Renal fibrosis in feline chronic kidney disease: known mediators and mechanisms of injury

Chronic kidney disease (CKD) is a common medical condition of ageing cats. In most cases the underlying aetiology is unknown, but the most frequently reported pathological diagnosis is renal tubulointerstitial fibrosis. Renal fibrosis, characterised by extensive accumulation of extra-cellular matrix within the interstitium, is thought to be the final common pathway for all kidney diseases and is the pathological lesion best correlated with function in both humans and cats. As a convergent pathway, renal fibrosis provides an ideal target for the treatment of CKD and knowledge of the underlying fibrotic process is essential for the future development of novel therapies. There are many mediators and mechanisms of renal fibrosis reported in the literature, of which only a few have been investigated in the cat. This article reviews the process of renal fibrosis and discusses the most commonly cited mediators and mechanisms of progressive renal injury, with particular focus on the potential significance to feline CKD

Error analysis for full discretizations of quasilinear parabolic problems on evolving surfaces

Convergence results are shown for full discretizations of quasilinear parabolic partial differential equations on evolving surfaces. As a semidiscretization in space the evolving surface finite element method is considered, using a regularity result of a generalized Ritz map, optimal order error estimates for the spatial discretization is shown. Combining this with the stability results for Runge--Kutta and BDF time integrators, we obtain convergence results for the fully discrete problems.Comment: -. arXiv admin note: text overlap with arXiv:1410.048

Neighbourhood blue space, health and wellbeing: The mediating role of different types of physical activity

This is the final version. Available on open access from Elsevier via the DOI in this recordBackground: Evidence suggests that living near blue spaces such as the coast, lakes and rivers may be good for health and wellbeing. Although greater levels of physical activity (PA) may be a potential mechanism, we know little about the types of PA that might account for this. Objectives: To explore the mediating role of: a) ‘watersports’ (e.g. sailing/canoeing); b) ‘on-land outdoor PA’ in natural/mixed settings (e.g. walking/running/cycling); and, c) ‘indoor/other PA’ (e.g. gym/squash) in the relationships between residential blue space availability and health outcomes. Methods: Using data from the Health Survey for England (n = 21,097), we constructed a path model to explore whether weekly volumes of each PA type mediate any of the relationships between residential blue space availability (coastal proximity and presence of freshwater) and self-reported general and mental health, controlling for green space density and a range of socio-economic factors at the individual- and area-level. Results: Supporting predictions, living nearer the coast was associated with better self-reported general and mental health and this was partially mediated by on-land outdoor PA (primarily walking). Watersports were more common among those living within 5kms of the coast, but did not mediate associations between coastal proximity and health. Presence of freshwater in the neighbourhood was associated with better mental health, but this effect was not mediated by PA. Conclusions: Although nearby blue spaces offer potentially easier access to watersports, relatively few individuals in England engage in them and thus they do not account for positive population health associations. Rather, the benefits to health from coastal living seem, at least in part, due to participation in land-based outdoor activities (especially walking). Further research is needed to explore the mechanisms behind the relationship between freshwater presence and mental health.Kone FoundationEuropean CommissionNational Institute for Health Research (NIHR)European Union Horizon 202

On the flow of non-axisymmetric perturbations of cylinders via surface diffusion

We study the surface diffusion flow acting on a class of general (non--axisymmetric) perturbations of cylinders $\mathcal{C}_r$ in ${\rm I \! R}^3$. Using tools from parabolic theory on uniformly regular manifolds, and maximal regularity, we establish existence and uniqueness of solutions to surface diffusion flow starting from (spatially--unbounded) surfaces defined over $\mathcal{C}_r$ via scalar height functions which are uniformly bounded away from the central cylindrical axis. Additionally, we show that $\mathcal{C}_r$ is normally stable with respect to $2 \pi$--axially--periodic perturbations if the radius $r > 1$,and unstable if $0 < r < 1$. Stability is also shown to hold in settings with axial Neumann boundary conditions.Comment: 20 pages, 1 figure, submitted for publicatio

Global solution to the Allen-Cahn equation with singular potentials and dynamic boundary conditions

We prove well-posedness results for the solution to an initial and boundary-value problem for an Allen-Cahn type equation describing the phenomenon of phase transitions for a material contained in a bounded and regular domain. The dynamic boundary conditions for the order parameter have been recently proposed by some physicists to account for interactions with the walls. We show our results using suitable regularizations of the nonlinearities of the problem and performing some a priori estimates which allow us to pass to the limit thanks to compactness and monotonicity arguments.Comment: Key words: Allen-Cahn equation, dynamic boundary conditions, maximal monotone graphs, initial boundary value problem, existence and uniqueness result

