수혜자와 공여자의 약물대사와 관련된 염기 다형성이 간이식 환자에서 Tacrolimus 서방형 제제의 약동학에 미치는 영향

학위논문(박사) -- 서울대학교대학원 : 의과대학 의학과, 2023. 2. 이광웅.Background: The effects of multidrug resistance-1 (MDR1), ABCC2, and P450 oxidoreductase (POR)*28 gene polymorphisms on tacrolimus metabolism following a switch to once-daily dosing have not been elucidated. We investigated the effects of recipient and donor CYP3A5, MDR1, ABCC2, and POR*28 polymorphisms on tacrolimus pharmacokinetics following a switch to once-daily tacrolimus dosing. Methods: Eighty-seven liver transplant recipients who were switched from twice- to once-daily tacrolimus dosing following living-donor liver transplantation and 81 matched donors were genotyped for CYP3A5, MDR1 (1236C>T, 2677G>T/A, and 3435C>T), ABCC2 (-24C>T, 1249G>A, and 3972C>T), and POR*28. Tacrolimus dose-adjusted trough levels (C0/dose) before and after the switch were determined and calculated based on past medical records. Recipients were divided into two groups, one group constituted of 38 patients with a C0/dose decrease of less than 30% following conversion (group 1) and the other constituted of 49 patients with a C0/dose decrease of ≥30% (group 2). Results: CYP3A5 *1/*3 and *3/*3 were more frequent in recipients in group 1 (60.5% vs. 36.8%), while CYP3A5 *1/*1 was more frequent in group 2 (59.2% vs. 32.7%) (p = 0.016). The proportions of donor ABCC2 1249G>A genotypes AA and AG were higher in group 2 than in group 1 (20.4% vs. 5.3%; p = 0.042). Conclusion: Recipient CYP3A5 polymorphism and donor ABCC2 1249G>A polymorphism affected tacrolimus pharmacokinetics following the switch to once-daily dosing. Dose adjustment to maintain therapeutic tacrolimus levels following the switch to once-daily dosing should be considered based on polymorphisms in both the recipient and donor.서론: MDR1, ABCC2, POR*28 유전자 다형성이 간이식 환자에서 하루 2회 복용하는 기존의 tacrolimus 제제에서 1회 복용하는 서방형 제제로 변경하였을 때 약물 대사에 미치는 영항은 현재까지 밝혀지지 않았다. 간이식 수혜자와 기증자의 CYP3A5, MDR1, ABCC2, POR*28 다형성이 tacrolimus 서방형 제제로 전환한 후에 tacrolimus 약동학에 미치는 영향을 조사하였다. 방법: 생체 간이식 후 기존의 tacrolimus 제제에서 서방형 제제로 전환한 87명의 간이식 수혜자들과 이에 대한 81명의 기증자들의 CYP3A5, MDR1(1236C>T, 2677G>T/A, 3435C>T), ABCC2(-24C>T, 1249G>A, 3972C>T), POR*28에 대한 유전자형을 분석하였다. 서방형 제제로 전환 전후의 tacrolimus 용량 대비 혈중 농도 (C0/dose)는 환자의 의무기록을 참조하여 계산 후에 결정되었다. 수혜자들은 두 그룹으로 나누어졌는데, 한 그룹은 전환 후 C0/dose의 감소가 30% 미만이거나 증가한 38명의 환자로 구성되었고 (그룹 1), 다른 그룹은 C0/dose의 감소가 30% 이상인 49명의 환자로 구성되었다 (그룹 2). 결과: 수혜자의 CYP3A5 *1/*3 및 *3/*3은 그룹 1에서 많았던 반면에 (60.5% vs. 36.8%), 수혜자의 CYP3A5 *1/*1은 그룹 2에서 더 많았다. (59.2% vs. 32.7%) (p = 0.016). 공여자의 ABCC2 1249G>A 유전자형 AA와 AG의 비율은 그룹 1보다 그룹 2에서 더 높았다 (20.4% vs. 5.3%; p = 0.042). 결론: 수혜자의 CYP3A5 다형성과 기증자의 ABCC2 1249G>A 다형성은 간이식 환자에서 tacrolimus를 서방형 제제로 전환한 후 약물 약동학에 영향을 주었다. 서방형 제제로 전환한 후 최소한의 tacrolimus의 혈중 농도를 유지하기 위해서 투여 용량의 조정은 수혜자와 기증자의 다형성에 근거하여 고려되어야 한다.Chapter 1. Introduction 1 Chapter 2. Methods 4 Chapter 3. Results 9 Chapter 4. Discussion 11 References 17 Tables 23 Figure 29 Abstract in Korean 30박

A multivariate process control scheme using multiple hypothesis testing

MasterWith the development of high-capacity computer storage and the rapidly growing ability to process large amounts of data, multivariate control charts have received increasing attention as a means for performing quality control analysis. Existing univariate and multivariate control charts are a sequential hypothesis testing approach to monitoring the process mean or variance using a single statistic plot. These charts can therefore be interpreted in terms of p-value. By adopting a p-value approach, a control chart can be used with a multiple comparison procedure. This thesis proposes a multiple hypothesis approach to developing new multivariate control schemes based on a novel error rate, the False Discovery Rate which is defined as the expected portion of true null hypothesis among the total number of rejected hypotheses, is used as a controlled error rate. To control the False Discovery Rate, the Benjamini-Hochberg procedure is used. This thesis proposes two different approaches based on existence of the plotted statistics distribution because this procedure requires p-values. For the multivariate Shewhart control chart, which is used for a known distribution, plotted Hotelling T^2 statistics are used to compute the corresponding p-values. The Benjamini-Hochberg procedure is then used to control the false discovery rate, which is applied to the proposed control scheme. Some numerical simulations are carried out to compare the performance of the proposed control scheme in terms of the average run length. The proposed method outperforms the ordinary multivariate Shewhart control chart in terms of average run length for all mean shifts.For the multivariate exponentially weighted moving average control chart, which is used for an unknown distribution, the nonparametric density estimation is used to estimate an in-control state distribution before computing p-values. The Benjamini-Hochberg procedure is then applied to develop a new procedure for controlling the False Discovery Rate. Some numerical simulations are performed to determine the performance of the proposed method in terms of the average run length. The performance of proposed method is better than that of the ordinary multivariate exponentially weighted moving average control chart in terms of average run length for all shift sizes.This thesis proposes new multivariate statistical process control schemes for controlling the False Discovery Rate. Both proposed methods are better than ordinary methods in terms of average run length for all shift sizes. Also, ordinary multivariate statistical process control methods assume the normality of the dataset. This assumption is not realistic. In other words, in most cases, the distribution of plotted statistics cannot be derived. Therefore, the proposed methods may be more powerful for practical use

Policy Issues in Advancement of Regional Financial System in Korea

본 연구는 우리나라의 지역금융 현황과 지역금융 활성화를 위한 제도를 살펴보고, 이를 활성화하기 위한 정책 방안을 제시하고 있다. 우리나라의 금융은 산업구조 조정 및 금융위기 극복 과정에서 지역간 성장 격차가 확대되어 상대적으로 성장이 더딘 지역 소재 중소기업, 자영업자, 중저소득층 등 금융접근이 제한된 계층에 대한 지원이 미약한 실정이다. 특히 금융의 서울 및 수도권 집중도가 높아 서울과 지방간 금융 인프라 및 서비스 격차가 심하고 수도권을 제외한 지역의 자금유출초가 두드러지고 있다. 지역금융활성화를 위해서는 지역금융 활동에 대한 금융기관 공시제도 구축, 지역밀착형 금융기관의 인프라 구축 및 업무영역 확대, 기존 지역금융 지원제도의 실효성 제고 등의 노력이 필요하다. 한편 적극적인 지역금융정책의 하나인 미국의 지역재투자법(Community Reinvestment Act)과 유사한 제도를 우리나라에 그대로 도입하는 것은 미국과 우리나라의 은행제도 및 지역발전 역사, 신용평가에 대한 인프라 구축, 공익활동 평가에 대한 신뢰성 차이 등의 이유로 부작용이 더 클 것으로 판단된다. 그러나 CRA 지표 및 평가시스템 등은 우리나라 지역금융 활성화를 위한 공시 제도 도입 및 이에 따른 인센티브 부여에 상당 부분 적용이 가능한 것으로 평가된다. This study proposes some policy measures through exploring the regional financial status and current policy for boosting regional financial system. Financial supports for small businesses located on region, self-employed businesses and low and medium-income people has been very constrained due to expand of growth gaps among region during industrial restructuring and financial crisis. In particular, most of funds are concentrated on Seoul and the surrounding areas. That is one reason why financial infra-structures and services in Seoul are superior to those in other areas. Also, outflow of capital in all regions except Seoul and the metropolitan areas has been increasing. In order to boost regional financial system, we need some policy measures such as constructing financial disclosure for regional financial services, building infra-structure and expanding business area for regional financial institutions, improving the effectiveness of existing regional financial boosting system. Meanwhile, It is difficult to legislate Community Reinvestment Act(CRA) which is one of the aggressive regional financial policy in the U.S. into Korea in that there are the differences between the U.S. and Korea's financial system such as banking system, the regional development history, infra-structure for the credit rating system and the evaluation of public service activities. However, some parts of the CRA such as indicators and evaluation system, can be applied to activate of financial disclosure and subsequently introduce of incentive system for boosting regional finance.2

Analysis of the dynamic behavior of isolated and non-isolated rectangular liquid storage structures

학위논문(박사)--서울大學校 大學院 :土木工學科,1997.Docto

憲法 不合致 決定의 立法府에 대한 羈束力과 그 實效性에 관한 硏究

학위논문(석사)--서울대학교 행정대학원 :행정학과 행정학전공,2000.Maste

Study of Polarized Electron Source at PAL

Maste

솔레노이드 집속 전자석을 가진 고휘도 고주파 광전자 총의 에미턴스 전개과정에 관한 연구

Docto