Prognostic variables and scores identifying the last year of life in COPD: a systematic review protocol

Introduction People living with advanced chronic obstructive pulmonary disease (COPD) suffer from significant morbidity, reduced quality of life and high mortality, and are likely to benefit from many aspects of a palliative care approach. Prognostic estimates are a meaningful part of decision-making and better evidence for such estimates would facilitate advance care planning. We aim to provide quality evidence on known prognostic variables and scores which predict a prognosis in COPD of <12 months for use in the community. Methods and analysis We will conduct a systematic review of randomised or quasi-randomised controlled trials, prospective and retrospective longitudinal cohort and case–control studies on prognostic variables, multivariate scores or models for COPD. The search will cover the period up to April 2016. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with data extraction using fields from the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist for multivariate models, and study quality will be assessed using a modified version of the Quality In Prognosis Studies (QUIPS) tool. Ethics and dissemination The results will be disseminated through peer-reviewed publications and national and international conference presentations

The Marangoni flow of soluble amphiphiles

Surfactant distribution heterogeneities at a fluid/fluid interface trigger the Marangoni effect, i.e. a bulk flow due to a surface tension gradient. The influence of surfactant solubility in the bulk on these flows remains incompletely characterized. Here we study Marangoni flows sustained by injection of hydrosoluble surfactants at the air/water interface. We show that the flow extent increases with a decrease of the critical micelle concentration, i.e. the concentration at which these surfactants self-assemble in water. We document the universality of the surface velocity field and predict scaling laws based on hydrodynamics and surfactant physicochemistry that capture the flow features.Comment: 5 pages, 4 figures, submitte

The mean curvature at the first singular time of the mean curvature flow

Consider a family of smooth immersions $F(\cdot,t): M^n\to \mathbb{R}^{n+1}$ of closed hypersurfaces in $\mathbb{R}^{n+1}$ moving by the mean curvature flow $\frac{\partial F(p,t)}{\partial t} = -H(p,t)\cdot \nu(p,t)$, for $t\in [0,T)$. We prove that the mean curvature blows up at the first singular time $T$ if all singularities are of type I. In the case $n = 2$, regardless of the type of a possibly forming singularity, we show that at the first singular time the mean curvature necessarily blows up provided that either the Multiplicity One Conjecture holds or the Gaussian density is less than two. We also establish and give several applications of a local regularity theorem which is a parabolic analogue of Choi-Schoen estimate for minimal submanifolds

Rapid Evolution of BRCA1 and BRCA2 in Humans and Other Primates

The maintenance of chromosomal integrity is an essential task of every living organism and cellular repair mechanisms exist to guard against insults to DNA. Given the importance of this process, it is expected that DNA repair proteins would be evolutionarily conserved, exhibiting very minimal sequence change over time. However, BRCA1, an essential gene involved in DNA repair, has been reported to be evolving rapidly despite the fact that many protein-altering mutations within this gene convey a significantly elevated risk for breast and ovarian cancers. Results: To obtain a deeper understanding of the evolutionary trajectory of BRCA1, we analyzed complete BRCA1 gene sequences from 23 primate species. We show that specific amino acid sites have experienced repeated selection for amino acid replacement over primate evolution. This selection has been focused specifically on humans and our closest living relatives, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). After examining BRCA1 polymorphisms in 7 bonobo, 44 chimpanzee, and 44 rhesus macaque (Macaca mulatta) individuals, we find considerable variation within each of these species and evidence for recent selection in chimpanzee populations. Finally, we also sequenced and analyzed BRCA2 from 24 primate species and find that this gene has also evolved under positive selection. Conclusions: While mutations leading to truncated forms of BRCA1 are clearly linked to cancer phenotypes in humans, there is also an underlying selective pressure in favor of amino acid-altering substitutions in this gene. A hypothesis where viruses are the drivers of this natural selection is discussed.National Institutes of Health R01-GM-093086, 8U42OD011197-13National Science Foundation BCS-07115972Burroughs Wellcome FundMolecular Bioscience

Nucleon-Meson Coupling Constants and Form Factors in the Quark Model

We demonstrate the calculation of the coupling constants and form factors required by effective hadron lagrangians using the quark model. These relations follow from equating expressions for strong transition amplitudes in the two approaches. As examples we derive the NNm nucleon-meson coupling constants and form factors for m = pi, eta, eta', sigma, a_0, omega and rho, using harmonic oscillator quark model meson and baryon wavefunctions and the 3P0 decay model; this is a first step towards deriving a quark-based model of the NN force at all separations. This technique should be useful in the application of effective lagrangians to processes in which the lack of data precludes the direct determination of coupling constants and form factors from experiment.Comment: 7 pages, 4 figures, 1 tabl

