28 results on '"Tsang SK"'
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2. BUCKLING BEHAVIOUR UNDER PRESSURE OF CYLINDRICAL SHELLS REINFORCED BY LIGHT RING STIFFENERS.
- Author
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TSANG, SK, primary and HARDING, JE, additional
- Published
- 1985
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3. Development of a Health Empowerment Programme to improve the health of working poor families: protocol for a prospective cohort study in Hong Kong.
- Author
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Fung CS, Yu EY, Guo VY, Wong CK, Kung K, Ho SY, Lam LY, Ip P, Fong DY, Lam DC, Wong WC, Tsang SK, Tiwari AF, and Lam CL
- Subjects
- Cohort Studies, Hong Kong, Humans, Poverty, Prospective Studies, Quality of Life, Self Care, Self Efficacy, Family Health, Health Knowledge, Attitudes, Practice, Health Literacy, Health Promotion methods, Health Services Accessibility, Health Status, Power, Psychological, Working Poor
- Abstract
Introduction: People from working poor families are at high risk of poor health partly due to limited healthcare access. Health empowerment, a process by which people can gain greater control over the decisions affecting their lives and health through education and motivation, can be an effective way to enhance health, health-related quality of life (HRQOL), health awareness and health-seeking behaviours of these people. A new cohort study will be launched to explore the potential for a Health Empowerment Programme to enable these families by enhancing their health status and modifying their attitudes towards health-related issues. If proven effective, similar empowerment programme models could be tested and further disseminated in collaborations with healthcare providers and policymakers., Method and Analysis: A prospective cohort study with 200 intervention families will be launched and followed up for 5 years. The following inclusion criteria will be used at the time of recruitment: (1) Having at least one working family member; (2) Having at least one child studying in grades 1-3; and (3) Having a monthly household income that is less than 75% of the median monthly household income of Hong Kong families. The Health Empowerment Programme that will be offered to intervention families will comprise four components: health assessment, health literacy, self-care enablement and health ambassador. Their health status, HRQOL, lifestyle and health service utilisation will be assessed and compared with 200 control families with matching characteristics but will not receive the health empowerment intervention., Ethics and Dissemination: This project was approved by the University of Hong Kong-the Hospital Authority Hong Kong West Cluster IRB, Reference number: UW 12-517. The study findings will be disseminated through a series of peer-reviewed publications and conference presentations, as well as a yearly report to the philanthropic funding body-Kerry Group Kuok Foundation (Hong Kong) Limited., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)
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- 2016
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4. Conceptualizing and Validating Marital Quality in Beijing: A Pilot Study.
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Zhang H, Xu X, and Tsang SK
- Abstract
Since the inception of the economic reform, marital relationship in urban China has undergone dramatic transformations. Though the burgeoning body of scholarly research has demonstrated that marital quality has increasingly become an important aspect of family life among married persons in urban China, both the conceptualization and measurement of marital quality remain underdeveloped. The purpose of this pilot study is to develop and validate a comprehensive and culturally appropriate marital quality scale, namely the Chinese Marital Quality Scale (CMQS). Results from the confirmatory factor analysis (CFA) conducted on a sample of 387 married persons from Beijing indicate that the CMQS can be conceptualized as a two-factorial and multidimensional construct, encompassing marital happiness, marital interaction, marital disagreement, marital problem, and marital instability. Additional statistical analyses also indicate that the CMQS has exhibited satisfactory reliability and concurrent validity. It is thus concluded that the CMQS is a reliable and valid instrument to measure marital quality in contemporary Beijing and possibly in other Chinese cities.
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- 2013
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5. Effects of chronic ketamine use on frontal and medial temporal cognition.
