Understanding causality and uncertainty in volcanic observations: an example of forecasting eruptive activity on Soufrière Hills Volcano, Montserrat

Following a cessation in eruptive activity it is important to understand how a volcano will behave in the future and when it may next erupt. Such an assessment can be based on the volcano's long-term pattern of behaviour and insights into its current state via monitoring observations. We present a Bayesian network that integrates these two strands of evidence to forecast future eruptive scenarios using expert elicitation. The Bayesian approach provides a framework to quantify the magmatic causes in terms of volcanic effects (i.e., eruption and unrest). In October 2013, an expert elicitation was performed to populate a Bayesian network designed to help forecast future eruptive (in-)activity at Soufrière Hills Volcano. The Bayesian network was devised to assess the state of the shallow magmatic system, as a means to forecast the future eruptive activity in the context of the long-term behaviour at similar dome-building volcanoes. The findings highlight coherence amongst experts when interpreting the current behaviour of the volcano, but reveal considerable ambiguity when relating this to longer patterns of volcanism at dome-building volcanoes, as a class. By asking questions in terms of magmatic causes, the Bayesian approach highlights the importance of using short-term unrest indicators from monitoring data as evidence in long-term forecasts at volcanoes. Furthermore, it highlights potential biases in the judgements of volcanologists and identifies sources of uncertainty in terms of magmatic causes rather than scenario-based outcomes

From social contract to 'social contrick' : the depoliticisation of economic policy-making under Harold Wilson, 1974–75

The 1974-79 Labour Governments were elected on the basis of an agreement with the TUC promising a redistribution of income and wealth known as the Social Contract. However, the Government immediately began to marginalise these commitments in favour of preferences for incomes policy and public expenditure cuts, which has led the Social Contract to be described as the 'Social Contrick'. These changes were legitimised through a process of depoliticisation, and using an Open Marxist framework and evidence from the National Archives, the paper will show that the Treasury's exchange rate strategy and the need to secure external finance placed issues of confidence at the centre of political debate, allowing the Government to argue there was no alternative to the introduction of incomes policy and the reduction of public expenditure

Celtic pilgrimage, past and present: from historical geography to contemporary embodied practices

Perigrinatio, the Latin term for pilgrimage was at the heart of the medieval Celtic church, but was this was understood and practised not only as a journey to a shrine, but more broadly as a spiritual journey, which could lead to an isolated hermitage or peripatetic evangelistic mission. In this paper, we outline the beliefs and practices of the broad assemblage known as the Celtic church, particularly the interleaving of pilgrimage, asceticism and landscape poetics, and how these have informed continued and renewed pilgrimage practices to sites of the early Celtic church by particular denominations, ecumenical groups and those interested in broader spiritualities. These sacred mobilities are explored through vignettes of embodied-emotionalspiritual practices situated in the landscapes and faith communities of Lough Derg,Ireland and the Isle of Man. They share geographical marginality, a focus on multiple Celtic saints and an enduring belief in the immanence of God, expressed through embodied spiritual practice in the landscape. However, they differ widely in matters of institutionalised structure, regulation, discursive scripting and gendered hierarchy, reflecting situated and denominational preferences for the ascetic and aesthetic spiritual legacies of the medieval Celtic church

Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research

Conceptualising spirituality for medical research and health service provision

The need to take account of spirituality in research and health services provision is assuming ever greater importance. However the field has long been hampered by a lack of conceptual clarity about the nature of spirituality itself. We do not agree with the sceptical claim that it is impossible to conceptualise spirituality within a scientific paradigm. Our aims are to 1) provide a brief over-view of critical thinking that might form the basis for a useful definition of spirituality for research and clinical work and 2) demystify the language of spirituality for clinical practice and research

Strategies to inhibit tumour associated integrin receptors: rationale for dual and multi-antagonists

YesThe integrins are a family of 24 heterodimeric transmembrane cell surface receptors. Involvement in cell attachment to the extracellular matrix, motility, and proliferation identifies integrins as therapeutic targets in cancer and associated conditions; thrombosis, angiogenesis and osteoporosis. The most reported strategy for drug development is synthesis of an agent that is highly selective for a single integrin receptor. However, the ability of cancer cells to change their integrin repertoire in response to drug treatment renders this approach vulnerable to the development of resistance and paradoxical promotion of tumor growth. Here, we review progress towards development of antagonists targeting two or more members of the RGD-binding integrins, notably αvβ3, αvβ5, αvβ6, αvβ8, α5β1, and αIIbβ3, as anticancer therapeutics

Induction of Eosinophil Apoptosis by the Cyclin-Dependent Kinase Inhibitor AT7519 Promotes the Resolution of Eosinophil-Dominant Allergic Inflammation

Eosinophils not only defend the body against parasitic infection but are also involved in pathological inflammatory allergic diseases such as asthma, allergic rhinitis and contact dermatitis. Clearance of apoptotic eosinophils by macrophages is a key process responsible for driving the resolution of eosinophilic inflammation and can be defective in allergic diseases. However, enhanced resolution of eosinophilic inflammation by deliberate induction of eosinophil apoptosis using pharmacological agents has not been previously demonstrated. Here we investigated the effect of a novel cyclin-dependent kinase inhibitor drug, AT7519, on human and mouse eosinophil apoptosis and examined whether it could enhance the resolution of a murine model of eosinophil-dominant inflammation in vivo.Eosinophils from blood of healthy donors were treated with AT7519 and apoptosis assessed morphologically and by flow-cytometric detection of annexin-V/propidium iodide staining. AT7519 induced eosinophil apoptosis in a concentration dependent manner. Therapeutic administration of AT7519 in eosinophil-dominant allergic inflammation was investigated using an established ovalbumin-sensitised mouse model of allergic pleurisy. Following ovalbumin challenge AT7519 was administered systemically at the peak of pleural inflammation and inflammatory cell infiltrate, apoptosis and evidence of macrophage phagocytosis of apoptotic eosinophils assessed at appropriate time points. Administration of AT7519 dramatically enhanced the resolution of allergic pleurisy via direct induction of eosinophil apoptosis without detriment to macrophage clearance of these cells. This enhanced resolution of inflammation was shown to be caspase-dependent as the effects of AT7519 were reduced by treatment with a broad spectrum caspase inhibitor (z-vad-fmk).Our data show that AT7519 induces human eosinophil apoptosis and enhances the resolution of a murine model of allergic pleurisy by inducing caspase-dependent eosinophil apoptosis and enhancing macrophage ingestion of apoptotic eosinophils. These findings demonstrate the utility of cyclin-dependent kinase inhibitors such as AT7519 as potential therapeutic agents for the treatment of eosinophil dominant allergic disorders

Mapping the visible and invisible topgraphies of place and landscape through sacred mobilities

Different forms of mobility produce specific situated experiences, and consequently orient the subject differently in relation to those places at particular times. Places and landscapes are agential, evoking and provoking emotional-affective and, in some cases spiritual, engagement. In common with spirituality, emotional ties reach across time and place, ultimately they are both carried within and catalysed by meaningful places and embodied experience of landscape. Sacred mobilities are meaningful and meaning-making journeys and practices which have religious or spiritual intent. Sacred mobilities reflect and give meaning to place and landscape attributes, including place attachment. Embodied mobilities intersect with place, wider landscapes and perceived or virtual spiritual realms in varied ways, producing ‘deep maps’ of individual and collective sensory, emotional-affective and spiritual experience in material, embodied psychological and virtual spaces. Participant accounts of guided pilgrimage and prayer walks are used to explore experience of place and landscape

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders