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- All Subjects: Operations Research
Description
In today's global market, companies are facing unprecedented levels of uncertainties in supply, demand and in the economic environment. A critical issue for companies to survive increasing competition is to monitor the changing business environment and manage disturbances and changes in real time. In this dissertation, an integrated framework is proposed using simulation and online calibration methods to enable the adaptive management of large-scale complex supply chain systems. The design, implementation and verification of the integrated approach are studied in this dissertation. The research contributions are two-fold. First, this work enriches symbiotic simulation methodology by proposing a framework of simulation and advanced data fusion methods to improve simulation accuracy. Data fusion techniques optimally calibrate the simulation state/parameters by considering errors in both the simulation models and in measurements of the real-world system. Data fusion methods - Kalman Filtering, Extended Kalman Filtering, and Ensemble Kalman Filtering - are examined and discussed under varied conditions of system chaotic levels, data quality and data availability. Second, the proposed framework is developed, validated and demonstrated in `proof-of-concept' case studies on representative supply chain problems. In the case study of a simplified supply chain system, Kalman Filtering is applied to fuse simulation data and emulation data to effectively improve the accuracy of the detection of abnormalities. In the case study of the `beer game' supply chain model, the system's chaotic level is identified as a key factor to influence simulation performance and the choice of data fusion method. Ensemble Kalman Filtering is found more robust than Extended Kalman Filtering in a highly chaotic system. With appropriate tuning, the improvement of simulation accuracy is up to 80% in a chaotic system, and 60% in a stable system. In the last study, the integrated framework is applied to adaptive inventory control of a multi-echelon supply chain with non-stationary demand. It is worth pointing out that the framework proposed in this dissertation is not only useful in supply chain management, but also suitable to model other complex dynamic systems, such as healthcare delivery systems and energy consumption networks.
ContributorsWang, Shanshan (Author) / Wu, Teresa (Thesis advisor) / Fowler, John (Thesis advisor) / Pfund, Michele (Committee member) / Li, Jing (Committee member) / Pavlicek, William (Committee member) / Arizona State University (Publisher)
Created2010
Description
Mathematical modeling and decision-making within the healthcare industry have given means to quantitatively evaluate the impact of decisions into diagnosis, screening, and treatment of diseases. In this work, we look into a specific, yet very important disease, the Alzheimer. In the United States, Alzheimer’s Disease (AD) is the 6th leading cause of death. Diagnosis of AD cannot be confidently confirmed until after death. This has prompted the importance of early diagnosis of AD, based upon symptoms of cognitive decline. A symptom of early cognitive decline and indicator of AD is Mild Cognitive Impairment (MCI). In addition to this qualitative test, Biomarker tests have been proposed in the medical field including p-Tau, FDG-PET, and hippocampal. These tests can be administered to patients as early detectors of AD thus improving patients’ life quality and potentially reducing the costs of the health structure. Preliminary work has been conducted in the development of a Sequential Tree Based Classifier (STC), which helps medical providers predict if a patient will contract AD or not, by sequentially testing these biomarker tests. The STC model, however, has its limitations and the need for a more complex, robust model is needed. In fact, STC assumes a general linear model as the status of the patient based upon the tests results. We take a simulation perspective and try to define a more complex model that represents the patient evolution in time.
Specifically, this thesis focuses on the formulation of a Markov Chain model that is complex and robust. This Markov Chain model emulates the evolution of MCI patients based upon doctor visits and the sequential administration of biomarker tests. Data provided to create this Markov Chain model were collected by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The data lacked detailed information of the sequential administration of the biomarker tests and therefore, different analytical approaches were tried and conducted in order to calibrate the model. The resulting Markov Chain model provided the capability to conduct experiments regarding different parameters of the Markov Chain and yielded different results of patients that contracted AD and those that did not, leading to important insights into effect of thresholds and sequence on patient prediction capability as well as health costs reduction.
The data in this thesis was provided from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). ADNI investigators did not contribute to any analysis or writing of this thesis. A list of the ADNI investigators can be found at: http://adni.loni.usc.edu/about/governance/principal-investigators/ .
Specifically, this thesis focuses on the formulation of a Markov Chain model that is complex and robust. This Markov Chain model emulates the evolution of MCI patients based upon doctor visits and the sequential administration of biomarker tests. Data provided to create this Markov Chain model were collected by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The data lacked detailed information of the sequential administration of the biomarker tests and therefore, different analytical approaches were tried and conducted in order to calibrate the model. The resulting Markov Chain model provided the capability to conduct experiments regarding different parameters of the Markov Chain and yielded different results of patients that contracted AD and those that did not, leading to important insights into effect of thresholds and sequence on patient prediction capability as well as health costs reduction.
The data in this thesis was provided from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). ADNI investigators did not contribute to any analysis or writing of this thesis. A list of the ADNI investigators can be found at: http://adni.loni.usc.edu/about/governance/principal-investigators/ .
ContributorsCamarena, Raquel (Author) / Pedrielli, Giulia (Thesis advisor) / Li, Jing (Thesis advisor) / Wu, Teresa (Committee member) / Arizona State University (Publisher)
Created2018
Description
With the increased demand for genetically modified T-cells in treating hematological malignancies, the need for an optimized measurement policy within the current good manufacturing practices for better quality control has grown greatly. There are several steps involved in manufacturing gene therapy. These steps are for the autologous-type gene therapy, in chronological order, are harvesting T-cells from the patient, activation of the cells (thawing the cryogenically frozen cells after transport to manufacturing center), viral vector transduction, Chimeric Antigen Receptor (CAR) attachment during T-cell expansion, then infusion into patient. The need for improved measurement heuristics within the transduction and expansion portions of the manufacturing process has reached an all-time high because of the costly nature of manufacturing the product, the high cycle time (approximately 14-28 days from activation to infusion), and the risk for external contamination during manufacturing that negatively impacts patients post infusion (such as illness and death).
The main objective of this work is to investigate and improve measurement policies on the basis of quality control in the transduction/expansion bio-manufacturing processes. More specifically, this study addresses the issue of measuring yield within the transduction/expansion phases of gene therapy. To do so, it was decided to model the process as a Markov Decision Process where the decisions being made are optimally chosen to create an overall optimal measurement policy; for a set of predefined parameters.
The main objective of this work is to investigate and improve measurement policies on the basis of quality control in the transduction/expansion bio-manufacturing processes. More specifically, this study addresses the issue of measuring yield within the transduction/expansion phases of gene therapy. To do so, it was decided to model the process as a Markov Decision Process where the decisions being made are optimally chosen to create an overall optimal measurement policy; for a set of predefined parameters.
ContributorsStarkey, Michaela (Author) / Pedrielli, Giulia (Thesis advisor) / Li, Jing (Committee member) / Wu, Teresa (Committee member) / Arizona State University (Publisher)
Created2020