The Anglo-French Rivalry and the Rise of British Finance, 1688-1720

학위논문 (석사)-- 서울대학교 대학원 : 정치외교학부, 2016. 2. 박종희.Why did Great Britain rise as a hegemon in the 18th century Europe? What was the role of sovereign borrowing in the process? Great Britain had access to unprecedented levels of war finances via the expansion of the debt market in the early eighteenth century, and its eventual success was reflected in Britains prodigal expenditure on military and naval equipment. Effective government borrowing has hitherto become one of the predominant factors in explaining the rise of Great Britain as a global hegemon in the eighteenth century. This dissertation focused on the eighteenth century Anglo-French rivalry underpinning British financial growth to argue that the pressure to financially outperform France provided Britain the incentives to implement schemes that restructured the debt market, from public ownership of debt to modern forms of private holdings. The two grand schemes were to convert the unfunded debt to the funded debt by inducing interest rate flexibility of loans and reducing the cost of debt via the sinking fund and the South Sea Bubble. The implementation of each scheme was triggered by financial developments in France. As a result, the two schemes committed Britain to lower the cost of its national debt and institutionalize private sector control over the national debt. The thesis, in particular, focuses on the financial developments from 1700 to 1720 because when distinguishing the different types of debt, the twenty years starting from 1700 to 1720 is the transitional period where old forms of debt are restructured to modern forms of funded debt. In other words, the ownership of the national debt restructures from the public sector to the private sector, typically in forms of the bond market. This dissertation has divided the twenty years into 1700-1710 and 1710-1720 to analyze major financial developments that enabled the restructuring of the national debt. From 1700 to 1710, two political events affected Britain to compete for its fiscal-military reputation over France, in order to secure finance in the debt market. Britains military outperformance over France and internationalization of the British debt market, made Britain increasingly reluctant to forgo its future finances by reneging its commitment. To sustain the inflow of investment from foreign creditors, reputation fiscal-military mattered and especially Britain had the pressure to consistently manifest her devotion to consistent implementation of debt servicing policies despite domestic complexities. From 1710 to 1720, Britain implemented two grand schemes that restructured British national debt from unfunded debt to modern forms of funded debt. Each of the schemes was achieved in response to the financial developments in France. The first scheme to lower the interest rate of the national debt was implemented by the Tories in 1711 via the founding of the South Sea Company. This scheme was triggered by developments in 1702 France where their saving banks were re-established and their Treasury notes were circulating faster via the lowered interest rate on the Treaty notes. The second scheme to repay the debt was implemented by the Whigs in 1716 in response to the seemingly rapid fiscal recovery of France via the development of the Mississippi Company in 1716. In response, Britain actively sought to repay their public debt via the sinking fund and lower the cost of debt further by generating the South Sea Bubble that encouraged the private sector to provide speculative incentives to absorb the old forms of debt to modern forms of government bonds. The thesis, thus, provides two significant implications for international political economy. First, this thesis shows how inter-state relations influence the trajectories of