Peritoneal carcinomatosis (PC), the intra-abdominal dissemination of malignancy, is equated with a 5-year survival of 15%, depending on the source. Appendiceal PC is a challenge to treat as cancer cells are embedded in copious amounts of mucin and are difficult to target. Oncolytic viruses (OVs) preferentially replicate and lyse cancer cells and present a targeted, novel strategy for PC. The hypothesis of this study is that appendiceal PC will show variable susceptibility to OVs and that protein expression in these tumours will predict OV replication efficiency. Human appendiceal PC infected ex-vivo with 4 different OVs displayed variable infectivity and replication by fluorescence microscopy and plaque assay. Immunohistochemistry analysis revealed differential expression of IRF3, pERK and TK in tumour compared to normal appendix. No correlation of protein expression with viral replication was observed. Personalizing OV therapy will be critical in the optimization of future care of patients treated with this modality.

Aims: To investigate the natural history of CHC, estimate the disease burden of CHC, and assess the cost-effectiveness of screening for CHC among immigrants living in Canada. Methods: A retrospective cohort study compared the prognosis of CHC between immigrant patients and native-born patients who had advanced fibrosis. A cross-sectional study assessed the association between obesity and hepatitis C viremia. The disease burden of CHC among immigrants was estimated through Markov cohort model. The cost-effectiveness of screening for CHC was assessed among immigrants. Results: The retrospective cohort study including 318 patients demonstrated that immigrant patients had significantly higher risk of hepatocellular carcinoma than Canadian-born patients (p=0.005). The hazard ratio associated with ‘immigrant’ for hepatocellular carcinoma in multivariate Cox proportional-hazards analyses reduced to the least and non-significant (p=0.318) after adjusting age and type 2 diabetes. The prevalence of obesity in 1118 individuals tested positive for hepatitis C antibody was 28.8%. Multiple regression analyses and propensity score methods suggested a significant association between obesity and hepatitis C viremia. The disease burden study estimated that immigrants with CHC had much shorter average life years (26.9 years vs. 39.1 years) and quality adjusted life years (20.6 years vs. 32.4 years) than the age matched immigrants without CHC. The cost-effectiveness study indicated that screening for CHC among immigrants from 183 countries (72.1% of immigrant population in Canada) had an incremental cost-effectiveness ratio less than $50,000 per quality adjusted life year gained. Conclusion: Immigrant patients with CHC could have a higher risk of HCC than native-born patients. The significant association between obesity and hepatitis C viremia could explain the observed high prevalence of type 2 diabetes in patients with CHC. CHC reduces the average life expectancy of immigrants with CHC more than 10 years. Screening for CHC is cost-effective among over 70% of immigrants living in Canada.

Objective: The primary aim of this study was to assess patients’ preferences between radiofrequency ablation (RFA) versus hepatic resection (HR) for the treatment of small hepatocellular carcinomas (HCC). Methods: Decision analysis was performed by using probability trade-off (PTO) technique to elicit patients’ preferences and the strength of their decisions. Results: The vast majority of the study population preferred RFA over HR (70% vs. 30%, p=0.001). Their initial choice changed if 5-year survival benefit after surgery was at least 14% superior to RFA and if the 3-year disease-free survival advantage was at least 13% better than ablation. Conclusions: The results of this study suggest that fully informed cirrhotic patients would prefer RFA if diagnosed with early stage HCC even if able to undergo surgery.

INTRODUCTION: The association of Sleep-Related Movement Disorders (SRMDs) such as Restless Legs Syndrome (RLS) and Periodic Limb Movements (PLMs) with cerebrovascular disease is underexplored. Emerging evidence links them to vascular disease, for which white matter hyperintensities (WMHs) are a well-recognized biomarker. METHODS: We conducted a cross-sectional hospital-based observational study in which high-risk TIA and minor stroke patients were assessed for vascular risk factors, WMHs and polysomnography-determined sleep variables. RESULTS: Ninety-seven patients were enrolled, of whom 44 completed polysomnography. Twenty-five percent had RLS, which was associated with lower quality of life. Independent of the effect of classical vascular risk factors, PLMs (but not RLS) were associated with WMHs on linear regression analyses (p=0.016). CONCLUSIONS: SRMDs are prevalent after minor stroke/TIA. RLS is associated with poor quality of life, while PLMs are associated with WMHs. Whether PLMs are implicated in the pathogenesis of WMHs or whether WMHs exacerbate PLMs remains uncertain.

