Results from regular monitoring of relativistic compact binaries like PSR 1913+16 are consistent with the dominant (quadrupole) order emission of gravitational waves (GWs). We show that observations ...associated with the binary black hole (BBH) central engine of blazar OJ 287 demand the inclusion of gravitational radiation reaction effects beyond the quadrupolar order. It turns out that even the effects of certain hereditary contributions to GW emission are required to predict impact flare timings of OJ 287. We develop an approach that incorporates this effect into the BBH model for OJ 287. This allows us to demonstrate an excellent agreement between the observed impact flare timings and those predicted from ten orbital cycles of the BBH central engine model. The deduced rate of orbital period decay is nine orders of magnitude higher than the observed rate in PSR 1913+16, demonstrating again the relativistic nature of OJ 287's central engine. Finally, we argue that precise timing of the predicted 2019 impact flare should allow a test of the celebrated black hole "no-hair theorem" at the 10% level.
Bleeding limits anticoagulant treatment in patients with acute coronary syndromes (ACS).
We investigated whether background concomitant antiplatelet therapy influences the effects of apixaban after ...ACS.
This study examined high-risk ACS patients who were treated with aspirin or aspirin plus clopidogrel and who were randomized to apixaban 5 mg twice daily or placebo. In a post-hoc analysis, we assessed whether the effect of apixaban on efficacy and safety outcomes varied by the concomitant antiplatelet regimen by using simple Cox modeling and marginal structural models with propensity scores and antiplatelet therapy as a time-dependent covariate.
At baseline, of 7,364 patients, 16.3% (n = 1,202) were on aspirin alone, and 79.0% (n = 5,814) were on aspirin plus clopidogrel. A total of 19.2% (n = 1,415) switched antiplatelet therapy during follow-up. No differential effect of apixaban versus placebo was observed for the composite endpoint of cardiovascular death, myocardial infarction, and ischemic stroke in patients taking aspirin (12.21 per 100 patient-years vs. 13.21 per 100 patient-years; adjusted hazard ratio HR: 0.91; 95% confidence interval CI: 0.62 to 1.32) or aspirin plus clopidogrel (13.22 vs. 14.24; adjusted HR: 0.95; 95% CI: 0.78 to 1.14; p(interaction)= 0.84). Compared with placebo, apixaban increased Thrombolysis In Myocardial Infarction major bleeding in patients taking aspirin (1.48 vs. 0.25; adjusted HR: 6.62; 95% CI: 0.75 to 51.73) and in patients taking aspirin plus clopidogrel (2.58 vs. 1.02; adjusted HR: 2.44; 95% CI: 1.34 to 4.45; p(interaction)= 0.41). Similar results were obtained with marginal structural models and in patients treated with and without percutaneous coronary intervention.
Post-ACS treatment with apixaban versus placebo showed no efficacy, but it increased bleeding regardless of concomitant therapy with aspirin alone or aspirin plus clopidogrel. (Apixaban for Prevention of Acute Ischemic Events 2 APPRAISE-2; NCT00831441).
Background Concomitant use of proton-pump inhibitors (PPIs) has been implicated in diminished antiplatelet response to clopidogrel and an increased risk of ischemic events, but primarily among ...patients undergoing percutaneous coronary intervention. We sought to examine the potential influence of interactions between PPIs and clopidogrel versus prasugrel on platelet reactivity and clinical outcomes after acute coronary syndromes (ACS) in patients managed medically without revascularization. Methods This analysis from the TRILOGY ACS trial focused upon the 7,243 ACS patients aged <75 years who were managed without revascularization, randomized to clopidogrel or prasugrel, and followed for a median of 17 months. Proton-pump inhibitor type and use were assessed at each study visit, and 2,049 of the patients in this cohort underwent serial platelet reactivity assessments. Results Proton-pump inhibitor use (23%) was similar between the clopidogrel and prasugrel groups at baseline and throughout the study. Median on-treatment platelet reactivity values were consistently lower with prasugrel versus clopidogrel irrespective of PPI use. For the primary end point (composite of cardiovascular death, myocardial infarction MI, or stroke), PPI use modified the unadjusted treatment effect of prasugrel versus clopidogrel (interaction P = .02). After adjusting for differences in baseline characteristics, this treatment effect modification was attenuated for the composite end point (interaction P = .06) but was significant for the MI component end point (interaction P = .01). Similarly, among patients on a PPI, the frequency of MI was significantly lower with prasugrel versus clopidogrel (hazard ratio = 0.61; 95% CI 0.42-0.88). These findings were similar by PPI type (omeprazole and pantoprazole). Conclusions Among ACS patients managed without revascularization, use of PPIs did not result in a differential antiplatelet response between prasugrel versus clopidogrel but was associated with a lower incidence of MI with prasugrel. These hypothesis-generating findings suggest that factors besides platelet reactivity may underlie the differential risk of MI observed by treatment assignment with PPI use.
