If a correlation exists between cost and project delivery system then this is crucial knowledge for any group organizing a new construction project. It has been observed anecdotally that the construction cost per student of public elementary schools has been observed to continue to increase in the state of Texas, even with the recent downturn in the economy. The recent economic depression in the USA has seen construction material costs stagnate and construction costs dropping. This is a direct result of the competitive nature of a market that has a lack of business. The issue of a rising cost at the time of a falling market is of more than a passing research interest to school superintendents and the people of Texas. This study investigated the relationship between cost and project delivery systems. A survey was sent to all school superintendents in Texas requesting recent data on elementary school enrollment, project delivery type and construction costs. One hundred and thirty six responses were received from one thousand and seventy six Texas school districts. A comparative means test was used to determine if a relationship exists between construction cost per student and project delivery system for public elementary schools in Texas. The research shows that Texas school districts are primarily using two types of project delivery systems for their new school construction, Construction Management at Risk and Competitive Sealed Proposals. After comparing the average construction cost per student for these two project delivery systems, the statistical analysis showed that Competitive Sealed Proposals cost approximately four thousand dollar less per student than Construction Management at Risk. The clear question is then as to why are districts using Construction Management at Risk when the comparative benefits of the contract type are not worth this amount of money per student.

The process for the incorporation, integration or collaboration of traditional healers into the National Health Care Delivery System of South Africa was marred by an array of mixed attitudes from all the parties concerned, namely traditional healers, patients, biomedical personnel, and the policy makers. The variety of approaches for inclusion of the traditional healers into the National Health Care System of South Africa was a further indication of the complexity of the situation. The possibility of functioning together between traditional healers and biomedical personnel existed before 1990 when the two groups met in Johannesburg in 1986 to discuss ways by which functioning together can be established. A series of meetings and discussions followed after which came the promulgation of the Chiropractors Homeopaths and Allied Health Services Professionals Act of 1996, which gives traditional healers their due recognition but does not include them as part of health care providers. The process of functioning together is a recommendation made by the World Health Organization and the most used terms for this functioning together is, incorporation, integration and collaboration. The process of incorporation can be realised by ensuring that both biomedical personnel and traditional healers remain autonomous, not controlling each other, respecting the existence of one another, as well as each other's own methods of healing. Integration was another method whereby the two health care systems can function together, even though integration differs in context from incorporation. Integration means that the traditional healers will have to function within the health care system under the directions of the biomedical personnel, whereby the patient receives a combination of both treatment methods depending on the problem or diagnosis. The third modality of getting the two health care systems to function together could be by collaboration. Collaboration was seen as a two sided effort whereby the healing methods of one are brought to fore and the most effective one is chosen to cure the patient's identified problem at that time. For the process of functioning together to be meaningful, it was necessary to get the government to review licensing the traditional healer's practices, so as to identify the healing techniques that are of value and use these to treat the patients. It was not really possible to clearly separate the three approaches because they all addressed the issue of having the two health care systems function together to increase health care services and fulfil the patients' health needs. For the purpose of this research the word incorporation was used. In South Africa the traditional healer is identified as the health care choice of 80-9036 of the black population. If this large number of black people uses traditional healing, then it becomes necessary to investigate the manner in which the traditional healer can be utilized effectively in the National Health Care Delivery System of South Africa to render the services that the patient needs for his/her health needs. It is for this reason that the researcher aimed at investigating the existing models of incorporation of traditional healers, the perceptions and attitudes of the traditional healers, biomedical personnel, patients and the policy makers regarding incorporation, their views on how this incorporation should be achieved, as well as how the incorporation of traditional healers into the National Health Care Delivery System of South Africa could be realised. A qualitative research design and theory generating approach was followed, and the research was conducted in two stages. In stage one qualitative research, participants were traditional healers, biomedical personnel, patients and policy makers, selected by means of non-probable purposive voluntary sampling. Data was collected by means of conducting semi-structured interviews with all the participants in the three identified provinces of South Africa. Field notes were recorded after each interview session. Data analysis was achieved by open coding. A co-coder and the researcher analysed the data independently after which consensus discussions took place to finalise the analysed data. Ethical principles were applied according to the guidelines of the Democratic Nurses Organisation of South Africa and the Department of Health. The second stage which was a theory generation approach, was used to formulate a model for the incorporation of the traditional healers into the National Health Care Delivery System of South African. / Thesis (Ph.D. (Nursing))--North-West University, Potchefstroom Campus, 2006

