Thesis (M. Phil. P.H.)--University of Sydney, 2008. / Title from title screen (viewed Oct. 8, 2008). Submitted in fulfilment of the requirements for the degree of Master of Philosophy in Public Health to the School of Public Health, Faculty of Medicine. Degree awarded 2008; thesis submitted 2007. Includes bibliography. Also available in print form.

Thesis (Ph.D.)--University of Alberta, 2010. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Department of Public Health Sciences. Title from pdf file main screen (viewed on April 28, 2010). Includes bibliographical references.

Thesis (Ph.D.) - University of Queensland, 2003. / Includes bibliography.

The advent of scRNA-seq has rapidly advanced our understanding of complex systems by enabling the researcher to look at the full transcriptional profile within each cell, with the potential to reveal intercellular communications within a tissue. To map these communications, I created SignallingSingleCell, an R package that provides an end-to-end approach for the analysis of scRNA-seq data, with a particular focus on building ligand and receptor signaling networks. Using these powerful techniques, we sought to dissect the heterogenous population of cells recently reported within the BMDC culture system. From this data we were able to determine the cell type composition, identify the different myeloid responses to similar stimuli, and unify recent conflicting studies about the populations within this system. We then applied these tools to study vitiligo, an autoimmune disease of the skin, to answer fundamental questions about the initiation and progression of disease. We found signatures of increased antigen presentation through MHC-I, loss of immunotolerance cytokines such as TGFB1 and IL-10, and changes in the complex chemokine circuits that influence T cell localization, including an essential role for CCR5 in Treg function. In order to identify and characterize the autoreactive T cells that are responsible for the targeted destruction of melanocytes, we then paired scRNA-seq with TCR-seq and MHC-II complexes loaded with melanocyte antigen. From this data we contrast the transcriptional state of melanocyte specific T cells to bystanders found within the skin and circulation.

Opioid use disorder (OUD) is one of the most pressing public health problems of our time, with staggering morbidity, social impact, and economic costs. Prescription opioids play a critical role in the opioid crisis as they increase exposure and availability in the general population, making them an attractive target for much needed prevention and risk mitigation strategies. Opioid exposure, including legitimate prescription use, leads to a variety of physiologic adaptations (e.g. dependence) that may be leveraged to understand and identify risk of misuse. Mobile health (mHealth) tools, including wearable sensors have great potential in this space, but have been underutilized. Of specific interest are digital biomarkers, or end-user generated physiologic or behavioral measurements that correlate with events of interest, health, or pathology. Preliminary data support the concept that wearable sensors can detect digital biomarkers of opioid use and may provide clues regarding individual physiologic adaptations to opioid use over time. This dissertation follows a path though the exploration and refinement of these digital biomarkers of opioid use in various clinical use cases. Longitudinal data from individuals treated with opioids for acute pain will be explored through various machine learning models to detect opioid use and to explore patient and treatment factors that impact model performance. Next, a signal processing approach will be undertaken to explore the effects of opioid agonism in a different population of individuals- those presenting with opioid toxicity and precipitated withdrawal. Both approaches will be combined to further refine the digital biomarker capabilities, this time with a focus on the difference between opioid naive and chronic users. And finally, usability, facilitators and barriers to use of a sensor-based monitoring system for opioids will be evaluated through a qualitative lens. Taken together, theses data support the development of a smart technology, driven by empirically derived algorithms which can be used to monitor opioid use, support safe prescribing practices, and reduce OUD and death.

No description available.

In order to ensure the generalizability of clinical research studies, researchers and study sponsors are tasked with making efforts to ensure that research participants are racially and ethnically representative of the population at large. However, minorities and women continue to be underrepresented in medical research studies. To encourage participation in medical research studies, researchers are often inclined to offer compensation for study participation. However, it is vital that researchers consider the ethical implications of monetizing participation in medical research studies. The first aim of this paper is to discuss the ethical ramifications of providing compensation for research participation. Additionally, this paper will critically analyze the various ways of handling financial compensation for participation in medical research studies involving experimental drugs, devices or surgical techniques. Information for this paper was gathered by conducting a literature review and by analyzing 121 semi-structured interviews. Using an ethical framework, and supported by qualitative data from the interviews, this paper will discuss the ethical concerns that researchers must consider when offering monetary compensation in exchange for participation in medical research. Overall, the paper aims to show that in order for clinical research to be conducted ethically, we must grant potential participants the autonomy to use their own decision making framework when deciding whether or not to participate in a medical research study. While a potential participant’s decision to join a research study in exchange for financial compensation may raise concerns to some people, autonomy requires that the research institution respect each individual’s own motivations and decisions. / Urban Bioethics

