International Journal for Numerical Methods in Biomedical Engineering

Clavicle fractures often exhibit markedly different clinical outcomes: some patients recover acceptable function despite shortening or displacement, whereas others with apparently similar deformity develop persistent pain, functional loss, or poor healing. To explain this distinction, we propose a minimal nonlinear mechanical model for prognostic analysis of clavicle fractures. The model describes the interaction between fracture-related shortening and compensatory shoulder-girdle posture through a reduced equilibrium equation incorporating stiffness, geometric nonlinearity, and shortening-posture coupling. Within this framework, we analyze equilibrium branches, local stability, and the emergence of critical thresholds. We show that post-fracture destabilization can be interpreted as a fold bifurcation, while more complex parameter dependence gives rise to cusp-type structures and multistability. These bifurcation mechanisms provide a mathematical explanation for sudden deterioration after injury or treatment, as well as for strong inter-individual variability. We further introduce an optimization principle based on a utility functional to guide treatment planning. The analysis predicts that the optimal safe correction should lie strictly below the bifurcation threshold, thereby generating a natural safety margin. Although the model is simplified and has not yet been calibrated against patient data, it nevertheless provides a theoretical framework for understanding why fracture prognosis may deteriorate abruptly near critical mechanical conditions and offers a dynamical-systems interpretation of empirical treatment thresholds used in clinical practice.

Cerebrospinal fluid (CSF) is a Newtonian fluid that bathes the brain and spinal cord and oscillates in response to the physiological periodic changes in brain volume, of which the cardiac cycle is a major driver. Understanding this motion is essential for clarifying its contribution to solute transport, waste clearance, and drug delivery. In this work, we study oscillatory and steady streaming flow in the cranial subarachnoid space using a lubrication-based theoretical framework. The model represents the cranial CSF compartment as a thin fluid layer bounded internally by the brain surface and externally by the dura, driven by time-dependent brain surface displacements. We first derive simplified governing equations for flow over an arbitrary smooth sphere-like brain surface and obtain analytical solutions for an idealised spherical geometry with uniform displacements. We then incorporate realistic displacement fields reconstructed from MRI measurements in healthy subjects and solve the reduced equations numerically. The results show that oscillatory forcing produces a steady streaming component that may enhance solute transport compared with diffusion alone. This work provides a mechanistic description of the flow generated by physiological brain motion and highlights the potential presence of steady streaming in cranial subarachnoid fluid dynamics.

Alzheimers disease (AD) is characterized by the accumulation of amyloid-{beta} (A{beta}), yet the specific link between plaque burden and cognitive decline remains a subject of intense investigation. This paper presents a mathematical model that simulates the coupled dynamics of A{beta} monomers, soluble oligomers, and fibrillar species in the brain tissue. By modifying existing moment equations to include a dedicated conservation equation for A{beta} monomers, the model explores how various microscopic processes, such as primary nucleation, surface-catalyzed secondary nucleation, fibril elongation, and fragmentation, contribute to macroscopic disease progression. Central to this study is the concept of "accumulated neurotoxicity" as a surrogate marker of biological age, defined as the time-integrated concentration of soluble A{beta} oligomers. Unlike plaque burden, accumulated neurotoxicity cannot be reversed, and the harm it causes depends critically on the sequence of events that produced it. Numerical results demonstrate that while plaque burden and neurotoxicity both increase over time, their relationship is non-linear and highly sensitive to the efficiency of protein degradation machinery. Specifically, impaired degradation leads to a rapid advancement of biological age relative to calendar age. The model further identifies oligomer dissociation and fibril fragmentation as potential protective mechanisms that can counterintuitively reduce neurotoxic burden by diverting monomers away from the soluble oligomer pool. These findings provide a quantitative framework for understanding why individuals with similar plaque burdens may experience vastly different cognitive outcomes, underscoring the importance of targeting soluble oligomers early in therapeutic interventions.

