Malaria is a life–threatening disease caused by Plasmodium spp and causes over one million deaths annually. The complex life cycle of the malaria parasite offers several points of attack for the antimalarial drugs. The rapid spread of resistance against antimalarial drugs, especially chloroquine and pyrimethamine–sulphadoxine, emphasises the need for new alternatives or modification of existing drugs. Artemisinin–based combination therapies (ACT’s) with different targets prevent or delay the development of drug resistance and therefore have been adopted as first–line therapy by all endemic countries. Proguanil–dapsone, an antifolate combination is more active than pyrimethamine–sulphadoxine and is being considered as an alternative to pyrimethamine–sulphadoxine. Artesunate–proguanil–dapsone is a new ACT that has wellmatched pharmacokinetics and is relatively rapidly eliminated; therefore there is a reduced risk of exposure to any single compound and potentially a decreasing risk of resistance. A few studies have been done on a triple fixed–dose combination therapy for malaria treatment and such a combination for artesunate, proguanil and dapsone are not currently investigated, manufactured or distributed. The aim of this study was to develop a triple fixed–dose combination for artesunate, proguanil and dapsone. The formulation was developed in three phases; basic formulation development, employing factorial design to obtain two possible optimised formulations and evaluating the optimised formulations. During the formulation development the most suitable manufacturing procedure and excipients were selected. A full 24 factorial design (four factors at two levels) was used to obtain the optimised formulations. As end–points to identify the optimised formulations, weight variation, friability, crushing strength and disintegration of the tablets, were used. Statistical analysis (one way ANOVA) was used to identify optimal formulations. To identify any interaction between the active pharmaceutical ingredients (API’s) and the API’s and excipients, differential scanning calorimetry was done. Flow properties of the powder mixtures (of the optimised formulations) were characterised by means of angle of repose; critical orifice diameter (COD); bulk density and tapped density; and flow rate. Tablets of the two optimised powder formulations were compressed. The tablets were evaluated and characterised in terms of weight variation, friability, crushing strength, disintegration and dissolution behaviour. Initial formulation development indicated that wet granulation was the most suitable manufacturing method. The results from the factorial design indicated that different amounts (% w/w) of the lubricant and binder as well as two different fillers influenced the weight variation, crushing strength and disintegration statistically significant. Two formulations containing two different fillers (microcrystalline cellulose or Avicel® PH 101, and lactose or Granulac® 200) were found to be within specifications and ideal for manufacturing. Tablets prepared from the FA formulation (formulation containing Avicel® PH 101) complied with the standards and guidelines for weight variation, friability, crushing strength and disintegration as set by the British Pharmacopoeia (BP). Tablets had an average crushing strength of 121.56 ± 0.022 N. Tablets disintegrated within 52.00 seconds and a maximum weight loss of 0.68% occurred during the friability test. Weight variation of the tablets prepared from the FG formulation (formulation containing Granulac® 200) complied with the standards. Average crushing strength was 91.99 ± 6.008 N and the tablets disintegrated within 140.00 seconds. Percentage friability (1.024%) did not comply with the guideline of a percentage friability of less than 1%, however, no cracked or broken tablets were seen. Dissolution showed that 98, 93 and 94% of artesunate, proguanil and dapsone were respectively released (of the label value) within 15 minutes for the FA formulations. Release of artesunate, proguanil and dapsone for the FG formulation was 62, 85 and 92% for the same time period. The release of the three API’s (the FG formulation) increased to 78, 89 and 92%, respectively, after 45 minutes. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2012.

