Anorexia nervosa is a serious and complex mental illness, where little is known of factors implicated in its maintenance. Current effective treatments for adolescent anorexia nervosa have shown promising outcomes, however a significant group of patients still remain unwell. One factor that contributes to a poor treatment outcome is comorbid anxiety. However, there is a lack of knowledge of anxiety related vulnerability factors in individuals with anorexia nervosa. A potentially useful anxiety related factor is intolerance of uncertainty (IU). Theoretically and clinically IU could be associated with eating disorder psychopathology and the need for control, often found in individuals with anorexia nervosa. This thesis comprises of a conceptual model of IU in anorexia nervosa, four studies that empirically examine IU and associated factors in relation to anorexia nervosa and a proposed future study. The first quantitative study investigates anxiety related factors in adults with anorexia nervosa and healthy controls. The two subsequent qualitative studies explore the meaning of uncertainty for adolescents with anorexia nervosa and their parents. The fourth study examines anxiety related factors in adolescents with anorexia nervosa, similar to study 1, and further investigates whether such factors along with beliefs about having an eating disorder and parental distress moderate/mediate response to treatment. Findings, suggest that IU and anxiety related factors are elevated in adults and adolescents with anorexia nervosa compared to the normal population and are positively associated with eating disorder psychopathology. Personal accounts from adolescents further reveal that IU is predominately a negative experience, while parents find uncertainty in relation to their child’s illness excessive and a source of distress. Results from the fourth study indicate that ambivalence in adolescents at the beginning of therapy predicts response to treatment. This thesis has brought to the forefront the construct of IU as a possible maintenance factor of anorexia nervosa. Data are discussed in relation to the proposed model of IU in anorexia nervosa and both theoretical and clinical implications are discussed.

Thesis (MSc (Biomedical Sciences))--Cape Peninsula University of Technology, 2018. / Background: Early detection of individuals who are at risk of developing Glucose Intolerance would decrease the morbidity and mortality associated with this disease. MicroRNA is one of the most widely studied biomolecules involved in epigenetic mechanisms, hence it offers unique opportunities in this regard. Circulating microRNAs are associated with disease pathogenesis during the asymptomatic stage of disease. This has therefore attracted a lot of attention as a potential biomarker for identifying individuals who have an increased risk of developing Glucose Intolerance. The identification of high risk biomarkers for Glucose Intolerance will go a long way to eliminate the possible complications that arise due to late diagnosis and treatment of Glucose Intolerance. This could ultimately lead to better ways to prevent, manage and control the Glucose Intolerance epidemic that is rampant worldwide. The aim of the study is to investigate expression of circulating microRNA’s in blood of mixed ancestry subjects with glucose intolerance. Methods: A quantitative cross-sectional study design involving 36 individuals [who were age, gender and BMI (Body Mass Index) matched] from a total population of 1989 participants of mixed ancestry descent, residing in Bellville South, South Africa was used. Participants were classified as controls (normoglycemic), pre-diabetic (preDM) and diabetic (DM) (screen detected diabetic) according to WHO criteria of 1998. MicroRNAs were extracted from serum using the Qiagen miRNeasy Serum/Plasma Kit (ThermoFisher). The purified micro RNAs were reverse-transcribed to cDNA (complementary deoxyribonucleic acid) using the Qiagen RT2 First Strand Kit. Then, using Qiagen miScript SYBR Green PCR kit and miScript miRNA PCR arrays (ThermoFisher), the real time polymerase chain reaction was done to determine the expression profile the circulating micro RNAs present in the serum of the participants. Results: The 36 participants were evenly divided into 3 groups of 12 participants each as mentioned earlier. There were significant differences between groups in the waist (cm) (p=0.0415) and waist/hip ratio (p=0.0011) with highest values in the DM group and lowest in the normal group. Clinical parameters varied significantly according to glycemic status. As expected, the FBG (mmol/L) (p<0.0001), 2 HRs Post Glucose (mmol/L) (p<0.0001), HbA1c (%) (p=0.0009), Fasting Insulin (mIU/L) (p=0.0039), were all highest in the DM and lowest in the control group. In contrast, the 2 HRs Post Insulin (mIU/L) (p = 0.0027) was highest in the preDM group and lowest in the normal group, while the Glucose/Insulin ratio (p=0.0477) was highest in the normal group and lowest in the preDM group. Triglycerides (mmol/L) (p=0.0043) and Total Chol (mmol/L) (p=0.0429) were significantly increased through the three groups, with highest values in the DM group and lowest in the normal group. Furthermore, 12 of the 84 miRNAs studied were expressed through all the 3 groups and they exhibited both inverse and positive correlations between the clinical parameters, especially the glucose parameters (Fasting blood glucose, 2 hours post glucose, Fasting blood insulin, 2 hours post insulin and Glycated Hemoglobin).

