A research report submitted in partial fulfilment of Mathematical Statistics Masters by Coursework and Research Report to the Faculty of Science, University of the Witwatersrand, Johannesburg, 2019 / The growing demand for generic drugs has led to an increase in the generic drug industry. As a result, there has been a growing demand for bioequivalence studies. The challenges with the bioequivalence studies arose with the method used to quantify bioavailability. Bioavailability is commonly estimated by the area under the concentration-time curve (AUC), which is traditionally estimated by Non-Compartmental Analysis (NCA) such as interpolation in aid of the trapezoidal rule. However, when the number of samples per subject is insufficient, the NCA estimates may be biased and this can result in incorrect conclusions about bioequivalence. Alternatively, AUC can be estimated by the Non-Linear Mixed Effect Model (NLMEM). The objective of this study is to evaluate bioequivalence on lnAUC estimated by using a NCA approach to those based on the lnAUC estimated by the NLMEM approach. The NCA and NLMEM approaches are compared on the resulting bias when the linear mixed effect model is used to analyse the lnAUC data estimated by each method. The methods are evaluated on simulated and real data. The 2x2 crossover designs of different sample sizes and sampling time intensities are simulated using two null hypotheses. In each crossover design, concentration profiles are simulated with different levels of between-subject variability, within-subject variability and residual error variance. A higher bias is obtained with the lnAUC estimated by the NCA approach for trials with a limited number of samples per subject. The NCA estimates provide satisfactory global TypeI-error results. The NLMEM fails to distinguish between the existing formulation differences when the residual variability is high. / TL (2020)

Polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) are common contaminants of sediment, soils and biological tissues. These compounds pose a significant risk to biological and ecosystem health and functioning due to these compounds being mutagenic, carcinogenic and are known to disrupt the endocrine system. The bioaccumulation and biomagnification potential that these compounds possess mean that they are capable of affecting the entire food chain and are not limited to the organisms that are directly in contact with the compounds Even though there has been an increase in the attention on identifying the presence and impacts that these compounds may have in South Africa, the level of attention is lower than what it is in other countries around the world. Although South Africa has guidelines in place for other pollutants, such as metals, there are no such guidelines in place to monitor PAHs and PCBs.. Industries are known to release both PAHs and PCBs, mainly from incomplete burning processes and the release of oils and fuels in the case of PAHs, and from heat transfer fluids in the case of PCBs. Durban Bay and surrounding areas of eThekwini, KwaZulu-Natal are highly industrialised with many aquatic systems, in which these contaminants are likely to deposit. The aim of this research was to determine the concentrations of these compounds by means of chemical analysis and additionally biological analysis, using the H4IIE-luc bioassay and compare these levels to international guideline levels. It was found that the concentrations of the 23 analysed PAHs were 6.5–3 235.6 ng.g-1 and the concentration of the PCBs analysed were 0–113.83 ng.g-1. Many sites were found to be in exceedance of the guideline limits, particularly in the harbour. Toxic equivalency factors (TEF) were used to gauge the toxic equivalency (TEQ) of the PAHs and PCBs that were found. The TEQs were generally low, and were below any guideline levels. The assay revealed the extract containing the PCBs had a bioassay equivalence (BEQ) of 0–93.54 pgTCDDeq. g-1 and the extract containing the PAHs of 0–776.08 pgTCDD-eq.g-1. With a proportion of the sites exceeding guideline limits. The BEQ results were two to three orders of magnitude greater than the TEQs calculated from the concentrations determined by the instrumental analysis, however, followed a similar trend. Additionally chemical analysis was not performed on a full suite of compounds that are able to elicit a response from the cells, which could be a reason why the BEQ and TEQ did not follow a similar trend among some of the samples. It would have been more beneficial to have performed chemical analysis on the 16 priority PAHs (as determined by the United States Environmental Protection Agency), the dioxin-like PCBs and polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDFs) which are all capable of eliciting a response from the cells and have TEF values. The areas that were most affected by contamination of these compounds was the harbour and surrounding canals, and there was point source contamination along the Umhlatuzana, Umbilo, and Amanzimnyana Rivers. All dl-PCBs should be chemically analysed at all the sample areas, as these cause adverse effects to biota. In addition to this, biota should be sampled to determine concentrations of the compounds to determine bioavailability and the degree of bioaccumulation in the food chain. Utilising biomarkers it would be possible to determine stresses of fish. / MSc (Environmental Sciences), North-West University, Potchefstroom Campus, 2014

Polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) are common contaminants of sediment, soils and biological tissues. These compounds pose a significant risk to biological and ecosystem health and functioning due to these compounds being mutagenic, carcinogenic and are known to disrupt the endocrine system. The bioaccumulation and biomagnification potential that these compounds possess mean that they are capable of affecting the entire food chain and are not limited to the organisms that are directly in contact with the compounds Even though there has been an increase in the attention on identifying the presence and impacts that these compounds may have in South Africa, the level of attention is lower than what it is in other countries around the world. Although South Africa has guidelines in place for other pollutants, such as metals, there are no such guidelines in place to monitor PAHs and PCBs.. Industries are known to release both PAHs and PCBs, mainly from incomplete burning processes and the release of oils and fuels in the case of PAHs, and from heat transfer fluids in the case of PCBs. Durban Bay and surrounding areas of eThekwini, KwaZulu-Natal are highly industrialised with many aquatic systems, in which these contaminants are likely to deposit. The aim of this research was to determine the concentrations of these compounds by means of chemical analysis and additionally biological analysis, using the H4IIE-luc bioassay and compare these levels to international guideline levels. It was found that the concentrations of the 23 analysed PAHs were 6.5–3 235.6 ng.g-1 and the concentration of the PCBs analysed were 0–113.83 ng.g-1. Many sites were found to be in exceedance of the guideline limits, particularly in the harbour. Toxic equivalency factors (TEF) were used to gauge the toxic equivalency (TEQ) of the PAHs and PCBs that were found. The TEQs were generally low, and were below any guideline levels. The assay revealed the extract containing the PCBs had a bioassay equivalence (BEQ) of 0–93.54 pgTCDDeq. g-1 and the extract containing the PAHs of 0–776.08 pgTCDD-eq.g-1. With a proportion of the sites exceeding guideline limits. The BEQ results were two to three orders of magnitude greater than the TEQs calculated from the concentrations determined by the instrumental analysis, however, followed a similar trend. Additionally chemical analysis was not performed on a full suite of compounds that are able to elicit a response from the cells, which could be a reason why the BEQ and TEQ did not follow a similar trend among some of the samples. It would have been more beneficial to have performed chemical analysis on the 16 priority PAHs (as determined by the United States Environmental Protection Agency), the dioxin-like PCBs and polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDFs) which are all capable of eliciting a response from the cells and have TEF values. The areas that were most affected by contamination of these compounds was the harbour and surrounding canals, and there was point source contamination along the Umhlatuzana, Umbilo, and Amanzimnyana Rivers. All dl-PCBs should be chemically analysed at all the sample areas, as these cause adverse effects to biota. In addition to this, biota should be sampled to determine concentrations of the compounds to determine bioavailability and the degree of bioaccumulation in the food chain. Utilising biomarkers it would be possible to determine stresses of fish. / MSc (Environmental Sciences), North-West University, Potchefstroom Campus, 2014

Are computer-administered versions of a multiple choice paper-pencil test equivalent? This study determined whether there were any significant differences between taking a traditional pencil-paper test and taking the same test using a computer. The literature has shown that there are intervening variables that have caused differences when not controlled. To prove equivalency between test modes, scores have to have similar means, dispersions, and shapes; the ranked-order of the scores must also be similar. Four tests were given over the course of a 16-week semester. The sample was divided, half taking paper-pencil tests and half taking the same test administered by a computer. The mode of administration was switched with each test administration. The analysis showed that, when the intervening variables were controlled, the two modes of administration were equivalent. The analysis used a 2x4 ANOVA, which showed no difference between test modes, but showed that each test administration was significantly different. The Levene statistic was used to test whether dispersions were equivalent and confidence intervals were established to test the kurtosis and skewness statistics. Finally, each of the test scores were transformed into their Normal Curve Equivalents so that Pearson's coefficient could be used to determine the equivalency of the ranked-orders.

The purpose of this study was to identify effective instructional programs for GED tests preparation for students in a large suburban school district. Three different nonrandom, unequal naturally occurring instructional groups at three different locations were examined. One group participated in a traditional instruction program, a second group in a test/retest program, and a third group in a computer-assisted program. The demographics of the district population, the GED population, and the individual study groups were catalogued and analyzed. The demographics of the GED population were similar to the district population but different from the GED passers. Student characteristics did affect GED success. Both quantitative and qualitative data were gathered. Random students in each of the three groups were interviewed about their experiences in GED preparation using a questionnaire. Quantitative data were analyzed using frequencies, means, correlations, and a multiple regression analysis. Since the GED credential is an alternative to the high school diploma, its use as a dropout alternative is important to every school district. The study found that instructional methods had little impact on students' success in receiving the GED credential. The overall success rate of students was low in each group. The student's reading achievement score, GPA, and IQ score were predictors of GED tests success. Little research has been done in the area of GED instruction; perhaps this lack of work is due to the known limited effectiveness of GED preparation. Districts hoping to build effective GED programs should screen students prior to admission to a GED program. High school GED instruction seems to be effective for students likely to be successful in the regular school setting but in need of an immediate credential because of pregnancy or parenting or the need to work full-time or the desire to begin college study. Districts should also design programs to help disenfranchised students in the regular program remain in school.

