<p><strong>Background </strong>The possibility of ageing independently during the past 2 decades assumed a meaning which comprises different aspects. It has been recognized, in studies involving older adults but also by important Health Organizations (such as WHO), that disability could originate from different causes: physical limitations, external causes (such as personal assistance or building barriers), individual causes (lifestyle, behavior, positive attitude) and societal factors. Measuring the level of disability in a comprehensive way could help predict the amount of help and the best resources needed for older adults to cope with disability and remain independent as much as possible. The SAGE scale has been developed to be a complete and easy to use tool to measure independence in older adults.<strong></strong></p> <p><strong>Objectives </strong>The aim of this thesis is to describe the methodology and the design of a study and to assess the validity and reliability of the SAGE scale.<strong></strong></p> <p><strong>Design </strong>SAGE validation will be measured in a cross sectional study, involving 240 older adults conveniently sampled from 3 different facilities in the Hamilton area. Community dwelling older adults, patients recovering from a stroke and subjects living in a nursing home, will be assessed at one point in time with the new tool (the SAGE scale) together with four widely used scales to assess cognitive abilities (Montreal Cognitive Assessment), functional abilities (The Franchay Activity Index), the modified-Rankin scale and the CSHA Clinical Frailty Scale. This thesis will describe the processes through which assess the content, construct and criterion validity. The hierarchical sequence of items will also be investigated as well as specificity and sensitivity of the new tool. <strong></strong></p> <p><strong>Conclusion </strong>The development of the SAGE was motivated by the recent need for an instrument able to capture all the activities that are important for the elderly to be able to age with dignity and independence. The results of this study, if positive, will be useful for further investigation of the SAGE, as a screening tool to recognize and detect early loss of independence in this group of individuals.<strong></strong></p> / Master of Science (MSc)

<p>Multi-faceted interventions that include some form of a clinical information system have been shown to improve primary care physicians' management of chronic diseases. The objective of this pilot study was to assess the feasibility of a cluster randomized controlled trial of a multi-faceted intervention, which includes a clinical information system, to improve the management of the chronic disease of tobacco use by physicians. Feasibility was assessed with respect to the use of a measurement tool (Smoking Status Identification Card) and use of a new smoking cessation management module in the clinical information system.</p> <p>Letters of invitation were sent out to the 65 primary care physicians (in 38 primary care practices) who were subscribed to the web-based clinical information system (P-PROMPT CDMS). Five physicians from 5 primary care practices agree.d to participate, who were stratified and then randomized to the intervention (2 primary care practices) or control group (3 primary care practices).</p> <p>Following the 12-week study period, SSIC completion reached the 90% threshold success criterion in 2 of the 5 primary care practices (one each from the intervention and control group). The intervention group demonstrated basic use of the new smoking cessation management module that reached 21.9% and 19.0% in each of the respective practices, which was below the 30% threshold success criterion. A preliminary evaluation of physician delivery of smoking cessation counselling demonstrated a trend to a higher percentage of Ministry of Health and Long-Term Care (MOHLTC) physician service billing codes submitted among the physicians in the intervention group, which may be indicative of greater smoking cessation counselling.</p> <p>It is concluded that a randomized controlled trial to test a multi-faceted intervention is not feasible with the current study design. Significant modifications to the current study design are required that can potentially be tested prior to progression to a larger trial.</p> / Master of Science (MS)

<p>The purpose of this investigation was 1) to establish an optimal technique for isolating osteoprogenitor cells in vitro using human femoral cancellous bone as a donor site, and 2) to evaluate the effects of various factors on differentiation of osteoprogenitor cultures. Two isolation techniques evaluated were enzyme digestion and primary explant technique. Furthermore, bone morphogenetic protein 2 (BMP-2) and doxycycline were supplemented in a dose dependent manner into various osteoprogenitor cell containing culture dishes. To compare isolation techniques and the effect of supplemented factors, we isolated cell populations from cancellous bone of the femoral neck from 7 and 6 patients, respectively, with osteoarthritis undergoing total hip replacement surgery. Bone derived osteoblasts and their bone nodules were identified using Von Kossa stain. The cell yield of the two isolation techniques was quantified by hemocytometer counts. The ability of the cells to differentiate into bone forming osteoblasts was evaluated by comparing numbers of Von Kossa positive nodule counts. Using alkaline phosphatase (ALP) staining, ALP quantitative assay and osteocalcin polymerase chain reaction, our study is the first attempt to determine the effects of doxycycline, along with the more commonly used BMP-2, on the differentiation of osteoblasts into bone forming colonies.</p> / Master of Science (MS)

