Background. In the United States, adolescents are the age group least likely to be aware of their HIV infection and linked to care in a timely manner, contributing to disproportionately low rates of viral suppression and increased risk of transmitting HIV to others. A major barrier to health care for adolescents relates to confidentiality concerns, such as fears that parent/guardian consent will be required or that parents, guardians, or others will be informed of test results. This suggests that state laws related to confidentiality in sexual and reproductive health services could influence their HIV testing practices. Guided by Andersen’s Behavioral Model of Health Services Use, this dissertation utilizes a large, representative sample of sexually active high school students from the 2019 state-level Youth Risk Behavior Surveillance System (YRBSS) to investigate the potential impact of five state-level confidentiality-relevant laws on U.S. adolescents’ HIV testing practices. Methods. Data on HIV testing and individual characteristics (i.e., potential individual-level confounders/covariates) were aggregated from 25 states that participated in the 2019 state-level YRBSS. Data on contextual characteristics (i.e., potential state-level confounders/covariates) were obtained from the United States Census Bureau and the Behavior Risk Factor Surveillance System. Information about state-level confidentiality-relevant laws was compiled from the Guttmacher Institute and the Center for HIV Law and Policy to create five variables indicating whether state laws were confidentiality-promoting at the time of the 2019 state-level YRBSS. Multilevel logistic regression was used to test the following hypotheses: 1. After adjusting for individual and contextual characteristics, confidentiality-promoting state laws will be positively associated with HIV testing among sexually active U.S. high school students, such that odds of self-reported lifetime HIV testing will be significantly higher when states (a) explicitly allow minors to consent to HIV testing, (b) do not have age of consent requirements, (c) do not permit parental/guardian notification, (d) protect the confidentiality of minors insured as dependents, and (e) do not have HIV-specific criminal laws that require disclosure to sexual and/or needle-sharing partners, as compared to states with non-confidentiality-promoting laws. 2. After adjusting for individual and contextual characteristics, sex will moderate the relationship between state-level confidentiality-relevant laws and HIV testing among sexually active U.S. high school students, such that associations between confidentiality-promoting state laws and self-reported lifetime HIV testing will significantly differ between males and females. 3. After adjusting for individual and contextual characteristics, young men who have sex with men (YMSM) status will moderate the relationship between state-level confidentiality-relevant laws and HIV testing among sexually active male high school students, such that associations between confidentiality-promoting state laws and lifetime HIV testing will be significantly stronger among males who report same-sex sexual contact than among males who report opposite-sex sexual contact only. Results. Findings supported the first hypothesis that parental notification not being permitted would be positively associated with HIV testing among sexually active U.S. high school students. After adjusting for individual (i.e., sex, grade level, race/ethnicity, sexual identity) and contextual (i.e., percentage of the state population aged 25 and older with a high school diploma or higher, median household income, lifetime HIV testing among adults) characteristics, odds of self-reported lifetime HIV testing were significantly higher in states that do not permit parent/guardian notification (adjusted odds ratio [aOR]: 1.07; 95% confidence interval [CI]: 1.04-1.11; p<.001) than in states that allow health care providers to inform parents or guardians that their child is seeking or receiving STI services. However, results did not support the hypothesis that the other confidentiality-promoting state laws would be positively associated with HIV testing among sexually active U.S. high school students; as compared to states with non-confidentiality-promoting laws, odds of self-reported lifetime HIV testing were significantly lower in states that explicitly allow minors to consent to HIV testing, do not have age requirements to consent to HIV testing, and do not have HIV-specific criminal laws that require disclosure. Results supported the second hypothesis that sex would moderate the relationship between state-level confidentiality-relevant laws and HIV testing among sexually active U.S. high school students, as associations between confidentiality-promoting state laws and lifetime HIV testing differed significantly between males and females. After adjusting for individual and contextual characteristics, the effects of living in a state without age requirements or HIV-specific criminal laws with disclosure requirements on lifetime HIV testing for females were 1.53 (CI: 1.07-2.20; p=.020) and 1.56 (CI: 1.16-2.10; p=.003) times those of males, respectively. Meanwhile, the effects of state laws that explicitly allow minors to consent to HIV testing, do not permit parental notification, and protect the confidentiality of minors insured as dependents on lifetime HIV testing for females were 0.73 (CI: 0.55-0.96; p=.025), 0.72 (CI: 0.52-0.99; p=.043), and 0.66 (CI: 0.48-0.90; p=.008) times those of males, respectively. Analyses with these data failed to reject the null hypothesis for the third [alternative] hypothesis that associations between confidentiality-promoting state laws and self-reported lifetime HIV testing would be significantly stronger among sexually active males who report same-sex sexual contact than among males who report opposite-sex sexual contact only. Conclusions. Findings provide evidence that parental notification not being permitted is associated with significantly increased odds of lifetime HIV testing among sexually active U.S. adolescents, and that sex differentially affects associations between state-level confidentiality-relevant laws and sexually active U.S. adolescents’ HIV testing practices. Parental/guardian notification not being permitted may increase access to and utilization of HIV testing among sexually active U.S. adolescents. Furthermore, confidentiality-promoting laws – particularly those that explicitly include HIV testing in the package of STI services to which minors may consent, do not permit health care providers to notify parents/guardians that their child is seeking or receiving STI services, and protect the confidentiality of minors insured as dependents – may facilitate access to and utilization of HIV testing for sexually active male adolescents. Altogether, this dissertation provides compelling preliminary evidence for efforts to better understand and address structural determinants of HIV and HIV prevention among sexually active U.S. adolescents. Results underscore the need for a comprehensive, multi-level approach to adolescent HIV prevention that goes beyond a focus on reducing individual-level risk factors to increase protective factors at the structural level (e.g., confidentiality-promoting state laws). To address HIV-related health inequities among young people in the United States, advocates must fight for the passage of state laws that protect adolescents’ right to confidential sexual and reproductive health care.

