• Communications for Statistical Applications and Methods
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• 제29권3호
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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 Chest Surgery
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• 제24권3호
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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.

• Journal of Radiation Protection and Research
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• 제24권4호
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• pp.225-230
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• 1999

본 연구는 이온화 방사선이 자주달개비 화분모세포의 미세핵 생성에 미치는 영향을 분석하여 선량-반응 관계를 수립하고자 수행되었다. 자주달개비의 화분모세포는 감수분열을 통하여 4개의 꽃가루로 발전되는 생식세포로서 분열과정 중에 방사선에 노출되면 염색체 조각이 분리되어 미세핵을 형성한다. 감마선 선량이 증가함에 따라 미세핵 생성률도 증가하였으며 특히 50 cGy까지의 선량범위에서 선량별 미세핵 생성률의 최대값은 뚜렷한 선량-반응관계를 보였다. 선량-반응 관계식을 통해 볼 때 1 cGy의 부가적 선량은 100 사분자당 최대 2개씩의 미세핵을 추가로 생성시키는 것으로 나타났다. 화분모세포 미세핵 생성률의 방사선 지표성은 생물학적 방사선량 감시를 위한 필수선결사항일 뿐 아니라 공해물질의 생체 위해성 검증, 수질과 토양의 건전성 평가 등에 대한 응용성을 갖고 있다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Current Trends in Toxicological Sciences
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• pp.137-137
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• 2002

Biologically Based Dose-Response (BBDR) models were developed using biomarkers for cancer risk assessment. To establish the relationship among biomarkers, exposure dose and tumor response, biomarkers in the lung, liver, stomach or blood were measured after a single or continuous administration of selected carcinogen (; BaP) in mice or rats.(omitted)

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2002년도 제9회 학술 발표회 프로그램과 논문초록
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• pp.25-26
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• 2002

The goal of radiation therapy is to maximize the tumor dose and to minimize the dose of normal tissue. In order to achieve this goal, the new radiation therapy techniques such as three dimensional conformal therapy or intensity modulated radiation therapy has been developed and tried to clinical application. The relationship between radiation dose and normal tissue response is an interesting subject in the radiation therapy field.(omitted)

• Toxicological Research
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• 제6권2호
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• pp.205-213
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• 1990

The regulation of neurotoxicants has usually been based upon setting reference doses by dividing a no observed adverse effect level (NOAEL) by uncertainty factors that theoretically account for interspecies and intraspecies extraploation of experimental results in animals to humans. Recently, we have proposed a four-step alternative procedure which provides quantitative estimates of risk as a function of dose. The first step is to establish a mathematical relationship between a biological effect or biomarker and the dose of chemical administered. The second step is to determine the distribution (variability) of individual measurements of biological effects or their biomarkers about the dose response curve. The third step is to define an adverse or abnormal level of a biological effect or biomarker in an untreated population. The fourth and final step is to combine the information from the first three steps to estimate the risk (proportion of individuals exceeding on adverse or abnormal level of a biological effect or biomarker) as a function of dose. The primary purpose of this report is to enhance the certainty of the first step of this procedure by improving our understanding of the relationship between a biomarker and dose of administered chemical. Several factors which need to be considered include: 1) the pharmacokinetics of the parent chemical, 2) the target tissue concentrations of the parent chemical or its bioactivated proximate toxicant, 3) the uptake kinetics of the parent chemical or metabolite into the target cell(s) and/or membrane interactions, and 4) the interaction of the chemical or metabolite with presumed receptor site(s). Because these theoretical factors each contain a saturable step due to definitive amounts of required enzyme, reuptake or receptor site(s), a nonlinear, saturable dose-response curve would be predicted. In order to exemplify this process, effects of the neurotoxicant, methlenedioxymethamphetamine (MDMA), were reviewed and analyzed. Our results and those of others indicate that: 1) peak concentrations of MDMA and metabolites are ochieved in rat brain by 30 min and are negligible by 24 hr, 2) a metabolite of MDMA is probably responsible for its neurotoxic effects, and 3) pretreatment with monoamine uptake blockers prevents MDMA neurotoxicity. When data generated from rats administerde MDMA were plotted as bilolgical effect (decreases in hippocampal serotonin concentrations) versus dose, a saturation curve best described the observed relationship. These results support the hypothesis that at least one saturable step is involved in MDMA neurotoxicity. We conclude that the mathematical relationship between biological effect and dose of MDMA, the first step of our quantitative neurotoxicity risk assessment procedure, should reflect this biological model information generated from the whole of the dose-response curve.

• Journal of health informatics and statistics
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• 제41권3호
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• pp.318-323
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• 2016

Objectives: Except the known risk factors for stroke, few studies have identified novel metabolic markers that could effectively detect stroke at an early stage. In this study, we explored the dose-response relationship between serum metabolites and the incidence of stroke. Methods: We studied 213 adults in the Korean Cancer Prevention Study-II (KCPS-II) biobank and estimated dose-response relationship between serum metabolites and stroke (42 cases and 171 controls). Three serum metabolites (Acetylcholine, HexadecylAcetylGlycerol, and 1-acetyl-2-formyl-sn-glycero-3-phosphocholine) were used in this study. The analysis included (1) exploratory nonlinear analysis, (2) estimation of flexion points and slopes at below and above the points. In the model to estimate risk of incidence of stroke, we controlled for conventional risk factors such as age, sex, systolic blood pressure, type 2 diabetes, triglyceride, and smoking status. Results: The relationship between incidence of stroke and log-transformed 1-acetyl-2-formyl-sn-glycero-3-phosphocholine was non-linear with flexion point around intensity score of 8.8, whereas other metabolites, log-transformed Acetylcholine and HexadecylAcetylGlycerol, showed negative linear patterns. Conclusions: The study suggests that metabolic markers are associated with incidence of stroke, particularly, at or above the flexion point. The study result may contribute to developing a novel system for precise stroke prediction.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.108-108
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• 1997

The effects of nalbuphine.HCI on the spontaneous locomotor activity and primary humoral immune response were investigated in ICR mice. Nalbuphine was intraperitoneally administered with the dose of 130, 260, 360 mg/kg in mice. The locomotor activity such as distance traveled was observed for 90min at 10min intervals. Nalbuphine showed the biphasic dose-response relationship on the spontaneous locomotor activity. IgM plaque forming cells(PFC) in splenocytes and IgM level in antiserum were significantly decreased depending on the dose of nalbuphine when nalbuphine was administered after the immunization, but slightly increased only at the low dose in the case of nabuphine administration after the immunization(SRBC).

• 대한화장품학회지
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• 제31권3호
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• pp.259-263
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• 2005

혈류량은 자외선 조사량 증가에 비례하여 증가되는 양상을 보였다. 홍반을 유발하는데 필요한 자외선량(MED)의 차이가 혈류량의 변화와 어떠한 관계가 있는지를 알아본 실험에서, MED가 30 mJ로 비교적 낮았던 피험자들의 경우, 혈류량은 MED를 지나서 급격하게 증가되는 양상을 관찰하였으나 30 mJ 이상에서 MED가 관찰되었던 피험자들의 경우에는 자외선 조사에 따른 혈류량의 변화가 급격한 변화 없이 계속 완만하게 증가되는 양상을 보였다.

• Journal of Ecology and Environment
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• 제37권4호
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• pp.195-200
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• 2014

The chances of accidental exposure are augmented as the application of ionizing radiation increases in various fields. Such accidental exposures may occur at nuclear power plants, laboratories, and hospitals. Cytogenetic assays have been used for estimating radiation dose in the situation of the accidents. The micronucleus assay has several advantages over the other cytogenetic methods as it is simple and fast. The present study aimed at investigation of the micronuclei frequencies in cytokinesis-block cells in human blood lymphocytes after ${\gamma}$-irradiation and at establishment of a standard dose response relationship. The samples of peripheral blood were obtained from 6 different donors aged between 24 and 30 years old. The bloods were irradiated in vitro with 0-5 Gy. A linear quadratic dose-response equation was obtained by scoring the micronuclei in binucleated cells; $y=27.87x^2+46.13x+2.08$ ($r^2=0.99$). Irradiation caused a significant decrease in the nuclear division index. Necrotic and apoptotic cells increased in number after irradiation in a dose-dependent manner. In conclusion, the conventional cytokinesis-block micronucleus assay has proven to be the great technique in biological dosimetry. Dose-response calibration curve derived from CMBN assay could be used to estimate the exposure dose during a radiological emergency.