• Communications for Statistical Applications and Methods
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• 제29권2호
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• pp.239-250
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• 2022

In many applications, we frequently encounter correlated multiple outcomes measured on the same subject. Joint modeling of such multiple outcomes can improve efficiency of inference compared to independent modeling. For instance, in developmental toxicity studies, fetal weight and number of malformed pups are measured on the pregnant dams exposed to different levels of a toxic substance, in which the association between such outcomes should be taken into account in the model. The number of malformations may possibly have many zeros, which should be analyzed via zero-inflated count models. Motivated by applications in developmental toxicity studies, we propose a Bayesian joint modeling framework for continuous and count outcomes with excess zeros. In our model, zero-inflated Poisson (ZIP) regression model would be used to describe count data, and a subject-specific random effects would account for the correlation across the two outcomes. We implement a Bayesian approach using MCMC procedure with data augmentation method and adaptive rejection sampling. We apply our proposed model to dose-response analysis in a developmental toxicity study to estimate the benchmark dose in a risk assessment.

• 대한본초학회지
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• 제30권6호
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• pp.47-53
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• 2015

Objectives : This study was performed to investigate the anti-diabetic effect of the fruit extract of Lycium chinense Mill(Lycii Fructus, LF) on multiple low-dose streptozotocin-induced diabetic rats.Methods : Male Sprague-Dawley rats were divided into three groups; normal, STZ-control, Lycii Fructus extractorally administrated 300 ㎎/㎏ group (STZ-LF). Diabetes was induced in rats by consecutive injection of streptozotocin (STZ) at doses of 30 ㎎/㎏ for 5 days. After 4 weeks, all rats were sacrificed, Fasting blood glucose, total cholesterol (CHO), triglyceride (TG) and HDL-Cholesterol were measured in sera of rats. Histopathological changes of pancreas, kidney, liver and lung tissues were observed by microscope after H&E, Periodic acid-Schiff (PAS) and Masson's trichrome staining. The changes of body weight, blood glucose, and food and water intake were also measured.Results : There were no differences in body, food intake and water intake in LF-administrated groups compared with STZ control group. However, LF extract significantly decreased the levels of serum glucose, CHO, TG and HDL-Cholesterol in diabetic rats. In histopathological analysis of kidney, liver and lung, LF-administrated groups showed the inhibition of morphological damage.Conclusions : These results suggest that LF have a biological action on multi low-dose STZ-induced diabetes in rats via decreasing the serum glucose, TG and TG levels and may protect the morphological changes of kidney, liver and lung.

• Radiation Oncology Journal
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• 제17권3호
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• pp.261-267
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• 1999

목적 : Multiple arc FSRT (fractionated stereotactic radiotherapy)와 conformal FSRT의 치료계획에 있어서 종양의 모양과 DVH (dose volume histogram)를 비교하여 두 기법간의 유용성에 대하여 논하고자 한다. 대상 및 방법 : 16명의 뇌종양 환자들을 대상으로 1997년 8월부터 1998년 12월까지 충남대학교병원 치료방사선과에서 112회의 FSRT를 실시하였다. 치료 전 모의치료에서 얻은 AP(Anterior-posterior), Lateral 필름상의 금속표지자의 좌표값을 ISOLOC프로그램에 입력하여 얻은 기준점과의 오차를 확인한 후 치료계획을 하였다. 치료계획은 종양용적과 종양표면적를 계산한 후 if (Irregular factor)를 고려하여 multiple arc FSRT 혹은 conformal FSRT를 선택하였다. Multiple arc FSRT는 종양의 IF값이 1-1.2인 경우에 고려하였고, conformal FSRT는 IF값이 1.3 이상인 경우에 고려한 후 종양용적에 대하여 처방선량 이상의 선량에 대한 DVH곡선에 의한 면적이 최소이면서 처방선량 이하의 선량에 대한 DVH곡선에 의한 면적이 최대가 되도록 하는 치료계획을 선택하여 평가하였다. 결과 : 치료전 모의치료에서 시행한 금속표지자의 좌표값을 ISOLOC프로그램에 입력하여 얻은 기준점과의 오차는 1 mm 이내였다. Huitlple arc FSRT는 누적DVH상에서 처방선량의 90, 91, 92, $93\%$에서 전체 종양용적을 포함하고 있었으며 평균값은 $90.6\%$이었고, conformal FSRT 는 누적DVH상에서 처방선량의 81, 85, 86, 87, $91\%$에서 전체 종양용적을 포함하고 있었으며 평균값은 $8\%$이었다. 두 방식 모두 결정장기들에는 최대선량의 $5\%$이하의 적은 선량이 조사되었다. 결론 : Multiple arc FSRT와 conformal FSRT를 IF를 기준으로 치료 계획하여 구형의 종양에 multiple arc FSRT를 시행하였으며, 불규칙한 모양의 종양에는 conformal FSRT를 시행하여 종양의 모양에 관계없이 적절한 FSRT치료계획을 수립할 수 있었다.

