Matching Items (3)
Filtering by

Clear all filters

151857-Thumbnail Image.png
Description
Controlled release formulations for local, in vivo drug delivery are of growing interest to device manufacturers, research scientists, and clinicians; however, most research characterizing controlled release formulations occurs in vitro because the spatial and temporal distribution of drug delivery is difficult to measure in vivo. In this work, in vivo

Controlled release formulations for local, in vivo drug delivery are of growing interest to device manufacturers, research scientists, and clinicians; however, most research characterizing controlled release formulations occurs in vitro because the spatial and temporal distribution of drug delivery is difficult to measure in vivo. In this work, in vivo magnetic resonance imaging (MRI) of local drug delivery is performed to visualize and quantify the time resolved distribution of MRI contrast agents. I find it is possible to visualize contrast agent distributions in near real time from local delivery vehicles using MRI. Three dimensional T1 maps are processed to produce in vivo concentration maps of contrast agent for individual animal models. The method for obtaining concentration maps is analyzed to estimate errors introduced at various steps in the process. The method is used to evaluate different controlled release vehicles, vehicle placement, and type of surgical wound in rabbits as a model for antimicrobial delivery to orthopaedic infection sites. I are able to see differences between all these factors; however, all images show that contrast agent remains fairly local to the wound site and do not distribute to tissues far from the implant in therapeutic concentrations. I also produce a mathematical model that investigates important mechanisms in the transport of antimicrobials in a wound environment. It is determined from both the images and the mathematical model that antimicrobial distribution in an orthopaedic wounds is dependent on both diffusive and convective mechanisms. Furthermore, I began development of MRI visible therapeutic agents to examine active drug distributions. I hypothesize that this work can be developed into a non-invasive, patient specific, clinical tool to evaluate the success of interventional procedures using local drug delivery vehicles.
ContributorsGiers, Morgan (Author) / Caplan, Michael R (Thesis advisor) / Massia, Stephen P (Committee member) / Frakes, David (Committee member) / McLaren, Alex C. (Committee member) / Vernon, Brent L (Committee member) / Arizona State University (Publisher)
Created2013
155092-Thumbnail Image.png
Description
In recent decades, marine ecologists have conducted extensive field work and experiments to understand the interactions between bacteria and bacteriophage (phage) in marine environments. This dissertation provides a detailed rigorous framework for gaining deeper insight into these interactions. Specific features of the dissertation include the design of a new deterministic

In recent decades, marine ecologists have conducted extensive field work and experiments to understand the interactions between bacteria and bacteriophage (phage) in marine environments. This dissertation provides a detailed rigorous framework for gaining deeper insight into these interactions. Specific features of the dissertation include the design of a new deterministic Lotka-Volterra model with n + 1 bacteria, n
+ 1 phage, with explicit nutrient, where the jth phage strain infects the first j bacterial strains, a perfectly nested infection network (NIN). This system is subject to trade-off conditions on the life-history traits of both bacteria and phage given in an earlier study Jover et al. (2013). Sufficient conditions are provided to show that a bacteria-phage community of arbitrary size with NIN can arise through the succession of permanent subcommunities, by the successive addition of one new population. Using uniform persistence theory, this entire community is shown to be permanent (uniformly persistent), meaning that all populations ultimately survive.

It is shown that a modified version of the original NIN Lotka-Volterra model with implicit nutrient considered by Jover et al. (2013) is permanent. A new one-to-one infection network (OIN) is also considered where each bacterium is infected by only one phage, and that phage infects only that bacterium. This model does not use the trade-offs on phage infection range, and bacterium resistance to phage. The OIN model is shown to be permanent, and using Lyapunov function theory, coupled with LaSalle’s Invariance Principle, the unique coexistence equilibrium associated with the NIN is globally asymptotically stable provided that the inter- and intra-specific bacterial competition coefficients are equal across all bacteria.

Finally, the OIN model is extended to a “Kill the Winner” (KtW) Lotka-Volterra model

of marine communities consisting of bacteria, phage, and zooplankton. The zooplankton

acts as a super bacteriophage, which infects all bacteria. This model is shown to be permanent.
ContributorsKorytowski, Daniel (Author) / Smith, Hal (Thesis advisor) / Gumel, Abba (Committee member) / Kuang, Yang (Committee member) / Gardner, Carl (Committee member) / Thieme, Horst (Committee member) / Arizona State University (Publisher)
Created2016
155408-Thumbnail Image.png
Description
Using a simple $SI$ infection model, I uncover the

overall dynamics of the system and how they depend on the incidence

function. I consider both an epidemic and endemic perspective of the

model, but in both cases, three classes of incidence

functions are identified.

In the epidemic form,

power incidences, where the infective portion $I^p$

Using a simple $SI$ infection model, I uncover the

overall dynamics of the system and how they depend on the incidence

function. I consider both an epidemic and endemic perspective of the

model, but in both cases, three classes of incidence

functions are identified.

In the epidemic form,

power incidences, where the infective portion $I^p$ has $p\in(0,1)$,

cause unconditional host extinction,

homogeneous incidences have host extinction for certain parameter constellations and

host survival for others, and upper density-dependent incidences

never cause host extinction. The case of non-extinction in upper

density-dependent

incidences extends to the case where a latent period is included.

Using data from experiments with rhanavirus and salamanders,

maximum likelihood estimates are applied to the data.

With these estimates,

I generate the corrected Akaike information criteria, which

reward a low likelihood and punish the use of more parameters.

This generates the Akaike weight, which is used to fit

parameters to the data, and determine which incidence functions

fit the data the best.

From an endemic perspective, I observe

that power incidences cause initial condition dependent host extinction for

some parameter constellations and global stability for others,

homogeneous incidences have host extinction for certain parameter constellations and

host survival for others, and upper density-dependent incidences

never cause host extinction.

The dynamics when the incidence function is homogeneous are deeply explored.

I expand the endemic considerations in the homogeneous case

by adding a predator into the model.

Using persistence theory, I show the conditions for the persistence of each of the

predator, prey, and parasite species. Potential dynamics of the system include parasite mediated

persistence of the predator, survival of the ecosystem at high initial predator levels and

ecosystem collapse at low initial predator levels, persistence of all three species, and much more.
ContributorsFarrell, Alexander E. (Author) / Thieme, Horst R (Thesis advisor) / Smith, Hal (Committee member) / Kuang, Yang (Committee member) / Tang, Wenbo (Committee member) / Collins, James (Committee member) / Arizona State University (Publisher)
Created2017