Matching Items (11)
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- All Subjects: Statistics
- Creators: Cheng, Dan
Description
Predicting resistant prostate cancer is critical for lowering medical costs and improving the quality of life of advanced prostate cancer patients. I formulate, compare, and analyze two mathematical models that aim to forecast future levels of prostate-specific antigen (PSA). I accomplish these tasks by employing clinical data of locally advanced prostate cancer patients undergoing androgen deprivation therapy (ADT). I demonstrate that the inverse problem of parameter estimation might be too complicated and simply relying on data fitting can give incorrect conclusions, since there is a large error in parameter values estimated and parameters might be unidentifiable. I provide confidence intervals to give estimate forecasts using data assimilation via an ensemble Kalman Filter. Using the ensemble Kalman Filter, I perform dual estimation of parameters and state variables to test the prediction accuracy of the models. Finally, I present a novel model with time delay and a delay-dependent parameter. I provide a geometric stability result to study the behavior of this model and show that the inclusion of time delay may improve the accuracy of predictions. Also, I demonstrate with clinical data that the inclusion of the delay-dependent parameter facilitates the identification and estimation of parameters.
ContributorsBaez, Javier (Author) / Kuang, Yang (Thesis advisor) / Kostelich, Eric (Committee member) / Crook, Sharon (Committee member) / Gardner, Carl (Committee member) / Nagy, John (Committee member) / Arizona State University (Publisher)
Created2017
Description
Coherent vortices are ubiquitous structures in natural flows that affect mixing and transport of substances and momentum/energy. Being able to detect these coherent structures is important for pollutant mitigation, ecological conservation and many other aspects. In recent years, mathematical criteria and algorithms have been developed to extract these coherent structures in turbulent flows. In this study, we will apply these tools to extract important coherent structures and analyze their statistical properties as well as their implications on kinematics and dynamics of the flow. Such information will aide representation of small-scale nonlinear processes that large-scale models of natural processes may not be able to resolve.
ContributorsCass, Brentlee Jerry (Author) / Tang, Wenbo (Thesis director) / Kostelich, Eric (Committee member) / Department of Information Systems (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Adaptive therapy utilizes competitive interactions between resistant and sensitive cells by keeping some sensitive cells to control tumor burden with the aim of increasing overall survival and time to progression. The use of adaptive therapy to treat breast cancer, ovarian cancer, and pancreatic cancer in preclinical models has shown significant results in controlling tumor growth. The purpose of this thesis is to draft a protocol to study adaptive therapy in a preclinical model of breast cancer on MCF7, estrogen receptor-positive, cells that have evolved resistance to fulvestrant and palbociclib (MCF7 R). In this study, we used two protocols: drug dose adjustment and intermittent therapy. The MCF7 R cell lines were injected into the mammary fat pads of 11-month-old NOD/SCID gamma (NSG) mice (18 mice) which were then treated with gemcitabine.<br/>The results of this experiment did not provide complete information because of the short-term treatments. In addition, we saw an increase in the tumor size of a few of the treated mice, which could be due to the metabolism of the drug at that age, or because of the difference in injection times. Therefore, these adaptive therapy protocols on hormone-refractory breast cancer cell lines will be repeated on young, 6-week old mice by injecting the cell lines at the same time for all mice, which helps the results to be more consistent and accurate.
