Microsatellite scanning of the immunogenome for associations with graft-versus-host disease following haematopoietic stem cell transplantation

PhD ThesisNon-HLA gene polymorphisms contribute to the immune response, leading to complications of haematopoietic stem cell transplantation (HSCT). A systematic approach using 4,321 microsatellite (MS) markers typing for 2,909 immune response genes (‘immunogenome’) on pooled DNA of 922 Japanese donors and recipients of HSCT was used to identify recipient and donor risk loci for graft-versus-host disease (GVHD). Splitting the population into discovery and confirmation cohorts (460/462 pairs), DNA pools were created for a 2-step pooled DNA screening. Fisher’s exact test for 2x2 (each MS allele) and 2xm Chi Square tests were performed, comparing allele frequencies of recipient/donor pools with GVHD grade 0-1 with those of GVHD grade 2-4. The independent, 2-step pooled DNA screening process has effectively reduced false-positive associations. In the final pooled DNA analysis, 17 (recipient) and 31 (donor) MS loci remained associated with risk or protection from GVHD and were further investigated by individual genotyping in the combined cohorts. Ten of these loci were confirmed to have consistent associations with GVHD; of these, two associations remained when applying multiple testing correction and multivariate statistics: D6S0035i (MAPK14, p=0.00035, OR=0.68) and D1S0818i (ELTD1, p=0.000078, OR=1.52). These findings implicate important new immunoregulatory genes with the process of moderate to severe acute GVHD. These data show that genetic susceptibility to GVHD following HSCT is complex and depends on multiple recipient and donor risk loci. Large-scale genomic screening with microsatellites on pooled DNA, here described for the first time in a HSCT population, is a useful method for the systematic evaluation of multigeneic traits.Research on Allergic Disease and Immunology (Health and Labor Science Research Grant H20-014, H23- 010), the Ministry of Health, Labor, and Welfare of Japan, through JMDP. Post-doctoral Fellowship from the Japan Society for Promotion of Science (JSPS), International Fellowship from the Kay Kendall Leukaemia Fund UK (KKLF) (grants No 291,297),The Great Britain Sasakawa Foundation (GBSF) Butterfield Award, Daiwa Anglo-Japanese Foundation

Epidemiology of intracranial stenosis in asymptomatic Asian subjects.

Tang, Suk Yan Amy.Thesis (M.Phil.)--Chinese University of Hong Kong, 2001.Includes bibliographical references (leaves [207]-[227]).Abstracts in English and Chinese.ACKNOWLEDGEMENTSABSTRACTSTABLE OF CONTENTS"LIST OF APPENDIX, TABLES & FIGURES"Chapter CHAPTER ONE --- INTRODUCTION --- p.1Chapter 1.1 --- Cerebrovascular disease --- p.1Chapter 1.1.1 --- Ischemic Stroke --- p.1Chapter 1.1.2 --- Hemorrhagic Stroke --- p.2Chapter 1.2 --- Laboratory diagnosis --- p.3Chapter 1.2.1 --- Transcranial Doppler ultrasonography --- p.4Chapter 1.2.1.1 --- Normal Brain --- p.4Chapter 1.2.1.2 --- Intracranial Large Artery Stenosis --- p.5Chapter 1.3 --- Asymptomatic Intracranial Stenosis --- p.6Chapter CHAPTER TWO --- LITERATURE REVIEW --- p.7Chapter 2.1 --- Global Stroke Facts --- p.7Chapter 2.2 --- Stroke Studies --- p.7Chapter 2.2.1 --- Risk profile of stroke --- p.7Chapter 2.2.2 --- Stroke epidemiological study --- p.8Chapter 2.2.2.1 --- Incidence --- p.8Chapter 2.2.2.2 --- Mortality --- p.10Chapter 2.2.2.3 --- Increased stroke rates with increased age --- p.12Chapter 2.2.2.4 --- Associated disease in stroke subjects --- p.12Chapter 2.2.3 --- Stroke risk factors --- p.13Chapter 2.3 --- Stroke Impact --- p.14Chapter 2.3.1 --- Stroke patients --- p.14Chapter 2.3.2 --- Medical burden --- p.15Chapter 2.3.3 --- Socioeconomic burden --- p.16Chapter 2.4 --- Stroke Prevention --- p.17Chapter 2.5 --- Stroke Facts in Hong Kong --- p.19Chapter 2.6 --- Stroke Facts in China --- p.21Chapter 2.7 --- Asymptomatic Intracranial Stenosis in Asian Subjects --- p.22Chapter 2.7.1 --- Asymptomatic individuals --- p.22Chapter 2.7.2 --- Intracranial occlusive disease --- p.23Chapter 2.8 --- Transcranial Doppler Sonography --- p.25Chapter CHAPTER THREE --- AIM & OBJECTIVES OF THE RESEARCH --- p.30Chapter 3.1 --- Aim of the research --- p.30Chapter 3.2 --- Objectives of this research --- p.30Chapter CHAPTER FOUR --- "CLINIC-BASED CROSS-SECTIONAL SCREENING IN AN URBAN CITY 226}0ؤ HONG KONG, THE PEOPLE'S REPUBLIC OF CHINA" --- p.31Chapter 4.1 --- Background & Purpose --- p.31Chapter 4.2 --- Methods --- p.34Chapter 4.2.1 --- Defining the population --- p.34Chapter 4.2.2 --- Procedures --- p.36Chapter 4.2.2.1 --- Standardized TCD Report Form --- p.39Chapter 4.2.2.2 --- Transcranial Doppler Screening --- p.39Chapter 4.2.2.3 --- Data collected --- p.40Chapter 4.2.3 --- Defining the Risk Factors --- p.43Chapter 4.3 --- Statistical Analyses --- p.45Chapter 4.3.1 --- Research Design --- p.46Chapter 4.3.2 --- Descriptive Summary --- p.46Chapter 4.3.2.1 --- Cross-tabulated between Gender --- p.46Chapter 4.3.2.2 --- Cross-tabulated between Normal & Abnormal MCA status --- p.47Chapter 4.3.3 --- Measures for Association --- p.48Chapter 4.3.3.1 --- Univariate analysis --- p.48Chapter 4.3.3.2 --- Multivariate analysis --- p.48Chapter 4.3.4 --- Modeling the Risks --- p.50Chapter 4.3.5 --- nfluence of the number of associated risk factors on the MCA status --- p.50Chapter 4.4 --- Result --- p.51Chapter 4.4.1 --- Baseline characteristics of all screened subjects by Gender --- p.51Chapter 4.4.1.1 --- Age by Gender --- p.53Chapter 4.4.1.2 --- "Medical History of HT, DM, Hyperlipidemia, IHD, Retinopathy and Albuminuria by Gender" --- p.55Chapter 4.4.1.3 --- Social habit in Smoking by Gender --- p.56Chapter 4.4.1.4 --- Body Mass Index and Waist-to-Hip Ratio by Gender --- p.57Chapter 4.4.2 --- Diseased Middle Cerebral Artery --- p.61Chapter 4.4.3 --- Characteristics between subjects with Normal TCD result and Abnormal TCD result in the MCA status --- p.62Chapter 4.4.3.1 --- Age --- p.64Chapter 4.4.3.2 --- Gender --- p.67Chapter 4.4.3.3 --- "Medical History of HT, DM, Hyperlipidemia, IHD, Retinopathy and Albuminuria" --- p.67Chapter 4.4.3.4 --- Social habit in cigarette smoking --- p.68Chapter 4.4.3.5 --- Body Mass Index and Waist-to-Hip Ratio --- p.71Chapter 4.4.3.6 --- "Other Measurements - on Blood Pressure, Fasting Plasma Glucose, HbAlc, Lipid profiles and Fibrinogen" --- p.79Chapter 4.4.4 --- Unadjusted Odds Ratio --- p.84Chapter 4.4.4.1 --- By contingency table method --- p.84Chapter 4.4.4.2 --- By logistic regression model --- p.86Chapter 4.4.5 --- Adjusted Odds Ratio --- p.92Chapter 4.4.5.1 --- Entering all explanatory variables: --- p.92Chapter 4.4.5.2 --- Using Forward and Backward Stepwise methods with the probability for entry of 0.05 and probability for removal of 0.10: --- p.95Chapter 4.4.5.3 --- Applying the Model-Building Strategy: --- p.100Chapter 4.4.6 --- Comparing the final fitted multiple logistic regression models made by the three approaches ： --- p.103Chapter 4.4.7 --- Probability and Odds derived from the logistic regression model --- p.110Chapter 4.4.8 --- Relationship between the diseased MCA and the number of significant risk indicators that the subjects associated with..