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At least 145 records · Page 8

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↗

Joint state-parameter estimation for the reduced fracture model via the united filter

Here, in this paper, we introduce an effective United Filter method for jointly estimating the solution state and physical parameters in flow and transport problems within fractured porous media. Fluid flow and transport in fractured porous media are critical in subsurface hydrology, geophysics, and reservoir geomechanics. Reduced fracture models, which represent fractures as lower-dimensional interfaces, enable efficient multi-scale simulations. However, reduced fracture models also face accuracy challenges due to modeling errors and uncertainties in physical parameters such as permeability and fracture geometry. To address these challenges, we propose a United Filter method, which integrates the Ensemble Score Filter (EnSF) for state estimation with the Direct Filter for parameter estimation. EnSF, based on a score-based diffusion model framework, produces ensemble representations of the state distribution without deep learning. Meanwhile, the Direct Filter, a recursive Bayesian inference method, estimates parameters directly from state observations. The United Filter combines these methods iteratively: EnSF estimates are used to refine parameter values, which are then fed back to improve state estimation. Numerical experiments demonstrate that the United Filter method surpasses the state-of-the-art Augmented Ensemble Kalman Filter, delivering more accurate state and parameter estimation for reduced fracture models. This framework also provides a robust and efficient solution for PDE-constrained inverse problems with uncertainties and sparse observations.

Bayesian inference↗

State Estimation for Distribution Networks with Asynchronous Sensors Using Stochastic Descent: Preprint

This paper investigates the problem of state estimation for distribution networks with asynchronous sensors comprising of a mix of smart meters and phasor measurement units (PMUs) with multiple sampling and reporting rates. We consider two independent scenarios of state estimation and tracking, with either voltages or currents as states. With these two sets, we investigate estimation under (a) full data, assuming all measurements are available and (b) limited data, where an online algorithmic approach is adopted to estimate the possibly time-varying states by processing measurements as and when available. The proposed algorithm, inspired by the classical Stochastic Gradient Descent (SGD) approach updates the states based on the previous estimate and the newly available measurements. Finally, we demonstrate the estimation and tracking efficacy through numerical simulations on the IEEE-37 test network, while also highlighting how estimation with currents as states leads to faster convergence.

asynchronous sensors↗

Ambient-Frequency-Data Based System-Level Inertia Estimation Using Physical Equation and its Practice on Hawaii Islands

Here, in this paper, a practical ambient-frequency-data-based inertia estimation method using a physical equation is proposed and validated by real measurement data from Hawaii island grids. With high renewable penetration, accurate inertia estimation is important and urgent. Ambient frequency oscillation always exists in power grids, so the proposed method has advantages of real-time inertia estimation and no need for additional disturbances. This paper first developed the physical equation for inertia estimation to offer a clear mechanism for easy implementation in practice. To apply the proposed method in actual grids, a practical method to extract the ambient frequency oscillation from frequency measurement is further proposed. The inertia estimation using the physical equation is validated by KIUC simulation data and HECO field data, in which error rates are around 2% and 8%, respectively. Practical inertia estimation is challenging due to the large amounts of resources contributing to the power grid's effective inertia, but the method provided in this paper can offer a novel way for practical inertia estimation, which can help renewable penetration to boost carbon-free grid.

14 SOLAR ENERGY↗

Robust Distributed State Estimator for Interconnected Transmission and Distribution Networks (Final Report RPPR-1)

