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Endovascular coil embolization is one of the primary treatment techniques for cerebral aneurysms. Although it is a well-established and minimally invasive method, it bears the risk of suboptimal coil placement which can lead to incomplete occlusion of the aneurysm possibly causing recurrence. One of the key features of coils is that they have an imprinted natural shape supporting the fixation within the aneurysm. For the spatial discretization, our mathematical coil model is based on the discrete elastic rod model which results in a dimension-reduced 1D system of differential equations. We include bending and twisting responses to account for the coils natural curvature and allow for the placement of several coils having different material parameters. Collisions between coil segments and the aneurysm wall are handled by an efficient contact algorithm that relies on an octree based collision detection. In time, we use a standard symplectic semi-implicit Euler time stepping method. Our model can be easily incorporated into blood flow simulations of embolized aneurysms. In order to differentiate optimal from suboptimal placements, we employ a suitable in silico Raymond-Roy-type occlusion classification and measure the local packing density in the aneurysm at its neck, wall region and core. We investigate the impact of uncertainties in the coil parameters and embolization procedure. To this end, we vary the position and the angle of insertion of the micro-catheter, and approximate the local packing density distributions by evaluating sample statistics., Competing Interests: Declarations Conflict of interest The authors declare that they have no conflict of interest., (© 2024. The Author(s).)

Purpose: Aortic dissection is associated with a high mortality rate. Although computational approaches have shed light on many aspects of the disease, a sensitivity analysis is required to determine the significance of different factors. Because of its complex geometry and high computational expense, the three-dimensional (3D) fluid-structure interaction (FSI) simulation is not a suitable approach for sensitivity analysis., Methods: We performed a Monte Carlo simulation (MCS) to investigate the sensitivity of hemodynamic quantities to the lumped parameters of our zero-dimensional (0D) model with numerically calculated lumped parameters. We performed local and global analyses on the effect of the model parameters on important hemodynamic quantities., Results: The MCS showed that a larger lumped resistance value for the false lumen and the tears result in a higher retrograde flow rate in the false lumen (the coefficient of variation, c v , i = 0.0183 , the sensitivity S X i σ = 0.54 , Spearman's coefficient, ρ s = 0.464 ). For the intraluminal pressure, our results show a significant role in the resistance and inertance of the true lumen (the coefficient of variation, c v , i = 0.0640 , the sensitivity S X i σ = 0.85 , and Spearman's coefficient, ρ s = 0.855 for the inertance of the true lumen)., Conclusion: This study highlights the necessity of comparing the results of the local and global sensitivity analyses to understand the significance of multiple lumped parameters. Because of the efficiency of the method, our approach is potentially useful to investigate and analyze medical planning., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Numerical simulations of head-related transfer functions (HRTFs) conventionally assume a rigid boundary condition for the pinna. The human pinna, however, is an elastic deformable body that can vibrate due to incident acoustic waves. This work investigates how sound-induced vibrations of the pinna can affect simulated HRTF magnitudes. The work will motivate the research question by measuring the sound-induced vibrational patterns of an artificial pinna with a high-speed holographic interferometric system. Then, finite element simulations are used to determine HRTFs for a tabletop model of the B&K 5128 head and torso simulator for a number of directions. Two scenarios are explored: one where the pinna is modeled as perfectly rigid, and another where the pinna is modeled as linear elastic with material properties close to that of auricular cartilage. The findings suggest that pinna vibrations have negligible effects on HRTF magnitudes up to 5 kHz. The same conclusion, albeit with less certainty, is drawn for higher frequencies. Finally, the importance of the elastic domain's material properties is emphasized and possible implications for validation studies on dummy heads 1as well as the limitations of the present work are discussed in detail., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

In this paper, a mathematical model based on spherical differential unit cell is proposed as a model for studying seasonal freeze-thaw soil space infinitesimal differential unit cell. From this model, the basic equations of permafrost moisture and heat flow motion are directly derived, then the linked equations form the permafrost water-heat coupled transport model. On this basis, the one-dimensional seasonal permafrost water-heat transport equation is derived. The model reduces the original spatial three-variable coordinate system (parallel hexahedron) into a coupled equation with a single spherical radius (R) as the independent variable, so the iterations of the numerical simulation algorithm is greatly reduced and the complexity is decreased. Finally, the model is used to simulate the seasonal freeze-thaw soil in the ShiHeZi region of Xinjiang, China. The principle of the simulation is to collect the soil temperature and humidity values of the region in layers and fixed-points using a homemade freeze-thaw soil sensor, after that we solve it by numerical calculation using MATLAB. The analysis results show that the maximum relative error of the model we proposed is 4.36, the minimum error is 0.98, and the average error is 2.515. The numerical simulation results are basically consistent with the measured data, then the proposed model is consistent with the matching states of permafrost moisture content and soil temperature in the region at different times. In addition, the experiments also demonstrate the reliability and accuracy of the model., Competing Interests: The authors have declared that no competing interests exist.

Coronavirus and its spread all over the world have been the most challenging crisis in 2020. Hospitals are categorized among the most vulnerable centers due to their presumably highest traffic of this virus. In this study, centrifugal isolation of coronavirus is successfully deployed for purifying hospitals' air using air conditioners and ducts, suggesting an efficient setup. Numerical simulations have been used to testify the proposed setup due to the complexities of using experimental investigation such as high cost and clinical hazards of the airborne SARS-CoV-2 in the air. Results show that a 20-cm pipe with an inlet velocity of 4 m/s constitutes the best choice for the separation and purification of air from the virus. The proposed scalable method also efficiently separates larger particles, but it can separate smaller particles too. Numerical results also suggest installing the air purifying system on the floor of the hospitals' room for maximum efficiency., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Compound-specific isotope analysis of chlorine (CSIA-Cl) is a practicable and high-performance approach for revelation of transformation processes and source identification of chlorinated organic pollutants. This study conducted CSIA-Cl for typical polychlorinated organic pollutants using gas chromatography-high resolution mass spectrometry (GCHRMS) with an alternate injection mode using perchloroethylene (PCE) and trichloroethylene (TCE) as model analytes. PCE and TCE standards from two manufacturers were employed for method development, and chlorine isotope ratio calculation schemes were evaluated by experiment and numerical simulation. The achieved precision (standard deviation of isotope ratios) was up to 0.21‰ for PCE and 0.43‰ for TCE. The limits of detection for CSIA-Cl of were 0.05 μg/mL (0.05 ng on column), and the linearities were 0.05-1 μg/mL. Two isotope ratio calculation schemes, i.e., one using complete molecular isotopologues and another using the first pair of neighboring chlorine isotopologues of each analyte, were evaluated in terms of accuracy and precision. The complete-isotopologue scheme showed evidently higher precision and was more competent to reflect trueness than the isotopologue-pair scheme and the two schemes could present completely different outcomes. The method has been successfully applied to PCE and TCE reagents from different suppliers, a trichloromethane reagent, and a plastic material. The relative isotope ratio variations (Δ 37 Cl) of PCE and TCE in the reagents and plastic material were from -1.84±0.7‰ to 15.12±0.85‰. The analytes from different sources could mostly be discerned from each other by chlorine isotope ratios. This study will be conducive to transformation process elucidation and source identification of for PCE and TCE, and facilitate CSIA-Cl using GC-MS for more polychlorinated organic pollutants, particularly in selection and optimization of isotope ratio calculation schemes., Competing Interests: Declaration of Competing Interest The authors have declared no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

The abdominal aorta is the largest artery in the abdominal cavity that supplies blood flows to vital organs through the complex visceral arterial branches, including the celiac trunk (the liver, stomach, spleen, etc.), the renal arteries (the kidneys) and the superior and inferior mesenteric arteries (the small and large intestine, pancreas, etc.). An accurate simulation of blood flows in this network of arteries is important for the understanding of the hemodynamics in various organs of healthy and diseased patients, but the computational cost is very high. As a result, most researchers choose to focus on a portion of the artery or use a low-dimensional approximation of the artery. In the present work, we introduce a parallel algorithm for the modeling of pulsatile flows in the abdominal aorta with branches to the primary organs, and an organ-based two-level method for calculating the resistances for the outflow boundary conditions. With this highly parallel approach, the simulation of the blood flow for a cardiac cycle of the anatomically detailed aorta can be obtained within a few hours, and the blood distribution to organs including liver, spleen and kidneys are also computed with certain accuracy. Moreover, we discuss the significant hemodynamic differences resulted from the influence of the peripheral branches. In addition, we examine the accuracy of the results with respect to the mesh size and time-step size and show the high parallel scalability of the proposed algorithm with up to 3000 processor cores.

