Understanding Antenatal Genetics Services in Sri Lanka: Current Landscape of Screening and Diagnostic Services and Contextual Factors Influencing Their Availability and Uptake

Background: Too little information is available on Sri Lanka’s current capacity to provide community genetic services—antenatal genetic services in particular—to understand whether building that capacity could further improve and reduce disparity in maternal and child health. This qualitative research project seeks to gather information on congenital disorders, routine antenatal care, and the current state of antenatal screening testing services within that routine antenatal to assess the feasibility of and the need for scaling up antenatal genetics services in Sri Lanka. Methods: Nineteen key informant (KI) interviews were conducted with stakeholders in antenatal care and genetic services. Seven focus group discussions were held with a total of 56 Public Health Midwives (PHMs), the health workers responsible for antenatal care at the field level. Transcripts for all interviews and FGDs were analyzed for key themes, and themes were categorized to address the specific aims of the project. Results: Antenatal genetic services play a minor role in antenatal care, with screening and diagnostic procedures available in the private sector and paid for out-of-pocket. KIs and PHMs expect that demand for antenatal genetic services will increase as patients’ purchasing power and knowledge grow but note that prohibitive abortion laws limit the ability of patients to act on test results. Genetic services compete for limited financial and human resources in the free public health system, and inadequate information on the prevalence of congenital disorders limits the ability to understand whether funding for services related to those disorders should be increased. A number of alternatives to scaling up antenatal genetic services within the free health system might be better suited to the Sri Lankan structural and social context. Conclusions: Scaling up antenatal genetic services within the public health system is not feasible in the current financial, legal, and human resource context. Yet current availability and utilization patterns contribute to regional and economic disparities, suggesting that stasis will not bring continued improvements in maternal and child health. More information on the burden of congenital disorders is necessary to fully understand if and how antenatal genetic service availability should be increased in Sri Lanka, but even before that information is gathered, examination of policies for patient referral, termination of pregnancy, and government support for individuals with genetic disease are steps that might bring extend improvements and reduce disparity in maternal and child health.

Outcomes after Unrelated Umbilical Cord Blood Transplantation for Children with Osteopetrosis.

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for most children with osteopetrosis (OP). Timing of HSCT is critical; therefore, umbilical cord blood transplantation (UCBT) is an attractive option. We analyzed outcomes after UCBT in 51 OP children. Median age at UCBT was 6 months. Seventy-seven percent of the cord blood grafts had 0 or 1 HLA disparity with the recipient. Conditioning regimen was myeloablative (mostly busulfan-based in 84% and treosulfan-based in 10%). Antithymocyte globulin was given to 90% of patients. Median number of total nucleated and CD34(+) cells infused was 14 × 10(7)/kg and 3.4 × 10(5)/kg, respectively. Median follow-up for survivors was 74 months. Cumulative incidence (CI) of neutrophil recovery was 67% with a median time to recovery of 23 days; 33% of patients had graft failure, 81% of engrafted patients had full donor engraftment, and 19% had mixed donor chimerism. Day 100 CI of acute graft-versus-host disease (grades II to IV) was 31% and 6-year CI of chronic graft-versus-host disease was 21%. Mechanical ventilation was required in 28%, and veno-occlusive disease was diagnosed in 16% of cases. Six-year overall survival rate was 46%. Comparative studies with other alternative donors should be performed to evaluate whether UCBT remains a valid alternative for children with OP without an HLA-matched donor.

A Model of Lung Tumor Angiogenesis in a Biomimetic Poly(ethylene glycol)-based Hydrogel System

Tumor angiogenesis is critical to tumor growth and metastasis, yet much is unknown about the role vascular cells play in the tumor microenvironment. A major outstanding challenge associated with studying tumor angiogenesis is that existing preclinical models are limited in their recapitulation of in vivo cellular organization in 3D. This disparity highlights the need for better approaches to study the dynamic interplay of relevant cells and signaling molecules as they are organized in the tumor microenvironment. In this thesis, we combined 3D culture of lung adenocarcinoma cells with adjacent 3D microvascular cell culture in 2-layer cell-adhesive, proteolytically-degradable poly(ethylene glycol) (PEG)-based hydrogels to study tumor angiogenesis and the impacts of neovascularization on tumor cell behavior.

