No description available.

This study examined the client's perspective of the therapeutic alliance using written statements collected from clients in a previous study (Bedi & Duff, 2008). The 125 statements describe factors clients believe to be fundamental in the development of a strong alliance with their counsellor. Fifty participants sorted the statements into thematically similar piles and then gave each pile of statements a title. Multivariate concept mapping statistical methods (The Concept Systems, 2008, Version 4) were used to obtain the most representative sort across participants. The resulting 14 categories and associated ratings for helpfulness (on the scale of 1-5) are represented on scaled Concept Maps. Category titles selected arc: Emotional Support, Ability to Relate, Sharing the Counsellor's Personal Experience, Good Boundaries, Interpersonal Demeanour, Body Language, Provided Resources and Homework, Availability, Planning and Approach, Directed Process Appropriately, Attentiveness, Approachable, Non-Judgemental, and Effective Listening. Female and male helpfulness evaluations were not statistically significantly different. / Graduate / 0621

No description available.

Aptamers are single-stranded oligonucleotides, DNA or RNA, which can bind to a myriad of targets such as ions, peptides, proteins, drugs, organic and inorganic molecules with high affinity and specificity. Aptamers are derived using combinatorial libraries comprised of a variable region flanked by two primer regions used for a process termed Systematic Evolution of Ligands by Exponential Enrichment (SELEX). The central theme of my thesis was to use this technology to develop aptamers able to bind to validated therapeutic targets, specifically the Tumour Necrosis Factor alpha (TNFα) and Carcinoembryonic Antigen (CEA), and block their biological functions. As well, I investigated the use of CEA and MUC1 binding aptamers as targeting agents to guide and detect the delivery of contrast agent-loaded liposomes in tumour-bearing mice using computed tomography (CT) imaging. Aptamer selections successfully identified a 25-base aptamer (VR11) that can bind with high affinity and specificity to TNFα. VR11 blocked TNFα signaling, prevented apoptosis, reduced nitric oxide (NO) production in cultured cells and was non-immunogenic when injected into C57BL/6 mice. As well, aptamers were derived to the IgV-like N-domain of CEA. Two DNA aptamers were isolated containing a 40-base variable region, N54 and N56, bearing anti- CEA homotypic adhesive properties. These aptamers are not cytotoxic or immunogenic and III are able to prevent CEA-mediated homotypic and heterotypic cell adhesion events. In addition, the pretreatment of murine cancer cells expressing CEA with these aptamers prior to their intraperitoneal injection into C57BL/6 mice resulted in the prevention of tumour foci formation. Finally, the in vivo targeting of nanoparticles such as pegylated liposomes to tumour cells was enhanced by introducing tumour marker-specific DNA aptamers on their surface. The CEA-specific aptamer N54 and a 40-base second generation aptamer MUC1-VR1 that recognizes the tumour-associated mucin MUC1 were incorporated into liposomes containing the CT contrast agent Omnipaque350™ and Cy5 to characterize their binding to CEA and MUC1-expressing cancer cells in vitro. Pharmacokinetic studies also revealed that the incorporation of these aptamers into pegylated liposomes significantly lenghthened their circulation half-lives to values that parrallel that of untargeted pegylated liposomes.

Aptamers are single-stranded oligonucleotides, DNA or RNA, which can bind to a myriad of targets such as ions, peptides, proteins, drugs, organic and inorganic molecules with high affinity and specificity. Aptamers are derived using combinatorial libraries comprised of a variable region flanked by two primer regions used for a process termed Systematic Evolution of Ligands by Exponential Enrichment (SELEX). The central theme of my thesis was to use this technology to develop aptamers able to bind to validated therapeutic targets, specifically the Tumour Necrosis Factor alpha (TNFα) and Carcinoembryonic Antigen (CEA), and block their biological functions. As well, I investigated the use of CEA and MUC1 binding aptamers as targeting agents to guide and detect the delivery of contrast agent-loaded liposomes in tumour-bearing mice using computed tomography (CT) imaging. Aptamer selections successfully identified a 25-base aptamer (VR11) that can bind with high affinity and specificity to TNFα. VR11 blocked TNFα signaling, prevented apoptosis, reduced nitric oxide (NO) production in cultured cells and was non-immunogenic when injected into C57BL/6 mice. As well, aptamers were derived to the IgV-like N-domain of CEA. Two DNA aptamers were isolated containing a 40-base variable region, N54 and N56, bearing anti- CEA homotypic adhesive properties. These aptamers are not cytotoxic or immunogenic and III are able to prevent CEA-mediated homotypic and heterotypic cell adhesion events. In addition, the pretreatment of murine cancer cells expressing CEA with these aptamers prior to their intraperitoneal injection into C57BL/6 mice resulted in the prevention of tumour foci formation. Finally, the in vivo targeting of nanoparticles such as pegylated liposomes to tumour cells was enhanced by introducing tumour marker-specific DNA aptamers on their surface. The CEA-specific aptamer N54 and a 40-base second generation aptamer MUC1-VR1 that recognizes the tumour-associated mucin MUC1 were incorporated into liposomes containing the CT contrast agent Omnipaque350™ and Cy5 to characterize their binding to CEA and MUC1-expressing cancer cells in vitro. Pharmacokinetic studies also revealed that the incorporation of these aptamers into pegylated liposomes significantly lenghthened their circulation half-lives to values that parrallel that of untargeted pegylated liposomes.

The primary aim of this work was to provide an alternative method of synthesis of the non-steroidal anti-inflammatory drug copper indomethacin (Cu-Indo) and to produce alternative forms of the drug to increase its marketability. Dense gases as anti-solvents were used to achieve these aims. The study involved the synthesis, purification, micronisation and co-precipitation of Cu-Indo with polyvinylpyrrolidone (PVP) using dense carbon dioxide as an anti-solvent. Initially the volumetric and solubility behaviours of the solvent???anti-solvent systems were investigated to determine the optimum processing conditions. The solubility of Cu-Indo in an expanded solution was found to be a complex function of the solvent and other solutes. Copper indomethacin was successfully synthesised and purified in a single vessel using dense carbon dioxide as an anti-solvent. Drug yields of 98 % and purities near 100 % were achieved at optimum conditions with the advantages of less residual solvent in the drug, less solvent waste, reduced processing time and increased yields over the conventional synthesis process. Copper indomethacin was produced in a variety of morphologies and particle sizes using dense carbon dioxide as an anti-solvent. An investigation of the effect of process parameters on the particle characteristics showed that solute concentration was the dominant variable. Spherical particles with diameters less than 8 mm were obtained at optimum conditions. The immediate benefit of micronising Cu-Indo was demonstrated with an eight fold increase in dissolution rate when compared to the conventionally produced drug. Polyvinylpyrrolidone was successfully co-precipitated with Cu-Indo using dense carbon dioxide as an anti-solvent. The PVP???Cu-Indo co-precipitates were found to increase the solubility of the drug in ethanol with a 36 fold solubility enhancement at optimum conditions. The use of dense carbon dioxide as anti-solvent in this work demonstrates the potential of the GAS and ASES processes in the pharmaceutical industry. Copper indomethacin was synthesised, purified and micronised in a single vessel at a substantial saving in terms of time and solvent usage. The micronisation of Cu-Indo and the formation of the PVP???Cu-Indo co-precipitate provided alternative forms of the drug substantially increasing its marketability.

Thesis (M.S.)--Auburn University, 2007. / Abstract. Vita. Includes survey instruments. Includes bibliographic references (ℓ. 60-68)

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 8 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.