Mass-conserved reaction-diffusion systems are used as mathematical models for various phenomena such as cell polarity. Numerical simulations of this system present transient dynamics in which multiple stripe patterns converge to spatially monotonic patterns. Previous studies indicated that the transient dynamics are driven by a mass conservation law and by variations in the amount of substance contained in each pattern, which we refer to as "pattern flux". However, it is challenging to mathematically investigate these pattern dynamics. In this study, we introduce a reaction-diffusion compartment model to investigate the pattern dynamics in view of the conservation law and the pattern flux. This model is defined on multiple intervals (compartments), and diffusive couplings are imposed on each boundary of the compartments. Corresponding to the transient dynamics in the original system, we consider the dynamics around stripe patterns in the compartment model. We derive ordinary differential equations describing the pattern dynamics of the compartment model and analyze the existence and stability of equilibria for the reduced ODE with respect to the boundary parameters. For a specific parameter setting, we obtained results consistent with previous studies. Moreover, we present that the stripe patterns in the compartment model are potentially stabilized by changing the parameter, which is not observed in the original system. We expect that the methodology developed in this paper is extendable to various directions, such as membrane-induced pattern control.

BackgroundConventional left ventricular assist device ramp metrics are load dependent, obscuring intrinsic myocardial recovery. A mechanistic, patient-specific representation of ventricular mechanics, identifiable from routine clinical data, could provide quantitative indices of intrinsic left ventricular (LV) function for longitudinal recovery surveillance. ObjectiveTo develop and verify a ramp-integrated, patient-specific model of HeartMate 3-assisted LV function that can yield indices of intrinsic myocardial contractility and remodeling. MethodsWe represented LV pressure-volume (PV) behavior with a PV envelope composed of a monotonic passive PV relation (pPVR) and a unimodal active PV relation (aPVR). We developed a parameterization procedure to infer the patient-specific shape of this envelope directly from routine ramp-test data. We then embedded the parameterized envelope within the PSCOPE framework, a hybrid platform that couples a lumped-parameter network to a physical HeartMate 3 flow loop, to reproduce clinical ramp hemodynamics. Percent residuals between simulated outputs and the corresponding clinical measurements verified the implementation of the PV envelope within PSCOPE. ResultsIn three HeartMate 3 recipients, the PSCOPE models reproduced ramp hemodynamics with residuals generally [≤] 20% across pump speeds and measured variables. Cardiac index residuals ranged from 0-18.5%, systemic and pulmonary arterial pressure residuals remained [≤] 18.4%, and pulmonary arterial wedge pressure residuals remained [≤] 20%. The PSCOPE models matched central venous pressure within [≤] 3 mmHg in all cases, although one setting yielded a 33.3% residual due to a low reference pressure. For one patient, the model reproduced ramp hemodynamics at a speed deliberately withheld from PV-envelope parameterization with residuals [≤] 10%, supporting cross-speed generalizability. Patient-specific PV envelopes also revealed clinically meaningful heterogeneity in LV diastolic stiffness, volume threshold for declining systolic function, operating PV points for peak systolic function, and contractile reserve. ConclusionsRamp-integrated parameterization of the monotonic pPVR and unimodal aPVR yields a compact, mechanistic PV envelope that is identifiable from routine clinical data and verifiable within PSCOPE. The resulting indices characterize intrinsic LV function and may enhance longitudinal recovery surveillance and inform LVAD management. Prospective multicenter validation is warranted to confirm the generalizability and clinical utility of this approach.

Despite its ubiquity in natural flows, the effects of turbulence on fish locomotion and behavior remain poorly understood. The prevailing hypothesis is that these effects depend on the spatial and temporal scales of the turbulence relative to the fishs size and swimming speed. But in conventional facilities, turbulence usually increases with mean flow, which forces higher swimming speeds and can leave these relative scales unchanged. We therefore present a novel experimental facility that leverages a jet array to decouple the turbulence from the mean flow and systematically control its scales. This approach allows the ratio of turbulent to fish inertial scales to be varied over an order of magnitude, providing a controlled framework for quantifying fish-turbulence interactions. The facility also supports experiments probing strategies fish may use to cope with turbulence, including collective behaviors. Insights from this work have broader implications for ecological studies and engineering applications, including the design of effective fishways and bio-inspired underwater vehicles.

