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The object of this study was to investigate the adequacy of a test battery for the differential diagnosis of early schizophrenia. A test battery consisting of a physiological test of autonomic nervous system reactivity, psychological tests of abstract-concrete attitude and the Sc (schizophrenia) scale of the Minnesota Multiphasic Personality Inventory was administered to an experimental group of 50 early schizophrenics and a control group of 50 patients suffering a functional disorder other than schizophrenia. Each subject of both groups was on his (her) first admission to a psychiatric institution. The groups were matched on the basis of age, sex and IQ. The test battery was found to statistically differentiate the two groups at the 2 per cent level and beyond, indicating that the test battery is adequate for differential diagnosis of early schizophrenia. No relationship was established for the expected correlation between autonomic nervous system hyporeactivity, impairment on tests of abstract-concrete attitude and an abnormal trend in the schizoid direction as measured by the Sc scale of the MMPI. It had been suggested that associative and affective functions in schizophrenia are impaired in a related fashion. The hypothesis that combination of loss of abstraction ability, schizoid personality trend and physiological phenomenon interpreted as "release" of the autonomic nervous system from higher (cortical) control was not confirmed. / Arts, Faculty of / Psychology, Department of / Graduate

Members of scientific disciplines and lay persons alike commonly hold the view that the practical work carried out by those very same members is theory governed. The problem undertaken by this study was to observe, in a psychiatric hospital, the practical work of psychotherapists, with the intent of characterizing the role played by theory in their work. An ethnographic approach was employed, and the research was focused on psychotherapy with patients diagnosed to be members of a single diagnostic category. The researcher began his fieldwork with the assumption that his knowledge of psychiatric theory would allow him to make sense of his observations. Contrary to his expectations, he was unable to discern the theoretical significance of the activities that he observed. This led the researcher to conclude that there was a "gap" between his knowledge and his observations. The researcher developed a number of plausible explanations for the "gap," none of which proved to be adequate. The "gap," in itself, raises a hitherto unacknowledged issue of the relationship between theory and practice. It is argued that the "gap" exists not only for the researcher, but also for any persons who would study a body of scientific theoretical knowledge, and then observe what purports to be the practical application of that knowledge. The "gap" seems to be integral to any theory-guided discipline. The study explicates, it is argued, a characteristic of scientific work. The lack of an adequate explanation for the "gap" is not a failing of the study, but rather points to the lack of a standard which specifies what "theory governed" means. Although the study presents us with a puzzle, it does not put into question the efficacy of theorizing with respect to the accomplishment of practical work in the clinical or any other disciplines. / Arts, Faculty of / Anthropology, Department of / Graduate

Ng, Kwun Kei. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 74-85). / Abstracts in English and Chinese. / Abstract (English) --- p.i / Abstract (Chinese) --- p.iii / Acknowledgement --- p.iv / Table of Contents --- p.vi / List of Tables --- p.viii / List of Figures --- p.ix / Chapter Chapter 1: --- Introduction --- p.1 / Rapid Naming in Chinese Dyslexic Children: A Glimpse --- p.1 / What is Rapid Naming --- p.2 / Processing Speed Deficit and RAN Deficit in Chinese Dyslexia --- p.5 / Consequence of Processing Speed Deficit: Automaticity --- p.12 / Automaticity and Attention --- p.16 / Discriminative Power of RAN Tasks --- p.19 / Object Rapid Naming --- p.19 / Letter Rapid Naming --- p.21 / Digit Rapid --- p.23 / Adopting ERP and Oddball Task to Investigate RAN Tasks --- p.25 / High-temporal-resolution Electrophysiological Signals --- p.25 / The Oddball Task --- p.26 / The ERPs --- p.28 / Current Study --- p.39 / Chapter Chapter 2: --- Method --- p.41 / Participants --- p.41 / Procedure --- p.41 / Oddball Stimulus Classification Tasks --- p.42 / The RAN Tasks --- p.44 / The Hong Kong Test of Specific Learning Difficulties in Reading and Writing --- p.44 / Chinese Phonology Segmental Test --- p.44 / Raven's Standard Progressive Matrices --- p.45 / Chapter Chapter 3: --- Results --- p.47 / Behavioural Results --- p.47 / ERP Results --- p.55 / Chapter Chapter 4: --- Discussion --- p.59 / Digit Naming and Digit Oddball in Chinese Dyslexia --- p.59 / Letter RAN --- p.63 / Oddball RTs and Response Execution --- p.65 / Limitations and Future Directions: The Issue of Task Demands and the Multiple Deficits Hypothesis --- p.66 / References --- p.74 / Appendix A: ERP Grand Average for the Object Oddball Task --- p.86 / Appendix B: ERP Grand Average for the Letter Oddball Task --- p.87 / Appendix C: ERP Grand Average for the Digit Oddball Task --- p.88

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This exploratory study used Diagnostic Content Validity (DCV) and the Clinical Diagnostic Validation (CDV) models proposed by Fehring (1986) to clinically identify and validate the defining characteristics for Alteration in Tissue Perfusion: Cardiac. The literature based Kelly Cardiac Assessment Tool (KCAT) was designed as the data collection tool. The diagnostic content validity of the KCAT was 0.70. Twenty subjects, 18 years old and older were selected from a population who were admitted as inpatients in a southwestern university affiliated hospital. Data were collected through patient interviews, independent nurse assessment, and review of laboratory data. Using the steps described in Fehring's CDV model (1986) one major defining characteristic and 13 minor defining characteristics were clinically validated. The tool CDV score was 0.62. The nursing diagnosis Alteration in Tissue Perfusion: Cardiac was clinically validated and one major and 13 minor defining characteristics were identified.

