Les maladies cardiovasculaires (MCV) sont d’une étiologie complexe et elles sont soumises à de nombreux facteurs environnementaux ainsi que génétiques. Malgré les succès obtenus, pendant la dernière décennie, et pour réduire la mortalité CV il est nécessaire l’identification de nouveaux biomarqueurs en utilisant des approches différentes. Cette thèse propose une approche intégrative pour découvrir de nouvelles associations génétiques associés avec les MCV. Nous avons d’abord réuni les résultats existants grâce à des GWAS précédents, puis nous avons recherché la pléiotropie de ces gènes et nous avons dirigé nos efforts vers une possible traduction des résultats obtenus dans l’application clinique. Nous avons détecté les effets pléiotropiques de différent gènes (IL-6R et ABO) avec différents phénotypes lipidiques et inflammatoires. Par ailleurs, nous avons trouvé quelques associations gène-genre intéressantes pour certains gènes étudiés (ABO et GNB3). Concernant l’implémentation clinique des connaissances obtenues par cette thèse, une SNP dans le gène TREM-1, pourrait être utilisé comme un marqueur de risque pour différentes maladies, et nous avons déposé un brevet Européen et nous envisageons de mener des essais cliniques de chez les patients. D’autre part, nous avons détecté une haplotype du gène IL6R qui pourrait être utilisés dans la médecine personnalisée. Nos résultats aident à mieux comprendre comment les gènes étudiés exercent leurs effets au niveau moléculaire, en influant finalement sur l’état des patients souffrant de MCV. Nous espérons que nos résultats vont être pris en compte pour faire progresser la médecine personnalisée / Cardiovascular diseases (CVD) are complex diseases where many environmental and genetic factors are involved. Although the genetic aetiology of the CVD has been extensively investigated the last two decades, alternative approaches are needed in order to keep advancing in the pathophysiology of CVD. In this thesis, we propose an integrative approach to discover new genetic associations potentially involved in CVD. We chose previous GWAS hits and we centred our efforts in studying the pleiotropic and gene-gender interaction effects. Finally, we focused on the implementation of personalized genome-based therapy of the results obtained. New pleiotropic effects were discovered in the IL-6R and ABO genes relating them with different inflammatory and lipid phenotypes. In addition, we studied the gene-gender interaction effects, finding some sex-specific associations in two of the genes studied (ABO and GNB3). Further, we centered our efforts in implementing the results obtained during the thesis at the clinical level. One SNP within the TREM-1 gene was associated with increased levels of its protein and could be used as a predictor or risk biomarker for different diseases. Due to the high potential of this SNP, we applied a European patent and we are planning to start clinical trials in patients. Also, one haplotype in the IL-6R gene could be used in the treatment of personalized medicine. During this thesis, we discovered new gene-phenotype associations involved in CVD and other diseases. Our results help to better understand how the studied genes are exerting their effects at the molecular level. Our results will hopefully be taken into account in future personalized treatments

Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2018-12-04T11:48:43Z No. of bitstreams: 1 Minéa Paschoaleto Fratelli.pdf: 1243825 bytes, checksum: abb36c611f6bf4ed93aa5e7af7fc4e90 (MD5) / Made available in DSpace on 2018-12-04T11:48:43Z (GMT). No. of bitstreams: 1 Minéa Paschoaleto Fratelli.pdf: 1243825 bytes, checksum: abb36c611f6bf4ed93aa5e7af7fc4e90 (MD5) Previous issue date: 2018-09-19 / The present work investigates how the Avaliação Diagnóstica and the Prova Semestral, elaborated by the São Paulo Municipal Department of Education, are appropriated by the intermediary agency, the Regional Board of Education, in view of two focuses: the educational system in a macro view and the school in a micro vision. From this perspective, the question arises as to how the appropriation and reflections on these evaluations are carried out, such as the work carried out by the DRE through the provision of materials on external evaluation, organization of pedagogical bulletins, training of management teams, teacher training and the work carried out by the school, which indicate what students have learned and what they need to learn. The appropriation of this evaluation instrument and the results of these evaluations becomes essential in a formative evaluation perspective and in the processes of regulation of teaching and learning in order to improve student performance and guarantee learning rights. It is known that there are