In this paper, we propose a generalized class of exponential type estimators for estimating the finite population mean using two auxiliary attributes under simple random sampling and stratified random sampling. The bias and mean squared error (MSE) of the proposed class of estimators are derived up to first order of approximation. Both empirical study and theoretical comparisons are discussed. Four populations are used to support the theoretical findings. It is observed that the proposed class of estimators perform better as compared to all other considered estimator in simple and stratified random sampling., Competing Interests: The authors have declared that no competing interests exist.

Atherosclerosis is a progressive disease that can significantly reduce blood supply to vital organs, being one of the main causes of death worldwide. In this work, a numerical and experimental study in 3D printed stenotic coronary arteries, considering both steady and pulsatile blood flow conditions, is presented. The results revealed that a degree of stenosis superior to 50% creates disturbed flows downstream of the contraction, with an accented increase in the wall shear stress measurements at the stenosis throat. Finally, the multiphase mixture was investigated and compared with a single-phase modelling, and only slight differences were observed right after the stenosis throat.

In the emerging field of 3D bioprinting, cell damage due to large deformations is considered a main cause for cell death and loss of functionality inside the printed construct. Those deformations, in turn, strongly depend on the mechano-elastic response of the cell to the hydrodynamic stresses experienced during printing. In this work, we present a numerical model to simulate the deformation of biological cells in arbitrary three-dimensional flows. We consider cells as an elastic continuum according to the hyperelastic Mooney-Rivlin model. We then employ force calculations on a tetrahedralized volume mesh. To calibrate our model, we perform a series of FluidFM[Formula: see text] compression experiments with REF52 cells demonstrating that all three parameters of the Mooney-Rivlin model are required for a good description of the experimental data at very large deformations up to 80%. In addition, we validate the model by comparing to previous AFM experiments on bovine endothelial cells and artificial hydrogel particles. To investigate cell deformation in flow, we incorporate our model into Lattice Boltzmann simulations via an Immersed-Boundary algorithm. In linear shear flows, our model shows excellent agreement with analytical calculations and previous simulation data.

A numerical approach is presented to efficiently simulate time-resolved 3D phase-contrast Magnetic resonance Imaging (or 4D Flow MRI) acquisitions under realistic flow conditions. The Navier-Stokes and Bloch equations are simultaneously solved with an Eulerian-Lagrangian formalism. A semi-analytic solution for the Bloch equations as well as a periodic particle seeding strategy are developed to reduce the computational cost. The velocity reconstruction pipeline is first validated by considering a Poiseuille flow configuration. The 4D Flow MRI simulation procedure is then applied to the flow within an in vitro flow phantom typical of the cardiovascular system. The simulated MR velocity images compare favorably to both the flow computed by solving the Navier-Stokes equations and experimental 4D Flow MRI measurements. A practical application is finally presented in which the MRI simulation framework is used to identify the origins of the MRI measurement errors., Competing Interests: This study was funded by ALARA Expertise (https://www.alara-expertise.fr/) and Spin Up (https://www.spin-up.fr/). Thomas Puiseux and Anou Sewonu are paid employees of Spin Up and Ramiro Moreno is paid employee of ALARA Expertise. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The nasal airway is an extremely complex structure, therefore grid generation for numerical prediction of airflow in the nasal cavity is time-consuming. This paper describes the development of a voxel-based model with a Cartesian structured grid, which is characterized by robust and automatic grid generation, and the simulation of the airflow and air-conditioning in an individual human nasal airway. Computed tomography images of a healthy adult nose were used to reconstruct a virtual three-dimensional model of the nasal airway. Simulations of quiet restful inspiratory flow were then performed using a Neumann boundary condition for the energy equation to adequately resolve the flow and heat transfer. General agreements of airflow patterns, which were a high-speed jet posterior to the nasal valve and recirculating flow that occupied the anterior part of the upper cavity, and temperature distributions of the airflow and septum wall were confirmed by comparing in-vivo measurements with numerical simulation results.

CFD has emerged as a promising diagnostic tool for clinical trials, with tremendous potential. However, for real clinical applications to be useful, overall statistical findings from large population samples (e.g., multiple cases and models) are needed. Fully resolved solutions are not a priority, but rather rapid solutions with fast turn-around times are desired. This leads to the issue of what are the minimum modelling criteria for achieving adequate accuracy in respiratory flows for large-scale clinical applications, with a view to rapid turnaround times. This study simulated a highly-resolved solution using the large eddy simulation (LES) method as a reference case for comparison with lower resolution models that included larger time steps and no turbulence modelling. Differences in solutions were quantified by pressure loss, flow resistance, unsteadiness, turbulence intensity, and hysteresis effects from multiple cycles. The results demonstrated that sufficient accuracy could be achieved with lower resolution models if the mean flow was considered. Furthermore, to achieve an established transient result unaffected by the initial start-up quiescent effects, the results need to be taken from at least the second respiration cycle. It was also found that the exhalation phase exhibited strong turbulence. The results are expected to provide guidance for future modelling efforts for clinical and engineering applications requiring large numbers of cases using simplified modelling approaches.

Atherosclerotic plaque in the femoral is the leading cause of peripheral artery disease (PAD), the worse consequence of which may lead to ulceration and gangrene of the feet. Numerical studies on fluid-structure interactions (FSI) of atherosclerotic femoral arteries enable quantitative analysis of biomechanical features in arteries. This study aims to investigate the hemodynamic performance and its interaction with femoral arterial wall based on the patient-specific model with multiple plaques (calcified and lipid plaques). Three types of models, calcification-only, lipid-only and calcification-lipid models, are established. Hyperelastic material coefficients of the human femoral arteries obtained from experimental studies are employed for all simulations. Oscillation of WSS is observed in the healthy downstream region in the lipid-only model. The pressure around the plaques in the two-plaque model is lower than that in the corresponding one-plaque models due to the reduction of blood flow domain, which consequently diminishes the loading forces on both plaques. Therefore, we found that stress acting on the plaques in the two-plaque model is lower than that in the corresponding one-plaque models. This finding implies that the lipid plaque, accompanied by the calcified plaque around, might reduce its risk of rupture due to the reduced the stress acting on it.

In order to have research on the deformation characteristics and mechanical properties of human red blood cells (RBCs), finite element models of RBC optical tweezers stretching and atomic force microscope (AFM) indentation were established. Non-linear elasticity of cell membrane was determined by using the neo-Hookean hyperelastic material model, and the deformation of RBC during stretching and indentation had been researched in ABAQUS, respectively. Considering the application of machine learning (ML) in material parameters identification, ML algorithm was combined with finite element (FE) method to identify the constitutive parameters. The material parameters were estimated according to the deformation characteristics of RBC obtained from the change of cell diameter with stretching force when RBC was stretched. The non-linear relationship between material parameter and RBC deformation was established by building a FE-model. The FE simulation of RBC stretching was used to construct the training set and the neural network trained by a large number of samples was used to predict the material parameter. With the predicted parameter, FE simulation of RBC under AFM indentation to explore the local deformation mechanism was completed.

In this study, flow field characteristics in the trachea region in a realistic human upper airway model were firstly measured by particle image velocimetry (PIV) in the air under three constant inhalation and exhalation conditions: 36 L/min, 64 L/min and 90 L/min, representing flow rates of 18 L/min, 32 L/min and 45 L/min in real human airway (the model was twice the size of a human airway). Computational fluid dynamics (CFD) analyses were performed on four turbulence models, with boundary conditions corresponding to the PIV experiments. The effects of flow rates and breathing modes on the airflow patterns were investigated. The CFD prediction results were compared with the PIV measurements and showed relatively good agreement in all cases. During inhalation, the higher the flow rates, the less significant the "glottal jet" phenomenon, and the smaller the area of the separation zone. The air in the nasal inhalation condition accelerated more dramatically after glottis. The SST-Transition model was the best choice for predicting inhalation velocity profiles. For exhalation condition, the maximum velocity was much smaller than that during inhalation due to the more uniform flow field. The exhalation flow rates and breathing modes had little effect on the flow characteristics in the trachea region. The RNG k - ε model and SST k - ω model were recommended to simulate the flow field in the respiratory tract during exhalation.

Credible computational fluid dynamic (CFD) simulations of aortic dissection are challenging, because the defining parallel flow channels-the true and the false lumen-are separated from each other by a more or less mobile dissection membrane, which is made up of a delaminated portion of the elastic aortic wall. We present a comprehensive numerical framework for CFD simulations of aortic dissection, which captures the complex interplay between physiologic deformation, flow, pressures, and time-averaged wall shear stress (TAWSS) in a patient-specific model. Our numerical model includes (1) two-way fluid-structure interaction (FSI) to describe the dynamic deformation of the vessel wall and dissection flap; (2) prestress and (3) external tissue support of the structural domain to avoid unphysiologic dilation of the aortic wall and stretching of the dissection flap; (4) tethering of the aorta by intercostal and lumbar arteries to restrict translatory motion of the aorta; and a (5) independently defined elastic modulus for the dissection flap and the outer vessel wall to account for their different material properties. The patient-specific aortic geometry is derived from computed tomography angiography (CTA). Three-dimensional phase contrast magnetic resonance imaging (4D flow MRI) and the patient's blood pressure are used to inform physiologically realistic, patient-specific boundary conditions. Our simulations closely capture the cyclical deformation of the dissection membrane, with flow simulations in good agreement with 4D flow MRI. We demonstrate that decreasing flap stiffness from [Formula: see text] to [Formula: see text] kPa (a) increases the displacement of the dissection flap from 1.4 to 13.4 mm, (b) decreases the surface area of TAWSS by a factor of 2.3, (c) decreases the mean pressure difference between true lumen and false lumen by a factor of 0.63, and (d) decreases the true lumen flow rate by up to 20% in the abdominal aorta. We conclude that the mobility of the dissection flap substantially influences local hemodynamics and therefore needs to be accounted for in patient-specific simulations of aortic dissection. Further research to accurately measure flap stiffness and its local variations could help advance future CFD applications.

Purpose: Modeling of hemolysis due to fluid stresses faces significant methodological challenges, particularly in geometries with turbulence or complex flow patterns. It is currently unclear how existing phenomenological blood-damage models based on laminar viscous stresses can be implemented into turbulent computational fluid dynamics simulations. The aim of this work is to generalize the existing laminar models to turbulent flows based on first principles, and validate this generalization with existing experimental data., Methods: A novel analytical and numerical framework for the simulation of flow-induced hemolysis based on the intermittency-corrected turbulent viscous shear stress (ICTVSS) is introduced. The proposed large-eddy simulation framework is able to seamlessly transition from laminar to turbulent conditions in a single flow domain by linking laminar shear stresses to dissipation of mechanical energy, accounting for intermittency in turbulent dissipation, and relying on existing power-law hemolysis models. Simulations are run to reproduce previously published hemolysis data with bovine blood in a benchmark geometry. Two sets of experimental data are relied upon to tune power-law parameters and justify that tuning. The first presents hemolysis measurements in a simple laminar flow, and the second is hemolysis in turbulent flow through the FDA benchmark nozzle. Validation is performed by simulation of blood injected into a turbulent jet of phosphate-buffered saline, with modifications made to account for the local concentration of blood., Results: Hemolysis predictions are found to be very sensitive to power-law parameters in the turbulent case, though a set of parameters is presented that both matches the turbulent data and is well-justified by the laminar data. The model is shown to be able to predict the general behavior of hemolysis in a second turbulent case. Results suggest that wall shear may play a dominant role in most cases., Conclusion: The ICTVSS framework of generalizing laminar power-law models to turbulent flows shows promise, but would benefit from further numerical validation and carefully designed experiments.

Remote sensing data are abundant, whereas surface in situ verification of atmospheric conditions is rare on Mars. Earth-based analogs could help gain an understanding of soil and atmospheric processes on Mars and refine existing models. In this work, we evaluate the applicability of the Weather Research and Forecasting (WRF) model against measurements from the Mars analog High Andes-Atacama Desert. Validation focuses on the surface conditions and on the surface energy budget. Measurements show that the average daily net radiation, global radiation, and latent heat flux amount to 131, 273, and about 10 W/m 2 , respectively, indicating extremely dry atmospheric conditions. Dynamically, the effect of topography is also well simulated. One of the main modeling problems is the inaccurate initial soil and surface conditions in the area. Correction of soil moisture based on in situ and satellite soil moisture measurements, as well as the removal of snow coverage, reduced the surface skin temperature root mean square error from 9.8°C to 4.3°C. The model, however, has shortcomings when soil condition modeling is considered. Sensible heat flux estimations are on par with the measurements (daily maxima around 500 W/m 2 ), but surface soil heat flux is greatly overestimated (by 150-500 W/m 2 ). Soil temperature and soil moisture diurnal variations are inconsistent with the measurements, partially due to the lack of water vapor representation in soil calculations.

This article presents a two-dimensional theoretical study of hemodynamics through a diseased permeable artery with a mild stenosis and an aneurysm present. The effect of metallic nanoparticles on the blood flow is considered, motivated by drug delivery (pharmacology) applications. Two different models are adopted to mimic non-Newtonian characteristics of the blood flow; the Casson (viscoplastic) fluid model is deployed in the core region and the Sisko (viscoelastic) fluid model employed in the peripheral (porous) region. The revised Buongiorno two-component nanofluid model is utilized for nanoscale effects. The blood is considered to contain a homogenous suspension of nanoparticles. The governing equations are derived by extending the Navier-Stokes equations with linear Boussinesq approximation (which simulates both heat and mass transfer). Natural (free) double-diffusive convection is considered to simulate the dual influence of thermal and solutal buoyancy forces. The conservation equations are normalised by employing appropriate non-dimensional variables. The transformed equations are solved numerically using the finite element method with the variational formulation scheme available in the FreeFEM++ code. A comprehensive mesh-independence study is included. The effect of selected parameters (thermophoresis, Brownian motion, Grashof number, thermo-solutal buoyancy ratio, Sisko parameter ratio, and permeability parameter) on velocity, temperature, nanoparticle concentration, and hemodynamic pressure have been calculated for two clinically important cases of arteries with stenosis and an aneurysm. Skin-friction coefficient, Nusselt number, volumetric flow rate, and resistance impedance of blood flow are also computed. Colour contours and graphs are employed to visualize the simulated blood flow characteristics. It is observed that by increasing the thermal buoyancy parameter, i.e. Grashof number ( Gr ), the nanoparticle concentration and temperature decrease, whereas velocity increases with an increment in the Brownian motion parameter ( Nb ). Furthermore, velocity decreases in the peripheral porous region with elevation in the Sisko material ratio ( m ) and permeability parameter ( k' ). The simulations are relevant to transport phenomena in pharmacology and nano-drug targeted delivery in haematology.

