231 research outputs found

    Undue Influence in Wills - Evidence - Testators\u27 Position Changes after In re Will of Ferrill

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    The role of networked learning in academics’ writing

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    This article explores academics’ writing practices, focusing on the ways in which they use digital platforms in their processes of collaborative learning. It draws on interview data from a research project that has involved working closely with academics across different disciplines and institutions to explore their writing practices, understanding academic literacies as situated social practices. The article outlines the characteristics of academics’ ongoing professional learning, demonstrating the importance of collaborations on specific projects in generating learning in relation to using digital platforms and for sharing and collaborating on scholarly writing. A very wide range of digital platforms have been identified by these academics, enabling new kinds of collaboration across time and space on writing and research; but challenges around online learning are also identified, particularly the dangers of engaging in learning in public, the pressures of ‘always-on’-ness and the different values systems around publishing in different forums

    Real Property

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    The effect of robenacoxib on the concentration of C-reactive protein in synovial fluid from dogs with osteoarthritis

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    Background: Robenacoxib is a novel and highly selective inhibitor of COX-2 in dogs and cats and because of its acidic nature is regarded as being tissue-selective. Thirty four dogs with stifle osteoarthritis secondary to failure of the cranial cruciate ligament were recruited into this study. Lameness, radiographic features, synovial cytology and C-reactive protein concentrations in serum and synovial fluid were assessed before and 28 days after commencing a course of Robenacoxib at a dose of 1 mg/kg SID.<p></p> Results: There was a significant reduction in the lameness score (P <0.01) and an increase in the radiographic score (P < 0.05) between pre- and post-treatment assessments. There was no difference between pre- (median 1.49 mg/l; Q1-Q3 0.56-4.24 mg/L) and post – (1.10 mg/L; 0.31-1.78 mg/L) treatment serum C-reactive protein levels although synovial fluid levels were significantly reduced (pre- : 0.44 mg/L; 0.23-1.62 mg/L; post- : 0.17 mg/L; 0.05-0.49 mg/L) (P < 0.05). There was no correlation between C-reactive protein concentrations in serum and matched synovial fluid samples.<p></p> Conclusions: Robenacoxib proved effective in reducing lameness in dogs with failure of the cranial cruciate ligament and osteoarthritis of the stifle joint. The drug also reduced levels of C-reactive protein in the synovial fluid taken from the affected stifle joint. Robenacoxib appears to reduce articular inflammation as assessed by C-reactive protein which supports the concept that Robenacoxib is a tissue-selective non-steroidal anti-inflammatory drug.<p></p&gt

    Vascular reactivity in pulmonary resistance arteries: influence of pulmonary hypertension and endothelin

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    The main aim of my research was to investigate the vascular reactivity of pulmonary resistance arteries in vitro, and assess any functional changes which may occur as a result of pulmonary hypertension. Particular influence was given to investigation of the vascular effects ET-1 in pulmonary arteries, and characterisation of the ET receptors present in these vessels. To investigate changes in vascular reactivity in pulmonary hypertension, a chronic hypoxic rat model was utilised. In control adult rats, ET-1 (non selective ETA/ETB receptor agonist) produced potent vasoconstrictor responses in both large extrapulmonary arteries (3-5 mm i.d.) and pulmonary resistance arteries (?150 m i.d.) whereas responses to SxS6c (selective ETB agonist) were observed only in pulmonary resistance arteries. The selective ETA receptor antagonist FR 139317 was more effective in attenuating ET-1 mediated vasoconstriction in larger calibre pulmonary arteries than in pulmonary resistance arteries. Therefore it was found that ETA receptors predominate in large calibre extrapulmonary arteries, but pulmonary resistance arteries contain populations of both ETA and ETB receptors mediating vasoconstriction. Young male rats exposed to 14-16 days chronic hypobaric (418 mmHg) hypoxia exhibited significantly increased pulmonary artery pressure, right ventricular hypertrophy and pulmonary vascular remodelling all of which are associated with the development of pulmonary hypertension. Responses to ET-1 were significantly augmented in chronic hypoxic rat pulmonary resistance arteries compared to age matched controls, and this potentiation appeared to be mediated via activation of ETA receptors

    Academics' experiences of networked professional learning

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    This paper explores academics' writing practices, focusing on the importance of digital platforms in their processes of collaborative learning. It draws on interview data from the first phase of a research project working closely with academics across different disciplines and institutions to explore their writing practices, adopting the perspective of understanding academic literacies as social practices. The paper outlines characteristics of academics' ongoing professional learning, demonstrating the importance of collaborations on specific projects in generating learning in relation to intellectual and disciplinary aspects of writing, writing strategies and structures, and using digital platforms. A very wide range of digital platforms have been identified by these academics, enabling new kinds of collaboration across time and space on writing and research; but challenges around online learning are also identified, particularly the dangers of engaging in learning in public, the pressures of 'alwayson'-ness, and the different values systems around publishing in different forums

    Transcriptomic analysis of sheep macrophages and their response to Lipopolysaccharide