several advances in the implementation of an evaluation policy, but the qualification of this is directly linked to the systemic character of the action. The approach used in the study is qualitative research. It is based on a bibliographical research - with a documentary study to know the history of the external evaluation system in the country and in the Municipal Department of Education - in addition to the materials produced by the SME and the DRE, for the formations that deal with the processes involved in the evaluation, which underpin this study. In addition, from an exploratory survey, semi-structured interviews were conducted with the DRE training team to understand what reports do from external evaluations and what processes are carried out until decision making because of what students need to learn. The survey revealed coherence between what is produced by the SME and the action that the DRE plans for schools, but indicates the necessary investment in decision making beyond the interpretation of the data / O presente trabalho investiga a maneira como a Avaliação Diagnóstica e a Prova Semestral, elaboradas pela Secretaria Municipal de Educação de São Paulo, são apropriadas pelo órgão intermediário, a Diretoria Regional de Educação, tendo em vista dois focos: o sistema educacional, em uma visão macro, e a escola, em uma visão micro. Nessa perspectiva, a indagação parte de como são realizadas a apropriação e as reflexões sobre essas avaliações, como é o trabalho realizado pela DRE a partir da disponibilização de materiais sobre a avaliação externa, organização de boletins pedagógicos, formação das equipes gestoras, formação de professores e acompanhamento do trabalho realizado pela escola, que indicam o que os alunos aprenderam e o que precisam aprender. A apropriação desse instrumento avaliativo e dos resultados dessas avaliações torna-se fundamental numa perspectiva de avaliação formativa e dos processos de regulação do ensino e da aprendizagem, com vistas à melhoria do desempenho dos alunos e à garantia dos direitos de aprendizagem. Sabe-se que há diversos avanços na implementação de uma política de avaliação, mas a qualificação dessa está diretamente ligada ao caráter sistêmico da ação. A abordagem utilizada no estudo é a da pesquisa qualitativa. Parte-se de uma pesquisa bibliográfica - com um estudo de natureza documental - para conhecer o histórico do sistema de avaliação externa no país e na Secretaria Municipal de Educação - além dos materiais produzidos pela SME e pela DRE, para as formações que tratam dos processos envolvidos na avaliação, as quais alicerçam este estudo. Além disso, a partir de uma pesquisa exploratória, entrevistas semiestruturadas foram produzidas, com a equipe formativa da DRE, para compreender que relatos fazem das avaliações externas e quais processos são realizados até a tomada de decisão em razão do que os alunos precisam aprender. A pesquisa revelou coerência entre o que é produzido pela SME e a ação que a DRE planeja para as escolas, mas indica o necessário investimento na tomada de decisão para além da interpretação dos dados

Este estudo tem como objetivo central avaliar a influência da secagem por aspersão de nanocápsulas de núcleo lipídico contendo tretinoína nos perfis in vitro de liberação e de penetração cutânea deste fármaco a partir de hidrogéis. Esses experimentos foram conduzidos empregando-se células de difusão de Franz, pele de abdome de porcos (fêmeas), regime de aplicação de doses infinitas e meio receptor composto por tampão fosfato pH 7,4 e etanol (70:30). A secagem por aspersão das suspensões de nanocápsulas, utilizando PVP e lactose (1:1, m/m) a 10% como adjuvantes, forneceu produtos com bons perfis de dispersão em água, bons rendimentos (próximos a 70%), baixos teores de substâncias voláteis, e teores do fármaco acima de 92%. O tipo de produto intermediário, suspensão aquosa ou respectivo pó, utilizado na produção de hidrogéis (G-LNC-TTN e G-LNC-TTN-SD, respectivamente) não influenciou no perfil de liberação in vitro da tretinoína, que se ajustou ao modelo de Higuchi. No estrato córneo houve diferenças nas quantidades de tretinoína penetradas a partir das duas formulações. O G-LNC-TTN levou a uma retenção exponencial do fármaco nessa camada, enquanto para o G-LNC-TTN-SD isso não ocorreu. Essa diferença foi associada à forma de organização das nanocápsulas na matriz do gel. Na epiderme e na derme, ambas as formulações permitiram a chegada de pequenas e constantes quantidades de tretinoína. No compartimento receptor da célula de Franz o fármaco não foi detectado. A pequena permeação da tretinoína para as camadas mais profundas da pele e para o meio receptor são indicativos de baixa absorção sistêmica, e também podem contribuir para a diminuição dos efeitos adversos