3,208 research outputs found

    Na(v )1.8-null mice show stimulus-dependent deficits in spinal neuronal activity

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    BACKGROUND: The voltage gated sodium channel Na(v )1.8 has a highly restricted expression pattern to predominantly nociceptive peripheral sensory neurones. Behaviourally Na(v )1.8-null mice show an increased acute pain threshold to noxious mechanical pressure and also deficits in inflammatory and visceral, but not neuropathic pain. Here we have made in vivo electrophysiology recordings of dorsal horn neurones in intact anaesthetised Na(v )1.8-null mice, in response to a wide range of stimuli to further the understanding of the functional roles of Na(v )1.8 in pain transmission from the periphery to the spinal cord. RESULTS: Na(v )1.8-null mice showed marked deficits in the coding by dorsal horn neurones to mechanical, but not thermal, -evoked responses over the non-noxious and noxious range compared to littermate controls. Additionally, responses evoked to other stimulus modalities were also significantly reduced in Na(v )1.8-null mice where the reduction observed to pinch > brush. The occurrence of ongoing spontaneous neuronal activity was significantly less in mice lacking Na(v )1.8 compared to control. No difference was observed between groups in the evoked activity to electrical activity of the peripheral receptive field. CONCLUSION: This study demonstrates that deletion of the sodium channel Na(v )1.8 results in stimulus-dependent deficits in the dorsal horn neuronal coding to mechanical, but not thermal stimuli applied to the neuronal peripheral receptive field. This implies that Na(v )1.8 is either responsible for, or associated with proteins involved in mechanosensation

    Structural Basis for Arsenate-Phosphate Discrimination

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    Unbalanced and unbalancing acts in the Early Years Foundation Stage: a critical discourse analysis of policy-led evidence on teaching and play from the office for standards in education in England (Ofsted)

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    This paper presents a critical analysis of a report by the Office for Standards in Education in England based on a survey of practitioners’ perspectives of play, focusing on children age 2–5 years in the Early Years Foundation Stage (EYFS). The report, ‘Teaching and play in the early years – a balancing act? A good practice survey to explore perceptions of teaching and play in the early years’ www.gov.uk/government/organisations/Ofsted addressed the ‘recurring myth’ that teaching and play are disconnected endeavours. Critical discourse and critical policy analysis are used to interrogate this report alongside interrelated texts, the socio-political context of production, the methods used to define policy versions of ‘good practice’ in play, and the resulting power effects within early childhood education (ECE). It is argued that this report exemplifies how the remit of Ofsted has extended to provide policy-led evidence that is based on the construction of ‘problems’ of practice, and the proposed solutions. The Ofsted version of teaching and play relies on circular discourses that reinforce the government’s standards and accountability agendas. This analysis reveals the extension from Ofsted’s remit of inspection, to a mandate for defining ‘quality’ and ‘good’ practice. These actions, relationships and processes constitute the ‘meaning-laden architectures’ [Fairclough, N., P. Graham, J. Lemke, and R. Wodak. 2004. “Introduction.” Critical Discourse Studies 1: 1–7] that connect discourse and power. Using the metaphor of a kaleidoscope, it is proposed that ‘Teaching and Play’, and related reports, represent unbalanced and unbalancing acts in which policy-led evidence, based on flawed and biased ‘research’, exerts power effects for children, families and practitioners

    Scaling up depot medroxyprogesterone acetate (DMPA): a systematic literature review illustrating the AIDED model

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    BACKGROUND: Use of depot medroxyprogesterone acetate (DMPA), often known by the brand name Depo-Provera, has increased globally, particularly in multiple low- and middle-income countries (LMICs). As a reproductive health technology that has scaled up in diverse contexts, DMPA is an exemplar product innovation with which to illustrate the utility of the AIDED model for scaling up family health innovations. METHODS: We conducted a systematic review of the enabling factors and barriers to scaling up DMPA use in LMICs. We searched 11 electronic databases for academic literature published through January 2013 (n = 284 articles), and grey literature from major health organizations. We applied exclusion criteria to identify relevant articles from peer-reviewed (n = 10) and grey literature (n = 9), extracting data on scale up of DMPA in 13 countries. We then mapped the resulting factors to the five AIDED model components: ASSESS, INNOVATE, DEVELOP, ENGAGE, and DEVOLVE. RESULTS: The final sample of sources included studies representing variation in geographies and methodologies. We identified 15 enabling factors and 10 barriers to dissemination, diffusion, scale up, and/or sustainability of DMPA use. The greatest number of factors were mapped to the ASSESS, DEVELOP, and ENGAGE components. CONCLUSIONS: Findings offer early empirical support for the AIDED model, and provide insights into scale up of DMPA that may be relevant for other family planning product innovations

