Thesis (Ph. D.)--University of Washington, 1996. / Vita. Includes bibliographical references (leaves [140]-147).

Thesis (Ph. D.)--Virginia Polytechnic Institute and State University, 1993. / Vita. Abstract. Includes bibliographical references (leaves 205-214). Also available via the Internet.

Thesis (Ph. D.)--Florida State University, 2005. / Advisor: John G. Dorsey, Florida State University, College of Arts and Sciences, Dept. of Chemistry and Biochemistry. Title and description from dissertation home page (viewed Jan. 25, 2006). Document formatted into pages; contains xxiii, 132 pages. Includes bibliographical references.

Thesis (M.S.)--Missouri University of Science and Technology, 2009. / Vita. The entire thesis text is included in file. Title from title screen of thesis/dissertation PDF file (viewed November 17, 2009) Includes bibliographical references (p. 61-62).

The investigations detailed in this dissertation have been conducted to address the paucity of pharmacokinetic information, in published literature, pertaining to cyclizine. The areas of investigation have included the selective quantitation of both cyclizine and its demethylated metabolite, norcyclizine in serum and urine, assessment of stability of both compounds in stored biological samples, dosage form analysis, dissolution rate testing of tablets, and bioavailability and pharmacokinetics following administration of an intravenous solution, and tablets to humans. High-performance liquid chromatography (HPLC) was used as the main analytical technique throughout these studies. An original HPLC method employing ultraviolet detection with a limit of quantitation of 5μg/ℓ was developed for the determination of cyclizine in serum and both cyclizine and norcyclizine in urine, Solid-phase extraction using extraction columns packed with reversed-phase C18 material, and followed by a simple phase-separation step proved successful for the accurate and precise isolation of the compounds. The validated method was applied to the analysis of serum and urine samples from a pilot study in which a single volunteer was administered 50mg of cyclizine hydrochloride. Several samples collected during the pilot study revealed the presence of both drug and metabolite in concentrations below the limit of detection. In order to improve the selectivity and sensitivity of the analytical method an HPLC method with electrochemical detection operating in the "oxidative-screen" mode was developed. The solid-phase extraction procedure was modified slightly and the method found to be precise, accurate, selective and highly sensitive with a limit of quantitation of Iμg/g/l for both cyclizine and norcyclizine in both serum and urine. This method was applied to the determination of both compounds after intravenous and oral administration of cyclizine to humans. HPLC with electrochemical detection was used for the analysis of samples collected during dissolution studies on the batch of tablets used for pharmacokinetic studies. In addition, this method was used to assess content uniformity of the tablets and of samples from the batch of intravenous ampoules of cyclizine lactate. Dissolution studies showed that all tablets tested passed the compendial specifications for cyclizine. Content uniformity assessment revealed that within-batch uniformity existed for both the tablets and ampoules and, therefore, variations in pharmacokinetic parameters for the drug would more than likely be as a result of inter- and intra-individual variability within the subject population. Pharmacokinetic information for cyclizine was obtained following administration of an intravenous bolus dose of cyclizine lactate as a solution, oral administration of cyclizine hydrochloride as a single dose of 50mg and as fixed multiple doses of 50mg every 8 hours for five days. Further information was acquired following administration of single doses of 100mg and 150mg cyclizine hydrochloride. Data collected from these studies were evaluated using both compartmental and non-compartmental techniques. Cyclizine was rapidly absorbed following oral administration with mean kₐ = 1.54 hr⁻¹ and was found to have an absolute bioavailability (F) of 0.47. The presence of norcyclizine in serum following oral and not intravenous dosing suggests cyclizine is susceptible to "first-pass" metabolism in either the gut wall or the I iver. Mean ClTOT determined following the intravenous dose was 0.865 ℓ/hr/kg. The mean ClTOT of 0.823 ℓ/hr/kg calculated following oral dosing, using a unique value of F for each subject compared favourahly with that obtained following intravenous dosing. Renal clearance of cyclizine is negligihle indicating that non-renal routes of elimination account for the majority of removal of cyclizine form the body. Cyclizine is extensively distributed and the mean Vz following an intravenous dose was 16.70 ℓ/kg. This value is lower than that calculated from all oral studies from which the mean Vz was determined to be 25.74 ℓ/kg. Cyclizine is eliminated slowly with a mean elimination t½ = 20.11 hours. Cyclizine dose not appear to follow dosedependent kinetics and therefore, inability to predict steady state levels are more than likely due to accumulation as a result of frequent dosing rather than saturation of elimination mechanisms. Modelling of intravenous data to one-compartment (lBCM), two-compartment (2BCM) and threecompartment models indicated that the pharmacokinetics of cyclizine can be adequately described by a 3BCM. The drug is rapidly distributed into a "shallow" peripheral compartment (α = 9.44 hr⁻¹ , and k₂₁ = 2.09 hr⁻¹ ), and slowly distributed to the "deep" peripheral compartment (β = 0.451 hr⁻¹ and k₃₁ = 0.120 hr⁻¹ ). Modelling of all oral data indicated that a 2BCM best described the pharmacokinetics of the drug, however, distribution to the peripheral compartment is not as rapid as to the "shallow" peripheral compartment following the intravenous dose. Mean distribution parameters were α = 0.64 hr⁻¹1 and, k₂₁ = 0.39 hr⁻¹. Mean CITOT following intravenous dosing of 0.70 ℓ/hr/kg was similar to the mean CIToT of 0.73 ℓ/hr/kg determined after oral dosing. The mean distribution volume at steady state determined following intravenous dosing (17.78 ℓ/kg) was lower than that obtained from the oral studies (25.52 ℓ/kg). The mean terminal elimination half-lives calculated for cyclizine following fitting of intravenous and oral data was 25.09 hours. In general, mean pharmacokinetic parameters calculated following titting of data to a 2BCM after oral administration correlate closely with those calculated using non-compartmental techniques. However, the pharmacokinetics following intravenous dosing are better described by a 3BCM and a close correlation between parameters estimated using noncompartmental techniques and compartmental techniques is evident when a 3BCM model is used.

