• Title/Summary/Keyword: Multiple-dose

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A Bayesian joint model for continuous and zero-inflated count data in developmental toxicity studies

  • Hwang, Beom Seuk
    • Communications for Statistical Applications and Methods
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    • v.29 no.2
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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.

Effect of the Lycii Fructus on multiple low-dose streptozotocin-induced diabetic rats (Streptozotocin 저용량 반복투여로 유도한 당뇨 흰쥐에서 구기자 추출물의 효능연구)

  • Oh, Tae Woo;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.30 no.6
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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.

The Comparison of DVH between Multiple arc FSRT and Conformal FSRT (Multiple arc FSRT와 Conformal FSRT의 DVH 비교)

  • Kim Ki-Hwan;Kim Jun-Sang;Jang JiYoung;Kim Jae-Sung;Kim Seong-Ho;Song Chang-Joon;Park Min-Kyu;Cho Moon-June
    • Radiation Oncology Journal
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    • v.17 no.3
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    • pp.261-267
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    • 1999
  • Purpose : In FSRT (Fractionated stereotactic radiotherapy) planning, we studied the usefulness between multiple arc FSRT and conformal FSRT by comparing tumor shape and DVH (dose volume histogram). Materials and Methods In Chungnam Univ. hospital, we had treated the sixteen patients with FSRT from Aug. 1997 to Dec. 1998. In choosing multiple arc FSRT or conformal FSRT, we had considered If (irregular factor) after calculating tumor volume and surface area. We had considered multiple arc FSRT if tumor shape was similar to sphere or the value of If was less than 1.25, conformal FSRT if tumor shape was very irregular or If was more than 1.3. For evaluation of treatment planning, we had considered the appropriate DVH for tumor volume and for critical organs. Results : The errors between reference point and the coordinates point on AP, Lat radiography were less than 1 mm before treatment. We had planned $3\~$5 arcs for multiple arc FSRT, $5\~6$ports for conformal FSRT. The mean dose distribution of tumor volume of cumulative DVH between multiple arc FSRT and conformal FSRT was 90.6, 85%, respectively. The dose of critical organs irradiated was less than $5\%$ maximum dose of cumulative DVH. Conclusion : We had obtained the similar value between multiple arc FSRT and conformal FSRT, so that we had appropriate treatment planning of FSRT for multiple arc FSRT and conformal FSRT according to tumor shape and size.

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New Techniques for Optimal Treatment Planning for LINAC-based Stereotactic Radiosurgery (LINAC 뇌정의적 방사선 수술시 새로운 최적 선량분포계획 시스템의 개발)

  • Suh Tae-suk
    • Radiation Oncology Journal
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    • v.10 no.1
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    • pp.95-100
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    • 1992
  • Since LINAC-based stereotactic radiosurgery uses multiple noncoplanar arcs, three-dimensional dose evaluation and many beam parameters, a lengthy computation time is required to optimize even the simplest case by a trial and error. The basic approach presented in this paper is to show promising methods using an experimental optimization and an analytic optimization The purpose of this paper is not to describe the detailed methods, but introduce briefly, proceeding research done currently or in near future. A more detailed description will be shown in ongoing published papers. Experimental optimization is based on two approaches. One is shaping the target volumes through the use of multiple isocenters determined from dose experience and testing. The other method is conformal therapy using a beam's eye view technique and field shaping. The analytic approach is to adapt computer-aided design optimization in finding optimum irradiation parameters automatically.

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Managerial Factors Influencing Dose Reduction of the Nozzle Dam Installation and Removal Tasks Inside a Steam Generator Water Chamber (증기발생기 수실 노즐댐 설치 및 제거작업의 피폭선량 저감에 영향을 주는 관리요인에 관한 연구)

  • Lee, Dhong Ha
    • Journal of the Ergonomics Society of Korea
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    • v.36 no.5
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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.

Impact of Photon-Counting Detector Computed Tomography on Image Quality and Radiation Dose in Patients With Multiple Myeloma

  • Alexander Rau;Jakob Neubauer;Laetitia Taleb;Thomas Stein;Till Schuermann;Stephan Rau;Sebastian Faby;Sina Wenger;Monika Engelhardt;Fabian Bamberg;Jakob Weiss
    • Korean Journal of Radiology
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    • v.24 no.10
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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.

Analysis of Dose Delivery Error in Conformal Arc Therapy Depending on Target Positions and Arc Trajectories (동적조형회전조사 시 표적종양의 위치변위와 조사반경의 변화에 따른 선량전달 오류분석)

  • Kang, Min-Young;Lee, Bo-Ram;Kim, You-Hyun;Lee, Jeong-Woo
    • Journal of radiological science and technology
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    • v.34 no.1
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    • pp.51-58
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    • 2011
  • The aim of the study is to analyze the dose delivery error depending on the depth variation according to target positions and arc trajectories by comparing the simulated treatment planning with the actual dose delivery in conformal arc therapy. We simulated the conformal arc treatment planning with the three target positions (center, 2.5 cm, and 5 cm in the phantom). For the experiments, IMRT body phantom (I’mRT Phantom, Wellhofer Dosimetry, Germany) was used for treatment planning with CT (Computed Tomography, Light speed 16, GE, USA). The simulated treatment plans were established by three different target positions using treatment planning system (Eclipse, ver. 6.5, VMS, Palo Alto, USA). The radiochromic film (Gafchromic EBT2, ISP, Wayne, USA) and dose analysis software (OmniPro-IMRT, ver. 1.4, Wellhofer Dosimetry, Germany) were used for the measurement of the planned arc delivery using 6 MV photon beam from linear accelerator (CL21EX, VMS, Palo Alto, USA). Gamma index (DD: 3%, DTA: 2 mm) histogram and dose profile were evaluated for a quantitative analysis. The dose distributions surrounded by targets were also compared with each plans and measurements by conformity index (CI), and homogeneity index (HI). The area covered by 100% isodose line was compared to the whole target area. The results for the 5 cm-shifted target plan show that 23.8%, 35.6%, and 37% for multiple conformal arc therapy (MCAT), single conformal arc therapy (SCAT), and multiple static beam therapy, respectively. In the 2.5 cm-shifted target plan, it was shown that 61%, 21.5%, and 14.2%, while in case of center-located target, 70.5%, 14.1%, and 36.3% for MCAT, SCAT, and multiple static beam therapy, respectively. The values were resulted by most superior in the MCAT, except the case of the 5 cm-shifted target. In the analysis of gamma index histogram, it was resulted of 37.1, 27.3, 29.2 in the SCAT, while 9.2, 8.4, 10.3 in the MCAT, for the target positions of center, shifted 2.5 cm and 5 cm, respectively. The fail proportions of the SCAT were 2.8 to 4 times as compared to those of the MCAT. In conclusion, dose delivery error could be occurred depending on the target positions and arc trajectories. Hence, if the target were located in the biased position, the accurate dose delivery could be performed through the optimization of depth according to arc trajectory.

Pharmacokinetics of 11-Hydroxyaclacinomycin X (ID-6105), a Novel Anthracycline, after i.v. Bolus Multiple Administration in Rats

  • Yoo Bo-Im;Ahan Kwang Bok;Kang Min Hee;Kwon Oh-Seung;Hong Young-Soo;Lee Jung Joon;Lee Hong Sub;Ryu Jung Su;Kim Tae Yong;Moon Dong-Cheul;Song Sukgil;Chung Youn Bok
    • Archives of Pharmacal Research
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    • v.28 no.4
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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.

Effects of Cyclophosphamide on Immunological Memory in Mice (Cyclophosphamide가 마우스의 면역기억에 미치는 영향)

  • Park, Young-Min;Park, Yoon-Kyu;Ahn, Woo-Sup;Ha, Tai-You
    • The Journal of the Korean Society for Microbiology
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    • v.22 no.2
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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.

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A Study on the Dose Changes Depending on the Shielding Block Type of Irradiation During Electron Beam Theraphy (전자선치료 시 조사부위 차폐물 형태에 따른 선량변화 연구)

  • Lee, Sun-Yeb;Park, Cheol-Soo;Lee, Jae-Seung;Goo, Eun-Hoe;Cho, Jae-Hwan;Kim, Eng-Chan;Moon, Soo-Ho;Kim, Jin-Soo;Park, Cheol-Woo;Dong, Kyung-Rae;Kweon, Dae-Cheol
    • Journal of radiological science and technology
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    • v.33 no.3
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    • pp.253-260
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    • 2010
  • The primary focus of this study was to explore the variation in dose distributions of electron beams between different types of construction structure of cut-out blocks embodied in electron cones, given that the structure is considered one of the causes of multiple scattered radiation from electrons which may affect dose distributions. For evaluation, two types of cut-out blocks, divergency and straight, manufactured for this study, were compared in terms of area of interval in distribution of dose, and flatness and symmetric state of surface being radiated. The results showed that divergency cut-out blocks reduced the lateral scattering effects on the thickness of cut-out blocks more substantially than straight ones, leading to more uniform dose distribution at baseline depth. Notably in divergency cut-out blocks, the high dose area decreased more significantly, and more uniform dose distribution was observed at the edge of the irradiated field. This points to a need to consider the characteristics of dose distribution of electron beams when setting up radiotherapy planing at the venues. Therefore, this study is significant as an exploratory work for ensuring high accuracy in dose delivery for patients.