PhD Thesis / Metabolomics offers a systemic approach to discover clinical biomarkers for early detection of chronic diseases while also revealing underlying mechanisms relevant to human disorders of complex aetiology. Metabolomic studies in support of chronic disease prevention have focused primarily on surrogate biofluids (e.g., serum, plasma) for analysis due to their routine and less invasive sample collection in a clinical setting. However, biofluids are non-organ specific and thus are reflective of confounding biochemical processes within the body that are often difficult to interpret. As a result, it is necessary to assess metabolite changes localized within tissues since they are the direct site of pathogenic processes, in order to obtain more robust and specific biomarkers. This thesis aims to contribute to new advances in biomarker discovery and tissue metabolomic studies using multiplexed separations together with innovative data workflows based on multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS). Chapter II introduces a high throughput yet targeted screening method for accurate quantification of serum γ‐glutamyl dipeptides from a cohort of overweight Japanese non-alcoholic steatohepatitis (NASH) patients that may allow for better risk assessment of long-term survivorship complementary to histopathology. Chapter III introduces a non-targeted metabolite profiling strategy for fasting plasma samples from prediabetic, older adults undergoing short-term step reduction (<1000 steps/day) in order to identify adaptive metabolic responses to abrupt changes in physical inactivity for early detection of sarcopenia in high-risk older persons. Chapter IV describes the first metabolomics study to characterize the human skeletal muscle metabolome from mass-restricted tissue biopsies together with matching plasma samples, which identified novel metabolic signatures associated with strenuous interval exercise, as well as treatment effects from high-dose bicarbonate pretreatment that delays the onset of muscle fatigue. Lastly, in Chapter V, metabolite coverage was expanded to include fatty acids for comprehensive characterization of murine placental tissue metabolome, which revealed sex-specific metabolic adaptations during gestation from maternal dams fed a standardized diet. In summary, this thesis contributes to new innovations in metabolomics for the discovery of novel biomarkers from blood and/or tissue specimens as required for early detection of chronic diseases relevant to population health, which were also used to validate the efficacy of therapeutic interventions based on physical activity to support healthy ageing. / Thesis / Doctor of Philosophy (PhD)

Since early 1983, the incidence and prevalence of heterosexually transmitted AIDS among women have increased at an alarming rate. However, due to the conceptualization of AIDS as a "gay male" disease, little research attention has been devoted to the prevention of HIV infection among women. The purpose of the current intervention was to test the utility of extending a behavioral social influence/diffusion of innovation approach to a group of heterosexual women. A randomized experimental field design was used to compare a community intervention (AIDS education materials plus the training of individuals identified as key opinion leaders to serve as peer behavior change agents) with a comparison intervention (AIDS education materials alone). The study was conducted at a small liberal arts college for women. Two dormitories were randomly assigned to either an intervention or comparison condition. Twenty-four women, living in the intervention dormitory, were identified as key opinion leaders among their female peers. These key opinion leaders then received information concerning the basic epidemiology of AIDS and other STDs, misconceptions about the transmission of AIDS/STDs among heterosexual women, gender constraints that impact health behavior change among women, and practical risk reduction strategies. Opinion leaders also received training in specific conversation skills to endorse HIV-protective behavior and to convey a change in normative sexual behavior to women living in the intervention dormitory. At pre- and post-intervention, 580 surveys were collected from both the intervention and comparison dormitories. Using an anonymous identification code, survey data were matched for 192 comparison and intervention participants. The major dependent variables included (a) AIDS/STD risk behavior knowledge, (b) perceived risk, (c) perception of peer norms for HIV-risky and HIV-protective behaviors, (d) stage of health behavior change, (e) intentions to practice safer sex, (f) socially and sexually assertive behavior, (g) HIV-risky sexual behavior, and (h) alcohol and drug use. Condom-taking behavior provided a nonreactive measure of behavioral intentions. A number of direct training effects were found for the key opinion leaders, including an increase in AIDS/STD risk behavior knowledge, conversation skills, and empathic assertion. However, there was no change in behavioral intentions, stage of change, perceptions of peer norms for HIV-protective behavior, or reported HIV-risky behavior. Analysis of covariance on posttest scores, using pretest scores as covariates, showed that, relative to the comparison participants, the intervention participants increased their AIDS/STD risk behavior knowledge and the number of AIDS/STD related peer conversations. No other treatment effects due to diffusion of innovation were found. The rate of risky sexual behavior for the intervention period was relatively low. However, descriptive statistics revealed a pattern of HIV-risky behavior in the current sample suggesting that HIV/STD risk may increase over time as a function of unprotected vaginal and oral intercourse and serial monogamy. The implication of these findings are discussed in terms of future interventions targeting heterosexual women. / Ph. D.