financial growth for a state. I argued that the international dimension or the Anglo-French rivalry provides a better explanation in explaining the restructuring of old forms of national debt to modern forms of national debt. Recasting the international dimension to the discussion suggests that international factors can equally, and more powerfully explain government finance. More importantly, however, this thesis provides implications for hegemonic rivalry and its effect on financial growth. Anglo-French rivalry played an important role in setting the foundation for the rise of British finance, and not necessarily the endogenous factors of the British hegemon. Anglo-French rivalry and the continental war in Europe provided Britain the pressure to go beyond domestic political complexities and consistently implement policies favorable to debt servicing.I. Introduction 1 1. Inter-state Politics and the Development of Credit 1 2. Question 4 3. Research Method 6 1) Subject 6 2) Reputational Rivalry and Credible Commitment 7 4. Outline of the Dissertation 9 II. Literature Review 12 1. Institutions that Promote Revenue 12 1) Taxation 12 2) Centralized Civil Administration 13 3) Determination to Act as a Major Power 14 2. Institutions that Veto Default 14 1) Multiple Veto Points 14 2) Partisan Politics 15 3) Private Institutions 17 3. Limits and Implications 17 1) Limits to the Institutions that Promote Revenue 17 2) Limits to the Institutions that Veto Default 20 4. Chapter Summary 21 III. Glorious Revolution and the Development of Debt 23 1. British State of Finance 23 1) State of Credit before the Glorious Revolution 23 2) State of Credit after the Glorious Revolution 26 2. Development of the Different Types of Debt 31 1) Terminable Annuities 32 2) Unfunded Debt 32 3) Funded Debt 32 3. Sovereign Debt Restructuring from 1700 to 1720 33 4. Chapter Summary 35 IV. Anglo-French Rivalry and the British Credit, 1700-1710 37 1. Britain as the Emerging War State 37 1) Embarkation of the Anglo-Dutch Alliance in 1688 37 2) Britain as a Balancer of Europe, 1700-1710 39 3) Military Reputation and the Flow of Credit, 1710-1710 40 2. Internationalization of the British Debt Market 41 1) Foreign Investments in Britain, 1700-1710 41 2) Fiscal Reputation and the Flow of Credit, 1700-1710 42 3. Chapter Summary 42 V. Anglo-French Rivalry and the British Credit, 1710-1720 44 1. Lowering the Cost of Debt 44 1) Interest Rate Flexibility and Creditor Confidence 44 2) Financial Innovations and the Low Interest Rate in France 46 3) The Tory Ministry and the Lowered Cost of Credit 47 2. The Grand Redemption Scheme 51 1) Deficit Reduction and State Credibility 51 2) The Mississippi Company and the Cheap Debt in France 52 3) South Sea Company and the Bargain for Private Ownership of Debt 53 3. Chapter Summary 58 VI. Conclusion 60 Figures 19 Figure II1. Total Revenue of France and England, 1660-1800 19 Figure III1. Military Spending Ratio of England, 1691-1760 30 Figure III2. Total Military Spending of the England, 1691-1760 31 Figure III3. Debt Charges of Great Britain, 1691-1750 34 Figure V1. Interest Paid to Bank of England, South Sea Company and East India Company, 1688-1750 51 Figure V2. Total Debt and Reimbursement of Britain, 1688-1740 57 Tables 16 Table II 1. Political Division over Issues 16 Table V 1. Public borrowing of English Government from 1708-1714 48 Table V 2. Private Sector Interest Rate on Public Borrowing, 1694-1750 49 Table V 3. Public borrowing of English Government from 1716-1720 55 Table V 4. Debt Charges of Britain 1716-1720 56 Appendix 62 Appendix 1. Total Revenue of England and France, 1680-1740 62 Appendix 2. Total Military Spending of England, 1691-1760 63 Appendix 3. Total Debt Charges in Britain, 1688-1750 66 Appendix 4 Interest Paid to the Private Sector, 1680-1740 69 Bibliography 70 국 문 초 록 77Maste