A passive device that attaches to the feet, called an exotendon, can reduce the energetic cost of running at moderate speeds, but its efficacy and optimal design parameters at higher speeds are unknown. Identifying optimal parameters at new speeds experimentally would require many experimental trials with different exotendon designs, which is challenging for participants at higher running speeds. We developed a muscle-driven simulation framework to predict the effect of various exotendon designs on the energetic cost of running at an experimentally untested speed (4 m/s). We used these predictions to select four designs, which we evaluated experimentally as users ran at this speed. The framework correctly predicted that an exotendon that reduced energetic cost at 2.7 m/s would also reduce energetic cost at 4 m/s (10% predicted vs. 5.7% measured) and that a short, stiff exotendon and a long, compliant exotendon would not significantly reduce energetic cost. However, exotendon parameters predicted by the simulation to maximize energetic savings did not significantly reduce energetic cost when evaluated experimentally. There was variability between participants in both the magnitude of maximum energy savings and the exotendon condition associated with those savings. In a 5-km time trial performed with and without the exotendon condition that elicited the largest energy savings for each participant during the experiment, we observed a lower average heart rate (-3.9 {+/-} 3.8 beats/min; P=0.03; mean {+/-} standard deviation) and increased cadence (15.9 {+/-} 9.6 steps/min; P=0.002) when participants ran with the exotendon but did not observe a statistically significant difference in finishing time (-13.5 {+/-} 24.6 sec; P=0.3). These results demonstrate exotendons can reduce energetic cost across multiple running speeds and that predictive simulations provide a framework for guiding experiments to evaluate assistive device designs. Author summaryDesigning assistive devices that help people move more efficiently usually requires many experimental trials. These studies can be time-consuming and physically demanding, especially when testing multiple device designs. In this study, we explored whether computer simulations could help guide the design of an assistive device for running called an exotendon. The exotendon is a simple elastic band that connects the feet and can help runners use less energy. Previous experiments showed that the device reduces the energy needed to run at moderate speeds, but it was unclear whether it would also work at faster speeds or which design would lead to energetic savings. We first used simulations of human running to test many possible exotendon designs at a faster speed. These simulations allowed us to identify promising designs before conducting experiments. We then tested a small number of these designs with runners. The experiments confirmed that the exotendon can reduce the energy required to run at faster speeds, although the efficacy of different designs varied between individuals. Our results show that computer simulations can help researchers rapidly evaluate a variety of assistive device ideas and focus experimental testing on the most promising designs.

Spectral similarity is often judged with a single metric such as RMSE, yet this can be misleading: physically different errors can produce similar scores. This is a critical limitation for computational biomechanics, where spectral agreement underpins both model validation and machine-learning loss design. Here, we develop a multi-metric framework for objective spectral biofidelity and test whether it better captures meaningful disagreement across complex frequency-domain responses. We evaluated 12 complementary similarity metrics, including CORA and ISO/TS 18571, using controlled spectral perturbations that mimic common real-world deviations such as resonance shifts, localized spikes, and broadband tilts. We then applied the framework to an SBI-tuned finite-element middle-ear model to assess convergence with training dataset size and robustness to measurement noise across repeated stochastic runs. No single metric performed reliably across all distortion types. Shape-based metrics tracked resonance morphology but could miss vertical scaling, whereas MaxError remained important for narrowband anomalies that smoother metrics underweighted. CORA and ISO 18571 did not consistently outperform simpler metrics. Rank aggregation using Borda count provided a robust consensus across metrics, enabling objective identification of training-data saturation and noise thresholds beyond which similarity rankings became unstable. These results show that spectral biofidelity cannot be reduced to a single norm. A multi-metric consensus provides a clearer and more physically meaningful basis for comparing experimental and simulated spectra, and offers a more defensible foundation for data-fidelity terms in physics-informed and simulation-based machine learning.

