1,029 research outputs found

    Tumor necrosis factor enhances the capsaicin sensitivity of rat sensory neurons

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    The capacity of the proinflammatory cytokines, tumor necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta), to modulate the sensitivity of isolated sensory neurons grown in culture to the excitatory chemical agent capsaicin was examined. Alterations in capsaicin sensitivity were assessed by quantifying the number of neurons labeled with cobalt after exposure to capsaicin and by recording the whole-cell response from a single neuron to the focal application of capsaicin. A 24 hr pretreatment of the neuronal cultures with TNF alpha (10 or 50 ng/ml), but not IL-1 beta (10 or 50 ng/ml), produced a concentration-dependent increase in the number of cobalt-labeled neurons after exposure to 100 nM capsaicin. The peak increase in the number of labeled neurons was attained after a 4 hr treatment with 10 ng/ml TNF alpha. Similarly, pretreatment with TNF alpha (10 ng/ml for 4, 12, and 24 hr) produced a greater than twofold increase in the average peak amplitude of the inward current evoked by 100 nM capsaicin. Both the TNF alpha-induced increase in labeling and current amplitude were blocked by treating the neuronal cultures with indomethacin before the addition of TNF alpha. Enhancement of the capsaicin-evoked current also was blocked by the specific cyclo-oxygenase-2 inhibitor SC-236. These results indicate that TNF alpha can enhance the sensitivity of sensory neurons to the excitation produced by capsaicin and that this enhancement likely is mediated by the neuronal production of prostaglandins. Isolated sensory neurons grown in culture may prove to be a useful model system in which to explore how prolonged exposure to mediators associated with chronic inflammation alter the regulatory pathways that modulate the excitability of the nervous system

    Complementary role of cardiac CT in the assessment of aortic valve replacement dysfunction

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    Aortic valve replacement is the second most common cardiothoracic procedure in the UK. With an ageing population, there are an increasing number of patients with prosthetic valves that require follow-up. Imaging of prosthetic valves is challenging with conventional echocardiographic techniques making early detection of valve dysfunction or complications difficult. CT has recently emerged as a complementary approach offering excellent spatial resolution and the ability to identify a range of aortic valve replacement complications including structural valve dysfunction, thrombus development, pannus formation and prosthetic valve infective endocarditis. This review discusses each and how CT might be incorporated into a multimodal cardiovascular imaging pathway for the assessment of aortic valve replacements and in guiding clinical management

    Precision scans of the pixel cell response of double sided 3D pixel detectors to pion and x-ray beams

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    hree-dimensional (3D) silicon sensors offer potential advantages over standard planar sensors for radiation hardness in future high energy physics experiments and reduced charge-sharing for X-ray applications, but may introduce inefficiencies due to the columnar electrodes. These inefficiencies are probed by studying variations in response across a unit pixel cell in a 55μm pitch double-sided 3D pixel sensor bump bonded to TimePix and Medipix2 readout ASICs. Two complementary characterisation techniques are discussed: the first uses a custom built telescope and a 120GeV pion beam from the Super Proton Synchrotron (SPS) at CERN; the second employs a novel technique to illuminate the sensor with a micro-focused synchrotron X-ray beam at the Diamond Light Source, UK. For a pion beam incident perpendicular to the sensor plane an overall pixel efficiency of 93.0±0.5% is measured. After a 10o rotation of the device the effect of the columnar region becomes negligible and the overall efficiency rises to 99.8±0.5%. The double-sided 3D sensor shows significantly reduced charge sharing to neighbouring pixels compared to the planar device. The charge sharing results obtained from the X-ray beam study of the 3D sensor are shown to agree with a simple simulation in which charge diffusion is neglected. The devices tested are found to be compatible with having a region in which no charge is collected centred on the electrode columns and of radius 7.6±0.6μm. Charge collection above and below the columnar electrodes in the double-sided 3D sensor is observed

    Constant photocurrent method to probe the sub-bandgap absorption in wide bandgap semiconductor films : the case of α-Ga2O3

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    The optical absorption coefficient is one of the fundamental properties of semiconductors and is critical to the development of optical devices. Herein, a revival of the constant photocurrent method is presented to measure sub-bandgap absorption in wide bandgap semiconductor films. The method involves maintaining a constant photocurrent by continually adjusting the impinging photon flux across the energy spectrum. Under such conditions, the reciprocal of the photon flux for uniformly absorbed light is proportional to the absorption coefficient. This method is applied to α-Ga 2O 3 and reveals that it can access the absorption coefficient from 1 × 10 5 cm −1 at the band edge (5.3 eV) to 0.8 cm −1 close to mid-bandgap (2.7 eV). Changes in the steepness of the absorption curve in the sub-bandgap region are in excellent agreement with defect states of α-Ga 2O 3 reported by deep level transient spectroscopy, indicating that the technique shows promise as a probe of energetically distributed defect states in thin film wide bandgap semiconductors

