1,045 research outputs found

    Intermediate behavior of Kerr tails

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    The numerical investigation of wave propagation in the asymptotic domain of Kerr spacetime has only recently been possible thanks to the construction of suitable hyperboloidal coordinates. The asymptotics revealed an apparent puzzle in the decay rates of scalar fields: the late-time rates seemed to depend on whether finite distance observers are in the strong field domain or far away from the rotating black hole, an apparent phenomenon dubbed "splitting". We discuss far-field "splitting" in the full field and near-horizon "splitting" in certain projected modes using horizon-penetrating, hyperboloidal coordinates. For either case we propose an explanation to the cause of the "splitting" behavior, and we determine uniquely decay rates that previous studies found to be ambiguous or immeasurable. The far-field "splitting" is explained by competition between projected modes. The near-horizon "splitting" is due to excitation of lower multipole modes that back excite the multipole mode for which "splitting" is observed. In both cases "splitting" is an intermediate effect, such that asymptotically in time strong field rates are valid at all finite distances. At any finite time, however, there are three domains with different decay rates whose boundaries move outwards during evolution. We then propose a formula for the decay rate of tails that takes into account the inter--mode excitation effect that we study.Comment: 16 page

    Eosinophil and T Cell Markers Predict Functional Decline in COPD Patients

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    BACKGROUND. The major marker utilized to monitor COPD patients is forced expiratory volume in one second (FEV1). However, asingle measurement of FEV1 cannot reliably predict subsequent decline. Recent studies indicate that T lymphocytes and eosinophils are important determinants of disease stability in COPD. We therefore measured cytokine levels in the lung lavage fluid and plasma of COPD patients in order to determine if the levels of T cell or eosinophil related cytokines were predictive of the future course of the disease. METHODS. Baseline lung lavage and plasma samples were collected from COPD subjects with moderately severe airway obstruction and emphysematous changes on chest CT. The study participants were former smokers who had not had a disease exacerbation within the past six months or used steroids within the past two months. Those subjects who demonstrated stable disease over the following six months (ΔFEV1 % predicted = 4.7 ± 7.2; N = 34) were retrospectively compared with study participants who experienced a rapid decline in lung function (ΔFEV1 % predicted = -16.0 ± 6.0; N = 16) during the same time period and with normal controls (N = 11). Plasma and lung lavage cytokines were measured from clinical samples using the Luminex multiplex kit which enabled the simultaneous measurement of several T cell and eosinophil related cytokines. RESULTS AND DISCUSSION. Stable COPD participants had significantly higher plasma IL-2 levels compared to participants with rapidly progressive COPD (p = 0.04). In contrast, plasma eotaxin-1 levels were significantly lower in stable COPD subjects compared to normal controls (p < 0.03). In addition, lung lavage eotaxin-1 levels were significantly higher in rapidly progressive COPD participants compared to both normal controls (p < 0.02) and stable COPD participants (p < 0.05). CONCLUSION. These findings indicate that IL-2 and eotaxin-1 levels may be important markers of disease stability in advanced emphysema patients. Prospective studies will need to confirm whether measuring IL-2 or eotaxin-1 can identify patients at risk for rapid disease progression.National Heart, Lung, and Blood Institute (NO1-HR-96140, NO1-HR-96141-001, NO1-HR-96144, NO1-HR-96143; NO1-HR-96145; NO1-HR-96142, R01HL086936-03); The Flight Attendant Medical Research Institute; the Jo-Ann F. LeBuhn Center for Chest Diseas

    The Levellers, political literacy and contemporary citizenship education in England

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    This paper analyses the concept of political literacy (as introduced in the 1998 Crick Report) in relation to Citizenship in the English National Curriculum. It argues that political literacy has not been sufficiently emphasised or facilitated within this foundation subject and that the concept is particularly important for students at a time of considerable political and social conflict in England (and elsewhere). The authors state that engagement with the ideas and practices of the Levellers (a political group writing and agitating at the time of the Civil Wars) could enable students and teachers to explore political literacy (especially the implications of social media) by looking at a political group who utilised mass pamphlettering as a form of political communication. The paper will also investigate the context of Citizenship within the English National Curriculum and some of the philosophical concerns around Citizenship education. It contains a section placing the Levellers in their contemporary and historiographical contexts