유전자 수준 변이 부담을 적용한 약물유전자와 질병유전자의 특성 분석

학위논문 (박사) -- 서울대학교 대학원 : 자연과학대학 협동과정 생물정보학전공, 2020. 8. 김주한.차세대 시퀀싱 기술이 발전함에 따라 전장 유전체에서의 변이 분포를 확인하는 것이 가능해졌다. 전통적인 단일 변이 기반 분석법은 드물게 발견되는 변이에 대한 통계적 파워가 떨어질 뿐만 아니라, 후보 변이가 발견되었다 하더라도 발견되는 모든 변이에 대해 그 기능적 중요도를 체계적으로 평가하기 어렵다는 점에서 변이와 표현형 간 연관 관계를 탐색하는데 한계가 있었다. 이러한 문제를 해결하기 위한 방법 중 하나로 특정 유전자 (혹은 영역)에서 발견된 변이들의 누적 효과를 통합하여 유전자 수준에서 표현형과의 연관 관계를 탐색하는 다양한 접근법이 제안되었다. 그 중, 통계 검정과 인구집단 수준의 유전자 점수는 접근 방법에는 차이가 있지만 유전자와 표현형 간 연관 관계를 탐색한다는 점에서 공통점이 있다. 반면, 유전자 수준의 변이 부담 점수 (GVB, Gene-wise Variant Burden score)는 주로 약물 유전체 분야에서 약물 부작용과의 연관성이 잘 정립된 유전자에서의 환자 개인에 대한 위험도를 예측하는 분석에서 다양하게 활용되었는데, 아직까지 그 유용성에 대해서 체계적으로 평가된 적이 없었다. 본 연구는 약물 유전체 분야 뿐만 아니라 희귀 질환, 복합 질환에서 GVB의 평가적, 탐색적 유용성을 평가하는 것을 목적으로 한다. 이를 위하여, 1000 지놈 프로젝트로 부터 얻은 2,504명의 건강한 사람의 전장 유전체 시퀀싱 데이터와 320명의 소아 백혈병 환자에 대한 엑솜 시퀀싱 데이터가 사용되었다. 모든 단백질 coding 유전자에 대하여, 각 유전자 내에서 발견된 변이의 위해도를 in silico 예측 점수를 통해 평가한 뒤, 유해하다고 판단되는 모든 변이의 효과를 통합하는 유전자 수준 변이 부담 점수를 계산하였다. 소아 급성 림프모구성 백혈병 환자의 6-mercaptopurine (6-MP) 약물 독성 예측에서 유전자 수준 변이 부담 점수의 임상성 유용성을 평가하기 위하여, 소아 백혈병 환자에서 6-MP 약물에 대한 예측 대비 실제 투약 비율 (DIP, dose intensity percentage)을 수집하였다. DIP를 임상적 종점 (clinical endpoint)으로 보고, 수신자 판단 특성 곡선 (Receiver operating characteristic (ROC) curve) 분석을 통해 유전자 수준 변이 부담 점수가 개인에 대한 약물 독성을 얼마나 잘 예측하는지 평가하였다. 민감도, 특이도, 양성 예측도, 음성 예측도, 그리고 정확도를 계산함으로써, 약물 유전체 분야에서 개인 약물 독성 예측에 사용되어온 가장 고전적인 방법인 스타 대립 유전자 기반의 하플로타이핑 방법론 (star allele-based haplotyping method)과 진단 정확도를 비교하였다. 더불어, 약물 부작용 이외에 희귀질환, 복합질환 등 다양한 유전 배경에서 유전자 수준 변이 부담 점수의 유용성을 평가하기 위하여, PharmGKB (The Pharmacogenomics Knowledge Base)와 DrugBank 데이터베이스로 부터 추출한 약물 유전자와 GAD (Genetic Association Database)로 부터 추출한 복합 질환 유전자, 그리고 OMIM (Online Mendelian Inheritance in Man)으로 부터 추출한 희귀질환 유전자를 사용하여 약물유전체 및 질병유전체에서의 유전자 수준 변이 부담 점수의 예측 성능을 평가하였다. 각 유전적 배경 (약물, 희귀, 복합 질환)에서 일곱개의 유전적 특성 (paralog와 singleton의 갯수, per-person mutability, CDS (coding sequence) 길이, PPI (protein-protein interaction) degree, 단백질 복잡도, 그리고 선택적 압력)의 분포 차이를 확인하고, 해당 특성을 반영하여 각 유전적 배경에 최적화 시킨 보정된 유전자 수준의 변이 부담 점수를 제안하였다. 추가로320명의 소아 백혈병 환자에 대한 엑솜 시퀀싱 데이터를 이용하여 NUDT15과 TPMT 이외에 치오퓨린 약물 독성과 연관을 보이는 새로운 유전자 마커를 탐색하고, GVB를 이용하여 새로운 유전자 마커의 단독 효과와 추가 효과를 평가하였다. 소아 백혈병 환자에서 유전자 수준의 변이 부담 점수를 활용한 6-MP 약물에 대한 독성 예측은 기존의 스타 대립 유전자 기반 분자 표현형 방법론과 비슷하거나 더 나은 결과를 보였다 (DIP ≤25 기준 AUCGVB=0.677, AUCstar-allele = 0.645). 유전자 수준 변이 부담 점수의 확장 가능성을 확인하기 위하여 다양한 유전 배경에서 그 성능을 평가해보면, 해당 점수는 약물 유전자 예측에 가장 효과적이었던 반면, 집단 수준의 점수를 제공하는 기존의 유전자 수준 방법론 (GDI, RVIS, 그리고 pLI)들은 희귀 질환 유전자 예측에 가장 효과적이어서 서로 상호 보완적인 역할을 한다는 것을 확인할 수 있었다. 특히 약물 유전자는 높은 paralog 갯수, 가장 낮은 PPI degree와 짧은 CDS 길이를 보였던 반면, 복합질환 유전자는 가장 적은 singleton 갯수, 높은 양성 선택과 per-person mutability, 희귀질환 유전자는 낮은 paralog 갯수와 가장 긴 CDS 길이, 높은 선택적 압력과 낮은 per-person mutability등, 유전적 배경 별로 매우 다른 분자 특성을 보였다. 특징적인 유전적 요소들의 효과를 반영했을 때, 유전자 수준 변이 부담 점수는 증가된 예측 성능을 보였다. 유전자 수준의 점수를 사용하여 새로운 바이오 마커인 CRIM1의 치오퓨린 독성 예측 성능을 평가한 결과, 기존에 잘 정립된 NUDT15과 TPMT에 추가적인 영향은 물론이고 독립적인 영향도 보이는 것으로 확인되었다. 