Made available in DSpace on 2017-07-21T14:19:28Z (GMT). No. of bitstreams: 1 Bruna Rossetto Delazeri.pdf: 4632056 bytes, checksum: 7b23d649c1cebd3b01425d6b2a960ae9 (MD5) Previous issue date: 2015-03-15 / Asian soybean rust caused by Phakopsora pachyrhizi, is one of the main phytosanitary problems of soybean in Brazil. Aiming to reduce the losses caused by the pathogen, the treatment of soybean seeds with fungicide fluquinconazole has motivated researchers to conduct studies and simulate their performance. The compilation of these various studies may be conducted by the meta-analysis, which is a probabilistic technique that produces a result which summarizes studies. In agricultural context, meta-analysis is used to perform empirical estimates of technical efficiency for the development of productivity and economic research of agriculture, such as the use of the fungicide fluquinconazole. Meta-analysis can be applied through existing software such as R, run through commands, and WMA, which operates through a graphical user interface for data entry made by the user. The results generated by both software are shown in graphical form without providing interactivity with the user, neither reproducing a friendly software and easy to understand interface. This study applied meta-analysis using the WMA Software, which uses R to calculate the statistical results, to determine the efficiency of fungicide fluquinconazole in soybean seed, used to minimize the impact of the asian rust disease in the crop productivity. To provide a dynamic display of obtained results by meta-analysis, this study created a method to identify the best information visualization technique to represent hierarchical data. This method was applied to identify which better visualization technique represented the graphic forest plot, namely, bifocal tree. Changes were made at the WMA, such as: incorporation of a new effect measure, change in the help system and font files and the implementation bifocal tree technique using Gephi as a support tool. The implementation allowed to create a more interactive environment for analyzing the results of the R and provides two display options for the user: basic and advanced. The advantages of the visualization are that the user can explore more the data and results. In this study it was observed that when fluquinconazole was used to minimize the effects caused by rust soybean productivity (yield) was improved. / A ferrugem asiática da soja, causada pelo fungo Phakopsora pachyrhizi, é um dos principais problemas fitossanitários da cultura da soja no Brasil. Visando diminuir os prejuízos causados pelo patógeno, o tratamento das sementes de soja com o fungicida fluquinconazol tem motivado pesquisadores a realizar estudos e simular seu desempenho. A compilação destes vários estudos pode ser realizada através da metanálise, que é uma técnica probabilística que produz um resultado que resume os estudos. No âmbito agrícola a metanálise é utilizada para realizar estimativas empíricas de eficiência para o desenvolvimento da produtividade e investigação econômica da agricultura, como é o caso do uso do fungicida fluquinconazol. A metanálise pode ser aplicada por meio de software existentes como por exemplo o R, executado através de comandos, e o WMA (Wizard Metanálise), que opera através de um interface gráfica para entrada de dados feita pelo usuário. Os resultados gerados por ambos são exibidos em forma gráfica sem proporcionar interatividade com o usuário, tampouco reproduzem uma interface amigável e de fácil compreensão. Este trabalho aplicou a metanálise através do WMA, que utiliza o R para o cálculo dos resultados estatísticos, para determinar a eficiência do fungicida fluquinconazol na semente da soja utilizada para minimizar o impacto causado pela doença da ferrugem asiática na produtividade da cultura. Para proporcionar uma visualização dinâmica dos resultados obtidos pela metanálise este trabalho criou um método de identificação da melhor técnica de visualização de informação para representar dados hierárquicos. Este método foi aplicado para identificar qual técnica de visualização melhor representava o gráfico forest plot, a saber, bifocal tree. Mudanças foram realizadas no WMA tais como: incorporação de uma nova medida de efeito, mudança no sistema de ajuda e dos arquivos fontes e adição da técnica bifocal tree usando como ferramenta de apoio o Gephi. A implementação permitiu criar um ambiente mais interativo para análise dos resultados obtidos pelo R e fornece duas opções de exibição para o usuário: básica e a avançada. As vantagens da visualização é que o usuário consegue explorar mais os dados e resultados. Neste trabalho observou-se que houve um ganho na taxa de produtividade da soja com a utilização do fluquinconazol, para minimizar os efeitos causados pela ferrugem.

