The role of molecular, clinical and socioeconomic factors in the long-term survival of axillary node negative breast cancer patients

The overall objective of this study was to investigate factors associated with long-term survival in axillary node negative (ANN) breast cancer patients. Clinical and biological factors included stage, histopathologic grade, p53 mutation, Her-2/neu amplification, estrogen receptor status (ER), progesterone receptor status (PR) and vascular invasion. Census derived socioeconomic (SES) indicators included median individual and household income, proportions of university educated individuals, housing type, "incidence" of low income and an indicator of living in an affluent neighbourhood. The effects of these measures on breast cancer-specific survival and competing cause survival were investigated. A cohort study examining survival among axillary node negative (ANN) breast cancer patients in the greater Toronto area commenced in 1 989. Patients were followed up until death, lost-to-follow up or study termination in 2004. Data were collected from several sources measuring patient demographics, clinical factors, treatment, recurrence of disease and survival. Census level SES data were collected using census geo-coding of patient addresses' at the time of diagnosis. Additional survival data were acquired from the Ontario Cancer Registry to enhance and extend the observation period of the study. Survival patterns were examined using KaplanMeier and life table procedures. Associations were examined using log-rank and Wilcoxon tests of univariate significance. Multivariate survival analyses were perfonned using Cox proportional hazards models. Analyses were stratified into less than and greater than 5 year survival periods to observe whether known markers of short-tenn survival were also associated with reductions in long-tenn survival among breast cancer patients. The 15 year survival probabilities in this cohort were: for breast cancerspecific survival 0.88, competing causes survival 0.89 and for overall survival 0.78. Estrogen receptor (ER) and progesterone receptor (PR) status (Hazard Ratio (HR) ERIPR- versus ER+/PR+, 8.15,95% CI, 4.74, 14.00), p53 mutation (HR, 3.88, 95% CI, 2.00, 7.53) and Her-2 amplification (HR, 2.66, 95% CI, 1.36, 5.19) were associated with significant reductions in short-tenn breast cancer-specific survival «5 years following diagnosis), however, not with long-term survival in univariate analyses. Stage, histopathologic grade and ERiPR status were the clinicallbiologieal factors that were associated with short-term breast cancer specific survival in multivariate results. Living in an affluent neighbourhood (top quintile of median household income compared to the rest of the population) was associated with the largest significant increase in long-tenn breast cancer-specific survival after adjustment for stage, histopathologic grade and treatment (HR, 0.36, 95% CI, 0.12, 0.89).

Completing the picture: the effects of video game practice on verbal and performance I.Q. scores in high functioning children

The strength and nature of the video game practice effect on tests of visual and perceptual skills were examined using high functioning Grades Four and Five students who had been tested with the WISC-R .for the purpose of gifted identification and placement. The control group, who did not own and .play video games on a sustained basis, and the experimental group, who did own a video game system and had some mastery of video games, including the -Nintendo game, "Tetris", were each composed of 18 juniorg:r;-ade students and were chosen from pre-existing conditions. The experimental group corresponded to the control group in terms of age, sex, and community. Data on the Verbal and Performance I.Q. Scores were· collected for both groups and the author was interested in the difference between the Verbal and Performance Scores within each group, anticipating a P > V outcome for the experimental group. The results showed a significant P > V difference in the experimental, video game playing group, as expected, but no significant difference between the Performance $cores of the control and experimental groups. The results, thus, indicated lower Verbal I.Q. Scores in the experimental group relat'ive to 'the control group.' The study conclu~ed that information about a sUbject's video game experience and "learhing style pref~rence is important for a clear interpretation of the Verbal and Performance I.Q. Scores of the WISC-R. Although the time spent on video game play may, 'indeed, increase P~rformance Scores relative to Verbal Scores for an individual, the possibilities exist that the time borrowed and spent away from language based activities may retard verbal growth and/or that the cognitive style associated with some Performance I.Q.subtests may have a negative effect on the approach to the tasks on the Verbal I.Q. Scale. The study also discussed the possibility that exposure to ,the video game experience, in pre-puberty, can provide spatial instruction which will result in improved spatial skills. strong spatial skills have been linked to improved performance and preference in mathematics, science, and engineering and it was suggested that appropriate video game play might be a way to involve girls more in the fields of mathematics and science.

