The human myometrium differentially expresses mTOR signalling components before and during pregnancy: Evidence for regulation by progesterone

Emerging studies implicate the signalling of the mammalian target of rapamycin (mTOR) in a number of reproductive functions. To this date, there are no data regarding the expression of mTOR signalling components in the human myometrium during pregnancy. We hypothesized that mTOR-related genes might be differentially expressed in term or preterm labour as well as in labour or non-labour myometria during pregnancy. Using quantitative RT-PCR we demonstrate for first time that there is a significant downregulation of mTOR, DEPTOR, and Raptor in preterm labouring myometria when compared to non-pregnant tissues taken from the same area (lower segment). We used an immortalized myometrial cell line (ULTR) as an in vitro model to dissect further mTOR signalling. In ULTR cells DEPTOR and Rictor had a cytoplasmic distribution, whereas mTOR and Raptor were detected in the cytoplasm and the nucleus, indicative of mTORC1 shuttling. Treatment with inflammatory cytokines caused only minor changes in gene expression of these components, whereas progesterone caused significant down-regulation. We performed a non-biased gene expression analysis of ULTR cells using Nimblegen human gene expression microarray (n = 3), and selected genes were validated by quantitative RT-PCR in progesterone treated myometrial cells. Progesterone significantly down-regulated key components of the mTOR pathway. We conclude that the human myometrium differentially expresses mTOR signalling components and they can be regulated by progesterone. This article is part of a Special Issue entitled 'Pregnancy and Steroids'.This research was funded by National Institutes of Health Grant ESO12961

Scaling Behaviour and Complexity of the Portevin-Le Chatelier Effect

The plastic deformation of dilute alloys is often accompanied by plastic instabilities due to dynamic strain aging and dislocation interaction. The repeated breakaway of dislocations from and their recapture by solute atoms leads to stress serrations and localized strain in the strain controlled tensile tests, known as the Portevin-Le Chatelier (PLC) effect. In this present work, we analyse the stress time series data of the observed PLC effect in the constant strain rate tensile tests on Al-2.5%Mg alloy for a wide range of strain rates at room temperature. The scaling behaviour of the PLC effect was studied using two complementary scaling analysis methods: the finite variance scaling method and the diffusion entropy analysis. From these analyses we could establish that in the entire span of strain rates, PLC effect showed Levy walk property. Moreover, the multiscale entropy analysis is carried out on the stress time series data observed during the PLC effect to quantify the complexity of the distinct spatiotemporal dynamical regimes. It is shown that for the static type C band, the entropy is very low for all the scales compared to the hopping type B and the propagating type A bands. The results are interpreted considering the time and length scales relevant to the effect.Comment: 35 pages, 6 figure

‘It stays with you’: multiple evocative representations of dance and future possibilities for studies in sport and physical cultures

This article considers the integration of arts-based representations via poetic narratives together with artistic representation on dancing embodiment so as to continue an engagement with debates regarding multiple forms/representations. Like poetry, visual images are unique and can evoke particular kinds of emotional and visceral responses, meaning that alternative representational forms can resonate in different and powerful ways. In the article, we draw on grandparent-grandchild interactions, narrative poetry, and artistic representations of dance in order to illustrate how arts-based methods might synergise to offer new ways of ‘knowing’ and ‘seeing’. The expansion of the visual arts into interdisciplinary methodological innovations is a relatively new, and sometimes contentious approach, in studies of sport and exercise. We raise concerns regarding the future for more arts-based research in the light of an ever-changing landscape of a neoliberal university culture that demands high productivity in reductionist terms of what counts as ‘output’, often within very restricted time-frames. Heeding feminist calls for ‘slow academies’ that attempt to ‘change’ time collectively, and challenge the demands of a fast-paced audit culture, we consider why it is worth enabling creative and arts-based methods to continue to develop and flourish in studies of sport, exercise and health, despite the mounting pressures to ‘perform’

Making and Sharing the Commons: Reimagining ‘the West’ as Riverlands, Sydney through a Dialogue between Design and Ethnography

Scholars from the social sciences and humanities are increasingly seeking to improve the relevance and social impact of their research beyond the academy. In this context, ‘designerly’ thinking and methods are being drawn on to inform social change agendas, and a range of new relationships and collaborations are forming around this node of activity. This article critically reflects on this trajectory through a dialogue between ethnography, design and theoretical principles from anthropology and human geography

The interview as narrative ethnography : seeking and shaping connections in qualitative research.

