A protocol for a systematic review of non-randomised evaluations of strategies to improve participant recruitment to randomised controlled trials

Peer reviewed

"Sexism in the Schools" conference at P.S. 41 about the changing roles of women in Africa and America

General note: Title and date provided by Bettye Lane.

"Sexism in the Schools" conference at P.S. 41 about the changing roles of women in Africa and America

General note: Title and date provided by Bettye Lane.

"Sexism in the Schools" conference at P.S. 41 about the changing roles of women in Africa and America

General note: Title and date provided by Bettye Lane.

The construction and characterization of new permeable rho antagonists and their roles after spinal cord injury

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Roles of CTCF and YY1 in T Cell Receptor Gene Rearrangement And T Cell Development

Diversity of T cell receptors (TCR) and immunoglobulins (Ig) is generated by V(D)J recombination of antigen receptor (AgR) loci. The Tcra-Tcrd locus is of particular interest because it displays a nested organization of Tcrd and Tcra gene segments and V(D)J recombination follows an intricate developmental program to assemble both TCRδ and TCRα repertoires. However, the mechanisms that dictate the developmental regulation of V(D)J recombination of the Tcra-Tcrd locus remain unclear.

We have previously shown that CCCTC-binding factor (CTCF) regulates Tcra gene transcription and rearrangement through organizing chromatin looping between CTCF- binding elements (CBEs). This study is one of many showing that CTCF functions as a chromatin organizer and transcriptional regulator genome-wide. However, detailed understanding of the impact of specific CBEs is needed to fully comprehend the biological function of CTCF and how CTCF influences the generation of the TCR repertoire during thymocyte development. Thus, we generated several mouse models with genetically modified CBEs to gain insight into the CTCF-dependent regulation of the Tcra-Tcrd locus. We revealed a CTCF-dependent chromatin interaction network at the Tcra-Tcrd locus in double-negative thymocytes. Disruption of a discrete chromatin loop encompassing Dδ, Jδ and Cδ gene segments allowed a single Vδ segment to frequently contact and rearrange to diversity and joining gene segments and dominate the adult TCRδ repertoire. Disruption of this loop also narrowed the TCRα repertoire, which, we believe, followed as a consequence of the restricted TCRδ repertoire. Hence, a single CTCF-mediated chromatin loop directly regulates TCRδ diversity and indirectly regulates TCRα diversity. In addition, we showed that insertion of an ectopic CBE can modify chromatin interactions and disrupt the rearrangement of particular Vδ gene segments. Finally, we investigated the role of YY1 in early T cell development by conditionally deleting YY1 in developing thymocytes. We found that early ablation of YY1 caused severe developmental defects in the DN compartment due to a dramatic increase in DN thymocyte apoptosis. Furthermore, late ablation of YY1 resulted in increased apoptosis of DP thymocytes and a restricted TCRα repertoire. Mechanistically, we showed that p53 was upregulated in both DN and DP YY1-deficient thymocytes. Eliminating p53 in YY1-deficient thymocytes rescued the survival and developmental defects, indicating that these YY1-dependent defects were p53-mediated. We conclude that YY1 is required to maintain cell viability during thymocyte development by thwarting the accumulation of p53.

Overall, this thesis work has shown that CTCF-dependent looping provides a central framework for lineage- and developmental stage-specific regulation of Tcra-Tcrd gene expression and rearrangements. In addition, we identified YY1 as a novel regulator of thymocyte viability.

The Roles of Phenotypic Plasticity and Plant-Microbe Interactions in the Evolution of Complex Traits in Boechera stricta

