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PURPOSE: The objective of this study was to implement computational fluid dynamics (CFD) simulations and aerosol characterization experiments to determine best-case spray drying conditions of a tobramycin excipient enhanced growth (Tobi-EEG) formulation for use in a pediatric air-jet dry powder inhaler (DPI). METHODS: An iterative approach was implemented in which sets of spray drying conditions were explored using CFD simulations followed by lead candidate selection, powder production and in vitro aerosol testing. CFD simulations of a small-particle spray dryer were performed to capture droplet drying parameters and surface-averaged temperature and relative humidity (RH) conditions in the powder collection region. In vitro aerosol testing was performed for the selected powders using the pediatric air-jet DPI, cascade impaction, and aerosol transport through a pediatric mouth-throat (MT) model to a tracheal filter. RESULTS: Based on comparisons of CFD simulations and in vitro powder performance, recommended drying conditions for small-particle powders with electrostatic collection include: (i) reducing the CFD-predicted drying parameters of κ(avg) and κ(max) to values below 3 µm(2)/ms and 114 µm(2)/ms, respectively; (ii) maintaining the Collector Surface RH within an elevated range, which for the Tobi-EEG formulation with l-leucine was 20–30 % RH; and (iii) ensuring that particles reaching the collector were fully dried, based on a mass fraction of solute CFD parameter. CONCLUSIONS: Based on the newly recommended spray dryer conditions for small particle aerosols, delivery performance of the lead Tobi-EEG formulation was improved resulting in >60% of the DPI loaded dose passing through the pediatric MT model.

Background The objective of this study was to develop a method to evaluate the effects of an aortic dissection on hemodynamic parameters by conducting a comparison with that of a healthy (nondissected) aorta. Open-source software will be implemented, no proprietary software/application will be used to ensure accessorily and repeatability, in all the data analysis and processing. Computed tomography (CT) images of aortic dissection are used for the model geometry segmentation. Boundary conditions from literature are implemented to computational fluid dynamics (CFD) to analyze the hemodynamic parameters. Methods A numerical simulation model was created by obtaining accurate 3-dimensional geometries of aortae from CT images. In this study, CT images of 8 cases of aortic dissection (Stanford type-A and type-B) and 3 cases of healthy aortae are used for the actual aorta model geometry segmentation. These models were exported into an open-source CFD software, OpenFOAM, where a simplified pulsating flow was simulated by controlling the flow pressure. Ten cycles of the pulsatile flow (0.50 sec/cycle) conditions, totaling 5 sec, were calculated. Results The pressure distribution, wall shear stress (WSS) and flow velocity streamlines within the aorta and the false lumen were calculated and visualized. It was found that the flow velocity and WSS had a high correlation in high WSS areas of the intermittent layer between the true and false lumen. Most of the Stanford type-A dissections in the study showed high WSS, over 38 Pa, at the systole phase. This indicates that the arterial walls in type-A dissections are more likely to be damaged with pulsatile flow. Conclusions Using CFD to estimate localized high WSS areas may help in deciding to treat a type-A or B dissection with a stent graft to prevent a potential rupture.

The configuration of proteins is critical for their biochemical behavior. Mechanical stresses that act on them can affect their behavior leading to the development of decease. The von Willebrand factor (vWF) protein circulating with the blood loses its efficacy when it undergoes non-physiological hemodynamic stresses. While often overlooked, extensional stresses can affect the structure of vWF at much lower stress levels than shear stresses. The statistical distribution of extensional stress as it applies on models of the vWF molecule within turbulent flow was examined here. The stress on the molecules of the protein was calculated with computations that utilized a Lagrangian approach for the determination of the molecule trajectories in the flow filed. The history of the stresses on the proteins was also calculated. Two different flow fields were considered as models of typical flows in cardiovascular mechanical devises, one was a Poiseuille flow and the other was a Poiseuille–Couette flow field. The data showed that the distribution of stresses is important for the design of blood flow devices because the average stress can be below the critical value for protein damage, but tails of the distribution can be outside the critical stress regime.