Phenylpropanolamine (PPA), a synthetic sympathomimetic amine structurally related to ephedrine has been widely used over t he past 40 years as a nasal decongestant and appetite suppressant. It has been the focus of much controversy concerning the efficacy of the drug in its use as an anorectic agent, and due to the side effects caused by the higher doses of PPA required for appetite suppression. Although extensively used, there is little information concerning the determination of PPA in biological fluids and on the pharmacokinetics of this drug. An adaptation of a published high-performance liquid chromatographic (HPLC) assay for PPA in serum and urine using U.V. detection at 210 nm is presented. PPA was separated in the reversed phase mode. The method has a limit of sensitivity of 5.0 ng/mL and 10.0 ng/mL in serum and urine respectively. Serum concentration data following a single 25 mg dose of phenylpropanolamine in human volunteers demonstrate the application of the analytical method for bioavailability and pharmacokinetic studies. After the administration of 25 mg, 50 mg or 100 mg PPA.HCl solutions to 5 human volunteers, a dose proportionality study demonstrated that PPA appears to exhibit linear kinetics. Linear one body compartment kinetics were assumed and the wagner-Nelson method used to transform in vivo serum data to absorption plots. The serum data were fitted to a model using nonlinear regression techniques to characterize the pharmacokinetic processes of PPA. The absorption of phenylpropanolamine appears to be discontinuous and the drug seems to favour a two body compartment model. The pharmacokinetic parameters obtained from a steady state study using multiple dosing of PPA.HCl solutions compared with those found from previous studies after the administration of sustained-release formulations. A plasma protein binding study using equilibrium dialysis demonstrated that PPA is not highly protein bound in the blood.

