PCR bias Toward the wild-type k-ras and p53 sequences: Implications for PCR detection of mutations and cancer diagnosis

PCR-based cancer diagnosis requires detection of rare mutations in k- ras, p53 or other genes. The assumption has been that mutant and wild-type sequences amplify with near equal efficiency, so that they are eventually present in proportions representative of the starting material. Work on factor IX suggests that this assumption is invalid for one case of near- sequence identity. To test the generality of this phenomenon and its relevance to cancer diagnosis, primers distant from point mutations in p53 and k-ras were used to amplify wild-type and mutant sequences from these genes. A substantial bias against PCR amplification of mutants was observed for two regions of the p53 gene and one region of k-ras. For k-ras and p53, bias was observed when the wild-type and mutant sequences were amplified separately or when mixed in equal proportions before PCR. Bias was present with proofreading and non-proofreading polymerase. Mutant and wild-type segments of the factor V, cystic fibrosis transmembrane conductance regulator and prothrombin genes were amplified and did not exhibit PCR bias. Therefore, the assumption of equal PCR efficiency for point mutant and wild-type sequences is invalid in several systems. Quantitative or diagnostic PCR will require validation for each locus, and enrichment strategies may be needed to optimize detection of mutants.

The acquisition and exercise of nephrology nursing expertise : A grounded theory study

Aims and objectives. This purpose of this study was to describe the process of expertise acquisition in nephrology nursing practice. Background. It has been recognized for a number of decades that experts, compared with other practitioners in a number of professions and occupations, are the most knowledgeable and effective, in terms of both the quantity and quality of output. Studies relating to expertise have been undertaken in a range of nursing contexts and specialties; to date, however, none have been undertaken which focus on nephrology nursing. Design. This study, using grounded theory methodology, took place in one renal unit in New South Wales, Australia and involved six non-expert and 11 expert nurses. Methods. Simultaneous data collection and analysis took place using participant observation, semi-structured interviews and review of nursing documentation. Findings. The study revealed a three-stage skills-acquisitive process that was identified as non-expert, experienced non-expert and expert stages. Each stage was typified by four characteristics, which altered during the acquisitive process; these were knowledge, experience, skill and focus. Conclusion. This was the first study to explore nephrology nursing expertise and uncovered new aspects of expertise not documented in the literature and it also made explicit other areas, which had only been previously implied. Relevance to clinical practice. Of significance to nursing, the exercise of expertise is a function of the recognition of expertise by others and it includes the blurring of the normal boundaries of professional practice. © 2006 Blackwell Publishing Ltd.

Sustainability criteria for Industrialised Building System (IBS) in Malaysia

As the sustainability awareness rises globally, the construction industry is under increasing pressure to improve efficiency and project delivery. The implementation of Industrialised Building Systems (IBS), for which utility components are built offsite, has the potential of promoting sustainability deliverables. This can be achieved by better control of production environment, minimising construction waste, using efficient building material energy, and stabilising work conditions. As a unique building technology, IBS has not been effectively implemented in Malaysia. Possible reasons may include limited understanding among stakeholders on the IBS potential and its relevance to sustainability. This warrants studies on the sustainability issues of IBS design, construction, operation and maintenance, A framework is being developed through research to assess performance criteria related to sustainability, which should be considered during IBS design and application in the most consistent and systematic way. This paper discusses how these sustainability performance criteria are examined in a continuing research project and the processes conducive to implementing sustainable IBS in Malaysia. Existing tools, indicators and guidelines are reviewed, analysed and grouped according to characteristics and application. The research also hopes to produce guidelines for stakeholders to incorporate sustainability issues and concepts into IBS applications.

