Non-alcoholic fatty liver disease : can ultrasound assist in early diagnosis of prediabetes and delay progression to type2 diabetes mellitus

Non Alcoholic Fatty Liver Disease (NAFLD) is a condition that is frequently seen but seldom investigated. Until recently, NAFLD was considered benign, self-limiting and unworthy of further investigation. This opinion is based on retrospective studies with relatively small numbers and scant follow-up of histology data. (1) The prevalence for adults, in the USA is, 30%, and NAFLD is recognized as a common and increasing form of liver disease in the paediatric population (1). Australian data, from New South Wales, suggests the prevalence of NAFLD in “healthy” 15 year olds as being 10%.(2) Non-alcoholic fatty liver disease is a condition where fat progressively invades the liver parenchyma. The degree of infiltration ranges from simple steatosis (fat only) to steatohepatitis (fat and inflammation) steatohepatitis plus fibrosis (fat, inflammation and fibrosis) to cirrhosis (replacement of liver texture by scarred, fibrotic and non functioning tissue).Non-alcoholic fatty liver is diagnosed by exclusion rather than inclusion. None of the currently available diagnostic techniques -liver biopsy, liver function tests (LFT) or Imaging; ultrasound, Computerised tomography (CT) or Magnetic Resonance Imaging (MRI) are specific for non-alcoholic fatty liver. An association exists between NAFLD, Non Alcoholic Steatosis Hepatitis (NASH) and irreversible liver damage, cirrhosis and hepatoma. However, a more pervasive aspect of NAFLD is the association with Metabolic Syndrome. This Syndrome is categorised by increased insulin resistance (IR) and NAFLD is thought to be the hepatic representation. Those with NAFLD have an increased risk of death (3) and it is an independent predictor of atherosclerosis and cardiovascular disease (1). Liver biopsy is considered the gold standard for diagnosis, (4), and grading and staging, of non-alcoholic fatty liver disease. Fatty-liver is diagnosed when there is macrovesicular steatosis with displacement of the nucleus to the edge of the cell and at least 5% of the hepatocytes are seen to contain fat (4).Steatosis represents fat accumulation in liver tissue without inflammation. However, it is only called non-alcoholic fatty liver disease when alcohol - >20gms-30gms per day (5), has been excluded from the diet. Both non-alcoholic and alcoholic fatty liver are identical on histology. (4).LFT’s are indicative, not diagnostic. They indicate that a condition may be present but they are unable to diagnosis what the condition is. When a patient presents with raised fasting blood glucose, low HDL (high density lipoprotein), and elevated fasting triacylglycerols they are likely to have NAFLD. (6) Of the imaging techniques MRI is the least variable and the most reproducible. With CT scanning liver fat content can be semi quantitatively estimated. With increasing hepatic steatosis, liver attenuation values decrease by 1.6 Hounsfield units for every milligram of triglyceride deposited per gram of liver tissue (7). Ultrasound permits early detection of fatty liver, often in the preclinical stages before symptoms are present and serum alterations occur. Earlier, accurate reporting of this condition will allow appropriate intervention resulting in better patient health outcomes. References 1. Chalasami N. Does fat alone cause significant liver disease: It remains unclear whether simple steatosis is truly benign. American Gastroenterological Association Perspectives, February/March 2008 www.gastro.org/wmspage.cfm?parm1=5097 Viewed 20th October, 2008 2. Booth, M. George, J.Denney-Wilson, E: The population prevalence of adverse concentrations with adiposity of liver tests among Australian adolescents. Journal of Paediatrics and Child Health.2008 November 3. Catalano, D, Trovato, GM, Martines, GF, Randazzo, M, Tonzuso, A. Bright liver, body composition and insulin resistance changes with nutritional intervention: a follow-up study .Liver Int.2008; February 1280-9 4. Choudhury, J, Sanysl, A. Clinical aspects of Fatty Liver Disease. Semin in Liver Dis. 2004:24 (4):349-62 5. Dionysus Study Group. Drinking factors as cofactors of risk for alcohol induced liver change. Gut. 1997; 41 845-50 6. Preiss, D, Sattar, N. Non-alcoholic fatty liver disease: an overview of prevalence, diagnosis, pathogenesis and treatment considerations. Clin Sci.2008; 115 141-50 7. American Gastroenterological Association. Technical review on nonalcoholic fatty liver disease. Gastroenterology.2002; 123: 1705-25

