Environmental Enteropathy and Fibroblast Growth Factor 21 are associated with early childhood growth in Bangladesh

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

The importance of mating system in translocation programs: reproductive success of released male bridled nailtail wallabies

Translocation is an important tool for the conservation of species that have suffered severe range reductions. The success of a translocation should be measured not only by the survival of released animals, but by the reproductive output of individuals and hence the establishment of a self-sustaining population. The bridled nailtail wallaby is an endangered Australian macropod that suffered an extensive range contraction to a single remaining wild population. A translocated population was established and subsequently monitored over a four year period. The aim of this study was to measure the reproductive success of released males using genetic tools and to determine the factors that predicted reproductive success. Captive-bred and wild-caught animals were released and we found significant variation in male reproductive success among release groups. Variation in reproductive success was best explained by individual male weight, survival and release location rather than origin. Only 26% of candidate males were observed to sire an offspring during the study. The bridled nailtail wallaby is a sexually dimorphic, polygynous macropod and reproductive success is skewed toward large males. Males over 5800 g were six times more likely to sire an offspring than males below this weight. This study highlights the importance of considering mating system when choosing animals for translocation. Translocation programs for polygynous species should release a greater proportion of females, and only release males of high breeding potential. By maximizing the reproductive output of released animals, conservation managers will reduce the costs of translocation and increase the chance of successfully establishing a self-sustaining population. (C) 2004 Elsevier Ltd. All rights reserved.

Vitamin B-12 release from P(HEMA-co-THFMA) in water and SBF: A model drug release study

A model drug release study on the ingress of water and Kokubo simulated body fluid (SBF) into poly(2-hydroxyethyl methacrylate) (THFMA) and its copolymers with tetrahydrofurfuryl methacrylate (THFMA) loaded with vitamin B-12 was undertaken over the temperature range 298-318 K. The polymers were studied as cylinders and were loaded with either 5 or 10 wt-% of the drug. The drug release from the polymers was found to follow a Fickian diffusion mechanism in the early stages of the drug release, with higher normalized release rates at higher temperatures and higher drug loadings. The normalized release rates were also found to be higher for the SBF solution than for water. The copolymer composition was found to have a significant effect on the rate of release of the drug, with the rate falling rapidly between HEMA mole fractions of 1.0 and 0.8, but for lower mole fractions of HEMA the normalized release rate decreased more slowly. This behaviour followed the trend found for the changes in the equilibrium penetrant contents for the copolymers.

Temporal and spatial transcriptional programs in murine kidney development

We have performed a systematic temporal and spatial expression profiling of the developing mouse kidney using Compugen long-oligonucleotide microarrays. The activity of 18,000 genes was monitored at 24-h intervals from 10.5-day-postcoitum (dpc) metanephric mesenchyme (MM) through to neonatal kidney, and a cohort of 3,600 dynamically expressed genes was identified. Early metanephric development was further surveyed by directly comparing RNA from 10.5 vs. 11.5 vs. 13.5dpc kidneys. These data showed high concordance with the previously published dynamic profile of rat kidney development (Stuart RO, Bush KT, and Nigam SK. Proc Natl Acad Sci USA 98: 5649-5654, 2001) and our own temporal data. Cluster analyses were used to identify gene ontological terms, functional annotations, and pathways associated with temporal expression profiles. Genetic network analysis was also used to identify biological networks that have maximal transcriptional activity during early metanephric development, highlighting the involvement of proliferation and differentiation. Differential gene expression was validated using whole mount and section in situ hybridization of staged embryonic kidneys. Two spatial profiling experiments were also undertaken. MM (10.5dpc) was compared with adjacent intermediate mesenchyme to further define metanephric commitment. To define the genes involved in branching and in the induction of nephrogenesis, expression profiling was performed on ureteric bud (GFP+) FACS sorted from HoxB7-GFP transgenic mice at 15.5dpc vs. the GFP- mesenchymal derivatives. Comparisons between temporal and spatial data enhanced the ability to predict function for genes and networks. This study provides the most comprehensive temporal and spatial survey of kidney development to date, and the compilation of these transcriptional surveys provides important insights into metanephric development that can now be functionally tested.