We present the results of our power spectral density analysis for the BL Lac object OJ 287, utilizing the Fermi-LAT survey at high-energy γ-rays, Swift-XRT in X-rays, several ground-based telescopes ...and the Kepler satellite in the optical, and radio telescopes at GHz frequencies. The light curves are modeled in terms of continuous-time autoregressive moving average (CARMA) processes. Owing to the inclusion of the Kepler data, we were able to construct for the first time the optical variability power spectrum of a blazar without any gaps across ∼6 dex in temporal frequencies. Our analysis reveals that the radio power spectra are of a colored-noise type on timescales ranging from tens of years down to months, with no evidence for breaks or other spectral features. The overall optical power spectrum is also consistent with a colored noise on the variability timescales ranging from 117 years down to hours, with no hints of any quasi-periodic oscillations. The X-ray power spectrum resembles the radio and optical power spectra on the analogous timescales ranging from tens of years down to months. Finally, the γ-ray power spectrum is noticeably different from the radio, optical, and X-ray power spectra of the source: we have detected a characteristic relaxation timescale in the Fermi-LAT data, corresponding to ∼150 days, such that on timescales longer than this, the power spectrum is consistent with uncorrelated (white) noise, while on shorter variability timescales there is correlated (colored) noise.
ABSTRACT OJ 287 is a quasi-periodic quasar with roughly 12 year optical cycles. It displays prominent outbursts that are predictable in a binary black hole model. The model predicted a major optical ...outburst in 2015 December. We found that the outburst did occur within the expected time range, peaking on 2015 December 5 at magnitude 12.9 in the optical R-band. Based on Swift/XRT satellite measurements and optical polarization data, we find that it included a major thermal component. Its timing provides an accurate estimate for the spin of the primary black hole, . The present outburst also confirms the established general relativistic properties of the system such as the loss of orbital energy to gravitational radiation at the 2% accuracy level, and it opens up the possibility of testing the black hole no-hair theorem with 10% accuracy during the present decade.
Abstract Recent epidemiological studies have indicated numerous associations between vascular and lifestyle related risk factors and incident dementia. However, evidence from randomised controlled ...trials (RCT) showing effectiveness of interventions aimed at these risk factors in preventing or postponing dementia onset is still lacking. Three large RCTs on multi-component interventions to prevent dementia (preDIVA, FINGER, MAPT) have been initiated in Europe to address these issues. Irrespective of some methodological differences, all three studies target cardiovascular and lifestyle related risk factors. Collaboration within the newly founded ‘European Dementia Prevention Initiative’ (EDPI) will allow for a comprehensive exploration of optimal target population, intervention and outcome measures, which are currently unknown. Combining data of the ongoing studies and running simulation analyses will facilitate determining the optimal design including accurate sample-size calculations for future multi-national clinical trials on dementia prevention. Interventions aiming at dementia prevention should be pragmatic and easy to implement on a large scale in different health care systems, without generating high additional costs or burden on participants or physicians. As the optimal age for intervention precedes the optimal age for outcome assessment, traditional trial designs might lead to suboptimal timing of either of the two. Separation of intervention and outcome assessment in time is a potential solution, but requires studies with very long follow-up. International collaboration of research groups with experience in dementia prevention studies and well-organised logistics for these major projects is pivotal to success for future large-scale dementia prevention studies. Founding of EDPI is an important first step in this direction.
