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Chapter 3.5.3 : Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure

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Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
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Figures

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FIGURE 1

Conceptual diagram of the experimental protocol for animal and human dose-response trials, resulting in the development of the required data for optimization. doi:10.1128/9781555818821.ch3.5.3.f1

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
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Estimated parameter cloud from bootstrap uncertainty analysis (10,000 iterations), ellipse represent the confidence intervals of the α and N parameters of the beta Poisson model.

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
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Optimized beta Poisson model with confidence intervals.

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
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Histogram of parameter for exponential model from 10,000 iteration bootstrap uncertainty analysis.

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
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Optimized exponential model with confidence intervals.

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
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FIGURE B2.1

shows the optimized beta Poisson model with 95th and 99th confidence intervals around the central model, with optimized α and parameters shown in Table B.2.

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
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Image of FIGURE B2.2
FIGURE B2.2

shows a cloud of bootstrapped α and values from 10,000 bootstrap iterations. The confidence intervals around the could are a replacement for simultaneous confidence intervals which would be required for these parameters.

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
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Image of FIGURE B3.1
FIGURE B3.1

Bootstrapped parameter uncertainty cloud (10,000 points) for beta Poisson model, showing confidence interval ellipses, unless simultaneous confidence intervals are developed these ellipses are best estimation of α and uncertainty.

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
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Image of FIGURE B3.2
FIGURE B3.2

Dose response model curve for beta Poisson model, with confidence intervals from 10,000 bootstrap iterations.

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
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Image of FIGURE B3.3
FIGURE B3.3

Bootstrapped parameter histogram from 10,000 iterations.

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
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Image of FIGURE B3.4
FIGURE B3.4

Dose response model curve for exponential model, with confidence intervals from 10,000 bootstrap iterations.

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
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Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
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Image of FIGURE 2
FIGURE 2

Age-dependent dose-response models, for each age group, merged within one large age-dependent model signified with the outer and inner 99% confidence intervals ( ). doi:10.1128/9781555818821.ch3.5.3.f2

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
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Image of FIGURE 3
FIGURE 3

Example of time postinoculation (TPI) dose-response models for in the mouse host. Note how as the TPI increases, the host becomes less susceptible, meaning that more dose is required to have an equitable affect on the host from previous TPI periods. doi:10.1128/9781555818821.ch3.5.3.f3

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
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References

