Matching Items (153)
Description
Background:
Data assimilation refers to methods for updating the state vector (initial condition) of a complex spatiotemporal model (such as a numerical weather model) by combining new observations with one or more prior forecasts. We consider the potential feasibility of this approach for making short-term (60-day) forecasts of the growth and spread of a malignant brain cancer (glioblastoma multiforme) in individual patient cases, where the observations are synthetic magnetic resonance images of a hypothetical tumor.
Results:
We apply a modern state estimation algorithm (the Local Ensemble Transform Kalman Filter), previously developed for numerical weather prediction, to two different mathematical models of glioblastoma, taking into account likely errors in model parameters and measurement uncertainties in magnetic resonance imaging. The filter can accurately shadow the growth of a representative synthetic tumor for 360 days (six 60-day forecast/update cycles) in the presence of a moderate degree of systematic model error and measurement noise.
Conclusions:
The mathematical methodology described here may prove useful for other modeling efforts in biology and oncology. An accurate forecast system for glioblastoma may prove useful in clinical settings for treatment planning and patient counseling.
ContributorsKostelich, Eric (Author) / Kuang, Yang (Author) / McDaniel, Joshua (Author) / Moore, Nina Z. (Author) / Martirosyan, Nikolay L. (Author) / Preul, Mark C. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2011-12-21
Description
Glioblastoma multiforme (GBMs) is the most prevalent brain tumor type and causes approximately 40% of all non-metastic primary tumors in adult patients [1]. GBMs are malignant, grade-4 brain tumors, the most aggressive classication as established by the World Health Organization and are marked by their low survival rate; the median survival time is only twelve months from initial diagnosis: Patients who live more than three years are considered long-term survivors [2]. GBMs are highly invasive and their diffusive growth pattern makes it impossible to remove the tumors by surgery alone [3]. The purpose of this paper is to use individual patient data to parameterize a model of GBMs that allows for data on tumor growth and development to be captured on a clinically relevant time scale. Such an endeavor is the rst step to a clinically applicable predictions of GBMs. Previous research has yielded models that adequately represent the development of GBMs, but they have not attempted to follow specic patient cases through the entire tumor process. Using the model utilized by Kostelich et al. [4], I will attempt to redress this deciency. In doing so, I will improve upon a family of models that can be used to approximate the time of development and/or structure evolution in GBMs. The eventual goal is to incorporate Magnetic Resonance Imaging (MRI) data into a parameterized model of GBMs in such a way that it can be used clinically to predict tumor growth and behavior. Furthermore, I hope to come to a denitive conclusion as to the accuracy of the Koteslich et al. model throughout the development of GBMs tumors.
ContributorsManning, Miles (Author) / Kostelich, Eric (Thesis director) / Kuang, Yang (Committee member) / Preul, Mark (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12
Description
Major Depressive Disorder (MDD) is a common mental disorder that can affect individuals at nearly every stage of life. Women are especially vulnerable to MDD in part, from ovarian hormone level fluctuations. In this thesis, I focused on MDD using a rat model in middle-age to explore potential sex differences in response to a corticosterone (CORT) – induced depressive-like state. Estradiol (E2), a naturally occurring steroid sex hormone in humans and rats, is implicated in mood changes, which is especially prominent during the menopause transition. CORT, a stress hormone, was used to create a depressive-like state in middle-aged female (F) and male (M) rats with their gonads surgically removed. This produced the following independent treatment groups: Sex (F, M), CORT (vehicle = V ml/kg, C 40mg/kg), E2 (V 0.1 ml, E 0.3µg/0.1ml). CORT and E2 injections were injected daily, s.c) for 7 days before behavioral testing began and continued throughout the study when behavior was assessed. For my honor’s thesis, I focused on the social interaction test and elevated plus maze to investigate whether CORT enhanced social avoidance and anxiety, and whether E2 mitigated the CORT effects. In the social interaction test, three new behaviors were assessed (interacting, grooming, and immobility) to better understand exploratory and anxiety profiles of the rats, and these behaviors were quantified over two 5-minute periods in the 10-minute trial. These new quantifications showed that for the female rats, C+E and V+V enhanced the interaction with the novel rat significantly more than an inanimate object, which was not observed in the females given CORT only or E2 only. The males in all conditions showed a significant preference for side with the novel rat compared to the object, however no treatment differences were observed. In both sexes, the overall time spent interacting decreased in the second five minutes of quantification compared to the first five minutes. No effects were observed with grooming or immobility, in part from the high variability across rats. For EPM, female rats treated with CORT and E2 exhibited a lower anxiety index than compared to female rats given CORT only, indicating that E2 mitigated the depressive-like effects of CORT. Males showed no CORT or E2 effects. The result in part supported my hypothesis, as the CORT-treated females exhibited reduced socialization and E2 improved socialization in CORT-treated females, as this was seen in the F-C-E group. Interestingly, CORT failed to produce a depressive-like effect in males in both behavioral tests, which was an unexpected outcome. These results suggest that administration of E2 with CORT mitigated the depressive-like state created by CORT in female rats, however failed to produce these outcomes in males. The outcome of this work will give us insight into the potential mechanisms that may contribute to sex differences with MDD.
ContributorsSladkova, Sara (Author) / Conrad, Cheryl (Thesis director) / Amdam, Gro (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of Life Sciences (Contributor)
Created2024-05