Shen, Jiayun. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 166-199). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

1997年，胎兒DNA被首次證實存在於母體血漿中。這一發現促進了無創產前診斷技術的發展。由於孕婦血漿中含大量來自母體的背景DNA，這給針對胎兒特異性DNA序列以外的產前診斷變得有挑戰性。近期開發的大規模平行測序技術把DNA定量精度提升到了一個空前的水平。本團隊已證實這一技術可應用於對胎兒染色體非整倍體和對胎兒全基因組的檢測。由於目前平行測序的費用仍相當昂貴，目標性測序技術可提高目標區域的數據比例從而降低測序成本。 / 在論文第一部分，本人論述了目標性測序在母體血漿DNA應用的可行性。本實驗採用雜交型富集技術對X染色體的外顯子進行富集。我們用平行測序比較了經由和未經富集處理的樣本。對比發現，經富集處理的樣本在目標區域的平均測序深度是未經富集處理樣本的213倍。目標區域的母體和胎兒DNA分子的富集程度相當。經富集處理後，目標區域的胎兒特異性等位基因的檢測率從3.5%提升至95.9%。 / 在論文第二部分，本人論述了目標性測序對胎兒21三體無創產前診斷的應用價值。我們對7，13，18和21號染色體上的單核苷酸多態性位點進行目標性測序。目標性測序數據顯示，在父源性21三體的樣本中，21號染色體上的胎兒特異性等位基因與共有性等位基因的比值上升約2倍。而在母源性21三體的樣本中，這一比值則下降約11%。本人採用電腦模擬實驗探討胎兒DNA濃度，有效等位基因數量和測序深度對檢測準確率的影響。 / 在論文第三部分，本人論述了目標性測序對胎兒單基因疾病無創產前診斷的應用。針對兩個需進行β地中海貧血產前診斷的家庭，我們對其β球蛋白基因進行目標性測序。我們用數字PCR技術推導了父母親β球蛋白基因區域的單倍型。經過相對性單倍型劑量分析，兩個胎兒的β地中海貧血遺傳狀況均得到了正確的推斷。其中一對夫婦位於致病區域的單倍型結構相近。 / 鑒於目標性測序技術可降低測序成本和提高目標序列的通量，其在血漿DNA的應用將有助於平行測序技術在無創性產前診斷、癌症診斷和移植監控等分子診斷學領域的發展。 / The presence of fetal DNA in the cell-free plasma of pregnant women was first reported in 1997. This discovery has facilitated the development of noninvasive prenatal diagnosis. The coexistence in maternal plasma of a minor population of fetal DNA among a major background of maternal DNA has posed challenges for extending noninvasive prenatal diagnostic applications that require analytical information beyond the detection of fetus-specific DNA sequences. The recent availability of massively parallel sequencing has enhanced the precision of DNA quantification to an unprecedented level. Our group has demonstrated the application of massively parallel sequencing in noninvasive prenatal diagnosis of chromosomal aneuploidies, as well as genome-wide fetal whole genome sequencing and mutational profiling. While the current costs of massively parallel sequencing are relatively expensive, targeted massively parallel sequencing may enhance the cost-effectiveness compared with the non-targeted approach because it increases the proportion of informative data from the regions-of-interest. / In the first part of this thesis, I have demonstrated the feasibility of targeted massively parallel sequencing in maternal plasma DNA. In this proof-of-principle study, hybridization-based target enrichment was used to enrich exons on chromosome X. Plasma DNA libraries with and without target enrichment were analyzed by massively parallel sequencing. For the targeted regions, the mean sequencing depth of the enriched samples was 213-fold higher than that of the non-enriched samples. Maternal and fetal DNA molecules were enriched to similar extents within the targeted regions. With target enrichment, the detection rate of fetus-specific alleles within the targeted regions increased from 3.5% to 95.9%. / In the second part of this thesis, I have demonstrated the potential application of targeted massively parallel sequencing of plasma DNA for noninvasive prenatal diagnosis of trisomy 21 using an allelic ratio approach. Targeted sequencing was used to enrich single nucleotide polymorphism loci on chr7, chr13, chr18 and chr21. The targeted sequencing data showed that the ratio between fetus-specific and shared alleles increased by approximately 2-fold on chr21 in a paternally-derived trisomy 21 case, and decreased by approximately 11% on chr21 for maternally-derived trisomy 21 cases. I have also used computer simulation to determine the impact of fractional fetal DNA concentration, number of informative alleles and sequencing depth on the detection accuracy. / In the third part of this thesis, I have demonstrated