Atherosclerosis is a process with inflammatory features and selective cyclooxygenase 2 (COX-2) inhibitors may potentially have antiatherogenic effects by virtue of inhibiting inflammation. However, ...by decreasing vasodilatory and antiaggregatory prostacyclin production, COX-2 antagonists may lead to increased prothrombotic activity. To define the cardiovascular effects of COX-2 inhibitors when used for arthritis and musculoskeletal pain in patients without coronary artery disease, we performed a MEDLINE search to identify all English-language articles on use of COX-2 inhibitors published between 1998 and February 2001. We also reviewed relevant submissions to the US Food and Drug Administration by pharmaceutical companies. Our search yielded 2 major randomized trials, the Vioxx Gastrointestinal Outcomes Research Study (VIGOR; 8076 patients) and the Celecoxib Long-term Arthritis Safety Study (CLASS; 8059 patients), as well as 2 smaller trials with approximately 1000 patients each. The results from VIGOR showed that the relative risk of developing a confirmed adjudicated thrombotic cardiovascular event (myocardial infarction, unstable angina, cardiac thrombus, resuscitated cardiac arrest, sudden or unexplained death, ischemic stroke, and transient ischemic attacks) with rofecoxib treatment compared with naproxen was 2.38 (95% confidence interval, 1.39-4.00; P =.002). There was no significant difference in cardiovascular event (myocardial infarction, stroke, and death) rates between celecoxib and nonsteroidal anti-inflammatory agents in CLASS. The annualized myocardial infarction rates for COX-2 inhibitors in both VIGOR and CLASS were significantly higher than that in the placebo group of a recent meta-analysis of 23 407 patients in primary prevention trials (0.52%): 0.74% with rofecoxib (P =.04 compared with the placebo group of the meta-analysis) and 0.80% with celecoxib (P =.02 compared with the placebo group of the meta-analysis). The available data raise a cautionary flag about the risk of cardiovascular events with COX-2 inhibitors. Further prospective trial evaluation may characterize and determine the magnitude of the risk.
ABSTRACT
We present the results of a multifrequency, multiscale radio polarimetric study with the Very Large Array (VLA) of the Seyfert 1 galaxy and BALQSO, Mrk 231. We detect complex total and ...polarized intensity features in the source. Overall, the images indicate the presence of a broad, one-sided, curved outflow towards the south which consists of a weakly collimated jet with poloidal inferred magnetic fields, inside a broader magnetized ‘wind’ or ‘sheath’ component with toroidal inferred magnetic fields. The model of a kpc-scale weakly collimated jet/lobe in Mrk 231 is strengthened by its C-shaped morphology, steep spectral index throughout, complexities in the magnetic field structures, and the presence of self-similar structures observed on the 10-parsec-scale in the literature. The ‘wind’ may comprise both nuclear starburst (close to the core) and active galactic nuclei winds, where the latter maybe the primary contributor. Moving away from the core, the ‘wind’ component may also comprise the outer layers (or ‘sheath’) of a broadened jet. The inferred value of the (weakly collimated) jet production efficiency, ηjet ∼ 0.01, is consistent with the estimates in the literature. The composite jet and wind outflow in Mrk 231 appears to be low-power and matter-dominated, and oriented at a small angle to our line of sight.
ABSTRACT
Radio relics are diffuse radio sources in galaxy clusters that are associated with merger shock waves. Detailed observations of radio relics in total intensity and in polarization show ...complex structures on kiloparsec scales. The relation between the observed features and the underlying morphology of the magnetic field is not clear. Using 3D magneto-hydrodynamical simulations, we study the polarized emission produced by a shock wave that propagates through a turbulent medium that resembles the intracluster medium. We model the polarized synchrotron emission on the basis of diffusive shock acceleration of cosmic ray electrons. We find that the synchrotron emission produced in a shocked turbulent medium can reproduce some of the observed features in radio relics. Shock compression can give rise to a high polarization fraction at the shock front and a partial alignment of the polarization E-vectors with the shock normal. Our work confirms that radio relics can also be formed in an environment with a tangled magnetic field. We also discuss the effect of Faraday rotation intrinsic to the source, and how our results depend on the angular resolution of observations.
