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At least 163 records · Page 9

Microgravity-Induced Physiological Fluid Redistribution: Computational Analysis to Assess Influence of Physiological Parameters

Space flight impacts human physiology in many ways, the most immediate being the marked cephalad (headward) shift of fluid upon introduction into the microgravity environment. This physiological response to microgravity points to the redistribution of blood and interstitial fluid as a major factor in the loss of venous tone and reduction in heart muscle efficiency which impact astronaut performance. In addition, researchers have hypothesized that a reduction in astronaut visual acuity, part of the Visual Impairment and Intracranial Pressure (VIIP) syndrome, is associated with this redistribution of fluid. VIIP arises within several months of beginning space flight and includes a variety of ophthalmic changes including posterior globe flattening, distension of the optic nerve sheath, and kinking of the optic nerve. We utilize a suite of lumped parameter models to simulate microgravity-induced fluid redistribution in the cardiovascular, central nervous and ocular systems to provide initial and boundary data to a 3D finite element simulation of ocular biomechanics in VIIP. Specifically, the lumped parameter cardiovascular model acts as the primary means of establishing how microgravity, and the associated lack of hydrostatic gradient, impacts fluid redistribution. The cardiovascular model consists of 16 compartments, including three cerebrospinal fluid (CSF) compartments, three cranial blood compartments, and 10 thoracic and lower limb blood compartments. To assess the models capability to address variations in physiological parameters, we completed a formal uncertainty and sensitivity analysis that evaluated the relative importance of 42 input parameters required in the model on relative compartment flows and compartment pressures. Utilizing the model in a pulsatile flow configuration, the sensitivity analysis identified the ten parameters that most influenced each compartment pressure. Generally, each compartment responded appropriately to parameter variations associated with itself and adjacent compartments. However, several unexpected interactions between components, such as between the choroid plexus and the lower capillaries, were found, and are due to simplifications in the formulation of the model. The analysis illustrates that highly influential parameters and those that have unique influences within the model formulation must be tightly controlled for successful model application.

gravitational physiology↗

Influence of Population Variation of Physiological Parameters in Computational Models of Space Physiology

The earliest manifestations of Visual Impairment and Intracranial Pressure (VIIP) syndrome become evident after months of spaceflight and include a variety of ophthalmic changes, including posterior globe flattening and distension of the optic nerve sheath. Prevailing evidence links the occurrence of VIIP to the cephalic fluid shift induced by microgravity and the subsequent pressure changes around the optic nerve and eye. Deducing the etiology of VIIP is challenging due to the wide range of physiological parameters that may be influenced by spaceflight and are required to address a realistic spectrum of physiological responses. Here, we report on the application of an efficient approach to interrogating physiological parameter space through computational modeling. Specifically, we assess the influence of uncertainty in input parameters for two models of VIIP syndrome: a lumped-parameter model (LPM) of the cardiovascular and central nervous systems, and a finite-element model (FEM) of the posterior eye, optic nerve head (ONH) and optic nerve sheath. Methods: To investigate the parameter space in each model, we employed Latin hypercube sampling partial rank correlation coefficient (LHSPRCC) strategies. LHS techniques outperform Monte Carlo approaches by enforcing efficient sampling across the entire range of all parameters. The PRCC method estimates the sensitivity of model outputs to these parameters while adjusting for the linear effects of all other inputs. The LPM analysis addressed uncertainties in 42 physiological parameters, such as initial compartmental volume and nominal compartment percentage of total cardiac output in the supine state, while the FEM evaluated the effects on biomechanical strain from uncertainties in 23 material and pressure parameters for the ocular anatomy. Results and Conclusion: The LPM analysis identified several key factors including high sensitivity to the initial fluid distribution. The FEM study found that intraocular pressure and intracranial pressure had dominant impact on the peak strains in the ONH and retro-laminar optic nerve, respectively; optic nerve and lamina cribrosa stiffness were also important. This investigation illustrates the ability of LHSPRCC to identify the most influential physiological parameters, which must therefore be well-characterized to produce the most accurate numerical results.

biomechanics↗

Modeling Microgravity Induced Fluid Redistribution Autoregulatory and Hydrostatic Enhancements