Neural network learning:theoretical foundations

This important work describes recent theoretical advances in the study of artificial neural networks. It explores probabilistic models of supervised learning problems, and addresses the key statistical and computational questions. Chapters survey research on pattern classification with binary-output networks, including a discussion of the relevance of the Vapnik Chervonenkis dimension, and of estimates of the dimension for several neural network models. In addition, Anthony and Bartlett develop a model of classification by real-output networks, and demonstrate the usefulness of classification with a "large margin." The authors explain the role of scale-sensitive versions of the Vapnik Chervonenkis dimension in large margin classification, and in real prediction. Key chapters also discuss the computational complexity of neural network learning, describing a variety of hardness results, and outlining two efficient, constructive learning algorithms. The book is self-contained and accessible to researchers and graduate students in computer science, engineering, and mathematics

Categorisation of activities of daily living of lower limb amputees during short-term use of a portable kinetic recording system : a preliminary study

The purpose of this preliminary study was to determine the relevance of the categorization of the load regime data to assess the functional output and usage of the prosthesis of lower limb amputees. The objectives were a) to introduce a categorization of load regime, b) to present some descriptors of each activity, and c) to report the results for a case. The load applied on the osseointegrated fixation of one transfemoral amputee was recorded using a portable kinetic system for 5 hours. The periods of directional locomotion, localized locomotion, and stationary loading occurred 44%, 34%, and 22% of recording time and each accounted for 51%, 38%, and 12% of the duration of the periods of activity, respectively. The absolute maximum force during directional locomotion, localized locomotion, and stationary loading was 19%, 15%, and 8% of the body weight on the anteroposterior axis, 20%, 19%, and 12% on the mediolateral axis, and 121%, 106%, and 99% on the long axis. A total of 2,783 gait cycles were recorded. Approximately 10% more gait cycles and 50% more of the total impulse than conventional analyses were identified. The proposed categorization and apparatus have the potential to complement conventional instruments, particularly for difficult cases.

Inhibition of p38 pathway leads to OA-like changes in a rat animal model

Objectives The p38 mitogen-activated protein kinase (MAPK) signal transduction pathway is involved in a variety of inflammatory responses, including cytokine generation, cell differentiation proliferation and apoptosis. Here, we examined the effects of systemic p38 MAPK inhibition on cartilage cells and osteoarthritis (OA) disease progression by both in vitro and in vivo approaches. Methods p38 kinase activity was evaluated in normal and OA cartilage cells by measuring the amount of phosphorylated protein. To examine the function of p38 signaling pathway in vitro, normal chondrocytes were isolated and differentiated in the presence or absence of p38 inhibitor; SB203580 and analysed for chondrogenic phenotype. Effect of systemic p38 MAPK inhibition in normal and OA (induced by menisectomy) rats were analysed by treating animals with vehicle alone (DMS0) or p38 inhibitor (SB203580). Damage to the femur and tibial plateau was evaluated by modified Mankin score, histology and immunohistochemistry. Results Our in vitro studies have revealed that a down-regulation of chondrogenic and increase of hypertrophic gene expression occurs in the normal chondrocytes, when p38 is neutralized by a pharmacological inhibitor. We further observed that the basal levels of p38 phosphorylation were decreased in OA chondrocytes compared with normal chondrocytes. These findings together indicate the importance of this pathway in the regulation of cartilage physiology and its relevance to OA pathogenesis. At in vivo level, systematic administration of a specific p38 MAPK inhibitor, SB203580, continuously for over a month led to a significant loss of proteoglycan; aggrecan and cartilage thickness. On the other hand, SB203580 treated normal rats showed a significant increase in TUNEL positive cells, cartilage hypertrophy markers such as Type 10 collagen, Runt-related transcription factor and Matrix metalloproteinase-13 and substantially induced OA like phenotypic changes in the normal rats. In addition, menisectomy induced OA rat models that were treated with p38 inhibitor showed aggravation of cartilage damage. Conclusions In summary, this study has provided evidence that the component of the p38 MAPK pathway is important to maintain the cartilage health and its inhibition can lead to severe cartilage degenerative changes. The observations in this study highlight the possibility of using activators of the p38 pathway as an alternative approach in the treatment of OA.