All organisms live in complex habitats that shape the course of their evolution by altering the phenotype expressed by a given genotype (a phenomenon known as phenotypic plasticity) and simultaneously by determining the evolutionary fitness of that phenotype. In some cases, phenotypic evolution may alter the environment experienced by future generations. This dissertation describes how genetic and environmental variation act synergistically to affect the evolution of glucosinolate defensive chemistry and flowering time in Boechera stricta, a wild perennial herb. I focus particularly on plant-associated microbes as a part of the plant’s environment that may alter trait evolution and in turn be affected by the evolution of those traits. In the first chapter I measure glucosinolate production and reproductive fitness of over 1,500 plants grown in common gardens in four diverse natural habitats, to describe how patterns of plasticity and natural selection intersect and may influence glucosinolate evolution. I detected extensive genetic variation for glucosinolate plasticity and determined that plasticity may aid colonization of new habitats by moving phenotypes in the same direction as natural selection. In the second chapter I conduct a greenhouse experiment to test whether naturally-occurring soil microbial communities contributed to the differences in phenotype and selection that I observed in the field experiment. I found that soil microbes cause plasticity of flowering time but not glucosinolate production, and that they may contribute to natural selection on both traits; thus, non-pathogenic plant-associated microbes are an environmental feature that could shape plant evolution. In the third chapter, I combine a multi-year, multi-habitat field experiment with high-throughput amplicon sequencing to determine whether B. stricta-associated microbial communities are shaped by plant genetic variation. I found that plant genotype predicts the diversity and composition of leaf-dwelling bacterial communities, but not root-associated bacterial communities. Furthermore, patterns of host genetic control over associated bacteria were largely site-dependent, indicating an important role for genotype-by-environment interactions in microbiome assembly. Together, my results suggest that soil microbes influence the evolution of plant functional traits and, because they are sensitive to plant genetic variation, this trait evolution may alter the microbial neighborhood of future B. stricta generations. Complex patterns of plasticity, selection, and symbiosis in natural habitats may impact the evolution of glucosinolate profiles in Boechera stricta.

Through the Lenses of Q’eqchi Maya: (Re)Framing the Story of Development in a Guatemalan Indigenous Community Through Participant-Created Photographs

The question of evaluations of development projects has been widely debated within the field of international development, with scholars and development practitioners calling for increased community-driven evaluations. However, there has been a paucity of research in community-led project evaluations, and a largely absent investigation utilizing visual anthropology/sociology methodologies. This paper seeks to shift this power by giving voice to the intended beneficiaries of an eco-tourism project in a rural indigenous Guatemala village. Through photographs taken by community members and corresponding interviews, this paper shows the way in which community members have and continue to reframe the idea of development in their village. Specifically, my analysis reveals how residents see changing forms of access, how they reframe ideas of beauty and modernization, and how they reframe their relationship to the land through Western conservation and private property ideals. This research thus provides an alternative narrative to the Western NGO’s evaluations and knowledge production, especially in respect to development and indigenous knowledge. By showing how community members are reframing the story of development, this paper demonstrates the usefulness of using participatory documentary photography in community-led evaluations, and helps balance the playing field by providing a much-needed alternative narrative of project evaluation.

Predicting Transcript Production Rates in Yeast With Sparse Linear Models

To provide biological insights into transcriptional regulation, a couple of groups have recently presented models relating the promoter DNA-bound transcription factors (TFs) to downstream gene’s mean transcript level or transcript production rates over time. However, transcript production is dynamic in response to changes of TF concentrations over time. Also, TFs are not the only factors binding to promoters; other DNA binding factors (DBFs) bind as well, especially nucleosomes, resulting in competition between DBFs for binding at same genomic location. Additionally, not only TFs, but also some other elements regulate transcription. Within core promoter, various regulatory elements influence RNAPII recruitment, PIC formation, RNAPII searching for TSS, and RNAPII initiating transcription. Moreover, it is proposed that downstream from TSS, nucleosomes resist RNAPII elongation.

Here, we provide a machine learning framework to predict transcript production rates from DNA sequences. We applied this framework in the S. cerevisiae yeast for two scenarios: a) to predict the dynamic transcript production rate during the cell cycle for native promoters; b) to predict the mean transcript production rate over time for synthetic promoters. As far as we know, our framework is the first successful attempt to have a model that can predict dynamic transcript production rates from DNA sequences only: with cell cycle data set, we got Pearson correlation coefficient Cp = 0.751 and coefficient of determination r2 = 0.564 on test set for predicting dynamic transcript production rate over time. Also, for DREAM6 Gene Promoter Expression Prediction challenge, our fitted model outperformed all participant teams, best of all teams, and a model combining best team’s k-mer based sequence features and another paper’s biologically mechanistic features, in terms of all scoring metrics.