Space flight induces a marked cephalad (headward) redistribution of blood and interstitial fluid potentially resulting in a loss of venous tone and reduction in heart muscle efficiency upon introduction into the microgravity environment. Using various types of computational models, we are investigating how this fluid redistribution may induce intracranial pressure changes, relevant to reported reductions in astronaut visual acuity, part of the Visual Impairment and Intracranial Pressure (VIIP) syndrome. Methods: We utilize a lumped parameter cardiovascular system (CVS) model, augmented by compartments comprising the cerebral spinal fluid (CSF) space, as the primary tool to describe how microgravity, and the associated lack of hydrostatic gradient, impacts fluid redistribution. Models of ocular fluid pressures and biomechanics then accept the output of the above model as boundary condition input to allow more detailed, local analysis (see IWS Abstract by Ethier et al.). Recently, we enhanced the capabilities our previously reported CVS model through the implementation of robust autoregulatory mechanisms and a more fundamental approach to the implementation of hydrostatic mechanisms. Modifying the approach of Blanco et al., we implemented auto-regulation in a quasi-static manner, as an averaged effect across the span of one heartbeat. This approach reduced the higher frequency perturbations from the regulatory mechanism and was intended to allow longer simulation times (days) than models that implement within-beat regulatory mechanisms (minutes). A more fundamental approach to hydrostatics was implemented by a quasi-1D approach, in which compartment descriptions include compartment length, orientation and relative position, allowed for modeling of body orientation, relative body positioning and, in the future, alternative gravity environments. At this time the inclusion of hydrostatic mechanisms supplies additional capabilities to train and validate the CVS model with terrestrial data. Results and Conclusions: With the implementation of auto-regulation and hydrostatic modeling capabilities, the model performs as expected in the maintaining the CA (Central Artery) compartment pressure when simulating orientations ranging from supine to standing. The model appears to generally overpredict heart rate and thus cardiac output, possibly indicating sensitivity to the nominal heart rate, which is used as an initial set point of the regulation mechanisms. Despite this sensitivity, the model performs consistently for many hours of simulation time, indicating the success of our quasi-static implementation approach.

biomechanics↗

Estimation of Lower-Body Kinetics from Loading Profile and Kinematics Alone, Without Measured Ground Reaction Forces

Biomechanical models of human motion can estimate kinetic outcomes, such as joint moments, joint forces and muscle forces. Typically, one performs an inverse dynamics (ID) analysis to compute joint moments from joint angles and measured external forces. Sometimes it is impractical to measure ground reaction forces and moments (GRF&M). We devised an empirical method for performing ID analysis of resistance exercises without measured GRF&M. The method solves the multibody dynamics equations of motion with four key assumptions about the GRF&M that reduce the number of unknowns. The assumptions are 1) negligible ground reaction moments, 2) fixed lateral/medial location of the center of pressure (COP), 3) equal fore/aft location of the COP between the feet, and 4) constant angle of the GRF vector relative to the vertical axis in the frontal plane. We used evaluation trials from a spaceflight countermeasure resistance training device to test this approach. Four participants performed squat and deadlift exercises at various loads. We compared results from traditional ID analysis to results without measured GRF&M using our method. We found that joint moment trajectories in the sagittal plane were qualitatively similar in shape between the two methods, and the amount of root mean squared error (RMSE), measured by difference in joint moment impulse, was typically under 10 percent. Non-sagittal joint moment trajectories, which are much lower in overall magnitude, were not qualitatively similar in shape between the two methods. Non-sagittal moments displayed much higher RMSE, with typical values well over 50 percent. These findings were further supported by validation metrics (Sprague and Geers' P and M metrics, Pearson's r correlation coefficient). Based on these findings, we concluded that useful kinetic results are obtained from ID analysis of squat and deadlift exercises, even when GRF&M are not measured, as long as the outcomes of interest lie in the sagittal plane.

