The relationship between brain invaded by tumor and consequent word retrieval deficits was investigated. Performance scores from 10 individuals who underwent craniotomy for tumor resection were obtained using contexts of constrained naming, verbal fluency, and picture description during pre- and post-craniotomy. This study described qualitative and quantitative differences of impairment to elucidate the nature and extent of naming impairment in individuals with cerebral hemisphere tumors. For all tasks, independent of group, performance decrements were reported pre-operatively in relation to normative data, with subsequent post-operative decline. This was particularly true for the Left Hemisphere Group who exhibited poorer performance than the Right Hemisphere Group. It was expected that the Frontal Group would have greater difficulty on tasks requiring intact frontal lobe function (i.e. Verbal Fluency), but the Non-Frontal Group performed more poorly. Surprisingly, the Frontal Lobe Group showed the smallest decrement, and the Non-Frontal and Left Hemisphere Groups showed the worst performance overall. Pre- and post-operatively, all subjects exhibited greater word retrieval deficits than normal controls during verbal fluency tasks. The overall disruption of word retrieval across tasks was predictable for time of examination, but not for site of lesion. The results of this study suggest that the word retrieval deficits of brain tumor patients may differ from traditional aphasia profiles. This knowledge may contribute to a better understanding of language processing and production in tumor-related aphasia.

Aphasia has a significant negative impact on an individual's ability to communicate in his or her daily living environment. When this environment offers limited communication opportunities, as is generally believed to be the case in long-term care facilities such as nursing homes, aphasic individuals may suffer doubly. These individuals have to deal not only with limited communication abilities, but they also have few avenues to use spared abilities. This investigation characterized the communication environments of three severely aphasic nursing home residents by determining their interactants (i.e., people with whom they interacted), where interactions took place, what information content was communicated in these interactions, and why this communication occurred. Data collection relied on direct observation of the aphasic individuals in their daily living environments and semi-structured interviews with their interactants. Findings revealed that all three aphasic individuals interacted with a wide variety of people, from those one would expect, such as nurses, to those who are not so obvious, such as hairdressers and maintenance staff members. The majority of communication occurred with Certified Nursing Assistants (CNAs). With respect to communication locations, most communication occurred either in the aphasic individuals' own rooms, in their dining rooms, or in the hallways of their nursing homes. Communication content was categorized as either Social Communication, Activities of Daily Living (ADL) Communication, Medical and Physical Well-being Communication, and Facility Survival Skills Communication. For all three aphasic individuals, Social Communication and ADL Communication were the primary topic areas. To answer the question of why communication occurred, interactions were characterized as either instrumental (task-based) or affective (socially-based). The aphasic individuals varied in the ratios of these two types of communication. Possible contributing factors to the different profiles included the length of time each individual had to adapt to both the sequelae of his or her stroke and his or her nursing home environs, as well as individual personality characteristics. Clinical implications from the findings are suggested.

Studies were initiated to determine if drip irrigation contributes to increased incidence of Charcoal Rot, caused by Macrophomina phaseolina , in melons in Arizona. Soil samples from furrow- and drip- (with and without plastic mulch) irrigated fields were analyzed for soil chemical and physical parameters: pH, moisture, salinity and temperature; and for microbial factors: inoculum density, mycorrhizal infection, nematode abundance, and basal respiration. Results show a significant decrease in pH and increase in temperature in drip versus furrow-irrigated soils. Also, the interaction of pH, salinity, moisture, and irrigation type was significant for inoculum density of M. phaseolina which was up to 150 times higher in drip irrigated fields. In greenhouse trials, disease incidence increased significantly as salinity of irrigation water increased, but was not affected by root-knot nematode. Therefore, soil characteristics of drip-irrigated soils may contribute to a soil environment conducive to an increase in Charcoal Rot in melon.