For a drug to have a therapeutic effect, it has to reach its site of action in sufficient quantities. The Pheroid drug delivery system enhances the absorption of drugs in various pharmacological categories and is the focus of this study. A number of patents are registered in various countries to protect its application. Pheroid technology is trademarked, but may for ease of reading, be called Pheroid(s) only. The Pheroid itself is composed of an organic carbon backbone composed of unsaturated fatty acids with some side-chain interactions that result in self-emulsifying characteristics. The resulting vesicles and nano-sponges can entrap hydrophilic, hydrophobic or amphiphilic compounds for biomedical and agricultural application and can be manipulated as to loading ability, mechanical resistance, permeability, size and solubility. Pheroid was investigated for its potential use in the areas of vaccines, peptide drugs, topical products and cosmeceuticals, antimicrobial treatments and agriculture. In all of these areas, the Pheroid has indeed shown applicability: the results showed improved uptake and/or efficacy of the entrapped chemical or biological compounds after administration by a number of administration routes. For oral administration, a precursor format, the pro-Pheroid, was used, wherein the vesicles and/or sponges are formed post-administration. Proof of concept studies on the in vivo absorption and bioavailability, as well as studies on in vitro efficacy of Pheroid-based formulations were carried out for antimicrobials, such as tuberculosis drugs, antimalarials and antiretrovirals. In all cases, the in vitro efficacy of the active compounds was increased, compared to well-known standard drug treatments. In a phase I bio-equivalence study, a Pheroid-containing combination formulation was compared against the comparative market leader. The results demonstrated that the bioavailability of the active compounds in the Pheroid was at least as good but mostly significantly better than that of the comparative medication. In addition, the incidence of side-effects was decreased in the case of the Pheroid formulations. Furthermore, in vitro results indicate that drug resistance can at least partially be negated. Pheroid technology may also be capable of protecting labile drugs such as peptides against degradation and increasing efficacy so that lower dosages can be administered less frequently and with fewer side effects. Based on in vitro and in vivo results, a number of products are currently in development. The application of Pheroid technology is potentially limitless and includes such areas as TB, malaria, cancer, AIDS, gene delivery, vaccines, patented medicines and generics and agriculture. / Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

The process for the incorporation, integration or collaboration of traditional healers into the National Health Care Delivery System of South Africa was marred by an array of mixed attitudes from all the parties concerned, namely traditional healers, patients, biomedical personnel, and the policy makers. The variety of approaches for inclusion of the traditional healers into the National Health Care System of South Africa was a further indication of the complexity of the situation. The possibility of functioning together between traditional healers and biomedical personnel existed before 1990 when the two groups met in Johannesburg in 1986 to discuss ways by which functioning together can be established. A series of meetings and discussions followed after which came the promulgation of the Chiropractors Homeopaths and Allied Health Services Professionals Act of 1996, which gives traditional healers their due recognition but does not include them as part of health care providers. The process of functioning together is a recommendation made by the World Health Organization and the most used terms for this functioning together is, incorporation, integration and collaboration. The process of incorporation can be realised by ensuring that both biomedical personnel and traditional healers remain autonomous, not controlling each other, respecting the existence of one another, as well as each other's own methods of healing. Integration was another method whereby the two health care systems can function together, even though integration differs in context from incorporation. Integration means that the traditional healers will have to function within the health care system under the directions of the biomedical personnel, whereby the patient receives a combination of both treatment methods depending on the problem or diagnosis. The third modality of getting the two health care systems to function together could be by collaboration. Collaboration was seen as a two sided effort whereby the healing methods of one are brought to fore and the most effective one is chosen to cure the patient's identified problem at that time. For the process of functioning together to be meaningful, it was necessary to get the government to review licensing the traditional healer's practices, so as to identify the healing techniques that are of value and use these to treat the patients. It was not really possible to clearly separate the three approaches because they all addressed the issue of having the two health care systems function together to increase health care services and fulfil the patients' health needs. For the purpose of this research the word incorporation was used. In South Africa the traditional healer is identified as the health care choice of 80-9036 of the black population. If this large number of black people uses traditional healing, then it becomes necessary to investigate the manner in which the traditional healer can be utilized effectively in the National Health Care Delivery System of South Africa to render the services that the patient needs for his/her health needs. It is for this reason that the researcher aimed at investigating the existing models of incorporation of traditional healers, the perceptions and attitudes of the traditional healers, biomedical personnel, patients and the policy makers regarding incorporation, their views on how this incorporation should be achieved, as well as how the incorporation of traditional healers into the National Health Care Delivery System of South Africa could be realised. A qualitative research design and theory generating approach was followed, and the research was conducted in two stages. In stage one qualitative research, participants were traditional healers, biomedical personnel, patients and policy makers, selected by means of non-probable purposive voluntary sampling. Data was collected by means of conducting semi-structured interviews with all the participants in the three identified provinces of South Africa. Field notes were recorded after each interview session. Data analysis was achieved by open coding. A co-coder and the researcher analysed the data independently after which consensus discussions took place to finalise the analysed data. Ethical principles were applied according to the guidelines of the Democratic Nurses Organisation of South Africa and the Department of Health. The second stage which was a theory generation approach, was used to formulate a model for the incorporation of the traditional healers into the National Health Care Delivery System of South African. / Thesis (Ph.D. (Nursing))--North-West University, Potchefstroom Campus, 2006

