The overall aim of this research was to explore why some hospitals are more successful than others at reducing the acquisition rates of multidrug-resistant organisms. Using a socio-ecological perspective on health systems adapted from works in ecological restoration, ecosystems management, and healthcare, a participatory comparative case study design was employed. The study was collaboratively conducted on a surgical unit at a Netherlands hospital with very low rates of multidrug-resistant organisms and a surgical unit in a Canadian hospital with higher rates of these pathogens. The cases were selected on the basis that they were both academic health sciences centres of similar size in publicly funded systems; yet, they reported differing rates of MDRO infections. Research methods included a total of six unit observations, nine practitioner-led photo walkabouts of the units (n=13), six photo elicitation focus groups with practitioners (n=26), and the review of relevant policies and procedures and related infection prevention and control data. Common findings across both cases include the perceived importance of engaged leadership, the presence of environmental design issues, a lack of antibiotic prescribing restrictions, and the frequent use of workarounds that may be problematic for infection prevention and control. Disparate findings between cases include differences in ratios of hospital beds per capita, bed occupancy rates, staffing practices, equipment cleaning processes, bed cleaning systems (centralized versus manual) and the presence, in one hospital, of an active grass roots Hygiene in Practice group engaging practitioners in several ongoing activities to promote infection prevention and control. There is a lack of comparable findings between the two cases on hand hygiene audit protocols, surveillance strategies, reporting of acquisition rates, and the nature and extent of high risk populations for community-acquired methicillin-resistant Staphylococcus aureus in the two hospitals catchment areas. The findings and methodological challenges identified in this study suggest that case selection in future comparative infection prevention and control case studies should be based on an expanded list of criteria. These criteria should include comparable audits, surveillance, and reporting practices and comparable demographic and other relevant data, such as data on the agricultural practices within and demographic attributes of vulnerable populations within the hospital catchment areas.

This study is one of the only investigations to examine the complex inter-relationships between immune status, cognitive functioning, and disease progression in school-aged, perinatally infected, HIV+ children on HAART over time and is the first to conduct long-term follow-up assessments beyond one year after initiating HAART. Previous research has shown that HIV+ children on HAART show stability in cognitive functioning for up to one year. The current study investigated cognitive functioning, as measured by the Wechsler Intelligence Scale for Children -III, as a function of immune functioning and disease progression over time in this sample. Overall, results showed that PIQ scores remained stable over the three time points. However, further analyses demonstrated that poorer immune status, as measured by CD4% <25, at the first time point significantly predicted lower Performance IQ (PIQ)scores and PIQ subtest scores at the third time point, even after controlling for covariates. Similarly, additional analyses revealed that PIQ scores significantly declined over time as a function of CD4% category at the first time point. Finally, scores on the PIQ, Verbal IQ (VIQ), Coding, Picture Arrangement, Symbol Search, and Arithmetic at the first time point were all significant predictors of more advanced disease progression, as measured by CDC C classification at follow-up. The clinical relevance of this study and recommendations for future research in this area are discussed

Discula destructiva, the causal agent of dogwood anthracnose, has caused severe mortality in dogwood over the last 30 years. Although considerable research has been done with dogwood anthracnose, the infection process by D. destructiva is still obscure. A resistant cultivar of Cornus florida, ‘Appalachian Spring’, was discovered and released by the Tennessee Agricultural Experiment Station. However, the resistance mechanisms are unknown. The objectives of this research were 1) to determine the sequence of events in the infection process of D. destructiva in C. florida and 2) to determine how host resistance affects infection events of D. destructiva on flowering dogwood. At 3 days after inoculation (DAI), majority of conidia germinated and hyphae were observed on the leaf surface. Direct penetration by D. destructiva hyphae was observed without appressorium formation. At 8 DAI, hyphae were aggregated between the cuticle and epidermis and grew intracellularly in epidermal cells, palisade parachyma, and spongy mesophyll cells. At 16 DAI, chloroplasts were intact but decompartmentalized and infection sites were clearly defined. Acervuli were detected at 20 DAI and were fully developed at 24 DAI on adaxial and abaxial leaf surfaces. Sporulation (ruptured acervuli) was observed at 20 DAI. This clear understanding of the infection process can be used to look for resistance mechanisms in dogwood germplasm. A resistant line would expect to slow or inhibit one or more infection events. There was no statistical difference between the percentages of germinated conidia on susceptible and resistant cultivars of flowering dogwood one day after inoculation (DAI). However, the resistant cultivar, ‘Appalachian Spring’, significantly suppressed the growth of D. destructiva conidial germ tubes at 2 DAI, 3 DAI and 4 DAI when compared to conidial germ tubes on leaves of the susceptible cultivar ‘Cloud 9’. Observed resistance may be due to smoother wax crystals on adaxial leaf surface and significantly thicker cuticle observed on leaves of ‘Appalachian Spring’. An unknown compound, observed highly concentrated in resistant but lower in susceptible cultivars, may be important as a resistance mechanism. These strategies reduced the inoculum potential of D. destructiva and play important roles in why ‘Appalachian Spring’ is resistant to dogwood anthracnose. These results provide new ways to use conidia germination test and germ tube growth measurement for detecting resistant cultivars.