Posttraumatic stress disorder (PTSD) is a common psychiatric disorder and is associated with impairment in multiple domains. Research on the development of PTSD symptoms is often limited by the use of cross-sectional designs and retrospective reports of pre-trauma factors. The trauma film paradigm allows for the measurement of pre-trauma factors to determine which variables serve as prospective predictors of posttraumatic stress symptom development. Two factors which may predict posttraumatic stress symptom development are distress intolerance and attentional control. Research suggests distress intolerance is related to posttraumatic stress symptoms, but this relationship has only been shown cross-sectionally. Research has further shown attention control prospectively predicts posttraumatic stress symptoms. Cross-sectional research also suggests attentional control moderates the relationship between distress intolerance and posttraumatic stress symptoms. The current study used the trauma film paradigm to investigate whether attentional control moderates the relationship between distress intolerance and posttraumatic stress symptoms. The current study findings were mixed, but suggest that attentional control does not moderate the association between distress intolerance and posttraumatic stress symptoms. These results suggest distress intolerance and attentional control may not be important variables in the development of posttraumatic stress symptoms.

This project uses Michel Foucault’s underdeveloped notion of “tolerated illegality” as a departure point for two converging inquiries. The first analyzes, and then critiques, dominant legal logics and values. This part argues that traditional legal philosophers exhibit a “disagreement without difference,” generally concurring that legal certainty and predictability enhance agency. Subsequently, this section critiques “formal legal” logic by linking it to science envy (specifically the desire for certainty and predictability), and highlighting its agency- limiting effects (e.g. the violence of law en-force-ment). The second part examines multiple dimensions of tolerated illegality, exploring the permutations of this complex socio-legal phenomenon. Here the implications of tolerated illegality are mapped across different domains, ranging from the dispossession of Indigenous peoples of their lands, to the latent ideologies embedded in superhero shows. This section also examines the idea of liberal “tolerance,” as well as the themes of power, domination, politics, bureaucracy, and authority. Ultimately, this project demonstrates that it is illuminating to study legality and (tolerated) illegality in tandem because although analyses of “formal legality” provide helpful analytical texture, the polymorphous and entangled nature of tolerated illegality makes clear just how restricted and artificial strict analyses of legality can be. / Graduate

Chronic heart failure (CHF) and type 2 diabetes mellitus (DM) remain primary causes of mortality. Furthermore ~25-30% of CHF patients have DM, and these diabetic heart failure (D-HF) patients have an adverse prognosis. However, as yet, very few studies have examined the D-HF population in comparison to matching CHF, DM, and control patients. Therefore the current thesis described four experimental studies examining exercise intolerance and skeletal muscle abnormalities in these patient populations. The first study of this thesis employed a novel exercise test (RISE-95) to better evaluate exercise intolerance in CHF and D-HF patients. This study confirmed previous clinical findings indicating that D-HF patients have a lower peak pulmonary oxygen uptake (V̇O2peak). Furthermore this study also demonstrated that nearly half of the cohort acutely increased V̇O2peak, the mechanism of which may elucidate potential therapeutic targets. To examine potential mechanisms contributing to exercise intolerance, the second study investigated skeletal muscle mitochondrial function in chest muscle biopsies obtained from control, DM, CHF and D-HF patients. This study identified that D-HF patients exhibit both quantitative and qualitative mitochondrial impairments, with the latter residing at complex I. The next study corroborated these findings in leg biopsies from the same patients. The final study uncovered potential mechanisms possibly contributing to skeletal muscle mitochondrial impairments, including an increased mitochondrial reactive oxygen species (ROS) production and downregulated expression of key mitochondrial genes. Furthermore this study revealed that D-HF patients exhibit a type II fibre-specific atrophy and capillary rarefaction. Collectively, these studies expand our current knowledge regarding exercise intolerance in D-HF patients and how skeletal muscle impairments may contribute to the worse symptoms and outcomes seen in this growing population. The findings from this thesis are expected to guide future research endeavours, which may identify potential therapeutic targets by which exercise intolerance may be ameliorated in these patients.