the feasibility of targeted massively parallel sequencing of maternal plasma DNA for noninvasive prenatal diagnosis of monogenic diseases. Targeted sequencing was used to enrich the β-globin gene region in two families undergoing prenatal diagnosis for β-thalassemia. Parental haplotypes of the β-globin gene region were deduced via digital polymerase chain reaction. Relative haplotype dosage analysis was performed successfully to determine the β-thalassemic status for the fetuses, including one family in which the parents had similar haplotype structures in the disease-causing region. / Because of its potential to save costs and increase throughput, targeted sequencing may catalyse the translation of massively parallel sequencing based molecular diagnostics into many fields, including noninvasive prenatal diagnosis, cancer diagnostics and transplantation monitoring. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Liao, Jiawei. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 147-155). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese. / ABSTRACT --- p.i / ACKNOWLEDGEMENTS --- p.vi / PUBLICATIONS --- p.vii / CONTRIBUTORS --- p.viii / TABLE OF CONTENTS --- p.ix / LIST OF TABLES --- p.xiii / LIST OF FIGURES --- p.xiv / LIST OF ABBREVIATIONS --- p.xvi / Chapter SECTION I : --- BACKGROUND --- p.1 / Chapter CHAPTER 1: --- Cell-free fetal DNA and targeted massively parallel sequencing --- p.2 / Chapter 1.1 --- Cell-free fetal DNA in maternal plasma --- p.2 / Chapter 1.2 --- NIPD by qualitative analysis --- p.3 / Chapter 1.2.1. --- Fetal sex assessment --- p.4 / Chapter 1.2.2. --- RHD genotyping --- p.5 / Chapter 1.2.3. --- Other implementations --- p.5 / Chapter 1.3 --- NIPD by quantitative analysis --- p.6 / Chapter 1.3.1. --- NIPD of chromosomal aneuploidies --- p.6 / Chapter 1.3.2. --- NIPD of autosomal recessive monogenic diseases --- p.8 / Chapter 1.4 --- Massively parallel sequencing of maternal plasma --- p.9 / Chapter 1.4.1. --- Massively parallel sequencing --- p.9 / Chapter 1.4.2. --- MPS-based NIPD of chromosomal aneuploidies --- p.11 / Chapter 1.4.3. --- MPS-based prenatal fetal whole-genome scanning --- p.15 / Chapter 1.5 --- Targeted massively parallel sequencing of maternal plasma --- p.19 / Chapter 1.5.1. --- Microdroplet-based PCR --- p.19 / Chapter 1.5.2. --- Molecular inversion probe --- p.20 / Chapter 1.5.3. --- On-array capture --- p.21 / Chapter 1.5.4. --- In-solution capture --- p.21 / Chapter 1.5.5. --- Implementation on plasma DNA --- p.22 / Chapter 1.6 --- Aims of this thesis --- p.29 / Chapter SECTION II : --- Feasibility of targeted MPS in maternal plasma DNA --- p.30 / Chapter CHAPTER 2: --- Targeted MPS of maternal plasma DNA permits efficient and unbiased detection of fetal alleles --- p.31 / Chapter 2.1 --- Introduction --- p.31 / Chapter 2.2 --- Methods --- p.34 / Chapter 2.2.1 --- Study participants and sample collection --- p.34 / Chapter 2.2.2 --- Sample processing and DNA extraction --- p.34 / Chapter 2.2.3 --- DNA quantification --- p.36 / Chapter 2.2.4 --- Microarray genotyping --- p.39 / Chapter 2.2.5 --- Plasma DNA library preparation --- p.39 / Chapter 2.2.6 --- Plasma DNA library validation --- p.40 / Chapter 2.2.7 --- Target enrichment --- p.44 / Chapter 2.2.8 --- Massively parallel sequencing and alignment --- p.45 / Chapter 2.3 --- Results --- p.48 / Chapter 2.3.1 --- Efficiency of target enrichment --- p.48 / Chapter 2.3.2 --- Sequence coverage within the targeted region --- p.53 / Chapter 2.3.3 --- Fetus-specific allele detection --- p.59 / Chapter 2.3.4 --- Fractional fetal DNA concentrations