This project’s objective is to develop a combined transmission and distribution state estimator which accounts for very large system size and model complexity (by way of distributing the computations) and large number of solar PV units connected to the distribution system on multiple feeders. The project not only provides a robust formulation and solution to this problem but also tests the solution by implementing it on a well-established large utility system. It introduces several improvements with respect to the state of the art in existing state estimation software: (a) The developed state estimator (SE) allows robust and accurate monitoring of bidirectional flows in distribution systems which result due to the distributed energy sources which are not observable and thus not incorporated in generation dispatch; (b) Large utility systems with tens of thousands of transmission buses and hundreds of thousands of distribution nodes are difficult to model as a single integrated system. This shortcoming is addressed by developing a “scalable distributed computational framework” which allows splitting the ultra large system models into several small subsystems and coordinating their solution by a robust and practical state estimation formulation; (c) Measurement errors irrespective of their locations are detected and removed by the developed state estimator. Historically, transmission and distribution systems were analyzed and operated as two independent systems. Given the non-transposed short feeder sections, unevenly loaded phases, strictly radial configuration and unidirectional power flows in the absence of remote generation, distribution system analysis was customized to account for these characteristics. However, some of these assumptions are no longer valid (non-radial configuration, bidirectional power flows) and thus distribution system analysis should be revisited. Furthermore, in the past, the interaction between the transmission and distribution systems was quite passive, where distribution substations were modeled as lumped loads in the transmission system model. With substantial generation injected by renewable generation located in the distribution systems, such modeling will no longer be accurate. The developed state estimator facilitates proper monitoring of the interactions between the transmission and distribution systems and enables smart dispatch of these units which are made observable by the state estimator.

24 POWER TRANSMISSION AND DISTRIBUTION↗

Worldwide Population Estimates for Small Geographic Areas

This chapter discusses the basis for these population estimates, scope, and limitations based on experiences in development of massive global population datasets and usage of these datasets as a basis for sampling design. It presents tools and approaches for using these georeferenced population estimates for complex household survey sampling. The chapter provides a unified resource for understanding current gridded population datasets, their use in survey research, and promising areas of future work toward improved population estimates. It includes an overview of popular gridded population datasets, common methodological frameworks for developing gridded population estimates, and discusses pros and cons for selecting a gridded population dataset from a survey perspective. The chapter focuses on survey methods that use gridded population estimates specifically. It highlights differences between census population estimates and gridded population estimates that may be relevant when planning data collection. The chapter presents a case study of gridded population data and sampling methods in Nigeria.

Amer, Safaa↗

In Search of a Cost-Effective Approach for Estimating Dam Passage Survival

Abstract Passage of downstream-migrating fishes through hydropower dams poses a management issue in rivers throughout the world. As such, regulations have been enacted at many locales to understand and limit fish losses by requiring dam passage survival estimation. However, limiting estimates of survival to the dam and immediate tailrace presents a challenge to researchers. In this study, two alternative release–recapture methods were used to estimate dam passage survival of juvenile salmonids through Lower Granite Dam on the Snake River, Washington, in 2018. One approach, the virtual/paired-release (ViPRe) model, was extensively used in the Columbia–Snake River basin at federally operated hydroelectric dams during 2010–2014. This existing approach uses three releases of tagged smolts to isolate dam passage survival, defined as survival from the upstream dam face to the tailrace mixing zone 1–2 km downstream of the dam. An alternative approach, the virtual release/dead-fish correction (ViRDCt) model, uses one live-release group paired with a release of dead tagged fish at the dam to estimate the same survival parameter. The alternative estimation approaches were tested on two spring out-migrating stocks, yearling Chinook Salmon Oncorhynchus tshawytscha and steelhead Oncorhynchus mykiss, and on a summer out-migrating stock of subyearling Chinook Salmon. The alternative estimates for these stocks were all within 1 SE. However, the ViRDCt model produced survival estimates with SEs that were 59% smaller than those of the existing ViPRe model and did so using 42% fewer tagged fish and one less downstream acoustic detection array. Because of the reduced sample size, nearly US$540,000 less in tag costs and 4,000 fewer labor-hours were required to implement the ViRDCt model compared to the ViPRe model. As such, the ViRDCt model represents a cost-effective and precise approach to characterizing dam passage survival.

59 BASIC BIOLOGICAL SCIENCES↗

DART-PFLOTRAN: An ensemble-based data assimilation system for estimating subsurface flow and transport model parameters