Background. The randomized controlled clinical trial is currently the most scientific method for evaluating the effect of medical interventions. The sample size of a trial is crucial for reliably estimating the effect. However, many clinical trials may not be sufficiently large in size to detect the effect of interventions assessed. Previous studies of the statistical power, a relative measure of the largeness of a study, were normally small, mainly examined trials with a statistically insignificant result and were flawed because of the biased or purely hypothetical estimate of the effect for the computation of the power. By using meta-analysis, we conducted this study with improved methods for estimating the power and included a larger number of trials. / Findings. A total of 2,923,912 patients from 2,872 clinical trials from 466 systematic reviews were included in the analyses of this thesis. Of the 466 systematic reviews, 24% (113) were identified from the five journals and the remaining 76% (353) were from the Cochrane Library. 1,000 trials and 1,583,204 patients were obtained from 113 systematic reviews identified in the journals, in which 13.7% (95% C.I.: 11.6%, 15.8%) of trials had a sufficient power and the overall power was 34.0% (95% C.I.: 33.7%, 34.3%). 1,872 trials and 1,340,708 patients were obtained from 353 systematic reviews identified in the Cochrane Library, in which 16.7% (95% C.I.: 15.0%, 18.4%) of trials had a sufficient power and the overall power was 37.8% (95% C.I.: 37.6%, 38.0%). (Abstract shortened by UMI.) / Methods. We identified trials from systematic reviews of clinical trials with binary outcomes published in five medical journals and the Cochrane Database of Systematic Reviews. We analyzed the power of trials with a significant result as well as those with an insignificant result. In estimating the power, we used the combined odds ratio of the meta-analysis as the estimate of the effect for trials from systematic reviews with a statistically significant result and a relative risk reduction of 25% for trials from systematic reviews with a statistically insignificant result. In addition to use of the conventional method to estimate the power, we also developed a new "counting method" that does not need any assumption about the effect. Furthermore, the power is also expressed as a relative and absolute difference between the number of subjects required for a power of 80% and that actually recruited by the trials. / Tsoi Kam Fai. / "July 2005." / Adviser: Jin Ling Tang. / Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0161. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 107-113). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Thesis (Ph. D.)--University of Texas Health Science Center at Houston, School of Public Health, 2008. / Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0769. Advisers: Claudia Pedroza; Asha S. Kapadia. Includes bibliographical references.

In questo lavoro si intende indagare l'effetto degli anti-oidici più diffusi al fine di individuare nuovi approcci per la ricerca sui fungicidi. Le analisi statistiche mostrano che meptildinocap, zolfo, metrafenone e penconazolo, somministrati a dosi di etichetta, prevengono le infezioni di Erysiphe necator qualora applicati fino a 12 giorni prima dell'inoculazione. Meptildinocap e zolfo conservano una buona efficacia anche se applicati fino a 9 e 6 giorni dopo l'inoculazione. Meptildinocap neutralizza il massimo numero di conidi entro 6 giorni dal trattamento. La meta-analisi multivariata eseguita su prove di campo dimostra che tutti i fungicidi riducono la gravità delle infezioni su grappolo oltre l'80%, qualora applicati da 3 a 13 volte a dosi di etichette secondo il criterio fenologico. Nonostante cyflufenamid, quinoxyfen, fenarimol, fenarimol+zolfo, propiconazolo e kresoxim-metil+boscalid siano significativamente più efficaci dello zolfo, la loro applicazione ripetuta rappresenta una condizione favorevole all’insorgenza di resistenze. L’ approccio chemio-metrico all’ analisi dei dati ottenuti da microanalisi in microscopia SEM a raggi X mostra che meptildinocap induce modificazioni nei rapporti tra Ca e Al e P e S sulla parete dei Chasmoteci trattati. Tali modificazioni sono probabilmente dovute al dissolvimento della membrana plasmatica. Questi nuovi approcci possono rappresentare un'utile integrazione ai metodi già noti. / In this work the effect of the most widespread fungicides used for Erysiphe necator management is investigated in order to test new approaches to fungicide research. ANCOVA and Tukey’s post hoc tests showed that meptyldinocap, sulfur, metrafenone and penconazole administrated at label rates prevent E. necator infections when applied up to 12 days before inoculation. Meptyldinocap and sulfur preserve a good efficacy even when applied until 9 and 6 days after inoculation. Meptyldinocap significantly increases E. necator conidia mortality within 6 days exposure. The multi-treatment meta-analysis performed on field trials shows that all fungicides reduce disease severity over 80% on vine bunches when applied from 3 to 13 times at label rates with the phenological criterion. Although cyflufenamid, quinoxyfen, fenarimol, fenarimol+sulfur, propiconazole and kresoxim-methyl+boscalid are significantly more effective than sulfur their repeated application in vineyard represents an important E. necator resistance risk. The application of chemo-metric approach to data earned by SEM X-ray microanalysis shows that meptyldinocap leads to modifications in the relationships between Ca and Al and P and S in treated Chasmothecia wall. Such modifications are probably due to the plasma membrane disruption. The new approaches tested here may represent a useful integration of already known methods.