Tam Wing Yin. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 82-100). / Abstracts in English and Chinese. / English abstrac --- p.I / 中文摘要 --- p.VI / Glossary --- p.X / Chapter Chapter 1. --- Background: / Chapter 1.1. --- Coronary heart disease in Hong Kong --- p.1 / Chapter 1.2. --- Coronary heart disease and atherosclerosis --- p.2 / Chapter 1.3. --- Pathogenesis of atherosclerosis --- p.2 / Chapter 1.4. --- Risk factors for atherosclerosis --- p.5 / Chapter 1.5. --- Homocysteine --- p.6 / Chapter 1.6. --- Folate --- p.10 / Chapter 1.7. --- Vitamin B12 --- p.13 / Chapter 1.8. --- Adhesion Molecules --- p.14 / Chapter 1.9. --- Phytoestrogen --- p.17 / Chapter 1.10. --- Secondary prevention of coronary artery disease --- p.20 / Chapter Chapter 2. --- "Heart disease, Danshen and Gegen in Chinese medicine" / Chapter 2.1. --- The record of Cardiac symptoms in Chinese Medicine --- p.24 / Chapter 2.2. --- Danshen (Salvia Miltriorrhiza) --- p.25 / Chapter 2.3. --- Gegen (Radix Pueraria) --- p.28 / Chapter Chapter 3. --- Surrogate atherosclerotic markers / Chapter 3.1. --- Flow-mediated dilatation of brachial artery (FMD) --- p.31 / Chapter 3.2. --- Carotid intima media thickness (IMT) --- p.32 / Chapter Chapter 4. --- Method / Chapter 4.1. --- Rational of the study --- p.33 / Chapter 4.2. --- Clinical protocol --- p.35 / Chapter 4.3. --- Measurement of plasma homocysteine --- p.38 / Chapter 4.4. --- Measurement of folate and vitamin B12 --- p.40 / Chapter 4.5. --- Measurement of soluble cellular adhesion molecules (CAMs) --- p.41 / Chapter 4.6. --- Measurement of plasma enterolactone --- p.43 / Chapter 4.7. --- Measurement of plasma hs-C-reactive protein --- p.44 / Chapter 4.8. --- Other laboratory tests --- p.45 / Chapter 4.9. --- High resolution ultrasound imaging --- p.46 / Chapter 4.10. --- Statistical analysis --- p.49 / Chapter 4.11. --- My contribution to this joint project --- p.49 / Chapter Chapter 5. --- Results / Chapter 5.1. --- Recruitment and outcomes of subjects --- p.51 / Chapter 5.2. --- Baseline characteristics --- p.53 / Chapter 5.3. --- Medical history and treatment received in the study subjects --- p.54 / Chapter 5.4. --- Safety profiles --- p.55 / Chapter 5.5. --- Severe adverse events --- p.56 / Chapter 5.6. --- Lipid profiles --- p.57 / Chapter 5.7. --- Secondary endpoints --- p.58 / Chapter 5.8. --- Primary endopoints --- p.59 / Chapter 5.9. --- The effect of statin usage on the primary endpoints / Chapter 5.10. --- The major determinant of the change in FMD by multivariate logistic regression / Chapter 5.11. --- Progress of lipid profiles and primary endpoints in the open label phase / Chapter Chapter 6. --- Discussion / Chapter 6.1. --- Brachial FMD --- p.66 / Chapter 6.2. --- Carotid IMT --- p.69 / Chapter 6.3. --- Brachial GTN --- p.70 / Chapter 6.4. --- Lipid-lowering effect --- p.72 / Chapter 6.5. --- Phytoestrogen --- p.72 / Chapter 6.6. --- Folate --- p.73 / Chapter 6.7. --- Vitamin B12 and glucose --- p.76 / Chapter 6.8. --- Summary of possible anti-atherogenic mechanism of D&G --- p.76 / Chapter 6.9. --- Placebo effect --- p.77 / Chapter 6.10. --- Safety profile --- p.77 / Chapter 6.11. --- Limitation of the study and suggestion of solution --- p.77 / Chapter 6.12. --- Suggestions and ummary of the future work --- p.79 / Chapter Chapter 7. --- Conclusions --- p.81 / References --- p.82

Chung, Jennifer Siu Toye. / "June 2008." / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 145-157). / Abstracts in English and Chinese, some text in appendix also in Chinese. / Abstract of Thesis in English --- p.i / Abstract of Thesis in Chinese --- p.iii / Acknowledgments --- p.v / List of Tables --- p.xi / List of Figures --- p.xiii / List of Abbreviations --- p.xiv / List of Publications and Presentations related to Thesis --- p.xvi / Contributions related to Thesis --- p.xvii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Introduction of the Thesis --- p.1 / Chapter 1.2 --- Review on Coronary Heart Disease --- p.3 / Chapter 1.2.1 --- Definition of Coronary Heart Disease --- p.3 / Chapter 1.2.2 --- Risk factors for the development of Coronary Heart Disease --- p.3 / Chapter 1.2.3 --- Worldwide Figures for Coronary Heart Disease --- p.9 / Chapter 1.2.4 --- Coronary Heart Disease in Asia Pacific --- p.10 / Chapter 1.2.5 --- Coronary Heart Disease in Hong Kong --- p.11 / Chapter 1.3 --- Dyslipidaemia --- p.14 / Chapter 1.3.1 --- Lipid Transport and Lipoprotein Metabolism --- p.14 / Chapter 1.3.2 --- Definition and Classification of Dyslipidaemia --- p.16 / Chapter 1.3.3 --- Coronary Heart Disease and Dyslipidaemia --- p.17 / Chapter 1.3.4 --- Lifestyle Modifications for the Management of Dyslipidaemia --- p.19 / Chapter 1.3.4.1 --- Dietary Measures --- p.20 / Chapter 1.3.4.2 --- Cigarette Smoking --- p.23 / Chapter 1.3.4.3 --- Physical Activity --- p.24 / Chapter 1.3.4.4 --- Weight Control --- p.25 / Chapter 1.3.5 --- Lipid-lowering Drug Therapy for Dyslipidaemia --- p.29 / Chapter 1.3.5.1 --- Statins --- p.31 / Chapter 1.3.5.2 --- Bile Acid Sequestrants --- p.35 / Chapter 1.3.5.3 --- Fibrates --- p.36 / Chapter 1.3.5.4 --- Ezetimibe --- p.37 / Chapter 1.3.5.5 --- Nicotinic Acid Group --- p.38 / Chapter 1.4 --- International Guidelines for Dyslipidaemic Management --- p.39 / Chapter 1.4.1 --- National Service Framework for Coronary Heart Disease (UK) --- p.39 / Chapter 1.4.1.1 --- National Service Framework Lipid-lowering Goals --- p.40 / Chapter 1.4.1.2 --- The Joint British Societies' Guidelines --- p.41 / Chapter 1.4.1.3 --- Achievement of the NSF Lipid Profile Targets --- p.42 / Chapter 1.4.2 --- National Cholesterol Education Program (United States) --- p.43 / Chapter 1.4.2.1 --- The Third Report of the National Cholesterol Education Program --- p.43 / Chapter 1.4.2.2 --- Review of Clinical Trials --- p.43 / Chapter 1.4.2.3 --- Low-Density Lipoprotein Cholesterol Goal Targets --- p.46 / Chapter 1.4.2.4 --- Compliance with the NCEP ATP III Guidelines --- p.48 / Chapter 1.4.3 --- Dyslipidaemic Guidelines for Study --- p.51 / Chapter 1.5 --- Clinical Pharmacy Services --- p.52 / Chapter 1.5.1 --- The Healthcare System in Hong Kong --- p.52 / Chapter 1.5.2 --- Clinical Pharmacy Services in Hong Kong --- p.54 / Chapter 1.5.3 --- Examples of successful Clinical Pharmacy Services --- p.55 / Chapter 1.5.3.1 --- Hypertension Clinic --- p.55 / Chapter 1.5.3.2 --- Diabetes Mellitus Clinic --- p.56 / Chapter 1.5.3.3 --- Smoking Cessation Clinic --- p.57 / Chapter 1.5.3.4 --- Anticoagulation Clinic --- p.57 / Chapter 1.5.3.5 --- Haematology-oncology Clinic --- p.57 / Chapter 1.5.4 --- Pharmacist-managed Lipid Clinics --- p.58 / Chapter 1.6 --- Objective & General Aims of the Study --- p.60 / Chapter 1.6.1 --- Objectives --- p.60 / Chapter 1.6.2 --- Study Hypothesis --- p.60 / Chapter 1.6.3 --- General Aims of the Study --- p.60 / Chapter Chapter 2 --- Methodology of Study --- p.62 / Chapter 2.1 --- Background Setting --- p.62 / Chapter 2.2 --- Subject Selection and Recruitment --- p.62 / Chapter 2.3 --- Intervention and Control Groups --- p.63 / Chapter 2.4 --- Validation of Survey --- p.67 / Chapter 2.5 --- Data Collection --- p.67 / Chapter 2.6 --- Outcome Measures --- p.68 / Chapter 2.6.1 --- Lipid value changes --- p.68 / Chapter 2.6.2 --- Compliance rate with medications --- p.68 / Chapter 2.6.3 --- Patient satisfaction survey assessment --- p.69 / Chapter 2.6.4 --- Time spent and Cost of clinical pharmacist --- p.69 / Chapter 2.7 --- Statistical Analysis --- p.70 / Chapter 2.7.1 --- Sample Size Calculation --- p.70 / Chapter 2.7.2 --- Methods of Statistical Analysis --- p.71 / Chapter Chapter 3 --- Results of Study --- p.72 / Chapter 3.1 --- Recruitment Details --- p.72 / Chapter 3.2 --- Demographic Characteristics of Patients --- p.73 / Chapter 3.3 --- Drug Therapy of Patients during Study Period --- p.75 / Chapter 3.4 --- LDL-C Lowering Potency of Statin Doses Prescribed --- p.80 / Chapter 3.5 --- Coronary Heart Disease Risk Category of Patients --- p.84 / Chapter 3.6 --- Lipid Profile Changes --- p.85 / Chapter 3.7 --- NCEP ATP III LDL-C Goal Attainment --- p.87 / Chapter 3.8 --- Relationship between Patient Characteristics and LDL-C Goal Attainment --- p.91 / Chapter 3.9 --- Compliance with Medications --- p.94 / Chapter 3.10 --- Pharmacist Intervention --- p.98 / Chapter 3.10.1 --- Range of Pharmacist Intervention --- p.98 / Chapter 3.10.2 --- Time spent by Pharmacist --- p.100 / Chapter 3.10.2.1 --- Time spent on Documentation --- p.100 / Chapter 3.10.2.2 --- Time spent on Direct Communication with Patients --- p.101 / Chapter 3.10.3 --- Cost of Clinical Pharmacy Service at the Lipid Clinic --- p.102 / Chapter 3.10.3.1 --- Cost of Pharmacist Involvement --- p.102 / Chapter 3.10.3.2 --- Potential Healthcare Cost Saving --- p.103 / Chapter 3.11 --- Clinical Pharmacy Service Satisfaction Survey --- p.105 / Chapter 3.11.1 --- Validation of Survey --- p.105 / Chapter 3.11.2 --- Questionnaire Survey for Intervention and Control Groups --- p.107 / Chapter 3.11.3 --- Physician Questionnaire Survey on Clinical Pharmacy Service --- p.110 / Chapter Chapter 4 --- Discussion --- p.111 / Chapter 4.1 --- Clinical Outcomes of Study --- p.111 / Chapter 4.1.1 --- Changes in Lipid Parameters --- p.111 / Chapter 4.1.2 --- Reduction in CHD risk --- p.113 / Chapter 4.1.3 --- Attainment in NCEP ATP III LDL-C goals --- p.114 / Chapter 4.1.4 --- Predictors for LDL-C Goal Attainment --- p.117 / Chapter 4.2 --- Drug-related Problems --- p.119 / Chapter 4.2.1 --- Statin Dosing and LDL-C Lowering Potency --- p.119 / Chapter 4.2.2 --- Adherence to Drug Therapy --- p.121 / Chapter 4.2.3 --- Polypharmacy --- p.126 / Chapter 4.2.4 --- Adverse Drug Events and Drug Interactions --- p.129 / Chapter 4.2.5 --- Patient Busy Lifestyle --- p.131 / Chapter 4.3 --- Role of Clinical Pharmacist --- p.133 / Chapter 4.3.1 --- Role of Pharmacist --- p.133 / Chapter 4.3.2 --- Multidisciplinary Team --- p.135 / Chapter 4.3.3 --- Healthcare Cost Saving --- p.137 / Chapter 4.4 --- Limitations of Study --- p.139 / Chapter 4.5 --- Further Study --- p.142 / Chapter Chapter 5 --- Conclusion --- p.144 / Chapter 5.1 --- Conclusion of Study --- p.144 / Bibliography --- p.145 / Appendices --- p.158 / Appendix I Data collection form --- p.158 / Appendix II Information sheet on study protocol to patient --- p.160 / Appendix III Patient consent form for study --- p.164 / Appendix IV Framingham risk scoring system for male --- p.165 / Appendix V Framingham risk scoring system for female --- p.166 / Appendix VI Patient educational leaflet --- p.167 / Appendix VII Physician-pharmacist communication sheet --- p.169 / Appendix VIII Telephone checklist --- p.170 / Appendix IX Questionnaire survey provided to Intervention Group --- p.172 / Appendix X Questionnaire survey provided to Control Group --- p.174 / Appendix XI Questionnaire survey provided to Physicians --- p.176

Problématique : Les enfants ayant survécu à un cancer présentent un risque accru de développer des complications cardiométaboliques à long terme par rapport à leurs pairs. Cette étude vise à évaluer la faisabilité et l’impact du volet nutritionnel de l’intervention multidisciplinaire VIE (Valorisation, Implication, Éducation) pendant le traitement du cancer pédiatrique sur les apports alimentaires et la santé cardiométabolique des enfants après la fin de leur traitement. L’aspect multidisciplinaire de cette intervention impliquait également l’activité physique et la psychologie. Méthodologie : La faisabilité de l’étude, évaluée un an après le début de l’intervention, a inclus le taux de rétention, de participation, d’assiduité, d’achèvement des mesures de l’étude et d’engagement des participants. Suite à l’intervention, les participants qui ont été exposés à VIE ont fait l’objet d’une évaluation de fin d’étude, tandis que les participants d’un groupe contrôle ont fait l’objet d’une évaluation unique. Les données ont été recueillies 1,3 ± 0,8 an après la fin du traitement dans le groupe d’intervention et 1,4 ± 0,8 an dans le groupe de contrôle. Des mesures nutritionnelles (journal alimentaire de 3 jours et rappel de 24 heures), anthropométriques (poids, taille, tour de taille, tour brachial, pli cutané), biochimiques (profil lipidique, HbA1c, vitamine D) et de pression artérielle ont été recueillies. Résultats : Après un an d’intervention, le taux de rétention était de 72,6 %, 258 rencontres ont été menées sur 362 planifiées (taux de présence 71,6 %) et la moitié des participants (50,8 %) avaient participé à au moins 4 rencontres de suivi. À l’évaluation de fin d’étude, 45 participants de l’étude VIE (10,2 ± 4,5 ans) ont été comparés à 77 contrôles (12,0 ± 5,6 ans). Par rapport aux contrôles, les participants à l’étude VIE consommaient moins de calories (1997 ± 669 vs. 1759 ± 513, p=0,042) et avaient des apports en calcium ajustés à l’énergie plus élevés (548 ± 240 mg/1000 kcal vs. 432 ± 197 mg/1000 kcal, p=0,005). Les participants à l’étude VIE avaient également tendance à consommer davantage de fibres totales (9,2 ± 3,4 g/1000 kcal contre 8,4 ± 2,8 g/1000 kcal, p=0,188) et de vitamine D (2,6 ± 2,0 g/1000 kcal contre 2,2 ± 2,0 g/1000 kcal, p=0,311) que les contrôles. Aucune différence entre les groupes n’a été constatée en ce qui concerne les résultats anthropométriques ou cardiométaboliques. Conclusion : Cette étude montre que le volet nutritionnel d’une intervention multidisciplinaire, mise en œuvre rapidement après le diagnostic de cancer, est faisable et peut avoir un impact positif sur le régime alimentaire des enfants et des adolescents. Une implantation multicentrique avec le projet VIE-Québec permettra d’augmenter l’étendue des retombées positives. / Background : Children who have survived cancer have an increased risk of developing long-term cardiometabolic complications compared to their peers. The aim of this study is to assess the feasibility and impact of the nutritional component of the multidisciplinary VIE (Valorisation, Implication, Éducation) intervention during pediatric cancer treatment on children's dietary intake and cardiometabolic health after the end of their treatment. The multidisciplinary aspect of this intervention involved also physical activity and psychology. Methods: Study feasibility, assessed one year after the start of the intervention, included retention, participation, attendance, completion of study measures and participant engagement. Following the intervention, participants who had been exposed to VIE underwent an end-of-study assessment, while participants in a control group underwent a one-off assessment. Data were collected 1.3 ± 0.8 years after the end of treatment in the intervention group and 1.4 ± 0.8 years in the control group. Nutritional (3-day food diary and 24-hour recall), anthropometric (weight, height, waist circumference, brachial circumference, skin fold), biochemical (lipid profile, HbA1c, vitamin D) and blood pressure measurements were collected. Results: After one year of intervention, the retention rate was 72.6%, 258 appointments were conducted out of 362 planned (71.6% attendance rate) and half of the participants (50.8%) had attended at least 4 follow-up appointment. At the end-of-study assessment, 45 VIE participants (10.2 ± 4.5 years) were compared with 77 controls (12.0 ± 5.6 years). Compared to controls, VIE participants consumed fewer calories (1997 ± 669 vs. 1759 ± 513, p=0.042) and had higher energy-adjusted calcium intakes (548 ± 240 mg/1000 kcal vs. 432 ± 197 mg/1000 kcal, p=0.005). VIE participants also tended to consume more total fiber (9,2 ± 3,4 g/1000 kcal vs. 8,4 ± 2,8 g/1000 kcal, p=0.188) and vitamin D (2,6 ± 2,0 g/1000 kcal vs. 2,2 ± 2,0 g/1000 kcal, p=0.311) than controls. There were no differences between the groups in terms of anthropometric or cardiometabolic outcomes. Conclusions : This study shows that the nutritional component of a multidisciplinary intervention, implemented rapidly after cancer diagnosis, is feasible and can have a positive impact on the diet of children and adolescents. A multicenter implementation via the VIE-Québec project will increase the extent of the positive impact.

Thesis (MBA)--Stellenbosch University, 2006. / ENGLISH ABSTRACT: HIV/AIDS is one of the most devastating pandemics the world has ever faced. SubSaharan Africa remains the region most affected where more two thirds of the total HIV positive population resides. Despite this region trying to grapple with many negative factors like political unrest, draughts, armed conflict, it now also have to content with HIV/AIDS. HIV/AIDS has already killed ten times more Africans than all of the armed conflicts on the African continent combined (The Washington Quarterly, 2001:191-196). Many of the Sub-Saharan countries are renowned for unemployment and poverty which can be partly be alleviated by economic growth. Studies by Bonnel (2000) concluded that a typical Sub-Saharan country with a 20% HIV/AIDS prevalence rate, would suffer a 2.6% reduction in GDP growth per annum. This indicates that South Africa, where an estimated S.5 million HIV positive people resides (the most in globe) and ever increasing HIV prevalence, is in a serious predicament. There are many interacting variables causing the negative socioeconomic decline. At organisational level direct and indirect costs attributable to HIV, results in a severe decline of profitability and jeopardises sustainable economic activity. Direct costs include costs for medical treatment, health insurance, funeral expenses, retirement and disability and costs to manage HIV in the workplace. Indirect costs include absenteeism and loss of productivity, retraining and recruiting of employees to fill deceased employees' places etc. Although South African organisations acknowledge and predict that HIV/AIDS will have an ever-increasing negative impact on their business, the response to dealing with this issue has been insufficient. The deficient response could be partly ascribed to a lack of guidance, deficient proof of cost effectiveness with no real measurement for the outcomes of intervention programs. This study will critically evaluate a KAPB (knowledge, attitude, perception and behaviour) survey as a second-generation HIV surveillance tool that could address these organisational concerns. KAPB surveys have advantages like providing guidance and increasing cost effectiveness of HIV programs, benchmarking interventions and providing a platform for communication design and feedback to stakeholders. These benefits should motivate organisations to initiate programs that address HIV at an organisational level. KAPB surveys evaluate four employee factors related to HIV - knowledge, attitudes, perception and sexual behaviour. This report will critically evaluate the appropriateness of measuring these factors and some tools used to measure these factors. Further elaboration of the methodology during the execution of a KAPB survey will highlight the current best practices identified in literature. The report will also highlight the obstacles and ways of negotiating them when conducting a KPAB survey. The study will conclude that a well -executed KAPB survey through its many benefits should motivate and assist organisations in designing and implementing HIV/AIDS programs. / AFRIKAANSE OPSOMMING: HIV is een van die ernstigste pandemies wat die wereld al ooit beleef het. Die state in die Sub-Sahara streek is die ergste geaffekteer en meer as twee derdes van die totale HIV positiewe populasie kom in die gebied voor. Die streek wat deurgaans geteister word deur politieke onrus, droogte, oorlog, moet nou ook probeer tred hou met MIV /VIGS. MIV/VIGS het tot op hede alreeds tien keer meer mense gedood as al die oorloë op die Afrika continent saam (The Washington Quarterly, 2001: 191-196). Die meeste van die state in Sub-Sahara word gekenmerk deur werkloosheid en armoede wat deels verlig kan word deur ekonomiese groei. Studies deur Bonnel (2000) het getoon dat die tipiese staat in Sub-Sahara, met 'n 20% MIV insidensie 'n vermindering van tot 2.6% groei in die GDP kan ondervind. Dit voorspel dat Suid-Afrika met 'n voorspelde 5.5 miljoen HIV positiewe inwoners (die meeste in die wereld) ekonomiese noodlot in die oog staar. Daar is verskeie faktore wat saamwerk om die negatiewe ekonomiese 'effek van MIV/VIGS te bewerkstellig. Organisasies se ekonomiese vooruitgang en oorlewing word bedreig deur direkte en indirect kostes van MIV. Direkte kostes wat organisasies moet aangaan sluit in mediese behandeling, mediese fonds bydraes, begrafnis onkostes, aftrede en ongeskiktheidspensioenbetalings. Indirekte kostes sluit in afwesighede, verlies aan produktiwiteit en die heropleiding en werwing van werknemers wat afgestorwe werknemers se plek moet neem. Ten spyte van die feit dat organisasies erken en voorspel dat MIV/VIGS 'n negatiewe impak op die ekonomies welvaart van organisasies sal hê, het weining van die organisasies aksie geneem om die probleem aan te spreek. 'n Moontlike rede vir die onvoldoende aksie kan toegeskryf word aan die tekort aan leiding, bewyse vir kostedoeltreffendheid en geen werklike maatstaf om die programme se resultate te evalueer. Hierdie studie sal KGPG (kennis, gevoelens, persepsie ' en gedrag) studies as 'n tweede generasie MIV opname, krities evalueer. KGPG studies bied verskeie voordele soos om leiding vir HIV programme te bied en verbeterde koste effetiwiteit van MIV programme te bewerkstellig. KGPG studies voorsien ook 'n maatstaf om MIV programme te evalueer en 'n kommunikaise platvorm tussen aandeelhouers. Hierdie voordele sal moontlik organisasies motiveer om aksie te neem en MIV in die organisasie aan te spreek. KGPG studies evalueer vier werknemer faktore met betrekking to MIV /VIGS. Die vier faktore is kennis, gevoelens, persepsie en seksuale gedrag. Die verslag sal die vier faktore krities evalueer vir toepaslikheid en ook fokus op die instrumente wat die faktore evalueer. Aanbevelings sal ook gemaak word ten opsigte van die korrekte en beste metodes wat gevold moet work tydens 'n KGPG studie. Die struikelblokke wat ondervind kan word tydens 'n KGPG studie asook hoe om dit te oorkom sal bespreek word. Die verslag sal bewys dat 'n KGPG studie wat uitgevoer word in Iyn met die beste praktyk baie waarde kan toevoeg tot organisasies ten opsigte van die beplanning en uitvoering van programme om MIV/VIGS te bekamp.

Natural exposure to Plasmodium falciparum’s asexual blood-stage results in protection against severe disease, but no vaccine using the widely-studied blood-stage antigens apical membrane antigen 1 (AMA1) or merozoite surface protein 1 (MSP1) has proven convincingly protective in clinical trials. Challenges include antigenic polymorphism, the apparent requirement for exceptionally high antibody concentrations for protection, and clinical-grade production of conformationally-accurate recombinant protein antigens followed by formulation with a human-compatible adjuvant. This thesis describes the generation of viral-vectored vaccines targeting ten less-studied blood-stage antigens, focusing upon antigens implicated in erythrocyte invasion. These vaccines were immunogenic in mice and rabbits. The rabbit antibodies raised were functionally active in the in vitro assay of parasite growth inhibitory activity (GIA). GIA with antibodies against one antigen, RH5, exceeded that achieved with antibodies against the ‘gold standard’ AMA1 or MSP1 antigens. This antigen’s amino acid sequence is relatively conserved between parasite strains. Importantly, and unlike anti-AMA1 and MSP1 antibodies, the GIA effects transcend genetically diverse strains. It was hypothesised that blockade of the interaction of RH5 with its receptor basigin was likely to be a mechanism of action of anti-RH5 antibodies. Vaccine-induced polyclonal anti-RH5 serum was found to be capable of blocking this interaction, as well as merozoite attachment to erythrocytes. A panel of RH5-specific monoclonal antibodies were raised: those which block the RH5-receptor interaction were capable of neutralising parasites. Minimal linear epitopes recognised by these antibodies were mapped, and are likely to be within or close to RH5’s receptor binding site. These data support prompt clinical testing of RH5-based vaccines, and shed light upon the mechanism of action of anti-RH5 antibodies. However substantial challenges remain in establishing whether this antigen, selected on the basis of the in vitro assay of GIA, will be capable of achieving in vivo protection against P. falciparum. Further work presented in this thesis addresses the use of quantitative PCR data to assess blood-stage vaccine efficacy in experimental human challenge with P. falciparum, and the use of surface plasmon resonance to establish more detailed characterisation of vaccine-induced antibody responses. Finally, the results of P. falciparum challenge of RH5-vaccinated Aotus nancymaae non-human primates are presented.