computational modeling↗

Study of Advanced Occupant Models to Quantify Injury Risk for eVTOL Vehicles

Urban transportation is currently evolving from traditional ground-based vehicles (cars, taxis, and buses) to include air-based electric vertical take-off and landing (eVTOL) vehicles which can be utilized for on-demand transportation, cargo transport, and emergency services. These new eVTOL vehicles are designed to be small, lightweight, and able to operate autonomously without user intervention. Safety is a big part of eventual eVTOL adoption, however gaps in the consideration of safety features exist. Anthropomorphic test devices (ATDs) are used in aerospace crashworthiness standards to quantify occupant injury risk and develop improved safety designs for emergency landing situations, but the ATDs currently used in aircraft certification requirements were developed many decades ago. Developments have occurred over the years involving ATD technology, which includes a host of newer and more biofidelic ATDs such as the Test Device for Human Occupant Restraint (THOR). Increased computing power has also allowed for detailed computational human body models (HBMs) to be created, such as the Global Human Body Model Consortium (GHBMC). This study aims to assess the capability of both HBMs and new ATD designs to identify injury mechanisms within eVTOL relevant emergency landing conditions. Finite element (FE) analysis was used to expand upon full-scale and seat level impact testing conducted by researchers at the National Aeronautics and Space Administration (NASA) to look at effects of occupant model configurations on prediction of injury. The GHBMC HBM and THOR ATD models were simulated in the seat level test conditions to characterize differences between these advanced assessment tools and traditional ATDs in the isolated seat loading environment. Results identified key differences in the responses from each of the models utilized and compared their impact response in head, neck, and spinal injury metrics. The THOR model identified potential risks for head injuries due to head impacts on the seat, however it predicted lower spinal loads than the other occupant surrogates. The GHBMC showed distinctly different biomechanical responses compared to the ATD. The GHBMC model is much more deformable than the ATDs and it exhibited higher distribution of forces and increased sensitivity to the duration of acceleration pulses. Both models incorporated into this study identified key mechanisms for injury that should be considered for passenger safety in the development of these novel aircraft. In addition, this study demonstrated the value of FE modeling for running a variety of complex human surrogates to identify potential injury mechanisms for consideration in regulation and development of new aircraft. Continued research in this field to improve validation these models will only lead to safer aircraft and more comprehensive safety measures.

Crashworthiness↗

Study of Advanced Occupant Models to Quantify Injury Risk for eVTOL Vehicles

Urban transportation is currently evolving from traditional ground-based vehicles (cars, taxis, and buses) to include air-based electric vertical take-off and landing (eVTOL) vehicles which can be utilized for on-demand transportation, cargo transport, and emergency services. These new eVTOL vehicles are designed to be small, lightweight, and able to operate autonomously without user intervention. Safety is a big part of eventual eVTOL adoption, however gaps in the consideration of safety features exist. Anthropomorphic test devices (ATDs) are used in aerospace crashworthiness standards to quantify occupant injury risk and develop improved safety designs for emergency landing situations, but the ATDs currently used in aircraft certification requirements were developed many decades ago. Developments have occurred over the years involving ATD technology, which includes a host of newer and more biofidelic ATDs such as the Test Device for Human Occupant Restraint (THOR). Increased computing power has also allowed for detailed computational human body models (HBMs) to be created, such as the Global Human Body Model Consortium (GHBMC). This study aims to assess the capability of both HBMs and new ATD designs to identify injury mechanisms within eVTOL relevant emergency landing conditions. Finite element (FE) analysis was used to expand upon full-scale and seat level impact testing conducted by researchers at the National Aeronautics and Space Administration (NASA) to look at effects of occupant model configurations on prediction of injury. The GHBMC HBM and THOR ATD models were simulated in the seat level test conditions to characterize differences between these advanced assessment tools and traditional ATDs in the isolated seat loading environment. Results identified key differences in the responses from each of the models utilized and compared their impact response in head, neck, and spinal injury metrics. The THOR model identified potential risks for head injuries due to head impacts on the seat, however it predicted lower spinal loads than the other occupant surrogates. The GHBMC showed distinctly different biomechanical responses compared to the ATD. The GHBMC model is much more deformable than the ATDs and it exhibited higher distribution of forces and increased sensitivity to the duration of acceleration pulses. Both models incorporated into this study identified key mechanisms for injury that should be considered for passenger safety in the development of these novel aircraft. In addition, this study demonstrated the value of FE modeling for running a variety of complex human surrogates to identify potential injury mechanisms for consideration in regulation and development of new aircraft. Continued research in this field to improve validation these models will only lead to safer aircraft and more comprehensive safety measures.

