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To optimize the ultraviolet (UV) water disinfection process, it is crucial to determine the ideal geometric dimensions of a corresponding model that enhance performance while minimizing the impact of uncertain photoreactor inputs. As water treatment directly affects people's lives, it is crucial to eliminate the risks associated with the non-ideal performance of disinfection photoreactors. Input uncertainties greatly affect photoreactor performance, making it essential to develop a robust optimization algorithm in advance to mitigate these effects and minimize the physical and financial resources required for constructing the photoreactors. In the suggested algorithm, a two-objective genetic algorithm is integrated with a non-intrusive polynomial chaos expansion (PCE) technique. Additionally, the Sobol sampling method is employed to select the necessary samples for understanding the system's behavior. An artificial neural network surrogate model is trained using sufficient data points derived from computational fluid dynamics (CFD) simulations. A novel type of UV photoreactors working based on exterior reflectors is chosen to optimize the process with three uncertain input parameters, including UV lamp power, UV transmittance of water, and diffusive fraction of the reflective surface. In addition, four geometrical design variables are considered to find the optimal configuration of the photoreactor. The standard deviation (SD) and the reciprocal of log reduction value (LRV) are set as the objective functions, calculated using PCE. The optimal design provides a LRV of 3.95 with SD of 0.2. The coefficient of variation (CoV) of the model significantly declines up to 7%, indicating the decreased sensitivity of the photoreactor to the input uncertainties. Additionally, it is discovered that the robust model exhibits minimal sensitivity to changes in reflectivity in various flow rates, and its output variability aligns with the SD obtained through robust optimization.

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BACKGROUND AND OBJECTIVE: Numerical simulations in electrocardiology are often affected by various uncertainties inherited from the lack of precise knowledge regarding input values including those related to the cardiac cell model, domain geometry, and boundary or initial conditions used in the mathematical modeling. Conventional techniques for uncertainty quantification in modeling electrical activities of the heart encounter significant challenges, primarily due to the high computational costs associated with fine temporal and spatial scales. Additionally, the need for numerous model evaluations to quantify ubiquitous uncertainties increases the computational challenges even further. METHODS: In the present study, we propose a non-intrusive surrogate model to perform uncertainty quantification and global sensitivity analysis in cardiac electrophysiology models. The proposed method combines an unsupervised machine learning technique with the polynomial chaos expansion to reconstruct a surrogate model for the propagation and quantification of uncertainties in the electrical activity of the heart. The proposed methodology not only accurately quantifies uncertainties at a very low computational cost but more importantly, it captures the targeted quantity of interest as either the whole spatial field or the whole temporal period. In order to perform sensitivity analysis, aggregated Sobol indices are estimated directly from the spectral mode of the polynomial chaos expansion. RESULTS: We conduct Uncertainty Quantification (UQ) and global Sensitivity Analysis (SA) considering both spatial and temporal variations, rather than limiting the analysis to specific Quantities of Interest (QoIs). To assess the comprehensive performance of our methodology in simulating cardiac electrical activity, we utilize the monodomain model. Additionally, sensitivity analysis is performed on the parameters of the Mitchell-Schaeffer cell model. CONCLUSIONS: Unlike conventional techniques for uncertainty quantification in modeling electrical activities, the proposed methodology performs at a low computational cost the sensitivity analysis on the cardiac electrical activity parameters. The results are fully reproducible and easily accessible, while the proposed reduced-order model represents a significant contribution to enhancing global sensitivity analysis in cardiac electrophysiology.