… --- p.112Chapter 4.4.8.1 --- Logistic regression analysis on number of risk indicators associated with the MCA status --- p.115Chapter 4.5 --- Discussion --- p.118Chapter 4.5.1 --- Research Design --- p.118Chapter 4.5.1.1 --- Advantage --- p.118Chapter 4.5.1.2 --- Disadvantage --- p.118Chapter 4.5.2 --- Sampling --- p.119Chapter 4.5.3 --- Data collected and Outcome variable classified --- p.119Chapter 4.5.3.1 --- Medical Record - Patients Characteristics --- p.119Chapter 4.5.3.2 --- Transcranial Doppler - Middle Cerebral Artery status --- p.120Chapter 4.5.4 --- Statistical Analyses --- p.121Chapter 4.5.4.1 --- Odds Ratio --- p.121Chapter 4.5.4.2 --- Logistic Regression Model --- p.122Chapter 4.5.4.3 --- Sources of Error --- p.123Chapter 4.5.5 --- Result --- p.125Chapter 4.5.5.1 --- Prevalence --- p.125Chapter 4.5.5.2 --- Risk indicators --- p.126Chapter CHAPTER FIVE --- "POPULATION-BASED CROSS-SECTIONAL SURVEY IN A RURAL VILLAGE OF HENAN, PEOPLE'S REPUBLIC OF CHINA" --- p.134Chapter 5.1 --- Background & Purpose --- p.134Chapter 5.2 --- Methods --- p.135Chapter 5.2.1 --- Defining the Population --- p.135Chapter 5.2.2 --- Procedures --- p.135Chapter 5.2.2.1 --- Standardized Screening Form --- p.136Chapter 5.2.2.2 --- Transcranial Doppler Examination --- p.137Chapter 5.2.3 --- Defining the Risk Factors --- p.137Chapter 5.3 --- Statistical Analyses --- p.140Chapter 5.3.1 --- Research Design --- p.141Chapter 5.3.2 --- Descriptive Summary --- p.141Chapter 5.3.2.1 --- Cross-tabulated between Gender --- p.141Chapter 5.3.2.2 --- Cross-tabulated between With & Without intracranial large artery stenosis --- p.142Chapter 5.3.3 --- Measures for Association --- p.143Chapter 5.3.3.1 --- Univariate analysis --- p.143Chapter 5.3.3.2 --- Multivariate analysis --- p.143Chapter 5.3.4 --- Modeling the Risks --- p.144Chapter 5.3.5 --- Influence of the number of associated risk factors on the prevalence of intracranial large artery stenosis --- p.144Chapter 5.4 --- Result --- p.145Chapter 5.4.1 --- Baseline characteristics of all examined villagers by Gender --- p.145Chapter 5.4.1.1 --- Age by Gender --- p.147Chapter 5.4.1.2 --- "Medical History of HT, DM and Heart disease by Gender" --- p.149Chapter 5.4.1.3 --- Social habit in Cigarette smoking and Alcoholic drinking by Gender --- p.149Chapter 5.4.1.4 --- "Family History of HT, DM, Stroke and Heart disease by Gender" --- p.149Chapter 5.4.1.5 --- Body Mass Index and Waist-to-Hip Ratio by Gender --- p.150Chapter 5.4.2 --- Distribution of the Diseased intracranial artery --- p.154Chapter 5.4.3 --- Characteristics between subjects with and without intracranial large artery stenosis --- p.155Chapter 5.4.3.1 --- Age --- p.157Chapter 5.4.3.2 --- Gender --- p.158Chapter 5.4.3.3 --- "Medical History of HT, DM and Heart disease" --- p.158Chapter 5.4.3.4 --- Social habit in cigarette smoking and alcohol drinking --- p.158Chapter 5.4.3.5 --- "Family History of HT, DM, Stroke and Heart Disease" --- p.159Chapter 5.4.3.6 --- Body Mass Index and Waist-to-Hip Ratio --- p.160Chapter 5.4.3.7 --- Other Measurements - on BP and Urine Glucose --- p.163Chapter 5.4.4 --- Unadjusted Odds Ratio --- p.165Chapter 5.4.4.1 --- By contingency table method --- p.165Chapter 5.4.4.2 --- By logistic regression model --- p.166Chapter 5.4.5 --- Adjusted Odds Ratio --- p.172Chapter 5.4.5.1 --- Entering all explanatory variables: --- p.172Chapter 5.4.5.2 --- Using the Stepwise methods available with the probability for entry is 0.05 and 0.10 for removal: --- p.175Chapter 5.4.5.3 --- Applying the Model-Building Strategy: --- p.180Chapter 5.4.6 --- Comparing the final multiple logistic regression models by the three approaches： --- p.182Chapter 5.4.7 --- Probability and Odds derived from the logistic regression model --- p.189Chapter 5.4.8 --- Relationship between the transcranial Doppler result on Intracranial large artery and the number of significant risk indicators that the subjects associated with --- p.190Chapter 5.4.8.1 --- Logistic Regression Model --- p.192Chapter 5.5 --- Discussion --- p.196Chapter 5.5.1 --- Research Design --- p.196Chapter 5.5.1.1 --- Advantage --- p.196Chapter 5.5.1.2 --- Disadvantage --- p.196Chapter 5.5.2 --- Sampling --- p.197Chapter 5.5.3 --- Data collected and the Outcome variable classified --- p.197Chapter 5.5.3.1 --- Self-Reported - Subjects Characteristics --- p.197Chapter 5.5.3.2 --- Transcranial Doppler - Intracranial Large Artery status --- p.198Chapter 5.5.4 --- Statistical Methods --- p.199Chapter 5.5.4.1 --- Odds Ratio --- p.199Chapter 5.5.4.2 --- Logistic Regression --- p.199Chapter 5.5.4.3 --- Sources of Error --- p.199Chapter 5.5.5 --- Result --- p.200Chapter 5.5.5.1 --- Prevalence --- p.200Chapter 5.5.5.2 --- Risk Indicators --- p.201Chapter CHAPTER SIX --- CONCLUSION --- p.204Chapter 6.1 --- The Clinic-based study of diseased middle cerebral artery among asymptomatic hong kong chinese --- p.204Chapter 6.2 --- The Population-base study of intracranial large artery stenosis among mid-aged & above chinese in rural china --- p.205REFERENCESAPPENDIXAppendix I Neuroimaging - Transcranial Doppler UltrasonographyAppendix II Statistical Methods"Appendix III (a) Standardized TCD report form used in PWH, Hong Kong (b) Standardized Screening Form used In Yuzhou, China"Appendix IV The ICD 9th Revision - Disease of the Circulatory System"Appendix V Prospective Hospital-Based study in Asia, AASAP (a) Standardized Data Collection From used in AASAP"Appendix VI Contributed in published paper

