Validation of Exercise Capacity as a Surrogate Endpoint in Exercise-Based Rehabilitation for Heart Failure: A Meta-Analysis of Randomized Controlled Trials

This is the final version. Available on open access from Elsevier via the DOI in this recordObjectives: This study sought to validate exercise capacity (EC) as a surrogate for mortality, hospitalization, and health-related quality of life (HRQOL). Background: EC is often used as a primary outcome in exercise-based cardiac rehabilitation (CR) trials of heart failure (HF) via direct cardiorespiratory assessment of maximum oxygen uptake (VO2peak) or through submaximal tests, such as the 6-min walk test (6MWT). Methods: After a systematic review, 31 randomized trials of exercise-based CR compared with no exercise control (4,784 HF patients) were included. Outcomes were pooled using random effects meta-analyses, and inverse variance weighted linear regression equations were fitted to estimate the relationship between the CR on EC and all-cause mortality, hospitalization, and HRQOL. Spearman correlation coefficient (ρ), R2 at trial level, and surrogate threshold effect (STE) were calculated. STE represents the intercept of the prediction band of the regression line with null effect on the final outcome. Results: Exercise-based CR is associated with positive effects on EC measured through VO2peak (+3.10 ml/kg/min; 95% confidence interval [CI]: 2.01 to 4.20) or 6MWT (+41.15 m; 95% CI: 16.68 to 65.63) compared to control. The analyses showed a low level of association between improvements in EC (VO2peak or 6MWT) and mortality and hospitalization. Moderate levels of correlation between EC with HRQOL were seen (e.g., R2 <52%; |ρ| < 0.72). Estimated STE was an increase of 5 ml/kg/min for VO2peak and 80 m for 6MWT to predict a significant improvement in HRQOL. Conclusions: The study results indicate that EC is a poor surrogate endpoint for mortality and hospitalization but has moderate validity as a surrogate for HRQOL. Further research is needed to confirm these findings across other HF interventions.National Institute for Health Research (NIHR)University of Exete

Analytic Metaphysics versus Naturalized Metaphysics: The Relevance of Applied Ontology

The relevance of analytic metaphysics has come under criticism: Ladyman & Ross, for instance, have suggested do discontinue the field. French & McKenzie have argued in defense of analytic metaphysics that it develops tools that could turn out to be useful for philosophy of physics. In this article, we show first that this heuristic defense of metaphysics can be extended to the scientific field of applied ontology, which uses constructs from analytic metaphysics. Second, we elaborate on a parallel by French & McKenzie between mathematics and metaphysics to show that the whole field of analytic metaphysics, being useful not only for philosophy but also for science, should continue to exist as a largely autonomous field

Coherent Parton Showers with Local Recoils

We outline a new formalism for dipole-type parton showers which maintain exact energy-momentum conservation at each step of the evolution. Particular emphasis is put on the coherence properties, the level at which recoil effects do enter and the role of transverse momentum generation from initial state radiation. The formulated algorithm is shown to correctly incorporate coherence for soft gluon radiation. Furthermore, it is well suited for easing matching to next-to-leading order calculations.Comment: 24 pages, 3 figure

Cascades with Adjoint Matter: Adjoint Transitions

A large class of duality cascades based on quivers arising from non-isolated singularities enjoy adjoint transitions - a phenomenon which occurs when the gauge coupling of a node possessing adjoint matter is driven to strong coupling in a manner resulting in a reduction of rank in the non-Abelian part of the gauge group and a subsequent flow to weaker coupling. We describe adjoint transitions in a simple family of cascades based on a Z2-orbifold of the conifold using field theory. We show that they are dual to Higgsing and produce varying numbers of U(1) factors, moduli, and monopoles in a manner which we calculate. This realizes a large family of cascades which proceed through Seiberg duality and Higgsing. We briefly describe the supergravity limit of our analysis, as well as a prescription for treating more general theories. A special role is played by N=2 SQCD. Our results suggest that additional light fields are typically generated when UV completing certain constructions of spontaneous supersymmetry breaking into cascades, potentially leading to instabilities.Comment: 29 pages, a few typos fixed, improved discussion, added figure; now there is 1 figur

Triglyceride-containing lipoprotein sub-fractions and risk of coronary heart disease and stroke: A prospective analysis in 11,560 adults

AIMS: Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke. METHODS: Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure. RESULTS: The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HDL-C). Thirteen sub-fractions were positively associated with coronary heart disease (odds ratio in the range 1.12 to 1.22), with the effect estimates for coronary heart disease being comparable in subgroup analysis of participants with and without type 2 diabetes, and were attenuated after adjustment for HDL-C and LDL-C. There was no evidence for a clear association of any triglyceride lipoprotein sub-fraction with stroke. CONCLUSIONS: Triglyceride sub-fractions are associated with increased risk of coronary heart disease but not stroke, with attenuation of effects on adjustment for HDL-C and LDL-C

