926 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)

    Primary and secondary prevention of preterm birth: a review of systematic reviews and ongoing randomized controlled trials

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    BACKGROUND: Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality. Interventions aimed at preventing PTB can be classified as primary, secondary, or tertiary prevention. OBJECTIVE: To conduct a review of systematic reviews on the effectiveness and safety of primary and secondary preterm birth prevention interventions. SEARCH STRATEGY: A systematic literature search of the Cochrane, PubMed/Medline, EMBASE and CINAHL databases was conducted on 2 September 2015, and updated on 21 November 2016. SELECTION CRITERIA: We included any published systematic review of randomized controlled trials (RCTs) or individual patient data (IPD) of RCTs related to primary or secondary prevention of PTB, published between 2005-2016 where gestational age at birth (of any interval) was a pre-specified outcome. Individual trials and non-systematic reviews were not eligible. DATA COLLECTION AND ANALYSIS: The population of interest was all pregnant women, regardless of PTB risk. The primary outcome was PTB < 37 weeks. MAIN RESULTS: In total, 112 reviews were included in this study. Overall there were 49 Cochrane and 63 non-Cochrane reviews. Eight were individual participant data (IPD) reviews. Sixty reviews assessed the effect of primary prevention interventions on risk of PTB. Positive effects were reported for lifestyle and behavioural changes (including diet and exercise); nutritional supplements (including calcium and zinc supplementation); nutritional education; screening for lower genital tract infections. Eighty-three systematic reviews were identified relating to secondary PTB prevention interventions. Positive effects were found for low dose aspirin among women at risk of preeclampsia; clindamycin for treatment of bacterial vaginosis; treatment of vaginal candidiasis; progesterone in women with prior spontaneous PTB and in those with short midtrimester cervical length; L-arginine in women at risk for preeclampsia; levothyroxine among women with tyroid disease; calcium supplementation in women at risk of hypertensive disorders; smoking cessation; cervical length screening in women with history of PTB with placement of cerclage in those with short cervix; cervical pessary in singleton gestations with short cervix; and treatment of periodontal disease. CONCLUSION: The overview serves as a guide to current evidence relevant to PTB prevention. Only a few interventions have been demononstrated to be effective, including cerclage, progesterone, low dose aspirin, and lifestyle and behavioural changes. For several of the interventions evaluated, there was insufficient evidence to assess whether they were effective or not

    Recovery of viral RNA and infectious foot-and-mouth disease virus from positive lateral-flow devices

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    Foot-and-mouth disease Virus (FMDV) is an economically important, highly contagious picornavirus that affects both wild and domesticated cloven hooved animals. In developing countries, the effective laboratory diagnosis of foot-and-mouth disease (FMD) is often hindered by inadequate sample preservation due to difficulties in the transportation and storage of clinical material. These factors can compromise the ability to detect and characterise FMD virus in countries where the disease is endemic. Furthermore, the high cost of sending infectious virus material and the biosecurity risk it presents emphasises the need for a thermo-stable, non-infectious mode of transporting diagnostic samples. This paper investigates the potential of using FMDV lateral-flow devices (LFDs) for dry transportation of clinical samples for subsequent nucleic acid amplification, sequencing and recovery of infectious virus by electroporation. FMDV positive samples (epithelial suspensions and cell culture isolates) representing four FMDV serotypes were applied to antigen LFDs: after which it was possible to recover viral RNA that could be detected using real-time RT-PCR. Using this nucleic acid, it was also possible to recover VP1 sequences and also successfully utilise protocols for amplification of complete FMD virus genomes. It was not possible to recover infectious FMDV directly from the LFDs, however following electroporation into BHK-21 cells and subsequent cell passage, infectious virus could be recovered. Therefore, these results support the use of the antigen LFD for the dry, non-hazardous transportation of samples from FMD endemic countries to international reference laboratories

    The association between pain diagram area, fear-avoidance beliefs, and pain catastrophising