Crashworthiness↗

Finite Element Modeling of Extravehicular Mobility Units for Use With Human Body Models – Motivation, Major Challenges, Use Cases and Preliminary Work

Finite element modeling of pressurized spacesuits and implementation with human body models offers many advantages over physical experimentation, but also presents significant challenges. A model of pressurized spacesuit softgoods was developed, integrated with an existing hardgoods model, and fitted to a human body model. Two representative loading scenarios were simulated: dynamic external suit loading and internal occupant-driven loading, to serve as proof-of-concept for the modeling techniques employed. The modeled interactions behaved as intended and illustrate that finite element models of pressurized spacesuits can be used in conjunction with human body models to assess the biomechanical behavior. Further model development and experimental validation are needed.

Finite Element↗

Finite Element Modeling of Extravehicular Mobility Units for Use With Human Body Models – Motivation, Major Challenges, Use Cases and Preliminary Work

Finite element modeling of pressurized spacesuits and implementation with human body models offers many advantages over physical experimentation, but also presents significant challenges. A model of pressurized spacesuit softgoods was developed, integrated with an existing hardgoods model, and fitted to a human body model. Two representative loading scenarios were simulated: dynamic external suit loading and internal occupant-driven loading, to serve as proof-of-concept for the modeling techniques employed. The modeled interactions behaved as intended and illustrate that finite element models of pressurized spacesuits can be used in conjunction with human body models to assess the biomechanical behavior. Further model development and experimental validation are needed.

Finite Element↗

Genetically Controlled Iron Oxide Biomineralization in Encapsulin Nanocompartments for Magnetic Manipulation of a Mammalian Cell Line

Magnetic nanoparticles have proven invaluable for biomechanical investigations due to their ability to exert localized forces. However, cellular delivery of exogenous magnetic agents often results in endosomal entrapment, thereby limiting their utility for manipulating subcellular structures. This study characterizes and exploits fully genetically controlled biomineralization of iron-oxide cores inside encapsulin nanocompartments to enable magnetic-activated cell sorting (MACS) and magnetic cell manipulation. The fraction of MACS-retained cells showed substantial overexpression of encapsulins and exhibited both para- and ferrimagnetic responses with magnetic moments of 10 -15 A m 2 per cell, comparable to standard exogenous labels for MACS. Electron microscopy revealed that MACS-retained cells contained densely packed agglomerates of ≈30 nm iron oxide cores consisting of ultrafine quasicrystalline ordered nuclei within an amorphous matrix of iron, oxygen, and phosphorus. Scanning transmission X-ray microscopy, X-ray absorption spectroscopy, and Raman microspectroscopy confirmed that the iron-oxide species are consistent with ferric oxide (Fe 2 O 3 ). In addition, the encapsulin-overexpressing MACS-retained cells can be manipulated by a magnetic needle and regrown in patterns determined by magnetic gradients. This study demonstrates that the formation of quasicrystalline iron oxide with mixed para/ferrimagnetic behavior in the cytosol of mammalian cells enables magnetic manipulation without the delivery of exogenous agents.

60 APPLIED LIFE SCIENCES↗

Anatomical and hydraulic responses to desiccation in emergent conifer seedlings

Premise The young seedling life stage is critical for reforestation after disturbance and for species migration under climate change, yet little is known regarding their basic hydraulic function or vulnerability to drought. Here, we sought to characterize responses to desiccation including hydraulic vulnerability, xylem anatomical traits, and impacts on other stem tissues that contribute to hydraulic functioning. Methods Larix occidentalis , Pseudotsuga menziesii , and Pinus ponderosa (all ≤6 weeks old) were imaged using x‐ray computed microtomography during desiccation to assess seedling biomechanical responses with concurrently measured hydraulic conductivity ( k s ) and water potential ( Ψ ) to assess vulnerability to xylem embolism formation and other tissue damage. Results In non‐stressed samples for all species, pith and cortical cells appeared circular and well hydrated, but they started to empty and deform with decreasing Ψ which resulted in cell tearing and eventual collapse. Despite the severity of this structural damage, the vascular cambium remained well hydrated even under the most severe drought. There were significant differences among species in vulnerability to xylem embolism formation, with 78% xylem embolism in L. occidentalis by Ψ of −2.1 MPa, but only 47.7% and 62.1% in P. ponderosa and P. menziesii at −4.27 and −6.73 MPa, respectively. Conclusions Larix occidentalis seedlings appeared to be more susceptible to secondary xylem embolism compared to the other two species, but all three maintained hydration of the vascular cambium under severe stress, which could facilitate hydraulic recovery by regrowth of xylem when stress is relieved.

Miller, Megan L.↗

Molecular Insights Into the Ionic Assembly of Poly-Galacturonic Acid Oligomers - Impact of Charge, Ionic Radius, and Polymer Functionalization

Pectin, a major class of matrix polysaccharides present in plant cell walls (PCW), contains widespread anionic saccharides that cross-link in the presence of cations. It modulates important functions such as cell-cell adhesion and determines the PCW's biomechanical properties. It is known that mono-, di-, and tri-valent cations facilitate cross-linking; however, significant knowledge gaps remain in understanding the structure and mechanism of pectin cross-linking. In this study, replica-exchange molecular dynamics (REMD) simulations were employed to elucidate the role of ionic charge, ionic radii, and functional groups on the cross-linking of homogalacturonan (HG), the most abundant pectin molecule. Our enhanced sampling approach in fully solvated environments suggests more effective cross-linking with higher-valent and smaller ions, and that the "zipper" conformation is more favorable than the prevalent "egg-box" conformation. These findings advance our fundamental understanding of pectin matrix structure in PCWs and provide a solid foundation to probe structure-property relationships in pectic polysaccharides.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Enabling AI-Accelerated Multiscale Modeling of Thrombogenesis at Millisecond and Molecular Resolutions on Supercomputers

We report the first congruent integration of HPC, AI, and multiscale modeling (MSM) for solving a mainstream biomechanical problem of thrombogenesis involving 6 million particles at record molecular-scale resolutions in space and at simulation rates of milliseconds per day. The two supercomputers, the IBM Summit-like AiMOS and our University’s SeaWulf, are used for scalability analysis of, and production runs with, the LAMMPS with our customization and AI augmentation and they attained optimal simulation speeds of 3,077 µs/day and 266 µs/day respectively. The long-time and large scales simulations enable the first study of the integrated platelet flowing, flipping, aggregating dynamics in one dynamically-coupled production run. The platelets’ angular and translational speeds, membrane particles’ speeds, and the membrane stress distributions are presented for the analysis of platelets’ aggregations.

Zhu, Yicong↗

Variational and phase response analysis for limit cycles with hard boundaries, with applications to neuromechanical control problems

Motor systems show an overall robustness, but because they are highly nonlinear, understanding how they achieve robustness is difficult. In many rhythmic systems, robustness against perturbations involves response of both the shape and the timing of the trajectory. This makes the study of robustness even more challenging. To understand how a motor system produces robust behaviors in a variable environment, we consider a neuromechanical model of motor patterns in the feeding apparatus of the marine mollusk Aplysia californica (Shaw et al. in J Comput Neurosci 38(1):25–51, 2015; Lyttle et al. in Biol Cybern 111(1):25–47, 2017). We established in (Wang et al. in SIAM J Appl Dyn Syst 20(2):701–744, 2021. https://doi.org/10.1137/20M1344974) the tools for studying combined shape and timing responses of limit cycle systems under sustained perturbations and here apply them to study robustness of the neuromechanical model against increased mechanical load during swallowing. Interestingly, we discover that nonlinear biomechanical properties confer resilience by immediately increasing resistance to applied loads. In contrast, the effect of changed sensory feedback signal is significantly delayed by the firing rates’ hard boundary properties. Our analysis suggests that sensory feedback contributes to robustness in swallowing primarily by shifting the timing of neural activation involved in the power stroke of the motor cycle (retraction). This effect enables the system to generate stronger retractor muscle forces to compensate for the increased load, and hence achieve strong robustness. The approaches that we are applying to understanding a neuromechanical model in Aplysia, and the results that we have obtained, are likely to provide insights into the function of other motor systems that encounter changing mechanical loads and hard boundaries, both due to mechanical and neuronal firing properties.