Dynamic group decision making

A common theme running throughout the three chapters of this thesis is dynamic recurring group decision making. The first chapter sets up a model with endogenous status-quo (dynamic bargaining model) in which decision makers are uncertain about their own future preferences. The main focus of the chapter is on how different bargaining protocols influence equilibrium decisions. The two protocols considered are i) implicit status-quo bargaining protocol in which present period policy serves as the status-quo for the next period and ii) explicit status-quo bargaining protocol in which the current decision involves both current policy and a possibly different status-quo for the future. The main observation of the chapter is that the former bargaining protocol leads to decisions diverging from the preferences of the actors involved even in the periods in which their preferences coincide, this divergence being driven by the concerns to maintain a bargaining position for the future. The latter bargaining protocol, on the other hand, delivers decisions fully reflecting preferences of the actors involved in the periods when these coincide, but may lead to decisions re ecting only the proposer's preferences. The second chapter shows how to construct equilibria in a class of dy-namic bargaining models in which players have fixed preferences over all the dimensions of a policy space. The construction applies both to one-dimensional and multi-dimensional policy spaces and delivers equilibria with simple and intuitive structure. The chapter works out several examples to show i) the multiplicity of equilibria and ii) the non-monotonicity of the existence of the simple equilibria in the underlying model parameters. The third paper is a collaborative work with Roman Horvath and Katerina Smidkova from the Czech National Bank currently published as a CNB working paper). The chapter analyses decision making in monetary policy committees, the decision making bodies of central banks. On the empirical side, the chapter shows that voting records of monetary policy committees are informative about their own future decisions. On the theoretical side, the chapter shows that the voting records' predictive power can be generated through theoretical models used in the group decision making literature