• Radiation Oncology Journal
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• 제10권1호
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• pp.95-100
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• 1992

LINAC 뇌정위적 방사선 수술은 multiple noncoplanar arc, 3 차원 선량 계산 및 많은 조사 변수들이 사용되기 때문에 간단한 경우에도 최적 선량분포를 얻기 위해서는 많은 시간이 요구된다. 본 논문에서는 실험적 방법과 분석적 방법을 통한 유용한 방법을 제시하기 위한 것으로서, 보다 자세한 방법 및 내용은 앞으로의 발표 논문에서 다루게 된다. 실험적 방법으로 2가지 방법에의하면, 첫번째 방법은 multiple isocenter를 이용하는 것이고, 두번째 방법은 beam's eye view와 field shaping을 이용한 conformal therapy이다. 분석적 방법은 최적 조사조건을 찾기 위하여 computer-aided design optimization 방법을 이용하는 것이다.

• 대한인간공학회지
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• 제36권5호
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• pp.559-568
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• 2017

Objective: The aim of this study is to investigate the effective managerial factors influencing dose reduction of the nozzle dam installation and removal tasks ranking within top 3 in viewpoint of average collective dose of nuclear power plant maintenance job. Background: International Commission on Radiation Protection (ICRP) recommended to reduce unnecessary dose and to minimize the necessary dose on the participants of maintenance job in radiation fields. Method: Seven sessions of nozzle dam installation and removal task logs yielded a multiple regression model with collective dose as a dependent variable and work time, number of participants, space doses before and after shield as independent variables. From the sessions in which a significant reduction in collective dose occurred, the effective managerial factors were elicited. Results: Work time was the most important factor contributing to collective dose reduction of nozzle dam installation and removal task. Introduction of new technology in nozzle dam design or maintenance job is the most important factor for work time reduction. Conclusion: With extended task logs and big data processing technique, the more accurate prediction model illustrating the relationship between collective dose reduction and effective managerial factors would be developed. Application: The effective managerial factors will be useful to reduce collective dose of decommissioning tasks as well as regular preventive maintenance tasks for a nuclear power plant.

• Korean Journal of Radiology
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• 제24권10호
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• pp.1006-1016
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• 2023

Objective: Computed tomography (CT) is an established method for the diagnosis, staging, and treatment of multiple myeloma. Here, we investigated the potential of photon-counting detector computed tomography (PCD-CT) in terms of image quality, diagnostic confidence, and radiation dose compared with energy-integrating detector CT (EID-CT). Materials and Methods: In this prospective study, patients with known multiple myeloma underwent clinically indicated whole-body PCD-CT. The image quality of PCD-CT was assessed qualitatively by three independent radiologists for overall image quality, edge sharpness, image noise, lesion conspicuity, and diagnostic confidence using a 5-point Likert scale (5 = excellent), and quantitatively for signal homogeneity using the coefficient of variation (CV) of Hounsfield Units (HU) values and modulation transfer function (MTF) via the full width at half maximum (FWHM) in the frequency space. The results were compared with those of the current clinical standard EID-CT protocols as controls. Additionally, the radiation dose (CTDIvol) was determined. Results: We enrolled 35 patients with multiple myeloma (mean age 69.8 ± 9.1 years; 18 [51%] males). Qualitative image analysis revealed superior scores (median [interquartile range]) for PCD-CT regarding overall image quality (4.0 [4.0-5.0] vs. 4.0 [3.0-4.0]), edge sharpness (4.0 [4.0-5.0] vs. 4.0 [3.0-4.0]), image noise (4.0 [4.0-4.0] vs. 3.0 [3.0-4.0]), lesion conspicuity (4.0 [4.0-5.0] vs. 4.0 [3.0-4.0]), and diagnostic confidence (4.0 [4.0-5.0] vs. 4.0 [3.0-4.0]) compared with EID-CT (P ≤ 0.004). In quantitative image analyses, PCD-CT compared with EID-CT revealed a substantially lower FWHM (2.89 vs. 25.68 cy/pixel) and a significantly more homogeneous signal (mean CV ± standard deviation [SD], 0.99 ± 0.65 vs. 1.66 ± 0.5; P < 0.001) at a significantly lower radiation dose (mean CTDIvol ± SD, 3.33 ± 0.82 vs. 7.19 ± 3.57 mGy; P < 0.001). Conclusion: Whole-body PCD-CT provides significantly higher subjective and objective image quality at significantly reduced radiation doses than the current clinical standard EID-CT protocols, along with readily available multi-spectral data, facilitating the potential for further advanced post-processing.