The effect of heavy ion irradiation on the stability of oxide phase of autoclaved Zircaloy 4 fuel tube material, has been studied using Glancing angle X-ray diffraction (GIXRD) technique after ...306 KeV Ar+9 ions irradiation at a dose of 3 × 1019 Ar+9/m2. To estimate the extent of damage, a simulation was carried out using “Stopping and Range of Ions in Matter (SRIM-2008)” computer program based on the Monte Carlo method. For the first time, the oxide formed in 0n1 irradiated fuel tube after 7600 MWD/T burn up in Pressurized Heavy Water Reactor (PHWR) has been characterized using GIXRD technique. The advantage of this technique is that the stress-induced phase transformation, which normally occurs during metallographic sample preparation for optical and electron microscopy, is eliminated. The un-irradiated autoclaved oxide in the steam environment (415 °C and 500 °C), both uniform as well as nodular oxide has been characterized using GIXRD, X-ray photo-electron spectroscopy (XPS), scanning electron microscopy (SEM) attached with Energy Dispersive spectroscopy (EDS). Cross-sectional transmission electron microscopy has been carried out in uniform oxide before and after heavy ion irradiation. It is observed that heavy ion and neutron irradiation induce monoclinic to tetragonal phase transformation in the oxide. Presence of significant fraction of tetragonal ZrO2 phase as well as sub-oxide Zr3O has been identified in the oxide layer near oxide-coolant interface in 0n1 irradiated in-pile sample whereas in unirradiated autoclaved oxide these phases are present in a small fraction near the oxide-metal interface. XPS analysis indicates the difference in the chemical state of alloying element in the oxide when autoclaving is carried out at different temperatures.
Summary Background Clusterin is a chaperone protein associated with treatment resistance and upregulated by apoptotic stressors such as chemotherapy. Custirsen is a second-generation antisense ...oligonucleotide that inhibits clusterin production. The aim of the SYNERGY trial was to investigate the effect of custirsen in combination with docetaxel and prednisone on overall survival in patients with metastatic castration-resistant prostate cancer. Methods SYNERGY was a phase 3, multicentre, open-label, randomised trial set at 134 study centres in 12 countries. Patients were eligible for participation if they had: metastatic castration-resistant prostate cancer and had received no previous chemotherapy; prostate-specific antigen greater than 5 ng/mL; and a Karnofsky performance score of 70% or higher. Patients were randomly assigned 1:1 centrally to either the docetaxel, prednisone, and custirsen combination or docetaxel and prednisone alone. Patients were not masked to treatment allocation. Randomisation was stratified by opioid use for cancer-related pain and radiographic evidence of progression. All patients received docetaxel 75 mg/m2 intravenously with 5 mg of prednisone orally twice daily. Patients assigned docetaxel, prednisone, and custirsen received weekly doses of custirsen 640 mg intravenously after three loading doses of 640 mg. The primary endpoint was overall survival analysed in the intention-to-treat population. Patients who received at least one study dose were included in the safety analysis set. This trial is registered with ClinicalTrials.gov , number NCT01188187 . The trial is completed and final analyses are reported here. Findings Between Dec 10, 2010, and Nov 7, 2012, 1022 patients were enrolled to the trial, of whom 510 were assigned docetaxel, prednisone, and custirsen and 512 were allocated docetaxel and prednisone. No difference in overall survival was recorded between the two groups (median survival 23·4 months 95% CI 20·9–24·8 with docetaxel, prednisone, and custirsen vs 22·0 months 19·5–24·0 with docetaxel and prednisone; hazard ratio HR 0·93, 95% CI 0·79–1·10; p=0·415). The most common adverse events of grade 3 or worse in the docetaxel, prednisone and custirsen group (n=501) compared with the docetaxel and prednisone alone group (n=499) were neutropenia (grade 3, 63 13% vs 28 6%; grade 4, 98 20% vs 77 15%), febrile neutropenia (grade 3, 52 10% vs 31 6%; grade 4, four 1% vs two <1%), and fatigue (grade 3, 53 11% vs 41 8%; grade 4, three 1% vs one <1%). One or more serious adverse events were reported for 214 (43%) of 501 patients treated with docetaxel, prednisone, and custirsen and 181 (36%) of 499 receiving docetaxel and prednisone alone. Adverse events were attributable to 23 (5%) deaths in the docetaxel, prednisone, and custirsen group and 24 (5%) deaths in the docetaxel and prednisone alone group. Interpretation Addition of custirsen to first-line docetaxel and prednisone was reasonably well tolerated, but overall survival was not significantly longer for patients with metastatic castration-resistant prostate cancer treated with this combination, compared with patients treated with docetaxel and prednisone alone. Funding OncoGenex Technologies.
To understand differences between asymptomatic colonized and infected states of indwelling medical devices, we sought to determine penile prosthesis biofilm composition, microbe-metabolite ...interaction networks, and association with clinical factors. Patients scheduled for penile prosthesis removal/revision were included. Samples from swabbed devices and controls underwent next-generation sequencing, metabolomics, and culture-based assessments. Biofilm formation from device isolates was reconstituted in a continuous-flow stir tank bioreactor. 93% of 27 analyzed devices harbored demonstrable biofilm. Seven genera including Faecalibaculum and Jeotgalicoccus were more abundant in infected than uninfected device biofilms (p < 0.001). Smokers and those with diabetes mellitus or cardiac disease had lower total normalized microbial counts than those without the conditions (p < 0.001). We identified microbe-metabolite interaction networks enriched in devices explanted for infection and pain. Biofilm formation was recapitulated on medical device materials including silicone, PTFE, polyurethane, and titanium in vitro to facilitate further mechanistic studies. Nearly all penile prosthesis devices harbor biofilms. Staphylococcus and Escherichia, the most common causative organisms of prosthesis infection, had similar abundance irrespective of infection status. A series of other uncommon genera and metabolites were differentially abundant, suggesting a complex microbe-metabolite pattern-rather than a single organism-is responsible for the transition from asymptomatic to infected or painful states.
