This is a study of drug delivery problems from hydrogels and it is mainly focused on the effects of the hydrogel's geometry on the behaviour of the release profile. Studying drug delivery also offers one the opportunity to delve into the physical mechanisms involved in the release process to better understand its theoretical implications. We can apply the well-developed theory of diffusion in order to understand many aspects of drug delivery. Thus, this thesis starts with a presentation of concepts and theories used in the following two articles (chapters). We go over the basic concept of drug delivery, followed by an introduction on diffusion. We then explain the ideas governing drug release and how we have modeled it. The tools used to generate our drug release platforms are presented followed by a discussion on characterizing the resulting drug release profiles. This thesis is presented as a series of two articles that have been submitted to peer-reviewed scientific journals. The first article presents a novel combinatorial technique used to obtain controlled drug delivery profiles. We use an exact enumeration diffusion model in order to obtain our drug release profiles and test its validity by comparing these results with analytical theory and widely used empirical tools. By using a genetic algorithm, we then show that it is possible to tailor the drug delivery platform in order to get a specific functional form of the release profile. The second article consists in testing two widely used empirical functions that are used in the literature to characterize drug release profiles. Several claims have been made regarding the interpretation of these functions and we have used our exact enumeration data to argue that although the functions fit the data relatively well on certain time scales, they do not necessarily convey reliable information about the mechanism of release. Finally, we conclude with preliminary work that was done on a second optimization technique to be used in controlling drug delivery profiles. The Metropolis simulated annealing was used to further optimize the design of the drug release platform and was shown to be quite effective, albeit being computationally demanding.

<p> The application of machine learning algorithms to analyze and determine disease related patterns in neuroimaging has emerged to be of extreme interest in Computer-Aided Diagnosis (CAD). This study is a small step towards categorizing Alzheimer's disease, Neurode-generative diseases, Psychiatric diseases and Cerebrovascular Small Vessel diseases using CAD. In this study, the SPECT neuroimages are pre-processed using powerful data reduction techniques such as Singular Value Decomposition (SVD), Independent Component Analysis (ICA) and Automated Anatomical Labeling (AAL). Each of the pre-processing methods is used in three machine learning algorithms namely: Artificial Neural Networks (ANNs), Support Vector Machines (SVMs) and k-Nearest Neighbors (k-nn) to recognize disease patterns and classify the diseases. While neurodegenerative diseases and psychiatric diseases overlap with a mix of diseases and resulted in fairly moderate classification, the classification between Alzheimer's disease and Cerebrovascular Small Vessel diseases yielded good results with an accuracy of up to 73.7%.</p><p>

The highly polymorphic DlS80 locus has no known genetic function. This variable number of tandem repeat (VNTR) has been valuable in forensic identification. We have obtained allelic and genotypic frequencies for five African populations (Benin, Cameroon, Egypt, Kenya and Rwanda), which could be employed as databases to identify individuals. The polymerase chain reaction, followed by vertical polyacrylamide gel electrophoresis and silver staining was our method of analysis. Allele frequencies were used to infer genetic associations using Phylip 3.5, Principal Component and G-test statistical programs. Tests for Hardy-Weinberg equilibrium were employed. Fst estimates and power of discrimination values were also determined for each of our populations. Our analyses of 28 additional populations demonstrated that the D1 S80 locus alone provided for the discrimination of major racial groups. Genetic homogeneity between the African groups was observed. We have generated a database useful for human differentiation and phylogenetic studies.

Mammalian C3 is a complement protein which consists of an α chain (125kDa) and β chain (75kDa) held together by a disulfide bond. The a chain contains a conserved thiolester site which provides the molecule with opsonic properties. The protein is synthesized as a single pro-C3 molecule which is post-translationally modified. C3 genes have been identified in organisms from different phyla, however, the shark C3 gene remains to be cloned. Sequence data from the shark will contribute to understanding further the evolution of this key protein. To obtain additional sequence data for shark C3 genes a cDNA library was constructed and screened with a DIG-labeled C3 probe. Fifty clones were isolated and sequenced. Analysis identified four sequences that yielded positive alignments with C3 of a variety of organisms including human C3. Deduced amino acid sequence analysis confirmed a β/α cut site (RRRR), the CR3 and properdin binding sites, the catalytic histidine, and the reactive thiolester sequence. In the shark there are at least two C3-like genes as the gene sequence obtained is distinct from that previously described.