For a drug to have a therapeutic effect, it has to reach its site of action in sufficient quantities. The Pheroid drug delivery system enhances the absorption of drugs in various pharmacological categories and is the focus of this study. A number of patents are registered in various countries to protect its application. Pheroid technology is trademarked, but may for ease of reading, be called Pheroid(s) only. The Pheroid itself is composed of an organic carbon backbone composed of unsaturated fatty acids with some side-chain interactions that result in self-emulsifying characteristics. The resulting vesicles and nano-sponges can entrap hydrophilic, hydrophobic or amphiphilic compounds for biomedical and agricultural application and can be manipulated as to loading ability, mechanical resistance, permeability, size and solubility. Pheroid was investigated for its potential use in the areas of vaccines, peptide drugs, topical products and cosmeceuticals, antimicrobial treatments and agriculture. In all of these areas, the Pheroid has indeed shown applicability: the results showed improved uptake and/or efficacy of the entrapped chemical or biological compounds after administration by a number of administration routes. For oral administration, a precursor format, the pro-Pheroid, was used, wherein the vesicles and/or sponges are formed post-administration. Proof of concept studies on the in vivo absorption and bioavailability, as well as studies on in vitro efficacy of Pheroid-based formulations were carried out for antimicrobials, such as tuberculosis drugs, antimalarials and antiretrovirals. In all cases, the in vitro efficacy of the active compounds was increased, compared to well-known standard drug treatments. In a phase I bio-equivalence study, a Pheroid-containing combination formulation was compared against the comparative market leader. The results demonstrated that the bioavailability of the active compounds in the Pheroid was at least as good but mostly significantly better than that of the comparative medication. In addition, the incidence of side-effects was decreased in the case of the Pheroid formulations. Furthermore, in vitro results indicate that drug resistance can at least partially be negated. Pheroid technology may also be capable of protecting labile drugs such as peptides against degradation and increasing efficacy so that lower dosages can be administered less frequently and with fewer side effects. Based on in vitro and in vivo results, a number of products are currently in development. The application of Pheroid technology is potentially limitless and includes such areas as TB, malaria, cancer, AIDS, gene delivery, vaccines, patented medicines and generics and agriculture. / Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

In this study, pharmaceutical-grade and food-grade linker-based lecithin self-emulsifying delivery systems (SEDS) were developed with a combination of lipophilic and hydrophilic linkers. These additives at suggested concentrations are safe for pharmaceutical and food applications. The ratio of surfactant lecithin and linkers in these systems was optimized to develop surfactant in oil preconcentrates. The preconcentrates containing different surfactant concentrations and oil were diluted with fed state simulated intestinal fluid to produce pseudo-ternary phase diagrams and to identify the formulations that produced self-emulsifying or self-microemulsifying delivery systems. Optimal SEDS preconcentrates were evaluated using a dialyzer model to simulate intestinal uptake. An uptake of 39.6 mg/cm2 for the pharmaceutical-grade SEDS was obtained within 72 minutes, which promises substantial improvement in the bioavailability of hydrophobic actives. The optimal uptake of 12.2 mg/cm2 for food-grade SEDS suggests enhancement in the bioavailability of omega-3 fatty acids.

