Expression and function of osteopontin variants in HCV-related liver disease and hepatocellular carcinoma.

Osteopontin (OPN) is a highly secreted multi-functional sialoprotein that is widely expressed in tissues, blood and urine. It is involved in a number of normal physiological functions, but is also significantly elevated in a number of cancers. While OPN is significantly expressed in hepatocellular carcinoma (HCC) little is known as to its role and if it is expressed in the pre-cancerous hepatitis C virus (HCV) infected liver. In this thesis we show that OPN is expressed in the liver and in HCC as three variants, the full-length protein OPN-A and two splice variants OPN-B and OPN-C. Through production of stable Huh-7 cells expressing the OPN variants, we show for the first time that all variants increase proliferation of a range of cultured hepatoma cell lines in a paracrine manner through interactions with the cell surface OPN receptor CD44. Similarly, OPN-A (and to a lesser extent OPN-B and –C) accelerated Huh-7 derived tumor growth in a nude mouse model. We also show for the first time expression of all three OPN variants in the non-diseased liver as it was previously thought that splicing was a feature specific for tumor cells. Clinically, OPN is known to be highly expressed in HCC, however, its expression in chronic hepatitis C is not well documented. In this thesis we show that OPN mRNA expression is elevated in the HCV-infected liver with a trend towards increased expression as liver disease progresses. Consistent with an increase in mRNA, serum OPN levels were also increased in the HCV-infected liver although we could find no correlation with degree of liver disease. However, our sample size was small and this section of the thesis needs repeating with a larger HCV-infected patient cohort. Furthermore, we show that elevated OPN expression is not specific to the HCV-infected liver as OPN is also elevated in the HBV-infected and alcoholic liver suggesting that HCV does not drive OPN expression but is more likely as a result of the inflammatory process in the viral infected liver. Interestingly we also show that there is a shift of OPN expression from bile duct epithelial cells in the non-diseased liver to the hepatocyte in the HCV-infected liver which raises the question as to the role of OPN in hepatocyte transformation to facilitate the development of HCC. Our evaluation of serum OPN expression also suggests that OPN has potential as both a diagnostic and potentially prognostic biomarker for not only HCC (arising from HBV and HCV infections and alcohol abuse) but also the earlier stages of HCV-related liver disease. This work for the first time characterises the expression of all OPN variants in the liver including HCC and may be useful for identifying targeted OPN-based therapeutic approaches for HCC and other cancers. Furthermore it also suggests that monitoring OPN in chronic hepatitis C may be useful in monitoring liver disease progression and early detection of HCC.Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 201

Factors To Consider Before Choosing A Single Gender Classroom In An Elementary School Setting

The research question addressed in this project was, what factors should parents consider before choosing a single gender classroom for their child? The author researched biological differences of boys and girls as found by Dr. Leonard Sax as well as perceptions and realities of boys and girls who have been exposed to single gender classrooms as seen in work by Rosemary Salomone and Michael Gurian. Qualitative and Quantitative research was conducted and the author discovered that students and teachers unanimously disagree with single gender classrooms for a variety of reasons

Development of crop wild relative conservation strategies for Norway

Climate change and anthropogenic activities threaten our global food security. One area of research that may help combat a future food crisis is the utilization of the genetic diversity available in wild plants. Crop wild relatives (CWR) are one such resource. They are the wild taxa most closely related to crops and from which diverse traits could be transferred to the crop. This project uses Norway as an example, to contribute towards methodologies to identify those CWR populations that are most important for conservation and use. This involves the creation of a priority list of CWR for Norway, $in$ $situ$ and $ex$ $situ$ diversity analysis of CWR populations, gap analysis and ecogeographic land characterization methodologies, predictive climate change analysis for CWR distributions and genetic diversity studies of taxa using Amplified Fragment Length Polymorphisms (AFLPs). Comprehensive $in$ $situ$ and $ex$ $situ$ national recommendations for the conservation of CWR in Norway are detailed. These include the incorporation of management plans for CWR populations within the Færder national park in Norway, the first instance of such conservation activities in Scandinavia. The scientific methods used and developed will help Norway meet its international obligations for conservation and use of genetic diversity of CWR and will contribute to the regional and global efforts to systematically conserve and utilize the diversity found in CWR