    Deep-Learning for Epicardial Adipose Tissue Assessment with Computed Tomography: Implications for Cardiovascular Risk Prediction

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    Background: Epicardial adipose tissue (EAT) volume is a marker of visceral obesity that can be measured in coronary computed tomography angiograms (CCTA). The clinical value of integrating this measurement in routine CCTA interpretation has not been documented./ Objectives: This study sought to develop a deep-learning network for automated quantification of EAT volume from CCTA, test it in patients who are technically challenging, and validate its prognostic value in routine clinical care./ Methods: The deep-learning network was trained and validated to autosegment EAT volume in 3,720 CCTA scans from the ORFAN (Oxford Risk Factors and Noninvasive Imaging Study) cohort. The model was tested in patients with challenging anatomy and scan artifacts and applied to a longitudinal cohort of 253 patients post-cardiac surgery and 1,558 patients from the SCOT-HEART (Scottish Computed Tomography of the Heart) Trial, to investigate its prognostic value./ Results: External validation of the deep-learning network yielded a concordance correlation coefficient of 0.970 for machine vs human. EAT volume was associated with coronary artery disease (odds ratio [OR] per SD increase in EAT volume: 1.13 [95% CI: 1.04-1.30]; P = 0.01), and atrial fibrillation (OR: 1.25 [95% CI:1.08-1.40]; P = 0.03), after correction for risk factors (including body mass index). EAT volume predicted all-cause mortality (HR per SD: 1.28 [95% CI: 1.10-1.37]; P = 0.02), myocardial infarction (HR: 1.26 [95% CI:1.09-1.38]; P = 0.001), and stroke (HR: 1.20 [95% CI: 1.09-1.38]; P = 0.02) independently of risk factors in SCOT-HEART (5-year follow-up). It also predicted in-hospital (HR: 2.67 [95% CI: 1.26-3.73]; P ≤ 0.01) and long-term post–cardiac surgery atrial fibrillation (7-year follow-up; HR: 2.14 [95% CI: 1.19-2.97]; P ≤ 0.01). Conclusions: Automated assessment of EAT volume is possible in CCTA, including in patients who are technically challenging; it forms a powerful marker of metabolically unhealthy visceral obesity, which could be used for cardiovascular risk stratification

    Impact of Xpert MTB/RIF for TB diagnosis in a primary care clinic with high TB and HIV prevalence in South Africa: a pragmatic randomised trial

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    Background: Xpert MTB/RIF is approved for use in tuberculosis (TB) and rifampicin-resistance diagnosis. However, data are limited on the impact of Xpert under routine conditions in settings with high TB burden. Methods and Findings: A pragmatic prospective cluster-randomised trial of Xpert for all individuals with presumptive (symptomatic) TB compared to the routine diagnostic algorithm of sputum microscopy and limited use of culture was conducted in a large TB/HIV primary care clinic. The primary outcome was the proportion of bacteriologically confirmed TB cases not initiating TB treatment by 3 mo after presentation. Secondary outcomes included time to TB treatment and mortality. Unblinded randomisation occurred on a weekly basis. Xpert and smear microscopy were performed on site. Analysis was both by intention to treat (ITT) and per protocol. Between 7 September 2010 and 28 October 2011, 1,985 participants were assigned to the Xpert (n = 982) and routine (n = 1,003) diagnostic algorithms (ITT analysis); 882 received Xpert and 1,063 routine (per protocol analysis). 13% (32/257) of individuals with bacteriologically confirmed TB (smear, culture, or Xpert) did not initiate treatment by 3 mo after presentation in the Xpert arm, compared to 25% (41/167) in the routine arm (ITT analysis, risk ratio 0.51, 95% CI 0.33–0.77, p = 0.0052). The yield of bacteriologically confirmed TB cases among patients with presumptive TB was 17% (167/1,003) with routine diagnosis and 26% (257/982) with Xpert diagnosis (ITT analysis, risk ratio 1.57, 95% CI 1.32–1.87, p<0.001). This difference in diagnosis rates resulted in a higher rate of treatment initiation in the Xpert arm: 23% (229/1,003) and 28% (277/982) in the routine and Xpert arms, respectively (ITT analysis, risk ratio 1.24, 95% CI 1.06–1.44, p = 0.013). Time to treatment initiation was improved overall (ITT analysis, hazard ratio 0.76, 95% CI 0.63–0.92, p = 0.005) and among HIV-infected participants (ITT analysis, hazard ratio 0.67, 95% CI 0.53–0.85, p = 0.001). There was no difference in 6-mo mortality with Xpert versus routine diagnosis. Study limitations included incorrect intervention allocation for a high proportion of participants and that the study was conducted in a single clinic. Conclusions: These data suggest that in this routine primary care setting, use of Xpert to diagnose TB increased the number of individuals with bacteriologically confirmed TB who were treated by 3 mo and reduced time to treatment initiation, particularly among HIV-infected participants
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