DNA technology for the detection of common genetic variants that predispose to thrombophilia

With the identification of common single locus point mutations as risk factors for thrombophilia, many DNA testing methodologies have been described for detecting these variations. Traditionally, functional or immunological testing methods have been used to investigate quantitative anticoagulant deficiencies. However, with the emergence of the genetic variations, factor V Leiden, prothrombin 20210 and, to a lesser extent, the methylene tetrahydrofolate reductase (MTHFR677) and factor V HR2 haplotype, traditional testing methodologies have proved to be less useful and instead DNA technology is more commonly employed in diagnostics. This review considers many of the DNA techniques that have proved to be useful in the detection of common genetic variants that predispose to thrombophilia. Techniques involving gel analysis are used to detect the presence or absence of restriction sites, electrophoretic mobility shifts, as in single strand conformation polymorphism or denaturing gradient gel electrophoresis, and product formation in allele-specific amplification. Such techniques may be sensitive, but are unwielding and often need to be validated objectively. In order to overcome some of the limitations of gel analysis, especially when dealing with larger sample numbers, many alternative detection formats, such as closed tube systems, microplates and microarrays (minisequencing, real-time polymerase chain reaction, and oligonucleotide ligation assays) have been developed. In addition, many of the emerging technologies take advantage of colourimetric or fluorescence detection (including energy transfer) that allows qualitative and quantitative interpretation of results. With the large variety of DNA technologies available, the choice of methodology will depend on several factors including cost and the need for speed, simplicity and robustness. © 2000 Lippincott Williams & Wilkins.

Use of first nucleotide change technology to determine the frequency of factor V Leiden in a population of Australian blood donors

Activated protein C resistance (APCR), the most common risk factor for venous thrombosis, is the result of a G to A base substitution at nucleotide 1691 (R506Q) in the factor V gene. Current techniques to detect the factor V Leiden mutation, such as determination of restriction length polymorphisms, do not have the capacity to screen large numbers of samples in a rapid, cost- effective test. The aim of this study was to apply the first nucleotide change (FNC) technology, to the detection of the factor V Leiden mutation. After preliminary amplification of genomic DNA by polymerase chain reaction (PCR), an allele-specific primer was hybridised to the PCR product and extended using fluorescent terminating dideoxynucleotides which were detected by colorimetric assay. Using this ELISA-based assay, the prevalence of the factor V Leiden mutation was determined in an Australian blood donor population (n = 500). A total of 18 heterozygotes were identified (3.6%) and all of these were confirmed with conventional MnlI restriction digest. No homozygotes for the variant allele were detected. We conclude from this study that the frequency of 3.6% is compatible with others published for Caucasian populations. In addition, the FNC technology shows promise as the basis for a rapid, automated DNA based test for factor V Leiden.

The role of cross-functional teams on the alignment between technology innovation effectiveness and operational effectiveness

Organisations are increasingly investing in complex technological innovations, such as enterprise information systems, with the aim of improving the operation of the business, and in this way gaining competitive advantage. However, the implementation of technological innovations tends to have an excessive focus on either technology innovation effectiveness, or the resulting operational effectiveness. Focusing on either one of them is detrimental to long-term performance. Cross-functional teams have been used by many organisations as a way of involving expertise from different functional areas in the implementation of technologies. The role of boundary spanning actors is discussed as they bring a common language to the cross-functional teams. Multiple regression analysis has been used to identify the structural relationships and provide an explanation for the influence of cross-functional teams, technology innovation effectiveness and operational effectiveness in the continuous improvement of operational performance. The findings indicate that cross functional teams have an indirect influence on continuous improvement of operational performance through the alignment between technology innovation effectiveness and operational effectiveness.