Graphical abstract, Highlights • A fractional guava fruit model with memory effect is developed. • Stability of the fractional model is discussed. • Existence and uniqueness of the solution is examined. • A numerical method is applied for numerical simulation. • Effect of various parameters is analyzed on guava borers and natural enemies., Introduction Fractional operators find their applications in several scientific and engineering processes. We consider a fractional guava fruit model involving a non-local additionally non-singular fractional derivative for the interaction into guava pests and natural enemies. The fractional guava fruit model is considered as a Lotka-Volterra nature. Objectives The main objective of this work is to study a guava fruit model associated with a non-local additionally non-singular fractional derivative for the interaction into guava pests and natural enemies. Methods Existence and uniqueness analysis of the solution is evaluated effectively by using Picard Lindelof approach. An approximate numerical solution of the fractional guava fruit problem is obtained via a numerical scheme. Results The positivity analysis and equilibrium analysis for the fractional guava fruit model is discussed. The numerical results are demonstrated to prove our theoretical results. The graphical behavior of solution of the fractional guava problem at the distinct fractional order values and at various parameters is discussed. Conclusion The graphical behavior of solution of the fractional guava problem at the distinct fractional order values and at various parameters shows new vista and interesting phenomena of the model. The results are indicating that the fractional approach with non-singular kernel plays an important role in the study of different scientific problems. The suggested numerical scheme is very efficient for solving nonlinear fractional models of physical importance.

Water removal which is a key treatment goal of automated peritoneal dialysis (APD) can be assessed cycle-by-cycle using remote patient monitoring (RPM). We analysed ultrafiltration patterns during night APD following a dry day (APDDD; no daytime fluid exchange) or wet day (APDWD; daytime exchange). Ultrafiltration for each APD exchange were recorded for 16 days using RPM in 14 patients. The distributed model of fluid and solute transport was applied to simulate APD and to explore the impact of changes in peritoneal tissue hydration on ultrafiltration. We found lower ultrafiltration (mL, median [first quartile, third quartile]) during first and second vs. consecutive exchanges in APDDD (−61 [−148, 27], 170 [78, 228] vs. 213 [126, 275] mL; p WD (81 [−8, 176], 81 [−4, 192] vs. 115 [4, 219] mL; NS). Simulations in a virtual patient showed that lower ultrafiltration (by 114 mL) was related to increased peritoneal tissue hydration caused by inflow of 187 mL of water during the first APDDD exchange. The observed phenomenon of lower ultrafiltration during initial exchanges of dialysis fluid in patients undergoing APDDD appears to be due to water inflow into the peritoneal tissue, re-establishing a state of increased hydration typical for peritoneal dialysis.

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.

Tracking and understanding data quality, analysis and reproducibility are critical concerns in the biological sciences. This is especially true in genomics where next generation sequencing (NGS) based technologies such as ChIP-seq, RNA-seq and ATAC-seq are generating a flood of genome-scale data. However, such data are usually processed with automated tools and pipelines, generating tabular outputs and static visualisations. Interpretation is normally made at a high level without the ability to visualise the underlying data in detail. Conventional genome browsers are limited to browsing single locations and do not allow for interactions with the dataset as a whole. Multi Locus View (MLV), a web-based tool, has been developed to allow users to fluidly interact with genomics datasets at multiple scales. The user is able to browse the raw data, cluster, and combine the data with other analysis and annotate the data. User datasets can then be shared with other users or made public for quick assessment from the academic community. MLV is publically available at https://mlv.molbiol.ox.ac.uk., Martin Sergeant et al. develop a web-based tool called Multi Locus View that allows researchers to interact with genomics datasets at multiple scales. Users can browse, annotate, combine or analyse raw data on this interface. The user datasets generated in this tool can also be made public. This tool is expected to increase public access to the entirety of genomic data.

We developed a multiscale model for simulating aggregation of multiple, free-flowing platelets in low-intermediate shear viscous flow, in which aggregation is mediated by the interaction of α(IIb)β(3) receptors on the platelets membrane and fibrinogen (Fg). This multiscale model uses coarse grained molecular dynamics (CGMD) for platelets at the microscales, and dissipative particle dynamics (DPD) for the shear flow at the macroscales, employing our hybrid aggregation force field for modeling molecular level receptor ligand bonds. We define an aggregation tensor and use it to quantify the molecular level contact characteristics between platelets in an aggregate. We perform numerical studies under different flow conditions for platelet doublets and triplets and evaluate the contact area, detaching force, and minimum distance between different pairs of platelets in an aggregate. We also present the dynamics of applied stress and velocity magnitude distributions on the platelet membrane during aggregation and quantify the increase in stress in the contact region under different flow conditions. Integrating the knowledge from our previously validated models, together with new aggregation scenarios, our model can dynamically quantify aggregation characteristics and map stress and velocity distribution on the platelet membrane which are difficult to measure in vitro, thus providing an insight into mechanotransduction bond formation response of platelets to flow induced shear stresses. This modeling framework, together with the tensor method for quantifying inter-platelet contact, can be extended to simulate and analyze larger aggregates and their adhesive properties.