Factors in the selection of patients for conditional release from their first psychiatric hospitalization

Objective: This study examined a sample of patients in Victoria, Australia, to identify factors in selection for conditional release from an initial hospitalization that occurred within 30 days of entry into the mental health system. Methods: Data were from the Victorian Psychiatric Case Register. All patients first hospitalized and conditionally released between 1990 and 2000 were identified (N = 8,879), and three comparison groups were created. Two groups were hospitalized within 30 days of entering the system: those who were given conditional release and those who were not. A third group was conditionally released from a hospitalization that occurred after or extended beyond 30 days after system entry. Logistic regression identified characteristics that distinguished the first group. Ordinary least-squares regression was used to evaluate the contribution of conditional release early in treatment to reducing inpatient episodes, inpatient days, days per episode, and inpatient days per 30 days in the system. Results: Conditional release early in treatment was used for 11 percent of the sample, or more than a third of those who were eligible for this intervention. Factors significantly associated with selection for early conditional release were those related to a better prognosis ( initial hospitalization at a later age and having greater than an 11th grade education), a lower likelihood of a diagnosis of dementia or schizophrenia, involuntary status at first inpatient admission, and greater community involvement ( being employed and being married). When the analyses controlled for these factors, use of conditional release early in treatment was significantly associated with a reduction in use of subsequent inpatient care.

Using interior point algorithms for the solution of linear programs with special structural features

Linear Programming (LP) is a powerful decision making tool extensively used in various economic and engineering activities. In the early stages the success of LP was mainly due to the efficiency of the simplex method. After the appearance of Karmarkar's paper, the focus of most research was shifted to the field of interior point methods. The present work is concerned with investigating and efficiently implementing the latest techniques in this field taking sparsity into account. The performance of these implementations on different classes of LP problems is reported here. The preconditional conjugate gradient method is one of the most powerful tools for the solution of the least square problem, present in every iteration of all interior point methods. The effect of using different preconditioners on a range of problems with various condition numbers is presented. Decomposition algorithms has been one of the main fields of research in linear programming over the last few years. After reviewing the latest decomposition techniques, three promising methods were chosen the implemented. Sparsity is again a consideration and suggestions have been included to allow improvements when solving problems with these methods. Finally, experimental results on randomly generated data are reported and compared with an interior point method. The efficient implementation of the decomposition methods considered in this study requires the solution of quadratic subproblems. A review of recent work on algorithms for convex quadratic was performed. The most promising algorithms are discussed and implemented taking sparsity into account. The related performance of these algorithms on randomly generated separable and non-separable problems is also reported.

Ocular biometric correlates of early-and late-onset myopia

Myopia is a refractive condition and develops because either the optical power of the eye is abnormally great or the eye is abnormally long, the optical consequences being that the focal length of the eye is too short for the physical length of the eye. The increase in axial length has been shown to match closely the dioptric error of the eye, in that a lmm increase in axial length usually generates 2 to 3D of myopia. The most common form of myopia is early-onset myopia (EO M) which occurs between 6 to 14 years of age. The second most common form of myopia is late-onset myopia (LOM) which emerges in late teens or early twenties, at a time when the eye should have ceased growing. The prevalence of LOM is increasing and research has indicated a link with excessive and sustained nearwork. The aim of this thesis was to examine the ocular biometric correlates associated with LOM and EOM development and progression. Biometric data was recorded on SO subjects, aged 16 to 26 years. The group was divided into 26 emmetropic subjects and 24 myopic subjects. Keratometry, corneal topography, ultrasonography, lens shape, central and peripheral refractive error, ocular blood flow and assessment of accommodation were measured on three occasions during an ISmonth to 2-year longitudinal study. Retinal contours were derived using a specially derived computer program. The thesis shows that myopia progression is related to an increase in vitreous chamber depth, a finding which supports previous work. The myopes exhibited hyperopic relative peripheral refractive error (PRE) and the emmetropes exhibited myopic relative PRE. Myopes demonstrated a prolate retinal shape and the retina became more prolate with myopia progression. The results show that a longitudinal, rather than equatorial, increase in the posterior segment is the principal structural correlate of myopia. Retinal shape, relative PRE and the ratio of axial length to corneal curvature have been indicated, in this thesis, as predictive factors for myopia onset and development. Data from this thesis demonstrates that myopia progression in the LOM group is the result of an increase in anterior segment power, owing to an increase in lens thickness, in conjunction with posterior segment elongation. Myopia progression in the EOM group is the product of a long posterior segment, which over-compensates for a weak anterior segment power. The weak anterior segment power in the EOM group is related to a combination of crystalline lens thinning and surface flattening. The results presented in this thesis confirm that posterior segment elongation is the main structural correlate in both EOM and LOM progression. The techniques and computer programs employed in the thesis are reproducible and robust providing a valuable framework for further myopia research and assessment of predictive factors.