The present study aims to compare spinal stability after two different minimally invasive techniques, the lateral lumbar interbody fusion (LLIF) and the transforaminal lumbar interbody fusion (TLIF) approaches. Two nonlinear three-dimensional finite element (FE) models of the L4-L5 functional spinal unit (FSU) were subjected to the loads that usually act on the lumbar spine. Findings show that the LLIF approach yields better results for torsion load case, due to the larger surface area of the implant. For extension, flexion and lateral bending loads, the TLIF approach presents smaller displacements probably due to the anterior placement of the cage and to the smaller damaged area of the annulus fibrosus.

Ultrasounds (US) has been used in the past decades as a non-invasive imaging modality. Although employed extensively in clinical applications for soft tissue imaging, the acoustic beams can also be used for sensing and actuation for biological implants. In this paper we present a unified three dimensional (3D) computational framework to simulate the performance and response of deeply implanted devices to US stimulation and composed by a double piezoelectric layer with different material composition and configurations. The model combines the temporally-invariant distribution of the scattered pressure field arising from the presence of scatterers and attenuators in the domain of simulation, with the time-delay propagation of waves caused by refraction, to solve the Forward Problem in US within the breast and lower abdominal regions. It was found that a lens-shaped implant produces higher peak echoes in the breast for frequencies ≤ 6 MHz whereas, in the liver, similar strengths are obtained for the lens and disk-shaped implants in the higher spectrum. Regarding material composition, a combination of LiNbO 3 with PZT-5A yielded higher amplitude signals, when the double layer thickness is comparable to the wavelength of excitation. Experimental validation of the proposed model was carried out in the presence of a synthetic anatomical phantom of the breast and water tank to investigate the acoustic signals generated by disk-shaped implants when stimulated by external US sources in the harmonic and impulsive regimes of wave propagation. The implantation of a double piezoelectric layer inside the human body can, in the future, provide a high resolution system for the detection of surgical site infection as well as tumour growth and other systemic inflammatory responses originating deeply in soft tissues.

More than eighty percent of pancreatic cancer involves ductal adenocarcinoma with an abundant desmoplastic extracellular matrix surrounding the solid tumor entity. This aberrant tumor microenvironment facilitates a strong resistance of pancreatic cancer to medication. Although various therapeutic strategies have been reported to be effective in mice with pancreatic cancer, they still need to be tested quantitatively in wider animal-based experiments before being applied as therapies. To aid the design of experiments, we develop a cell-based mathematical model to describe cancer progression under therapy with a specific application to pancreatic cancer. The displacement of cells is simulated by solving a large system of stochastic differential equations with the Euler-Maruyama method. We consider treatment with the PEGylated drug PEGPH20 that breaks down hyaluronan in desmoplastic stroma followed by administration of the chemotherapy drug gemcitabine to inhibit the proliferation of cancer cells. Modeling the effects of PEGPH20 + gemcitabine concentrations is based on Green's fundamental solutions of the reaction-diffusion equation. Moreover, Monte Carlo simulations are performed to quantitatively investigate uncertainties in the input parameters as well as predictions for the likelihood of success of cancer therapy. Our simplified model is able to simulate cancer progression and evaluate treatments to inhibit the progression of cancer.

Purpose: In the present paper, the magnetic drug targeting using drug coated Fe 3 O 4 nanoparticles to the stenosis region of the vessel was investigated. The problem was solved for various magnetic numbers. Moreover, the effect of the location of the wire, as a magnetic source, on the MDT was studied., Methods: The governing equations of continuity, momentum and volume fraction were solved by taking into account the effects of kelvin force and magnetophoresis. Finite volume method is used for discretization of unsteady two-phase flow equations., Results: In low magnetic numbers, the most important phenomenon is the gradual formation of drug droplet on the location of the wire. The drug drop holds the drug near the target tissue for a long time and has a positive role in the MDT as a source of drug over time. Also, in high magnetic numbers, the amount of drug in the tissue is also high at the time of the formation of the droplet. However, the number of vortices formed in the flow increases, and this leads to get the target further away from the tissue. Two main phenomena of drug droplet formation and vortices generation were observed as positive and negative factors in MDT, respectively. The results showed that in a specific magnetic number, the MDT function could be optimal. If the wire is located in the upstream region of the stenosis, it will have a small positive effect on the concentration of the drug in the target tissue.

Objective: To investigate the effect of nasal septum perforation (SP) with different locations and sizes on nasal airflow by means of numerical simulation. Methods: Two healthy persons with normal nasal anatomy were enrolled in this study, including a 45 years old male (case 1) and a 36 years old female (case 2). Nasal CT data was used as the basis to create nasal airway numerical models of nasal SP with different locations (anterior caudal, central caudal, posterior caudal and anterior cranial) and sizes (diameter of 10 mm and 5 mm respectively). The inspiratory airflow characteristics (nasal cavity volume, nasal cavity wall area, pressure, nasal resistance, temperature, airflow velocity, wall shear stress, airflow-rate partitioning and vortex) of these nasal airway numerical models were simulated and analyzed. Pearson correlation analysis was performed between nasal resistances, airflow temperature and nasal cavity wall area. Results: In terms of pressure and nose resistance, the anterior caudal and larger size SP lead to more obvious variation of pressure distribution, and increased nasal resistance was especially found in the nasal cavity with anterior and medium caudal SP. In terms of temperature, the anterior (caudal and cranial) and larger size SP had significant effect on local temperature gradient as same as the anterior cranial and smaller size SP. Nasal heating efficiency was lower in nasal model with the anterior and larger size SP than that in the normal model. The temperature difference from the nostril to the end of nasal septum had positive correlation with nasal cavity wall area ( R (2) value of case 1 and case 2 was 0.69, 0.41, respectively, all P< 0.01). In terms of airflow velocity, the anterior caudal and cranial SP had more significant effect on the average airflow velocity in the nasal cavity. The anterior and medium caudal SP could make the airflow distribution in the asymmetric bilateral nasal cavity more unbalanced compared to the bilateral symmetrical nasal models. The anterior and medium SP resulted in a more pronounced vortex distribution than the posterior SP. Conclusions: The effect of SP on nasal cavity is related to its location and size. The anterior and larger size SP shows more negative influence on intranasal pressure, nasal resistance, heat transmission efficiency, airflow-rate partitioning than the posterior and smaller size SP.