General Argyres-Douglas Theory

We construct a large class of Argyres-Douglas type theories by compactifying six dimensional (2,0) A_N theory on a Riemann surface with irregular singularities. We give a complete classification for the choices of Riemann surface and the singularities. The Seiberg-Witten curve and scaling dimensions of the operator spectrum are worked out. Three dimensional mirror theory and the central charges a and c are also calculated for some subsets, etc. Our results greatly enlarge the landscape of N=2 superconformal field theory and in fact also include previous theories constructed using regular singularity on the sphere.Comment: 55 pages, 20 figures, minor revision and typos correcte

Nonlinear Localization in Metamaterials

Metamaterials, i.e., artificially structured ("synthetic") media comprising weakly coupled discrete elements, exhibit extraordinary properties and they hold a great promise for novel applications including super-resolution imaging, cloaking, hyperlensing, and optical transformation. Nonlinearity adds a new degree of freedom for metamaterial design that allows for tuneability and multistability, properties that may offer altogether new functionalities and electromagnetic characteristics. The combination of discreteness and nonlinearity may lead to intrinsic localization of the type of discrete breather in metallic, SQUID-based, and ${\cal PT}-$symmetric metamaterials. We review recent results demonstrating the generic appearance of breather excitations in these systems resulting from power-balance between intrinsic losses and input power, either by proper initialization or by purely dynamical procedures. Breather properties peculiar to each particular system are identified and discussed. Recent progress in the fabrication of low-loss, active and superconducting metamaterials, makes the experimental observation of breathers in principle possible with the proposed dynamical procedures.Comment: 19 pages, 14 figures, Invited (Review) Chapte

Measuring every particle's size from three-dimensional imaging experiments

Often experimentalists study colloidal suspensions that are nominally monodisperse. In reality these samples have a polydispersity of 4-10%. At the level of an individual particle, the consequences of this polydispersity are unknown as it is difficult to measure an individual particle size from microscopy. We propose a general method to estimate individual particle radii within a moderately concentrated colloidal suspension observed with confocal microscopy. We confirm the validity of our method by numerical simulations of four major systems: random close packing, colloidal gels, nominally monodisperse dense samples, and nominally binary dense samples. We then apply our method to experimental data, and demonstrate the utility of this method with results from four case studies. In the first, we demonstrate that we can recover the full particle size distribution {\it in situ}. In the second, we show that accounting for particle size leads to more accurate structural information in a random close packed sample. In the third, we show that crystal nucleation occurs in locally monodisperse regions. In the fourth, we show that particle mobility in a dense sample is correlated to the local volume fraction.Comment: 7 pages, 5 figure

Theorems on existence and global dynamics for the Einstein equations

This article is a guide to theorems on existence and global dynamics of solutions of the Einstein equations. It draws attention to open questions in the field. The local-in-time Cauchy problem, which is relatively well understood, is surveyed. Global results for solutions with various types of symmetry are discussed. A selection of results from Newtonian theory and special relativity that offer useful comparisons is presented. Treatments of global results in the case of small data and results on constructing spacetimes with prescribed singularity structure or late-time asymptotics are given. A conjectural picture of the asymptotic behaviour of general cosmological solutions of the Einstein equations is built up. Some miscellaneous topics connected with the main theme are collected in a separate section.Comment: Submitted to Living Reviews in Relativity, major update of Living Rev. Rel. 5 (2002)

Coherent quantum phase slip

A hundred years after discovery of superconductivity, one fundamental prediction of the theory, the coherent quantum phase slip (CQPS), has not been observed. CQPS is a phenomenon exactly dual to the Josephson effect: whilst the latter is a coherent transfer of charges between superconducting contacts, the former is a coherent transfer of vortices or fluxes across a superconducting wire. In contrast to previously reported observations of incoherent phase slip, the CQPS has been only a subject of theoretical study. Its experimental demonstration is made difficult by quasiparticle dissipation due to gapless excitations in nanowires or in vortex cores. This difficulty might be overcome by using certain strongly disordered superconductors in the vicinity of the superconductor-insulator transition (SIT). Here we report the first direct observation of the CQPS in a strongly disordered indium-oxide (InOx) superconducting wire inserted in a loop, which is manifested by the superposition of the quantum states with different number of fluxes. Similarly to the Josephson effect, our observation is expected to lead to novel applications in superconducting electronics and quantum metrology.Comment: 14 pages, 3 figure