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Dopamine (DA) is a neurotransmitter involved in attention, goal oriented behavior, movement, reward learning, and short term and working memory. For the past four decades, mathematical and computational modeling approaches have been useful in DA research, and although every modeling approach has limitations, a model is an efficient way to

Dopamine (DA) is a neurotransmitter involved in attention, goal oriented behavior, movement, reward learning, and short term and working memory. For the past four decades, mathematical and computational modeling approaches have been useful in DA research, and although every modeling approach has limitations, a model is an efficient way to generate and explore hypotheses. This work develops a model of DA dynamics in a representative, single DA neuron by integrating previous experimental, theoretical and computational research. The model consists of three compartments: the cytosol, the vesicles, and the extracellular space and forms the basis of a new mathematical paradigm for examining the dynamics of DA synthesis, storage, release and reuptake. The model can be driven by action potentials generated by any model of excitable membrane potential or even from experimentally induced depolarization voltage recordings. Here the model is forced by a previously published model of the excitable membrane of a mesencephalic DA neuron in order to study the biochemical processes involved in extracellular DA production. After demonstrating that the model exhibits realistic dynamics resembling those observed experimentally, the model is used to examine the functional changes in presynaptic mechanisms due to application of cocaine. Sensitivity analysis and numerical studies that focus on various possible mechanisms for the inhibition of DAT by cocaine provide insight for the complex interactions involved in DA dynamics. In particular, comparing numerical results for a mixed inhibition mechanism to those for competitive, non-competitive and uncompetitive inhibition mechanisms reveals many behavioral similarities for these different types of inhibition that depend on inhibition parameters and levels of cocaine. Placing experimental results within this context of mixed inhibition provides a possible explanation for the conflicting views of uptake inhibition mechanisms found in experimental neuroscience literature.
ContributorsTello-Bravo, David (Author) / Crook, Sharon M (Thesis advisor) / Greenwood, Priscilla E (Thesis advisor) / Baer, Steven M. (Committee member) / Castaneda, Edward (Committee member) / Castillo-Chavez, Carlos (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Statistical Methods have been widely used in understanding factors for clinical and public health data. Statistical hypotheses are procedures for testing pre-stated hypotheses. The development and properties of these procedures as well as their performance are based upon certain assumptions. Desirable properties of statistical tests are to maintain validity and

Statistical Methods have been widely used in understanding factors for clinical and public health data. Statistical hypotheses are procedures for testing pre-stated hypotheses. The development and properties of these procedures as well as their performance are based upon certain assumptions. Desirable properties of statistical tests are to maintain validity and to perform well even if these assumptions are not met. A statistical test that maintains such desirable properties is called robust. Mathematical models are typically mechanistic framework, used to study dynamic interactions between components (mechanisms) of a system, and how these interactions give rise to the changes in behavior (patterns) of the system as a whole over time.

In this thesis, I have developed a study that uses novel techniques to link robust statistical tests and mathematical modeling methods guided by limited data from developed and developing regions in order to address pressing clinical and epidemiological questions of interest. The procedure in this study consists of three primary steps, namely, data collection, uncertainty quantification in data, and linking dynamic model to collected data.

The first part of the study focuses on designing, collecting, and summarizing empirical data from the only national survey of hospitals ever conducted regarding patient controlled analgesia (PCA) practices among 168 hospitals across 40 states, in order to assess risks before putting patients on PCA. I used statistical relational models and exploratory data analysis to address the question. Risk factors assessed indicate a great concern for the safety of patients from one healthcare institution to other.

In the second part, I quantify uncertainty associated with data obtained from James A Lovell Federal Healthcare Center to primarily study the effect of Benign Prostatic Hypertrophy (BPH) on sleep architecture in patients with Obstructive Sleep Apnea (OSA). Patients with OSA and BPH demonstrated significant difference in their sleep architecture in comparison to patients without BPH. One of the ways to validate these differences in sleep architecture between the two groups may be to carry out a similar study that evaluates the effect of some other chronic disease on sleep architecture in patients with OSA.

Additionally, I also address theoretical statistical questions such as (1) how to estimate the distribution of a variable in order to retest null hypothesis when the sample size is limited, and (2) how changes on assumptions (like monotonicity and nonlinearity) translate into the effect of the independent variable on the outcome variable. To address these questions we use multiple techniques such as Partial Rank Correlation Coefficients (PRCC) based sensitivity analysis, Fractional Polynomials, and statistical relational models.

In the third part, my goal was to identify socio-economic-environment-related risk factors for Visceral Leishmaniasis (VL) and use the identified critical factors to develop a mathematical model to understand VL transmission dynamics when data is highly underreported. I primarily studied the role of age-specific- susceptibility and epidemiological quantities on the dynamics of VL in the Indian state of Bihar. Statistical results provided ideas on the choice of the modeling framework and estimates of model parameters.