Exercise limitation is a hallmark of chronic obstructive pulmonary disease (COPD) and countering this is a major therapeutic goal. Chapter 1 considers the factors contributing to exercise intolerance with particular reference to the respective roles of ventilatory limitation and skeletal muscle dysfunction. A review of the strategies studied or currently used to counter exercise limitation then follows. Chapter 2 describes the methodology of the assessments of exercise limitation used in this thesis, along with an evaluation of other currently available techniques. Chapter 3 describes how different means of body composition evaluation can effect the functional conclusions made from the data obtained. Assessment of peak exercise capacity related to muscle mass was found to be underestimated by anthropometry in comparison to air displacement plethysmography or bioelectrical impedance. It is concluded that inter-method differences in estimation of fat-free mass are large enough to require that a single methodology of assessment is used for comparative evaluations. Chapter 4 describes a trial of creatine supplementation, both in isolation and in combination with exercise training. Muscle mass, strength and endurance, and health status were all enhanced by creatine, with or without exercise training. Whole body exercise capacity, when examined by field and laboratory tests, was not affected. It is concluded that creatine may be a potentially useful ergogenic agent for use in COPD patients. Chapter 5 describes a crossover study of formoterol, a long acting bronchodilator, in advanced COPD patients with poor spirometric response to bronchodilation. Formoterol is shown to decrease exercise induced dynamic hyperinflation and breathlessness during activities. An equivocal effect on exercise tolerance is demonstrated. This study supports the rational for the use of long acting bronchodilators in symptomatically limited COPD patients, largely irrespective of individuals lung function response to bronchodilator. Chapter 6 considers the implications of the work performed and suggests lines of investigation for future research.

Thesis (MSc (Biomedical Technology))--Cape Peninsula University of Technology, 2017. / Background: Telomeres are DNA-proteins situated at the ends of linear chromosomes, responsible for genome stabilization. A link has been previously described between leucocyte telomere length (LTL) and age-related inflammatory disorders such as atherosclerosis, rheumatoid arthritis and cancer. Since diabetes mellitus has been described as a chronic inflammatory condition, it has been hypothesized that there is significant LTL shortening in individuals with dysglycaemia. Aim: To investigate leucocyte telomere length in patients with pre-diabetes, newly diagnosed, known diabetics on treatment and to compare the results to normoglycaemic individuals. Methods: A total of 205 eligible subjects (78% women) median age 56 years, from the Bellville-South community were followed-up between 2008 and 2011. Baseline and follow-up data collections included glucose tolerance status, anthropometric, blood pressure, lipids, insulin, γ-glutamyl transferase, cotinine, and HbA1c. In all participants, telomere length was measured using the absolute telomere q-PCR method performed on a Bio-Rad MiniOpticon Detector. Results: Although there was a change in individuals’ glycaemic status over the 3 years, no significant differences were observed in LTL across glycaemic status: (Baseline p = 0.7618, 3 Year Follow-up p = 0.2204). However, in a multiple regression model, adjusted for age and gender, LTL was negatively associated with age and GGT, and positively associated with high density lipoproteins (HDL) (all p < 0.05). Discussion and conclusion: This research study was the first longitudinal study of LTL in Africans. We show that LTL shortening is not evident within three years, nor is it associated with glycaemia. Our findings also corroborate previous notions associating LTL with age. The lack of association between LTL and glycaemia has been previously reported, however further studies are required using larger sample and broader BMI spread.

A nutritional method commonly used to deliver feedings to premature infants is the use of a gavage tube. To measure for any undigested breastmilk or formula, a gastric aspirate is checked prior to the next feeding. There is a gap in practice as to what to do if these aspirates signify feeding intolerance. The project question centered on identifying evidence-based guidelines in the literature that would help to define best practices related to feeding intolerance of gavage-fed infants. The Johns Hopkins Nursing Evidence-Based Practice model and the Appraisal of Guidelines Research and Evaluation provided the frameworks for gathering and evaluating evidence as well as the process used in forming the practice guideline. The primary methods employed were a team approach that included a Neonatal Intensive Care Unit (NICU) Project Team and NICU expert opinion along with a literature review conducted by the doctor of nursing practice student. The NICU Project Team collected the NICU experts' input via surveys they developed and distributed as well as e-mails to authors identified from the literature review. The surveys yielded a 76% response rate from the registered nurses and a 59% response rate from the medical providers. All data collected were shared and descriptive statistics were used to evaluate the data. One of the central research findings was that gastric aspirates should no longer be routinely obtained on stable infants and, if used in evaluating feeding intolerance, they must be used in combination with other indicators. An enteral feeding guideline was developed to reflect this finding that can be shared with other NICUs and nurseries in the United States and globally to decrease the morbidity and mortality of neonates.

<p>This essay argues that Harry Potter and the Philosopher’s Stone helps young people to better understand social intolerance and racial prejudice in today’s society. Specific examples will be analyzed with the aid of New Critical close reading.</p>

Thesis (Ph. D.)--Oklahoma State University, 2006. / Vita. Includes bibliographical references.