The enantioselective population pharmacokinetics of intravenous ketorolac in children using a stereoselective assay suitable for microanalysis

Objective: To describe the effect of age and body size on enantiomer selective pharmacokinetic (PK) of intravenous ketorolac in children using a microanalytical assay. Methods: Blood samples were obtained at 0, 15 and 30 min and at 1, 2, 4, 6, 8 and 12 h after a weight-dependent dose of ketorolac. Enantiomer concentration was measured using a liquid chromatography tandem mass spectrometry method. Non-linear mixed-effect modelling was used to assess PK parameters. Key findings: Data from 11 children (1.7–15.6 years, weight 10.7–67.4 kg) were best described by a two-compartment model for R(+), S(−) and racemic ketorolac. Only weight (WT) significantly improved the goodness of fit. The final population models were CL = 1.5 × (WT/46)0.75, V1 = 8.2 × (WT/46), Q = 3.4 × (WT/46)0.75, V2 = 7.9 × (WT/46), CL = 2.98 × (WT/46), V1 = 13.2 × (WT/46), Q = 2.8 × (WT/46)0.75, V2 = 51.5 × (WT/46), and CL = 1.1 × (WT/46)0.75, V1 = 4.9 × (WT/46), Q = 1.7 × (WT/46)0.75 and V2 = 6.3 × (WT/46)for R(+), S(−) and racemic ketorolac. Conclusions: Only body weight influenced the PK parameters for R(+) and S(−) ketorolac. Using allometric size scaling significantly affected the clearances (CL, Q) and volumes of distribution (V1, V2).

A question of fit:cultural and individual differences in interpersonal justice perceptions

This study examined the link between employees’ adult attachment orientations and perceptions of line managers’ interpersonal justice behaviors, and the moderating effect of national culture (collectivism). Participants from countries categorized as low collectivistic (N = 205) and high collectivistic (N = 136) completed an online survey. Attachment anxiety and avoidance were negatively related to interpersonal justice perceptions. Cultural differences did not moderate the effects of avoidance. However, the relationship between attachment anxiety and interpersonal justice was non-significant in the Southern Asia (more collectivistic) cultural cluster. Our findings indicate the importance of ‘fit’ between cultural relational values and individual attachment orientations in shaping interpersonal justice perceptions, and highlight the need for more non-western organizational justice research.

Fair price and its effect on willingness to purchase

The purpose of the present research is to demonstrate the influence of a fair price (independent of the subjective evaluation of the price magnitude) on buyers' willingness to purchase. The perceived fairness of a price is conceived to have three components: perceived equity, perceived need, and inferred compliance of the seller to the process rules of pricing. These components reflect the Theories of Distributive Justice (as adjusted for conditions of need) and Procedural Justice.^ The effect of the three components of a fair price on willingness to purchase is depicted in a theoretically causal chain model. Based on the Theories of Dissonance and Attribution, conditions of inequity and need activate concerns for Procedural Justice. Under conditions of inequity and need, buyers tend to infer that the seller has not complied with the generally accepted pricing practices, thus violating the social norms of Procedural justice. Inferred violations of Procedural Justice influence the buyer's attitude toward the seller. As predicted by the Theory of Reasoned Action, attitude is then positively related to willingness to purchase.^ The model was tested with a survey-based experiment conducted with 408 respondents. Two levels of both equity and need were manipulated with scenarios, a common research method in studies of Distributive and Procedural Justice. The data were analyzed with a structural equation model using LISREL. Although the effect of the "need" manipulation was insignificant, the results indicated a good fit of the model (Chi-square = 281, Degrees of Freedom = 104, Goodness of Fit Index =.924). The conclusion is that the fairness of a price does have a significant effect on willingness to purchase, independent of the subjective evaluation of the objective price. ^

Dietary adequacy in community-dwelling older Chinese adults living in South Florida