before and after enrichment --- p.63 / Chapter 2.4 --- Discussion --- p.66 / Chapter SECTION III : --- NIPD of trisomy 21 by targeted MPS of maternal plasma DNA --- p.71 / Chapter CHAPTER 3: --- NIPD of fetal trisomy 21 by allelic ratio analysis using targeted MPS of maternal plasma DNA --- p.72 / Chapter 3.1 --- Introduction --- p.72 / Chapter 3.2 --- Methods --- p.74 / Chapter 3.2.1 --- Study participants and sample collection --- p.74 / Chapter 3.2.2 --- Sample processing and DNA extraction --- p.74 / Chapter 3.2.3 --- Targeted MPS of plasma DNA libraries --- p.74 / Chapter 3.2.4 --- F-S ratio calculation --- p.76 / Chapter 3.2.5 --- Microarray genotyping --- p.78 / Chapter 3.2.6 --- Computer simulation --- p.78 / Chapter 3.3 --- Results --- p.80 / Chapter 3.3.1 --- Efficiency of target enrichment --- p.80 / Chapter 3.3.2 --- Estimation of fractional fetal DNA concentrations --- p.83 / Chapter 3.3.3 --- F-S ratio calculation using non-targeted sequencing data --- p.83 / Chapter 3.3.4 --- F-S ratio calculation using targeted sequencing data --- p.85 / Chapter 3.3.5 --- Computer simulation --- p.85 / Chapter 3.4 --- Discussion --- p.90 / Chapter SECTION IV : --- NIPD of monogenic diseases by targeted MPS of maternal plasma DNA --- p.94 / Chapter CHAPTER 4: --- NIPD of monogenic diseases by targeted MPS of maternal plasma: application to Beta-thalassemia --- p.95 / Chapter 4.1 --- Introduction --- p.95 / Chapter 4.2 --- Methods --- p.98 / Chapter 4.2.1 --- Sample collection and DNA extraction --- p.98 / Chapter 4.2.2 --- Microarray-based genotyping --- p.100 / Chapter 4.2.3 --- Targeted MPS of plasma DNA libraries --- p.100 / Chapter 4.2.4 --- Genotyping by Sanger sequencing --- p.103 / Chapter 4.2.5 --- Haplotyping by digital PCR --- p.105 / Chapter 4.2.6 --- RHDO analysis --- p.105 / Chapter 4.3 --- Results --- p.110 / Chapter 4.3.1 --- Effectiveness of targeted sequencing --- p.110 / Chapter 4.3.2 --- Determination of fetal HBB genotype in the first family --- p.112 / Chapter 4.3.3 --- Determination of fetal HBB genotype in the second family --- p.113 / Chapter 4.4 --- Discussion --- p.115 / Chapter SECTION V : --- CONCLUDING REMARKS --- p.120 / Chapter CHAPTER 5: --- Conclusion and future perspectives --- p.121 / Chapter 5.1 --- Targeted MPS in plasma DNA --- p.121 / Chapter 5.2 --- Targeted MPS in NIPD of chromosomal aneuploidies --- p.124 / Chapter 5.3 --- Targeted MPS in NIPD of monogenic diseases --- p.126 / Chapter Appendix I: --- Primer names and sequences for genotyping and haplotyping of βeta-globin gene cluster region --- p.128 / Chapter Appendix II: --- Primers used in PCRs and sequencing for the parents in the first family --- p.132 / Chapter Appendix III: --- Primers used in PCRs and sequencing for the parents in the second family --- p.138 / Chapter Appendix IV: --- RHDO analysis on maternal plasma DNA in the first family --- p.140 / Chapter Appendix V: --- RHDO analysis on maternal plasma DNA in the second family --- p.145 / References --- p.147

Yip Lung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references. / Abstracts in English and Chinese. / Chapter 1 --- Introduction / Chapter 1.1 --- Heart and Lung Diseases --- p.1 / Chapter 1.1.1 --- Hong Kong --- p.1 / Chapter 1.1.2 --- China --- p.2 / Chapter 1.1.3 --- the United States of America (USA) --- p.3 / Chapter 1.2 --- Auscultation --- p.3 / Chapter 1.2.1 --- Introduction of Auscultation --- p.4 / Chapter 1.2.2 --- Comparison between Auscultation and Ultrasound --- p.6 / Chapter 1.3 --- Stethoscope --- p.7 / Chapter 1.3.1 --- History of Stethoscope --- p.7 / Chapter 