5-Fluorouracil (5FU) is a pyrimidine analogue, indicated for the therapy of proliferative skin diseases such as actinic keratosis (AK), superficial basal cell carcinoma and psoriasis. It has also been used for the treatment of solid tumours like colorectal, breast and liver carcinomas for nearly 40 years. Although 5FU has always been administered parenterally and orally, metabolism is rapid and absorption is erratic. Several severe side-effects are also commonly associated with 5FU therapy, including myelosuppression, hand-foot syndrome and gastrointestinal effects. Seeing that 5FU is an important part of the treatment of several malignant and pre-malignant disorders, it would be advantageous to find a delivery route and delivery system that negate absorption and metabolic variation and decrease side-effects. The transdermal route provides a promising alternative to the above-mentioned conventional delivery routes, solving most of the problems associated with parenteral and oral administration. That being said, the formidable barrier situated in the skin is not easily breached. The stratum corneum, the outermost skin layer, is mostly lipophilic in nature, preventing hydrophilic molecules such as 5FU from entering. 5FU-containing creams and lotions are currently commercially available, but absorption is still very limited. The transdermal absorption from these formulations has been compared to that obtained with the use of new transdermal delivery vehicles, with the newer formulations proving to be promising. It was decided to entrap 5FU in a novel therapeutic system, in the form of the Pheroid™ system, to increase its transdermal penetration. Pheroid™ vesicles are stable spherical structures in a unique, emulsion-like formulation, and fall in the submicron range. The main components of the Pheroid™ system are the ethyl esters of the essential fatty acids linoleic acid and linolenic acid, as well as the cys-form of oleic acid, and water. The formulation is saturated with nitrous oxide (N20). Although Pheroid™ vesicles may resemble other lipid-based vehicles, such as liposomes and micro-emulsions, they are unique in the sense that they have inherent therapeutic qualities as well. The Pheroid™ formulation can be specifically manipulated to yield different types of vesicles, ensuring a fast transport rate, high entrapment efficiency, rapid delivery and stability of the delivery system for a specific drug. In this study, 5FU was entrapped in the Pheroid™ formulation. Transdermal permeation studies were then performed to evaluate the influence of this delivery system on the transdermal flux of 5FU. Vertical Franz diffusion cells were utilised to determine the transdermal penetration of 5FU. Only Caucasian female abdominal skin was used to minimise physiological variables. Diffusion studies were done over 12 hour periods, with the entire receptor phase being withdrawn at predetermined intervals. Samples were analysed using high performance liquid chromatography (HPLC), after which the cumulative concentration of active was plotted against time. The linear portion of this graph represents the flux of 5FU through the skin. It was found that there were differences in the results between formulations containing 5FU in a phosphate buffer solution (PBS)-based Pheroid™ and water-based Pheroid™, though the difference was not statistically significant. The 0.5 % 5FU in water-based Pheroid™ resulted in a significantly bigger yield than the control (1 % 5FU in water) as well as a significant difference to the 1 % 5FU in PBS-based Pheroid™ formulation. In general the water-based Pheroid™ formulations had greater average cumulative concentrations, yields and fluxes than the other formulations. The fluxes obtained with the water-based Pheroid™ formulations also correlated well with a previous study done by Kilian (2004). Thus it can be concluded that the Pheroid™ therapeutic delivery system enhances the transdermal penetration of 5FU. Water-based Pheroid™ formulations proved to be more effective than PBS-based Pheroid™ formulations. It can also be concluded that a 0.5 % 5FU in water-based Pheroid™ formulation can be used instead of a 1 % formulation, because there were no statistically significant differences between the two formulations. This would be advantageous - patient compliance can be enhanced because of a more tolerable formulation with fewer side effects, while manufacturing cost is lowered by using a lower concentration of active. It is recommended that some aspects of the study be investigated further to optimise the transdermal delivery of 5FU using the Pheroid™ therapeutic system. These aspects include optimising the composition of the Pheroid formulation, investigating the entrapment process of 5FU within Pheroid™ spheres, the influence of PBS and water as basis of the Pheroid™ formulation and the amount of 5FU remaining in the epidermis after the 12 hour period of the diffusion study. Keywords: 5-Fluorouracil, Franz diffusion cell, Heat separated epidermis, Skin penetration, Transdermal, Drug delivery system, Pheroid™ / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.

