9,649 research outputs found

    Patient advocate perspectives on involvement in HTA: An international snapshot

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    Editorial

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    An introduction to this re-launch edition of the journal by the new members of the editorial tea

    Characterisation of the regulation of growth by nitric oxide signalling in Drosophila melanogaster

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    The molecular mechanisms that control growth appear to be conserved across the animal kingdom, with nitric oxide regulation of cell proliferation and growth being found to be very significant. Indeed, in Drosophila larval development and mammalian systems NO has been shown to be particularly important in these processes, and previous work in our laboratory has identified the Drosophila forkhead transcription factor dFOXO as a critical target through which NO signalling exerts its regulatory effects on growth, although little is currently known concerning the precise mechanisms involved. Accordingly, in this thesis, we investigate the processes through which NO may modulate growth and demonstrate that targeted expression of a constitutively active NO Synthase to whole larval salivary glands or clones of cells within the glands, results in reduced endoreplication and growth as measured by nuclear size. Targeted over expression of dFOXO itself is shown to result in similar phenotypes, and subsequent molecular analysis of potential signalling targets required for this inhibition of growth reveals that dFOXO, Thor and Myc expression are regulated in vivo by NO. To elucidate if NO acts directly on dFOXO, the genetic interaction of components of the insulin signalling pathway is analysed, exploiting RNA interference to assay what components are necessary for the NO signal to be effectively transduced, and it is demonstrated that NO control of growth is not through sGC, one of the most significant known targets for NOmediated regulation in other organisms. We subsequently investigated the roles of Thor, a Drosophila 4E-binding protein, and the kinase, Lk6, homologues of which are known to be important in growth regulation in other organisms, and thus potential effectors of NO and dFOXO. However our data demonstrated that neither Thor nor Lk6 are required for the inhibition of growth by NO. Interestingly a potential anti-oncogenic effect of NO signalling was also revealed following analysis of interactions between NO and Ras or Myc induced growth in which NO was able reduce the overgrowth produce by both these oncogenes. Overall this research confirms dFOXO as an essential target for NO induced inhibition of growth. The work also eliminates two dFOXO transcription targets, Thor and Lk6, as necessary for NO to regulate growth

    Architecture as the background to collective life

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    This project develops an approach towards the arrangement and design of the primary elements - public facilities and spaces - that necessarily complement the provision of subsidised housing in South Africa. The historical response to the housing shortage in South Africa has been the provision of a remarkable number of individual housing units, but with insufficient funds and attention given to the urban infrastructure, public spaces and facilities that go hand in hand with housing in livable urban environments. This project considers a subsidy housing project where the social facilities are considered upfront, and are seen as an opportunity to create interesting, people-centred places in the development - this thesis is the search for an architecture which forms the backdrop, and framework for growth, for collective urban life. This paper is structured around six sections: thinking, siting, urban design, programming, making and designing. These sections explore, respectively, the theoretical proposal with regards to social facilities and public spaces, the strategic siting of an area of subsidised housing and its associated primary elements, an urban design proposal for the whole development, the programming of the whole site and the individual cluster of facilities that I consider in more detail, the spatial and technological realisation of the public fronts of three case study buildings, and finally the exploration and manifestation of these ideas through a design. My project is being done in conjunction with another student, Rob Richardson, who is looking at creative housing within the limit of the government subsidy. Together we make a proposal for an overall living environment which takes the form of an acupunctural insertion of subsidised housing and the associated primary elements into an area of Wynburg, Cape Town

    The Influence of Accelerometer Cut Points on Determining the Percent of Preschool-Age Children Meeting Physical Activity Guidelines

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    Reduced physical activity is thought to be a major contributor to energy imbalance and obesity in children and adolescents. A challenge for researchers is selecting a tool that will accurately measure physical activity, especially in young children. A current tool that is used is an accelerometer. This study had two objectives. The first examined if different sets of accelerometer cut points developed for preschool-age children would produce the same physical activity results when identical raw data were run through them. Through the use of accelerometer data the second objective aimed to determine the percent of children who met the physical activity guidelines for 3 to 5 year olds, which recommend 180 minutes of combined light to vigorous activity each day. Participants wore accelerometers for 7 consecutive days. Raw accelerometer data were run through five sets of accelerometer cut points. A paired t-test was used to compare the minutes per day reported in sedentary, light, moderate to vigorous, and light to vigorous physical activity. The light to vigorous results calculated from the five sets of cut points were used to determine the percent of children who were meeting the physical activity recommendation. While some of the cut points when compared against each other did produce equal results within a particular physical activity threshold, no overall sets of cut points produced the same levels of physical activity across all activity thresholds. Two sets of cut points classified the same percent of participants (10.67%) as achieving the recommended 180 minutes of activity. A large range of participants (87.33%-0.33%) met the recommendations based on the other sets of cut points. The cut points chosen to process raw accelerometer data influenced the reported levels of physical activity
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