ContributorsConti, Aviona (Author) / Maley, Carlo (Thesis director) / Blattman, Joseph (Committee member) / Seyedi, Sareh (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
This dissertation comprises two projects: (i) Multiple testing of local maxima for detection of peaks and change points with non-stationary noise, and (ii) Height distributions of critical points of smooth isotropic Gaussian fields: computations, simulations and asymptotics. The first project introduces a topological multiple testing method for one-dimensional domains to detect signals in the presence of non-stationary Gaussian noise. The approach involves conducting tests at local maxima based on two observation conditions: (i) the noise is smooth with unit variance and (ii) the noise is not smooth where kernel smoothing is applied to increase the signal-to-noise ratio (SNR). The smoothed signals are then standardized, which ensures that the variance of the new sequence's noise becomes one, making it possible to calculate $p$-values for all local maxima using random field theory. Assuming unimodal true signals with finite support and non-stationary Gaussian noise that can be repeatedly observed. The algorithm introduced in this work, demonstrates asymptotic strong control of the False Discovery Rate (FDR) and power consistency as the number of sequence repetitions and signal strength increase. Simulations indicate that FDR levels can also be controlled under non-asymptotic conditions with finite repetitions. The application of this algorithm to change point detection also guarantees FDR control and power consistency. The second project focuses on investigating the explicit and asymptotic height densities of critical points of smooth isotropic Gaussian random fields on both Euclidean space and spheres.The formulae are based on characterizing the distribution of the Hessian of the Gaussian field using the Gaussian orthogonally invariant (GOI) matrices and the Gaussian orthogonal ensemble (GOE) matrices, which are special cases of GOI matrices. However, as the dimension increases, calculating explicit formulae becomes computationally challenging. The project includes two simulation methods for these distributions. Additionally, asymptotic distributions are obtained by utilizing the asymptotic distribution of the eigenvalues (excluding the maximum eigenvalues) of the GOE matrix for large dimensions. However, when it comes to the maximum eigenvalue, the Tracy-Widom distribution is utilized. Simulation results demonstrate the close approximation between the asymptotic distribution and the real distribution when $N$ is sufficiently large.
Contributorsgu, shuang (Author) / Cheng, Dan (Thesis advisor) / Lopes, Hedibert (Committee member) / Fricks, John (Committee member) / Lan, Shiwei (Committee member) / Zheng, Yi (Committee member) / Arizona State University (Publisher)
Created2023
Description
Tracking disease cases is an essential task in public health; however, tracking the number of cases of a disease may be difficult not every infection can be recorded by public health authorities. Notably, this may happen with whole country measles case reports, even such countries with robust registration systems. Eilertson et al. (2019) propose using a state-space model combined with maximum likelihood methods for estimating measles transmission. A Bayesian approach that uses particle Markov Chain Monte Carlo (pMCMC) is proposed to estimate the parameters of the non-linear state-space model developed in Eilertson et al. (2019) and similar previous studies. This dissertation illustrates the performance of this approach by calculating posterior estimates of the model parameters and predictions of the unobserved states in simulations and case studies. Also, Iteration Filtering (IF2) is used as a support method to verify the Bayesian estimation and to inform the selection of prior distributions. In the second half of the thesis, a birth-death process is proposed to model the unobserved population size of a disease vector. This model studies the effect of a disease vector population size on a second affected population. The second population follows a non-homogenous Poisson process when conditioned on the vector process with a transition rate given by a scaled version of the vector population. The observation model also measures a potential threshold event when the host species population size surpasses a certain level yielding a higher transmission rate. A maximum likelihood procedure is developed for this model, which combines particle filtering with the Minorize-Maximization (MM) algorithm and extends the work of Crawford et al. (2014).
ContributorsMartinez Rivera, Wilmer Osvaldo (Author) / Fricks, John (Thesis advisor) / Reiser, Mark (Committee member) / Zhou, Shuang (Committee member) / Cheng, Dan (Committee member) / Lan, Shiwei (Committee member) / Arizona State University (Publisher)
Created2022
Description
One of the premier technologies for studying human brain functions is the event-related functional magnetic resonance imaging (fMRI). The main design issue for such experiments is to find the optimal sequence for mental stimuli. This optimal design sequence allows for collecting informative data to make precise statistical inferences about the inner workings of the brain. Unfortunately, this is not an easy task, especially when the error correlation of the response is unknown at the design stage. In the literature, the maximin approach was proposed to tackle this problem. However, this is an expensive and time-consuming method, especially when the correlated noise follows high-order autoregressive models. The main focus of this dissertation is to develop an efficient approach to reduce the amount of the computational resources needed to obtain A-optimal designs for event-related fMRI experiments. One proposed idea is to combine the Kriging approximation method, which is widely used in spatial statistics and computer experiments with a knowledge-based genetic algorithm. Through case studies, a demonstration is made to show that the new search method achieves similar design efficiencies as those attained by the traditional method, but the new method gives a significant reduction in computing time. Another useful strategy is also proposed to find such designs by considering only the boundary points of the parameter space of the correlation parameters. The usefulness of this strategy is also demonstrated via case studies. The first part of this dissertation focuses on finding optimal event-related designs for fMRI with simple trials when each stimulus consists of only one component (e.g., a picture). The study is then extended to the case of compound trials when stimuli of multiple components (e.g., a cue followed by a picture) are considered.
