The relationship between music and emotions has been the focus of the study of musical experience. However, previous studies have focused in particular on what psychologists understand as the "basic emotions", which are rigorously defined. This thesis argues that the focus on basic emotions has indeed limited our understanding of what we feel when we listen to music. A narrative review of the recent literature has been carried out to closely examine the existing findings and limitations of previous studies have been revealed. In addition, a positive tendency is observed in listeners' responses to music. Participants' ratings of happiness were overwhelmingly high among different music excerpts. This suggests that listeners tend to feel positive when they listen to music regardless of the specific emotions aroused by music (e.g. happiness and sadness). The high level of happiness observed in the review may actually point to the experience of pleasure. Taking this as a starting point, this study moves on to introduce the psychological notion of pleasure and how it can be applied to the study of musical experience. The experience of pleasure involves an evaluation process and is not necessarily tied up with particular emotions. The relationship between pleasure and musical expectations is also explored. An explorative empirical study has been carried out to investigate listeners' experiences of pleasure and emotions when they listen to music. Participants listened to several music excerpts and they had to report the affective response induced by the excerpts in them. They also gave ratings to the level of pleasure they experienced with the music excerpts. Results show that different excerpts induced different responses in the participants, but the levels of pleasure they experienced towards different excerpts were not significantly different. Taken together, this study suggests that pleasure is commonly experienced when we listen to music and it is a psychological experience independent of emotions. A better understanding of musical pleasure can lead to a more comprehensive understanding of our musical experience. / published_or_final_version / Music / Master / Master of Philosophy

Introduction: Dementia refers to impairments of memory and other cognitive functions with consequent decline in activities of daily living. Besides cognitive symptoms, demented patients can also exhibit behavioral and psychological symptoms of dementia (BPSD), which are stressors leading to family caregivers’ burden. Physical activity may give rise to benefits in cognitive function, and may reduce behavioral symptoms and caregivers’ burden. However, most previous studies were reported from Caucasian populations. There was no previous report on the relationship of physical activity in dementia patients on family caregiver’s burden in Hong Kong Chinese older adults. Objectives: The objective of this study was to investigate the associations of physical activity level with cognitive function, behavioral and psychological symptoms and caregivers’ burden in dementia patients in Hong Kong Chinese population. Method: This was a cross-sectional study. 201 dementia patients who were screened by the inclusion and exclusion criteria were recruited from the Geriatric Clinic in Queen Mary Hospital, Hong Kong, from May 2013 to August 2013. Social demographic information and comorbid diseases information were collected from all subjects. Subjects were then assessed with the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL), Physical Activity Scale for the Elderly (PASE), as well as Neuropsychiatric Inventory (NPI). Subjects’ family caregivers were assessed with Zarit Burden Interview (ZBI). Main outcome measures: The outcome measures for the cognitive function were the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). The outcome measures for BPSD and caregiver’s burden were the Neuropsychiatric Inventory (NPI) and Zarit Burden Interview (ZBI), respectively. Results: We screened a total of 239 subjects in the Geriatric Clinic of Queen Mary Hospital. 201 subjects (70 males and 131 females) were recruited. 38 participants were excluded according to the exclusion criteria. The score means (SD) of the recruited were: PASE =27.5 (23.9); ADCS-ADL=45.3 (14.5); MMSE=17.3 (5.4); MoCA=9.9 (5.3); NPI=9.5 (9.7); ZBI=33.3 (14.8). In bivariate analysis, the PASE score was significantly associated with the MMSE score (rho=0.259, p<0.001), the MoCA score (rho=0.311, p<0.001), the NPI score (rho=-0.225, p=0.001), and the ZBI score (rho=-0.253, p<0.001). In multivariate analyses, using general linear models, the PASE score was independently associated with the MMSE (F=5.57, p=0.001) and MoCA (F=7.10, p<0.001) scores, after adjusting for significant confounders in bivariate analyses (i.e. age, education and gender). The PASE was also independently associated with