Malaria is a life–threatening disease caused by Plasmodium spp and causes over one million deaths annually. The complex life cycle of the malaria parasite offers several points of attack for the antimalarial drugs. The rapid spread of resistance against antimalarial drugs, especially chloroquine and pyrimethamine–sulphadoxine, emphasises the need for new alternatives or modification of existing drugs. Artemisinin–based combination therapies (ACT’s) with different targets prevent or delay the development of drug resistance and therefore have been adopted as first–line therapy by all endemic countries. Proguanil–dapsone, an antifolate combination is more active than pyrimethamine–sulphadoxine and is being considered as an alternative to pyrimethamine–sulphadoxine. Artesunate–proguanil–dapsone is a new ACT that has wellmatched pharmacokinetics and is relatively rapidly eliminated; therefore there is a reduced risk of exposure to any single compound and potentially a decreasing risk of resistance. A few studies have been done on a triple fixed–dose combination therapy for malaria treatment and such a combination for artesunate, proguanil and dapsone are not currently investigated, manufactured or distributed. The aim of this study was to develop a triple fixed–dose combination for artesunate, proguanil and dapsone. The formulation was developed in three phases; basic formulation development, employing factorial design to obtain two possible optimised formulations and evaluating the optimised formulations. During the formulation development the most suitable manufacturing procedure and excipients were selected. A full 24 factorial design (four factors at two levels) was used to obtain the optimised formulations. As end–points to identify the optimised formulations, weight variation, friability, crushing strength and disintegration of the tablets, were used. Statistical analysis (one way ANOVA) was used to identify optimal formulations. To identify any interaction between the active pharmaceutical ingredients (API’s) and the API’s and excipients, differential scanning calorimetry was done. Flow properties of the powder mixtures (of the optimised formulations) were characterised by means of angle of repose; critical orifice diameter (COD); bulk density and tapped density; and flow rate. Tablets of the two optimised powder formulations were compressed. The tablets were evaluated and characterised in terms of weight variation, friability, crushing strength, disintegration and dissolution behaviour. Initial formulation development indicated that wet granulation was the most suitable manufacturing method. The results from the factorial design indicated that different amounts (% w/w) of the lubricant and binder as well as two different fillers influenced the weight variation, crushing strength and disintegration statistically significant. Two formulations containing two different fillers (microcrystalline cellulose or Avicel® PH 101, and lactose or Granulac® 200) were found to be within specifications and ideal for manufacturing. Tablets prepared from the FA formulation (formulation containing Avicel® PH 101) complied with the standards and guidelines for weight variation, friability, crushing strength and disintegration as set by the British Pharmacopoeia (BP). Tablets had an average crushing strength of 121.56 ± 0.022 N. Tablets disintegrated within 52.00 seconds and a maximum weight loss of 0.68% occurred during the friability test. Weight variation of the tablets prepared from the FG formulation (formulation containing Granulac® 200) complied with the standards. Average crushing strength was 91.99 ± 6.008 N and the tablets disintegrated within 140.00 seconds. Percentage friability (1.024%) did not comply with the guideline of a percentage friability of less than 1%, however, no cracked or broken tablets were seen. Dissolution showed that 98, 93 and 94% of artesunate, proguanil and dapsone were respectively released (of the label value) within 15 minutes for the FA formulations. Release of artesunate, proguanil and dapsone for the FG formulation was 62, 85 and 92% for the same time period. The release of the three API’s (the FG formulation) increased to 78, 89 and 92%, respectively, after 45 minutes. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2012.

Le sujet principal de cette thèse est le développement d’un contrôle commande intelligentpour une prothèse de main robotique avec des parties souples qui comporte: (i) uneinterface homme–machine permettant de contrôler notre prothèse, (ii) et des stratégiesde contrôle améliorant les performances de la main robotique. Notre approche tientcompte : 1. du développement d’une interaction intuitive entre l'homme et la prothèse facilitantl'utilisation de la main, d'un système d’interaction entre l’utilisateur et la mainreposant sur l'acquisition de signaux ElectroMyoGrammes superficiels (sEMG) aumoyen d'un dispositif placé sur l'avant-bras du patient. Les signaux obtenus sontensuite traités avec un algorithme basé sur l'intelligence artificielle, en vued'identifier automatiquement les mouvements désirés par le patient.2. du contrôle de la main robotique grâce à la détection du contact avec l’objet et de lathéorie du contrôle hybride.Ainsi, nous concentrons notre étude sur : (i) l’établissement d’une relation entre lemouvement du membre supérieur et les signaux sEMG, (ii) les séparateurs à vaste margepour classer les patterns obtenues à partir des signaux sEMG correspondant auxmouvements de préhension, (iii) le développement d'un système de reconnaissance depréhension à partir d'un dispositif portable MyoArmbandTM, (iv) et des stratégieshybrides de contrôle commande de force-position de notre main robotique souple. / The target of this thesis disertation is to develop a new Smart control of a soft robotic hand prosthesis for the soft robotic hand prosthesis called ProMain Hand, which is characterized by:(i) flexible interaction with grasped object, (ii) and friendly-intuitive interaction between human and robot hand. Flexible interaction results from the synergies between rigid bodies and soft bodies, and actuation mechanism. The ProMain hand has three fingers, each one is equipped with three phalanges: proximal, medial and distal. The proximal and medial are built with rigid bodies,and the distal is fabricated using a deformable material. The soft distal phalange has a new smart force sensor, which was created with the aim to detect contact and force in the fingertip, facilitating the control of the hand. The friendly intuitive human-hand interaction is developed to facilitate the hand utilization. The human-hand interaction is driven by a controller that uses the superficial electromyographic signals measured in the forearm employing a wearable device. The wearable device called MyoArmband is placed around the forearm near the elbow joint. Based on the signals transmitted by the wearable device, the beginning of the movement is automatically detected, analyzing entropy behavior of the EMG signals through artificial intelligence. Then, three selected grasping gesture are recognized with the following methodology: (i) learning patients entropy patterns from electromyographic signals captured during the execution of selected grasping gesture, (ii) performing a support vector machine classifier, using raw entropy data extracted in real time from electromyographic signals.

Avec l’avènement des dispositifs nomades tels que les smartphones et les tablettes, la reconnaissance automatique de l’écriture manuscrite cursive à partir d’un signal en ligne est devenue durant les dernières décennies un besoin réel de la vie quotidienne à l’ère numérique. Dans le cadre de cette thèse, nous proposons de nouvelles stratégies pour un système de reconnaissance de mots manuscrits en-ligne. Ce système se base sur une méthode collaborative segmentation/reconnaissance et en utilisant des analyses à deux niveaux : caractère et bi-caractères. Plus précisément, notre système repose sur une segmentation de mots manuscrits en graphèmes afin de créer un treillis à L niveaux. Chaque noeud de ce treillis est considéré comme un caractère potentiel envoyé à un moteur de Reconnaissance de Caractères Isolés (RCI) basé sur un SVM. Pour chaque noeud, ce dernier renvoie une liste de caractères associés à une liste d’estimations de probabilités de reconnaissance. Du fait de la grande diversité des informations résultant de la segmentation en graphèmes, en particulier à cause de la présence de morceaux de caractères et de ligatures, l’injection de chacun des noeuds du treillis dans le RCI engendre de potentielles ambiguïtés au niveau du caractère. Nous proposons de lever ces ambiguïtés en utilisant des modèles de bi-caractères, basés sur une régression logistique dont l’objectif est de vérifier la cohérence des informations à un niveau de reconnaissance plus élevé. Finalement, les résultats renvoyés par le RCI et l’analyse des modèles de bi-caractères sont utilisés dans la phase de décodage pour parcourir le treillis dans le but de trouver le chemin optimal associé à chaque mot dans le lexique. Deux méthodes de décodage sont proposées (recherche heuristique et programmation dynamique), la plus efficace étant basée sur de la programmation dynamique. / With the advent of mobile devices such as tablets and smartphones over the last decades, on-line handwriting recognition has become a very highly demanded service for daily life activities and professional applications. This thesis presents a new approach for on-line handwriting recognition. This approach is based on explicit segmentation/recognition integrated in a two level analysis system: character and bi-character. More specifically, our system segments a handwritten word in a sequence of graphemes to be then used to create a L-levels lattice of graphemes. Each node of the lattice is considered as a character to be submitted to a SVM based Isolated Character Recognizer (ICR). The ICR returns a list of potential character candidates, each of which is associated with an estimated recognition probability. However, each node of the lattice is a combination of various segmented graphemes. As a consequence, a node may contain some ambiguous information that cannot be handled by the ICR at character level analysis. We propose to solve this problem using "bi-character" models based on Logistic Regression, in order to verify the consistency of the information at a higher level of analysis. Finally, the recognition results provided by the ICR and the bi-character models are used in the word decoding stage, whose role is to find the optimal path in the lattice associated to each word in the lexicon. Two methods are presented for word decoding (heuristic search and dynamic programming), and dynamic programming is found to be the most effective.