<p>Human atherosclerosis is a disease of the blood vessel wall caused by an interplay between inflammatory, thrombotic, and lipid factors. A contributing or causal role for infection in that inflammatory response was first proposed in the 19th century, and with the advent of more sophisticated diagnostic techniques, a new search for a microbiologic etiology of human atherosclerosis has been rekindled. In this thesis, I examine methods for investigating whether infections contribute to human atherosclerotic cardiovascular disease. I explore three different technologies: serology (measuring antibody), inflammatory markers (as risk markers and as surrogates for infections), and the direct measurement of bacterial or viral DNA in the bloodstream. I examine three different study designs: cross-sectional, case-control, and cohort. Chlamydia pneumoniae , an obligate intracellular bacterium, is the primary focus of these studies. In addition, cytomegalovirus and other infections are included as controls, with the a priori expectation that these other infections would not be related to cardiovascular disease. We found a relationship between cardiovascular disease and C. pneumoniae antibody status in a small case-control study, but found no independent association in a large, prospective study. Inflammatory markers were measured in the prospective study, and were associated with cardiovascular events, yet no clear association between inflammation and infection was found. However, in developing methods for directly detecting bacterial and viral DNA in the bloodstream, we found that serology itself was not associated with current detection of bacterial DNA. Furthermore, we found a strong relationship between C. pneumoniae and smoking, and conclude that future studies need to examine the interaction between infection, inflammation, and smoking status.</p> / Doctor of Philosophy (PhD)

<p>Overexpression and amplification of the neu proto-oncogene have been implicated in the development of aggressive human breast cancer. To investigate the effect of mammary gland-specific expression of the neu protooncogene, transgenic mice carrying the unactivated neu gene under the transcriptional control of the mouse mammary tumor virus (MMTV) promoter/enhancer were established. Overexpression of neu in the mammary tumors was associated with elevated Neu intrinsic tyrosine kinase activity and the stochastic development of focal mammary tumors which frequently metastasized. These observations provide the first direct evidence that expression of the proto-oncogenic form of neu results in a heritable development of metastatic mammary tumors.</p> <p>Another potent tyrosine kinase activity that has been implicated in the genesis of murine mammary tumors is that associated with polyomavirus middle T antigen (PyV MTAg). Expression of MMTV/PyV middle T antigen in the mammary glands of transgenic mice resulted in the induction of multifocal mammary tumors which frequently metastasized to the lung. The potent transforming activity of PyV MTAg can, in part, be attributed to its ability to associate with an activate a number of e-Src family tyrosine kinases (e-Src, e-Yes, and Fyn). In order to assess the role of individual members of the e-Src family of tyrosine kinases in PyV MTAg induced mammary tumorigenesis, I have crossed the MMTV/PyV middle T fusion gene with mice bearing disrupted c-src or e-yes alleles. Mice expressing the PyV middle T transgene in the absence of functional c-Src rarely developed metastatic mammary tumors. However, transgenic mice expressing the PyV MTAg in mammary epithelium lacking functional c-Yes developed multifocal mammary tumors with kinetics comparable to MMTV/PyV middle T strains possessing a functional c-Yes. These findings suggest that c-Src tyrosine kinase activity is required for PyV MTAg induced mammary tumorigenesis and also illustrate a in vivo genetic approach to dissect mitogenic signal transduction pathways.</p> / Doctor of Philosophy (PhD)

