A validated patient-specific FSI model for vascular access in haemodialysis

The flow rate inside arteriovenous fistulas is many times higher than physiological flow and is accompanied by high wall shear stress resulting in low patency rates. A fluid–structure interaction finite element model is developed to analyse the blood flow and vessel mechanics to elucidate the mechanisms that can lead to failure. The simulations are validated against flow measurements obtained from magnetic resonance imaging data

Regression of tricuspid regurgitation after two-stage arterial switch operation for failing systemic ventricle after atrial inversion operation

AbstractThe cases of five patients with previous Senning ( n = 4) or Mustard ( n = 1) operations and failing systemic ventricles in whom banding of the pulmonary artery was performed as an interim step toward an arterial switch procedure are reported. The rise in the ratio of left to right mean systolic ventricular pressure, from 0.35 before operation to 0.90 during operation and 0.80 on the first postoperative day, caused a shift of the ventricular septum from a leftward to a midline or nearly midline position. This shift was associated with a reduction of tricuspid regurgitation. At a median interval of 5.1 months after pulmonary artery banding, the mean left ventricular posterior wall thickness had increased to 8.2 mm, versus 5 mm before operation, and the mean left ventricular myocardial mass index had increased to 90 gm/m2, versus 55.6 gm/m2 before operation. After the arterial switch operation, which was performed in four patients, the tricuspid regurgitation decreased to a trivial amount ( n = 1) or disappeared completely ( n = 3). (J THORAC CARDIOVASC SURG 1996;111:342-7

Dynamics of FitzHugh-Nagumo excitable systems with delayed coupling

Small lattices of $N$ nearest neighbor coupled excitable FitzHugh-Nagumo systems, with time-delayed coupling are studied, and compared with systems of FitzHugh-Nagumo oscillators with the same delayed coupling. Bifurcations of equilibria in N=2 case are studied analytically, and it is then numerically confirmed that the same bifurcations are relevant for the dynamics in the case $N>2$. Bifurcations found include inverse and direct Hopf and fold limit cycle bifurcations. Typical dynamics for different small time-lags and coupling intensities could be excitable with a single globally stable equilibrium, asymptotic oscillatory with symmetric limit cycle, bi-stable with stable equilibrium and a symmetric limit cycle, and again coherent oscillatory but non-symmetric and phase-shifted. For an intermediate range of time-lags inverse sub-critical Hopf and fold limit cycle bifurcations lead to the phenomenon of oscillator death. The phenomenon does not occur in the case of FitzHugh-Nagumo oscillators with the same type of coupling.Comment: accepted by Phys.Rev.

B-cell activating factor (BAFF) plasma level at the time of chronic GvHD diagnosis is a potential predictor of non-relapse mortality

Biological markers for risk stratification of chronic GvHD (cGvHD) could improve the care of patients undergoing allogeneic hematopoietic stem cell transplantation. Increased plasma levels of B-cell activating factor (BAFF), chemokine (C-X-C motif) ligand 9 (CXCL9) and elafin have been associated with the diagnosis, but not with outcome in patients with cGvHD. We evaluated the association between levels of these soluble proteins, measured by ELISA at the time of cGvHD diagnosis and before the initiation of therapy, with non-relapse-mortality (NRM). Based on the log-transformed values, factor levels were divided into tertiles defined respectively as low, intermediate, and high levels. On univariable analysis, BAFF levels were significantly associated with NRM, whereas CXCL9 and elafin levels were not. Both low (⩽2.3 ng/mL, hazard ratio (HR)=5.8, P=0.03) and high (>5.7 ng/mL, HR=5.4, P=0.03) BAFF levels were associated with a significantly higher NRM compared with intermediate BAFF level. The significant effect of high or low BAFF levels persisted in multivariable analysis. A subset of cGvHD patients had persistently low BAFF levels. In conclusion, our data show that BAFF levels at the time of cGvHD diagnosis are associated with NRM, and also are potentially useful for risk stratification. These results warrant confirmation in larger studies

Real-space local polynomial basis for solid-state electronic-structure calculations: A finite-element approach

We present an approach to solid-state electronic-structure calculations based on the finite-element method. In this method, the basis functions are strictly local, piecewise polynomials. Because the basis is composed of polynomials, the method is completely general and its convergence can be controlled systematically. Because the basis functions are strictly local in real space, the method allows for variable resolution in real space; produces sparse, structured matrices, enabling the effective use of iterative solution methods; and is well suited to parallel implementation. The method thus combines the significant advantages of both real-space-grid and basis-oriented approaches and so promises to be particularly well suited for large, accurate ab initio calculations. We develop the theory of our approach in detail, discuss advantages and disadvantages, and report initial results, including the first fully three-dimensional electronic band structures calculated by the method.Comment: replacement: single spaced, included figures, added journal referenc