    Effectively managing headteacher performance:final report.

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    This document is one of a set of reports about the study of the effective management of headteacher performance in schools in England. This report is the full report, including the executive summary; details about the framework and design of the study; a review of the international literature on performance management of senior leaders in education and related sectors; analysis of empirical data collected for the study; discussion of significant issuesarising from the analysis; and a summary of main findings and implications drawing on the analysis and review of literature.We recommend that you read all the reports to understand the research fully. These documents are available on from gov.uk. The complete set of reports includes the following: Research brief A summary of key areas for consideration by governors and those directly involved in the process of headteacher performance management. Full reportThe full report, including the executive summary; details about the framework and design of the study; a review of the international literature on performance management of senior leaders in education and related sectors; analysis of empirical data collected for the study; discussion of significant issues arising from the analysis; and a summary of main findings and implications drawing on the analysis and review of literature. Case Studies (Annexe A)Ten case studies drawn from the research to illustrate approaches to headteacher performance management in a variety of schools and school groups around England. Vignettes (Annexe B)Twelve examples of important research themes contextualised in specific school settings

    Charge-transfer dynamics at the dye-semiconductor interface of photocathodes for solar energy applications

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    This article describes a comparison between the photophysical properties of two charge-transfer dyes adsorbed onto NiO via two different binding moieties. Transient spectroscopy measurements suggest that the structure of the anchoring group affects both the rate of charge recombination between the dye and NiO surface and the rate of dye regeneration by an iodide/triiodide redox couple. This is consistent with the performance of the dyes in p-type dye sensitised solar cells. A key finding was that the recombination rate differed in presence of the redox couple. This has important implications on the study of electron transfer at dye|semiconductor interfaces for solar energy applications

    From Ideas to Practice, Pilots to Strategy: Practical Solutions and Actionable Insights on How to Do Impact Investing

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    This report is the second publication in the World Economic Forum's Mainstreaming Impact Investing Initiative. The report takes a deeper look at why and how asset owners began to include impact investing in their portfolios and continue to do so today, and how they overcame operational and cultural constraints affecting capital flow. Given that impact investing expertise is spread among dozens if not hundreds of practitioners and academics, the report is a curation of some -- but certainly not all -- of those leading voices. The 15 articles are meant to provide investors, intermediaries and policy-makers with actionable insights on how to incorporate impact investing into their work.The report's goals are to show how mainstream investors and intermediaries have overcome the challenges in the impact investment sector, and to democratize the insights and expertise for anyone and everyone interested in the field. Divided into four main sections, the report contains lessons learned from practitioner's experience, and showcases best practices, organizational structures and innovative instruments that asset owners, asset managers, financial institutions and impact investors have successfully implemented

    Ni Mg mixed metal oxides for p-type dye-sensitized solar cells

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    Mg Ni mixed metal oxide photocathodes have been prepared by a mixed NiCl2/MgCl2 sol-gel process. The MgO/NiO electrodes have been extensively characterized using physical and electrochemical methods. Dye-sensitized solar cells have been prepared from these films and the higher concentrations of MgO improved the photovoltage of these devices, however, there was a notable drop in photocurrent with increasing Mg2+. Charge extraction and XPS experiments revealed that the cause of this was a positive shift in the energy of the valence band which decreased the driving force for electron transfer from the NiO film to the dye and therefore the photocurrent. In addition, increasing concentrations of MgO increases the volume of pores between 0.500 to 0.050 ÎŒm, while reducing pore volumes in the mesopore range (less than 0.050 ÎŒm) and lowering BET surface area from approximately 41 down to 30 m2 g-1. A MgO concentration of 5% was found to strike a balance between the increased photovoltage and decreased photocurrent, possessing a BET surface area of 35 m2 g-1 and a large pore volume in both the meso and macropore range, which lead to a higher overall power conversion efficiency than NiO alone

