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A sample of 154,893 patient responses from the Customer Satisfaction Survey database was drawn for 1999 to 2000. Average patient satisfaction levels consistently appeared to be high (between 6, very satisfied, and 7, completely satisfied, on the 7-point rating scale). Hierarchical regression results essentially replicated all three major constructs of an earlier theoretical attitude model. Refinements included adjustment and addition of categorical age and military beneficiary status for individual patient variables, addition of two beliefs about the care itself, substitution of waiting time variables, and addition of reason for visit situation variables. Hypothesis test results indicated that patient satisfaction constructs were homogeneous across the uniformed services for patients from all service branches, both enrolled and not enrolled within TRICARE regions, and among branch of service medical center, hospital, and clinic facilities. The final attitude model coefficient of multiple determinations obtained was R2 = 0.701 [F(25,154,867) = 14,539.33, p < 0.0001]. [ABSTRACT FROM AUTHOR]

Theoretical models of the human heart valves are useful tools for understanding and characterizing the dynamics of healthy and diseased valves. Enabled by advances in numerical modeling and in a range of disciplines within experimental biomechanics, recent models of the heart valves have become increasingly comprehensive and accurate. In this paper, we first review the fundamentals of native heart valve physiology, composition and mechanics in health and disease. We will then furnish an overview of the development of theoretical and experimental methods in modeling heart valve biomechanics over the past three decades. Next, we will emphasize the necessity of using multiscale modeling approaches in order to provide a comprehensive description of heart valve biomechanics able to capture general heart valve behavior. Finally, we will offer an outlook for the future of valve multiscale modeling, the potential directions for further developments and the challenges involved.

The regulation of valvular endothelial phenotypes by the hemodynamic environments of the human aortic valve is poorly understood. The nodular lesions of calcific aortic stenosis (CAS) develop predominantly beneath the aortic surface of the valve leaflets in the valvular fibrosa layer. However, the mechanisms of this regional localization remain poorly characterized. In this study, we combine numerical simulation with in vitro experimentation to investigate the hypothesis that the previously documented differences between valve endothelial phenotypes are linked to distinct hemodynamic environments characteristic of these individual anatomical locations. A finite-element model of the aortic valve was created, describing the dynamic motion of the valve cusps and blood in the valve throughout the cardiac cycle. A fluid mesh with high resolution on the fluid boundary was used to allow accurate computation of the wall shear stresses. This model was used to compute two distinct shear stress waveforms, one for the ventricular surface and one for the aortic surface. These waveforms were then applied experimentally to cultured human endothelial cells and the expression of several pathophysiological relevant genes was assessed. Compared to endothelial cells subjected to shear stress waveforms representative of the aortic face, the endothelial cells subjected to the ventricular waveform showed significantly increased expression of the "atheroprotective" transcription factor Kruppel-like factor 2 (KLF2) and the matricellular protein Nephroblastoma overexpressed (NOV), and suppressed expression of chemokine Monocyte-chemotactic protein-1 (MCP-1). Our observations suggest that the difference in shear stress waveforms between the two sides of the aortic valve leaflet may contribute to the documented differential side-specific gene expression, and may be relevant for the development and progression of CAS and the potential role of endothelial mechanotransduction in this disease.

Functional endothelialized networks constitute a critical building block for vascularized replacement tissues, organ assist devices, and laboratory tools for in vitro discovery and evaluation of new therapeutic compounds. Progress towards realization of these functional artificial vasculatures has been gated by limitations associated with the mechanical and surface chemical properties of commonly used microfluidic substrate materials and by the geometry of the microchannels produced using conventional fabrication techniques. Here we report on a method for constructing microvascular networks from polystyrene substrates commonly used for tissue culture, built with circular cross-sections and smooth transitions at bifurcations. Silicon master molds are constructed using an electroplating process that results in semi-circular channel cross-sections with smoothly varying radii. These master molds are used to emboss polystyrene sheets which are then joined to form closed bifurcated channel networks with circular cross-sections. The mechanical and surface chemical properties of these polystyrene microvascular network structures enable culture of endothelial cells along the inner lumen. Endothelial cell viability was assessed, documenting nearly confluent monolayers within 3D microfabricated channel networks with rounded cross-sections.