Naturally occurring food antimicrobials such as plant essential oils are receiving tremendous interest as intervention systems to enhance microbiological safety and quality. Poor water solubility of essential oils makes it difficult to incorporate them in foods, impacting visual appearance, antimicrobial effectiveness, and possibly organoleptic properties. Engineered nanoscale delivery systems can principally solve these challenges, but those based on low-cost food ingredients and inexpensive and scalable processes are currently scarce. This dissertation presents a simple and scalable two-step technology to prepare nano-delivery systems. The first encapsulation step, based on emulsion-evaporation, involves preparing emulsions composed of an oil phase with thymol or eugenol, major compounds in extracts from thyme and clove respectively, in hexane and an aqueous phase with conjugates of whey protein isolate and maltodextrin, followed by evaporation of hexane by spray drying. The second step is to hydrate spray dried capsules to enable the formation of nanoscale particles. The encapsulation performance and dispersion characteristics were affected by amounts and types of conjugates (ratio of protein: maltodextrin and maltodextrin chain length), volume fraction and composition of the oil phase. The optimal conditions corresponded to 55.8 % encapsulation efficiency and 12.6 % loading for thymol and 47.9 % encapsulation efficiency and 7.9 % loading for eugenol. Dispersions prepared from the identified capsules contained particles smaller than 100 nm and were transparent at pH 3.0-7.0 and 0-50 mM before and after heating at 80°C for 15 min. Nano-dispersions and free oil were tested for antimicrobial activity against Escherichia coli O157:H7, Listeria monocytogenes, Staphylococcus aureus, and Salmonella typhimurium. Nano-dispersed and free antimicrobials had similar effectiveness at various pH and temperatures in tryptic soy broth and apple cider, while in 2 % reduced fat milk, nano-dispersed antimicrobials were consistently more effective than unencapsulated ones. Therefore, the commercially viable nanoscale technology presented in this study enables the delivery of lipophilic antimicrobials for enhanced microbial safety and quality, without compromising visual appearance of foods, especially clear beverages.

The present work addresses poor bone/implant integration and severe bone defects. In both conditions external stimuli is required for new bone to form. A multilayered functional implant coating, comprised of an inner layer of crystalline titanium dioxide (TiO2) and an outer layer of hydroxyapatite (HAP), loaded with bone morphogenetic protein-2 (BMP-2), was proposed as a tool for providing both improved initial bone formation and long-term osseointegration. The in vitro characterization of the implant coatings showed that TiO2 and HAP were more favorable for cell viability, cell morphology and initial cell differentiation, compared to native titanium oxide. Furthermore, significantly higher cell differentiation was observed on surfaces with BMP-2, indicating that a simple soaking process can be used for incorporating bioactive molecules. Moreover, the results suggest that there could be a direct interaction between BMP-2 and HAP, which prolongs the retention of the growth factor, improving its therapeutic effect. For treating severe bone defects a strategy involving BMP-2 delivery from hyaluronan hydrogels was explored. The hydrogels were prepared from two reactive polymers – an aldehyde-modified hyaluronan and a hydrazide-modified poly(vinyl alcohol). Upon mixing, the two components formed a chemically crosslinked hydrogel. In this work the mixing of the hydrogel components was optimized by rheological measurements. Furthermore, an appropriate buffer was selected for in vitro experiments by studying the swelling of hydrogels in PBS and in cell culture medium. A detection method, based on radioactive labeling of BMP-2 with 125I was used to monitor growth factor release both in vitro and in vivo. The results showed a biphasic release profile of BMP-2, where approximately 16 %  and 3 % of the growth factor remained inside the hydrogel after 4 weeks in vitro and in vivo, respectively. The initial fast release phase corresponded to the early ectopic bone formation observed 8 d after injection of the hydrogel formulation in the thigh muscle of rats. The hydrogel formulation could be improved by incorporation of HAP powder into the hydrogel formulation. Furthermore, bone formation could be increased by pre-incubation of the premixed hydrogel components inside the syringe prior to injection. Crushed hydrogels were also observed to induce more bone formation compared to solid hydrogels, when implanted subcutaneously in rats. This was thought to be due to increased surface area of the hydrogel, which allowed for improved cell infiltration.