Introduction: Electromagnetic interference (EMI) of cardiovascular implantable electronic devices (CIED) can lead to malfunctions and pose a danger for implant carriers. The increased use of DC technologies, e.g. in electric mobility, creates more static fields representing an increasing hazard for implant carriers.Areas covered: A combination of approaches was used to determine thresholds for EMI by static fields. A literature search was conducted to identify relevant EMI mechanisms and to extract possible thresholds. The literature search revealed four interference mechanisms caused by static magnetic fields and none for static electric fields. Due to the scarce information on motion-induced EMI, numerical simulations were performed to obtain a threshold. The simulation results were evaluated using medical product standards and benchmark tests on commercially available CIEDs. The results show that motion-induced interference should not occur below the activation of the magnetic safety switch (reed switch or Hall-effect sensor, MSS).Expert opinion: The determined threshold for motion-induced EMI at 24.8 mT shows that the MSS activation is still the most relevant mechanism that can occur at 0.8 mT. Limit values for the general population do not protect implant carriers from EMI.

Non-anatomical placement may occur during the surgical implantation of the meniscal implant, and its influence on the resulting biomechanics of the knee joint has not been systematically studied. The purpose of this study was to evaluate the biomechanical effects of non-anatomical placement of the meniscal implant on the knee joint during a complete walking cycle. Three-dimensional finite element (FE) analyses of the knee joint were performed, based on the model developed from magnetic resonance images and the loading conditions derived from the gait pattern of a healthy male subject, for the following physiological conditions: (i) knee joint with intact native meniscus, (ii) medial meniscectomized knee joint, (iii) knee joint with anatomically placed meniscal implant, and (iv) knee joint with the meniscal implant placed in four different in vitro determined non-anatomical locations. While the native menisci were modeled using the nonlinear hyperelastic Holzapfel-Gasser-Ogden (HGO) constitutive model, the meniscal implant was modeled using the isotropic hyperelastic neo-Hookean model. Placement of the meniscal implant in the non-anatomical lateral-posterior and lateral-anterior locations significantly increased the peak contact pressure in the medial compartment. Placement of the meniscal implant in non-anatomical locations significantly altered the tibial rotational kinematics and increased the total force acting at the meniscal horns. Results suggest that placement of the meniscal implant in non-anatomical locations may restrain its ability to be chondroprotective and may initiate or accelerate cartilage degeneration. In conclusion, clinicians should endeavor to place the implant as closest as possible to the anatomical location to restore the normal knee biomechanics.

Background Radial self-navigated (RSN) whole-heart coronary cardiovascular magnetic resonance angiography (CCMRA) is a free-breathing technique that estimates and corrects for respiratory motion. However, RSN has been limited to a 1D rigid correction which is often insufficient for patients with complex respiratory patterns. The goal of this work is therefore to improve the robustness and quality of 3D radial CCMRA by incorporating both 3D motion information and nonrigid intra-acquisition correction of the data into a framework called focused navigation (fNAV). Methods We applied fNAV to 500 data sets from a numerical simulation, 22 healthy subjects, and 549 cardiac patients. In each of these cohorts we compared fNAV to RSN and respiratory resolved extradimensional golden-angle radial sparse parallel (XD-GRASP) reconstructions of the same data. Reconstruction times for each method were recorded. Motion estimate accuracy was measured as the correlation between fNAV and ground truth for simulations, and fNAV and image registration for in vivo data. Percent vessel sharpness was measured in all simulated data sets and healthy subjects, and a subset of patients. Finally, subjective image quality analysis was performed by a blinded expert reviewer who chose the best image for each in vivo data set and scored on a Likert scale 0–4 in a subset of patients by two reviewers in consensus. Results The reconstruction time for fNAV images was significantly higher than RSN (6.1 ± 2.1 min vs 1.4 ± 0.3, min, p