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1. U.S. EPA. 2011. Exposure Factors Handbook 2011 Edition (Final). U.S. Environmental Protection Agency, Washington DC, EPA/600/R-09/052F.
2. Dufour AP, Evans O, Behymer TD, Cantu R. 2006. Water ingestion during swimming activities in a pool: a pilot study. J Water Health 4(4):425430.[PubMed]
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4. Buchanan RL, Whiting RC. 1998. Risk assessment: a means of linking HACCP plans and public health. J Food Prot 61(11):15311534.[PubMed]
5. Weir MH, Haas CN. 2011. A model for in-vivo delivered dose estimation for inhaled bacillus anthracis spores in humans with interspecies extrapolation. Environ Sci Technol 45(13):58285833.[CrossRef]
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7. Teunis PF. 1997. Infectious gastro-enteritis - opportunities for dose response modeling. National Instiute of Public Health and the Environment, Bilthoven, The Netherlands, 284 550 003.
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17. Coulliette AD, Enger KS, Weir MH, Rose JB. 2013. Risk reduction assessment of waterborne Salmonella and Vibrio by a chlorine contact disinfectant point-of-use device. Int J Hyg Environ Health 216(3):355361.[CrossRef]
18. Fischer Walker CL, Rudan I, Liu L, Nair H, Theodoratou E, Bhutta ZA, O'Brien KL, Campbell H, Black RE. 2013. Global burden of childhood pneumonia and diarrhoea. The Lancet 381(9875):14051416.[CrossRef]
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20. Lopman BA, Vennema H, Kohli E, Pothier P, Sanchez A, Negredo A, Buesa J, Schreier E, Reacher M, Brown D, Gray J, Iturriza M, Gallimore C, Bottiger B, Hedlund K-O, Torven M, von Bonsdorff C-H, Manula L, Poljsak-Prijatlj M, Zimsek J, Reuter G, Szucs G, Melegh B, Svennson L, von Dujnhoven Y, Koopmans MPG. 2004. Increase in Viral Gastroenteritis Outbreaks in Europe and Epidemic Spread of New Norovirus Variant. The Lancet 363:682688.[CrossRef]
21. Tamrakar SB, Haas CN. 2008. Dose-response model for Burkholderia pseudomallei (melioidosis). J Appl Microbiol 105:13611371.[PubMed][CrossRef]
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24. Van Hartesveldt FR. 1992. In Pandemic of Influenza: The Urban Impact in the Western World. Edwin Mellen Press, Lewiston, NY, pp. 121144.
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26. Wolbach S. 1919. Comments on the pathology and bacteriology of fatal influenza cases, as observed at camp Devens, Mass. Johns Hopkins Hosp Bull 30:104109.
27. Weir MH, Haas CN. 2009. Quantification of the effects of age on the dose response of variola major in suckling mice. Hum Ecol Risk Assess Int J 15 (6):12451256.[CrossRef]
28. Huang Y, Bartrand TA, Haas CN, Weir MH. 2009. Incorporating time postinoculation into a dose-response model of yersinia pestis in mice. J Appl Microbiol 107:727735.[PubMed][CrossRef]
29. Hartley HO, Sielken RL. 1977. A biometrics invited paper. estimation of ‘Safe Doses’ in carcinogenic experiments. Biometrics 33:130.[PubMed][CrossRef]
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32. Clewell HJ, Gentry PR, Convington TR, Sarangapani R, Teeguarden JG. 2004. Evaluation of the Potential Impacts of Age-and-Gender-Specific Pharmacokinetic Differences in Tissue Dosimetry. Toxicol Sci 79 (2):381393.[PubMed][CrossRef]
33. Bjorkman S. 2005. Prediction of drug disposition in infants and children by means of Physiologically Based Pharmacokinetic (PBPK) Modelling: theophylline and midazolam as model drugs. Br J Clin Pharmacol 59:691704.[PubMed][CrossRef]
34. Gutting BW, Nichols TL, Channel SR, Gearhart JM, Andrews GA, Berger AE, Mackie RS, Watson BJ, Taft SC, Overheim KA, Sherwood RL. 2012. Inahaltional anthrax (Ames aerosol) in naive and vaccinated New Zealand rabbits: characterizing the spread of bacteria from lung deposition to bacteremia. Front Cell Infect Microbiol 2(87):12.[PubMed][CrossRef]
35. Gutting BW, Channel SR, Berger AE, Gearhart JM, Andrews GA, Sherwood RL, Nichols TL. 2008. Mathematically Modeling Inhalational Antrhax - Successive Advances in Modeling Applied to Updated Data Help in Estimating Risks from Inahaltional Anthrax. Microbe 3(2):78.
36. Gutting BW, Gaske KS, Schilling AS, Slaterbeck AF, Sobota L, Mackie RS, Buhr TL. 2005. Differential susceptibility of macrophage cell lines to bacillus anthracis - Vollum 1B. Toxicol In Vitro 19(2):221229.[PubMed][CrossRef]
37. Weir MH. 2009. Development of Physiologically Based Pathogen Transport and Kinetics Model for Inhalation of Bacillus anthracis Spores. Drexel University, Philadelphia, PA.

Tables

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Humans exposed to buffered oral exposure

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
Generic image for table
Untitled

Humans exposed to Giardia duodenalis oral exposure

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
Generic image for table
TABLE B2.1

Example dose-response data

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
Generic image for table
TABLE B2.2

MLE output for the exponential and beta Poisson models

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
Generic image for table
TABLE B2.3

Goodness of fit analysis comparing the deviance (Y) to the χ critical value at confidence interval of 0.05 and degrees of freedom of 4 for exponential and 3 for beta Poisson

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
Generic image for table
TABLE B2.4

Best fitting analysis comparing the difference between deviances (Δ) to a χ critical value at confidence interval of 0.05 and 1 degree of freedom

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
Generic image for table
TABLE B3.1

Original dose-response data before bootstrap iteration

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3
Generic image for table
TABLE B3.2.

Randomly sampled dose-response data after a single bootstrap iteration

Citation: Weir M. 2016. Dose-Response Modeling and Use: Challenges and Uncertainties in Environmental Exposure, p 3.5.3-1-3.5.3-17. In Yates M, Nakatsu C, Miller R, Pillai S (ed), Manual of Environmental Microbiology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818821.ch3.5.3

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