Metrics and models to support the development of hybrid information systems

The research described here concerns the development of metrics and models to support the development of hybrid (conventional/knowledge based) integrated systems. The thesis argues from the point that, although it is well known that estimating the cost, duration and quality of information systems is a difficult task, it is far from clear what sorts of tools and techniques would adequately support a project manager in the estimation of these properties. A literature review shows that metrics (measurements) and estimating tools have been developed for conventional systems since the 1960s while there has been very little research on metrics for knowledge based systems (KBSs). Furthermore, although there are a number of theoretical problems with many of the `classic' metrics developed for conventional systems, it also appears that the tools which such metrics can be used to develop are not widely used by project managers. A survey was carried out of large UK companies which confirmed this continuing state of affairs. Before any useful tools could be developed, therefore, it was important to find out why project managers were not using these tools already. By characterising those companies that use software cost estimating (SCE) tools against those which could but do not, it was possible to recognise the involvement of the client/customer in the process of estimation. Pursuing this point, a model of the early estimating and planning stages (the EEPS model) was developed to test exactly where estimating takes place. The EEPS model suggests that estimating could take place either before a fully-developed plan has been produced, or while this plan is being produced. If it were the former, then SCE tools would be particularly useful since there is very little other data available from which to produce an estimate. A second survey, however, indicated that project managers see estimating as being essentially the latter at which point project management tools are available to support the process. It would seem, therefore, that SCE tools are not being used because project management tools are being used instead. The issue here is not with the method of developing an estimating model or tool, but; in the way in which "an estimate" is intimately tied to an understanding of what tasks are being planned. Current SCE tools are perceived by project managers as targetting the wrong point of estimation, A model (called TABATHA) is then presented which describes how an estimating tool based on an analysis of tasks would thus fit into the planning stage. The issue of whether metrics can be usefully developed for hybrid systems (which also contain KBS components) is tested by extending a number of "classic" program size and structure metrics to a KBS language, Prolog. Measurements of lines of code, Halstead's operators/operands, McCabe's cyclomatic complexity, Henry & Kafura's data flow fan-in/out and post-release reported errors were taken for a set of 80 commercially-developed LPA Prolog programs: By re~defining the metric counts for Prolog it was found that estimates of program size and error-proneness comparable to the best conventional studies are possible. This suggests that metrics can be usefully applied to KBS languages, such as Prolog and thus, the development of metncs and models to support the development of hybrid information systems is both feasible and useful.

Resveratrol inhibits the release of soluble fms-like tyrosine kinase (sFlt-1) from human placenta

Objective - Soluble vascular endothelial growth factor receptor–1 (also know as soluble fms-like tyrosine kinase [sFlt]-1) is a key causative factor of preeclampsia. Resveratrol, a plant phytoalexin, has antiinflammatory and cardioprotective properties. We sought to determine the effect of resveratrol on sFlt-1 release. Study Design - Human umbilical vein endothelial cells, transformed human trophoblast-8 (HTR/SVneo)-8/SVneo trophoblast cells, or placental explants were incubated with cytokines and/or resveratrol. Conditioned media were assayed for sFlt-1 by enzyme-linked immunosorbent assay and cell proteins used for Western blotting. Results - Resveratrol inhibited cytokine-induced release of sFlt-1 from normal placental explants and from preeclamptic placental explants. Preincubation of human umbilical vein endothelial cells or HTR-8/SVneo cells with resveratrol abrogated sFlt-1 release. Resveratrol prevented the up-regulation of early growth response protein-1 (Egr-1), a transcription factor necessary for induction of the vascular endothelial growth factor receptor–1 gene and caused up-regulation of heme oxygenase–1, a cytoprotective enzyme found to be dysfunctional in preeclampsia. Conclusion - In summary, resveratrol can inhibit sFlt-1 release and up-regulate heme oxygenase–1; thus, may offer therapeutic potential in preeclampsia.