59 BASIC BIOLOGICAL SCIENCES↗

Scalable multiscale modeling of platelets with 100 million particles

Here, we developed the core components of the AI-aided multiple time stepping algorithm for multiscale modeling of cell dynamics. This algorithm was implemented and analyzed on two supercomputer architectures with an application of simulating the aggregation of 250 platelets, or 102 million particles. To scale on these computers with complex memory and network architectures with GPUs, we devised a biomechanics-informed task mapping scheme to optimize load imbalance, communications, and memory utilization. Our simulations, scaling well up to 192 nodes on a Summit-like supercomputer with a peak speed of 11 petaflops, achieved a rate of 423 μs/day which is 500 times faster than the conventional algorithm using static time step and this has enabled studies of record size blood clots at record spatial–temporal resolutions. Additionally, we discovered the sensitive dependence of the scalability and execution time on the methods of decomposition, CPU–GPU coupling, and task mapping.

97 MATHEMATICS AND COMPUTING↗

Intramedullary Unicortical Button and All-Suture Anchors Provide Similar Maximum Strength for Onlay Distal Biceps Tendon Repair

To evaluate the biomechanical profile of onlay distal biceps repair with an intramedullary unicortical button versus all-suture anchors under cyclic loading and maximal load to failure. Twenty paired fresh-frozen human cadaveric elbows were randomized to onlay distal biceps repair with either a single intramedullary button or with two 1.35-mm all-suture anchors. A 1.3-mm high tensile strength tape was used in a Krackow stitch to suture the tendons in both groups. Specimens and repair constructs were loaded for 3,000 cycles and then loaded to failure. Maximum load to failure, mode of failure, and construct elongation were recorded. Mean (± standard deviation) maximum load to failure for the unicortical intramedullary button and all-suture anchor repairs were 503.23 ± 141.77 N and 537.33 ± 262.13 N (P = .696), respectively. Mean maximum displacement after 3,000 cycles (± standard deviation) was 4.17 ± 2.05 mm in the button group and 2.06 ± 1.05 mm in the suture anchor group (P = .014). Mode of failure in the button group was suture tape rupture in 7 specimens, failure at the tendon–suture interface in 2 specimens, and button pullout in 1 specimen. Anchor pullout was the mode of failure in all suture anchor specimens. There were no tendon ruptures or radial tuberosity fractures in either group. In conclusion, this study demonstrates that onlay distal biceps repair with 2 all-suture anchors has similar maximum strength to repair with an intramedullary button and that both are viable options for fixation.

60 APPLIED LIFE SCIENCES↗

Finite elements for Matérn-type random fields: Uncertainty in computational mechanics and design optimization

This work highlights an approach for incorporating realistic uncertainties into scientific computing workflows based on finite elements, focusing on prevalent applications in computational mechanics and design optimization. We leverage Matérn-type Gaussian random fields (GRFs) generated using the SPDE method to model aleatoric uncertainties, including environmental influences, variating material properties, and geometric ambiguities. Our focus lies on delivering practical GRF realizations that accurately capture imperfections and variations and understanding how they impact the predictions of computational models as well as the shape and topology of optimized designs. Here we describe a numerical algorithm based on solving a generalized SPDE to sample GRFs on arbitrary meshed domains. The algorithm leverages established techniques and integrates seamlessly with the open-source finite element library MFEM and associated scientific computing workflows, like those found in industrial and national laboratory settings. Our solver scales efficiently for large-scale problems and supports various domain types, including surfaces and embedded manifolds. We showcase its versatility through biomechanics and topology optimization applications, emphasizing the potential to influence these domains. The flexibility and efficiency of SPDE-based GRF generation empowers us to run large-scale optimization problems on 2D and 3D domains, including finding optimized designs on embedded surfaces, and to generate design features and topologies beyond the reach of conventional techniques. Moreover, these capabilities allow us to model and quantify geometric uncertainties on reconstructed submanifolds, such as the interpolated surfaces of cerebral aneurysms provided by postprocessing CT scans. In addition to offering benefits in these specific domains, the proposed techniques transcend specific applications and generalize to arbitrary forward and backward problems in uncertainty quantification involving finite elements.