Background: Social anxiety disorder (SAnD) is a highly prevalent condition, characterised by an intense fear of social or performance situations where individuals worry about being negatively evaluated by others. An up to date systematic review of the effectiveness of cognitive behavioural therapies for SAnD is required to guide practice. Objectives: To assess the efficacy and acceptability of cognitive behavioural therapy (CBT) compared with treatment as usual/waiting list (TAU/WL) for individuals with SAnD. Search methods: We searched the Cochrane Depression, Anxiety and Neurosis Group (CCDAN) Controlled Trials Register and conducted supplementary searches of MEDLINE, PsycInfo, EMBASE, and international trial registers (ICTRP; ClinicalTrials.gov) in October 2011 and CINAHL in October 2012. We also searched reference lists of retrieved articles, and contacted trial authors for information on ongoing/completed trials. Selection criteria: Randomised and quasi-randomised controlled trials undertaken in out-patient settings, involving adults aged 18-75 years with a primary diagnosis of SAnD, assigned either to CBT or TAU/WL. Data collection and analysis Data on patients, interventions and outcomes were extracted by two review authors independently, and the Risk of bias in each study was assessed. The primary outcomes were social anxiety reduction (based on relative risk (RR) of clinical response and mean difference in symptom reduction), and treatment acceptability (based on RR of attrition). Results: Thirteen studies (715 participants) were included in the review, of which 11 studies (599 participants) contributed data to meta-analyses. Based on four studies, CBT was more effective than TAU/WL in achieving clinical response at post-treatment (RR 3.60, 95% CI 1.35 to 9.57), and on eleven studies (599 participants) it was more effective than TAU/WL in reducing symptoms of social anxiety. No significant difference was found between CBT and TAU/WL for attrition. No significant difference was demonstrated for social anxiety at follow-up and no studies examined follow-up data for clinical response or attrition. Authors' conclusions: The available evidence suggests that cognitive behavioural therapy might be effective in reducing anxiety symptoms for the short-term treatment of SAnD. However, the body of evidence comparing CBT with TAU/WL is small and heterogeneous.

