Yes / Vascular calcification is a complex biological process that is a hallmark of atherosclerosis. While macrocalcification confers plaque stability, microcalcification is a key feature of highrisk atheroma and is associated with increased morbidity and mortality. Positron emission tomography and X-ray computed tomography (PET/CT) imaging of atherosclerosis using 18F-sodium fluoride (18F-NaF) has the potential to identify pathologically high-risk nascent microcalcification. However, the precise molecular mechanism of 18F-NaF vascular uptake is still unknown. Here we use electron microscopy, autoradiography, histology and preclinical and clinical PET/CT to analyse 18F-NaF binding. We show that 18F-NaF adsorbs to calcified deposits within plaque with high affinity and is selective and specific. 18F-NaF PET/CT imaging can distinguish between areas of macro- and microcalcification. This is the only currently available clinical imaging platform that can non-invasively detect microcalcification in active unstable atherosclerosis. The use of 18F-NaF may foster new approaches to developing treatments for vascular calcification.

This thesis investigates the development of medical research at the Otago Medical School in Dunedin, New Zealand under Sir Charles Hercus, Dean from 1937-1958. It also explores his interest and participation in research from his student days and the years before becoming Dean, as well as the influence of the First World War on his career. The study draws upon unpublished material in New Zealand archives and a collection of student projects investigating public health issues. Hercus, as Professor of Public Health and Bacteriology incorporated these projects into the curriculum in the early 1920s. The thesis uses many original papers published in scientific and medical journals by Hercus and his colleagues at the School. Building on a base of archival material including contemporary newspaper accounts, which have lately become available on the Papers Past website, this thesis draws together the individual disease studies undertaken by other thesis writers to give an account of Hercus’s achievements in fostering medical research. A key finding of this thesis is that Hercus was instrumental in building up the research capability of the School. He accomplished this through his own investigations and by helping to establish the New Zealand Medical Research Council. The thesis illustrates the multitude of studies that Hercus undertook personally or facilitated others to pursue, beyond the elimination of endemic goitre, for which he perhaps is best known. Another outcome of this study is an understanding of the difficult path that scientists faced in the early years of the twentieth century in New Zealand if they wished to carry out research. This thesis follows the origins of the Department of Scientific Research in the 1920s and the frequent collaboration Hercus made with scientists outside of the School. It will also demonstrate Hercus’s compassion and foresight in employing several Jewish refugee doctors as researchers at the School, who brought expertise into the research programmes. The era was one of great interest in improving the health and wellbeing of a generation affected by wars and deprivation caused by them. A key finding of this thesis is that researchers at the School took steps to mitigate these through making New Zealand more self-sufficient in foodstuffs and to improve the national diet. As well, Hercus lobbied for the establishment of a School of Physical Education within the university to improve the physical fitness of the population.

published_or_final_version / Community Medicine / Master / Master of Public Health

Pancreatic cancer is a devastating disease that leaves patients with a very poor prognosis and few therapeutic options. Many of the treatment options available are the same that have been used for almost 2 decades. There is a dire need for both novel treatments for this disease as well as novel strategies of treatment. This body of work will introduce and provide evidence in support of a novel combination therapy for pancreatic cancer treatment, a novel strategy of modifying currently used chemotherapeutics for pancreatic cancer therapy, and a novel transgenic preclinical mouse model of pancreatic cancer. Sabutoclax, an antagonist of the anti-apoptotic Bcl-2 proteins, and Minocycline, a commonly used antibiotic, show potent synergy when used in combination in both pancreatic cancer cells and in multiple immune-deficient and immune-competent mouse models of pancreatic cancer. Sabutoclax alone is capable of inducing cell cycle arrest and apoptosis in cells and its cytotoxicity is enhanced significantly when combined with Minocycline. This combination results in the loss of Stat3 activation both in vitro and in vivo, which is essential for its toxicity. It also inhibits tumor growth and prolongs survival in the KPC transgenic mouse model of pancreatic cancer. Also presented here are studies that demonstrate efficacy in vivo of modified versions of Gemcitabine and Paclitaxel. These drugs are linked to a peptide that shows specificity for the EphA2 receptor, which is overexpressed on the surface of pancreatic cancer cells and only minimally on normal cells. This peptide results in increased cellular uptake of drug, as it is bypassing its normal mechanism of entry. These normal mechanisms are often dysregulated in cancer, leading to decreased uptake and drug resistance. The use of these modified drugs show significantly increased tumor growth inhibition as compared to the parent drug alone. Finally, we provide data on the characterization of a novel transgenic mouse model of pancreatic cancer. This model, the Pan Met View (PMV) mouse, combines the commonly used KPC transgenic mouse model of pancreatic cancer and a mouse that expresses a Luciferase reporter gene under the control of the cancer-specific promoter, CCN1. Our data shows that double transgenic PMV mice can now be used to follow primary tumor and metastasis development in real time by Bioluminescent imaging (BLI) through disease progression and potentially therapy. This strategy will enhance the use of genetically engineered mouse models (GEMMS) to study cancer initiation and progression with potential to non-invasively monitor therapy. These chapters present novel and exciting data that have the potential to open multiple avenues of translational study and result in significant advances in pancreatic cancer therapy.

"May 2004" / Bibliography: leaves 172-184. / xvi, 186 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (D.Nurs.)--University of Adelaide, Dept. of Clinical Nursing, 2004

The thesis is an analysis of the birth of the Rhesus (Rh) Factor Research Programme in the Faculty of Medicine, University of Manitoba. Rh Factor is one of the blood groups which can lead a pregnant mother to react to her baby’s blood and destroy it. Research on this disorder yielded one of Manitoba’s most profound medical discoveries. The account reveals that three elements contributed to this research, namely the researcher, the circumstances and chance. The narrative identifies the researcher, Dr. Bruce Chown, as a major influence in the development of the Faculty of Medicine, University of Manitoba. The conditions nationally and locally that enabled him to succeed in his research are examined. The role of chance in his picking a research subject is considered. The story of Bruce Chown and the start of the Rh research illustrates the beginnings of medical research in Manitoba. The primary sources for the study were the Archives of the University of Manitoba, Archives Manitoba and the National Archives Ottawa.

The thesis is an analysis of the birth of the Rhesus (Rh) Factor Research Programme in the Faculty of Medicine, University of Manitoba. Rh Factor is one of the blood groups which can lead a pregnant mother to react to her baby’s blood and destroy it. Research on this disorder yielded one of Manitoba’s most profound medical discoveries. The account reveals that three elements contributed to this research, namely the researcher, the circumstances and chance. The narrative identifies the researcher, Dr. Bruce Chown, as a major influence in the development of the Faculty of Medicine, University of Manitoba. The conditions nationally and locally that enabled him to succeed in his research are examined. The role of chance in his picking a research subject is considered. The story of Bruce Chown and the start of the Rh research illustrates the beginnings of medical research in Manitoba. The primary sources for the study were the Archives of the University of Manitoba, Archives Manitoba and the National Archives Ottawa.

Thesis (Ph. D.)--UCLA, 2008. / Vita. Includes bibliographical references (leaves 276-312).

Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliography.

Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliography.