Thesis (Ph. D.)--University of Missouri-Columbia, 1996. / Typescript. Vita. Includes bibliographical references (leaves 237-256). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 1996. / Typescript. Vita. Includes bibliographical references (leaves 237-256). Also available on the Internet.

Thesis (M.A.) - Carleton University, 2007. / Includes bibliographical references (p. 68-82). Also available in electronic format on the Internet.

Thesis (Ph. D.)--Virginia Polytechnic Institute and State University, 1992. / Vita. Abstract. Includes bibliographical references (leaves 133-145). Also available via the Internet.

Thesis (Ph. D.)--University of Notre Dame, 2006. / Thesis directed by George S. Howard for the Department of Psychology. "December 2006." Includes bibliographical references (leaves 49-52).

Thesis (Ph.D. in Epidemiology) -- University of Colorado at Denver and Health Sciences Center, 2005. / Typescript. Includes bibliographical references (leaves 83-102).

Dairy farms can apply anaerobic digestion (AD) as a manure management system, while producing renewable energy. Ultimately, this can reduce greenhouse gas (GHG) emissions. There is much research work that has quantified the changes in emissions due to AD. However, important methodologies such as the Intergovernmental Panel on Climate Change (IPCC) Guidelines, rely only on a small sample of the accumulated scientific findings in the field. This thesis improves the robustness of these methodologies by applying data-driven techniques to estimate values of the energy output of AD systems and their consequent effect in GHG emissions. For this purpose, meta-analyses techniques are applied to mathematically combine metrics from 155 non-standardised research publications (i.e. with different boundaries, scopes and functional units). As a first step, a novel database is created by systematically searching for relevant articles and assessing them against defined criteria. The database is divided in two parts. Given that the offset of GHGs is highly dependent on the energy output of AD system, empirical methane yields (i.e. key metric of AD performance) are collected in Part I of the database. GHG released from different farm activities are input to Part II of the database. To quantify the change in emissions from these activities, standard baseline and AD scenarios are defined. The second step of the meta-analysis consists of applying uni- and multi-variate tests to the database. For Part I, methane yields are analysed in terms of type of digesters. From the batch digesters, new maximum methane yields are proposed based on the combined results of 42 peer reviewed articles. These results offer better estimates than default values of methane yields from the 2007 Guidelines of the IPCC, which only consider two studies. For continuously stirred tank digesters and semi-continuous digesters lower methane yields are revealed. Multi-variate analysis of methane yields together with operating conditions and manure composition, enable the identification of clusters. These groups of variables can be useful to build potential AD scenarios in dairy farms. For Part II of the database, relative changes in emissions between the activities in the standardised baseline and AD scenarios, are examined. It is found, through meta-analysis, that replacing raw manure by anaerobically-treated manure (i.e. digestate) in storage tanks and for field- application, mitigates baseline emissions by 38.7% and 6.9%, respectively. These relative changes can be used to estimate emissions from digestate, being more specific and evidence-based than the current methodology from the IPCC. In addition, relative changes found for offset of fossil fuels by biogas generated in the AD scenarios indicate a reduction of baseline emissions by 9.0%. Only methane leaks from digesters significantly increase the baseline emissions (by 7.4%). Finally, results found by meta-analyses of methane yields and changes in emissions are applied to four dairy farm case studies. The work presented in the case studies demonstrates the benefits of enhancing the robustness of methods to estimate the effect of AD on GHG emissions from dairy farms.

