Estimating glomerular filtration rate in acute coronary syndromes: Different equations, different mortality risk prediction

AIMS: Renal dysfunction is a powerful predictor of adverse outcomes in patients hospitalized for acute coronary syndrome. Three new glomerular filtration rate (GFR) estimating equations recently emerged, based on serum creatinine (CKD-EPIcreat), serum cystatin C (CKD-EPIcyst) or a combination of both (CKD-EPIcreat/cyst), and they are currently recommended to confirm the presence of renal dysfunction. Our aim was to analyse the predictive value of these new estimated GFR (eGFR) equations regarding mid-term mortality in patients with acute coronary syndrome, and compare them with the traditional Modification of Diet in Renal Disease (MDRD-4) formula. METHODS AND RESULTS: 801 patients admitted for acute coronary syndrome (age 67.3±13.3 years, 68.5% male) and followed for 23.6±9.8 months were included. For each equation, patient risk stratification was performed based on eGFR values: high-risk group (eGFR<60ml/min per 1.73m2) and low-risk group (eGFR⩾60ml/min per 1.73m2). The predictive performances of these equations were compared using area under each receiver operating characteristic curves (AUCs). Overall risk stratification improvement was assessed by the net reclassification improvement index. The incidence of the primary endpoint was 18.1%. The CKD-EPIcyst equation had the highest overall discriminate performance regarding mid-term mortality (AUC 0.782±0.20) and outperformed all other equations (ρ<0.001 in all comparisons). When compared with the MDRD-4 formula, the CKD-EPIcyst equation accurately reclassified a significant percentage of patients into more appropriate risk categories (net reclassification improvement index of 11.9% (p=0.003)). The CKD-EPIcyst equation added prognostic power to the Global Registry of Acute Coronary Events (GRACE) score in the prediction of mid-term mortality. CONCLUSION: The CKD-EPIcyst equation provides a novel and improved method for assessing the mid-term mortality risk in patients admitted for acute coronary syndrome, outperforming the most widely used formula (MDRD-4), and improving the predictive value of the GRACE score. These results reinforce the added value of cystatin C as a risk marker in these patients.

Dynamic instabilities in scalar neural field equations with space-dependent delays

In this paper we consider a class of scalar integral equations with a form of space-dependent delay. These non-local models arise naturally when modelling neural tissue with active axons and passive dendrites. Such systems are known to support a dynamic (oscillatory) Turing instability of the homogeneous steady state. In this paper we develop a weakly nonlinear analysis of the travelling and standing waves that form beyond the point of instability. The appropriate amplitude equations are found to be the coupled mean-field Ginzburg-Landau equations describing a Turing-Hopf bifurcation with modulation group velocity of O(1). Importantly we are able to obtain the coefficients of terms in the amplitude equations in terms of integral transforms of the spatio-temporal kernels defining the neural field equation of interest. Indeed our results cover not only models with axonal or dendritic delays but those which are described by a more general distribution of delayed spatio-temporal interactions. We illustrate the predictive power of this form of analysis with comparison against direct numerical simulations, paying particular attention to the competition between standing and travelling waves and the onset of Benjamin-Feir instabilities.

Modeling electrocortical activity through improved local approximations of integral neural field equations

Neural field models of firing rate activity typically take the form of integral equations with space-dependent axonal delays. Under natural assumptions on the synaptic connectivity we show how one can derive an equivalent partial differential equation (PDE) model that properly treats the axonal delay terms of the integral formulation. Our analysis avoids the so-called long-wavelength approximation that has previously been used to formulate PDE models for neural activity in two spatial dimensions. Direct numerical simulations of this PDE model show instabilities of the homogeneous steady state that are in full agreement with a Turing instability analysis of the original integral model. We discuss the benefits of such a local model and its usefulness in modeling electrocortical activity. In particular we are able to treat "patchy'" connections, whereby a homogeneous and isotropic system is modulated in a spatially periodic fashion. In this case the emergence of a "lattice-directed" traveling wave predicted by a linear instability analysis is confirmed by the numerical simulation of an appropriate set of coupled PDEs. Article published and (c) American Physical Society 2007