Visit-to-visit variability in blood pressure (BP) increases stroke risk, independent of mean BP. However, its physiological validity, the ideal method of measurement and the mechanisms increasing cardiovascular risk are unclear. In meta-analyses of individual patient data, I pooled associations between BP variability and risk of stroke, all cardiovascular events and death. I then determined antihypertensive drug-class differences in cardiovascular risk, intra-individual (I-VR) and inter-individual BP variability (M-VR). In 500 Oxford Vascular Study (OXVASC) patients undergoing thrice-daily home (HBPM) and awake ambulatory monitoring (ABPM), associations between mean, maximum or variability in BP (CV-BP) were determined with premorbid BP, hypertensive arteriopathy (creatinine, aortic stiffness, cognitive impairment, stroke versus TIA and leukoaraiosis) and cardiovascular events. In 200 patients, I determined associations with pulsatility or stiffness (pulse wave velocity) in cerebral and aortic vessels. There was a 21% and 27% increased risk of stroke and myocardial infarction per standard deviation of CV-SBP in 318700 patients, independent of mean SBP. In 244,479 patients, SBP variability was reduced by CCBs and diuretics within (I-VR=0.89, 95% CI=0.82-0.96, p=0.0001) and between individuals (M-VR 0.83, 0.77-0.89, p<0.0001), especially in the first year of treatment, explaining drug class differences in stroke risk (OR=0.76, 0.68-0.87, p<0.0001). In OXVASC, drug class differences on day-to-day SBP variability were greatest immediately after waking. Residual hypertension after treatment on HBPM but not ABPM (BP>135/85) predicted recurrent cardiovascular events (HR 2.82, 1.44-5.51, p=0.002 vs. 1.48, 0.68-3.23, p=0.33), reflecting stronger associations with premorbid BP and hypertensive arteriopathy, due largely to inaccuracy of ABPM in patients aged >65 years. Furthermore, day-to-day maximum and CV-SBP were associated with premorbid BP, hypertensive arteriopathy and cardiovascular events, with no additional predictive value of mean SBP when analysed with maximum SBP. Maximum SBP was greater in men and CV-SBP in women, whilst age and creatinine determined both. Increased stroke risk may partly be due to the association between BP variability and cerebral pulsatility, which was correlated with leukoaraiosis (p=0.01) and determined by aortic stiffness (p=0.016) and pulsatility (p<0.001). BP variability is clinically significant and physiologically valid, and is treatable with CCBs and diuretics. After TIA or minor stroke, HBPM best identifies residual hypertension and demonstrates the predictive value of BP variability and maximum BP, but associated arterial changes might explain some of the increased stroke risk.

Stroke is the 2nd leading cause of death in the UK and worldwide. 150,000 people have a stroke each year in the UK (ischaemic stroke being the most common) and a significant proportion of NHS resources go towards the treatment of these individuals (~£2.8 billion). Twin and family history studies have shown that having affected relatives makes you between 30 and 76% more likely to suffer a stroke, suggesting that there is a genetic component to the disease. So far, no genes have been convincingly associated with stroke. Intermediate traits may be useful tools for identifying genetic factors in complex disease. For stroke, two commonly used intermediate traits are carotid intima-media thickness (CIMT) and white matter hyperintensities (WMHs), which both show high heritabilities. These traits have both been studied widely for associations with many candidate gene polymorphisms. In this thesis I systematically reviewed the literature for all genetic association studies of these two traits. Where particular associations have been studied in large numbers I meta-analysed the available data, developing novel methods for meta-analysis of genetic association data. I found there was substantial heterogeneity and small study bias in the literature and most polymorphisms have still been studied in too small numbers to make accurate conclusions. Apolipoprotein E (APOE) ε is the only polymorphism which shows a consistent association with CIMT, even when only the largest studies are analysed (MD 8μm (95% CI 6 to 11) between E4 and E3, and E3 and E2). No polymorphism has shown a convincing association with WMHs and interestingly APOE appears unlikely to be associated with this trait. This is consistent with previous work that shows that APOE is associated with large artery but not small artery stroke. Taking this hypothesis I attempted to investigate the association of APOE comparing patients who have had a large artery stroke with those who have had a small artery stroke in the Edinburgh Stroke Study cohort. However, genotyping of this polymorphism failed and I present investigatory analyses of problems from the genotyping laboratory.