ContributorsAlrumayh, Amani (Author) / Kao, Ming-Hung (Thesis advisor) / Stufken, John (Committee member) / Reiser, Mark R. (Committee member) / Pan, Rong (Committee member) / Cheng, Dan (Committee member) / Arizona State University (Publisher)
Created2019
Description
Bivariate responses that comprise mixtures of binary and continuous variables are common in medical, engineering, and other scientific fields. There exist many works concerning the analysis of such mixed data. However, the research on optimal designs for this type of experiments is still scarce. The joint mixed responses model that is considered here involves a mixture of ordinary linear models for the continuous response and a generalized linear model for the binary response. Using the complete class approach, tighter upper bounds on the number of support points required for finding locally optimal designs are derived for the mixed responses models studied in this work.
In the first part of this dissertation, a theoretical result was developed to facilitate the search of locally symmetric optimal designs for mixed responses models with one continuous covariate. Then, the study was extended to mixed responses models that include group effects. Two types of mixed responses models with group effects were investigated. The first type includes models having no common parameters across subject group, and the second type of models allows some common parameters (e.g., a common slope) across groups. In addition to complete class results, an efficient algorithm (PSO-FM) was proposed to search for the A- and D-optimal designs. Finally, the first-order mixed responses model is extended to a type of a quadratic mixed responses model with a quadratic polynomial predictor placed in its linear model.
In the first part of this dissertation, a theoretical result was developed to facilitate the search of locally symmetric optimal designs for mixed responses models with one continuous covariate. Then, the study was extended to mixed responses models that include group effects. Two types of mixed responses models with group effects were investigated. The first type includes models having no common parameters across subject group, and the second type of models allows some common parameters (e.g., a common slope) across groups. In addition to complete class results, an efficient algorithm (PSO-FM) was proposed to search for the A- and D-optimal designs. Finally, the first-order mixed responses model is extended to a type of a quadratic mixed responses model with a quadratic polynomial predictor placed in its linear model.
ContributorsKhogeer, Hazar Abdulrahman (Author) / Kao, Ming-Hung (Thesis advisor) / Stufken, John (Committee member) / Reiser, Mark R. (Committee member) / Zheng, Yi (Committee member) / Cheng, Dan (Committee member) / Arizona State University (Publisher)
Created2020
Description
Efforts to treat prostate cancer have seen an uptick, as the world’s most commoncancer in men continues to have increasing global incidence. Clinically, metastatic
prostate cancer is most commonly treated with hormonal therapy. The idea behind
hormonal therapy is to reduce androgen production, which prostate cancer cells
require for growth. Recently, the exploration of the synergistic effects of the drugs
used in hormonal therapy has begun. The aim was to build off of these recent
advancements and further refine the synergistic drug model. The advancements I
implement come by addressing biological shortcomings and improving the model’s
internal mechanistic structure. The drug families being modeled, anti-androgens,
and gonadotropin-releasing hormone analogs, interact with androgen production in a
way that is not completely understood in the scientific community. Thus the models
representing the drugs show progress through their ability to capture their effect
on serum androgen. Prostate-specific antigen is the primary biomarker for prostate
cancer and is generally how population models on the subject are validated. Fitting
the model to clinical data and comparing it to other clinical models through the
ability to fit and forecast prostate-specific antigen and serum androgen is how this
improved model achieves validation. The improved model results further suggest that
the drugs’ dynamics should be considered in adaptive therapy for prostate cancer.
