Regulation of anti-inflammatory gene expression in vascular endothelial cells by EPAC1

Suppressor of cytokine signalling 3 (SOCS3) is a potent inhibitor of pro-inflammatory pathways involved in atherogenesis and the development of neo-intimal hyperplasia (NIH), which contributes to the in-stent re-stenosis responsible for the failure of percutaneous coronary intervention (PCI) procedures. We have shown that cyclic AMP sensor EPAC1 triggers induction of the SOCS3 gene in vascular endothelial cells (VECs), thereby attenuating interleukin 6 (IL-6)-mediated pro-inflammatory signalling. We propose that EPAC1 localisation to the nuclear pore controls cyclic AMP-mediated activation of a C/EBPβ/c-Jun transcriptional complex, leading to SOCS3 induction and suppression of pro-inflammatory signalling. Future work in this area will involve an integrated approach to determine the wider significance of the EPAC1-C/EBPβ/c-Jun pathway in controlling human VEC function and identify new therapeutic targets for management of chronic inflammation in vascular settings

Edge-region grouping in figure-ground organization and depth perception.

Edge-region grouping (ERG) is proposed as a unifying and previously unrecognized class of relational information that influences figure-ground organization and perceived depth across an edge. ERG occurs when the edge between two regions is differentially grouped with one region based on classic principles of similarity grouping. The ERG hypothesis predicts that the grouped side will tend to be perceived as the closer, figural region. Six experiments are reported that test the predictions of the ERG hypothesis for 6 similarity-based factors: common fate, blur similarity, color similarity, orientation similarity, proximity, and flicker synchrony. All 6 factors produce the predicted effects, although to different degrees. In a 7th experiment, the strengths of these figural/depth effects were found to correlate highly with the strength of explicit grouping ratings of the same visual displays. The relations of ERG to prior results in the literature are discussed, and possible reasons for ERG-based figural/depth effects are considered. We argue that grouping processes mediate at least some of the effects we report here, although ecological explanations are also likely to be relevant in the majority of cases

Changing quantum reference frames

We consider the process of changing reference frames in the case where the reference frames are quantum systems. We find that, as part of this process, decoherence is necessarily induced on any quantum system described relative to these frames. We explore this process with examples involving reference frames for phase and orientation. Quantifying the effect of changing quantum reference frames serves as a first step in developing a relativity principle for theories in which all objects including reference frames are necessarily quantum.Comment: 21 pages, 6 figures, comments welcome; v2 added some references; v3 published versio

Defining and characterising structural uncertainty in decision analytic models

An inappropriate structure for a decision analytic model can potentially invalidate estimates of cost-effectiveness and estimates of the value of further research. However, there are often a number of alternative and credible structural assumptions which can be made. Although it is common practice to acknowledge potential limitations in model structure, there is a lack of clarity about methods to characterize the uncertainty surrounding alternative structural assumptions and their contribution to decision uncertainty. A review of decision models commissioned by the NHS Health Technology Programme was undertaken to identify the types of model uncertainties described in the literature. A second review was undertaken to identify approaches to characterise these uncertainties. The assessment of structural uncertainty has received little attention in the health economics literature. A common method to characterise structural uncertainty is to compute results for each alternative model specification, and to present alternative results as scenario analyses. It is then left to decision maker to assess the credibility of the alternative structures in interpreting the range of results. The review of methods to explicitly characterise structural uncertainty identified two methods: 1) model averaging, where alternative models, with different specifications, are built, and their results averaged, using explicit prior distributions often based on expert opinion and 2) Model selection on the basis of prediction performance or goodness of fit. For a number of reasons these methods are neither appropriate nor desirable methods to characterize structural uncertainty in decision analytic models. When faced with a choice between multiple models, another method can be employed which allows structural uncertainty to be explicitly considered and does not ignore potentially relevant model structures. Uncertainty can be directly characterised (or parameterised) in the model itself. This method is analogous to model averaging on individual or sets of model inputs, but also allows the value of information associated with structural uncertainties to be resolved.

Modelling Hen Harrier Dynamics to Inform Human-Wildlife Conflict Resolution : A Spatially-Realistic, Individual-Based Approach

Peer reviewedPublisher PD

Simple individual-based models effectively represent Afrotropical forest bird movement in complex landscapes

