Melanoma is the leading cause of skin cancer-related death. The STAT3 (signal transducer and activator of transcription 3) and TLR4 (toll-like receptor 4) signaling pathways have been shown to be activated in melanoma. Activation of each of the two pathways can promote melanoma growth, angiogenesis and metastasis. Suppressing TLR4 signaling or STAT3 signaling has been proposed as an approach for melanoma management although the TLR4/STAT3 pathway has not yet been established in melanoma. Atractylodis Macrocephalae Rhizoma (Baizhu in Chinese), a Qi-tonifying Chinese medicinal herb, is commonly prescribed by Chinese medicine doctors for treating melanoma. Our previous studies demonstrated that atractylenolide II (AT-II), isolated from Atractylodis Macrocephalae Rhizoma, could induce apoptosis, and inhibit proliferation and migration in B16 melanoma cells. However, the antimelanoma properties of AT-II and the underlying molecular mechanisms have not been fully understood. In this study, we further investigated the antimelanoma effects of AT-II in vivo and in vitro, and explored the TLR4/STAT3 signaling-related mechanism of action of AT-II. In conclusion, we established the TLR4/STAT3 pathway in melanoma, which provides novel insight into melanoma pathophysiology. We demonstrated that AT-II exerted antimelanoma effects in vivo and in vitro, and inhibition of TLR4/STAT3 signaling contributed to these effects. These findings advanced our understanding of the antimelanoma properties and the underlying mechanism of action of AT-II, and provided a chemical and pharmacological justification for the clinical application of Atractylodis Macrocephalae Rhizoma in melanoma management. This contribution is significant because it is one step in a continuum of research that is expected to lead to future clinical trials of AT-II as a novel antimelanoma agent. Results showed that AT-II induced apoptosis, and inhibited proliferation, migration and invasion in multiple melanoma cells, and significantly inhibited melanoma growth, angiogenesis and metastasis in mice. AT-II suppressed the activation of STAT3 and Src (a STAT3 upstream tyrosine kinase) in mouse melanoma tissues and inhibited the EGFR/Src/STAT3 signaling in cultured melanoma cells. The free binding energy of AT-II with EGFR (an upstream receptor tyrosine kinase of STAT3) was relatively low in molecular docking assays, suggesting that AT-II might inhibit EGFR activation via other molecules. We found that activation of TLR4 enhanced EGFR/Src/STAT3 signaling in melanoma cells, and activation of the TLR4/STAT3 pathway contributed to melanoma progression in vivo and in vitro. These observations suggested that the TLR4/STAT3 pathway was established in melanoma. Molecular docking showed that AT-II could bind to the TLR4/MD-2 receptor complex. AT-II reduced the binding of LPS (a TLR4 ligand) to TLR4, and inhibited LPS-triggered activation of EGFR/Src/STAT3 signaling as well as LPS or MPLAs (synthetic monophosphoryl lipid A, a TLR4 agonist) induced invasion in melanoma cells. Overexpression of a constitutively active variant of STAT3 (STAT3C) in A375 cells diminished anti-proliferative, apoptotic and anti-invasive effects of AT-II; and overexpression of an active form of TLR4 in A375 cells diminished AT-II-exerted anti-invasive effects in cultured cells, and attenuated the inhibitory effects of AT-II on tumor growth and angiogenesis in mice. These suggested that suppression of TLR4/STAT3 signaling contributed to the antimelanoma effects of AT-II.

