1,274 research outputs found

    The ACUTE (Ambulance CPAP: Use, Treatment effect and economics) feasibility study: a pilot randomised controlled trial of prehospital CPAP for acute respiratory failure

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    Background: Acute respiratory failure (ARF) is a common and life-threatening medical emergency. Standard prehospital management involves controlled oxygen therapy and disease-specific ancillary treatments. Continuous positive airway pressure (CPAP) is a potentially beneficial alternative treatment that could be delivered by emergency medical services. However, it is uncertain whether this treatment could work effectively in United Kingdom National Health Service (NHS) ambulance services and if it represents value for money. Methods: An individual patient randomised controlled external pilot trial will be conducted comparing prehospital CPAP to standard oxygen therapy for ARF. Adults presenting to ambulance service clinicians will be eligible if they have respiratory distress with peripheral oxygen saturation below British Thoracic Society (BTS) target levels, despite titrated supplemental oxygen. Enrolled patients will be allocated (1:1 simple randomisation) to prehospital CPAP (O_two system) or standard oxygen therapy using identical sealed boxes. Feasibility outcomes will include incidence of recruited eligible patients, number of erroneously recruited patients and proportion of cases adhering to allocation schedule and treatment, followed up at 30 days and with complete data collection. Effectiveness outcomes will comprise survival at 30 days (definitive trial primary end point), endotracheal intubation, admission to critical care, length of hospital stay, visual analogue scale (VAS) dyspnoea score, EQ-5D-5L and health care resource use at 30 days. The cost-effectiveness of CPAP, and of conducting a definitive trial, will be evaluated by updating an existing economic model. The trial aims to recruit 120 patients over 12 months from four regional ambulance hubs within the West Midlands Ambulance Service (WMAS). This sample size will allow estimation of feasibility outcomes with a precision of < 5%. Feasibility and effectiveness outcomes will be reported descriptively for the whole trial population, and each trial arm, together with their 95% confidence intervals. Discussion: This study will determine if it is feasible, acceptable and cost-effective to undertake a full-scale trial comparing CPAP and standard oxygen treatment, delivered by ambulance service clinicians for ARF. This will inform NHS practice and prevent inappropriate prehospital CPAP adoption on the basis of limited evidence and at a potentially substantial cost. Trial registration: ISRCTN12048261. Registered on 30 August 2017. http://www.isrctn.com/ISRCTN1204826

    Targeted knock-down of miR21 primary transcripts using snoMEN vectors induces apoptosis in human cancer cell lines

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    We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2

    Spin and Chirality Effects in Antler-Topology Processes at High Energy e+ee^+e^- Colliders

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    We perform a model-independent investigation of spin and chirality correlation effects in the antler-topology processes e+eP+P(+D0)(Dˉ0)e^+e^-\to\mathcal{P}^+\mathcal{P}^-\to (\ell^+ \mathcal{D}^0) (\ell^-\mathcal{\bar{D}}^0) at high energy e+ee^+e^- colliders with polarized beams. Generally the production process e+eP+Pe^+e^-\to\mathcal{P}^+\mathcal{P}^- can occur not only through the ss-channel exchange of vector bosons, V0\mathcal{V}^0, including the neutral Standard Model (SM) gauge bosons, γ\gamma and ZZ, but also through the ss- and tt-channel exchanges of new neutral states, S0\mathcal{S}^0 and T0\mathcal{T}^0, and the uu-channel exchange of new doubly-charged states, U\mathcal{U}^{--}. The general set of (non-chiral) three-point couplings of the new particles and leptons allowed in a renormalizable quantum field theory is considered. The general spin and chirality analysis is based on the threshold behavior of the excitation curves for P+P\mathcal{P}^+\mathcal{P}^- pair production in e+ee^+e^- collisions with longitudinal and transverse polarized beams, the angular distributions in the production process and also the production-decay angular correlations. In the first step, we present the observables in the helicity formalism. Subsequently, we show how a set of observables can be designed for determining the spins and chiral structures of the new particles without any model assumptions. Finally, taking into account a typical set of approximately chiral invariant scenarios, we demonstrate how the spin and chirality effects can be probed experimentally at a high energy e+ee^+e^- collider.Comment: 50 pages, 14 figures, 6 tables, matches version published in EPJ

