• Title/Summary/Keyword: Dose-response Relationship

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Estimating dose-response curves using splines: a nonparametric Bayesian knot selection method

  • Lee, Jiwon;Kim, Yongku;Kim, Young Min
    • 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.

Individualization of Heparin and Protamine Dosage using a Dose-response Curve during Extracorporeal Circulation (체외순환중 용량반응곡선을 이용한 헤파린과 프로타민 투여량의 결정)

  • Won, Yong-Sun;No, Jun-Ryang
    • 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.

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Dose-Response Relationship of Micronucleus Frequency in Pollen Mother Cells of Tradescantia (자주달개비 화분모세포 미세핵 생성률의 방사선량-반응 관계)

  • Kim, Jin-Kyu;Song, Hi-Sup;Hyun, Soung-Hee
    • Journal of Radiation Protection and Research
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    • v.24 no.4
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    • pp.225-230
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    • 1999
  • This study was carried out to investigate the radiation dose-response of micronucleus frequencies in Tradescantia pollen mother cells. The number of micronuclei increased in the tetrads as a result of chromosome deletion after irradiation. The maximal frequency of micronuclei showed a good dose-response relationship in the range of dose $0{\sim}50$ cGy. On the basis of the relationship, a dose of 1 cGy results maximally in two additional micronuclei in 100 tetrads. The radiation dose-response relationship of micronucleus occurrence is prerequisite to biological monitoring of radiations. The micronucleus assay can be applied to biological risk assessment of environmental toxicants, and to integrity test of water or soils of interest.

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The Linear No-Threshold Model in Epidemiological Studies: An Example of Radiation Exposure (역학연구에서의 비역치선형모델: 방사선 노출 사례)

  • Won Jin Lee
    • 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.

BIOLOGICALLY BASED DOSE-RESPONSE (BBDR) MODELING USING BIOMARKERS FOR CANCEER RISK ASSESSMENT

  • Song, Hyun-Sue;Lee, Byung-Mu
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05a
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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)

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Preliminary Study of Neuronal Response to Dose Distribution of Radiation with MR Spectroscopy

  • Ahn, Seung-Do;Yi, Byoung-Young;Lee, Jung-Hee
    • Proceedings of the Korean Biophysical Society Conference
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    • 2002.06b
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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)

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BIOLOGICALLY-BASED DOSE-RESPONSE MODEL FOR NEUROTOXICITY RISK ASSESSMENT

  • Slikker, William Jr.;Gaylor, David W.
    • Toxicological Research
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    • v.6 no.2
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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.

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Dose-response Relationship between Serum Metabolomics and the Risk of Stroke (혈청 대사체와 뇌졸중 발생위험의 용량반응 분석)

  • Jee, Yon Ho;Jung, Keum Ji;Lim, Youn-Hee;Lee, Yeseung;Park, Youngja;Jee, Sun Ha
    • Journal of health informatics and statistics
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    • v.41 no.3
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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.

The Effects of Nalbuphine on the Spontaneous locomotor activity and Primary Humoral Immune response in mice.

  • Yun, Hee-Eun;Kwak, Young-Hee;Pyo, Myoung-Yun
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1997.04a
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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).

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Relationship between UV-induced MED and Perfusion Value Assessed by Laser Doppler Perfusion Imager (Laser Doppler Perfusion Imager (LDPI)로 측정한 자외선 조사부위의 혈류량과 최소 홍반량(MED)과의 상관관계)

  • Kim, Nam-Soo;Lee, Kyung-Hoon
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.31 no.3 s.52
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    • pp.259-263
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    • 2005
  • The aim of the present study is to evaluate relationship between UV-induced MED and perfusion value assessed by Laser Doppler Perfusion Imager. In this study, A increasing linear relationship is seen between perfusion and dose (p<0.05). The dose-response curve show a steep slope in the case of lower MED values group after MED point, For higher MED group, increase with a gentle slope.