- Author
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Chan KW, Lee TM, Siu AM, Wong DP, Kam CM, Tsang SK, and Chan CC
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- Attention drug effects, Case-Control Studies, Dose-Response Relationship, Drug, Female, Humans, Male, Memory Disorders chemically induced, Neuropsychological Tests, Verbal Learning drug effects, Young Adult, Cognition Disorders chemically induced, Excitatory Amino Acid Antagonists adverse effects, Ketamine adverse effects, Language Disorders chemically induced, Substance-Related Disorders complications
- Abstract
Background: Recreational ketamine use has been on the rise worldwide. Previous studies have demonstrated that it disrupts various memory systems, but few studies have examined how it affects learning and frontal functioning. The present study investigates the effects of repeated ketamine self-administration on frontal fluency, attention, learning, and memory along the verbal/nonverbal axis., Methods: Twenty-five ketamine users and 30 healthy controls took a battery of neuropsychological tests. Frontal fluency was measured by the Verbal Fluency Test for semantic organization ability and the Figural Fluency Test for nonverbal executive functioning. Learning and memory were measured with the Chinese Auditory-Verbal Learning Test for acquisition and retention abilities of verbal information, as well as with the Continuous Visual Memory Test for nonverbal information. Participants also took several tests tapping subdomains of attention. To test for the potential effects of other drug use, 10 polydrug controls were included for comparison with the ketamine users and healthy controls., Results: Ketamine users had impaired verbal fluency, cognitive processing speed, and verbal learning. Verbal learning impairment was strongly correlated with estimated lifetime ketamine use. Ketamine users showed no impairments in figural fluency, sustained attention, selective attention, visual learning, or verbal/nonverbal memory. However, heavier lifetime ketamine use was significantly correlated with deficits in verbal memory (both immediate recall and delayed recall) and visual recognition memory. Deficits in cognitive processing speed and verbal learning persisted even after polydrug controls were included in the control group, but their inclusion did make the impairment in verbal fluency barely reach statistical significance., Conclusions: This study suggests that repeated ketamine use causes differential impairment to multiple domains of frontal and medial temporal functioning, possibly specific to verbal information processing., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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6. Validation of the Chinese version of the Gamblers' Belief Questionnaire (GBQ-C).
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Wong SS and Tsang SK
- Subjects
- Adolescent, Asian People, Child, Factor Analysis, Statistical, Female, Humans, Language, Male, Psychometrics instrumentation, Reproducibility of Results, Surveys and Questionnaires standards, Culture, Gambling psychology
- Abstract
A growing body of evidence is documenting the significant role of cognitive factors in influencing gambling behaviors. Although measures of cognitive biases have been developed, further validation of these scales is needed among non-Western samples. The 21-item Gamblers' Belief Questionnaire was originally developed and validated by Steenbergh et al. (in Psychol. Addict. Behav., 16: 143-149, 2002). The scale then has been widely used in the gambling research of the West. The present study was designed to examine and validate the Chinese version of Gamblers' Belief Questionnaire (GBQ-C) using 258 Chinese participants. Confirmatory factor analyses indicated the 2-factor model provided a good fit to the data as evidenced by various model fit indices (CFI = .91, RMSEA = .08 and SRMR = .05). Additional evidence for the validity of the GBQ-C was provided by significant correlations with other relevant measures (range .40-.75). In sum, the present study provides support for the GBQ-C as a valuable tool for assessing gambling cognitions among Chinese samples.
- Published
- 2012
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7. Self-determination as a psychological and positive youth development construct.
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Hui EK and Tsang SK
- Subjects
- Adolescent, Concept Formation, Persons with Disabilities, Humans, Motivation, Parenting psychology, Psychological Theory, Students, Teaching, Adolescent Development, Personal Autonomy
- Abstract
This paper presents a review of self-determination as a positive youth development construct. The definition and conceptualization of the concept are examined from the perspective of self-determination theory and the functional theory of self-determination. Theories of self-determination from the perspective of motivation and skills enhancement are examined. Factors contributing to self-determination, such as autonomy-supportive teaching and parenting style, culture, efficacy of intervention programmes, and the educational benefits of self-determination for students, are discussed. Strategies to promote self-determination in an educational context and implications for further research and practice are discussed.
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- 2012
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8. Self-efficacy as a positive youth development construct: a conceptual review.