In the analysis of current life science datasets, we often encounter scenarios in which the application of asymptotic theory to hypothesis testing can be problematic. Besides improved asymptotic results, permutation/simulation-based tests are a general approach to address this issue. However, these randomized tests can impose a massive computational burden, for example, in scenarios in which large numbers of statistical tests are computed, and the specified significance level is very small. Stopping rules aim to assess significance with the smallest possible number of draws while controlling the probabilities of errors due to statistical uncertainty. In this communication, we derive a general stopping rule, QUICK-STOP, based on the sequential testing theory that is easy to implement, controls the error probabilities rigorously, and is nearly optimal in terms of expected draws. In a simulation study, we show that our approach outperforms current stopping approaches for general randomized tests by factor 10 and does not impose an additional computational burden. We illustrate our approach by applying our stopping rule to a single-variant analysis of a whole-genome sequencing study for lung function., (© 2019 Wiley Periodicals, Inc.)

Left ventricular assist device (LVAD) provides an effective artificial support system to the heart patients. Despite the improved life survival rate, complications like hemolysis, blood trauma, and thrombus formation still limit the performance of the blood pump. The geometrical aspects of blood pumps majorly influence the hemodynamics, therefore these devices must be carefully engineered. In this work, several versions of centrifugal blood pumps are simulated using ANSYS-CFX to propose a best compatible design for LVAD. A hemodynamic levitation approach for the impeller is also suggested to overcome the cost and weight issue associated with the magnetic levitation. The blood flow is modeled by implementing Bird-Carreau model and its turbulence is solved using the SST turbulence model. The influence of the blade profile, blade tip width, blade numbers, and splitter blades on the hemodynamic characteristics through the pump is observed. An optimum design of centrifugal blood pump for the assistance of failed ventricle is proposed that can effectively pump the blood from the left ventricle to the ascending aorta. The proposal can be adopted by LVAD designers to have hemodynamically tuned efficient product., (© 2019 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Objective: Biodegradable stents represent a new technological development in the field of cardiovascular angioplasty. The stent geometry plays a crucial role in determining stent performance., Methods: This study describes four stent models with various strut geometries (circular, triangular, hexagonal, and spline) and identical links. The performance of the various stents is assessed by modeling the processes of compression and balloon expansion using experimental and numerical techniques., Results: Four adjustable variables related to radial strength, foreshortening rate, maximum expanded diameter and coverage are considered in this studies. The maximum stress distributions from our numerical analysis are in agreement with the experimental fracture measurements., Conclusion: Analysis of the stent parameters indicates that the hexagonal geometry is a relatively good stent strut design. The results described in this paper will be useful in further optimization studies and for the development of stents with a higher radial strength and increased fracture resistance.

Loop-mediated isothermal amplification or LAMP has been identified to be an efficient technology for point-of-care diagnostics. Paper-based LAMP technique has tremendous potential in replacing the existing tube-based technology as the manufacturing cost of a paper-based device is comparatively lower and easy-to-use. LAMP-based paper diagnostic device for Mycobacterium tuberculosis (MTB) detection is of extreme importance as it will help in early and rapid diagnosis of the affected patients. The fabrication of these devices requires assessment of design parameters on the extent of LAMP amplification reaction. Hence, CFD studies would be extremely beneficial from the design perspective. The current work presents an insight into the CFD simulations for LAMP amplification reaction on a porous paper membrane (nitrocellulose membrane). The convection-diffusion-reaction model is solved on a COMSOL Multiphysics 5.0 platform. Studies on effect of pore size, aspect ratio and initial DNA concentration on the extent of DNA amplification reaction have been carried out. The current paper-based technique is effective in detecting a minimum of 5 copies of DNA contrasting the previous semi-quantitative technique which demonstrated the detection of minimum 98 copies. Overall, the simulation results displayed almost 96% enhancement in the DNA amplification rate on paper membrane. Graphical abstract Graphical abstract for the computational study of DNA amplification reaction via LAMP technique on a porous paper membrane.

Platelet activation induced by shear stresses and non-physiological flow field generated by bileaflet mechanical heart valves (BMHVs) leads to thromboembolism, which can cause fatal consequences. One of the causes of platelet activation could be intermittent regurgitation, which arises due to asynchronous movement and rebound of BMHV leaflets during the valve closing phase. In this numerical study, the effect of intermittent regurgitation on the platelet activation potential of BMHVs was quantified by modeling a BMHV in the straight and anatomic aorta at implantation tilt angles 0°, 5°, 10°, and 20°. A fully implicit Arbitrary Lagrangian-Eulerian-based Fluid-Structure Interaction formulation was adopted with blood modeled as a multiphase, non-Newtonian fluid. Results showed that the intermittent regurgitation and consequently the platelet activation level increases with the increasing implantation tilt of BMHV. For the straight aorta, the leaflet of the 20° tilted BMHV underwent a rebound of approximately 20° after initially closing, whereas the leaflet of the 10°, 5°, and 0° tilted BMHVs underwent a rebound of 8.5°, 3°, and 0°, respectively. For the anatomic aorta, the leaflet of the 20° tilted BMHV underwent a rebound of approximately 24° after initially closing, whereas the leaflet of the 10°, 5°, and 0° tilted BMHVs underwent a rebound of 14°, 10°, and 7°, respectively. For all the implantation orientations of BMHVs, intermittent regurgitation and platelet activation were always higher in the anatomic aorta than in the straight aorta. The study concludes that the pivot axis of BMHV must be implanted parallel to the aortic root's curvature to minimize intermittent regurgitation and platelet activation., (© 2019 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

We conducted regional scale CO2 simulations using the Weather Research and Forecasting model (WRF) coupled with the Vegetation Photosynthesis and Respiration Model (VPRM). We contrasted simulated concentrations with column, ground and aircraft observations during the Korea-United States Air Quality (KORUS-AQ) 2016 field campaign. Overall, WRF-VPRM slightly underestimates CO2 concentrations at ground and column monitoring sites, but it significantly underestimates at an inland tower measurement site, especially within the stable (nocturnal) boundary layer in nighttime. The model successfully captures the airborne vertical profiles but showed a large offset within the planetary boundary layer (PBL) in the areas surrounding Seoul and around the Taeahn point source emissions in the west coastal area of the Korean Peninsula. A case study flight intended to capture Chinese influence observed no clear signals of long-range transport of CO2, due mainly to the much larger magnitude of background CO2 concentrations. The calculated Net Ecosystem Exchange (NEE) with flux measurements at a tower site in the South Korean Peninsula has also been evaluated comparing with CO2 flux measurements at a flux tower site, resulting in the underestimation by less than a factor of 1., Competing Interests: The authors have declared that no competing interests exist.

A common problem when analyzing models, such as mathematical modeling of a biological process, is to determine if the unknown parameters of the model can be determined from given input-output data. Identifiable models are models such that the unknown parameters can be determined to have a finite number of values given input-output data. The total number of such values over the complex numbers is called the identifiability degree of the model. Unidentifiable models are models such that the unknown parameters can have an infinite number of values given input-output data. For unidentifiable models, a set of identifiable functions of the parameters are sought so that the model can be reparametrized in terms of these functions yielding an identifiable model. In this work, we use numerical algebraic geometry to determine if a model given by polynomial or rational ordinary differential equations is identifiable or unidentifiable. For identifiable models, we present a novel approach to compute the identifiability degree. For unidentifiable models, we present a novel numerical differential algebra technique aimed at computing a set of algebraically independent identifiable functions. Several examples are used to demonstrate the new techniques., Competing Interests: The authors have declared that no competing interests exist.

Purpose: In-stent restenosis (ISR) is related to local haemodynamics in the arteries after stent intervention. However, the haemodynamics of stents implanted into tapered vessels is rarely studied and remains unclear. This study aimed to study the haemodynamic performance of a stent in a tapered artery to reveal the haemodynamic differences between tapered and cylindrical stents after stent implantation and guide the stent selection for the treatment of coronary artery stenosis., Methods: Cylindrical and tapered stents were implanted into the tapered arteries. A model of a cylindrical stent implanted into a cylindrical artery was established as the contrast model. Using the finite element method, the flow velocity and wall shear stress distribution of the three models were compared., Results: At t 1 , t 2 , t 3 and t 4 , the flow rate of the tapered artery with tapered stents (TT) after the implantation increased by 8.59, 3.80, 12.81 and 3.66%, respectively. In addition, the wall shear stress in the tapered arteries of TT was 23.48, 36.67, 13.00 and 8.06% higher than that of the tapered arteries with cylindrical stents (TC)., Conclusions: The implantation of a tapered stent in the tapered artery can effectively improve intravascular haemodynamics. The tapered stent allows the tapered artery to obtain better haemodynamics and reduces the probability of ISR.

Background: During endovascular aneurysm repair (EVAR), complex iliac anatomy is a source of complications such as unintentional coverage of the hypogastric artery. The aim of our study was to evaluate ability to predict coverage of the hypogastric artery using a biomechanical model simulating arterial deformations caused by the delivery system., Methods: The biomechanical model of deformation has been validated by many publications. The simulations were performed on 38 patients included retrospectively, for a total of 75 iliac arteries used for the study. On the basis of objective measurements, two groups were formed: one with "complex" iliac anatomy (n = 38 iliac arteries) and the other with "simple" iliac anatomy (n = 37 iliac arteries). The simulation enabled measurement of the lengths of the aorta and the iliac arteries once deformed by the device. Coverage of the hypogastric artery was predicted if the deformed renal/iliac bifurcation length (L pre ) was less than the length of the implanted device (L stent -measured on the postoperative computed tomography [CT]) and nondeformed L pre was greater than L stent ., Results: Nine (12%) internal iliac arteries were covered unintentionally. Of the coverage attributed to perioperative deformations, 1 case (1.3%) occurred with simple anatomy and 6 (8.0%) with complex anatomy (P = 0.25). All cases of unintentional coverage were predicted by the simulation. The simulation predicted hypogastric coverage in 35 cases (46.7%). There were therefore 26 (34.6%) false positives. The simulation had a sensitivity of 100% and a specificity of 60.6%. On multivariate analysis, the factors significantly predictive of coverage were the iliac tortuosity index (P = 0.02) and the predicted margin between the termination of the graft limb and the origin of the hypogastric artery in nondeformed (P = 0.009) and deformed (P = 0.001) anatomy., Conclusions: Numerical simulation is a sensitive tool for predicting the risk of hypogastric coverage during EVAR and allows more precise preoperative sizing. Its specificity is liable to be improved by using a larger cohort., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Vortex structures, as one of the most important features of cardiac flow, have a crucial impact on the left ventricle function and pathological conditions. These swirling flows are closely related to the presence of turbulence in left ventricle which is investigated in the current study. Using an extended model of the left heart, including a fluid-structure interaction (FSI) model of the mitral valve with a realistic geometry, the effect of using two numerical turbulent models, k-ε and Spalart-Allmaras (SA), on diastolic flow patterns is studied and compared with results from laminar flow model. As a result of the higher dissipation rate in turbulent models (k-ε and SA), vortices are larger and stronger in the laminar flow model. Comparing E/A ratio in the three models (Laminar, k-ε, and SA) with experimental data from healthy subjects, it is concluded that the results from k-ε model are more accurate.

The arterial pulse wave (PW) is a rich source of information on cardiovascular (CV) health. It is widely measured by both consumer and clinical devices. However, the physical determinants of the PW are not yet fully understood, and the development of PW analysis algorithms is limited by a lack of PW data sets containing reference CV measurements. Our aim was to create a database of PWs simulated by a computer to span a range of CV conditions, representative of a sample of healthy adults. The typical CV properties of 25-75 yr olds were identified through a literature review. These were used as inputs to a computational model to simulate PWs for subjects of each age decade. Pressure, flow velocity, luminal area, and photoplethysmographic PWs were simulated at common measurement sites, and PW indexes were extracted. The database, containing PWs from 4,374 virtual subjects, was verified by comparing the simulated PWs and derived indexes with corresponding in vivo data. Good agreement was observed, with well-reproduced age-related changes in hemodynamic parameters and PW morphology. The utility of the database was demonstrated through case studies providing novel hemodynamic insights, in silico assessment of PW algorithms, and pilot data to inform the design of clinical PW algorithm assessments. In conclusion, the publicly available PW database is a valuable resource for understanding CV determinants of PWs and for the development and preclinical assessment of PW analysis algorithms. It is particularly useful because the exact CV properties that generated each PW are known. NEW & NOTEWORTHY First, a comprehensive literature review of changes in cardiovascular properties with age was performed. Second, an approach for simulating pulse waves (PWs) at different ages was designed and verified against in vivo data. Third, a PW database was created, and its utility was illustrated through three case studies investigating the determinants of PW indexes. Fourth, the database and tools for creating the database, analyzing PWs, and replicating the case studies are freely available.

Column selection and experimental design are recognized to be wear-and-tear processes to obtain a good fingerprinting result with comprehensive two dimensional gas chromatography (GC × GC). The processes involve a large number of experiments for analysis of each sample due to the optimized conditions depending on the selected column sets. In this study, the analytical solutions of time summation model combined with temperature dependent linear solvation energy relationship (LSER) were derived for constant flow separation in GC × GC. The derived equations allow calculation of analyte retention time in first and second dimensional separation ( 1 t R and 2 t R ), under temperature program separation employing any column combination with known LSER database. As a result, optimization software was developed enabling simulation of several hundred thousand GC × GC results (fingerprints) for separation of each sample. Good correlations between our predicted results and the results obtained with the previously established numerical approach, were obtained with the R 2 of 1.000 and 0.998 for simulation of 1 t R and 2 t R , respectively. The developed approaches were further applied to simulation of 96,000 individual fingerprints in temperature programmed GC × GC, with the focus on application of 16 column sets including non-ionic liquid and ionic liquid (IL) stationary phases for separation of 678 model compounds. These approaches resulted in the computational time of 1 day compared with 1 year provided by the numerical method. Best column sets and experimental conditions (secondary column lengths and temperature programs) could then be extracted according to maximizing number of separated peaks in separation, which represents the quality of each fingerprinting., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Human phonation is based on the interaction between tracheal airflow and laryngeal dynamics. This fluid-structure interaction is based on the energy exchange between airflow and vocal folds. Major challenges in analyzing the phonatory process in-vivo are the small dimensions and the poor accessibility of the region of interest. For improved analysis of the phonatory process, numerical simulations of the airflow and the vocal fold dynamics have been suggested. Even though most of the models reproduced the phonatory process fairly well, development of comprehensive larynx models is still a subject of research. In the context of clinical application, physiological accuracy and computational model efficiency are of great interest. In this study, a simple numerical larynx model is introduced that incorporates the laryngeal fluid flow. It is based on a synthetic experimental model with silicone vocal folds. The degree of realism was successively increased in separate computational models and each model was simulated for 10 oscillation cycles. Results show that relevant features of the laryngeal flow field, such as glottal jet deflection, develop even when applying rather simple static models with oscillating flow rates. Including further phonatory components such as vocal fold motion, mucosal wave propagation, and ventricular folds, the simulations show phonatory key features like intraglottal flow separation and increased flow rate in presence of ventricular folds. The simulation time on 100 CPU cores ranged between 25 and 290 hours, currently restricting clinical application of these models. Nevertheless, results show high potential of numerical simulations for better understanding of phonatory process., (Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Physarum polycephalum, a single-celled, multinucleate slime mould, is a seemingly simple organism, yet it exhibits quasi-intelligent behaviour during extension, foraging, and as it adapts to dynamic environments. For these reasons, Physarum is an attractive target for modelling with the underlying goal to uncover the physiological mechanisms behind the exhibited quasi-intelligence and/or to devise novel algorithms for solving complex computational problems. The recent increase in modelling studies on Physarum has prompted us to review the latest developments in this field in the context of modelling and computing alike. Specifically, we cover models based on (i) morphology, (ii) taxis, and (iii) positive feedback dynamics found in top-down and bottom-up modelling techniques. We also survey the application of each of these core features of Physarum to solving difficult computational problems with real-world applications. Finally, we highlight some open problems in the field and present directions for future research., (Copyright © 2018. Published by Elsevier B.V.)