Women's experiences of their perineum following childbirth: expectations, reality and returning to normality The aim of the study was to explore the feelings, perceptions and experiences of women in relation to their perineum following childbirth in the early postnatal period. A grounded theory approach was used for collecting and analysing data from eleven diaries and seven interviews with broad questions about how the perineum, following a vaginal birth, affected the way daily living activities were carried out. Initially purposeful sampling was utilised to recruit women but as important issues emerged recruitment continued through theoretical sampling. Following childbirth women expressed a strong desire to get back to normal reflecting the core theme `striving for normality'. Normality in this context meant doing normal things and feeling like their normal selves. Much of what the women described doing during the early postnatal period was related to achieving that goal and linked to the following categories: `preparing for the unknown', `experiencing the unexpected', `adjusting to reality', `getting back to normal' and `recovery of self'. The main theoretical idea that emerged from this study and derived directly from the data is that: If women are able to successfully adjust to their new and often unexpected reality after the birth of their baby, and begin to reclaim their selves and their world, then they experience a return to their normality. The data demonstrates and clarifies three distinct but related aspects. Firstly, coping with the unexpected consequences of childbirth meant that the women frequently made adjustments to how they carried out essential activities such as walking, sitting and passing urine, in order to try and carry on as normal. The second aspect related to daily activities that were not essential but which women felt necessary to undertake because of social expectations. These included housework and shopping. The third aspect related to how the women felt about their body as a result of the perineal trauma they sustained, and what helped them to feel like their `normal selves' again. These interrelated stages form a framework that reflects Maslow's lower order, hierarchy of needs, within the humanistic psychology paradigm. Implications for practice include the need to improve care in areas of preparing women having their first baby, listening to women as part of the assessment of perineal pain following birth and the need for continuity of care from the same midwife in order for women to appropriately manage their perineal experience.

With the advance of gene expression data in the bioinformatics field, the questions which frequently arise, for both computer and medical scientists, are which genes are significantly involved in discriminating cancer classes and which genes are significant with respect to a specific cancer pathology. Numerous computational analysis models have been developed to identify informative genes from the microarray data, however, the integrity of the reported genes is still uncertain. This is mainly due to the misconception of the objectives of microarray study. Furthermore, the application of various preprocessing techniques in the microarray data has jeopardised the quality of the microarray data. As a result, the integrity of the findings has been compromised by the improper use of techniques and the ill-conceived objectives of the study. This research proposes an innovative hybridised model based on genetic algorithms (GAs) and artificial neural networks (ANNs), to extract the highly differentially expressed genes for a specific cancer pathology. The proposed method can efficiently extract the informative genes from the original data set and this has reduced the gene variability errors incurred by the preprocessing techniques. The novelty of the research comes from two perspectives. Firstly, the research emphasises on extracting informative features from a high dimensional and highly complex data set, rather than to improve classification results. Secondly, the use of ANN to compute the fitness function of GA which is rare in the context of feature extraction. Two benchmark microarray data have been taken to research the prominent genes expressed in the tumour development and the results show that the genes respond to different stages of tumourigenesis (i.e. different fitness precision levels) which may be useful for early malignancy detection. The extraction ability of the proposed model is validated based on the expected results in the synthetic data sets. In addition, two bioassay data have been used to examine the efficiency of the proposed model to extract significant features from the large, imbalanced and multiple data representation bioassay data.

The physicochemical features that affect cell-membrane permeability of bacteria are currently not well understood. Due to the lack of tools to predict penetration of the bacterial envelope, the discovery and development of novel antibiotics is at a standstill. For this reason, the increasing spread of resistant bacteria has become a major threat to public health because these pathogens remain unchallenged. To understand how intrinsic properties, such as porins and efflux pumps, of Gram-negative bacteria influence membrane permeability and consequently, antibiotic uptake, we have developed a systematic approach to evaluate the penetration of various compounds into several strains of Escherichia coli. We study Wild Type, a porin (ompR) knockout, and an efflux pump (tolC) knockout to measure the effects that these physicochemcial properties have on antibacterial uptake. Minimum inhibitory concentrations are calculated for eighteen different compounds when tested against these three strains of E. coli. Next, compound accumulation is assessed through LC-MS/MS analysis and killing kinetics are observed. Through this, a relationship between chemical structure and bacterial membrane permeability can be identified, thus a better understanding of the roles of porins and efflux pumps in the development of antimicrobial resistance is gained.

