751 research outputs found

    When the Bubble Bursts: A Spatial Interrogation of Spanish Crisis in José Ángel Mañas’ Sospecha

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    José Ángel Mañas’s detective novel Sospecha investigates the consequences of the 2008 economic crisis by focusing on the unsustainable development of the Madrid urban area. I argue that the novel’s depiction of the Spanish capital serves as a case study for coming to terms with the identity and effects of crisis. By employing elements of the police procedural, Sospecha creates multiple trajectories through these suburban communities, allowing the novel to trace the impacts of a globalized economic model that presents these spaces as products of consumption. In turn, it is the spatial production of the city’s urban periphery that becomes the crime under investigation. However, the cause of the crimes themselves remain unresolved, suggesting a pessimistic and ultimately powerless interrogation of the social and economic factors that fuel the crisis and also impede Spain’s recovery

    Identifying stochastic oscillations in single-cell live imaging time series using Gaussian processes

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    Multiple biological processes are driven by oscillatory gene expression at different time scales. Pulsatile dynamics are thought to be widespread, and single-cell live imaging of gene expression has lead to a surge of dynamic, possibly oscillatory, data for different gene networks. However, the regulation of gene expression at the level of an individual cell involves reactions between finite numbers of molecules, and this can result in inherent randomness in expression dynamics, which blurs the boundaries between aperiodic fluctuations and noisy oscillators. Thus, there is an acute need for an objective statistical method for classifying whether an experimentally derived noisy time series is periodic. Here we present a new data analysis method that combines mechanistic stochastic modelling with the powerful methods of non-parametric regression with Gaussian processes. Our method can distinguish oscillatory gene expression from random fluctuations of non-oscillatory expression in single-cell time series, despite peak-to-peak variability in period and amplitude of single-cell oscillations. We show that our method outperforms the Lomb-Scargle periodogram in successfully classifying cells as oscillatory or non-oscillatory in data simulated from a simple genetic oscillator model and in experimental data. Analysis of bioluminescent live cell imaging shows a significantly greater number of oscillatory cells when luciferase is driven by a {\it Hes1} promoter (10/19), which has previously been reported to oscillate, than the constitutive MoMuLV 5' LTR (MMLV) promoter (0/25). The method can be applied to data from any gene network to both quantify the proportion of oscillating cells within a population and to measure the period and quality of oscillations. It is publicly available as a MATLAB package.Comment: 36 pages, 17 figure

    Current State of Type 1 Diabetes Immunotherapy: Incremental Advances, Huge Leaps, or More of the Same?

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    Thus far, none of the preclinically successful and promising immunomodulatory agents for type 1 diabetes mellitus (T1DM) has conferred stable, long-term insulin independence to diabetic patients. The majority of these immunomodulators are humanised antibodies that target immune cells or cytokines. These as well as fusion proteins and inhibitor proteins all share varying adverse event occurrence and severity. Other approaches have included intact putative autoantigens or autoantigen peptides. Considerable logistical outlays have been deployed to develop and to translate humanised antibodies targeting immune cells, cytokines, and cytokine receptors to the clinic. Very recent phase III trials with the leading agent, a humanised anti-CD3 antibody, call into question whether further development of these biologics represents a step forward or more of the same. Combination therapies of one or more of these humanised antibodies are also being considered, and they face identical, if not more serious, impediments and safety issues. This paper will highlight the preclinical successes and the excitement generated by phase II trials while offering alternative possibilities and new translational avenues that can be explored given the very recent disappointment in leading agents in more advanced clinical trials

    Parents' and clinicians' views of an interactive booklet about respiratory tract infections in children: a qualitative process evaluation of the EQUIP randomised controlled trial