    The melting curve of Ni to 1 Mbar

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    International audienceThe melting curve of Ni has been determined to 125 GPa using laser-heated diamond anvil cell (LH-DAC) experiments in which two melting criteria were used: firstly, the appearance of liquid diffuse scattering (LDS) during in situ X-ray diffraction (XRD) and secondly, plateaux in temperature vs. laser power functions in both in situ and off-line experiments. Our new melting curve, defined by a Simon–Glatzel fit to the data where T M ( K ) = [ ( P M 18.78 ± 10.20 + 1 ) ] 1 / 2.42 ± 0.66 × 1726 , is in good agreement with the majority of the theoretical studies on Ni melting and matches closely the available shock wave melting data. It is however dramatically steeper than the previous off-line LH-DAC studies in which determination of melting was based on the visual observation of motion aided by the laser speckle method. We estimate the melting point ( T M ) of Ni at the inner-core boundary (ICB) pressure of 330 GPa to be T M = 5800 ± 700 K ( 2 σ ) , within error of the value for Fe of T M = 6230 ± 500 K determined in a recent in situ LH-DAC study by similar methods to those employed here. This similarity suggests that the alloying of 5–10 wt.% Ni with the Fe-rich core alloy is unlikely to have any significant effect on the temperature of the ICB, though this is dependent on the details of the topology of the Fe–Ni binary phase diagram at core pressures. Our melting temperature for Ni at 330 GPa is ∌2500 K higher than that found in previous experimental studies employing the laser speckle method. We find that those earlier melting curves coincide with the onset of rapid sub-solidus recrystallization, suggesting that visual observations of motion may have misinterpreted dynamic recrystallization as convective motion of a melt. This finding has significant implications for our understanding of the high-pressure melting behaviour of a number of other transition metals

    Continuous-flow left ventricular assist device outflow graft stenting: Indications and outcomes

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    Introduction: Stenosis in the continuous-flow left ventricular assist device (CF-LVAD) outflow graft can be caused by various mechanical and anatomical factors. Increasingly, percutaneous management has been utilized to re-establish adequate CF-LVAD flow. We sought to evaluate indications for such interventions and their outcomes. Methods: An electronic search was performed to identify all studies in the English literature reporting CF-LVAD outflow graft stenting for various etiologies. Twenty-one studies consisting of 26 patients were included in the analysis. Results: Median patient age was 59 years [45.8-67.0] and 65.4% (17/26) were male. 58.3% (14/24) of patients had HeartWare HVAD, 37.5% (9/24) had HeartMate II LVAD, and 4.2% (1/24) had HeartMate III LVAS. Median time from device placement to outflow graft stenting was 24.0 months [7.8-30.4]. 76.9% of patients (20/26) presented with heart failure. 34.6% (9/26) had outflow graft thrombosis, 34.6% (9/26) stenosis, 11.5% (3/26) kinking, 11.5% (3/26) pseudoaneurysm, 3.8% (1/26) external graft compression, and 3.8% (1/26) had a bronchialarterial fistula. 88.5% (23/26) procedures led to immediate flow improvement with the remaining 11.5% (3/26) receiving additional stenting. Post-intervention flows were significantly improved (4.7 L/min [4.1-4.8] post-intervention vs 2.9 L/min [2.0-3.5] initial, p=0.01). 96.2% (25/26) patients were discharged from the hospital. The 30-day mortality was 6.7% (1/15). Overall mortality during the median follow-up of 90 days [7.0-240.0] was 9.5% (2/21). Discussion: Outflow graft stenting appears to effectively alleviate CF-LVAD outflow graft obstruction with low mortality. Longer-term follow up is necessary to determine the longevity of such an intervention but early results are promising
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