La mastoïdite aiguë est l'une des complications les plus courantes de l'otite moyenne aiguë chez les enfants de moins de deux ans. Selon notre revue de la littérature, aucune directive nationale ou internationale ni étude prospective n’ont été émises concernant la sécurité des traitements de relai antibiotiques oraux ou intraveineux en période post-opératoire des mastoïdites aiguës sans complication intracrânienne. L’objectif de cette étude est de comparer les traitements antibiotiques post-opératoires oraux et intraveineux des mastoïdites aiguës sans complication intracrânienne chez l’enfant. Une étude de cohorte rétrospective par consultation de dossiers hospitaliers a été effectuée. Deux groupes d'enfants (n = 29) ayant subi une intervention chirurgicale appropriée, ont été comparés selon leurs données démographiques, selon le type d'antibiotiques utilisés en période postopératoire, selon la durée de leur hospitalisation ainsi que selon la prévalence des complications. Les deux groupes ont révélé des durées équivalentes d'hospitalisation et de traitement. Le groupe ayant reçu un traitement antibiotique intraveineux a présenté 14,3% de complications mineures (n = 2) et 7,1% de complications majeures (n = 1). Le groupe ayant reçu un traitement antibiotique oral a présenté 6,7% de complications mineures (n = 1) mais aucune complication majeure. Cette étude soutient l'idée que, dans la population pédiatrique, un drainage chirurgical adéquat des mastoïdites aiguës sans complication intracrânienne peut être suivi par un traitement antibiotique oral en toute sécurité avec des résultats similaires au traitement intraveineux post-opératoire. / Acute mastoiditis is one of the most common complication of acute otitis media in children under two years old. To our knowledge, neither guidelines have been published nor prospective study has compared the oral and intravenous post-operative antibiotic treatments of mastoïditis. Our objective was to compare the oral and intravenous post-operative treatments of pediatric acute mastoiditis without intracranial complication. A retrospective cohort study was done. Two groups of children (n = 29) diagnosed with acute mastoiditis without intracranial complication, who has been operated, were compared by the demographics, the type of antibiotics, the durations of hospitalization and postoperative treatment and the incidence of complications. Both groups had equivalent duration of hospitalization and postoperative treatment. The intravenous group had 14,3% of minor complications (n = 2) and 7,1% of major complications (n = 1). The oral group had 6,7% of minor complications (n = 1) without any major complication. This study supports the notion that, in the pediatric population, adequate surgical drainage of acute mastoiditis without intracranial complication can be followed by discharge with oral antibiotics to achieve the same satisfactory and safe outcomes of intravenous treatment.