결론적으로, 서로 다른 유전적 배경을 가지는 표현형에는 각 특성을 반영하는 서로 다른 접근법이 필요하며, 유전자 수준 변이 부담 점수는 특히 집단 수준의 점수가 아니라 개개인에 대한 점수를 따로 제공한다는 이점이 있기 때문에 약물에 대한 반응성 차이가 사람 간 유전적 다양성으로 설명되는 약물 유전체 분야에서 그 쓰임이 가장 높을 것으로 판단된다.The advent of next-generation sequencing technologies has empowered researchers with the ability to catalogue and predict the contribution of many different types of clinically relevant genetic variants. The traditional single variant-based analysis is limited since the rarity limits the statistical power of associating rare variants with phenotypes, requiring a large sample size. To alleviate this problem, gene-based (or region-based) approaches that aggregate the impact of multiple variants in a gene (or a region) have been proposed. The recently published Gene-wise Variant Burden (GVB) score, a score that integrates the overall deleterious impacts of multiple variants on a gene in an individual-specific manner, has been previously utilized in the field of pharmacogenetics, but the utility of the score has not been systematically evaluated. In this study, a comprehensive evaluation of the utility of GVB was performed in translating genotype information into phenotype across PGx, complex-disease, and Mendelian-disease genes. GVB scores were computed and assigned for protein-coding genes for each of the 2504 individual genomes from the 1000 Genomes Project (1KGP) and 320 pediatric acute lymphoblastic leukemia (ALL) patients. To assess the utility of GVB scoring method in quantifying the potential contributing effect of variants on enzymatic activity, we performed a comparison study of the conventional star allele-based haplotyping and GVB scoring methods for predicting the last cycle 6-mercaptopurine (6-MP) dose intensity percentage (DIP) as an indicator for 6-MP intolerance of ALL patients with NUDT15 and/or TPMT deficiency. DIP prediction accuracies of GVB and star allele-based predictions were compared using AUROC (Area Under the Receiver Operating Curve) analysis. To define high-risk DIP groups, specificity, sensitivity, PPV, and NPV was computed under the binary classification model with nine different cutoff levels (i.e., 5%, 10%, 15%, 25%, 35%, 45%, 60%, 80%, 100%). Furthermore, a comprehensive comparison of the accuracy of GVB with the accuracies of the RVIS and GDI was performed in predicting the wide variety of functional gene subcategories using receiver operating characteristics (ROC) curve analysis. Comprehensive genomic characterizations of PGx, complex-disease, and Mendelian-disease genes were performed using the following seven molecular genetic features: number of paralogs, number of singletons, per-person mutability, PPI degree, CDS length, McDonald-Kreitman neutrality index (NI), and protein complexity. A condition-specific score adjustment scheme that could augment the performance by leveraging the genetic knowledge about underlying genetic architectures was suggested. The