The bHLH protein TAL1 (SCL) is a critical regulator of vertebrate hematopoiesis and is misregulated in T-cell acute lymphoblastic leukemia (T-ALL). This thesis studied chromatin looping interactions at the TAL1 locus – defining the first structural model which accounts for a number of phenomena associated with TAL1, its flanking genes and its relationship with its functional paralogue LYL1. The chromosome conformation capture (3C) and its high-throughput variant 4C-array technologies have been applied to characterise the chromatin interactions. Intriguing chromatin organisations have been identified at the TAL1 and LYL1 loci, which are closely associated with transcriptional regulation, chromosomal abnormality and regulatory remodelling through evolution. Firstly, in TAL1 expressing cells, the locus adopts a “cruciform” configuration – forming an active chromatin hub which brings together the TAL1 promoters, its stem cell and erythroid enhancers, and two CTCF/Rad21-bound insulators. Secondly, loss of a GATA1-containing complex bound by the TAL1 erythroid enhancer and its promoter is sufficient to disrupt the formation of the hub and the entire cruciform structure and results in decreased TAL1 expression. Thirdly, it demonstrates that genes flanking TAL1 are also dependent on this hub and that TAL1 promoters interact directly with intron 1 of the neighbouring STIL gene. This TAL1/STIL interaction also provides a structural link between the DNA sequences which mediate micro-deletions in 25% of cases of T-ALL. Finally, it demonstrates that a GATA1-dependent chromatin looping mechanism also exists at the LYL1 locus which is strikingly similar to that mediating contact between the TAL1 promoter and its erythroid enhancer. Conservation of core chromatin looping at the TAL1 and LYL1 loci may account for some aspects of their functional relationships. It also suggests that looping mechanisms at both loci could also facilitate cis-regulatory maintenance and/or remodelling during vertebrate evolution.

The theory of metastatic cascade suggests that vasculature plays a central role in the metastatic processes by being the major route of spreading. Two main circulatory systems in the body are responsible for cancer cell dissemination; the blood vascular system and the lymphatic system. However, comparing between these circulatory systems, much less is known about lymphatic vessels, with few studies being conducted about the initial steps of metastasis. In the first part of this project, a series of 202 formalin fixed paraffin embedded (FFPE) cutaneous melanoma sections were stained with D2-40, CD34 and CD68 to identify lymphatics, blood vessels and macrophages respectively, to examine vessel distribution and the involvement of inflammatory infiltrate in mediating vascular invasion (VI). Sections were also stained by conventional haematoxylin and eosin (H&E), to assess VI, and results compared against those obtained by immunohistochemistry (IHC) that allow discrimination of lymphatic and blood vessel invasion. It was found that lymphatics are mainly located at the peritumoural area of the tumour but intratumoural lymphatics are present and appeared to be functional based on the presence of tumour emboli in the vessels. In addition, vascular invasion in melanoma is mainly lymphatic vessel invasion with H&E assessment underestimating its incidence. Lymphatic vessel invasion were significantly associated with markers of aggressive disease which suggest their importance in melanoma. Lymphatic vessel invasion was also associated with a high macrophage count, suggesting a role for macrophage in mediating the process of metastatic via lymphatic vessels. In the second part of this project, the adhesion pattern of melanoma and breast cancer cell lines to blood and lymphatic endothelial cell models; large vessel versus microvessel and primary versus immortalised cells were compared. In addition, the effect of macrophage secreted cytokines; TNF-α and IL-1β, tumour conditioned media and macrophage conditioned media on the adhesive process were also studied. Both melanoma and breast cancer cells exhibited a higher level of adhesion to blood compared to the lymphatic endothelial cells. IL-1β stimulation of endothelial cells, tumour cells or both together showed a significant increased in the percentage of adhered tumour cells to the endothelial cell models with a higher increased to the lymphatic endothelial cells. A significant increased