Bakgrund. En effektiv behandling för hiv kom år 1996. Behandlingen för hiv kan orsaka en rad biverkningar som skulle kunna påverka följsamheten. Minskad följsamhet har lett till läkemedelsresistens. Syfte. Syftet är att undersöka upplevelser av följsamhet hos personer som lever med hiv under antiretroviral tablettbehandling (ART). Metod. En litteraturstudie med kvalitativ ansats. Resultat. 12 vetenskapliga artiklar ligger till grund för litteraturstudiens resultat. Majoriteten av personer som lever med hiv (PLH) hittade egna strategier för att hitta motivation till att uppnå följsamhet. Depressiva symtom och substansberoende var i flertalet fall en hindrande faktor för PLH:s följsamhet. PLH:s omgivning och nätverk var både en motverkande faktor och en hjälpsam faktor för PLH:s följsamhet. För PLH, som inte hade råd med mat eller som hade en instabil levnadssituation, upplevde svårigheter med att uppnå följsamhet. Hur PLH kände sig bemötta av vårdgivare påverkade följsamheten. För PLH var det viktigt för PLH att känna sig delaktiga i sin vård gällande ART och biverkningar. Hjälpmedel och patientutbildning var verktyg som kunde underlätta för PLH att uppnå följsamhet. Rutiner visade sig vara väsentligt för PLH att uppnå följsamhet. Slutligen var biverkningar till följd av ART en hindrande faktor för att uppnå följsamhet. Konklusion. Biverkningar, samsjuklighet med psykisk ohälsa samt stigma var de främsta faktorerna som hindrade PLH att uppnå följsamhet. Vidare kunskapsutveckling behövs för att minska biverkningar, behandla samsjuklighet och motarbeta stigmatisering för att PLH lättare ska upprätthålla följsamheten. Endel av kunskapsutvecklingen är att den grundutbildade sjuksköterskan behöver bredare kunskap. / Background. The effective treatment for HIV was available in 1996. The treatment for HIV causes several side effects that could have an impact on adherence. Low adherence has led to medical resistance. Aim. The aim is to explore experiences of adherence by people living with HIV with ongoing antiretroviral pill treatment (ART). Method. A literature study with a qualitative approach. Result. This study is based on 12 scientific articles. The majority of people living with HIV (PLH) discovered their own strategies to find motivation in being adherent. Depressed mood and substance addiction were a hindering factor in being adherent. The network and surrounding of PLH were either a discouraging or facilitating factor to adherence. PLH with food insecurity and homelessness experienced difficulties adhering to ART. Clinicians approach to PLH influenced the rate of adherence. It was essential that PLH was involved in their own care regarding ART and side effects. Utilities and patient education were useful tools to facilitate adherence. Routines were shown to be essential for PLH in being adherent. Lastly, side effects due to ART were a hindering factor in achieving adherence. Conclusion. Side effects, comorbidity with mental illness and stigma were the main factors hindering PLH in achieving adherence. Further research is needed to reduce side effects, treat comorbidity and counteract stigma to facilitate adherence. The further research is needed to broaden the knowledge of registered nurses.

Chemotherapy Induced Peripheral Neuropathy (CIPN) is known to impact negatively on patients' quality of life. It has been reported that these patients tend to have sensitivity thresholds to stimuli, such as pain and temperature, that are different from those of normal subjects. The effect of chemotherapeutic agents on the central nervous system (CNS) has been observed; however, most of the mechanisms involved are not exactly understood. A quantitative investigation into the temperature sensitivity changes in the spinal cords and brains of chemotherapy patients would provide important information in understanding the side effects of this treatment modality. In the first part of the project, the temperature perceptional changes in terms of brain activation patterns of the chemotherapy patients with CIPN are studied using brain function MRI. In the second part of the project, the structural changes of the brain and spinal cord of chemotherapy patients with CIPN are studied using diffusion tensor imaging (DTI). High b-value (b = 1500 s/mm2) and low b-value (b=650 s/mm2) settings will be use during the spinal cord DTI scans. Due to the sample size limitation, no comparison between healthy volunteers and CIPN patients can be done based on the existing temperature fMRI data. However, the developed temperature fMRI protocol shows good reliability in detecting temperature response. Based on the spinal cord DTI result using b = 1500 s/mm2, decrease in FA value has been observed. The corresponding FA values of CIPN patient and healthy volunteers are 0.28±0.10 and 0.41±0.02 , respectively. (t-test = 2.63 >2.447, p=0.05 level of significant) However, no significant difference is observed in other diffusion parameters. This results also suggests that application of high b-value setting is more suitable as it is better at detecting diffusion at microstructure. / Thesis / Doctor of Philosophy (PhD)