Reliable estimates of dispersal rates between habitat patches (i.e. functional connectivity) are critical for predicting long-term effects of habitat fragmentation on population persistence. Connectivity measures are frequently derived from least cost path or graph-based approaches, despite the fact that these methods make biologically unrealistic assumptions. Individual-based models (IBMs) have been proposed as an alternative as they allow modelling movement behaviour in response to landscape resistance. However, IBMs typically require excessive data to be useful for management. Here, we test the extent to which an IBM requiring only an uncomplicated set of movement rules [the 'stochastic movement simulator' (SMS)] can predict animal movement behaviour in real-world landscapes. Movement behaviour of two forest birds, the Cabanis's greenbul Phyllastrephus cabanisi (a forest specialist) and the white-starred robin Pogonocichla stellata (a habitat generalist), across an Afrotropical matrix was simulated using SMS. Predictions from SMS were evaluated against a set of detailed movement paths collected by radiotracking homing individuals. SMS was capable of generating credible predictions of bird movement, although simulations were sensitive to the cost values and the movement rules specified. Model performance was generally highest when movement was simulated across low-contrasting cost surfaces and when virtual individuals were assigned low directional persistence and limited perceptual range. SMS better predicted movements of the habitat specialist than the habitat generalist, which highlights its potential to model functional connectivity when species movements are affected by the matrix. Synthesis and applications. Modelling the dispersal process with greater biological realism is likely to be critical for improving our predictive capability regarding functional connectivity and population persistence. For more realistic models to be widely applied, it is vital that their application is not overly complicated or data demanding. Here, we show that given relatively basic understanding of a species' dispersal ecology, the stochastic movement simulator represents a promising tool for estimating connectivity, which can help improve the design of functional ecological networks aimed at successful species conservation

Rural entrepreneurial space and identity: A study of local tour operators and ‘the Nenets’ indigenous reindeer herders

The tourism industry is a capitalist activity concerned with the production, accumulation and distribution of wealth. Power is an important arena for research in this respect as diverse outcomes for the local economy in general, and its players specifically, provide important aspects to study when considering the lives of rural entrepreneurs. However, it may be argued that whilst Marxist theorists using critical approaches on power have tended to focus on issues around the equality of power relations between actors or stakeholders, the inherently spatial nature of power has received less emphasis. This paper focuses on an exploration of the spatiality of power which surrounds entrepreneurship and tourism industry development. The conceptual framework, based on the application of Lefebvre’s (1991) concepts supplemented by Gaventa’s (2004) power cube, is placed within the broader context of Marx Political Economy and Historical Materialism. The main value of Lefebvre’s (1991) work for the current research is seen in his notion of space as an ‘ensemble’ formed from i) representational space (or our conception of it); ii) spatial practices, which are our interaction with physical and material aspects of space; and, iii) the spaces of representation, or our lived space. They are intertwined dimensions and therefore intradependent (Theobald 1997). These three types of dialectically inter-related spaces are merged into a single ensemble which forms our experience of social space. Gaventa (2006) extends this further with the introduction of power through space and explores the visible, hidden, and invisible forms of power which are negotiated at different spatial scales and which are experienced as closed, invited, or (re)claimed. The case study geographic area examined is in transition from Socialism to Capitalism with the tourism industry at early stages of its development. For this, reason entrepreneurial activity and power struggles over the key business asset, the landscape, are currently being played out. Literature theorising rural entrepreneurship (Marlow et al 2014) and especially the notion of skills and training for diversifying rural enterprise (Vik and McElwee 2011; Pyysiäinen et al 2006) is an important context here. This is particularly born out in the relationships between the indigenous reindeer herders, ‘the Nenets’, local tour operators, and the local government of Yamal in the Yamal-Nenets Autonomous Okrug (YNAO) of the Russian Federation which provides the core material. The research has been conducted through an ethnographic field study with indigenous reindeer herder communities as well as interviews with local stakeholders. This allows for insights into the spatiality of power surrounding rural entrepreneurial space and tourism enterprise to be gained

Is primary angioplasty cost effective in the UK? Results of a comprehensive decision analysis

Objective: To assess the cost effectiveness of primary angioplasty, compared with medical management with thrombolytic drugs, to achieve reperfusion after acute myocardial infarction ( AMI) from the perspective of the UK NHS. Design: Bayesian evidence synthesis and decision analytic model. Methods: A systematic review was conducted and Bayesian statistical methods used to synthesise evidence from 22 randomised control trials. Resource utilisation was based on UK registry data, published literature and national databases, with unit costs taken from routine NHS sources and published literature. Main outcome measure: Costs from a health service perspective and outcomes measured as quality-adjusted life years (QALYs). Results: For the base case, the incremental cost-effectiveness ratio of primary angioplasty was pound 9241 for each additional QALY, with a probability of being cost effective of 0.90 for a cost-effectiveness threshold of pound 20 000. Results were sensitive to variations in the additional time required to initiate treatment with primary angioplasty. Conclusions: Primary angioplasty is cost effective for the treatment of AMI on the basis of threshold cost-effectiveness values used in the NHS and subject to a delay of up to about 80 minutes. These findings are mainly explained by the superior mortality benefit and the prevention of non-fatal outcomes associated with primary angioplasty for delays of up to this length

Predicting and understanding spatio-temporal dynamics of species recovery : implications for Asian crested ibis Nipponia nippon conservation in China

Acknowledgements This work was supported by the National Natural Science Foundation of China (No. 31372218) and cofunded by the China Scholarship Council (CSC) and the ITC Research Fund, Enschede, the Netherlands. We thank Shaanxi Hanzhong Crested Ibis National Nature Reserve for sharing the data of nest site locations. We are grateful to Brendan Wintle, Justin Travis and two anonymous reviewers for helpful comments on a previous version of the manuscript.Peer reviewedPublisher PD