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The main aim of the thesis was to measure antidepressant (AD) non-compliance, to determine which factors are closely associated with AD non-compliance and the consequences of prolonged AD non-compliance in the private health sector of South Africa. The empirical study followed an observational, prospective, cohort study using longitudinal medicine claims data provided by a nationally representative Pharmaceutical Benefit Management company (PBM) from 1 January 2006 to 31 December 2011. Failure to respond to AD treatment and achieving remission has severe neurobiological and clinical consequences. The clinical consequences include increased social and functional impairment, higher risk for recurrence and relapse of a depressive episode, a weak treatment outcome, significant increase in treatment cost, over-utilization of health care systems, and ultimately an increased suicide risk. However, the neurobiological consequences are much more far reaching. One of the more serious yet under-recognized neurobiological complications of AD non-compliance is the development of antidepressant discontinuation syndrome (ADS), which is the result of non-compliance or the abrupt discontinuation of AD treatment. Altered serotonergic dysfunction appears central to ADS so that how an antidepressant targets serotonin will determine its relative risk for inducing ADS and thereby affect later treatment outcome. Low ADS risk with agomelatine versus other antidepressants can be ascribed to its unique pharmacokinetic characteristics as well as its distinctive actions on serotonin, including melatonergic, monoaminergic and glutamatergic-nitrergic systems. After the first four months only 34% (n=12 397) of patients were compliant. What’s more a statistically significant association was found between active ingredient consumed and compliance (p < 0.0001). Only 26.2% of patients who received amitriptyline-containing products were complaint compared to 38.8% and 38.7% in the cases of venlafaxine and duloxetine, respectively. The current study found that females have a significantly higher prevalence of MDD and HIV/AIDS when compared to males. The co-morbidity between HIV/AIDS and major depressive disorder (MDD) had a significant effect on AD treatment compliance as patients diagnosed with both HIV/AIDS and MDD (74.43. ± 32.03, 95%Cl: 71.51-77.34) displayed a lower compliance vs. MDD patients (80.94% ± 29.44, 95%Cl: 80.56-81.33). Noteworthy, observations were that 75% (p < 0.0217; Cramer’s V = 0.0388) of venlafaxine and 28.6% (p < 0.0197; Cramer’s V = -0.0705) of the paroxetine items were compliant in patients diagnosed with both HIV/AIDS and MDD. The overall compliance (35.19% acceptable compliance; n = 42 869) of patients taking both ADs and GDs was weak. In the group receiving both AD and GDs, an increased AD treatment period was associated with a significant increase (p < 0.0001) in AD compliance (406.60 days; 95%Cl: 403.20 – 409.90 vs. 252.70 days; 95%Cl: 250.20 – 255.20). In this cohort amitriptyline (29.57%), mirtazapine (31.36%) and fluoxetine (32.29%) were associated with the lowest levels of compliance, while duloxetine (40.67%) was found to have the highest compliance. Lastly, ADs with highest non-compliance were associated with an increase use in GDs. Alprazolam (n = 10 201) and zolpidem (n = 9 312) were the most frequently dispensed GDs in combination with AD treatment. In conclusion the current study confirms that AD non-compliance is as big an obstacle in developing countries as it is in developed countries. Antidepressant treatment non-compliance has far reaching consequences especially with the development of ADS which further complicates MDD and might be a precursor for the development of TRD. Several factors were found to be closely associated with AD treatment non-compliance which include; pharmacological class of AD, gender, chronic co-morbid illnesses and a short treatment period. / PhD (Pharmacy Practice), North-West University, Potchefstroom Campus, 2015

The main aim of the thesis was to measure antidepressant (AD) non-compliance, to determine which factors are closely associated with AD non-compliance and the consequences of prolonged AD non-compliance in the private health sector of South Africa. The empirical study followed an observational, prospective, cohort study using longitudinal medicine claims data provided by a nationally representative Pharmaceutical Benefit Management company (PBM) from 1 January 2006 to 31 December 2011. Failure to respond to AD treatment and achieving remission has severe neurobiological and clinical consequences. The clinical consequences include increased social and functional impairment, higher risk for recurrence and relapse of a depressive episode, a weak treatment outcome, significant increase in treatment cost, over-utilization of health care systems, and ultimately an increased suicide risk. However, the neurobiological consequences are much more far