M. Tech. / Phototobiomodulation (PBM), also known as low level laser therapy (LLLT) or photobiostimulation, is a non-invasive form of therapy that utilizes low intensity laser light or irradiation to provide healing. However, in order for healing to be successful certain laser parameters need to be taken into consideration i.e. fluence (dosage), wavelength and power density. Laser therapy has been used for various medical applications and fields. Multiple cytokines and growth factors are involved in wound healing including Interleukin (IL)-1, IL-6 and Tumour Necrosis Factor alpha (TNF- a). In diseased state(s) such as diabetes mellitus (DM) or psoriasis, these growth factors or cytokines are either found elevated or decreased depending on various factors and for abnormally prolonged periods. However, inflammatory cytokines are usually elevated. Phototherapy has been reported to accelerate wound healing, attenuate pain and cease inflammation. However, the effect of phototherapy on cytokine modulation has not been explored extensively, especially under various stress mechanisms. Furthermore, the pathway that laser irradiation induces on modulated pro-inflammatory cytokines has not been clearly elucidated as scientists typically report on the up- or down-regulated expression of cytokines. Numerous authors have reported on the efficacy of laser irradiation to enhance the rate of wound healing and proliferation in normal and diabetic cells or tissue; however, literature that has demonstrated the latter on hypoxic insulted cells is inadequate. In this study hypoxic insult was induced as it is one of the factors that usually prolong the healing process in diabetic wounds. Prior to commencing with the main study, a pilot study was done to exclude the effect of osmotic pressure on cells grown in media containing additional glucose, and thus simulating a diabetic model iv in vitro. Mannitol was used as a control since it is not absorbed by the cells. The study involved four groups namely: normal, normal wounded, mannitol wounded and diabetic wounded cells with each group having a non-irradiated control. Mannitol wounded and diabetic wounded cells had a final concentration of 30 mM mannitol and glucose respectively. A wavelength of 636 nm at a fluence of 5 J/cm2 was used on day 1; experiments were repeated four times and all tests were done in duplicate. Cellular responses (Trypan Blue, adenosine triphosphate (ATP) and lactate dehydrogenase (LDH)) and morphological changes were assessed after 1 h incubation post-irradiation in both irradiated and non-irradiated cultures.

M.Tech. (Homoeopathy) / Haemostasis is defined as the arrest of bleeding by formation of a haemostatic plug or clot. The herb Arnica montana interferes with this process thus resulting in increased bleeding. Homoeopathic physicians use Arnica montana in a potentised form for the treatment of post-operative swelling, pain and ecchymosis but little is known on what effect this potentised form of Arnica montana has on blood coagulation and bleeding time. This study forms part of a three part in vivo study to determine the effects of various homoeopathic potencies of Arnica montana on blood coagulation. This was done by measuring the Bleeding Time (BT), activated Partial Thromboplastin Time (aPTT) and the International Normalised Ratio (INR) of Prothrombin Time (PT). The aim of this particular study is to investigate the in vivo effect of Arnica montana 30C on blood coagulation and Bleeding Time. This study is a double blind, placebo controlled study that took place over a period of two weeks. A total sample group for the three part study consisted of eighty healthy participants between the ages of eighteen to thirty five. Consenting participants that met the criteria were randomised into four groups of twenty each. One group for each part of the three part study were the experimental group and one group was allocated to the placebo group that was shared by all three studies. BT was taken as well as blood samples which underwent coagulation tests (aPTT and INR). Twenty participants received Arnica montana 30C in 20% ethanol and twenty participants received an identical bottle containing 20% ethanol. After two weeks another blood sample was taken where all three coagulation test measurements were repeated. The results of the BT, INR and aPTT were analysed using Statkon Statistical Package for Social Sciences. This showed no statistical difference between the experimental or control group with regard to BT, INR and aPTT. The results indicate that Arnica montana 30C appears to have no effect on Bleeding Time..

No description available.