the NPI score (F=2.89, p=0.037). The PASE score was not an independent predictor of the ZBI score. However, the subjects’ ADCS-ADL score (F=15.65, p<0.001), and the NPI score (F=8.55, p=0.004) were independent predictors of the caregiver’s ZBI score. / published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Breast cancer is the most common cancer in females worldwide. RIP140 was one of the first proteins recognized as nuclear receptor transcriptional cofactor which interacts with several nuclear receptors. RIP140 plays a central role in metabolic tissues with multifunctional co-regulation. It is an essential protein required for energy homeostasis and mammary gland development. RIP140 has been found to be involved in development of breast cancer in response to estrogen. RIP140 is recruited by estrogen receptors in the presence of estrogen. Increasing levels of estrogen and RIP140 stimulate their transcription and regulate proliferation and differentiation of mammary glands. We hypothesize that RIP140 may be over expressed in breast cancer and may be correlated with clinicopathological features and may thus serve as a possible new prognostic marker in breast cancer. In our study, the correlation between the RIP140 expression and survival was investigated by immunohistochemistry (IHC), and analyzed by Pearson’s chi-square and Kaplan Meier analysis. Cox regression analysis was performed to examine the relationship between clinic-pathological parameters and the survival. Total of one hundred and eighteen breast cancer samples were examined for the RIP140 staining localization in breast cancer cells. Our results showed that the IHC staining of RIP140 was observed in both cytoplasm and nucleus of breast cancer cells. The ER positive staining was significantly correlated with high nuclear expression of RIP140, but not RIP140 cytoplasmic expression. Thus nuclear RIP140 expression was examined for correlation with other clinic-pathological features and patient survival. The correlation between nuclear RIP140 expression and clinic-pathological features by Pearson’s chi-square test showed that high RIP140 nuclear staining score is associated with ER positive status (p-value=0.041) and tumor stage (p-value=0.008). Kaplan Meier test shown that nuclear RIP140 expression is not significant associated with either overall survival or disease-specific survival. However, a trend of high nuclear RIP140 score was observed with poorer overall and disease-specific survival though not statistically significant. To conclude, our results suggest RIP140 is not a useful prognostic marker for breast cancer. Further investigation with larger sample size is necessary to improve the statistical significance of the test. / published_or_final_version / Pathology / Master / Master of Medical Sciences

Introduction Depression can lead to long term health burden; while alcohol is now also one of the global burdens of diseases. This review is trying to investigate how healthy population can be at risk when the trends of alcohol consumption are increasing. Methods and Results This review studied 11 journals out of 1096 literature in PubMed / Medline / PsyInfo for alcohol and depression association via prospective cohort or longitudinal study. Results varied in outcomes measured and no conclusion on developed causality with alcohol and depression. Discussions Some significant associations may be observed at heavy use of alcohol or binge drinking groups. Young adolescents association was not as significant as adult studies results. Some stratification on gender difference is also non-conclusive. Population on heavy drinking and dependency are at risk of developing depression. Conclusions Future perspectives in research like the need of developing high quality research and more on population approach studies focusing on alcohol and depression should be carried. Prevention of alcohol-related problems especially in young people or population as a whole should include policies reducing overall alcohol consumption, or reducing the rates of high-risk drinking. / published_or_final_version / Public Health / Master / Master of Public Health

Objective: To review in the literature on the association between diabetes and background exposure of dioxins among general population. Method: Systematic review on studies the association of background dioxin exposure and diabetes among general population, published from January 1960 to July 2013 in PubMed, and from January 1979 to July 2013 in China National Knowledge Infrastructure (CNKI). Result: A total of nine articles (including seven cross-sectional studies, one longitudinal study and one cohort study) out of 111 articles from PubMed and 5 articles from CNKI were included in the systematic review. Five out of nine studies found a positive association between background exposure to dioxins or dioxins-like compounds and the risk of diabetes whilst two studies reported an inverse association between dioxins and insulin concentrations or IGF-I serum levels. Two studies reported positive significant relation of dioxins and diabetes in women but not in men. Discussion: Based on this systematic review, the association of background dioxins exposure and diabetes among general population remains unclear. Given the crosssection design of the studies, causal relation between dioxin exposure and diabetic risks cannot be drawn. / published_or_final_version / Public Health / Master / Master of Public Health