Cytokine-mediated communication is a central mechanism by which immune cells coordinate activation, differentiation and proliferation. While mechanistic reaction-diffusion models provide detailed descriptions of cytokine secretion and uptake at the cellular scale, their computational cost limits their applicability to large and densely packed cell populations. Previously employed approximations of cytokine diffusion fields rely on assumptions that neglect the influence of cellular geometry and volume exclusion. In this work, we study a macroscopic description of cytokine diffusion and reaction dynamics based on homogenization techniques, rigorously linking microscopic reaction-diffusion formulations to effective continuum models. The resulting homogenized equations replace discrete responder cells with a continuous density, while retaining essential features of cellular uptake and excluded-volume effects. Further, we show that in regimes with approximate radial symmetry, classical Yukawa-type solutions emerge as limiting cases of the homogenized model, provided appropriate correction factors are included. Overall, our approach allows efficient multiscale modeling of cytokine signaling in complex immune-cell environments.

Atrial fibrillation (AF) promotes blood stasis and thrombus formation, most often within the left atrial appendage (LAA), and can lead to stroke or transient ischemic attack (TIA). Time-resolved contrast-enhanced computed tomography (4D CT) captures left atrial (LA) opacification and washout, but it does not directly provide quantitative stasis metrics such as blood residence time. Patient-specific computational fluid dynamics (CFD) can quantify LA/LAA residence time, yet routine clinical use is limited by computational cost and sensitivity to patient-specific boundary conditions. Here, we present two complementary approaches to infer time-resolved 3D residence time fields directly from contrast dynamics. First, a physics-informed neural network (PINN) treats contrast as a passive scalar and jointly reconstructs velocity and residence time by enforcing the incompressible Navier-Stokes equations and transport equations for contrast concentration and residence time in moving, patient-specific LA anatomies. Second, an indicator dilution theory (IDT) formulation computes voxelwise, time-resolved residence time maps from contrast time curves alone by constructing a PV-referenced impulse response and modeling transport with a tank-in-series model with spatially dependent parameters. Both methods are benchmarked against patient-specific CFD in six cases spanning diverse LA function, including three patients with TIA or thrombus in the LAA and three patients free of events. Both approaches reproduce expected spatial and temporal trends, with higher residence time in the distal LAA and higher LAA residence time in cases with TIA or thrombus. IDT demonstrates the closest agreement with CFD across the full range of residence times and produces maps in seconds, facilitating clinical translation. In contrast, the PINN additionally recovers phase-dependent atrial flow structures, but tends to smooth and underestimate the highest residence-time regions and requires hours of training. Together, these results support a scalable workflow in which IDT enables rapid stasis screening from contrast CT, and PINNs provide a complementary pathway for detailed, patient-specific hemodynamic inference when full-field flow information is needed.

Understanding how cells migrate through confined environments is crucial for elucidating fundamental biological processes, including cancer invasion, immune surveillance, and tissue morphogenesis. The nucleus, as the largest and stiffest cellular organelle, often limits cellular deformability, making it a key factor in migration through narrow pores or highly constrained spaces. In this work, we introduce a geometric surface partial differential equation (GS-PDE) model in which the cell plasma membrane and nuclear envelope are described as evolving energetic closed surfaces governed by force-balance equations. We replicate the results of a biophysical experiment, where a microfluidic device is used to impose compressive stresses on cells by driving them through narrow microchannels under a controlled pressure gradient. The model is validated by reproducing cell entry into the microchannels. A parametric sensitivity analysis highlights the dominant influence of specific parameters, whose accurate estimation is essential for faithfully capturing the experimental setup. We found that surface tension and confinement geometry emerge as key determinants of translocation efficiency. Although tailored to this specific setup for validation purposes, the framework is sufficiently general to be applied to a broad range of cell mechanics scenarios, providing a robust and flexible tool for investigating the interplay between cell mechanics and confinement. It also offers a solid foundation for future extensions integrating more complex biochemical processes such as active confined migration.

