Long-term interleukin-6 levels and subsequent risk of coronary heart disease: Two new prospective studies and a systematic review

Background The relevance to coronary heart disease (CHD) of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6), may be underestimated because such mediators are short acting and prone to fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined as nonfatal myocardial infarction [MI] or fatal CHD) in two population-based cohorts, involving serial measurements to enable correction for within-person variability. We updated a systematic review to put the new findings in context. Methods and Findings Measurements were made in samples obtained at baseline from 2,138 patients who had a first-ever nonfatal MI or died of CHD during follow-up, and from 4,267 controls in two cohorts comprising 24,230 participants. Correction for within-person variability was made using data from repeat measurements taken several years apart in several hundred participants. The year-to-year variability of IL-6 values within individuals was relatively high (regression dilution ratios of 0.41, 95% confidence interval [CI] 0.28-0.53, over 4 y, and 0.35, 95% CI 0.23-0.48, over 12 y). Ignoring this variability, we found an odds ratio for CHD, adjusted for several established risk factors, of 1.46 (95% CI 1.29-1.65) per 2 standard deviation (SD) increase of baseline IL-6 values, similar to that for baseline C-reactive protein. After correction for within-person variability, the odds ratio for CHD was 2.14 (95% CI 1.45-3.15) with long-term average ("usual'') IL-6, similar to those for some established risk factors. Increasing IL-6 levels were associated with progressively increasing CHD risk. An updated systematic review of electronic databases and other sources identified 15 relevant previous population-based prospective studies of IL-6 and clinical coronary outcomes (i.e., MI or coronary death). Including the two current studies, the 17 available prospective studies gave a combined odds ratio of 1.61 (95% CI 1.42-1.83) per 2 SD increase in baseline IL-6 (corresponding to an odds ratio of 3.34 [95% CI 2.45-4.56] per 2 SD increase in usual [long-term average] IL-6 levels). Conclusions Long-term IL-6 levels are associated with CHD risk about as strongly as are some major established risk factors, but causality remains uncertain. These findings highlight the potential relevance of IL-6-mediated pathways to CH

On the Relationship Between Complex Potentials and Strings of Projection Operators

It is of interest in a variety of contexts, and in particular in the arrival time problem, to consider the quantum state obtained through unitary evolution of an initial state regularly interspersed with periodic projections onto the positive $x$-axis (pulsed measurements). Echanobe, del Campo and Muga have given a compelling but heuristic argument that the state thus obtained is approximately equivalent to the state obtained by evolving in the presence of a certain complex potential of step-function form. In this paper, with the help of the path decomposition expansion of the associated propagators, we give a detailed derivation of this approximate equivalence. The propagator for the complex potential is known so the bulk of the derivation consists of an approximate evaluation of the propagator for the free particle interspersed with periodic position projections. This approximate equivalence may be used to show that to produce significant reflection, the projections must act at time spacing less than 1/E, where E is the energy scale of the initial state.Comment: 29 pages, LaTex, 4 figures. Substantial revision

Quantum measurement in a family of hidden-variable theories

The measurement process for hidden-configuration formulations of quantum mechanics is analysed. It is shown how a satisfactory description of quantum measurement can be given in this framework. The unified treatment of hidden-configuration theories, including Bohmian mechanics and Nelson's stochastic mechanics, helps in understanding the true reasons why the problem of quantum measurement can succesfully be solved within such theories.Comment: 16 pages, LaTeX; all special macros are included in the file; a figure is there, but it is processed by LaTe

Optical properties of correlated materials -- Generalized Peierls approach and its application to VO2

The aim of the present paper is to present a versatile scheme for the computation of optical properties of solids, with particular emphasis on realistic many-body calculations for correlated materials. Geared at the use with localized basis sets, we extend the commonly known lattice "Peierls substitution" approach to the case of multi-atomic unit cells. We show in how far this generalization can be deployed as an approximation to the full Fermi velocity matrix elements that enter the continuum description of the response of a solid to incident light. We further devise an upfolding scheme to incorporate optical transitions, that involve high energy orbitals that had been downfolded in the underlying many-body calculation of the electronic structure. As an application of the scheme, we present results on a material of longstanding interest, vanadium dioxide, VO2. Using dynamical mean-field data of both, the metallic and the insulating phase, we calculate the corresponding optical conductivities, elucidate optical transitions and find good agreement with experimental results.Comment: 15 pages, 6 figure

On Uniqueness of the Jump Process in Quantum Measurement Theory

We prove that, contrary to the standard quantum theory of continuous observation, in the formalism of Event Enhanced Quantum Theory the stochastic process generating individual sample histories of pairs (observed quantum system, observing classical apparatus) is unique. This result gives a rigorous basis to the previous heuristic argument of Blanchard and Jadczyk. Possible implications of this result are discussed.Comment: 31 pages, LaTeX, article; e-mail contact [email protected]