Two dimensional, steady state, and incompressible blood and bile flows through the liver lobules are numerically simulated. Two different geometric models A and B are proposed to study the effects of lobule structure on the fluid flow behaviour. In Model A, the lobule tissue is represented as a hexagonal shape porous medium with a set of flow channels at its vertices accounting for the hepatic artery, portal and central veins along with bile ductules. Model B is a channelized porous medium constructed by adding a set of flow channels, representing the bile canaliculies and lobule sinusoids, to Model A. The bile and blood flow through the lobule is simulated by the finite element approach, based on the Darcy/Brinkman equations in the lobule tissue and the Navier-Stokes (or Stokes) equations in the flow channels. In Model B, a transmission factor on the boundaries of the bile canaliculies is introduced to connect the bile and blood flows. First, a single regular lobule is utilized to exhibit the fluid flow pattern through the liver lobule represented by proposed geometric models. Then, the model is extended to a group of liver lobules to demonstrate the flow through a liver slice represented by irregular lobules. Numerical results indicate that the Darcy and Brinkman equations provide nearly the same solutions for Model A and similar solutions with a little difference for Model B. It is shown that the existence of sinusoids and bile canaliculies inside the liver lobules has noticeable effects on its fluid flow pattern, in terms of pressure and velocity fields.

Advanced imaging techniques generate large datasets capable of describing the structure and kinematics of tissue spreading in embryonic development, wound healing, and the progression of many diseases. These datasets can be integrated with mathematical models to infer biomechanical properties of the system, typically identifying an optimal set of parameters for an individual experiment. However, these methods offer little information on the robustness of the fit and are generally ill-suited for statistical tests of multiple experiments. To overcome this limitation and enable efficient use of large datasets in a rigorous experimental design, we use the approximate Bayesian computation rejection algorithm to construct probability density distributions that estimate model parameters for a defined theoretical model and set of experimental data. Here, we demonstrate this method with a 2D Eulerian continuum mechanical model of spreading embryonic tissue. The model is tightly integrated with quantitative image analysis of different sized embryonic tissue explants spreading on extracellular matrix (ECM) and is regulated by a small set of parameters including forces on the free edge, tissue stiffness, strength of cell-ECM adhesions, and active cell shape changes. We find statistically significant trends in key parameters that vary with initial size of the explant, e.g., for larger explants cell-ECM adhesion forces are weaker and free edge forces are stronger. Furthermore, we demonstrate that estimated parameters for one explant can be used to predict the behavior of other similarly sized explants. These predictive methods can be used to guide further experiments to better understand how collective cell migration is regulated during development., Competing Interests: The authors have declared that no competing interests exist.

Bone remodeling remains a highly researched topic investigated by many strands of science. The main purpose of this work is formulating a new computational framework for biological simulation, extending the version of the bone remodeling model previously proposed by Komarova. Thus, considering only the biological aspect of the remodeling process, the action of osteoclasts and osteoblasts is taken into account as well as its impact on bone mass. It is conducted a spatiotemporal analysis of a remodeling cycle obtaining a dynamic behavior of bone cells very similar to the biological process already described in the literature. The numerical example used is based on bone images obtained with scanning electron microscopy. During simulation, it is possible to observe the variation of bone's architecture through isomaps. These maps are obtained through the combination of biological bone remodeling models with three distinct numerical techniques-finite element method (FEM), radial point interpolation method (RPIM), and natural neighbor radial point interpolation method (NNRPIM). A study combining these numerical techniques allows to compare their performance. Ultimately, this work supports the inclusion of meshless methods due to their smoother results and its easiness to be combined with medical images from CT scans and MRI., (© 2019 John Wiley & Sons, Ltd.)

The membrane or interfacial viscosity is an important property in many multiphase and biofluidic situations, such as the red blood cell dynamics and emulsion stability. The immersed boundary method (IBM), which incorporates the dynamic flow-membrane interaction via force distribution and velocity interpolation, has been extensively employed in simulations of such systems. Unfortunately, direct implementation of membrane viscosity in IBM suffers severe numerical instability, which causes an IBM calculation to break down before generating any useful results. Few attempts have been recently reported; however, several concerns exist in these attempts, such as the inconsistency to the classical definition of membrane viscosity, the inability to model the shear and dilatational viscosities separately, the unjustified mathematical formulations, and the complicated algorithms and computation. To overcome these concerns, in this paper, we propose a finite difference approach for implementing membrane viscosity in immersed boundary simulations. The viscous stress is obtained via finite difference approximations to the differential strain-stress relationship, with the help of a subsampling scheme to reduce the numerical noise in the calculated strain rates. This simple method has also avoided the complicated matrix calculations in previous attempts, and hence, a better computational efficiency is expected. Detailed mathematical description of the method and key steps for its implementation in immersed boundary programs are provided. Validation and illustration calculations are performed, and our results are compared with analytical solutions and previous publications with satisfactory agreement. The influences of membrane mesh resolution and simulation time step are also examined; and the results show no indication that our finite difference method has downgraded the general IBM accuracy. Based on these simulations and analysis, we believe that our method would be a better choice for future IBM simulations of capsule dynamics with viscoelastic membranes., (© 2019 John Wiley & Sons, Ltd.)

Background: Validating new techniques for fetal cardiovascular magnetic resonance (CMR) is challenging due to random fetal movement that precludes repeat measurements. Consequently, fetal CMR development has been largely performed using physical phantoms or postnatal volunteers. In this work, we present an open-source simulation designed to aid in the development and validation of new approaches for fetal CMR. Our approach, fetal extended Cardiac-Torso cardiovascular magnetic resonance imaging (Fetal XCMR), builds on established methods for simulating CMR acquisitions but is tailored toward the dynamic physiology of the fetal heart and body. We present comparisons between the Fetal XCMR phantom and data acquired in utero, resulting in image quality, anatomy, tissue signals and contrast., Methods: Existing extended Cardiac-Torso models are modified to create maternal and fetal anatomy, combined according to simulated motion, mapped to CMR contrast, and converted to CMR data. To provide a comparison between the proposed simulation and experimental fetal CMR images acquired in utero, images from a typical scan of a pregnant woman are included and simulated acquisitions were generated using matching CMR parameters, motion and noise levels. Three reconstruction (static, real-time, and CINE), and two motion estimation methods (translational motion, fetal heart rate) from data acquired in transverse, sagittal, coronal, and short-axis planes of the fetal heart were performed to compare to in utero acquisitions and demonstrate feasibility of the proposed simulation framework., Results: Overall, CMR contrast, morphologies, and relative proportions of the maternal and fetal anatomy are well represented by the Fetal XCMR images when comparing the simulation to static images acquired in utero. Additionally, visualization of maternal respiratory and fetal cardiac motion is comparable between Fetal XCMR and in utero real-time images. Finally, high quality CINE image reconstructions provide excellent delineation of fetal cardiac anatomy and temporal dynamics for both data types., Conclusion: The fetal CMR phantom provides a new method for evaluating fetal CMR acquisition and reconstruction methods by simulating the underlying anatomy and physiology. As the field of fetal CMR continues to grow, new methods will become available and require careful validation. The fetal CMR phantom is therefore a powerful and convenient tool in the continued development of fetal cardiac imaging.