In the conclusion, this study addressed three primary theoretical modeling-related questions (1) how to analyze collected data when sample size limited, and how modeling assumptions varies results of data analysis? (2) Is it possible to identify hidden associations and nonlinearity of these associations using such underpowered data and (3) how statistical models provide more reasonable structure to mathematical modeling framework that can be used in turn to understand dynamics of the system.
ContributorsGonzalez, Beverly, 1980- (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Mubayi, Anuj (Thesis advisor) / Nuno, Miriam (Committee member) / Arizona State University (Publisher)
Created2015
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Description
Chronic diseases are the leading causes of death in the United States. Dietary behaviors influence the risk of developing multiple chronic diseases. The U.S. population consumes too few fruits and vegetables and too much sugar sweetened beverages (SSB) and fast food. The Social Ecological Model (SEM) was created as a

Chronic diseases are the leading causes of death in the United States. Dietary behaviors influence the risk of developing multiple chronic diseases. The U.S. population consumes too few fruits and vegetables and too much sugar sweetened beverages (SSB) and fast food. The Social Ecological Model (SEM) was created as a framework for health promotion interventions. The SEM organizes factors that can influence health into five layers: intrapersonal factors, interpersonal processes, institutional/organizational factors, community factors, and public policy. Each layer can influence dietary behaviors and other layers.

This work aims to understand how the community layer, represented by the food environment, moderates the association of two other layers and dietary behaviors: the interpersonal layer, represented by receiving health care provider’s (HCP) advice to lose weight, and the policy layer, represented by participation in the Supplemental Nutrition Assistance Program (SNAP), and a policy change within the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).

Participant data were obtained from a household telephone survey of 2,211 adults in four cities in New Jersey from two cross-sectional panels in 2009-10 and 2014. Community food data were purchased and classified according to previously established protocol. Interaction and stratified analyses determined the differences in the association between HCP advice, SNAP participation, and time (for WIC participants) and eating behaviors by the food environment.

Interaction and stratified analyses revealed that HCP advice was associated with a decrease in SSB consumption when participants lived near a small grocery store, or far from a supermarket, limited service restaurant (LSR), or convenience store. SNAP participation was associated with a higher SSB consumption when respondents lived close to a small grocery store, supermarket, and LSR. There were no differences in fruit and vegetable consumption between two time points among WIC participants, or by food outlet.

The food environment, part of the community layer of SEM, moderated the relationship between the interpersonal layer and dietary behaviors and the policy layer and dietary behaviors. The association between HCP advice and dietary behaviors and SNAP participation and dietary behaviors were both influenced by the food environment in which participants lived.
ContributorsLorts, Cori Elizabeth (Author) / Ohri-Vachaspati, Punam (Thesis advisor) / Adams, Marc (Committee member) / Hooker, Steven (Committee member) / Roberto, Anthony (Committee member) / Tasevska, Natasha (Committee member) / Arizona State University (Publisher)
Created2017
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Description
This dissertation explores the impact of environmental dependent risk on disease dynamics within a Lagrangian modeling perspective; where the identity (defined by place of residency) of individuals is preserved throughout the epidemic process. In Chapter Three, the impact of individuals who refuse to be vaccinated is explored. MMR vaccination and

This dissertation explores the impact of environmental dependent risk on disease dynamics within a Lagrangian modeling perspective; where the identity (defined by place of residency) of individuals is preserved throughout the epidemic process. In Chapter Three, the impact of individuals who refuse to be vaccinated is explored. MMR vaccination and birth rate data from the State of California are used to determine the impact of the anti-vaccine movement on the dynamics of growth of the anti-vaccine sub-population. Dissertation results suggest that under realistic California social dynamics scenarios, it is not possible to revert the influence of anti-vaccine

contagion. In Chapter Four, the dynamics of Zika virus are explored in two highly distinct idealized environments defined by a parameter that models highly distinctive levels of risk, the result of vector and host density and vector control measures. The underlying assumption is that these two communities are intimately connected due to economics with the impact of various patterns of mobility being incorporated via

the use of residency times. In short, a highly heterogeneous community is defined by its risk of acquiring a Zika infection within one of two "spaces," one lacking access to health services or effective vector control policies (lack of resources or ignored due to high levels of crime, or poverty, or both). Low risk regions are defined as those with access to solid health facilities and where vector control measures are implemented routinely. It was found that the better connected these communities are, the existence of communities where mobility between risk regions is not hampered, lower the overall, two patch Zika prevalence. Chapter Five focuses on the dynamics of tuberculosis (TB), a communicable disease, also on an idealized high-low risk set up. The impact of mobility within these two highly distinct TB-risk environments on the dynamics and control of this disease is systematically explored. It is found that collaboration and mobility, under some circumstances, can reduce the overall TB burden.
ContributorsMoreno Martínez, Victor Manuel (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Kang, Yun (Committee member) / Mubayi, Anuj (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Background: Children’s fruit and vegetable consumption in the United States is lower than recommended. School lunch is an opportunity for students to be exposed to fruits and vegetables and potentially increase their daily intake. The purpose of this study is to examine the relationship between tray color and fruit and