Ensemble-based Data Assimilation (EDA), based on the Monte Carlo approach, has been effectively applied to estimate model parameters through inverse modeling in subsurface flow and transport problems. However, implementation of EDA approach involves a complicated workflow that include setting up and executing ensemble forward model simulations, processing observations and model simulation results for parameter updates, and repeat for sequential or iterative EDA. To facilitate the management of such workflow and lower the barriers for adopting EDA-based parameter estimation in subsurface science, we develop a generic software frame-work linking the Data Assimilation Research Testbed (DART) with a massively parallel subsurface FLOw and TRANsport code PFLOTRAN. The new DART-PFLOTRAN leverages both the core data assimilation engines in DART and the computational power afforded by PFLOTRAN. In addition to the standard smoother and filtering options, DART-PFLOTRAN enables an iterative EDA workflow based on the Ensemble Smoother for Multiple Data Assimilation method (ES-MDA) to improve estimation accuracy for nonlinear forward problems. Here, we verify the implementation of ES-MDA in DART-PFLOTRAN using two synthetic cases designed to estimate static permeability and dynamic exchange fluxes across the riverbed, respectively, from continuous temperature measurements made across a depth profile. One-dimensional hydro-thermal simulations are performed in both cases to relate temperature responses with the parameters of interest. In the case of estimating dynamic parameters, we demonstrate the flexibility of DART-PFLOTRAN in automating sequential ES-MDA workflow, which will significantly reduce the time researchers spend on managing complex workflows in similar applications. Both studies yield accurate estimations of the parameters compared to their synthetic truth, while ES-MDA leads to more accurate estimation when a high level of nonlinearity exist between observed responses and unknown parameters. With a code base in Python and Fortran, DART-PFLOTRAN paves the way for applications in large-scale subsurface inverse modeling by automating the complex workflow of sequential ES-MDA that can be executed on various computing platforms.

97 MATHEMATICS AND COMPUTING↗

Parametric estimation of Poisson's ratio for thin hinged-hinged plates

Cornu's method is an elegant calculation besieged by an impractical approach to obtain accurate estimates for Poisson's ratio. Conventionally, Cornu's method requires several components, and each component can adversely affect the accuracy of the measurement. Furthermore, Cornu's conventional method requires a long beam because beams with short length-to-width ratios cause the estimate of Poisson's ratio to diverge from the true value of Poisson's ratio. We believe that, with the right modifications, Cornu's method can become an attractive approach to obtaining precise estimates for Poisson's ratio from mode shapes. Here we use finite element simulations to show how to use Cornu's method to estimate Poisson's ratio from a mode shape. Our modified Cornu's method removes knife-edges and loading components for a hinged-hinged plate under steady-state excitation. Given the true value of Poisson's ratio, as a performance specification, we show that simple parametric expressions can fit estimates for Poisson's ratio for different length-to-width ratios of thin hinged-hinged plates. Additionally, we show that estimates for Poisson's ratio from higher modes align with the results from the first mode and explain our expectation for this outcome. Furthermore, our results challenge the idea that anticlastic, monoclastic, and synclastic deformation uniquely correspond to positive, zero, and negative estimates of Poisson's ratio, respectively. With the emergence of materials-by-design, we expect that this parametric technique will be able to assist in experimental qualification of thin beam and plate structures with respect to the desired value of Poisson's ratio.

42 ENGINEERING↗

Uncertainty quantification of the convolutional neural networks on permeability estimation from micro-CT scanned sandstone and carbonate rock images

Rock permeability is one of the most crucial properties affecting subsurface fluid flow behaviors. To accurately and robustly estimate the permeability, Digital Rock Physics, including micro-CT scanning technology and direct flow simulations on scanned images, has prevailed in recent years. Besides, machine learning techniques such as convolutional neural networks (CNNs) have been widely adopted and achieved success in permeability estimations directly from rock images. However, existing ML methods used for permeability estimation from rock images lack uncertainty quantification that causes unreliable predictions and overconfident estimations on out-of-distribution (OOD) samples. Here, in this work, we propose a PI3NN-CNN framework to address this problem. PI3NN-CNN consists of a CNN model for absolute permeability estimation and a PI3NN method to quantify the estimation uncertainty. It is able to quantify the uncertainty for in-distribution (InD) data with a desired confidence level, and identify OOD samples to avoid overconfident predictions. We demonstrate the method using micro-CT scanned images from two sandstone and two carbonate rocks. We found that PI3NN-CNN generates accurate predictions for InD samples, while producing high-quality prediction uncertainties regardless of the prediction accuracy. Meanwhile, PI3NN-CNN identifies OOD samples using its special network initialization scheme. The unique feature of PI3NN-CNN makes it applicable to more complex real-world image-based data for robust learning and predictions without overconfident estimations when the ground-truth information is unavailable.