Exploring the role of the governing body (board) in information technology governance : a study of Australian universities

In this thesis, I advance the understanding of information technology (IT) governance research and corporate governance research by considering the question “How do boards govern IT?” The importance of IT to business has increased over the last decade, but there has been little academic research which has focused on boards and their role in the governance of IT (Van Grembergen, De Haes and Guldentops, 2004). Most of the research on information technology governance (ITG) has focused on advancing the understanding and measurement of the components of the ITG model (Buckby, Best & Stewart, 2008; Wilkin & Chenhall, 2010), a model recommended by the IT Governance Institute (2003) as ‘best practice’ for boards to use in governing IT. IT governance is considered to be the responsibility of the board and is said to form an important subset of an organisation’s corporate governance processes (Borth & Bradley, 2008). Boards need to govern IT as a result of the large capital investment in IT resources and high dependency on IT by organisations. Van Grembergen, De Haes and Guldentops (2004) and De Haes & Van Grembergen (2009) indicate that corporate governance matters are not able to be effectively discharged unless IT is being governed properly, and call for further specific research on the role of the board in ITG. Researchers also indicate that the link between corporate governance and IT governance has been neglected (Borth & Bradley, 2008; Musson & Jordan, 2005; Bhattacharjya & Chang, 2008). This thesis will address this gap in the ITG literature by providing the bridge between the ITG and corporate governance literatures. My thesis uses a critical realist epistemology and a mixed method approach to gather insights into my research question. In the first phase of my research I develop a survey instrument to assess whether boards consider the components of the ITG model in governing IT. The results of this first study indicated that directors do not conceptualise their role in governing IT using the elements of the ITG model. Thus, I moved to focus on whether prominent corporate governance theories might elucidate how boards govern IT. In the second phase of the research, I used a qualitative inductive case based study to assess whether agency, stewardship and resource dependence theories explain how boards govern IT in Australian universities. As the first in-depth study of university IT governance processes, my research contributes to the ITG research field by revealing that Australian university board governance of IT is characterized by a combination of agency theory and stewardship theory behaviours and processes. The study also identified strong links between a university’s IT structure and evidence of agency and stewardship theories. This link provides insight into the structures element of the emerging enterprise governance of IT framework (Van Grembergen, De Haes & Guldentops, 2004; De Haes & Van Grembergen, 2009; Van Grembergen & De Haes, 2009b; Ko & Fink, 2010). My research makes an important contribution to governance research by identifying a key link between corporate and ITG literatures and providing insight into board IT governance processes. The research conducted in my thesis should encourage future researchers to continue to explore the links between corporate and IT governance research.

Decision support to green technology implementation on Australian university campuses

As the societal awareness on sustainability is gaining momentum worldwide, the higher education sector is expected to take the lead in education, research and the promotion of sustainable development. Universities have the diversity of skills and knowledge to explore new concepts and issues, the academic freedom to offer unbiased observations, and the capacity to engage in experimentation for solutions. There is a global trend that universities have realized and responded to sustainability challenge. By adopting green technologies, buildings on university campuses have the potential to offer highly productive and green environments for a quality learning experience for students, while minimising environmental impacts. Despite the potential benefits and metaphorical link to sustainability, few universities have moved towards implementing Green Roof and Living Wall on campuses widely, which have had more successful applications in commercial and residential buildings. Few past research efforts have examined the fundamental barriers to the implementation of sustainable projects on campuses from organizational level. To address this deficiency, an on-going research project is undertaken by Queensland University of Technology in Australia. The research is aimed at developing a comprehensive framework to facilitate better decision making for the promotion of Green Roof and Living Wall application on campuses. It will explore and highlight organizational factors as well as investigate and emphasize project delivery issues. Also, the critical technical indicators for Green Roof and Living Wall implementation will be identified. The expected outcome of this research has the potential to enhance Green Roof and Living Wall delivery in Australian universities, as a vital step towards realizing sustainability in higher education sectors.

Post-PC devises : a summary of early iPad technology

In just under 3 months worldwide sales of Apple's iPad tablet device stood at over 3 million units sold. The iPad device, along with rival products signify a shift in the way in which print and other media products are purchased and consumed by users. While facing initial skepticism about the uptake of the device numerous industries have been quick to adapt the device to their specific needs. Based around a newly developed six point typology of “post PC” device utility this project undertook a significant review of publicly available material to identify worldwide trends in iPad adoption and use within the tertiary sector.