Nearly three hundred thousand maternal deaths occur worldwide every year. More than 99% of deaths occur in developing countries. The use of skilled birth attendants is low in those countries where maternal mortality rates are high and most of these deaths could be prevented if skilled birth attendant services were available. Only 36 percent of women use skilled birth attendants in Nepal. There are many reasons for non-use of skilled birth attendant services, such as inequalities, lack of access to services, role of gender and culture and lack of women’s autonomy in decision-making. The purpose of this study was to explore the views, experiences and perceptions of women influencing utilisation of skilled birth attendants in rural Nepal. Listening to the women’s voices and views were central to this study in order to understand why women use or does not use skilled birth attendants. Women’s individual characteristics, family, community and organisation factors are interconnected in regards to uptake of skilled birth attendants, as well as policy factors. A case-study approach using mixed methods was taken to explore the women’s experiences and perceptions in a hill district of western Nepal. Interviews were conducted with 24 ‘new mothers’ aged 18-49 years and five mothers-in-law, two husbands and a father-in-law. A survey was conducted of 100 qualified skilled birth attendants (doctors, nurses and midwives) to understand service providers view towards women’s use of skilled birth attendant in two hospitals (one private and one public hospital): 56 SBAs responded. The qualitative data were analysed using a thematic analysis approach and descriptive statistics were derived from the quantitative data. The study found that individual characteristic of women, the location and infrastructure of health facilities, cultural and gender factors, including women’s expectations and preferences about skilled care use, affected uptake of skilled birth attendant services. Socio-cultural and political contexts were found to be interconnected in health service utilisation. Socio-economic inequality based on caste and gender, access to qualitative services and women’s lack of autonomy are some of the factors that influence the uptake of care by skilled birth attendants. This study asserts that capturing women’s experiences and perceptions is essential in order to improve the uptake of skilled birth attendants. Understanding women's views and voices provided a clear picture of what women want and need during pregnancy and childbirth. The empirical evidence derived from this study about the poor standards of care received in hospital and the preference for locally based services could be used along with other evidence to review current policy and inform future plans. Development should be aimed at improving professional standards and access while making maternal health services in Nepal more women-centred.

In the past 5 years, almost 100,000 children have been internationally adopted. Research suggests that many of these children have growth and developmental delays, but few large scale studies have been completed. In the current study data obtained from a restrospective chart review of 534 children followed in the International Adoption Clinic at Cincinnati Children’s Hospital Medical Center between 1999 and 2007 was analyzed. Prevalence of developmental delays and sensory processing issues initially and after 6 months in country, the relationship of delays/issues with previously identified risk factors, and the frequency of recommendations for early intervention (EI) and therapy services were all examined. Results demonstrated the following: 1) Development: most children fell > 1SD below the mean in at least one developmental domain (Vineland Developmental Motor Scales) initially, however improvements in developmental scores were noted between initial and follow up visits. The number of children with a delay in at least one domain dropped from 58% (initial visit) to 44% (follow up). Developmental scores at six months had the strongest correlation with age at time of adoption; children adopted at older ages had lower scores at follow up. 2) Sensory processing: Infant/toddler sensory profile scores for children aged 1-3 were compared at initial and follow up visits. The percentage of children with atypical scores in at least one area of sensory processing decreased from 68% initially to 48% by follow up. Similarly, children > 3 years of age demonstrated improvements in sensory processing; at follow up, only 15% had an atypical total score on the short sensory profile compared to 42% initially. 3) Referral: Referral data was available for 61% of children; of these approximately half received a recommendation for additional services. Most referrals were for EI services (31%); 22% received a referral to speech therapy, and 12% received referrals to PT and OT. Consistent with other work, a significant number of internationally adopted children demonstrate delays in developmental skills and sensory processing abilities. Although improvements in these areas were generally noted, developmental delays and sensory processing issues remained for some children 6 months after adoption. Over half of the children received recommendations for additional services; this number increased for those with more significant delays.