Microfluidic devices, such as the tumor-on-a-chip (ToC), allow for the delivery of multiple drugs as desired for various therapies such as cancer treatment. Due to the complexity involved, visualizing, and gaining knowledge of the performance of such devices through experimentation alone is difficult if not impossible. In this paper, we performed a numerical simulation study on ToC performance, which focuses on the ability to combine multiple nanodrugs and optimized ToC performance. The numerical simulations of the chip performance were performed based on the typical chip design and operating parameters, as well as the established governing equations, boundary conditions, and fluid-structure interaction. The effect of cell injection time and position, inlet flow rate, number of inlets, medium viscosity, and cell concentration on the chip performance in terms of shear stress and cell distribution were examined. The results illustrate the profound effect of operation parameters, thus allowing for rigorously determining operational parameters to prevent spheroids ejection from microwells and to restrict the shear stresses within a physiological range. Also, the results show that triple-inlets can increase the uniformity of cell distribution in comparison with single or double inlets. Based on the simulation results, the architecture of the primary ToC was further optimized, resulting in a novel design that enables applying multiple, yet simultaneous, nanodrugs with optimal drug combination as desired for an individual patient. Furthermore, our simulations on the optimized chip showed a uniform cell distribution required for uniform-sized tumor spheroids generation, and complete medium exchange. Taken together, this study not only illustrates that numerical simulations are effective to visualize the ToCs performance, but also develops a novel ToC design optimized for nanodrug-based combination therapy.

Magnetic drug delivery known as smart technique in medicine is basically according to combining the drug inside capsules with the magnetic property or attaching the drug with magnetic surfaces at the micro- and nanoscale. In the present study, magnetic drug delivery in the aortic artery has been investigated. To approach the more realistic problem conditions of blood flow rheology, the effect of parameters such as non-Newtonian viscosity and oscillating input has been put into consideration. Also, the investigated geometrical parameters of arteries of the aortic arch have been chosen similar to the real size. The results indicate that an increase in the diameter of microparticles rises the efficiency of particles absorption. In addition, the influence of changing the direction of the wire carrying electricity and thus changing the direction of magnetic field on magnetic drug delivery has been examined in the geometry of the aortic arc and it is found that the highest particle absorption efficiency takes place in the case that the wire is parallel to the direction of y-axis. As an example, the results show that the rate of absorption efficiency for particles with 3 µm dia is 26.83% and 19.39% when the wire generating magnetic field is parallel to the direction of y-axis and z-axis, respectively, and this value is 10.91% for the case without a magnetic field. The number of particles released from different part of the aortic arch also is affected by the direction of magnetic field. This value illustrates that the percentage of particles released from different states, is equal when the magnetic field is absent and the wire carrying electricity is parallel to y-axis and z-axis. However, the number of particles released from the 2 outputs of the left carotid and left subclavian is less than the other 2 states (i.e., the state when there is not a magnetic field, and the state when the electric current direction is parallel to the y-axis direction) for the state when the wire carrying current is parallel to the z-axis.

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.

Failure and major reoperation after internal fixation (IF) in mature femoral bones are common and proper selection of fixation method may reduce the rate of reoperations. Investigating the mechanical behavior of the human femoral diaphysis, this article studies effect of mechanical properties and geometry of the bone on selection of IF method. To this aim, we calculated the bone mineral density in human femurs, and then, using computed tomography scan, we obtained geometry and nonhomogeneous properties of the bone. Finite element (FE) models of osteotomised femurs were reinforced using four types of screws with a locking compression plate (LCP). We performed buckling and 4-point bending simulations, and results of these simulations represent critical buckling loads, maximum von Mises stresses, and strains around the screws and the central defect. To evaluate FE analysis, we employed the compressive experiments and compared load vs. displacement curves with FE results. Results corresponding to intact, osteotomised, and reinforced states are compared together, and the effect of cortical and unicortical screws in LCPs is studied. The FE results showed that application of identical prophylactic IF for two persons with identical injuries in the same conditions bring quite inverse results. As a consequence, evaluation of osteoporosis, elastic modulus, and morphometric data are required before fixation and screw selection. Besides, for short diaphysis, unicortical screws have maximum strengthening factor in bending. While for long samples, these types of screws can be the worst option, application of cortical screws results to maximum strength in comparison with other types.

