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Isothermal nucleic acid amplification tests (NAATs) are a vital tool for point-of-care (POC) diagnostics. These assays are well-suited for rapid, low-cost POC diagnostics for infectious diseases compared to traditional PCR tests conducted in central laboratories. There has been significant development of POC NAATs using paper-based diagnostic devices because they provide an affordable, user-friendly, and easy to store format; however, the difficulties in integrating separate liquid components, resuspending dried reagents, and achieving a low limit of detection hinder their use in commercial applications. Several studies report low assay efficiencies, poor detection output, and poorer limits of detection in porous membranes compared to traditional tube-based protocols. Recombinase polymerase amplification is a rapid, isothermal NAAT that is highly suited for POC applications, but requires viscous reaction conditions that has poor performance when amplifying in a porous paper membrane. In this work, we show that we can dramatically improve the performance of membrane-based recombinase polymerase amplification (RPA) of HIV-1 DNA and viral RNA by employing a coin cell-based vibration mixing platform. We achieve a limit of detection of 12 copies of DNA per reaction, nearly 50% reduction in time to threshold (from ∼10 minutes to ∼5 minutes), and an overall fluorescence output increase up to 16-fold when compared to unmixed experiments. This active mixing strategy enables reactions where the target and reaction cofactors are isolated from each other prior to the reaction. We also demonstrate amplification using a low-cost vibration motor for both temperature control and mixing, without the requirement of any additional heating components.

Dimethyl methylphosphonate (DMMP) is often used as a chemical surrogate for organophosphate nerve agents, as it exhibits similar physiochemical properties while having significantly lower toxicity. Continuous hydrolysis of DMMP in hot-compressed water is performed at temperatures from 200 to 300 °C, pressures of 20 and 30 MPa, and residence times from 30 to 80 s to evaluate the effects of pressure and temperature on reaction kinetics. DMMP hydrolysis is observed to follow pseudo-first-order reaction behavior, producing methylphosphonic acid and methanol as the only detectable reaction products. This is significant for the practical implementation of a continuous hydrothermal reactor for chemical warfare agent neutralization, as the process only yields stable, less-toxic compounds. Pressure has no discernible effect on the hydrolysis rate in compressed liquid water. Pseudo-first-order Arrhenius parameters are determined, with an activation energy of 90.17 ± 5.68 kJ/mol and a pre-exponential factor of 10 7.51±0.58 s -1 .

Background: The SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) randomized 2,521 patients with moderate heart failure (HF) to amiodarone, placebo drug, or implantable cardioverter-defibrillator (ICD) therapy. Original trial follow-up ended October 31, 2003. Over a median 45.5-month follow-up, amiodarone, compared with placebo, did not affect survival, whereas randomization to an ICD significantly decreased all-cause mortality by 23%., Objectives: This study sought to describe the extended treatment group survival of the SCD-HeFT cohort., Methods: Mortality outcomes for the 1,855 patients alive at the end of the SCD-HeFT trial were collected between 2010 and 2011. These data were combined with the 666 deaths from the original study to compare long-term outcomes overall and for key pre-specified subgroups., Results: Median (25th to 75th percentiles) follow-up was 11.0 (10.0 to 12.2) years. On the basis of intention-to-treat analysis, the ICD group had overall survival benefit versus placebo drug (hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.76 to 0.98; p = 0.028). When treatment benefit was examined as a function of time from randomization, attenuation of the ICD benefit was observed after 6 years (p value for the interaction = 0.0015). Subgroup analysis revealed long-term ICD benefit varied according to HF etiology and New York Heart Association (NYHA) functional class: ischemic HF HR: 0.81; 95% CI: 0.69 to 0.95; p = 0.009; nonischemic HF HR: 0.97; 95% CI: 0.79 to 1.20; p = 0.802; NYHA functional class II HR: 0.76; 95% CI: 0.65 to 0.90; p = 0.001; NYHA functional class III HR: 1.06; 95% CI: 0.86 to 1.31; p = 0.575., Conclusions: Follow-up of SCD-HeFT patients to 11 years demonstrated heterogenous treatment-related patterns of long-term survival with ICD benefit most evident at 11 years for ischemic HF patients and for those with NYHA functional class II symptoms at trial enrollment. (SCD-HeFT 10 Year Follow-up [SCD-HeFT10 Yr]; NCT01058837)., (Copyright © 2020 American College of Cardiology Foundation. All rights reserved.)

