The Volume of the Past Light-Cone and the Paneitz Operator

We study a conjecture involving the invariant volume of the past light-cone from an arbitrary observation point back to a fixed initial value surface. The conjecture is that a 4th order differential operator which occurs in the theory of conformal anomalies gives $8\pi$ when acted upon the invariant volume of the past light-cone. We show that an extended version of the conjecture is valid for an arbitrary homogeneous and isotropic geometry. First order perturbation theory about flat spacetime reveals a violation of the conjecture which, however, vanishes for any vacuum solution of the Einstein equation. These results may be significant for constructing quantum gravitational observables, for quantifying the back-reaction on spacetime expansion and for alternate gravity models which feature a timelike vector field.Comment: 22 pages, no figures, 5 tables. Version 2 substantially extended to cover nonzero spatial curvature, and with simplified derivation

Ticagrelor : clinical development and future potential

Platelets participate centrally in atherothrombosis, resulting in vessel occlusion and ischaemia. Consequently, optimisation of antiplatelet regimens has the potential to further reduce the residual burden of morbidity and mortality associated with atherosclerosis. Ticagrelor is a potent oral platelet P2Y12 receptor antagonist that (1) inhibits a central amplification pathway of platelet activation directly as well as via an active metabolite, (2) has a rapid onset and offset of antiplatelet action that remains consistent in the circulation during twice-daily administration and is amenable to reversal, (3) has inverse agonist properties, and (4) demonstrates pleiotropic effects that contribute to anti-thrombotic, anti-inflammatory and vasodilatory properties. These advantageous characteristics of ticagrelor have translated to beneficial clinical outcomes in patients with acute coronary syndromes or ischaemic stroke, during prolonged maintenance therapy in specific high-risk populations, and following percutaneous coronary intervention but not definitively following coronary artery bypass graft surgery or in peripheral artery disease patients. Novel innovative strategies aim to reduce the risk of bleeding during dual antiplatelet therapy via shortening the duration of treatment and replacing the standard-of-care with ticagrelor monotherapy. In cases where aspirin is an essential component in secondary prevention, dose modification when combined with ticagrelor may hypothetically provide desirable clinical outcomes following appropriate clinical assessment as predicted by pharmacological studies. Overall, the future management of acute coronary syndromes could potentially involve the dichotomisation of antithrombotic therapies, whereby only those with high-risk of ischaemia, without a high-risk of bleeding, receive ticagrelor plus very-low-dose aspirin, while ticagrelor monotherapy is administered to the remaining majority

Cosmology with a long range repulsive force

We consider a class of cosmological models in which the universe is filled with a (non-electric) charge density that repels itself by means of a force carried by a vector boson with a tiny mass. When the vector's mass depends upon other fields, the repulsive interaction gives rise to an electromagnetic barrier which prevents these fields from driving the mass to zero. This can modify the cosmology dramatically. We present a very simple realization of this idea in which the vector's mass arises from a scalar field. The electromagnetic barrier prevents this field from rolling down its potential and thereby leads to accelerated expansion.Comment: 15 pages, 8 figures, LaTeX (version accepted for publication in PRD). 3 new figures, extended discussion of observational consequence

The SuperCOSMOS Sky Survey. Paper III: Astrometry

In this, the third in a series of three papers concerning the SuperCOSMOS Sky Survey, we describe the astrometric properties of the database. We describe the algorithms employed in the derivation of the astrometric parameters of the data, and demonstrate their accuracies by comparison with external datasets using the first release of data, the South Galactic Cap survey. We show that the celestial coordinates, which are tied to the International Celestial Reference Frame via the Tycho-2 reference catalogue, are accurate to better than +/- 0.2 arcsec at J,R=19,18 rising to +/- 0.3 arcsec at J,R=22,21 with positional dependent systematic effects from bright to faint magnitudes at the +/- 0.1 arcsec level. The proper motion measurements are shown to be accurate to typically +/- 10 mas/yr at J,R=19,18 rising to +/- 50 mas/yr at J,R=22,21 and are tied to zero using the extragalactic reference frame. We show that the zeropoint errors in the proper motions are 17 and are no larger than 10 mas/yr for R < 17 mas/yr.Comment: 15 pages, 12 figures; accepted for publication in MNRA

