case using both maximum likelihood and Bayesian approaches. We present two nonparametric methods for estimating the unknown joint population distribution of model parameter values in a pharmacokinetic/pharmacodynamic (PK/PD) dataset. The first method is the NP Adaptive Grid (NPAG). The second is the NP Bayesian (NPB) algorithm with a stick-breaking process to construct a Dirichlet prior. Our objective is to compare the performance of these two methods using a simulated PK/PD dataset. Our results showed excellent performance of NPAG and NPB in a realistically simulated PK study. This simulation allowed us to have benchmarks in the form of the true population parameters to compare with the estimates produced by the two methods, while incorporating challenges like unbalanced sample times and sample numbers as well as the ability to include the covariate of patient weight. We conclude that both NPML and NPB can be used in realistic PK/PD population analysis problems. The advantages of one versus the other are discussed in the paper. NPAG and NPB are implemented in R and freely available for download within the Pmetrics package from www.lapk.org.
قيم البحث
اقرأ أيضاً
This paper offers a general and comprehensive definition of the day-of-the-week effect. Using symbolic dynamics, we develop a unique test based on ordinal patterns in order to detect it. This test uncovers the fact that the so-called day-of-the-week
effect is partly an artifact of the hidden correlation structure of the data. We present simulations based on artificial time series as well. Whereas time series generated with long memory are prone to exhibit daily seasonality, pure white noise signals exhibit no pattern preference. Since ours is a non parametric test, it requires no assumptions about the distribution of returns so that it could be a practical alternative to conventional econometric tests. We made also an exhaustive application of the here proposed technique to 83 stock indices around the world. Finally, the paper highlights the relevance of symbolic analysis in economic time series studies.
We propose a non-parametric extrapolation method based on constrained Gaussian processes for configuration interaction methods. Our method has many advantages: (i) applicability to small data sets such as results of {it ab initio} methods, (ii) flexi
bility to incorporate constraints, which are guided by physics, into the extrapolation model, (iii) providing predictions with quantified extrapolation uncertainty, etc. In the present study, we show an application to the extrapolation needed in full configuration interaction method as an example.
We propose a framework for Bayesian non-parametric estimation of the rate at which new infections occur assuming that the epidemic is partially observed. The developed methodology relies on modelling the rate at which new infections occur as a functi
on which only depends on time. Two different types of prior distributions are proposed namely using step-functions and B-splines. The methodology is illustrated using both simulated and real datasets and we show that certain aspects of the epidemic such as seasonality and super-spreading events are picked up without having to explicitly incorporate them into a parametric model.
We consider non-parametric estimation and inference of conditional moment models in high dimensions. We show that even when the dimension $D$ of the conditioning variable is larger than the sample size $n$, estimation and inference is feasible as lon
g as the distribution of the conditioning variable has small intrinsic dimension $d$, as measured by locally low doubling measures. Our estimation is based on a sub-sampled ensemble of the $k$-nearest neighbors ($k$-NN) $Z$-estimator. We show that if the intrinsic dimension of the covariate distribution is equal to $d$, then the finite sample estimation error of our estimator is of order $n^{-1/(d+2)}$ and our estimate is $n^{1/(d+2)}$-asymptotically normal, irrespective of $D$. The sub-sampling size required for achieving these results depends on the unknown intrinsic dimension $d$. We propose an adaptive data-driven approach for choosing this parameter and prove that it achieves the desired rates. We discuss extensions and applications to heterogeneous treatment effect estimation.
Non-coding RNA molecules fold into precise base pairing patterns to carry out critical roles in genetic regulation and protein synthesis. We show here that coupling systematic mutagenesis with high-throughput SHAPE chemical mapping enables accurate b
ase pair inference of domains from ribosomal RNA, ribozymes, and riboswitches. For a six-RNA benchmark that challenged prior chemical/computational methods, this mutate-and-map strategy gives secondary structures in agreement with crystallographic data (2 % error rates), including a blind test on a double-glycine riboswitch. Through modeling of partially ordered RNA states, the method enables the first test of an interdomain helix-swap hypothesis for ligand-binding cooperativity in a glycine riboswitch. Finally, the mutate-and-map data report on tertiary contacts within non-coding RNAs; coupled with the Rosetta/FARFAR algorithm, these data give nucleotide-resolution three-dimensional models (5.7 {AA} helix RMSD) of an adenine riboswitch. These results highlight the promise of a two-dimensional chemical strategy for inferring the secondary and tertiary structures that underlie non-coding RNA behavior.
سجل دخول لتتمكن من نشر تعليقات
التعليقات
جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