A challenge facing nutrition care providers and the Chinese community is how to improve and maintain dietary adequacy (DA) and quality of life (QoL) in older Chinese Americans. Little is known about the factors contributing to DA and the relationships between DA and QoL among community-dwelling older Chinese adults in South Florida. A DA model and a QoL model were hypothesized. ^ Structured interviews with 100 Chinese Floridians, ages ≥60, provided data to test the hypothesized models, using structured equation modeling. Participants (mean age ± SD = 70.9 + 6.8 years) included 59% females, 98% foreign-born, 23% non-English speakers, and 68% residents of Florida for 20 years or more. The findings supported the study hypotheses: an excellent goodness-of-fit of the DA model (χ2/DF (7) = .286; CFI = 1.000; TLI = 1.704; NFI = .934; RMSEA < .001, 90% CI < .0001 to < .001; SRMR = .033; AIC = 30.000; and BIC = 66.472) and an excellent goodness-of-fit of the QoL model (χ2/DF (6) = .811; CFI = 1.000; TLI = 1.013; NFI = .979; RMSEA < .001, 90% CI < .001 to .116; SRMR = .0429; AIC = 34.869; and BIC = 73.946). ^ The DA model consisted of a structure of four indicators (i.e. Body Mass Index, food practices, diet satisfaction, and appetite) and one intervening variable (i.e. combining nutrient adequacy with nutritional risk). BMI was the strongest, most reliable indicator of DA with the highest predictability coefficient (.63) and the ability to differentiate between participants with different DA levels. The QoL model consisted of a two-dimensional construct with one indicator (i.e. physical function) and one intervening variable (i.e. combining loneliness with social resources, depression, social function, and mental health). Physical function had the strongest predictability coefficient (.89), while other indicators contributed to QoL indirectly. When integrating the DA model to the QoL model, DA appears to influence QoL via indirect pathways. ^ It is necessary to include a precise measure of BMI as the basis for assessing DA in this population. Important goals of dietary interventions should be improving physical function and alleviating social and emotional isolation. ^

The inclusion of differentially assessed lands in urban growth model calibration: a comparison of two approaches using SLEUTH

This research sought to understand the role that differentially assessed lands (lands in the United States given tax breaks in return for their guarantee to remain in agriculture) play in influencing urban growth. Our method was to calibrate the SLEUTH urban growth model under two different conditions. The first used an excluded layer that ignored such lands, effectively rendering them available for development. The second treated those lands as totally excluded from development. Our hypothesis was that excluding those lands would yield better metrics of fit with past data. Our results validate our hypothesis since two different metrics that evaluate goodness of fit both yielded higher values when differentially assessed lands are treated as excluded. This suggests that, at least in our study area, differential assessment, which protects farm and ranch lands for tenuous periods of time, has indeed allowed farmland to resist urban development. Including differentially assessed lands also yielded very different calibrated coefficients of growth as the model tried to account for the same growth patterns over two very different excluded areas. Excluded layer design can greatly affect model behavior. Since differentially assessed lands are quite common through the United States and are often ignored in urban growth modeling, the findings of this research can assist other urban growth modelers in designing excluded layers that result in more accurate model calibration and thus forecasting.

Development of safety performance functions for SafetyAnalyst applications in Florida

In 2010, the American Association of State Highway and Transportation Officials (AASHTO) released a safety analysis software system known as SafetyAnalyst. SafetyAnalyst implements the empirical Bayes (EB) method, which requires the use of Safety Performance Functions (SPFs). The system is equipped with a set of national default SPFs, and the software calibrates the default SPFs to represent the agency's safety performance. However, it is recommended that agencies generate agency-specific SPFs whenever possible. Many investigators support the view that the agency-specific SPFs represent the agency data better than the national default SPFs calibrated to agency data. Furthermore, it is believed that the crash trends in Florida are different from the states whose data were used to develop the national default SPFs. In this dissertation, Florida-specific SPFs were developed using the 2008 Roadway Characteristics Inventory (RCI) data and crash and traffic data from 2007-2010 for both total and fatal and injury (FI) crashes. The data were randomly divided into two sets, one for calibration (70% of the data) and another for validation (30% of the data). The negative binomial (NB) model was used to develop the Florida-specific SPFs for each of the subtypes of roadway segments, intersections and ramps, using the calibration data. Statistical goodness-of-fit tests were performed on the calibrated models, which were then validated using the validation data set. The results were compared in order to assess the transferability of the Florida-specific SPF models. The default SafetyAnalyst SPFs were calibrated to Florida data by adjusting the national default SPFs with local calibration factors. The performance of the Florida-specific SPFs and SafetyAnalyst default SPFs calibrated to Florida data were then compared using a number of methods, including visual plots and statistical goodness-of-fit tests. The plots of SPFs against the observed crash data were used to compare the prediction performance of the two models. Three goodness-of-fit tests, represented by the mean absolute deviance (MAD), the mean square prediction error (MSPE), and Freeman-Tukey R2 (R2FT), were also used for comparison in order to identify the better-fitting model. The results showed that Florida-specific SPFs yielded better prediction performance than the national default SPFs calibrated to Florida data. The performance of Florida-specific SPFs was further compared with that of the full SPFs, which include both traffic and geometric variables, in two major applications of SPFs, i.e., crash prediction and identification of high crash locations. The results showed that both SPF models yielded very similar performance in both applications. These empirical results support the use of the flow-only SPF models adopted in SafetyAnalyst, which require much less effort to develop compared to full SPFs.