    The validation analysis of the INSHORE system: a precise and efficient coastal survey system

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    Government and environmental entities are becoming increasingly concerned with qualifying and quantifying the erosion effects that are observed in sandy shores. Correspondingly, survey methodologies that gather data for such erosion studies are increasingly being demanded. The responsible entities are continually broadening their areas of interest, are concerned in the establishment of regular monitoring programmes and are demanding high accuracy from the geo-spatial data that is collected. The budget available for such monitoring activities, however, does not parallel the trend in the increasing demand for quality specifications. Survey methodologies need improvement to meet these requirements. We have developed a new land-based survey system-the INSHORE system-that is ideal for low cost, highly efficient and highly precise coastal surveys. The INSHORE system uses hi-tech hardware that is based on high-grade global positioning system (GPS) receivers and a laser distance sensor combined with advanced software algorithms. This system enables the determination of the ground coordinates of the surveyed areas with a precision of 1 to 2 cm, without having a sensor in contact with the ground surface. The absence of physical contact with the ground makes this system suitable for high-efficiency surveys. The accuracy of the positioning, which is based on advanced differential GPS processing, is enhanced by considering the estimated attitude of the GPS receiver holding structure and eliminates undesirable offsets. This paper describes the INSHORE survey system and presents the results of validation tests that were performed in a sandy shore environment

    Involvement of Noradrenergic Neurotransmission in the Stress- but not Cocaine-Induced Reinstatement of Extinguished Cocaine-Induced Conditioned Place Preference in Mice: Role for β-2 Adrenergic Receptors

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    The responsiveness of central noradrenergic systems to stressors and cocaine poses norepinephrine as a potential common mechanism through which drug re-exposure and stressful stimuli promote relapse. This study investigated the role of noradrenergic systems in the reinstatement of extinguished cocaine-induced conditioned place preference by cocaine and stress in male C57BL/6 mice. Cocaine- (15 mg/kg, i.p.) induced conditioned place preference was extinguished by repeated exposure to the apparatus in the absence of drug and reestablished by a cocaine challenge (15 mg/kg), exposure to a stressor (6-min forced swim (FS); 20–25°C water), or administration of the α-2 adrenergic receptor (AR) antagonists yohimbine (2 mg/kg, i.p.) or BRL44408 (5, 10 mg/kg, i.p.). To investigate the role of ARs, mice were administered the nonselective β-AR antagonist, propranolol (5, 10 mg/kg, i.p.), the α-1 AR antagonist, prazosin (1, 2 mg/kg, i.p.), or the α-2 AR agonist, clonidine (0.03, 0.3 mg/kg, i.p.) before reinstatement testing. Clonidine, prazosin, and propranolol failed to block cocaine-induced reinstatement. The low (0.03 mg/kg) but not high (0.3 mg/kg) clonidine dose fully blocked FS-induced reinstatement but not reinstatement by yohimbine. Propranolol, but not prazosin, blocked reinstatement by both yohimbine and FS, suggesting the involvement of β-ARs. The β-2 AR antagonist ICI-118551 (1 mg/kg, i.p.), but not the β-1 AR antagonist betaxolol (10 mg/kg, i.p.), also blocked FS-induced reinstatement. These findings suggest that stress-induced reinstatement requires noradrenergic signaling through β-2 ARs and that cocaine-induced reinstatement does not require AR activation, even though stimulation of central noradrenergic neurotransmission is sufficient to reinstate