Cosmic rays beyond the boundary of the heliosphere

In August of 2012 the Voyager 1 space probe has left the solar-wind bubble of ionized gas we call the heliosphere and entered the denser and colder environment of the interstellar cloud surrounding the solar system. Energetic charged particles underwent dramatic changes past the heliopause: the heliospheric ions disappeared completely, while the galactic cosmic rays were for the first time measured in their unmodulated state. The interstellar medium turned out to be almost entirely devoid of turbulent magnetic fluctuations, therefore the transport of cosmic rays is governed by a large-scale geometry of the magnetic field. We discuss observations of heliospheric ions, including anomalous cosmic rays, near the heliopause transition, and propose interpretations of the measured intensities and pitch-angle distributions based on gradient drift in a weakly nonuniform magnetic field. The heliopause transition appears to be permeated by magnetic flux tubes connected to the interstellar space and facilitating particle escape. These flux tubes may be a product of interchange instability driven by a plasma pressure gradient across the heliopause. The curvature of magnetic field lines and the anti-sunward gradient in plasma kinetic pressure provide conditions favorable for an interchange. The two flux tube crossings by the spacecraft allowed an indirect measurement of the plasma radial velocity near the heliopause

Parametrisations of the D -> K l nu form factor and the determination of \hat{g}

The vector form factor f_+(t) of the semileptonic decay D -> K l nu, measured recently with a high accuracy, can be used to determine the strong coupling constant g_{D_s^* D K}. The latter is related to the normalised coupling \hat{g} releveant in heavy-meson chiral perturbation theory. This determination relies on the estimation of the residue of the form factor at the D_s^* pole and thus on an extrapolation of the form factor in the unphysical region (m_D-m_K)^2<t<(m_D+m_K)^2. We test this extrapolation for several parametrisations of the form factors by determining the value of \hat{g}, whose value can be compared to other (experimental and theoretical) estimates. Several unsophisticated parametrisations, differing by the amount of physical information that they embed, are shown to pass this test. An apparently more elaborated parametrisation of form factors, the so-called z-expansion, is at variance with the other models, and we point out some significant shortcomings of this parametrisation for the problem under consideration.Comment: 16 pages, 2 figures. A few references added. Accepted for publication in JoP

Energetic Particle Anisotropies at the Heliospheric Boundary. II. Transient Features and Rigidity Dependence

In the preceding paper, we showed that large second-order anisotropies of heliospheric ions measured by the Voyager 1 space probe during the August 2012 boundary crossing event could be explained by a magnetic shear across the heliopause preventing particles streaming along the magnetic field from escaping the inner heliosheath. According to Stone et al., the penetration distance of heliospheric ions into the outer heliosheath had a strong dependence on the particle's Larmor radius. By comparing hydrogen, helium, and oxygen ions with the same energy per nucleon, these authors argued that this effect must be attributed to larger cyclotron radii of heavier species rather than differences in velocity. We propose that gradient drift in a nonuniform magnetic field was the cause of both the large second-order anisotropies and the spatial differentiation based on the ion's rigidity. A latitudinal gradient of magnetic field strength of about 10% per AU between 2012.7 and 2012.9 could have provided drift motion sufficient to match both LECP and CRS Voyager 1 observations. We explain the transient intensity dropout observed prior to the heliocliff using flux tube structures embedded in the heliosheath and magnetically connected to interstellar space. Finally, this paper reports a new indirect measurement of the plasma radial velocity at the heliopause on the basis of the time difference between two cosmic-ray telescopes measuring the same intensity dropout

First Order Vortex Dynamics

A non-dissipative model for vortex motion in thin superconductors is considered. The Lagrangian is a Galilean invariant version of the Ginzburg--Landau model for time-dependent fields, with kinetic terms linear in the first time derivatives of the fields. It is shown how, for certain values of the coupling constants, the field dynamics can be reduced to first order differential equations for the vortex positions. Two vortices circle around one another at constant speed and separation in this model.Comment: 22pages, no figures, tex fil

On accuracy of PDF divergence estimators and their applicability to representative data sampling

Generalisation error estimation is an important issue in machine learning. Cross-validation traditionally used for this purpose requires building multiple models and repeating the whole procedure many times in order to produce reliable error estimates. It is however possible to accurately estimate the error using only a single model, if the training and test data are chosen appropriately. This paper investigates the possibility of using various probability density function divergence measures for the purpose of representative data sampling. As it turned out, the first difficulty one needs to deal with is estimation of the divergence itself. In contrast to other publications on this subject, the experimental results provided in this study show that in many cases it is not possible unless samples consisting of thousands of instances are used. Exhaustive experiments on the divergence guided representative data sampling have been performed using 26 publicly available benchmark datasets and 70 PDF divergence estimators, and their results have been analysed and discussed