1.3.2 --- New Electronic Stethoscope --- p.14 / Chapter 1.4 --- Main Purpose of the Study --- p.16 / Chapter 1.5 --- Organization of Thesis --- p.16 / References --- p.18 / Chapter 2 --- A New Electronic Stethoscope's Head / Chapter 2.1 --- Introduction --- p.20 / Chapter 2.2 --- Biopotential Electrode --- p.21 / Chapter 2.2.1 --- Flexible Electrode --- p.21 / Chapter 2.2.2 --- Laplacian Electrocardiogram --- p.22 / Chapter 2.3 --- Transducer --- p.25 / Chapter 2.4 --- Design of the Head of Stethoscope --- p.26 / Chapter 2.5 --- Experimental Results --- p.27 / Chapter 2.5.1 --- Bias Voltage of Condenser Microphone --- p.27 / Chapter 2.5.2 --- Frequency Response of New Stethoscope's Head --- p.29 / Chapter 2.6 --- Discussion --- p.30 / Chapter 2.7 --- Section Summary --- p.31 / References --- p.33 / Chapter 3 --- Signal Pre-processing Unit / Chapter 3.1 --- Introduction --- p.35 / Chapter 3.2 --- High Input Impedance IC Amplifier --- p.36 / Chapter 3.3 --- Voltage Control Voltage Source High Pass Filter Circuit --- p.37 / Chapter 3.4 --- Multiple Feed Back Low Pass Filter Circuit --- p.39 / Chapter 3.5 --- Overall Circuit --- p.41 / Chapter 3.6 --- Experimental Results --- p.43 / Chapter 3.7 --- Discussion --- p.46 / Chapter 3.8 --- Section Summary --- p.47 / References --- p.48 / Chapter 4 --- Central Platform / Chapter 4.1 --- Introduction --- p.49 / Chapter 4.2 --- Adaptive Filter --- p.49 / Chapter 4.2.1 --- Introduction to Adaptive Filtering --- p.49 / Chapter 4.2.2 --- Least-Mean-Square (LMS) Algorithm --- p.51 / Chapter 4.2.3 --- Applications --- p.52 / Chapter 4.3 --- Offline Processing --- p.54 / Chapter 4.3.1 --- WINDAQ and MATLAB --- p.55 / Chapter 4.3.2 --- Direct Reference Algorithm --- p.57 / Chapter 4.3.3 --- Determination of Parameters in DRA --- p.62 / Chapter 4.3.4 --- Experimental Results of DRA --- p.67 / Chapter 4.3.5 --- Acoustic Waveform Based Algorithm --- p.72 / Chapter 4.3.6 --- Experimental Results of AWBA --- p.81 / Chapter 4.4 --- Online Processing --- p.85 / Chapter 4.4.1 --- LABVIEW --- p.85 / Chapter 4.4.2 --- Automated Gain Control --- p.88 / Chapter 4.4.3 --- Implementation of LMS adaptive filter --- p.89 / Chapter 4.4.4 --- Experimental Results of Online-AGC --- p.92 / Chapter 4.5 --- Discussion --- p.93 / Chapter 4.6 --- Section Summary --- p.97 / References --- p.98 / Chapter 5 --- Conclusion and Further Development / Chapter 5.1 --- Conclusion of the Main Contribution --- p.100 / Chapter 5.2 --- Future Works --- p.102 / Chapter 5.2.1 --- Modification of the Head of Stethoscope --- p.102 / Chapter 5.2.2 --- Validation of Abnormal Breath --- p.102 / Chapter 5.2.3 --- Low Frequency Analysis --- p.102 / Chapter 5.2.4 --- AGC-AWBA Approach --- p.102 / Chapter 5.2.5 --- Standalone Device --- p.103 / Chapter 5.2.6 --- Demand on Stethoscope --- p.109 / References --- p.110 / Appendix / Chapter A.1 --- Determination of parameters in VCVS High Pass Filter --- p.106 / Chapter A.2 --- Determination of parameters in MFB Low Pass Filter --- p.110 / Chapter A.3 --- Source code of DRA (MATLAB) --- p.114 / Chapter A.4 --- Source code of AWBA (MATLAB) --- p.129 / Chapter A.5 --- Source code of online AGC (LABVIEW) --- p.134