The objective of the work presented in this thesis was to explore the role of potential alternatives to platelet transfusions and specifically to investigate whether desmopressin could be used for treatment of thrombocytopenia or platelet dysfunction. Patients with thrombocytopenia or platelet dysfunction are often treated with platelet transfusions to treat or prevent bleeding. However the evidence for the efficacy of platelet transfusion is limited and there is some evidence of harm. I have focused on thrombocytopenic patients with haematological malignancies or critically ill patients, who are amongst the groups most commonly treated with platelet transfusions. The aims of this research were to determine: 1. If levels of Von Willebrand factor (VWF) or other measures of haemostasis are predictive of bleeding in severe thrombocytopenia; 2. Whether VWF compensates for thrombocytopenia in vitro; 3. The evidence for the efficacy of desmopressin in all patients undergoing surgery or invasive procedures; 4. The evidence for desmopressin for platelet dysfunction or thrombocytopenia; 5. If it is feasible to use desmopressin to treat critically ill thrombocytopenic patients in a clinical trial. To identify derangements of haemostasis that may signify candidates for alternatives to platelet transfusions, I analysed blood samples from an observational trial of fifty patients with haematological malignancies and profound thrombocytopenia due to intensive chemotherapy. I used a panel of tests to investigate measures of primary haemostasis, thrombin generation, cross-linked fibrin formation and fibrinolysis. Using multivariable logistic regression, I found no consistent correlation between any measures of haemostasis and the risk of clinically significant bleeding. VWF antigen levels were the best predictor of clinically significant bleeding on the same day (odds ratio 0.31, 95% confidence interval 0.10 to 0.98, p=0.047) but were not predictive of severe bleeding over the 24 hours after the test (odds ratio 0.48, 95% confidence interval 0.10 to 2.34, p=0.36). In a separate set of experiments, I evaluated thrombus formation under flow in thrombocytopenia. This technique was sensitive to the platelet count . Addition of exogenous VWF to thrombocytopenic blood resulted in improvement in thrombus formation, suggesting that agents that affect or influence VWF pathways might have a role. Desmopressin can be used to increase VWF levels, so leading on from my laboratory experiments; I used systematic reviews and meta-analyses to assess whether desmopressin could be used in unselected patients to reduce bleeding peri-operatively. I identified 62 randomised controlled trials. Overall there was no evidence of benefit for administering desmopressin to unselected patients. However further analysis of eleven randomised controlled trials that focused on patients with platelet dysfunction found that desmopressin resulted in transfusion of fewer units of red cells (equivalent to a 25% reduction compared to control), less blood loss (equivalent to a 23% reduction compared to control) and a lower risk of requiring a re-operation due to bleeding (Peto odds ratio 0.39, 95% confidence interval 0.18 to 0.84). There was no evidence for an increase in thrombotic events. There was no randomised controlled trial evidence for perioperative desmopressin for patients with thrombocytopenia. These specific research gaps were addressed by designing new clinical trials. I have commenced a randomised controlled feasibility trial of desmopressin versus placebo for critically ill patients with thrombocytopenia undergoing invasive procedures. This trial is ongoing and is the first randomised trial evaluating peri-procedural desmopressin in thrombocytopenia. The programme of work arising from this research has the potential to benefit a large number of patients by preventing bleeding and reducing exposure to allogeneic blood components such as platelets. The results presented in this thesis are exploratory but are an important step on a path towards larger trials using desmopressin as an alternative, or adjunct to platelet transfusion.

Orientador: Vania dos Santos Nunes Nogueira / Resumo: Objetivo: esta revisão sistemática da literatura e metanálise comparou a taxa da mortalidade na acromegalia com a taxa esperada na população geral dos estudos publicados antes de 2009 versus estudos publicados após. Métodos: foram criadas três estratégias de busca gerais e adaptáveis às bases de dados eletrônicas na área da saúde: Embase (1980–2015), Pubmed (1966–2016) e Biblioteca Virtual da Saúde (1982–2016). Foram incluídos estudos observacionais em que a mortalidade na acromegalia foi comparada à da população geral, por meio do número de mortes observadas nessa doença em comparação à taxa de mortalidade esperada para população geral (O/E). A partir do O/E, recalculamos todos os Standardized Mortality Ratio (SMR) e os seus respectivos intervalos de confiança (IC) que foram plotados em uma metanálise. Resultados: foram identificadas 1005 referências, dois revisores independentemente leram os títulos e resumos desses artigos. Dos 27 estudos potencialmente elegíveis, 23 foram incluídos e quatro foram excluídos por não preencherem os critérios de elegibilidade. A mortalidade geral na acromegalia foi significativamente superior a da população geral (SMR: 1,66, IC 1,44 - 1,93, p < 0,00001, I2 84%). Separando os artigos publicados a partir de 2009, a mortalidade na acromegalia não foi significativamente diferente 1,29 (IC 0,95-1,76, p=0,10, I2 86%). Nas análises por subgrupo de acordo com o status da doença, sete estudos consideraram como curados os pacientes que apresentaram a n... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Objective: This systematic literature review and meta-analysis compared the mortality rate in acromegaly with the expected rate in the general population of studies published before 2009 versus studies published after. Methods: three general and adaptive search strategies were created from the electronic databases in the health area: Embase (1980-2015), Pubmed (1966-2016) and Virtual Health Library. Observational studies were included in which the mortality in acromegaly was compared to the general population, the number of deaths observed compared to the expected mortality rate in the general population (O/E). From O/E, we recalculated all the Standardized Mortality Ratio (SMR) and their respective confidence intervals (CI) that were plotted in a meta-analysis. Results: 1005 references were identified and two reviewers independently read the titles and abstracts of these articles. Of the 27 potentially eligible studies, 23 were included and four were excluded because they did not meet the eligibility criteria. Overall mortality in acromegaly was significantly higher than the general population (SMR: 1.66, CI 1.44 - 1.93, p <0.00001, I² 84%). Analyzing articles published as of 2009, the mortality in acromegaly was not significantly different, SMR 1.29 (CI 0.95-1.76, p = 0.10, I² 86%). In subgroup analyzes according to disease status, seven studies considered patients with IGF-1 normalization associated with random GH <2.5 ng / mL as cured. In these individuals, the SMR was 0.... (Complete abstract click electronic access below) / Mestre