Energy-Momentum Tensor of Particles Created in an Expanding Universe

We present a general formulation of the time-dependent initial value problem for a quantum scalar field of arbitrary mass and curvature coupling in a FRW cosmological model. We introduce an adiabatic number basis which has the virtue that the divergent parts of the quantum expectation value of the energy-momentum tensor are isolated in the vacuum piece of , and may be removed using adiabatic subtraction. The resulting renormalized is conserved, independent of the cutoff, and has a physically transparent, quasiclassical form in terms of the average number of created adiabatic `particles'. By analyzing the evolution of the adiabatic particle number in de Sitter spacetime we exhibit the time structure of the particle creation process, which can be understood in terms of the time at which different momentum scales enter the horizon. A numerical scheme to compute as a function of time with arbitrary adiabatic initial states (not necessarily de Sitter invariant) is described. For minimally coupled, massless fields, at late times the renormalized goes asymptotically to the de Sitter invariant state previously found by Allen and Folacci, and not to the zero mass limit of the Bunch-Davies vacuum. If the mass m and the curvature coupling xi differ from zero, but satisfy m^2+xi R=0, the energy density and pressure of the scalar field grow linearly in cosmic time demonstrating that, at least in this case, backreaction effects become significant and cannot be neglected in de Sitter spacetime.Comment: 28 pages, Revtex, 11 embedded .ps figure

Energy-Momentum Tensor of Cosmological Fluctuations during Inflation

We study the renormalized energy-momentum tensor (EMT) of cosmological scalar fluctuations during the slow-rollover regime for chaotic inflation with a quadratic potential and find that it is characterized by a negative energy density which grows during slow-rollover. We also approach the back-reaction problem as a second-order calculation in perturbation theory finding no evidence that the back-reaction of cosmological fluctuations is a gauge artifact. In agreement with the results on the EMT, the average expansion rate is decreased by the back-reaction of cosmological fluctuations.Comment: 19 pages, no figures.An appendix and references added, conclusions unchanged, version accepted for publication in PR

PIK3CA mutation in HPV-associated OPSCC patients receiving deintensified chemoradiation

PIK3CA is the most frequently mutated gene in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Prognostic implications of such mutations remain unknown. We sought to elucidate the clinical significance of PIK3CA mutations in HPV-associated OPSCC patients treated with definitive chemoradiation (CRT). Seventyseven patients with HPV-associated OPSCC were enrolled on two phase II clinical trials of deintensified CRT (60 Gy intensitymodulated radiotherapy with concurrent weekly cisplatin). Targeted next-generation sequencing was performed. Of the 77 patients, nine had disease recurrence (two regional, four distant, three regional and distant). Thirty-four patients had mutation( s) identified; 16 had PIK3CA mutations. Patients with wild-type-PIK3CA had statistically significantly higher 3-year disease-free survival than PIK3CA-mutant patients (93.4%, 95% confidence interval [CI] = 85.0% to 99.9% vs 68.8%, 95% CI = 26.7% to 89.8%; P=.004). On multivariate analysis, PIK3CA mutation was the only variable statistically significantly associated with disease recurrence (hazard ratio = 5.71, 95% CI = 1.53 to 21.3; P=.01). PIK3CA mutation is associated with worse diseasefree survival in a prospective cohort of newly diagnosed HPV-associated OPSCC patients treated with deintensified CRT

Red Queen Coevolution on Fitness Landscapes

Species do not merely evolve, they also coevolve with other organisms. Coevolution is a major force driving interacting species to continuously evolve ex- ploring their fitness landscapes. Coevolution involves the coupling of species fit- ness landscapes, linking species genetic changes with their inter-specific ecological interactions. Here we first introduce the Red Queen hypothesis of evolution com- menting on some theoretical aspects and empirical evidences. As an introduction to the fitness landscape concept, we review key issues on evolution on simple and rugged fitness landscapes. Then we present key modeling examples of coevolution on different fitness landscapes at different scales, from RNA viruses to complex ecosystems and macroevolution.Comment: 40 pages, 12 figures. To appear in "Recent Advances in the Theory and Application of Fitness Landscapes" (H. Richter and A. Engelbrecht, eds.). Springer Series in Emergence, Complexity, and Computation, 201

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types