Cortical folding-the process of forming the characteristic gyri (hills) and sulci (valleys) of the cortex-is a highly dynamic process that results from the interaction between gene expression, cellular mechanisms, and mechanical forces. Like many other cells, neurons are sensitive to their mechanical environment. Because of this, cortical growth may not happen uniformly throughout gyri and sulci after the onset of cortical folding, which is accompanied by patterns of tension and compression in the surrounding tissue. Here, as an extension of our previous work, we introduce a biomechanically coupled growth model to investigate the importance of interaction between biological growth and mechanical cues during brain development. Our earlier simulations of cortical growth consisted of a homogeneous growing cortex attached to an elastic subcortex. Here, we let the evolution of cortical growth depend on a geometrical quantity-the mean curvature of the cortex-to achieve preferential growth in either gyri or sulci. As opposed to the popular pre-patterning hypothesis, our model treats inhomogeneous cortical growth as the result of folding rather than the cause. The model is implemented numerically in a commercial finite element software Abaqus/Explicit in Abaqus reference manuals, Dassault Systemes Simulia, Providence (2019) by writing user-defined material subroutine (VUMAT). Our simulations show that gyral-sulcal thickness variations are a phenomenon particular to low stiffness ratios. In comparison with cortical thickness measurements of [Formula: see text] human brains via a consistent sampling scheme, our simulations with similar cortical and subcortical stiffnesses suggest that cortical growth is higher in gyri than in sulci.

Purpose: this study aims to quantify the patient-specific hemodynamics of complex conduit routing configurations of coronary artery bypass grafting (CABG) operation which are specifically suitable for off-pump surgeries. Coronary perfusion efficacy and local hemodynamics of multiple left internal mammary artery (LIMA) with sequential and end-to-side anastomosis are investigated. Using a full anatomical model comprised of aortic arch and coronary artery branches the optimum perfusion configuration in multi-vessel coronary artery stenosis is desired. Methodology: two clinically relevant CABG configurations are created using a virtual surgical planning tool where for each configuration set, the stenosis level, anastomosis distance and angle were varied. A non-Newtonian computational fluid dynamics solver in OpenFOAM incorporated with resistance boundary conditions representing the coronary perfusion physiology was developed. The numerical accuracy is verified and results agreed well with a validated commercial cardiovascular flow solver and experiments. For segmental performance analysis, new coronary perfusion indices to quantify deviation from the healthy scenario were introduced. Results: the first simulation configuration set;-a CABG targeting two stenos sites on the left anterior descending artery (LAD), the LIMA graft was capable of 31 mL/min blood supply for all the parametric cases and uphold the healthy LAD perfusion in agreement with the clinical experience. In the second end-to-side anastomosed graft configuration set;-the radial artery graft anastomosed to LIMA, a maximum of 64 mL/min flow rate in LIMA was observed. However, except LAD, the obtuse marginal (OM) and second marginal artery (m2) suffered poor perfusion. In the first set, average wall shear stress (WSS) were in the range of 4 to 35 dyns/cm(2)for in LAD. Nevertheless, for second configuration sets the WSS values were higher as the LIMA could not supply enough blood to OM and m2. Conclusion: the virtual surgical configurations have the potential to improve the quality of operation by providing quantitative surgical insight. The degree of stenosis is a critical factor in terms of coronary perfusion and WSS. The sequential anastomosis can be done safely if the anastomosis angle is less than 90 degrees regardless of degree of stenosis. The smaller proposed perfusion index value,O(0.04 - 0) x 10(2), enable us to quantify the post-op hemodynamic performance by comparing with the ideal healthy physiological flow., Scientific and Technological Research Council of Turkey (TÜBİTAK); 1003 Priority-Research Program Grant; European Union (EU); Horizon 2020; European Research Council (ERC) Proof of Concept Grant; KidsSurgicalPlan

Transcatheter aortic valve replacement (TAVR) strongly depends on the calcification patterns, which may lead to a malapposition of the stented valve and complication onsets in terms of structure kinematics and paravalvular leakage (PVL). From one anatomical-resembling model of the aortic root, six configurations with different calcific deposits were built. TAVR fluid-structure interaction simulations predicted different outcomes for the different calcifications patterns in terms of the final valve configuration in the implantation site and the PVL estimations. In particular models with deposits along the cups coaptation resulted in mild PVL, while those with deposits along the attachment line in moderate PVL.