In initial studies, 344SQ cells, a highly metastatic, murine lung adenocarcinoma cell line, were characterized alone in 3D in PEG hydrogels. 344SQ cells formed spheroids in 3D culture and secreted proangiogenic growth factors into the conditioned media that significantly increased with exposure to transforming growth factor beta 1 (TGF-β1), a potent tumor progression-promoting factor. Vascular cells alone in hydrogels formed tubule networks with localized activated TGF-β1. To study cancer cell-vascular cell interactions, the engineered 2-layer tumor angiogenesis model with 344SQ and vascular cell layers was employed. Large, invasive 344SQ clusters developed at the interface between the layers, and were not evident further from the interface or in control hydrogels without vascular cells. A modified model with spatially restricted 344SQ and vascular cell layers confirmed that observed 344SQ cluster morphological changes required close proximity to vascular cells. Additionally, TGF-β1 inhibition blocked endothelial cell-driven 344SQ migration.

Two other lung adenocarcinoma cell lines were also explored in the tumor angiogenesis model: primary tumor-derived metastasis-incompetent, murine 393P cells and primary tumor-derived metastasis-capable human A549 cells. These lung cancer cells also formed spheroids in 3D culture and secreted proangiogenic growth factors into the conditioned media. Epithelial morphogenesis varied for the primary tumor-derived cell lines compared to 344SQ cells, with far less epithelial organization present in A549 spheroids. Additionally, 344SQ cells secreted the highest concentration of two of the three angiogenic growth factors assessed. This finding correlated to 344SQ exhibiting the most pronounced morphological response in the tumor angiogenesis model compared to the 393P and A549 cell lines.

Overall, this dissertation demonstrates the development of a novel 3D tumor angiogenesis model that was used to study vascular cell-cancer cell interactions in lung adenocarcinoma cell lines with varying metastatic capacities. Findings in this thesis have helped to elucidate the role of vascular cells in tumor progression and have identified differences in cancer cell behavior in vitro that correlate to metastatic capacity, thus highlighting the usefulness of this model platform for future discovery of novel tumor angiogenesis and tumor progression-promoting targets.

L’engagement au développement professionnel des infirmières œuvrant en centre hospitalier universitaire : une étude qualitative descriptive.

Le développement professionnel (DP) des infirmières est essentiel et déterminant dans l’obtention d’une meilleure qualité de soins. Pour se réaliser, le développement professionnel nécessite un engagement individuel des infirmières elles-mêmes. Or, une disparité est observée en centre hospitalier universitaire (CHU) entre la volonté exprimée par les infirmières de poursuivre leur DP et leur assiduité dans les activités de développement offertes par les organisations. L’objectif de cette étude qualitative est de décrire la perception des infirmières œuvrant en CHU (n=8) en regard des facteurs organisationnels susceptibles de favoriser leur engagement à poursuivre leur développement professionnel. Cette analyse a été effectuée à partir de huit entrevues individuelles semi-dirigées réalisées auprès d’infirmières œuvrant dans le secteur de chirurgie du CHU Sainte-Justine. Les résultats démontrent que de nombreux facteurs organisationnels et individuels. Les principaux facteurs influant sur l’engagement des infirmières sont : a) un environnement favorable au DP; b) l’accessibilité au DP et; c) des modalités de DP variées. Les modalités les plus favorables sont celles favorisant leur autonomie et incitant leur implication. En conclusion, pour obtenir un maximum d’engagement des infirmières, les organisations doivent présenter une offre de DP variée et structurée, répondant aux besoins professionnels des infirmières, tout en mitigeant l’impact des contraintes liées à leur fonction et à leur vie personnelle.