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Tsang SK, Hui EK, and Law BC
- Subjects
- Adolescent, Behavior, Cognition, Concept Formation, Culture, Female, Humans, Male, Motivation, Social Behavior, Thinking, Adolescent Development, Psychology methods, Self Efficacy
- Abstract
Self-efficacy denotes people's beliefs about their ability to perform in different situations. It functions as a multilevel and multifaceted set of beliefs that influence how people feel, think, motivate themselves, and behave during various tasks. Self-efficacy beliefs are informed by enactive attainment, vicarious experience, imaginal experiences, and social persuasion as well as physical and emotional states. These beliefs are mediated by cognitive, motivational, affective, and selection processes to generate actual performance. Self-efficacy development is closely intertwined with a person's experiences, competencies, and developmental tasks in different domains at different stages in life. This paper reviews the literature to outline the definition and theoretical conceptualizations of the construct originally devised by Bandura that have flourished since the 1990s. Drawing from the studies of the construct to assess self-efficacy, and to inform positive youth development, the paper will present the determinants of the development of self-efficacy beliefs and identify the connection between self-efficacy and adolescent developmental outcomes. The paper will conclude with strategies to enhance youth self-efficacy and proposals for future research directions.
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- 2012
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9. Positive identity as a positive youth development construct: a conceptual review.
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Tsang SK, Hui EK, and Law BC
- Subjects
- Adolescent, Female, Humans, Interpersonal Relations, Male, Models, Psychological, Adolescent Development, Self Concept
- Abstract
Identity is a core construct in psychology because it refers to how a person addresses issues dealing with who that person is. Important theorists studying the concept of identity, like Erikson, Marcia, and Higgins, assert that identity is organized,is learned, and is dynamic, and a subjective evaluation of an individual's identity has emotional consequences for that individual. Adolescents who can cultivate a clear and positive identity after their developmental struggles during adolescence often advance more smoothly into adulthood. This paper reviews literature on the nature and structure of identity and examines its importance on adolescent developmental outcomes. It traces significant determinants of identity and proposes strategies for cultivation of positive identity. Observations on current research gaps in the study of identity and future research directions will also be discussed.
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- 2012
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10. Bystander position taking in school bullying: the role of positive identity, self-efficacy, and self-determination.
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Tsang SK, Hui EK, and Law BC
- Subjects
- Adolescent, Adolescent Behavior psychology, Adolescent Development, Aggression psychology, Child, Curriculum, Hong Kong, Humans, Mental Competency psychology, Students psychology, Bullying psychology, Personal Autonomy, Reinforcement, Psychology, Schools organization & administration, Self Efficacy, Social Support
- Abstract
School bullying has become an explicit, burgeoning problem challenging the healthy development of children and adolescents in Hong Kong. Many bullying prevention and intervention programs focus on victims and bullies, with bystanders treated as either nonexistent or irrelevant. This paper asserts that bystanders actually play pivotal roles in deciding whether the bullying process and dynamics are benign or adversarial. Bystanders' own abilities and characteristics often influence how they respond to victims and bullies. "P.A.T.H.S. to Adulthood: A Jockey Club Youth Enhancement Scheme" (P.A.T.H.S. = Positive Adolescent Training through Holistic Social Programmes) is an evidence-based positive youth development program which shows that primary intervention programs have constructive impacts on junior secondary school students' beliefs and behavior. This paper asserts that intrapsychic qualities, namely identity, self-efficacy, and self-determination, greatly influence how bystanders react in school bullying situations. The paper also explains how classroom-based educational programs based on the P.A.T.H.S. model have been designed to help junior secondary school students strengthen these characteristics, so that they can be constructive bystanders when they encounter school bullying.
- Published
- 2011
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11. Parent engagement in youth drug prevention in Chinese families: advancement in program development and evaluation.
- Author
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Tsang SK
- Subjects
- Adolescent, Adolescent Behavior psychology, Asian People psychology, Hong Kong, Humans, Parents education, Substance-Related Disorders psychology, Adolescent Development, Family Relations, Parents psychology, Program Development methods, Program Evaluation methods, Substance-Related Disorders prevention & control
- Abstract
The escalating youth drug abuse problem in Hong Kong has attracted intense attention from the government, schools, and youth service professionals. Most preventive efforts have focused directly on positive youth development, very often through school programs delivered to secondary school students. There have been limited efforts to engage parents even though it is obvious that the family is actually the primary context of children and youth development. This paper will assert the importance of parental engagement in youth drug-prevention work, discuss some barriers in such parental involvement, present some promising local attempts and their strengths and limitations, and propose that sustained efforts are needed to build up theory-driven and evidence-based resources for Chinese communities on the subject.
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- 2011
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12. Combating school bullying through developmental guidance for positive youth development and promoting harmonious school culture.