Moreover, our framework shows its capability of identifying generalizable fea- tures by interpreting the highly predictive models, and thereby provide support for associated hypothesized mechanisms about transcriptional regulation. With the learned sparse linear models, we got results supporting the following biological insights: a) TFs govern the probability of RNAPII recruitment and initiation possibly through interactions with PIC components and transcription cofactors; b) the core promoter amplifies the transcript production probably by influencing PIC formation, RNAPII recruitment, DNA melting, RNAPII searching for and selecting TSS, releasing RNAPII from general transcription factors, and thereby initiation; c) there is strong transcriptional synergy between TFs and core promoter elements; d) the regulatory elements within core promoter region are more than TATA box and nucleosome free region, suggesting the existence of still unidentified TAF-dependent and cofactor-dependent core promoter elements in yeast S. cerevisiae; e) nucleosome occupancy is helpful for representing +1 and -1 nucleosomes’ regulatory roles on transcription.

Weathering the crisis? Managing democracy at a national broadcaster

With post-2008 political and economic crises as its backdrop, this inquiry into the political roles and functions of public service broadcasting (PSB) in Ireland is principally concerned with examining the capacities for and actuality of critical and counter-hegemonic professional journalistic and institutional mediations of crisis. Recognising the diversity of influences on the normative identity of Irish PSB, the dissertation adopts a sociological approach that acknowledges the systemic embedding of media institutions in the broader field of power. An initial tracing of the formative impacts of endogenous and exogenous forces on the democratic horizons of PSB suggests that the present crisis conjuncture does not represent promising terrain for engendering critical crisis and recovery imaginaries. A methodologically diverse intra-institutional empirical research agenda aims to explore at close hand Irish PSB’s contingent navigation of crisis, encompassing ethnographic observation in the newsroom, practitioner interviews and textual analysis of broadcast output. These methods afford close analysis of practices of journalistic production and reflexivity, self-conceptions of the journalistic habitus, and ideological affinities of crisis framings in broadcast output. These analyses are supplemented by a participant observation study of the possibilities for public agenda-building in a key institutional venue of public participation in broadcasting governance. The findings offer an evidential basis for the arguments that the crisis has prompted only minimal changes to professional norms and practices of representation and inclusion; that journalistic crisis framings tend toward effecting hegemonic repair by lending support to neoliberal crisis and recovery imaginaries; and that the institutional openings for the building of public counterpower are highly constrained. The overall conclusion is made that the normative democratic orientation embedded in the professional and institutional projects of public service broadcasting help render it ill-equipped to act as a re-democratising countervailing power against the democratic regressions engendered by the present crisis of democratic capitalism.

Désensibilisation morale et légitimation de l'intimidation entre pairs au secondaire

Cette thèse doctorale, qui prend la forme de quatre articles, est une étude corrélationnelle mettant en relation le raisonnement moral et la légitimation des dynamiques d’intimidation par les pairs chez des adolescents de 3ème secondaire. L’objectif principal poursuivi était d’examiner la contribution de la désensibilisation morale aux conduites adoptées par les adolescents lors d’incidents d’intimidation à l’école. L’objectif secondaire était d’examiner l’importance accordée respectivement à des standards de conduite issus des domaines moral, conventionnel et personnel chez les adolescents impliqués dans des incidents d’intimidation. Le premier article expose la problématique de la légitimation des dynamiques d’intimidation par les jeunes en faisant état des croyances normatives et des caractéristiques des environnements scolaires qui y sont associées. L’article discute de l’écart qui s’observe entre l’opposition affirmée de la majorité des adolescents face aux conduites d’intimidation et leur récurrence dans les milieux scolaires et vient compléter une première section décrivant les conséquences de l’intimidation pour les communautés scolaires. Le deuxième article s’inscrit dans le cadre théorique de cette thèse et fait état des connaissances sur le raisonnement moral des élèves impliqués dans des dynamiques d’intimidation. Il présente une explication des conduites d’intimidation dans la perspective de la théorie des domaines de la connaissance sociale et dans celle de la théorie de l’agentivité morale. Ces approches ont été retenues pour opérationnaliser le concept de désensibilisation morale afin de rencontrer les objectifs de recherche poursuivis. Le troisième article rapporte la démarche utilisée pour vérifier l’hypothèse d’une relation positive entre les conduites d’intimidation et l’acceptabilité d’incidents d’intimidation hypothétiques, de même que l’hypothèse d’une relation positive entre les conduites d’intimidation et le désengagement moral chez les adolescents impliqués. Le quatrième article rapporte la démarche utilisée pour examiner les justifications sociomorales émises par différents profils d’adolescents impliqués dans des incidents d’intimidation de façon à associer leur conduite avec les domaines de connaissances normatives auxquels se rattachent leurs justifications. Les résultats obtenus sont ensuite discutés au chapitre suivant afin de mettre en évidence la contribution de chacune des approches morales retenues à l’explication des conduites en contexte d’intimidation et les caractéristiques du raisonnement moral associées aux rôles adoptés et des pistes d’intervention sont offertes. Finalement, cette thèse doctorale conclue que seul le niveau moyen de désengagement moral, un indice global de l’adhésion à des croyances normatives antisociales, contribue statistiquement à l’explication des conduites adoptées lors d’incident d’intimidation au-delà du sexe des participants. Quant au raisonnement sociomoral, il informe davantage sur la façon dont les circonstances d’incidents d’intimidation sont reliées à la désensibilisation morale des jeunes impliqués. Les adolescents qui prennent activement la défense de pairs intimidés étaient caractérisés par un raisonnement moral plus uniforme, tandis que le raisonnement des élèves qui intimident et de ceux qui demeurent passifs était caractérisé par la subordination de principes moraux, respectivement en faveur d’impératifs à caractère conventionnel et d’impératifs à caractère personnel.