Orientador: Marcos da Cunha Lopes Virmond / Resumo: Introdução: Indivíduos que estão em estreita associação ou proximidade com pacientes com hanseníase têm maior chance de adquirir a doença. A eficácia da quimioprofilaxia na prevenção da hanseníase nos contatos dos pacientes afetados para um ótimo controle da doença ainda não é clara. Métodos: pesquisas eletrônicas de Medline, EMBASE, CENTRAL e LILACS até outubro de 2017 foram realizadas para identificar estudos elegíveis. As listas de referência de estudos potencialmente elegíveis foram revisadas. Incluímos ensaios clínicos randomizados (RCTs) que compararam a quimioprofilaxia com placebo para a prevenção da infecção da hanseníase em contatos de pacientes afetados. O par de revisores examinou de forma independente artigos elegíveis, extraiu dados e avaliou o risco de viés. A abordagem GRADE foi utilizada para avaliar a certeza geral da evidência. Resultados: seis ECRs, incluindo 52.483 participantes, se mostraram elegíveis. Os resultados sugeriram uma redução estatisticamente significativa na hanseníase clínica em contatos até dois anos (Rácio de Risco (RR) 0,32, Intervalo Confidencial (IC) 0,11 0,62; p <0,0007; I2 = 70%, p = 0,07; evidência de qualidade) e de dois a cinco anos de seguimento (RR 0,51, IC 95% 0,29, 0,89; p = 0,02; I2 = 80%, p <0,0005; evidência de baixa qualidade) com o uso de 6 quimioprofilaxia em comparação com placebo. No entanto, os resultados sugeriram uma redução não significativa na hanseníase clínica nos contatos ao longo de cinco anos (RR 0,77, IC 95%... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: Individuals who are in close association or proximity with leprosy patients have a greater chance of acquiring the disease. The effectiveness of chemoprophylaxis in preventing leprosy in contacts of affected patients for optimal disease control remains unclear. Methods: Electronic searches of Medline, EMBASE, CENTRAL, and LILACS up to October 2017 were conducted to identify eligible studies. Reference lists of potentially eligible studies were reviewed. We included randomized controlled trials (RCTs) comparing chemoprophylaxis with placebo for the prevention of leprosy infection in contacts of affected patients. Pair of reviewers independently screened eligible articles, extracted data, and assessed risk of bias. The GRADE approach was used to rate overall certainty of the evidence. Results: Six RCTs including 52,483 participants proved eligible. Results suggested a statistically significantly reduction in clinical leprosy in contacts both up to two years (Risk Ratio (RR) 0.32, 95% Confidential Interval (CI) 0.17, 0.62; p < 0.0007; I 2 =70%, p=0.07; low-quality evidence) and from two to five years of follow-up (RR 0.51, 95% CI 0.29, 0.89; p=0.02; I 2 =80%, p < 0.0005; low-quality evidence) with the use of chemoprophylaxis in comparison to placebo. However, results suggested a non-significant reduction in clinical leprosy in contacts over five years (RR 0.77, 95% CI 0.46, 1.28; p =0.31; I 2 =48%, p=0.16; low-quality evidence). Conclusions: Low-quality evidence show... (Complete abstract click electronic access below) / Mestre