187 research outputs found
A low concentration of Tacrolimus/semifluorinated alkane (SFA) eyedrop suppresses intraocular inflammation in experimental models of uveitis
Exploring industry level capabilities in the UK Creative Industries
The competitive dynamics of the UK’s Creative Industries has changed considerably over the past decade and perhaps none more so than in the Publishing Industry. There is no doubt that this industry continues to undergo structural changes that compel firms to adapt and transform their business in response to the dynamic nature of competitive environment. Industries have long been examined by researchers from a strategic perspective with various themes of inquiry relating to; industry structure and positioning, industry evolution and development, industry lifecycle, industry change and industry consolidation. This paper argues that ‘industry analysis’ could usefully draw on Dynamic Capabilities Theory which argues for the strategic adaptation and reconfiguration of firm resources and capabilities in order to address a rapidly changing competitive environment. This paper will present empirical findings from a comparative time-series analysis (1997-2014) of the UK Publishing Industry and compare it to other industries categorised within the UK’s Creative Industries. In doing so, this analysis will add to the limited knowledge base on industry level dynamic capabilities and extend our knowledge on inter-industry comparisons in performance following the reconfiguration of industry resources
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Semi-direct allorecognition
Adaptive CD8 T-cell immunity is the principal arm of the cellular alloimmune response, but its development requires help. This can be provided by CD4 T cells that recognize alloantigen "indirectly," as self-restricted allopeptide, but this process remains unexplained, because the target epitopes for CD4 and CD8 T-cell recognition are "unlinked" on different cells (recipient and donor antigen presenting cells (APCs), respectively). Here, we test the hypothesis that the presentation of intact and processed MHC class I alloantigen by recipient dendritic cells (DCs) (the "semidirect" pathway) allows linked help to be delivered by indirect-pathway CD4 T cells for generating destructive cytotoxic CD8 T-cell alloresponses. We show that CD8 T-cell-mediated rejection of murine heart allografts that lack hematopoietic APCs requires host secondary lymphoid tissue (SLT). SLT is necessary because within it, recipient dendritic cells can acquire MHC from graft parenchymal cells and simultaneously present it as intact protein to alloreactive CD8 T cells and as processed peptide alloantigen for recognition by indirect-pathway CD4 T cells. This enables delivery of essential help for generating cytotoxic CD8 T-cell responses that cause rapid allograft rejection. In demonstrating the functional relevance of the semidirect pathway to transplant rejection, our findings provide a solution to a long-standing conundrum as to why SLT is required for CD8 T-cell allorecognition of graft parenchymal cells and suggest a mechanism by which indirect-pathway CD4 T cells provide help for generating effector cytotoxic CD8 T-cell alloresponses at late time points after transplantation.This work was supported by a British Heart Foundation project grant, the National Institute of Health Research Cambridge Biomedical Research Centre and the National Institute of Health Research Blood and Transplant Research Unit. SH was supported by an Academy of Medical Sciences / Wellcome Trust starter grant and the European Society for Organ Transplantation Junior Basic Science Research Grant. JA and IH were supported by Wellcome Trust Clinical Research Training Fellowships and Raymond and Beverly Sackler Scholarships.This is the author accepted manuscript. The final version is available from PNAS via http://dx.doi.org/10.1073/pnas.151353311
‘Block and basin’ style rift basins: sedimentological insights from the Mississippian Fell Sandstone Formation
The block and basin tectonostratigraphic framework for the northern Pennine (rift) Basin, within which buoyant granite intrusions core intra-basin fault-bounded blocks, has long held traction. However, many of the elements of this framework are rooted in primitive tectonic models and, perhaps unsurprisingly, corresponding depositional models often reflect this. Using sedimentological and sedimentary provenance approaches, the synrift (Mississippian) fluvio-deltaic Fell Sandstone Formation and age-equivalent strata within the northern Pennine Basin are examined. Highlighted divergences from classically depicted models relate to occurrences of pre-Carboniferous basement domes or monoclines, which are unbounded by major vertically displacing (>100 m) fault systems. Such structures in the northern Pennine Basin are all granite-cored and their origins are associated with their buoyancy and flexural isostatic processes. One such basement dome, the Cheviot Block, confined and deflected the Fell Sandstone fluvio-deltaic system from the west, causing locally elevated net sand content and variations in the dominant palaeodrainage direction. Central parts of the Alston Block, which forms a regional monocline along an east–west axis, were comparatively uplifted because of flexural isostatic responses to granite intrusions. The findings presented are at variance not only with classically depicted depositional models for the region, but also with more general depictions of dominantly normal fault-driven rift basin systems
Augmentation of Recipient Adaptive Alloimmunity by Donor Passenger Lymphocytes within the Transplant.
