Alzheimer’s disease (AD) is a neurodegenerative disorder with no existing cure. Since cognitive control influences saccade behaviour, saccades provide a valuable tool when studying cognitive changes in healthy and pathological aging. This thesis aims to evaluate differences in predictive capacity and working memory between cognitively normal older adults (NC) and mild AD patients using customized saccade paradigms and a battery of neuropsychological tests. In the predictive paradigm, we hypothesize that AD participants would display a decreased level of prediction, predictive capacity and learning capacity. In the memory-guided paradigm, we hypothesize that AD participants would have a decreased ability to maintain fixation and capacity to retain information and reproduce it correctly. Overall, we found that in the predictive paradigm, NC displayed a greater degree of prediction than AD participants. However, both groups had an optimal level of prediction at intermediate inter-stimulus intervals (ISI) (750 and 1000 ms). As ISI increased, both groups, although more so in AD, elicited a greater proportion of SRTs below -200 ms and -400 ms. This may suggest that as ISI increased, participants switched from a predictive to an anticipatory/guessing strategy. At an ISI of 500 ms, NC’s learning capacity was greater than AD participants. Cognitive scores of neuropsychological tests did not correlate with learning capacity in NC. However, learning capacity in AD participants was positively correlated with working memory capacity and attentional control. The memory-guided paradigm revealed AD participants completed less viable trials, less correct trials, and had more combined directional and timing errors than NC. Cognitive correlations showed that NC’s working memory capacity positively correlated with the frequency of correct trials, whilst negatively correlating with saccade errors. Since AD participants completed 10% of viable trials correctly, the task may have been too difficult for AD participants to comprehend, rendering correlations invalid. These findings suggest that although the predictive paradigm does not solely assess for prediction, it may provide a measure to cognitively differentiate NC from AD patients, and detect AD severity. Since the memory-guided paradigm may be too difficult for AD participants, it may provide a better indicator of cognitive changes associated with healthy aging. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2013-05-21 18:54:19.492

La réalisation de prédictions précises et surprenantes est une pratique essentielle des sciences empiriques et la confirmation de ces prédictions semble représenter l’un de leurs principaux succès théoriques et pratiques. Ainsi de nombreux scientifiques et épistémologues attribuent-ils aux succès prédictifs le pouvoir de confirmer des hypothèses, d’influencer le cours de l’histoire scientifique, voire de révéler quelles théories reflètent la réalité. Pourtant les prédictions s’appuient souvent sur des représentations simplifiées, idéalisées ou fictionnelles de la réalité. L’objectif de cette thèse est d’analyser l’activité prédictive pour comprendre en quoi consistent les succès prédictifs et quelle portée on peut légitimement leur conférer. L’enjeu de cette analyse est notamment de savoir si une théorie ayant engendré un succès prédictif peut être considérée comme vraie ou partiellement vraie.La première partie de la thèse est consacrée à l’analyse de l’activité prédictive et conclut qu’il existe une pluralité de raisonnements et de succès prédictifs. La deuxième partie étudie l’influence de ces succès sur l’évolution d’une discipline, la cosmologie, de 1917 à nos jours et montre que les scientifiques attribuent de l’importance aux prédictions qui indiquent la capacité prédictive d’une hypothèse ou d’une théorie. Dans la troisième partie, je soutiens que le rôle des prédictions dans le choix rationnel des hypothèses est de permettre de juger de leur fécondité. La quatrième partie étudie les limites de la portée des succès prédictifs en montrant qu’ils ne permettent pas de savoir quels aspects des théories dont ils sont issus reflètent la réalité. / Deriving precise and surprising predictions is a key feature of scientific activity. The confirmation of these predictions by severe tests seems to represent major theoretical and practical successes in the field of empirical sciences. Therefore, many scientists and philosophers of science view predictive successes as having an important weight in scientific change, theory choice and for the identification of true claims about reality. However, predictions are often derived from simplified or idealised representations of real-world systems. The aim of this dissertation is to analyse the predictive activity of empirical sciences in order to circumscribe the scope of predictive success. First, I claim that predictive successes come in many forms and structures. In the second part, I investigate the impact of successful predictions in the history of modern cosmology since 1917 and argue that scientists value predictions attesting the predictive capacity of new hypotheses. In a third part, I examine the weight of successful predictions in the confirmation of hypotheses and claim that they serve as a proxy for one of the most important virtues of theories: fruitfulness. The last part is dedicated to the limits of scientific successes and shows that novel predictions cannot help us to circumscribe which posits of scientific theories are worthy of belief.