The spectra presented correspond with the research article entitled "Kinetics of Formic Acid Decomposition in Subcritical and Supercritical Water - A Raman Spectroscopic Study" [1]. Data set contains in situ Raman spectra of the quenched effluent stream, which includes varied concentrations of formic acid, water, CO, CO 2 , and H 2 as reaction products. Each spectrum is collected downstream of the subcritical or supercritical water gasification of formic acid, which occurs at a specified temperature, residence time, a constant pressure of 25 MPa, and a constant initial feedstock concentration of 3.6 wt% formic acid. Additionally, calibration spectra of formic acid in water, and spectra of pure carbon dioxide and high concentration formic acid are provided for model development. Finally, a MATLAB code used for baseline subtraction of raw data files is included with the dataset. The full dataset is hosted in Mendeley Data, https://doi.org/10.17632/hjn8xwskng.1., (© 2020 The Author(s).)

The halteres of flies are mechanosensory organs that serve a crucial role in the control of agile flight, providing sensory input for rapid course corrections to perturbations. Derived from hind wings, halteres are actively flapped and are thus subject to a variety of inertial forces as the fly undergoes complex flight trajectories. Previous analyses of halteres modelled them as a point mass, showing that Coriolis forces lead to subtle deflections orthogonal to the plane of flapping. By design, these models could not consider the effects of force gradients associated with a mass distribution, nor could they reveal three-dimensional spatio-temporal patterns of strain that result from those forces. In addition, diversity in the geometry of halteres, such as shape and asymmetries, could not be simply modelled with a point mass on a massless rod. To study the effects of mass distributions and asymmetries, we examine the haltere subject to both flapping and body rotations using three-dimensional finite-element simulations. We focus on a set of simplified geometries, in which we vary the stalk and bulb shape. We find that haltere mass distribution gives rise to two unreported deformation modes: (i) halteres twist with a magnitude that strongly depends on stalk and bulb geometry and (ii) halteres with an asymmetric mass distribution experience out-of-plane bending due to centrifugal forces, independent of body rotation. Since local strains at the base of the haltere drive deformations of mechanosensory neurons, we combined measured neural encoding mechanisms with our structural analyses to predict the spatial and temporal patterns of neural activity. This activity depends on both the flapping and rotation dynamics, and we show how the timing of neural activity is a viable mechanism for rotation-rate encoding. Our results provide new insights in haltere dynamics and show the viability for timing-based encoding of fly body rotations by halteres.

Optimizing an industrial-scale supercritical water gasification process requires detailed knowledge of chemical reaction pathways, rates, and product yields. Laboratory-scale reactors are employed to develop this knowledge base. The rationale behind designs and component selection of continuous flow, laboratory-scale supercritical water gasification reactors is analyzed. Some design challenges have standard solutions, such as pressurization and preheating, but issues with solid precipitation and feedstock pretreatment still present open questions. Strategies for reactant mixing must be evaluated on a system-by-system basis, depending on feedstock and experimental goals, as mixing can affect product yields, char formation, and reaction pathways. In-situ Raman spectroscopic monitoring of reaction chemistry promises to further fundamental knowledge of gasification and decrease experimentation time. High-temperature, high-pressure spectroscopy in supercritical water conditions is performed, however, long-term operation flow cell operation is challenging. Comparison of Raman spectra for decomposition of formic acid in the supercritical region and cold section of the reactor demonstrates the difficulty in performing quantitative spectroscopy in the hot zone. Future designs and optimization of continuous supercritical water gasification reactors should consider well-established solutions for pressurization, heating, and process monitoring, and effective strategies for mixing and solids handling for long-term reactor operation and data collection.

Implantable-cardioverter defibrillators (ICD) detect and terminate life-threatening ventricular tachyarrhythmia with electric shocks after they occur. This puts patients at risk if they are driving or in a situation where they can fall. ICD's shocks are also very painful and affect a patient's quality of life. It would be ideal if ICDs can accurately predict the occurrence of ventricular tachyarrhythmia and then issue a warning or provide preventive therapy. Our study explores the use of ICD data to automatically predict ventricular arrhythmia using heart rate variability (HRV). A 5 minute and a 10 second warning system are both developed and compared. The participants for this study consist of 788 patients who were enrolled in the ICD arm of the Sudden Cardiac Death-Heart Failure Trial (SCD-HeFT). Two groups of patient rhythms, regular heart rhythms and pre-ventricular-tachyarrhythmic rhythms, are analyzed and different HRV features are extracted. Machine learning algorithms, including random forests (RF) and support vector machines (SVM), are trained on these features to classify the two groups of rhythms in a subset of the data comprising the training set. These algorithms are then used to classify rhythms in a separate test set. This performance is quantified by the area under the curve (AUC) of the ROC curve. Both RF and SVM methods achieve a mean AUC of 0.81 for 5-minute prediction and mean AUC of 0.87-0.88 for 10-second prediction; an AUC over 0.8 typically warrants further clinical investigation. Our work shows that moderate classification accuracy can be achieved to predict ventricular tachyarrhythmia with machine learning algorithms using HRV features from ICD data. These results provide a realistic view of the practical challenges facing implementation of machine learning algorithms to predict ventricular tachyarrhythmia using HRV data, motivating continued research on improved algorithms and additional features with higher predictive power., Competing Interests: The authors have declared that no competing interests exist.

People with transtibial amputation often experience skin breakdown due to the pressures and shear stresses that occur at the limb-socket interface. The purpose of this research was to create a transtibial finite element model (FEM) of a contemporary prosthesis that included complete socket geometry, two frictional interactions (limb-liner and liner-socket), and an elastomeric liner. Magnetic resonance imaging scans from three people with characteristic transtibial limb shapes (i.e., short-conical, long-conical, and cylindrical) were acquired and used to develop the models. Each model was evaluated with two loading profiles to identify locations of focused stresses during stance phase. The models identified five locations on the participants' residual limbs where peak stresses matched locations of mechanically induced skin issues they experienced in the 9 months prior to being scanned. The peak contact pressure across all simulations was 98 kPa and the maximum resultant shear stress was 50 kPa, showing reasonable agreement with interface stress measurements reported in the literature. Future research could take advantage of the developed FEM to assess the influence of changes in limb volume or liner material properties on interface stress distributions. Graphical abstract Residual limb finite element model. Left: model components. Right: interface pressures during stance phase.

A run-to-run optimization controller uses a reduced set of measurement parameters, in comparison to more general feedback controllers, to converge to the best control point for a repetitive process. A new run-to-run optimization controller is presented for the scanning fiber device used for image acquisition and display. This controller utilizes very sparse measurements to estimate a system energy measure and updates the input parameterizations iteratively within a feedforward with exact-inversion framework. Analysis, simulation, and experimental investigations on the scanning fiber device demonstrate improved scan accuracy over previous methods and automatic controller adaptation to changing operating temperature. A specific application example and quantitative error analyses are provided of a scanning fiber endoscope that maintains high image quality continuously across a 20 °C temperature rise without interruption of the 56 Hz video.

A set of protocols was created to characterize prosthetic liners across six clinically relevant material properties. Properties included compressive elasticity, shear elasticity, tensile elasticity, volumetric elasticity, coefficient of friction (CoF), and thermal conductivity. Eighteen prosthetic liners representing the diverse range of commercial products were evaluated to create test procedures that maximized repeatability, minimized error, and provided clinically meaningful results. Shear and tensile elasticity test designs were augmented with finite element analysis (FEA) to optimize specimen geometries. Results showed that because of the wide range of available liner products, the compressive elasticity and tensile elasticity tests required two test maxima; samples were tested until they met either a strain-based or a stress-based maximum, whichever was reached first. The shear and tensile elasticity tests required that no cyclic conditioning be conducted because of limited endurance of the mounting adhesive with some liner materials. The coefficient of friction test was based on dynamic coefficient of friction, as it proved to be a more reliable measurement than static coefficient of friction. The volumetric elasticity test required that air be released beneath samples in the test chamber before testing. The thermal conductivity test best reflected the clinical environment when thermal grease was omitted and when liner samples were placed under pressure consistent with load bearing conditions. The developed procedures provide a standardized approach for evaluating liner products in the prosthetics industry. Test results can be used to improve clinical selection of liners for individual patients and guide development of new liner products.