58 GEOSCIENCES↗

Combining Remotely Sensed Evapotranspiration and an Agroecosystem Model to Estimate Center‐Pivot Irrigation Water Use at High Spatio‐Temporal Resolution

Abstract Estimating irrigation water use accurately is critical for sustainable irrigation and studying terrestrial water cycle in irrigated croplands. However, irrigation is not monitored in most places, and current estimations of irrigation water use has coarse spatial and/or temporal resolutions. This study aims to estimate irrigation water use at the daily and field scale through the proposed model‐data fusion framework, which is achieved by particle filtering with two configurations (concurrent, CON, and sequential, SEQ) by assimilating satellite‐based evapotranspiration (ET) observations into an advanced agroecosystem model, ecosys . Two types of experiments using synthetic and real ET observations were conducted to study the efficacy of the proposed framework for estimating irrigation water use at the irrigated fields in eastern and western Nebraska, United States. The experiments using synthetic ET observations indicated that, for two major sources of uncertainties of ET difference between observations and model simulations, which are bias and noise, noise had larger impacts on degrading the estimation performance of irrigation water use than bias. For the experiments using real ET observations, monthly and annual estimations of irrigation water use matched well with farmer irrigation records, with Pearson correlation coefficient ( r ) around 0.80 and 0.50, respectively. Although detecting daily irrigation records was very challenging, our method still gave a good performance with RMSE, BIAS, and r around 2.90, 0.03, and 0.4 mm/d, respectively. Our proposed model‐data fusion framework for estimating irrigation water use at high spatio‐temporal resolution could contribute to regional water management, sustainable irrigation, and better tracking terrestrial water cycle.

Environmental Sciences & Ecology↗

DESI DR1 Ly α 1D power spectrum: Validation of estimators

The Data Release 1 (DR1) of the Dark Energy Spectroscopic Instrument (DESI) is the largest sample to date for small-scale Lyα forest cosmology, accessed through its one-dimensional power spectrum (P 1D ). The Lyα forest P 1D is extracted from quasar spectra that are highly inhomogeneous (both in wavelength and between quasars) in noise properties due to intrinsic properties of the quasar, atmospheric and astrophysical contamination, and also sensitive to low-level details of the spectral extraction pipeline. We employ two estimators in DR1 analysis to measure P 1D : the optimal estimator and the fast Fourier transform (FFT) estimator. To ensure robustness of our DR1 measurements, we validate these two power spectrum and covariance matrix estimation methodologies against the challenging aspects of the data. First, using a set of 20 synthetic 1D realizations of DR1, we derive the masking bias corrections needed for the FFT estimator and the continuum fitting bias needed for both estimators. We demonstrate that both estimators, including their covariances, are unbiased with these corrections using the Kolmogorov-Smirnov test. Second, we substantially extend our previous suite of CCD image simulations to include 675,000 quasars, allowing us to accurately quantify the pipeline's performance. This set of simulations reveals biases at the highest k values, corresponding to a resolution error of a few percent. We base the resolution systematics error budget of DR1 P 1D on these values, but do not derive corrections from them since the simulation fidelity is insufficient for precise corrections.

Lyman alpha forest↗

Local Group timing argument and virial theorem mass estimators from cosmological simulations

ABSTRACT We identify Local Group (LG) analogues in the IllustrisTNG cosmological simulation, and use these to study two-mass estimators for the LG: One based on the timing argument (TA) and one based on the virial theorem (VT). Including updated measurements of the Milky Way-M31 tangential velocity and the cosmological constant, we show that the TA mass estimator slightly overestimates the true median LG-mass, though the ratio of the TA to the true mass is consistent at the approximate 90 per cent c.l.. These are in broad agreement with previous results using dark matter-only simulations. We show that the VT estimator better estimates the true LG-mass, though there is a larger scatter in the virial mass to true mass ratio relative to the corresponding ratio for the TA. We attribute the broader scatter in the VT estimator to several factors, including the predominantly radial orbits for LG satellite galaxies, which differs from the VT assumption of isotropic orbits. With the systematic uncertainties we derive, the updated measurements of the LG mass at 90 per cent c.l. are $4.75_{-2.41}^{+2.22} \times 10^{12}$ M⊙ from the TA and $2.0_{-1.5}^{+2.1} \times 10^{12}$ M⊙ from the VT. We consider the LMC’s effect on the TA and VT LG mass estimates, and do not find exact LMC–MW–M31 analogues in the Illustris simulations. However, in LG simulations with satellite companions as massive as the LMC, we find that the effect on the TA and VT estimators is small, though we need further studies on a larger sample of LMC–MW–M31 systems to confirm these results.