L'insula est une structure complexe impliquée dans une variété de fonctions. Les études de connectivité par traçage chez les primates non humains ont révélé une multitude de connexions corticales entre l'insula et les lobes frontal (cortex orbitofrontal, cortex préfrontal, régions cingulaires, aire motrice supplémentaire), pariétal (cortex somatosensoriel primaire et secondaire) et temporal (pôle temporal, cortex auditif, cortex prorhinal et entorhinal). Les études de tractographie chez l'humain ont révélé des connexions structurelles similaires, mais n'ont pas rapporté de connexion avec le cortex cingulaire, malgré que cette structure soit reconnue comme étant fonctionnellement connectée à l’insula. Ce projet vise à approfondir la recherche sur la connectivité structurelle entre ces deux structures ainsi que d'autres régions connues comme étant fonctionnellement connectées à l'insula, à l'aide d'un échantillon plus grand et des plus récentes méthodes en tractographie par l’imagerie à haute résolution de diffusion angulaire basée sur des a priori anatomiques. En analysant les données de 46 participants adultes en bonne santé, notre étude rapporte un large éventail de connexions entre l’insula et les lobes frontal, temporal, pariétal et occipital ainsi que les régions limbiques, suivant un patron d’organisation rostrocaudal. Notamment, nous démontrons pour la première fois une connexion structurelle claire entre l’insula et les gyri cingulaire, parahippocampique, supramarginal et angulaire ainsi que le précunéus et les régions occipitales. / The insula is a complex structure involved in a wide range of functions. Tracing studies on non-human primates reveal a wide array of cortical connections in the frontal (orbitofrontal and prefrontal cortices, cingulate areas, and supplementary motor area), parietal (primary and secondary somatosensory cortices) and temporal (temporal pole, auditory, prorhinal and entorhinal cortices) lobes. However, recent human tractography studies have not observed connections between the insula and the cingulate cortices, although these structures are thought to be functionally intimately connected. In this work, we try to unravel the structural connectivity between these regions and other known functionally connected structures, benefiting from a higher number of subjects and the latest state-of-the-art high angular resolution diffusion imaging (HARDI) tractography algorithms with anatomical priors. By performing a HARDI tractography analysis on 46 young normal adults, our study reveals a wide array of connections between the insula and the frontal, temporal, parietal and occipital lobes as well as limbic regions, with a rostro-caudal organization in line with tracing studies in macaques. Notably, we reveal for the first time in humans a clear structural connectivity between the insula and the cingulate, parahippocampal, supramarginal and angular gyri as well as the precuneus and occipital regions.

Introduction : L’hypophosphatémie survient couramment après hépatectomie partielle. La régénération du foie était l’explication initiale. Cependant, les pertes rénales de phosphate observées récemment suggèrent que l’hypophosphatémie est probablement d’origine rénale. Nous avons donc mesuré la fraction d’excrétion urinaire de phosphate (FePO4) après hépatectomie partielle et nous avons étudié le rôle de la parathormone (PTH) et des phosphatonines dans cette hypophosphatémie. Méthodes : Les taux sériques de phosphate, de calcium ionisé, de PTH intacte, de « fibroblast growth factor- 23 » (FGF-23) intact et carboxyle-terminal, de FGF-7, de la « frizzled-related protein-4 » (FRP-4) et de HCO3- ainsi que le pH et la FePO4 ont été mesurés avant la chirurgie et aux jours postopératoires (po) 1, 2, 3, 5 et 7, chez 18 patients ayant subi une résection hépatique partielle. Résultats : Le phosphate sérique était à son plus bas niveau (0,66 ± 0,33 mmol/l; p < 0,001) au jour po 2. La FePO4 culminait à 25,07 ± 2,26 % au jour po 1 (p < 0,05) et était associée avec le taux de la parathormone intacte (r = 0,65; p = 0,006). Le calcium ionisé sérique diminuait à 1,1 ± 0,01 mmol/l, (p < 0,01) en même temps que la parathormone intacte s’élevait à 8,8 ± 0,9 pmol/l, (p < 0,01) au jour po 1; ces deux paramètres étaient inversement corrélés (r = -0,062; p = 0,016). Le FGF-23 intact atteignait son plus bas niveau à 7,8 ± 6,9 pg/ml (p < 0,001), au jour po 3; les valeurs de FGF-23 étaient corrélées avec la diminution du phosphate sérique aux jours po 0, 3, 5 et 7 (p < 0,001). Le FGF-23 carboxyle-terminal, le FGF-7 et la FRP-4 n’étaient pas reliés au phosphate sérique ni à la FePO4. Conclusion : L’hypophosphatémie observée après résection hépatique partielle est liée à une augmentation de la FePO4 qui est sans aucune relation avec les FGF-23 intact ou carboxyle-terminal, le FGF-7 et la FRP-4. La PTH intacte était associée avec la FePO4 uniquement au jour po 1. L’hypophosphatémie après résection hépatique est secondaire à d’autres facteurs non encore identifiés. / Background: Post-hepatectomy hypophosphatemia, first associated with metabolic demands by the regenerating liver, has recently been related to an excessive fractional urinary phosphate excretion (FePO4). We decided to investigate the role of parathyroid hormone (PTH) and of phosphatonins in the latter finding. Methods: Serum phosphate (PO4), ionized calcium (Ca++), HCO3-, pH and FePO4, Intact PTH, carboxyl-terminal and Intact fibroblast growth factor 23 (FGF-23), FGF-7 and frizzled related-protein-4 (FRP-4) were measured before and serially on post-operative days 1, 2, 3, 5 and 7, in 18 patients undergoing liver resection. Results: Serum PO4 was lowest (0.66 ± 0.33 mmol/l; p < 0.001) on po day 2. FePO4 peaked at 25.07 ± 2.26 % on po day 1 (p < 0.05) and was associated with Intact PTH levels (r = 0.65, p = 0.006). Decreased Ca++ levels (1.1 ± 0.01 mmol/l; p < 0.01) and increased Intact PTH levels (8.8 ± 0.9 pmol/l; p < 0.01) observed on po day 1 were negatively related (r = -0.62, p = 0.016). Intact FGF-23 decreased to its nadir 7.8 ± 6.9 pg/ml (p < 0.001), on po day 3 and was correlated with PO4 levels on po days 0, 3, 5 and 7 (p < 0.001). Carboxyl-terminal FGF-23, FGF-7 and FRP-4 levels could not be related either to PO4 concentrations or FePO4. Conclusion: Post-hepatectomy hypophosphatemia is related to an increased FePO4 unrelated to Intact FGF-23 or carboxyl-terminal FGF-23, FGF-7 or FRP-4. I-PTH contributes to excessive FePO4 on po day 1 but not thereafter. Other factors not yet defined should explain post hepatectomy hypophosphatemia.