Abstract To be able to acquire, produce, and comprehend language, precise central auditory processing (CAP), neural processes utilized for managing auditory input, is essential. However, the auditory environments are not always optimal for CAP because noise levels in children’s daily environments can be surprisingly high. In young children, CAP and its developmental trajectory as well as the influence of noise on it have scarcely been investigated. Event-related potentials (ERPs) offer promising means to study different stages of CAP in small children. Sound processing, preattentive auditory discrimination, and attention shifting processes can be addressed with obligatory responses, mismatch negativity (MMN), and novelty P3 of ERPs, respectively. In this thesis the developmental trajectory of CAP from 2 to 4 years of age as well as noise-induced changes on it, were investigated. In addition, the feasibility of the multi-feature paradigm with syllable stimuli and novel sounds in children was evaluated. To this end, obligatory responses (P1, N2, and N4) and MMNs for consonant, frequency, intensity, vowel, and vowel duration changes, as well as novelty P3 responses, were recorded in a silent condition and with babble noise using the multi-feature paradigm. The participants were voluntary, typically developing children. Significant P1, N2, N4, and MMN responses were elicited at both ages. Also a significant novelty P3, studied at the age of 2 years, was found. From 2 to 4 years, the P1 and N2 latencies shortened. The amplitudes of N2, N4, and MMNs increased and the increment was the largest at frontal electrode locations. During noise, P1 decreased, N2 increased, and the latency of N4 diminished as well as MMNs degraded. The noise-induced changes were largely similar at both ages. In conclusion, the multi-feature paradigm with five syllable deviant types and novel sounds was found to be an appropriate measure of CAP in toddlers. The changes in ERP morphology from 2 to 4 years of age suggest maturational changes in CAP. Noise degraded sound encoding, representation forming, and auditory discrimination. The children were similarly vulnerable to hampering effects of noise at both ages. Thus, noise might potentially harmfully influence language processing and thereby its acquisition in childhood. / Tiivistelmä Kielen omaksumiselle, tuottamiselle sekä ymmärtämiselle on tärkeää tarkka keskushermostollinen kuulotiedon käsittely eli ne hermostolliset prosessit, joita käytetään kuullun aineksen käsittelyyn. Kuunteluympäristöt eivät kuitenkaan aina ole optimaalisia kuulotiedon käsittelylle, sillä melutasot lasten elinympäristöissä voivat olla hyvinkin korkeita. Pienten lasten kuulotiedon käsittelyä, sen kehittymistä ja melun vaikutusta siihen on tutkittu vähän. Kuuloherätevasteet ovat toimiva tapa tarkastella pienten lasten kuulotiedon käsittelyä eri näkökulmista. Äänen käsittelyä, esitietoista kuuloerottelua ja tarkkaavuuden siirtymistä voidaan tarkastella obligatoristen vasteiden, poikkeavuusnegatiivisuuden ja novelty P3 -vasteiden avulla. Tässä väitöskirjassa tarkastellaan kuulotiedon käsittelyn kehittymistä kahden vuoden iästä neljän vuoden ikään sekä melun vaikutusta siihen. Lisäksi arvioidaan tavuärsykkeitä ja poikkeavia ääniä sisältävän monipiirreparadigman soveltuvuutta lapsitutkimuksiin. Tutkimuksissa