High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10(-8)) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.
Fluid dynamic forces in centrifugal blood pump impellers are of key importance in destruction of red blood cells (RBCs) because high rotational speed leads to strong interaction between the impeller and the RBCs. In this paper, three-dimensional models of five different blade geometries are investigated numerically using the commercial software CFX-TASCflow, and the streaklines of RBCs are obtained using the Lagrangian particle tracking method. In reality, RBCs pass through the pump along complicated paths resulting in a highly irregular loading condition for each RBC. In order to enable the prediction of blood damage under the action of these complex-loading conditions, a cumulative damage model for RBCs was adopted in this paper. The numerically simulated percent hemoglobin (%HB) released as RBCs traversed the impeller and volute was examined. It was observed that the residence time of particles in the blade passage is a critical factor in determining hemolytic effects. This, in turn, is a function of the blade geometry. In addition, it was observed that the volute profile is an important influence on the computed HB% released.
This paper experimentally investigates the effects of microhole eccentricity on the slip lengths of Stokes flow in microchannels with the bottom wall made of microhole arrays. The wettability of such microhole structures fabricated by the replica molding of polydimethylsiloxane is first analyzed measuring both static and dynamic contact angles. Subsequently, the drag reduction performance of the microchannels with such hydrophobic microhole surfaces is evaluated. The results indicate that the impact of microhole eccentricity on drag reduction performance correlates well with the contact angle hysteresis rather than with the static contact angle. Furthermore, microhole arrays with large normalized width and zero eccentricity show the minimum contact angle hysteresis of 18.7°. In these microchannels, the maximum percentage increase in the relative velocity is 39% corresponding to a slip length of 2.49 μm. For the same normalized width, increasing the normalized eccentricity to 2.6 increases the contact angle hysteresis to 36.5° that eventually reduces the percentage increase in relative velocity and slip length down to 16% and 0.91 μm, respectively. The obtained results are in qualitative agreement with the existing theoretical and numerical models. These findings provide additional insights in the design and fabrication of efficient micropatterned channels for reducing the flow resistance, and leave open questions for theoreticians to further investigate in this field.
This article experimentally shows that the wetting property of a micropatterned surface is a function of the center-to-center offset distance between successive pillars in a column, referred to here as eccentricity. Studies were conducted on square micropatterns which were fabricated on a silicon wafer with pillar eccentricity ranging from 0 to 6 μm for two different pillar diameters and spacing. Measurement results of the static as well as the dynamic contact angles on these surfaces revealed that the contact angle decreases with increasing eccentricity and increasing relative spacing between the pillars. Furthermore, quantification of the contact angle hysteresis (CAH) shows that, for the case of lower pillar spacing, CAH could increase up to 41%, whereas for the case of higher pillar spacing, this increment was up to 35%, both corresponding to the maximum eccentricity of 6 μm. In general, the maximum obtainable hydrophobicity corresponds to micropillars with zero eccentricity. As the pillar relative spacing decreases, the effect of eccentricity on hydrophobicity becomes more pronounced. The dependence of the wettability conditions of the micropatterned surface on the pillar eccentricity is attributed to the contact line deformation resulting from the changed orientation of the pillars. This finding provides additional insights in design and fabrication of efficient micropatterned surfaces with controlled wetting properties.
A comprehensive review of current analytical models, experimental techniques, and influencing factors is carried out to highlight the current challenges in this area. The study of fluid-solid boundary conditions has been ongoing for more than a century, starting from gas-solid interfaces and progressing to that of the more complex liquidsolid case. Breakthroughs have been made on the theoretical and experimental fronts but the mechanism behind the phenomena remains a puzzle. This paper provides a review of the theoretical models, and numerical and experimental investigations that have been carried out till date. Probable mechanisms and factors that affect the interfacial discontinuity are also documented.