Objective The objective of the present study is to explore the associations of health expenditures and cause-specific mortality among countries at different stages of economic development. Methodology Scatter plot and simple linear regression were used to estimate whether there was an association between health expenditures and cause-specific mortality. The statistical significance levels were set at p < 0.05. Mortalities due to all causes, and three specific causes of the global burden of disease (GBD) were used. The three kinds of cause-specific mortalities were: communicable, maternal, perinatal and nutritional conditions (CMPN), non-communicable disease and injuries. Countries were grouped into four income groups according to the standard issued by World Bank in 2012. Result This study suggested general government expenditure on health, as a percentage of total government expenditure, was inversely associated with the three cause-specific mortalities, especially in high income group. Conclusion: This study showed an inverse association between healthcare expenditure and cause-specific mortalities. The Law of Health Transition has been once again evidenced. In developed countries, non-communicable diseases contributed to more deaths compared with mortality from communicable, maternal, perinatal and nutritional conditions (CMPN). While in less-developed countries, they were facing higher mortalities; CMPN was still a major cause of death, especially among children. / published_or_final_version / Public Health / Master / Master of Public Health

Indoor living wall is a newly developed greening technology that make use of facade to green the interior side of building. Owing to the limited land space in Hong Kong, indoor living wall becomes a new greening alternative in the urban area. Currently, there are three common types of systems: Felt, modular and trellis. Although outdoor living wall is more popular, indoor type is gaining more popularity as it can bring certain environmental benefits to building occupants. However, the construction and operations of indoor living wall will also cause damage to the environment. Under this circumstances, it is important to evaluate the environmental benefits and drawbacks of different indoor living wall systems and thus to find out the most beneficial one. The methodologies used in this study includes literature review, life cycle assessment (LCA), questionnaire and a technical visit. Through studying the literature, the current development and the knowledge gap is identified. This method is also used for summarizing the air purification ability of indoor plants and the living wall. After gaining the fundamental knowledge of the topics, LCA will be conducted to assess the environmental damage of resources, human health and ecosystem. The modular and felt systems under different disposal scenarios will be compared. The LCA results show that modular system has more benefits than the felt system. Also, using recycled material and disposal method is more environmentally friendly than landfills. Afterwards, technical visits to Exchange Tower and IFC 1 is carried out to find out the difficulties encountered during the operation of the living wall. Finally, an online survey is launched which aims at collecting public attitude towards implementation of the indoor living wall as well as how the system affects their psycho. The public shows a supportive attitude for the implementation of system, and they do think the system can help them to reduce stress and pressure. Recommendations are made for the design considerations and the way to enhance benefits. The suggestions on planning and environmental performance of indoor living wall are summarized in the form of checklists. / published_or_final_version / Environmental Management / Master / Master of Science in Environmental Management

Background: Sudden arrhythmia death syndrome (SADS) is a genotypically and phenotypically heterogeneous condition that might produce fatal ventricular arrhythmia in otherwise healthy individuals. Congenital long QT syndrome (LQTS) is the most common type of SADS with a frequency of 1 in 2500 individuals. Up to 13 genes have been shown to be associated with LQTS and genetic testing has a role in disease diagnosis, prognostication, treatment guidance, cascade testing, and reproductive counseling. Interdisciplinary care is the standard but such service is unavailable in Hong Kong. Objectives: In this study, we aim to evaluate the clinical characteristics of a local cohort of pediatric patients with LQTS, establish the practicability of a model on interdisciplinary delivery of care for SADS, and explore the process of genetic counseling in Chinese families with LQTS from the perspective of discourse analysis. Method: Pediatric patients with LQTS and their families were recruited from the Department of Paediatric Cardiology, Queen Mary Hospital between 1 January 2011 and 31 December 2012. With informed consent, patients underwent genetic testing for 6 LQTS genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2). Clinical characteristics were documented and the process of pre-test and post-test counseling was videotaped and transcribed. Data was mapped and analyzed for discourse strategies in the focal themes of uncertainty management in risk communication. Results: 19 patients were identified, 9 were male, with the corrected QT interval (QTc) ranging from 460-619ms. Mode of presentation included syncope (n=9), ventricular tachycardia (n=2), convulsion (n=1) and as incidental finding (n=7). Pathogenic mutations were identified in 9 patients (LQT1=3, LQT2=4, LQT3=1, LQT5=1), likely pathogenic mutations in 2 (LQT2), unclassified variants in 2, and no mutation in 6. Patients with pathogenic and likely pathogenic mutations had significantly longer mean QTc than those without such mutations (p=0.046). Three mutations, all in the LQT2 genes, represented novel mutations. All 3 patients with mutations in the pore-looping forming domains of the KCNH2 (LQT2) channel had personal or family histories of malignant arrhythmia or sudden cardiac death compatible with previously reported genotype-phenotype correlation. Eight families involving 18 family members underwent cascade testing, and family mutations were identified in 10 individuals from 6 families. Autosomal dominant transmission was the likely mode of inheritance in these 6 families. Counseling sessions involved the joint input from clinical geneticist, genetic counsellor and pediatric cardiologist. Discourse analysis on 2 counseling sessions of a selected family with unclassified variants revealed increased uncertainty after genetic testing in the index patient and family members. Strategies used to mitigate uncertainty included abstraction, generalization and categorization. Conclusion: Genetic testing was crucial in the comprehensive assessment of patients with congenital LQTS, and we demonstrated a feasible model to delivery interdisciplinary care for patients with SADS in Hong Kong. The process of genetic counseling is highly complex and deserves further examination. / published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Medical Sciences

Biliary atresia (BA) is a rare and severe cholestatic disease in neonates characterized by an idiopathic inflammatory process affecting both intra- and extra-hepatic bile ducts, causing cholestasis and ultimately leading to obliteration of the biliary tract. Through a previous genome-wide-association-study (GWAS) on Han Chinese, we discovered association of the 10q24.2 region encompassing ADD3 and XPNPEP1 gene. But disease pathogenesis and genetic architecture of BA is still obscure. We mapped the 10q24.2 association locus with 107 single nucleotide polymorphisms (SNPs) on 339 Han Chinese patients and 401 matched controls, follow-up studies of the association signals were performed. We revealed the common risk haplotype encompassing 5 tagging-SNPs, capturing the risk-predisposing alleles in 10q24.2 [logistic regression p=5.32x10-11; odds ratio, OR:2.38; confidence interval, CI:(2.14-2.62)]. No deleterious rare variants (RVs) residing on the risk haplotype were found, dismissing the theory of “synthetic” association. Moreover, the BA-associated potential regulatory SNPs correlated ADD3 gene expression (linear regression p=0.0030). Remarkably, the risk haplotype frequency coincides with BA incidences in the general population, and, positive selection (favoring the derived alleles that arose from mutations) was evident at the ADD3 locus. Our finding suggested the complexity of BA genetic architecture and role of environmental effects in the disease. We then revisited BA GWAS dataset and annotated the association signals with expression quantitative trail loci (eQTL) information available on normal adult livers. We did not see excessive enrichment of BA associated SNPs in liver eQTLs. We speculate that the liver eQTLs currently available relate to adulthood liver function and are not necessarily involved in liver development, adaptation to oxidative stress, or inflammation changes seen in BA pathophysiology. To investigate whether rare alleles can predispose to BA, we called copy number variations (CNVs) from the GWAS Affymetrix gene chip 5.0. We obtained 86 BA private CNVs distributed among 131 BA patients were compared to the CNV profile of 11,943 database samples and 846 hypertension disease samples. Assuming that pathogenic CNVs interrupt dosage-sensitive genes, we prioritized the dosage-sensitive genes and the pathogenic CNVs by integrating multiple lines of evidence. Through gene set enrichment analysis we found that the ‘core’ genes affected by BA CNVs were members of the Calcium signaling pathway, which has been involved in the pathogenesis of polycystic liver and kidney diseases. Further we initiated the survey on rare coding variants in BA through Exome sequencing 23 BA liver genomes, while patients’ blood DNA and parental DNA would be examined in the validation stage to validate de novo mutations, including somatic mosaicism in liver. We found inherited deleterious mutations in polycystic liver and kidney disease genes in BA patients, and the role of these mutations in BA pathogenesis is being investigated. Functional validation of the BA variants identified in this study is compulsory given the overall obscurity of BA pathogenesis. Together, this study presents a comprehensive catalog of both common and rare variants implicated in BA. We hope that our findings will contribute to enriching the BA-associated genetic network. / published_or_final_version / Surgery / Doctoral / Doctor of Philosophy

Esophageal cancer (EC), which is geographically diverse, has only a 10.7% five-year survival rate. One of the histologic forms, esophageal squamous cell carcinoma (ESCC), in Hong Kong accounts for 81.5% of the total EC cases and its five-year survival rate is only ~14%, due to its high frequency of metastasis. In our previous studies, functional complementation study of chromosome 9 defects led to the discovery of a novel tumor suppressor gene, Deleted in Esophageal Cancer 1 (DEC1), mapping to 9q32. DEC1 was shown to reduce tumorigenicity in a mouse model and its expression was shown to be associated with lymph node metastasis, early onset of ESCC, and familial ESCC development in a tissue microarray (TMA) study. Moreover, DNAJ (Hsp40) homologue subfamily B member 6 (DNAJB6), a molecular co-chaperone protein and the focus of the current study, was identified as a DEC1-interacting protein through a yeast two-hybrid screening. The interaction was further confirmed by the GST pull-down assay and co-localization studies. Using a TMA constructed with ESCC tissues from Hong Kong, the clinical relevance of DNAJB6 expression was demonstrated. In the present study, the role of DNAJB6 in ESCC was investigated using cell line-based in vivo and in vitro studies. DNAJB6 was shown to be down-regulated in ESCC cell lines. The two isoforms of DNAJB6 have distinct subcellular localizations, with DNAJB6a mainly localized to the nucleus and DNAJB6b diffused throughout the cell. Existence of a functional nuclear localization signal peptide and a functional nuclear export signal peptide was verified in DNAJB6a and DNAJB6b, respectively. In vitro evidence of possible DNAJB6a truncation was found. In vivo subcutaneous nude mice tumorigenicity assays showed that over-expression of DNAJB6a, but not DNAJB6b, suppresses tumor growth at the primary site, while DNAJB6a silencing enhances tumor growth. The suppressive effect of DNAJB6a depends on nuclear localization of the protein and the HPD tripeptide motif in the N-terminal J domain. In vitro function studies show that DNAJB6a over-expression impairs cell proliferation by suppressing G1/S transition. AKT1 phosphorylation is down-regulated in DNAJB6a over-expressed cells, leading to up-regulation of p27KIP1 protein expression and down-regulation of cyclin E1 protein expression, the G1/S transition promoter, in an AKT1-dependent manner. DNAJB6a silencing results in the opposite effect. Over-expression of DNAJB6b, but not DNAJB6a, instead suppresses lung colonization in an experimental metastasis assay, and prolongs survival of the mice. Silencing of DNAJB6a in immortalized normal esophageal epithelial cells initially induces a senescence-like phenotype with greatly reduced proliferation possibly due to oncogenic stress from up-regulation of AKT1 phosphorylation and cyclin E1 protein expression, but promotes EMT-like molecular alterations by up-regulating STAT3 phosphorylation and TWIST1 protein expression and resumes proliferation after prolonged culture. In summary, these results suggest that DNAJB6 plays a critical role in ESCC initiation, development, and metastasis and provides valuable insight into the understanding of ESCC tumorigenesis and metastasis. This suggests its usefulness as a biomarker candidate for detecting early ESCC tumor initiation. / published_or_final_version / Clinical Oncology / Doctoral / Doctor of Philosophy