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BACKGROUND AND PURPOSE: In the Netherlands, 2 protocols have been standardized for PT among the 3 proton centers: a robustness evaluation (RE) to ensure adequate CTV dose and a model-based selection (MBS) approach for IMPT patient-selection. This multi-institutional study investigates (i) inter-patient and inter-center variation of target dose from the RE protocol and (ii) the robustness of the MBS protocol against treatment errors for a cohort of head-and-neck cancer (HNC) patients treated in the 3 Dutch proton centers. MATERIALS AND METHODS: Clinical treatment plans of 100 HNC patients were evaluated. Polynomial Chaos Expansion (PCE) was used to perform a comprehensive robustness evaluation per plan, enabling the probabilistic evaluation of 100,000 complete fractionated treatments. PCE allowed to derive scenario distributions of clinically relevant dosimetric parameters to assess CTV dose (D99.8%/D0.2%, based on a prior photon plan calibration) and tumour control probabilities (TCP) as well as the evaluation of the dose to OARs and normal tissue complication probabilities (NTCP) per center. RESULTS: For the CTV70.00, doses from the RE protocol were consistent with the clinical plan evaluation metrics used in the 3 centers. For the CTV54.25, D99.8% were consistent with the clinical plan evaluation metrics at center 1 and 2 while, for center 3, a reduction of 1 GyRBE was found on average. This difference did not impact modelled TCP at center 3. Differences between expected and nominal NTCP were below 0.3 percentage point for most patients. CONCLUSION: The standardization of the RE and MBS protocol lead to comparable results in terms of TCP and the NTCPs. Still, significant inter-patient and inter-center variation in dosimetric parameters remained due to clinical practice differences at each institution. The MBS approach is a robust protocol to qualify patients for PT.

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This research introduces a novel global sensitivity analysis (GSA) framework for agent-based models (ABMs) that explicitly handles their distinctive features, such as multi-level structure and temporal dynamics. The framework uses Grassmannian diffusion maps to reduce output data dimensionality and sparse polynomial chaos expansion (PCE) to compute sensitivity indices for stochastic input parameters. To demonstrate the versatility of the proposed GSA method, we applied it to a non-linear system dynamics model and epidemiological and economic ABMs, depicting different dynamics. Unlike traditional GSA approaches, the proposed method enables a more general estimation of parametric sensitivities spanning from the micro level (individual agents) to the macro level (entire population). The new framework encourages the use of manifold-based techniques in uncertainty quantification, enhances understanding of complex spatio-temporal processes, and equips ABM practitioners with robust tools for detailed model analysis. This empowers them to make more informed decisions when developing, fine-tuning, and verifying models, thereby advancing the field and improving routine practice for GSA in ABMs.

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This study applies non-intrusive polynomial chaos expansion (NIPCE) surrogate modeling to analyze the performance of a rotary blood pump (RBP) across its operating range. We systematically investigate key parameters, including polynomial order, training data points, and data smoothness, while comparing them to test data. Using a polynomial order of 4 and a minimum of 20 training points, we successfully train a NIPCE model that accurately predicts pressure head and axial force within the specified operating point range ([0-5000] rpm and [0-7] l/min). We also assess the NIPCE model's ability to predict two-dimensional velocity data across the given range and find good overall agreement (mean absolute error = 0.1 m/s) with a test simulation under the same operating condition. Our approach extends current NIPCE modeling of RBPs by considering the entire operating range and providing validation guidelines. While acknowledging computational benefits, we emphasize the challenge of modeling discontinuous data and its relevance to clinically realistic operating points. We offer open access to our raw data and Python code, promoting reproducibility and accessibility within the scientific community. In conclusion, this study advances comprehensive NIPCE modeling of RBP performance and underlines how critically NIPCE parameters and rigorous validation affect results.

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Introduction: In clinical practice, hemodynamics-based functional indices, such as fractional flow reserve (FFR) and wall shear stress (WSS), are useful in assessing the severity and risk of rupture of atherosclerotic lesions. Computational fluid dynamics (CFD) is widely used to predict these indices noninvasively. Method: In this study, uncertainty quantification and sensitivity analysis are performed for the computational prediction of WSS and FFR directly from 3D-0D coupled CFD simulations on idealized stenotic coronary models. Five geometric parameters (proximal, mid, and distal lengths of stenosis; reference lumen diameter; and stenosis severity) and two physiological parameters (mean aortic pressure and microcirculation resistance) are considered as uncertain input variables. Results: When employing the true values of stenosis severity and mean aortic pressure, a discernible reduction of 25% and 9.5% in the uncertainty of the computed proximal WSS, respectively. In addition, degree of stenosis, reference lumen diameter, and coronary resistance contributed the uncertainty of computed FFR, accounting for 41.2%, 31.9%, and 24.6%, respectively. Conclusion: This study demonstrated that accurate measurement of the degree of stenosis and mean aortic pressure is crucial for improving the computational prediction of WSS. In contrast, the reference lumen diameter, degree of stenosis, and coronary resistance are the most impactful parameters for FFR.