    Observation of an Exotic S=+1S=+1 Baryon in Exclusive Photoproduction from the Deuteron

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    In an exclusive measurement of the reaction γdK+Kpn\gamma d \to K^+ K^- p n, a narrow peak that can be attributed to an exotic baryon with strangeness S=+1S=+1 is seen in the K+nK^+n invariant mass spectrum. The peak is at 1.542±0.0051.542\pm 0.005 GeV/c2^2 with a measured width of 0.021 GeV/c2^2 FWHM, which is largely determined by experimental mass resolution. The statistical significance of the peak is 5.2±0.6σ5.2 \pm 0.6 \sigma. The mass and width of the observed peak are consistent with recent reports of a narrow S=+1S=+1 baryon by other experimental groups.Comment: 5 pages, 5 figure

    Measurement of Beam-Spin Asymmetries for Deep Inelastic π+\pi^+ Electroproduction

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    We report the first evidence for a non-zero beam-spin azimuthal asymmetry in the electroproduction of positive pions in the deep-inelastic region. Data have been obtained using a polarized electron beam of 4.3 GeV with the CLAS detector at the Thomas Jefferson National Accelerator Facility (JLab). The amplitude of the sinϕ\sin\phi modulation increases with the momentum of the pion relative to the virtual photon, zz, with an average amplitude of 0.038±0.005±0.0030.038 \pm 0.005 \pm 0.003 for 0.5<z<0.80.5 < z < 0.8 range.Comment: 5 pages, RevTEX4, 3 figures, 2 table

    Measurement of the Polarized Structure Function σLT\sigma_{LT^\prime} for p(e,ep)πop(\vec{e},e'p)\pi^o in the Δ(1232)\Delta(1232) Resonance Region

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    The polarized longitudinal-transverse structure function σLT\sigma_{LT^\prime} has been measured in the Δ(1232)\Delta(1232) resonance region at Q2=0.40Q^2=0.40 and 0.65 GeV2^2. Data for the p(e,ep)πop(\vec e,e'p)\pi^o reaction were taken at Jefferson Lab with the CEBAF Large Acceptance Spectrometer (CLAS) using longitudinally polarized electrons at an energy of 1.515 GeV. For the first time a complete angular distribution was measured, permitting the separation of different non-resonant amplitudes using a partial wave analysis. Comparison with previous beam asymmetry measurements at MAMI indicate a deviation from the predicted Q2Q^2 dependence of σLT\sigma_{LT^{\prime}} using recent phenomenological models.Comment: 5 pages, LaTex, 4 eps figures: to be published in PRC/Rapid Communications. Version 2 has revised Q^2 analysi

    First Measurement of Transferred Polarization in the Exclusive e p --> e' K+ Lambda Reaction

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    The first measurements of the transferred polarization for the exclusive ep --> e'K+ Lambda reaction have been performed in Hall B at the Thomas Jefferson National Accelerator Facility using the CLAS spectrometer. A 2.567 GeV electron beam was used to measure the hyperon polarization over a range of Q2 from 0.3 to 1.5 (GeV/c)2, W from 1.6 to 2.15 GeV, and over the full center-of-mass angular range of the K+ meson. Comparison with predictions of hadrodynamic models indicates strong sensitivity to the underlying resonance contributions. A non-relativistic quark model interpretation of our data suggests that the s-sbar quark pair is produced with spins predominantly anti-aligned. Implications for the validity of the widely used 3P0 quark-pair creation operator are discussed.Comment: 6 pages, 4 figure
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