Cost effectiveness of antimicrobial catheters in the intensive care unit : Addressing uncertainty in the decision

Introduction: Some types of antimicrobial-coated central venous catheters (A-CVC) have been shown to be cost-effective in preventing catheter-related bloodstream infection (CR-BSI). However, not all types have been evaluated, and there are concerns over the quality and usefulness of these earlier studies. There is uncertainty amongst clinicians over which, if any, antimicrobial-coated central venous catheters to use. We re-evaluated the cost-effectiveness of all commercially available antimicrobialcoated central venous catheters for prevention of catheter-related bloodstream infection in adult intensive care unit (ICU) patients. Methods: We used a Markov decision model to compare the cost-effectiveness of antimicrobial-coated central venous catheters relative to uncoated catheters. Four catheter types were evaluated; minocycline and rifampicin (MR)-coated catheters; silver, platinum and carbon (SPC)-impregnated catheters; and two chlorhexidine and silver sulfadiazine-coated catheters, one coated on the external surface (CH/SSD (ext)) and the other coated on both surfaces (CH/SSD (int/ext)). The incremental cost per qualityadjusted life-year gained and the expected net monetary benefits were estimated for each. Uncertainty arising from data estimates, data quality and heterogeneity was explored in sensitivity analyses. Results: The baseline analysis, with no consideration of uncertainty, indicated all four types of antimicrobial-coated central venous catheters were cost-saving relative to uncoated catheters. Minocycline and rifampicin-coated catheters prevented 15 infections per 1,000 catheters and generated the greatest health benefits, 1.6 quality-adjusted life-years, and cost-savings, AUD $130,289. After considering uncertainty in the current evidence, the minocycline and rifampicin-coated catheters returned the highest incremental monetary net benefits of $948 per catheter; but there was a 62% probability of error in this conclusion. Although the minocycline and rifampicin-coated catheters had the highest monetary net benefits across multiple scenarios, the decision was always associated with high uncertainty. Conclusions: Current evidence suggests that the cost-effectiveness of using antimicrobial-coated central venous catheters within the ICU is highly uncertain. Policies to prevent catheter-related bloodstream infection amongst ICU patients should consider the cost-effectiveness of competing interventions in the light of this uncertainty. Decision makers would do well to consider the current gaps in knowledge and the complexity of producing good quality evidence in this area.

Setting hospital infection control policy : a decision-making framework incorporating health economics and healthcare epidemiology