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Hui EK, Tsang SK, and Law BC
- Subjects
- Adolescent, Adolescent Behavior psychology, Child, Child Guidance organization & administration, Counseling, Faculty, Forgiveness, Hong Kong, Humans, Social Behavior, Social Support, Students psychology, Violence psychology, Young Adult, Adolescent Development, Bullying psychology, Child Guidance methods, Schools organization & administration, Violence prevention & control
- Abstract
Bullying and violence, which can bring detrimental effects, are situations which young people have to face in their process of development. Though school bullying has been a spreading and explicit problem in Hong Kong schools, most of the programs or guidelines dealing with the problem lack citywide, recognized initiatives and the effectiveness of these programs is unknown due to the lack of evaluation. The present paper discusses preventing school bullying from a developmental guidance perspective, using the positive youth development paradigm and promoting the values of harmony and forgiveness at the whole-school level to cultivate a harmonious school culture as a way of combating school bullying.
- Published
- 2011
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13. Subjective outcome evaluation of the project P.A.T.H.S.: Findings based on the perspective of the program implementers (secondary 1 program).
- Author
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Tsang SK, Hui EK, Shek DT, and Law BC
- Subjects
- Adolescent, Aging, Humans, Models, Educational, Surveys and Questionnaires, Education, Program Evaluation
- Abstract
The aim of the current study was to replicate the subjective outcome evaluation based on program implementers in the first year (2006/07 school year) of the Full Implementation Phase (Secondary 1 level) of the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes). After the completion of the Tier 1 program in the 2007/08 school year, 1324 implementers from 213 schools completed a Subjective Outcome Evaluation Form for instructors in order to assess their views of the program, themselves, and the perceived effectiveness of the program. Reliability test indicated the questionnaire was internally consistent. The results showed that, similar to the first year of implementation, high proportions of the respondents had positive perceptions of the program and their own performance. Regarding the perceived effectiveness of the program, roughly 90% of the respondents thought the program was helpful. A statistically significant increase in positive responses was also found in some items of perceived effectiveness in the second year of implementation. Possible factors contributing to such changes, including accumulation of experience and skill enhancement of the implementers, as well as stronger support from the schools, are discussed.
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- 2010
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14. The Chinese Parental Stress Scale: psychometric evidence using Rasch modeling on clinical and nonclinical samples.
- Author
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Leung C and Tsang SK
- Subjects
- Adult, Child, Female, Hong Kong, Humans, Male, Middle Aged, Models, Statistical, Personality, Parents psychology, Psychometrics, Stress, Psychological ethnology, Surveys and Questionnaires
- Abstract
In this study, we examined the psychometric properties of the Parental Stress Scale (PSS; Berry & Jones, 1995) with Chinese parents. Participants included 162 parents recruited through primary schools and 38 parents with children with attention deficit hyperactivity disorder (ADHD). Rasch analysis results indicated that 2 items were outside the accepted fit statistics range and that the Likert scale response categories were not functioning properly. We identified a reduced 16-item scale with 5 categories as unidimensional, with a person reliability of .86; the Likert scale response categories worked well. The revised PSS correlated with measures of child behavior and parenting stress and could differentiate between the 2 groups of parents.
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- 2010
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15. Cough mixture abuse as a novel cause of folate deficiency: a prospective, community-based, controlled study.
- Author
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Au WY, Tsang SK, Cheung BK, Siu TS, Ma ES, and Tam S
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- Adult, Case-Control Studies, Data Collection, Dental Caries chemically induced, Erythrocyte Indices, Female, Folic Acid Deficiency blood, Folic Acid Deficiency epidemiology, Hemoglobins analysis, Hong Kong epidemiology, Humans, Incidence, Male, Mass Screening, Nervous System Diseases chemically induced, Platelet Count, Prospective Studies, Substance-Related Disorders blood, Substance-Related Disorders epidemiology, Vitamin B 12 Deficiency blood, Vitamin B 12 Deficiency chemically induced, Vitamin B 12 Deficiency epidemiology, Antitussive Agents adverse effects, Codeine adverse effects, Dextromethorphan adverse effects, Folic Acid Deficiency chemically induced, Substance-Related Disorders complications
- Abstract
Cough mixture abuse has been reported to cause severe folate deficiency and neurological defects. We carried out a prospective case-controlled survey to confirm this association and define the incidence and severity of the problem. A total of 57 cough mixture abusers and 47 other substance abusers (controls) were studied. When compared with controls, cough mixture abusers had a high incidence of low folate levels that could only be detected by screening.
