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Vicini Paolo Pierce Crispin H. Dills Russell L. Morgan Michael S. Kalman David A. 《Risk analysis》1999,19(6):1127-1134
Physiologically-based toxicokinetic (PBTK) models are widely used to quantify whole-body kinetics of various substances. However, since they attempt to reproduce anatomical structures and physiological events, they have a high number of parameters. Their identification from kinetic data alone is often impossible, and other information about the parameters is needed to render the model identifiable. The most commonly used approach consists of independently measuring, or taking from literature sources, some of the parameters, fixing them in the kinetic model, and then performing model identification on a reduced number of less certain parameters. This results in a substantial reduction of the degrees of freedom of the model. In this study, we show that this method results in final estimates of the free parameters whose precision is overestimated. We then compared this approach with an empirical Bayes approach, which takes into account not only the mean value, but also the error associated with the independently determined parameters. Blood and breath 2H8-toluene washout curves, obtained in 17 subjects, were analyzed with a previously presented PBTK model suitable for person-specific dosimetry. Model parameters with the greatest effect on predicted levels were alveolar ventilation rate QPC, fat tissue fraction VFC, blood-air partition coefficient Kb, fraction of cardiac output to fat Qa/co and rate of extrahepatic metabolism Vmax-p. Differences in the measured and Bayesian-fitted values of QPC, VFC and Kb were significant (p < 0.05), and the precision of the fitted values Vmax-p and Qa/co went from 11 ± 5% to 75 ± 170% (NS) and from 8 ± 2% to 9 ± 2% (p < 0.05) respectively. The empirical Bayes approach did not result in less reliable parameter estimates: rather, it pointed out that the precision of parameter estimates can be overly optimistic when other parameters in the model, either directly measured or taken from literature sources, are treated as known without error. In conclusion, an empirical Bayes approach to parameter estimation resulted in a better model fit, different final parameter estimates, and more realistic parameter precisions. 相似文献
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Angela K. Dills 《Economic inquiry》2018,56(1):304-316
This paper tests how the race and ethnicity of one's college classmates affect academic performance. Incoming students at a Catholic college are assigned to their first semester, team‐taught, required course. Statistical tests support that this assignment is uncorrelated with a variety of student characteristics. Controlling for team fixed effects and student characteristics, I find evidence of racial peer effects that differ for white students and students of color. White students earn higher grades in classes with more students of color. Students of color with more nonwhite classmates earn lower grades; these effects occur exclusively among those with lower SAT scores. (JEL I21, I28) 相似文献
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