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INTRODUCTION: Primary blast lung injury causes intrapulmonary haemorrhage. A number of case reports have suggested the efficacy of recombinant activated factor VII (rFVIIa) in the treatment of diffuse alveolar haemorrhage from a range of medical causes, but its efficacy in blast lung is unknown. The aim of this study was to investigate whether nebulised rFVIIa attenuates the haemorrhagic effects of blast lung injury in an animal model. METHODS: Terminally anaesthetised rabbits subjected to blast lung injury were randomised to receive either rFVIIa or placebo via a nebuliser. The primary outcome was the level of blood iron-transferrin complex, a marker of the extent of blast lung injury, analysed using low temperature electron paramagnetic resonance spectroscopy. RESULTS: Blast exposure led to a significant fall in iron-bound transferrin in both groups of animals (p<0.001), which remained depressed during the study. There were no significant differences in iron-transferrin between the rFVIIa and placebo treatment groups over the duration of the study (p=0.081), and there was no trend towards elevated iron-transferrin in the rFVIIa-treated group once drug treatment had started. There was suggestive evidence of systemic absorption of rFVIIa given via the inhaled route. CONCLUSION: A single dose of nebulised rFVIIa did not attenuate pulmonary haemorrhage in a rabbit model of blast lung injury. As there was some evidence of systemic absorption, the inhaled route does not avoid the concern about potential thromboembolic complications from administration of rFVIIa.
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Traumatismos por Explosión/complicaciones , Factor VIIa , Hemorragia , Lesión Pulmonar/complicaciones , Administración por Inhalación , Animales , Modelos Animales de Enfermedad , Factor VIIa/administración & dosificación , Factor VIIa/uso terapéutico , Femenino , Hemorragia/tratamiento farmacológico , Hemorragia/etiología , Hemorragia/prevención & control , Nebulizadores y Vaporizadores , Conejos , Distribución Aleatoria , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéuticoRESUMEN
Millimeter-wave imaging diagnostics, with large poloidal span and wide radial range, have been developed on the EAST tokamak for visualization of 2D electron temperature and density fluctuations. A 384 channel (24 poloidal × 16 radial) Electron Cyclotron Emission Imaging (ECEI) system in F-band (90-140 GHz) was installed on the EAST tokamak in 2012 to provide 2D electron temperature fluctuation images with high spatial and temporal resolution. A co-located Microwave Imaging Reflectometry (MIR) will be installed for imaging of density fluctuations by December 2016. This "4th generation" MIR system has eight independent frequency illumination beams in W-band (75-110 GHz) driven by fast tuning synthesizers and active multipliers. Both of these advanced millimeter-wave imaging diagnostic systems have applied the latest techniques. A novel design philosophy "general optics structure" has been employed for the design of the ECEI and MIR receiver optics with large aperture. The extended radial and poloidal coverage of ECEI on EAST is made possible by innovations in the design of front-end optics. The front-end optical structures of the two imaging diagnostics, ECEI and MIR, have been integrated into a compact system, including the ECEI receiver and MIR transmitter and receiver. Two imaging systems share the same mid-plane port for simultaneous, co-located 2D fluctuation measurements of electron density and temperature. An intelligent remote-control is utilized in the MIR electronics systems to maintain focusing at the desired radial region even with density variations by remotely tuning the probe frequencies in about 200 µs. A similar intelligent technique has also been applied on the ECEI IF system, with remote configuration of the attenuations for each channel.
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A 2D microwave imaging reflectometer system has been developed to visualize electron density fluctuations on the DIII-D tokamak. Simultaneously illuminated at four probe frequencies, large aperture optics image reflections from four density-dependent cutoff surfaces in the plasma over an extended region of the DIII-D plasma. Localized density fluctuations in the vicinity of the plasma cutoff surfaces modulate the plasma reflections, yielding a 2D image of electron density fluctuations. Details are presented of the receiver down conversion electronics that generate the in-phase (I) and quadrature (Q) reflectometer signals from which 2D density fluctuation data are obtained. Also presented are details on the control system and backplane used to manage the electronics as well as an introduction to the computer based control program.