Patient-specific four-chamber electromechanical models provide a physics-constrained framework for investigating whole-heart cardiac physiology and disease mechanisms. Identifying which model parameters impact whole-heart function is important for understanding cellular-, tissue-, and organ-scale determinants of cardiac performance and for calibrating patient-specific models. However, previous global sensitivity analyses of cardiac electromechanical models have typically been performed on a single heart, and systematic evaluation of how parameter influence compares across anatomically different subjects remains limited. We created four-chamber electromechanical models using cardiac MRI from five healthy subjects (n = 5). The models simulated atrial and ventricular cellular electrophysiology, calcium dynamics, and active contraction, with heterogeneous fibre orientation, transversely isotropic tissue mechanics, pericardial constraint, and a closed-loop cardiovascular system providing physiological boundary conditions. In total, 46 parameters described the integrated model. Using Gaussian process emulators, we performed multi-scale global sensitivity analysis to evaluate the relative contribution of model parameters to left and right atrial and ventricular function. Across all anatomies, the most influential parameters were systemic and pulmonary resistances, ventricular end-diastolic pressures, and the venous reference pressure, highlighting the dominant role of haemodynamic loading conditions in governing pressure- and volume-based outputs. A chamber-level analysis of atrioventricular coupling revealed a phase-dependent pattern. Atrial pressures were predominantly governed by global haemodynamic parameters (> 90% of total sensitivity), atrial filling volumes showed substantial ventricular influence ({approx}40-55% across anatomies), and atrial end-systolic volumes were primarily determined by intrinsic atrial parameters ({approx}60-65%). These patterns were consistent across subjects despite differences in anatomy. We show that, in healthy male subjects, inter-individual anatomical variation does not substantially change the ranking of dominant parameters. This work provides a repeatable modelling and sensitivity analysis framework and establishes a benchmark reference for whole-heart electromechanical modelling in healthy hearts. Author summaryComputational models of the heart can simulate cardiac physiology in unprecedented detail, but these models contain many parameters whose influence on predicted function is not fully understood. We built patient-specific four-chamber heart models from MRI scans of five healthy subjects and used statistical methods to systematically test how 46 model parameters affect simulated cardiac performance. Across all five subjects, we found that the haemodynamic loading parameters, including systemic and pulmonary vascular resistance, ventricular filling pressures, and the venous reference pressure, consistently had the greatest influence on the model outputs, regardless of differences in individual heart anatomy. This finding suggests that in healthy resting conditions, the boundary conditions of the cardiovascular system, rather than individual differences in heart geometry or electrical properties, are the primary drivers of whole-heart function. We also found a structured coupling pattern between the upper and lower heart chambers, where global haemodynamic parameters dominate atrial pressure regulation, ventricular mechanics shape atrial filling, and intrinsic atrial properties control atrial emptying. This work provides a benchmark dataset of five anatomically detailed heart models and a sensitivity analysis framework to guide calibration of future cardiac digital twin models.

