Do antioxidants (vitamins C, E) improve outcomes in patients with coronary artery disease?

Antioxidant supplements of vitamins E and C do not reduce cardiovascular death in people with coronary artery disease. Vitamin E supplementation, in a variety of doses, does not decrease the incidence of cardiovascular or all-cause mortality (grade of recommendation: A, 4 high quality randomized controlled trials [RCTs]). There is no evidence that vitamin C decreases mortality in patients at risk for coronary disease (grade of recommendation: A, meta-analysis of 3 small RCTs). Combination antioxidant regimens (Vitamins E, C, and betacarotene) seem safe, but do not decrease mortality or incidence of major coronary and vascular events (grade recommendation: A, 1 high-quality RCT)

A measure of majorisation emerging from single-shot statistical mechanics

The use of the von Neumann entropy in formulating the laws of thermodynamics has recently been challenged. It is associated with the average work whereas the work guaranteed to be extracted in any single run of an experiment is the more interesting quantity in general. We show that an expression that quantifies majorisation determines the optimal guaranteed work. We argue it should therefore be the central quantity of statistical mechanics, rather than the von Neumann entropy. In the limit of many identical and independent subsystems (asymptotic i.i.d) the von Neumann entropy expressions are recovered but in the non-equilbrium regime the optimal guaranteed work can be radically different to the optimal average. Moreover our measure of majorisation governs which evolutions can be realized via thermal interactions, whereas the nondecrease of the von Neumann entropy is not sufficiently restrictive. Our results are inspired by single-shot information theory.Comment: 54 pages (15+39), 9 figures. Changed title / changed presentation, same main results / added minor result on pure bipartite state entanglement (appendix G) / near to published versio

Robustness and Generalization

We derive generalization bounds for learning algorithms based on their robustness: the property that if a testing sample is "similar" to a training sample, then the testing error is close to the training error. This provides a novel approach, different from the complexity or stability arguments, to study generalization of learning algorithms. We further show that a weak notion of robustness is both sufficient and necessary for generalizability, which implies that robustness is a fundamental property for learning algorithms to work

Comparative Skull Morphology of Uropeltid Snakes (Alethinophidia: Uropeltidae) with Special Reference to Disarticulated Elements and Variation

Uropeltids form a diverse clade of highly derived, fossorial snakes that, because of their phylogenetic position among other alethinophidian lineages, may play a key role in understanding the early evolution of cranial morphology in snakes. We include detailed osteological descriptions of crania and mandibles for eight uropeltid species from three nominal genera (Uropeltis, Rhinophis, and Brachyophidium) and emphasize disarticulated elements and the impact of intraspecific variation on previously proposed morphological characters used for phylogenetic analysis. Preliminary analysis of phylogenetic relationships strongly supports a clade composed exclusively of species of Plectrurus, Uropeltis, and Rhinophis. However, monophyly of each of those genera and Melanophidium is not upheld. There is moderate support that Sri Lankan species (e.g., Rhinophis and Uropeltis melanogaster) are monophyletic with respect to Indian uropeltids. Previously proposed characters that are phylogenetically informative include the shape of the nasals, length of the occipital condyle, level of development of the posteroventral process of the dentary, and participation of the parietal in the optic foramen. Additionally, thirty new features that may be systematically informative are identified and described, but were not verified for their utility. Such verification must await availability of additional disarticulated cranial material from a larger sample of taxa. All characters require further testing through increased focus on sources and patterns of intraspecific variation, inclusion of broader taxonomic samples in comparative studies, and exploration of skeletal development, sexual dimorphism, and biogeographic patterns. Additionally, trends in the relative enlargement of the sensory capsules, reduction in cranial ossification and dentition, fusion of elements, and the appearance of novel morphological conditions, such as the structure and location of the suspensorium, may be related to fossoriality and miniaturization in some uropeltid taxa, and may complicate analysis of relationships within Uropeltidae and among alethinophidian snakes

Phylogeny of snakes (Serpentes): combining morphological and molecular data in likelihood Bayesian and parsimony analyses