This work presents a general methodology to analyze three-dimensional Freedericksz transitions in twisted-nematic liquid crystal (LC) bilayers. Using two equivalent coupled electromechanical ...variational formulations, the problem is treated as a bifurcation instability triggered by an externally applied electric field. Specifically, we consider LC bilayer materials anchored between two bounding plates and subjected to an electric field across the bilayer thickness. The plates are also twisted by an overall angle leading to different orientations of the directors in each layer. We first evaluate the corresponding ground state of the director field, and subsequently, we analyze the bifurcation problem by using a combined analytical-numerical method leading to a one-dimensional finite element discretization of the resulting stiffness matrix of the system. An analytical solution for the zero-twist bilayer is also obtained. The developed methodology is used to study the effect of the volume fraction of the constituents forming the bilayer upon the resulting critical electric field and corresponding eigenmodes. We find that by assembling a relatively thin 5CB layer with a thicker 7E layer, one can obtain periodic Freedericksz transitions (i.e. local modes) even for a zero-twist LC bilayer. We also show that when a 5CB material is assembled together with another electrically similar LC, such as a PCH12, the combined LC bilayer can exhibit an even lower Freedericksz transition than a LC of the same thickness consisting of any of the two constituents alone.
We study the variations in the Cyclotron Resonant Scattering Feature (CRSF) during 2011 outburst of the high mass X-ray binary 4U 0115+63 using observations performed with Suzaku, RXTE, Swift and ...INTEGRAL satellites. The wide-band spectral data with low-energy coverage allowed us to characterize the broad-band continuum and detect the CRSFs. We find that the broad-band continuum is adequately described by a combination of a low temperature (kT ∼ 0.8 keV) blackbody and a power law with high energy cutoff (E
cut ∼ 5.4 keV) without the need for a broad Gaussian at ∼10 keV as used in some earlier studies. Though winds from the companion can affect the emission from the neutron star at low energies (<3 keV), the blackbody component shows a significant presence in our continuum model. We report evidence for the possible presence of two independent sets of CRSFs with fundamentals at ∼11 and ∼15 keV. These two sets of CRSFs could arise from spatially distinct emitting regions. We also find evidence for variations in the line equivalent widths, with the 11 keV CRSF weakening and the 15 keV line strengthening with decreasing luminosity. Finally, we propose that the reason for the earlier observed anticorrelation of line energy with luminosity could be due to modelling of these two independent line sets (∼11 and ∼15 keV) as a single CRSF.
To determine the prevalence and content of discussions regarding physical activity (PA) promotion between individuals with a current or past diagnosis of cancer and their oncology care team.
Design ...and Procedure: A cross-sectional survey on PA discussion between individuals with a current or past diagnosis of cancer and their oncology care team was conducted at a single timepoint.
Eligible participants were adults with a current or past diagnosis of cancer at any time point in their cancer treatment who had a pre-scheduled appointment with their oncology care team.
A total of 100 participants completed the survey. PA-related discussions happened in 41% of the patient-provider interactions and 66% of respondents reported PA discussions at some point during care. No significant association occurred between cancer type, stage, or treatment status and PA discussions at any timepoint (all
's > 0.05). Most respondents were satisfied with the education provided on PA (54%); however, only 37% were sufficiently active. Those receiving education from their medical oncologist were more likely to be 'sufficiently active' (
= 0.020) according to the Godin Leisure Time Exercise Questionnaire.
Most respondents discuss PA with an oncology care provider at some point during their cancer treatment; however, few are sufficiently active. Future research is needed to determine strategies to facilitate PA promotion and close the gap between discussions and actual physical activity behavior.
We have studied the optimum deposition conditions for the improvement of oxygen and carbon dioxide gas barrier performance of functional diamond-like carbon (DLC) thin films. The a-C:H: a-C:H:Si, ...a-C:H:N and ta-C:N thin films with 10–400nm thickness were deposited on polyethylene terephthalate (PET) substrates by the radio frequency plasma-enhanced chemical vapour deposition method. To study the microstructure of the PET coated films, we have used the Raman spectroscopy, X-ray photoelectron spectroscopy, nano-indentation and surface profilometry. The gas barrier property were analysed and found that the a-C:H:N's are 5–10 times better gas barrier properties than that of uncoated PET substrates. These thin layer PET coated thin films could be use in food packaging and biomedical applications.
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•Oxygen and carbon dioxide gas barrier performance of functionalized DLC thin films•For this study, Raman spectroscopy, X-ray photoelectron spectroscopy and Nano-indentation are used.•The gas barrier properties of a-C:H:N's are 5–10 times better than that of uncoated PET substrates.
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