computational GVB exhibited as an improved or at least comparable predictor than the empirical star allele-based haplotypes for determining subjects with increased risk of 6-MP intolerance in pediatric ALL patients measured by the last cycle 6-MP DIP (DIP ≤25 AUCGVB=0.677, AUCstar-allele = 0.645). The GVB score is considered to be a powerful gene-level scoring method for the prioritization of pharmacogenes, while the other gene-level scores performed best in prioritizing Mendelian-disease genes. A general outline of genetic condition-dependent analysis scheme, in which optimized strategies can be developed by applying the condition-specific patterns of molecular genetic features, was exhibited. In the exploratory analysis, GVB can be used as an evaluation method which can aggregate the functional variants impact identified in novel candidate genes. The traditional two-gene model (NUDT15 and TPMT) for predicting 6-MP DIP <25% was outperformed by the three-gene model that included CRIM1. Overall, the GVB score—as a fully individualized and quantitative gene-level scoring system—can improve the ability to prioritize clinically important PGx variants and to understand the genetic architectures of common complex diseases. The findings of the present study suggest that different strategies are necessary depending on different genetic backgrounds for improving personal-genome interpretations in the context of pharmacogenetics and common- and rare-disease phenotypes in the era of personal genomics.제1장 서론 15 1.1 통계 테스트 16 1.2 유전자 수준의 점수 기반 시스템 19 1.2.1 인구 집단 기반의 점수 시스템 19 1.2.2 개인화된 점수 시스템 21 1.3 유전자 수준 변이 부담 점수의 최적화 26 1.3.1 변이 수준 점수의 역치 최적화 26 1.3.2 변이 수준 점수 통합 방법 29 제 2장 소아급성 림프모구성 백혈병 환자의 6-MP 약물 독성 예측에서 유전자 수준 변이 부담 점수의 임상적 유용성 평가 31 2.1 연구배경 31 2.2 재료 및 방법론 34 2.2.1 환자군 설정과 임상 데이터 수집 34 2.2.2 유전자 단위의 변이 부담 점수 계산 36 2.2.3 스타 대립 유전자 추론 및 분자 표현형 변환 37 2.2.4 진단적 정확도 예측 38 2.3 결과 39 2.3.1 유전자 단위의 변이 부담 점수와 스타 대립 유전자 기반 방법론 간 연관성 39 2.3.2 유전자 단위의 변이 부담 점수와 스타 대립 유전자 기반 방법론 간 약물 독성 군 예측 성능의 비교 45 2.3.3 유전자 단위의 변이 부담 점수와 스타 대립 유전자 기반 방법론 간 약물 독성 군 예측 정확도의 비교 48 2.4 고찰 50 제 3장 유전자 수준의 변이 부담 점수: 약물, 복합질환, 그리고 희귀질환 연관 유전자에 대한 유전적 특성화 53 3.1 연구배경 53 3.2 재료 및 방법론 57 3.2.1 GVB 계산 57 3.2.2 포괄적인 유전 카테고리에 대한 유전자 목록 수집 58 3.2.3 유전자 특이적인 분자 유전적 특성 60 3.2.4 분자 유전 특성을 사용한 GVB 점수 보정 61 3.3 결과 62 3.3.1 GVB, RVIS, 그리고 GDI 점수의 특징 비교 62 3.3.2다양한 유전적 카테고리에서 GVB 의 예측 성능 평가 64 3.3.3약물, 복합질환, 희귀질환 유전자에 대한 유전적 특성화 71 3.3.4약물, 복합질환, 희귀질환 유전자의 유전적 조성 76 3.4 고찰 80 제 4장 NUDT15과 TPMT에 모두 변이를 가지고 있지 않은 소아 백혈병 환자에서 치오퓨린 연관 유전자의 탐색 88 4.1 연구배경 88 4.2 재료 및 방법론 90 4.2.1 환자군 90 4.2.2 엑솜 시퀀싱과 데이터 분석 91 4.2.3 단일- 그리고 다중 유전자를 사용한 치오퓨린 독성 예측 정확도 93 4.3 결과 94 4.3.1 환자군에 대한 설명 94 4.3.2 NUDT15과 TPMT 이외의 치오퓨린 독성 후보 유전자 97 4.3.3 CRIM1 변이와 치오퓨린 독성 간 연관성 평가 100 4.3.4치오퓨린 독성에 대한 NUDT15, TPMT, 그리고 CRIM1의 복합 유전자 효과 105 4.3.5 치오퓨린 독성에 대한 단일 유전자 효과 107 4.3.6 NUDT15, TPMT, 그리고 CRIM1의 예측 정확도 평가 110 4.4 고찰 116 제 5장 고찰 120 참고문헌 123 영문 초록 131Docto