目的：結直腸癌是世界上第三常見惡性腫瘤，結腸鏡檢查是診斷的金標准。但其創傷性、昂貴的設備以及人力的需求阻礙了廣泛應用。本研究評估了糞便miRNA作為非損傷性分子生物標記物篩查結直腸腺瘤和腫瘤的可行性，並深入探究了致癌miRNA的基因靶點。 / 方法：我們評估了糞便miRNAs的穩定性以及檢測的可重復性。糞便樣本收集自88例結腸直腸癌患者，57例結直腸息肉患者和101名健康對照，用實時定量逆轉錄PCR檢測miRNA水平。所有候選miRNA標記物在配對的癌及癌旁組織中進行驗証。我們共測試了糞便中7種miRNAs，包括前期報道在結直腸癌中上調的miR-21和miR-92a(第一部分)，以及在667個miRNA中在結直腸癌上調最高的5個miRNA(第二部分)。我們研究了它們的水平與腫瘤分期及位置的關系。並隨訪了病人經腫瘤或腺瘤切除術后其糞便miRNA水平，從而証實它們是否與腫瘤相關。我們應用了彗星試驗、細胞活力試驗、集落形成試驗，以及細胞凋亡分析試驗研究了miR-18a在腫瘤的發展過程中的作用(第三部分)。 / 結果：第一部分，我們確定糞便miRNA的穩定性，能被實時定量逆轉錄PCR檢測並顯示高重復性。糞便miR-92a標記物的靈敏度和特異性分別為71.6%和73.3%，miR-21分別為55.7%和73.3%。MiR-92a水平顯示遠端結直腸癌比近端結直腸癌的檢測具有更高靈敏度，晚期腺瘤比小息肉更具靈敏度。腫瘤切除后，miR-21和miR-92a水平顯著下降。 / 第二部分，基於結直腸腫瘤miRNA的表型，我們發現糞便miR-18a, miR-20a, miR-135b和miR-221能作為標記物鑒別結直腸癌，miR-18a (敏感度: 51.1%, 特異性: 90.1%); miR-20a (72.7%, 81.2%) ; miR-135b (81.8%, 68.3%); miR-221 (69.3%, 77.2%)。腫瘤切除后，這四種標記物會顯著下降。MiR-135b和miR-221也能鑒別腺瘤。四種標記物對遠近端結腸癌的檢測無顯著差異。 / 第三部分，通過程序和熒光素酶報告基因活性預測和驗証，我們發現一種重要的DNA修復蛋白---共濟失調毛細血管擴張突變(ATM)是miR-18a的靶蛋白。MiR-18a的異位表達減弱細胞DNA雙鏈損傷修復機制，導致腫瘤發生的易感性。 / 結論：我們發現糞便中miR-21, miR-92a, miR-18a, miR-20a, miR-135b 和miR-221標記物能夠鑒別結直腸癌。MiR-92a, miR-135b 和miR-221能鑒別結直腸腺瘤。MiR-18a抑制共濟失調毛細血管擴張突變基因表達並減弱細胞DNA雙鏈損傷修復機制。糞便miRNA是結直腸癌篩查的有效生物標記物。 / Objective: Colorectal cancer (CRC) is the third most common cancer worldwide. Colonoscopy is the current gold standard for diagnosing CRC. However, its invasive nature, the cost of equipment and the demand for manpower have hampered the wide application of this procedure. This study evaluated the feasibility of using stool-based miRNA as non-invasive biomarkers for the screening of colorectal adenoma and cancer, and investigated the gene target of a candidate oncogenic miRNA. / Methods: The reproducibility of detection and stability of stool-based miRNAs were first evaluated. Stool samples were collected from 88 CRC patients, 57 patients with colorectal polyp and 101 healthy controls MiRNA levels were detected by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). AII candidate miRNA markers were validated in a cohort of paired tumor and adjacent normal tissues. In total, we tested 7 miRNAs in the stool, including miR-21 and miR-92a which were reported to be up-regulated in CRC in previous studies (part one), and 5 miRNAs which were found to be the most up-regulated in colorectal tumor based on the profiling of 667 miRNAs (part two). Their levels with tumor stage and location were evaluated. Their change in level was followed up in a subset of patients after the removal of tumor or adenoma. We investigated miR-18a for its function in cancer development using comet assay, cell viability assay, colony formation assay, and analysis on apoptosis (part three). / Results: In part one, we found stool miRNAs stable and detectable with high reproducibility by qRT-PCR. In detecting CRC, stool miR-92a had a sensitivity of 71.6% and a specificity of 73.3%, stool miR-21 had a sensitivity of 55.7% and a specificity of 73.3%. Stool miR-92a level had higher sensitivity for distal CRC than proximal CRC, and a higher sensitivity for advanced adenoma than minor polyps. The removal of tumor resulted in reduced stool miR-21 and miR-92a levels. / In part two, based on miRNA profiling of CRC tumors, we found that stool-based miR-18a, miR-20a, miR-135b, and miR-221 can discriminate colorectal cancer patients from healthy individuals: miR-18a (sensitivity: 