The human ovarian carcinoma cell line, A2780s, and its variant, A2780cp, provide an isogenic tumour model for examining factors which determine intrinsic radiosensitivity. A2780s demonstrates sensitivity to ionization radiation while A2780cp is relatively radioresistant (surviving fraction following a 2 Gy dose is 0.083 and 0.43, respectively). The increased radioresistance of A2780cp can not be explained by greater cellular recovery, neither from sublethal nor potentially lethal damage. Moreover, A2780s demonstrates significantly greater (P &lt; 0.05) sublethal and potentially lethal damage recovery than A2780cp. The induction of double strand breaks (dsb), as measured by asymmetric field inversion gel electrophoresis (AFIGE), is identical in these cell lines. Dsb rejoining efficiency is similar between A2780s and A2780cp. Initially, rejoining kinetic experiments reveal that A2780s is deficient in the slow phase of rejoining, while A2780cp is not (80% of dsb remain for A2780s vs 29% A2780cp) (P &lt; 0.01). This deficiency however, is not reproduced in residual dsb experiments and further analysis reveals that it may be an artifact of the normalization process. When the level of residual dsb as a function of dose is examined, the slopes are similar for both cell lines and the only significant difference is seen for the highest dose used, 150 Gy (50% for A2780s and 33% for A2780cp) (P &lt; 0.05). Finally, the cell-free fidelity assay demonstrates that for blunt-cut plasmid, no differences exist in the rejoining efficiency of nuclear extracts. The ligation infidelity of blunt-cut plasmid however, is significantly less (P &lt; 0.05) in A2780cp extracts (0.021 for A2780s vs 0.0030 for A2780cp). Therefore, neither the induction of dsb, nor the efficiency of dsb repair can explain observed differences in radiosensitivity. The fidelity of rejoining however, is significantly greater in the resistant variant and may, in part, explain these differences.

Damage to the immune system of exposed individuals renders the host susceptible to opportunistic infection and disease. The purpose of this investigation was to contribute to the understanding of mechanisms underlying depression of host immune responses following radiation exposure. Peripheral blood mononuclear cells (PBMC) of mice irradiated with 0-700 rad $\gamma$-whole body irradiation (WBI) were analyzed by flow cytometry (FCA). Natural killer (NK) cells and CD4+ T lymphocytes were selectively enhanced following radiation exposure, demonstrating radioresistance of these cell types over other PBMC, while B lymphocytes were dramatically radiosensitive. Dextran sulfate mobilization of mononuclear cells (MNC) from lymphoid tissues into the blood revealed that the same pattern of MNC loss had occurred throughout the lymphoid tissues. PBMC alterations reflected similar changes occurring in previous studies of splenic mononuclear cells $\{$1$\}$, and may promote immune dysregulation. The role of apoptosis in radiation-induced injury to the immune system in the low to intermediate dose range (0 to 400 rad) was investigated in PBMC. 25 rad induced apoptosis in PBMC above the unirradiated control within 2 hours post-irradiation; apoptosis induction increased with higher doses (100-400 rad). Additionally, the impact of ionizing radiation on NK cell function was assessed. 24 hours following radiation exposure, NK cytotoxicity against YAC-1 target cells was depressed by doses of 25 or 50 rad, with little change in the 100 to 400 rad range. By day 7, NK cytolytic potential was reduced or unaffected by doses lower than 200 rad, while a single exposure of 400 rad enhanced cytotoxicity. The results of this investigation have furthered our understanding of factors which may be important in the impairment of immune responses post-irradiation.

[No abstract available] / Education, Faculty of / Graduate

The design of a two-dimensional polarcardiograph and the use of two such two-dimensional devices to calculate the third polar coordinate together with the circuitry necessary to derive and amplify a set of voltages proportional to the Cartesian coordinates x, y, and z is described. Although the technique used for obtaining the polar coordinates is similar to that used in other instruments, the circuitry is somewhat different. This is dictated in part by the fact that this device is completely transistorized. Both the Frank and RAFE networks are available for the transformation from patient signals to a set of signals proportional to the Cartesian coordinates x, y, and z. Restoration of the base-line at the optimum time during the cardiac cycle is achieved through a system of gated feedback which is activated by a predictor circuit. The predictor is triggered by an automatic trigger selector. A threshold circuit is associated with each angle output in order to set the output to some predetermined value when the input signal level is so small as to make the angle output indeterminate. / Applied Science, Faculty of / Electrical and Computer Engineering, Department of / Graduate