associados à terapia tópica com essa substância. A secagem das suspensões de nanocápsulas de núcleo lipídico, nas condições utilizadas, forneceu um intermediário em potencial para a produção de formas farmacêuticas semissólidas contendo tretinoína. / This study’s central goal is to assess the influence of spray-drying lipid core nanocapsules on tretinoin in vitro release profiles as well as skin penetration/permeation from hydrogels. These experiments were conducted employing Franz diffusion cells, pig abdominal skin (female), infinite doses regimen and receptor medium composed of phosphate buffer pH 7.4 and ethanol (70:30). Spray-drying of the nanocapsules suspensions, using PVP and lactose (1:1, m/m) at 10% (m/v) as drying adjuvant provided powders with good water dispersion profiles, good yields (around 70%), low volatile substances contents, in addition to drug contents above 92%. Interchanging intermediate products, aqueous suspension or respective powder, used in hydrogel formulation (G-LNC-TTN and G-LNC-TTN-SD, respectively) caused no influence on tretinoin in vitro release profile which was adjusted by Higuchi model. In corneum stratum there were differences in tretinoin quantities which penetrated from those formulations. The G-LNC-TTN provided an exponential retention of the drug on this skin’s layer, although G-LNC-TTN-SD did not. This difference was associated with the nanocapsules organization form in hydrogel matrix. In epidermis and dermis both formulations allowed permeation of constant and low tretinoin quantities. Moreover, at receptor fluid the drug was not detected. The low tretinoin permeation for deeper skin layers and for receptor fluid is low systemic absorption indicative, furthermore, may contribute in reducing adverse effects associated with tretinoin topical therapy. In given conditions, spray-drying of lipid core nanocapsules provided a potential intermediate for production of semi solids pharmaceutical forms containing tretinoin.

A indústria mineradora do país sofre constantemente com problemas ambientais devido à qualidade e volume de rejeitos gerados durante o processo de extração do minério. Os volumes gerados demandam grandes áreas para armazenagem e consequentemente obras complexas de contenção dos rejeitos. A engenharia geotécnica busca entender o comportamento mecânico de depósitos destes rejeitos através do uso de ensaios tanto de campo como de laboratório. Para isso utiliza ferramentas e procedimentos consagrados no meio técnico seguindo normas e procedimentos estabelecidos e consagrados mundialmente. No entendimento do comportamento mecânico dos solos argilosos, as análises são desenvolvidas em termos de tensões totais, já para os solos arenosos em termos de tensões efetivas. Todavia, para solos com granulometria intermediária, não se tem um consenso no que se refere à interpretação do comportamento mecânicos a partir de ensaios de campo Este trabalho apresenta resultados de ensaios de DMT e CPTU conduzidos em diferentes velocidades de penetração no intervalo de aproximadamente 1 e 57 mm/s, em depósito de rejeito de mineração, para avaliar tanto a influência da velocidade sobre as medidas do ensaio, quanto a transição das condições de fluxo ao redor do piezocone e durante a expansão da membrana do dilatômetro. Um equipamento simples e de baixo custo foi desenvolvido para monitorar a poropressão no centro da lâmina do DMT e dados são interpretados à luz das condições de drenagem impostas durante a execução do ensaio. Resultados indicam que as leituras e os valores de P0 e P1 são medidas de tensão total e por este motivo influenciadas pela magnitude da poropressão gerada durante a penetração da lâmina. Um novo Fator de Velocidade adimensional “Vt” é proposto para identificar possíveis efeitos de consolidação que ocorrem durante a penetração do piezocone e orientações são dadas para utilização de CPTU e DMT em solos de permeabilidade dentro do intervalo de 10-6 a 10-3 cm/s. / The mining industry of the country constantly suffers from environmental problems due to the quality and volume of waste generated during the mineral extraction process. Volumes generated require large areas for storage and consequently complex works of tailings. The geotechnical engineering seeks to understand the mechanical behavior of deposits of this waste by using assays well as laboratory and field. To this end tools and procedures laid down in the technical means following established rules and procedures consecrated worldwide. In the understanding of the mechanical behavior of clay soils, the analyzes are developed in terms of total stresses and for sandy soils in terms of effective stress. However, in soils with intermediate particle size, there is no consensus concerning the interpretation of the mechanical