Employment Preparation Programmes (EPPs) are not part of the Special Education Integrated Programme (SEIP) curriculum in Malaysia, and no specific operational guidance is provided to schools regarding them. EPPs are, however, currently performed in a non-uniform way in some schools. This study concerns the early establishment of EPPs in the SEIP in Malaysia. Within the context of the study it is important to note that the partnership programme between schools and outside collaborators is not yet fully established in all secondary schools in Malaysia as stipulated in the Malaysian Education Blueprint (2013-2025). This study aims to explore the implementation of EPPs; delineate the hindrances for special educators, teachers and heads of departments; and, identify the areas of improvement needed to establish vocational educational programmes as early as possible to assist special needs learners towards an independent life through employability. In order to achieve these aims a qualitative study using case study design has been carried out. Semi-structured interviews of Special Education Teachers and Department Heads were undertaken as the main method to elicit data from a purposive sample of fifteen EPP participants. Data was also collected about special needs learners' activities and other relevant emerging themes using an observational method in a real-life setting that included two observations in each EPP at each of the five schools, making 20 observation sessions in total. Relevant documents including official documents from Ministry of Education, modules outlines were also collected from the respective schools and subsequently subject to documentary analysis. To enhance the trustworthiness of the findings, data was triangulated and analysed in light of the Malaysian Education Blueprint along with other previous literature. Findings indicated that leadership and management; academic background knowledge and mastering vocational skills; the social and physical environment; and, collaboration and coordination play an important role in harnessing the potential of special needs learners. The contribution to knowledge of this study is the formation of a framework to clarify the issues impeding effective the implementation of Employment Preparation Programme, and the establishment of key priorities within that implementation effort. Overall, it is argued that this study exemplifies how important it is that the implementation of EPP needs to become an integral part of schools as organisations. Key words: Employment Preparation Programmes, Special Education Integrated Programme, Special educators, Special needs learners.

The use of Cognitive Behaviour Therapy (CBT) as a means to support adolescents diagnosed with Asperger syndrome is gaining interest and has recently been applied in a school setting (Grieg and Mackay, 2005; Sofronoff et al., 2005). The present study explores the use of CBT to support a pupil diagnosed with Asperger syndrome delivered by an educational psychologist in the pupil’s school setting. This application of CBT employed a ‘formulation’ approach in which a programme was written and then adapted in situ to meet the pupil’s needs. The CBT programme consisted of 7 weekly sessions of CBT lasting approximately 40 minutes each of the sessions were delivered in school in the morning prior to the start of lessons. The findings of the present study were analysed using a novel application of Realistic Evaluation methodology (RE) of a CBT intervention in addition to the pre and post CBT measures RE as a methodology seeks to consider the context of an intervention and its potential to triggering mechanisms that could facilitate or limit the progress of introduced intervention. The present study is an exploratory case study, employing a single case design within a realist evaluation framework, to describe the role of the context as a mediating or limiting factor on a CBT intervention. A year 8 pupil with a diagnosis of Asperger syndrome, referred to as B, attended a mainstream secondary school in the West Midlands. It was observed that there were changes for B in terms of his reported social communication and in his cognition. The exploration of the CBT intervention by RE analysis suggested that specific mechanisms were triggered in school and contributed to the observed outcomes. Conclusions are discussed in terms of the usefulness of this methodological approach but also for wider EP practice.

After providing an overview of the context of the study, initially arguments are presented as to why adopting a character based, as opposed to rules or consequences based moral theory is preferential for investigations into the Internet. The ensuing empirical research involves an in-depth and systematic survey undertaken in two sequential phases; phase one comprised a questionnaire chiefly aimed at providing a statistical exploration of the key issues identified in the literature review and phase two involved semi-structured group interviews which were designed to provide additional qualitative data on one particular moral issue - cyber-bullying. This evidence shows that the Internet presents both risks and opportunities for the development of character virtues; in particular, the moral virtues of honesty and compassion. The research demonstrates that it is the character virtues of Internet users, as well as the features of the technology itself, that ultimately determines online behaviour. These findings have implications for those tasked with developing strategies for dealing with online moral issues, and attest to an urgent need for the development of new interventions that will help educate the next generation as virtuous digital citizens.