Mechanical heart valves (MHVs) are widely used to replace diseased heart valves, but it may suffer from cavitation due to the rapid closing velocity of the leaflets, resulting in the damage of red blood cells and platelets. The aim of this study is to apply computational fluid dynamics (CFD) method to investigate the cavitation in bileaflets mechanical heart valves (BMHVs) and discuss the effects of the conduit and leaflet geometries on cavitation intensity. Firstly, CFD method together with moving-grid technology were applied and validated by comparing with experimental results obtained from other literature. Then the leaflets movement and the flow rate of BMHVs with different conduit geometries and leaflet geometries are compared. At last, the duration time of the saturated vapor pressure and the closing velocity of leaflets at the instant of valve closure were used to represent the cavitation intensity. Larger closing velocity of leaflets at the instant of valve closure means higher cavitation intensity. For BMHVs with different conduit geometries, the conduit with Valsalva sinuses has the maximum cavitation intensity and the straight conduit has the minimum cavitation intensity, but the leaflets cannot reach the fully opened state in a straight conduit. For BMHVs with different leaflet geometries, in order to minimize the cavitation intensity, the leaflets are better to have a large thickness and a small rotational radius. CFD method is a promising method to deal with cavitation in BMHVs, and the closing velocity of leaflets has the same trend with the cavitation intensity. By using CFD method, the effects of the conduit geometry and the leaflet geometry on cavitaion in BMHVs are found out.

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.

The adhesion of a circulating tumor cell (CTC) in a three-dimensional curved microvessel was numerically investigated. Simulations were first performed to characterize the differences in the dynamics and adhesion of a CTC in the straight and curved vessels. After that, a parametric study was performed to investigate the effects of the applied driven force density f (or the flow Reynolds number Re) and the CTC membrane bending modulus Kb on the CTC adhesion. Our simulation results show that the CTC prefers to adhere to the curved vessel as more bonds are formed around the transition region of the curved part due to the increased cell-wall contact by the centrifugal force. The parametric study also indicates that when the flow driven force f (or Re) increases or when the CTC becomes softer (Kb decreases), the bond formation probability increases and the bonds will be formed at more sites of a curved vessel. The increased f (or Re) brings a larger centrifugal force, while the decreased Kb generates more contact areas at the cell-wall interface, both of which are beneficial to the bond formation. In the curved vessel, it is found that the site where bonds are formed the most (hotspot) varies with the applied f and the Kb. For our vessel geometry, when f is small, the hotspot tends to be within the first bend of the vessel, while as f increases or Kb decreases, the hotspot may shift to the second bend of the vessel.

Amoeboid cells often migrate using pseudopods, which are membrane protrusions that grow, bifurcate, and retract dynamically, resulting in a net cell displacement. Many cells within the human body, such as immune cells, epithelial cells, and even metastatic cancer cells, can migrate using the amoeboid phenotype. Amoeboid motility is a complex and multiscale process, where cell deformation, biochemistry, and cytosolic and extracellular fluid motions are coupled. Furthermore, the extracellular matrix (ECM) provides a confined, complex, and heterogeneous environment for the cells to navigate through. Amoeboid cells can migrate without significantly remodeling the ECM using weak or no adhesion, instead utilizing their deformability and the microstructure of the ECM to gain enough traction. While a large volume of work exists on cell motility on 2D substrates, amoeboid motility is 3D in nature. Despite recent progress in modeling cellular motility in 3D, there is a lack of systematic evaluations of the role of ECM microstructure, cell deformability, and adhesion on 3D motility. To fill this knowledge gap, here we present a multiscale, multiphysics modeling study of amoeboid motility through 3D-idealized ECM. The model is a coupled fluid‒structure and coarse-grain biochemistry interaction model that accounts for large deformation of cells, pseudopod dynamics, cytoplasmic and extracellular fluid motion, stochastic dynamics of cell-ECM adhesion, and microstructural (pore-scale) geometric details of the ECM. The key finding of the study is that cell deformation and matrix porosity strongly influence amoeboid motility, while weak adhesion and microscale structural details of the ECM have secondary but subtle effects.

This work aimed to determine the influence of strengthening or weakening of the transversus abdominis (TrA) muscle on loads in the lumbar spine using musculoskeletal modelling methods. The input kinematic data of two positions (a standing position and a position during a sitting-down task) were angles in the elbow joint (0°;4°), shoulder joint (0°;3°), hip joint (0°;75°) and knee joint (0°;69°) as well as the torso tilt angle (0°;32°). It was shown that a change in the TrA physiological cross section area (PCSA) has a crucial impact on lumbar spine loads (2xTrA PCSA causes a reduction in the force in joint L5-S1 by 11% for a standing position and by 25% for a sitting-down position) and value of intra-abdominal pressure.

