• Title/Summary/Keyword: reaction probability

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Maximum tolerated dose estimations using various stopping rules in phase I clinical trial (제 1상 임상시험에서 다양한 멈춤 규칙을 이용한 최대허용용량 추정법)

  • Jeon, Soyoung;Kim, Dongjae
    • The Korean Journal of Applied Statistics
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    • v.35 no.2
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    • pp.251-263
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    • 2022
  • Phase I clinical trial is called 'Dose finding study'. It is first step of experimenting on humans with new drugs developed through animal experiments or vitro experiments. The important area of interest in designing Phase I clinical trial is determining the dose that acceptable level to the patients and provides the greatest efficacy. In this paper, we explain about methods to determine the maximum tolerated dose using various stopping rules. The SM3, NM, Rim, J3, BSM methods are compared through simulation. And we consider how the methods might be reformed. As a result of the simulation, BSM estimated the MTD closest to the target toxicity probability. J3 method required the least number of subjects. These results are due to the feature of the stopping rules of both methods. The BSM adds 2 or 1 subject at the same dose level when there is a toxic reaction. In addition, the J3 method has a smaller number of subjects than the other methods. If the methods are improved by combining these features, MTD can be estimated more efficiently. If the total number of subjects can be reduced while using the stopping rule of the BSM, accurate estimation is possible for a small number of subjects.

A Study on the Incidence of Side Effects according to the Number of Beams in Intensity-modulated Radiation Therapy for Prostate Cancer using 15 MV (15 MV를 이용한 전립샘암 세기조절 방사선치료 시 빔의 개수에 따른 부작용 발생률에 관한 연구)

  • Joo-Ah Lee
    • Journal of the Korean Society of Radiology
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    • v.17 no.3
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    • pp.481-487
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    • 2023
  • In this study, we analyzed the incidence of side effects of photoneutron dose according to the number of beams during intensity-modulated radiotherapy of prostate cancer using 15 MV. The radiation treatment plan design for intensity-modulated radiation therapy for prostate cancer was established with a prescription dose of 220 cGy per dose and a total of 7260 cGy for 33 treatments. The linear accelerator used in the experiment is Varian's True Beam STx (Varian, USA). Photoneutron dose was generated by using 15 MV energy in the planning target volume (PTV). The treatment plan was designed with IMRT 5, 7, and 9 portals using the Eclipse System (Varian Ver 10.0, USA). An optically stimulated luminescence albedo neutron dosimeter (Landauer Inc., USA) was used to measure photoneutron dose. IMRT 5 portals, 1.7 per 1,000, 7 portals, 1.8 per 1,000, 9 portals, 2.0 per 1,000 were calculated as the probability of experiencing side effects on the thyroid gland due to photoneutron dose. This study studies the risk of secondary radiation exposure dose that can occur during intensity-modulated radiation therapy, and it is considered that it will be used as useful data in relation to stochastic effects in the future.

A prognosis discovering lethal-related genes in plants for target identification and inhibitor design (식물 치사관련 유전자를 이용하는 신규 제초제 작용점 탐색 및 조절물질 개발동향)

  • Hwang, I.T.;Lee, D.H.;Choi, J.S.;Kim, T.J.;Kim, B.T.;Park, Y.S.;Cho, K.Y.
    • The Korean Journal of Pesticide Science
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    • v.5 no.3
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    • pp.1-11
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    • 2001
  • New technologies will have a large impact on the discovery of new herbicide site of action. Genomics, combinatorial chemistry, and bioinformatics help take advantage of serendipity through tile sequencing of huge numbers of genes or the synthesis of large numbers of chemical compounds. There are approximately $10^{30}\;to\;10^{50}$ possible molecules in molecular space of which only a fraction have been synthesized. Combining this potential with having access to 50,000 plant genes in the future elevates tile probability of discovering flew herbicidal site of actions. If 0.1, 1.0 or 10% of total genes in a typical plant are valid for herbicide target, a plant with 50,000 genes would provide about 50, 500, and 5,000 targets, respectively. However, only 11 herbicide targets have been identified and commercialized. The successful design of novel herbicides depends on careful consideration of a number of factors including target enzyme selections and validations, inhibitor designs, and the metabolic fates. Biochemical information can be used to identify enzymes which produce lethal phenotypes. The identification of a lethal target site is an important step to this approach. An examination of the characteristics of known targets provides of crucial insight as to the definition of a lethal target. Recently, antisense RNA suppression of an enzyme translation has been used to determine the genes required for toxicity and offers a strategy for identifying lethal target sites. After the identification of a lethal target, detailed knowledge such as the enzyme kinetics and the protein structure may be used to design potent inhibitors. Various types of inhibitors may be designed for a given enzyme. Strategies for the selection of new enzyme targets giving the desired physiological response upon partial inhibition include identification of chemical leads, lethal mutants and the use of antisense technology. Enzyme inhibitors having agrochemical utility can be categorized into six major groups: ground-state analogues, group specific reagents, affinity labels, suicide substrates, reaction intermediate analogues, and extraneous site inhibitors. In this review, examples of each category, and their advantages and disadvantages, will be discussed. The target identification and construction of a potent inhibitor, in itself, may not lead to develop an effective herbicide. The desired in vivo activity, uptake and translocation, and metabolism of the inhibitor should be studied in detail to assess the full potential of the target. Strategies for delivery of the compound to the target enzyme and avoidance of premature detoxification may include a proherbicidal approach, especially when inhibitors are highly charged or when selective detoxification or activation can be exploited. Utilization of differences in detoxification or activation between weeds and crops may lead to enhance selectivity. Without a full appreciation of each of these facets of herbicide design, the chances for success with the target or enzyme-driven approach are reduced.

