Experimentally-calibrated population of models predicts and explains inter-subject variability in cardiac cellular\ud electrophysiology

Cellular and ionic causes of variability in the electrophysiological activity of hearts from individuals of the same species are unknown. However, improved understanding of this variability is key to enable prediction of the response of specific hearts to disease and therapies. Limitations of current mathematical modeling and experimental techniques hamper our ability to provide insight into variability. Here we describe a methodology to unravel the ionic determinants of inter-subject variability exhibited in experimental recordings, based on the construction and calibration of populations of models. We illustrate the methodology through its application to rabbit Purkinje preparations, due to their importance in arrhythmias and safety pharmacology assessment. We consider a set of equations describing the biophysical processes underlying rabbit Purkinje electrophysiology and we construct a population of over 10,000 models by randomly assigning specific parameter values corresponding to ionic current conductances and kinetics. We calibrate the model population by closely comparing simulation output and experimental recordings at three pacing frequencies. We show that 213 of the 10,000 candidate models are fully consistent with the experimental dataset. Ionic properties in the 213 models cover a wide range of values, including differences up to ±100% in several conductances. Partial correlation analysis shows that particular combinations of ionic properties determine the precise shape, amplitude and rate dependence of specific action potentials. Finally, we demonstrate that the population of models calibrated using data obtained under physiological conditions quantitatively predicts the action potential duration prolongation caused by exposure to four concentrations of the potassium channel blocker dofetilide

Bimanual wheelchair propulsion by people with severe hemiparesis after stroke

Purpose: Individuals who require manual wheelchairs after stroke are typically taught to ambulate with compensatory propulsion (i.e., using their non-paretic arm and foot), risking disuse of the paretic arm. We investigated whether stroke survivors can instead ambulate in a bimanual, lever-driven wheelchair that requires the paretic arm to contribute half the propulsive input. Materials and methods: Seventeen individuals with chronic stroke and severe hemiparesis (upper extremity Fugl–Meyer scores between 10 and 24) participated across two experiments. In the first experiment, participants (n = 12) ambulated in straight paths. In the second experiment, participants (n = 12) also performed turns, using an improved version of the wheelchair that incorporated handbrakes. Twelve unimpaired controls also completed the second experiment. Motion capture and EMG were used to compare biomechanics between groups. Results: Altogether, 15 of 17 participants with stroke could ambulate 30 m in straight paths, and 9 of 12 could turn 1800° entirely under the power of their paretic arm. Participants with stroke exhibited largely healthy biomechanics, with minimal shoulder hiking/leaning or trunk inclination. Their arm muscle EMG patterns were similar to those used by unimpaired participants, excepting delayed elbow extensor activation. Conclusions: Individuals with severe arm impairment in the chronic stage of stroke retain sufficient strength and coordination with their paretic arm to manoeuvre bimanual, lever-driven wheelchairs. We suggest bimanual, lever-driven propulsion should be explored in stroke rehabilitation practice as an alternative to compensatory wheelchair propulsion, as it has the potential to exercise healthy movement synergies, which may in turn help drive use-dependent motor recovery.Implications for rehabilitation Severe arm impairment arising after stroke does not generally eliminate the motor dexterity needed to bimanually propel a manual wheelchair, provided that the wheelchair is modified to remove the requirement to grasp and release the push rim. Such exercise appears a good candidate to facilitate rehabilitation outcomes because it depends on alternating muscle activity and improving elbow extension. Such wheelchair propulsion involves largely normal biomechanics; shoulder hiking and leaning are absent and trunk inclination is rare

TUBERCULOSE: UMA REVISÃO DE LITERATURA

A Tuberculose (TB) doença é causada pelo Mycobacterium tuberculosis, tendo as vias aéreas como principal via de transmissão, apresentando-se sob as formas clínicas pulmonar e extrapulmonar. A via de infecção tuberculosa é quase sempre inalatória. A doença acomete principalmente pessoas na faixa etária entre 20 e 49 anos. A incidência no gênero masculino normalmente é superior à do gênero feminino e, a forma pulmonar é a forma clínica da doença que mais acomete a população. O padrão para o diagnóstico da TB é a baciloscopia e cultura com a identificação da espécie. Segundo o Ministério da Saúde, o esquema básico de quimioprofilaxia para adultos e adolescentes é realizado por um período de seis meses, composto pelos seguintes medicamentos: Rifampicina (R), Isoniazida (H), Pirazinamida (Z) e Etambutol (E). De acordo com Ministério de Saúde, existem duas medidas preventivas eficazes contra a tuberculose: a vacinação e a quimioprofilaxia. A vacinação com a BCG é a medida mais comum para prevenção da TB é indicada para crianças de 0 a 4 anos de idade e a proteção imunitária pode manter-se por 10 a 15 anos. O Programa Nacional de Controle da Tuberculose é responsável pela redução das fontes de infecção, diagnóstico, tratamento e pela distribuição dos medicamentos que são fornecidos gratuitamente a todos os doentes registrados e acompanhados nas Unidades de Saúde, levando à consequente redução da incidência, prevalência e mortalidade causada pela TB.Palavras-chave: Tuberculose. M. tuberculosis. Diagnóstico. Tratamento

Affine Toda model coupled to matter and the string tension in QCD2_{2}

The $sl(2)$ affine Toda model coupled to matter (ATM) is shown to describe various features, such as the spectrum and string tension, of the low-energy effective Lagrangian of QCD$_{2}$ (one flavor and $N$ colors). The corresponding string tension is computed when the dynamical quarks are in the {\sl fundamental} representation of SU(N) and in the {\sl adjoint} representation of SU(2).Comment: LaTex, 10 pages. Revised version to appear in Phys. Rev.