The purpose of this thesis is to understand the impact of brand experience and brand image on consumers’ perceptions of trust in the context of the UK financial services sector. Since the financial crisis in 2008, trust has been an issue for financial services brands with scandals surfacing continually such as the “Libor Scandal” in 2012 (BBC News, 2013); the manipulation of foreign exchange markets by proprietary traders in large banking institutions (Financial Times, 2014); a number of banks being fined a total of £2.7 bn (BBC News, 2013) and so on. In these kinds of scenarios of declining trust, it is of paramount importance that financial services brands not only focus on their brand identity but also consistently deliver a favourable brand experience and build a strong brand image to contribute in the restoration of trust in financial services. Therefore, this study makes a timely contribution by providing a nuanced understanding of how and to what extent brand experience and brand image impact consumers’ perception of trust in the context of financial services from an interdisciplinary perspective. The theoretical model incorporating brand experience, brand image and a number of important interdisciplinary trust constructs has been developed from the interdisciplinary literature on trust and brand (Mayer et al., 1995; Aaker, 1997; McKnight et al., 1998; McKnight and Chervany, 2001-2002; McKnight et al., 2002; Mayer et al., 2007; Ennew and Sekhon, 2007; Ennew et al., 2011; Brakus et al., 2009) through inductive top-down theorising (Shepherd and Sutcliffe, 2011). The model explains the relationship between a number of brand and trust constructs. It proposes that in the context of financial services sector, where the perceived risk is high, trusting belief positively impacts trusting intention (H1); the structural assurance dimension of institutional trust has a positive effect on trusting belief (H2) and on trusting intention (H3); the situational normality dimension of institutional trust has a positive effect on trusting belief (H4) and on trusting intention (H5); the faith in humanity dimension of dispositional trust has a positive effect on trusting belief (H6) and on structural assurance dimension of institutional trust (H7) – whereas the trusting stance dimension of dispositional trust has a positive impact on trusting intention (H8) and on structural assurance dimension of institutional trust (H9). The theoretical model also proposes that a positive brand experience has a positive impact on trusting belief (H10) and likewise a positive brand image has a positive impact on trusting belief (H11). As part of theory testing following an objectivism ontological and positivism epistemological position, a survey-based quantitative approach was employed to test the hypotheses. Under the auspices of a large MNC with offices in the major cities of UK and in many countries of the world, a sample was drawn from its UK based employees, which was reasonably representative of the UK population. As the respondents were asked to answer questions about their main bank, any male or female who lives in the UK and has a UK bank account would qualify as being suitable subjects for this research. A total of 420 paper based questionnaires were distributed to this sample through customer services operatives and managers. Of them 301 questionnaires returned, 300 were usable and one was incomplete, thus resulting in a response rate of 71.46%. The measurement scale for trusting belief was adopted from Ennew and Sekhon (2007) and Ennew et al. (2011) trust index; the measurement scales for brand experience and brand image were adapted from Brakus et al. (2009) brand experience scale and from Aaker (1997) brand personality scale respectively – both of them were further validated in the context of financial services sector. The measurement scales for trusting intention, institutional trust and dispositional trust were developed from interdisciplinary trust literature (Mayer et al., 1995; McKnight et al., 1998; McKnight and Chervany, 2001-2002; Ennew and Sekhon, 2007; Ennew et al., 2011) and further validated. To test the factor structure and to identify poorly-performing items and scale reliability, Exploratory Factor Analysis (EFA) was conducted followed by Confirmatory Factor Analysis (CFA) for checking uni-dimensionality and validity (Garbing and Hamilton, 1996; Cadogan et al., 2009) of the measurement scales using Lisrel 8.80. Finally, hypotheses were tested through Structural Equation Modelling (SEM). The findings validate the interdisciplinary brand-trust theories: out of eleven hypotheses tested, nine hypotheses were accepted and two hypotheses were partially accepted. The study sheds light on the role of institutional trust and dispositional trust on financial services consumers’ overall perception of trust through influencing their trusting belief and trusting intention; and underscores the importance of having a sound and strong financial structure to engender trust. Furthermore, it reveals that although consumers have noticed the efforts of financial services institutions and regulators in putting an overarching structure for financial systems in place, they are not fully convinced that the current situation is typical and normal. The study found strong links between consumers’ perception of a positive brand image and on their perception of trusting belief. In unveiling the relationship between brand experience and trusting belief, the study found that the affective dimension of brand experience has a significant influence in influencing consumers trusting belief, whereas the intellectual dimension of brand experience is not viewed favourably by the financial services consumers. This research contributes to convergent theories of trust and mutually inclusive theories of trust and brand through adopting an interdisciplinary approach. In particular, it contributes to theory application by operationalising an interdisciplinary brand-trust conceptual model. The findings bring valuable insights that contribute towards the integrated brand-trust literature and validate the interdisciplinary theory of trust that centres around the seminal work of Mayer et al. (1995), McKnight et al. (1998), McKnight and Chervany (2001-2002) and Tan and Sutherland (2004). The research shows the impact of brand experience, brand image, institutional trust, and dispositional trust on consumers’ overall perceptions of trust in the context of the financial services sector. In addition, the study makes a methodological contribution through developing measurement scales for trusting intention, institutional trust and dispositional trust, which are particularly suitable for the financial services sector; and also by validating brand experience and brand image scales for financial services. Due to the divergent interdisciplinary perspectives of trust, the literature on trust still remains divided especially in its conceptualisation of the constructs. Hence this study makes an attempt to bring harmony to an on-going debate around trust. It also incites a debate whether trust in the context of the financial services sector should be conceptualised and operationalised from a single disciplinary perspective or through employing an interdisciplinary approach; and whether the issues of trust and branding should be treated as integrated phenomena or not. The study is of relevance to managers and policy makers, for it will inform them of the importance of institutional trust, dispositional trust, brand image and brand experience on consumers’ overall perceptions of trust; and provide them with more sophisticated measures for brand experience and brand image for financial services, which in turn will create an opportunity for them to develop more effective branding strategy. The measures of trusting intention, institutional trust and dispositional trust that have been developed especially for the financial services sector as part of this study also offer significant implications for practice. In the light of this study, policy makers, commercial organisations and other interested stakeholders in the financial services sector can measure and track trust in a more comprehensive manner than previously. They will be able to monitor changes in perceptions of trust more accurately and in a more regular fashion, understanding the level of changes on each kind of trust and the reasons for these changes in the overall perceptions of trust. This will also help firms to develop a more effective strategy to restore or enhance consumers’ perceptions of trust as it provides policy makers and firms with guidance regarding where a particular focus on types of trust should be given.