한국의 수직적 해외투자모델은 지속 가능한가?

학위논문 (석사)-- 서울대학교 국제대학원 : 국제학과, 2015. 2. 안덕근.The aim of this thesis is to analyze the changing relationship between Korean outbound FDI and the intermediate exports over time. The earlier studies regarding the impact of FDI on the home country‟s exports have been determining if it is a substitute or a complement. Recent Korean studies generally confirmed the positive relation between FDI outflow and trade, characterizing Korean outbound FDI as 'vertical FDI'. However, these previous studies have not considered the fact that this effect cannot be fixed, and a transition from 'vertical FDI' to 'horizontal FDI' could appear if the circumstance changes. To complement this limitation, this paper examines whether the transition from 'vertical FDI' to 'horizontal FDI' happened or not in the Korean manufacturing sector over previous decade. First, how the correlation between 'Korean outbound FDI' and 'Korean intermediate exports' changes from 2001 to 2010 is analyzed.Afterward, how the factors like 'the host country market condition' and 'the investor's condition' affect the trend of this linkage is also examined. The 'least square model' analysis, using panel data from 40 countries and 14 manufacturing industries, show that the vertical specialization and the complementary impact of the outbound FDI have been intensified in the Korean manufacturing sector as a whole. However, in the industry-wise analysis, 11 among 14 industries have experienced the transition from 'vertical FDI' to 'horizontal FDI' while the FDI of 3 industries, taking 40% of the total outbound FDI on average, have displayed an opposite trend. As for the investor's size, the correlation between the outbound FDI of big investors and Korean intermediate exports has been weakened while the opposite has been seen in the small investors' cases. This empirical result implies that the transition from 'vertical FD' to 'horizontal FDI' generally happens in the analysis of industry dimension, and that it is also possible to sustain 'vertical FDI' depending on 'the success of effort to secure the comparative advantage in the high value stages' and 'the drastic increase of world demand for that industry's products'. Furthermore, it can be said that if this vertical FDI takes a majority portion in the whole FDI composition, it can make the whole outbound FDI trend in country level vertically specialized.ABSTRACT CHAPTER I. INTRODUCTION 1.1. Background 1.2. Recent Trends CHAPTER II. LITERATURE REVIEW 2.1. How to Define „Vertical FDI?‟ 2.2. What Happens in the linkage between the Outbound FDI and the Vertical Trade? 2.2.1. Theoretical Review 2.2.2. Empirical Review CHAPTER III. THE LINKAGE BETWEEN THE OUTBOUND FDI & THE VERTICAL TRADE 3.1. Research Question and Hypothesis 3.2. Methodology 3.2.1. Basic Regression Equation 3.2.2. Regression Equations about the Factors Affecting the Linkage 3.2.3. Overall Variables CHAPTER IV. Empirical Analysis & Finding 4.1. The Linkage between the Outbound FDI and the Vertical Trade 4.2. The Factors Affecting the Linkage CHAPTER V. CONCLUSION BIBLOGRAPHY KOREAN ABSTRACTMaste

Prevalence of and Risk Factors for Diseases in Korean Americans and Native Koreans Undergoing Health Checkup

BACKGROUND: Korean Americans constitute the fifth largest subgroup in the Asian American population. Despite their increasing population, research and guidelines regarding their health status assessment and disease screening are lacking. This study aimed to compare the prevalence of diseases in Korean Americans and native Koreans to determine the risk factors and guidelines for disease screening. METHODS: Patients who visited the Gangnam Severance Hospital from February 2010 to May 2015 for a health checkup were enrolled in this study. Baseline characteristics, laboratory data, and the organs (stomach, colon, thyroid, brain, prostate, lung, liver, kidney, pancreas, adrenal gland, and heart) of patients were examined. Data regarding patients' dietary patterns were also obtained. Overall, 1,514 Korean Americans (group 1) and 1,514 native Koreans (group 2) were enrolled. RESULTS: The following diseases were more prevalent in group 1 than in group 2: reflux esophagitis (12.9% vs. 10%), gastric ulcer (3.0% vs. 5.5%), colorectal polyp (37.7% vs. 28.7%), hemorrhoids (32.2% vs. 29.9%), and benign prostatic hyperplasia (30.2% vs. 14.3%). Although not statistically significant, coronary artery disease has a high prevalence rate of >20% in both groups. Dietary patterns were not significant between the two groups. CONCLUSION: This study showed that the prevalence of several diseases in Korean Americans differed from that observed in native Koreans. Therefore, a foundation for setting up new guidelines for disease screening among Korean Americans is established.ope

Predictive factors for inadequate bowel preparation using low-volume polyethylene glycol (PEG) plus ascorbic acid for an outpatient colonoscopy

Low-volume polyethylene glycol (PEG) plus ascorbic acid solutions are widely used for bowel cleansing before colonoscopy. This study aimed to investigate the pre-endoscopic predictive factors for inadequate preparation in subjects receiving low-volume PEG plus ascorbic acid. A prospective study was performed at Gangnam Severance Hospital, Korea, from June 2016 to December 2016. All participants received low-volume PEG plus ascorbic acid solutions for outpatient colonoscopy. The split-dose bowel preparation was administered in subject with morning colonoscopy while same day bowel preparation was used for afternoon colonoscopy. 715 patients were enrolled (mean age 56.1 years, 54.4% male), of which 138 (19.3%) had an inadequate bowel preparation. In multivariable analysis, cirrhosis (OR 4.943, 95% CI 1.191-20.515), low (less than 70%) compliance for three-day low-residual diet (OR 2.165, 95% CI 1.333-3.515), brown liquid rectal effluent (compared with clear or semi-clear effluent) (OR 7.604, 95% CI, 1.760-32.857), and longer time interval (>= 2 hours) between last defecation and colonoscopic examination (OR 1.841, 95% CI, 1.190-2.849) were found as an independent predictors for inadequate preparation. These predictive factors may be useful in guiding additional intervention to improve quality of bowel preparation.ope

Effects of Ramosetron on Gastrointestinal Transit of Guinea Pig

Background/Aims A selective 5-hydroxytryptamine (5-HT) type 3 receptor antagonist, ramosetron, inhibits stress-induced abnormal defecation in animals and is currently used as a therapeutic drug for irritable bowel syndrome with diarrhea. The aim of this study is to investigate the effect of ramosetron on altered gastrointestinal (GI) transit. Methods Male guinea pigs weighing approximately 300 g were used. The effect of ramosetron was investigated on altered GI transit induced by thyrotropin-releasing hormone (TRH), 5-HT, or mustard oil (MO). GI transit was evaluated by the migration of charcoal mixture from the pylorus to the most distal point, and expressed as a percentage (%) of charcoal migration (cm) of the total length of total small intestine (cm). Results The average charcoal transit was 51.3 ± 20.1% in the control (vehicle) group, whereas in the ramosetron group charcoal moved 56.6 ± 21.9%, 46.9 ± 9.14% and 8.4 ± 5.6% of the total small intestine at the concentrations of 10, 30 and 100 ?g/kg, respectively. GI transit after administration of TRH (100 ?g/kg), 5-HT (10 mg/kg) or MO (10 mg/kg) was accelerated compared to vehicle (5-HT, 94.9 ± 9.22%; TRH, 73.4 ± 14.7%; MO, 81.0 ± 13.7%). Ramosetron inhibited GI transit altered by 5-HT, TRH or MO. Conclusions Ramosetron modulated GI transit. We suggest that ramosetron may be therapeutically useful for those with accelerated upper GI transit.ope

The Multifaceted Effects of Agmatine on Functional Recovery after Spinal Cord Injury through Modulations of BMP-2/4/7 Expressions in Neurons and Glial Cells

Presently, few treatments for spinal cord injury (SCI) are available and none have facilitated neural regeneration and/or significant functional improvement. Agmatine (Agm), a guanidinium compound formed from decarboxylation of L-arginine by arginine decarboxylase, is a neurotransmitter/neuromodulator and been reported to exert neuroprotective effects in central nervous system injury models including SCI. The purpose of this study was to demonstrate the multifaceted effects of Agm on functional recovery and remyelinating events following SCI. Compression SCI in mice was produced by placing a 15 g/mm2 weight for 1 min at thoracic vertebra (Th) 9 segment. Mice that received an intraperitoneal (i.p.) injection of Agm (100 mg/kg/day) within 1 hour after SCI until 35 days showed improvement in locomotor recovery and bladder function. Emphasis was made on the analysis of remyelination events, neuronal cell preservation and ablation of glial scar area following SCI. Agm treatment significantly inhibited the demyelination events, neuronal loss and glial scar around the lesion site. In light of recent findings that expressions of bone morphogenetic proteins (BMPs) are modulated in the neuronal and glial cell population after SCI, we hypothesized whether Agm could modulate BMP- 2/4/7 expressions in neurons, astrocytes, oligodendrocytes and play key role in promoting the neuronal and glial cell survival in the injured spinal cord. The results from computer assisted stereological toolbox analysis (CAST) demonstrate that Agm treatment dramatically increased BMP- 2/7 expressions in neurons and oligodendrocytes. On the other hand, BMP- 4 expressions were significantly decreased in astrocytes and oligodendrocytes around the lesion site. Together, our results reveal that Agm treatment improved neurological and histological outcomes, induced oligodendrogenesis, protected neurons, and decreased glial scar formation through modulating the BMP- 2/4/7 expressions following SCI.ope