Chronic rejection of solid organ allografts remains the major cause of transplant failure. Donor-derived tissue-resident lymphocytes are transferred to the recipient during transplantation, but their impact on alloimmunity is unknown. Using mouse cardiac transplant models, we show that graft-versus-host recognition by passenger donor CD4 TÂ cells markedly augments recipient cellular and humoral alloimmunity, resulting in more severe allograft vasculopathy and early graft failure. This augmentation is enhanced when donors were pre-sensitized to the recipient, is dependent upon avoidance of host NK cell recognition, and is partly due to provision of cognate help for allo-specific B cells from donor CD4 TÂ cells recognizing B cell MHC class II in a peptide-degenerate manner. Passenger donor lymphocytes may therefore influence recipient alloimmune responses and represent a therapeutic target in solid organ transplantation.This work was supported by a British Heart Foundation project grant, the National Institute of Health Research Cambridge Biomedical Research Centre and the National Institute of Health Research Blood and Transplant Research Unit. IGH and JMA were supported by a Wellcome Trust Clinical Research Training Fellowship and Raymond and Beverly Sackler Scholarship. KSP was supported by an Academy of Medical Sciences / Wellcome Trust starter grant.This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/j.celrep.2016.04.00
Contexto, conteúdo e processo da mudança estratégica em uma empresa estatal do setor elétrico brasileiro
Erratum to:Effects of a physical activity and nutrition program in retirement villages: a cluster randomised controlled trial
Abstract Background This cluster randomised controlled trial aimed to determine if a 6- month home-based intervention could improve the physical activity and dietary behaviours of adults aged 60 to 80 years living in retirement villages located in Perth, Western Australia. Methods Participants (n = 363) from 38 retirement villages were recruited into the trial and allocated to the intervention (n = 197: 17 sites) or control (n = 166: 21 sites) group and were blinded. Previously validated instruments-Fat and Fibre Barometer and International Physical Activity Questionnaire, along with anthropometric measures (weight, height, waist and hip circumferences) and blood pressure were collected at baseline and 6 -month time period. Comparisons between intervention and control groups were undertaken pre- and post- intervention using univariate chi-square and t-tests. Multi-level mixed regression analyses were then conducted to ascertain the effects of the intervention on changes in the outcome variables over time and between groups. Results A total of 139 (70.5%) intervention and 141 (84.9%) control group participants completed the program and post-test assessments. The intervention group demonstrated significant increases in time (80 min more per week on average) devoted to moderate-intensity physical activity, engagement in strength exercises (from 23.7% to 48.2%), frequency of fruit consumed as well as fat avoidance and fibre intake scores, in addition to a 0.5 kg mean reduction in weight post program, whereas no apparent changes were observed in the control group. Mixed regression results further confirmed statistically significant improvements in weight loss (p < 0.05), engagement in strength exercises (p < 0.001) and fruit intake (p = 0.012) by the intervention participants at post-test relative to their controls. Conclusions Retirement offers a time to reassess lifestyle, and adopt positive health enhancing physical activity and dietary behaviours. This intervention was successful in improving weight, engagement in strength exercises, increasing levels of moderate-intensity physical activity and consumption of fruit among retirement village residents. Further investigation is needed on how to better engage retirement village managers in such programs. Trial registration Australia and New Zealand Clinical Trial Registry (ACTRN12612001168842) registered November 2, 2012
Anatomical Specializations for Nocturnality in a Critically Endangered Parrot, the Kakapo (Strigops habroptilus)
The shift from a diurnal to nocturnal lifestyle in vertebrates is generally associated with either enhanced visual sensitivity or a decreased reliance on vision. Within birds, most studies have focused on differences in the visual system across all birds with respect to nocturnality-diurnality. The critically endangered Kakapo (Strigops habroptilus), a parrot endemic to New Zealand, is an example of a species that has evolved a nocturnal lifestyle in an otherwise diurnal lineage, but nothing is known about its' visual system. Here, we provide a detailed morphological analysis of the orbits, brain, eye, and retina of the Kakapo and comparisons with other birds. Morphometric analyses revealed that the Kakapo's orbits are significantly more convergent than other parrots, suggesting an increased binocular overlap in the visual field. The Kakapo exhibits an eye shape that is consistent with other nocturnal birds, including owls and nightjars, but is also within the range of the diurnal parrots. With respect to the brain, the Kakapo has a significantly smaller optic nerve and tectofugal visual pathway. Specifically, the optic tectum, nucleus rotundus and entopallium were significantly reduced in relative size compared to other parrots. There was no apparent reduction to the thalamofugal visual pathway. Finally, the retinal morphology of the Kakapo is similar to that of both diurnal and nocturnal birds, suggesting a retina that is specialised for a crepuscular niche. Overall, this suggests that the Kakapo has enhanced light sensitivity, poor visual acuity and a larger binocular field than other parrots. We conclude that the Kakapo possesses a visual system unlike that of either strictly nocturnal or diurnal birds and therefore does not adhere to the traditional view of the evolution of nocturnality in birds
Effects of school-based interventions on mental health stigmatization: a systematic review
Stigmatizing, or discriminatory, perspectives and behaviour, which target individuals on the basis of their mental health, are observed in even the youngest school children. We conducted a systematic review of the published and unpublished, scientific literature concerning the benefits and harms of school-based interventions, which were directed at students 18 years of age or younger to prevent or eliminate such stigmatization. Forty relevant studies were identified, yet only a qualitative synthesis was deemed appropriate. Five limitations within the evidence base constituted barriers to drawing conclusive inferences about the effectiveness and harms of school-based interventions: poor reporting quality, a dearth of randomized controlled trial evidence, poor methods quality for all research designs, considerable clinical heterogeneity, and inconsistent or null results. Nevertheless, certain suggestive evidence derived both from within and beyond our evidence base has allowed us to recommend the development, implementation and evaluation of a curriculum, which fosters the development of empathy and, in turn, an orientation toward social inclusion and inclusiveness. These effects may be achieved largely by bringing especially but not exclusively the youngest children into direct, structured contact with an infant, and likely only the oldest children and youth into direct contact with individuals experiencing mental health difficulties. The possible value of using educational activities, materials and contents to enhance hypothesized benefits accruing to direct contact also requires investigation. Overall, the curriculum might serve as primary prevention for some students and as secondary prevention for others
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