The prediction of polypharmacy side effects is crucial to reduce the mortality and morbidity of patients suffering from complex diseases. However, its experimental prediction is unfeasible due to the many possible drug combinations, leaving in silico tools as the most promising way of addressing this problem. This thesis improves the performance and robustness of a state-of-the-art graph convolutional network designed to predict polypharmacy side effects, by feeding it with complexity properties of the drug-protein network. The modifications also involve the creation of a direct pipeline to reproduce the results and test it with different datasets. / För att minska dödligheten och sjukligheten hos patienter som lider av komplexa sjukdomar är det avgörande att kunna förutsäga biverkningar från polyfarmaci. Att experimentellt förutsäga biverkningarna är dock ogenomförbart på grund av det stora antalet möjliga läkemedelskombinationer, vilket lämnar in silico-verktyg som det mest lovande sättet att lösa detta problem. Detta arbete förbättrar prestandan och robustheten av ett av det senaste grafiska faltningsnätverken som är utformat för att förutsäga biverkningar från polyfarmaci, genom att mata det med läkemedel-protein-nätverkets komplexitetsegenskaper. Ändringarna involverar också skapandet av en direkt pipeline för att återge resultaten och testa den med olika dataset.

Advances in breast cancer detection and oncology treatment modalities have prolonged the survival time for the cancer population, which is officially the largest group of cancer survivors among women in the western world, including South Africa (Brem & Kumar, 2011; Fisher, Dolbeault, Sultan & Bredart, 2014; Herbst, 2011; Reyes-Gibby, et al., 2012). In the light of shocking statistics and ever rising numbers of cancer, especially breast cancer, the time is ripe for further research in the domain of psycho-oncology and has motivated the researcher, due to her interest and involvement in breast cancer, to make this her field of research. Despite the need for a bio-psycho-social approach when treating cancer patients there is little literature available on the psychological interventions in South Africa where the majority of research studies previously conducted in South Africa have generally focused on the bio-medical aspects of cancer (Albrecht, 2009; Venter, 2014). To comprehend the paradigm of psycho-oncology, which is the backbone of this study, a theoretical framework was attained from Engel’s humanistic or psychological model (caring) and Pasteur’s biomedical model (curing) (Borrel-Carrio, Suchman, & Epstein, 2004). The primary aim of this study was to explore the lived experiences of breast cancer patients concerning their diagnosis, treatment and survivorship and unique needs for psycho-oncological interventions through their own “voices”. The research was conducted within a qualitative framework with a case study method of inquiry employing open-ended style interviews and psychotherapeutic sessions with five purposely sampled breast cancer patients. Two qualitative questionnaires were also used for triangulation purposes. Transcripts of all the therapeutic sessions were analysed using interpretive analysis where categories and themes were developed and described in full. Findings indicated that in spite the extensive proof that breast cancer causes numerous sexual and psychological complications during active treatment and afterwards, patients still feel that they have no “platform” to express their emotions and sexual issues within the oncology framework, or that there is enough and sufficient assistance to attend to their needs. e The researcher hopes that this study will make a valuable contribution to research in the field of psycho-oncology in South Africa and to indicate new realities of the chronicity of breast cancer and treatment complications that demand psychotherapeutic interventions in cancer care and that the study will initiate new ways of understanding the role of psychology and the psychologist in the medical world of cancer. The researcher hopes that by offering an understanding of participants’ unique experiences of this process, practitioners will have insight when working therapeutically with this population and empower them to have a quality of life, even within the boundaries of their illness. / Psychology / D. Litt. et Phil. (Psychology)