reaching. One of the more serious yet under-recognized neurobiological complications of AD non-compliance is the development of antidepressant discontinuation syndrome (ADS), which is the result of non-compliance or the abrupt discontinuation of AD treatment. Altered serotonergic dysfunction appears central to ADS so that how an antidepressant targets serotonin will determine its relative risk for inducing ADS and thereby affect later treatment outcome. Low ADS risk with agomelatine versus other antidepressants can be ascribed to its unique pharmacokinetic characteristics as well as its distinctive actions on serotonin, including melatonergic, monoaminergic and glutamatergic-nitrergic systems. After the first four months only 34% (n=12 397) of patients were compliant. What’s more a statistically significant association was found between active ingredient consumed and compliance (p < 0.0001). Only 26.2% of patients who received amitriptyline-containing products were complaint compared to 38.8% and 38.7% in the cases of venlafaxine and duloxetine, respectively. The current study found that females have a significantly higher prevalence of MDD and HIV/AIDS when compared to males. The co-morbidity between HIV/AIDS and major depressive disorder (MDD) had a significant effect on AD treatment compliance as patients diagnosed with both HIV/AIDS and MDD (74.43. ± 32.03, 95%Cl: 71.51-77.34) displayed a lower compliance vs. MDD patients (80.94% ± 29.44, 95%Cl: 80.56-81.33). Noteworthy, observations were that 75% (p < 0.0217; Cramer’s V = 0.0388) of venlafaxine and 28.6% (p < 0.0197; Cramer’s V = -0.0705) of the paroxetine items were compliant in patients diagnosed with both HIV/AIDS and MDD. The overall compliance (35.19% acceptable compliance; n = 42 869) of patients taking both ADs and GDs was weak. In the group receiving both AD and GDs, an increased AD treatment period was associated with a significant increase (p < 0.0001) in AD compliance (406.60 days; 95%Cl: 403.20 – 409.90 vs. 252.70 days; 95%Cl: 250.20 – 255.20). In this cohort amitriptyline (29.57%), mirtazapine (31.36%) and fluoxetine (32.29%) were associated with the lowest levels of compliance, while duloxetine (40.67%) was found to have the highest compliance. Lastly, ADs with highest non-compliance were associated with an increase use in GDs. Alprazolam (n = 10 201) and zolpidem (n = 9 312) were the most frequently dispensed GDs in combination with AD treatment. In conclusion the current study confirms that AD non-compliance is as big an obstacle in developing countries as it is in developed countries. Antidepressant treatment non-compliance has far reaching consequences especially with the development of ADS which further complicates MDD and might be a precursor for the development of TRD. Several factors were found to be closely associated with AD treatment non-compliance which include; pharmacological class of AD, gender, chronic co-morbid illnesses and a short treatment period. / PhD (Pharmacy Practice), North-West University, Potchefstroom Campus, 2015

New ventures are rather often founded by more than one person. Still, we do not know much about how these venture teams are formed, develop and finally dissolve. The manner in which the venture team roles develop when there is more than one owner is also a neglected area in the entrepreneurship research. It is argued in this thesis that the most prolific way of studying the venture team process and the venture team roles process is in relation to the innovation process. The over-all aim of this thesis is to explore what kinds of theoretical, conceptual, empirical and methodological insights are achieved by studying innovation processes in new ventures in a transformative institutional context, from the team-level of analysis. The empirical materials are a pilot-case (Tetra Pak) and an in-depth extended case-study from the publishing sector in Poland (Proszynski i S-ka, from 1985 to 2003). The method used in the thesis is a retrospective process approach with a phasic analysis of the polyphonical narratives of the experiences of key persons as well as data from archives. In the final analysis, a number of propositions are presented that relate to how the venture team process and the venture team roles process develop over extended time periods and in relation to the innovation process. The conclusions are that the team as a level of analysis helps us to theoretically understand and explain phenomena such as periods of divergence in the innovation process; the process of social commitments in the venture team; and how a venture team develops over time to a balanced and experienced expert leadership team. Methodologically, it is claimed that the polyphonical data collection gives more comprehensive, valid and reliable measurements of the innovation process. Finally, this thesis contributes with a story of the transformation of the Polish society and economy described in an unusual way via employing the team as a level of analysis.