There has been an upsurge in the use of Complementary and Alternate Medicines (CAMs) in both developed and developing countries. Although herbal medicines have been in use for many centuries, their quality, safety and efficacy are still of major concern. Many countries are in the process of integrating CAMs into conventional health care systems based on the knowledge and use of traditional medicines. The quality control (QC) of herbal products usually presents a formidable analytical challenge in view of the complexity of the constituents in plant material and the commercial non-availability of appropriate qualified reference standards. Sceletium, a genus belonging to the family Aizoaceae, has been reported to contain psychoactive alkaloids, specifically mesembrine, mesembrenone, mesembrenol and some other related alkaloids. Sceletium is marketed as dried plant powder and as phyto-pharmaceutical dosage forms. Sceletium products and plant material marketed through health shops and on the internet are associated with unjustified claims of specific therapeutic efficacy and may be of dubious quality. Validated analytical methods to estimate Sceletium alkaloids have not previously been reported in the scientific literature and the available methods have focused only on qualitative estimation. Furthermore, since appropriate markers were not commercially available for use as reference standards, a primary objective of this study was to isolate relevant compounds, qualify them as reference standards which could be applied to develop appropriate validated qualitative and quantitative analytical methods for fingerprinting and assay of Sceletium plant material and dosage forms. The alkaloidal markers mesembrine, mesembrenone and ∆⁷ mesembrenone were isolated by solvent extraction and chromatography from dried plant material. Mesembranol and epimesembranol were synthesised by hydrogenation of the isolated mesembrine using the catalyst platinum (IV) oxide and then further purified by semi-preparative column chromatography. All compounds were subjected to analysis by ¹H, ¹³C, 2-D nuclear magnetic resonance and liquid chromatography-tandem mass spectroscopy. Mesembrine was converted to hydrochloride crystals and mesembranol was isolated as crystals from the hydrogenation reaction mass. These compounds were analysed and characterised by X-ray crystallography. A relatively simple HPLC method for the separation and quantitative analysis of five relevant alkaloidal components in Sceletium was developed and validated. The method was applied to determine the alkaloids in plant material and dosage forms containing Sceletium. An LCMS method developed during the study provided accurate identification of the five relevant Sceletium alkaloids. The method was applied for the quantitative analysis and QC of Sceletium plant material and its dosage forms. This LCMS method was found to efficiently ionize the relevant alkaloidal markers in order to facilitate their detection, identification and quantification in Sceletium plant material as well as for the assay and QC of dosage forms containing Sceletium. The chemotaxonomy of some Sceletium species and commercially available Sceletium dosage forms were successfully studied by the LCMS method. The HPLC and LCMS methods were also used to monitor the bio-conversion of some of the alkaloids while processing the plant material as per traditional method of fermentation. Additionally a high resolution CZE method was developed for the separation of several Sceletium alkaloids in relatively short analysis times. This analytical method was used successfully to fingerprint the alkaloids and quantify mesembrine in Sceletium and its products. Sceletium species grown under varying conditions at different locations, when analyzed, showed major differences in their composition of alkaloids and an enormous difference was found to exist between the various species with respect to the presence and content of alkaloids. Sceletium and its products marketed through health shops and the internet may thus have problems with respect to the quality and related therapeutic efficacy. The QC of Sceletium presents a formidable challenge as Sceletium plants and products contain a complex mixture of compounds. The work presented herein contributes to a growing body of scientific knowledge to improve the QC standards of herbal medicines and also to provide vital information regarding the selection of plant species and information on the specific alkaloidal constituents to the cultivators of Sceletium and the manufacturers of its products.

