1,770 research outputs found
An XMM-Newton observation of the extreme Narrow Line Seyfert 1 Galaxy, Mrk 359
We present XMM-Newton observations of Mrk 359, the first Narrow Line Seyfert
1 galaxy discovered. Even among NLS1s, Mrk 359 is an extreme case with
extraordinarily narrow optical emission lines. The XMM-Newton data show that
Mrk 359 has a significant soft X-ray excess which displays only weak absorption
and emission features. The (2-10) keV continuum, including reflection, is
flatter than the typical NLS1, with Gamma approximately 1.84. A strong emission
line of equivalent width approximately 200 eV is also observed, centred near
6.4 keV. We fit this emission with two line components of approximately equal
strength: a broad iron-line from an accretion disc and a narrow, unresolved
core. The unresolved line core has an equivalent width of approximately 120 eV
and is consistent with fluorescence from neutral iron in distant reprocessing
gas, possibly in the form of a `molecular torus'. Comparison of the narrow-line
strengths in Mrk 359 and other low-moderate luminosity Seyfert 1 galaxies with
those in QSOs suggests that the solid angle subtended by the distant
reprocessing gas decreases with increasing AGN luminosity.Comment: Accepted for publication in MNRA
Isolated human pulmonary artery structure and function pre‐ and post‐cardiopulmonary bypass surgery
Background: Pulmonary dysfunction is a known complication after cardiac surgery using cardiopulmonary bypass, ranging from subclinical functional changes to prolonged postoperative ventilation, acute lung injury, and acute respiratory distress syndrome. Whether human pulmonary arterial function is compromised is unknown. The aim of the present study was to compare the structure and function of isolated and cannulated human pulmonary arteries obtained from lung biopsies after the chest was opened (pre–cardiopulmonary bypass) to those obtained at the end of cardiopulmonary bypass (post–cardiopulmonary bypass) from patients undergoing coronary artery bypass graft surgery.
Methods and Results: Pre‐ and post–cardiopulmonary bypass lung biopsies were received from 12 patients undergoing elective surgery. Intralobular small arteries were dissected, cannulated, pressurized, and imaged using confocal microscopy. Functionally, the thromboxane mimetic U46619 produced concentration‐dependent vasoconstriction in 100% and 75% of pre‐ and post–cardiopulmonary bypass arteries, respectively. The endothelium‐dependent agonist bradykinin stimulated vasodilation in 45% and 33% of arteries pre‐ and post–cardiopulmonary bypass, respectively. Structurally, in most arteries smooth muscle cells aligned circumferentially; live cell viability revealed that although 100% of smooth muscle and 90% of endothelial cells from pre–cardiopulmonary bypass biopsies had intact membranes and were considered viable, only 60% and 58%, respectively, were viable from post–cardiopulmonary bypass biopsies.
Conclusions: We successfully investigated isolated pulmonary artery structure and function in fresh lung biopsies from patients undergoing heart surgery. Pulmonary artery contractile tone and endothelium‐dependent dilation were significantly reduced in post–cardiopulmonary bypass biopsies. The decreased functional responses were associated with reduced cell viability.
Clinical Trial Registration: URL: http://www.isrctn.com/ISRCTN34428459. Unique identifier: ISRCTN 34428459.</p
The signalling channel of Central Bank interventions:modelling the Yen/US dollar exchange rate
This paper presents a theoretical framework analysing the signalling channel of exchange rate interventions as an informational trigger. We develop an implicit target zone framework with learning in order to model the signalling channel. The theoretical premise of the model is that interventions convey signals that communicate information about the exchange rate objectives of the central bank. The model is used to analyse the impact of Japanese FX interventions during the period 1999--2011 on the yen/US dollar dynamics
X-ray Absorption and Reflection in Active Galactic Nuclei
X-ray spectroscopy offers an opportunity to study the complex mixture of
emitting and absorbing components in the circumnuclear regions of active
galactic nuclei, and to learn about the accretion process that fuels AGN and
the feedback of material to their host galaxies. We describe the spectral
signatures that may be studied and review the X-ray spectra and spectral
variability of active galaxies, concentrating on progress from recent Chandra,
XMM-Newton and Suzaku data for local type 1 AGN. We describe the evidence for
absorption covering a wide range of column densities, ionization and dynamics,
and discuss the growing evidence for partial-covering absorption from data at
energies > 10 keV. Such absorption can also explain the observed X-ray spectral
curvature and variability in AGN at lower energies and is likely an important
factor in shaping the observed properties of this class of source.