The 1920s and 1930s were a period of rapid urban growth and intensive changes to rural Indian geography through the construction of irrigation project to increase agricultural output. The work of several key researchers at this time demonstrated that these projects could lead to an increase in malaria prevalence. However, this period was also the site of a complicated entanglement of environmentalist and bacteriological thinking, which sometimes resulted in a disconnect between the research and the fieldwork that impacted the quality of research and the message malaria researchers were trying to send to the British administration in India. / Graduate

A new metric for the quantitative and qualitative evaluation of bone stiffness is introduced. It is based on the spectral decomposition of stiffness matrix computed with finite element method. The here proposed metric is defined as an amplitude rescaled eigenvalues of stiffness matrix. The metric contains unique information on the principal stiffness of bone and reflects both bone shape and material properties. The metric was compared with anthropometrical measures and was tested for sex sensitivity on pelvis bone. Further, the smallest stiffness of pelvis was computed under a certain loading condition and analyzed with respect to sex and direction. The metric complements anthropometrical measures and provides a unique information about the smallest bone stiffness independent from the loading configuration and can be easily computed by state-of-the-art subject specified finite element algorithms.

A Amiotrofia Espinhal Progressiva (AEP) é uma doença autossômica recessiva que afeta os motoneurônios do corno anterior da medula espinhal, acarretando hipotonia e fraqueza muscular. A partir do conhecimento do mecanismo molecular da AEP, abriu-se um campo para testes clínicos com agentes farmacológicos que possam aumentar o nível da proteína SMN2. Diversas drogas com esta ação estão sendo testadas na tentativa de encontrar um possível tratamento para esta trágica doença. O ácido valpróico (AV), droga muito utilizada para o tratamento da epilepsia mostrou ter a propriedade de ativar o promotor do gene da proteína SMN2, aumentando a sua produção. Tendo em vista que não há uniformização do sistema de avaliação clínica dos resultados do tratamento em diferentes países, foi elaborado um protocolo selecionando métodos de avaliação fáceis, rápidos e já validados a fim de verificar se o AV é eficaz para manter ou melhorar a força muscular dos pacientes com AEP. Os métodos selecionados foram: escala Medical Research Council (MRC) para força muscular; Hammersmith motor ability score para habilidade motora; goniometria das principais articulações; cronometragem de tempo despendido para deambular, quando possível; índice de Barthel para atividades da vida diária e, por fim, um questionário para verificar as modalidades de fisioterapia e hidroterapia em uso. Vinte e dois pacientes com AEP tipo II e III, com idades variando de 2 a 18 anos, medicados com AV, foram avaliados a cada três meses durante um ano, totalizando cinco visitas, das quais a primeira ocorreu nos dias anteriores ao início do tratamento. Os resultados dos testes demonstraram que, durante o seguimento de um ano, os pacientes obtiveram melhora na habilidade motora, porém não na força muscular, o que é um resultado extremamente positivo. Crianças com idade menor ou igual a 6 anos mostraram melhores ganhos quanto à habilidade motora. / Spinal Muscular Atrophy (SMA) is an autosomal recessive disorder that affects the spinal motoneurons, resulting in hypotonia and muscle weakness. The knowledge of the molecular mechanism of SMA has originated new researches including clinical trials with pharmacological agents that increase SMN2 protein level. Many drugs with this action are being tested with the aim of finding a possible treatment for this severe disease. The valproic acid (VA), a well-known drug used to treat epilepsy has the property of activating the SMN2 gene promoter and then to increase SMN2 protein level. Since there isnt an uniform system for the clinical evaluation of the treatment results, we selected a set of easy, fast and already validated methods to evaluate if the VA is effective to stabilize or improve the motor function in patients with SMA. The selected methods were: Medical Research Council scale (MRC) to muscular strength; Hammersmith motor ability score to motor ability; goniometry of the main joints; time to walk when possible; Barthel índex for daily activities, and a questionnaire to verify the types of physiotherapy and hydrotherapy in use. Twenty two patients with SMA II and III, aged between 2 and 19 years, and treated with VA were evaluated every three months during the period of one year; the first evaluation occurred immediately before the onset of the treatment. The results of the tests demonstrated that along the period of 12 months the patients didnt gain muscle strength but improved their motor ability, that can be considered a positive result. Children aged six years or younger had a higher gain in motor ability along the period of the study.