This thesis described the development of new strategies for the preparation of micro- and nano-structured polymer materials. In particular, this thesis focused on: i) the synthesis of polymer particles in microreactors, and ii) the self-assembly of inorganic nanorods. First, this thesis presented the synthesis of polymer particles and capsules with pre-determined sizes and narrow size distributions (CV<2%) in continuous microfluidic reactors. The method includes (i) the emulsification of monomers in a microfluidic flow-focusing device and (ii) in-situ solidification of droplets via photopolymerization. This microfluidic synthesis provides a novel strategy for the control over the shapes, compositions, and morphologies of polymer particles. In particular, we demonstrated the control over particle shapes by producing polymer ellipsoids, disks, rods, hemispheres, plates, and bowls. We produced polymer particles loaded with dyes, liquid crystals, quantum dots, and magnetic nanoparticles. We generated core-shell particles, microcapsules, Janus and three-phasic polymer particles. Control over the number of cores per droplet was achieved by manipulating the flow rates of liquids in the microchannels. We further investigated the hydrodynamic mechanism underlying the emulsification of droplets, which helps in guiding scientists and engineers to utilize this technique. Second, we described the self-assembly of inorganic nanorods by using a striking analogy between amphiphilic ABA triblock copolymers and the hydrophilic nanorods tethered with hydrophobic polystyrene chains at both ends. We organized metal nanorods in structures with various geometries such as nanorings, nanochains, bundles, bundled nanochains, and nanospheres by tuning solely the quality of solvents. The self-assembly was tunable and reversible. This approach paved the way for the organization of anisotropic nanoparticles by using the strategies that are well-established for the self-assembly of block copolymers. We further described a systematic study of the self-assembly of polymer-tethered gold nanorods as a function of solvent composition in the system and the molecular weight of the polystyrene blocks. We found that the structure of the polymer pom-poms played an important role on the organization of polymer-tethered gold NRs. The 'supramolecular' assembly was governed by the competition between the end-to-end and side-by-side association of NRs and resulted in the controlled variation of the plasmonic properties of NRs, reflected in a 3-D plasmonic graph.

