648 research outputs found

    Molecular Studies on Plasmodium During Development in the Mosquito

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    Among the factors that regulate transmission of malaria are host-derived immune factors which can inhibit the progression of Plasmodium through the mosquito. This thesis addresses whether members of a family of LCCL/lectin Adhesive–like Proteins (LAPs) could act as feasible targets to elicit an antibody-mediated blockade in parasite transmission. The LAP family comprises six putatively secreted multidomain proteins which appear conserved among Plasmodium species and other apicomplexan parasites. Studies utilise the Plasmodium berghei rodent malaria parasite as an experimental system to evaluate the potential transmission-blocking activity of antibodies raised against LAPs. Regions of the proteins were selected for heterologous expression in Escherichia coli. Eight recombinant proteins were successfully expressed and were used as antigens to generate antisera in mice. Following immunogenicity tests, antisera against regions of LAP1, LAP3, LAP4 and LAP6 were selected for further characterisation and tested for antimalarial transmission-blocking activity. A combination of in vitro and in vivo assays revealed that the presence of anti-LAP antibodies did not inhibit parasite development. Whilst not conclusively excluding their potential, this work provided no further evidence to support the inclusion of LAPs as candidates for transmission-blocking vaccines. Immunolocalisation studies using anti-LAP1 antibodies revealed that the protein is expressed in cytoplasmic regions of female gametocytes and to a lesser extent in female gametes. Although it has been proposed that LAP expression may cease following fertilisation, PbLAP1 was detected in the cytoplasm of developing zygotes and intriguingly was subsequently found to concentrate in compartments of the P. berghei ookinete corresponding to the crystalloids. Antisera against regions of LAP1, LAP3, LAP4 and LAP6 were all found to similarly label the distinct electron dense cellular compartments. Furthermore, observation of Pblap mutant ookinetes by light microscopy indicated deficiencies in the formation of crystalloids. A transient cellular compartment, formed in the ookinete and subsequently fragmenting during early stages of oocyst development, roles of the crystalloid remain unknown. The association between LAPs and the crystalloids however leads to potential insights into the biological roles of the LAP family, the crystalloids, and the cellular processes of Plasmodium sporogony. Through microarray analysis, a comparison of the transcriptional profiles of P. berghei Δlap1 and wild-type ookinetes was made, detecting 274 differentially expressed genes and thereby indicating that the absence of PbLAP1 and resulting deficiency in crystalloid formation may have several knock-on effects on cellular processes important to Plasmodium development in the mosquito

    Learning participation as systems practice

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    We describe an evolving praxeology for Systems Practice for managing complexity built on 30 years of developing supported open learning opportunities in the area of Systems within the curriculum of The Open University (UK). We ground this description in two specific examples of how notions of participation are incorporated conceptually and practically into a learners programme of study by considering: (i) the postgraduate course 'Environmental Decision Making. A Systems Approach' (T860) and (ii) the undergraduate course 'Managing complexity. A systems approach' (T306)

    Exploring A Space For Emergent Learning To Occur: Encouraging creativity And Innovation In The Workplace

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    This research set out to explore perceptions about the concept of an emergent learning space within private organisations, as the current literature on learning does not adequately differentiate between organised learning and emergent learning. The research objectives explored the existence of, and perceived level of organisational encouragement and support for, emergent learning. Utilising a grounded research approach, the researcher was able to explore how organisations can and do provide a space for emergent learning to occur. In support of social constructionist learning theory, it has shown that this space for emergent learning is strongly influenced by three main factors: the existence of peer discussions, active two-way communications between managers and staff, and a have a go coaching style of management. Constructivist learning theory was supported by the findings that many managers and employees actively seek out opportunities for creativity and innovation, through their own initiative and motivation. Emergent learning is further positively influenced by the existence of and support for organised training programs in the workplace, and the particular company structure and availability of resources. At the edge of chaos, the space for emergent learning was supported by strong two-way communications between managers and staff; the have a go management coaching style; willing peer discussions; ready access to training programs; the company structure and its resources, and the individuals own initiative and motivation. Factors that discouraged the creation of a space for emergent learning to occur were shown to be a resistance to change and insufficient time. The significance of this research lies in two areas. Firstly, the research contributes to the literature on emergent learning in organisations, and provides definition of and support for this type of learning. Secondly, the research assists in the often-cited need for improvement of managerial skills within organisations, by providing managers with ways in which they can ensure their organisations thrive in the 21st century through the active encouragement and support for emergent learning in the workplace