Rational planning for the delivery of health care services is the primary concern of this thesis. Various aspects of the demand for, and the supply and characteristics of these services are discussed, since an understanding of these topics is essential to rational planning. Chapter I examines the relative importance of the influences of health care services, socio-economic structures and life styles on individual and societal health status. Various criteria for the evaluation of health care services and for the allocation of societal resources between health care services and other social services influencing health and well-being are discussed. Chapter II deals with consumer behaviour and the demand for medical services. This discussion entails Individual perception of medical needs, factors influencing health knowledge, sources and effectiveness of health information dissemination, and various factors which inhibit utilization. Chapter III is concerned with the supply of health care services, their financing and interrelationships. In particular, the role, characteristics, and costs of physician and hospital services are examined. Chapter IV discusses the resolution of supply and demand with an emphasis on financial considerations and the organizational arrangements between the various components of supply. Chapter V reviews and discusses some of the major problems of various techniques which have been employed to forecast future health care service requirements. Various aspects of future modes of health care delivery are discussed. Chapter VI presents a simulation model which may be used as an aid in regional planning of health care services. Chapter VII illustrates several results for various simulated conditions and strategies. Chapter VIII suggests future improvements to the simulation model and describes several possible experiments which are being planned. / Business, Sauder School of / Graduate

This thesis is concerned with a cognitive-behavioural approach toward location theory. Specifically it deals with the 'site characteristics' of medical practice sites and their relationships to the 'Degree of Specialism' and 'Need Constructs' of the physicians operant from the sites. The 'Need Construct' of physicians is seen to vary between actors as a result of the different temporal and functional practice characteristics found within the Medical Community. The practice site location decisions of specialist physicians are seen to be dependent on the actor's 'internal needs' for complex functional linkages with other specialist physicians and with medical facilities such as hospitals and diagnostic radiology and laboratory sites. Primary care physicians in contrast are seen as making practice site location decisions in response to the 'external needs' of their patients and hence, adopt sites minimizing inconvenience to this group. Physicians are thus seen, through function and functioning as adopting sites possessing those characteristics that will satisfy their dominant set of needs. Hence, physicians with a high 'Degree of Specialism' adopt sites with a high degree of linkage with other physicians and ancilliary medical facilities, whereas physicians with a low 'Degree of Specialism' adopt sites to minimize inconvenience to their patients. In order to test the hypotheses derived from the above conceptual structure, an interview survey was conducted in Vancouver, British Columbia, Canada. Instruments were developed and pre-tested using standard psychometric techniques to measure the 'Degree of Specialism' and the 'Need Construct' of a physician actor. The 'site characteristics' of a medical practice site were measured on nine variables falling into two groups. Group one comprised those variables measuring the relative-locational aspects of a practice site to other physician practice sites, diagnostic facilities, hospitals, etc., whereas group two comprised variables measuring intrinsic qualities of the site such as the number of physicians practicing from the site. A random sample of twenty primary care physicians and twenty specialist physicians were interviewed to provide the data for the study. A hypothesis testing and correlation analysis was performed on the data to test the study hypotheses. These analyses confirmed that statistically significant relationships existed between the 'Degree of Specialism' and the 'Need Construct' of an actor, between the 'Need Construct' and the 'Practice Site Characteristics' of an actor and between the 'Degree of Specialism' and the 'practice Site Characteristics' of an actor. It was also shown that there existed statistically significant differences between the 'site characteristics' of Specialist and Primary Care physicians. This was also the case for the "Need Constructs' of the two groups. On the basis of the analyses conducted it was concluded that the conceptual structure of the study provided useful insights into the processes of physician site adoption. Recommendations for further research suggest that two fruitful areas of study would be to investigate, over time, changes in the spatial pattern of the medical community relating this to changes in the functional structure of the profession and to investigate explicitly the relationships between the 'Degree of Specialism', 'Need Constructs', and, 'Time Budgets' of physician actors. / Arts, Faculty of / Geography, Department of / Graduate