Background: Children’s fruit and vegetable consumption in the United States is lower than recommended. School lunch is an opportunity for students to be exposed to fruits and vegetables and potentially increase their daily intake. The purpose of this study is to examine the relationship between tray color and fruit and vegetable selection, consumption, and waste at lunch.

Methods: Study participants (n=1469) were elementary and middle school students who ate school lunch on the day of data collection. Photographs and weights (to nearest 2 g) were taken of fruits and vegetables on students’ trays before and after lunch. Trained research assistants viewed photographs and sorted trays into variable categories: color of main tray, presence/absence of secondary fruit/vegetable container, and color of secondary fruit/vegetable container. Fruit and vegetable selection, consumption, and waste were calculated using tray weights. Negative binomial regression models adjusted for gender, grade level, race/ethnicity, free/reduced price lunch status, and within-school similarities were used to examine relationships between tray color and fruit and vegetable selection, consumption, and waste.

Results: Findings indicated that students with a light tray selected (IRR= 0.44), consumed (IRR=0.73) and wasted (IRR=0.81) less fruit and vegetables. Students without a secondary fruit/vegetable container selected (IRR=0.66) and consumed (IRR=0.49) less fruit and vegetables compared to those with a secondary container. Light or clear secondary fruit and vegetable containers were related to increased selection (IRR=2.06 light, 2.30 clear) and consumption (IRR=1.95 light, 2.78 clear) compared to dark secondary containers, while light secondary containers were related to decreased waste (IRR= 0.57).

Conclusion: Tray color may influence fruit and vegetable selection, consumption, and waste among students eating school lunch. Further research is needed to determine if there is a cause and effect relationship. If so, adjusting container colors may be a practical intervention for schools hoping to increase fruit and vegetable intake among students.
ContributorsWeight, Raquelle (Author) / Bruening, Meg (Thesis advisor) / Adams, Marc (Committee member) / Martinelli, Sarah (Committee member) / Arizona State University (Publisher)
Created2020
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Description
Background: Studies show that rural schools may be less supportive of student fruit/vegetable (FV) consumption, but few studies have investigated the relationship between school locale and FVs. The aim of this research is to analyze the relationship between school locale (rural vs. urban) and students’ FV selection, consumption, and waste

Background: Studies show that rural schools may be less supportive of student fruit/vegetable (FV) consumption, but few studies have investigated the relationship between school locale and FVs. The aim of this research is to analyze the relationship between school locale (rural vs. urban) and students’ FV selection, consumption, and waste in elementary, middle, and high schools. Methods: A cross-sectional analysis of 37 Arizona schools evaluated differences in the selection, consumption, and waste of fresh FVs from students (n=2525; 45.7% female; 41% non-white; mean age=11.6±3.3; 23.5% rural) using objective plate waste measures. Zero-inflated negative binomial regressions examined differences in FV grams selected, consumed, and wasted by urban vs. rural locale, adjusted for sociodemographics and school. Results: The percent of students who selected, consumed, and wasted zero grams of FVs were 14%, 21%, 20%, respectively. Among students with some (non-zero amounts), the average selected, consumed, and wasted FVs were 115.0±81.4g, 51.7.5±65.1g, 65.2±66.7g, respectively. Rural students (versus urban) had lower odds of selecting (OR=0.75), consuming (OR=0.78), and wasting (OR=0.71) any FVs, after adjusting for covariates. However, among students with some FVs on their plates, rural students selected (IRR=1.40), consumed (IRR=1.18) and wasted (IRR=1.62) more grams of FVs. Conclusions: Rural students had reduced odds of selecting and consuming any FVs, but with lower odds of waste, perhaps due to reduced selection. Once some FVs were on the tray, likelihood of consumption and waste by rural students were greater. Results support interventions targeting rural students’ FV intake to reduce waste.
ContributorsJepson, Molly Eilish (Author) / Bruening, Meg (Thesis advisor) / Adams, Marc (Committee member) / Grgich, Traci (Committee member) / Arizona State University (Publisher)
Created2021