Effects of low doses of quinpirole on production of 50 kHz vocalizations in Wistar rats

Rats emit two distinct types of ultrasonic vocalizations in adulthood: 22 kHz (aversive situation), and 50 kHz calls (appetitive situation). The present project is focussed on pharmacological studies of 50 kHz vocalizations. The 50 kHz calls are elicited from dopaminergic activation in the meso limbic pathway and are emitted in such appetitive situations as social contact(s), sexual encounters, food reward, etc. Eighty-five male rats were stereotaxically implanted with bilateral guide cannulae in the nucleus accumbens shell (A= 9.7, L= 1.2, V= 6.7). Quinpirole, a D2/D3 dopaminergic agonist, was injected in low doses to the nucleus accumbens shell in an attempt to elicit 50 kHz vocalizations. A dose response was obtained for the low dose range of quinpirole for six doses: 0.025 Jlg, 0.06 Jlg, 0.12 Jlg, 0.25 Jlg, 0.5 Jlg, and 1.0 Jlg. It was found that only application of the 0.25 Jlg dose of quinpirole and the 7 Jlg dose of amphetamine (positive control) significantly increased the total number of 50 kHz calls (p < 0.006 and p < 0.004 respectively); and particularly significantly increased the frequency modulated type of these calls (p < 0.01, and p < 0.006 respectively). In a double injection procedure, the dose of 0.25 Jlg quinpirole was antagonized with raclopride (D2 antagonist) or U99194A maleate (D3 antagonist) in an attempt to antagonize the response. The 0.25 Jlg dose of quinpirole was successfully antagonized by pre-treatment with an equimolar dose of U99194A maleate (p < 0.008) but not with raclopride. The 7Jlg amphetamine response was also antagonized with an equimolar dose of raclopride. Based on these results, it seems that low doses of quinpirole, particularly the 0.25 Jlg dose, are capable of increasing 50 kHz vocalizations in rats and do so by activation of the D3 dopamine receptor. This is not a biphasic response as seen with locomotor studies. Also noteworthy is the increase in frequency modulated 50 kHz calls elicited by the 0.25 Jlg dose of quinpirole indicating a possible increase in positive affect.

The implications of being an international medical graduate (IMG) in Canadian society : a qualitative study of foreign-trained physicians' resettlement, sense of identity and health status

This qualitative research study used grounded theory methodology to explore the settlement experiences and changes in professional identity, self esteem and health status of foreign-trained physicians (FTPs) who resettled in Canada and were not able to practice their profession. Seventeen foreign-trained physicians completed a pre-survey and rated their health status, quality of life, self esteem and stress before and after coming to Canada. They also rated changes in their experiences of violence and trauma, inclusion and belonging, and racism and discrimination. Eight FTPs from the survey sample were interviewed in semi-structured qualitative interviews to explore their experiences with the loss of their professional medical identities and attempts to regain them during resettlement. This study found that without their medical license and identity, this group of FTPs could not fully restore their professional, social, and economic status and this affected their self esteem and health status. The core theme of the loss of professional identity and attempts to regain it while being underemployed were connected with the multifaceted challenges of resettlement which created experiences of lowered selfesteem, and increased stress, anxiety and depression. They identified the re-licensing process (cost, time, energy, few residency positions, and low success rate) as the major barrier to a full and successful settlement and re-establishment of their identities. Grounded research was used to develop General Resettlement Process Model and a Physician Re-licensing Model outlining the tasks and steps for the successfiil general resettlement of all newcomers to Canada with additional process steps to be accomplished by foreign-trained physicians. Maslow's Theory of Needs was expanded to include the re-establishment of professional identity for this group to re-establish levels of safety, security, belonging, self-esteem and self-actualization. Foreign-trained physicians had established prior professional medical identities, self-esteem, recognition, social status, purpose and meaning and bring needed human capital and skills to Canada. However, without identifying and addressing the barriers to their full inclusion in Canadian society, the health of this population may deteriorate and the health system of the host country may miss out on their needed contributions.

Decision analysis of the effectiveness of lung cancer screening using autofluorescence bronchoscopy and computed tomography