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Artificial Intelligence and Machine learning have been widely used in various fields of mathematical computing, physical modeling, computational science, communication science, and stochastic analysis. Approaches based on Deep Artificial Neural Networks (DANN) are very popular in our days. Depending on the learning task, the exact form of DANNs is determined via their multi-layer architecture, activation functions and the so-called loss function. However, for a majority of deep learning approaches based on DANNs, the kernel structure of neural signal processing remains the same, where the node response is encoded as a linear superposition of neural activity, while the non-linearity is triggered by the activation functions. In the current paper, we suggest to analyze the neural signal processing in DANNs from the point of view of homogeneous chaos theory as known from polynomial chaos expansion (PCE). From the PCE perspective, the (linear) response on each node of a DANN could be seen as a 1st degree multi-variate polynomial of single neurons from the previous layer, i.e. linear weighted sum of monomials. From this point of view, the conventional DANN structure relies implicitly (but erroneously) on a Gaussian distribution of neural signals. Additionally, this view revels that by design DANNs do not necessarily fulfill any orthogonality or orthonormality condition for a majority of data-driven applications. Therefore, the prevailing handling of neural signals in DANNs could lead to redundant representation as any neural signal could contain some partial information from other neural signals. To tackle that challenge, we suggest to employ the data-driven generalization of PCE theory known as arbitrary polynomial chaos (aPC) to construct a corresponding multi-variate orthonormal representations on each node of a DANN. Doing so, we generalize the conventional structure of DANNs to Deep arbitrary polynomial chaos neural networks (DaPC NN). They decompose the neural signals that travel through the multi-layer structure by an adaptive construction of data-driven multi-variate orthonormal bases for each layer. Moreover, the introduced DaPC NN provides an opportunity to go beyond the linear weighted superposition of single neurons on each node. Inheriting fundamentals of PCE theory, the DaPC NN offers an additional possibility to account for high-order neural effects reflecting simultaneous interaction in multi-layer networks. Introducing the high-order weighted superposition on each node of the network mitigates the necessity to introduce non-linearity via activation functions and, hence, reduces the room for potential subjectivity in the modeling procedure. Although the current DaPC NN framework has no theoretical restrictions on the use of activation functions. The current paper also summarizes relevant properties of DaPC NNs inherited from aPC as analytical expressions for statistical quantities and sensitivity indexes on each node. We also offer an analytical form of partial derivatives that could be used in various training algorithms. Technically, DaPC NNs require similar training procedures as conventional DANNs, and all trained weights determine automatically the corresponding multi-variate data-driven orthonormal bases for all layers of DaPC NN. The paper makes use of three test cases to illustrate the performance of DaPC NN, comparing it with the performance of the conventional DANN and also with plain aPC expansion. Evidence of convergence over the training data size against validation data sets demonstrates that the DaPC NN outperforms the conventional DANN systematically. Overall, the suggested re-formulation of the kernel network structure in terms of homogeneous chaos theory is not limited to any particular architecture or any particular definition of the loss function. The DaPC NN Matlab Toolbox is available online and users are invited to adopt it for own needs.