Urinary active transforming growth factor ß in feline chronic kidney disease

The cytokine transforming growth factor beta 1 (TGF-β1) has been widely implicated in the development and progression of renal fibrosis in chronic kidney disease (CKD) in humans and in experimental models. The aims of this study were to assess the association between urinary active TGF-β1 and (a) development of CKD in a cross-sectional study, (b) deterioration of renal function over 1 year in a longitudinal study, and (c) renal histopathological parameters in cats. A human active TGF-β1 ELISA was validated for use in feline urine. Cross-sectional analysis revealed no significant difference in urinary active TGF-β1:creatinine ratio (aTGF-β1:UCr) between groups with differing renal function. Longitudinally, non-azotaemic cats that developed CKD demonstrated a significant (P = 0.028) increase in aTGF-β1:UCr approximately 6 months before the development of azotaemia, which remained elevated (P = 0.046) at diagnosis (approximately 12 months prior, 8.4 pg/mg; approximately 6 months prior, 22.2 pg/mg; at CKD diagnosis, 24.6 pg/mg). In the histopathology study, aTGF-β1:UCr was significantly higher in cats with moderate (P = 0.02) and diffuse (P = 0.005) renal fibrosis than in cats without fibrosis. Cats with moderate renal inflammation had significantly higher urinary active aTGF-β1 concentrations than cats with mild (P = 0.035) or no inflammatory change (P = 0.004). The parameter aTGF-β1:UCr was independently associated with Log urine protein:creatinine ratio in a multivariable analysis of clinicopathological parameters and interstitial fibrosis score in a multivariable analysis of histopathological features. These results suggest that urinary aTGF-β1 reflects the severity of renal pathology. Increases in urinary aTGF-β1 followed longitudinally in individual cats may indicate the development of CKD

Investigation of E. coli and Virus Reductions Using Replicate, Bench-Scale Biosand Filter Columns and Two Filter Media

The biosand filter (BSF) is an intermittently operated, household-scale slow sand filter for which little data are available on the effect of sand composition on treatment performance. Therefore, bench-scale columns were prepared according to the then-current (2006–2007) guidance on BSF design and run in parallel to conduct two microbial challenge experiments of eight-week duration. Triplicate columns were loaded with Accusand silica or crushed granite to compare virus and E. coli reduction performance. Bench-scale experiments provided confirmation that increased schmutzdecke growth, as indicated by decline in filtration rate, is the primary factor causing increased E. coli reductions of up to 5-log10. However, reductions of challenge viruses improved only modestly with increased schmutzdecke growth. Filter media type (Accusand silica vs. crushed granite) did not influence reduction of E. coli bacteria. The granite media without backwashing yielded superior virus reductions when compared to Accusand. However, for columns in which the granite media was first backwashed (to yield a more consistent distribution of grains and remove the finest size fraction), virus reductions were not significantly greater than in columns with Accusand media. It was postulated that a decline in surface area with backwashing decreased the sites and surface area available for virus sorption and/or biofilm growth and thus decreased the extent of virus reduction. Additionally, backwashing caused preferential flow paths and deviation from plug flow; backwashing is not part of standard BSF field preparation and is not recommended for BSF column studies. Overall, virus reductions were modest and did not meet the 5- or 3-log10 World Health Organization performance targets

Comparative Genetic Studies of Native and Introduced Coccinellidae in North America

During the past four decades, several species of aphidophagous Coccinellidae became established in North America, including Coccinella septempunctata, Harmonia axyridis, Hippodamia variegata, and Propylea quatuordecimpunctata. After their establishment, unknown circumstances favoured a rapid increase in population densities and distribution of H. axyridis and C. septempunctata at localities hundreds and thousands of kilometers from their release sites. Propylea quatuordecimpunctata and Hippodamia variegata have spread more slowly after becoming established in northeastern North America. Comparative studies based upon allozyme variation in these four introduced species and in six native North American species of ladybird beetles revealed no significant differences in genetic diversities. Genetic variation, assessed by allelic diversity and heterozygosity, was uncorrelated with the establishment and spread of these predatory species in North America. All ladybirds studied show a remarkable degree of dispersion with little detectable population subdivision