The word "cancer" has different meanings for different people. In general, it is synonymous with fatality, either imminent or in the forseeable future. How each person perceives and attributes meaning to this personal experience, varies according to idiosyncratic factors. These factors are constituted by each individual's unique internal make up and by external influences and it is the combination of the multiplicity of factors that bring about the personal attributions of meaning for each individual. The thesis examines the attributions of meaning of a sample of 42 women with breast cancer, through administration of a semi-structured interview and questionnaire, with follow up interviews. The theoretical concepts which are explored, examine the shift away from the traditional, Newtonian, linear-causal, neutral observer model (as in the traditional medical model), towards an ecosystemic, a-causal, contextual, holistic stance. Ecosystemic thinking is utilised in this research work, and this way of thinking is applied to the findings. In addition, a qualitative, descriptive approach is adopted, so that an in depth emphasis rather than a quantitative, empirical view of the patients in the sample, is undertaken. The applied questionaire focuses on the patient's experience of cancer diagnosis, with more specific reference to the side effects of the chemotherapy. The emphasis is towards the issue of anticipatory nausea and emesis and the possible use of hypnosis in relation to these effects. Each patient's attribution of meaning to these aspects forms the core of the thesis. The study discloses the wide variety of attributions of meaning held by different women in a similar predicament towards different aspects of that predicament. Concomitantly, the study highlights the limitations of the traditional, medical model which contribute to diminishing the personal understanding of each patient, and the impact of this on both treatment and outcome for each patient. / Psychology / D.Phil. (Psychology)

Résumé : Les méthodes de détection de similarités de sites de liaison servent entre autres à la prédiction de fonction et à la prédiction de cibles croisées. Ces méthodes peuvent aider à prévenir les effets secondaires, suggérer le repositionnement de médicament existants, identifier des cibles polypharmacologiques et des remplacements bio-isostériques. La plupart des méthodes utilisent des représentations basées sur les atomes, même si les champs d’interaction moléculaire (MIFs) représentent plus directement ce qui cherche à être identifié. Nous avons développé une méthode bio-informatique, IsoMif, qui détecte les similarités de MIF entre différents sites de liaisons et qui ne nécessite aucun alignement de séquence ou de structure. Sa performance a été comparée à d’autres méthodes avec des bancs d’essais, ce qui n’a jamais été fait pour une méthode basée sur les MIFs. IsoMif performe mieux en moyenne et est plus robuste. Nous avons noté des limites intrinsèques à la méthodologie et d’autres qui proviennent de la nature. L’impact de choix de conception sur la performance est discuté. Nous avons développé une interface en ligne qui permet la détection de similarités entre une protéine et différents ensembles de MIFs précalculés ou à des MIFs choisis par l’utilisateur. Des sessions PyMOL peuvent être téléchargées afin de visualiser les similarités identifiées pour différentes interactions intermoléculaires. Nous avons appliqué IsoMif pour identifier des cibles croisées potentielles de drogues lors d’une analyse à large échelle (5,6 millions de comparaisons). Des simulations d’arrimage moléculaire ont également été effectuées pour les prédictions significatives. L’objectif est de générer des hypothèses de repositionnement et de mécanismes d’effets secondaires observés. Plusieurs exemples sont présentés à cet égard. / Abstract : Methods that detect binding site similarities between proteins serve for the prediction of function and the identification of potential off-targets. These methods can help prevent side-effects, suggest drug repurposing and polypharmacological strategies and suggest bioisosteric replacements. Most methods use atom-based representations despite the fact that molecular interaction fields (MIFs) represents more closely the nature of what is meant to be identified. We developped a computational algorithm, IsoMif, that detects MIF similarities between binding sites. We benchmark IsoMif to other methods which has not been previously done for a MIF-based method. IsoMif performed best in average and more consistently accross datasets. We highlight limitations intrinsic to the methodology or to nature. The impact of design choices on performance is discussed. We built a freely available web interface that allows the detection of similarities between a protein and pre-calculated MIFs or user defined MIFs. PyMOL sessions can be downloaded to visualize similarities for the different intermolecular interactions. IsoMif was applied for a large-scale analysis (5,6 millions of comparisons) to predict offtargets of drugs. Docking simulations of the drugs in the binding site of their top hits were performed. The primary objective is to generate hypotheses that can be further investigated and validated regarding drug repurposing opportunities and side-effect mechanisms.

