Thesis ((M. Pharm. (Pharmaceutics)) -- University of Limpopo, 2019 / Epilepsy is the fourth most common neurological disorder after migraine, stroke and Alzheimer’s disease and it affects about fifty million people worldwide. Careful consideration should be taken when deciding to initiate treatment in epilepsy as it should consider the balance between the possibility of further seizures and their associated risks, including the possible risk of sudden expected death, inconvenience and the risks of taking regular medication for each individual. In the early 1980’s, the first-line treatment for epilepsy was polytherapy. This was due to findings that smaller doses of two drugs rather than larger doses of one drug can achieve synergistic effects or less drug toxicity. However, following more trials on the treatment of epilepsy, this was later changed to monotherapy as first-line treatment. Despite the change, patients remain uncontrolled on a single anti-epileptic drug, thus they are initiated on polytherapy, one such combination being carbamazepine in combination with sodium valproate. The use of these in combination has pharmacological threats such as compliance, the control of side effects and the achievement of synergistic effects. The development of a Fixed Dose Combination (FDC) has often been used to resolve pharmacological threats, and this study aims to develop a fixed dose combination tablet of carbamazepine and sodium valproate to resolve the pharmacological threats in epilepsy. Samples of carbamazepine and sodium valproate and a physical mixture (1:1 w/w) of both drugs and excipients were prepared for compatibility with thermal analysis and spectroscopy techniques. Data was analysed by comparing the DSC curves, FTIR spectra, XRPD peaks and TAM analysis of carbamazepine and sodium valproate alone and in their physical mixture (1:1 w/w) and with excipients. Both carbamazepine and sodium valproate were evaluated for flowability using angle of repose, tapped and bulk density, compressibility index and particle size distribution. To formulate the proposed FDC tablet of carbamazepine and sodium valproate, direct compression and wet granulation methods were employed. The tablets were then evaluated for official and non-official post formulation parameters (weight variation, crushing strength, friability, diameter and thickness, and disintegration) according to BP and USP standards. A standardised HPLC method was developed and validated for analytical procedures. Dissolution studies were conducted xiii according to USP methods to verify and quantify the release of the APIs from the FDC tablet. Carbamazepine and sodium valproate were tested for compatibility with excipients using DSC, FTIR, XRPD and TAM analysis. The overall results confirmed that carbamazepine and sodium valproate are compatible, with each other and the excipients used in the study. Powder flow of carbamazepine and sodium valproate was poor, hence they were subjected to granulation prior to compression to improve flowability. The specifications of the fixed-dose combination were developed in accordance with the FDA’s quality by design concept and WHO recommendations. The tablets were subjected to non-official and official pharmacopoeial tests, and passed all the tests. Dissolution studies according to a USP method were conducted to verify and quantify the release of the APIs in the fixed-dose combination. The initial dissolution rate (DRi) of carbamazepine and sodium valproate in the SLS dissolution medium was rapid as required for an immediate release formulation. The study aimed at developing a fixed dose combination of carbamazepine and sodium valproate to try to reduce the burden of taking more than one tablet for epilepsy. Based on the results obtained from preformulation studies to assay of the final product, the study was successful. / Chieta bursary and HWseta

South Africa has the largest HIV-infected population in the world, with 2015 estimates of 7 million people living with HIV and 180,000 AIDS-related deaths. The South African government began scale-up of a public-sector HIV care and treatment program in 2004, and by the end of 2015, 3.4 million HIV-infected individuals were on antiretroviral therapy (ART). When scale-up began in South Africa, ART was only available to HIV-infected individuals with CD4 counts ≤200 cells/µL or WHO clinical stage 4 disease. In 2010, treatment was extended to patients who were pregnant or who had tuberculosis and a CD4 ≤350 cells/µL, and in 2011, eligibility was extended to all patients with CD4 ≤350 cells/µL. In 2013 patients with WHO clinical stage 3 disease became eligible. In 2015, the eligibility threshold was increased to CD4 ≤500 cells/µL, and in 2016, the South African National Department of Health announced that the country would implement a “test and treat” strategy, offering free ART to all HIV-infected individuals, regardless of CD4 count. This dissertation examines the effectiveness of several expansions and modifications to South Africa’s treatment program. In study 1, we investigated whether the 2011 extension of HIV treatment to patients with CD4 counts ≤350 cells/µL successfully increased the number of newly-eligible patients on treatment (those with CD4 counts between 201–350 cells/µL) without crowding out previously-eligible patients with more severe disease (CD4 counts ≤200 cells/µL), focusing on a network of rural clinics in KwaZulu-Natal. We found encouraging results, with newly-eligible patients (CD4 201–350) initiating treatment at a greater frequency (73.0 additional patients per month; 95% CI: 42.1; 103.9) and 47% faster than before (95% CI: 19%; 82%), while previously eligible patients (CD4 ≤200) experienced no decline in the number of patients initiating treatment or the speed of treatment uptake. In study 2, we evaluated whether the introduction of a single-pill fixed-dose combination (FDC) treatment for ART initiators in South Africa had an impact on attrition from care compared to the previously-recommended multiple-pill regimen. We focused on an urban clinic in Johannesburg, using four different clinic attendance measures to define attrition (generally a combined measure of loss to follow-up and mortality). An intention-to-treat analysis revealed an estimated 11.3 percentage point decrease in attrition (95% CI: -22.0; -0.6) associated with the policy change, while a regression discontinuity analysis estimated an 18.0 percentage point drop in attrition (95% CI: -33.6; -2.4) associated with single-pill FDC treatment relative to multiple pills, controlling for unmeasured confounding. In study 3, we used stratified instrumental variable analysis to examine whether the effect of FDCs on attrition varied across subsets of the patient population in the same Johannesburg clinic we evaluated in study 2. We saw larger effects among women (RD -0.25; 95% CI: -0.42; -0.09), non-anemic patients (RD -0.24; 95% CI: -0.41; -0.08), patients with early-stage (as opposed to advanced) clinical disease (RD -0.20; 95% CI: -0.32; -0.07), and those with high CD4 counts (for CD4 ≥350 cells/µL, RD -0.58; 95% CI: -1.58; 0.42). These results suggest that healthier patients saw the greatest improvement in retention in care following the switch from multiple-pill to single-pill regimens. In an era where the healthiest HIV-infected patients are now being targeted for ART treatment, FDCs can play a large role in preventing attrition from care. These three studies depict an HIV program that has successfully grown to treat increasing numbers of patients using up-to-date strategies of care. Given the immense scale and cost of South Africa’s HIV treatment program, it is important to continue to monitor its effectiveness, especially as it introduces new treatments and strategies and adapts to the changing epidemic.