The Decolonization of Northwest Community College

In 1996, the authors of the Canadian Royal Commission on Aboriginal Peoples concluded Canadian educational policy had been based on the false assumption of the superiority of European worldviews. The report authors recommended the transformation of curriculum and schools to recognize that European knowledge was not universal. Aboriginal researcher Battiste believes the current system of Canadian education causes Aboriginal children to face cognitive imperialism and cognitive assimilation and that this current practice of cultural racism in Canada makes educational institutions a hostile environment for Aboriginal learners. In order to counter this cultural racism, Battiste calls for the decolonization of education. In 2005, the president of Northwest Community College (NWCC), publicly committed to decolonizing the college in order to address the continuing disparity in educational attainment between Aboriginal and non-Aboriginal learners. Upon the president’s departure in 2010, the employees of NWCC were left to define for themselves the meaning of decolonization. This qualitative study was designed to build a NWCC definition of colonization and decolonization by collecting researcher observations, nine weeks of participant blog postings, and pre and post blog Word survey responses drawn from a purposeful sample of six Aboriginal and six non-Aboriginal NWCC employees selected from staff, instructor and administrator employee groups. The findings revealed NWCC employees held multiple definitions of colonization and decolonization which did not vary between employee groups, or based on participant gender; however, differences were found based on whether the participants were Aboriginal or non-Aboriginal. Both Aboriginal and non-Aboriginal participants thought decolonization was a worthy goal for the college. Aboriginal participants felt hopeful that decolonization would happen in the future and thought decolonization had to do with moving forward to a time when they would be valued, respected, empowered, unashamed, safe, and viewed as equal to non-Aboriginals. Non-Aboriginal participants were unsure if decolonization was possible because it would require going back in time to restore the Aboriginal way of life. When non-Aboriginal participants felt their thoughts were not being valued or they were being associated with colonialism, they felt angry and guarded and were uncomfortable with Aboriginal participants expressing anger towards Colonizers.

Three Essays on Taxation, Growth and Consumption

The purpose of this dissertation is to examine three distributional issues in macroeconomics. First I explore the effects fiscal federalism on economic growth across regions in China. Using the comprehensive official data set of China for 31 regions from 1952 until 1999, I investigate a number of indicators used by the literature to measure federalism and find robust support for only one such measure: the ratio of local total revenue to local tax revenue. Using a difference-in-difference approach and exploiting the two-year gap in the implementation of a tax reform across different regions of China, I also identify a positive relationship between fiscal federalism and regional economic growth. The second paper hypothesizes that an inequitable distribution of income negatively affects the rule of law in resource-rich economies and provides robust evidence in support of this hypothesis. By investigating a data set that contains 193 countries and using econometric methodologies such as the fixed effects estimator and the generalized method of moments estimator, I find that resource-abundance improves the quality of institutions, as long as income and wealth disparity remains below a certain threshold. When inequality moves beyond this threshold, the positive effects of the resource-abundance level on institutions diminish quickly and turn negative eventually. This paper, thus, provides robust evidence about the endogeneity of institutions and the role income and wealth inequality plays in the determination of long-run growth rates. The third paper sets up a dynamic general equilibrium model with heterogeneous agents to investigate the causal channels which run from a concern for international status to long-run economic growth. The simulation results show that the initial distribution of income and wealth play an important role in whether agents gain or lose from globalization.

Self-efficacy in depression: Bridging the gap between competence and real-world functioning

Background: Depression is the largest contributing factor to years lost to disability, and symptom remission does not always result in functional improvement. Comprehensive analysis of functioning requires investigation both of the competence to perform behaviours, as well as actual performance in the real world. Further, two independent domains of functioning have been proposed: adaptive (behaviours conducive to daily living skills and independent functioning) and interpersonal (behaviours conducive to the successful initiation and maintenance of social relationships). To date, very little is known about the relationship between these constructs in depression, and the factors that may play a key role in the disparity between competence and real-world performance in adaptive and interpersonal functioning. Purpose: This study used a multidimensional (adaptive and interpersonal functioning), multi-level (competence and performance) approach to explore the potential discrepancy between competence and real-world performance in depression, specifically investigating whether self-efficacy (one’s beliefs of their capability to perform particular actions) predicts depressed individuals’ underperformance in the real world relative to their ability. A comparison sample of healthy participants was included to investigate the level of depressed individuals’ impairment, across variables, relative to healthy individuals. Method: Forty-two participants with depression and twenty healthy participants without history of, or current, psychiatric illness were recruited in the Kingston, Ontario community. Competence, self-efficacy, and real-world functioning all in both adaptive and interpersonal domains, and symptoms were assessed during a single-visit assessment. Results: Relative to healthy individuals, depressed individuals showed significantly poorer adaptive and interpersonal competence, adaptive and interpersonal functioning, and significantly lower self-efficacy for adaptive and interpersonal behaviours. Self-efficacy significantly predicted functional disability both in the domain of adaptive and interpersonal functioning. Interpersonal self-efficacy accounted for significant variance in the discrepancy between interpersonal competence and functioning. Conclusions: The current study provides the first data regarding relationships among competence, functioning, and self-efficacy in depression. Self-efficacy may play an important role in the deployment of functional skills in everyday life. This has implications for therapeutic interventions aimed at enhancing depressed individuals’ engagement in functional activities. There may be additional intrinsic or extrinsic factors that influence the relationships among competence and functioning in depression.