tumour cell adhesion was also observed with macrophage conditioned media and this effect seemed to be associated with the amount of IL-1β present. Interestingly, the increased adhesion effect observed with this supernatant was removed with the use of interleukin-1 converting enzyme (ICE) inhibitor. Expression of adhesion molecules; CLEVER-1, ICAM-1 and VCAM-1 were examined to study which adhesion molecules might regulate the process of tumour-endothelial interactions. Stimulation of endothelial cell models with IL-1β did not show any significant altered CLEVER-1 expression suggesting that although CLEVER-1 is an important lymphatic specific adhesion molecule, it may not be the principle regulator of tumour-endothelial interactions. This process may be regulated by ICAM-1 and VCAM-1 in which the expression increased significantly upon stimulation with IL-1β. In the third part of this study, the effect of TNF-α, IL-1β, tumour conditioned media and macrophage conditioned media stimulation on melanoma and breast cancer cell migration were investigated using wound healing assays. Following exposure to TNF-α and IL-1β, a significant increase in the percentage of wound closure was observed and the increase was higher in IL-1β stimulated cells. Similarly, when tumour cells were exposed to macrophage conditioned media, there was an increase in the percentage of wound closure compared to control cells. The effect of IL-1β and macrophage conditioned media on breast cancer cell migration across blood and lymphatic endothelial cells were also studied using Boyden chamber transmigration assay. Significant increased in tumour cells transmigration was observed with IL-1β stimulation, with similar affinity across both endothelial cell types. However, when cells were stimulated with macrophage supernatant from lipopolysaccharide (LPS) stimulated macrophages, an increase transmigratory effect was notably observed to the lymphatic endothelial cells. Interestingly, the increased adhesion effect was removed with the used of ICE inhibitors. The last part of this study dealt with IL-1β expression in breast tissue samples. 1511 early stage breast cancer tissue microarray samples were stained with commercially available IL-1β antibody to examine the association with lymphatic vessel invasion, clinicopathological variables and clinical outcome. High IL-1β expression in tumour cells was significantly associated with the absence of both intra-tumoural and peri-tumoural lymphatic vessel invasion. A significant association was also observed between low IL-1β expression in tumour cells with breast cancer specific survival and disease free interval. In conclusion, lymphatic vessels have been found to play a significant role in breast cancer and melanoma cells progression by being the major route for vascular dissemination. In the in-vitro settings, this study has shown that IL-1β, with macrophages as the main producer, could regulate tumour cell invasion especially to the lymphatic circulation. This project has yielded some important results towards understanding of the lymphatic vasculature and modulation of lymphatic vessel invasion. However, more studies are needed to enable translation of research into clinical management of cancer.

Many angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce mortality after acute myocardial infarction (AMI), yet no study has investigated if this is a class effect. Discharge prescription data were analyzed for patients ≥65 years old hospitalized for AMI in Quebec between 1996 and 1998. Among those prescribed an ACE inhibitor (n = 6,287), the association between the specific drug prescribed and mortality following AMI was studied using Cox proportional-hazards models. A propensity score analysis compared short-acting with long-acting ACE inhibitors to account for confounding by indication. / After adjusting for potentially confounding variables, enalapril, fosinopril, and captopril appeared less effective than ramipril at reducing mortality---hazard ratios (and 95% CI): 1.38 (1.01 to 1.89), 1.47 (1.05 to 2.05), and 1.46 (1.05 to 2.03), respectively. Lisinopril appeared to be as effective as ramipril. Short-acting ACE inhibitors were associated with higher mortality than long-acting ACE inhibitors, but only in certain subgroups. / Among patients prescribed an ACE inhibitor following AMI, it appears that the mortality benefits differ according to the specific drug prescribed.

No description available.