Predictors of developmental gains in children enrolled in an early intervention setting

The purpose of this research was to determine whether initial developmental delay, site of intervention, frequency of intervention, age of the child, socio-economic status (SES), gender and ethnicity significantly predict developmental gains in a group of children enrolled in an early intervention setting. The records of 134 children enrolled in an inner-city program in Miami, Florida were reviewed for inclusion in this study. ^ Demographic variables, site placement and treatment frequencies were collected during a retrospective chart review. Level of delay was expressed using the developmental quotient and developmental gain was calculated using the mean gain on age equivalent scores or developmental tests. A multiple regression analysis was performed to determine which of the above variables significantly predicted developmental gains. Multivariate analysis compared developmental gains for all the developmental domains based on intervention site (center versus home-based) while controlling for developmental delay. ^ Children made greater developmental gains if they had higher developmental quotients and if they were younger at the time services were initiated. Frequency of intervention significantly improved developmental outcomes in children attending center-based programs. Children attending center-based programs also made significantly greater gains in gross motor skills compared to children attending home-based programs. ^ These findings emphasize the importance of early screening and referral of children with developmental delay and adjusting intervention for the child's developmental quotient. Children should receive intense treatment to maximize results. Decisions regarding program placement should be individualized according to the child's unique developmental pattern. Policy and program decisions affecting the curriculum of a child in early intervention need to reflect these multivariate considerations. ^

The perceptions of best mentoring practices in an early literacy intervention project: A case study of nine coaches

There is significant national evidence the language development of four year-olds is a critical area for later school success (Brooks-Gunn, Fuligni, & Berlin, 2003; Cunningham, & Stanovich, 1998). This study originated as part of Literacy Intervention X (LIX), a larger national study conducted to examine the effectiveness of early literacy curricula implemented in subsidized childcare centers. The professional development of childcare center providers is key to improving the quality of subsidized care. In exploring the mentoring practices of nine LIX literacy coaches, the researcher investigated the perceptions of what best mentoring practices facilitated the implementation of literacy curricula by childcare providers. A qualitative case study was conducted using a combination of participant observer notes, document analysis, and focus group semi-structured interviews. The researcher is a participant observer, one of the nine Literacy Coaches. The best mentoring practices from the perspective of the literacy coaches are related to building relationships including trust, mutual respect, support, empathy, and encouragement with the childcare providers, the center directors, and with fellow literacy coaches. Clear, constant, and consistent communication with the childcare providers was a vital mentoring practice in building a relationship between the literacy coach and childcare provider. Another best mentoring practice in building a relationship with the childcare provider was the perceptions of the literacy coaches as co-learners in the mentoring process. The best mentoring practices highlighted in this study exemplified the kind of effective professional development that builds on the strengths of the childcare providers and does not disrupt the childcare centers or the services provided by the subsidized childcare programs that meet the needs of children and families. The experience of these nine literacy coaches, including their perceptions of effective mentoring practices, along with lesson learned about relationships, mentoring team structures, and general project design sheds light on the challenge of mentoring subsidized childcare providers in future literacy intervention projects.

Comparative administrative reform: The rhetoric and reality of the Civil Service reform programs in Uganda and Tanzania

Administrative reform is a challenging endeavor for both developed and developing countries alike. For developing countries, the challenge is greater because numerous reforms are implemented concurrently sometimes under conditions of resource scarcity and political instability. So far there is no consensus as to what makes some reforms succeed and others fail. The current study seeks to fill that gap by offering an empirical comparative analysis of the administrative reforms initiated in Uganda and Tanzania since the early 1990s. The purpose of the study is to explain the similarities and differences, and give reasons for the successes and failures of the reform programs in the two countries. It focuses on four major areas; the size of the civil service, pay reform, capacity building, and ethics and accountability. Data were collected via in-depth face to face interviews with 35 key government officials and the content analysis of various documents. The results indicate that the reforms generated initial substantial reduction in the size of the public services in both countries. In Uganda, the traditional civil service was reduced from 140,500 in 1990 to 41,730 in 2004; while in Tanzania Ministries, Departments, and Agencies were reduced by 25%. Pay reform has generated substantial increases in civil servants' salaries in both countries but in Uganda, the government has not been able to abide by the pay strategy while in Tanzania the strategy guides the increments. Civil Service capacity building efforts have focused on enhancing the skills of the personnel. Training needs assessments were undertaken in all ministries in Uganda and a training policy was formulated. In Tanzania, the training needs assessments are still under way and a training policy has not yet been developed. Ethics and accountability are great challenges in both countries, but in Tanzania, there is more political will and commitment to improve the integrity of the civil service. The findings reveal that although Uganda started the reform with much more rigor and initial success, Tanzania has surpassed it and has a more stable, consistent, and promising reform record. This is because Uganda's leadership lacks political legitimacy. The country has since the late 1990s experienced a civil war in the northern and western parts of the country while Tanzania has benefitted from relative peace and high level political legitimacy.