Background: Lung cancer (LC) is the leading cause of cancer death in the developed world. Most cancers are associated with tobacco smoking. A primary hope for reducing lung cancer has been prevention of smoking and successful smoking cessation programs. To date, these programs have not been as successful as anticipated. Objective: The aim of the current study was to evaluate whether lung cancer screening combining low dose computed tomography with autofluorescence bronchoscopy (combined CT & AFB) is superior to CT or AFB screening alone in improving lung cancer specific survival. In addition, the extent of improvement and ideal conditions for combined CT & AFB screening were evaluated. Methods: We applied decision analysis and Monte Carlo simulation modeling using TreeAge Software to evaluate our study aims. Histology- and stage specific probabilities of lung cancer 5-year survival proportions were taken from Surveillance and Epidemiologic End Results (SEER) Registry data. Screeningassociated data was taken from the US NCI Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), National Lung Screening Trial (NLST), and US NCI Lung Screening Study (LSS), other relevant published data and expert opinion. Results: Decision Analysis - Combined CT and AFB was the best approach at Improving 5-year survival (Overall Expected Survival (OES) in the entire screened population was 0.9863) and in lung cancer patients only (Lung Cancer Specific Expected Survival (LOSES) was 0.3256). Combined screening was slightly better than CT screening alone (OES = 0.9859; LCSES = 0.2966), and substantially better than AFB screening alone (OES = 0.9842; LCSES = 0.2124), which was considerably better than no screening (OES = 0.9829; LCSES = 0.1445). Monte Carlo simulation modeling revealed that expected survival in the screened population and lung cancer patients is highest when screened using CT and combined CT and AFB. CT alone and combined screening was substantially better than AFB screening alone or no screening. For LCSES, combined CT and AFB screening is significantly better than CT alone (0.3126 vs. 0.2938, p< 0.0001). Conclusions: Overall, these analyses suggest that combined CT and AFB is slightly better than CT alone at improving lung cancer survival, and both approaches are substantially better than AFB screening alone or no screening.

Patterns and correlates of tobacco use among young adults at college and university

This thesis describes college and university students' smoking behaviours and examines whether socioenvironmental and personal characteristics experienced during adolescence are differentially associated with their smoking participation. Results show more college students than university students currently smoke (37% and 21 % respectively) and more began smoking prior to post-secondary school (93% and 84% respectively). Early age of onset of alcohol use increased the odds of current smoking (main effect model, OR = 8.56 CI = 6.47, 11.33), especially for university students (interaction effect model, b = 2.35 CI = 7.50, 14.64). Lower levels of high school connectedness were associated with increased odds of current smoking but for university students only (interaction effect model, b = -0.15 CI = 0.84, 0.88). While limitations associated with convenience sampling and low response rate exist, this is the first Canadian study to examine college and university students separately. I t reveals that tobacco control programming needs to differ for college and university students, and early alcohol prevention and school engagement programs for adolescents may influence tobacco use. Given that both educational pathway and use of tobacco are associated with SES, future research may consider examining in more detail, SES-related socioenvironmental variables.

THE PREVALENCE AND PREDICTION OF PULMONARY FIBROSIS IN AN

This thesis describes an ancillary project to the Early Diagnosis of Mesothelioma and Lung Cancer in Prior Asbestos Workers study and was conducted to determine the effects of asbestos exposure, pulmonary function and cigarette smoking in the prediction of pulmonary fibrosis. 613 workers who were occupationally exposed to asbestos for an average of 25.9 (SD=14.69) years were sampled from Sarnia, Ontario. A structured questionnaire was administered during a face-to-face interview along with a low-dose computed tomography (LDCT) of the thorax. Of them, 65 workers (10.7%, 95%CI 8.12—12.24) had LDCT-detected pulmonary fibrosis. The model predicting fibrosis included the variables age, smoking (dichotomized), post FVC % splines and post- FEV1% splines. This model had a receiver operator characteristic area under the curve of 0.738. The calibration of the model was evaluated with R statistical program and the bootstrap optimism-corrected calibration slope was 0.692. Thus, our model demonstrated moderate predictive performance.

Voices of the Undereducated in Adult Education and Training in Ontario: A Phenomenographic Approach

This doctoral study was an exploration of the qualitatively different ways in which undereducated adults (at or below a high school level of formal education) reported their experiences of participation in adult education and training (AET) programmes offered by publicly funded school boards or their arms-length affiliate in the province of Ontario. In light of a low participation rate in the Canadian AET system by undereducated adults, the rationale was to examine whether or not AET programmes are meeting the needs of undereducated adults beyond a narrow focus on an instrumental approach associated with human capital development. This study was located in a theoretical framework consisting of (a) learning theory, (b) motivations for participation, (c) general barriers to participation, (d) structural barriers to participation, and (e) transformative learning. The purposive sample consisted of 11 participants between the ages of 18-58 who were drawn from service providers in 4 geographic regions of Ontario. Data collection consisted of (a) demographics, (b) voice recordings from face-to-face participant interviews, (c) participant weekly critical incident reports, and (d) researcher reflexive journal notes. Data were analyzed in accordance with a phenomenographic approach within a constructivist/interpretivist research paradigm. Findings revealed 4 qualitatively different ways in which undereducated adult learners reported their experiences of participation in AET and were reported as the voice of (a) security, (b) engagement, (c) relationship, and (d) competency. Implications to theory and practice and to further inquiry were outlined.