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- 2007
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16. Brief report: application of the TEACCH program on Chinese pre-school children with autism--Does culture make a difference?
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Tsang SK, Shek DT, Lam LL, Tang FL, and Cheung PM
- Subjects
- Autistic Disorder diagnosis, Child, Preschool, China, Female, Humans, Male, Surveys and Questionnaires, Asian People, Autistic Disorder therapy, Culture, Education, Special, Program Development, Teaching methods
- Abstract
A longitudinal study was conducted on 34 children with autism to evaluate the usefulness of the Treatment and Education of Autistic and related Communication Handicapped Children (TEACCH) program for Chinese pre-school children in Hong Kong. Eighteen children received full-time center-based TEACCH program training. The control group included 16 children who received different types of individualized or group training but not TEACCH program training. Instruments validated in Hong Kong were used to assess the children's cognitive, social adaptive functioning and developmental abilities before and during the training at 6-month intervals for 12 months. Children in the experimental group showed better outcomes at posttest. They also showed progress in different developmental domains over time. The study provided initial support for the effectiveness of using the TEACCH program with Chinese children.
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- 2007
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17. Self-efficacy as a positive youth development construct: conceptual bases and implications for curriculum development.
- Author
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Tsang SK and Hui EK
- Subjects
- Adolescent, Culture, Female, Hong Kong, Humans, Male, Sex Factors, Adolescent Development, Concept Formation, Curriculum, Self Efficacy
- Abstract
Self-efficacy denotes people's beliefs about their capabilities to perform in different situations. It functions as a multilevel and multifaceted set of beliefs that influence how people feel, think, motivate themselves, and behave. Self-efficacy beliefs are informed by enactive attainment, vicarious experience, imaginal experiences, social persuasion, as well as physical and emotional states. These beliefs are mediated by cognitive, motivational, affective, and selection processes to generate actual performance. Self-efficacy development is closely intertwined with a person's experiences, competencies, and developmental tasks in different domains at different life stages. This paper outlines the conceptualization of the construct and presents how its determinants are used in Positive Adolescent Training through Holistic Social Programmes (P.A.T.H.S.), supported by the Hong Kong Jockey Club Charities Trust, to help adolescents cultivate self-efficacy.
- Published
- 2006
18. Self-determination as a positive youth development construct: conceptual bases and implications for curriculum development.
- Author
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Hui EK and Tsang SK
- Subjects
- Adolescent, Culture, Female, Hong Kong, Humans, Male, Sex Factors, Adolescent Development, Concept Formation, Curriculum, Personal Autonomy
- Abstract
This paper outlines the conceptualization of self-determination from the perspectives of motivation, skills enhancement and positive youth development. Self-determination, as a positive youth development construct in the Hong Kong Positive Youth Development Program (P.A.T.H.S.), refers to young people's ability to set goals and make choices according to his/her own thinking. In accordance with adolescents' developmental needs, the key components which cultivate self-determination in this Curriculum include self-awareness, goal setting, problem solving and choice making. Eight Units are devised which target at cultivating self-determination as a positive youth construct. In addition, other Units which targets at fostering bonding, social, emotional, cognitive competence, self-efficacy and self-identity also reinforce the cultivation of self-determination. This paper also includes strategies which schools may adopt to foster an autonomy supportive learning environment.
- Published
- 2006
19. Positive identity as a positive youth development construct: conceptual bases and implications for curriculum development.
- Author
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Tsang SK and Yip FY
- Subjects
- Adolescent, Culture, Female, Hong Kong, Humans, Male, Sex Factors, Adolescent Development, Concept Formation, Curriculum, Self Concept
- Abstract
According to the theories of Erikson, Marcia, and Higgins, adolescents who can cultivate a clear and positive identity after their developmental struggles in adolescence often advance more smoothly into adulthood. Identity is organized, learned, and dynamic, and subjective evaluation of an individual's identity has emotional consequences for that individual. This paper discusses literature on the nature and importance of identity and presents strategies such as self-esteem enhancement, management of exploration and commitment, as well as reduction of self-discrepancies to help adolescents develop functional identity. Significant determinants of a person's identity development, namely gender and cultural issues, are also addressed as they are important in designing the "Positive Identity Development" package of Positive Adolescent Training through Holistic Social Programmes (P.A.T.H.S.), supported by the Hong Kong Jockey Club Charities Trust, to help adolescents develop a positive identity.
- Published
- 2006
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20. Cough mixture abuse in pregnancy, folate deficiency, and neural tube defects?
- Author
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Tsang SK and Au WY
- Subjects
- Adult, Female, Humans, Infant, Newborn, Infant, Newborn, Diseases chemically induced, Male, Pregnancy, Pregnancy Complications chemically induced, Antitussive Agents adverse effects, Folic Acid Deficiency chemically induced, Neural Tube Defects chemically induced, Substance-Related Disorders complications
- Published
- 2005
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21. Psychometric properties of the Chinese version of the Psycho-educational Profile-Revised (CPEP-R).
- Author
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Shek DT, Tsang SK, Lam LL, Tang FL, and Cheung PM
- Subjects
- Asian People statistics & numerical data, Autistic Disorder ethnology, Autistic Disorder psychology, Autistic Disorder rehabilitation, Child, Preschool, Developmental Disabilities ethnology, Developmental Disabilities psychology, Developmental Disabilities rehabilitation, Female, Hong Kong, Humans, Male, Psychometrics statistics & numerical data, Reproducibility of Results, Asian People psychology, Autistic Disorder diagnosis, Developmental Disabilities diagnosis, Early Intervention, Educational, Needs Assessment statistics & numerical data, Neuropsychological Tests statistics & numerical data, Personality Assessment statistics & numerical data
- Abstract
The purpose of this study was to examine the reliability and validity of the Chinese version of the Psycho-educational Profile-Revised (PEP-R). The Chinese PEP-R (CPEP-R) was administered to 63 preschool children with symptoms of autistic disorder recruited from special child-care centers in Hong Kong. Results showed that the scales of the CPEP-R were internally consistent, reliable across raters and temporally stable. Regarding the concurrent validity of the CPEP-R, the developmental score and developmental age assessed by the CPEP-R were significantly correlated with the Merrill-Palmer Scale of Mental Tests and the Hong Kong Based Adaptive Behavior Scale. The Behavioral Scale of the CPEP-R was also significantly related to the Childhood Autism Rating Scale. Besides replicating the findings in the Western context, the present study suggests that the psychometric properties of the PEP-R are stable across cultures and the related findings support the cross-cultural reliability of the tool.
- Published
- 2005
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22. Use of MCSS to design small targeted libraries: application to picornavirus ligands.
- Author
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Joseph-McCarthy D, Tsang SK, Filman DJ, Hogle JM, and Karplus M
- Subjects
- Benzimidazoles metabolism, Binding Sites, Capsid metabolism, Crystallography, X-Ray, Ligands, Models, Molecular, Poliovirus chemistry, Poliovirus drug effects, Protein Binding, Protein Conformation, Rhinovirus chemistry, Rhinovirus drug effects, Structure-Activity Relationship, Benzimidazoles chemistry, Capsid chemistry, Combinatorial Chemistry Techniques methods, Poliovirus metabolism, Rhinovirus metabolism
- Abstract
Computational methods were used to design structure-based combinatorial libraries of antipicornaviral capsid-binding ligands. The multiple copy simultaneous search (MCSS) program was employed to calculate functionality maps for many diverse functional groups for both the poliovirus and rhinovirus capsid structures in the region of the known drug binding pocket. Based on the results of the MCSS calculations, small combinatorial libraries consisting of 10s or 100s of three-monomer compounds were designed and synthesized. Ligand binding was demonstrated by a noncell-based mass spectrometric assay, a functional immuno-precipitation assay, and crystallographic analysis of the complexes of the virus with two of the candidate ligands. The P1/Mahoney poliovirus strain was used in the experimental studies. A comparison showed that the MCSS calculations had correctly identified the observed binding site for all three monomer units in one ligand and for two out of three in the other ligand. The correct central monomer position in the second ligand was reproduced in calculations in which the several key residues lining the pocket were allowed to move. This study validates the computational methodology. It also illustrates that subtle changes in protein structure can lead to differences in docking results and points to the importance of including target flexibility, as well as ligand flexibility, in the design process.