Atherosclerosis preferentially occurs near the junction of branching vessels, where blood recirculation tends to occur (Malek et al. in J Am Med Assoc 282(21):2035-2042, 1999, https://doi.org/10.1001/jama.282.21.2035 ). For decades, CFD has been used to predict flow patterns such as separation and recirculation zones in hemodynamic models, but those predictions have rarely been validated with experimental data. In the context of verification and validation (VV), we first conduct a CFD benchmark calculation that reproduces the vortex detection experiments of Karino and Goldsmith (1980) with idealised branching blood vessels (Karino and Goldsmith in Trans. Am. Soc. Artif. Internal Organs 26:500-506, 1980). The critical conditions for the formation of recirculation vortices, the so-called critical Reynolds numbers, are the main parameters for comparison with the experimental data to demonstrate the credibility of the CFD workflow. We then characterise the wall shear stresses and develop a surrogate model for the size of formed vortices.An automated parametric study generating more than 12,000 CFD simulations was performed, sweeping the geometries and flow conditions found in the experiments by Karino and Goldsmith. The flow conditions were restricted to steady-state laminar flow, with a range of inflow Reynolds numbers up to 350, with various flow ratios between the main branch outlet and side branch outlet. The side branch diameter was scaled relative to the main branch diameter, ranging from 1.05/3 to 3/3; and the branching angles ranged in size from [Formula: see text] to [Formula: see text]. Recirculation vortices were detected by the inversion of the velocity vector at certain locations, as well as by the inversion of the wall shear stress (WSS) vector.The CFD simulations demonstrated good agreement with the experimental data on the critical Reynolds numbers. The spatial distributions of WSS on each branch were analysed to identify potential regions of disease. Once a vortex is formed, the size of the vortex increases by the square root of the Reynolds number. The CFD data was fitted to a surrogate model that accurately predicts the vortex size without the need to run computationally more expensive CFD simulations.This benchmark study validates the CFD simulation of vortex detection in idealised branching vessels under comprehensive flow conditions. This work also proposes a surrogate model for the size of the vortex, which could reduce the computational requirements in the studies related to branching vessels and complex vascular systems.

An image-based numerical algorithm is presented for simulating blood flow through the liver tissue. First, a geometric model is constructed by applying image processing techniques on a real microscopic image of a liver tissue. Then, incompressible blood flow through liver lobules is simulated. Effects of tissue heterogeneity and deformity, presence/absence of the second central vein in a particular lobule, and apparent sinusoids density in the liver cross section on the blood flow are investigated. Numerical results indicate that the existence of thick low permeability vascular septum, high permeability sinusoids, and lobule tissue heterogeneity can considerably affect interlobular and intralobular blood flow.

In this paper, a HIV-TB co-infection model is explored which incorporates a non-linear treatment rate for TB. We begin with presenting a HIV-TB co-infection model and analyze both HIV and TB sub-models separately. The basic reproduction numbers corresponding to HIV-only, TB-only and the HIV-TB full model are computed. The disease-free equilibrium point of the HIV sub-model is shown to be locally as well as globally asymptotically stable when its corresponding reproduction number is less than unity. The HIV-only model exhibits a transcritical bifurcation. On the other hand, for the TB sub-model, the disease-free equilibrium point is locally asymptotically stable but may not be globally asymptotically stable. We have also analyzed the full HIV-TB co-infection model. Numerical simulations are performed to investigate the effect of treatment rate in the presence of resource limitation for TB infected individuals, which emphasize the fact that to reduce co-infection from the population programs to accelerate the treatment of TB should be implemented.

A solid multi-layered concentric sphere with Gaussian space source is considered as the tissue model for magnetic hyperthermia treatment. The generalized dual-phase-lag model of bioheat transfer is used to describe the behavior of heat transport in tissue in the hyperthermia treatment process for accounting the local non-equilibrium effect. The effects of blood perfusion with the transient temperature are included in the tissue model. The hybrid numerical scheme based on Laplace transform, change of variables, and the modified discretization technique is extended to solve the present problem. The analytical solution for constant heat generation in the inner sphere is presented and evidences the accuracy and rationality of the present numerical results. In an ideal hyperthermia treatment, all the diseased tissues should be selectively heated without affecting any healthy tissue. Attempting to achieve the ideal temperature distribution, the thermal dose is estimated at the specified condition. The corresponding thermal efficacy of tumor damage has also been assessed based on the Arrenius equation.