Self-management of cancer treatment-related fatigue, nausea, vomiting and oral mucositis in Chinese cancer patients

Background: Treatment-related symptoms continue to place a significant burden on many cancer patients. Many side effects require patients to engage in a range of self-management actions. While some studies have explored self-management of treatment-related side effects in Western settings, very few studies were identified that described the self-management practices of cancer patients in China. Objective: The purposes of this study are to: (1) Investigate Chinese cancer patients. self-management behaviours in dealing with the fatigue, nausea/vomiting and oral mucositis that result from treatment, as well as the perceived effectiveness of these behaviours and related self-efficacy in performing them. (2) Explore factors influencing symptom self-management behaviours using the Cancer Symptom Self-management Framework based on Grey, Knafl and McCorkle.s (2006) self-management framework as a guide. Methods: This study was divided into two phases. Phase One consisted of the translation and modification of two instruments. The adaptation of these instruments to ensure applicability in the Chinese context was achieved through semi-structured interviews with six cancer patients, and content evaluation with eight experienced oncology nurses. A pilot study was conducted with nine cancer patients to trial the questionnaire set in the Chinese context. Based on the results of Phase One, Phase Two involved a cross-sectional survey of Chinese cancer patients undergoing cancer treatment using these instruments. A total of 277 chemotherapy patients with fatigue and/or nausea and vomiting, and 100 radiotherapy patients with oral mucositis were surveyed. Results: Participants in this study reported a variety of self-management behaviours to cope with fatigue, nausea, vomiting and oral mucositis. There are some consistencies as well disparities between strategies that are frequently used and those rated as effective. For fatigue self-management, participants were more likely to use strategies related to rest and sleep, while activity enhancement strategies were rated as achieving higher relief. For nausea and vomiting self-management, dietary modification and taking medication were most frequently used and rated as moderately effective. Psychological strategies were used by more than a third of participants and were rated as mildly effective. Some other infrequently used strategies, such as distraction by keeping busy and acupressure, were rated as moderately effective. For oral mucositis self-management, having soft, bland food and keeping the mouth moisturised were most frequently reported and they were rated as achieving moderate relief. A prescribed mouthwash was used by most but not all participants and brought moderate relief. In general, patients had low-to-moderate self-efficacy in nausea and vomiting self-management behaviours, moderate self-efficacy in fatigue self-management behaviours, and low-to-moderate self-efficacy in oral mucositis self-management behaviours. In terms of the factors influencing symptom self-management, different predictors were identified affecting engagement in fatigue, nausea/vomiting and oral mucositis self-management behaviours. Self-efficacy scores of different behaviours were consistently found to be a positive predictor of the relief level from corresponding behaviours, after controlling for other variables. Perceived social support from health care professionals was identified as an important factor influencing nausea and vomiting self-management behaviours, while neighbourhood support was important for fatigue self-management. In addition, symptom distress was identified as an important factor influencing nausea and vomiting self-management. Conclusion: Similar to reports from overseas, Chinese cancer patients initiate a wide range of self-management behaviours in response to treatment-related side effects. While some behaviours were reported to provide relief, many did not. Given these results, this study has a number of practical implications for health care professionals, particularly in relation to developing tailored self-management programs for fatigue, nausea, vomiting and oral mucositis. Additionally, this study suggests a number of theoretical implications and directions for future research. It is envisaged that these recommendations may pave the way for further studies understanding and promoting cancer symptom self-management in Chinese people affected by cancer.

Barriers to information technology governance adoption : a preliminary empirical investigation

The adoption of IT Governance (ITG) continues to be an important topic for research. Many researchers have focused their attention on how these practices are currently being implemented in the many diverse areas and industries. Literature shows that a majority of these studies have only been based on industries and organizations in developed countries. There exist very few researches that look specifically within the context of a developing country. Furthermore, there seems to be a lack of research on identifying the barriers or inhibitors to IT Governance adoption within the context of an emerging yet still developing Asian country. This research sets out to justify, substantiate and improve on a priori model developed to study the barriers to the adoption of ITG practice using qualitative data obtained through a series of semi-structured interviews conducted on organizations in Malaysia.

Chlorzoxazone, an SK-type potassium channel activator used in humans, reduces excessive alcohol intake in rats