PurposeLarge quantities of human pluripotent stem cells (hPSCs) are required for clinical applications. 3D suspension cultures are suitable for large scale manufacturing of hPSCs but yield, viability and quality are affected by the hydrodynamic environment. This paper characterizes the hydrodynamic environment inside vertical wheel bioreactors (VWBRs) as a function of size and agitation rates, measures its effect on cell aggregation and proliferation, and proposes the use of Lagrangian-based shear stress and energy dissipation rate (EDR) exposures to support scale-up. MethodsIn silico: Transient, 3D, turbulent flow simulations are conducted for two VWBR sizes (100, 500 mL) at five agitation rates between 20 and 80 rpm. Trajectories of cell aggregates of sizes from 200 to 1,000 microns are calculated, and shear stress and EDR exposures are collected along these trajectories. In vitro: ESI-017 hPSCs were cultured in VWBRs for 6 days. Aggregation efficiency and daily fold ratios were calculated based on cell counts and initial inoculation density. ResultsAggregate size, agitation rate and bioreactor size modulate cell aggregate exposures to EDR and shear stress, which significantly depart from maximum or volume average metrics used for scale-up. Combined in vitro/in silico results show EDR affects aggregation efficiency, cell counts and aggregate size, and has a small effect on daily fold ratios but a significant effect on total fold ratio. ConclusionHistory of trajectory-based cell aggregate exposures to EDRs provide a better scale-up basis for VWBRs than volume-averaged EDR. Shear stress does not significantly affect hPSC aggregation, proliferation and expansion in VWBRs under the tested conditions.

ObjectivePulsed field ablation (PFA) relies on irreversible electroporation to create nonthermal cardiac lesions, yet real-time indicators of electroporation progression and validated lethal electric field thresholds remain limited. This study aimed to develop a bioimpedance-based metric for real-time monitoring of cardiac electroporation, evaluate the impact of myocardial anisotropy under electroporation conditions, and derive waveform-specific lethal electric field thresholds. IntroductionCurrent PFA procedures lack direct intraoperative feedback on lesion formation, and uncertainty remains regarding the role of myocardial fiber orientation in shaping electric field distributions. Because electroporation dynamically alters tissue electrical properties, monitoring these changes during treatment may improve prediction of ablation outcomes. MethodsPFA was delivered to fresh ex vivo porcine ventricular tissue using clinically relevant and energy-matched waveforms with pulse widths from 1 to 100 {micro}s. Inter-burst broadband electrical impedance spectroscopy was performed using a low-voltage diagnostic waveform to quantify burst-resolved impedance changes. Lesions were visualized using metabolic staining, then finite element models incorporating nonlinear electroporation-dependent conductivity were used to compare anisotropic and homogenized electric field distributions. Lethal electric field thresholds were estimated by fitting simulated contours to measured lesion areas and validated using uniform electric fields generated by a parallel electrode array. ResultsAcross all waveforms, impedance measurements showed a rapid initial decrease followed by stabilization, indicating early electroporation saturation. Burst-to-burst percent change in impedance slope provided a consistent, waveform-agnostic metric of electroporation progression. Lesion morphology was not systematically influenced by fiber orientation, and modeling demonstrated that electroporation-induced conductivity increases homogenized tissue anisotropy. Lethal electric field thresholds increased with decreasing pulse width, ranging from 517 {+/-} 46 V/cm (100 {micro}s) to 1405 {+/-} 55 V/cm (1 {micro}s), and were validated under uniform field conditions. ConclusionBioimpedance-assisted monitoring enables real-time assessment of cardiac electroporation, while electroporation-induced homogenization supports simplified modeling and standardized PFA treatment design.

Intervertebral disc degeneration (IVDD) compromises disc structures and mechanics, yet systematic evaluations of the mechanical responses and their relationship to morphological changes in preclinical models remain limited. This systematic review and meta-analysis synthesized mechanical and morphological alterations following experimental disc injury in in vivo animal models. Searches of MEDLINE, EMBASE and Web of Science databases were conducted in accordance with PRISMA guidelines. Study quality and risk of bias were assessed using modified CAMARADES and SYRCLE tools. Twenty-eight studies were included. Pooled analyses showed significant reductions in stiffness, Youngs modulus, and disc height, and significant increases in range of motion and degeneration grade, indicating both mechanical and structural deterioration. Youngs modulus appeared to be the most sensitive marker of functional degeneration. By contrast, creep and other viscoelastic responses showed non-significant changes. High heterogeneity was evident across studies, reflecting variability in injury models, species, timepoints, and testing methods. Evidence of publication bias was detected in several domains, and moderate methodological quality was noted with overall insufficient blinding and lack of sample size calculations. In vivo animal models of IVDD demonstrate robust and consistent mechanical and morphological degeneration after injury. Youngs modulus is a sensitive mechanical indicator, supporting its use in future preclinical research. Standardization of outcome definitions, methodology, and reporting is essential to improve comparability and enhance translation of preclinical findings to clinical research.