and key words The final thesis discuss idiomatic expressions, which includes words related to animal kingdom. An essential point of the whole thesis was creation of a list of all relevant Danish idioms. There was found their Danish definitions as well and subsequently also their Czech equivalent words. Equivalent degree was found by all words. The thesis is divided into theoretical part and practical part. The first one describes idiomacity and phraseology as a whole and compares Danish and Czech works on this topic. Other subjects, which is needed in the practical part, is discussed. Deep analysis of the list of the idioms is the content of the practical part of the thesis. Main topics is perception of animals in Czech and Danish, degree of their mutual equivalency and some other specific subjects related to animal idioms. Key words: animal kingdom, Czech, Danish, equivalency, etymology, phraseology

Desde 1964, o Brasil tem lançado programas de políticas públicas para melhorar o acesso da população aos medicamentos considerados essenciais. Em 1999, com a criação da Agência Nacional de Vigilância Sanitária e a introdução dos medicamentos genéricos no mercado brasileiro, o Brasil passou a ter três classes de medicamentos disponíveis no mercado farmacêutico: referência, similar e genérico. O objetivo deste estudo foi avaliar a bioequivalência e intercambialidade entre dois antipsicóticos (referência e similar) utilizados pelo Instituto de Psiquiatria do Hospital das Clínicas da Universidade de São Paulo, contendo 2 mg de risperidona. Foi desenvolvido e validado um método analítico que emprega a cromatografia líquida de alta eficiência acoplada à espectrometria de massas para a determinação da risperidona (RSP) e seu principal metabólito a 9-hidroxirisperidona (9OH-RSP) em plasma. Para se avaliar a bioequivalência entre os medicamentos foram recrutados 22 voluntários sadios, os quais participaram do estudo clínico conduzido de forma cruzada e aleatória. As coletas sanguíneas para o ensaio de bioequivalência foram realizadas em tubos heparinizados (5 mL) e os tempos de coleta foram 0 (antes da medicação); 0,25; 0,5; 1; 1,5; 3; 5; 8; 12; 24; 48; 72; 96 e 120 horas após a administração da medicação. A determinação da bioequivalência entre os dois medicamentos deu-se através da comparação dos parâmetros farmacocinéticos: concentração plasmática máxima (Cmax), tempo para atingir a concentração plasmática máxima (Tmax) e área sobre a curva de decaimento plasmático (ASCT). Os resultados obtidos foram submetidos à análise de variância (ANOVA) e foi adotado o intervalo de confiança de 90% (IC 90%). Os valores médios para Cmax, Tmax e ASCT para RSP para os medicamentos referência e teste foram 16,02 ng/mL; 1,5 h e 348,94 ng.h/mL e 12,65 ng/mL; 1,5 h e 286,03 ng.h/mL, respectivamente. Já os valores médios para Cmax, Tmax e ASCT para 9OH-RSP para os medicamentos referência e teste foram 21,00 ng/mL; 5,0 h e 821,40 ng.h/mL e 17,85 ng/mL; 5,0 h e 632,92 ng.h/mL. Os valores de IC 90% para Cmax e ASCT para RSP para os medicamentos referência e teste foram 74 a 82% e 76 a 85%, respectivamente, e os valores de IC 90% para os mesmos parâmetros para 9OH-RSP foram 83 a 87% e 75 a 78%, respectivamente. Os resultados demonstraram diferenças significativas entre os medicamentos testados, o que permite concluir que os mesmos não são bioequivalentes e, portanto, não podem ser intercambiáveis / Brazil has launched programmes of public policies aiming to improve essential medicines access for the population since 1964. It was created in 1999 the National Agency for Sanitary Vigilance, which introduced the generic medicines in the Brazilian market, which already had the reference and the pharmaceutical equivalent ones. The objective of this study was to evaluate the bioequivalence and interchangeability between two antipsychotics (reference and pharmaceutical equivalent) used by the Institute of Psychiatry, Hospital of the Universidade de São Paulo, containing 2 mg of risperidone. It was developed and validated a high-performance liquid chromatography coupled to mass spectrometry method for the determination in plasma of risperidone (RSP) and its main metabolite, 9- hydroxy-risperidone (9OH-RSP). To assess bioequivalence between the medicines it was recruited 22 healthy volunteers, which took part in a clinical cross and random studies. The blood collections were performed on heparinizades tubes (5 ml) and runtimes collections were 0 (before medication); 0.25; 0.5; 1; 1.5; 3; 5; 8; 12; 24; 48; 72; 96 and 120 hours after the administration of medication. The determination of bioequivalence between the two drugs was achieved by a comparison of the following pharmacokinetic parameters: plasma concentration (Cmax), time to achieve Cmax (Tmax), and area under the plasma concentration-time curve (AUCT). Results were subjected to analysis of variance (ANOVA), adopting a confidence interval CI 90%. The average values for Cmax, Tmax and AUCT for RSP were 16.02 ng/ml, 1.5 h and 348.94 ng.h/ml for reference medicines and 12.65 ng/ml, 1.5 h and 286.03 ng.h/ml for testing ones. The average values for Cmax, Tmax and AUCT for 9OH-RSP were 21.00 ng/ml, 5.0 h and 821.40 ng.h/ml for reference medicines and 17.85 ng/ml, 5.0 h and 632.92 ng.h/ml for testing ones. CI 90% for Cmax and AUC (RSP) were 74-82% and 76-85%, respectively. The CI 90% for the same parameters for 9OH-RSP was 83-87% for reference medicines and 75-78% for testing ones. There was significant difference between the products tested, thus one can conclude they are not bioequivalents, therefore cannot be interchanged