In the context of working towards a more equitable society, where emphasis is increasingly being placed on promoting equal opportunities for all those accessing the education system, it has been recognised that parents have the right to be heard on matters relating to their child‟s special educational needs. Parents play a vital role in contributing to their child‟s overall well-being, and although professionals may strive to work in partnership with parents, partnership is far from achieved in many cases, with some parents remaining "voiceless" or seemingly „unreachable‟. This thesis (Volume One) was produced as part of the written requirements for the Doctoral training in Educational and Applied Child Psychology and comprises four chapters. Chapter one provides an overview of the volume of work, and alerts the reader to my identity as a researcher and a Trainee Educational Psychologist (TEP) and my epistemological position within this. Chapter Two provides a review of the critical literature relating to parent-professional working and looks at the factors that have been identified as contributing to effective partnership. Chapter Three describes a small scale research study that explored parents‟ lived experiences of working with professionals in relation to their child‟s special educational needs, and sought to explore the ways in which partnership working could be improved so that parents felt that they had a voice. The research employed case study methodology to explore participants‟ lived experiences, and data were analysed using Thematic Analysis. Chapter Four contains final reflections relating to the use of case study methodology as an approach to exploratory research and considers how the study has contributed to my practice as an Educational Psychologist (EP).

In this thesis eight robust and reliable LC-MS/MS methods were developed and validated to analyze atorvastatin, clopidogrel, furosemide, itraconazole, loratadine, naproxen, nisoldipine and sunitinib in human plasma. The active metabolites 2-hydroxyatorvastatin, 4-hydroxyatorvastatin, hydroxyitraconazole, descarboethoxy-loratadine, 4-hydroxynisoldipine and N-desethylsunitinib were also included in the corresponding methods. Due to the different physical, chemical and pharmacokinetic properties of the analytes a wide spectrum regarding sample preparation techniques, chromatography and mass spectrometric detection was covered. Protein precipitation methods were developed for furosemide, itraconazole, naproxen, nisoldipine and sunitinib. Liquid-liquid extraction methods were developed for atorvastatin, clopidogrel and loratadine. Criteria to choose protein precipitation or liquid-liquid extraction were the final plasma concentrations of the drugs, which are mainly dependant on the dose, bioavailability and t1/2 and of course cost-effectiveness. Altogether, the methods have a concentration range from 0.001 ng/mL (LLOQ of clopidogrel) to 50000 ng/mL (highest calibration point for naproxen), covering 5 x 107 orders of magnitude. The runtime of the methods ranged from 2 to 4 minutes, facilitating a high sample throughput. All developed methods were validated according to recent guidelines as they were used to analyze sampes from clinical trials. Excellent linearity, intra-day and inter-day precision and accuracy were observed in the validated calibration ranges. Hemolyzed, lipemic and different batches of human plasma as well as sample dilution did not affect the determiantion of the analytes. Clopidogrel, loratadine, nisoldipine and sunitinib and if available their metabolites were subjected to a matrix effect test, resulting in no influence of different batches of human plasma on the analytical methods. Noteworthy is clopidogrel that shows a slight effect on one of the two used mass spectrometers. However, that effect was reproducible and did therefore not affect clopidogrel determination. No evidence of instability during chromatography, extraction and sample storage processes for all analytes except 4-hydroxyatorvastatin was found, for which a significant decrease was observed after three months. During incurred sample reanalysis of study samples 95 % of the samples were within ±15 % with respect to the first analysis. Moreover, the atorvastatin, loratadine and clopidogrel method were compared on two generations of triple quadrupole mass spectrometers, the API 3000™ and the API 5000™. The new ion source and the changes in the ion path of the API 5000™ provided higher sensitivity, the extend depending on the substance. However, the API 3000™ had very good precision in the performed system comparison. The validated methods showed excellent performance and quality data during routine sample analysis of eight clinical trials. Moreover, they are suitable for high sample throughput due to their short run times. / In dieser Dissertation wurden acht robuste und verlässliche LC-MS/MS-Methoden zur Analyse von Atorvastatin, Clopidogrel, Furosemid, Itraconazol, Loratadin, Naproxen Nisoldipin und Sunitinib in Humanplasma entwickelt und validiert. Außerdem enthalten die Methoden die aktiven Metaboliten 2-Hydroxyatorvastatin, 4-Hydroxyatorvastatin, Hydroxyitraconazol, Descarboethoxyloratadin, 4-Hydroxynisoldipin und N-Desethylsunitinib. Wegen der unterschiedlichen physikalischen, chemischen und pharmakokinetischen Eigenschaften der Analyten, deckt diese Arbeit ein weites Spektrum bezüglich Probenaufarbeitung, Chromatographie und Massenspektrometrie ab. Präzipitationsmethoden wurden für Furosemid, Itraconazol, Naproxen, Nisoldipin und Sunitinib entwickelt. Flüssig-flüssig-Extraktionen wurden für Atorvastatin, Clopidogrel und Loratadin entwickelt. Kriterien für die Auswahl von Präzipitation oder Extraktion waren die erwartete Plasmakonzentration, die im Wesentlichen von der Dosis, Bioverfügbarkeit und Halbwertszeit abhängig ist, und natürlich Kosteneffektivität. Insgesamt erstrecken sich die Methoden über einen Kalibrierbereich von 0.001 ng/mL (LLOQ von Clopidogrel) bis zu 50000 ng/mL (HLOQ von Naproxen), das entspricht 5x107 Größenordnungen. Die Laufzeiten pro Probe liegen im Bereich von zwei bis vier Minuten, was einen sehr hohen Probendurchsatz ermöglicht. Alle in dieser Arbeit entwickelten Methoden wurden gemäß aktueller Richtlinien (FDA, GLP) validiert und verwendet um Proben aus Pharmakokinetikstudien zu analysieren. Ausgezeichnete Linearität, Präzision und Genauigkeit zeichnen diese Methoden aus. Hämolysiertes, lipämisches und verschiedene Batches von Humanplasma, sowie Vorverdünnung hatten bei keiner Methode Einfluss auf die Bestimmung der Analyten. Clopidogrel, Loratadin, Nisoldipin und Sunitinib und gegebenenfalls deren Metabolite wurden einem Matrix-Effekt-Test unterzogen. Dabei wurde festgestellt, dass keine der Methoden durch die Probenmatrix beeinflusst wurde. Erwähnenswert ist Clopidogrel, da an einem der Massenspektrometer ein leichter Effekt beobachtet werden konnte, der sich auf alle untersuchten Matrices gleich auswirkte und somit keinen Einfluss auf die gesamte Methode hatte. Weiterhin fand sich bei keiner der untersuchten Substanzen ein Hinweis auf Instabilität während der Probenlagerung, -aufarbeitung und -messung, außer bei 4-Hydroxyatorvastatin, dessen Konzentration nach drei Monaten signifikant abnahm. Während der Reanalyse von Studienproben (incurred samples) lagen über 95 % der Proben innerhalb von ±15 % im Vergleich zur ersten Messung. Außerdem wurden die Methoden zur Bestimmung von Atorvastatin, Loratadin und Clopidogrel an zwei Generationen von Massenspektrometern verglichen, nämlich dem API 3000™ und dem API 5000™. Die neue Ionenquelle und die Verbesserungen im Ionenpfad beim API 5000™ ermöglichten - abhängig von der analysierten Substanz - höhere Sensitivität. Allerdings konnte das API 3000™ bei den durchgeführten Experimenten mit einer hohen Präzision aufwarten. Die validierten Methoden zeigten im Alltagbetrieb bei der Messung von acht klinischen Studien hervorragende Performance und Qualitätsdaten. Darüber hinaus sind die Methoden aufgrund ihrer kurzen Laufzeiten ideal für Messungen die einen hohen Probendurchsatz erfordern.