• 대한방사선기술학회지:방사선기술과학
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• 제34권1호
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• pp.51-58
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• 2011

본 연구의 목적은 회전조사 시 표적종양의 위치변위와 갠트리의 조사반경에 의한 치료깊이 변화에 따른 모의치료계획 결과와 선량전달 결과상의 오차를 분석하고자 하였다. 깊이 변위가 가장 이상적인 경우, 즉 팬텀의 중심에 표적이 위치한 경우와 한쪽으로 2.5 cm, 5 cm씩 치우친 경우로 나누어 모의실험하였다. 표적의 위치 변화에 따른 모의치료계획을 실시하기 위하여 IMRT Body 팬톰(I'mRT Phantom, Wellhofer Dosimetry, Germany)를 이용하여 전산화단층촬영장치(Computed Tomography, Light speed 16, GE, USA)로 데이터를 획득하였다. 획득된 영상을 이용하여 치료계획장치(Treatment Planning System, Eclipse, ver. 6.5, VMS, Palo Alto, USA)를 이용하여 정중앙, 2.5 cm, 5 cm에 가상의 치료표적을 만들어 모의치료계획을 수립하였다. 선형가속기(CL21EX, VMS, Palo Alto, USA)의 6 MV 광자선과 최근 개발된 Gafchromic 필름(EBT2, ISP, Wayne, USA)을 이용하여 선량분포를 측정하였고, 선량분석프로그램(OmniPro-IMRT, ver. 1.4, Wellhofer Dosimetry, Germany)을 이용하여 모의치료계획 데이터와 측정 데이터를 정량적으로 분석하였다. 분석프로그램으로 횡축방향 선량분포 프로파일(Cross-plane profile)과 선량분포를 정량적으로 분석하기 위하여 감마인덱스(DD: 3%, DTA: 2 mm) 히스토그람을 이용하였다. 표적과 표적주변의 선량분포는 Conformity index(CI), Homogeneity index(HI)를 이용하여 정량적으로 분석하였다. 치료표적 전체체적에 대한 100% 선량분포에 포함되는 체적을 비교하여 분석하였다. 표적의 위치가 5 cm 에 있는 경우 다문동적회전조사(Multiple Conformal Arc Therapy, MCAT)는 23.8%, 단일동적회전조사(Single Conformal Arc Therapy, SCAT)는 35.6%, 고정조사는 37%였고, 표적이 2.5 cm에 있는 경우 MCAT 61%, SCAT 21.5%, 고정조사 14.2%로 분석되었다. 표적의 위치가 중앙에 있는 경우 MCAT 70.5%, SCAT 14.1%, 고정조사 36.3%로 나타났다. 표적의 위치가 5 cm 치우쳐 있는 경우를 제외하고 MCAT의 100% 선량분포에 포함되는 체적이 가장 크게 나타났다. 감마인덱스 히스토그램 분석결과, SCAT의 경우 37.1, 27.3, 29.2로 MCAT의 경우 9.2, 8.4, 10.3에 비해 최소 2.8배, 최대 4배 오차가 크게 나타났다. 결론적으로, 동적조형회전조사 시 표적종양의 위치변이와 조사반경의 변화에 따라 선량전달오류의 가능성을 알 수 있었으며 치료표적의 위치가 정중앙이 아닐 경우, 깊이와 회전반경을 최적화함으로써 정확한 선량 전달을 할 수 있다고 생각한다.