Epigenome editing of the CFTR-locus for treatment of cystic fibrosis

Background: Mechanisms governing the diversity of CFTR gene expression throughout the body are complex. Multiple intronic and distal regulatory elements are responsible for regulating differential CFTR expression across tissues. Methods: Drawing on published data, 18 high-priority genomic regions were identified and interrogated for CFTR-enhancer function using CRISPR/dCas9-based epigenome editing tools. Each region was evaluated by dCas9p300 and dCas9KRAB for its ability to enhance or repress CFTR expression, respectively. Results: Multiple genomic regions were tested for enhancer activity using CRISPR/dCas9 epigenome editing. dCas9p300 mediates a significant increase in CFTR mRNA levels when targeted to the promoter and a region 44 kb upstream of the transcriptional start site in a CFTR-low expressing cell line. Multiple gRNAs targeting the promoter induced a robust increase in CFTR protein levels. In contrast, dCas9KRAB-mediated repression is much more robust with 10 of the 18 evaluated genomic regions inducing CFTR protein knockdown. To evaluate the therapeutic efficacy of modulating CFTR gene regulation, dCas9p300 was used to induce elevated levels of CFTR from the endogenous locus in ΔF508/ΔF508 human bronchial epithelial cells. Ussing chamber studies demonstrated a synergistic increase in ion transport in response to CRISPR-induced expression of ΔF508 CFTR mRNA along with VX809 treatment. Conclusions: CRISPR/dCas9-based epigenome-editing provides a previously unexplored tool for interrogating CFTR enhancer function. Here, we demonstrate that therapeutic interventions that increase the expression of CFTR may improve the efficacy of CFTR modulators. A better understanding CFTR regulatory mechanisms could uncover novel therapeutic interventions for the development of cystic fibrosis therapies

A Model for the Development of the Rhizobial and Arbuscular Mycorrhizal Symbioses in Legumes and Its Use to Understand the Roles of Ethylene in the Establishment of these two Symbioses

We propose a model depicting the development of nodulation and arbuscular mycorrhizae. Both processes are dissected into many steps, using Pisum sativum L. nodulation mutants as a guideline. For nodulation, we distinguish two main developmental programs, one epidermal and one cortical. Whereas Nod factors alone affect the cortical program, bacteria are required to trigger the epidermal events. We propose that the two programs of the rhizobial symbiosis evolved separately and that, over time, they came to function together. The distinction between these two programs does not exist for arbuscular mycorrhizae development despite events occurring in both root tissues. Mutations that affect both symbioses are restricted to the epidermal program. We propose here sites of action and potential roles for ethylene during the formation of the two symbioses with a specific hypothesis for nodule organogenesis. Assuming the epidermis does not make ethylene, the microsymbionts probably first encounter a regulatory level of ethylene at the epidermis–outermost cortical cell layer interface. Depending on the hormone concentrations there, infection will either progress or be blocked. In the former case, ethylene affects the cortex cytoskeleton, allowing reorganization that facilitates infection; in the latter case, ethylene acts on several enzymes that interfere with infection thread growth, causing it to abort. Throughout this review, the difficulty of generalizing the roles of ethylene is emphasized and numerous examples are given to demonstrate the diversity that exists in plants

Microstructural changes in the irradiated and osteoradionecrotic bone: a SEM study

Radiation exposure is a major health concern due to bone involvement including mandible, causing deleterious effects on bone metabolism, and healing with an increasing risk of infection and osteoradionecrosis. This study aims to investigate the radiotherapy-induced microstructural changes in the human mandible by scanning electron microscopy (SEM). Mandibular cortical bone biopsies were obtained from control, irradiated, and patients with osteoradionecrosis (ORN). Bone samples were prepared for light microscopy and SEM. The SEM images were analyzed for the number of osteons, number of Haversian canal (HC), diameter of osteon (D.O), the diameter of HC (D.HC), osteonal wall thickness (O.W.Th), number of osteocytes, and number of osteocytic dendrites. The number of osteons, D.O, D.HC, O.W.Th, the number of osteocytes, and osteocytic dendrites were significantly decreased in both irradiated and ORN compared to controls (p 5 years mean radiation biopsy interval). The underlying microscopic damage in bone increases its susceptibility and contributes further to radiation-induced bone changes or even ORN.Metabolic health: pathophysiological trajectories and therap