There has been an emergence of novel psychoactive substances (NPS) in forensic casework globally. Although the reported prevalence of these compounds has been relatively low in comparison to traditional drugs of abuse, published case studies suggest that some NPS have significant pharmacological effects that may cause severe impairment and/or death. Because of these effects, it is important that toxicology laboratories have the capability of identifying these compounds to complete a comprehensive toxicological analysis for human performance and post-mortem investigations. Recently, mass spectrometry has gained favor over traditional screening assays such as immunoassays for the identification of NPS in biological specimens. This trend is mainly a result of the fact that mass spectrometry provides the required sensitivity and selectivity for a broader range of analytes. High resolution tandem mass spectrometry has been suggested for analysis of NPS, as this technique further increases selectivity by increasing mass accuracy and providing MS/MS spectral data. The main goal of the present study was to investigate the applicability of using high resolution mass spectrometry to screen for and confirm a large number of novel psychoactive substances. The present study consisted of three main tasks, which included 1) the creation of a large high resolution MS/MS spectral library and database, 2) the development of a solid phase extraction (SPE) method and acquisition methods, and 3) a collision induced dissociation (CID) study of regioisomeric NPS compounds. The MS/MS spectral library created contains spectral data for 252 NPS. In addition, 875 NPS entities were included in the compound database. The library and database can be used by toxicology laboratories to aid in the identification of NPS in casework using MS/MS spectral data and full scan MS data, respectively. The analytical method developed used SPE and high resolution mass spectrometry (HRMS). The HRMS method demonstrated limits of detection ranging from 0.5- 5 ng/mL for NPS from various structural drug classes. The CID experiments demonstrated that relative ion abundance alone could be used to differentiate some sets of regioisomers. The present work can aid toxicology laboratories in the identification of NPS and demonstrates the applicability of HRMS for their screening and confirmation.