79 ASTRONOMY AND ASTROPHYSICS↗

Accurate shear estimation with fourth-order moments

ABSTRACT As imaging surveys progress in exploring the large-scale structure of the Universe through the use of weak gravitational lensing, achieving sub-per cent accuracy in estimating shape distortions caused by lensing, or shear, is imperative for precision cosmology. In this paper, we extend the Fourier power function shapelets (FPFS) shear estimator using fourth-order shapelet moments and combine it with the original second-order shear estimator to reduce galaxy shape noise. We calibrate this novel shear estimator analytically to a sub-per cent level-accuracy using the AnaCal framework. This higher order shear estimator is tested with realistic image simulations, and after analytical correction for the detection/selection bias and noise bias, the multiplicative shear bias $|m|$ is below $3\times 10^{-3}$ (99.7 per cent confidence interval) for both isolated and blended galaxies. Once combined with the second-order FPFS shear estimator, the shape noise is reduced by $\sim 35~{{\ \rm per\ cent}}$ for isolated galaxies in simulations with Hyper Suprime-Cam and Vera C. Rubin Observatory Legacy Survey of Space and Time observational conditions. However, for blended galaxies, the effective number density does not significantly improve with the combination of the two estimators. Based on these results, we recommend exploration of how this framework can further reduce the systematic uncertainties in shear due to point spread function leakage and modelling error, and potentially provide improved precision in shear inference in high-resolution space-based images.

79 ASTRONOMY AND ASTROPHYSICS↗

Bootstrapping outperforms community‐weighted approaches for estimating the shapes of phenotypic distributions

Abstract Estimating phenotypic distributions of populations and communities is central to many questions in ecology and evolution. These distributions can be characterized by their moments (mean, variance, skewness and kurtosis) or diversity metrics (e.g. functional richness). Typically, such moments and metrics are calculated using community‐weighted approaches (e.g. abundance‐weighted mean). We propose an alternative bootstrapping approach that allows flexibility in trait sampling and explicit incorporation of intraspecific variation, and show that this approach significantly improves estimation while allowing us to quantify uncertainty. We assess the performance of different approaches for estimating the moments of trait distributions across various sampling scenarios, taxa and datasets by comparing estimates derived from simulated samples with the true values calculated from full datasets. Simulations differ in sampling intensity (individuals per species), sampling biases (abundance, size), trait data source (local vs. global) and estimation method (two types of community‐weighting, two types of bootstrapping). We introduce the traitstrap R package, which contains a modular and extensible set of bootstrapping and weighted‐averaging functions that use community composition and trait data to estimate the moments of community trait distributions with their uncertainty. Importantly, the first function in the workflow, trait_fill , allows the user to specify hierarchical structures (e.g. plot within site, experiment vs. control, species within genus) to assign trait values to each taxon in each community sample. Across all taxa, simulations and metrics, bootstrapping approaches were more accurate and less biased than community‐weighted approaches. With bootstrapping, a sample size of 9 or more measurements per species per trait generally included the true mean within the 95% CI. It reduced average percent errors by 26%–74% relative to community‐weighting. Random sampling across all species outperformed both size‐ and abundance‐biased sampling. Our results suggest randomly sampling ~9 individuals per sampling unit and species, covering all species in the community and analysing the data using nonparametric bootstrapping generally enable reliable inference on trait distributions, including the central moments, of communities. By providing better estimates of community trait distributions, bootstrapping approaches can improve our ability to link traits to both the processes that generate them and their effects on ecosystems.