Submitted by Mario BC (mario@bc.ufrpe.br) on 2016-08-15T12:27:23Z No. of bitstreams: 1 Diogenes Virginio do Nascimento.pdf: 1474487 bytes, checksum: 048118961940a4468c5c60cb32deca19 (MD5) / Made available in DSpace on 2016-08-15T12:27:23Z (GMT). No. of bitstreams: 1 Diogenes Virginio do Nascimento.pdf: 1474487 bytes, checksum: 048118961940a4468c5c60cb32deca19 (MD5) Previous issue date: 2015-07-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This work is related to knowledge of Pedotransfer functions (PTF), enabling an understanding about water soil content influenced by soil properties and analyzes to generate PTFs. This study aimed was proposed pedotransfer functions (PTF) based on hydro-physical soil properties and organic carbon to estimate soil moisture. The study was conducted in the area owned by Santa Teresa Plant in Goiana City, PE (7º36'56 "S 34º59'19" W) with sugarcane crop (Saccharum spp) irrigated by Lateral Move System. Field capacity (θfc) and wilting point (θwp) were assumed by dependent variables. Sand, silt, clay, soil bulk density and organic carbon were adopted as independent variables. Pedotransfer functions generated in this study estimate soil moisture to matric potential at -10 kPa, equivalent to θfc, in sandy soils and at -33 kPa to clay soils and matric potential at -1.500 kPa to θwp in 0-20; 20-40 e 40-60cm soil depth. These functions were classified as “Point PTF”, since estimated specific points to matric potential to soil water retention. Statistical indices and graphic analyses (1:1 ratio) between model-predicted and observed data were used to evaluate PTFs performance. The following statistical indices were used: Correlation coefficient (r), Concordance index (d), Maximum error (ME), Square root mean squared error normalized (RMSE), Coefficient of residual mass (CRM), Mean absolute error (MAE), Performance Index (c) and Determination coefficient (R²). Statistical indices that evaluate generated models to estimate soil water content indicated high performance for most of PTFs and good correlation between observed and estimated values at matric potential studied in all soil layers analyzed. Thus, retention water estimated by PTFs can be an interesting alternative to support irrigation management at sugarcane. / Esta dissertação é referente aos conhecimentos sobre Funções de Pedotransferência (FPT), possibilitando um entendimento relacionado ao conteúdo de água no solo a partir das influências nas propriedades do solo e nas análises estabelecidas para gerar as FPTs. O objetivo deste trabalho foi gerar funções de pedotransferência com base em atributos físico-hídricos do solo e a relação do carbono orgânico para estimar a umidade do solo. O trabalho foi realizado na área pertencente à Usina Santa Teresa localizada no município de Goiana, PE (7º36’56”S 34º59’19”W), em área cultivada com cana-de-açúcar (Saccharum spp) irrigada por sistema Lateral Móvel Linear. As variáveis adotadas como dependentes foram umidade na capacidade de campo (θcc) e umidade no ponto de murcha permanente (θpmp) e as variáveis independentes foram areia, silte, argila, densidade do solo e carbono orgânico. As funções de pedotransferência foram geradas a partir do método de regressão linear múltipla aplicando a técnica de stepwise backward elimination para seleção das variáveis candidatas ao modelo. Assim, as FPT geradas estimam o conteúdo de água no solo equilibrada nos potenciais mátricos equivalentes à umidade na capacidade de campo de -10kPa para solos arenosos, -33kPa para solos argilosos e ao ponto de murcha permanente de -1500kPa, nas camadas de 0-20; 20-40 e 40-60cm, totalizando 99 amostras. Essas funções foram classificadas como FPT pontuais, uma vez que, estima pontos específicos aplicados nas tensões de interesse para retenção de água no solo. O desempenho das Funções de pedotransferência foram analisadas graficamente pela relação 1:1, entre os dados estimados versus dados observados e por meio dos seguintes indicadores estatísticos: Coeficiente de correlação (r), Índice de concordância (d), Erro máximo (ME), Raiz quadrada do erro médio quadrático normalizado (RMSE), Coeficiente de massa residual (CRM), Erro absoluto médio (EAM), Índice de desempenho (c) e coeficiente de determinação (R²). Os índices estatísticos, que avaliam os modelos gerados para estimar a umidade volumétrica no solo estudado, apresentaram valores que indicam elevado desempenho para a maioria das FPTs e boa correlação entre os valores observados e estimados nas tensões estudadas e em todas as camadas de solo analisadas. Assim, a estimativa da retenção de água no solo por meio da FPTs apresenta-se como uma alternativa para auxiliar as técnicas adotadas no manejo de irrigação da cana-de-açúcar.