Background: Hepatocellular Carcinoma (HCC) is the third most common cause of cancer related death worldwide and is often diagnosed by measuring serum Alpha-fetoprotein (AFP); a stand-alone biomarker with limited diagnostic proficiency. To compensate for this, AFP is commonly used in conjunction with high performance imaging and radiological methods. However, as the burden of HCC is predominantly in the developing world where such technologies are not readily available, it is imperative that efforts are made to pursue the discovery of novel, high performance, easy to measure and robust biomarkers. With the aim of improving on the diagnostic ability of AFP, our project focuses on the study of plasma proteins as identified by Mass Spectrometry (MS) in order to investigate differences seen in the respective proteomes of controls and subjects with liver cirrhosis (LC) and HCC. Methods: Matrix Assisted Laser Desorption Ionization Time-of-Flight MS (MALDI-TOF MS) was first attempted on weak cation exchange (WCX) fractionated plasma in a pilot selection of forty subjects. On the main case-control group, quantitative MS analysis using liquid chromatography electro spray ionization quadrupole time-of-flight (LC-ESI Q-TOF) was conducted on 339 subjects using a pooled expression profiling approach. Enzyme-linked immunosorbent assays (ELISA) and 1 and 2Dimentional electrophoresis methods were performed to validate and detail candidate protein levels and modification patters in individual and pooled subjects. The human plasma used for the MS based protein discovery experiments was collected as part of a five year Liver Cancer Case-control Study (Gambia, West Africa). A smaller set of samples from subjects who formed a spectrum of non-liver disease controls, LC and HCC were obtained from the Jos University Teaching Hospital (JUTH) in Nigeria and ELISA and gel electrophoresis assays conducted on them to confirm the trends and differences seen in the Gambian subject set. Results: Bioinformatic evaluation of MALDI-TOF data highlighted peak masses 2444m/z, 2583m/z and 2559m/z to have high diagnostic abilities based on area under curve (AUC) statistics of >0.75. Of these polypeptide fragments, one was identified as the plasma glycoprotein, alpha chain fibrinogen. Results from the large-scale label free discovery experiments indicated twenty-six proteins to be differentially expressed between the three subject groups. These prospective markers include proteins previously linked to HCC as well as novel candidates, namely glutathione peroxidase 3, serum amyloid p, carboxypeptidase N and complement factors I and H which have not been implicated in the context of HCC diagnostics. Direct measurement of Hemopexin (HPX), alpha-1-antitrypsin (α1AT), apolipoprotein A1 (Apo A1) and complement component 3 (CC3) levels confirmed their change in abundance in LC and HCC versus control patients. Further biochemical characterization of glycosylated HPX isolated from glycoprotein enriched plasma sample pools showed evidence of isoelectric point shifts, indicating differential glycosylation patterns in high mannose structures of HPX which may be disease stage linked. The direct measurements of HPX, α1AT, Apo A1 & CC3 conducted on the independent Nigerian subject group also confirmed much of the trends reported from the Gambia Liver Cancer Study (GLCS) plasma. Conclusions: The independently validated, significant changes in the quantitative expression of ApoA1, α1AT, CC3 and HPX could be exploited for development into high-performance affordable assays, usable in the diagnosis and monitoring of HCC and LC patients. The unique signatures observed for most of these proteins, from liver disease free controls to LC and HCC suggest their involvement in independent pathways. As such, combining some or all of these four markers within a diagnostic panel could offer a much-needed boost in robustness and accuracy for AFP. The differences in the processing and molecular weight separation of these proteins also offers a novel inroad into biomarker identification. These suggested disease specific signatures could with further study offer highly specific biomarkers able to discern the key stages that predispose individuals to hepatocarcinogenesis. Impact: This is the first MS based discovery and extensive validation study on West African subjects whose primary cause of HCC are the Hepatitis B Virus (HBV) and fungal toxins.

With the spread of the Human Immuno-Deficiency Virus and sexually transmitted diseases, it is extremely important for sexually active individuals to protect themselves properly if they decide to engage in sexual intercourse. Knowledge of HIV and the Acquired Immune Deficiency Syndrome has been associated with safer sexual practices, but knowledge alone does not totally explain risky sexual practices. This study examined how 154 college students' knowledge of HIV/AIDS, relationship status, perceptions of condom use, and perceptions of personal risk affect condom use during sexual intercourse. The impact of trust and love justifications along with the approval of peers were also examined. Perceptions of condom use and perceptions of personal risk were compared by gender and ethnicity; how perception of personal risk is related to condom use and condom use intentions was also examined. Condom use intention was found to be a significant predictor of condom use, and a significant difference of means for condom use intentions was reported between individuals who used condoms during their last experience with sexual intercourse and those who did not use condoms during their last sexual experience