rekisteröitiin monipiirreparadigman avulla obligatorisia vasteita (P1, N2 ja N4); konsonantin, taajuuden, intensiteetin, vokaalin ja vokaalin keston muutokselle syntyneitä MMN-vasteita sekä novelty P3 -vasteita hiljaisuudessa ja taustamelussa. Tutkimuksen osallistujat olivat vapaaehtoisia tyypillisesti kehittyviä lapsia. Molemmilla tutkimuskerroilla P1, N2, N4 ja MMN poikkesivat merkitsevästi nollatasosta samoin kuin kaksivuotiailta tutkittu novelty P3. Kahden vuoden iästä neljään vuoteen P1- ja N2-vasteiden latenssi lyheni sekä N2, N4 ja MMN vahvistuivat, muutoksen ollessa suurinta frontaalisilla elektrodeilla. Melun aikana P1 heikkeni, N2 vahvistui ja N4-vasteen latenssi lyhentyi. Lisäksi MMN-vaste heikkeni. Melun aiheuttamat muutokset olivat samankaltaisia sekä kahden että neljän vuoden iässä. Johtopäätöksenä voidaan todeta viittä eri tavuärsyketyyppiä ja yllättäviä ääniä sisältävän monipiirreparadigman olevan toimiva menetelmä taaperoiden kuulotiedon käsittelyn tutkimiseen. Kahden ja neljän ikävuoden välillä tapahtuvat muutokset vasteissa kuvastavat kehityksellisiä muutoksia kuulotiedon käsittelyssä. Melu heikentää äänitiedon peruskäsittelyä, edustumien muodostumista ja esitietoista kuuloerottelua. Lapset olivat lähes yhtä alttiita melun vaikutuksille sekä kahden että neljän vuoden iässä. Melu voi siis haitata kielen prosessointia ja sen omaksumista.

Les systèmes infrarouges sont essentiels pour fournir aux forces armées une capacité de reconnaissance des menaces. En contexte opérationnel, ces systèmes sont contraints au temps-réel et à l’accès à des taux de fausses alarmes faibles. Ceci implique la détection des menaces parmi de nombreux objets non-pertinents.Dans ce document, nous combinons des OneClass-SVM pour une décision multiclasse avec rejet(préservant la fausse-alarme). En apprentissage, nous sélectionnons les variables pour contrôler la parcimonie du moteur de décision.Nous présentons également un classifieur original, le Discriminative OneClass-SVM, combinant les propriétés du C-SVM et du OneClass-SVM dans le contexte multiclasse. Ce détecteur de nouveauté n’a pas de dépendance au nombre de classes. Ceci permet une utilisation sur des données à grande échelle.Nos expériences sur des données réelles démontrent l’intérêt des propositions pour les systèmes fortement contraints, face aux méthodes de référence. / Infrared systems are keys to provide automatic control of threats to military forces. Such operational systems are constrained to real-time processing and high efficiency (low false-alarm rate) implying the recognition of threats among numerous irrelevant objects.In this document, we combine OneClass Support Vector Machines (SVM) to discriminate in the multiclass framework and to reject unknown objects (preserving the false-alarm rate).While learning, we perform variable selection to control the sparsity of the decision functions. We also introduce a new classifier, the Discriminative OneClass-SVM. It combines properties of both the biclass-SVM and the OneClass-SVM in a multiclass framework. This classifier detects novelty and has no dependency to the amount of categories, allowing to tackle large scale problems. Numerical experiments, on real world infrared datasets, demonstrate the relevance of our proposals for highly constrained systems, when compared to standard methods.