Background: In the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), a significant fraction of the patients with congestive heart failure ultimately did not die suddenly of arrhythmic causes. Patients with CHF will benefit from better tools to identify if implantable cardioverter-defibrillator (ICD) therapy is needed., Objectives: We aimed to identify predictor variables from baseline SCD-HeFT patients' R-R intervals that correlate to arrhythmic sudden cardiac death (SCD) and mortality and to design an ICD therapy screening test., Methods: Ten predictor variables were extracted from prerandomization Holter data from 475 patients enrolled in the ICD arm of the SCD-HeFT by using novel and traditional heart rate variability methods. All variables were correlated to SCD using the Mann-Whitney-Wilcoxon test and receiver operating characteristic analysis. ICD therapy screening tests were designed by minimizing the cost of false classifications. Survival analysis, including log-rank test and Cox models, was also performed., Results: A short-term fractal exponent, α1, and a long-term fractal exponent, α2, from detrended fluctuation analysis, the ratio of low- to high-frequency power, the number of premature ventricular contractions per hour, and the heart rate turbulence slope are all statistically significant for predicting the occurrences of SCD (P < .001) and survival (log-rank, P < .01). The most powerful multivariate predictor tool using the Cox proportional hazards regression model was α2 with a hazard ratio of 0.0465 (95% confidence interval 0.00528-0.409; P < .01)., Conclusion: Predictor variables extracted from R-R intervals correlate to the occurrences of SCD and distinguish survival functions among patients with ICDs in SCD-HeFT. We believe that SCD prediction models should incorporate Holter-based R-R interval analysis to refine ICD patient selection, especially to exclude patients who are unlikely to benefit from ICD therapy., (Copyright © 2015 Heart Rhythm Society. All rights reserved.)

Insects perform fast rotational manoeuvres during flight. While two insect orders use flapping halteres (specialized organs evolved from wings) to detect body dynamics, it is unknown how other insects detect rotational motions. Like halteres, insect wings experience gyroscopic forces when they are flapped and rotated and recent evidence suggests that wings might indeed mediate reflexes to body rotations. But, can gyroscopic forces be detected using only changes in the structural dynamics of a flapping, flexing insect wing? We built computational and robotic models to rotate a flapping wing about an axis orthogonal to flapping. We recorded high-speed video of the model wing, which had a flexural stiffness similar to the wing of the Manduca sexta hawkmoth, while flapping it at the wingbeat frequency of Manduca (25 Hz). We compared the three-dimensional structural dynamics of the wing with and without a 3 Hz, 10° rotation about the yaw axis. Our computational model revealed that body rotation induces a new dynamic mode: torsion. We verified our result by measuring wing tip displacement, shear strain and normal strain of the robotic wing. The strains we observed could stimulate an insect's mechanoreceptors and trigger reflexive responses to body rotations., (© 2015 The Author(s) Published by the Royal Society. All rights reserved.)

Insect wings deform significantly during flight. As a result, wings act as aeroelastic structures wherein both the driving motion of the structure and the aerodynamic loading of the surrounding fluid potentially interact to modify wing shape. We explore two key issues associated with the design of compliant wings: over a range of driving frequencies and phases of pitch-heave actuation, how does wing stiffness influence (1) the lift and thrust generated and (2) the relative importance of fluid loading on the shape of the wing? In order to examine a wide range of parameters relevant to insect flight, we develop a computationally efficient, two-dimensional model that couples point vortex methods for fluid force computations with structural finite element methods to model the fluid-structure interaction of a wing in air. We vary the actuation frequency, phase of actuation, and flexural stiffness over a range that encompasses values measured for a number of insect taxa (10-90 Hz; 0-π rad; 10(-7)-10(-5) N m(2)). We show that the coefficients of lift and thrust are maximized at the first and second structural resonant frequencies of the system. We also show that even in regions of structural resonance, fluid loading never contributes more than 20% to the development of flight forces.

Observations of underwater noise from impact pile driving were made with a vertical line array. Previous studies [Reinhall and Dahl, J. Acoust. Soc. Am. 130, 1209-1216 (2011)] show that the dominant underwater noise from impact driving is from the Mach wave associated with the radial expansion of the pile that propagates down the pile at supersonic speed after impact. Here precise estimates of the vertical arrival angles associated with the down- and up-going Mach wave are made via beam forming, and the energy budget of the arrival structure is quantified.

Background: The current gold standard of bladder cancer surveillance, endoscopic visualization, is manually manipulated and still has significant room for improvement in performance and controls., Methods: This paper reports our developments toward automated bladder surveillance that employs a shape memory alloy-based machine-controlled scanning mechanism. In conjunction with the electro-mechanical advances, we use modified commercial post-processing computer vision software capable of converting cystoscopic video of the bladder into stitched panoramas., Results: Experimental results conducted on a synthetic bladder demonstrate that this computer-aided scanning tool can help 82% of the entire bladder surface being scanned. Although the panoramic stitching algorithm increases the field of view and generates reasonable results in many cases, some image matching failures result in incompleteness in its full panoramic reconstruction., Conclusion: Our current study ensures that the automated steering mechanism can follow the desired trajectory to scan the surface of the bladder but must be improved. The current reconstruction algorithm needs further modification. Our methodology may constitute a first step in suggesting a new automated and computer-aided bladder surveillance system.

