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1.
J Theor Biol ; 592: 111895, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-38969168

RESUMO

In HIV drug therapy, the high variability of CD4+ T cells and viral loads brings uncertainty to the determination of treatment options and the ultimate treatment efficacy, which may be the result of poor drug adherence. We develop a dynamical HIV model coupled with pharmacokinetics, driven by drug adherence as a random variable, and systematically study the uncertainty quantification, aiming to construct the relationship between drug adherence and therapeutic effect. Using adaptive generalized polynomial chaos, stochastic solutions are approximated as polynomials of input random parameters. Numerical simulations show that results obtained by this method are in good agreement, compared with results obtained through Monte Carlo sampling, which helps to verify the accuracy of approximation. Based on these expansions, we calculate the time-dependent probability density functions of this system theoretically and numerically. To verify the applicability of this model, we fit clinical data of four HIV patients, and the goodness of fit results demonstrate that the proposed random model depicts the dynamics of HIV well. Sensitivity analyses based on the Sobol index indicate that the randomness of drug effect has the greatest impact on both CD4+ T cells and viral loads, compared to random initial values, which further highlights the significance of drug adherence. The proposed models and qualitative analysis results, along with monitoring CD4+ T cells counts and viral loads, evaluate the influence of drug adherence on HIV treatment, which helps to better interpret clinical data with fluctuations and makes several contributions to the design of individual-based optimal antiretroviral strategies.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adesão à Medicação , Carga Viral , Humanos , Fármacos Anti-HIV/uso terapêutico , Linfócitos T CD4-Positivos/virologia , Simulação por Computador , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Modelos Biológicos , Método de Monte Carlo , Processos Estocásticos , Incerteza
2.
J Math Biol ; 89(1): 13, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38879850

RESUMO

In this paper, we introduce the numerical strategy for mixed uncertainty propagation based on probability and Dempster-Shafer theories, and apply it to the computational model of peristalsis in a heart-pumping system. Specifically, the stochastic uncertainty in the system is represented with random variables while epistemic uncertainty is represented using non-probabilistic uncertain variables with belief functions. The mixed uncertainty is propagated through the system, resulting in the uncertainty in the chosen quantities of interest (QoI, such as flow volume, cost of transport and work). With the introduced numerical method, the uncertainty in the statistics of QoIs will be represented using belief functions. With three representative probability distributions consistent with the belief structure, global sensitivity analysis has also been implemented to identify important uncertain factors and the results have been compared between different peristalsis models. To reduce the computational cost, physics constrained generalized polynomial chaos method is adopted to construct cheaper surrogates as approximations for the full simulation.


Assuntos
Simulação por Computador , Modelos Cardiovasculares , Peristaltismo , Processos Estocásticos , Peristaltismo/fisiologia , Incerteza , Humanos , Conceitos Matemáticos , Animais , Coração/fisiologia , Modelos Biológicos , Dinâmica não Linear
3.
Bioengineering (Basel) ; 11(7)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39061812

RESUMO

As magnetic field strength in Magnetic Resonance Imaging (MRI) technology increases, maintaining the specific absorption rate (SAR) within safe limits across human head tissues becomes challenging due to the formation of standing waves at a shortened wavelength. Compounding this challenge is the uncertainty in the dielectric properties of head tissues, which notably affects the SAR induced by the radiofrequency (RF) coils in an ultra-high-field (UHF) MRI system. To this end, this study introduces a computational framework to quantify the impacts of uncertainties in head tissues' dielectric properties on the induced SAR. The framework employs a surrogate model-assisted Monte Carlo (MC) technique, efficiently generating surrogate models of MRI observables (electric fields and SAR) and utilizing them to compute SAR statistics. Particularly, the framework leverages a high-dimensional model representation technique, which constructs the surrogate models of the MRI observables via univariate and bivariate component functions, approximated through generalized polynomial chaos expansions. The numerical results demonstrate the efficiency of the proposed technique, requiring significantly fewer deterministic simulations compared with traditional MC methods and other surrogate model-assisted MC techniques utilizing machine learning algorithms, all while maintaining high accuracy in SAR statistics. Specifically, the proposed framework constructs surrogate models of a local SAR with an average relative error of 0.28% using 289 simulations, outperforming the machine learning-based surrogate modeling techniques considered in this study. Furthermore, the SAR statistics obtained by the proposed framework reveal fluctuations of up to 30% in SAR values within specific head regions. These findings highlight the critical importance of considering dielectric property uncertainties to ensure MRI safety, particularly in 7 T MRI systems.

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