Synephrine-containing dietary supplement precipitating apical ballooning syndrome in a young female

Apical ballooning syndrome (ABS) is a unique reversible cardiomyopathy that is frequently precipitated by emotional or physical stress. In addition, the few drugs reported to precipitate ABS were either illegal or strictly controlled for medical use. This paper reports a case of ABS precipitated by a dietary supplement. Our case accentuates the potential risk of dietary supplements containing synephrine, which is uncontrolled and available to the general public. Therefore, the Korea Food and Drug Administration should regulate these dietary supplements, and warn healthcare workers and the general public of the potential hazards of the indiscriminate abuse of dietary supplements.ope

A simple scoring model for advanced colorectal neoplasm in asymptomatic subjects aged 40-49 years

BACKGROUND: Limited data are available for advanced colorectal neoplasm in asymptomatic individuals aged 40-49 years. We aimed to identify risk factors and develop a simple prediction model for advanced colorectal neoplasm in these persons. METHODS: Clinical data were collected on 2781 asymptomatic subjects aged 40-49 years who underwent colonoscopy for routine health examination. Subjects were randomly allocated to a development or validation set. Logistic regression analysis was used to determine predictors of advanced colorectal neoplasm. RESULTS: The prevalence of overall and advanced colorectal neoplasm was 20.2 and 2.5% respectively. Older age (45-49 years), male sex, positive serology of Helicobacter pylori, and high triglyceride and low high-density lipoprotein (HDL) levels were independently associated with an increased risk of advanced colorectal neoplasm. BMI (body mass index) was not significant in multivariable analysis. We developed a simple scoring model for advanced colorectal neoplasm (range 0-9). A cutoff of ≥4 defined 43% of subjects as high risk for advanced colorectal neoplasm (sensitivity, 79%; specificity, 58%; area under the receiver operating curve = 0.72) in the validation datasets. CONCLUSION: Older age (45-49 years), male sex, positive serology of H. pylori, high triglyceride level, and low HDL level were identified as independent risk factors for advanced colorectal neoplasm.ope

Advanced Colonic Neoplasia at Follow-up Colonoscopy According to Risk Components and Adenoma Location at Index Colonoscopy: A Retrospective Study of 1,974 Asymptomatic Koreans

Background/Aims: We aimed to estimate the cumulative incidence of advanced colonic neoplasia and analyze the risk factors for advanced colonic neoplasia according to risk components and adenoma location at index colonoscopy. Methods: We reviewed 1,974 subjects who underwent a follow-up colonoscopy after a complete screening colonoscopy and the removal of all polyps. We estimated the cumulative incidence of a subsequent advanced neoplasia according to risk groups (normal, low-risk, and high-risk). Risk factors were analyzed by risk components (≥3 adenomas, adenoma ≥1 cm, and villous-type adenoma) and adenoma location. Results: Overall, 111 advanced neoplasias (5.6%) were newly diagnosed at the follow-up colonoscopy. The 3-year cumulative incidences of advanced neoplasia were 0.8%, 3.1%, and 10.2% in the normal, low-risk, and high-risk groups, respectively (p<0.0001), and the 5-year cumulative incidences were 2.2%, 8.6%, and 20.2%, respectively (p<0.0001). Age ≥60 years (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.21 to 2.63), right-sided colonic adenoma (HR, 1.74; 95% CI, 1.13 to 2.66), ≥3 adenomas (HR, 2.00; 95% CI, 1.22 to 3.28), and adenomas ≥1 cm in size (HR, 2.03; 95% CI, 1.20 to 3.44) in the index colonoscopy were independent risk factors for subsequent development of advanced neoplasia. Conclusions: Right-sided colonic adenoma, ≥3 adenomas, adenomas ≥1 cm, and age ≥60 years at the index colonoscopy were significant risk factors for advanced neoplasia following a complete screening colonoscopy and removal of all polyps.ope