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The two-dimensional mm-wave imaging reflectometer (MIR) on DIII-D is a multi-faceted device for diagnosing electron density fluctuations in fusion plasmas. Its multi-channel, multi-frequency capabilities and high sensitivity permit visualization and quantitative diagnosis of density perturbations, including correlation length, wavenumber, mode propagation velocity, and dispersion. The two-dimensional capabilities of MIR are made possible with 12 vertically separated sightlines and four-frequency operation (corresponding to four radial channels). The 48-channel DIII-D MIR system has a tunable source that can be stepped in 500 µs increments over a range of 56 to 74 GHz. An innovative optical design keeps both on-axis and off-axis channels focused at the cutoff surface, permitting imaging over an extended poloidal region. The integrity of the MIR optical design is confirmed by comparing Gaussian beam calculations to laboratory measurements of the transmitter beam pattern and receiver antenna patterns. Measurements are presented during the density ramp of a plasma discharge to demonstrate unfocused and focused MIR signals.
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A 2D electron cyclotron emission imaging (ECEI) system has been developed for measurement of electron temperature fluctuations in the HL-2A tokamak. It is comprised of a front-end 24 channel heterodyne imaging array with a tunable RF range spanning 75-110 GHz, and a set of back-end ECEI electronics that together generate 24 × 8 = 192 channel images of the 2nd harmonic X-mode electron cyclotron emission from the HL-2A plasma. The simulated performance of the local oscillator (LO) optics and radio frequency (RF) optics is presented, together with the laboratory characterization results. The Gaussian beams from the LO optics are observed to properly cover the entire detector array. The ECE signals from the plasma are mixed with the LO signal in the array box, then delivered to the electronics system by low-loss microwave cables, and finally to the digitizers. The ECEI system can achieve temporal resolutions of ~µs, and spatial resolutions of 1 cm (radially) and 2 cm (poloidally).
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A new TEXTOR electron cyclotron emission imaging system has been developed and employed, providing a diagnostic with new features and enhanced capabilities when compared to the legacy system it replaces. Optical coupling to the plasma has been completely redesigned, making use of new minilens arrays for reduced optical aberration and providing the new feature of vertical zoom, whereby the vertical coverage is now remotely adjustable on a shot-by-shot basis from 20-35 cm. Other innovations, such as the implementation of stacked quasioptical planar notch filters, allow for the diagnostic to be operated without interruption or degradation in performance during electron cyclotron resonance heating. Successful commissioning of the new diagnostic and a demonstration of the improved capabilities are presented in this paper, along with a discussion of the new technologies employed.
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Natural killer (NK) cell activity is impaired in iron-deficient rats. Natural killer cells destroy tumor cells; therefore, iron-deficient rats may be less able to combat cancer growth. Natural killer cell cytotoxicity, both basal and interferon gamma (IFN gamma)-stimulated, was studied in moderately and severely iron-deficient rats challenged with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Female weanling rats were fed ad libitum semipurified diets containing 8, 13 or 42 mg Fe/kg. A pair-fed group was fed the 42 mg Fe/kg diet at the level consumed by the 8 mg Fe/kg group. Following 6 wk of dietary treatment, DMBA-treated rats received a single intragastric dose of DMBA. Dietary treatment was continued. Rats were killed at 1, 4, 8, 14 and 20 wk post-DMBA treatment. Natural killer cell cytotoxicity (both basal and IFN gamma-stimulated) was analyzed. Feeding the 13 mg Fe/kg diet resulted in lower NK cell activity (P = 0.006) and greater tumor burden (P = 0.045) and tumor incidence. Interferon gamma treatment relieved the lower NK cell cytotoxicity observed in moderate iron deficiency. Feeding the 8 mg Fe/kg diet impaired NK cell activity (P = 0.006), but tumor burden and incidence were less than in moderate iron deficiency. In this model, iron deficiency, particularly moderate iron deficiency, contributed to cancer development and compromised NK cell cytotoxicity.
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9,10-Dimetil-1,2-benzantraceno/toxicidad , Deficiencias de Hierro , Células Asesinas Naturales/inmunología , Neoplasias Mamarias Experimentales/inmunología , Animales , Peso Corporal , Femenino , Hierro/administración & dosificación , Hierro/metabolismo , Hígado/metabolismo , Neoplasias Mamarias Experimentales/inducido químicamente , Ratas , Ratas Endogámicas , Bazo/inmunologíaRESUMEN
Pediatric methadone intoxication may present with clinically unusual findings which could cause confusion to the inexperienced practitioner. We present a case of pediatric methadone overdose, address clinical nuances pertinent to these overdoses, and discuss measures aimed at limiting these potentially catastrophic exposures.