Radon gas may be a major air quality hazard issue inside the home. Radon (222Rn) comes from the natural breakdown of radioactive uranium (238U) via radium (226Ra) in soil, rocks, and water. Radon and its progeny contribute more than 50% of the total radiation dose to the human population due to inhalation; it can result in severe and fatal lung disease. This investigation has determined the radon concentrations in seventy-seven domestic houses in a mountainous area of Hamadan in Iran which were monitored using track-etch detectors of type CR-39 exposed for three month periods. The arithmetic mean radon concentration in Hamadan buildings was determined to be 80 Bqm-3 and also an average indoor annual effective dose equivalent for the Hamadan city population was calculated as 1.5 mSv. Maximum radon concentrations were noted during the winter and spring season. In addition to this, 28 water wells were monitored by utilizing a Sarad Doseman detector at hourly intervals over extended periods. Radon measurements were also carried out in the nearby Alisadr show cave, using Solid State Nuclear Track etch Detectors (SSNTDs) during the winter and the spring periods. In the cave, the average annual effective geometric and arithmetic mean dose for guides was 28.1 and 34.2 mSv respectively. The dose received by visitors was very low. Hamadan city is built on alluvial fan deposits which are the source of the local water supply. The data from the wells shows that the groundwater in these alluvial deposits influences the flux of radon. The atmospheric radon concentration measurement in wells above the water surface ranged from 1,000 Bqm-3 to 36,600 Bqm-3. There is evidence that radon-rich ground waters play a significant role in the transport of radon through the alluvial fan system. There is evidence that the radon concentrations in homes in Hamadan are greatly influenced by the porous nature of the underlying geology and the movement of groundwater within the alluvial fan.

The aims of this study were to explore professionals’ and clients’ experiences of diagnosis and treatment of auditory verbal hallucinations with a view to identifying important clinical issues for counselling psychologists. Six professionals, three psychologists and three psychiatrists, who had worked with people who hear voices, alongside four clients who hear voices, volunteered and participated in a semi-structured interview. These interviews were transcribed and analysed using Interpretative Phenomenological Analysis (IPA) as described by Smith, Flowers and Larkin (2009). A table of super-ordinate and sub-ordinate themes was created as a result of this analysis. A number of themes arose from both groups of participants’ experiences. The main themes that arose for the professionals was: professional ambivalence; varying theories on causes of voices; perspectives on diagnosis and formulation; perspectives on medication; thoughts on working therapeutically; and, thinking on recovery. The themes that arose from the clients’ experiences were feelings about diagnosis and experiences of treatment. This research concludes that there is professional ambivalence in working with people who hear voices that is caused by a lack of certainty about the causes of the phenomenon alongside a lack of training in working with clients who have symptoms of psychosis. This impacts clients in several ways. The clients in this study were not offered the option to have any involvement in their own care and none of them were offered therapy as a treatment option. The study also concludes that psychiatric diagnosis does not consider all pertinent information related to clients’ issues which can lead to inconsistency in the diagnosis of clients who hear voices.

Submitted in fulfillment of the requirements for the degree of Doctor of Technology: Quality Management, Durban University of Technology, 2014. / Hearing conservation in the industrial setting has mainly focussed on the harmful effects of noise exposure on the auditory system. This study investigated the co-exposure to noise and ototoxic chemicals on the auditory system of workers engaged by labour brokers. It examined the adequacy of current occupational health and safety legislation to address chemically induced hearing loss and makes recommendations at a policy level to protect workers’ hearing at the workplace. This study is an exploratory cross-sectional field case study in an industrial setting. A sample of 300 workers was drawn from a rubber factory involved in the manufacture of components for the motor, shoe and plumbing industries in the metropolitan area of Durban. Purposive sampling was undertaken amongst a cohort of day shift workers which constituted the research subjects. The research tools used in the study included the completion of the NoiseChem questionnaire, conducting pure tone audiometric testing on research subjects, monitoring noise exposure levels and performing chemical air monitoring of the ambient environment. This study confirms that a segment of the research subjects were exposed to both ototoxic chemicals and noise. Chemical exposure of research subjects was within legal permissible limits in most instances. Noise exposure exceeded the noise rating limit of 85 dBA in certain work areas. Multiple regression analysis revealed that there was a slight trend towards co-exposure to chemicals and noise being risk factors for hearing loss with an odds ratio of 1.7 (95% CI = 0.34 – 8.57) but the p value was not significant. No significant association with hearing loss was evident for workers exposed to chemical only with odds ratio of 0.41 (95% CI = 0.11 – 1.53, p = 0.19) and noise only with odds ratio of 0.87 (95% CI = 0.32 – 2.31, p = 0.78). The study indicated that workers exposed to both ototoxic chemicals and noise may be more susceptible to hearing loss in their current jobs. The study draws attention to policy gaps in the Occupational Health and Safety Act and proposes changes to address the shortcomings. / D