This study investigates closed kinematic chain biomechanics in cycling with a focus on knee joint loading. Data from 16 cyclists collected on a standardized ergometer were analyzed in OpenSim using inverse dynamics, static optimization, and joint reaction analysis. To keep the pipeline consistent across all subjects, the report summarizes right-knee outputs over a steady-state interval between 120 and 124 s. Peak knee joint moments ranged from 15.79 to 44.85 Nm (mean 30.49 {+/-} 7.66 Nm), while peak resultant knee reaction forces ranged from 1187.61 to 3309.04 N (mean 2317.19 {+/-} 728.19 N). Static optimization showed strong contributions from the rectus femoris and vastus lateralis during power production, with additional stabilization from the biceps femoris long head and gastrocnemius medialis. Mean peak muscle activation was highest for the rectus femoris (0.72 {+/-} 0.19), followed by the biceps femoris long head (0.66 {+/-} 0.20). Mean peak muscle force was highest for the vastus lateralis (1078.1 {+/-} 305.8 N) and rectus femoris (994.1 {+/-} 379.2 N). The results confirm substantial inter-subject variability in knee loading and support the use of personalized training or rehabilitation strategies when cycling is used for performance development or joint recovery.

Tuberculosis (TB) remains a leading cause of death globally, with early mortality often driven by severe malnutrition and human immuno-deficiency virus (HIV) co-infection. Traditional survival analyses identify risk factors but remain associative, failing to capture the dynamic physiological collapse preceding death. In a novel interdisciplinary adaptation, we applied the Merton jump-diffusion structural framework from quantitative finance to model survival as a state of biological solvency, in which mortality occurs when a stochastic health trajectory crosses a critical failure threshold. We analysed a retrospective cohort of 15,182 TB patients in Cameroon over two decades. Adjusted body mass index (BMI) was conceptualized as a proxy for health capital and modeled using a stochastic process accounting for individual recovery trends, physiological instability, and acute clinical shocks. The study included predominantly young adult males (median age: 33 years) with a median BMI of 20.7 kg/m2. HIV co-infection was present in 35% of patients. The overall mortality rate during the 240 days follow-up period was 7.0%, with 55.1% of deaths occurring within the first 30 days. The model identified a critical failure threshold at BMI 17.329 kg/m2. HIV co-infection emerged as a key driver of metabolic instability, significantly increasing physiological volatility. Statistical validation confirmed that sudden clinical shocks were necessary to explain observed mortality patterns. The resulting Distance-to-Death (DtD) metric slightly outperformed standard associative extended Cox models in predicting survival, achieving a higher discriminative ability in testing set (Harrells C-index: 0.781 vs. 0.772; p = 0.038). Patients stratified into the highest-risk category showed a mortality rate of 16.7%, compared with 1.6% in the most stable group.This study bridges financial engineering and clinical epidemiology, offering a mechanistic understanding of how physiological reserves and metabolic instability determine survival. To support clinical application, we developed an interactive digital triage tool enabling identification of high-risk patients in resource-limited settings. Author summaryTuberculosis remains a major cause of death worldwide, particularly in people with poor nutrition or co-infection with HIV. In this study, we explored a new way to understand why some patients survive while others do not. We adapted a method originally used in finance to track the "health reserves" of patients over time, using body weight and related measures to estimate how close someone is to a critical health threshold. Our approach captures both gradual health decline and sudden medical complications, such as severe infections or rapid deterioration. By applying this method to a large group of patients in Cameroon, we found that a very low body weight is a strong warning sign for impending death and that HIV infection makes health outcomes less predictable. We also created a simple scoring tool that can help doctors identify patients at greatest risk, so that life-saving interventions and closer monitoring can be prioritized. This work bridges mathematical modeling and clinical care, offering a new way to assess patient vulnerability and improve outcomes in resource-limited settings.