The Evolution and Reform of Summary Trials in Canadian Military Justice

There is a place where a Canadian citizen can be sent to 30 days detention, by someone who is not a judge, without being represented by counsel, and without having a meaningful right to appeal. It is the summary trial system of the Canadian Armed Forces. This thesis analyses that system and suggests reforms. It is aimed at those who have an interest in improving the administration of military justice at the unit level but want to sufficiently understand the issues before doing so. Through a classic legal approach with elements of legal history and comparative law, this study begins by setting military justice in the Canadian legal firmament. The introductory chapter also explains fundamental concepts, first and foremost the broader notion of discipline, for which summary trial is one of the last maintaining tools. Chapter II describes the current system. An overview of its historical background is first given. Then, each procedural step is demystified, from investigation until review. Chapter III identifies potential breaches of the Charter, highlighting those that put the system at greater constitutional risk: the lack of judicial independence, the absence of hearing transcript, the lack of legal representation and the disparity of treatment between ranks. Alternatives adopted in the Canadian Armed Forces and in foreign jurisdictions, from both common law and civil law traditions, in addressing similar challenges are reviewed in Chapter IV. Chapter V analyses whether the breaches could nevertheless be justified in a free and democratic society. Its conclusion is that, considering the availability of reasonable alternatives, it would be hard to convince a court that the current system is a legitimate impairment of the individual’s legal rights. The conclusion Chapter presents options to address current challenges. First, the approach of ‘depenalization’ taken by the Government in recent Bill C-71 is analysed and criticised. The ‘judicialization’ approach is advocated through a series of 16 recommendations designed not only to strengthen the constitutionality of the system but also to improve the administration of military justice in furtherance of service members’ legal rights.

An Examination of Current Approaches to Integrative Indigenous and Western Knowledge System Implementation in Water Research and Management: A Case Study Encompassing the Colonized Geographies of Canada, Australia, New Zealand, and the United States

The commodification of natural resources and the pursuit of continuous growth has resulted in environmental degradation, depletion, and disparity in access to these life-sustaining resources, including water. Utility-based objectification and exploitation of water in some societies has brought us to the brink of crisis through an apathetic disregard for present and future generations. The ongoing depletion and degradation of the world’s water sources, coupled with a reliance on Western knowledge and the continued omission of Indigenous knowledge to manage our relationship with water has unduly burdened many, but particularly so for Indigenous communities. The goal of my thesis research is to call attention to and advance the value and validity of using both Indigenous and Western knowledge systems (also known as Two-Eyed Seeing) in water research and management to better care for water. To achieve this goal, I used a combined systematic and realist review method to identify and synthesize the peer-reviewed, integrative water literature, followed by semi-structured interviews with first authors of the exemplars from the included literature to identify the challenges and insights that researchers have experienced in conducting integrative water research. Findings suggest that these authors recognize that many previous attempts to integrate Indigenous knowledges have been tokenistic rather than meaningful, and that new methods for knowledge implementation are needed. Community-based participatory research methods, and the associated tenets of balancing power, fostering trust, and community ownership over the research process, emerged as a pathway towards the meaningful implementation of Indigenous and Western knowledge systems. Data also indicate that engagement and collaborative governance structures developed from a position of mutual respect are integral to the realization of a given project. The recommendations generated from these findings offer support for future Indigenous-led research and partnerships through the identification and examination of approaches that facilitate the meaningful implementation of Indigenous and Western knowledge systems in water research and management. Asking Western science questions and seeking Indigenous science solutions does not appear to be working; instead, the co-design of research projects and asking questions directed at the problem rather than the solution better lends itself to the strengths of Indigenous science.