Les antipsychotiques atypiques sont des options de traitement de première ligne pour la schizophrénie. Cependant, la prise d’antipsychotiques atypiques, comme l’olanzapine, est associée à des effets secondaires métaboliques : l’augmentation du poids, la dyslipidémie et l’intolérance au glucose. Les mécanismes en lien avec ces effets secondaires sont à ce jour peu connus. Ce mémoire étudie l’évolution de différents paramètres, tant au niveau biométrique (poids, IMC, circonférence abdominale), qu’au niveau sérique (bilan lipidique, glycémie à jeun, insuline, leptine, ghreline) et clinique (mesures des symptômes positifs, négatifs et généraux de la schizophrénie, de même que des comportements alimentaires) chez des sujets schizophrènes, traités pendant 16 semaines avec l’olanzapine. Des examens de résonance magnétique, structurale et fonctionnelle, ont été effectués au début et à la fin du traitement d’olanzapine chez les sujets schizophrènes et chez un groupe de sujets contrôles afin d’identifier les régions cérébrales dont les volumes ou les activations pourraient être associés aux mécanismes d’effets secondaires métaboliques. Nos résultats confirment l’émergence de multiples effets secondaires métaboliques, associés à des modifications des comportements alimentaires, en lien avec la prise d’olanzapine auprès de notre échantillon. Des associations ont été retrouvées entre les changements métaboliques et les volumes de plusieurs régions cérébrales, notamment les hippocampes, les précunei et le gyrus orbitofrontal droit. De plus, des différences en terme d’activations cérébrales entre les sujets contrôles et les patients schizophrènes, qui ont été accentuées par le traitement d’olanzapine, ont aussi été décrites notamment au niveau amygdalien, cérébelleux et des insulas, suggérant l’implication de mécanismes neuronaux dans l’apparition des troubles métaboliques associés aux antipsychotiques atypiques. / Atypical antipsychotics are first line treatment options for schizophrenia. Nevertheless atypical antipsychotics, such as olanzapine, are associated with metabolic adverse effects: weight gain, dyslipidemia and glucose intolerance. Mechanisms underlying these side effects are still poorly understood. This thesis represents a study of the evolution of biometric (body weight, BMI, abdominal circumference), biological (lipid profile, fasting glucose, insulin, leptin, ghrelin) and clinical parameters (positive, negative and general symptoms of schizophrenia as well as eating behavior measures) in schizophrenia patients treated with olanzapine during 16 weeks. Healthy subjects and schizophrenia patients passed structural and functional magnetic resonance examinations (one examination for healthy controls and two examinations for schizophrenia patients, one at the beginning and one after 16 weeks of olanzapine treatment) in order to identify cerebral regions where grey matter volumes or activations could be associated with metabolic side effects mechanisms. Our results confirm that various metabolic adverse effects emerged in our sample of patients during the 16 weeks olanzapine treatment. Eating behavior changes have also been associated with specific metabolic changes. Many associations have been found between cerebral volumes (e.g. bilateral hippocampi and précunei and right orbitofrontal cortex) and metabolic changes. Moreover, cerebral activations differences between healthy controls and schizophrenia patients, that were increased following olanzapine treatment, were also described in the amygdala, cerebellum and insulas, suggesting that neuronal mechanisms were involved in the development of metabolic disorders associated with atypical antipsychotics.