Consideration of self-consistent models for local AGN indicates that X-ray
spectra likely comprise a combination of absorption and reflection effects from
material originating within a few light days of the black hole as well as on
larger scales. It is likely that AGN X-ray spectra may be strongly affected by
the presence of disk-wind outflows that are expected in systems with high
accretion rates, and we describe models that attempt to predict the effects of
radiative transfer through such winds, and discuss the prospects for new data
to test and address these ideas.Comment: Accepted for publication in the Astronomy and Astrophysics Review. 58
pages, 9 figures. V2 has fixed an error in footnote
Wind from the black-hole accretion disk driving a molecular outflow in an active galaxy
Powerful winds driven by active galactic nuclei (AGN) are often invoked to
play a fundamental role in the evolution of both supermassive black holes
(SMBHs) and their host galaxies, quenching star formation and explaining the
tight SMBH-galaxy relations. Recent observations of large-scale molecular
outflows in ultra-luminous infrared galaxies (ULIRGs) have provided the
evidence to support these studies, as they directly trace the gas out of which
stars form. Theoretical models suggest an origin of these outflows as
energy-conserving flows driven by fast AGN accretion disk winds. Previous
claims of a connection between large-scale molecular outflows and AGN activity
in ULIRGs were incomplete because they were lacking the detection of the
putative inner wind. Conversely, studies of powerful AGN accretion disk winds
to date have focused only on X-ray observations of local Seyferts and a few
higher redshift quasars. Here we show the clear detection of a powerful AGN
accretion disk wind with a mildly relativistic velocity of 0.25c in the X-ray
spectrum of IRAS F11119+3257, a nearby (z = 0.189) optically classified type 1
ULIRG hosting a powerful molecular outflow. The AGN is responsible for ~80% of
the emission, with a quasar-like luminosity of L_AGN = 1.5x10^46 erg/s. The
energetics of these winds are consistent with the energy-conserving mechanism,
which is the basis of the quasar mode feedback in AGN lacking powerful radio
jets.Comment: Revised file including the letter, methods and supplementary
information. Published in the March 26th 2015 issue of Natur
Copper Chaperone for Cu/Zn Superoxide Dismutase is a sensitive biomarker of mild copper deficiency induced by moderately high intakes of zinc
BACKGROUND: Small increases in zinc (Zn) consumption above recommended amounts have been shown to reduce copper (Cu) status in experimental animals and humans. Recently, we have reported that copper chaperone for Cu/Zn superoxide dismutase (CCS) protein level is increased in tissues of overtly Cu-deficient rats and proposed CCS as a novel biomarker of Cu status. METHODS: Weanling male Wistar rats were fed one of four diets normal in Cu and containing normal (30 mg Zn/kg diet) or moderately high (60, 120 or 240 mg Zn/kg diet) amounts of Zn for 5 weeks. To begin to examine the clinical relevance of CCS, we compared the sensitivity of CCS to mild Cu deficiency, induced by moderately high intakes of Zn, with conventional indices of Cu status. RESULTS: Liver and erythrocyte CCS expression was significantly (P < 0.05) increased in rats fed the Zn-60 and/or Zn-120 diet compared to rats fed normal levels of Zn (Zn-30). Erythrocyte CCS expression was the most sensitive measure of reduced Cu status and was able to detect a decrease in Cu nutriture in rats fed only twice the recommended amount of Zn. Liver, erythrocyte and white blood cell CCS expression showed a significant (P < 0.05) inverse correlation with plasma and liver Cu concentrations and caeruloplasmin activity. Unexpectedly, rats fed the highest level of Zn (Zn-240) showed overall better Cu status than rats fed a lower level of elevated Zn (Zn-120). Improved Cu status in these rats correlated with increased duodenal mRNA expression of several Zn-trafficking proteins (i.e. MT-1, ZnT-1, ZnT-2 and ZnT-4). CONCLUSION: Collectively, these data show that CCS is a sensitive measure of Zn-induced mild Cu deficiency and demonstrate a dose-dependent biphasic response for reduced Cu status by moderately high intakes of Zn
Perspectives of ammunition users on the use of lead ammunition and its potential impacts on wildlife and humans
This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement:
All data supporting the results in this paper are available from Zenodo (digital repository): https://zenodo.org/record/2653514#.XMbMXKbsZD8 (Newth et al., 2019).1. Recent national and international policy initiatives have aimed to reduce the exposure of humans and wildlife to lead from ammunition. Despite restrictions, in the
UK, lead ammunition remains the most widespread source of environmental lead
contamination to which wildlife may be exposed.
2. The risks arising from the use of lead ammunition and the measures taken to
mitigate these have prompted intense and sometimes acrimonious discussion between stakeholder groups, including those advancing the interests of shooting,
wildlife conservation, public health and animal welfare.
3. However, relatively little is known of the perspectives of individual ammunition
users, despite their role in adding lead to the environment and their pivotal place
in any potential changes to practice. Using Q‐methodology, we identified the perspectives of ammunition users in the UK on lead ammunition in an effort to bring
forward evidence from these key stakeholders.