prostate cancer is most commonly treated with hormonal therapy. The idea behind
hormonal therapy is to reduce androgen production, which prostate cancer cells
require for growth. Recently, the exploration of the synergistic effects of the drugs
used in hormonal therapy has begun. The aim was to build off of these recent
advancements and further refine the synergistic drug model. The advancements I
implement come by addressing biological shortcomings and improving the model’s
internal mechanistic structure. The drug families being modeled, anti-androgens,
and gonadotropin-releasing hormone analogs, interact with androgen production in a
way that is not completely understood in the scientific community. Thus the models
representing the drugs show progress through their ability to capture their effect
on serum androgen. Prostate-specific antigen is the primary biomarker for prostate
cancer and is generally how population models on the subject are validated. Fitting
the model to clinical data and comparing it to other clinical models through the
ability to fit and forecast prostate-specific antigen and serum androgen is how this
improved model achieves validation. The improved model results further suggest that
the drugs’ dynamics should be considered in adaptive therapy for prostate cancer.
ContributorsReckell, Trevor (Author) / Kostelich, Eric (Thesis advisor) / Kuang, Yang (Committee member) / Mahalov, Alex (Committee member) / Arizona State University (Publisher)
Created2020
Description
Acoustic emission (AE) signals have been widely employed for tracking material properties and structural characteristics. In this study, the aim is to analyze the AE signals gathered during a scanning probe lithography process to classify the known microstructure types and discover unknown surface microstructures/anomalies. To achieve this, a Hidden Markov Model is developed to consider the temporal dependency of the high-resolution AE data. Furthermore, the posterior classification probability and the negative likelihood score for microstructure classification and discovery are computed. Subsequently, a diagnostic procedure to identify the dominant AE frequencies that were used to track the microstructural characteristics is presented. In addition, machine learning methods such as KNN, Naive Bayes, and Logistic Regression classifiers are applied. Finally, the proposed approach applied to identify the surface microstructures of additively manufactured Ti-6Al-4V and show that it not only achieved a high classification accuracy (e.g., more than 90\%) but also correctly identified the microstructural anomalies that may be subjected to further investigation to discover new material phases/properties.
ContributorsSun, Huifeng (Author) / Yan, Hao (Thesis advisor) / Fricks, John (Thesis advisor) / Cheng, Dan (Committee member) / Arizona State University (Publisher)
Created2020
Description
Inside cells, axonal and dendritic transport by motor proteins is a process that is responsible for supplying cargo, such as vesicles and organelles, to support neuronal function. Motor proteins achieve transport through a cycle of chemical and mechanical processes. Particle tracking experiments are used to study this intracellular cargo transport by recording multi-dimensional, discrete cargo position trajectories over time. However, due to experimental limitations, much of the mechanochemical process cannot be directly observed, making mathematical modeling and statistical inference an essential tool for identifying the underlying mechanisms. The cargo movement during transport is modeled using a switching stochastic differential equation framework that involves classification into one of three proposed hidden regimes. Each regime is characterized by different levels of velocity and stochasticity. The equations are presented as a state-space model with Markovian properties. Through a stochastic expectation-maximization algorithm, statistical inference can be made based on the observed trajectory. Regime predictions and particle location predictions are calculated through an auxiliary particle filter and particle smoother. Based on these predictions, parameters are estimated through maximum likelihood. Diagnostics are proposed that can assess model performance and therefore also be a form of model selection criteria. Model selection is used to find the most accurate regime models and the optimal number of regimes for a certain motor-cargo system. A method for incorporating a second positional dimension is also introduced. These methods are tested on both simulated data and different types of experimental data.
ContributorsCrow, Lauren (Author) / Fricks, John (Thesis advisor) / McKinley, Scott (Committee member) / Hahn, Paul R (Committee member) / Reiser, Mark (Committee member) / Cheng, Dan (Committee member) / Arizona State University (Publisher)
Created2021