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).

Gas chromatographic electron capture negative ionization mass spectrometric (GC/ECNI/MS) determination of unique fluorinated compounds in the sediments of Lake Ontario and the effect of high-boiling alcohols (as injection solvents) on chromatographic behaviour of polycyclic aromatic hydrocarbons in gas chromatography

Part I - Fluorinated Compounds A method has been developed for the extraction, concentration, and determination of two unique fluorinated compounds from the sediments of Lake Ontario. These compounds originated from a common industrial landfill, and have been carried to Lake Ontario by the Niagara River. Sediment samples from the Mississauga basin of Lake Ontario have been evaluated for these compounds and a depositional trend was established. The sediments were extracted by accelerated solvent extraction (ASE) and then underwent clean-up, fractionation, solvent exchange, and were concentrated by reduction under nitrogen gas. The concentrated extracts were analyzed by gas chromatography - electron capture negative ionization - mass spectrometry. The depositional profile determined here is reflective of the operation of the landfill and shows that these compounds are still found at concentrations well above background levels. These increased levels have been attributed to physical disturbances of previously deposited contaminated sediments, and probable continued leaching from the dumpsite. Part II - Polycyclic Aromatic Hydrocarbons Gas chromatography/mass spectrometry is the most common method for the determination of polycyclic aromatic hydrocarbons (PAHs) from various matrices. Mass discrimination of high-boiling compounds in gas chromatographic methods is well known. The use of high-boiling injection solvents shows substantial increase in the response of late-eluting peaks. These solvents have an increased efficiently in the transfer of solutes from the injector to the analytical column. The effect of I-butanol, I-pentanol, cyclopentanol, I-hexanol, toluene and n-octane, as injection solvents, was studied. Higher-boiling solvents yield increased response for all PAHs. I -Hexanol is the best solvent, in terms of P AH response, but in this solvent P AHs were more susceptible to chromatographic problems such as peak splitting and tailing. Toluene was found to be the most forgiving solvent in terms of peak symmetry and response. It offered the smallest discrepancies in response, and symmetry over a wide range of initial column temperatures.

X-ray diffraction of a gram-negative bacterial membrane mimetic

This thesis applies x-ray diffraction to measure he membrane structure of lipopolysaccharides and to develop a better model of a LPS bacterial melilbrane that can be used for biophysical research on antibiotics that attack cell membranes. \iVe ha'e Inodified the Physics department x-ray machine for use 3.'3 a thin film diffractometer, and have lesigned a new temperature and relative humidity controlled sample cell.\Ve tested the sample eel: by measuring the one-dimensional electron density profiles of bilayers of pope with 0%, 1%, 1G :VcJ, and 100% by weight lipo-polysaccharide from Pse'udo'lTwna aeTuginosa. Background VVe now know that traditional p,ntibiotics ,I,re losing their effectiveness against ever-evolving bacteria. This is because traditional antibiotic: work against specific targets within the bacterial cell, and with genetic mutations over time, themtibiotic no longer works. One possible solution are antimicrobial peptides. These are short proteins that are part of the immune systems of many animals, and some of them attack bacteria directly at the membrane of the cell, causing the bacterium to rupture and die. Since the membranes of most bacteria share common structural features, and these featuret, are unlikely to evolve very much, these peptides should effectively kill many types of bacteria wi Lhout much evolved resistance. But why do these peptides kill bacterial cel: '3 , but not the cells of the host animal? For gramnegative bacteria, the most likely reason is that t Ileir outer membrane is made of lipopolysaccharides (LPS), which is very different from an animal :;ell membrane. Up to now, what we knovv about how these peptides work was likely done with r !10spholipid models of animal cell membranes, and not with the more complex lipopolysa,echaricies, If we want to make better pepticies, ones that we can use to fight all types of infection, we need a more accurate molecular picture of how they \vork. This will hopefully be one step forward to the ( esign of better treatments for bacterial infections.

Peer Motivational Climate and its Relationship with Positive and Negative Affect in Intramural Sports

The study of peers as an influence on sport participation has received minimal exploration. The purpose of this cross-sectional study was to determine how peer created motivational climates (task-involved and ego-involved) impact positive and negative affective states of intramural sport participants post-participation. Three hundred and fifteen intramural sport participants (N=315) at a Canadian university completed a questionnaire after participating in their intramural sport. Hierarchical regression analyses and MANCOVAs were used to examine the effects of peer motivational climates on positive and negative affect. Results revealed that task-involved peer climates are more conducive of positive affective states post-participation whereas ego-involved climates result in lesser positive affective states and more negative affective states. Teams that promote improvement and effort instead of intra-team competition and conflict will have more positive recreational sport experiences. Future research should explore other psychological outcomes that can result from peer created motivational climates in recreational sport team settings.

Photograph Negative - Donald Ziraldo working wine equipment

A photograph negative of Donald Ziraldo working a machine.

Photograph Negative - Donald Ziraldo working in wine production

A photograph negative of Donald Ziraldo working in wine production. The date is unknown, but thought to be between 1975 & 1978.

Informing the structure of subjective well-being through examining changes in life satisfaction, positive affect, and negative affect

Subjective well-being (SWB) refers to how individuals evaluate and experience their lives in positive ways, and encompasses global judgments of life satisfaction (LS), as well as the frequency of positive and negative affect (PA and NA, respectively) in one’s life. To inform the current ambiguity concerning the structure of SWB, the aim of this Masters thesis was to evaluate the structure of SWB based on whether the three components of SWB change together or independently naturally, over time and following experimental manipulation. In Study 1, associations among changes in LS, PA, and NA were evaluated using a longitudinal approach tracking natural changes in the components over periods of three months and three years. Results indicated that change in one component was related to change in the other two components. In Study 2, an experimental design was used to manipulate each SWB component individually, and evaluate changes in all three components following each manipulation. Manipulation materials designed to target LS only were effective (i.e., led to heightened focus on LS, and not PA or NA) and created an increase in both LS and PA. Manipulation materials designed to target PA and NA only were not effective (i.e., led to heightened focus on the target component, as well as on LS). Furthermore, in both studies the strength of an individual’s SWB (assessed in terms of structural consistency and structural ambivalence in Study 1 and Study 2, along with subjective ambivalence in Study 2) did not consistently moderate the degree to which changes in the components were associated with one another. Together, these findings indicate that the structure of SWB may be complex and dynamic, rather than static. Alternatively, the components of SWB may not be easily manipulated in isolation of one another. Implications for existing structural models of SWB are discussed.

Alleviating Negative Spillover of a Brand-Harm Crisis: Sensegiving vs. Sensehiding in a Competitor’s Denial Response Strategy

A brand-harm crisis not only affects the scandalized brand, but may also influence competing brands. Thus, marketers of competing brands need to develop response strategies for reducing negative spillover effects. This research takes a competitor’s perspective and introduces two types of response strategies used to convey a sense of denial: sensegiving and sensehiding. It also investigates how the effects of response strategies are contingent upon brand relatedness and individual thinking styles. The results from three experimental studies show that using a sensegiving strategy reduces negative spillover effects more than using a sensehiding strategy. Additionally, the studies suggest that the observed difference in the effects of response strategy tends to be greater when the level of brand relatedness is high than when it is low. However, individual thinking styles (holistic vs. analytic) seem to have little impact on consumers’ responses to the two denial strategies. This research contributes to the brand-harm crisis literature and provides novel insights into a competitor’s response to potential negative spillover effects.

Surface display of proteins by Gram-negative bacterial autotransporters

Affiliation: Faculté de Médecine Vétérinaire, Université de Montréal

Negative affect mediates the relationship between the Cortisol Awakening Response and Conduct Problems in boys

Ce mémoire débute avec deux chapitres portant sur les problèmes des conduites et la régulation du stress, notamment sur l’axe hypothalamique-pituitaire-surrénal (HPS). Ensuite, la littérature est résumée et nous voyons que les études qui cherchent à établir un lien entre les problèmes des conduites et l’axe HPS ont trouvé des résultats différents et parfois contradictoires. Le chapitre suivant illustre les problèmes méthodologiques qui pourraient expliquer ces résultats différents. Vient ensuite l’étude présentée dans ce mémoire qui cherche à établir un lien entre la réponse cortisolaire à l’éveil (RCE), considérée comme un bon indice du fonctionnent de l’axe HPS, et les problèmes de conduites chez l’enfant. De plus, les émotions négatives ont été associées avec les problèmes des conduites ainsi qu’aux dysfonctions de l’axe HPS, notamment le RCE. L’étude présentée dans ce mémoire cherche aussi à établir si les émotions négatives pourrait être une variable médiatrice dans la relation potentielle entre la RCE et les problèmes des conduites. L’étude révèle que pour les garçons mais pas pour les filles, une RCE réduite est associée avec les émotions négatives, ce qui est successivement associé avec les problèmes des conduites. Le dernier chapitre du mémoire examine les implications théoriques de cette médiatisation et propose également des pistes psychobiologiques pour expliquer les différences sexuelles observées.

Non-negative matrix decomposition approaches to frequency domain analysis of music audio signals

On étudie l’application des algorithmes de décomposition matricielles tel que la Factorisation Matricielle Non-négative (FMN), aux représentations fréquentielles de signaux audio musicaux. Ces algorithmes, dirigés par une fonction d’erreur de reconstruction, apprennent un ensemble de fonctions de base et un ensemble de coef- ficients correspondants qui approximent le signal d’entrée. On compare l’utilisation de trois fonctions d’erreur de reconstruction quand la FMN est appliquée à des gammes monophoniques et harmonisées: moindre carré, divergence Kullback-Leibler, et une mesure de divergence dépendente de la phase, introduite récemment. Des nouvelles méthodes pour interpréter les décompositions résultantes sont présentées et sont comparées aux méthodes utilisées précédemment qui nécessitent des connaissances du domaine acoustique. Finalement, on analyse la capacité de généralisation des fonctions de bases apprises par rapport à trois paramètres musicaux: l’amplitude, la durée et le type d’instrument. Pour ce faire, on introduit deux algorithmes d’étiquetage des fonctions de bases qui performent mieux que l’approche précédente dans la majorité de nos tests, la tâche d’instrument avec audio monophonique étant la seule exception importante.

Guidelines for Reducing the Negative Public Health Impacts of Medical Tourism

Étude de cas / Case study

Corticospinal excitability not affected by negative motor imagery or intention

Bien que l’imagerie motrice positive ait été bien étudiée et est utilisée en réhabilitation, l’effet de l’imagerie motrice négative est beaucoup moins connu. Le but de cette recherche était de définir si l’intention et/ou l’imagerie motrice négative serait en mesure de réduire l’effet d’une stimulation magnétique transcrânienne (SMT) sur le cortex moteur. Vingt participants ont reçu trente stimulations de SMT dans trois situations différentes : En restant passif, en portant une attention particulière aux sensations dans leur main ou en tentant de réduire l’effet de la SMT. La moitié des participants ont utilisé une stratégie d’imagerie motrice, l’autre moitié leur intention. Dans les deux cas, l’amplitude dans la condition de modulation n’a pas été réduite de façon significative.

When Disability Rhymes with Negative Bias: A Response to Verpaelst

Commentaire / Commentary