Agreement between cystatin-C and creatinine based eGFR estimates after a 12-month exercise intervention in patients with chronic kidney disease

Background: Estimation of GFR (eGFR) using formulae based on serum creatinine concentrations are commonly used to assess kidney function. Physical exercise can increase creatinine turnover and lean mass; therefore, this method may not be suitable for use in exercising individuals. Cystatin-C based eGFR formulae may be a more accurate measure of kidney function when examining the impact of exercise on kidney function. The aim of this study was to assess the agreement of four creatinine and cystatin-C based estimates of GFR before and after a 12-month exercise intervention. Methods: One hundred forty-two participants with stage 3–4 chronic kidney disease (CKD) (eGFR 25–60 mL/min/1.73 m2) were included. Subjects were randomised to either a Control group (standard nephrological care [n = 68]) or a Lifestyle Intervention group (12 months of primarily aerobic based exercise training [n = 74]). Four eGFR formulae were compared at baseline and after 12 months: 1) MDRDcr, 2) CKD-EPIcr, 3) CKD-EPIcys and 4) CKD-EPIcr-cys. Results: Control participants were aged 63.5[9.4] years, 60.3% were male, 42.2% had diabetes, and had an eGFR of 40.5 ± 8.9 ml/min/1.73m2. Lifestyle Intervention participants were aged 60.5[14.2] years, 59.5% were male, 43.8% had diabetes, and had an eGFR of 38.9 ± 8.5 ml/min/1.73m2. There were no significant baseline differences between the two groups. Lean mass (r = 0.319, p  <  0.01) and grip strength (r = 0.391, p  <  0.001) were associated with serum creatinine at baseline. However, there were no significant correlations between cystatin-C and the same measures. The Lifestyle Intervention resulted in significant improvements in exercise capacity (+ 1.9 ± 1.8 METs, p  <  0.001). There were no changes in lean mass in both Control and Lifestyle Intervention groups during the 12 months. CKD-EPIcys was considerably lower in both groups at both baseline and 12 months than CKD-EPIcr (Control = − 10.5 ± 9.1 and − 13.1 ± 11.8, and Lifestyle Intervention = − 7.9 ± 8.6 and − 8.4 ± 12.3 ml/min/1.73 m2), CKD-EPIcr-cys (Control = − 3.6 ± 3.7 and − 4.5 ± 4.5, and Lifestyle Intervention = − 3.6 ± 3.7 and − 2.5 ± 5.5 ml/min/1.73 m2) and MDRDcr (Control = − 9.3 ± 8.4 and − 12.0 ± 10.7, Lifestyle Intervention = − 6.4 ± 8.4 and − 6.9 ± 11.2 ml/min/1.73 m2). Conclusions: In CKD patients participating in a primarily aerobic based exercise training, without improvements in lean mass, cystatin-C and creatinine based eGFR provided similar estimates of kidney function at both baseline and after 12 months of exercise training. Trial registration: The trial was registered at www.anzctr.org.au (Registration Number ANZCTR12608000337370) on the 17/07/2008 (retrospectively registered)

Neural field models with threshold noise

The original neural field model of Wilson and Cowan is often interpreted as the averaged behaviour of a network of switch like neural elements with a distribution of switch thresholds, giving rise to the classic sigmoidal population firing-rate function so prevalent in large scale neuronal modelling. In this paper we explore the effects of such threshold noise without recourse to averaging and show that spatial correlations can have a strong effect on the behaviour of waves and patterns in continuum models. Moreover, for a prescribed spatial covariance function we explore the differences in behaviour that can emerge when the underlying stationary distribution is changed from Gaussian to non-Gaussian. For travelling front solutions, in a system with exponentially decaying spatial interactions, we make use of an interface approach to calculate the instantaneous wave speed analytically as a series expansion in the noise strength. From this we find that, for weak noise, the spatially averaged speed depends only on the choice of covariance function and not on the shape of the stationary distribution. For a system with a Mexican-hat spatial connectivity we further find that noise can induce localised bump solutions, and using an interface stability argument show that there can be multiple stable solution branches

The development of an accreditation scheme for accredited exercise physiologists

Background: Accredited Exercise Physiologists provide exercise services for people living with chronic disease, disability or injury and are recognised in Australia as Accredited Exercise Physiologists (AEP) under a national certification system administered by Exercise and Sport Science Australia (ESSA). A major breakthrough occurred for the AEP in 2006 when the Australian Department of Health and Ageing approved the AEP to deliver clinical exercise services for people with chronic medical conditions under the taxpayer-funded national health scheme, Medicare Australia. Aims: In light of these developments, the authors recognised the need for new accreditation criteria, and our report summarises the work that we did on behalf of the profession and ESSA in restructuring the accreditation system. Methods and Outcomes: We first performed a background study that defined the scope of practice of the AEP and benchmarked the AEP against other allied health professions in Australia and Clinical Exercise Physiologists internationally. We then constructed a new set of accreditation criteria comprising sets of pathologyspecific knowledge and experiences, together with a set of generic standards including communication, professional behaviour and risk management. All participating Australian universities (18 out of 27 responded) and 29 practitioner experts were then invited to provide comment and input into the draft guidelines. There was strong support for the new system that was implemented nationally on 1 January 2008 and is now administered by ESSA. Conclusions: This work has stimulated an unprecedented level of activity in the Australian university sector in developing new curricula in clinical exercise science and practice, and is intended to lead to improved standards of clinical exercise practice.<br /