This thesis described the development of new strategies for the preparation of micro- and nano-structured polymer materials. In particular, this thesis focused on: i) the synthesis of polymer particles in microreactors, and ii) the self-assembly of inorganic nanorods. First, this thesis presented the synthesis of polymer particles and capsules with pre-determined sizes and narrow size distributions (CV<2%) in continuous microfluidic reactors. The method includes (i) the emulsification of monomers in a microfluidic flow-focusing device and (ii) in-situ solidification of droplets via photopolymerization. This microfluidic synthesis provides a novel strategy for the control over the shapes, compositions, and morphologies of polymer particles. In particular, we demonstrated the control over particle shapes by producing polymer ellipsoids, disks, rods, hemispheres, plates, and bowls. We produced polymer particles loaded with dyes, liquid crystals, quantum dots, and magnetic nanoparticles. We generated core-shell particles, microcapsules, Janus and three-phasic polymer particles. Control over the number of cores per droplet was achieved by manipulating the flow rates of liquids in the microchannels. We further investigated the hydrodynamic mechanism underlying the emulsification of droplets, which helps in guiding scientists and engineers to utilize this technique. Second, we described the self-assembly of inorganic nanorods by using a striking analogy between amphiphilic ABA triblock copolymers and the hydrophilic nanorods tethered with hydrophobic polystyrene chains at both ends. We organized metal nanorods in structures with various geometries such as nanorings, nanochains, bundles, bundled nanochains, and nanospheres by tuning solely the quality of solvents. The self-assembly was tunable and reversible. This approach paved the way for the organization of anisotropic nanoparticles by using the strategies that are well-established for the self-assembly of block copolymers. We further described a systematic study of the self-assembly of polymer-tethered gold nanorods as a function of solvent composition in the system and the molecular weight of the polystyrene blocks. We found that the structure of the polymer pom-poms played an important role on the organization of polymer-tethered gold NRs. The 'supramolecular' assembly was governed by the competition between the end-to-end and side-by-side association of NRs and resulted in the controlled variation of the plasmonic properties of NRs, reflected in a 3-D plasmonic graph.

Virtual reality (VR) has become an important tool in the study of human balance. It has also been used as a training tool for seated balance and assistive mobility devices. The objective was to design a system that can be used to investigate the effect of VR on trunk muscles during perturbed sitting and perform a preliminary study with two subjects. A spherical system was designed that rotated 26º in the pitch and roll plane at three speeds. The corresponding muscle activity was recorded using EMG in the presence and absence of VR during perturbed sitting. The design was capable of performing the required motions. The results showed a maximum of 31.8% and a minimum of 3.66% muscle activity, relative to maximum voluntary contraction. Our findings suggested that our developed system was successfully able to detect a noticeable effect of VR under perturbed sitting on the subjects’ EMG responses.

Title: Influence of the compensation program for athletes in the Greco-Roman wrestling. Objectives: This diploma thesis concerned with an evaluation of the postural and phasic muscles on the group of ten Greco-Roman wrestling fighters at the age from 16 to 17. Methods: For the assessment of the muscular inequality we used input and output measurements and based on the findings we have chosen the intervention program according to recommended literature. We applied the intervention program to the training units for four months. At the end of the diploma thesis we evaluated the significance of our program using output measurements according to the captured photographs, which we evaluated: fulfilled = 1, failed = 2. We used the Wilcox test to calculate the statistical significance. Results: The worst results were found in the area of postural muscles of m.erector truncata and phasic muscles of m.rhomboideus. The best results were achieved in the area of postural muscles of m.sternocleidomastoideus in a forward bend and in the area of the biceps femoris. The best results of the phasic muscles were achieved in the area of m.rhomboideus. At the end of this thesis it is statistically confirmed that applied intervention program eventually results in the significant difference between the initial and final...