The present series of investigations examined the diagnostic accuracy of the Cognitive Examination (CAMCOG) from the Cambridge Mental Disorders of the Elderly Examination (CAMDEX) in the differential diagnosis of various dementing conditions. Specifically, this study examined: (a) the degree to which the CAMCOG would differentiate normal individuals from patients with Alzheimer's Disease (AD) and from those suffering from non-AD dementing conditions, (b) the extent to which the CAMCOG would distinguish between patients suffering from organic dementing conditions, those having functional psychiatric disorders, and normal persons, and (c) whether the CAMCOG would offer an improvement in diagnostic accuracy over a widely used screening instrument (i.e., the Mini-Mental Status Examination, MMSE) when attempting to differentially diagnose dementing patients and normal cohorts.A review of the literature was presented with an emphasis on the difficulties in establishing differential diagnosis, inaccuracies in diagnosis, the importance of improved diagnostic accuracy, and the use of neuropsychological measures in the assessment and diagnosis of patients suffering from dementing illnesses. Further, research relevant to ancillary diagnostic techniques, the various neuropsychologicalapproaches used in evaluating and diagnosing mental disorders in the elderly, and studies investigating the utility of specific cognitive/neuropsychological measures in the differential diagnosis of dementing diseases was presented.The results of these investigations revealed that the CAMCOG provides excellent diagnostic sensitivity and specificity when differentiating normal persons from clinically diagnosed AD patients and when distinguishing between individuals with an organic-dementing condition and normal adults. The CAMCOG was found to be less effective in differentiating AD and non-AD dementia patients and in distinguishing between patients suffering from organic dementia versus specified psychiatric disorders. Finally, the CAMCOG demonstrated a slight improvement in diagnostic accuracy over the Mini-Mental Status Examination. These results were discussed in terms of their support for the utility of the CAMCOG as an excellent screening measure when used to differentiate patients suffering from various dementia-producing disease states and normal persons. / Department of Educational Psychology

Early detection of Alzheimer's disease (AD) and related dementias in the elderly is critical for improving treatment methods and is a necessary component for improving public health interventions. One of the earliest and most common behavioral syndromes of AD is apathy and is associated with executive dysfunction. Apathy in AD is often misdiagnosed as depression due to an overlap in symptoms. Studies that have found depression to be associated with executive dysfunction have not always controlled for the presence of apathy. The Geriatric Depression Scale (GDS) is a widely used instrument designed to assess depression in the elderly. This study utilized the GDS and a set of standard neuropsychological instruments to investigate the relationship between apathy, depression, and executive functions in individuals with AD and related dementias. The first objective of this study was to determine if apathy has a greater impact on executive functions compared to depression in AD and related dementias. The second objective was to determine the effectiveness of the GDS as a screen for apathy. The results of the analyses did not support the hypotheses. However, exploratory analyses suggested a possible non-linear relationship with apathy and various levels of dementia severity. Exploratory analysis also suggested mean levels of endorsement for apathy varied by diagnosis. Further research is warranted to investigate this relationship and the GDS endorsement patterns for caregivers regarding their impression of the demented individual.

No description available.

No description available.