Copyright © 2007 The Natural history MuseumThe phylogeny of living and fossil snakes is assessed using likelihood and parsimony approaches and a dataset combining 263 morphological characters with mitochondrial (2693 bp) and nuclear (1092 bp) gene sequences. The ‘no common mechanism’ (NCMr) and ‘Markovian’ (Mkv) models were employed for the morphological partition in likelihood analyses; likelihood scores in the NCMr model were more closely correlated with parsimony tree lengths. Both models accorded relatively less weight to the molecular data than did parsimony, with the effect being milder in the NCMr model. Partitioned branch and likelihood support values indicate that the mtDNA and nuclear gene partitions agree more closely with each other than with morphology. Despite differences between data partitions in phylogenetic signal, analytic models, and relative weighting, the parsimony and likelihood analyses all retrieved the following widely accepted groups: scolecophidians, alethinophidians, cylindrophiines, macrostomatans (sensu lato) and caenophidians. Anilius alone emerged as the most basal alethinophidian; the combined analyses resulted in a novel and stable position of uropeltines and cylindrophiines as the second-most basal clade of alethinophidians. The limbed marine pachyophiids, along with Dinilysia and Wonambi, were always basal to all living snakes. Other results stable in all combined analyses include: Xenopeltis and Loxocemus were sister taxa (fide morphology) but clustered with pythonines (fide molecules), and Ungaliophis clustered with a boine-erycine clade (fide molecules). Tropidophis remains enigmatic; it emerges as a basal alethinophidian in the parsimony analyses (fide molecules) but a derived form in the likelihood analyses (fide morphology), largely due to the different relative weighting accorded to data partitions.Michael S. Y. Lee, Andrew F. Hugall, Robin Lawson & John D. Scanlo

Reference values for healthy human myocardium using a T1 mapping methodology: results from the International T1 Multicenter cardiovascular magnetic resonance study

BACKGROUND:T1 mapping is a robust and highly reproducible application to quantify myocardial relaxation of longitudinal magnetisation. Available T1 mapping methods are presently site and vendor specific, with variable accuracy and precision of T1 values between the systems and sequences. We assessed the transferability of a T1 mapping method and determined the reference values of healthy human myocardium in a multicenter setting.METHODS:Healthy subjects (n = 102; mean age 41 years (range 17-83), male, n = 53 (52%)), with no previous medical history, and normotensive low risk subjects (n=113) referred for clinical cardiovascular magnetic resonance (CMR) were examined. Further inclusion criteria for all were absence of regular medication and subsequently normal findings of routine CMR. All subjects underwent T1 mapping using a uniform imaging set-up (modified Look- Locker inversion recovery, MOLLI, using scheme 3(3)3(3)5)) on 1.5 Tesla (T) and 3 T Philips scanners. Native T1-maps were acquired in a single midventricular short axis slice and repeated 20 minutes following gadobutrol. Reference values were obtained for native T1 and gadolinium-based partition coefficients, lambda and extracellular volume fraction (ECV) in a core lab using standardized postprocessing.RESULTS:In healthy controls, mean native T1 values were 950 +/- 21 msec at 1.5 T and 1052 +/- 23 at 3 T. lambda and ECV values were 0.44 +/- 0.06 and 0.25 +/- 0.04 at 1.5 T, and 0.44 +/- 0.07 and 0.26 +/- 0.04 at 3 T, respectively. There were no significant differences between healthy controls and low risk subjects in routine CMR parameters and T1 values. The entire cohort showed no correlation between age, gender and native T1. Cross-center comparisons of mean values showed no significant difference for any of the T1 indices at any field strength. There were considerable regional differences in segmental T1 values. lambda and ECV were found to be dose dependent. There was excellent inter- and intraobserver reproducibility for measurement of native septal T1.CONCLUSION:We show transferability for a unifying T1 mapping methodology in a multicenter setting. We provide reference ranges for T1 values in healthy human myocardium, which can be applied across participating sites

Rationale and design of the United Kingdom Heart Failure with Preserved Ejection Fraction Registry

\ua9 Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.Objective: Heart failure with preserved ejection fraction (HFpEF) is a common heterogeneous syndrome that remains imprecisely defined and consequently has limited treatment options and poor outcomes. Methods: The UK Heart Failure with Preserved Ejection Fraction Registry (UK HFpEF) is a prospective data-enabled cohort and platform study. The study will develop a large, highly characterised cohort of patients with HFpEF. A biobank will be established. Deep clinical phenotyping, imaging, multiomics and centrally held national electronic health record data will be integrated at scale, in order to reclassify HFpEF into distinct subgroups, improve understanding of disease mechanisms and identify new biological pathways and molecular targets. Together, these will form the basis for developing diagnostics and targeted therapeutics specific to subgroups. It will be a platform for more effective and efficient trials, focusing on subgroups in whom targeted interventions are expected to be effective, with consent in place to facilitate rapid recruitment, and linkage for follow-up. Patients with a diagnosis of HFpEF made by a heart failure specialist, who have had natriuretic peptide levels measured and a left ventricular ejection fraction >40% are eligible. Patients with an ejection fraction between 40% and 49% will be limited to no more than 25% of the cohort. Conclusions: UK HFpEF will develop a rich, multimodal data resource to enable the identification of disease endotypes and develop more effective diagnostic strategies, precise risk stratification and targeted therapeutics. Trial registration number: NCT05441839