The complexity and lack of coordination of the U.S. health care system is especially challenging for older adults, many of whom have multiple chronic conditions. The faith community is a potential partner to assist them, due to strong religiosity of older adults and specific characteristics of faith communities. This study explores the knowledge and practices of faith community nurses (FCNs) in meeting care coordination needs of older adults and identifies a model of gap-filling by FCN practice. An approach combining both quantitative and qualitative approaches was used. A survey was distributed to all known FCNs in Kentucky. From the 60 respondents, 15 FCNs were selected for personal interviews, and six care recipients were also interviewed. Survey data revealed a relatively older workforce, M=57 years, with 73% in nursing for more than 20 years. All served as FCNs in their own congregations, mostly as volunteers. FCNs relied on informal rather than formal assessments, with little consistency in type of health-related information obtained from congregants. The combined interview data revealed themes including, strong grounding in faith, sense of congregational family, reliance on general nursing assessment skills, intentional empowerment, bridging expanses, trust, and continuity. Findings suggest that FCNs in Kentucky identify and fill significant gaps in health care for older adults. Spirituality and religious rituals were important for FCNs and those they served. Congregants sought out FCNs to answer questions, interpret medical information, and assist with health care interactions. The stability of the FCNs in the lives of congregations was regarded as important; congregants counted on FCNs presence through transitions in health. A model to explain FCN intervention was developed based on integration of a social ecological perspective with the WHO International Classification of Functioning, Disability, and Health. This model reflects contextual factors that occur throughout nested environments that surround each individual, including immediate family, congregational family, health and social care systems, and societal policies. FCNs serve as a bridge between and among these nested environments, connecting them and facilitating change within each level.

5-Fluorouracil (5FU) is a pyrimidine analogue, indicated for the therapy of proliferative skin diseases such as actinic keratosis (AK), superficial basal cell carcinoma and psoriasis. It has also been used for the treatment of solid tumours like colorectal, breast and liver carcinomas for nearly 40 years. Although 5FU has always been administered parenterally and orally, metabolism is rapid and absorption is erratic. Several severe side-effects are also commonly associated with 5FU therapy, including myelosuppression, hand-foot syndrome and gastrointestinal effects. Seeing that 5FU is an important part of the treatment of several malignant and pre-malignant disorders, it would be advantageous to find a delivery route and delivery system that negate absorption and metabolic variation and decrease side-effects. The transdermal route provides a promising alternative to the above-mentioned conventional delivery routes, solving most of the problems associated with parenteral and oral administration. That being said, the formidable barrier situated in the skin is not easily breached. The stratum corneum, the outermost skin layer, is mostly lipophilic in nature, preventing hydrophilic molecules such as 5FU from entering. 5FU-containing creams and lotions are currently commercially available, but absorption is still very limited. The transdermal absorption from these formulations has been compared to that obtained with the use of new transdermal delivery vehicles, with the newer formulations proving to be promising. It was decided to entrap 5FU in a novel therapeutic system, in the form of the Pheroid™ system, to increase its transdermal penetration. Pheroid™ vesicles are stable spherical structures in a unique, emulsion-like formulation, and fall in the submicron range. The main components of the Pheroid™ system are the ethyl esters of the essential fatty acids linoleic acid and linolenic acid, as well as the cys-form of oleic acid, and water. The formulation is saturated with nitrous oxide (N20). Although Pheroid™ vesicles may resemble other lipid-based vehicles, such as liposomes and micro-emulsions, they are unique in the sense that they have inherent therapeutic qualities as well. The Pheroid™ formulation can be specifically manipulated to yield different types of vesicles, ensuring a fast transport rate, high entrapment efficiency, rapid delivery and stability of the delivery system for a specific drug. In this study, 5FU was entrapped in the Pheroid™ formulation. Transdermal permeation studies were then performed to evaluate the influence of this delivery system on the transdermal flux of 5FU. Vertical Franz diffusion cells were utilised to determine the transdermal penetration of 5FU. Only Caucasian female abdominal skin was used to minimise physiological variables. Diffusion studies were done over 12 hour periods, with the entire receptor phase being withdrawn at predetermined intervals. Samples were analysed using high performance liquid chromatography (HPLC), after which the cumulative concentration of active was plotted against time. The linear portion of this graph represents the flux of 5FU through the skin. It was found that there were differences in the results between formulations containing 5FU in a phosphate buffer solution (PBS)-based Pheroid™ and water-based Pheroid™, though the difference was not statistically significant. The 0.5 % 5FU in water-based Pheroid™ resulted in a significantly bigger yield than the control (1 % 5FU in water) as well as a significant difference to the 1 % 5FU in PBS-based Pheroid™ formulation. In general the water-based Pheroid™ formulations had greater average cumulative concentrations, yields and fluxes than the other formulations. The fluxes obtained with the water-based Pheroid™ formulations also correlated well with a previous study done by Kilian (2004). Thus it can be concluded that the Pheroid™ therapeutic delivery system enhances the transdermal penetration of 5FU. Water-based Pheroid™ formulations proved to be more effective than PBS-based Pheroid™ formulations. It can also be concluded that a 0.5 % 5FU in water-based Pheroid™ formulation can be used instead of a 1 % formulation, because there were no statistically significant differences between the two formulations. This would be advantageous - patient compliance can be enhanced because of a more tolerable formulation with fewer side effects, while manufacturing cost is lowered by using a lower concentration of active. It is recommended that some aspects of the study be investigated further to optimise the transdermal delivery of 5FU using the Pheroid™ therapeutic system. These aspects include optimising the composition of the Pheroid formulation, investigating the entrapment process of 5FU within Pheroid™ spheres, the influence of PBS and water as basis of the Pheroid™ formulation and the amount of 5FU remaining in the epidermis after the 12 hour period of the diffusion study. Keywords: 5-Fluorouracil, Franz diffusion cell, Heat separated epidermis, Skin penetration, Transdermal, Drug delivery system, Pheroid™ / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.

Triple fortification of salt with vitamin A, iron, and iodine has been investigated in the past to reduce micronutrient deficiencies in the developing world. The objective is to develop integrated nutrient delivery technology by microencapsulating a self-emulsifying drug delivery system (SEDDS) made of surfactants and a bioactive compound, retinyl palmitate. The SEDDS is used to enhance absorption of the vitamin A through food systems and to achieve targeted release of the active ingredient. Encapsulating vitamin A was difficult when using the spray dryer and the enteric coating, Aquacoat®. Losses of the micronutrient after a three month storage period ranged from 50-99% at both 25°C/20% RH and 45°C/60% RH. The result of a matrix encapsulation and poor coating formation contributed to the high losses. Further investigation of coating systems with the aim of stabilizing all three samples for a six month storage period such as using other encapsulating methods is recommended.

Triple fortification of salt with vitamin A, iron, and iodine has been investigated in the past to reduce micronutrient deficiencies in the developing world. The objective is to develop integrated nutrient delivery technology by microencapsulating a self-emulsifying drug delivery system (SEDDS) made of surfactants and a bioactive compound, retinyl palmitate. The SEDDS is used to enhance absorption of the vitamin A through food systems and to achieve targeted release of the active ingredient. Encapsulating vitamin A was difficult when using the spray dryer and the enteric coating, Aquacoat®. Losses of the micronutrient after a three month storage period ranged from 50-99% at both 25°C/20% RH and 45°C/60% RH. The result of a matrix encapsulation and poor coating formation contributed to the high losses. Further investigation of coating systems with the aim of stabilizing all three samples for a six month storage period such as using other encapsulating methods is recommended.