The underwater noise from impact pile driving is studied using a finite element model for the sound generation and parabolic equation model for propagation. Results are compared with measurements using a vertical line array deployed at a marine construction site in Puget Sound. It is shown that the dominant underwater noise from impact driving is from the Mach wave associated with the radial expansion of the pile that propagates down the pile after impact at supersonic speed. The predictions of vertical arrival angle associated with the Mach cone, peak pressure level as function of depth, and dominant features of the pressure time series compare well with corresponding field observations., (© 2011 Acoustical Society of America)

The steady state response motion of a base excited cantilever beam with circular cross-section excited by a unidirectional displacement will fall along a straight line. However, achieving straight-line motion with a real cantilever beam of circular cross-section is difficult to accomplish. This is due to the fact that nonlinear effects, small deviations from circularity, asymmetric boundary conditions, and actuator cross coupling can induce whirling. The vast majority of previous work on cantilever beam whirling has focused on the effects of system nonlinearities. We show that whirling is a much broader problem in the design of resonant beam scanners in that the onset of whirling does not depend on large amplitude of motion. Rather, whirling is the norm in real systems due to small system asymmetries and actuator cross coupling. It is therefore necessary to control the growth of the whirling motion when a unidirectional beam motion is desired. We have developed a novel technique to identify the two eigen directions of the beam. Base excitation generated by virtual electrodes along these orthogonal eigen axes of the cantilever beam system generates tip vibration without whirl. This leads to accurate open loop control of the motion of the beam through the combined actuation of two pairs of orthogonally placed actuator electrodes.

Arthritis is a chronic, debilitating disease affecting one in six people in the United States annually. One of the most promising surgical treatments is total joint replacement. After decades of development, some joint replacement (arthroplasty) systems such as the hip and knee enjoy high success rates while others, particularly newer ones for the ankle, have disappointing survival rates. The goal of this study was to investigate, develop, and test a methodology to assess implant osteointegration, specifically for the talar component of a total ankle prosthesis. A vibrometry technique using Doppler ultrasound was developed to non-invasively determine osteointegration clinically. This methodology was evaluated via preliminary experimentation, along with another validation methodology, to access whether design criteria have been met in order to initiate a clinical study of the technique. Bench-top and cadaveric testing demonstrated that the Doppler ultrasound technique could distinguish the level of osteointegration between loose and fixed implant components. The laser vibrometry technique, used for the validation of the ultrasound technique intraoperatively, was also shown to be functional and indicative of the ultrasound technique's testing results. This methodology can provide a much needed tool to determine the integration of implants non-invasively in the clinical and surgical setting, thus allowing each patient's rehabilitation program to be monitored and tailored to maximize the osteointegration and survival rate of their total joint replacement., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Given the advantages of cystoscopic exams compared with other procedures available for bladder surveillance, it would be beneficial to develop an improved automated cystoscope. We develop and propose an active programmable remote steering mechanism and an efficient motion sequence for bladder cancer detection and postoperative surveillance. The continuous and optimal path of the imaging probe can enable a medical practitioner to readily ensure that images are produced for the entire surface of the bladder in a controlled and uniform manner. Shape memory alloy (SMA) based segmented actuators disposed adjacent to the distal end of the imaging probe are selectively activated to bend the shaft to assist in positioning and orienting the imaging probe at a plurality of points selected to image all the interior of the distended bladder volume. The bending arc, insertion depth, and rotational position of the imaging probe are automatically controlled based on patient-specific data. The initial prototype is tested on a 3D plastic phantom bladder, which is used as a proof-of-concept in vitro model and an electromagnetic motion tracker. The 3D tracked tip trajectory results ensure that the motion sequencing program and the steering mechanism efficiently move the image probe to scan the entire inner tissue layer of the bladder. The compared experimental results shows 5.1% tip positioning error to the designed trajectory given by the simulation tool. The authors believe that further development of this concept will help guarantee that a tumor or other characteristic of the bladder surface is not overlooked during the automated cystoscopic procedure due to a failure to image it.