The purpose of this study was to test whether the computer-administered College Level Examination Program (CLEP) General Examination in English Composition produced scores equivalent to those obtained from the traditional paper-and-pencil version. The CLEP examination and its adaptation for computer administration and the results of a pilot study are presented. The subjects in this study were volunteers who took the CLEP English Composition Examination in order to earn college credit and were randomly assigned to either the computer-first or paper-and-pencil-first groups. Each subject took both forms of the examination with approximately one half of the subjects taking each version first. Analysis of variance failed to detect a significant effect for test form or an interaction of test form and order of administration. Equivalence reliability coefficients and internal consistency coefficients also indicated that the computer administration did not significantly alter the results of the examination. In general, the results of this study support the hypothesis that the computer-administered version of the CLEP General Examination in English Composition produces results equivalent to those obtained from the traditional paper-and-pencil version.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 126-143).

The purpose of this study was to determine whether student outcomes are a function of participation in different modes of delivery in an Opticianry program at the community college level. First, the intent was to determine whether differences in instructional delivery methods and background characteristics impact student performance in an Opticianry program. The three instructional delivery methods were traditional face-to-face instruction, online delivery, and a hybrid format where students take theory courses online and attend face-to-face laboratories on campus. A second objective was to determine the role of background variables such as student age, which was the age when entering the Opticianry program classified in three categories: Young Adults (18-24), Middle Age (25-33), and Older Adults (34 & >). To meet the purpose of the study and its driving questions, a non-experimental explanatory research design relying on survey data collection strategies was used. Data collection was conducted during a six-week period using an online survey available through Survey Monkey. The survey was used to identify instructional delivery method, perception of job preparedness, and perception of program quality. A two-way ANOVA was used to analyze the relationship between independent variables (delivery method and age) and a dependent variable (GPA, national certification score, workplace preparation score, and quality of instruction score). Two hundred and eighty six graduates of the Hillsborough Community College Opticianry Program from 2006-2012 were contacted for participation. One hundred and twelve graduates completed the survey representing a response rate of 39%. The results indicated no significant difference in the outcomes of Opticianry program graduates related to instructional delivery method or age. Based on the overall results in the study, the overall conclusion is that students in the Opticianry program should achieve similar outcomes whether they complete the program online, on campus, or in a hybrid format. The results of the study provide support for the idea that it is possible to provide equivalent technician preparation using a variety of instructional delivery methods. The study adds to a limited body of knowledge about the impact of participation in online or hybrid courses compared to traditional courses in technical preparation. The outcomes provide support that distance education is a promising strategy for increasing access to adult learners seeking flexible opportunities for technical preparation. The results should also reduce the reluctance of institutions offering career and technical education programs, to offer complete programs via distance learning in fear that distance students will not achieve program outcomes equivalent to face-to-face students. The study has generated positive comparative evidence of student performance as a function of instructional method, and documented students' evaluative perspectives about their occupational readiness and program quality.