• Journal of Food Hygiene and Safety
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• v.19 no.1
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• pp.19-24
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• 2004

Dose-response models in microbial risk assessment can be divided into biologically plausible models and empirical models. Biologically plausible models are formed by the assumptions in dose distribution of microbes, host sensitivity to microbes, and minimal infectious dose of microbes : there are Exponential model and $\beta$-Poisson model, representatively. Empirical models are mainly used to express the toxicity of chemicals : there are Weibull-Gamma model etc. Deviance function (Y) is used to fit available data to dose-response models, and some dose-response models for food-borne pathogens are developed in humans and experimental animals.

• Communications for Statistical Applications and Methods
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• v.29 no.3
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• pp.287-299
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• 2022

In radiation epidemiology, the excess relative risk (ERR) model is used to determine the dose-response relationship. In general, the dose-response relationship for the ERR model is assumed to be linear, linear-quadratic, linear-threshold, quadratic, and so on. However, since none of these functions dominate other functions for expressing the dose-response relationship, a Bayesian semiparametric method using splines has recently been proposed. Thus, we improve the Bayesian semiparametric method for the selection of the tuning parameters for splines as the number and location of knots using a Bayesian knot selection method. Equally spaced knots cannot capture the characteristic of radiation exposed dose distribution which is highly skewed in general. Therefore, we propose a nonparametric Bayesian knot selection method based on a Dirichlet process mixture model. Inference of the spline coefficients after obtaining the number and location of knots is performed in the Bayesian framework. We apply this approach to the life span study cohort data from the radiation effects research foundation in Japan, and the results illustrate that the proposed method provides competitive curve estimates for the dose-response curve and relatively stable credible intervals for the curve.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5107-5111
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• 2016

Background: Epidemiological studies have indicated an increasing incidence of radiation induced secondary cancer (SC) in breast cancer patients after radiotherapy (RT), most commonly in the contra-lateral breast (CLB). The present study was conducted to estimate the SC risk in the CLB following 3D conformal radiotherapy techniques (3DCRT) including wedge field and forward intensity modulated radiotherapy (fIMRT) based on the organ equivalent dose (OED). Material and Methods: RT plans treating the chest wall with conformal wedge field and fIMRT plans were created for 30 breast cancer patients. The risks of radiation induced cancer were estimated for the CLB using dose-response models: a linear model, a linear-plateau model and a bell-shaped model with full dose response accounting for fractionated RT on the basis of OED. Results: The plans were found to be ranked quite differently according to the choice of model; calculations based on a linear dose response model fIMRT predict statistically significant lower risk compared to the enhanced dynamic wedge (EDW) technique (p-0.0089) and a non-significant difference between fIMRT and physical wedge (PW) techniques (p-0.054). The widely used plateau dose response model based estimation showed significantly lower SC risk associated with fIMRT technique compared to both wedge field techniques (fIMRT vs EDW p-0.013, fIMRT vs PW p-0.04). The full dose response model showed a non-significant difference between all three techniques in the view of second CLB cancer. Finally the bell shaped model predicted interestingly that PW is associated with significantly higher risk compared to both fIMRT and EDW techniques (fIMRT vs PW p-0.0003, EDW vs PW p-0.0032). Conclusion: In conclusion, the SC risk estimations of the CLB revealed that there is a clear relation between risk associated with wedge field and fIMRT technique depending on the choice of model selected for risk comparison.

• Journal of Food Hygiene and Safety
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• v.14 no.4
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• pp.319-326
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• 1999

Recently, it is continuously rising to concern about the health risk being induced by microorganisms in food such as Escherichia coli O157:H7 and Listeria monocytogenes. Various organizations and regulatory agencies including U.S.FPA, U.S.DA and FAO/WHO are preparing the methodology building to apply microbial quantitative risk assessment to risk-based food safety program. Microbial risks are primarily the result of single exposure and its health impacts are immediate and serious. Therefore, the methodology of risk assessment differs from that of chemical risk assessment. Microbial quantitative risk assessment consists of tow steps; hazard identification, exposure assessment, dose-response assessment and risk characterization. Hazard identification is accomplished by observing and defining the types of adverse health effects in humans associated with exposure to foodborne agents. Epidemiological evidence which links the various disease with the particular exposure route is an important component of this identification. Exposure assessment includes the quantification of microbial exposure regarding the dynamics of microbial growth in food processing, transport, packaging and specific time-temperature conditions at various points from animal production to consumption. Dose-response assessment is the process characterizing dose-response correlation between microbial exposure and disease incidence. Unlike chemical carcinogens, the dose-response assessment for microbial pathogens has not focused on animal models for extrapolation to humans. Risk characterization links the exposure assessment and dose-response assessment and involve uncertainty analysis. The methodology of microbial dose-response assessment is classified as nonthreshold and thresh-old approach. The nonthreshold model have assumption that one organism is capable of producing an infection if it arrives at an appropriate site and organism have independence. Recently, the Exponential, Beta-poission, Gompertz, and Gamma-weibull models are using as nonthreshold model. The Log-normal and Log-logistic models are using as threshold model. The threshold has the assumption that a toxicant is produce by interaction of organisms. In this study, it was reviewed detailed process including risk value using model parameter and microbial exposure dose. Also this study suggested model application methodology in field of exposure assessment using assumed food microbial data(NaCl, water activity, temperature, pH, etc.) and the commercially used Food MicroModel. We recognized that human volunteer data to the healthy man are preferred rather than epidemiological data fur obtaining exact dose-response data. But, the foreign agencies are studying the characterization of correlation between human and animal. For the comparison of differences to the population sensitivity: it must be executed domestic study such as the establishment of dose-response data to the Korean volunteer by each microbial and microbial exposure assessment in food.

