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DOI10.1111/risa.12688
Modeling Rabbit Responses to Single and Multiple Aerosol Exposures of Bacillus anthracis Spores
Coleman, Margaret E.; Marks, Harry M.; Bartrand, Timothy A.; Donahue, Darrell W.; Hines, Stephanie A.; Comer, Jason E.; Taft, Sarah C.
发表日期2017-05-01
ISSN0272-4332
卷号37期号:5页码:943-957
英文摘要

Survival models are developed to predict response and time-to-response for mortality in rabbits following exposures to single or multiple aerosol doses of Bacillus anthracis spores. Hazard function models were developed for a multiple-dose data set to predict the probability of death through specifying functions of dose response and the time between exposure and the time-to-death (TTD). Among the models developed, the best-fitting survival model (baseline model) is an exponential dose-response model with a Weibull TTD distribution. Alternative models assessed use different underlying dose-response functions and use the assumption that, in a multiple-dose scenario, earlier doses affect the hazard functions of each subsequent dose. In addition, published mechanistic models are analyzed and compared with models developed in this article. None of the alternative models that were assessed provided a statistically significant improvement in fit over the baseline model. The general approach utilizes simple empirical data analysis to develop parsimonious models with limited reliance on mechanistic assumptions. The baseline model predicts TTDs consistent with reported results from three independent high-dose rabbit data sets. More accurate survival models depend upon future development of dose-response data sets specifically designed to assess potential multiple-dose effects on response and time-to-response. The process used in this article to develop the best-fitting survival model for exposure of rabbits to multiple aerosol doses of B. anthracis spores should have broad applicability to other host-pathogen systems and dosing schedules because the empirical modeling approach is based upon pathogen-specific empirically-derived parameters.


英文关键词Hazard function;survival analysis;time and dose dependency
语种英语
WOS记录号WOS:000403450300010
来源期刊RISK ANALYSIS
来源机构美国环保署
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/62606
作者单位US EPA, Natl Homeland Secur Res Ctr, 26 West Martin Luther King Dr, Cincinnati, OH 45268 USA
推荐引用方式
GB/T 7714
Coleman, Margaret E.,Marks, Harry M.,Bartrand, Timothy A.,et al. Modeling Rabbit Responses to Single and Multiple Aerosol Exposures of Bacillus anthracis Spores[J]. 美国环保署,2017,37(5):943-957.
APA Coleman, Margaret E..,Marks, Harry M..,Bartrand, Timothy A..,Donahue, Darrell W..,Hines, Stephanie A..,...&Taft, Sarah C..(2017).Modeling Rabbit Responses to Single and Multiple Aerosol Exposures of Bacillus anthracis Spores.RISK ANALYSIS,37(5),943-957.
MLA Coleman, Margaret E.,et al."Modeling Rabbit Responses to Single and Multiple Aerosol Exposures of Bacillus anthracis Spores".RISK ANALYSIS 37.5(2017):943-957.
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