- Published
- 2001
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23. Kinetic analysis of the effect of poliovirus receptor on viral uncoating: the receptor as a catalyst.
- Author
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Tsang SK, McDermott BM, Racaniello VR, and Hogle JM
- Subjects
- Capsid metabolism, HeLa Cells, Humans, Kinetics, Models, Theoretical, Poliovirus drug effects, Receptors, Virus metabolism, Antiviral Agents pharmacology, Poliovirus physiology, Receptors, Virus physiology
- Abstract
We examined the role of soluble poliovirus receptor on the transition of native poliovirus (160S or N particle) to an infectious intermediate (135S or A particle). The viral receptor behaves as a classic transition state theory catalyst, facilitating the N-to-A conversion by lowering the activation energy for the process by 50 kcal/mol. In contrast to earlier studies which demonstrated that capsid-binding drugs inhibit thermally mediated N-to-A conversion through entropic stabilization alone, capsid-binding drugs are shown to inhibit receptor-mediated N-to-A conversion through a combination of enthalpic and entropic effects.
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- 2001
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24. A structurally biased combinatorial approach for discovering new anti-picornaviral compounds.
- Author
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Tsang SK, Cheh J, Isaacs L, Joseph-McCarthy D, Choi SK, Pevear DC, Whitesides GM, and Hogle JM
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- Animals, Antiviral Agents chemistry, Antiviral Agents pharmacology, Capsid metabolism, Cytopathogenic Effect, Viral drug effects, Drug Evaluation, Preclinical, HeLa Cells, Humans, In Vitro Techniques, Picornaviridae metabolism, Radioligand Assay, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Antiviral Agents chemical synthesis, Combinatorial Chemistry Techniques methods, Drug Design, Picornaviridae drug effects
- Abstract
Background: Picornaviruses comprise a family of small, non-enveloped RNA viruses. A common feature amongst many picornaviruses is a hydrophobic pocket in the core of VP1, one of the viral capsid proteins. The pocket is normally occupied by a mixture of unidentified, fatty acid-like moieties, which can be competed out by a family of capsid-binding, antiviral compounds. Many members of the Picornaviridae family are pathogenic to both humans and livestock, yet no adequate therapeutics exist despite over a decade's worth of research in the field. To address this challenge, we developed a strategy for rapid identification of capsid-binding anti-picornaviral ligands. The approach we took involved synthesizing structurally biased combinatorial libraries that had been targeted to the VP1 pocket of poliovirus and rhinovirus. The libraries are screened for candidate ligands with a high throughput mass spectrometry assay., Results: Using the mass spectrometry assay, we were able to identify eight compounds from a targeted library of 75 compounds. The antiviral activity of these candidates was assessed by (i) measuring the effect on the kinetics of viral uncoating and (ii) the protective effect of each drug in traditional cell-based assays. All eight of the candidates exhibited antiviral activity, but three of them were particularly effective against poliovirus and rhinovirus., Conclusions: The results illustrate the utility of combining structure-based design with combinatorial chemistry. The success of our approach suggests that assessment of small, targeted libraries, which query specific chemical properties, may be the best strategy for surveying all of chemical space for ideal anti-picornaviral compounds.
- Published
- 2001
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25. Stabilization of poliovirus by capsid-binding antiviral drugs is due to entropic effects.
- Author
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Tsang SK, Danthi P, Chow M, and Hogle JM
- Subjects
- Antiviral Agents pharmacology, Microbial Sensitivity Tests, Molecular Conformation, Poliovirus drug effects, Protein Binding, Receptors, Virus antagonists & inhibitors, Temperature, Thermodynamics, Antiviral Agents metabolism, Capsid metabolism, Poliovirus chemistry, Poliovirus metabolism
- Abstract
When poliovirus attaches to its receptor or is heated in hypotonic buffers, the virion undergoes an irreversible conformational transition from the native 160 S (or N) particle to the 135 S (or A) particle, which is believed to mediate cell entry. The first-order rate constants for the thermally induced transition have been measured as a function of temperature for virus alone and for complexes of the virus with capsid-binding drugs that inhibit the receptor and thermally mediated conversion. Although the drugs have minimum inhibitory concentrations (MIC) that differ by almost three orders of magnitude, the activation energies for the N to A transition for the drug complexes (145 kcal/mol) were indistinguishable from each other or from that of the virus alone. We conclude that the antiviral activity of these drugs derives from a novel mechanism in which drug-binding stabilizes the virions through entropic effects., (Copyright 2000 Academic Press.)
- Published
- 2000
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26. Molecular tectonic model of virus structural transitions: the putative cell entry states of poliovirus.
- Author
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Belnap DM, Filman DJ, Trus BL, Cheng N, Booy FP, Conway JF, Curry S, Hiremath CN, Tsang SK, Steven AC, and Hogle JM
- Subjects
- Capsid chemistry, Cryoelectron Microscopy, Crystallography, X-Ray, Image Processing, Computer-Assisted, Models, Biological, Models, Molecular, Nucleic Acid Conformation, Poliovirus metabolism, Protein Conformation, RNA, Viral chemistry, RNA, Viral ultrastructure, Receptors, Virus metabolism, Virion chemistry, Virion ultrastructure, Capsid ultrastructure, Membrane Proteins, Poliovirus chemistry, Poliovirus ultrastructure
- Abstract
Upon interacting with its receptor, poliovirus undergoes conformational changes that are implicated in cell entry, including the externalization of the viral protein VP4 and the N terminus of VP1. We have determined the structures of native virions and of two putative cell entry intermediates, the 135S and 80S particles, at approximately 22-A resolution by cryo-electron microscopy. The 135S and 80S particles are both approximately 4% larger than the virion. Pseudoatomic models were constructed by adjusting the beta-barrel domains of the three capsid proteins VP1, VP2, and VP3 from their known positions in the virion to fit the 135S and 80S reconstructions. Domain movements of up to 9 A were detected, analogous to the shifting of tectonic plates. These movements create gaps between adjacent subunits. The gaps at the sites where VP1, VP2, and VP3 subunits meet are plausible candidates for the emergence of VP4 and the N terminus of VP1. The implications of these observations are discussed for models in which the externalized components form a transmembrane pore through which viral RNA enters the infected cell.
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- 2000
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27. Thyroid hemiagenesis accompanying a thyroglossal duct cyst: a case report.
- Author
-
Tsang SK and Maher J
- Subjects
- Humans, Iodine Radioisotopes, Male, Middle Aged, Radionuclide Imaging, Thyroglossal Cyst diagnostic imaging, Thyroglossal Cyst embryology, Thyroid Gland diagnostic imaging, Thyroid Gland embryology, Thyroglossal Cyst complications, Thyroid Gland abnormalities
- Abstract
A case of thyroid hemiagenesis discovered incidentally in a patient presenting with a thyroglossal duct cyst is reported. Thyroid embryology is briefly reviewed. Various characteristics of thyroid hemiagenesis and thyroglossal duct cysts are explored.
- Published
- 1998
- Full Text
- View/download PDF
28. Reliability and factor structure of the Chinese GHQ-30 for parents with preschool mentally handicapped children.
- Author
-
Shek DT and Tsang SK
- Subjects
- Adaptation, Psychological, Child, Preschool, China, Consumer Behavior, Education of Persons with Intellectual Disabilities, Factor Analysis, Statistical, Female, Humans, Male, Parent-Child Relations, Parenting psychology, Psychometrics, Reproducibility of Results, Cross-Cultural Comparison, Intellectual Disability psychology, Parents psychology, Personality Inventory statistics & numerical data
- Abstract
The Chinese version of the General Health Questionnaire (GHQ-30) was administered to 381 parents of preschool mentally handicapped children, along with other instruments that assessed their stress, mental health, coping styles, and care-giving patterns. The GHQ-30 was found to have high internal consistency as a scale and high item-total correlations for most of the items. Factor analysis with a four-factor solution showed that four factors were abstracted from the scale, namely, anxiety, depression, interpersonal dysfunctioning, and inadequate coping. It also was found that the factors extracted could be reproduced reliably in two random subsamples and that the factor structure derived from the present sample corresponds to the previously reported data on the dimensionality of the Chinese GHQ-30.
- Published
- 1995
- Full Text
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