Development, validation and uncertainty analysis of quantitative structure and activity relationship models for Log P of disinfection by -products

Hydrophobicity as measured by Log P is an important molecular property related to toxicity and carcinogenicity. With increasing public health concerns for the effects of Disinfection By-Products (DBPs), there are considerable benefits in developing Quantitative Structure and Activity Relationship (QSAR) models capable of accurately predicting Log P. In this research, Log P values of 173 DBP compounds in 6 functional classes were used to develop QSAR models, by applying 3 molecular descriptors, namely, Energy of the Lowest Unoccupied Molecular Orbital (ELUMO), Number of Chlorine (NCl) and Number of Carbon (NC) by Multiple Linear Regression (MLR) analysis. The QSAR models developed were validated based on the Organization for Economic Co-operation and Development (OECD) principles. The model Applicability Domain (AD) and mechanistic interpretation were explored. Considering the very complex nature of DBPs, the established QSAR models performed very well with respect to goodness-of-fit, robustness and predictability. The predicted values of Log P of DBPs by the QSAR models were found to be significant with a correlation coefficient R2 from 81% to 98%. The Leverage Approach by Williams Plot was applied to detect and remove outliers, consequently increasing R 2 by approximately 2% to 13% for different DBP classes. The developed QSAR models were statistically validated for their predictive power by the Leave-One-Out (LOO) and Leave-Many-Out (LMO) cross validation methods. Finally, Monte Carlo simulation was used to assess the variations and inherent uncertainties in the QSAR models of Log P and determine the most influential parameters in connection with Log P prediction. The developed QSAR models in this dissertation will have a broad applicability domain because the research data set covered six out of eight common DBP classes, including halogenated alkane, halogenated alkene, halogenated aromatic, halogenated aldehyde, halogenated ketone, and halogenated carboxylic acid, which have been brought to the attention of regulatory agencies in recent years. Furthermore, the QSAR models are suitable to be used for prediction of similar DBP compounds within the same applicability domain. The selection and integration of various methodologies developed in this research may also benefit future research in similar fields.

English Language Learners: A Correlational Study of the Relationship Between A Proficiency Level Assessment and End of Course Test Scores at one Georgia High School

Understanding the language of one’s cultural environment is important for effective communication and function. As such, students entering U.S. schools from foreign countries are given access to English to Speakers of Other Languages (ESOL) programs and they are referred to as English Language Learner (ELL) students. This dissertation examined the correlation of ELL ACCESS Composite Performance Level (CPL) score to the End of Course tests (EOCTs) and the Georgia High School Graduation Tests (GHSGTs) in the four content courses (language arts, mathematics, science, and social studies). A premise of this study was that English language proficiency is critical in meeting or exceeding state and county assessment standards. A quantitative descriptive research design was conducted using Cross-sectional archival data from a secondary source. There were 148 participants from school years 2011-2012 to 2013- 2014 from Grades 9-12. A Pearson product moment correlation was run to assess the relationship between the ACCESS CPL (independent variable) and the EOCT scores and the GHSGT scores (dependent variables). The findings showed that there was a positive correlation between ACCESS CPL scores and the EOCT scores where language arts showed a strong positive correlation and mathematics showed a positive weak correlation. Also, there was a positive correlation between ACCESS CPL scores and GHSGT scores where language arts showed a weak positive correlation. The results of this study indicated that that there is a relationship between the stated variables, ACCESS CPL, EOCT and GHSGT. Also, the results of this study showed that there were positive correlations at varying degrees for each grade levels. While the null hypothesis for Research Question 1 and Research Question 2 were rejected, there was a slight relationship between the variables.