The objectives of this project were: 1) to study the spatial interactions of single nucleotide polymorphisms (SNPs) related to fungicide resistance within Botrytis cinerea populations isolated from grapes; 2) to study the spatial distribution patterns of SNPs related to fungicide resistance within B. cinerea populations in grape and within B. squamosa populations in onion; and 3) to compute sampling curves relative to mean SNP incidence estimation. In a first experiment, B. cinerea isolates were collected following a quadrat-based design (100 10x10m quadrats) in two commercial vineyards. The presence of 9 SNPs related to resistance to iprodione, boscalid, azoxystrobin and fenhexamid were detected using PCR-RFLP, PIRA-PCR and RT-qPCR assays. These data were spatially referenced and considered as a multivariate point pattern in a given vineyard. Spatial point patterns were analyzed by pairs, using an extension of Diggle's procedure for the analysis of nearest-neighbor distances. In this randomization testing procedure, the cumulative relative frequency distribution of the inter-SNP distances was used to characterize the spatial relationship between SNPs related to fungicide resistance. In the second experiment, two SNPs known to be responsible for boscalid resistance and one SNP known to be responsible for dicarboximide resistance in B. cinerea on grape were studied, in addition to one SNP responsible for dicarboximide resistance in B. squamosa on onion. One onion field was sampled in 2009 and another one was sampled in 2010 for B. squamosa, and two vineyards were sampled in 2011 for B. cinerea, for a total of four sampled sites. Sampling was carried following the same design as in the first experiment, except 10 samples were collected in each quadrat. Samples were analyzed by RFLP-PCR. The characterization of spatial distribution patterns was made through the fitting of discrete probability distributions. The level of mutations obtained in the first experiment was 90%, 64%, 67%, 33% and 1% for G143A, I86S, H272R, H272Y and N230I, respectively. Our results show that three spatial relationships can arise when spatial point patterns representing the presence of SNPs related to fungicide resistance are compared by pairs: spatial exclusiveness (12%), spatial co-existence (31%) and absence of a spatial relationship (56%). Despite the fact that more than one half of the pairs of SNPs tested showed no spatial relationship, the presence of about a third of inclusive spatial relationships supports the models of co-existence between sensitive and resistant strains postulated in the literature, but suggests a higher level of complexity in the resistant-sensitive interactions. In the second experiment, the beta-binomial distribution was found to fit the data better than the binomial distribution for all data sets. This indicates local SNP aggregation among sampling units, as supported by estimates of the parameter θ of the beta-binomial distribution ranging from 0.09 to 0.23, with an overall median value of 0.20. On the basis of the spatial distribution patterns of SNP incidence that we found in Botrytis populations, sampling curves were developed for various levels of precision, emphasizing the importance of sampling for early detection of fungicide resistance in plant disease epidemiology. / Les objectifs de ce projet étaient: 1) d'étudier les interactions spatiales entre polymorphismes nucléotidiques simples (PNS) associés à la résistance aux fongicides dans les populations de Botrytis cinerea provenant de raisins infectés; 2) d'étudier les patrons de distribution spatiale des PNS associés à la résistance aux fongicides au sein de populations de B. cinerea provenant de vignobles et de populations de Botrytis squamosa dans des champs d'oignions; et 3) de développer des courbes d'échantillonnages associées à l'estimation de l'incidence moyenne des PNS. Dans une première expérience, des isolats de B. cinerea ont été récoltés dans deux vignobles commerciaux en suivant une grille d'échantillonnage de 100 quadrats de 10x10m. La présence de 9 PNS associés à la résistance à l'iprodione, au boscalid, à l'azoxystrobine et au fenhexamid a été détectée par PCR-RFLP, PIRA-PCR et RT-qPCR. Les données ont été référencées spatialement et pour chaque vignoble, considérées comme un patron ponctuel multivarié. Les analyses ont été réalisées par paire, à l'aide d'une extension de la méthode de Diggle pour l'analyse des distances aux plus proches voisins. Dans cette procédure de test par randomisation, la distribution des fréquences relatives cumulatives des distances inter-PNS est utilisée afin de caractériser les patrons de relation spatiale entre PNS associés à la résistance aux fongicides. Dans une deuxième expérience, deux PNS associés à la