The Island Image: A Means of Segmentation

The success of tourism, at a destination, is often accredited to the strength of its marketing; yet, the marketing environment is changing at a fast pace where developments in digital technology have had a profound effect on marketing strategies. Furthermore, the increased accessibility of long and short haul travel has resulted in greater competition for tourist visits among destinations. Such changes present a challenge for cold water island destinations with a seasonal tourism product and limited resources for destination marketing. The ability of such destinations to adopt target marketing strategies, using meaningful segmentation criterion, is of great importance for their future success. For cold water islands, it is vital that the promotional message resonates with the target audience, as such, an image segmentation is proposed. Although tourist segmentation is well practiced in tourism research, existing studies focus on socio-demographic or behavioural segmentation. Few studies have conducted image based segmentation, thus, this thesis explores the feasibility of image segmentation in cold water island destinations; using the Isles of Scilly as a case study. In this thesis image segmentation is used to develop a typology of visitors to the Isles of Scilly, and the intrinsic relationships between destination image, motivation, behaviour, evaluation and place attachment are also explored. Due to the difficulties in measuring image, a mixed method approach was adopted and a concurrent triangulation design employed. Quantitative data were collected from 500 ii respondents visiting the Isles of Scilly, by means of a face-to-face questionnaire, and a further 15 in-depth interviews formed the qualitative sample. Quantitative data were analysed using Exploratory Factor Analysis and K-means Cluster Analysis, while qualitative data were analysed using Thematic Content Analysis. The findings of this thesis revealed the feasibility of image segmentation, through the creation of a six-fold typology of visitors to the Isles of Scilly. Both theoretical and practical implications were derived from this study. The most significant theoretical contribution of this research is that offered to the understanding of image segmentation, as this is the first study conducted in the context of cold water islands. Theoretical contributions were also made with regard to the intrinsic relationships between destination image and motivation, behaviour, evaluation and place attachment. While findings of this study agreed with those of past research, valuable contributions are also offered. Notably, this study adds to a body of work relating to the relationships between complex image and motivation, on-site behaviour, evaluation and place attachment. Additionally, this study adds to tourism knowledge, where the role of on-site behaviour in the formation of positive image, and the influence of participation in special interest tourism, on the formation of destination image are identified. Furthermore, practical recommendations are provided in relation to marketing of the Isles of Scilly where lucrative image segments are identified. Finally, through the understanding of destination image, this thesis proposes seasonal marketing campaigns and the development of special interest tourism, with a focus on wildlife, in order to successfully promote and develop tourism in the Isles of Scilly

The Impact of Family-Based Interventions on Adolescent Glycemic Control: A Systematic Review of the Literature

poster abstractObjective: Glycemic control is a major source of family conflict among adolescents with type 1 diabetes and their parents. Family conflict is a determinant of how well adolescents will maintain glycemic control throughout adolescence; thus, family conflict resolution is a crucial step to managing their diagnosis. The purpose of this systematic review is to evaluate the effectiveness of family-based interventions on glycemic control of adolescents with type 1 diabetes. Methods: Databases utilized were Medline Ovid, PsycINFO, and Web of Science. Inclusion criteria for the studies selected included: peer-reviewed studies conducted in the United States; published between January 1994 to December 2014; and evaluated a family-based intervention’s effectiveness on adolescent diabetic glycemic control. Results: 11 studies met the criteria. Methods used to resolve family conflict included teamwork interventions, tailored interventions, behavioral family systems therapy, and family problem-solving management. Six studies did not show any significant influence on glycemic control. The only significant results on lowering glycemic control were found when a12-month follow-up was completed. Behavioral family systems therapy and family problem-solving management were found to be significant in improving adolescent glycemic control. Conclusion: It is crucial for healthcare providers to be aware of effective family-based interventions to help resolve family conflict and promote healthy glycemic control among adolescents with type 1 diabetes. Interventions specifically designed to address family conflict will not only foster healthy family relationships, but will target adolescents struggling to maintain adequate glycemic control. Results from this review shows that interventions based on family systems therapy and problem-solving management seem to be most effective. Future research is needed to replicate these findings in larger, more diverse samples

Spatial variation in exhumation rates across Ladakh and the Karakoram: New apatite fission track data from the Eastern Karakoram, NW India