Mediating Influence of Physical Fitness on the Relationship between Academic Performance and Motor Proficiency

We explored the potential mediating influence of physical fitness on the relationship between academic performance and motor proficiency in children. 1864 students (F:926, M:938, age 11.91 (SD:0.34). Academic achievement was derived from an average of standardized tests of reading, writing, and math. The Bruininks-Oseretsky Test of Motor Performance (short-form) determined motor proficiency. Fitness (peak oxygen uptake) was established with the Léger 20-m Shuttle Run Test. OLS regression identified several significant predictors of academic performance. After controlling for age (p=0.0135), gender (p<0.0001), and parental education (p<0.0001), motor proficiency (p<0.0001), was significant. After adding physical fitness (p=0.0030) to the model the effect of motor proficiency remained significant however the point estimate was reduced from 0.0034 (p<0.0001) to 0.0026 (p<0.0001). These results suggest that physical fitness plays a mediating role on the relationship between academic performance and motor proficiency although both aerobic fitness and motor proficiency have independent roles.

Personality traits and individual differences predict changes in postural control under conditions of height-induced postural threat

This thesis explored whether individual characteristics could predict changes in postural control in young adults under conditions of height-induced postural threat. Eighty-two young adults completed questionnaires to assess trait anxiety, trait movement reinvestment, physical risk-taking, and previous experience with height-related activities. Tests of static (quiet standing) and anticipatory (rise to toes) postural control were completed under conditions of low and high postural threat manipulated through changes in surface height. Individual characteristics were able to significantly predict changes in static, but not anticipatory postural control. Trait movement reinvestment and physical risk-taking were the most influential predictors. Evidence was provided that changes in fear and physiological arousal mediated the relationship between physical risk-taking and changes in static postural control. These results suggest that individual characteristics shape the postural strategy employed under threatening conditions and may be important for clinicians to consider during balance assessment and treatment protocols.

Simulation-Based Finite and Large Sample Tests in Multivariate Regressions.

In the context of multivariate linear regression (MLR) models, it is well known that commonly employed asymptotic test criteria are seriously biased towards overrejection. In this paper, we propose a general method for constructing exact tests of possibly nonlinear hypotheses on the coefficients of MLR systems. For the case of uniform linear hypotheses, we present exact distributional invariance results concerning several standard test criteria. These include Wilks' likelihood ratio (LR) criterion as well as trace and maximum root criteria. The normality assumption is not necessary for most of the results to hold. Implications for inference are two-fold. First, invariance to nuisance parameters entails that the technique of Monte Carlo tests can be applied on all these statistics to obtain exact tests of uniform linear hypotheses. Second, the invariance property of the latter statistic is exploited to derive general nuisance-parameter-free bounds on the distribution of the LR statistic for arbitrary hypotheses. Even though it may be difficult to compute these bounds analytically, they can easily be simulated, hence yielding exact bounds Monte Carlo tests. Illustrative simulation experiments show that the bounds are sufficiently tight to provide conclusive results with a high probability. Our findings illustrate the value of the bounds as a tool to be used in conjunction with more traditional simulation-based test methods (e.g., the parametric bootstrap) which may be applied when the bounds are not conclusive.

Simulation-Based Finite-Sample Normality Tests in Linear Regressions

In the literature on tests of normality, much concern has been expressed over the problems associated with residual-based procedures. Indeed, the specialized tables of critical points which are needed to perform the tests have been derived for the location-scale model; hence reliance on available significance points in the context of regression models may cause size distortions. We propose a general solution to the problem of controlling the size normality tests for the disturbances of standard linear regression, which is based on using the technique of Monte Carlo tests.

Localisation des aires cérébrales impliquées dans le rappel de mots : validation d’un protocole d’imagerie optique

Jusqu'à récemment, les patients souffrant d'épilepsie réfractaire aux traitements médicamenteux étaient destinés à un avenir incertain. Le recours à la chirurgie comme traitement alternatif offre l'espoir de mener un jour une vie normale. Pour déterminer si un patient peut bénéficier d’une intervention chirurgicale, une évaluation complète est cruciale. Les méthodes d’évaluation préchirurgicale ont connu des progrès importants au cours des dernières décennies avec le perfectionnement des techniques d’imagerie cérébrale. Parmi ces techniques, la spectroscopie proche infrarouge (SPIR), aussi connue sous le nom d’imagerie optique, présente de nombreux avantages (coût, mobilité du participant, résolution spatiale et temporelle, etc.). L’objectif principal de cette étude est de développer un protocole d'évaluation préchirurgicale de la mémoire. Une tâche de mémoire verbale incluant l’encodage, le rappel immédiat et le rappel différé de listes de mots a été administrée à dix adultes sains lors d’un enregistrement en imagerie optique. Les résultats obtenus suggèrent l’activation bilatérale des aires préfrontales antérieures et dorsolatérales ainsi que des aires temporales antérieures et moyennes. Les aires préfrontales et temporales antérieures semblent modulées par les différents processus mnésiques et la position du rappel dans le temps. La première fois qu’une liste est rappelée, l’activité hémodynamique est plus élevée que lors des rappels subséquents, et ce, davantage dans l’hémisphère gauche que dans l’hémisphère droit. Cette étude constitue la première étape dans le processus de validation du protocole à des fins cliniques auprès de patients épileptiques.