The dynamics of neural fields on bounded domains: an interface approach for Dirichlet boundary conditions

Continuum neural field equations model the large scale spatio-temporal dynamics of interacting neurons on a cortical surface. They have been extensively studied, both analytically and numerically, on bounded as well as unbounded domains. Neural field models do not require the specification of boundary conditions. Relatively little attention has been paid to the imposition of neural activity on the boundary, or to its role in inducing patterned states. Here we redress this imbalance by studying neural field models of Amari type (posed on one- and two-dimensional bounded domains) with Dirichlet boundary conditions. The Amari model has a Heaviside nonlinearity that allows for a description of localised solutions of the neural field with an interface dynamics. We show how to generalise this reduced but exact description by deriving a normal velocity rule for an interface that encapsulates boundary effects. The linear stability analysis of localised states in the interface dynamics is used to understand how spatially extended patterns may develop in the absence and presence of boundary conditions. Theoretical results for pattern formation are shown to be in excellent agreement with simulations of the full neural field model. Furthermore, a numerical scheme for the interface dynamics is introduced and used to probe the way in which a Dirichlet boundary condition can limit the growth of labyrinthine structures

Robustness and Enhancement of Neural Synchronization by Activity-Dependent Coupling

We study the synchronization of two model neurons coupled through a synapse having an activity-dependent strength. Our synapse follows the rules of Spike-Timing Dependent Plasticity (STDP). We show that this plasticity of the coupling between neurons produces enlarged frequency locking zones and results in synchronization that is more rapid and much more robust against noise than classical synchronization arising from connections with constant strength. We also present a simple discrete map model that demonstrates the generality of the phenomenon.Comment: 4 pages, accepted for publication in PR

Dynamics of a ring of pulse-coupled oscillators: group-theoretic approach

We use group-theoretic methods to analyze phase-locking in a ring of identical integrate-and-fire oscillators with distributed delays. It is shown how certain phase-locked solutions emerge through symmetry breaking bifurcations as some characteristic delay of the system is varied. The reduction to a phase-coupled model in the weak coupling regime is discussed

Democratization in a passive dendritic tree : an analytical investigation

One way to achieve amplification of distal synaptic inputs on a dendritic tree is to scale the amplitude and/or duration of the synaptic conductance with its distance from the soma. This is an example of what is often referred to as “dendritic democracy”. Although well studied experimentally, to date this phenomenon has not been thoroughly explored from a mathematical perspective. In this paper we adopt a passive model of a dendritic tree with distributed excitatory synaptic conductances and analyze a number of key measures of democracy. In particular, via moment methods we derive laws for the transport, from synapse to soma, of strength, characteristic time, and dispersion. These laws lead immediately to synaptic scalings that overcome attenuation with distance. We follow this with a Neumann approximation of Green’s representation that readily produces the synaptic scaling that democratizes the peak somatic voltage response. Results are obtained for both idealized geometries and for the more realistic geometry of a rat CA1 pyramidal cell. For each measure of democratization we produce and contrast the synaptic scaling associated with treating the synapse as either a conductance change or a current injection. We find that our respective scalings agree up to a critical distance from the soma and we reveal how this critical distance decreases with decreasing branch radius

Depolarization induced suppression of excitation and the emergence of ultraslow rhythms in neural networks

Ultraslow fluctuations (0.01-0.1 Hz) are a feature of intrinsic brain activity of as yet unclear origin. We propose a candidate mechanism based on retrograde endocannabinoid signaling in a synaptically coupled network of excitatory neurons. This is known to cause depolarization-induced suppression of excitation (DISE), which we model phenomenologically. We construct emergent network oscillations in a globally coupled network and show that for strong synaptic coupling DISE can lead to a synchronized population burst at the frequencies of resting brain rhythms. © 2010 The American Physical Society

Limits and dynamics of stochastic neuronal networks with random heterogeneous delays

Realistic networks display heterogeneous transmission delays. We analyze here the limits of large stochastic multi-populations networks with stochastic coupling and random interconnection delays. We show that depending on the nature of the delays distributions, a quenched or averaged propagation of chaos takes place in these networks, and that the network equations converge towards a delayed McKean-Vlasov equation with distributed delays. Our approach is mostly fitted to neuroscience applications. We instantiate in particular a classical neuronal model, the Wilson and Cowan system, and show that the obtained limit equations have Gaussian solutions whose mean and standard deviation satisfy a closed set of coupled delay differential equations in which the distribution of delays and the noise levels appear as parameters. This allows to uncover precisely the effects of noise, delays and coupling on the dynamics of such heterogeneous networks, in particular their role in the emergence of synchronized oscillations. We show in several examples that not only the averaged delay, but also the dispersion, govern the dynamics of such networks.Comment: Corrected misprint (useless stopping time) in proof of Lemma 1 and clarified a regularity hypothesis (remark 1