A flexible high-resolution sensor capable of measuring the distribution of pressure beneath the foot via a microfabricated optical waveguide system is presented. The uniqueness of the system is in its batch fabrication process, which involves a microfabrication molding technique with polydimethylsiloxane (PDMS) as the optical medium. The sensor manufacturing technique is described in detail, the optical performance of the waveguides is quantified and the effect of using a matching fluid to improve fiber-coupling efficiency is demonstrated. Mechanical loading tests were performed on a 4 x 4 array with a 2-mm spacing between sensing elements. Loading displacement curves were obtained using a 0 to 0.4 mm triangle loading profile. A force of 0.28 N applied to one of the sensing elements produced a displacement of a 0.325 mm and 39% change in the output light intensity. Multiple loadings were conducted to demonstrate the repeatability of the sensor. A force image algorithm with a two-layer neural network system was used to identify four load magnitudes and four different shaped applicators. All four shapes were successfully identified with the neural network.

Background and Aim of the Study: The dynamics of the mitral valve result from the synergy of left heart geometry, local blood flow and tissue integrity. Herein is presented the first coupled fluid-structure computational model of the mitral valve in which valvular kinematics result from the interaction of local blood flow and a continuum representation of valvular microstructure., Methods: The diastolic geometry of the mitral valve was assembled from previously published experimental data. Anterior and posterior leaflets were modeled as networks of entangled collagen fibers, embedded in an isotropic matrix. The resulting non-linear continuum description of mitral tissue was implemented in a three-dimensional membrane formulation. Chordal tension-only behavior was defined from experimental tensile tests. The computational model considered the valve immersed in a domain of Newtonian blood, with an experimentally determined viscosity corresponding to a shear rate of 180 s(-1) at 37 degrees C. Ventricular and atrial pressure curves were applied to ventricular and atrial surfaces of the blood domain., Results: Peak closing flow and volume were 51 ml/s and 1.17 ml, respectively. Papillary muscle force ranged dynamically between 0.0 and 2.6 N. Acoustic pressure (RMS) was found to be 3.3 Pa, with a peak frequency of 72 Hz at 0.064 s from the onset of systole. Model predictions showed excellent agreement with available transmitral flow, papillary force and first heart sound (S1) acoustic data., Conclusion: The addition of blood flow and an experimentally driven microstructural description of mitral tissue represent a significant advance in computational studies of the mitral valve. This model will be the foundation for future computational studies on the effect of pathophysiological tissue alterations on mitral valve competence.

Lower-limb complications associated with diabetes include the development of plantar ulcers that can lead to infection and subsequent amputation. While we know from force-plate analyses that medial/lateral and anterior/posterior shear components of ground-reaction forces exist, little is known about the actual distribution of these stresses during daily activities or about the role that shear stresses play in causing plantar ulceration. Furthermore, one critical reason why these data have not been obtained previously is the lack of a validated, widely used, commercially available shear sensor, partly because of the various technical issues associated with measuring shear. In this study, we present a novel means of transducing plantar pressure and shear stress with a fiber-optic sensor. The pressure/shear sensor consists of an array of optical fibers lying in perpendicular rows and columns separated by elastomeric pads. We constructed a map of normal and shear stresses based on observed macrobending through the intensity attenuation from the physical deformation of two adjacent perpendicular fibers. Initial results show that this sensor exhibits low noise and responds to applied normal and shear loads with good repeatability.

Background: Many diseases that affect the mitral valve are accompanied by the proliferation or degradation of tissue microstructure. The early acoustic detection of these changes may lead to the better management of mitral valve disease. In this study, we examine the nonstationary acoustic effects of perturbing material parameters that characterize mitral valve tissue in terms of its microstructural components. Specifically, we examine the influence of the volume fraction, stiffness and splay of collagen fibers as well as the stiffness of the nonlinear matrix in which they are embedded., Methods and Results: To model the transient vibrations of the mitral valve apparatus bathed in a blood medium, we have constructed a dynamic nonlinear fluid-coupled finite element model of the valve leaflets and chordae tendinae. The material behavior for the leaflets is based on an experimentally derived structural constitutive equation. The gross movement and small-scale acoustic vibrations of the valvular structures result from the application of physiologic pressure loads. Material changes that preserved the anisotropy of the valve leaflets were found to preserve valvular function. By contrast, material changes that altered the anisotropy of the valve were found to profoundly alter valvular function. These changes were manifest in the acoustic signatures of the valve closure sounds. Abnormally, stiffened valves closed more slowly and were accompanied by lower peak frequencies., Conclusion: The relationship between stiffness and frequency, though never documented in a native mitral valve, has been an axiom of heart sounds research. We find that the relationship is more subtle and that increases in stiffness may lead to either increases or decreases in peak frequency depending on their relationship to valvular function.