L’hypoalbuminémie est une trouvaille fréquente chez le patient brulé mais sa relation avec la morbidité et mortalité n’a pas été bien établie. Objectif : Déterminer si l’hypoalbuminémie dans les premières 24 heures suivant l’admission est associée avec la dysfonction d’organes (mesurée avec le score SOFA) chez les patients présentant des brûlures graves. Méthodologie : Nous avons révisé les dossiers médicaux des patients adultes avec de brûlures de 20% ou plus de surface corporelle admis pendant les premières 24 heures à l’unité de grands brulés du CHUM entre les années 2008 et 2009. Nous avons utilisé un modèle de régression linéaire multivariée pour déterminer si l’hypoalbuminémie était un prédicteur indépendant de la dysfonction d’organes. Résultats : 56 sujets ont été analysés. L’analyse de régression linéaire multiple a montré qu’en contrôlant pour l’âge, le sexe, la surface corporelle brûlée et les brûlures par inhalation, l’hypoalbuminémie pendant les premières 24 heures suivant l’admission est un prédicteur indépendant de la dysfonction d’organes. Une concentration d’albumine ≤30g/L est aussi associée à une augmentation de la dysfonction d’organes [score SOFA au jour 0 (p = 0.005), jour 1 (p = 0.005), moyenne de la première semaine (p = 0.004)], mais n’est pas associée avec la mortalité (p = 0.061). Conclusions : L’hypoalbuminémie est associée avec la dysfonction d’organes chez les patients brulés. À la différence de facteurs non modifiables comme l’âge, le sexe, la surface corporelle brûlée et la présence de brûlures par inhalation, la correction de l’hypoalbuminémie peut être un objectif intéressant pour un futur essai clinique. / Hypoalbuminemia is a common finding in burn patients, but its association with increased morbidity and mortality has not been well established. Objective: We have assessed if hypoalbuminemia in the first 24 hours of admission is associated with organ dysfunction in patients with severe burns. Methods: For a two year period (2008-2009), we reviewed the chart of burn adult patients with a total body surface area ≥ 20% admitted in our unit in the first 24 hours following the burn injury. A multiple linear regression analysis was conducted to assess hypoalbuminemia as an independent predictor of organ dysfunction. Results: 56 patients were analyzed. Multiple linear regression analysis showed that hypoalbuminemia in the first 24 hours of admission was an independent predictor of organ dysfunction. Serum albumin concentration ≤ 30 g/L was associated with a two-fold increased in organ dysfunction [SOFA scores at day 0 (p = 0.005), day 1 (p = 0.005) and first week mean values (p = 0.004), but not with mortality (p = 0.061). Conclusion: Hypoalbuminemia is associated with organ dysfunction in burn patients. Unlike unmodifiable predictors such as age, burn surface and inhalation burn, correction of hypoalbuminemia might represent a goal for a future trial in burn patients.

