Evaluating statistical methods used to estimate the number of postsynaptic receptors.

Calcium levels in spines play a significant role in determining the sign and magnitude of synaptic plasticity. The magnitude of calcium influx into spines is highly dependent on influx through N-methyl D-aspartate (NMDA) receptors, and therefore depends on the number of postsynaptic NMDA receptors in each spine. We have calculated previously how the number of postsynaptic NMDA receptors determines the mean and variance of calcium transients in the postsynaptic density, and how this alters the shape of plasticity curves. However, the number of postsynaptic NMDA receptors in the postsynaptic density is not well known. Anatomical methods for estimating the number of NMDA receptors produce estimates that are very different than those produced by physiological techniques. The physiological techniques are based on the statistics of synaptic transmission and it is difficult to experimentally estimate their precision. In this paper we use stochastic simulations in order to test the validity of a physiological estimation technique based on failure analysis. We find that the method is likely to underestimate the number of postsynaptic NMDA receptors, explain the source of the error, and re-derive a more precise estimation technique. We also show that the original failure analysis as well as our improved formulas are not robust to small estimation errors in key parameters.

Evaluation of flood preparedness in public health facilities in Eastern Province, Sri Lanka

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

Methods of sensory evaluation of quality and application of statistical methods in sensory evaluation problems with special reference to fishery products

The quality of raw and processed fishery products depend on several factors like physiological conditions at the time of capture, morphological differences, rigor mortis, species, rate of icing and subsequent storage conditions. Sensory evaluation is still the most reliable method for evaluation of the freshness of raw processed fishery products. Sophisticated methods like Intelectron fish tester, cell fragility technique and chemical and bacteriological methods like estimation of trimethylamine, hypoxanthine, carbonyl compounds, volatile acid and total bacterial count have no doubt been developed for accessing the spoilage in fish products.

Becoming Peer Health Leaders: A Mixed-Methods Evaluation of a Youth Leadership Camp Preparing Peer Leaders for Participation in a Health Promotion Initiative.

Youth are critical partners in health promotion, but the process of training young people to become meaningfully involved is challenging. This mixed-methods evaluation considered the impact of a leadership camp in preparing 42 grade seven students to become peer health leaders in a ‘heart health’ initiative. The experiences of participants and their sense of agency were explored. Data were collected from pre and post camp surveys, focus groups, student journals and researcher observations. Findings indicate that relationships with peers and adults were key to agency development, and participants appeared to broaden their perspectives on the meanings of ‘health’ and ‘leadership.’ Significant changes on two sub-scales of the Harter Perceived Competence Scale for Children were also found. Suggestions for practice and further research are provided.

Novel Statistical Methods in Quantitative Genetics : Modeling Genetic Variance for Quantitative Trait Loci Mapping and Genomic Evaluation

This thesis develops and evaluates statistical methods for different types of genetic analyses, including quantitative trait loci (QTL) analysis, genome-wide association study (GWAS), and genomic evaluation. The main contribution of the thesis is to provide novel insights in modeling genetic variance, especially via random effects models. In variance component QTL analysis, a full likelihood model accounting for uncertainty in the identity-by-descent (IBD) matrix was developed. It was found to be able to correctly adjust the bias in genetic variance component estimation and gain power in QTL mapping in terms of precision.  Double hierarchical generalized linear models, and a non-iterative simplified version, were implemented and applied to fit data of an entire genome. These whole genome models were shown to have good performance in both QTL mapping and genomic prediction. A re-analysis of a publicly available GWAS data set identified significant loci in Arabidopsis that control phenotypic variance instead of mean, which validated the idea of variance-controlling genes.  The works in the thesis are accompanied by R packages available online, including a general statistical tool for fitting random effects models (hglm), an efficient generalized ridge regression for high-dimensional data (bigRR), a double-layer mixed model for genomic data analysis (iQTL), a stochastic IBD matrix calculator (MCIBD), a computational interface for QTL mapping (qtl.outbred), and a GWAS analysis tool for mapping variance-controlling loci (vGWAS).

How valuable are multiple treatment comparison methods in evidence-based health-care evaluation?

Objectives To compare the use of pair-wise meta-analysis methods to multiple treatment comparison (MTC) methods for evidence-based health-care evaluation to estimate the effectiveness and cost-effectiveness of alternative health-care interventions based on the available evidence. Methods Pair-wise meta-analysis and more complex evidence syntheses, incorporating an MTC component, are applied to three examples: 1) clinical effectiveness of interventions for preventing strokes in people with atrial fibrillation; 2) clinical and cost-effectiveness of using drug-eluting stents in percutaneous coronary intervention in patients with coronary artery disease; and 3) clinical and cost-effectiveness of using neuraminidase inhibitors in the treatment of influenza. We compare the two synthesis approaches with respect to the assumptions made, empirical estimates produced, and conclusions drawn. Results The difference between point estimates of effectiveness produced by the pair-wise and MTC approaches was generally unpredictable—sometimes agreeing closely whereas in other instances differing considerably. In all three examples, the MTC approach allowed the inclusion of randomized controlled trial evidence ignored in the pair-wise meta-analysis approach. This generally increased the precision of the effectiveness estimates from the MTC model. Conclusions The MTC approach to synthesis allows the evidence base on clinical effectiveness to be treated as a coherent whole, include more data, and sometimes relax the assumptions made in the pair-wise approaches. However, MTC models are necessarily more complex than those developed for pair-wise meta-analysis and thus could be seen as less transparent. Therefore, it is important that model details and the assumptions made are carefully reported alongside the results.

Evaluation of statistical methods used in obtaining broadcast ratings. Report pursuant to section 136 of the legislative reorganization act of 1946, Public law 601, 79th Cong., and House resolution 108, 87th Cong.

Includes bibliography.

Development and psychometric evaluation of a new team effectiveness scale for all types of community adult mental health teams:a mixed-methods approach

Defining 'effectiveness' in the context of community mental health teams (CMHTs) has become increasingly difficult under the current pattern of provision required in National Health Service mental health services in England. The aim of this study was to establish the characteristics of multi-professional team working effectiveness in adult CMHTs to develop a new measure of CMHT effectiveness. The study was conducted between May and November 2010 and comprised two stages. Stage 1 used a formative evaluative approach based on the Productivity Measurement and Enhancement System to develop the scale with multiple stakeholder groups over a series of qualitative workshops held in various locations across England. Stage 2 analysed responses from a cross-sectional survey of 1500 members in 135 CMHTs from 11 Mental Health Trusts in England to determine the scale's psychometric properties. Based on an analysis of its structural validity and reliability, the resultant 20-item scale demonstrated good psychometric properties and captured one overall latent factor of CMHT effectiveness comprising seven dimensions: improved service user well-being, creative problem-solving, continuous care, inter-team working, respect between professionals, engagement with carers and therapeutic relationships with service users. The scale will be of significant value to CMHTs and healthcare commissioners both nationally and internationally for monitoring, evaluating and improving team functioning in practice.

Evaluation of Some Statistical Methods for the Identification of Differentially Expressed Genes

Microarray platforms have been around for many years and while there is a rise of new technologies in laboratories, microarrays are still prevalent. When it comes to the analysis of microarray data to identify differentially expressed (DE) genes, many methods have been proposed and modified for improvement. However, the most popular methods such as Significance Analysis of Microarrays (SAM), samroc, fold change, and rank product are far from perfect. When it comes down to choosing which method is most powerful, it comes down to the characteristics of the sample and distribution of the gene expressions. The most practiced method is usually SAM or samroc but when the data tends to be skewed, the power of these methods decrease. With the concept that the median becomes a better measure of central tendency than the mean when the data is skewed, the tests statistics of the SAM and fold change methods are modified in this thesis. This study shows that the median modified fold change method improves the power for many cases when identifying DE genes if the data follows a lognormal distribution.

Quality evaluation of cortex berberidis from different geographical origins by simultaneous high performance liquid chromatography combined with statistical methods

Purpose: To develop an effective method for evaluating the quality of Cortex berberidis from different geographical origins. Methods: A simple, precise and accurate high performance liquid chromatography (HPLC) method was first developed for simultaneous quantification of four active alkaloids (magnoflorine, jatrorrhizine, palmatine, and berberine) in Cortex berberidis obtained from Qinghai, Tibet and Sichuan Provinces of China. Method validation was performed in terms of precision, repeatability, stability, accuracy, and linearity. Besides, partial least squares discriminant analysis (PLS-DA) and one-way analysis of variance (ANOVA) were applied to study the quality variations of Cortex berberidis from various geographical origins. Results: The proposed HPLC method showed good linearity, precision, repeatability, and accuracy. The four alkaloids were detected in all samples of Cortex berberidis. Among them, magnoflorine (36.46 - 87.30 mg/g) consistently showed the highest amounts in all the samples, followed by berberine (16.00 - 37.50 mg/g). The content varied in the range of 0.66 - 4.57 mg/g for palmatine and 1.53 - 16.26 mg/g for jatrorrhizine, respectively. The total content of the four alkaloids ranged from 67.62 to 114.79 mg/g. Moreover, the results obtained by the PLS-DA and ANOVA showed that magnoflorine level and the total content of these four alkaloids in Qinghai and Tibet samples were significantly higher (p < 0.01) than those in Sichuan samples. Conclusion: Quantification of multi-ingredients by HPLC combined with statistical methods provide an effective approach for achieving origin discrimination and quality evaluation of Cortex berberidis. The quality of Cortex berberidis closely correlates to the geographical origin of the samples, with Cortex berberidis samples from Qinghai and Tibet exhibiting superior qualities to those from Sichuan.