Objectives: The persistent shortage of donor organs for lung transplantation illustrates the need for new strategies in organ replacement therapy. Pulmonary tissue engineering aims at developing viable hybrid tissue for patients with chronic respiratory failure., Methods: Dual-chamber polymer constructs that mimic the characteristics of the pulmonary air-blood interface were fabricated by microfabrication techniques using the biocompatible polymer polydimethylsiloxane. One compartment ("vascular chamber") was designed as a capillary network to mimic the pulmonary microvasculature. The other compartment ("parenchymal chamber") was designed to permit gas exchange. Immortalized mouse lung epithelium cells (MLE-12) were cultured on the surface of polystyrene microcarrier beads. These beads were subsequently injected into the parenchymal chamber of the dual-chamber microsystems. The vascular compartment was perfused with cell culture medium in a bioreactor and the construct was maintained in culture for 1 week., Results: The microcarriers evenly distributed MLE-12 cells on the parenchymal compartment surface. Confluent cell layers were confirmed by fluorescent and electron microscopy. Adequate proliferation of MLE-12 cells within the construct was monitored via the DNA content. Viability of the cells was maintained over 1 week. Finally, cellular specificity and functional capacity in situ were demonstrated by immunostaining for proSP-B and proSP-C (alveolar epithelium), and by using MLE-12 cells transfected to overexpress green fluorescent protein., Conclusion: We conclude that functional hybrid microsystems mimicking the basic building plan of alveolar tissue can be engineered in vitro.

The aortic heart valve undergoes geometric and mechanical changes over time. The cusps of a normal, healthy valve thicken and become less extensible over time. In the disease calcific aortic stenosis (CAS), calcified nodules progressively stiffen the cusps. The local mechanical changes in the cusps, due to either normal aging or pathological processes, affect overall function of the valve. In this paper, we propose a computational model for the aging aortic valve that connects local changes to overall valve function. We extend a previous model for the healthy valve to describe aging. To model normal/uncomplicated aging, leaflet thickness and extensibility are varied versus age according to experimental data. To model calcification, initial sites are defined and a simple growth law is assumed. The nodules then grow over time, so that the area of calcification increases from one model to the next model representing greater age. Overall valve function is recorded for each individual model to yield a single simulation of valve function over time. This simulation is the first theoretical tool to describe the temporal behavior of aortic valve calcification. The ability to better understand and predict disease progression will aid in design and timing of patient treatments for CAS.

Patients with bicuspid aortic valve (BAV) are more likely to develop a calcific aortic stenosis (CAS), as well as a number of other ailments, as compared to their cohorts with normal tricuspid aortic valves (TAV). It is currently unknown whether the increase in risk of CAS is caused by the geometric differences between the tricuspid and bicuspid valves or whether the increase in risk is caused by the same underlying factors that produce the geometric difference. CAS progression is understood to be a multiscale process, mediated at the cell level. In this study, we employ multiscale finite-element simulations of the valves. We isolate the effect of one geometric factor, the number of cusps, in order to explore its effect on multiscale valve mechanics, particularly in relation to CAS. The BAV and TAV are modeled by a set of simulations describing the cell, tissue, and organ length scales. These simulations are linked across the length scales to create a coherent multiscale model. At each scale, the models are three-dimensional, dynamic, and incorporate accurate nonlinear constitutive models of the valve leaflet tissue. We compare results between the TAV and BAV at each length scale. At the cell-scale, our region of interest is the location where calcification develops, near the aortic-facing surface of the leaflet. Our simulations show the observed differences between the tricuspid and bicuspid valves at the organ scale: the bicuspid valve shows greater flexure in the solid phase and stronger jet formation in the fluid phase relative to the tricuspid. At the cell-scale, however, we show that the region of interest is shielded against strain by the wrinkling of the fibrosa. Thus, the cellular deformations are not significantly different between the TAV and BAV in the calcification-prone region. This result supports the assertion that the difference in calcification observed in the BAV versus TAV may be due primarily to factors other than the simple geometric difference between the two valves.

