Loop Quantum Gravity and Ultra High Energy Cosmic Rays

There are two main sets of data for the observed spectrum of ultra high energy cosmic rays (those cosmic rays with energies greater than $\sim 4 \times 10^{18}$ eV), the High Resolution Fly's Eye (HiRes) collaboration group observations, which seem to be consistent with the predicted theoretical spectrum (and therefore with the theoretical limit known as the Greisen-Zatsepin-Kuzmin cutoff), and the observations from the Akeno Giant Air Shower Array (AGASA) collaboration group, which reveal an abundant flux of incoming particles with energies above $1 \times 10^{20}$ eV violating the Greisen-Zatsepin-Kuzmin cutoff. As an explanation of this anomaly it has been suggested that quantum-gravitational effects may be playing a decisive role in the propagation of ultra high energy cosmic rays. In this article we take the loop quantum gravity approach. We shall provide some techniques to establish and analyze new constraints on the loop quantum gravity parameters arising from both sets of data, HiRes and AGASA . We shall also study their effects on the predicted spectrum for ultra high energy cosmic rays. As a result we will state the possibility of reconciling the AGASA observations.Comment: 18 pages, latex, 4 figure

Towards the QFT on Curved Spacetime Limit of QGR. I: A General Scheme

In this article and a companion paper we address the question of how one might obtain the semiclassical limit of ordinary matter quantum fields (QFT) propagating on curved spacetimes (CST) from full fledged Quantum General Relativity (QGR), starting from first principles. We stress that we do not claim to have a satisfactory answer to this question, rather our intention is to ignite a discussion by displaying the problems that have to be solved when carrying out such a program. In the present paper we propose a scheme that one might follow in order to arrive at such a limit. We discuss the technical and conceptual problems that arise in doing so and how they can be solved in principle. As to be expected, completely new issues arise due to the fact that QGR is a background independent theory. For instance, fundamentally the notion of a photon involves not only the Maxwell quantum field but also the metric operator - in a sense, there is no photon vacuum state but a "photon vacuum operator"! While in this first paper we focus on conceptual and abstract aspects, for instance the definition of (fundamental) n-particle states (e.g. photons), in the second paper we perform detailed calculations including, among other things, coherent state expectation values and propagation on random lattices. These calculations serve as an illustration of how far one can get with present mathematical techniques. Although they result in detailed predictions for the size of first quantum corrections such as the gamma-ray burst effect, these predictions should not be taken too seriously because a) the calculations are carried out at the kinematical level only and b) while we can classify the amount of freedom in our constructions, the analysis of the physical significance of possible choices has just begun.Comment: LaTeX, 47 p., 3 figure

Safety-by-design and engineered nanomaterials: the need to move from theory to practice

As the governance of engineered nanomaterials (ENMs) evolves, innovations in the prevention, mitigation, management, and transfer of risk shape discussion of how nanotechnology may mature and reach various marketplaces. Safety-by-Design (SbD) is one leading concept that, while equally philosophy as well as risk-based practice, can uniquely help address lingering uncertainties and concerns stemming from regulatory evaluation of ENM risk across worker, consumer, and environmental safety. This paper provides a discussion on the SbD concept across different disciplines aiming to identify different approaches and needs to meet regulatory requirements—ultimately, we argue that SbD is evolving both to meet the needs and discourse of various disciplines, and to apply within differing marketplaces and national regulatory structures. Understanding how SbD has evolved within ENM can yield a more practical application and development of SbD, and help guide or unify national and international ENM governance around a core set of safety-driven principles

Shedding Light on The Role of Keratinocyte-Derived Extracellular Vesicles on Skin-Homing Cells

Extracellular vesicles (EVs) are secretory lipid membranes with the ability to regulate cellular functions by exchanging biological components between different cells. Resident skin cells such as keratinocytes, fibroblasts, melanocytes, and inflammatory cells can secrete different types of EVs depending on their biological state. These vesicles can influence the physiological properties and pathological processes of skin, such as pigmentation, cutaneous immunity, and wound healing. Since keratinocytes constitute the majority of skin cells, secreted EVs from these cells may alter the pathophysiological behavior of other skin cells. This paper reviews the contents of keratinocyte-derived EVs and their impact on fibroblasts, melanocytes, and immune cells to provide an insight for better understanding of the pathophysiological mechanisms of skin disorders and their use in related therapeutic approaches

Sensitivity of the Cherenkov Telescope Array to a dark matter signal from the Galactic centre

We provide an updated assessment of the power of the Cherenkov Telescope Array (CTA) to search for thermally produced dark matter at the TeV scale, via the associated gamma-ray signal from pair-annihilating dark matter particles in the region around the Galactic centre. We find that CTA will open a new window of discovery potential, significantly extending the range of robustly testable models given a standard cuspy profile of the dark matter density distribution. Importantly, even for a cored profile, the projected sensitivity of CTA will be sufficient to probe various well-motivated models of thermally produced dark matter at the TeV scale. This is due to CTA's unprecedented sensitivity, angular and energy resolutions, and the planned observational strategy. The survey of the inner Galaxy will cover a much larger region than corresponding previous observational campaigns with imaging atmospheric Cherenkov telescopes. CTA will map with unprecedented precision the large-scale diffuse emission in high-energy gamma rays, constituting a background for dark matter searches for which we adopt state-of-the-art models based on current data. Throughout our analysis, we use up-to-date event reconstruction Monte Carlo tools developed by the CTA consortium, and pay special attention to quantifying the level of instrumental systematic uncertainties, as well as background template systematic errors, required to probe thermally produced dark matter at these energies.</p

Sensitivity of the Cherenkov Telescope Array for probing cosmology and fundamental physics with gamma-ray propagation

The Cherenkov Telescope Array (CTA), the new-generation ground-based observatory for $\gamma$-ray astronomy, provides unique capabilities to address significant open questions in astrophysics, cosmology, and fundamental physics. We study some of the salient areas of $\gamma$-ray cosmology that can be explored as part of the Key Science Projects of CTA, through simulated observations of active galactic nuclei (AGN) and of their relativistic jets. Observations of AGN with CTA will enable a measurement of $\gamma$-ray absorption on the extragalactic background light with a statistical uncertainty below 15% up to a redshift $z=2$ and to constrain or detect $\gamma$-ray halos up to intergalactic-magnetic-field strengths of at least 0.3pG. Extragalactic observations with CTA also show promising potential to probe physics beyond the Standard Model. The best limits on Lorentz invariance violation from $\gamma$-ray astronomy will be improved by a factor of at least two to three. CTA will also probe the parameter space in which axion-like particles could constitute a significant fraction, if not all, of dark matter. We conclude on the synergies between CTA and other upcoming facilities that will foster the growth of $\gamma$-ray cosmology

Multimessenger NuEM Alerts with AMON

The Astrophysical Multimessenger Observatory Network (AMON), has developed a real-time multi-messenger alert system. The system performs coincidence analyses of datasets from gamma-ray and neutrino detectors, making the Neutrino-Electromagnetic (NuEM) alert channel. For these analyses, AMON takes advantage of sub-threshold events, i.e., events that by themselves are not significant in the individual detectors. The main purpose of this channel is to search for gamma-ray counterparts of neutrino events. We will describe the different analyses that make-up this channel and present a selection of recent results

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)