Quantitative Derivation of Effective Evolution Equations for the Dynamics of Bose-Einstein Condensates

This thesis proves certain results concerning an important question in non-equilibrium quantum statistical mechanics which is the derivation of effective evolution equations approximating the dynamics of a system of large number of bosons initially at equilibrium (ground state at very low temperatures). The dynamics of such systems are governed by the time-dependent linear many-body Schroedinger equation from which it is typically difficult to extract useful information due to the number of particles being large. We will study quantitatively (i.e. with explicit bounds on the error) how a suitable one particle non-linear Schroedinger equation arises in the mean field limit as number of particles N → ∞ and how the appropriate corrections to the mean field will provide better approximations of the exact dynamics. In the first part of this thesis we consider the evolution of N bosons, where N is large, with two-body interactions of the form N³ᵝv(Nᵝ⋅), 0≤β≤1. The parameter β measures the strength and the range of interactions. We compare the exact evolution with an approximation which considers the evolution of a mean field coupled with an appropriate description of pair excitations, see [18,19] by Grillakis-Machedon-Margetis. We extend the results for 0 ≤ β < 1/3 in [19, 20] to the case of β < 1/2 and obtain an error bound of the form p(t)/Nᵅ, where α>0 and p(t) is a polynomial, which implies a specific rate of convergence as N → ∞. In the second part, utilizing estimates of the type discussed in the first part, we compare the exact evolution with the mean field approximation in the sense of marginals. We prove that the exact evolution is close to the approximate in trace norm for times of the order o(1)√N compared to log(o(1)N) as obtained in Chen-Lee-Schlein [6] for the Hartree evolution. Estimates of similar type are obtained for stronger interactions as well.

All-regime Lagrangian-Remap numerical schemes for the gas dynamics equations. Applications to the large friction and low Mach coefficients

In this talk, we propose an all regime Lagrange-Projection like numerical scheme for the gas dynamics equations. By all regime, we mean that the numerical scheme is able to compute accurate approximate solutions with an under-resolved discretization with respect to the Mach number M, i.e. such that the ratio between the Mach number M and the mesh size or the time step is small with respect to 1. The key idea is to decouple acoustic and transport phenomenon and then alter the numerical flux in the acoustic approximation to obtain a uniform truncation error in term of M. This modified scheme is conservative and endowed with good stability properties with respect to the positivity of the density and the internal energy. A discrete entropy inequality under a condition on the modification is obtained thanks to a reinterpretation of the modified scheme in the Harten Lax and van Leer formalism. A natural extension to multi-dimensional problems discretized over unstructured mesh is proposed. Then a simple and efficient semi implicit scheme is also proposed. The resulting scheme is stable under a CFL condition driven by the (slow) material waves and not by the (fast) acoustic waves and so verifies the all regime property. Numerical evidences are proposed and show the ability of the scheme to deal with tests where the flow regime may vary from low to high Mach values.

An Optimal Order Interior Penalty Discontinuous Galerkin Discretization of the Compressible Navier-Stokes Equations

In this article we propose a new symmetric version of the interior penalty discontinuous Galerkin finite element method for the numerical approximation of the compressible Navier-Stokes equations. Here, particular emphasis is devoted to the construction of an optimal numerical method for the evaluation of certain target functionals of practical interest, such as the lift and drag coefficients of a body immersed in a viscous fluid. With this in mind, the key ingredients in the construction of the method include: (i) An adjoint consistent imposition of the boundary conditions; (ii) An adjoint consistent reformulation of the underlying target functional of practical interest; (iii) Design of appropriate interior-penalty stabilization terms. Numerical experiments presented within this article clearly indicate the optimality of the proposed method when the error is measured in terms of both the L_2-norm, as well as for certain target functionals. Computational comparisons with other discontinuous Galerkin schemes proposed in the literature, including the second scheme of Bassi & Rebay, cf. [11], the standard SIPG method outlined in [25], and an NIPG variant of the new scheme will be undertaken.