4. Views were characterised by two statistically and qualitatively distinct perspectives: (a) Open to change—comprised ammunition users that refuted the view that
lead ammunition is not a major source of poisoning in wild birds, believed that
solutions to reduce the risks of poisoning are needed, were happy to use non‐lead
alternatives and did not feel that the phasing out of lead shot would lead to the
demise of shooting; and (b) Status quo—comprised ammunition users who did not
regard lead poisoning as a major welfare problem for wild birds, were ambivalent
about the need for solutions and felt that lead shot is better than steel at killing
and not wounding an animal. They believed opposition to lead ammunition was
driven more by a dislike of shooting than evidence of any harm.
5. Adherents to both perspectives agreed that lead is a toxic substance. There was
consensus that involvement of stakeholders from all sides of the debate was desirable and that to be taken seriously by shooters, information about lead poisoning
should come from the shooting community
Cost effectiveness of recombinant factor VIIa for treatment of intracerebral hemorrhage
<p>Abstract</p> <p>Background</p> <p>Phase I/II placebo-controlled clinical trials of recombinant Factor VIIa (rFVIIa) suggested that administration of rFVIIa within 4 hours after onset of intracerebral hemorrhage (ICH) is safe, limits ICH growth, and improves outcomes. We sought to determine the cost-effectiveness of rFVIIa for acute ICH treatment, using published Phase II data. We hypothesized that rFVIIa would have a low marginal cost-effectiveness ratio (mCER) given the poor neurologic outcomes after ICH with conventional management.</p> <p>Methods</p> <p>We performed an incremental cost-effectiveness analysis from the societal perspective, considering conventional management vs. 80 ug/kg rFVIIa treatment for acute ICH cases meeting Phase II inclusion criteria. The time frame for the analysis was 1. 25 years: data from the Phase II trial was used for 90 day outcomes and rFVIIa complications – arterial thromboembolic events (ATE). We assumed no substantial cost differences in care between the two strategies except: 1) cost of rFVIIa (for an 80 mcg/kg dose in an 80 kg patient, assumed cost of 50,000/QALY over a wide range of sensitivity analyses. Sensitivity analyses showed that the cost of rFVIIa must exceed 50,000/QALY. Varying the cost and/or reducing the utility of health states following ATE did not impact results.</p> <p>Conclusion</p> <p>Based on data from preliminary trials, treating selected ICH patients with rFVIIa results in lower cost and improved clinical outcomes. This potential cost-effectiveness must be considered in light of the Phase III trial results.</p
Identification of elderly fallers by muscle strength measures
For efficient prevention of falls among older adults, individuals at a high risk of falling need to be identified. In this study, we searched for muscle strength measures that best identified those individuals who would fall after a gait perturbation and those who recovered their balance. Seventeen healthy older adults performed a range of muscle strength tests. We measured maximum and rate of development of ankle plantar flexion moment, knee extension moment and whole leg push-off force, as well as maximum jump height and hand grip strength. Subsequently, their capacity to regain balance after tripping over an obstacle was determined experimentally. Seven of the participants were classified as fallers based on the tripping outcome. Maximum isometric push-off force in a leg press apparatus was the best measure to identify the fallers, as cross-validation of a discriminant model with this variable resulted in the best classification (86% sensitivity and 90% specificity). Jump height and hand grip strength were strongly correlated to leg press force (r = 0.82 and 0.59, respectively) and can also be used to identify fallers, although with slightly lower specificity. These results indicate that whole leg extension strength is associated with the ability to prevent a fall after a gait perturbation and might be used to identify the elderly at risk of falling
Tumor Endothelium Marker-8 Based Decoys Exhibit Superiority over Capillary Morphogenesis Protein-2 Based Decoys as Anthrax Toxin Inhibitors
Anthrax toxin is the major virulence factor produced by Bacillus anthracis. The toxin consists of three protein subunits: protective antigen (PA), lethal factor, and edema factor. Inhibition of PA binding to its receptors, tumor endothelium marker-8 (TEM8) and capillary morphogenesis protein-2 (CMG2) can effectively block anthrax intoxication, which is particularly valuable when the toxin has already been overproduced at the late stage of anthrax infection, thus rendering antibiotics ineffectual. Receptor-like agonists, such as the mammalian cell-expressed von Willebrand factor type A (vWA) domain of CMG2 (sCMG2), have demonstrated potency against the anthrax toxin. However, the soluble vWA domain of TEM8 (sTEM8) was ruled out as an anthrax toxin inhibitor candidate due to its inferior affinity to PA. In the present study, we report that L56A, a PA-binding-affinity-elevated mutant of sTEM8, could inhibit anthrax intoxication as effectively as sCMG2 in Fisher 344 rats. Additionally, pharmacokinetics showed that L56A and sTEM8 exhibit advantages over sCMG2 with better lung-targeting and longer plasma retention time, which may contribute to their enhanced protective ability in vivo. Our results suggest that receptor decoys based on TEM8 are promising anthrax toxin inhibitors and, together with the pharmacokinetic studies in this report, may contribute to the development of novel anthrax drugs
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