Cette thèse vise à proposer un modèle théorique et une méthodologie permettant d’effectuer des analyses linguistiques fines des textes, permettant de rendre compte des éléments utiles des courriers à savoir : le motif/objet du courrier, l’émetteur et le destinataire du courrier. L’approche doit permettre un traitement efficace des verrous technologiques du TAL, et spécialement le problème du figement et plus particulièrement des séquences verbales figées. Il s’agit d’un phénomène extrêmement fréquent dans toutes les langues, présenté comme une des sources de difficultés majeures pour la recherche d’information et la veille dans les documents dits non structurés. La thèse comprendra une partie applicative démontrant l’efficacité de la théorie proposee, et aboutissant à un système de traitement automatique des courriers. Par ailleurs, la démarche méthodologique aboutissant aux ressources linguistiques doit permettre de définir un outil d’apprentissage automatique de ces ressources qui pourra ainsi être appliqué à de nouveaux types de documents. / The aim of this thesis is to propose a theoretic model and a methodology to make fine linguistic text analysis. That can represent elements useful in mails like: message purposes, message addressee or sender. This approach must permit an efficient processing of NLP technology issues, especially in the fixity problematic and mainly on fixed verbal sequences. This phenomenon is extremely recurrent in all languages. It is introduced as a main issue for information retrieval in unstructured documents. This thesis will include an applicative part showing the relevance of the proposed theory and to make a system to automatically process mails. Moreover, the methodology which creating linguistically resources must permit to define an automatic learning resources tool which can be applied on new kind of documents.

Magister Legum - LLM / This research aims to explore the available legislative protection afforded to atypical employment, with specific reference to fixed-term workers. Atypical, employed workers, such as fixed-term workers, are often exploited as they do not always enjoy the same rights as typical employees. Hence, they are in a precarious position with regard to employee benefits and rights. Common law provides for the automatic termination of a fixed-term contract of employment on a specific date, typically either as stipulated in the contract or upon completion of a project or task. The Constitution of South Africa, however, provides for the right to fair labour practices for everyone. In 2014 section 186(1)(b) of the Labour Relations Act (LRA) was amended, while section 198B was added as a completely new section. Together these sections are aimed at providing increased protection to fixed-term workers.

The master´s thesis entitled The issue of obstacles on roads deals with the analysis of accidents with a obstacle in a selected area in the Czech Republic. The main purpose of the master´s thesis is to find out the details of the occurrence of traffic accidents with a obstacle and their other properties (type of obstacle, accident time, climatic conditions etc.).

京都大学 / 0048 / 新制・課程博士 / 博士(経済学) / 甲第18037号 / 経博第490号 / 新制||経||268(附属図書館) / 30895 / 京都大学大学院経済学研究科経済学専攻 / (主査)教授 西山 慶彦, 准教授 奥井 亮, 講師 末石 直也 / 学位規則第4条第1項該当 / Doctor of Economics / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20975号 / 医博第4321号 / 新制||医||1026(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 川上 浩司, 教授 鈴木 茂彦, 教授 開 祐司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・論文博士 / 博士(理学) / 乙第13201号 / 論理博第1560号 / 新制||理||1635(附属図書館) / 京都大学大学院理学研究科数学・数理解析専攻 / (主査)教授 宍倉 光広, 教授 泉 正己, 教授 國府 寛司 / 学位規則第4条第2項該当 / Doctor of Science / Kyoto University / DFAM

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