Maitner, Brian S.↗

A Bayesian Approach to Regional Decadal Predictability: Sparse Parameter Estimation in High-Dimensional Linear Inverse Models of High-Latitude Sea Surface Temperature Variability

Stochastic reduced models are an important tool in climate systems whose many spatial and temporal scales cannot be fully discretized or underlying physics may not be fully accounted for. One form of reduced model, the linear inverse model (LIM), has been widely used for regional climate predictability studies—typically focusing more on tropical or midlatitude studies. However, most LIM fitting techniques rely on point estimation techniques deriving from fluctuation–dissipation theory. In this methodological study we explore the use of Bayesian inference techniques for LIM parameter estimation of sea surface temperature (SST), to quantify the skillful decadal predictability of Bayesian LIM models at high latitudes. We show that Bayesian methods, when compared to traditional point estimation methods for LIM-type models, provide better calibrated probabilistic skill, while simultaneously providing better point estimates due to the regularization effect of the prior distribution in high-dimensional problems. We compare the effect of several priors, as well as maximum likelihood estimates, on 1) estimating parameter values on a perfect model experiment and 2) producing calibrated 1-yr SST anomaly forecast distributions using a preindustrial control run of the Community Earth System Model (CESM). Finally, we employ a host of probabilistic skill metrics to determine the extent to which an LIM can forecast SST anomalies at high latitudes. We find that the choice of prior distribution has an appreciable impact on estimation outcomes, and priors that emphasize physically relevant properties enhance the model’s ability to capture variability of SST anomalies.

54 ENVIRONMENTAL SCIENCES↗

Forced Component Estimation Statistical Method Intercomparison Project (ForceSMIP)

Anthropogenic climate change is unfolding rapidly, yet its regional manifestation can be obscured by internal variability. A primary goal of climate science is to identify the externally forced climate response from among the noise of internal variability. Separating the forced response from internal variability can be addressed in climate models by using a large ensemble to average over different possible realizations of internal variability. However, with only one realization of the real world, it is a major challenge to isolate the forced response directly in observations. In the Forced Component Estimation Statistical Method Intercomparison Project (ForceSMIP), contributors used existing and newly developed statistical and machine learning methods to estimate the forced response over 1950–2022 within individual realizations of the climate system. Participants used neural networks, linear inverse models, fingerprinting methods, and low-frequency component analysis, among other approaches. These methods were trained using large ensembles from multiple climate models and then applied to observations. Here, we evaluate method performance within large ensembles and investigate the estimates of the forced response in observations. Our results show that many different types of methods are skillful for estimating the forced response in climate models, though the relative skill of individual methods varies depending on the variable and evaluation metric. Methods with comparable skill in models can give a wide range of estimates of the forced response pattern in observations, illustrating the epistemic uncertainty in forced response estimates. ForceSMIP gives new insights into the forced response in observations, its uncertainty, and methods for its estimation.

Climate attribution↗

How robust are estimates of key parameters in standard viral dynamic models?

Mathematical models of viral infection have been developed, fitted to data, and provide insight into disease pathogenesis for multiple agents that cause chronic infection, including HIV, hepatitis C, and B virus. However, for agents that cause acute infections or during the acute stage of agents that cause chronic infections, viral load data are often collected after symptoms develop, usually around or after the peak viral load. Consequently, we frequently lack data in the initial phase of viral growth, i.e., when pre-symptomatic transmission events occur. Missing data may make estimating the time of infection, the infectious period, and parameters in viral dynamic models, such as the cell infection rate, difficult. However, having extra information, such as the average time to peak viral load, may improve the robustness of the estimation. Here, we evaluated the robustness of estimates of key model parameters when viral load data prior to the viral load peak is missing, when we know the values of some parameters and/or the time from infection to peak viral load. Although estimates of the time of infection are sensitive to the quality and amount of available data, particularly pre-peak, other parameters important in understanding disease pathogenesis, such as the loss rate of infected cells, are less sensitive. Viral infectivity and the viral production rate are key parameters affecting the robustness of data fits. Fixing their values to literature values can help estimate the remaining model parameters when pre-peak data is missing or limited. We find a lack of data in the pre-peak growth phase underestimates the time to peak viral load by several days, leading to a shorter predicted growth phase. On the other hand, knowing the time of infection (e.g., from epidemiological data) and fixing it results in good estimates of dynamical parameters even in the absence of early data. While we provide ways to approximate model parameters in the absence of early viral load data, our results also suggest that these data, when available, are needed to estimate model parameters more precisely.

59 BASIC BIOLOGICAL SCIENCES↗