Call number: LD2668 .T4 1955 E44 / Master of Science

Dissertation submitted in partial compliance with the requirements for the Master’s Degree in Technology: Chiropractic, Durban University of Technology, 2011. / Background: Low back pain is a common condition and affects most people at least once in their lives. The causes of low back pain (LBP) are numerous and may include non-specific mechanical causes, or specific causes which may be of a more serious nature. Researchers have tried to link specific history and physical examination findings with certain disorders, but as of yet, have been unsuccessful. Research has shown that x-rays may be over utilized and the guidelines for referral are not always adhered to. Furthermore, there is a paucity of literature on the role of x-rays in influencing the management of patients with low back pain. Objectives: The objectives of this retrospective study were: 1) to determine the relationship between the clinical and the radiographic diagnoses of patients with LBP, 2) to record the consultation at which a lumbar spine x-ray was requested by the student or clinician and the reasons thereof, 3) to record the suspected clinical diagnoses and management of the selected patients prior to referral for lumbar spine x-rays, 4) to determine the number of incidental radiographic findings in the selected patients’ x-rays, and 5) to determine any change in the clinical diagnoses and management following radiographic reporting of the selected patients’ x-rays. Method: The Chiropractic Day Clinic (CDC) at the Durban University of Technology (DUT) archives were searched for lumbar spine radiographs and the corresponding patient files of patients who presented with LBP from 1 January 1997 to 31 July 2010. Data collection was in a stepwise process with the anteroposterior and lateral lumbar spine x-rays being read first, without any knowledge of the patient’s main complaint and then the corresponding patient files were evaluated and selected clinical variables were recorded. Statistical analysis included the use of frequency counts, percentages, mean, standard deviation and range for the descriptive objectives. Diagnoses were categorized into specific groups and indicator variables were used to construct two-by-two tables of absence or presence of radiographic vs. clinical diagnosis for each specific diagnosis to determine any possible associations. Results: The mean age of the patients was 43.9 (± 16.9) years and the number of male and female patients were 40 and 34 respectively. It was not possible to correlate the clinical and radiographic diagnoses because the categories were too different for any statistical test to be performed. Spondylosis was the most common radiographic finding. The majority of the lumbar spine x-rays were requested at the first consultation. No suitable reason for obtaining the x-ray was provided in 14.6% of the x-rays requested and 20.7% were requested to examine for an unspecified pathology. Of the 74 patients in this study, 44 patients did not have a change in diagnosis, which means that 59.5% of the diagnoses stayed the same after x-ray examination. However, in 30 (40.5%) of cases the clinical diagnosis was changed following x-ray examination. This may indicate an overuse of x-rays at the CDC. Most patients were diagnosed with the non specific mechanical causes of low back pain. A wide range of treatment modalities were utilized both before and after x-rays were taken, including soft tissue therapies, electrotherapies and spinal manipulation. Following x-ray imaging there was a greater use of spinal manipulation ie. 62% versus only 39% of cases prior to imaging. Conclusion: Lumbar spine x-rays may be over utilised at the CDC but their findings were influential in the diagnosis and management in 30 (40.5%) of the patients. The majority of the clinical diagnoses were of the mechanical or non-specific causes of low back pain. / Durban University of Technology.

Many research questions in dysphagia research require frame-by-frame annotation of anatomical landmarks visible in videofluorographs as part of the research workflow, which can be a tedious and error prone process. Such annotation is done manually using image analysis tools, is error prone, and characterized by poor rater reliability. In this thesis, a computer-assisted workflow that uses a point tracking technique based on the Kanade-Lucas-Tomasi tracker to semi-automate the annotation process, is developed and evaluated. Techniques to semi-automate the annotation process have been explored but none have had their research value demonstrated. To demonstrate the research value of a workflow based on point tracking in enhancing the annotation process, the developed workflow was used to perform an enhanced version of the recently published Coordinate Mapping swallowing study annotation technique to determine several swallowing parameters. Evaluation was done on eight swallow studies obtained from a variety of clinical sources and showed that the workflow produced annotation results with clinically insignificant spatial errors. The workflow has the potential to significantly enhance research processes that require frame-by-frame annotation of anatomical landmarks in videofluorographs as part of their data preparation steps, by reducing the total time required to annotate clinical cases