Estimation of whole body muscle, adipose/fat mass, validation in health and during weight loss. Development of prediction equations using MRI as reference method

Background: Body composition is affected by diseases, and affects responses to medical treatments, dosage of medicines, etc., while an abnormal body composition contributes to the causation of many chronic diseases. While we have reliable biochemical tests for certain nutritional parameters of body composition, such as iron or iodine status, and we have harnessed nuclear physics to estimate the body’s content of trace elements, the very basic quantification of body fat content and muscle mass remains highly problematic. Both body fat and muscle mass are vitally important, as they have opposing influences on chronic disease, but they have seldom been estimated as part of population health surveillance. Instead, most national surveys have merely reported BMI and waist, or sometimes the waist/hip ratio; these indices are convenient but do not have any specific biological meaning. Anthropometry offers a practical and inexpensive method for muscle and fat estimation in clinical and epidemiological settings; however, its use is imperfect due to many limitations, such as a shortage of reference data, misuse of terminology, unclear assumptions, and the absence of properly validated anthropometric equations. To date, anthropometric methods are not sensitive enough to detect muscle and fat loss. Aims: The aim of this thesis is to estimate Adipose/fat and muscle mass in health disease and during weight loss through; 1. evaluating and critiquing the literature, to identify the best-published prediction equations for adipose/fat and muscle mass estimation; 2. to derive and validate adipose tissue and muscle mass prediction equations; and 3.to evaluate the prediction equations along with anthropometric indices and the best equations retrieved from the literature in health, metabolic illness and during weight loss. Methods: a Systematic review using Cochrane Review method was used for reviewing muscle mass estimation papers that used MRI as the reference method. Fat mass estimation papers were critically reviewed. Mixed ethnic, age and body mass data that underwent whole body magnetic resonance imaging to quantify adipose tissue and muscle mass (dependent variable) and anthropometry (independent variable) were used in the derivation/validation analysis. Multiple regression and Bland-Altman plot were applied to evaluate the prediction equations. To determine how well the equations identify metabolic illness, English and Scottish health surveys were studied. Statistical analysis using multiple regression and binary logistic regression were applied to assess model fit and associations. Also, populations were divided into quintiles and relative risk was analysed. Finally, the prediction equations were evaluated by applying them to a pilot study of 10 subjects who underwent whole-body MRI, anthropometric measurements and muscle strength before and after weight loss to determine how well the equations identify adipose/fat mass and muscle mass change. Results: The estimation of fat mass has serious problems. Despite advances in technology and science, prediction equations for the estimation of fat mass depend on limited historical reference data and remain dependent upon assumptions that have not yet been properly validated for different population groups. Muscle mass does not have the same conceptual problems; however, its measurement is still problematic and reference data are scarce. The derivation and validation analysis in this thesis was satisfactory, compared to prediction equations in the literature they were similar or even better. Applying the prediction equations in metabolic illness and during weight loss presented an understanding on how well the equations identify metabolic illness showing significant associations with diabetes, hypertension, HbA1c and blood pressure. And moderate to high correlations with MRI-measured adipose tissue and muscle mass before and after weight loss. Conclusion: Adipose tissue mass and to an extent muscle mass can now be estimated for many purposes as population or groups means. However, these equations must not be used for assessing fatness and categorising individuals. Further exploration in different populations and health surveys would be valuable.

Fractional differential equations with dependence on the Caputo-Katugampola derivative

In this paper we present a new type of fractional operator, the Caputo–Katugampola derivative. The Caputo and the Caputo–Hadamard fractional derivatives are special cases of this new operator. An existence and uniqueness theorem for a fractional Cauchy type problem, with dependence on the Caputo–Katugampola derivative, is proven. A decomposition formula for the Caputo–Katugampola derivative is obtained. This formula allows us to provide a simple numerical procedure to solve the fractional differential equation.