Recent measurements demonstrate that the "background" stratospheric aerosol layer is persistently variable rather than constant, even in the absence of major volcanic eruptions. Several independent ...data sets show that stratospheric aerosols have increased in abundance since 2000. Near-global satellite aerosol data imply a negative radiative forcing due to stratospheric aerosol changes over this period of about -0.1 watt per square meter, reducing the recent global warming that would otherwise have occurred. Observations from earlier periods are limited but suggest an additional negative radiative forcing of about -0.1 watt per square meter from 1960 to 1990. Climate model projections neglecting these changes would continue to overestimate the radiative forcing and global warming in coming decades if these aerosols remain present at current values or increase.
We demonstrate the use of a ring-shaped Bose-Einstein condensate as a rotation sensor by measuring the interference between two counter-propagating phonon modes imprinted azimuthally around the ring. ...We observe rapid decay of the excitations, quantified by quality factors of at most Q ≈ 27. We numerically model our experiment using the c-field methodology, allowing us to estimate the parameters that maximise the performance of our sensor. We explore the damping mechanisms underlying the observed phonon decay, and identify two distinct Landau scattering processes that each dominate at different driving amplitudes and temperatures. Our simulations reveal that Q is limited by strong damping of phonons even in the zero temperature limit. We perform an experimental proof-of-principle rotation measurement using persistent currents imprinted around the ring. We demonstrate a rotation sensitivity of up to
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in the atomic shot-noise limit. This is a significant improvement over the shot-noise-limited
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sensitivity obtained by Marti et al. Phys. Rev. A 91, 013602 (2015) for a similar setup.
To design a new model of proliferative vitreoretinopathy (PVR) that would not rely on the addition of exogenous cells. The release of endogenous cells from surrounding attachments seems to be an ...early event in the pathogenesis of PVR. Because the proteolytic enzyme dispase dissociates tissues, the hypothesis was that an intraocular injection of dispase could trigger events that would cause PVR. The requirement for a surgical retinal break at the time of dispase injection was also examined.
One eye of Dutch Belted rabbits was injected with 0.003 U to 1.0 U dispase in the subretinal space or vitreous cavity. Control rabbits received a saline injection. An intentional retinal tear was created in animals in some groups. Observations were made for at least 10 weeks after surgery.
Proliferative vitreoretinopathy developed in response to subretinal or intravitreal dispase, with or without creation of a controlled retinal break. Increased severity of PVR correlated with increasing doses of dispase. Evidence of PVR included preretinal membranes, distortion of myelin wings and retinal vessels, fixed retinal folds, and traction retinal detachment. Proliferative vitreoretinopathy did not develop in saline-treated control animals.
Dispase initiated the development of PVR without the addition of exogenous cells, growth factors, or cytokines typically found in PVR membranes. A cascade of events was probably triggered by dispase, causing native cells and factors to produce PVR. The dispase model of PVR was technically easy to perform, permitted a clear view of the retina, and had a high success rate in development of PVR.
A recently developed matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) method to spatially profile the location and distribution of multiple N-linked glycan species in ...frozen tissues has been extended and improved for the direct analysis of glycans in clinically derived formalin-fixed paraffin-embedded (FFPE) tissues. Formalin-fixed tissues from normal mouse kidney, human pancreatic and prostate cancers, and a human hepatocellular carcinoma tissue microarray were processed by antigen retrieval followed by on-tissue digestion with peptide N-glycosidase F. The released N-glycans were detected by MALDI-IMS analysis, and the structural composition of a subset of glycans could be verified directly by on-tissue collision-induced fragmentation. Other structural assignments were confirmed by off-tissue permethylation analysis combined with multiple database comparisons. Imaging of mouse kidney tissue sections demonstrates specific tissue distributions of major cellular N-linked glycoforms in the cortex and medulla. Differential tissue distribution of N-linked glycoforms was also observed in the other tissue types. The efficacy of using MALDI-IMS glycan profiling to distinguish tumor from non-tumor tissues in a tumor microarray format is also demonstrated. This MALDI-IMS workflow has the potential to be applied to any FFPE tissue block or tissue microarray to enable higher throughput analysis of the global changes in N-glycosylation associated with cancers.
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