Evaluation of methods for cultivating limbal mesenchymal stromal cells

Background: Mesenchymal stromal cells (MSC) with similar properties to bone marrow derived mesenchymal stromal cells (BM-MSC) have recently been grown from the limbus of the human cornea. We presently contribute to this novel area of research by evaluating methods for culturing human limbal MSC (L-MSC). Methods: Four basic strategies are compared: serum-supplemented medium (10% foetal bovine serum; FBS), standard serum-free medium supplemented with B-27, epidermal growth factor, and fibroblast growth factor 2, or one of two commercial serum-free media including Defined Keratinocyte Serum Free Medium (Invitrogen), and MesenCult-XF (Stem Cell Technologies). The phenotype of resulting cultures was examined using photography, flow cytometry (for CD34, CD45, CD73, CD90, CD105, CD141, CD271), immunocytochemistry (α-sma), differentiation assays (osteogenesis, adipogenesis, chrondrogenesis), and co-culture experiments with human limbal epithelial (HLE) cells. Results: While all techniques supported to varying degrees establishment of cultures, sustained growth and serial propagation was only achieved in 10% FBS medium or MesenCult-XF medium. Cultures established in 10% FBS medium were 70-80% CD34-/CD45-/CD90+/CD73+/CD105+, approximately 25% α-sma+, and displayed multi-potency. Cultures established in MesenCult-XF were >95% CD34-/CD45-/CD90+/CD73+/CD105+, 40% CD141+, rarely expressed α-sma, and displayed multi-potency. L-MSC supported growth of HLE cells, with the largest epithelial islands being observed in the presence of MesenCult-XF-grown L-MSC. All HLE cultures supported by L-MSC widely expressed the progenitor cell marker ∆Np63, along with the corneal differentiation marker cytokeratin 3. Conclusions: We conclude that MesenCult-XF® is a superior culture system for L-MSC, but further studies are required to explore the significance of CD141 expression in these cells.

Review of statistical methods for disease mapping

Cancer poses an undeniable burden to the health and wellbeing of the Australian community. In a recent report commissioned by the Australian Institute for Health and Welfare(AIHW, 2010), one in every two Australians on average will be diagnosed with cancer by the age of 85, making cancer the second leading cause of death in 2007, preceded only by cardiovascular disease. Despite modest decreases in standardised combined cancer mortality over the past few decades, in part due to increased funding and access to screening programs, cancer remains a significant economic burden. In 2010, all cancers accounted for an estimated 19% of the country's total burden of disease, equating to approximately $3:8 billion in direct health system costs (Cancer Council Australia, 2011). Furthermore, there remains established socio-economic and other demographic inequalities in cancer incidence and survival, for example, by indigenous status and rurality. Therefore, in the interests of the nation's health and economic management, there is an immediate need to devise data-driven strategies to not only understand the socio-economic drivers of cancer but also facilitate the implementation of cost-effective resource allocation for cancer management...

A time series analysis of presentations to Queensland health facilities for alcohol-related conditions, following the increase in 'alcopops' tax

Objective: In response to concerns about the health consequences of high-risk drinking by young people, the Australian Government increased the tax on pre-mixed alcoholic beverages ('alcopops') favoured by this demographic. We measured changes in admissions for alcohol-related harm to health throughout Queensland, before and after the tax increase in April 2008. Methods: We used data from the Queensland Trauma Register, Hospitals Admitted Patients Data Collection, and the Emergency Department Information System to calculate alcohol-related admission rates per 100,000 people, for 15 - 29 year-olds. We analysed data over 3 years (April 2006 - April 2009), using interrupted time-series analyses. This covered 2 years before, and 1 year after, the tax increase. We investigated both mental and behavioural consequences (via F10 codes), and intentional/unintentional injuries (S and T codes). Results: We fitted an auto-regressive integrated moving average (ARIMA) model, to test for any changes following the increased tax. There was no decrease in alcohol-related admissions in 15 - 29 year-olds. We found similar results for males and females, as well as definitions of alcohol-related harms that were narrow (F10 codes only) and broad (F10, S and T codes). Conclusions: The increased tax on 'alcopops' was not associated with any reduction in hospital admissions for alcohol-related harms in Queensland 15 - 29 year-olds.