Master of Science / Department of Psychology / Gary L. Brase / In 2006, the Center for Disease Control and Prevention recommended the revision of state HIV testing laws. With these recommendations, more low-risk individuals are tested regardless of their risk group. However, there is a greater chance of a false positive test result for low-risk individuals than for high-risk individuals. Additionally, previous research found that doctors and HIV counselors in Germany did not accurately communicate the relationship between risk factors and false positive tests (Gigerenzer, Hoffrage, & Ebert, 1998). This study aimed to (1) compare the findings of the 1998 German sample to HIV hotline counselors in the United States in 2011; and (2) to investigate the ability of students to calculate the conditional probability of HIV for a low-risk individual after receiving a positive test, based on idealized transcripts of conversations with HIV hotline counselors. The first study found that HIV hotline counselors use both verbal expressions of risk and percentages to communicate HIV testing statistics. Additionally, 2011 American counselors were more aware of the chance of false positives and false negatives than compared to the 1998 German sample. However, no 2011 American counselors were able to provide an accurate positive predictive value for a low-risk woman. The second study found low performance among students in the calculation of the positive predictive value. Performance was facilitated by a natural frequency format for high numerate individuals. There were different patterns of results for the General Numeracy Scale and the Subjective Numeracy Scale. This would suggest that these two scales might be measuring different constructs. These findings are consistent with the two theories supporting the Frequency Effect, namely the Frequentist Hypothesis and the Nested Sets Hypothesis. Additionally, this research suggests computation of the conditional risk of HIV is facilitated by a natural frequency format. Teaching techniques have been developed and demonstrate long lasting improvement in health related computations. If a few hours of training is all that it takes to communicate these life and death statistics in a manner that is consistent with reasoning, health practitioners and students should be required to have more education in communicating and computing probabilities.

Master of Science / School of Journalism and Mass Communications / Nancy Muturi / This study was an examination of the determinants of disordered eating development among female collegiate distance runners. More specifically, the study examined the impact of thinness-emphasizing and thinness-promoting messages disseminated by mass media and running-specific media, and how those messages affected disordered eating among a sample of female collegiate distance runners. It also examines current female collegiate distance runners’ attitudes toward disordered eating, subjective norms from referent individuals close to female collegiate distance runners regarding disordered eating, and female collegiate distance runners’ perceived behavioral control regarding disordered eating—which was divided into various internal and external control factors either inhibiting or facilitating disordered eating among them. The study was qualitative in nature and assumed a multi-method approach. It included an online, anonymous, self-administered questionnaire among 166 current NCAA Division I female distance runners; four small, confidential focus groups with current NCAA Division I female distance runners from four different teams; and 16 in-depth interviews with professional distance runners, dietitians, coaches, physicians, and sports psychologists. The study sought to answer four research questions—each based on an element of the study’s guiding theory, the theory of planned behavior (Ajzen, 1991). Overall, the study found media messages, attitudes, subjective norms, and various internal and external control factors all facilitated disordered eating among NCAA Division I female distance runners. Based upon these findings, the study offers recommendations for practitioners in the field of health communication, coaches, academic institutions with cross country and track teams, and female collegiate distance runners.