Stenosis in the bifurcated coronary artery has attracted wide attention among the researchers. Many investigations have been carried out by means of Computational Fluid Dynamics (CFD) to better understand the physical mechanism inside the stenotic bifurcated artery. However, the main focus of the existing publications is limited to the variation of hemodynamic parameters affected by the stenosis and bifurcation structure. The present study aims to make further evaluations of stenosis development and diagnostic lesion assessments based on the critical values of hemodynamic and practical diagnostic parameters. The bifurcated coronary artery with initial stenosis source has been studied in 2 D unsteady model. Different locations of initial stenosis source have been found to greatly affect the orientation of the further stenosis development. In addition, different stenosis severities (diameter stenosis: 30%, 50% and 70%), different stenosis lengths (3 mm, 6 mm and 9 mm) and different pulse rates (75 bpm, 100 bpm and 120 bpm) as controlling parameters have been investigated.

Purpose Physiological motion and partial volume effect (PVE) significantly degrade the quality of cardiac positron emission tomography (PET) images in the fast-beating hearts of rodents. Several Super-resolution (SR) techniques using a priori anatomical information have been proposed to correct motion and PVE in PET images. Ultrasound is ideally suited to capture real-time high-resolution cine images of rodent hearts. Here, we evaluated an ultrasound-based SR method using simultaneously acquired and co-registered PET-CT-Ultrafast Ultrasound Imaging (UUI) of the beating heart in closed-chest rodents. Procedures The method was tested with numerical and animal data (n = 2) acquired with the non-invasive hybrid imaging system PETRUS that acquires simultaneously PET, CT, and UUI. Results We showed that ultrasound-based SR drastically enhances the quality of PET images of the beating rodent heart. For the simulations, the deviations between expected and mean reconstructed values were 2 % after applying SR. For the experimental data, when using Ultrasound-based SR correction, contrast was improved by a factor of two, signal-to-noise ratio by 11 %, and spatial resolution by 56 % (~ 0.88 mm) with respect to static PET. As a consequence, the metabolic defect following an acute cardiac ischemia was delineated with much higher anatomical precision. Conclusions Our results provided a proof-of-concept that image quality of cardiac PET in fast-beating rodent hearts can be significantly improved by ultrasound-based SR, a portable low-cost technique. Improved PET imaging of the rodent heart may allow new explorations of physiological and pathological situations related with cardiac metabolism. Electronic supplementary material The online version of this article (10.1007/s11307-020-01512-w) contains supplementary material, which is available to authorized users.

Incretin hormones glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) play a major role in regulation of postprandial glucose and the development of type 2 diabetes mellitus. The incretins are rapidly metabolized, primarily by the enzyme dipeptidyl‐peptidase 4 (DPP4), and the neutral endopeptidase (NEP), although the exact metabolization pathways are unknown. We developed a physiologically‐based (PB) quantitative systems pharmacology model of GLP‐1 and GIP and their metabolites that describes the secretion of the incretins in response to intraduodenal glucose infusions and their degradation by DPP4 and NEP. The model describes the observed data and suggests that NEP significantly contributes to the metabolization of GLP‐1, and the traditional assays for the total GLP‐1 and GIP forms measure yet unknown entities produced by NEP. We further extended the model with a PB pharmacokinetics/pharmacodynamics model of the DPP4 inhibitor sitagliptin that allows predictions of the effects of this medication class on incretin concentrations.

Design optimization for cementless hip prosthesis signifies one of the key topics of research to improve its performances. However, majority of the studies have not considered the presence of uncertainties while it has been shown that a deterministic optimization leads to an unreliable design. In this paper, a multi-objective reliability-based design optimization (MORBDO) procedure is proposed for cementless hip prosthesis design. The proposed methodology consists in combining the finite element simulation (FES), surrogating techniques and optimization procedure. The constructed meta-models are validated and compared using different measures such as error predictions and cross-validation (CV). The results show that the constrained non-dominated sorting genetic algorithm (C-NSGA-II) coupled with the hybrid method (HM) was capable to generate well-distributed reliable Pareto solutions.

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 proces...

This paper is focused on specification of conditions at failure in bovine cortical bone. Both experimental and analytical studies are conducted. The experimental part includes a series of novel direct shear tests which examine the sensitivity of shear strength to the applied normal stress for different orientations of the sample microstructure. These experiments are supplemented by standard axial compression and tension tests in order to define and quantify a general form of failure criterion. The analytical part examines two different methodologies, viz. critical plane approach and microstructure tensor approach, for defining the anisotropic strength criterion. A procedure for identification of material parameters is outlined which is based on the results of the performed material tests.