• The Korean Journal of Applied Statistics
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• v.25 no.4
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• pp.633-640
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• 2012

Biological methods are described for the assay of certain substances and preparations whose potency cannot be adequately assured by chemical or physical analysis. The principle applied through these assays is of a comparison with a standard preparation to determine how much of the examined substance produces the same biological effects as a given quantity (the Unit) of the standard preparation. In these dilution assays, to estimate the relative potencies of the unknown preparations to the standard preparations, it is necessary to compare dose-response relationships of standard and unknown preparations. The dose-response relationship in the dilution assay is non-linear and sigmoid when a wide range of doses is applied. The parallel line model (applied to the dose region with the steepest slope) is used to estimate the relative potency. In this paper, the statistical theory in the parallel line model is explained with an application to a dilution assay data. The parallel line method is implemented in a SAS program and is available at the author's homepage(http://cafe.daum.net/go.analysis).

• Proceedings of the Korean Society of Medical Physics Conference
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• 2002.09a
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• pp.174-176
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• 2002

A total of 134 patients with stage 1 of non-small cell lung cancer treated by carbon ion beam of HIMAC NIRS were investigated for control rate and delivered dose. The delivered dose of every patient was converted to biological effective dose (BED) of LQ model using fraction number, dose per fraction and alpha beta ratio which shows the maximum correlation between BED and tumor control. The BED of every patient was classified to establish a BED response curve for control. Assuming fraction numbers, dose response curves were introduced from BED response curve. The total doses to realize several control rates were obtained for the treatment of small fraction number.

• Journal of Pharmaceutical Investigation
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• v.39 no.5
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• pp.373-379
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• 2009

This study was conducted to develop a pharmacokinetic-pharmacodynamic (PK/PD) model of a direct thrombin inhibitor, argatroban to predict the concentration-effect profiles in rats. Argatroban was i.v. injected to rats at 0. 2, 0.8 and 3.2 mg/kg doses (n = 4-5 per dose), and plasma drug levels were determined by a validated LC/MS/MS assay. The pharmacokinetics of argatroban was linear over the i.v. dose range studied. The thrombin time (TT) and the activated partial thromboplastin time (aPTT) were measured in rat plasma and they were found to linearly increase with increasing the dose. A 2-compartment pharmacokinetic model linked with an indirect response pharmacodynamic model was successfully utilized to evaluate the drug concentration-response relationship.

• International Journal of Control, Automation, and Systems
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• v.1 no.3
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• pp.282-288
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• 2003

It is known that HIV (Human Immunodeficiency Virus) infection, which causes AIDS after some latent period, is a dynamic process that can be modeled mathematically. Effects of available anti-viral drugs, which prevent HIV from infecting healthy cells, can also be included in the model. In this paper we illustrate control theory can be applied to a model of HIV infection. In particular, the drug dose is regarded as control input and the goal is to excite an immune response so that the symptom of infected patient should not be developed into AIDS. Finite horizon optimal control is employed to obtain the optimal schedule of drug dose since the model is highly nonlinear and we want maximum performance for enhancing the immune response. From the simulation studies, we found that gradual reduction of drug dose is important for the optimality. We also demonstrate the obtained open-loop optimal control is vulnerable to parameter variation of the model and measurement noise. To overcome this difficulty, we finally present nonlinear receding horizon control to incorporate feedback in the drug treatment.

• 제어로봇시스템학회:학술대회논문집
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• 2003.10a
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• pp.1951-1956
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• 2003

It is known that HIV (Human Immunodeficiency Virus) infection, which causes AIDS after some latent period, is a dynamic process that can be modeled mathematically. Effects of available anti-viral drugs, which prevent HIV from infecting healthy cells, can also be included in the model. In this paper we illustrate control theory can be applied to a model of HIV infection. In particular, the drug dose is regarded as control input and the goal is to excite an immune response so that the symptom of infected patient should not be developed into AIDS. Finite horizon optimal control is employed to obtain the optimal schedule of drug dose since the model is highly nonlinear and we want maximum performance for enhancing the immune response. From the simulation studies, we find that gradual reduction of drug dose is important for the optimality. We also demonstrate the obtained open-loop optimal control is vulnerable to parameter variation of the model and measurement noise. To overcome this difficulty, we finally present nonlinear receding horizon control to incorporate feedback in the drug treatment.

• The Korean Journal of Pain
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• v.20 no.2
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• pp.92-99
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• 2007

Background: A correlation between a T-type voltage activated calcium channel (VACC) and pain mechanism has not yet been established. The purpose of this study is to find out the effect of ethosuximide and mibefradil, representative selective T-type VACC blockers on postoperative pain using an incisional pain model of rats. Methods: After performing a plantar incision, rats were stabilized on plastic mesh for 2 hours. Then, the rats were injected with ethosuximide or mibefradil, intraperitoneally and intrathecally. The level of withdrawal threshold to the von Frey filament near the incision site was determined and the dose response curves were obtained. Results: After an intraperitoneal ethosuximide or mibefradil injection, the dose-response curve showed a dose-dependent increase of the threshold in a withdrawal reaction. After an intrathecal injection of ethosuximide, the threshold of a withdrawal reaction to mechanical stimulation increased and the increase was dose-dependent. After an intrathecal injection of mibefradil, no change occurred in either the threshold of a withdrawal reaction to mechanical stimulation or a dose-response curve. Conclusions: The T-type VACC blockers in a rat model of postoperative pain showed the antihyperalgesic effect. This effect might be due to blockade of T-type VACC, which was distributed in the peripheral nociceptors or at the supraspinal level. Further studies of the effect of T-type VACC on a pain transmission mechanism at the spinal cord level would be needed.