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The Effects of Monoamine Oxidase A CA Repeat Polymorphism on Behavioral Trait and Clinical Characteristics in Korean Male Alcoholics (단가아민 산화제 A CA 반복 유전자 다형성이 한국 알코올의존 남자환자의 행동특성과 임상양상에 미치는 영향)

  • Lee, Jung-Sik;Yang, Byung-Hwan;Lee, Kyung-Mee;Kim, Hong-Kwan;Kim, Yong-In;Chai, Young-Gyu
    • Korean Journal of Biological Psychiatry
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    • v.7 no.1
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    • pp.64-73
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    • 2000
  • There are several candidate genes in genetic study of alcoholism. Among them, allelic associations have been reported between MAOA CA repeat polymorphism and alcohol dependence, recently. And also, several studies have been investigated genotype-phenotype relationships between MAOA CA repeat polymorphism and clinical manifestations. The authors tried to identify differences in allelic frequency of MAOA CA repeat polymorphism between alcohol dependence and controls, and in behavioral trait and clinical characteristics according to MAOA CA repeat polymorphism. We also tried to investigate genotype-phenotype relationships between MAOA CA repeat polymorphism and behavioral trait such as aggression. We examined 49 male patients with alcohol dependence(DSM-IV) who had been admitted in Yong-In Mental Hospital from June 1st 1998 to October 31th 1998. We performed semistructured interview for demographic and clinical characteristics. Self-report questionnaire for BDHI(Buss-Durkey Hostility Inventory) was given to all subject at least 4weeks later after admission. Using polymerase chain reaction and polyacrylamide gel electrophoresis, MAOA CA repeat polymorphism were observed in 52 male controls and 49 male patients with alcohol dependence. We devided alcoholic patients into two groups according to allelic length of MAOA CA repeat polymorphism ; alcoholics with short alleles(${\leq}$119bp, N=20) and alcoholics with long alleles(${\geq}$123bp, N=29). T-test, ${\chi}^2$-test and Fisher exact probability test were used for statistical analysis. There were no significant differences in frequency of each allele and short and long alleles of MAOA CA repeat polymorphism between alcoholics and controls. But there were significant differences in clinical symptoms and behavioral trait between alcoholics with short and long alleles. In clinical symptoms, alcoholics with long alleles used alcohol more frequently during one month before admission, had much more maximum amount of beer drinking and reported withdrawal seizure more frequently than with short alleles. In contrary, alcoholics with short alleles expressed depressed mood and guilty feeling more frequently and wanted complete abstinence as a treatment goal more frequently than with long alleles. In behavioral trait, alcoholics with long alleles had higher total aggression score and showed much more self-assertive attitude(subscale of expression of aggression) than with short alleles. Allelic length of MAOA CA repeat polymorphism was correlated with self-assertive attitude and accounted for 9% of the variance of self-assertive attitude. And also, predictable variables of allelic length of MAOA CA repeat polymorphism were drinking frequency and self-assertive attitude. Our findings suggest that MAOA CA repeat polymorphism may provide some behavior modifying role especially in self-assertive attitude and indirect symptom modifying role in Korean male alcoholics.