résistance de B. cinerea au boscalid et un PNS associé à la résistance de B. cinerea aux dicarboximides ont été étudiés dans la vigne, en plus d'un PNS associé à la résistance de B. squamosa aux dicarboximides dans l'oignion. Pour B. squamosa, deux champs ont été échantillonnés, un en 2009 et un en 2010, et pour B. cinerea, deux champs ont été échantillonnés en 2011, pour un total de quatre sites d'échantillonnage. L'échantillonnage a été réalisé en suivant le même dispositif expérimental que pour la première expérience, à la différence que 10 échantillons ont été prélevés dans chaque quadrat. Les échantillons ont été analysés par PCR-RFLP, et les patrons de distribution spatiale ont été caractérisés sur base de l'ajustement des lois de distributions. Dans la première expérience, les proportions de PNS étaient de 90%, 64%, 67%, 33% et 1% pour G143A, I86S, H272R, H272Y et N230I, respectivement. Ces résultats démontrent que, lorsque les PNS associés à la résistance aux fongicides sont comparés par paires, trois types de relation spatiale peuvent survenir: l'absence de relation spatiale (56%), l'inclusion spatiale (31%) et l'exclusion spatiale (12%). En dépit du fait que plus de la moitié des paires de PNS testées ne montraient aucune relation spatiale, la présence de relation spatiale inclusive (31%) supporte les modèles de coexistence entre phénotypes sensibles et résistants, mais suggère un niveau de complexité supérieur. Pour la seconde expérience, la distribution bêta-binomiale s'ajustait mieux aux données que la distribution binomiale pour tous les jeux de données. Les valeurs estimées de l'indice d'agrégation θ étaient comprises entre 0.09 et 0.23 (valeur médiane de 0.20), indiquant une agrégation locale des PNS au sein d'une même unité d'échantillonnage. Finalement, en se basant sur les niveaux d'agrégation observés, des courbes d'échantillonnages ont été calculées pour différentes incidences de PNS et différents niveaux de précision. Ces résultats mettent ainsi l'emphase sur l'importance de l'échantillonnage pour une détection rapide de la résistance aux fongicides en épidémiologie.

Mycoparasitism, the direct attack of one fungus on another, is a complex process that involves sequential events, including recognition, attack and subsequent penetration and killing of the host. The cellular interaction between Stachybotrys elegans a mycoparasite of the soilborne plant pathogen Rhizoctonia solani begins with molecular and chemical interactions that lead to expression of several genes or components of signaling pathways, and secretion of many metabolite biomarkers. Transcriptional changes of several mycoparasitism-induced genes (oxidoreductase, cytochrome P450 monooxygenase, carboxylesterase, and O-methyltransferase) during an extended period of interaction were associated with the formation of excessive coils and infection pegs which are required for limiting the growth of the pathogen. Hyphae and sclerotia of R. solani triggered different expression patterns of these genes, which is a clear indication that multiple regulatory mechanisms might be involved during the mycoparasitic process. In response to attack, hyphal and sclerotial cells of R. solani had elevated expression of pyridoxal reductase, a precursor of vitamin B6 or its derivatives which are known as antioxidants and quenchers of reactive oxygen species. The high elevated expression of some genes belonging to the mycoparasite and the host suggests that these genes play an important role during the mycoparasitic process and host defense, respectively. As a first step toward understanding the molecular basis of signal transduction during the cross talk between S. elegans and R. solani, the cloning and complete characterization of smkA, the first MAP kinase (MAPK/ERK1/2) gene from S. elegans was accomplished. At the transcriptional level, smkA was significantly induced in response to hyphal parasitism compared to parasitized sclerotia. However, under starvation condition, smkA levels were significantly induced at a later stage of growth. Western blot analysis against ERK1/2 showed an increase in their phosphorylated forms when S. elegans was grown under starvation condition compared to that detected in response to mycoparasitism. A higher abundance of phosphorylated ERK1/2 at the third day of interaction compared to that estimated under starvation condition was detected by applying LC–MS/MS. Direct Infusion Orbitrap MS (DI-MS) and robust bioinformatics tools highlighted a total of 486 metabolites as biomarkers in parasitized cells of R. solani, and in cells from monocultures of R. solani. Carboxylic acids and alkaloids were the predominant chemical groups in parasitized cells compared to those in R. solani monocultures indicating their role in the mycoparasitism. The