Reflection traveltime tomography and the maximum entropy principle

Conventional reflection tomography creates an estimate of subsurface seismic velocity structure by inverting a set of seismic traveltime data. This is achieved by solving a least-squares optimisation problem that finds the velocity and depth model that minimises the difference between raytraced and measured traveltimes. Obtaining the traveltime data can be difficult as manual picking of reflection times is required and all picked reflection events must be associated with the reflector depths defined in the model. Even with good traveltime data the optimisation problem is very non-linear and the surface restriction of the sources and receivers makes the problem generally underdetermined. These issues result in severe ambiguity and local minima problems. This thesis shows that modifications to the conventional reflection tomography algorithm can make it a more practical and reliable procedure that is less likely to be trapped by local minima. The ray tracing procedure is changed so that reflector depths are not necessary and automatic traveltime interpretation can be successful. Entropy constraints are introduced (after being justified) which prevent unwarranted velocity structure from appearing. This feature adds significant stability and reduces the ambiguity problems. Staged smoothing of the optimisation function helps avoid local minima. Synthetic data examples show that the algorithm can be very effective on noise free data. Adding noise to synthetic data reduces the algorithms effectiveness, but inversions of real data sets produces updated velocity fields that result in superior pre-stack depth migrations

A conceptual plan for the provision of reception facilities in the Philippines

This dissertation synthesizes a conceptual plan for the provision of reception facilities to improve marine environmental protection in the Philippines. The study is premised on the perception that the various pollution control measures formulated by the Philippine Coast Guard, which are mandated to address ship source pollution, are not being implemented due to the absence or severe inadequacy of the needed reception facilities in ports. The extent of maritime activities is presented while the various legislation, rules and regulations adopted by the Government concerning marine environmental protection in general, and the provision of reception facilities in particular, are examined. In the same manner, existing operations of port reception facilities and waste management practice in the Philippines are also examined. The operational modalities of reception facilities of selected countries are considered and evaluated for their adaptability within the Philippine setting and especially the particular aspect of financing and cost recovery which is considered a critical issue.‘ With the foregoing, strategic considerations were formulated for the provision of reception facilities that should be initiated by the Philippine authorities in participation with the private sector. The concluding chapter summarizes the necessary approaches for the provision of reception facilities, which has been considered an important complimentary provision of MARPOL 73/78, in the Philippine setting. It is hoped that the plan will guide and influence concerned authorities and private enterprises to achieve total marine environmental protection, parallel with the IMO’s objective of “Safer Ships and Cleaner_Oceans”

Unbalanced manual flow line operating characteristics.

This thesis studies the operating behaviour of the manual unpaced lines, which are the most important of the flow lines' systems. The lines examined are unbalanced and six types of imbalance are considered, namely, the imbalances of mean service times, coefficients of variation (Covars), buffers'capacities, means and Covars, means and buffers, and Covars and buffers. It is argued that the deep understanding of the behavioural characteristics of such lines, contributes towards the achievement of practical solutions to many of their problems. The lines are simulated under both steady and non-steady states conditions, with positively skewed weibull work times distributions, different values of line length (N), buffer capacity (B), degree of imbalance (DI), and pattern of imbalance, utilizing full factorial designs.The data are subjected to the analysis of variance, multiple regression, multiple comparisons with control, pairwise comparisons, canonical correlation, and utilitv analysis A simple utility approach is also explored briefly.Some of the important conclusions for all the unbalanced lines' investigations are:(1) At least one unbalanced pattern generates superior idle time (I) and/or mean buffer level (ABL), over those of a balanced line. The superiority in I decreases as DI rises, whereas the advantage in ABL reduces as DI is decreased.(2) The DI of the best unbalanced pattern can substantially or moderately be increased and still yields approximately equal I to that of a balanced configuration.(3) If a line is unbalanced in the wrong direction, significantly inferior performance to that of a balanced design will result.(4) The unbalanced patterns' I tends to decrease, when N and DI reduce and B increases, while ABL falls directly with B.(5) The I's transient size increases as N and B become higher and DI increases, while the ABL's transient size rises whenever B reduces

Current Topics on Risk Analysis: ICRA6 and RISK2015 Conference

Peer ReviewedPostprint (published version