    The National Lung Matrix Trial of personalized therapy in lung cancer

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    The majority of targeted therapies for non-small-cell lung cancer (NSCLC) are directed against oncogenic drivers that are more prevalent in patients with light exposure to tobacco smoke1,2,3. As this group represents around 20% of all patients with lung cancer, the discovery of stratified medicine options for tobacco-associated NSCLC is a high priority. Umbrella trials seek to streamline the investigation of genotype-based treatments by screening tumours for multiple genomic alterations and triaging patients to one of several genotype-matched therapeutic agents. Here we report the current outcomes of 19 drug–biomarker cohorts from the ongoing National Lung Matrix Trial, the largest umbrella trial in NSCLC. We use next-generation sequencing to match patients to appropriate targeted therapies on the basis of their tumour genotype. The Bayesian trial design enables outcome data from open cohorts that are still recruiting to be reported alongside data from closed cohorts. Of the 5,467 patients that were screened, 2,007 were molecularly eligible for entry into the trial, and 302 entered the trial to receive genotype-matched therapy—including 14 that re-registered to the trial for a sequential trial drug. Despite pre-clinical data supporting the drug–biomarker combinations, current evidence shows that a limited number of combinations demonstrate clinically relevant benefits, which remain concentrated in patients with lung cancers that are associated with minimal exposure to tobacco smoke

    Inflammation in sputum relates to progression of disease in subjects with COPD: a prospective descriptive study

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    BACKGROUND: Inflammation is considered to be of primary pathogenic importance in COPD but the evidence on which current understanding is based does not distinguish between cause and effect, and no single mechanism can account for the complex pathology. We performed a prospective longitudinal study of subjects with COPD that related markers of sputum inflammation at baseline to subsequent disease progression. METHODS: A cohort of 56 patients with chronic bronchitis was characterized in the stable state at baseline and after an interval of four years, using physiological measures and CT densitometry. Sputum markers of airway inflammation were quantified at baseline from spontaneously produced sputum in a sub-group (n = 38), and inflammation severity was related to subsequent disease progression. RESULTS: Physiological and CT measures indicated disease progression in the whole group. In the sub-group, sputum myeloperoxidase correlated with decline in FEV(1 )(rs = -0.344, p = 0.019, n = 37). LTB4 and albumin leakage correlated with TLCO decline (rs = -0.310, p = 0.033, rs = -0.401, p = 0.008, respectively, n = 35) and IL-8 correlated with progression of lung densitometric indices (rs = -0.464, p = 0.005, n = 38). CONCLUSION: The data support a principal causative role for neutrophilic inflammation in the pathogenesis of COPD and suggest that the measurement of sputum inflammatory markers may have a predictive role in clinical practice

    Earthquake source parameters and scaling relationships in Hungary (central Pannonian basin)

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    Abstract Fifty earthquakes that occurred in Hungary (central part of the Pannonian basin) with local magnitude ML ranging from 0.8 to 4.5 have been analyzed. The digital seismograms used in this study were recorded by six permanent broad-band stations and twenty short-period ones at hypocentral distances between 10 and 327 km. The displacement spectra for P- and SH-waves were analyzed according to Brune’s source model. Observed spectra were corrected for path-dependent attenuation effects using an independent regional estimate of the quality factor QS. To correct spectra for near-surface attenuation, the k parameterwas calculated, obtaining it fromwaveforms recorded at short epicentral distances. The values of the k parameter vary between 0.01 to 0.06 s with a mean of 0.03 s for P-waves and between 0.01 to 0.09 s with a mean of 0.04 s for SH-waves. After correction for attenuation effects, spectral parameters (corner frequency and low-frequency spectral level) were estimated by a grid search algorithm. The obtained seismic moments range from4.21×1011 to 3.41×1015 Nm (1.7≤Mw ≤4.3). The source radii are between 125 and 1343 m. Stress drop values vary between 0.14 and 32.4 bars with a logarithmic mean of 2.59 bars (1 bar = 105 Pa). From the results, a linear relationship between local andmomentmagnitudes has been established. The obtained scaling relations show slight evidence of self-similarity violation. However, due to the high scatter of our data, the existence of self-similarity cannot be excluded

    FDG PET/CT in carcinoma of unknown primary

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    Carcinoma of unknown primary (CUP) is a heterogeneous group of metastatic malignancies in which a primary tumor could not be detected despite thorough diagnostic evaluation. Because of its high sensitivity for the detection of lesions, combined 18F-fluoro-2-deoxyglucose positron emission tomography (FDG PET)/computed tomography (CT) may be an excellent alternative to CT alone and conventional magnetic resonance imaging in detecting the unknown primary tumor. This article will review the use, diagnostic performance, and utility of FDG PET/CT in CUP and will discuss challenges and future considerations in the diagnostic management of CUP
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