Please read the abstract in the section 00front of this document / Dissertation (M Inst Agrar (Land Use Planning))--University of Pretoria, 2007. / Agricultural Economics, Extension and Rural Development / M Inst Agrar / unrestricted

Given the growing interest in the field of Corporate Social Responsibility Disclosure (CSRD), especially in developing countries, this thesis adopts neo-institutional theory to investigate the extent and types of CSRD practices and factors influencing its adoption in oil and gas companies operating in Libya. Two methods of data collection were used: namely, semi-structured interviews and annual reports. The semi-structured interviews were conducted first with 14 oil and gas firms’ managers working in Libya, to identify the factors influencing CSRD adoption, and second with 6 external actors to confirm or reject such claims. The second method involved a collection of 106 annual reports for the period 2009-2013, to first identify the extent and types of CSRD practices, and second to proceed with a regression test to assess the relationship between CSRD determinants and the extent of CSRD practices. The findings from the qualitative analysis show that managers perceive a diversity of coercive, mimetic and normative pressures interplay to influence CSRD in the Libyan context. Particularly, the adoption of CSRD is influenced by the state through its governance body - the National Oil Corporation (NOC), foreign business partners, other foreign-owned companies’ behaviour, the need to uphold firms’ reputation, and pressures to meet societal expectations. Other determinants identified include government ownership, parent company factors, board size, board meeting, firm size, age, presence of CSR committee, and profitability. Furthermore, the absence of clear legal requirements, a shortage of knowledge and awareness, the absence of civil society organisations, the absence of the Environmental General Authority’s (EGA) role, and a lack of motivation from the government were found to act as major impediments to CSRD development. The findings obtained from the quantitative analysis show that the level of CSRD is low when compared with Western countries, but in relative terms, the most disclosed types of CSR information were related to the human resources and environment. Moreover, the findings obtained from the CSRD regression model suggest that CSRD practice is positively associated with government ownership, joint venture ownership, foreign ownership, frequency of board meetings, parent company factor, and firm size. However, CSRD has no statistically significant relationship with board size, CSR committee, and age of the company, while profitability is negatively associated with CSRD practices. These results contribute towards the literature adding to the knowledge of CSRD practices’ “implementation”, by empirically providing evidence for the context of CSRD in Libya. This is achieved by explaining how specific external and internal determinants contribute to or impede the development of CSRD practices. These findings, therefore, could be useful to corporate regulators and policy makers in developing a more focussed agenda of CSRD activity, when considering regulations for disclosure.

The purpose of this study was to investigate whether there is regional variation in the abundance and habitat use of tiger sharks (Galeocerdo cuvier) within in a model seagrass ecosystem. Abundance was determined with catch rates on drumlines and habitat preferences were investigated using acoustic tracking of large tiger sharks (n=4). I found spatiotemporal variation in the probability of catching at least one shark and in catch rates on days sharks were caught. In general, sharks were present throughout more of the year and in higher abundances in the northern region. Habitat use also varied between regions. In the northern region, sharks moved randomly with respect to habitat, while in the southern region sharks preferred shallow habitats. Although preliminary, these results suggest that large predator abundance and habitat use may vary over relatively small spatial scales and that such variation may be useful for elucidating their ecological role.

Nurses who work with people who use drugs in the Downtown Eastside of Vancouver (DTES), British Columbia are on the forefront in advancing a harm reduction framework in very controversial, cutting-edge practice environments. The purpose of this study was to explore how these nurses, using the framework of harm reduction, make sense of their nursing practice. It is hoped that the results of this study may advance adopting a harm reduction framework in nursing practice, education and policy development and serve as the foundation for further nursing research. This study utilized a qualitative interpretive descriptive methodology to gather data from eight nurses who work with people who use drugs in harm reduction practice environments. The nurses were divided into two focus groups and data was collected through a semi-structured focus group interview. Following initial data analysis, each focus group was reconvened and a second semi-structured group interview was held to clarify and to further discuss the emerging themes. The data analysis proceeded simultaneously with the interviews utilizing a process of constant comparative analysis. I completed the thematic analysis as I moved between the transcripts and identified commonalties and variations within the emerging themes. Ultimately, I described one overarching theme, which encapsulated the range of experiences described by the nurses. The theme that I identified was: meeting people where they are at. The importance to the nurses of both the therapeutic nurse-client relationship and a commitment to praxis were apparent. In conclusion, the value the nurses placed on "meeting people where they are at" was integral in gaining an understanding of how they make sense of their nursing work. / Applied Science, Faculty of / Nursing, School of / Graduate