<p>Clopidogrel is an antiplatelet substance that prevents blood coagulation in the arteries. It is an inactive pro drug that becomes activated after first-pass metabolism by the liver. The active metabolite of clopidogrel is 2-oxoclopidogrel, which is unstable therefore pharmacokinetic data is obtained by measuring the inactive metabolite clopidogrel acid in plasma. Clopidogrel is taken orally in tablet form. The aim of this project was to develop a LC-MS/MS method for quantification of clopidogrel and its metabolite in plasma.</p><p> </p><p>The method has been developed by optimizing the sample preparation. Different extraction procedures and extraction columns were tested, for example, by changing the extraction column from a C8 silica sorbent to Oasis HLB (a polymer sorbent). Different internal standards were evaluated as a result of discovering the signal suppression of the previous internal standard clopidogrel acid.  Flupentixol was found to be the best candidate.</p>

La découverte, la caractérisation et le dosage de biomarqueurs ont permis douvrir de nouveaux horizons tant en thérapeutique que dans létablissement dune médecine personnalisée. Dans un contexte danalyse en milieu complexe, lapplication de techniques fiables, sensibles, exactes et de haute résolution est de rigueur. Dans ce but, le couplage de la spectrométrie de masse à une technique séparative telle que la chromatographie liquide (LC-MS) ou lélectrophorèse capillaire (CE-MS) offre des potentialités intéressantes. Une méthode de dosage de la cysdopa, un marqueur du mélanome, dans le plasma par LC-MS a été mise au point. Une étape préliminaire dextraction en phase solide sur un support hybride alliant des interactions de type hydrophobe, hydrophile et échangeurs de cations a conduit à lobtention dexcellents taux de récupération. Les conditions chromatographiques assurant la séparation de la cysdopa des composés endogènes susceptibles dinterférer et les paramètres de la détection par spectrométrie de masse en tandem ont été optimisés. La présence déventuels effets de la matrice a été investiguée en détails. Une étude de la stabilité de la cysdopa dans les différentes conditions opératoires a été réalisée répondant ainsi aux normes préscrites par la FDA. Ensuite, une validation complète de la méthode en milieu plasmatique selon lapproche faisant appel aux profils dexactitude sur une gamme de concentration allant de 1,6 à 200 ng/ml a été menée avec succès démontrant ladéquation de la méthode. Enfin, une étude pilote ainsi quune validation en cours détude ont permis de tester cette méthode de dosage. La seconde technique mise en oeuvre consiste en lapplication du couplage CE-MS à lanalyse de lhepcidine, un petit peptide régulant le métabolisme du fer. Les conditions électrophorétiques assurant la séparation de ce peptide des constituants dun mélange type ont été déterminées. Le traitement de la paroi interne du capillaire et laddition dune cyclodextrine nont pas permis dans la présente application daméliorer la sélectivité et lefficacité des pics. Lutilisation dun électrolyte de haute force ionique associé à laddition dun modificateur organique a par contre offert les meilleures performances. Une approche multivariée en deux temps (criblage puis modélisation) a été appliquée pour loptimisation des paramètres CE-MS. Les effets principaux du voltage du capillaire et de la pression du gaz nébulisant se sont révélés être significatifs tout comme leffet quadratique de ce dernier ainsi que les interactions entre la concentration en électrolyte et le voltage du capillaire dune part et la pression du gaz nébulisant dautre part. Finalement, la sensibilité en terme de rapport signal/bruit a été comparée en CE-UV et CE-MS établissant les potentialités du couplage CE-MS pour lanalyse de peptides. Discovery, caracterization and determination of biomarkers provide new perspectives in therapeutics and establishment of personnal medecine. Analysis in complex matrix requires reliable, sensitive, accurate and high resolution techniques. To achieve this, coupling of mass spectrometry with separative techniques such as liquid chromatography (LC-MS) or capillary electrophoresis (CE-MS) offer interesting potentialities. A method for the determination of cysdopa, a melanoma biomarker, in human plasma was developed using LC-MS. Solid phase extraction in mixed mode, combining hydrophobic, hydrophilic and cation exchange interactions led to excellent recovery. The chromatographic conditions ensuring separation of cysdopa from potential by interfering endogenous compounds and tandem mass spectrometry detection parameters were optimised. The presence of matrix effect was investigated in detail. A full stability study was then performed according to FDA requirements. Finally, a complete validation of the method in plasma following the approach of accuracy profiles over a concentration range from 1,6 to 200 ng/ml was successfully performed, demonstrating adequacy of the developed method. A pilot study and an in-study validation were finally perfomed to test this assay method. The second implemented technique consists in the application of CE-MS coupling to hepcidin analysis, a small peptide regulating iron metabolism. Electrophoretic conditions ensuring separation of hepcidin from model peptides have been determined. Resolution and/or efficiency were not improved by using coated capillaries or by adding a cyclodextrin. A high ionic strength electrolyte associated to the addition of an organic modifier provided the best performance. A multivariate approach (screening and modeling) was applied to the optimisation of CE-MS parameters. The principal effet of capillary voltage and nebulizing gas pressure were significant as well as the quadratic effet of the last parameter and the interactions of electrolyte concentration and, for one part, capillary voltage and, for another part, nebulizing gas pressure. Finally, sensitivity with respect to signal/noise ratio was compared between CE-UV and CE-MS, assessing potentialities of CE-MS for peptide analysis.