The construction and characterization of new permeable rho antagonists and their roles after spinal cord injury

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Exploring Perceptions of Middle Class Urban Indian Women Regarding Socio-Cultural Deterrents Influencing Participation in Adult and Continuing Educational Programs

Unlike its childhood counterpart, adult and continuing education is a voluntary activity, where adult learners partake in educational programs for the sake of realizing some explicit or implicit goal. The purpose of this study was to explore the association between socio-cultural influences and deterrents to participation of middle class urban Indian women in adult and continuing educational programs. Darkenwald and Merriam’s (1982) theory of non-participation was selected as the theoretical lens used to guide this study. This study involved collecting qualitative data to analyze participant views and was collected through 16 semi-structured interviews to explore participants’ individual perceptions concerning socio-cultural deterrents influencing participation of middle class urban Indian women in adult and continuing educational programs. Qualitative data were analyzed to discover emerging themes and sub-themes. In the second phase of the study, a modified Deterrent to Participation Scale – General (DPS-G) was used to measure data collected from the surveys completed by participants, that included specific demographic questions. Descriptive statistics were used to examine the relationships between the demographic questions and the deterrent identified on the DPS-G. The interview and survey data were used convergently to understand the relationship between socio-cultural influences and deterrents impacting participant participation in adult and continuing educational programs. The findings of the study indicated that the biggest socio-cultural influence deterring participation among middle class urban Indian women in adult and continuing educational programs is marriage. It is an Indian social norm that comes with a set of pre-defined roles and expectations, and married women find themselves consumed by fulfilling the marital and familial expectations and responsibilities and participation in adult and continuing educational program is furthest from their mind. Middle class urban Indian women do realize the importance of educational pursuits, but do not feel that they can, after marriage. They are open, however, to pursuing adult educational programs in the form of short-term skill development programs leading to income generation, although they would lead primarily to home-based work enterprises.

Student Financial Aid:The Roles of Loans and Grants (Working Paper 37)

This paper addresses the roles of loans and grants as forms of student financial aid. It begins with a simple choice model where individuals decide to pursue post-secondary studies if i) the net benefits of doing so are positive and ii) no financing or liquidity constraints stand in their way. The effects of loans and grants on these two elements of the schooling decision are then discussed. It is argued that based on equity, efficiency, and fiscal considerations, loans are generally best suited for helping those who want to go but face financing constraints, whereas grants are more appropriate for increasing the incentives for individuals from disadvantaged backgrounds to further their studies. Loan subsidies, which make loans part-loan and part-grant, are also discussed, including how they might be used to address “debt aversion”. Given that subsidised loans have a grant (subsidy) element, while grants help overcome the credit constraints upon which loans are targeted, the paper then attempts to establish some general rules for providing loans, for subsidising the loans awarded, and for giving “pure” grants. It concludes with an application of these principles in the form of a recent proposal for reforming the student financial system in Canada. *