The main expansion of the discovery of genetic variants associated with complex diseases has occurred during the last decade. This expansion has been accompanied, and in some sense motivated, by the desire to use this information to improve the predictive capacity of many diseases with an unidentified familial component, including coronary heart disease (CHD), with the aim of translating this genetic knowledge into clinical practice. This doctoral thesis is structured in two lines of investigation that address distinct aspects of this issue, first to evaluate the possible role of genetic variation in a candidate gene in modulating CHD risk, and second to evaluate whether genetic information can be used to improve risk assessment tools used in clinical practice. In the first research line (described in Part I), we investigate the contribution of genetic variation in one of the most widely-studied genes in cardiovascular genetics, ESR1, which encodes the Oestrogen receptor α protein. We provide a solid meta-analysis of evidence regarding the most widely-studied variant in this gene and we further explore the role of a broad range of common and uncommon variants in this gene in CHD risk. Using these approaches, we find no evidence of association between the genetic variants studied and CHD risk. However, although we can confidently accept that common genetic polymorphisms are not associated with cardiovascular disease, we cannot discard the possibility that other types of variation in this gene (for instance epigenetic variation) could modify susceptibility to cardiovascular disease, or that other elements of this pathway are associated with an increased risk of CHD. In this research I have provided a reliable answer to this long running unanswered question in cardiovascular genetics, allowing research to re-focus on other elements of this system or other pathways. In the second line, we explored the possible utility of genetic information obtained from genome-wide association studies (GWAS) in prediction of 10-year risk of CHD events by adding this information to cardiovascular risk functions. We have followed the recommendations proposed by the American Heart Association for evaluating the utility of novel biomarkers in clinical practice, and have demonstrated that although the magnitudes of the effects of these genetic variants on CHD risk are modest, there is a tendency towards improvement in the capacity of the risk functions to predict future CHD events. The translation of genetic information into clinical practice was one of the main motivations for the investment in genome-wide association studies, and my research represents one of the first efforts to explore this possibility. / L’expansió principal pel que fa al descobriment de variants genètiques associades amb malalties complexes s’ha dut a terme durant la última dècada. Aquesta expansió ha estat acompanyada, i d’alguna forma motivada, pel desig d’usar aquesta informació per millorar la capacitat de predicció d’aquelles malalties on hi és present un cert component familiar però en les que no es coneixien les variants que conferien un major risc de patir la malaltia, entre elles la cardiopatia isquèmica (CI). La present tesis doctoral està estructurada en dues línies d’investigació que avaluen el possible rol d’un gen candidat en la susceptibilitat de la CI i també avalua la millora en la capacitat de predicció d’un esdeveniment coronari de les eines usades habitualment en la pràctica clínica mitjançant la inclusió d’informació genètica. Més concretament, la primera línea d’investigació es centra en la contribució de la variació genètica en un dels gens més estudiats en relació amb CI: el gen que codifica pel receptor d’estrogens alfa (ESR1). En aquesta línea hem proveït un sòlid meta-anàlisis entre la variant més àmpliament estudiada d’aquest gen i risc coronari i també hem explorat el paper de la majoria de les variants comunes descrites en aquest gen i risc de CI. Mitjançant cap dels anàlisis hem trobat evidència d’associació entre les variants genètiques en aquest gen i el risc de CI. No obstant