• Communications for Statistical Applications and Methods
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• v.11 no.3
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• pp.597-607
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• 2004

The primary interest of drug development studies is identifying the lowest dose level producing a desirable effect over that of the zero-dose control, which is referred as the minimum effective dose (MED). In this paper, we suggest a nonparametric procedure for identifying the MED with binary or ordered categorical response data. Proposed test and Williams' test are compared by Monte Carlo simulation study and discussed.

• Journal of Chest Surgery
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• v.24 no.3
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• pp.253-260
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• 1991

The adequacy of anticoagulation with heparin during cardiopulmonary bypass, and precise neutralization with protamine at the conclusion of cardiopulmonary bypass, were important. In sixty children undergoing cardiopulmonary bypass, ACT and heparin dose-response curve were studied. Total dose of heparin before bypass were 2.80$\pm$0.74 mg/kg and the amount of protamine administered after bypass were 3.0$\pm$1.23 mg/kg. So protamine: heparin ratio was 1.07: l.c After administration of protamine which dose is calculated with heparin dose-response curve, ACTs were returned to normal range[mean 114.8 $\pm$13 second]. The heparin sensitivity and its half-life do not have relationship with age, weight, height, surface area and urine amount during operation. And there are too much individual variations in heparin sensitivity and its half-life. So conventional heparin protocols can overestimate or underestimate the amount of heparin and protamine. Heparin dose-response curve makes it possible to maintain anticoagulation in a safe range during bypass with adequate amount of heparin individually. At the conclusion of bypass, this curve can be used to predict the precise amount of protamine amount of protamine needed for neutralization of the heparin. But heparin dose-response curve to be used clinically, further studies will be needed about relationship between ACT and heparin level in the high range, influence of hemodilution and hypothermia to ACT and discrepancy between true adequate amount of protamine and calculated amount by heparin dose-response curve.

• Clinical and Experimental Reproductive Medicine
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• v.45 no.4
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• pp.183-188
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• 2018

Objective: The purpose of this retrospective study was to evaluate the appropriateness of various follicle-stimulating hormone (FSH) starting doses in expected normal responders based on the nomogram developed by La Marca et al. Methods: A total of 117 first in vitro fertilization cycles performed from 2011 to 2017 were selected. All women were expected normal responders and used a recombinant FSH and flexible gonadotropin-releasing hormone antagonist protocol. The FSH starting dose was empirically determined (150, 225, or 300 IU). The FSH starting dose indicated by La Marca's nomogram was determined using female age and serum $anti-M{\ddot{u}}llerian$ hormone or basal FSH levels. If the administered dose was exactly the same as the proposed dose, the cycle was assigned to the concordant group (34 cycles). If not, it was assigned to the discordant group (83 cycles). Optimal ovarian response was defined as a total of 8-14 oocytes, hypo-response as < 8 oocytes, and hyper-response as > 14 oocytes. Results: Between the concordant and discordant group, ovarian response (optimal, 32.4% vs. 27.7%; hypo-response, 55.9% vs. 54.2%; and hyper-response, 11.8% vs. 18.1%) and the number of total or mature oocytes were similar. Ovarian hyperstimulation syndrome was rare in both groups (0% vs. 1.2%). The implantation rate, clinical pregnancy rate, miscarriage rate, and live birth rate were all similar. Conclusion: The use of the proposed FSH starting dose determined using La Marca's nomogram did not enhance the optimal ovarian response rate or pregnancy rate in expected normal responders. Individualization of the FSH starting dose by La Marca's nomogram appears to have no distinct advantages over empiric choice of the dose in expected normal responders.

• 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.

• 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.

• Korean Journal of Clinical Pharmacy
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• v.14 no.1
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• pp.1-10
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• 2004

Studies of oxaliplatin, 5-fluorouracil and leucovorin in pretreated metastatic colorectal cancer showed that oxaliplatin dose intensity is important prognostic factor for objective response rates and progression-free-survival (PFS). To evaluate response rates, PFS and toxicity according to oxaliplatin dose intensity, we retrospectively analyzed data from patients with metastatic colorectal cancer received oxaliplatin,5-fluorouracil, leucovorin regimens. Sixty-three patients were reviewed in this study, 42 patients received low dose intensity oxaliplatin (LDI: $\leq85\;mg/m^2/2wks$) and 21 patients high dose intensity oxaliplatin (HDI: $>85\;mg/m^2/2wks$). Objective responses occurred in 10 $(47.7\%)$ HDI patients and 9 $(21.4\%)$ LDI patients (p = 0.014). Median PFS was 24.7 weeks in HDI group, with $45.1\%$ of HDI patients progression free at 6 months, and 20.5 weeks in LDI group, with $33.5\%$ of LDI patients progression free at 6 months (p = 0.344). Increased oxaliplatin dose intensity was not associated with neutropenia, thrombocytopenia, neuropathy, nausea and vomiting. This study showed that oxaliplatin dose intensification significantly improves objective response rate in pretreated metastatic colorectal cancer without increasing severe toxicity.

• Environmental Mutagens and Carcinogens
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• v.19 no.2
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• pp.108-111
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• 1999

Correlation between the tumorigenic dose (TD) and the maximum tolerated dose (MTD) was examined to search for the most relevant TD values related to the MTD. Using benzo(a)pyrene (B(a)P) 2-yr bioassay data, correlation coefficients between values of $TD_{1-}$50/ and the MTD were estimated from linearized or non-linearlized dose-response curves. The highest correlation coefficients (0.9966-1.0000) were obtained from T $D_{1-}$10/ in linearized dose-response curves while the highest (0.9966-1.0000) were estimated from $TD _{5-}$10/ in non-linearized dose-response eurves. These data suggest that TDs-lo were more closely related to the MTD than the ,$TD_{5-}$10/ in B(a)P 2-yr bioassay and that in lieu of the $TD_{50}$ they could be efficiently applicable to risk assessment and management.ent.

• 대한예방의학회:학술대회논문집
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• 1994.02a
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• pp.412-415
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• 1994

The fundamental assumption that thresholds exist for noncarcinogenic toxic effects of chemicals is reviewed; this assumption forms the basis for the no-observed-effect level/ safety-factor (NOEL/SF) approach to risk assessment for such effects. The origin and evolution of the NOEL/SF approach are traced, and its limitations are discussed. The recently proposed use of dose-response modeling to estimate a benchmark dose as a replacement for the NOEL is explained. The possibility of expanding dose-response modeling of non carcinogenic effects to include the estimation of assumed thresholds is discussed. A new method for conversion of quantitative toxic responses to a probability scale for risk assessment via dose-response modeling is outlined.

• Journal of Radiation Protection and Research
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• v.43 no.3
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• pp.97-106
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• 2018

Background: A cargo container scanner using a high-energy X-ray generates a fan beam X-ray to acquire a transmitted image. Because the generated X-rays by LINAC may affect the image quality and radiation protection of the system, it is necessary to acquire accurate information about the generated X-ray beam distribution. In this paper, a diode-based multi-channel spatial dose measuring device for measuring the X-ray dose distribution developed for measuring the high energy X-ray beam distribution of the container scanner is described. Materials and Methods: The developed high-energy X-ray spatial dose distribution measuring device can measure the spatial distribution of X-rays using 128 diode-based X-ray sensors. And precise measurement of the beam distribution is possible through automatic positioning in the vertical and horizontal directions. The response characteristics of the measurement system were evaluated by comparing the signal gain difference of each pixel, response linearity according to X-ray incident dose change, evaluation of resolution, and measurement of two-dimensional spatial beam distribution. Results and Discussion: As a result, it was found that the difference between the maximum value and the minimum value of the response signal according to the incident position showed a difference of about 10%, and the response signal was linearly increased. And it has been confirmed that high-resolution and two-dimensional measurements are possible. Conclusion: The developed X-ray spatial dose measuring device was evaluated as suitable for dose measurement of high energy X-ray through confirmation of linearity of response signal, spatial uniformity, high resolution measuring ability and ability to measure spatial dose. We will perform precise measurement of the X-ray beamline in the container scanning system using the X-ray spatial dose distribution measuring device developed through this research.

• Journal of Environmental Health Sciences
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• v.50 no.4
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• pp.229-236
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• 2024

The linear no-threshold (LNT) model is an assumption that explains the dose-response relationship for health risks, allowing for linear extrapolation from high doses to low doses without a threshold. The selection of an appropriate model for low-dose risk evaluation is a critical component in the risk assessment process for hazardous agents. This paper reviews the LNT model in light of epidemiological evidence from major international consortia studying ionizing radiation. From a scientific perspective, substantial evidence supporting the LNT model has been observed in epidemiological studies of low-dose ionizing radiation exposure, although some findings suggest non-linear dose relationships for certain cancer sites and variations across populations. From a practical standpoint, the LNT remains the most useful model for radiation protection purposes, with no alternative dose-response relationship proving more appropriate. It is important to note that the LNT model does not directly reflect the magnitude of risk at the population level, and this distinction should be clearly communicated to the public. While applying the LNT model as the principal basis for radiation protection, continuous research into various dose-response relationships is crucial for advancing our understanding.