The increasing prevalence of Alzheimer’s disease poses a considerable socioeconomic challenge in the years ahead. There are few clinical treatments available and none capable of halting or slowing the progressive nature of the condition. Despite decades of experimental research and testing over 300 interventions in transgenic mouse models of the condition, clinical success has remained elusive. Deepening our understanding of how such studies have been conducted is likely to provide insights which could inform future preclinical and clinical research. Therefore I performed a systematic review and meta-analysis on interventions tested in transgenic mouse models of Alzheimer’s disease. My systematic search was performed by electronically searching for publications reporting the efficacy of interventions tested in transgenic models of Alzheimer's disease. Across these publications I extracted data regarding study characteristics and reported study quality alongside outcome data for pathology (i.e. plaque burden, amyloid beta species, tau, cellular infiltrates and neurodegeneration) and neurobehaviour. From these data I calculated estimates of efficacy using random effects meta-analysis and subsequently investigated the potential impact of study quality and study characteristics on observed effect size. My search identified 427 publications, 357 interventions and 55 transgenic models representing 11, 688 animals and 1774 experiments. There were a number of principal concerns regarding the dataset: (i) the reported study quality of such studies was relatively low; less than 1 in 5 publications reported blinded assessment of outcome or random allocation to group and no studies reported a sample size calculation, (ii) the depth of data on any individual intervention was relatively poor-only 16 interventions had outcomes described in 5 or more publications and (iii) publication bias analyses suggested 1 in 5 pathological and 1 in 7 neurobehavioural experiments remain unpublished. Where I inspected relationships between outcomes, meta-regression identified a number of notable associations. Changes in amyloid beta 40 were reflective of changes in amyloid beta 42 (R2 = 0.84, p<0.01) and within the Morris water maze changes in the ‘training’ acquisition phase could explain 44% of the changes in the probe ‘test’ phase (p<0.05). Additionally, I identified measures of neurodegeneration as the best pathological predictors of changes in neurobehaviour (R2 = 0.72, p<0.01). Collectively this work identifies a number of potential weaknesses within in vivo modelling of Alzheimer’s disease and demonstrates how the use of empirical data can inform both preclinical and clinical studies.

Cell cycle (CC) and TP53 regulatory networks are frequently deregulated in cancer. While numerous genome-wide studies of TP53 and CC-regulated genes have been performed, significant variation between studies has made it difficult to assess regulation of any given gene of interest. To overcome the limitation of individual studies, we developed a meta-analysis approach to identify high confidence target genes that reflect their frequency of identification in independent datasets. Gene regulatory networks were generated by comparing differential expression of TP53 and CC-regulated genes with chromatin immunoprecipitation studies for TP53, RB1, E2F, DREAM, B-MYB, FOXM1 and MuvB. RNA-seq data from p21-null cells revealed that gene downregulation by TP53 generally requires p21 (CDKN1A). Genes downregulated by TP53 were also identified as CC genes bound by the DREAM complex. The transcription factors RB, E2F1 and E2F7 bind to a subset of DREAM target genes that function in G1/S of the CC while B-MYB, FOXM1 and MuvB control G2/M gene expression. Our approach yields high confidence ranked target gene maps for TP53, DREAM, MMB-FOXM1 and RB-E2F and enables prediction and distinction of CC regulation. A web-based atlas at www.targetgenereg.org enables assessing the regulation of any human gene of interest.

Reliability Generalization (RG) is a meta-analytic method that examines the sources of measurement error variance for scores for multiple studies that use a certain instrument or group of instruments that measure the same construct (Vacha-Haase, Henson, & Caruso, 2002). Researchers have been conducting RG studies for over 10 years since it was first discussed by Vacha-Haase (1998). Henson and Thompson (2002) noted that, as RG is not a monolithic technique; researchers can conduct RG studies in a variety of ways and include diverse variables in their analyses. Differing recommendations exist in regards to how researchers should retrieve, code, and analyze information when conducting RG studies and these differences can affect the conclusions drawn from meta-analytic studies (Schmidt, Oh, & Hayes, 2009) like RG. The present study is the first comprehensive review of both current RG practices and RG recommendations. Based upon the prior research findings of other meta-analytic review papers (e.g., Dieckmann, Malle, & Bodner 2009), the overarching hypothesis was that there would be differences between current RG practices and best practice recommendations made for RG studies. Data consisted of 64 applied RG studies and recommendation papers, book chapters, and unpublished papers/conference papers. The characteristics that were examined included how RG researchers: (a) collected studies, (b) organized studies, (c) coded studies, (d) analyzed their data, and (e) reported their results. The results showed that although applied RG researchers followed some of the recommendations (e.g., RG researchers examined sample characteristics that influenced reliability estimates), there were some recommendations that RG researchers did not follow (e.g., the majority of researchers did not conduct an a priori power analysis). The results can draw RG researchers’ attentions to areas where there is a disconnect between practice and recommendations as well as provide a benchmark for assessing future improvement in RG implementation.