això, i encara que podem acceptar que les variants genètiques comunes d’aquest gen no estan associades amb esdeveniments coronaris, no podem descartar que altres tipus de variació en aquest gen (com per exemple variació epigenètica) pugui estar modificant la susceptibilitat a patir un esdeveniment coronari, ni tampoc que altres elements de la mateixa cadena de senyalització estiguin associats amb la malaltia. En la segona línea d’investigació, hem explorat el possible paper de les variants genètiques, obtingudes mitjançant estudis d’associació global del genoma (GWAS), en la millora de la capacitat de predicció a 10 anys dels esdeveniments coronaris, mitjançant la seva addició en les funcions de risc cardiovascular clàssiques. Hem seguit les recomanacions proposades per la American Heart Association per l’avaluació en la pràctica clínica de nous biomarcadors, i hem demostrat que, tot i que la magnitud de l’associació d’aquestes variants és modesta, hi ha una tendència cap a la millora de la capacitat de predicció de les funcions de risc.

Les résultats des quelques études examinant le lien entre la présence de symptômes dépressifs et le décrochage divergent. De telles divergences pourraient s’expliquer par certaines caractéristiques individuelles clés comme le sexe ou l’âge, qui pourraient modérer le lien entre les symptômes dépressifs et le décrochage. Cette étude a pour double objectif 1) d’évaluer le lien entre la présence de symptômes dépressifs mesurés à différents moments au secondaire et le décrochage scolaire, et 2) d’examiner les variations possibles en fonction du sexe. Des données auto-rapportées (sur la présence de symptômes dépressifs en secondaire 1, 2 et 3) et administratives (sur le décrochage scolaire) obtenues auprès d’une cohorte composée de 6272 jeunes du secondaire ont été utilisées. Les résultats révèlent qu’après l’inclusion de variables de contrôles importantes, il n’y a pas d’association entre la dépression et le décrochage scolaire. De plus, ils indiquent que le sexe ne joue pas de rôle modérateur, c’est-à-dire qu’il n’y a pas de lien entre la dépression et le décrochage ni chez les filles, ni chez les garçons. Ces résultats suggèrent que les conclusions divergentes des études précédentes sur le sujet pourraient refléter le manque de considération d’une variété, mais surtout d’un nombre suffisants de facteurs confondants. Ils réitèrent aussi l’importance des facteurs de risque déjà connus du décrochage et suggèrent que les interventions se centrant l’humeur dépressive doivent faire partie de programmes visant en parallèle d’autres problématiques plus étroitement associées au décrochage. / Studies examining potential links between depressive symptoms and dropout have yielded inconsistent results. These inconsistencies could be explained by potential moderating effects of key individual characteristics, such as gender or age. This study has two main objectives: 1) to measure the association between depressive symptoms as measured at different grades during high school and dropout, and 2) to examine the possible impact of gender as a moderator variable. We used self-reported data to assess depressive symptoms in 7th, 8th and 9th grade and official administrative data to determine dropout status among a cohort of 6,272 high-school students. Results indicate that after controlling for a variety of potentially confounding variables, the association between depression and dropout was no longer significant. Furthermore, the analysis indicate that gender does not play a moderating role, meaning that there is no link between depression and dropping out among girls, nor boys. These results suggest that the conflicting results observed in the literature may reflect a difference in the variety and, more importantly, the number of variables used to control for confounding effect. Furthermore, the results reiterate the importance of known dropout risk factors for dropout and suggest that preventive interventions focusing on depressive symptoms should be part of larger programs also aiming at other factors more closely related to school dropout.