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Study on the Photoneutrons Produced in 15 MV Medical Linear Accelerators : Comparison of Three-Dimensional Conformal Radiotherapy and Intensity-Modulated Radiotherapy (15 MV 의료용 선형가속기에서 발생되는 광중성자의 선량 평가 - 3차원입체조형방사선치료와 세기조절방사선치료의 비교 -)

  • Yang, Oh-Nam;Lim, Cheong-Hwan
    • Journal of radiological science and technology
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    • v.35 no.4
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    • pp.335-343
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    • 2012
  • Intensity-modulated radiotherapy(IMRT) have the ability to provide better dose conformity and sparing of critical normal tissues than three-dimensional radiotherapy(3DCRT). Especially, with the benefit of health insurance in 2011, its use now increasingly in many modern radiotherapy departments. Also the use of linear accelerator with high-energy photon beams over 10 MV is increasing. As is well known, these linacs have the capacity to produce photonueutrons due to photonuclear reactions in materials with a large atomic number such as the target, flattening filters, collimators, and multi-leaf collimators(MLC). MLC-based IMRT treatments increase the monitor units and the probability of production of photoneutrons from photon-induced nuclear reactions. The purpose of this study is to quantitatively evaluate the dose of photoneutrons produced from 3DCRT and IMRT technique for Rando phantom in cervical cancer. We performed the treatment plans with 3DCRT and IMRT technique using Rando phantom for treatment of cervical cancer. An Rando phantom placed on the couch in the supine position was irradiated using 15 MV photon beams. Optically stimulated luminescence dosimeters(OSLD) were attached to 4 different locations (abdomen, chest, head and neck, eyes) and from center of field size and measured 5 times each of locations. Measured neutron dose from IMRT technique increased by 9.0, 8.6, 8.8, and 14 times than 3DCRT technique for abdomen, chest, head and neck, and eyes, respectively. When using IMRT with 15 MV photonbeams, the photoneutrons contributed a significant portion on out-of-field. It is difficult to prevent high energy photon beams to produce the phtoneutrons due to physical properties, if necessary, It is difficult to prevent high energy photon beams to produce the phtoneutrons due to physical properties, if necessary, it is need to provide the additional safe shielding on a linear accelerator and should therefore reduce the out-of-field dose.

Development of the Risk Evaluation Model for Rear End Collision on the Basis of Microscopic Driving Behaviors (미시적 주행행태를 반영한 후미추돌위험 평가모형 개발)

  • Chung, Sung-Bong;Song, Ki-Han;Park, Chang-Ho;Chon, Kyung-Soo;Kho, Seung-Young
    • Journal of Korean Society of Transportation
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    • v.22 no.6
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    • pp.133-144
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    • 2004
  • A model and a measure which can evaluate the risk of rear end collision are developed. Most traffic accidents involve multiple causes such as the human factor, the vehicle factor, and the highway element at any given time. Thus, these factors should be considered in analyzing the risk of an accident and in developing safety models. Although most risky situations and accidents on the roads result from the poor response of a driver to various stimuli, many researchers have modeled the risk or accident by analyzing only the stimuli without considering the response of a driver. Hence, the reliabilities of those models turned out to be low. Thus in developing the model behaviors of a driver, such as reaction time and deceleration rate, are considered. In the past, most studies tried to analyze the relationships between a risk and an accident directly but they, due to the difficulty of finding out the directional relationships between these factors, developed a model by considering these factors, developed a model by considering indirect factors such as volume, speed, etc. However, if the relationships between risk and accidents are looked into in detail, it can be seen that they are linked by the behaviors of a driver, and depending on drivers the risk as it is on the road-vehicle system may be ignored or call drivers' attention. Therefore, an accident depends on how a driver handles risk, so that the more related risk to and accident occurrence is not the risk itself but the risk responded by a driver. Thus, in this study, the behaviors of a driver are considered in the model and to reflect these behaviors three concepts related to accidents are introduced. And safe stopping distance and accident occurrence probability were used for better understanding and for more reliable modeling of the risk. The index which can represent the risk is also developed based on measures used in evaluating noise level, and for the risk comparison between various situations, the equivalent risk level, considering the intensity and duration time, is developed by means of the weighted average. Validation is performed with field surveys on the expressway of Seoul, and the test vehicle was made to collect the traffic flow data, such as deceleration rate, speed and spacing. Based on this data, the risk by section, lane and traffic flow conditions are evaluated and compared with the accident data and traffic conditions. The evaluated risk level corresponds closely to the patterns of actual traffic conditions and counts of accident. The model and the method developed in this study can be applied to various fields, such as safety test of traffic flow, establishment of operation & management strategy for reliable traffic flow, and the safety test for the control algorithm in the advanced safety vehicles and many others.