Contested dominance modifies the anovulatory consequences of social subordination in female marmosets

Dominance status among female marmosets is reflected in agonistic behavior and ovarian function. Socially dominant females receive submissive behavior from subordinates, while exhibiting normal ovulatory function. Subordinate females, however, receive agonistic behavior from dominants, while exhibiting reduced or absent ovulatory function. Such disparity in female fertility is not absolute, and groups with two breeding females have been described. The data reported here were obtained from 8 female-female pairs of captive female marmosets, each housed with a single unrelated male. Pairs were classified into two groups: “uncontested” dominance (UD) and “contested” dominance (CD), with 4 pairs each. Dominant females in UD pairs showed significantly higher frequencies (4.1) of agonism (piloerection, attack and chasing) than their subordinates (0.36), and agonistic behaviors were overall more frequently displayed by CD than by UD pairs. Subordinates in CD pairs exhibited more agonistic behavior (2.9) than subordinates in UD pairs (0.36), which displayed significantly more submissive (6.97) behaviors than their dominants (0.35). The data suggest that there is more than one kind of dominance relationship between female common marmosets. Assessment of progesterone levels showed that while subordinates in UD pairs appeared to be anovulatory, the degree of ovulatory disruption in subordinates of CD pairs was more varied and less complete. We suggest that such variation in female-female social dominance relationships and the associated variation in the degree and reliability of fertility suppression may explain variations of the reproductive condition of free-living groups of common marmosets

Local Seafood Availability in San Diego, California Seafood Markets

Like many developed coastal cities, San Diego, California has strong geographic and recreational ties to the adjacent ocean, but weak culinary ones. Less than 10% of the seafood consumed in the U.S., and San Diego in particular, is domestic. The popularity and abundance of farmers’ markets and other local markets in San Diego indicates an interest among producers and the public alike in cultivating local, diverse food systems, but this trend has been slower to catch on for seafood. The goal of this project was, therefore, to define and begin to understand the influences on the patterns of locally sourced, domestic seafood availability in San Diego. This study focused on seafood availability in seafood markets including researching market websites and contacting seafood counter managers to determine the general frequency (consistent, occasional, none) at which the markets sold seafood produced by San Diego fishermen or aquafarmers. Seafood market locations were mapped, and demographic and spatial information was gathered for each market’s zip code. The results of the study revealed that only 8% of San Diego’s 86 seafood markets consistently carried San Diego-sourced seafood, and 14% of markets carried it on occasion. Increased density of these local seafood markets was correlated with proximity to the coast, with almost 80% of the markets located within 2 km of the coast. Neither per capita income nor racial diversity was correlated with local seafood market density, indicating that factors contributing to coastal isolation matter more than wealth or diversity in determining where local seafood is sold. The geographic disparity in local seafood availability may be due to a variety of factors, including a small fishing fleet, prevalence of imported seafood, limited waterfront and urban infrastructure needed to support a local seafood system, and a lack of public awareness about local fisheries. Information gleaned from this study can inform further investigation into the influences on local, equitable seafood systems, as well as help consumers, producers and marketers to make informed decisions about seafood purchases and marketing efforts.

Pratiquer l’égalité entre les femmes et les hommes au sein des organisations : étude de cas des ONG au Mali.