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    Sheep are ruminant animals, highly adapted to exploit pastures of low biological value and an economically important livestock species. They also provide a useful animal model for multiple areas of human medicine. Their productivity is compromised by many viral, bacterial, fungal, protozoan and helminthic pathogens. The innate immune system evolves under stringent selective pressure from pathogens. In this project, I aimed to identify genes involved in innate immunity in sheep by dissecting the transcriptome of sheep macrophages. The analysis focussed on identification of genes that may be associated with either disease susceptibility or resistance traits. The project formed part of the broader transcriptomic atlas for sheep. A method was established and validated for the production of sheep bone marrow derived macrophages (BMDMs) grown in macrophage colony‐stimulating factor (CSF1). These cells responded to bacterial Lipopolysaccharide (LPS), an archetypal agonist of the pattern recognition receptor, TLR4, with induction of inflammatory cytokines, but unlike rodent macrophages, sheep produced no nitric oxide. Bone marrow‐derived macrophages were produced from male (n=3) and female (n=3) Scottish Blackface X Texel animals used in The Sheep Atlas project, and mRNA was isolated from the cells at 0, 2, 4, 7 and 24 hours following stimulation. Two different protocols of mRNA preparation were used. For 0 and 7 hour samples, samples were depleted of rRNA, and RNA‐Seq was carried out at a depth of 100 million reads. For all samples in the time course (including 0 and 7), mRNA was prepared by polyA selection, and RNA‐Seq was performed at lower depth (25 million reads) and a detailed analysis of the different outcomes is presented. Two pipelines, Kallisto and StringTie were used to identify and quantify transcripts in the LPS time course transcriptomic data, along with other subsets of innate immune cells from the wider atlas. The former pipeline provides quantitative known transcript expression estimates, the latter generates novel transcript and gene models. Analysing the transcriptional signatures of these samples provided insight into the metabolic, regulatory and innate response pathways that sheep share with other animals, with both Myeloid differentiation primary response 88 protein (MYD88) dependent and independent pathways being activated following LPS stimulation, with hundreds of the same downstream cytokines being highly expressed in response, such as TNF and many interleukins as seen in other species innate responses. It has also highlighted aspects of the response that separate sheep from other animals, such as their metabolism and biosynthesis of steroid and tryptophan as well as demonstrating differences in specific expression of certain genes. Two highly regulated and expressed genes noted during the peak response at 7hrs (ENSOARG00000005159 and ENSOARG00000006889), were both assigned a functional annotation as being the protease inhibitor Serpin family B member 2 gene (SERPINB2). This appears to be a gene duplication. This sheep expression profile of SERPINB2 is shared with mice but distinct from humans and pigs. Similar to other animals, individual animals were found to vary markedly in their transcriptional response to LPS, demonstrating hyper, early and delayed responses between the individuals. The current reference transcriptome OarV3.1 contains 28757 transcripts, of which only 18488 are functionally annotated. More than 85% of all reference transcripts were detected in sheep macrophages and over 300 candidate annotations for genes identified only by Ensembl sheep (Ovis aries) gene ID (ENSOARG) numbers were manually assigned a functional annotation by clustering co‐expression estimates using the network analysis tool, Miru and inferring function by ‘guilt by association’ of these unknown genes which demonstrated similar expression profiles to those with known function. The nearest orthologues and synteny with other species were used to validate these suspected annotations. A select few examples include PYD and CARD domain containing gene (PYCARD), all the early growth response factors and many of the C‐X‐C Motif chemokines. In summary, this project identified multiple sheep‐specific aspects of the innate immune response, whilst assigning hundreds of genes a functional annotation and detecting new transcript models for multiple known genes. Many regulated, highly expressed, multi exoned, novel gene models have also been identified which are worthy of future investigation

    Shoulder Injuries in US Astronauts Related to EVA Suit Design

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    Introduction: For every one hour spent performing extravehicular activity (EVA) in space, astronauts in the US space program spend approximately six to ten hours training in the EVA spacesuit at NASA-Johnson Space Center's Neutral Buoyancy Lab (NBL). In 1997, NASA introduced the planar hard upper torso (HUT) EVA spacesuit which subsequently replaced the existing pivoted HUT. An extra joint in the pivoted shoulder allows increased mobility but also increased complexity. Over the next decade a number of astronauts developed shoulder problems requiring surgical intervention, many of whom performed EVA training in the NBL. This study investigated whether changing HUT designs led to shoulder injuries requiring surgical repair. Methods: US astronaut EVA training data and spacesuit design employed were analyzed from the NBL data. Shoulder surgery data was acquired from the medical record database, and causal mechanisms were obtained from personal interviews Analysis of the individual HUT designs was performed as it related to normal shoulder biomechanics. Results: To date, 23 US astronauts have required 25 shoulder surgeries. Approximately 48% (11/23) directly attributed their injury to training in the planar HUT, whereas none attributed their injury to training in the pivoted HUT. The planar HUT design limits shoulder abduction to 90 degrees compared to approximately 120 degrees in the pivoted HUT. The planar HUT also forces the shoulder into a forward flexed position requiring active retraction and extension to increase abduction beyond 90 degrees. Discussion: Multiple factors are associated with mechanisms leading to shoulder injury requiring surgical repair. Limitations to normal shoulder mechanics, suit fit, donning/doffing, body position, pre-existing injury, tool weight and configuration, age, in-suit activity, and HUT design have all been identified as potential sources of injury. Conclusion: Crewmembers with pre-existing or current shoulder injuries or certain anthropometric body types should conduct NBL EVA training in the pivoted HUT
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