Sub-Inhibitory Antibiotics Enhance Virulence, Persistence, and Pathogenesis of Uropathogens

In addition to their bactericidal effects, antibiotics are potent signal mediators at sub-inhibitory levels in the environment. The ability to modulate community structure in this niche raises concerns over their capacity to influence pathogenesis in patients during antibiotic therapy. This concept forms the basis of this thesis, and is explored using models of prophylactic therapy for recurrent urinary tract infection (UTI) management. Sub-inhibitory ciprofloxacin, ampicillin, and gentamicin were found to augment virulence in vitro, increasing adherence and urothelial cell invasion in uropathogenic Escherichia coli (UPEC) and Staphylococcus saprophyticus. In addition, biofilm formation was increased, and swarming motility decreased. In UPEC, the effect of antibiotics on these processes was abolished in SOS-deficient strains. Trans-urethral inoculation of mice with ciprofloxacin-primed S. saprophyticus or UPEC significantly increased bacterial burden in both bladders and kidneys at one and 14 days post-inoculation (dpi). Sub-therapeutic ciprofloxacin supplemented in the drinking water of chronically infected mice significantly increased bacterial urine load. In addition, mice previously infected but clinically resolved suffered recurrences. These mice had impaired urinary polymorphonuclear leukocyte infiltrates, in part due to antibiotic-dependent cytokine suppression during initial infection. Prophylactic intervention had no significant effect on UPEC clearance, but did significantly increase bacterial intracellular bladder reservoirs, raising concerns over the clinical efficacy of this management strategy and risks of promoting persistent infection. The inability of antibiotics to clear infection in prophylaxis models was attributed to the presence of MDT persister cells. Sub-inhibitory antibiotic pre-treatments were found to increase persister fractions, but this effect was abolished in SOS-deficient strains. Conducting these assays with UPEC isolated from recurrent UTI patients revealed an enriched persister fraction compared to organisms cleared with standard antibiotic therapy, suggesting persister traits are either selected for during prolonged antibiotic treatment or initially contribute to therapy failure. This work represents the first attempt to illustrate that observed sub-inhibitory, pathogen associated antibiotic-dependent changes in vitro have significant in vivo consequences. It is hoped that this research will lead to a re-examination of how antibiotics are administered for management of patients suffering from recurrent UTI and other chronic diseases

Advertising skepticism among adolescents : an extension into the social marketing arena

The youth market is of considerable importance to those selling commercial products as well as to those seeking to discourage unhealthy or risky behaviours ('social marketers'). One of the key challenges for social marketing is the development of effective messages. Advertising skepticism, an individual characteristic, has been shown to mediate the effectiveness of commercial ad appeals. However, similar research in the social marketing arena is lacking, although sorely needed. This study seeks to fill a gap by conceptualizing the construct of skepticism toward social advertising. We develop a measure for this construct in relation to ads seeking to discourage adolescents from risky behaviours such as smoking and drinking and driving, and in a cross-cultural context. Based on an extensive literature review, and input from adolescents and expert judges, this measure was pre-tested using over 210 junior college (Cegep) and undergraduate students, and its reliability and validity investigated. Subsequently, a refined version of this measure was used in a study where 232 responses were obtained from high school students in two different schools--one French and one English. Results obtained indicate that the scale possesses many desirable psychometric properties, and provide further evidence of its validity. Results also indicate that commercial ad skepticism and social ad skepticism are clearly distinct constructs. For instance, while the former is significantly correlated with parental communication style, the latter is not, although both are affected by a particular type of peer influence. In other findings, adolescents' skeptical attitudes toward social ads were significantly correlated with various risky behaviour perceptions. Finally, additional exploratory tests showed that age and language influence an adolescent's skeptical attitudes toward ads

Excluded from Our City: Clement of Alexandria and the Porous Frontier of Early Christian Identity