Acts of counter-subjectification in qualitative research are always present but are often submerged in accounts that seek to locate the power of subjectification entirely with the researcher. This is particularly so when talking to people about sensitive issues. Based on an interview-based study of infertility and reproductive disruption among British Pakistanis in Northeast England, we explore how we, as researchers, sought and were drawn into various kinds of connections with the study participants; connections that were actively and performatively constructed through time. The three of us that conducted interviews are all female academics with Ph.Ds in anthropology, but thereafter our backgrounds, life stories and experiences diverge in ways that intersected with those of our informants in complex and shifting ways. We describe how these processes shaped the production of narrative accounts and consider some of the associated analytical and ethical implications

Economic and health-related quality of life outcomes of whiplash associated disorders

STUDY DESIGN: This study examines the links between severity of whiplash associated disorder and costs and health outcomes OBJECTIVE.: The aim of this study was to estimate the economic costs and health state utilities associated with disability levels and recovery trajectories following acute whiplash injury. SUMMARY OF BACKGROUND DATA: Data used were from the Managing Injuries of the Neck Trial, which collected information on 3,851 people over a 12 month period following acute whiplash injury. METHODS: Effects of whiplash associated disorder severity on economic costs (measured from a societal perspective and separately from a health and personal social services perspective) were estimated using two-part regression models, comprising probability of incurring a cost and the total cost, given one was incurred. Effects on health state utilities (measured using the EQ-5D and SF-6D) were estimated using ordinary least squares regression, and two-part models as for costs. RESULTS: There was a direct relationship between severity of disability following acute whiplash injury and economic costs. Between baseline and 4 months, average societal costs for those with no disability were £99.55 (UK£, 2009 prices), increasing to £668.53 for those with complete disability. Average societal costs for the whole sample were £234.15 over the first 4 months, decreasing to £127.51 between 8 and 12 months. Conversely, utility scores decreased with increased disability. The average EQ-5D utility score was 0.934 at 4 months for those with no disability, decreasing to 0.033 for those with complete disability. The average EQ-5D utility score for the whole sample increased from 0.587 immediately post-injury to 0.817 at 12 months. Relative costs and disutilities generated by the multivariate models are also presented by disability level and recovery trajectory. CONCLUSIONS: These results provide estimates of the costs and health state utilities associated with disability levels and recovery trajectories following acute whiplash injury. They can be used to inform estimates of the cost-effectiveness of interventions targeting whiplash associated disorders

Embedding creativity in the university computing curriculum

We explore the need for embedding creativity in the UK Higher Education computing curriculum and some of the challenges associated with this. We identify some of the initiatives and movements in this area and discuss some of the work that has been carried out. We then describe some of the ways we have tried to meet these challenges and reflect on our degree of success with respect to the goal of producing graduates who are fit for the myriad of job opportunities they will come across in a rapidly changing technology landscape. Finally, we make a number of recommendations

Use of systemic therapies in adults with atopic dermatitis:12-month results from the European prospective observational study in patients eligible for systemic therapy for atopic dermatitis (EUROSTAD)

Background The European Prospective Observational Study in Patients Eligible for Systemic Therapy for Atopic Dermatitis (EUROSTAD) is an ongoing observational study aiming to describe characteristics of patients with atopic dermatitis (AD) treated with systemic therapy over time and the management of their disease in a real-world setting. Methods Data from patients enrolled in EUROSTAD between March 2017 and April 2019 were analyzed for systemic therapy use and treatment change over 12 months. Results 288 patients reported taking systemic medications; 42.7% received cyclosporine, 35.3% dupilumab, 28.1% methotrexate, 25.4% oral corticosteroids, 6.8% azathioprine, 6.1% injectable corticosteroids, and 3.4% mycophenolate. The median duration of treatment was 1.1 months for oral systemic corticosteroids, 3.2 months for injectable corticosteroids, 4.8 months for cyclosporine, 7.3 months for methotrexate, and 14.9 months for dupilumab. The most frequent reasons for stopping treatment included lack of efficacy, patient decision, adverse events, and disease well controlled. Conclusion The 12-month interim EUROSTAD study analysis highlights the current trends and outcomes of systemic treatments for moderate-to-severe AD. Among all systemic treatments for AD, dupilumab was the least likely to be discontinued, whereas cyclosporine and corticosteroids, whilst effective, were primarily limited to episodic flare management consistent with treatment guidelines

Roadmaps to Utopia: Tales of the Smart City

Notions of the Smart City are pervasive in urban development discourses. Various frameworks for the development of smart cities, often conceptualized as roadmaps, make a number of implicit claims about how smart city projects proceed but the legitimacy of those claims is unclear. This paper begins to address this gap in knowledge. We explore the development of a smart transport application, MotionMap, in the context of a £16M smart city programme taking place in Milton Keynes, UK. We examine how the idealized smart city narrative was locally inflected, and discuss the differences between the narrative and the processes and outcomes observed in Milton Keynes. The research shows that the vision of data-driven efficiency outlined in the roadmaps is not universally compelling, and that different approaches to the sensing and optimization of urban flows have potential for empowering or disempowering different actors. Roadmaps tend to emphasize the importance of delivering quick practical results. However, the benefits observed in Milton Keynes did not come from quick technical fixes but from a smart city narrative that reinforced existing city branding, mobilizing a growing network of actors towards the development of a smart region. Further research is needed to investigate this and other smart city developments, the significance of different smart city narratives, and how power relationships are reinforced and constructed through them