Arrival Times, Complex Potentials and Decoherent Histories

We address a number of aspects of the arrival time problem defined using a complex potential of step function form. We concentrate on the limit of a weak potential, in which the resulting arrival time distribution function is closely related to the quantum-mechanical current. We first consider the analagous classical arrival time problem involving an absorbing potential, and this sheds some light on certain aspects of the quantum case. In the quantum case, we review the path decomposition expansion (PDX), in which the propagator is factored across a surface of constant time, so is very useful for potentials of step function form. We use the PDX to derive the usual scattering wave functions and the arrival time distribution function. This method gives a direct and geometrically appealing account of known results (but also points the way to how they can be extended to more general complex potentials). We use these results to carry out a decoherent histories analysis of the arrival time problem, taking advantage of a recently demonstrated connection between pulsed measurements and complex potentials. We obtain very simple and plausible expressions for the class operators (describing the amplitudes for crossing the origin during intervals of time) and show that decoherence of histories is obtained for a wide class of initial states (such as simple wave packets and superpositions of wave packets). We find that the decoherent histories approach gives results with a sensible classical limit that are fully compatible with standard results on the arrival time problem. We also find some interesting connections between backflow and decoherence.Comment: 43 page

Prospective evaluation of an artificial intelligence-enabled algorithm for automated diabetic retinopathy screening of 30 000 patients.

BACKGROUND/AIMS: Human grading of digital images from diabetic retinopathy (DR) screening programmes represents a significant challenge, due to the increasing prevalence of diabetes. We evaluate the performance of an automated artificial intelligence (AI) algorithm to triage retinal images from the English Diabetic Eye Screening Programme (DESP) into test-positive/technical failure versus test-negative, using human grading following a standard national protocol as the reference standard. METHODS: Retinal images from 30 405 consecutive screening episodes from three English DESPs were manually graded following a standard national protocol and by an automated process with machine learning enabled software, EyeArt v2.1. Screening performance (sensitivity, specificity) and diagnostic accuracy (95% CIs) were determined using human grades as the reference standard. RESULTS: Sensitivity (95% CIs) of EyeArt was 95.7% (94.8% to 96.5%) for referable retinopathy (human graded ungradable, referable maculopathy, moderate-to-severe non-proliferative or proliferative). This comprises sensitivities of 98.3% (97.3% to 98.9%) for mild-to-moderate non-proliferative retinopathy with referable maculopathy, 100% (98.7%,100%) for moderate-to-severe non-proliferative retinopathy and 100% (97.9%,100%) for proliferative disease. EyeArt agreed with the human grade of no retinopathy (specificity) in 68% (67% to 69%), with a specificity of 54.0% (53.4% to 54.5%) when combined with non-referable retinopathy. CONCLUSION: The algorithm demonstrated safe levels of sensitivity for high-risk retinopathy in a real-world screening service, with specificity that could halve the workload for human graders. AI machine learning and deep learning algorithms such as this can provide clinically equivalent, rapid detection of retinopathy, particularly in settings where a trained workforce is unavailable or where large-scale and rapid results are needed

Supergravity p-branes revisited: extra parameters, uniqueness, and topological censorship

We perform a complete integration of the Einstein-dilaton-antisymmetric form action describing black p-branes in arbitrary dimensions assuming the transverse space to be homogeneous and possessing spherical, toroidal or hyperbolic topology. The generic solution contains eight parameters satisfying one constraint. Asymptotically flat solutions form a five-parametric subspace, while conditions of regularity of the non-degenerate event horizon further restrict this number to three, which can be related to the mass and the charge densities and the asymptotic value of the dilaton. In the case of a degenerate horizon, this number is reduced by one. Our derivation constitutes a constructive proof of the uniqueness theorem for $p$-branes with the homogeneous transverse space. No asymptotically flat solutions with toroidal or hyperbolic transverse space within the considered class are shown to exist, which result can be viewed as a demonstration of the topological censorship for p-branes. From our considerations it follows, in particular, that some previously discussed p-brane-like solutions with extra parameters do not satisfy the standard conditions of asymptotic flatness and absence of naked singularities. We also explore the same system in presence of a cosmological constant, and derive a complete analytic solution for higher-dimensional charged topological black holes, thus proving their uniqueness.Comment: Revtex4, no figure

New Solution for Neutrino Masses and Leptogenesis in Adjoint SU(5)

We investigate baryogenesis via leptogenesis and generation of neutrino masses and mixings through the Type I plus Type III seesaw plus an one-loop mechanism in the context of Renormalizable Adjoint SU(5) theory. One light neutrino remains massless, because the contributions of three heavy Majorana fermions \rho_0, \rho_3 and \rho_8 to the neutrino mass matrix are not linearly independent. However none of these heavy fermions is decoupled from the generation of neutrino masses. This opens a new range in parameter space for successful leptogenesis, in particular, allows for inverted hierarchy of the neutrino masses.Comment: 16 pages, 4 figures; references added and typos fixe