• Safety and Health at Work
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• v.9 no.3
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• pp.290-295
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• 2018

Background: There is little information on the dose-response relationship between exposure to occupational carcinogenic agents and mesothelioma. This study aimed to investigate this association as well as the existence of agents other than asbestos that might cause mesothelioma. Methods: The Swedish component of the Nordic Occupational Cancer (NOCCA) study consists of 6.78 million individuals with detailed information on occupation. Mesothelioma diagnoses recorded in 1961-2009 were identified through linkage to the Swedish Cancer Registry. We determined cumulative exposure, time of first exposure, and maximum exposure intensity by linking data on occupation to the Swedish NOCCA job-exposure matrix, which includes 29 carcinogenic agents and corresponding exposure for 283 occupations. To assess the risk of mesothelioma, we used conditional logistic regression models to estimate hazard ratios and 95% confidence intervals. Results: 2,757 mesothelioma cases were identified in males, including 1,416 who were exposed to asbestos. Univariate analyses showed not only a significant excess risk for maximum exposure intensity, with a hazard ratio of 4.81 at exposure levels 1.25-2.0 fb/ml but also a clear dose-response effect for cumulative exposure with a 30-, 40-, and 50-year latency time. No convincing excess risk was revealed for any of the other carcinogenic agents included in the Swedish NOCCA job-exposure matrix. Conclusion: When considering asbestos exposure, past exposure, even for short periods, might be enough to cause mesothelioma of the pleura later in life.

• Journal of Radiation Protection and Research
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• v.23 no.1
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• pp.17-23
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• 1998

Dose response relationships for one of biological end-points (gene mutation) in somatic cells of Tradescantia 4430 clones were studied using neutrons coming out of a californium-252 isotopic source. And the relative biological effectiveness (RBE) of neutrons in relation to X-rays in the induction of TSH pink mutations was assessed. Inflorescences were irradiated with X-ray from X-ray generator and neutrons from $^{252}Cf$ source. Irradiated cuttings were incubated with aeration in neutrient solution under the controlled condition. For more than 4 weeks after irradiation cell mutations were scored. Pink mutation frequencies were calculated from the pooled data for the peak interval (days 6 to 13 post-irradiation). Somatic cell mutations in TSH showed linear dose response relationships in the range of neutron doses available for the experiment. The RBE values estimated for neutrons in relation to X-rays were in the range 3.1 to 6.8, which were much lower than normally recognized value.

• 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.

• Nutrition Research and Practice
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• v.15 no.3
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• pp.329-345
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• 2021

BACKGROUD/OBJECTIVES: Evidence has suggested an association between serum vitamin D and metabolic syndrome (MetS), but prospective studies are very limited. The objective was to assess the dose-response association between serum vitamin D concentration and MetS risk using a systematic review and meta-analysis of updated observational studies. MATERIALS/METHODS: Using MEDLINE, PubMed, and Embase, a systematic literature search was conducted through February 2020 and the references of relevant articles were reviewed. A random-effects model was used to estimate the summary odds ratio/relative risk and 95% confidence interval (CI). Heterogeneity among studies was evaluated with I² statistic. In total, 23 observational studies (19 cross-sectional studies, and four cohort studies) were included in the meta-analysis. RESULTS: The pooled estimates (95% CI) for MetS per 25-nmol/L increment in serum vitamin D concentration were 0.80 (95% CI, 0.76-0.84; I² = 53.5) in cross-sectional studies, and 0.85 (95% CI, 0.72-0.98; I² = 85.8) in cohort studies. Similar results were observed, irrespectively of age of study population, study location, MetS criteria, and adjustment factors. There was no publication bias for the dose-response meta-analysis of serum vitamin D concentrations and MetS. CONCLUSIONS: Dose-response meta-analysis demonstrated that a 25-nmol/L increment in the serum vitamin D concentration was associated with 20% and 15% lower risks of MetS in cross-sectional studies and cohort studies, respectively.