Automatic acoustic classification and diagnosis of mitral valve disease remain outstanding biomedical problems. Although considerable attention has been given to the evolution of signal processing techniques, the mechanics of the first heart sound generation has been largely overlooked. In this study, the haemodynamic determinants of the first heart sound were examined in a computational model. Specifically, the relationship of the transvalvular pressure and its maximum derivative to the time-frequency content of the acoustic pressure was examined. To model the transient vibrations of the mitral valve apparatus bathed in a blood medium, a dynamic, non-linear, fluid-coupled finite element model of the mitral valve leaflets and chordae tendinae was constructed. It was found that the root mean squared (RMS) acoustic pressure varied linearly (r2= 0.99) from 0.010 to 0.259 mmHg, following an increase in maximum dP/dt from 415 to 12470 mm Hg s(-1). Over that same range, peak frequency varied non-linearly from 59.6 to 88.1 Hz. An increase in left-ventricular pressure at coaptation from 22.5 to 58.5mm Hg resulted in a linear (r2= 0.91) rise in RMS acoustic pressure from 0.017 to 1.41mm Hg. This rise in transmitral pressure was accompanied by a non-linear rise in peak frequency from 63.5 to 74.1 Hz. The relationship between the transvalvular pressure and its derivative and the time-frequency content of the first heart sound has been examined comprehensively in a computational model for the first time. Results suggest that classification schemes should embed both of these variables for more accurate classification.

Objectives: Progressive aortic root dilatation and an increased aortic root elastic modulus have been documented in persons with Marfan syndrome. To examine the effect of aortic root dilatation and increased elastic modulus on leaflet stress, strain, and coaptation, we used a finite-element model., Methods: The normal model incorporated the geometry, tissue thickness, and anisotropic elastic moduli of normal human roots and valves. Four Marfan models were evaluated, in which the diameter of the aortic root was dilated by 5%, 15%, 30%, and 50%. Aortic root elastic modulus in the 4 Marfan models was doubled. Under diastolic pressure, regional stresses and strains were evaluated, and the percentage of leaflet coaptation was calculated., Results: Root dilatation and stiffening significantly increased regional leaflet stress and strain compared with normal levels. Stress increases ranged from 80% to 360% and strain increases ranged from 60% to 200% in the 50% dilated Marfan model. Leaflet stresses and strains were disproportionately high at the attachment edge and coaptation area. Leaflet coaptation was decreased by approximately 20% in the 50% root dilatation model., Conclusions: Increasing root dilatation and root elastic modulus to simulate Marfan syndrome significantly increases leaflet stress and strain and reduces coaptation in an otherwise normal aortic valve. These alterations may influence the decision to use valve-sparing aortic root replacement procedures in patients with Marfan syndrome.

A fractionally differenced (FD) process is used to model aerothermal turbulence data, and the model parameters are estimated via wavelet techniques. Theory and results are presented for three estimators of the FD parameter: an "instantaneous" block-independent least squares estimator and block-dependent weighted least squares and maximum likelihood estimators. Confidence intervals are developed for the block-dependent estimators. We show that for a majority of the aerothermal turbulence data studied herein, there is a strong departure from the theoretical Kolmogorov turbulence over finite ranges of scale. A time-scale-dependent inertial range statistic is developed to quantify this departure.

Aortic valve incompetence due to aortic root dilation may be surgically corrected by resuspension of the native valve within a vascular graft. This study was designed to examine the effect of graft shape and material properties on aortic valve function, using a three-dimensional finite-element model of the human aortic valve and root. First, the normal root elements in the model were replaced with graft elements, in either a cylindrical or a "pseudosinus" shape. Next, the elements were assigned the material properties of either polyethylene terephthalate, expanded polytetrafluoroethylene, or polyurethane. Diastolic pressures were applied, and stresses, strains, and coaptation were recorded for the valve, root, and graft. Regarding shape, the cylindrical graft models increased the valve stresses by up to 173%, whereas the root-shaped graft model increased valve stresses by up to 40% as compared to normal. Regarding material properties, the polyurethane models demonstrated valve stress, strain, and coaptation values closest to normal, for either root shape. Graft shape had a greater effect on the simulated valve function than did the material property of the graft. Optimizing the shape and material design of the graft may result in improved longevity of the spared valve if a normal environment is restored.