The main aim of this thesis is to implement a voltage-controlled oscillator for a Galileo/GPS receiver with a center frequency of 1.5 GHz in 150 nm CMOS process. As the designed VCO has to be integrated in a phase locked loop, VCO gain is selected high enough for the PLL to lock even with process variations. A new state of art architecture called double harmonic tuned VCO is selected and designed for this GPS application. It uses a complex combination of inductors and capacitors to reduce phase-noise of the VCO by suppressing second harmonic oscillations in the tail node of VCO. The designed VCO shows significant improvement in phase-noise performance compared to a normal LC tank VCO by reducing phase-noise around 4 dBc/Hz. The VCO has a phase-noise of -128 dBc/Hz at 1 MHz offset from center frequency with a power consumption of 5 mW and a tuning range of about 257 MHz for a 1 V tuning voltage range.

The main research of this thesis includes three sections. The purpose of first part is to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of 8 macrolide antibiotics and lincosamides inside fish tissue, including erythromycin (ERM), oleandomycin (OLD), kitasamycin (KIT), tylosin (TYL), josamycin (JOS), spiramycin (SPM), tilmicosin (TIL), and lincomycin (LIN). Homogenized samples are first extracted with acetonitrile, dehydrated with sodium sulphate anhydrous, and then condensed. After the residue was redissolved in methanol and the extracts were partitioned with n-hexane to remove lipids, the sample is filterced and detected by LC/MS-MS using chromatography columns of Agilent HC-C18 (5£gm, 150 mm ¡Ñ4.6 mm). The mobile phase A was 5mM ammonium acetate containing 0.1% formic acid, while the mobile phase B was acetonitrile. The analysis of 8 macrolide antibiotics and lincosamides can be achieved within 10 minutes with electrospray ionization-tandem mass spectrometry in positive mode using multiple reaction monitoring (MRM) for simultaneous detection. The second part is to verify the method by regulation of European Union (EU) resolution scheme (2002/657/EC). In the case where the drug is set as allowed drug, the recovery rate under gradient addition according to MRL is between 93.64% to 106.67%, and the CV is between 0.27% to 7.17%. In the case where the drug is set as prohibited drug, the recovery rate under gradient addition according to MRPL is between 96.35%~104.88%, and the CV is between 6.77%~13.91%. As a result, the decision limit (CC£\) and the Detection capability (CC£]) of the 8 macrolide antibiotics and lincosamides is between 0.24 to 0.40£gg kg-1 and 0.33 to 0.49£gg kg-1. The last section is to evaluate the stability of drugs in fish body under domestic preservation and process methods on fish, including refrigeration at -20¢J and cold storage at 4 ¢J. The test is implemented by adding the drug into fish tissue according to MRL and detecting the antibiotics residue after regulated 40 days. Besides, the effect on activity of drug residue in fish body after boiling at 100 ¢J is compared. The results show that the residual amount of spiramycin, josamycin, tilmicosin, and lincomycin is below 35% while that of erythromycin, oleandomycin, kitasamycin, and tylosin will be below 20%. Therefore, the drugs including erythromycin, josamycin, tylosin, and lincomycin will stay stably in fish tissue if they are stored under -20 ¢J. However, it may affect human health if the fish contains such antibiotic residues is not boiled.