Mesure de l’activité physique par accélérométrie : validation et précision de la mesure

Introduction : Les accéléromètres sont actuellement les appareils les plus utilisés pour mesurer le niveau d’activité physique, et ce, parce qu'ils évaluent les niveaux d'activité physique de façon objective. Toutefois, les mouvements humains sont difficiles à mesurer, et de nombreuses limitations doivent être prises en considération pour la bonne utilisation des accéléromètres. Les études présentées s’intéressent donc à la validité de la fonction podomètre des accéléromètres ainsi qu’à la validation de la composante accéléromètre d’un nouvel appareil multicapteur (SenseDoc). Méthode : Les sujets ayant participé à la première étude, qui consistait en la validation de la fonction podomètre des accéléromètres, ont marché sur un tapis roulant à trois vitesses différentes (2,5 km/h, 3,5 km/h et 4,8 km/h) pendant 5 minutes par palier. Un accéléromètre (ActiGraph GT3X) porté à la ceinture a enregistré le nombre de pas tandis qu'une caméra a enregistré la marche des participants. Pour la seconde étude, les participants portaient un accéléromètre Actigraph et un SenseDoc à la hanche. Les données brutes des accéléromètres et la mesure de la consommation d’oxygène par calorimétrie indirecte ont été mesurées lors de 14 activités réalisées en laboratoire allant de sédentaires à vigoureuses. Résultats : La première étude indique que les accéléromètres ont détecté seulement 53 % des pas à 2,5 km/h, 82 % à 3,5 km/h et 91 % à 4,8 km/h pour les personnes non obèses. Pour les personnes obèses, l'accéléromètre a détecté 47 % des pas à 2.5 km/h, 67 % à 3.5 km/h et 100 % à 4.8 km/h, des résultats significativement différents des personnes non obèses. La seconde étude confirme pour sa part que le SenseDoc est un outil valide de mesure du niveau d’activité physique. Les accéléromètres possèdent une bonne capacité prédictive de la dépense énergétique avec des valeurs de R carré de 0,84 et 0,80 respectivement pour l'Actigraph et le SenseDoc. Conclusion : À vitesse de marche lente, les accéléromètres sous-estiment le nombre de pas, et ce, dans une plus large mesure chez les personnes obèses que chez les personnes non obèses. Également, une méthode valide et transparente de transformation de données brutes d’accélérométrie a été divulguée dans l’étude avec le SenseDoc. Les travaux présentés dans ce mémoire visent à améliorer l’utilisation en milieu clinique et en recherche des accéléromètres et ouvrent la voie à une plus grande uniformité entre les études utilisant différents types d’accéléromètres.

Mesures subjectives et épidémiologie : problèmes méthodologiques liés à l'utilisation des techniques psychométriques

L’utilisation des mesures subjectives en épidémiologie s’est intensifiée récemment, notamment avec la volonté de plus en plus affirmée d’intégrer la perception qu’ont les sujets de leur santé dans l’étude des maladies et l’évaluation des interventions. La psychométrie regroupe les méthodes statistiques utilisées pour la construction des questionnaires et l’analyse des données qui en sont issues. Ce travail de thèse avait pour but d’explorer différents problèmes méthodologiques soulevés par l’utilisation des techniques psychométriques en épidémiologie. Trois études empiriques sont présentées et concernent 1/ la phase de validation de l’instrument : l’objectif était de développer, à l’aide de données simulées, un outil de calcul de la taille d’échantillon pour la validation d’échelle en psychiatrie ; 2/ les propriétés mathématiques de la mesure obtenue : l’objectif était de comparer les performances de la différence minimale cliniquement pertinente d’un questionnaire calculée sur des données de cohorte, soit dans le cadre de la théorie classique des tests (CTT), soit dans celui de la théorie de réponse à l’item (IRT) ; 3/ son utilisation dans un schéma longitudinal : l’objectif était de comparer, à l’aide de données simulées, les performances d’une méthode statistique d’analyse de l’évolution longitudinale d’un phénomène subjectif mesuré à l’aide de la CTT ou de l’IRT, en particulier lorsque certains items disponibles pour la mesure différaient à chaque temps. Enfin, l’utilisation de graphes orientés acycliques a permis de discuter, à l’aide des résultats de ces trois études, la notion de biais d’information lors de l’utilisation des mesures subjectives en épidémiologie.

A Data Mining Approach for the Identification of Adverse Drug Events (ADE) resulting from Drug-Drug Interactions (DDI) to improve pharmacovigilance

In the current study, epidemiology study is done by means of literature survey in groups identified to be at higher potential for DDIs as well as in other cases to explore patterns of DDIs and the factors affecting them. The structure of the FDA Adverse Event Reporting System (FAERS) database is studied and analyzed in detail to identify issues and challenges in data mining the drug-drug interactions. The necessary pre-processing algorithms are developed based on the analysis and the Apriori algorithm is modified to suit the process. Finally, the modules are integrated into a tool to identify DDIs. The results are compared using standard drug interaction database for validation. 31% of the associations obtained were identified to be new and the match with existing interactions was 69%. This match clearly indicates the validity of the methodology and its applicability to similar databases. Formulation of the results using the generic names expanded the relevance of the results to a global scale. The global applicability helps the health care professionals worldwide to observe caution during various stages of drug administration thus considerably enhancing pharmacovigilance

Towards the development of a new wavelet for ECG classification

In this paper an attempt has been made to determine the number of Premature Ventricular Contraction (PVC) cycles accurately from a given Electrocardiogram (ECG) using a wavelet constructed from multiple Gaussian functions. It is difficult to assess the ECGs of patients who are continuously monitored over a long period of time. Hence the proposed method of classification will be helpful to doctors to determine the severity of PVC in a patient. Principal Component Analysis (PCA) and a simple classifier have been used in addition to the specially developed wavelet transform. The proposed wavelet has been designed using multiple Gaussian functions which when summed up looks similar to that of a normal ECG. The number of Gaussians used depends on the number of peaks present in a normal ECG. The developed wavelet satisfied all the properties of a traditional continuous wavelet. The new wavelet was optimized using genetic algorithm (GA). ECG records from Massachusetts Institute of Technology-Beth Israel Hospital (MIT-BIH) database have been used for validation. Out of the 8694 ECG cycles used for evaluation, the classification algorithm responded with an accuracy of 97.77%. In order to compare the performance of the new wavelet, classification was also performed using the standard wavelets like morlet, meyer, bior3.9, db5, db3, sym3 and haar. The new wavelet outperforms the rest

Qualitätssicherung in der Physiotherapie: Evaluation von Performance-Tests

Hintergrund und Ziel: Ausgehend von einem Forschungsdefizit im Bereich von Performance-Tests, das von der Arbeitsgruppe um Bührlen et al. (2002) gekennzeichnet wurde, war es das Ziel der Arbeit einen Performance-Tests of lower limb activities (Polla) zu validieren. Methode: In einer Längsschnittstudie wurden die Ergebnisse einer sechswöchigen physiotherapeutischen Behandlung an einem 19-75jährigem orthopädisch-traumatologisch orientierten Patientenkollektiv (n=81) mit dem Polla und dem SF-36 Fragebogen erfasst. Ergebnisse: Die Ergebnisse machen eine gute Absicherung der Teststatistik deutlich. Bei ausgezeichneter Intrarater- (n=29) sowie guter Interrater-Reliabilität (n=32) weist die Konsistenzanalyse eine zufrieden stellende Zuverlässigkeit auf. Die Kriteriumsvalidität macht moderate Zusammenhänge zwischen dem Polla und den Dimensionen Schmerz, Körperliche Rollenfunktion und Körperliche Funktionsfähigkeit des SF-36 deutlich. Über die Standardized Response Mean zeigen die Instrumente eine große Änderungssensitivität, die nur für den Polla auch zum Follow-up (n=26) gilt. Schlussfolgerung: Der Polla ist ein kostenloses Testverfahren mit hoher praktischer Relevanz, wobei aus zeitökonomischen Gründen eine modifizierte Form des Polla mit nur zehn Items und einem gemessenen Test zu empfehlen ist.