Accurate cardiac motion estimation from medical images such as ultrasound is important for clinical evaluation. We present a novel regularisation layer for cardiac motion estimation that will be applied after image registration and demonstrate its effectiveness. The regularisation utilises a spatio-temporal model of motion, b-splines of Fourier, to fit to displacement fields from pairwise image registration. In the process, it enforces spatial and temporal smoothness and consistency, cyclic nature of cardiac motion, and better adherence to the stroke volume of the heart. Flexibility is further given for inclusion of any set of registration displacement fields. The approach gave high accuracy. When applied to human adult Ultrasound data from a Cardiac Motion Analysis Challenge (CMAC), the proposed method is found to have 10% lower tracking error over CMAC participants. Satisfactory cardiac motion estimation is also demonstrated on other data sets, including human fetal echocardiography, chick embryonic heart ultrasound images, and zebrafish embryonic microscope images, with the average Dice coefficient between estimation motion and manual segmentation at 0.82–0.87. The approach of performing regularisation as an add-on layer after the completion of image registration is thus a viable option for cardiac motion estimation that can still have good accuracy. Since motion estimation algorithms are complex, dividing up regularisation and registration can simplify the process and provide flexibility. Further, owing to a large variety of existing registration algorithms, such an approach that is usable on any algorithm may be useful.
Critical aortic stenosis (AS) of the fetal heart causes a drastic change in the cardiac biomechanical environment. Consequently, a substantial proportion of such cases will lead to a single-ventricular birth outcome. However, the biomechanics of the disease is not well understood. To address this, we performed Finite Element (FE) modelling of the healthy fetal left ventricle (LV) based on patient-specific 4D ultrasound imaging, and simulated various disease features observed in clinical fetal AS to understand their biomechanical impact. These features included aortic stenosis, mitral regurgitation (MR) and LV hypertrophy, reduced contractility, and increased myocardial stiffness. AS was found to elevate LV pressures and myocardial stresses, and depending on severity, can drastically decrease stroke volume and myocardial strains. These effects are moderated by MR. AS alone did not lead to MR velocities above 3 m/s unless LV hypertrophy was included, suggesting that hypertrophy may be involved in clinical cases with high MR velocities. LV hypertrophy substantially elevated LV pressure, valve flow velocities and stroke volume, while reducing LV contractility resulted in diminished LV pressure, stroke volume and wall strains. Typical extent of hypertrophy during fetal AS in the clinic, however, led to excessive LV pressure and valve velocity in the FE model, suggesting that reduced contractility is typically associated with hypertrophy. Increased LV passive stiffness, which might represent fibroelastosis, was found to have minimal impact on LV pressures, stroke volume, and wall strain. This suggested that fibroelastosis could be a by-product of the disease progression and does not significantly impede cardiac function. Our study demonstrates that FE modelling is a valuable tool for elucidating the biomechanics of congenital heart disease and can calculate parameters which are difficult to measure, such as intraventricular pressure and myocardial stresses.
This paper experimentally evaluates the combined effects of eccentricity, relative spacing, and viewing directions on the wetting conditions and the three-phase contact line shapes of hydrophobic surfaces patterned with discrete micropillars. Different techniques to depict the tortuosity of the contact line between the water droplet and microstructured surfaces are presented. First, square micropillars with different values of normalized eccentricity, , and relative spacing, , were fabricated using double casting replication technique. Subsequently, the contact angles were measured along different viewing angles by gradually rotating the sample from to . The contact angle distribution was found as a periodic function of viewing angle whose period depends on the micropillar eccentricity. The results showed that anisotropy increases by increasing the micropillar eccentricity or decreasing the pillar relative spacing. However, the effect of changing the micropillar eccentricity was much more pronounced. Micropillars with and smaller showed maximum degrees of anisotropic wetting and droplet distortion corresponding to 7% and 15%, respectively. Using the measured droplet aspect ratio, corrugated shapes of the three-phase contact line of the micropillars were also reconstructed. Finally, a simple yet effective semi-analytical model, based on Fourier series curve-fitting of the experimental data, was developed to describe the equilibrium 3D shape of the droplet on anisotropic surfaces. Experimental and simulation results reveal that the degrees of anisotropic wetting and droplet distortion were directly proportional to the energy barriers of the system resulting from noncircular corrugated shape of the three-phase contact line. The obtained results may further shed light on the underlying mechanism influencing anisotropic wetting on micropatterned surfaces.
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