    The use of milk for the surveillance of foot-and-mouth disease

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    Effective surveillance of foot-and-mouth disease (FMD) is of the utmost importance in order to understand the disease risks and implement effective control strategies. Epidemiological data obtained for FMD is mostly obtained through recognition and reporting of clinical cases by farmers which has several limitations. For example, under-reporting of disease is common, due to deficiencies in veterinary infrastructure, the effort involved for sample collection, or the repercussions of control measures for farmers. Diagnostic sample types, usually vesicular epithelium and fluid, are invasive and labour intensive to obtain, and can only be collected from acutely infected animals. Therefore, animals with sub-clinical FMD infection (particularly those in vaccinated herds) may not be identified but may still contribute to disease transmission. It is likely, therefore, that the true prevalence of FMD is not accurately known in parts of the world where the disease is endemic. Consequently, the requirement exists for a simple approach for FMD surveillance that does not rely on farmer reporting. Milk is a non-invasive sample type routinely collected from dairy farms and has been utilised for the surveillance of a number of other diseases. Despite numerous publications suggesting the potential of milk as a valuable sample type for foot-and-mouth disease (FMD) surveillance, empirical studies have mainly focused on the risk of transmission via milk, or the detection of FMD virus (FMDV) in milk from individual animals. This thesis aimed to expand on previous studies to determine the utility of milk and its limitations for the surveillance of FMD at the individual and herd level, using data collected from experimental and field studies. A highly sensitive and specific high-throughput RNA extraction and real-time rRT-PCR was optimised and utilised for FMDV RNA genome identification throughout the project. Using this method, it was demonstrated that FMDV RNA genome could be detected up to 28 days post infection using milk samples collected from individual cows. Further analysis using serotyping or lineage-specific rRT-PCR assays and VP1 sequencing of milk samples collected from individual cows in northern Tanzania highlighted the use of milk as a suitable alternative to more invasive sample types such as epithelium. Additionally, storage and shipment condition simulations performed demonstrated good stability of FMDV RNA genome within milk samples. Following these experiments, the potential use of pooled milk for herd–level FMD surveillance was investigated. Two proof-of-concept pilot studies were performed comparing the rRT-PCR results of pooled milk samples collected from both a large-scale dairy farm in Saudi Arabia and milk pooling facilities supplied by smallholder dairy farms in Kenya, with farmer reports of clinical disease. Results supported laboratory limit of detection studies, demonstrating that FMDV could be detected from milk pools of up 10,000 litres, even when there were low numbers of clinical cases. Furthermore, both studies suggested the detection of subclinical infection in milk samples, where disease was not reported. Data from pilot studies performed in this thesis therefore support the use of milk as a simple, non-invasive approach for herd-level FMD surveillance. Further field studies are required to determine the full utility of this method before it may be implemented for targeted/risk-based surveillance alongside existing surveillance systems to facilitate improved knowledge of FMD epidemiology, or for use in FMD contingency plans

    Summit-University Community Survey: Results and Technical Report.

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    Prepared for the Summit-University Planning Council by the Minnesota Center for Survey Research, University of Minnesota

    The influence of anatomy app use on chiropractic students’ learning outcomes: a randomised controlled trial

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    Background: Anatomy apps supplement traditional learning; however, it is unknown if their use can improve students' outcome. The present study examined whether the use of anatomy apps improved student performance on a neuroanatomy assessment. Methods: Second-year anatomy students, enrolled in a Bachelor of Science with Chiropractic Major program, were randomly allocated to experimental and control groups in July 2015. Students completed the Self-Directed Learning Readiness Scale (SDLRS). The experimental group had access to iPads with four anatomy apps for three weekly classes (1.5 h each). One week after the last class, students were assessed by an online 30-question neuroanatomy test. Linear regression was used to examine the association between test scores and app use, gender, previous anatomy unit score and SDLRS scores. Students' views on apps were collected by focus group discussion immediately after the test. Results: Completed questionnaires were obtained from n = 25 control and n = 25 experimental students. There was no association between app use and neuroanatomy assessment score (B = 1.75, 95 % CI: -0.340-3.840, p = 0.099). Only previous anatomy unit score (B = 0.348, 95 % CI: 0.214-0.483, p < 0.001) affected neuroanatomy assessment scores. Students favored apps with clinical images and features including identification pins, sliding bars and rotatable 3D images. Conclusions: App use did not enhance learning outcomes in a second-year anatomy unit
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