Ensuring student success : the role of support services in improving the quality of the student learning experience

This paper is based on the premise that universities have an obligation to provide adequate student support services, such as learning assistance (that is, assistance with academic writing and other study skills) and that in order to be effective such services must be responsive to the wider policy and social implications of student attrition and retention. The paper outlines briefly some of the factors that have influenced the development of learning assistance practices in Australia and America. This is followed by an account of experiences at one Australian metropolitan university where learning assistance service provision shifted from a decentralised, faculty-based model to a centralised model of service delivery. This shift was in response to concerns about lack of quality and consistency in a support model dependent upon faculty resources yet a follow up study identified other problems in the centralised delivery of learning assistance services. These problems, clustered under the heading contextualised versus decontextualised learning assistance, include the relevance of generic learning assistance services to students struggling with specific course related demands; the apparent tensions between challenging students and assisting students at risk of failure; and variations in the level of collaboration between learning advisers and academic staff in supporting students in the learning environment. These problems are analysed using the theoretical modelling derived from the tools made available through cultural historical activity theory and expansive visibilisation (Engeström & Miettinen, 1999).

Politics and school education in Australia : a case of shifting purposes

Purpose – The paper aims to argue that there has been a privileging of the private (social mobility) and economic (social efficiency) purposes of schooling at the expense of the public (democratic equality) purposes of schooling. Design/methodology/approach – The paper employs a literature review, policy and document analysis. Findings – Since the late 1980s, the schooling agenda in Australia has been narrowed to one that gives primacy to purposes of schooling that highlight economic orientations (social efficiency) and private purposes (social mobility). Practical implications – The findings have wider relevance beyond Australia, as similar policy agendas are evident in many other countries raising the question as to how the shift in purposes of education in those countries might mirror those in Australia. Originality/value – While earlier writers have examined schooling policies in Australia and noted the implications of managerialism in relation to these policies, no study has analysed these policies from the perspective of the purposes of schooling. Conceptualising schooling, and its purposes in particular, in this way refocuses attention on how societies use their educational systems to promote (or otherwise) the public good.

Evaluating medical information retrieval

This paper presents a framework for evaluating information retrieval of medical records. We use the BLULab corpus, a large collection of real-world de-identified medical records. The collection has been hand coded by clinical terminol- ogists using the ICD-9 medical classification system. The ICD codes are used to devise queries and relevance judge- ments for this collection. Results of initial test runs using a baseline IR system are provided. Queries and relevance judgements are online to aid further research in medical IR. Please visit: http://koopman.id.au/med_eval.

Association of inducible nitric oxide synthase with asthma severity, total serum immunoglobulin E and blood eosinophil levels

Background Nitric oxide is released by immune, epithelial and endothelial cells, and plays an important part in the pathophysiology of asthma. Objective To investigate the association of inducible nitric oxide synthases (iNOS) gene repeat polymorphisms with asthma. Methods 230 families with asthma (842 individuals) were recruited to identify and establish the genetic association of iNOS repeats with asthma and associated phenotypes. Serum nitric oxide levels in selected individuals were measured and correlated with specific genotypes. Multiple logistic regression analysis was performed to determine the effect of age and sex. Results A total of four repeats—a (CCTTT)n promoter repeat, a novel intron 2 (GT)n repeat (BV680047), an intron 4 (GT)n repeat (AFM311ZB1) and an intron 5 (CA)n repeat (D17S1878)—were identified and genotyped. A significant transmission distortion to the probands with asthma was seen for allele 3 of the AFM311ZB1 gene (p = 0.006). This allele was also found to be significantly associated with percentage blood eosinophils (p<0.001) and asthma severity (p = 0.04). Moreover, it was functionally correlated with high serum nitric oxide levels (p = 0.006). Similarly, the promoter repeat was found to be associated with serum total immunoglobulin (Ig)E (p = 0.028). Individuals carrying allele 4 of this repeat have high serum IgE (p<0.001) and nitric oxide levels (p = 0.03). Conclusion This is the first study to identify the repeat polymorphisms in the iNOS gene that are associated with severity of asthma and eosinophils. The functional relevance of the associated alleles with serum nitric oxide levels was also shown. Therefore, these results could be valuable in elucidating the role of nitric oxide in asthma pathogenesis.

Endogenous mortality, human capital and economic growth

We consider growth and welfare effects of lifetime-uncertainty in an economy with human capital-led endogenous growth. We argue that lifetime uncertainty reduces private incentives to invest in both physical and human capital. Using an overlapping generations framework with finite-lived households we analyze the relevance of government expenditure on health and education to counter such growth-reducing forces. We focus on three different models that differ with respect to the mode of financing of education: (i) both private and public spending, (ii) only public spending, and (iii) only private spending. Results show that models (i) and (iii) outperform model (ii) with respect to long-term growth rates of per capita income, welfare levels and other important macroeconomic indicators. Theoretical predictions of model rankings for these macroeconomic indicators are also supported by observed stylized facts.