Cette thèse analyse les pratiques d’égalité entre les femmes et les hommes au sein des organisations non gouvernementales (ONG) maliennes qui ont reçu du financement canadien. En effet, l’aide publique au développement a subi des transformations majeures depuis les années 1950. L’une de ces transformations a été le rôle important joué par les ONG dans les années 1990, à la suite de l’adoption des politiques d’ajustements structurels et de la fin de la monopolisation par l’État en ce qui a trait à l’aide publique pour les projets de développement. Entre autres, les ONG ont été sollicitées pour promouvoir les politiques d’égalité entre hommes et femmes. L’importance des ONG dans l’aide publique au développement a créé des relations de dépendances vis-à-vis des bailleurs de fonds qui imposent des conditionnalités. Nos résultats ont montré que les bailleurs de fonds exigent l’égalité entre les sexes en ce qui concerne les bénéficiaires des programmes, mais, paradoxalement, ne l’exigent pas à l’intérieur des ONG et dans leurs ressources humaines. En analysant la composition du personnel de huit ONG maliennes, nos résultats montrent que 34 % du personnel sont des femmes alors que 66 % sont des hommes, ce qui démontre un déséquilibre assez important en matière de parité. Cependant, une analyse plus fine nous indique que les pratiques d’égalité entre femmes et hommes dans les structures et dans la gestion des ressources humaines diffèrent d’une ONG à une autre. Ces pratiques dépendent beaucoup de la volonté et des valeurs des gestionnaires. Notre recherche a fait ressortir plusieurs explications de cette disparité au niveau de l’emploi des femmes. Les raisons souvent mentionnées étaient : 1) la nécessité d’avoir du personnel compétent, 2) la conciliation famille-travail, 3) le contexte socioculturel, 4) l’interprétation de la religion musulmane en matière d’égalité. En effet, nos résultats ont démontré que sous l’influence des bailleurs de fonds les ONG se sont professionnalisées, que l’impact de la professionnalisation a été différent selon le genre et que celle-ci s’est faite aux dépens des femmes. Ainsi, certains gestionnaires, quel que soit leur sexe, préfèrent recruter plus d’hommes parce qu’ils les jugent plus compétents.Nos résultats confirment la théorie du plafond de verre qui met en exergue le fait que les femmes ont de la difficulté à accéder à des postes de responsabilité. Nos résultats ont aussi démontré qu’au Mali, le contexte socioculturel et la religion jouent un grand rôle dans les relations sociales et surtout en ce qui concerne la place des femmes au sein de la société.

Effect of Wealth on Health Care Seeking Behavior And Out of Pocket Health Expenditure in Malawi

Thesis (Master's)--University of Washington, 2016-06

Investigation of the Nucleation and Growth of Colloidal Indium Phosphide: from Molecular Precursors to Semiconductor Nanocrystals through In37P20(O2CR)51 as a Magic-Size Intermediate

Thesis (Ph.D.)--University of Washington, 2016-06

Is "football for all" safe for all? : Cross-Sectional Study of Disparities as Determinants of 1-Year Injury Prevalence in Youth Football Programs

Football (soccer) is endorsed as a health-promoting physical activity worldwide. When football programs are introduced as part of general health promotion programs, equal access and limitation of pre-participation disparities with regard to injury risk are important. The aim of this study was to explore if disparity with regard to parents' educational level, player body mass index (BMI), and self-reported health are determinants of football injury in community-based football programs, separately or in interaction with age or gender. Methodology/Principal Findings Four community football clubs with 1230 youth players agreed to participate in the cross-sectional study during the 2006 season. The study constructs (parents' educational level, player BMI, and self-reported health) were operationalized into questionnaire items. The 1-year prevalence of football injury was defined as the primary outcome measure. Data were collected via a postal survey and analyzed using a series of hierarchical statistical computations investigating associations with the primary outcome measure and interactions between the study variables. The survey was returned by 827 (67.2%) youth players. The 1-year injury prevalence increased with age. For youths with parents with higher formal education, boys reported more injuries and girls reported fewer injuries than expected; for youths with lower educated parents there was a tendency towards the opposite pattern. Youths reporting injuries had higher standardized BMI compared with youths not reporting injuries. Children not reporting full health were slightly overrepresented among those reporting injuries and underrepresented for those reporting no injury. Conclusion Pre-participation disparities in terms of parents' educational level, through interaction with gender, BMI, and self-reported general health are associated with increased injury risk in community-based youth football. When introduced as a general health promotion, football associations should adjust community-based youth programs to accommodate children and adolescents with increased pre-participation injury risk.