This thesis draws attention to understand how firms in the B2B commodity industry seek to utilize value-creating activities to achieve competitive advantage, which is also the overall purpose of this thesis. The premise of this thesis is of empirical nature, thus empirically applicable and experienced by other companies inside the commodity industry. In order to reach the purpose of this thesis a case study of Alpha International, Beta and Delta has been carried out which involved personal interviews with different respondents from the companies. The theoretical framework involves a description of competitive strategy, value creation, value chain, value proposition and finally value delivery. The empirical study is based on building a framework of how the companies create value by using different value creating activities.   In the analysis the theoretical framework is related to the results of the empirical study. It is here discussed how the different case companies value creating activities leads to a competitive advantage. In addition to analyzing the value creation activities; the value proposition of the case companies is analyzed and how these are delivered. It is concluded that the case companies studied seeks to utilize value-creating activities to achieve competitive advantage in many different ways.   Generally speaking, it is found that the case companies most commonly try to achieve similar types of value; delivery reliability and quality. However this is achieved in different ways; through different types of activities such as services, different types of integration strategies or a certain type of technology that surrounds the product offering that is utilized by different types of labor in the companies. The companies also have different ways in offering and communicating the value towards the customer by using a value proposition; depending on what type of benefit the customer seeks. At last, discussion and implications are given to present managerial and theoretical implications together with further research.

The performance of the century-old irrigation system of Pakistan (i.e. warabandi) has been evaluated using socio-economic data gathered by the author in multiple farmers?? surveys (n=278) conducted in Indus Basin of Pakistan. In the surveyed regions, the warabandi system was performing poorly. In-built rigidity in water allocations was found as main reason behind its poor performance. The results from the farmers?? surveys also revealed that the objective of increasing irrigation water productivity would never be attained under the warabandi arrangements. Hence, a completely new concept that could replace the warabandi system and improve the productivity of limited irrigation water should be introduced. My aim was to find a better way to allocate the scarce water resource between farmers. In this study, I have introduced a new concept for determining water allocations among the farmers, which is based on a multicriterion decision making (MCDM) approach. The consideration of multiple criteria in irrigation water allocations would improve irrigation water productivity. Upon an extensive survey of well-known MCDM methods, I concluded that all previously existing MCDM methods were using subjective inputs, usually from a single modeller, to establish priorities of alternatives and therefore, a predetermined solution could easily be obtained. I have developed an approach based on conjoint analysis which removes that subjectivity from the chosen MCDM method (i.e. ELECTRE). Interval scales and relative importance criteria weights, two usually subjective inputs in ELECTRE, are objectively estimated from the conjoint analysis study. For that purpose, the author designed a conjoint questionnaire and administered it to 62 farmer respondents in face-to-face interviews. Conjoint analysis, which does not appear to have been previously used in water resources or allocation studies, is a method for creating the interval scales and the relative criteria weights objectively from the respondents?? judgements on the importance of conjoint objects. The objective estimation of these two important factors is a completely new development which can assist in the unbiased determination of the best division or allocation of scarce water resources between farmers. The approach is applied, as a demonstration, to a region with nine distributary watercourses to determine which of the distributaries should have the highest priority for allocation of the regional water.