behavior from field trials. This paper presents the results of DMT and CPTU test conducted at different penetration rates in the range of about 1 to 57 mm / s in mining waste deposit to evaluate both the effect of speed on the measurements of the test, as the transition the flow conditions around the piezocone and during the expansion of the dilatometer membrane. A simple and inexpensive equipment has been developed to monitor the pore pressure in the center of the DMT blade and data are interpreted in the light of the imposed drainage conditions during the test. Results indicate that the readings that the P0 and P1 are total stress measurements and for this reason influenced by the magnitude of pore pressure generated during penetration of DMT blade. A new dimensionless Velocity Factor "Vt" is proposed to identify potential consolidation effects occurring during the penetration of piezocone and guidance is provided for use CPTU and DMT in soil permeability in the range 10-6 to 10-3 cm/s.

En Afrique, les métropoles fleurissent sur le continent, avec leur florilège d’espérance et de défis. Le rural est en crise et les taux de croissance urbaine explosent, posant l’inévitable problème de l’alimentation des urbains. L’agriculture urbaine et périurbaine est très présente car elle répond à nombre d’enjeux des villes africaines : elle pourvoit des revenus à despopulations formées aux pratiques agricoles, notamment les migrants; elle fournit des produits alimentaires périssables adaptées aux urbains, en autre des légumes et de la viande ; et elle permet l’aménagement de zones inconstructibles ou périurbaines alors que l’intervention publique est insuffisante dans ce domaine. L’agriculture urbaine et périurbaine des villes du Sud est multifonctionnelle. Cependant elle est peu reconnue par les institutions et rarement incluse dans les plans de développement urbains, ce qui grève son avenir et sa durabilité. La particularité de cette agriculture est d’être en concurrence avec les activités urbaines pour les ressources, notamment pour le foncier. Dans deux villes, Yaoundé et Accra, l’activité agricole trouve sa place dans des espaces spécifiques, des bas-fonds, des open space, des terrains inconstructibles, des jardins et des cours, des parcelles qui attendent d’être construites, des villages périurbains menacés, etc. Elle se déploie sur des espaces intermédiaires, entre le rural et l’urbain, entre le droit coutumier et le droit légal, entre la tradition et la modernité. En fonction de l’âge, du genre et de la position dans la hiérarchie coutumière etfamiliale, les droits sont différents, que ce soit pour cultiver, pour prêter ou louer ou pour vendre, sans oublier les procédures légales qui octroient un titre foncier. Les stratégies de production dépendent grandement de l’accès au foncier et contrairement à ce qui se passe généralement en milieu rural, ce ne sont pas forcément ceux qui ont le plus de sécuritéfoncière qui sont le plus innovants. / In sub-saharan Africa, metropolises propser bringing chanllenges and hope. The rural regions are in crisis and the rates of urban growth explode, raising the inevitable problem of the food supply of the urban population. The urban and periurban agriculture is very present because she answers number of issues of the African cities: it provides income to agricultural populations, in particular the migrants; it supplies perishable foodstuffs adapted to the urban market, like vegetables and meat; and it allows the development of unbuildable or periurban zones while the public intervention is insufficient inthis domain. The urban and periurban agriculture in the South is multifunctional. However it is little recognized by institutions and rarely included in the urban plans of development, what burdens its future and its durability. The peculiarity of this agriculture is to be in competition with the urban activities for the resources, in particular for the land. In two cities, Yaounde and Accra, the agricultural activity tooks place in specific spaces, shoals, open space, unbuildable grounds, gardens andbackyards, plots of land which wait to be built, threatened periurban villages, etc. It deploys on intermediate spaces, between the rural and the urban, between the common law and the legal right, between the tradition and the modernity.According to the age, to the genre and to the position in the customary and family hierarchy, the rights are different, whether it is to cultivate, to give or rent or to sell, without forgetting the legal procedures which grant a land title. The strategies of production depend largely on the access to the land and contrary to what takes place generally in rural areas, it are not necessarily the ones which have most land security which are the most innovative.