97 MATHEMATICS AND COMPUTING↗

Personalized and uncertainty-aware coronary hemodynamics simulations: From Bayesian estimation to improved multi-fidelity uncertainty quantification

Non-invasive simulations of coronary hemodynamics have improved clinical risk stratification and treatment outcomes for coronary artery disease, compared to relying on anatomical imaging alone. However, simulations typically use empirical approaches to distribute total coronary flow amongst the arteries in the coronary tree, which ignores patient variability, the presence of disease, and other clinical factors. Further, uncertainty in the clinical data often remains unaccounted for in the modeling pipeline. We present an end-to-end uncertainty-aware pipeline to (1) personalize coronary flow simulations by incorporating vessel-specific coronary flows as well as cardiac function; and (2) predict clinical and biomechanical quantities of interest with improved precision, while accounting for uncertainty in the clinical data. We assimilate patient-specific measurements of myocardial blood flow from clinical CT myocardial perfusion imaging to estimate branch-specific coronary artery flows. Simulated noise in the clinical data is used to estimate the joint posterior distributions of the model parameters using adaptive Markov Chain Monte Carlo sampling. Additionally, the posterior predictive distribution for the relevant quantities of interest is determined using a new approach combining multi-fidelity Monte Carlo estimation with non-linear, data-driven dimensionality reduction. This leads to improved correlations between high- and low-fidelity model outputs. Our framework accurately recapitulates clinically measured cardiac function as well as branch-specific coronary flows under measurement noise uncertainty. We observe substantial reductions in confidence intervals for estimated quantities of interest compared to single-fidelity Monte Carlo estimation and state-of-the-art multi-fidelity Monte Carlo methods. This holds especially true for quantities of interest that showed limited correlation between the low- and high-fidelity model predictions. In addition, the proposed multi-fidelity Monte Carlo estimators are significantly cheaper to compute than traditional estimators, under a specified confidence level or variance. The proposed pipeline for personalized and uncertainty-aware predictions of coronary hemodynamics is based on routine clinical measurements and recently developed techniques for CT myocardial perfusion imaging. The proposed pipeline offers significant improvements in precision and reduction in computational cost.

Bayesian parameter estimation↗

From observation to replication: machine-learning-driven quantification and replication of fine-scale fish kinematics and behavior

Long-term quantification of fish behavior is essential for aquatic ecology, wildlife telemetry, and biomechanical device development. However, the observation duration required to obtain reliable behavioral and kinematic metrics remains unclear, and few tools exist to physically reproduce natural swimming motion for controlled experimentation. We address these challenges by developing a generalizable framework that models behavioral reliability (Spearman–Brown reliability index) as a function of observation duration and derives metric-specific monitoring thresholds. Using juvenile white sturgeon (Acipenser transmontanus) as a case study, we demonstrate that the minimum duration needed for reliable estimates varies substantially across kinematic features: to exceed a reliability of 0.8, total distance traveled requires 12 days, average curvature (mm?¹) 15 days, tail-beat frequency (Hz) 8 days, and average speed (body length/s) 17 days. We further bridge digital analysis and physical testing by developing a hardware-in-the-loop simulator that reconstructs machine-learning-derived swimming kinematics with high fidelity (correlation coefficient 0.98–0.99, RMSE 1.22–1.27 mm over a 5-minute segment). This platform enables realistic, repeatable motion stimuli for evaluating aquatic sensing technologies and bio-integrated devices under controlled conditions. Together, these contributions provide a scalable approach for designing long-term behavioral studies and a data-driven connection between ecological observation and robotic experimentation.

Hwang, SungJoo↗