Modeling some real phenomena by fractional differential equations

This paper deals with fractional differential equations, with dependence on a Caputo fractional derivative of real order. The goal is to show, based on concrete examples and experimental data from several experiments, that fractional differential equations may model more efficiently certain problems than ordinary differential equations. A numerical optimization approach based on least squares approximation is used to determine the order of the fractional operator that better describes real data, as well as other related parameters.

Solutions of Tikhonov functional equations and applications to multiplication operators on Szegö spaces

We consider a natural representation of solutions for Tikhonov functional equations. This will be done by applying the theory of reproducing kernels to the approximate solutions of general bounded linear operator equations (when defined from reproducing kernel Hilbert spaces into general Hilbert spaces), by using the Hilbert-Schmidt property and tensor product of Hilbert spaces. As a concrete case, we shall consider generalized fractional functions formed by the quotient of Bergman functions by Szegö functions considered from the multiplication operators on the Szegö spaces.

Finite time extinction for nonlinear fractional evolution equations and related properties

The finite time extinction phenomenon (the solution reaches an equilibrium after a finite time) is peculiar to certain nonlinear problems whose solutions exhibit an asymptotic behavior entirely different from the typical behavior of solutions associated to linear problems. The main goal of this work is twofold. Firstly, we extend some of the results known in the literature to the case in which the ordinary time derivative is considered jointly with a fractional time differentiation. Secondly, we consider the limit case when only the fractional derivative remains. The latter is the most extraordinary case, since we prove that the finite time extinction phenomenon still appears, even with a non-smooth profile near the extinction time. Some concrete examples of quasi-linear partial differential operators are proposed. Our results can also be applied in the framework of suitable nonlinear Volterra integro-differential equations.

Finite time extinction for nonlinear fractional evolution equations and related properties.

The finite time extinction phenomenon (the solution reaches an equilibrium after a finite time) is peculiar to certain nonlinear problems whose solutions exhibit an asymptotic behavior entirely different from the typical behavior of solutions associated to linear problems. The main goal of this work is twofold. Firstly, we extend some of the results known in the literature to the case in which the ordinary time derivative is considered jointly with a fractional time differentiation. Secondly, we consider the limit case when only the fractional derivative remains. The latter is the most extraordinary case, since we prove that the finite time extinction phenomenon still appears, even with a non-smooth profile near the extinction time. Some concrete examples of quasi-linear partial differential operators are proposed. Our results can also be applied in the framework of suitable nonlinear Volterra integro-differential equations.

The Becker-Döring equations with exponentially size-dependent rate coefficients

This paper is concerned with an analysis of the Becker-Döring equations which lie at the heart of a number of descriptions of non-equilibrium phase transitions and related complex dynamical processes. The Becker-Döring theory describes growth and fragmentation in terms of stepwise addition or removal of single particles to or from clusters of similar particles and has been applied to a wide range of problems of physicochemical and biological interest within recent years. Here we consider the case where the aggregation and fragmentation rates depend exponentially on cluster size. These choices of rate coefficients at least qualitatively correspond to physically realistic molecular clustering scenarios such as occur in, for example, simulations of simple fluids. New similarity solutions for the constant monomer Becker-Döring system are identified, and shown to be generic in the case of aggregation and fragmentation rates that depend exponentially on cluster size.

Coagulation equations with mass loss

We derive and solve models for coagulation with mass loss arising, for example, from industrial processes in which growing inclusions are lost from the melt by colliding with the wall of the vessel. We consider a variety of loss laws and a variety of coagulation kernels, deriving exact results where possible, and more generally reducing the equations to similarity solutions valid in the large-time limit. One notable result is the effect that mass removal has on gelation: for small loss rates, gelation is delayed, whilst above a critical threshold, gelation is completely prevented. Finally, by forming an exact explicit solution for a more general initial cluster size distribution function, we illustrate how numerical results from earlier work can be interpreted in the light of the theory presented herein.