A ortopedia e a odontologia têm especial interesse às tecnologias biocompatíveis que apresentam a fase alfa do fosfato tricálcico (α-TCP), pois estas são capazes de formar hidroxiapatita deficiente em cálcio, similar à óssea. Porém, a baixa resistência mecânica limita sua aplicação. A fim de superar essa limitação, foi agregada acrilamida ao cimento α-TCP, com redutor de líquido, originando o cimento α-TCP de dupla pega. A partir disso foram desenvolvidos compostos à base de cimento de α-TCP e α-TCP de dupla pega agregados dos fármacos sulfato de gentamicina, cloridratos de lidocaína, bupivacaína e levobupivacaína e testada sua funcionalidade como sistemas de liberação de fármacos. Não existem dados bibliográficos sobre liberação de fármacos por sistemas de cimento α-TCP de dupla pega. A metodologia utilizada foi qualiquantitativa. Para as diferenças analíticas considerou-se o intervalo de confiança de 95% com nível de significância menor que 5% (p<0,05). O estudo compreendeu três fases. Na Fase 1 foram elaborados corpos de prova à base de cimento α-TCP e α-TCP de dupla pega com e sem (grupo-controle) adição de fármacos. Na Fase 2 os biomateriais estudados foram caracterizados por difração de raios X, espectroscopia de absorção no infravermelho com transformada de Fourier, microscopia eletrônica de varredura, resistência mecânica a compressão axial, densidade, porosidade e absorção de líquido; sendo também proposta a análise da porosidade por meio de imagens. A Fase 3 corresponde ao estudo da cinética da liberação dos fármacos in vitro, onde os corpos de prova foram imersos em solução tampão fosfato pH 7,0 e as amostras analisadas por meio de UV-vis. A liberação do antibiótico também foi avaliada por Espectroscopia de Impedância Eletroquímica (EIS), como proposta inovadora. Conforme os resultados, ambos os cimentos funcionaram como sistemas de liberação dos fármacos. Tanto o sistema hidrogel, quanto os fármacos não modificaram as propriedades estruturais do cimento. O sistema com hidrogel apresentou melhor resistência mecânica. A difusão Fickiana foi o principal mecanismo envolvido no processo de liberação dos fármacos, com menor influência do relaxamento das cadeias. A técnica de EIS mostrou-se promissora para avaliação de liberação de fármacos. / To better regulate it is necessary to know the new Technologies. Orthopedics and dentistry have demonstrated special interest in biocompatible technologies that present the alpha phase of tricalcium phosphate (α-TCP), whit can form calcium-deficient hydroxyapatite (like bone hydroxyapatite). However, its application is limited by the low mechanical resistance. To overcome this limitation, acrylic hydrogel containing liquid reducer was added to the α-TCP cement, resulting in the α-TCP double setting cement. From this, composites of α-TCP and α-TCP double setting cements aggregates of the drugs gentamicin sulfate, lidocaine, bupivacaine and levobupivacaine hydrochlorides were developed and the functionality drug delivery systems was tested. There isn't bibliographic data about drugs release systems by α-TCP double setting cement. Qualitative and quantitative methodologies were applied. For the analytical differences, we considered the 95% confidence interval with a level of significance lower than 5% (p <0.05). It comprised three different phases. In Phase 1, an α-TCP and α-TCP double setting cement specimens were prepared with and without (control group) drugs addition. In Phase 2, the studied biomaterials were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, compression mechanical resistance, density, porosity and liquid absorption, being also proposed of the porosity analysis by images. The Phase 3 corresponds to the study of the in vitro drug release kinetics. The specimens were immersed in phosphate buffer solution pH 7.0 and the samples analyzed by UV-vis. As an innovative proposal, drug release was also assessed using Electrochemical Impedance Spectroscopy (EIS). According to the results, both cements functioned as controlled drug delivery systems. The hydrogel improved the properties of cement moreover the drugs did not impair these properties. Fick diffusion was the main mechanism involved in the process of drug release by composites, with a minor influence of polymer chain relaxation. The EIS technique proved to be promising for the evaluation of drug release.