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Objective. The Dutch proton robustness evaluation protocol prescribes the dose of the clinical target volume (CTV) to the voxel-wise minimum (VWmin) dose of 28 scenarios. This results in a consistent but conservative near-minimum CTV dose (D98%,CTV). In this study, we analyzed (i) the correlation between VWmin/voxel-wise maximum (VWmax) metrics and actually delivered dose to the CTV and organs at risk (OARs) under the impact of treatment errors, and (ii) the performance of the protocol before and after its calibration with adequate prescription-dose levels.Approach. Twenty-one neuro-oncological patients were included. Polynomial chaos expansion was applied to perform a probabilistic robustness evaluation using 100,000 complete fractionated treatments per patient. Patient-specific scenario distributions of clinically relevant dosimetric parameters for the CTV and OARs were determined and compared to clinical VWmin and VWmax dose metrics for different scenario subsets used in the robustness evaluation protocol.Main results. The inclusion of more geometrical scenarios leads to a significant increase of the conservativism of the protocol in terms of clinical VWmin and VWmax values for the CTV and OARs. The protocol could be calibrated using VWmin dose evaluation levels of 93.0%-92.3%, depending on the scenario subset selected. Despite this calibration of the protocol, robustness recipes for proton therapy showed remaining differences and an increased sensitivity to geometrical random errors compared to photon-based margin recipes.Significance. The Dutch proton robustness evaluation protocol, combined with the photon-based margin recipe, could be calibrated with a VWmin evaluation dose level of 92.5%. However, it shows limitations in predicting robustness in dose, especially for the near-maximum dose metrics to OARs. Consistent robustness recipes could improve proton treatment planning to calibrate residual differences from photon-based assumptions.

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BACKGROUND AND PURPOSE: In the Netherlands, head-and-neck cancer (HNC) patients are referred for proton therapy (PT) through model-based selection (MBS). However, treatment errors may compromise adequate CTV dose. Our aims are: (i) to derive probabilistic plan evaluation metrics on the CTV consistent with clinical metrics; (ii) to evaluate plan consistency between photon (VMAT) and proton (IMPT) planning in terms of CTV dose iso-effectiveness and (iii) to assess the robustness of the OAR doses and of the risk toxicities involved in the MBS. MATERIALS AND METHODS: Sixty HNC plans (30 IMPT/30 VMAT) were included. A robustness evaluation with 100,000 treatment scenarios per plan was performed using Polynomial Chaos Expansion (PCE). PCE was applied to determine scenario distributions of clinically relevant dosimetric parameters, which were compared between the 2 modalities. Finally, PCE-based probabilistic dose parameters were derived and compared to clinical PTV-based photon and voxel-wise proton evaluation metrics. RESULTS: Probabilistic dose to near-minimum volume v = 99.8% for the CTV correlated best with clinical PTV-D98% and VWmin-D98%,CTV doses for VMAT and IMPT respectively. IMPT showed slightly higher nominal CTV doses, with an average increase of 0.8 GyRBE in the median of the D99.8%,CTV distribution. Most patients qualified for IMPT through the dysphagia grade II model, for which an average NTCP gain of 10.5 percentages points (%-point) was found. For all complications, uncertainties resulted in moderate NTCP spreads lower than 3 p.p. on average for both modalities. CONCLUSION: Despite the differences between photon and proton planning, the comparison between PTV-based VMAT and robust IMPT is consistent. Treatment errors had a moderate impact on NTCPs, showing that the nominal plans are a good estimator to qualify patients for PT.

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In material science and engineering, the estimation of material properties and their failure modes is associated with physical experiments followed by modeling and optimization. However, proper optimization is challenging and computationally expensive. The main reason is the highly nonlinear behavior of brittle materials such as concrete. In this study, the application of surrogate models to predict the mechanical characteristics of concrete is investigated. Specifically, meta-models such as polynomial chaos expansion, Kriging, and canonical low-rank approximation are used for predicting the compressive strength of two different types of concrete (collected from experimental data in the literature). Various assumptions in surrogate models are examined, and the accuracy of each one is evaluated for the problem at hand. Finally, the optimal solution is provided. This study paves the road for other applications of surrogate models in material science and engineering.

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This article presents a novel approach for assessing the effects of residual stresses in laser-directed energy deposition (L-DED). The approach focuses on exploiting the potential of rapidly growing tools such as machine learning and polynomial chaos expansion for handling full-field data for measurements and predictions. In particular, the thermal expansion coefficient of thin-wall L-DED steel specimens is measured and then used to predict the displacement fields around the drilling hole in incremental hole-drilling tests. The incremental hole-drilling test is performed on cubic L-DED steel specimens and the displacement fields are visualized using a 3D micro-digital image correlation setup. A good agreement is achieved between predictions and experimental measurements.

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This study aimed to estimate the distribution of the whole-body averaged specific absorption rate (WBSAR) using several measurable physique parameters for Chinese adult population exposed to environmental electromagnetic fields (EMFs) of current wireless communication frequencies, and to discuss the effects of these physique parameters in the frequency-dependent dosimetric results. The physique distribution of Chinese adults was obtained from the National Physical Fitness and Health Database comprising 81,490 adult samples. The number of physique parameters used to construct the surrogate model was reduced to three via mutual information analysis. A stochastic method with 40 deterministic simulations was used to generate frequency-dependent and gender-specific surrogate models for WBSAR via polynomial chaos expansion. In the simulations, we constructed anatomically correct models conforming to the targeted physique parameters via deformable human modelling technique, which was based on deep learning from the image database including 767 Chinese adults. Thereafter, we analysed the sensitivity of the physique parameters to WBSAR by covariance-based Sobol decomposition. The results indicated that the generated models were consistent with the targeted physique parameters. The estimated dosimetric results were validated using finite-difference time-domain simulations (the error was < 6% across all the investigated frequencies for WBSAR). The novelty of the study included that it demonstrated the feasibility of estimating the individual WBSAR using a limited number of physique parameters with the aid of surrogate modelling. In addition, the population-based distribution of the WBSAR in Chinese adults was firstly presented in the manuscript. The results also indicated that the different combinations of physique parameter, dependent on genders and frequencies, significantly influenced the WBSAR, although the general conservativeness of the guidelines of the International Commission on Non-Ionizing Radiation and Protection can be confirmed in the surveyed population.

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Recently a lumped-parameter model of the cardiovascular system was proposed to simulate the hemodynamics response to partial hepatectomy and evaluate the risk of portal hypertension (PHT) due to this surgery. Model parameters are tuned based on each patient data. This work focuses on a global sensitivity analysis (SA) study of such model to better understand the main drivers of the clinical outputs of interest. The analysis suggests which parameters should be considered patient-specific and which can be assumed constant without losing in accuracy in the predictions. While performing the SA, model outputs need to be constrained to physiological ranges. An innovative approach exploits the features of the polynomial chaos expansion method to reduce the overall computational cost. The computed results give new insights on how to improve the calibration of some model parameters. Moreover the final parameter distributions enable the creation of a virtual population available for future works. Although this work is focused on partial hepatectomy, the pipeline can be applied to other cardiovascular hemodynamics models to gain insights for patient-specific parameterization and to define a physiologically relevant virtual population.

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Planning the defossilization of energy systems while maintaining access to abundant primary energy resources is a non-trivial multi-objective problem encompassing economic, technical, environmental, and social aspects. However, most long-term policies consider the cost of the system as the leading indicator in the energy system models to decrease the carbon footprint. This paper is the first to develop a novel approach by adding a surrogate indicator for the social and economic aspects, the energy return on investment (EROI), in a whole-energy system optimization model. In addition, we conducted a global sensitivity analysis to identify the main parameters driving the EROI uncertainty. This method is illustrated in the 2035 Belgian energy system for several greenhouse gas (GHG) emissions targets. Nevertheless, it can be applied to any worldwide or country energy system. The main results are threefold when the GHG emissions are reduced by 80%: (i) the EROI decreases from 8.9 to 3.9; (ii) the imported renewable gas (methane) represents 60 % of the system primary energy mix; (iii) the sensitivity analysis reveals this fuel drives 67% of the variation of the EROI. These results raise questions about meeting the climate targets without adverse socio-economic impact, demonstrating the importance of considering the EROI in energy system models.

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The central aortic pressure (CAP) provides insights into the prediction, prevention, diagnosis, and treatment of cardiovascular disease, but can't be directly measured non-invasively. Therefore, the development of a noninvasive CAP estimation method based on the non-invasively measured peripheral pressure waveform is critical for clinical decisions based on the CAP. Some existing widely applied methods, such as the generalized transfer function (GTF) method relating measured peripheral pressure to the CAP, do not or only partly account for inter-subject or intra-subject variability of the cardiovascular system. To overcome this pitfall, we propose a subject-specific central aortic pressure estimation method in this paper. The novel method presented can derive an accurate aortic pressure from the peripheral pressure based on an individualized pulse wave propagation model using a GTF method as a first guess. To develop a strategy to personalize a pulse wave propagation model one usually needs to optimize many input parameters. Therefore, we present a two-step approach with the screening method of Morris and the adaptive sparse generalized polynomial chaos expansion (agPCE) algorithm for the sensitivity analysis of the wave propagation model. First, for a-priori defined output of the model, a subset of important parameters is identified using the screening method of Morris. Next, a quantitative variance-based sensitivity analysis is performed using agPCE. This approach is applied to a 1D pulse wave propagation model to get the personalized parameters of the pulse wave propagation model for the estimation of a subject-specific central aortic pressure waveform and is validated with 26 patients. Compared with the GTF method, the proposed method showed better performance in estimating the central aortic pulse wave and predicting the parameters.

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In this paper, a spectral approach is used to formulate and solve robust optimal control problems for compartmental epidemic models, allowing the uncertainty propagation through the optimal control model to be represented by a polynomial expansion of its stochastic state variables. More specifically, a statistical moment-based polynomial chaos expansion is employed. The spectral expansion of the stochastic state variables allows the computation of their main statistics to be carried out, resulting in a compact and efficient representation of the variability of the optimal control model with respect to its random parameters. The proposed robust formulation provides the designers of the optimal control strategy of the epidemic model the capability to increase the predictability of the results by simply adding upper bounds on the variability of the state variables. Moreover, this approach yields a way to efficiently estimate the probability distributions of the stochastic state variables and conduct a global sensitivity analysis. To show the practical implementation of the proposed approach, a mathematical model of COVID-19 transmission is considered. The numerical results show that the spectral approach proposed to formulate and solve robust optimal control problems for compartmental epidemic models provides healthcare systems with a valuable tool to mitigate and control the impact of infectious diseases.

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Mathematical models of thrombosis are currently used to study clinical scenarios of pathological thrombus formation. As these models become more complex to predict thrombus formation dynamics high computational cost must be alleviated and inherent uncertainties must be assessed. Evaluating model uncertainties allows to increase the confidence in model predictions and identify avenues of improvement for both thrombosis modeling and anti-platelet therapies. In this work, an uncertainty quantification analysis of a multi-constituent thrombosis model is performed considering a common assay for platelet function (PFA-100®). The analysis is facilitated thanks to time-evolving polynomial chaos expansions used as a parametric surrogate for the full thrombosis model considering two quantities of interest; namely, thrombus volume and occlusion percentage. The surrogate is thoroughly validated and provides a straightforward access to a global sensitivity analysis via computation of Sobol' coefficients. Six out of 15 parameters linked to thrombus consitution, vWF activity, and platelet adhesion dynamics were found to be most influential in the simulation variability considering only individual effects; while parameter interactions are highlighted when considering the total Sobol' indices. The influential parameters are related to thrombus constitution, vWF activity, and platelet to platelet adhesion dynamics. The surrogate model allowed to predict realistic PFA-100® closure times of 300,000 virtual cases that followed the trends observed in clinical data. The current methodology could be used including common anti-platelet therapies to identify scenarios that preserve the hematological balance.

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In this study, we address three important challenges related to disease transmissions such as the COVID-19 pandemic, namely, (a) providing an early warning to likely exposed individuals, (b) identifying individuals who are asymptomatic, and (c) prescription of optimal testing when testing capacity is limited. First, we present a dynamic-graph based SEIR epidemiological model in order to describe the dynamics of the disease propagation. Our model considers a dynamic graph/network that accounts for the interactions between individuals over time, such as the ones obtained by manual or automated contact tracing, and uses a diffusion-reaction mechanism to describe the state dynamics. This dynamic graph model helps identify likely exposed/infected individuals to whom we can provide early warnings, even before they display any symptoms and/or are asymptomatic. Moreover, when the testing capacity is limited compared to the population size, reliable estimation of individual's health state and disease transmissibility using epidemiological models is extremely challenging. Thus, estimation of state uncertainty is paramount for both eminent risk assessment, as well as for closing the tracing-testing loop by optimal testing prescription. Therefore, we propose the use of arbitrary Polynomial Chaos Expansion, a popular technique used for uncertainty quantification, to represent the states, and quantify the uncertainties in the dynamic model. This design enables us to assign uncertainty of the state of each individual, and consequently optimize the testing as to reduce the overall uncertainty given a constrained testing budget. These tools can also be used to optimize vaccine distribution to curb the disease spread when limited vaccines are available. We present a few simulation results that illustrate the performance of the proposed framework, and estimate the impact of incomplete contact tracing data.

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BACKGROUND AND PURPOSE: Scenario-based robust optimization and evaluation are commonly used in proton therapy (PT) with pencil beam scanning (PBS) to ensure adequate dose to the clinical target volume (CTV). However, a statistically accurate assessment of the clinical application of this approach is lacking. In this study, we assess target dose in a clinical cohort of neuro-oncological patients, planned according to the DUPROTON robustness evaluation consensus, using polynomial chaos expansion (PCE). MATERIALS AND METHODS: A cohort of the first 27 neuro-oncological patients treated at HollandPTC was used, including realistic error distributions derived from geometrical and stopping-power prediction (SPP) errors. After validating the model, PCE-based robustness evaluations were performed by simulating 100.000 complete fractionated treatments per patient to obtain accurate statistics on clinically relevant dosimetric parameters and population-dose histograms. RESULTS: Treatment plans that were robust according to clinical protocol and treatment plansin which robustness was sacrificed are easily identified. For robust treatment plans on average, a CTV dose of 3 percentage points (p.p.) more than prescribed was realized (range +2.7 p.p. to +3.5 p.p.) for 98% of the sampled fractionated treatments. For the entire patient cohort on average, a CTV dose of 0.1 p.p. less than prescribed was achieved (range -2.4 p.p. to +0.5 p.p.). For the 6 treatment plans in which robustness was clinically sacrificed, normalized CTV doses of 0.98, 0.94(7)1, 0.94, 0.91, 0.90 and 0.89 were realized. The first of these was clinically borderline non-robust. CONCLUSION: The clinical robustness evaluation protocol is safe in terms of CTV dose as all plans that fulfilled the clinical robustness criteria were also robust in the PCE evaluation. Moreover, for plans that were non-robust in the PCE-based evaluation, CTV dose was also lower than prescribed in the clinical evaluation.

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In the present study, the effect of physical and operational uncertainties on the hydrodynamic and hemocompatibility characteristics of a centrifugal blood pump designed by the U.S. food and drug administration is investigated. Physical uncertainties include the randomness in the blood density and viscosity, while the operational uncertainties are composed of the pump rotational speed, mass flow rate, and turbulence intensity. The non-intrusive polynomial chaos expansion has been employed to conduct the uncertainty quantification analysis. Additionally, to assess each stochastic parameter's influence on the quantities of interest, the sensitivity analysis is utilized through the Sobol' indices. For numerical simulation of the pump's blood flow, the SST [Formula: see text] turbulence model and a power-law model of hemolysis were employed. The pump's velocity field is profoundly affected by the rotational speed in the bladed regions and the mass flow rate in other zones. Furthermore, the hemolysis index is dominantly sensitive to blood viscosity. According to the results, pump hydraulic characteristics (i.e., head and efficiency) show a more robust behavior than the hemocompatibility characteristics (i.e., hemolysis index) regarding the operational and physical uncertainties. Finally, it was found that the probability distribution function of the hemolysis index covers the experimental measurements.

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