This thesis aimed to the identification of immune biomarkers of mycobacterial infection for better diagnosis of tuberculosis (TB) and also focused on new vaccination strategies with a particular emphasis on the immune responses in the respiratory tract using murine models. Since the lung is the natural habitat for the M. tuberculosis, we reasoned that immune responses detected locally in the lungs would be good correlates of infection (Paper I). Likewise, immune responses induced in the respiratory tract following immunization would be more effective against mycobacterial infection. We showed that cytokines (IL-12, TNF, and IFN-γ) and cytokine receptors (sTNFR1 and sTNFR2) together with specific antibodies in the respiratory tract correlated better with the bacterial burden in the organs. In Paper II, we investigated the role of the BCG vaccination as a priming vaccine in a heterologous prime-boost immunization protocol. The results showed that the neonatal BCG vaccination primed the immune system for a relevant antigen and showed a generalized adjuvant effect. Using this immunization protocol, protective immune responses in the lungs were generated independently of the route used for the booster immunization. In Paper III, We showed that exposure to mycobacterial antigens during the gestational period led to antigen transportation from the mother to the fetus and this resulted in an early priming of the fetal immune system. Immunization with the same antigen during the postnatal life increased antigen-specific recall IFN-γ responses and protection against infection. We examined the role of innate immunity for the induction of acquired immune responses upon immunization with mycobacterial antigens using TLR2 deficient mice (Paper IV). Our data indicated that suboptimal innate immune responses in the TLR2-/- mice might compromise the induction of acquired immune responses. Overall, the current findings suggested that a better understanding of the mucosal immunity would be useful for the improvement of diagnostic procedures and the development of efficient vaccines against TB. / At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript

Sexually transmitted infections (STIs) and unplanned pregnancy are significant public health concerns. Abstinence-only until marriage (AOUM) and abstinence pledge programs have received a significant amount of government funding in an attempt to address these problems. Despite receiving over two billion dollars in funding, the programs have not been shown to be effective in achieving their stated goals. In addition, there are significant concerns about the content of AOUM curriculums, including medical inaccuracy and use of outdated gender stereotypes.

In healthcare, personal protective equipment (PPE) are sometimes misused due to improper skill acquisition or skill decay before clinical practice. Training is often didactic or web-based but it is unclear whether these methods transfer to effective physical performance. There is no standard method to evaluate these competencies and scheduling or space restrictions can limit physical practice. A Delphi survey produced relevant checklist and global rating items for evaluating use of PPE. Principles from skill learning and human-computer interaction were combined with the survey results to develop an interactive computer-based simulation for procedural practice of these skills. The assessment tool differentiated between experienced and newly-trained users and demonstrated inter-rater reliability. Learners rated their satisfaction with the simulation similar to a provincial online tutorial and pilot studies with the simulation demonstrated that learners practiced for a longer period when using the simulation as compared to the provincial online tutorial.

