Application for the 4W Model of Drowning for Prevention, Rescue and Treatment, Research and Education

Previous research has been published about the 4W model of drowning and its four constituent variables (Avramidis, Butterly & Llewellyn, 2007; 2009a; 2009b; 2009c; 2009d; Avramidis, McKenna, Long, Butterly, & Llewellyn, 2010). We presently summarize and suggest applications of the model for the general public, aquatic safety professionals, injury epidemiologists and policy makers

Beyond a Passive Conduit: Implications of Lymphatic Biology for Kidney Diseases

The kidney contains a network of lymphatic vessels that clear fluid, small molecules, and cells from the renal interstitium. Through modulating immune responses and via crosstalk with surrounding renal cells, lymphatic vessels have been implicated in the progression and maintenance of kidney disease. In this Review, we provide an overview of the development, structure, and function of lymphatic vessels in the healthy adult kidney. We then highlight the contributions of lymphatic vessels to multiple forms of renal pathology, emphasizing CKD, transplant rejection, and polycystic kidney disease and discuss strategies to target renal lymphatics using genetic and pharmacologic approaches. Overall, we argue the case for lymphatics playing a fundamental role in renal physiology and pathology and treatments modulating these vessels having therapeutic potential across the spectrum of kidney disease

Endothelial-epithelial communication in polycystic kidney disease: Role of vascular endothelial growth factor signalling

Whereas targeting the cyst epithelium and its molecular machinery has been the prevailing clinical strategy for polycystic kidney disease, the endothelium, including blood vasculature and lymphatics, is emerging as an important player in this disorder. In this Review, we provide an overview of the structural and functional alterations to blood vasculature and lymphatic vessels in the polycystic kidney. We also discuss evidence for vascular endothelial growth factor signalling, otherwise critical for endothelial cell development and maintenance, as being a fundamental molecular pathway in polycystic kidney disease and a potential therapeutic target for modulating cyst expansion

Mechanisms and cell lineages in lymphatic vascular development.

Lymphatic vessels have critical roles in both health and disease and their study is a rapidly evolving area of vascular biology. The consensus on how the first lymphatic vessels arise in the developing embryo has recently shifted. Originally, they were thought to solely derive by sprouting from veins. Since then, several studies have uncovered novel cellular mechanisms and a diversity of contributing cell lineages in the formation of organ lymphatic vasculature. Here, we review the key mechanisms and cell lineages contributing to lymphatic development, discuss the advantages and limitations of experimental techniques used for their study and highlight remaining knowledge gaps that require urgent attention. Emerging technologies should accelerate our understanding of how lymphatic vessels develop normally and how they contribute to disease

The Biological Significance and Implications of Planar Cell Polarity for Nephrology

The orientation of cells in two-dimensional and three-dimensional space underpins how the kidney develops and responds to disease. The process by which cells orientate themselves within the plane of a tissue is termed planar cell polarity. In this Review, we discuss how planar cell polarity and the proteins that underpin it govern kidney organogenesis and pathology. The importance of planar cell polarity and its constituent proteins in multiple facets of kidney development is emphasised, including ureteric bud branching, tubular morphogenesis and nephron maturation. An overview is given of the relevance of planar cell polarity and its proteins for inherited human renal diseases, including congenital malformations with unknown aetiology and polycystic kidney disease. Finally, recent work is described outlining the influence of planar cell polarity proteins on glomerular diseases and highlight how this fundamental pathway could yield a new treatment paradigm for nephrology

High fludarabine exposure and relationship with treatment-related mortality after nonmyeloablative hematopoietic cell transplantation.

Despite its common use in nonmyeloablative preparative regimens, the pharmacokinetics of fludarabine are poorly characterized in hematopoietic cell transplantation (HCT) recipients and exposure-response relationships remain undefined. The objective of this study was to evaluate the association between plasma F-ara-A exposure, the systemically circulating moiety of fludarabine, and engraftment, acute GVHD, TRM and OS after HCT. The preparative regimen consisted of CY 50 mg/kg/day i.v. day -6; plus fludarabine 30-40 mg/m²/day i.v. on days -6 to -2 and TBI 200 cGy on day -1. F-ara-A pharmacokinetics were carried out with the first dose of fludarabine in 87 adult patients. Median (range) F-ara-A area-under-the-curve (AUC((0-∞))) was 5.0 μg h/mL (2.0-11.0), clearance 15.3 L/h (6.2-36.6), C(min) 55 ng/mL (17-166) and concentration on day(zero) 16.0 ng/mL (0.1-144.1). Despite dose reductions, patients with renal insufficiency had higher F-ara-A exposures. There was strong association between high plasma concentrations of F-ara-A and increased risk of TRM and reduced OS. Patients with an AUC((0-∞)) greater than 6.5 μg h/mL had 4.56 greater risk of TRM and significantly lower OS. These data suggest that clinical strategies are needed to optimize dosing of fludarabine to prevent overexposure and toxicity in HCT

Editorial: Quaternary revolutions

PublishedEditorialJournalEditorialThe QRA@50 meeting was organized by a team of people including the editors, John Catt, Catherine Souch, Tom Hill, Danni Pearce and a team of postgraduates and staff from the Royal Geographical Society-Institute of British Geographers (RGS-IBG). It was made possible by support from a number of sponsors, including RGS-IBG, van Walt, Beta Analytic Ltd, the Natural History Museum, Wiley-Blackwell and C3W (Climate Change Consortium of Wales). We would like to thank the reviewers of all the papers for their comments and suggested improvements to the papers

A robust and efficient hybrid solver for crystal plasticity

Conventional crystal plasticity (CP) solvers are based on a Newton-Raphson (NR) approach which use an initial guess for the free variables (often stress) to be solved. These solvers are limited by a finite interval of convergence and often fail when the free variable falls outside this interval. Solution failure results in the reduction of the time increment to be solved, thus convergence of the CP solver is a bottleneck which determines the computational cost of the simulation. The numerical stability of the slip law in its inverted form offers a solver that isn't vulnerable to poor pre-conditioning (initial guess) and can be used to progress to a solution from a stable starting point (i.e., from zero slip rate γ˙pk=0 s−1). In this paper, a novel formulation that enables the application of the slip law in its inverted form is introduced; this treats all slip systems as independent by approximating the Jacobian as a diagonal matrix, thus overcomes ill-defined and singular Jacobians associated with previous approaches. This scheme was demonstrated to offer superior robustness and convergence rate for a case with a single slip system, however the convergence rate for extreme cases with several active slip systems was relatively poor. Here, we introduce a novel ‘hybrid scheme’ that first uses the reverse scheme for the first stage of the solution, and then transitions to the forward scheme to complete the solution at a higher convergence rate. Several examples are given for pointwise calculations, followed by CPFEM simulations for FCC copper and HCP Zircaloy-4, which demonstrated solver performance in practise. The performance of simulations using the hybrid scheme was shown to require six to nine times fewer increments compared to the conventional forward scheme solver based on a free variable of stress and initial guess based on a fully elastic increment

Positive approximations of the inverse of fractional powers of SPD M-matrices

This study is motivated by the recent development in the fractional calculus and its applications. During last few years, several different techniques are proposed to localize the nonlocal fractional diffusion operator. They are based on transformation of the original problem to a local elliptic or pseudoparabolic problem, or to an integral representation of the solution, thus increasing the dimension of the computational domain. More recently, an alternative approach aimed at reducing the computational complexity was developed. The linear algebraic system $\cal A^\alpha \bf u=\bf f$, $0< \alpha <1$ is considered, where $\cal A$ is a properly normalized (scalded) symmetric and positive definite matrix obtained from finite element or finite difference approximation of second order elliptic problems in $\Omega\subset\mathbb{R}^d$, $d=1,2,3$. The method is based on best uniform rational approximations (BURA) of the function $t^{\beta-\alpha}$ for $0 < t \le 1$ and natural $\beta$. The maximum principles are among the major qualitative properties of linear elliptic operators/PDEs. In many studies and applications, it is important that such properties are preserved by the selected numerical solution method. In this paper we present and analyze the properties of positive approximations of $\cal A^{-\alpha}$ obtained by the BURA technique. Sufficient conditions for positiveness are proven, complemented by sharp error estimates. The theoretical results are supported by representative numerical tests

Accreditation council for graduate medical education (ACGME) annual anesthesiology residency and fellowship program review: a "report card" model for continuous improvement

<p>Abstract</p> <p>Background</p> <p>The Accreditation Council for Graduate Medical Education (ACGME) requires an annual evaluation of all ACGME-accredited residency and fellowship programs to assess program quality. The results of this evaluation must be used to improve the program. This manuscript describes a metric to be used in conducting ACGME-mandated annual program review of ACGME-accredited anesthesiology residencies and fellowships.</p> <p>Methods</p> <p>A variety of metrics to assess anesthesiology residency and fellowship programs are identified by the authors through literature review and considered for use in constructing a program "report card."</p> <p>Results</p> <p>Metrics used to assess program quality include success in achieving American Board of Anesthesiology (ABA) certification, performance on the annual ABA/American Society of Anesthesiology In-Training Examination, performance on mock oral ABA certification examinations, trainee scholarly activities (publications and presentations), accreditation site visit and internal review results, ACGME and alumni survey results, National Resident Matching Program (NRMP) results, exit interview feedback, diversity data and extensive program/rotation/faculty/curriculum evaluations by trainees and faculty. The results are used to construct a "report card" that provides a high-level review of program performance and can be used in a continuous quality improvement process.</p> <p>Conclusions</p> <p>An annual program review is required to assess all ACGME-accredited residency and fellowship programs to monitor and improve program quality. We describe an annual review process based on metrics that can be used to focus attention on areas for improvement and track program performance year-to-year. A "report card" format is described as a high-level tool to track educational outcomes.</p