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    BACKGROUND: The development of clinical practice guidelines for managing spinal pain have been informed by a biopsychosocial framework which acknowledges that pain arises from a combination of psychosocial and biomechanical factors. There is an extensive body of evidence that has associated various psychosocial factors with an increased risk of experiencing persistent pain. Clinicians require instruments that are brief, easy to administer and score, and capable of validly identifying psychosocial factors. The pain diagram is potentially such an instrument. The aim of our study was to examine the association between pain diagram area and psychosocial factors. METHODS: 183 adults, aged 20–85, with spinal pain were recruited. We administered a demographic checklist; pain diagram; 11-point Numerical Rating Scale assessing pain intensity; Pain Catastrophising Scale (PCS); MOS 36 Item Short Form Health Survey (SF-36); and the Fear Avoidance Beliefs Questionnaire (FABQ). Open source software, GIMP, was used to calculate the total pixilation area on each pain diagram. Linear regression was used to examine the relationship between pain diagram area and the following variables: age; gender; pain intensity; PCS total score; FABQ-Work scale score; FABQ-Activity scale score; and SF-36 Mental Health scale score. RESULTS: There were no significant associations between pain diagram area and any of the clinical variables. CONCLUSION: Our findings showed that that pain diagram area was not a valid measure to identify psychosocial factors. Several limitations constrained our results and further studies are warranted to establish if pain diagram area can be used assess psychosocial factors

    Evaluation of two lyophilized molecular assays to rapidly detect foot-and-mouth disease virus directly from clinical samples in field settings

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    Accurate, timely diagnosis is essential for the control, monitoring and eradication of foot‐and‐mouth disease (FMD). Clinical samples from suspect cases are normally tested at reference laboratories. However, transport of samples to these centralized facilities can be a lengthy process that can impose delays on critical decision making. These concerns have motivated work to evaluate simple‐to‐use technologies, including molecular‐based diagnostic platforms, that can be deployed closer to suspect cases of FMD. In this context, FMD virus (FMDV)‐specific reverse transcription loop‐mediated isothermal amplification (RT‐LAMP) and real‐time RT‐PCR (rRT‐PCR) assays, compatible with simple sample preparation methods and in situ visualization, have been developed which share equivalent analytical sensitivity with laboratory‐based rRT‐PCR. However, the lack of robust ‘ready‐to‐use kits’ that utilize stabilized reagents limits the deployment of these tests into field settings. To address this gap, this study describes the performance of lyophilized rRT‐PCR and RT‐LAMP assays to detect FMDV. Both of these assays are compatible with the use of fluorescence to monitor amplification in real‐time, and for the RT‐LAMP assays end point detection could also be achieved using molecular lateral flow devices. Lyophilization of reagents did not adversely affect the performance of the assays. Importantly, when these assays were deployed into challenging laboratory and field settings within East Africa they proved to be reliable in their ability to detect FMDV in a range of clinical samples from acutely infected as well as convalescent cattle. These data support the use of highly sensitive molecular assays into field settings for simple and rapid detection of FMDV

    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

    Factors influencing responsiveness to feedback: on the interplay between fear, confidence, and reasoning processes

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    Self-appraisal has repeatedly been shown to be inadequate as a mechanism for performance improvement. This has placed greater emphasis on understanding the processes through which self-perception and external feedback interact to influence professional development. As feedback is inevitably interpreted through the lens of one’s self-perceptions it is important to understand how learners interpret, accept, and use feedback (or not) and the factors that influence those interpretations. 134 participants from 8 health professional training/continuing competence programs were recruited to participate in focus groups. Analyses were designed to (a) elicit understandings of the processes used by learners and physicians to interpret, accept and use (or not) data to inform their perceptions of their clinical performance, and (b) further understand the factors (internal and external) believed to influence interpretation of feedback. Multiple influences appear to impact upon the interpretation and uptake of feedback. These include confidence, experience, and fear of not appearing knowledgeable. Importantly, however, each could have a paradoxical effect of both increasing and decreasing receptivity. Less prevalent but nonetheless important themes suggested mechanisms through which cognitive reasoning processes might impede growth from formative feedback. Many studies have examined the effectiveness of feedback through variable interventions focused on feedback delivery. This study suggests that it is equally important to consider feedback from the perspective of how it is received. The interplay observed between fear, confidence, and reasoning processes reinforces the notion that there is no simple recipe for the delivery of effective feedback. These factors should be taken into account when trying to understand (a) why self-appraisal can be flawed, (b) why appropriate external feedback is vital (yet can be ineffective), and (c) why we may need to disentangle the goals of performance improvement from the goals of improving self-assessment
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