Muito além da delimitação de bordas para a ficção, o documentário, o filme-ensaio, o experimental e outros tantos, percebemos que há um amálgama entre esses territórios na linguagem audiovisual contemporânea. Esta pesquisa busca investigar espaços de hibridação, compreender suas aproximações e distanciamentos. Para isso, selecionamos como objetos de estudo dois filmes brasileiros, ambos dos diretores Karim Aïnouz e Marcelo Gomes: o curta documental Sertão de acrílico azul piscina (2004) e o longa ficcional Viajo porque preciso, volto porque te amo (2009). Na análise da tessitura narrativa das obras, pretendemos elaborar um espaço de intersecção, um entremeio narrativo a partir de suas camadas indexadoras, considerando a emissão e a produção das obras. Da mesma forma, na esfera da recepção discursiva, abordamos a necessidade da construção de um modo de leitura hibridizante, que dê conta das impressões e sensações percebidas pelo espectador em seu contato com esses filmes, compostos a partir de um entremeio, cujas fronteiras não podem ser delimitadas senão por um vasto espaço de intersecção. / Far beyond the delimitation of borders for fiction, documentary, essay film, experimental and so many, we realize that there is an amalgamation between these territories in contemporary audiovisual language. This research aims to investigate hybridization spaces, in order to understand their approximations and distances. With this purpose, we have selected as objects of study two Brazilian films, both directed by Karim Aïnouz and Marcelo Gomes: the documentary Sertão de acrílico azul piscina (2004) and the fiction I travel because I have to, I come back because I love you (Viajo porque preciso, volto porque te amo, 2009). In the analysis of the films narrative structure, we intend to elaborate a space of intersection, an intermediate narrative from its indexing layers, considering the emission and the production of the works. Similarly, in the sphere of discursive reception, we approach the need to construct a hybridized reading mode, sufficiency for the impressions and sensations perceived by the viewer in his or her contact with these films, composed of an intersection, which borders should not be bounded unless by a vast space of intersection.

xv, 76 p. : ill. (some col.) Includes 4 video files. / Improved understanding of pharyngeal arch (PA) patterning and morphogenesis can reveal critical insights into the origins of craniofacial diseases, such as Fraser syndrome. PAs contain mesenchymal condensations, which give rise to most of the facial skeleton in vertebrates. Studies of Endothelin1 signaling reveal that the skeleton derived from the first two PAs are patterned into dorsal, intermediate, and ventral domains. Previous work has indicated that endothelin targets, including the Dlx genes, homeotically pattern dorsal versus ventral PA identity. I show that the Dlx gene family plays a vital role in PA intermediate-domain identity establishment. In WT fish, the PA intermediate domain is delineated by combined expression of all Dlx genes. Reduction of Dlx gene function results in loss of intermediate-domain identity. Conversely, ventral expansion of Dlx expression, seen in hand2 mutants, results in ventral expansion of intermediate-domain identity. Hence, PA intermediate-domain identity is defined by co-expression of Dlx genes. Epithelial-mesenchymal interactions play an important part in PA intermediate-domain morphogenesis. Zebrafish fras1 (epithelially expressed) and itga8 (mesenchymally expressed) mutants also show specific defects within intermediate-domain skeleton and epithelia. Facial phenotypes in fras1;itga8 double mutants look extremely similar to either single mutant, suggesting that fras1 and itga8 might participate in the same epithelial-mesenchymal interaction during PA intermediate-domain formation. Our developmental studies reveal that fras1 - and itga8 -dependent epithelial segmentation of the PA intermediate domain stabilizes developing skeletal elements. Lesions in human FRAS1 underlie many cases of Fraser syndrome, and this work provides an excellent developmental model for the craniofacial defects found in Fraser syndrome. Loss of either Dlx or fras1 function produces defects in the PA intermediate domain, yet seemingly during different developmental periods. Nonetheless, combined reduction of both Dlx and fras1 function synergistically increases skeletal defects, implying a molecular connection between early (Dlx -mediated) pattern formation and later (fras1 -mediated) pattern stabilization. Elucidation of the Dlx-fras1 interaction is an interesting topic which may unveil new molecules pertinent to Fraser syndrome. Supplemental movies highlighting skeletal and epithelial morphogenesis accompany this dissertation. / Committee in charge: Judith S. Eisen, Chairperson; Charles B. Kimmel, Advisor; John H. Postlethwait, Member; Chris Q. Doe, Member; Kennith E. Prehoda, Outside Member

A prática da engenharia geotécnica dispõe de métodos consagrados para obtenção de parâmetros constitutivos através de ensaios de campo aplicados a solos argilosos, que apresentam resposta não drenada, e a solos granulares, que apresentam resposta drenada. Solos que possuem granulometria intermediária podem apresentar resposta parcialmente drenada, trazendo incertezas na obtenção de parâmetros geotécnicos estimados a partir destes ensaios. Este trabalho apresenta resultados de ensaios de campo conduzidos em diferentes velocidades, em dois depósitos de granulometria intermediária, para avaliar tanto a influência da velocidade sobre as medidas do ensaio, quanto a transição das condições de fluxo ao redor do piezocone. O primeiro local de estudo é caracterizado por um depósito natural localizado no município de Joinville/SC, constituído na camada analisada de solo siltoso. O segundo local é caracterizado por um depósito de resíduo de mineração de ouro localizado no município de Barrocas/BA, constituído na camada analisada de silte arenoso. Ensaios de piezocone em velocidade padrão buscaram primeiramente verificar a estratigrafia do terreno e definir uma camada mais homogênea para concentrar as análises. Ensaios de dissipação foram realizados para obtenção dos parâmetros de fluxo. Ensaios de piezocone com variação de velocidade compreenderam o intervalo de 0,5 mm/s a 45 mm/s no depósito natural e 0,3 mm/s a 57 mm/s no resíduo de mineração de ouro. Adicionalmente, amostras foram coletadas para caracterização dos materiais. Os resultados dos ensaios de piezocone nos dois depósitos estudados mostraram que a diminuição da velocidade gerou aumento da resistência e redução da poro-pressão e que o aumento da velocidade não gerou mudanças significativas, sugerindo que os ensaios em velocidade padrão são predominantemente não drenados. As análises em termos de velocidade adimensional mostraram que a transição de não drenado para parcialmente drenado ocorre em torno de uma velocidade normalizada V da ordem de 300 e a transição de parcialmente drenado para drenado ocorre em V inferior a 5 no resíduo de mineração de ouro. Já no depósito de solo natural a transição não pode ser avaliada com clareza devido ao sistema complexo de macrodrenagem, típico de solos residuais. Por fim, foi proposta uma metodologia que busca identificar o grau de drenagem ocorrido nos ensaios, com base na curva de drenagem estabelecida do solo, e converter