Characterization of low-temperature cooling histories and associated exhumation rates is critical for deciphering the recent evolution of orogenic regions. However, these may vary significantly over relatively short distances within orogens. It is pertinent therefore to constrain cooling histories and hence exhumation rates across major tectonic boundaries. We report the first apatite fission track ages from the Karakoram Fault Zone in the Eastern Karakoram range, which forms part of the western margin of the Tibetan Plateau. Ten samples, from elevations of 3477–4875m, have apatite fission track dates from 3.3 ± 0.3 Ma to 7.4± 1.1Ma. The ages correspond to modeled average erosional exhumation rates of 0.67+ 0.27-0.18mm/yr across the Eastern Karakoram. The results are consistent with a trend northward from the Indus suture zone, across the Ladakh terrane and into the Karakoram, in which tectonic uplift associated with crustal thickening increases toward the north, raising elevation and promoting glaciation and generation of extreme relief. As a result, erosion and exhumation rates increase south to north. Present-day precipitation on the other hand varies little within the study area and on a larger scale decreases southwest to northeast across this portion of the orogen. The Eastern Karakoram results highlight the diverse patterns of exhumation driven by regional variations in tectonic response to collision along the western margin of Tibet

Thermochronologic constraints on the late Cenozoic exhumation history of the Gurla Mandhata metamorphic core complex, Southwestern Tibet

This is the publisher's version, also available electronically from http://onlinelibrary.wiley.com/doi/10.1002/2013TC003302/abstractHow the Tibetan plateau is geodynamically linked to the Himalayas is a topic receiving considerable attention. The Karakoram fault plays key roles in describing the structural relationship between southern Tibet and the Himalayas. In particular, considerable debate exists at the southeastern end of the Karakoram fault, where its role is interpreted in two different ways. One interpretation states that slip along the dextral Karakoram fault extends eastward along the Indus-Yalu suture zone, bypassing the Himalayas. The other interprets that fault slip is fed southward into the Himalayan thrust belt along the Gurla Mandhata detachment (GMD). To evaluate these competing models, the late Miocene history of the GMD was reconstructed from thermokinematic modeling of zircon (U-Th)/He data. Three east-west transects reveal rapid cooling of the GMD footwall from 8.0 ± 1.3 Ma to 2.6 ± 0.7 Ma. Model simulations show a southward decrease in slip magnitude and rate along the GMD. In the north, initiation of the GMD range between 14 and 11 Ma with a mean fault slip rate of 5.0 ± 0.9 mm/yr. The central transect shows an initiation age from 14 to 11 Ma with a mean fault slip rate of 3.3 ± 0.6 mm/yr. In the south, initiation began between 15 and 8 Ma with a mean fault slip rate of 3.2 ± 1.6 mm/yr. The initiation ages and slip rates match the Karakoram fault across several timescales, supporting the idea that the two are kinematically linked. Specifically, the data are consistent with the GMD acting as an extensional stepover, with slip transferred southward into the Himalayas of western Nepal

Informing evaluation of a smartphone application for people with acquired brain injury: a stakeholder engagement study

Background Brain in Hand is a smartphone application (app) that allows users to create structured diaries with problems and solutions, attach reminders, record task completion and has a symptom monitoring system. Brain in Hand was designed to support people with psychological problems, and encourage behaviour monitoring and change. The aim of this paper is to describe the process of exploring the barriers and enablers for the uptake and use of Brain in Hand in clinical practice, identify potential adaptations of the app for use with people with acquired brain injury (ABI), and determine whether the behaviour change wheel can be used as a model for engagement. Methods We identified stakeholders: ABI survivors and carers, National Health Service and private healthcare professionals, and engaged with them via focus groups, conference presentations, small group discussions, and through questionnaires. The results were evaluated using the behaviour change wheel and descriptive statistics of questionnaire responses. Results We engaged with 20 ABI survivors, 5 carers, 25 professionals, 41 questionnaires were completed by stakeholders. Comments made during group discussions were supported by questionnaire results. Enablers included smartphone competency (capability), personalisation of app (opportunity), and identifying perceived need (motivation). Barriers included a physical and cognitive inability to use smartphone (capability), potential cost and reliability of technology (opportunity), and no desire to use technology or change from existing strategies (motivation). The stakeholders identified potential uses and changes to the app, which were not easily mapped onto the behaviour change wheel, e.g. monitoring fatigue levels, method of logging task completion, and editing the diary on their smartphone. Conclusions The study identified that both ABI survivors and therapists could see a use for Brain in Hand, but wanted users to be able to personalise it themselves to address individual user needs, e.g. monitoring activity levels. The behaviour change wheel is a useful tool when designing and evaluating engagement activities as it addresses most aspects of implementation, however additional categories may be needed to explore the specific features of assistive technology interventions, e.g. technical functions