ICU nurses' experiences and perspectives of caring for obstetric patients in intensive care: A qualitative study

Aims and objectives.  The aim of this study was to gain an understanding of the experiences and perspectives of intensive care nurses caring for critically ill obstetric patients. Background.  Current literature suggests critically ill obstetric patients need specialised, technically appropriate care to meet their specific needs with which many intensive care nurses are unfamiliar. Furthermore, there is little research and evidence to guide the care of this distinct patient group. Design.  This study used a descriptive qualitative design. Methods.  Two focus groups were used to collect data from 10 Australian intensive care units nurses in May 2007. Open-ended questions were used to guide the discussion. Latent content analysis was used to analyse the data set. Each interview lasted no longer than 60 minutes and was recorded using audio tape. The full interviews were transcribed prior to in-depth analysis to identify major themes. Results.  The themes identified from the focus group interviews were competence with knowledge and skills for managing obstetric patients in the intensive care unit, confidence in caring for obstetric patients admitted to the intensive care unit and acceptance of an expanded scope of practice perceived to include fundamental midwifery knowledge and skills. Conclusion.  The expressed lack of confidence and competence in meeting the obstetric and support needs of critically ill obstetric women indicates a clear need for greater assistance and education of intensive care nurses. This in turn may encourage critical care nurses to accept an expanded role of clinical practice in caring for critically ill obstetric patients. Relevance to clinical practice.  Recognition of the issues for nurses in successfully caring for obstetric patients admitted to an adult intensive care setting provides direction for designing education packages, ensuring specific carepaths and guidelines are in place and that support from a multidisciplinary team is available including midwifery staff.

Designing university, government and industry community engagement to build informed and effective interventions in the area of road safety

Individuals, community organisations and industry have always been involved to varying degrees in efforts to address the Queensland road toll. Traditionally, road crash prevention efforts have been led by state and local government organisations. While community and industry groups have sometimes become involved (e.g. Driver Reviver campaign), their efforts have largely been uncoordinated and under-resourced. A common strength of these initiatives lies in the energy, enthusiasm and persistence of community-based efforts. Conversely, a weakness has sometimes been the lack of knowledge, awareness or prioritisation of evidence-based interventions or their capacity to build on collaborative efforts. In 2000, the Queensland University of Technology’s Centre for Accident Research and Road Safety – Queensland (CARRS-Q) identified this issue as an opportunity to bridge practice and research and began acknowledging a selection of these initiatives, in partnership with the RACQ, through the Queensland Road Safety Awards program. After nine years it became apparent there was need to strengthen this connection, with the Centre establishing a Community Engagement Workshop in 2009 as part of the overall Awards program. With an aim of providing community participants opportunities to see, hear and discuss the experiences of others, this event was further developed in 2010, and with the collaboration of the Queensland Department of Transport and Main Roads, the RACQ, Queensland Police Service and Leighton Contractors Pty Ltd, a stand-alone Queensland Road Safety Awards Community Engagement Workshop was held in 2010. Each collaborating organisation recognised a need to mobilise the community through effective information and knowledge sharing, and recognised that learning and discussion can influence lasting behaviour change and action in this often emotive, yet not always evidence-based, area. This free event featured a number of speakers representing successful projects from around Australia and overseas. Attendees were encouraged to interact with the speakers, to ask questions, and most importantly, build connections with other attendees to build a ‘community road safety army’ all working throughout Australia on projects underpinned by evaluated research. The workshop facilitated the integration of research, policy and grass-roots action enhancing the success of community road safety initiatives. For collaboration partners, the event enabled them to transfer their knowledge in an engaged approach, working within a more personal communication process. An analysis of the success factors for this event identified openness to community groups and individuals, relevance of content to local initiatives, generous support with the provision of online materials and ongoing communication with key staff members as critical and supports the view that the university can directly provide both the leadership and the research needed for effective and credible community-based initiatives to address injury and death on the roads.