The behavior of blood cells and vessel compliance significantly influence hemodynamic parameters, which are closely related to the development of aortic dissection. Here the two-phase non-Newtonian model and the fluid-structure interaction (FSI) method are coupled to simulate blood flow in a patient-specific dissected aorta. Moreover, three-element Windkessel model is applied to reproduce physiological pressure waves. Important hemodynamic indicators, such as the spatial distribution of red blood cells (RBCs) and vessel wall displacement, which greatly influence the hemodynamic characteristics are analyzed. Results show that the proximal false lumen near the entry tear appears to be a vortex zone with a relatively lower volume fraction of RBCs, a low time-averaged wall shear stress (TAWSS) and a high oscillatory shear index (OSI), providing a suitable physical environment for the formation of atherosclerosis. The highest TAWSS is located in the narrow area of the distal true lumen which might cause further dilation. TAWSS distributions in the FSI model and the rigid wall model show similar trend, while there is a significant difference for the OSI distributions. We suggest that an integrated model is essential to simulate blood flow in a more realistic physiological environment with the ultimate aim of guiding clinical treatment.

The interaction of active faults as a factor affecting the mechanisms of large earthquakes has been observed in many places. Most aftershock and clustering earthquake sequences do not recur on the main seismogenic fault but are controlled by fault interactions with adjacent seismic structures. Four groups of conceptual models were generated in this study to determine how the geometry of the seismogenic faults controls the distributions of stress fields and earthquakes. The influences of the fault length ratio, center distance, overlap ratio, echelon distance and fault opening angle were considered in a 2D viscoelastic model. The results indicate that the interaction in the slipping zone is larger when collinear interacting faults are more closely positioned, with one fault lengthening. For noncollinear faults, the interaction is stronger as the inner tips pass each other, which impedes their growth after some degree of overlap. Additionally, fault interaction at the slipping zone becomes stronger as the opening angle approaches 180°. We further generated a 3D viscoelastic model of fault interactions in Central North China Block and applied the finite element method to analyze the relationship between distributions of earthquakes and fault geometry. The calculated results reveal well-matched higher stress and maximum shear strain concentrations in the southern part of the Fen-wei Graben Zone than in other zones in Central North China Block, which can be explained by the longer faults, shorter center distances, shorter overlap lengths and larger opening angles. The stress distributions and fault interactions should be considered in long-term seismic hazard assessment in these zones., Competing Interests: The authors have declared that no competing interests exist.

In this paper we apply some higher order symplectic numerical methods to analyze the dynamics of 3-site Toda lattices (reduced to relative coordinates). We present benchmark numerical simulations that has been generated from the HOMsPY (Higher Order Methods in Python) library. These results provide detailed information of the underlying Hamiltonian system. These numerical simulations reinforce the claim that the symplectic numerical methods are highly accurate qualitatively and quantitatively when applied not only to Hamiltonian of the Toda lattices, but also to other physical models. Excepting exactly integrable models, these symplectic numerical schemes are superior, efficient, energy preserving and suitable for a long time integrations, unlike standard non-symplectic numerical methods which lacks preservation of energy (and other constants of motion, when such exist)., Competing Interests: The authors have declared that no competing interests exist.

In this paper, a novel 3D numerical method has been developed to simulate red blood cells (RBCs) based on the interaction between a shell-like solid structure and a fluid. RBC is assumed to be a thin shell encapsulating an internal fluid (cytoplasm) which is submerged in an external fluid (blood plasma). The approach is entirely based on the smoothed particle hydrodynamics (SPH) method for both fluid and the shell structure. Both cytoplasm and plasma are taken to be incompressible Newtonian fluid. As the kinematic assumptions for the shell, Reissner-Mindlin theory has been introduced into the formulation. Adopting a total Lagrangian (TL) formulation for the shell in the realm of small strains and finite deflection, the presented computational tool is capable of handling large displacements and rotations. As an application, the deformation of a single RBC while passing a stenosed capillary has been modeled. If the rheological behavior of the RBC changes, for example, due to some infection, it is reflected in its deformability when it passes through the microvessels. It can severely affect its proper function which is providing the oxygen and nutrient to the living cells. Hence, such numerical tools are useful in understanding and predicting the mechanical behavior of RBCs. Furthermore, the numerical simulation of stretching an RBC in the optical tweezers system is presented and the results are verified. To the best of authors' knowledge, a computational tool purely based on the SPH method in the framework of shell-fluid interaction for RBCs simulation is not available in the literature.

Purpose: Effective treatment of patients with terminal heart failure and preserved ejection fraction (HFpEF) is an unmet medical need. The aim of this study was to investigate a novel valveless pulsatile pump as a therapeutic option for the HFpEF population through comprehensive in silico investigations., Methods: The pump was simulated in a numerical model of the cardiovascular system of four HFpEF phenotypes and compared to a typical case of heart failure with reduced ejection fraction (HFrEF). The proposed pump, which was modeled as being directly connected to the left ventricle, features a single valveless inlet and outlet cannula and is driven in co-pulsation with the left ventricle. We collected hemodynamics for two different pump volumes (30 and 60 mL)., Results: In all HFpEF conditions, the 30 mL pump improved the cardiac output by approximately 1 L/min, increased the mean arterial pressure by > 11% and lowered the mean left atrial pressure by > 30%. With the larger (60 mL) stroke volume, these hemodynamic improvements were more pronounced. In the HFrEF condition however, these effects were three times less in magnitude., Conclusions: In this simulation study, the valveless pulsatile device improves hemodynamics in HFpEF patients by increasing the total stroke volume. The hemodynamic benefits are achieved with a small device volume comparable to implantable rotary blood pumps.

Fluid homeostasis is required for life. Processes involved in fluid balance are strongly related to exchanges at the microvascular level. Computational models have been presented in the literature to analyze the microvascular-interstitial interactions. As far as we know, none of those models consider a physiological description for the lymphatic drainage-interstitial pressure relation. We develop a computational model that consists of a network of straight cylindrical vessels and an isotropic porous media with a uniformly distributed sink term acting as the lymphatic system. In order to describe the lymphatic flow rate, a non-linear function of the interstitial pressure is defined, based on literature data on the lymphatic system. The proposed model of lymphatic drainage is compared to a linear one, as is typically used in computational models. To evaluate the response of the model, the two are compared with reference to both physiological and pathological conditions. Differences in the local fluid dynamic description have been observed using the non-linear model. In particular, the distribution of interstitial pressure is heterogeneous in all the cases analyzed. The resulting averaged values of the interstitial pressure are also different, and they agree with literature data when using the non-linear model. This work highlights the key role of lymphatic drainage and its modeling when studying the fluid balance in microcirculation for both to physiological and pathological conditions, e.g. uremia., (Copyright © 2018 Elsevier Inc. All rights reserved.)