Study of Interplanetary Magnetic Field with Ground State Alignment

We demonstrate a new way of studying interplanetary magnetic field -- Ground State Alignment (GSA). Instead of sending thousands of space probes, GSA allows magnetic mapping with any ground telescope facilities equipped with spectropolarimeter. The polarization of spectral lines that are pumped by the anisotropic radiation from the Sun is influenced by the magnetic realignment, which happens for magnetic field (<1G). As a result, the linear polarization becomes an excellent tracer of the embedded magnetic field. The method is illustrated by our synthetic observations of the Jupiter's Io and comet Halley. Polarization at each point was constructed according to the local magnetic field detected by spacecrafts. Both spatial and temporal variations of turbulent magnetic field can be traced with this technique as well. The influence of magnetic field on the polarization of scattered light is discussed in detail. For remote regions like the IBEX ribbons discovered at the boundary of interstellar medium, GSA provides a unique diagnostics of magnetic field.Comment: 11 pages, 19 figures, published in Astrophysics and Space Scienc

A parametrization of the growth index of matter perturbations in various Dark Energy models and observational prospects using a Euclid-like survey

We provide exact solutions to the cosmological matter perturbation equation in a homogeneous FLRW universe with a vacuum energy that can be parametrized by a constant equation of state parameter $w$ and a very accurate approximation for the Ansatz $w(a)=w_0+w_a(1-a)$. We compute the growth index \gamma=\log f(a)/\log\Om_m(a), and its redshift dependence, using the exact and approximate solutions in terms of Legendre polynomials and show that it can be parametrized as $\gamma(a)=\gamma_0+\gamma_a(1-a)$ in most cases. We then compare four different types of dark energy (DE) models: $w\Lambda$CDM, DGP, $f(R)$ and a LTB-large-void model, which have very different behaviors at z\gsim1. This allows us to study the possibility to differentiate between different DE alternatives using wide and deep surveys like Euclid, which will measure both photometric and spectroscopic redshifts for several hundreds of millions of galaxies up to redshift $z\simeq 2$. We do a Fisher matrix analysis for the prospects of differentiating among the different DE models in terms of the growth index, taken as a given function of redshift or with a principal component analysis, with a value for each redshift bin for a Euclid-like survey. We use as observables the complete and marginalized power spectrum of galaxies $P(k)$ and the Weak Lensing (WL) power spectrum. We find that, using $P(k)$, one can reach (2%, 5%) errors in $(w_0, w_a)$, and (4%, 12%) errors in $(\gamma_0, \gamma_a)$, while using WL we get errors at least twice as large. These estimates allow us to differentiate easily between DGP, $f(R)$ models and $\Lambda$CDM, while it would be more difficult to distinguish the latter from a variable equation of state parameter or LTB models using only the growth index.}Comment: 29 pages, 7 figures, 6 table

A new approach to cosmological perturbations in f(R) models

We propose an analytic procedure that allows to determine quantitatively the deviation in the behavior of cosmological perturbations between a given f(R) modified gravity model and a LCDM reference model. Our method allows to study structure formation in these models from the largest scales, of the order of the Hubble horizon, down to scales deeply inside the Hubble radius, without employing the so-called "quasi-static" approximation. Although we restrict our analysis here to linear perturbations, our technique is completely general and can be extended to any perturbative order.Comment: 21 pages, 2 figures; Revised version according to reviewer's suggestions; Typos corrected; Added Reference

Short-Baseline Neutrino Oscillations at a Neutrino Factory

Within the framework of three-neutrino and four-neutrino scenarios that can describe the results of the LSND experiment, we consider the capabilities of short baseline neutrino oscillation experiments at a neutrino factory. We find that, when short baseline (L \alt 100 km) neutrino factory measurements are used together with other accelerator-based oscillation results, the complete three-neutrino parameter space can best be determined by measuring the rate of $\nu_e \to \nu_\tau$ oscillations, and measuring CP violation with either $\nu_e \to \nu_\mu$ or $\nu_\mu \to \nu_\tau$ oscillations (including the corresponding antineutrino channels). With measurements of CP violation in both $\nu_e \to \nu_\mu$ and $\nu_\mu \to \nu_\tau$ it may be possible to distinguish between the three- and four-neutrino cases.Comment: 16 pages, Revtex (single-spaced), 8 postscript figures, uses epsf.st

Threats to the validity of the Collegiate Learning Assessment (CLA+) as a measure of critical thinking skills and implications for Learning Gain

The University of Reading Learning Gain project is a three-year longitudinal project to test and evaluate a range of available methodologies and to draw conclusions on what might be the right combination of instruments for the measurement of Learning Gain in higher education. This paper analyses the validity of a measure of critical thinking skills, the Collegiate Learning Assessment (CLA+) and the implications of using this standardised test as a proxy for Learning Gain. The paper reviews five inferences regarding the interpretations and use of test scores: construct representation, scoring, generalisation, extrapolation and decision-making. Each section reviews some of the available evidence in support of the claims the CLA+ makes and the threats to their validity. The possible impact of these issues on Learning Gain in the UK is considered