Digital volume correlation (DVC) has become the benchmark experimental technique for full-field strain measurement in bone mechanics. In our previous work we developed a novel data-driven image mechanics (D2IM) approach that learns from DVC data and predicts displacement fields directly from undeformed X-ray computed tomography (XCT) images, deriving strain fields from such predictions. However, strain fields derived through numerical differentiation of displacement fields amplify high-frequency noise, and regularization techniques compromise spatial resolution while incurring substantial computational costs. Here we propose the upgrade D2IM-Strain to predict strain fields directly from XCT images of bone. Two prediction strategies were compared: displacement-derived strain and direct strain prediction. The direct strain prediction model significantly improved accuracy particularly for strain magnitudes below 10000{micro}{varepsilon}, taken as a representative threshold value for bone tissue yielding in compression. In addition, the direct approach reduced false-positive high-strain classifications by 75%. By eliminating numerical differentiation, the approach reduces noise amplification while maintaining computational efficiency. These findings represent a critical step toward developing robust data-driven volume correlation methods for hierarchical materials.

Head rotation is the leading cause of diffuse brain injuries from cycling accidents, with severe, long-term or even fatal consequences. Here, we present a novel helmet safety technology, the Release Layer System (RLS), designed to enhance conventional helmets and reduce the likelihood of such injuries. RLS is located on the outer side of the helmet and thus gets impacted first. The force of the impact activates a rolling mechanism triggering the release of an outer polycarbonate panel, thereby dispersing and transforming a substantial portion of the incident rotational energy. To evaluate the effectiveness of the technology, we conducted oblique impact tests on three popular helmet types, in conventional and RLS-equipped configurations, at three impact locations. RLS-equipped helmets reduced Peak Angular Velocity (PAV) by 57-66%, averaged across impact locations, compared to their conventional counterparts. This corresponds to a 68-86% reduction in the probability of an AIS2+ brain injury, as estimated by the Brain Injury Criterion. The most notable improvement was observed at the pYrot location (front impacts, mid-sagittal plane), with up to 85% PAV reduction. Testing across headforms further demonstrated the effectiveness of the technology in mitigating head rotation irrespective of variations in evaluation setups. This work introduces a novel mechanism for rotational impact mitigation and provides evidence of its potential benefits compared with conventional helmets. As an outer-layer approach, RLS may offer an alternative pathway for managing rotational kinematics in future helmet designs.

Optimizing assistive wearable devices is crucial for their efficacy and user adoption, yet state-of-the-art methods like Human-in-the-Loop Optimization (HILO) and biomechanical modeling face limitations. HILO is time-consuming and often restricted to optimizing control parameters, while inverse dynamics assumes invariant kinematics, which is unreliable for adaptive human-device interaction. Predictive simulation offers a powerful alternative, enabling computational exploration of design spaces. However, existing approaches often lack systematic optimization frameworks and rigorous validation against experimental data. To address this, we developed a Design Optimization Platform that integrates predictive simulations within a two-level optimization structure for personalizing assistive device design. This paper primarily validates the platforms predictive simulations against a publicly available dataset of the passive Biarticular Thigh Exosuit (BATEX), assessing its reliability. Our findings show that the model can sufficiently predict the kinematics and major muscle activations, except for the pelvis tilt and some biarticular muscles. The key finding is that successful identification of personalized optimal BATEX stiffness parameters needs acceptable prediction of metabolic cost trends, not their precise values. Our analysis further reveals that the models accuracy in predicting Vasti muscle activation in the baseline condition is a significant indicator of its success in predicting metabolic cost trends. This demonstrates that accurate prediction of performance trends is more important for effective simulation-based design optimization than perfect biomechanical accuracy, advancing targeted and efficient assistive device development.