Residential property not only provides in the basic needs of a person, but is also an indicator of an individual's wealth. The buying and selling of immovable property is complicated and the average person relies on the services of estate agents and banks. The research problem was formulated as follows: Property valuers and estate agents with access to the same information sources determine different market values for the same property. The research problem was researched by means of a literature study and empirical study. The methodology used by property valuers was described in the literature study. How estate agents determine the value of property was researched by means of an empirical study. From the literature study a model was proposed to determine the value of residential property. The information gathered in the empirical study was compared with this model to provide an answer to the research problem. OPSOMMING Residensiële eiendom voorsien nie net in een van die mees basiese behoeftes van 'n mens nie, maar is ook een van die grootste aanduiders van 'n individu se welvaart. Die koop en verkoop van onroerende eiendom is 'n ingewikkelde en die deursnee persoon maak daarom van eiendomsagente en banke gebruik. Die navorsingsprobleem is as volg geformuleer: Eiendomswaardeerders en eiendoms¬agente met toegang tot dieselfde inligtingsbronne bepaal verskillende waardes vir die¬selfde eiendom. Die navorsingsprobleem is deur middel van ʼn literatuurstudie en ʼn empiriese ondersoek nagevors. Die werksaamhede en metodologie wat eiendomswaardeerders gebruik, is aan die hand van die literatuurstudie beskryf. Hoe eiendomsagente te werk gaan om die waarde van eiendom te bepaal is deur middel van ʼn empiriese ondersoek nagevors. Uit die literatuurstudie is daar ʼn model voorgestel vir die bepaling van die waarde van residensiële eiendom. Die inligting wat met die empiriese ondersoek versamel is, is met die model vergelyk om antwoorde op die navorsingsprobleem te verskaf. / Public Administration / M. Tech. (Real Estate)

À l'horizon 2050, environ un tiers de notre population sera âgée de soixante-cinq ans et plus. Les travaux de l'équipe AFIRM du TIMC-IMAG visent à surveiller les personnes âgées à domicile pour détecter une perte d'autonomie le plus précocement possible. Pour ce faire, les travaux de cette thèse tentent d'objectiver les critères ADL ou les grilles de type AGGIR, en classifiant de manière automatique les différentes activités de la vie quotidienne d'une personne par l'intégration de capteurs, créant un Habitat Intelligent pour la Santé (HIS).<br />L'appartement HIS possède des détecteurs de présence infrarouges (localisation), des contacteurs de porte (utilisation de certaines commodités), un capteur de température et d'hygrométrie dans la salle de bains et des microphones (classification des sons/ reconnaissance de la parole avec l'équipe GETALP du LIG). Un capteur cinématique embarqué détecte les transferts posturaux (reconnaissance de formes avec la transformée en ondelettes) et les périodes de marche (analyse fréquentielle).<br />La première partie de ce manuscrit présente la réalisation du capteur cinématique et les algorithmes associés puis une première validation sur des sujets jeunes suivi de la mise en place et de la validation des autres capteurs de l'appartement HIS et enfin l'algorithme de classification des sept activités de la vie quotidienne reconnues (hygiène, élimination, préparation et prise de repas, repos, habillage/déshabillage, détente et communication), par l'intermédiaire des séparateurs à vaste marge. La seconde partie décrit le protocole expérimental pour valider cette classification et discute de la généralisation des premiers résultats présentés.

Residential property not only provides in the basic needs of a person, but is also an indicator of an individual's wealth. The buying and selling of immovable property is complicated and the average person relies on the services of estate agents and banks. The research problem was formulated as follows: Property valuers and estate agents with access to the same information sources determine different market values for the same property. The research problem was researched by means of a literature study and empirical study. The methodology used by property valuers was described in the literature study. How estate agents determine the value of property was researched by means of an empirical study. From the literature study a model was proposed to determine the value of residential property. The information gathered in the empirical study was compared with this model to provide an answer to the research problem. OPSOMMING Residensiële eiendom voorsien nie net in een van die mees basiese behoeftes van 'n mens nie, maar is ook een van die grootste aanduiders van 'n individu se welvaart. Die koop en verkoop van onroerende eiendom is 'n ingewikkelde en die deursnee persoon maak daarom van eiendomsagente en banke gebruik. Die navorsingsprobleem is as volg geformuleer: Eiendomswaardeerders en eiendoms¬agente met toegang tot dieselfde inligtingsbronne bepaal verskillende waardes vir die¬selfde eiendom. Die navorsingsprobleem is deur middel van &#329; literatuurstudie en &#329; empiriese ondersoek nagevors. Die werksaamhede en metodologie wat eiendomswaardeerders gebruik, is aan die hand van die literatuurstudie beskryf. Hoe eiendomsagente te werk gaan om die waarde van eiendom te bepaal is deur middel van &#329; empiriese ondersoek nagevors. Uit die literatuurstudie is daar &#329; model voorgestel vir die bepaling van die waarde van residensiële eiendom. Die inligting wat met die empiriese ondersoek versamel is, is met die model vergelyk om antwoorde op die navorsingsprobleem te verskaf. / Public Administration and Management / M. Tech. (Real Estate)