Advances in computer technology such as faster processors, better data compression schemes, and cheaper audio and video devices have made it possible to integrate multimedia into the computing environment. Desktop conferencing evolved as a plausible result of this multimedia revolution. The bandwidth granted for these conferencing applications is restricted in most cases by the speed of the modem device connected to the network. Poor performance of multimedia conferencing over the Internet can be attributed to two main factors: local and remote induced effects. Local effects are induced by bandwidth sharing between different media components, operating system limitations, or poor design. Remote effects include all Internet related problems such as unfairness, nonguaranteed quality of service, congestion, etc. Both effects are addressed in this study and some solutions are proposed. The primary goal is to maintain audio quality and prevent video from degrading audio performance. We study characteristics of video and audio traffic sources of conferencing applications following the H.323 set of standards defined by the International Telecommunication Union (ITU). The media traffic uses the Real-time Transport Protocol (RTP) and User Datagram Protocol (UDP) as their transport vehicle over IP network protocol. Tradeoffs involved in the choice of multimedia traffic parameters are presented. Our measurements were carried out on audio and video codecs defined in G.723.1 and H.263 specifications respectively, both drafted by the ITU. This dissertation investigates traffic multiplexing issues at the host, and the interaction of conferencing media components as they are multiplexed locally in a shared bandwidth transport medium. Lack of appropriate multiplexing algorithms can lead to one or more media components oversubscribing to the shared bandwidth and penalizing other participants. These local effects can contribute significantly to traffic delay or abuse of the network bandwidth. We propose the “bit rate adjuster” (BRA) algorithm and use it the network bandwidth. We propose the “bit rate adjuster” (BRA) algorithm and use it for regulating media flow. The algorithm compensates for video local effects induced by packet preparation or processing to allow for better audio performance. A new performance qualifier is introduced and used in the evaluation process. Further on the remote side, we investigate reactive mechanisms used to recover media flow performance degradation caused by shared bandwidth traffic effects. We overview feedback mechanisms based on the Real-time Control Protocol (RTCP). We uncover its limitation on applications connected to the Internet through narrow bandwidth pipes. We propose an alternative approach that predicts and prevents the loss of audio packets before it occurs based on local computation of audio jitter. We also propose a mechanism that recovers audio traffic from jitter and latency effects introduced by the Internet shared medium. These approaches improve the audio performance significantly in multimedia conferencing sessions. / Graduate