a resistência à penetração parcialmente drenada em uma condição não drenada para permitir a utilização dos resultados e interpretação através das teorias consagradas. / In geotechnical engineering practice, a series of methods has been established for obtaining constitutive parameters from field tests applied to clay soils (considering the response fully undrained) and sandy soils (considering the penetration response as drained). Soils with intermediate particle sizes may present partial drained response, which introduces uncertainties in the assessment of constitutive parameters. This paper presents results of field tests carried out at different penetration rates in two silty deposits to assess both the influence of rate effects on measured test results, as well as the transition of flow conditions around the piezocone. The first site is characterized by a natural deposit located in the city of Joinville/SC. The second site is characterized by a deposit of gold mining tailings in the city of Barrocas/BA. Piezocone tests performed in standard velocity were used to verify the site stratigraphy and define the presence of more homogeneous layers to concentrate the analysis of rate effects. Dissipation tests were conducted to obtain flow parameters characteristics of the deposit. Piezocone were tested with penetration rates in the range of 0.5mm/s to 45mm/s in the natural deposit and 0.3mm/s to57mm/sin the gold mining tailing. Additionally, samples were collected for characterization of materials. The results of the piezocone tests showed that the cone resistance increases with decreasing penetration rate while pore pressure reduces, and that tests performed under standard penetration rate are mainly undrained in the tested field. The analysis in terms of normalized velocity showed that transition between undrained and partially drained occurs for value of V around 300 and the transition between partially drained and drained occurs for value of V lower than 5 in the gold mining tailing. The transition in the natural deposit cannot be verified clearly due to the complex system of macro drainage typical of residual soils. Finally, a method was proposed to identify the degree of drainage occurring in penetration tests based on the soil drainage characteristic curve, and to convert the cone tip resistance measured under partially drained conditions into a value that corresponds to undrained conditions. This correction would enable the use and interpretation of results following methods currently adopted in engineering practice.

No description available.

Thesis (Ph.D. (Language Education)) --University of Limpopo, 2018 / Despite the introduction of a number of educational policies and measures (for example, the Foundation for Learning Campaign, the National Reading Strategy (2008), Integrated National Literacy and Numeracy Strategy (INLNS) (Department of Basic Education, 2011), Certificate in Primary English Language Teaching (CiPELT)) in 2012-13 to increase the quality of education during and over twenty three years of democracy in South Africa, there are still problems with regard to reading levels of rural South African learners in the intermediate phase. The in/ability to read at grade level, still persist even after the introduction of teaching of English as a subject from Grade 1 in all schools as prescribed by CAPS. Available literature on reading in/abilities in South African schools concedes that the problem lies in the primary schools. The aim of this study was to investigate and determine an effective approach to teaching reading skills in the intermediate phase. I employed convergent parallel design as both the quantitative and qualitative strands were used concurrently and equally. The convergent parallel design is suitable for this study as it allows me to compare and contrast quantitative statistical results with qualitative findings for corroboration and validation purposes. The four main approaches which are; Phonemic awareness, Read-aloud, Shared Reading and Guided Group Reading were tested through the employment of an intervention administered to individual groups of grade 4 learners applying a particular approach for seven weeks. In the light of the aim of the study, it is clear from data presentation that Read-aloud approach yielded better results in terms of developing and promoting reading skills in the rural intermediate phase. Results of post-intervention comprehension test show that the Read-aloud group had remarkable improvement in terms of the number of learners who could read at an acceptable level. Teachers’ experiences about an effective approach were explored through the questionnaire and interviews; and their responses corroborated findings from learners’ post-intervention comprehension test. Nevertheless, Group Guided Reading should not be ignored as the group that was taught reading using this approach had significant improvement that was corroborated by teacher participants’ responses in both the questionnaire and interviews. Thus, in this study I argue that Read-aloud promote and develop reading skills in the rural intermediate phase.