In healthcare, personal protective equipment (PPE) are sometimes misused due to improper skill acquisition or skill decay before clinical practice. Training is often didactic or web-based but it is unclear whether these methods transfer to effective physical performance. There is no standard method to evaluate these competencies and scheduling or space restrictions can limit physical practice. A Delphi survey produced relevant checklist and global rating items for evaluating use of PPE. Principles from skill learning and human-computer interaction were combined with the survey results to develop an interactive computer-based simulation for procedural practice of these skills. The assessment tool differentiated between experienced and newly-trained users and demonstrated inter-rater reliability. Learners rated their satisfaction with the simulation similar to a provincial online tutorial and pilot studies with the simulation demonstrated that learners practiced for a longer period when using the simulation as compared to the provincial online tutorial.

In healthcare, personal protective equipment (PPE) are sometimes misused due to improper skill acquisition or skill decay before clinical practice. Training is often didactic or web-based but it is unclear whether these methods transfer to effective physical performance. There is no standard method to evaluate these competencies and scheduling or space restrictions can limit physical practice. A Delphi survey produced relevant checklist and global rating items for evaluating use of PPE. Principles from skill learning and human-computer interaction were combined with the survey results to develop an interactive computer-based simulation for procedural practice of these skills. The assessment tool differentiated between experienced and newly-trained users and demonstrated inter-rater reliability. Learners rated their satisfaction with the simulation similar to a provincial online tutorial and pilot studies with the simulation demonstrated that learners practiced for a longer period when using the simulation as compared to the provincial online tutorial.

In healthcare, personal protective equipment (PPE) are sometimes misused due to improper skill acquisition or skill decay before clinical practice. Training is often didactic or web-based but it is unclear whether these methods transfer to effective physical performance. There is no standard method to evaluate these competencies and scheduling or space restrictions can limit physical practice. A Delphi survey produced relevant checklist and global rating items for evaluating use of PPE. Principles from skill learning and human-computer interaction were combined with the survey results to develop an interactive computer-based simulation for procedural practice of these skills. The assessment tool differentiated between experienced and newly-trained users and demonstrated inter-rater reliability. Learners rated their satisfaction with the simulation similar to a provincial online tutorial and pilot studies with the simulation demonstrated that learners practiced for a longer period when using the simulation as compared to the provincial online tutorial.

Executive functions are important cognitive processes critical for survival. Damage to the prefrontal cortex impairs executive functions, such as working memory, decision making and set-shifting. Interestingly, patients diagnosed with different psychiatric disorders are also impaired in executive functions, especially in the set-shift domain, often measured by the Wisconsin Card Sorting Task (WCST). Set-shifting is an essential cognitive process, in that it allows the individual to suppress non-reinforcing strategies and engage in new rewarding strategies. To date, little is known about the etiology of executive dysfunction in psychiatric disorders. However, some epidemiological and serological experiments have shown strong correlations between prenatal infection and the increased risk to develop psychiatric disorders in the adult offspring. One study found that schizophrenic patients pre-exposed to a prenatal infection perseverated more during the WCST, than non-pre-exposed patients. Despite these findings, there are still numerous limitations (e.g., ethical concerns) when conducting these studies. Thus, animal models are important and can further elucidate the etiology of executive dysfunctions in psychiatric disorders. Prenatal infection animal models have consistently shown that inflammation during gestation in rodents induces behavioural, anatomical and cognitive changes in the adult offspring similar to psychiatric patients. However, no studies have investigated the effects of prenatal infection on set-shifting in the adult offspring. Therefore, the present thesis examined whether prenatal treatment with PolyI:C (a viral mimetic) during middle/late gestation of the rat would induce cognitive inflexibilities (i.e., set-shifting and reversal learning in an operant based task analogous to the WCST) in the adult male and female offspring. The results showed PolyI:C male offspring perseverated during the set-shift but had fewer regressive errors during the reversal learning day. PolyI:C treated female offspring were not impaired during any of the test days; however, females were slower to respond to the lever and required more training when compared the male rats. Taken together, these results give support for prenatal infection in inducing cognitive inflexibility, by potentially altering the PFC in the adult offspring. MS-based thesis: Zhang, Y., Cazakoff, B. N., Thai, C. A., & Howland, J. G. (2011). Prenatal exposure to a viral mimetic alters behavioural flexibility in male, but not female, rats. Neuropharmacology, [epub ahead of print]. doi:10.1016/j.neuropharm.2011.02.022