Factors influencing the implementation of substance use prevention programs in elementary schools

Prevention scientists have called for more research on the factors affecting the implementation of substance use prevention programs. Given the lack of literature in this area, coupled with evidence that children as early as elementary school engage in substance use, the purpose of this study was to identify the factors that influence the implementation of substance use prevention programs in elementary schools. This study involved a mixed methods approach comprised of a survey and in-person interviews. Sixty-five guidance counselors and teachers completed the survey, and 9 guidance counselors who completed the survey were interviewed individually. Correlation analyses and hierarchical multiple regression were conducted. Quantitative findings revealed ease of implementation most frequently influenced program implementation, followed by beliefs about the program's effectiveness. Qualitative findings showed curriculum modification as an important theme, as well as difficulty of program implementation. The in-person interviews also shed light on three interrelated themes influencing program implementation – The Wheel, time, and scheduling. Results indicate the majority of program providers modified the curriculum in some way. Implications for research, policy, and practice are discussed, and areas for future research are suggested.^

Comparative Administrative Reform: The Rhetoric and Reality of the Civil Service Reform Programs in Uganda and Tanzania

Administrative reform is a challenging endeavor for both developed and developing countries alike. For developing countries, the challenge is greater because numerous reforms are implemented concurrently sometimes under conditions of resource scarcity and political instability. So far there is no consensus as to what makes some reforms succeed and others fail. The current study seeks to fill that gap by offering an empirical comparative analysis of the administrative reforms initiated in Uganda and Tanzania since the early 1990s. The purpose of the study is to explain the similarities and differences, and give reasons for the successes and failures of the reform programs in the two countries. It focuses on four major areas; the size of the civil service, pay reform, capacity building, and ethics and accountability. Data were collected via in-depth face to face interviews with 35 key government officials and the content analysis of various documents. The results indicate that the reforms generated initial substantial reduction in the size of the public services in both countries. In Uganda, the traditional civil service was reduced from 140,500 in 1990 to 41,730 in 2004; while in Tanzania Ministries, Departments, and Agencies were reduced by 25%. Pay reform has generated substantial increases in civil servants’ salaries in both countries but in Uganda, the government has not been able to abide by the pay strategy while in Tanzania the strategy guides the increments. Civil Service capacity building efforts have focused on enhancing the skills of the personnel. Training needs assessments were undertaken in all ministries in Uganda and a training policy was formulated. In Tanzania, the training needs assessments are still under way and a training policy has not yet been developed. Ethics and accountability are great challenges in both countries, but in Tanzania, there is more political will and commitment to improve the integrity of the civil service. The findings reveal that although Uganda started the reform with much more rigor and initial success, Tanzania has surpassed it and has a more stable, consistent, and promising reform record. This is because Uganda’s leadership lacks political legitimacy. The country has since the late 1990s experienced a civil war in the northern and western parts of the country while Tanzania has benefitted from relative peace and high level political legitimacy.

An Investigation of the Features and Effectiveness of the Full-Day Early Learning Kindergarten Program in Ontario

This dissertation includes two studies. Study 1 is a qualitative case study that describes enactment of the main components of a high fidelity Full-Day Early Learning Kindergarten (FDELK) classroom, specifically play-based learning and teacher-ECE collaboration. Study 2 is a quantitative analysis that investigates how effectively the FDELK program promotes school readiness skills, namely self-regulation, literacy, and numeracy, in Kindergarteners. To describe the main components of an FDELK classroom in Study 1, a sub-sample of four high fidelity case study schools were selected from a larger case study sample. Interview data from these schools’ administrators, educators, parents, and community stakeholders were used to describe how the main components of the FDELK program enabled educators to meet the individual needs of students and promote students’ SR development. In Study 2, hierarchical regression analyses of 32,207 students’ self-regulation, literacy, and numeracy outcomes using 2012 Ontario Early Development Instrument (EDI) data revealed essentially no benefit for students participating in the FDELK program when compared to peers in Half-Day or Alternate-Day Kindergarten programs. Being older and female predicted more positive SR and literacy outcomes. Age and gender accounted for limited variance in numeracy outcomes. Results from both studies suggest that the Ontario Ministry of Education should take steps to improve the quality of the FDELK program by incorporating evidence-based guidelines and goals for play, reducing Kindergarten class sizes to more effectively scaffold learning, and revising curriculum expectations to include a greater focus on SR, literacy, and numeracy skills.