Background Alcoholism imposes a tremendous social and economic burden. There are relatively few pharmacological treatments for alcoholism, with only moderate efficacy, and there is considerable interest in identifying additional therapeutic options. Alcohol exposure alters SK-type potassium channel (SK) function in limbic brain regions. Thus, positive SK modulators such as chlorzoxazone (CZX), a US Food and Drug Administration–approved centrally acting myorelaxant, might enhance SK function and decrease neuronal activity, resulting in reduced alcohol intake. Methods We examined whether CZX reduced alcohol consumption under two-bottle choice (20% alcohol and water) in rats with intermittent access to alcohol (IAA) or continuous access to alcohol (CAA). In addition, we used ex vivo electrophysiology to determine whether SK inhibition and activation can alter firing of nucleus accumbens (NAcb) core medium spiny neurons. Results Chlorzoxazone significantly and dose-dependently decreased alcohol but not water intake in IAA rats, with no effects in CAA rats. Chlorzoxazone also reduced alcohol preference in IAA but not CAA rats and reduced the tendency for rapid initial alcohol consumption in IAA rats. Chlorzoxazone reduction of IAA drinking was not explained by locomotor effects. Finally, NAcb core neurons ex vivo showed enhanced firing, reduced SK regulation of firing, and greater CZX inhibition of firing in IAA versus CAA rats. Conclusions The potent CZX-induced reduction of excessive IAA alcohol intake, with no effect on the more moderate intake in CAA rats, might reflect the greater CZX reduction in IAA NAcb core firing observed ex vivo. Thus, CZX could represent a novel and immediately accessible pharmacotherapeutic intervention for human alcoholism. Key Words: Alcohol intake; intermittent; neuro-adaptation; nucleus accumbens; SK potassium channel

Nursing Sans Frontieres: A Three Year Case Study of Multi-State Registration of Support Nursing Practice Using Information Technology

Objective: To highlight the registration issues for nurses who wish to practice nationally, particularly those practicing within the telehealth sector. Design: As part of a national clinical research study, applications were made to every state and territory for mutual recognition of nursing registration and fee waiver for telenursing cross boarder practice for a period of three years. These processes are described using a case study approach. Outcome: The aim of this case study was to achieve registration in every state and territory of Australia without paying multiple fees by using mutual recognition provisions and the cross-border fee waiver policy of the nurse regulatory authorities in order to practice telenursing. Results: Mutual recognition and fee waiver for cross-border practice was granted unconditionally in two states: Victoria (Vic) and Tasmania (Tas), and one territory: the Northern Territory (NT). The remainder of the Australian states and territories would only grant temporary registration for the period of the project or not at all, due to policy restrictions or nurse regulatory authority (NRA) Board decisions. As a consequence of gaining fee waiver the annual cost of registration was a maximum of $145 per annum as opposed to the potential $959 for initial registration and $625 for annual renewal. Conclusions: Having eight individual nurses Acts and NRAs for a population of 265,000 nurses would clearly indicate a case for over regulation in this country. The structure of regulation of nursing in Australia is a barrier to the changing and evolving role of nurses in the 21st century and a significant factor when considering workforce planning.

Proteasome inhibitors trigger NOXA-mediated apoptosis in melanoma and myeloma cells

Patients with metastatic melanoma or multiple myeloma have a dismal prognosis because these aggressive malignancies resist conventional treatment. A promising new oncologic approach uses molecularly targeted therapeutics that overcomes apoptotic resistance and, at the same time, achieves tumor selectivity. The unexpected selectivity of proteasome inhibition for inducing apoptosis in cancer cells, but not in normal cells, prompted us to define the mechanism of action for this class of drugs, including Food and Drug Administration-approved bortezomib. In this report, five melanoma cell lines and a myeloma cell line are treated with three different proteasome inhibitors (MG-132, lactacystin, and bortezomib), and the mechanism underlying the apoptotic pathway is defined. Following exposure to proteasome inhibitors, effective killing of human melanoma and myeloma cells, but not of normal proliferating melanocytes, was shown to involve p53-independent induction of the BH3-only protein NOXA. Induction of NOXA at the protein level was preceded by enhanced transcription of NOXA mRNA. Engagement of mitochondrial-based apoptotic pathway involved release of cytochrome c, second mitochondria-derived activator of caspases, and apoptosis-inducing factor, accompanied by a proteolytic cascade with processing of caspases 9, 3, and 8 and poly(ADP)-ribose polymerase. Blocking NOXA induction using an antisense (but not control) oligonucleotide reduced the apoptotic response by 30% to 50%, indicating a NOXA-dependent component in the overall killing of melanoma cells. These results provide a novel mechanism for overcoming the apoptotic resistance of tumor cells, and validate agents triggering NOXA induction as potential selective cancer therapeutics for life-threatening malignancies such as melanoma and multiple myeloma.