increase in relative intensity of R. solani-derived indole biomarker, 11-hydroxycanthin-6-one, is indicative of a defense reaction against S. elegans. This study provides new knowledge that can be exploited for plant disease management strategies and for research dealing with biotechnology such as genetic engineering and/or biomarker-assisted plant breeding. / Le mycoparasitisme est un procédé complexe par lequel un champignon en attaque un autre par une série d'événements, soit l'identification, l'attaque et la pénétration subséquente et la mort de l'hôte. L'interaction cellulaire entre Stachybotrys elegans, un mycoparasite du cryptogame Rhizoctonia solani, est caractérisée par des interactions moléculaires et chimiques résultant en l'expression de plusieurs gènes ou composantes de mécanismes de transduction du signal ainsi que la sécrétion de plusieurs métabolites biomarqueurs. Des changements dans la transcription de plusieurs gènes (oxydoréductase, cytochrome P450 monooxygénase, carboxylesterase, et O-méthyltransférase) activés par le mycoparasitisme durant une longue période d'interaction sont associés à l'enroulement et au développement de tubes pénétrants de type infectieux tous deux requis pour limiter la croissance du pathogène. Les hyphes et les sclérotes de R. solani ont initié différents patrons d'expression génique indiquant clairement que plusieurs mécanismes de régulation sont impliqués lors du mycoparasitisme. En réponse à l'attaque, des cellules d'hyphes et de sclérotes ont exprimé abondamment la pyridoxal réductase qui est un précurseur de la vitamine B6 ou de ses dérivés connue pour leur effet antioxydant. Une augmentation dans l'expression de certains gènes appartenant au mycoparasite et à l'hôte suggère que ceux-ci jouent un rôle important lors du mycoparasitisme et de la défense de l'hôte, respectivement. Afin de comprendre la base moléculaire de la transduction du signal durant l'échange entre S. elegans et R. solani, le clonage et la caractérisation complète de smkA, le premier gène codant pour une MAP kinase (MAPK/ERK1/2) chez S. elegans, ont été accomplis. Au niveau de la transcription, smkA a été induit significativement en réponse au parasitisme des hyphes en comparaison avec les sclérotes parasités. Toutefois, en absence de nutriments, les transcrits de smkA ont été induits significativement à un stade de croissance plus avancé. Une analyse par immunobuvardage contre ERK1/2 a démontré une augmentation de la traduction des formes phosphorylées de ces protéines lorsque S. elegans était cultivé en absence de nutriments en comparaison avec la quantité détectée lors du mycoparasitisme. Grâce à la méthode LC–MS/MS, une plus grande concentration des formes phosphorylées de ERK1/2 a été détectée au troisième jour d'interaction en comparaison avec celle estimée en absence de nutriments. À l'aide de la spectrométrie de masse Orbitrap (DI-MS) et d'outils de bioinformatique, 486 métabolites biomarqueurs ont été détectés dans les cellules parasitées de R. solani et dans les cellules provenant de monocultures de R. solani. En comparaison avec les monocultures de R. solani, les groupes chimiques prédominants dans les cellules parasitées étaient les acides carboxyliques et les alkaloids ce qui les associe au mycoparasitisme. L'augmentation de l'intensité relative du biomarqueur d'alkaloid dérivé de R. solani, 11- hydroxycanthin-6-one, est un indicateur de la réaction défensive contre S. elegans. Les résultats de cette recherche apportent de nouvelles connaissances utiles à la phytoprotection et à la recherche en biotechnologie comme le génie génétique et/ou la sélection végétale assistée par biomarqueurs.

Two experiments studied the effectiveness of Imitation and Listener Uncertainty as speech training techniques for profoundly hearing-impaired children. In the first study, a single-subject design was employed with two children who were trained on /$ int$/ and /r/ in words using alternating treatments. Results showed short term benefits for both treatments, but better retention and better generalization to spontaneous speech for the Listener Uncertainty approach. In the second study, 33 children were matched as closely as possible and randomly assigned to the Imitation Group, Listener Uncertainty Group or Control Group. Students in the treatment groups were trained on fricatives in words, phrases and sentences. Plosives were used as control phonemes. Results indicated significant improvement on production of trained and untrained words for both treatments, with higher scores for Listener Uncertainty. However, there was no difference between the treatment groups and control group on ability to generalize target sounds to spontaneous speech. Effects of context and phoneme position were also examined.