• Korean Journal of Head & Neck Oncology
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• v.14 no.1
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• pp.61-69
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• 1998

Objectives: The response rate of the radioactive iodine(RI) therapy with low dose was variable. Only a few studies reported the response and complication rate with high dose. The goal of this study was to access the ablation and complication rate after high dose of RI therapy (more than 100mCi) and to evaluate the factors affect the results. Material and Methods: During a period of 12 years, 225 patients received high dose of RI from 100 to 200mCi depending on the RI uptake in the whole body after total thyroidectomy. 100mCi of RI was given to 123 patients for ablation who showed the uptake only in the thyroid bed. 150mCi was given to another 84 patients for ablation who had uptake confined to the neck. The other 21 patients took more than 200mCi of RI because the whole body scan showed distant metastasis. Among these patients, the ablation and the complication rate was investigated. Results: Elevated level of the serum thyroglobulin(Tg) decreased less than 5ng/ml after RI therapy in all patients except two in the first group. The second group showed reduction of the serum Tg in 93%. Eighteen of the 21 patients in the third group are still alive after RI therapy. There were no fatal complications after high dose RI therapy and most of the complications were minimal and transient. The complication rate was not related with the dose of RI, age, sex, DNA flowcytometry, serum thyroglobulin level and the extent of node dissection. Conclusion: We concluded that RI therapy with high dose was very effective for thyroid ablation after operation and it also showed excellent results with minimal complications for treatment of metastatic lesions.

• Radiation Oncology Journal
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• v.37 no.3
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• pp.193-200
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• 2019

Purpose: To explore the role of salvage radiotherapy (RT) for recurrent thymoma as an alternative to surgery. Materials and Methods: Between 2007 and 2015, 47 patients who received salvage RT for recurrent thymoma at Yonsei Cancer Center were included in this study. Recurrent sites included initial tumor bed (n = 4), pleura (n = 19), lung parenchyma (n = 10), distant (n = 9), and multiple regions (n = 5). Three-dimensional conformal and intensity-modulated RT were used in 29 and 18 patients, respectively. Median prescribed dose to gross tumor was 52 Gy (range, 30 to 70 Gy), with equivalent doses in 2-Gy fractions (EQD₂). We investigated overall survival (OS), progression-free survival (PFS), and patterns of failure. Local failure after salvage RT was defined as recurrence at the target volume receiving >50% of the prescription dose. Results: Median follow-up time was 83 months (range, 8 to 299 months). Five-year OS and PFS were 70% and 22%, respectively. The overall response rate was 97.9%; complete response, 34%; partial response, 44.7%; and stable disease, 19.1%. In multivariate analysis, histologic type and salvage RT dose (≥52 Gy, EQD₂) were significantly associated with OS. The high dose group (≥52 Gy, EQD₂) had significantly better outcomes than the low dose group (5-year OS: 80% vs. 59%, p = 0.046; 5-year PFS: 30% vs. 14%, p=0.002). Treatment failure occurred in 34 patients; out-of-field failure was dominant (intra-thoracic recurrence 35.3%; extrathoracic recurrence 11.8%), while local failure rate was 5.8%. Conclusion: Salvage RT for recurrent thymoma using high doses and advanced precision techniques produced favorable outcomes, providing evidence that recurrent thymoma is radiosensitive.

• 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.

• Progress in Medical Physics
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• v.32 no.4
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• pp.179-184
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• 2021

This study aimed to determine the optimal thickness of the active layer and scan mode for a flexible radiochromic film (F-RCF) based on the active lithium salt of pentacosa-10,12-diynoic acid (LiPCDA). F-RCFs of 90, 120, 140, and 170-㎛ thickness were fabricated using LiPCDA. Several pieces of the F-RCFs were exposed to doses ranging from 0 to 3 Gy. Transmission and reflection modes were used to scan the irradiated F-RCFs. Their dose-response curves were obtained using a second-order polynomial equation. Their sensitivity was evaluated for both scanning modes, and the uniformity of the batch was also examined. For both the transmission and reflection modes, the sensitivity increased as the film thickness increased. For the reflection mode, the dose response increased dramatically under 1 Gy. The value of the net optical density varied rapidly as the thickness of the film increased. However, the dose-response curves showed a supralinear-curve relationship at doses greater than 2 Gy. The sensitivity of the reflection scan at doses greater than 2 Gy was higher than that of the reflection scan within 0-2 Gy. The sensitivity steadily decreased with increasing doses, and the sensitivity of the two modes was within 0.1 to 0.2 at 2 Gy and was saturated beyond that. For the transmission scan, the sensitivity was approximately 0.2 at 3 Gy. For the intra-batch test result, the maximum net optical density difference of the intra-batch was 5.5% at 2 Gy and 7.4% at 0.2 Gy in the transmission and reflection scans, respectively. In the low-dose range, film thickness of more than 120-㎛ was proper in the transmission mode. In contrast, the transmission mode showed a better result compared to the reflection mode. Therefore, the proper scan mode should be selected according to the dose range.

• 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).

• 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.