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    Background: ‘When should I worry?’ is an interactive booklet for parents of children presenting with respiratory tract infections (RTIs) in primary care and associated training for clinicians. A randomised controlled trial (the EQUIP study) demonstrated that this intervention reduced antibiotic prescribing and future consulting intentions. The aims of this qualitative process evaluation were to understand how acceptable the intervention was to clinicians and parents, how it was implemented, the mechanisms for any observed effects, and contextual factors that could have influenced its effects.<p></p> Methods: Semi-structured interviews were conducted with 20 parents and 13 clinicians who participated in the trial. Interviews were audio-recorded and transcribed verbatim. Data were analysed using a framework approach, which involved five stages; familiarisation, development of a thematic framework, indexing, charting, and interpretation.<p></p> Results: Most parents and clinicians reported that the ‘When should I worry’ interactive booklet (and online training for clinicians) was easy to use and valuable. Information on recognising signs of serious illness and the usual duration of illness were most valued. The interactive use of the booklet during consultations was considered to be important, but this did not always happen. Clinicians reported lack of time, lack of familiarity with using the booklet, and difficulty in modifying their treatment plan/style of consultation as barriers to use. Increased knowledge and confidence amongst clinicians and patients were seen as key components that contributed to the reductions in antibiotic prescribing and intention to consult seen in the trial. This was particularly pertinent in a context where decisions about the safe and appropriate management of childhood RTIs were viewed as complex and parents reported frequently receiving inconsistent messages. Conclusions: The ‘When should I worry’ booklet, which is effective in reducing antibiotic prescribing, has high acceptability for clinicians and parents, helps address gaps in knowledge, increases confidence, and provides a consistent message. However, it is not always implemented as intended. Plans for wider implementation of the intervention in health care settings would need to address clinician-related barriers to implementation

    Designing for active engagement, enabling resilience and fostering environmental change

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    Contemporary societies are increasingly distancing themselves from nature; driven by rapid urbanisation, biodiversity loss, lack of connection, industrialisation, loss of green space and parental fear… all factors are reducing our care/empathy for nature. Conservation and grass roots reporting highlight nature’s wellbeing, requires impactful citizen led responses. Youth leaders of our time are holding up a mirror to adult humankind, stating ‘our world is on fire’, and demanding action. It is well known that interactions with the natural world provide health benefits, resilience, and prove transformative to our attitude, values and behaviour. The My Naturewatch project facilitates people’s engagement with their local environment, and by doing so, helps its comprehension. Observations of nature help connect, engage, and foster custodians, at a time where growing separation from wildlife necessitates active engagement. The work specifically challenges our understanding of ‘designed engagement(s)’, not as passive activities but as impactful active engagements, open to all. This article proposes criteria encouraging public participation within the natural world. It presents value to NGOs, change makers, design agents, individual agents and funding bodies. Thirty experts from design, ecology, conservation, museology, engagement, rewilding, wildlife and community work, were interviewed, informing ‘design for environmental change through active engagement’. The work identifies design’s role, in creating interventions that better engage people with the surrounding natural world, yielding long-term mutual benefits. The objective fosters active public nature engagement, identifying barriers, opportunities, and pitfalls, leading to nature engaged interaction(s)

    To choose or not to choose: how to deal with China's growing power and influence

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    This paper collects 10 items published on the ASPI blog The Strategist by eight authors on one of the most important public policy issues of this decade and beyond: how to deal with China’s growing power and influence. The hope is that this debate will start to identify points of shared thinking and expose the areas where further work is needed to improve the quality of policy outcomes. ASPI will continue to publish on the topic. There is no more important subject for the future of Australia and for a stable Asia–Pacific

    The role of cost-effectiveness analysis in the development of indicators to support incentive-based behaviour in primary care in England

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    In England, general practitioners are incentivized through a national pay-for-performance scheme to adopt evidence-based quality improvement initiatives using a portfolio of Quality and Outcomes Framework (QOF) indicators. We describe the development of the methods used to assess the cost-effectiveness of these pay-for-performance indicators and how they have contributed to the development of new indicators. Prior to analysis of new potential indicators, an economic subgroup of the National Institute for Health and Care Excellence (NICE) Indicator Advisory Committee is formed to assess evidence on the cost-effectiveness of potential indicators in terms of the health benefits gained, compared to the cost of the intervention and the cost of the incentive. The expert subgroup is convened to reach consensus on the amounts that could potentially be paid to general practices for achieving new indicators. Indicators are also piloted in selected general practices and evidence gathered about their practical implementation. The methods used to assess economic viability of new pilot indicators represent a pragmatic and effective way of providing information to inform recommendations. Current policy to reduce QOF funding could shift the focus from national (QOF) to local schemes, with economic appraisal remaining central
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