In the Paedagogus, the second volume of his three major works, Clement of Alexandria develops a “Christian” ethic and sense of identity, which is dependent on one’s “habits, deeds, and passions.”1 The work itself is directed toward “you who are children” and is intended to instruct Christians in matters of character and behavior.2 Though he is preoccupied with attempting to educate—rather, allowing his understanding of Christ to educate—Christians in regard to appropriate behaviors and values, thereby defining and maintaining a unique sense of Christian identity in late second century Alexandria, he is also at home in a culture of Greek and Jewish philosophy and literature. As an educated, Greek-speaking, Alexandrian Christian, with a significant indebtedness to both Plato and Philo, Clement is an ideal figure to engage with when concerned with questions of identity among early Christians. By applying modern theoretical frameworks and studies on identity, I aim to examine Clement’s ideal and demonstrate how intertwined and permeated it is by that which he seeks to exclude. His aim of trying to regulate behavior in order to maintain a distinct group cohesion is part of what is best understood as the process of identity. 1 Clement, Paedagogus, 1.1.1. 2 Clement, Paedagogus, 1.1.1

Hepatitis C Core-Antigen Testing from Dried Blood Spots

In order to expand hepatitis C virus (HCV) screening, a change in the diagnostic paradigm is warranted to improve accessibility and decrease costs, such as utilizing dried blood spot (DBS) collection. In our study, blood from 68 patients with chronic HCV infection was spotted onto DBS cards and stored at the following temperatures for one week: −80 ◦C, 4 ◦C, 21 ◦C, 37 ◦C, and alternating 37 ◦C and 4 ◦C; to assess whether temperature change during transportation would affect sensitivity. Sample was eluted from the DBS cards and tested for HCV antibodies (HCV-Ab) and HCV core antigen (core-Ag). HCV-Abs were detected from 68/68 DBS samples at −80 ◦C, 4 ◦C, 21 ◦C, and 67/68 at 37 ◦C and alternating 37 ◦C and 4 ◦C. Sensitivity of core-Ag was as follows: 94% (−80 ◦C), 94% (4 ◦C), 91% (21 ◦C), 93% (37 ◦C), and 93% (37 ◦C/4 ◦C). Not only did temperature not greatly affect sensitivity, but sensitivities are higher than previously reported, and support the use of this assay as an alternative to HCV RNA. We then completed a head-to-head comparison (n = 49) of venous versus capillary samples, and one versus two DBS. No difference in core-Ag sensitivity was observed by sample type, but there was an improvement when using two spots. We conclude that HCV-Abs and core-Ag testing from DBS cards has high diagnostic accuracy and could be considered as an alternative to HCV RNA in certain settings

Cicatriser le centre de Montréal: projet d'infrastructure publique au-dessus d'une autoroute (Canada)

Face à la problématique de congestion, conséquence de la démocratisation de l'automobile et du déplacement des aires d'habitation qui s'en suit, l'idéologie fonctionnaliste d'un urbanisme prétendument moderne croit pouvoir répondre aux maux de l'urbain par la production massive d'infrastructures autoroutières. La réalité urbaine contemporaine érige ainsi d'invisibles frontières au détriment des tissus existants et des métriques piétonnes. Montréal, alors capitale économique du Canada, décide, au contraire de sa sœur Toronto, d'épargner son ancien front portuaire, désormais tombé en désuétude, et choisit d'aménager l'axe autoroutier intra-urbain à la frontière des quartiers de l'ancienne ville. L'autoroute Ville-Marie, déployée en tranchée d'Est en Ouest forme une nouvelle “fortification” à l'échelle urbaine, isolant le Vieux-Montréal du reste de la ville, notamment la portion Sud du centre-ville où s'établissent les grandes institutions. L'immense vide linéaire, progressivement investit par de grands bâtiments à vocation internationale sera pourtant laissé tel quel à son moment le plus important, soit en devanture de l'Hôtel de ville et du Champ de Mars, vestige des anciennes fortifications. Toutefois, ce vide généré par le passage de l'infrastructure autoroutière aura permis l'établissement des infrastructures souterraines du métro et le réseau souterrain piétonnier. L'intervention proposée tirera ainsi à même les qualités et problématiques du contexte. En permettant la cicatrisation d'un tissu trop longtemps laissé ouvert, elle propose une réponse infrastructurelle aux besoins urbains des institutions de la ville nouvelle, tout en tirant profit de l'attractivité publique et récréative de la ville ancienne

Excluded from Our City: Clement of Alexandria and the Porous Frontier of Early Christian Identity

In the Paedagogus, the second volume of his three major works, Clement of Alexandria develops a “Christian” ethic and sense of identity, which is dependent on one’s “habits, deeds, and passions.”1 The work itself is directed toward “you who are children” and is intended to instruct Christians in matters of character and behavior.2 Though he is preoccupied with attempting to educate—rather, allowing his understanding of Christ to educate—Christians in regard to appropriate behaviors and values, thereby defining and maintaining a unique sense of Christian identity in late second century Alexandria, he is also at home in a culture of Greek and Jewish philosophy and literature. As an educated, Greek-speaking, Alexandrian Christian, with a significant indebtedness to both Plato and Philo, Clement is an ideal figure to engage with when concerned with questions of identity among early Christians. By applying modern theoretical frameworks and studies on identity, I aim to examine Clement’s ideal and demonstrate how intertwined and permeated it is by that which he seeks to exclude. His aim of trying to regulate behavior in order to maintain a distinct group cohesion is part of what is best understood as the process of identity. 1 Clement, Paedagogus, 1.1.1. 2 Clement, Paedagogus, 1.1.1

Les inégalités de genre en matière de patrimoine chez les personnes seules dans les contextes canadiens et québécois

De plus en plus d’études s’intéressent aux inégalités de patrimoine entre les différents groupes sociaux, cette ressource étant particulièrement importante dans un contexte de vieillissement de la population. Jusqu’à présent toutefois, peu de recherches se sont penchées sur les différences de genre en matière de patrimoine, surtout dans les contextes canadiens et québécois. Le présent article comble ce manque en comparant la richesse accumulée des hommes et des femmes ne vivant pas avec un autre adulte au Canada et au Québec. À l’aide de régressions quantiles et de l’Enquête sur la sécurité financière, nous décrivons les écarts de patrimoine entre les hommes et les femmes aux 25e, 50e et 90e percentiles. Nos résultats indiquent que des inégalités existent, surtout au 90e percentile, et qu’elles sont magnifiées par la présence d’enfant(s). Les écarts de richesse sont expliqués en partie par les différences de revenus entre les hommes et les femmes, mais aussi par la propension plus faible des femmes d’être propriétaires d’entreprise et d’avoir reçu un héritage comparativement aux hommes.A growing body of research addresses the issue of wealth inequality between social groups, accumulated wealth being critical to well-being in the context of population aging. Thus far, however, this line of work has dedicated relatively little attention to the issue of gender wealth disparities, especially in the Canadian and Québécois contexts. We help fill in this gap by exploring net worth differences between men and women who do not live with another adult in Canada and Québec. Using quantile regressions and data from the Survey of Financial Security, we describe gender wealth gaps at the 25th, 50th and 90th percentiles of the net worth distribution. We find significant wealth disparities between men and women, especially at the 90th percentile and conditional on having children in the household. Those gaps are explained in part when accounting for gender wage disparities, but other factors are also at play, including gender differences in business ownership and the receipt of private transfers

Development of a scale to measure skepticism of social advertising among adolescents

A significant amount of research has looked at the effectiveness of social marketing to teenagers, but teenagers' skeptical response to social advertising has not been considered. In this study, we review the relevant literature, develop a measure of social advertising skepticism with desirable psychometric properties, and show that social ad skepticism is distinct from the (commercial) ad skepticism that has been previously studied. We also develop a model of the antecedents and correlates of social advertising skepticism and test it using a sample of high-school students. Our results show that peer influence and reactance play a prominent role in an adolescent's skepticism of social and commercial ads. They also show that skeptical attitudes toward social ads are significantly correlated with reduced perceptions of the risks of some behaviors.Ad skepticism Social marketing Teenagers Peer influence Adolescents