In the last three decades, a growing body of research has suggested that using a mix or system of human resources management (HRM) practices can lead to superior organizational performance. These practices (such as selective recruitment and hiring procedures, performance-based compensation systems, employee participation, and training and development) have been referred to as high performance work systems (HPWS) and originated from the study of strategic human resource management (SHRM), where researchers have examined the impact of these systems on organizational performance outcomes. The relationship between HRM and organizational performance has received increasing interest from scholars and practitioners in the field of public administration. Scholars strive to identify the effects of HRM practices on organizational performance based on the notion that these practices will lead to enhanced attitudinal outcomes, such as organizational commitment, job satisfaction, and motivation, which will have positive impacts on organizational performance. This study contributes to further our understanding of the impact of management on performance in public organizations through empirical evidence drawn from theories of HRM. The growing interest among scholars in understanding the effects of management on performance presumes that the adoption of best practices will lead to improvements in organizational performance. The purpose of this mixed-methods study is to examine the effects of HPWS practices on individual worker attitudes in international governmental organizations (IGOs) by reporting the results of a staff survey and follow-up interviews conducted on a cross-section of the United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) employees. The UNRWA is an international relief and human development Agency with a quasi-governmental role, delivering essential public services to over five million registered Palestinian refugees. UNRWA services include education, healthcare, social services, and emergency aid. In 2006, the UNRWA began a comprehensive reform program to strengthen its management capacity. Accordingly, one of the main achievements of the reform process is the deployment of new HRM systems that included recruitment strategies, performance appraisals, training and development, and compensation and rewards systems. The underlying message of the reform process has been adopting HPWS practices, which is the object of this study. Since the 1990s, the UNRWA has become increasingly interested in policy analysis and organizational research. Especially because of recent changes in the Agency’s management style, the UNRWA has become more focused on integrating knowledge and management research into its work. Therefore, when the researcher sought permission to examine the effects of the newly adopted HPWS practices on employee attitudes, the staff and upper management were very collaborative and co-operative. Surveys and interviews were conducted with program administrators, operations directors, and field staff, representing employees from different countries with varying lengths of service as well as an extensive range of levels of education and professional backgrounds. A total of 505 questionnaires were distributed in seven service departments and a total of 234 usable responses were obtained. In addition to questionnaires, a total of 10 face-to-face interviews were conducted to explore the data obtained from questionnaires and to understand further the implications of applying HPWS practices in an IGO context. Statistical analysis of the survey data and interviews provided a representation of the effects of four bundles of HPWS adopted by the organization (independent variables), on four worker attitude measures (dependent variables). The four independent variables are the HPWS practices that are the most common and most accepted in the HRM literature: staffing and recruitment, compensation and rewards, performance appraisal, and training and development. The four dependent variables are employee commitment, job satisfaction, motivation, and intention to quit. Preliminary statistical analysis consisted of descriptive statistics for all study variables, as well as Cronbach’s alpha for measuring the internal consistency reliability coefficients for all the survey subscales to examine its internal consistency. Four research hypotheses were tested using multiple regression analyses and Pearson correlation coefficients in an attempt to estimate the net effect of each of the independent variables and understand the relationship between study variables. The bivariate relationships between the dependent and independent variables have shown that the relationships are in the anticipated directions. One of the main conclusions regarding the effects of specific HPWS practices in an IGO context is that some practices, such as training and development, outperform other practices, such as staffing and recruitment. These findings are consistent with previous research on multinational corporations operating in different national contexts, and other studies comparing the effects of HPWS in different industries. The results also indicated that HPWS practices have synergistic and complementary effects on each of the employee attitudes that exceed their individual effects. Therefore, in order to expand our understanding of the effects of HPWS on organizational performance, different variables need to be considered such as national context, industry, and other organizational factors may moderate the HRM–performance relationship. The findings of this study support previous studies in this stream of research. The qualitative data were used to verify quantitative data and provide insights that were difficult to gain from surveys alone. The qualitative data indicated that more effective implementation and administration of HPWS practices would lead to better employee outcomes. In other words, the newly announced austerity measures negatively influence perceptions towards the newly implemented HPWS, which may also have influenced employee attitude outcomes.

This study examines management and organizational models, specifically the Healthy Organization and High-Performing Workplace (HPW) models. Because a HPW can also be a Healthy Organization, the models are joined to create the Healthy High-Performing Workplace (HHPW) model. The experience of members within a particular organization, known herein as Company X, is examined. The study addresses the questions: does Company X display HHPW qualities? If Company X does display HHPW qualities, does it always exercise HHPW practices? Finally, what does this mean in terms of the workforce? Organizational culture theory is used to explain how expectations, norms, behaviours, and values are constructed and transmitted, and how organizational structures influence the environment and the employee experience. Data consists of interviews (n=12) and secondary sources. The findings support that Company X displays HHPW characteristics. However, when project deadlines are near or overdue and profit is at risk, certain HHPW practices are ignored.

Using archival analysis and interviews this study examined the career pathways, learning experiences, and athletic experiences of 11 high-performance head hockey coaches who played goal in ice hockey. Guided by the learning situations discussed in Wright, Trudel, and Culver (2007) the interviews revealed four important learning experiences common to all the coaches: coach interactions, books and videotapes, coach clinics and academic education, and experiences related to playing and coaching. Like Werthner and Trudel (2009) the results indicated that certain similarities aside, each coach’s career pathway is idiosyncratic with elite athletic experience being an important, but not imperative, aspect of high-performance coaches’ career development. The findings provide insight into how these individuals acquired their coaching knowledge and provide a more complete picture of the developmental pathways associated with becoming a high-performance head hockey coach.