• Archives of Pharmacal Research
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• 제28권4호
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• pp.476-482
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• 2005

We investigated the pharmacokinetics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, after intravenous (i.v.) bolus administration at a multiple dose every 24 h for 5 days in rats. To analyze ID-6105 levels in biological samples, we used an HPLC-based method which was validated in a pharmacokinetic study by suitable criteria. The concentrations of ID-6105 after the multiple administration for 5 days were not significantly different from the results after the single administration. The $t_{1/2\alpha}, t_{l/2\beta}, V_{dss}, and CL_{t}$ after the multiple administration were not significantly different from the values after the single administration. Moreover, the concentrations of ID-6105 1 min at day 1-5 after i.v. bolus multiple administration did not show the significant difference. Of the various tissues, ID-6105 mainly distributed to the kidney, lung, spleen, adrenal gland, and liver after i.v. bolus multiple administration. ID-6105 concentrations in the kidney or lung 2 h after i.v. bolus administration were comparable to the plasma concentration shortly after i.v. bolus administration. However, the ID-6105 concentrations in various tissues 48 h after i.v. bolus administration decreased to low levels. ID-6105 was excreted largely in the bile after i.v. bolus multiple administration at the dose of 3 mg/kg. The amounts of ID-6105 found in the bile by 12 h or in the urine by 48 h after the administration were calculated to be $14.1\% or 4.55\%$ of the initial dose, respectively, indicating that ID-6105 is mostly excreted in the bile. In conclusion, ID-6105 was rapidly cleared from the blood and transferred to tissues, suggesting that ID-6105 might not be accumulated in the blood following i.v. bolus multiple dosages of 3 mg/kg every 24 h for 5 days. By 48 h after i.v. bolus administration, ID-6105 concentrations in various tissues had decreased to very low levels. The majority of ID-6105 appears to be excreted in the bile.

• 대한미생물학회지
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• 제22권2호
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• pp.175-184
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• 1987

The use of alkylating agent cyclophosphamide(CY), a widely used antitumor drug is well known as a potent immunosuppressant and has been used as a probe for investigating the functional capabilities of lymphocyte subsets of both T and B cells that play an important role in the regulation of the immune response. The present study was undertaken in an effort to assess the effects of CY on immunological memory in murine model. CY, given as a single dose of CY(250mg/kg) before sensitization with sheep red blood cells(SRBC) enhanced the primary response of Arthus and delayed-type hypersensitivity(DTH), as measured by footpad swelling reaction, but suppressed their tertiary DTH response. The similar CY pretreatment enhanced both the primary and tertiary hemagglutinin(HA) responses to SRBC, and the tertiary antibody response against polyvinylpyrroridone(PVP), a thymus-independent antigen but not the primary response against PVP. CY, given as a single dose of 250mg/kg 2 days before the primary immunization and two doses of 100mg/kg 2 days before the secondary and tertiary immunization, markedly suppressed the tertiary DTH and HA responses to SRBC. However, CY, given as small multiple daily doses(10mg/kg) over 4 days before sensitization but not after sensitization, enhanced the secondary HA response to SRBC. Contact sensitivity to dinitrofluorobenzene(DNFB) was suppressed by the drug, given either as a single large dose(300mg/kg) or as multiple dose(10mg/kg) administered 2 days before, together with or after DNFB sensitization. This suppression was more pronounced and more significant when CY was given as multiple dose. However, the enhancement of the secondary contact sensitivity to DNFB by CY was not clear-cut. The splenectomy appears to increase the enhancing effect of CY on contact sensitivity. These results suggest that CY selectively influences the immune response depending on the time of the drug administration relative to immunization and that the secondary or tertiary immune response involve memory cells with different susceptibilities to CY. Moreover, these results suggest that multiple low doses may sesectivley inhibit suppressor T cell proliferation involving DTH, HA or contact sensitivity without effecting helper T cells, but high doses presumably inhibit helper T cells and suppressor T cells with effecting B cells.

• 대한방사선기술학회지:방사선기술과학
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• 제33권3호
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• pp.253-260
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• 2010

전자의 다중산란에 의한 선량분포를 좌우하는 다양한 원인으로서 조사통에 삽입되는 차폐물의 제작형태에 따른 전자선의 선량분포를 알고자 하였다. 실험을 위하여 선속 확산현상을 고려한 차폐물(divergency cut-out block)과 선속 확산현상을 고려하지 않은 차폐물(straight cut-out block)을 제작하고 선량분포 구간 면적과 조사면 평탄도 및 대칭도를 비교하였다. 결과적으로 선속 확산현상을 고려한 차폐물이 선속 확산현상을 고려하지 않은 차폐물보다 차폐물 두께에 대한 측방산란효과가 현저하게 감소함으로서 기준점 깊이에서 균등한 선량분포를 이루었다. 특히 선속 확산현상을 고려한 차폐물일수록 고 선량 영역이 현저하게 감소하였으며 조사면 경계부에서 균일한 선량분포를 이루었다. 이는 환자의 투여선량의 정확도를 증가시키기 위한 모형 연구로서 전자선의 선량분포 특성을 고려한 방사선치료계획을 수립해야 할 것이다.