Made available in DSpace on 2014-06-11T19:31:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-11-27Bitstream added on 2014-06-13T19:20:14Z : No. of bitstreams: 1 peixoto_tp_dr_botfmvz.pdf: 7218430 bytes, checksum: 805d30dbbb4d65e7a3083c5277367671 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A proposta do presente trabalho foi a de comparar o tratamento convencional a base de colírio com o sistema de liberação controlada no tratamento de ceratites por Staphylococcus aureus por ciprofloxacina. Foram utilizados 20 coelhos, divididos em quatro grupos. Os grupos G1, G3 e G4 foram inoculados com 2,5μl da bactéria (108UFC) no estroma corneano. O grupo G2 não recebeu a aplicação do inóculo. O tratamento foi realizado com solução fisiológica para o grupo G1 (a cada seis horas por cinco dias), micropartículas de poli-lactatoco- glicolato (PLGA) contendo ciprofloxacina nos grupos G2 e G4, e colírio de ciprofloxacina no grupo G3 (a cada seis horas por cinco dias). Humor aquoso foi coletado no quinto dia de tratamento para análise por High-performance liquid chromatography (HPLC) da quantidade de ciprofloxacina na câmara anterior. As concentrações médias obtidas foram de 0,013μg/ml, 0,3μg/ml e 0,03μg/ml para os grupos G2, G3 e G4 respectivamente. Swab e biópsia da superfície ocular foram coletados para cultura no quinto dia de experimento. Apenas um animal do grupo G1 teve cultura positiva para S. aureus no material processado. Exame histopatológico revelou a presença bacteriana em todos os animais do grupo G1 e em dois animais do G3. Também foi constatado uma leve reação inflamatória no local da aplicação do sistema de liberação controlada. A análise dos dados mostrou que o tratamento com as micropartículas de PLGA foi eficaz no tratamento de ceratite bacteriana, eliminando completamente a presença de S. aureus e não sendo completamente biocompatível e biodegradável após cinco dias. / The proposal of this study was to compare the conventional treatment with eye drops with the controlled delivery system of PLGA, in the treatment of Staphylococcus aureus keratitis with ciprofloxacin. We used 20 rabbits, divided into four groups. The groups G1, G3 and G4 were inoculated with the bacterial 2.5μl (108UFC) in the corneal stroma. The G2 group did not receive the application of inoculum. The treatment was performed with basic saline solution in G1 (every six hours for five days), microparticles of poly-lactate co-glycolate (PLGA) containing ciprofloxacin in G2 and G4, and ciprofloxacin eye drops in group G3 (every six hours for five days). Aqueous humor was collected on the last day of treatment for analysis by High-performance liquid chromatography (HPLC) of the amount of ciprofloxacin in the anterior chamber. The average concentrations were obtained from 0013μg/ml, 0.3μg/ml and 0.03μg/ml for G2, G3 and G4 respectively. Swab and biopsy of the ocular surface were collected for culture on the fifth day of experiment. Only one animal in the G1 had positive culture for S. aureus in the processed material. Histological examination showed a bacterial presence in all animals of G1 and two animals of G3. It was also noted some light inflammatory reaction at the site of application of the controlled release. Data analysis showed that treatment with the microparticles of PLGA was effective in treating bacterial keratitis, completely eliminating the presence of S. aureus, not being completely biocompatible and biodegradable after five days.

abstract: The semiconductor manufacturing business model provides unique challenges for the design and construction of supporting fabrication facilities. To accommodate the latest semiconductor processes and technologies, manufacturing facilities are constantly re-tooled and upgraded. Common to this sector of construction is the retrofit project environment. This type of construction project introduces a multitude of existing conditions constraints and functions entirely differently than traditional new-build projects. This facility conversion process is further constrained by owner needs for continuous manufacturing operations and a compressed design/construction schedule to meet first-to-market milestones. To better control the variables within this project environment, Building Information Modeling (BIM) workflows are being explored and introduced into this project typology. The construction supply-chain has also increased their focus on offsite construction techniques to prefabricate components in a controlled environment. The goal is to overlap construction timelines and improve the productivity of workers to meet the increasingly demanding schedules and to reduce on-site congestion. Limited studies exist with regards to the manufacturing retrofit construction environment, particularly when focusing on the effectiveness of BIM and prefabrication workflows. This study fills the gap by studying labor time utilization rates for Building Information Modeling workflows for prefabrication of MEP (mechanical/electrical/plumbing) and process piping equipment in a retrofit construction environment. A semiconductor manufacturing facility serves as a case-study for this research in which the current state process for utilizing BIM for prefabrication is mapped and analyzed. Labor time utilization is studied through direct observation in relation to the current state modeling process. Qualitative analysis of workflows and quantitative analysis of labor time utilization rates provide workflow interventions which are implemented and compared against the current state modeling process. This research utilizes a mixed-method approach to explore the hypothesis that reliable/trusted geometry is the most important component for successful implementation of a BIM for prefabrication workflow in a retrofit environment. The end product of this research is the development of a prefaBIM framework for the introduction of a dynamic modeling process for retrofit prefabrication which forms the basis for a model-based delivery system for retrofit prefabrication. / Dissertation/Thesis / Doctoral Dissertation Construction 2016