There has been much interest in the use of therapeutics based on ribonucleic acid interference(RNAi) to inhibit synthesis of mutant proteins ever since Elbashir et al. (Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K. and Tuschl, T., 2001. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 411, 494-498.) found that synthetic double stranded small interfering ribonucleic acids (siRNAs) can initiate this evolutionarily conserved process in mammalian cells. Since RNAi is able to target single genes and therefore mitigate the underlying molecular pathology of diseases, RNAi-based therapeutics will most likely benefit monogenic neurodegenerative diseases such as Huntington’s disease. It is however particularly difficult to deliver exogenous materials such as siRNAs into neurons in vivo as the blood-brain barrier (BBB) isolates the brain from the vascular system and prevents permeation of most materials. Neurons also do not take up exogenous materials readily. Therefore, effective delivery of siRNAs into the brain remains one of the biggest challenges impeding their use as a potential neurotherapeutic. Layered double hydroxide (LDH) nanoparticles are a class of anionic clay materials that have demonstrated great potential as a DNA (deoxyribonucleic acid) delivery system for a variety of mammalian cell lines due to their unique physiochemical properties. This thesis examined the feasibility of LDH as a siRNA delivery system for cultured neurons and demonstrated that the delivered siRNAs are able to effectively down-regulate synthesis of a target protein with minimal toxicity. Experiments were conducted using double stranded DNAs (dsDNAs) initially, and siRNAs were then used to verify these results. It was shown that nucleic acids(dsDNAs and siRNAs) could successfully intercalate into pristine LDHs to form nucleic acid-LDH complexes that had properties suitable for use as a delivery system in mammalian cells. These studies established that LDHs and nucleic acid-LDH complexes were biocompatible with neurons isolated from embryonic day 17.5 mouse cerebral cortex, suggesting that LDH can be used for nucleic acid delivery into cultured neurons. LDHs were also shown to successfully deliver nucleic acids into a non-neural mammalian cell line (NIH 3T3 cells). Finally, this thesis demonstrated for the first time that LDHs were able to deliver siRNAs into neurons, providing encouraging preliminary evidence that sequence specific gene silencing of the Mus Musculus Deleted in Colorectal Cancer (DCC) gene had occurred. However, down-regulation of the DCC protein did not occur consistently, suggesting that further optimisation is needed to improve the efficacy of siRNA-LDH complexes to inhibit expression of target protein in neurons. In future, LDHs should be further developed as an efficient siRNA delivery system for therapeutic gene silencing in the central nervous system using a neurodegenerative disease model such as the Huntington’s disease mouse model, which closely phenocopies the human disease. This model will allow the in vivo efficacy of these nanoparticles to be tested and subsequently improved in order to deliver siRNAs locally and systematically into the brain.

There has been much interest in the use of therapeutics based on ribonucleic acid interference(RNAi) to inhibit synthesis of mutant proteins ever since Elbashir et al. (Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K. and Tuschl, T., 2001. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 411, 494-498.) found that synthetic double stranded small interfering ribonucleic acids (siRNAs) can initiate this evolutionarily conserved process in mammalian cells. Since RNAi is able to target single genes and therefore mitigate the underlying molecular pathology of diseases, RNAi-based therapeutics will most likely benefit monogenic neurodegenerative diseases such as Huntington’s disease. It is however particularly difficult to deliver exogenous materials such as siRNAs into neurons in vivo as the blood-brain barrier (BBB) isolates the brain from the vascular system and prevents permeation of most materials. Neurons also do not take up exogenous materials readily. Therefore, effective delivery of siRNAs into the brain remains one of the biggest challenges impeding their use as a potential neurotherapeutic. Layered double hydroxide (LDH) nanoparticles are a class of anionic clay materials that have demonstrated great potential as a DNA (deoxyribonucleic acid) delivery system for a variety of mammalian cell lines due to their unique physiochemical properties. This thesis examined the feasibility of LDH as a siRNA delivery system for cultured neurons and demonstrated that the delivered siRNAs are able to effectively down-regulate synthesis of a target protein with minimal toxicity. Experiments were conducted using double stranded DNAs (dsDNAs) initially, and siRNAs were then used to verify these results. It was shown that nucleic acids(dsDNAs and siRNAs) could successfully intercalate into pristine LDHs to form nucleic acid-LDH complexes that had properties suitable for use as a delivery system in mammalian cells. These studies established that LDHs and nucleic acid-LDH complexes were biocompatible with neurons isolated from embryonic day 17.5 mouse cerebral cortex, suggesting that LDH can be used for nucleic acid delivery into cultured neurons. LDHs were also shown to successfully deliver nucleic acids into a non-neural mammalian cell line (NIH 3T3 cells). Finally, this thesis demonstrated for the first time that LDHs were able to deliver siRNAs into neurons, providing encouraging preliminary evidence that sequence specific gene silencing of the Mus Musculus Deleted in Colorectal Cancer (DCC) gene had occurred. However, down-regulation of the DCC protein did not occur consistently, suggesting that further optimisation is needed to improve the efficacy of siRNA-LDH complexes to inhibit expression of target protein in neurons. In future, LDHs should be further developed as an efficient siRNA delivery system for therapeutic gene silencing in the central nervous system using a neurodegenerative disease model such as the Huntington’s disease mouse model, which closely phenocopies the human disease. This model will allow the in vivo efficacy of these nanoparticles to be tested and subsequently improved in order to deliver siRNAs locally and systematically into the brain.