A leading theory for why we sleep focuses on memory consolidation - the process of stabilizing and strengthening newly acquired memories into long-term storage. Consolidation of memory for cognitive strategies and problem-solving skills is enhanced as compared to a period of daytime wakefulness. Importantly, sleep preferentially enhances memory for the cognitive strategy per se, over-and-above the motor skills that are used to execute the strategy. Although it has been known for some time that sleep benefits this type of memory, it is not known how this process unfolds during sleep, or how sleep transforms this memory trace in the brain. Sleep is classified into rapid eye movement (REM) sleep and non-REM (NREM) sleep. The role of REM sleep for consolidation of memory for problem-solving skills remains controversial. In addition, little attention has been paid to the possible distinct roles of phasic REM sleep (i.e., when bursts of eye movements occur) and tonic REM sleep (i.e., the presence of isolated eye movements and the absence of eye movement bursts). REM sleep might favour procedural memory consolidation for cognitive strategies and problem-solving skills, and the specific role of REM sleep in this process might be discernible only by differentiating between phasic and tonic REM states. In addition, fMRI studies have revealed that sleep-related consolidation of the memory trace for simple motor procedural skills is associated with strengthened activity of, and functional connectivity between, key memory-related brain areas (i.e., hippocampal, striatal, and neocortex). However, fMRI techniques have not yet been employed to investigate sleep-related consolidation of procedural memory for cognitive strategies and problem-solving skills. Participants (n=60) performed a procedural memory task involving a cognitive strategy while undergoing functional magnetic resonance imaging (fMRI) before and after a condition of Sleep, Nap, or Wake. Those in the Sleep and Nap condition underwent polysomnography (PSG) to further study the learning-related changes in sleep macrostructure and microstructure. This thesis not only shows that a period of sleep or a nap afford a greater benefit to memory consolidation of a procedural strategy than a period of wake, but more specifically: In Study 1, during sleep, phasic REM sleep theta power was directly associated with overnight improvement on the task, whereas tonic REM sleep sensorimotor rhythm power was greater following a night of learning compared to a non-learning control night. In Study 2, we show that distinct hippocampal, striatal, and cortical areas associated with strategy learning are preferentially enhanced. Study 3 reveals that the functional communication among these brain areas is greater following sleep compared to a daytime nap or day of wakefulness. Sleep-related changes in brain activation and functional connectivity were both correlated with improved performance from before to after a period of sleep. Overall, findings from this thesis support the benefit of sleep at the behavioural and systems level for consolidating procedural memory involving cognitive strategies used to solve problems. The findings suggest that the multifaceted nature of REM sleep must be examined separately by its phasic and tonic states, to identify the active role of REM sleep for consolidating memory. Further, the consolidation of the memory trace is reflected through activation of, and communication between hippocampal, striatal, and neocortical brain areas. In summary, this thesis shows that sleep actively consolidates memory for cognitive strategies and problem-solving skills.

A fundamental question in the neurobiological study of drug addiction concerns the mechanisms mediating the motivational effects of chronic drug withdrawal. According to one theory, drugs of abuse activate opposing motivational processes after both acute and chronic drug use. The negative experience of withdrawal is the opponent process of chronic drug use that drives relapse to drug-seeking and -taking, making the identification of the neurobiological substrates mediating withdrawal an issue of central importance in addiction research. In this thesis, I identify the involvement of the neurotransmitters dopamine (DA) and corticotropin-releasing factor (CRF) in the opponent motivational a- and b-processes occurring after acute and chronic nicotine administration. I report that acute nicotine stimulates an initial aversive a-process followed by a rewarding opponent b-process, and chronic nicotine stimulates a rewarding a-process followed by an aversive opponent b-process (withdrawal). These responses can be modeled using a place conditioning paradigm. I demonstrate that the acute nicotine a-process is mediated by phasic dopaminergic activity and the DA receptor subtype-1 (D1R) but not by tonic dopaminergic activity and the DA receptor subtype-2 (D2R) or CRF activity, and the opponent b-process is neither DA- nor CRF-mediated. I also demonstrate that the chronic nicotine a-process is DA- but not CRF-mediated, and that withdrawal from chronic nicotine (the b-process) decreases tonic but not phasic DA activity in the ventral tegmental area (VTA), an effect that is D2R- but not D1R-mediated. I show that a specific pattern of signaling at D1Rs and D2Rs mediates the motivational responses to acute nicotine and chronic nicotine withdrawal, respectively, by demonstrating that both increasing or decreasing signaling at these receptors prevents the expression of the conditioned motivational response. Furthermore, I report that the induction of nicotine dependence increases CRF mRNA in VTA DA neurons, and that blocking either the upregulation of CRF mRNA or the activation of VTA CRF receptors prevents the anxiogenic and aversive motivational responses to withdrawal from chronic nicotine. The results described in this thesis provide novel evidence of a VTA DA/CRF system, and demonstrate that both CRF and a specific pattern of tonic DA activity in the VTA are necessary for the aversive motivational experience of nicotine withdrawal.