39 research outputs found

    Environmental Hazard Analysis - a Variant of Preliminary Hazard Analysis for Autonomous Mobile Robots

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    © 2014, Springer Science+Business Media Dordrecht. Robot manufacturers will be required to demonstrate objectively that all reasonably foreseeable hazards have been identified in any robotic product design that is to be marketed commercially. This is problematic for autonomous mobile robots because conventional methods, which have been developed for automatic systems do not assist safety analysts in identifying non-mission interactions with environmental features that are not directly associated with the robot’s design mission, and which may comprise the majority of the required tasks of autonomous robots. In this paper we develop a new variant of preliminary hazard analysis that is explicitly aimed at identifying non-mission interactions by means of new sets of guidewords not normally found in existing variants. We develop the required features of the method and describe its application to several small trials conducted at Bristol Robotics Laboratory in the 2011–2012 period

    Heterochronic faecal transplantation boosts gut germinal centres in aged mice

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    Ageing is a complex multifactorial process associated with a plethora of disorders, which contribute significantly to morbidity worldwide. One of the organs significantly affected by age is the gut. Age-dependent changes of the gut-associated microbiome have been linked to increased frailty and systemic inflammation. This change in microbial composition with age occurs in parallel with a decline in function of the gut immune system, however it is not clear if there is a causal link between the two. Here we report that the defective germinal centre reaction in Peyer’s patches of aged mice can be rescued by faecal transfers from younger adults into aged mice and by immunisations with cholera toxin, without affecting germinal centre reactions in peripheral lymph nodes. This demonstrates that the poor germinal centre reaction in aged animals is not irreversible, and that it is possible to improve this response in older individuals by providing appropriate stimuli

    PROMISING THE DREAM: changing destination image of London through the effect of website place

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    Drawing on theories of place identity and social identity, this study aims to fill a gap in place identity studies regarding the effect of a place website on the destination image of customers/visitors/tourists. The research addresses three questions: (1) what are the main impacts of tourists’ attitude on place identity and the place website, (2) what are the factors that influence destination image, and (3) what are the main impacts of a favorable destination image? The favorability of a destination image is reflected by the extent to which visitors positively regard that place website. Results reveal the importance of the destination image in enhancing the intention to revisit and recommend. Also, visitors’ satisfaction impacts on their intention to revisit and recommend the place. Significant implications for place managers and researchers are highlighted

    Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

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    Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants

    American Gut: an Open Platform for Citizen Science Microbiome Research

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    McDonald D, Hyde E, Debelius JW, et al. American Gut: an Open Platform for Citizen Science Microbiome Research. mSystems. 2018;3(3):e00031-18

    Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

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    Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

    The Semiotic Fractures of Vulnerable Bodies: Resistance to the Gendering of Legal Subjects

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    While the turn to vulnerability in law responds to a recurrent critique by feminist scholars on the disembodiment of legal personhood, this article suggests that the mobilization of vulnerability in the criminal courts does not necessarily offer female drug mules a direct path to justice. Through an analysis of sentencing appeals of female drug mules in England and Wales, this article presents a feminist critique of the dispositif of the person and its relation to vulnerability. Discourses on drug mules’ vulnerability mobilize the trope of the colonial victim in need of protection, which is often translated into legal mercy. But mercy is rather an expression of biopower which inscribes not only fragility onto the bodies of drug mules by figuring them as exemplar paradigms of colonial subjectivity, but also reinvigorates the dispositif of gender implicit in the legal person. In this set-up, it would appear as if law and politics totalize the registers of life, in this case the contours of vulnerable body. The article suggests we must revisit the image of the wounded body in order to carve out a space for resistance. Drawing on Elaine Scarry and Judith Butler, it suggests vulnerable bodies are marked by a semiotic openness, which renders them subject to appropriation but also able to signify the precarity produced by the law through their resistance to representation
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