A novel microfluidics-based bilayer device with a discrete parenchymal chamber modeled upon hepatic organ architecture is described. The microfluidics network was designed using computational models to provide appropriate flow behavior based on physiological data from human microvasculature. Patterned silicon wafer molds were used to generate films with the vascular-based microfluidics network design and parenchymal chamber by soft lithography. The assembled device harbors hepatocytes behind a nanoporous membrane that permits transport of metabolites and small proteins while protecting them from the effects of shear stress. The device can sustain both human hepatoma cells and primary rat hepatocytes by continuous in vitro perfusion of medium, allowing proliferation and maintaining hepatic functions such as serum protein synthesis and metabolism. The design and fabrication processes are scalable, enabling the device concept to serve as both a platform technology for drug discovery and toxicity, and for the continuing development of an improved liver-assist device.

A set of multiscale simulations has been created to examine the dynamic behavior of the human aortic valve (AV) at the cell, tissue, and organ length scales. Each model is fully three-dimensional and includes appropriate nonlinear, anisotropic material models. The organ-scale model is a dynamic fluid-structure interaction that predicts the motion of the blood, cusps, and aortic root throughout the full cycle of opening and closing. The tissue-scale model simulates the behavior of the AV cusp tissue including the sub-millimeter features of multiple layers and undulated geometry. The cell-scale model predicts cellular deformations of individual cells within the cusps. Each simulation is verified against experimental data. The three simulations are linked: deformations from the organ-scale model are applied as boundary conditions to the tissue-scale model, and the same is done between the tissue and cell scales. This set of simulations is a major advance in the study of the AV as it allows analysis of transient, three-dimensional behavior of the AV over the range of length scales from cell to organ.

One of the principal challenges facing the field of tissue engineering over the past 2 decades has been the requirement for large-scale engineered constructs comprising precisely organized cellular microenvironments. For vital organ assist and replacement devices, microfluidic-based systems such as the microcirculation, biliary, or renal filtration and resorption systems and other functional elements containing multiple cell types must be generated to provide for viable engineered tissues and clinical benefit. Over the last several years, microfabrication technology has emerged as a versatile and powerful approach for generating precisely engineered scaffolds for engineered tissues. Fabrication process tools such as photolithography, etching, molding, and lamination have been established for applications involving a range of biocompatible and biodegradable polymeric scaffolding materials. Computational fluid dynamic designs have been used to generate scaffold designs suitable for microvasculature and a number of organ-specific constructs; these designs have been translated into 3-dimensional scaffolding using microfabrication processes. Here a brief overview of the fundamental microfabrication technologies used for tissue engineering will be presented, along with a summary of progress in a number of applications, including the liver and kidney.

The conventional interpretation of the Hawking-Moss (HM) solution implies a transition rate between vacua that depends only on the values of the potential in the initial vacuum and at the top of a potential barrier, leading to the implausible conclusion that transitions to distant vacua can be as likely as those to a nearby one. I analyze this issue using a nongravitational example with analogous properties. I show that such HM bounces do not give reliable rate calculations, but are instead related to the probability of finding a quasistable configuration at a local potential maximum.

This paper presents a shell finite element formulation appropriate for simulating the heart valve leaflet mechanics, including three-dimensional (3D) stress and strain effects. A 4-node mixed-interpolation shell is formulated in convected coordinates. This shell model is made capable of handling arbitrary 3D material models by use of an algorithm that satisfies the shell stress assumption at every element integration point. A method for tracking the fiber direction is incorporated. The resulting shell element operates under the same conditions as a standard 4-node shell element with 5 degrees of freedom per node, but extends the modeling capabilities to handle large-deformation and anisotropic behavior.