Punching Shear Behavior of UHPC Flat Slabs

At the Institute of Structural Engineering of the Faculty of Civil Engineering, Kassel University, series tests of slab-column connection were carried out, subjected to concentrated punching load. The effects of steel fiber content, concrete compressive strength, tension reinforcement ratio, size effect, and yield stress of tension reinforcement were studied by testing a total of six UHPC slabs and one normal strength concrete slab. Based on experimental results; all the tested slabs failed in punching shear as a type of failure, except the UHPC slab without steel fiber which failed due to splitting of concrete cover. The post ultimate load-deformation behavior of UHPC slabs subjected to punching load shows harmonic behavior of three stages; first, drop of load-deflection curve after reaching maximum load, second, resistance of both steel fibers and tension reinforcement, and third, pure tension reinforcement resistance. The first shear crack of UHPC slabs starts to open at a load higher than that of normal strength concrete slabs. Typically, the diameter of the punching cone for UHPC slabs on the tension surface is larger than that of NSC slabs and the location of critical shear crack is far away from the face of the column. The angle of punching cone for NSC slabs is larger than that of UHPC slabs. For UHPC slabs, the critical perimeter is proposed and located at 2.5d from the face of the column. The final shape of the punching cone is completed after the tension reinforcement starts to yield and the column stub starts to penetrate through the slab. A numerical model using Finite Element Analysis (FEA) for UHPC slabs is presented. Also some variables effect on punching shear is demonstrated by a parametric study. A design equation for UHPC slabs under punching load is presented and shown to be applicable for a wide range of parametric variations; in the ranges between 40 mm to 300 mm in slab thickness, 0.1 % to 2.9 % in tension reinforcement ratio, 150 MPa to 250 MPa in compressive strength of concrete and 0.1 % to 2 % steel fiber content. The proposed design equation of UHPC slabs is modified to include HSC and NSC slabs without steel fiber, and it is checked with the test results from earlier researches.

Intrinsic test of independence in contingency tables

A condition needed for testing nested hypotheses from a Bayesian viewpoint is that the prior for the alternative model concentrates mass around the small, or null, model. For testing independence in contingency tables, the intrinsic priors satisfy this requirement. Further, the degree of concentration of the priors is controlled by a discrete parameter m, the training sample size, which plays an important role in the resulting answer regardless of the sample size. In this paper we study robustness of the tests of independence in contingency tables with respect to the intrinsic priors with different degree of concentration around the null, and compare with other “robust” results by Good and Crook. Consistency of the intrinsic Bayesian tests is established. We also discuss conditioning issues and sampling schemes, and argue that conditioning should be on either one margin or the table total, but not on both margins. Examples using real are simulated data are given

Rendimiento operativo de la tamizacion doble ajustada por raza para la deteccion de aneuploidias en poblacion colombiana

Actualmente, los algoritmos utilizados para la detección de alteraciones cromosómicas se han basado en los resultados obtenidos de poblaciones caucásicas, afrocaribeñas y asiáticas, las cuales, no tienen las mismas características de la raza mestiza. De allí, surgió el interés de realizar un estudio que permitiera determinar los valores de los marcadores serológicos, empleados en la tamización de aneuploidías, en población latina, para establecer un punto de corte ajustado a la raza mestiza. Se encuentra en desarrollo un estudio de validación de prueba diagnóstica, cuyos avances se presentan a continuación. En esta investigación, hasta el momento, se han incluido 1418 pacientes entre 11-13.6 semanas, sometidas a tamización combinada para la detección de aneuploidías. Se realizó un ajuste por raza de valores de medianas y sus múltiplos para los marcadores y se determinó el rendimiento operativo de la prueba luego de dicho ajuste. Posteriormente, se realizó una comparación entre ambas pruebas. Los niveles de B-hCG son 17.1 % más bajos en población mestiza colombiana, comparado con población caucásica y los niveles de PAPP-A son 19% inferiores. Las tasas de detección de la prueba, utilizando los valores convencionales, son del 60 % y, luego del ajuste por raza, es del 53 %. Haciendo el cálculo de riesgo, utilizando los nuevos múltiplos de mediana, no existen diferencias en aplicar la tamización con los valores convencionales entre las semanas 11 y 12 pero, en semana 13, los valores aplicados a población caucásica presentan una mejor tasa de detección que utilizar la prueba ajustada.