51.1%, specificitiy: 90.1%); miR-20a (72.7%, 81.2%); miR-135b (8 1.8%, 68.3%); miR-221 (69.3%, 77.2%). Levels of these 4 stool-based markers dropped after removal of tumors. Stool-based miR-135b and miR-221 also discriminated patients with adenoma from healthy individuals. MiR-18a, miR-20a, miR-135b and miR-221 showed no desparity in detecting proximal or distal colon cancer. / In part three, based on in silico prediction and validation with luciferase reporter activity, we identified Ataxia Telangiectasia Mutated (ATM ), a protein crucial to DNA repair, as a target of miR-18a. Ectopic expression miR-18a attenuates DNA double strand break repair mechanism, creating a genetic predisposition to the development of cancer. / Conclusion: Stool-based miR-21, miR-92a, miR-18a, miR-20a, miR-135b and miR-221 can discriminate patients with CRC from healthy individuals. Notably, a subset of these miRNAs (miR-92a, miR-135b, and miR-221) can discriminate patients with colorectal adenoma from healthy individuals MiR-18a suppressed ATM gene expression and attenuated cellular repair mechanism to DNA double strand breaks. Stool-based miRNAs are useful CRC screening biomarkers. / 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. / Detailed summary in vernacular field only. / Wu, Chung Wah. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 80-92). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Chapter CHAPTER ONE --- INTRODUCTION --- p.1 / Chapter 1.1 --- Colorectal cancer --- p.1 / Chapter 1.2 --- Current screening methods --- p.3 / Chapter 1.2.1 --- Colonoscopy --- p.3 / Chapter 1.2.2 --- Sigmoidoscopy --- p.4 / Chapter 1.2.3 --- Stool-based tests --- p.4 / Chapter 1.2.3.1 --- Fecal occult blood test --- p.5 / Chapter 1.2.3.2 --- Stool-based DNA test --- p.6 / Chapter 1.2.3.3 --- Stool-based RNA and protein test --- p.7 / Chapter 1.3 --- MiRNA and its role in cancer --- p.8 / Chapter 1.4 --- Aims of study --- p.9 / Chapter CHAPTER TWO --- METHODOLOGY --- p.10 / Chapter 2.1 --- Subjects and sample collection --- p.10 / Chapter 2.2 --- MiRNA extraction in tissue and stool samples --- p.13 / Chapter 2.3 --- MiRNA quantitation by quantitative reverse transcription quantitative reverse transcription polymerase chain reaction --- p.14 / Chapter 2.4 --- Determining the stability of miRNA in stool samples --- p.15 / Chapter 2.5 --- Determining the reproducibility of miRNA quantitation in stool samples --- p.16 / Chapter 2.6 --- Reverse transcription for miRNA array --- p.16 / Chapter 2.7 --- Quantitative polymerase chain reaction for miRNA array --- p.16 / Chapter 2.8 --- Cell culture, miRNA precursors and transfection --- p.17 / Chapter 2.9 --- Dual-luciferase reporter assay --- p.17 / Chapter 2.10 --- Quantitative reverse transcription polymerase chain reaction for mRNA --- p.19 / Chapter 2.11 --- Western blot analysis --- p.19 / Chapter 2.12 --- Comet assay --- p.19 / Chapter 2.13 --- Colony formation and cell viability assay --- p.20 / Chapter 2.14 --- Annexin V apoptosis assay --- p.21 / Chapter 2.15 --- Statistics --- p.21 / Chapter CHAPTER THREE --- RESULTS --- p.23 / Chapter 3.1 --- PART 1 --- p.23 / Chapter 3.1.1 --- Stability of miRNA detection in stool samples --- p.23 / Chapter 3.1.2 --- Reproducibility of miRNA quantitation in stool samples --- p.23 / Chapter 3.1.3 --- Detection and normalization of miRNA levels --- p.25 / Chapter 3.1.4 --- Expression of miR-21 and miR-92a in CRC tissue samples --- p.28 / Chapter 3.1.5 --- Levels of stool-based miR-21 and miR-92a in CRC and polyp patients --- p.30 / Chapter 3.1.6 --- Sensitivity of stool-based miR-21 and miR-92a towards colorectal cancer and polyps --- p.32 / Chapter 3.1.7 --- Association of stool-based miR-21 and miR-92a with clinicopathological features --- p.34 / Chapter 3.1.8 --- Follow-up on stool miR-21 and miR-92a levels after removal of lesion --- p.37 / Chapter 3.2 --- Part 2 --- p.39 / Chapter 3.2.1 --- MiRNA profiling in colorectal tumors --- p.39 / Chapter 3.2.2 --- Validation of miRNA profiling results --- p.41 / Chapter 3.2.3 --- Candidate miRNA levels in stool samples of CRC and adenoma patients --- p.44 / Chapter 3.2.4 --- Sensitivities and specificities of miRNA candidates for adenoma and CRC --- p.47 / Chapter 3.2.5 --- Sensitivties of miRNA candidates based on tumor location --- p.49 / Chapter 3.2.6 --- Follow-up on stool miRNA levels after removal of lesion --- p.51 / Chapter 3.2.7 --- Association of stool-based miRNAs with nodal involvement in CRC --- p.53 / Chapter 3.2.8 --- Establishing the miRNA marker panel --- p.55 / Chapter 3.3 --- Part 3 --- p.57 / Chapter 3.3.1 --- In Silico prediction of miR-18a target and validation by luciferase assay --- p.57 / Chapter 3.3.2 --- Expression and correlation between miR-18a and ATM in paired colorectal tumor tissue, cell lines and normal colon biopsies --- p.60 / Chapter 3.3.3 --- Regulation of double strand DNA damaga recovery by miR-18a --- p.62 / Chapter 3.3.4 --- Cell sensitization to genotoxin by miR-18a --- p.64 / Chapter 3.3.5 --- Effect of miR-18a on genotoxin induced apoptosis --- p.66 / Chapter CHAPTER FOUR --- DISCUSSION --- p.68 / Chapter 4.1 --- Stability and detection reproducibility of stool-based miRNA --- p.68 / Chapter 4.2 --- Stool-based miRNAs for screening colorectal cancer and polyps/adenomas --- p.69 / Chapter 4.2.1 --- MiR-21 --- p.69 / Chapter 4.2.2 --- MiR-18a, miR-20a and miR-92a --- p.70 / Chapter 4.2.3 --- MiR -135b and miR -221 --- p.71 / Chapter 4.2.4 --- MiR -31 --- p.72 / Chapter 4.3 --- Discriminating proximal and distal CRC --- p.73 / Chapter 4.4 --- Evaluation of stool-based miRNA level after removal of lesions --- p.74 / Chapter 4.5 --- MiRNA marker panel --- p.74 / Chapter 4.6 --- Advantages of stool-based miRNA tests --- p.75 / Chapter 4.7 --- Ataxia telangiectasia mutated as the direct target of miR -18a --- p.75 / Chapter 4.8 --- Future directions for study --- p.78 / Chapter 4.9 --- Conclusion --- p.78 / REFERENCES --- p.80 / PUBLICATIONS --- p.93

The purpose of this study is to develop a technique by which a physician may use a predetermined data base to derive a preliminary diagnosis for a patient with a given set of symptoms. The technique will not yield an absolute diagnosis, but rather will point the way to a set of most likely diseases upon which the physician may concentrate his efforts. There will be no reliance upon a data base compiled from poorly kept medical records with non-standardization of terminology. While this study produces a workable tool for the physician to use in the process of medical diagnosis, the ultimate responsibility for the patient's welfare must still rest with the physician.

Thesis (M.S.)--University of Michigan, 1988.