This paper presents a finite element formulation suitable for large-strain modeling of biological tissues and uses this formulation to implement an accurate finite element model for mitral valve leaflet tissue. First, an experimentally derived strain energy function is obtained from literature. This function is implemented in finite elements using the mixed pressure-displacement formulation. A modification is made to aid in maintaining positive definiteness of the stiffness matrix at low strains. The numerical implementation is shown to be accurate in representing the analytical model of material behavior. The mixed formulation is useful for modeling of soft biological tissues in general, and the model presented here is applicable to finite element simulation of mitral valve mechanics.

Objective: We describe the MR imaging findings of patients who underwent laparoscopic renal lesion cryoablation., Materials and Methods: Twenty-one patients (men, 11; women, 10; age range, 36-84 years; average age, 65.5 years; SD, 11.9) with 23 small renal masses (< or =4 cm) underwent laparoscopic renal lesion cryoablation. Twenty patients (22 masses) underwent follow-up MR imaging on the first day after surgery, 12 (13 masses) at 1 month, 16 (18 masses) at 3 months, 14 (15 masses) at 6 months, and 12 (12 masses) at 12 months. Three radiologists retrospectively reviewed MR images for the signal intensity, characteristics, and size of cryolesions. CT-guided needle biopsy was performed 6 months after cryoablation (18 patients) and no evidence of malignancy was discovered., Results: Including all lesions at all times on T1-weighted images, cryolesion signal intensity was isointense to renal parenchyma (47/76, 61.8%) or isointense with hyper- or hypointense foci (7/76, 9.2%). On T2-weighted images, almost all lesions (72/76, 94.7%) were isointense or hypointense, and there was a hypointense rim between the cryolesion and renal parenchyma in 38.2% of lesions (29/76). A thin peripheral rim of enhancement was noted in 19.7% (14/74) of lesions. Cryolesions decreased in size an average of 61.5% (SD, 22.82; n = 12) at 1 month, 78.7% (SD, 13.5; n = 17) at 3 months, 83.5% (SD, 24.3; n = 15) at 6 months, and 94.2% (SD, 8.1; n = 11) at 1 year after cryoablation (one patient was not scanned 1 day after cryoablation and was not included in our calculations)., Conclusion: After renal cryoablation, MR imaging revealed common signal characteristics such as low-signal-intensity rims on T2-weighted images, enhancement patterns such as thin peripheral rims, and interval size changes.

Severe coronary artery disease may occur early in the course of mucopolysaccharidosis. The authors present radiologic, scintigraphic, and pathologic findings in five patients with Hurler syndrome. Thallium-201 myocardial scintigraphy and selective coronary angiography obtained within 2 days to 6 months were correlated in five patients. Postmortem examination of the coronary arteries was obtained in one patient within hours of angiography. Interobserver agreement on grading of scintigraphic abnormalities was poor. Nonspecific findings on Tl-201 studies included septal abnormalities in all five patients. Scintigraphic findings were corroborated by angiography and postmortem results in only 3 of 5 patients. Our findings suggest that resting Tl-201 scintigraphy has limited value in the detection of coronary artery disease in patients with Hurler syndrome.

Rationale and Objectives: We asked our nonradiologist colleagues to evaluate and comment on the most desirable format for radiology education., Methods: Questionnaires were distributed to 631 nonradiologist physicians affiliated with the University of Minnesota and representing all medical specialties and academic ranks. Three hundred twenty-seven surveys were returned after one mailing., Results: Residency was retrospectively noted to be indispensable for consolidating knowledge of radiology. The overwhelming majority of clinicians in all specialties believed that formal radiologic instruction should be mandatory for medical students (279 of 322; 87%). Film interpretation was believed to be an indispensable part of a medical student radiology rotation (226 of 321; 70%), but many clinicians indicated a need for additional training. A marked disparity in the perceived level of confidence in interpreting radiologic tests during medical school and residency between those who had and those who had not received formal radiologic instruction during medical school was evident. This difference in perceived level of confidence was present even among the most experienced clinicians., Conclusions: Collectively, the nonradiologist clinicians emphasized the need for a mandatory and clinically oriented radiology curriculum during medical school.