Background: Idiopathic root dilatation often results in dysfunction of an otherwise normal aortic valve. To examine the effect of root dilatation on leaflet stress, strain, and coaptation, we utilized a finite element model., Methods: The normal model incorporated the geometry, tissue thickness, stiffness, and collagen fiber alignment of normal human roots and valves. We evaluated four dilatation models in which diameters of the aortic root were dilated by 5%, 15%, 30%, and 50%. Regional stress and strain were evaluated and leaflet coaptation percent was calculated under diastolic pressure., Results: Root dilatation significantly increased regional leaflet stress and strain beyond that found in the normal model. Stress increases ranged from 57% to 399% and strain increases ranged from 39% to 189% in the 50% dilatation model. Leaflet stress and strain were disproportionately high at the attachment edge and coaptation area. Leaflet coaptation was decreased by 18% in the 50% root dilatation model., Conclusions: Idiopathic root dilatation significantly increases leaflet stress and strain and reduces coaptation in an otherwise normal aortic valve. These alterations may affect valve-sparing aortic root replacement procedures.

Objective: The treatment of choice for aortic valve insufficiency due to root dilatation has become root replacement with aortic valve sparing. However, root replacement with a synthetic graft may result in altered valve stresses. The purpose of this study was to compare the stress/strain patterns in the spared aortic valve in different root replacement procedures by means of finite element modeling., Methods: Our finite element model of the normal human root and valve was modified to simulate and evaluate three surgical techniques: (1) "cylindrical" graft sutured below the valve at the anulus, (2) "tailored" graft sutured just above the valve, and (3) "pseudosinus" graft, tailored and sutured below the valve at the anulus. Simulated diastolic pressures were applied, and stresses and strains were calculated for the valve, root, and graft. Leaflet coaptation was also quantified., Results: All three root replacement models demonstrated significantly altered leaflet stress patterns as compared with normal patterns. The cylindrical model showed the greatest increases in stress (16%-173%) and strain (10%-98%), followed by the tailored model (stress +10%-157%, strain +9%-36%). The pseudosinus model showed the smallest increase in stress (9%-28%) and strain (2%-31%), and leaflet coaptation was closest to normal., Conclusion: Valve-sparing techniques that allow the potential for sinus space formation (tailored, pseudosinus) result in simulated leaflet stresses that are closer to normal than the cylindrical technique. Normalized leaflet stresses in the clinical setting may result in improved longevity of the spared valve.

Background and Aim of the Study: The effect of aging on aortic valve and root function was examined using a three-dimensional finite element model of the aortic root and valve., Methods: Three models representing normal (< 35 years), middle (35-55 years) and older (> 55 years) age groups, were created by assigning tissue thickness and stiffness that increased with age (using ANSYS software). Diastolic pressure was applied; stresses and strains were then evaluated for the valve and root, and percent leaflet coaptation was calculated., Results: Leaflet stresses were increased with aging, whereas leaflet strain and coaptation were decreased with aging. Specifically, leaflet stresses were increased by 6-14% in the middle-age model, and by 2-11% in the older-age model, as compared with normal in specified leaflet regions. Conversely, leaflet strains were decreased by 27-41% and 42-50% in the middle-age and older-age models, respectively. This reduced strain resulted in markedly decreased coaptation (9% and 30% reduction for middle- and older-age models). In the root, stress remained fairly constant with age, but strain in the root was progressively reduced with age (11% and 35% reduction for the middle and older-age models, respectively)., Conclusions: In these models, increased stiffness and thickness due to aging reduces leaflet deformation and restricts coaptation. Clinically, valvular regurgitation may result due to leaflet thickening and stiffening with normal aging. Our model can now be utilized to evaluate the root-valve relationship in the presence of bioprosthetic valves or root replacements.

The asymmetry of the aortic valve and aortic root may influence their biomechanics, yet was not considered in previous valve models. This study developed an anatomically representative model to evaluate the regional stresses of the valve within the root environment. A finite-element model was created from magnetic-resonance images of nine human valve-root specimens, carefully preserving their asymmetry. Regional thicknesses and anisotropic material properties were assigned to higher-order elastic shell elements representing the valve and root. After diastolic pressurization, peak principal stresses were evaluated for the right, left, and noncoronary leaflets and root walls. Valve stresses were highest in the noncoronary leaflet (538 kPa vs right 473 kPa vs left 410 kPa); peak stresses were located at the free margin and belly near the coaptation surfaces (averages 537 and 482 kPa for all leaflets, respectively). Right and noncoronary sinus stresses were 21% and 10% greater than the left sinus. In all sinuses, stresses near the annulus were higher than near the sinotubular junction. Stresses vary across the valve and root, likely due to their inherent morphologic asymmetry and stress sharing. These factors may influence bioprosthetic valve durability and the incidence of isolated sinus dilatation.