Modelagem estatística e atribuições dos eventos de precipitação extrema na Amazônia brasileira

Intense precipitation events (IPE) have been causing great social and economic losses in the affected regions. In the Amazon, these events can have serious impacts, primarily for populations living on the margins of its countless rivers, because when water levels are elevated, floods and/or inundations are generally observed. Thus, the main objective of this research is to study IPE, through Extreme Value Theory (EVT), to estimate return periods of these events and identify regions of the Brazilian Amazon where IPE have the largest values. The study was performed using daily rainfall data of the hydrometeorological network managed by the National Water Agency (Agência Nacional de Água) and the Meteorological Data Bank for Education and Research (Banco de Dados Meteorológicos para Ensino e Pesquisa) of the National Institute of Meteorology (Instituto Nacional de Meteorologia), covering the period 1983-2012. First, homogeneous rainfall regions were determined through cluster analysis, using the hierarchical agglomerative Ward method. Then synthetic series to represent the homogeneous regions were created. Next EVT, was applied in these series, through Generalized Extreme Value (GEV) and the Generalized Pareto Distribution (GPD). The goodness of fit of these distributions were evaluated by the application of the Kolmogorov-Smirnov test, which compares the cumulated empirical distributions with the theoretical ones. Finally, the composition technique was used to characterize the prevailing atmospheric patterns for the occurrence of IPE. The results suggest that the Brazilian Amazon has six pluvial homogeneous regions. It is expected more severe IPE to occur in the south and in the Amazon coast. More intense rainfall events are expected during the rainy or transitions seasons of each sub-region, with total daily precipitation of 146.1, 143.1 and 109.4 mm (GEV) and 201.6, 209.5 and 152.4 mm (GPD), at least once year, in the south, in the coast and in the northwest of the Brazilian Amazon, respectively. For the south Amazonia, the composition analysis revealed that IPE are associated with the configuration and formation of the South Atlantic Convergence Zone. Along the coast, intense precipitation events are associated with mesoscale systems, such Squall Lines. In Northwest Amazonia IPE are apparently associated with the Intertropical Convergence Zone and/or local convection.

Mineralogical, geochemical and magnetic signatures of surface sediments from the Canadian Beaufort Shelf and Amundsen Gulf (Canadian Arctic)

Mineralogical, geochemical, magnetic, and siliciclastic grain-size signatures of 34 surface sediment samples from the Mackenzie-Beaufort Sea Slope and Amundsen Gulf were studied in order to better constrain the redox status, detrital particle provenance, and sediment dynamics in the western Canadian Arctic. Redox-sensitive elements (Mn, Fe, V, Cr, Zn) indicate that modern sedimentary deposition within the Mackenzie-Beaufort Sea Slope and Amundsen Gulf took place under oxic bottom-water conditions, with more turbulent mixing conditions and thus a well-oxygenated water column prevailing within the Amundsen Gulf. The analytical data obtained, combined with multivariate statistical (notably, principal component and fuzzy c-means clustering analyses) and spatial analyses, allowed the division of the study area into four provinces with distinct sedimentary compositions: (1) the Mackenzie Trough-Canadian Beaufort Shelf with high phyllosilicate-Fe oxide-magnetite and Al-K-Ti-Fe-Cr-V-Zn-P contents; (2) Southwestern Banks Island, characterized by high dolomite-K-feldspar and Ca-Mg-LOI contents; (3) the Central Amundsen Gulf, a transitional zone typified by intermediate phyllosilicate-magnetite-K-feldspar-dolomite and Al-K-Ti-Fe-Mn-V-Zn-Sr-Ca-Mg-LOI contents; and (4) mud volcanoes on the Canadian Beaufort Shelf distinguished by poorly sorted coarse-silt with high quartz-plagioclase-authigenic carbonate and Si-Zr contents, as well as high magnetic susceptibility. Our results also confirm that the present-day sedimentary dynamics on the Canadian Beaufort Shelf is mainly controlled by sediment supply from the Mackenzie River. Overall, these insights provide a basis for future studies using mineralogical, geochemical, and magnetic signatures of Canadian Arctic sediments in order to reconstruct past variations in sediment inputs and transport pathways related to late Quaternary climate and oceanographic changes.

Economic Evaluations of State Policies

Thesis (Ph.D.)--University of Washington, 2016-08

Understanding of genetic test results for osteogenesis imperfecta by attorneys and child welfare workers in non-accidental injury cases

Thesis (Ph.D.)--University of Washington, 2016-08