Background: Reducing rates of healthcare acquired infection has been identified by the Australian Commission on Safety and Quality in Health Care as a national priority. One of the goals is the prevention of central venous catheter-related bloodstream infection (CR-BSI). At least 3,500 cases of CR-BSI occur annually in Australian hospitals, resulting in unnecessary deaths and costs to the healthcare system between $25.7 and $95.3 million. Two approaches to preventing these infections have been proposed: use of antimicrobial catheters (A-CVCs); or a catheter care and management ‘bundle’. Given finite healthcare budgets, decisions about the optimal infection control policy require consideration of the effectiveness and value for money of each approach. Objectives: The aim of this research is to use a rational economic framework to inform efficient infection control policy relating to the prevention of CR-BSI in the intensive care unit. It addresses three questions relating to decision-making in this area: 1. Is additional investment in activities aimed at preventing CR-BSI an efficient use of healthcare resources? 2. What is the optimal infection control strategy from amongst the two major approaches that have been proposed to prevent CR-BSI? 3. What uncertainty is there in this decision and can a research agenda to improve decision-making in this area be identified? Methods: A decision analytic model-based economic evaluation was undertaken to identify an efficient approach to preventing CR-BSI in Queensland Health intensive care units. A Markov model was developed in conjunction with a panel of clinical experts which described the epidemiology and prognosis of CR-BSI. The model was parameterised using data systematically identified from the published literature and extracted from routine databases. The quality of data used in the model and its validity to clinical experts and sensitivity to modelling assumptions was assessed. Two separate economic evaluations were conducted. The first evaluation compared all commercially available A-CVCs alongside uncoated catheters to identify which was cost-effective for routine use. The uncertainty in this decision was estimated along with the value of collecting further information to inform the decision. The second evaluation compared the use of A-CVCs to a catheter care bundle. We were unable to estimate the cost of the bundle because it is unclear what the full resource requirements are for its implementation, and what the value of these would be in an Australian context. As such we undertook a threshold analysis to identify the cost and effectiveness thresholds at which a hypothetical bundle would dominate the use of A-CVCs under various clinical scenarios. Results: In the first evaluation of A-CVCs, the findings from the baseline analysis, in which uncertainty is not considered, show that the use of any of the four A-CVCs will result in health gains accompanied by cost-savings. The MR catheters dominate the baseline analysis generating 1.64 QALYs and cost-savings of $130,289 per 1.000 catheters. With uncertainty, and based on current information, the MR catheters remain the optimal decision and return the highest average net monetary benefits ($948 per catheter) relative to all other catheter types. This conclusion was robust to all scenarios tested, however, the probability of error in this conclusion is high, 62% in the baseline scenario. Using a value of $40,000 per QALY, the expected value of perfect information associated with this decision is $7.3 million. An analysis of the expected value of perfect information for individual parameters suggests that it may be worthwhile for future research to focus on providing better estimates of the mortality attributable to CR-BSI and the effectiveness of both SPC and CH/SSD (int/ext) catheters. In the second evaluation of the catheter care bundle relative to A-CVCs, the results which do not consider uncertainty indicate that a bundle must achieve a relative risk of CR-BSI of at least 0.45 to be cost-effective relative to MR catheters. If the bundle can reduce rates of infection from 2.5% to effectively zero, it is cost-effective relative to MR catheters if national implementation costs are less than $2.6 million ($56,610 per ICU). If the bundle can achieve a relative risk of 0.34 (comparable to that reported in the literature) it is cost-effective, relative to MR catheters, if costs over an 18 month period are below $613,795 nationally ($13,343 per ICU). Once uncertainty in the decision is considered, the cost threshold for the bundle increases to $2.2 million. Therefore, if each of the 46 Level III ICUs could implement an 18 month catheter care bundle for less than $47,826 each, this approach would be cost effective relative to A-CVCs. However, the uncertainty is substantial and the probability of error in concluding that the bundle is the cost-effective approach at a cost of $2.2 million is 89%. Conclusions: This work highlights that infection control to prevent CR-BSI is an efficient use of healthcare resources in the Australian context. If there is no further investment in infection control, an opportunity cost is incurred, which is the potential for a more efficient healthcare system. Minocycline/rifampicin catheters are the optimal choice of antimicrobial catheter for routine use in Australian Level III ICUs, however, if a catheter care bundle implemented in Australia was as effective as those used in the large studies in the United States it would be preferred over the catheters if it was able to be implemented for less than $47,826 per Level III ICU. Uncertainty is very high in this decision and arises from multiple sources. There are likely greater costs to this uncertainty for A-CVCs, which may carry hidden costs, than there are for a catheter care bundle, which is more likely to provide indirect benefits to clinical practice and patient safety. Research into the mortality attributable to CR-BSI, the effectiveness of SPC and CH/SSD (int/ext) catheters and the cost and effectiveness of a catheter care bundle in Australia should be prioritised to reduce uncertainty in this decision. This thesis provides the economic evidence to inform one area of infection control, but there are many other infection control decisions for which information about the cost-effectiveness of competing interventions does not exist. This work highlights some of the challenges and benefits to generating and using economic evidence for infection control decision-making and provides support for commissioning more research into the cost-effectiveness of infection control.

Nursing and Midwifery Services Strategic Directions, 2011-2015

This document presents the newly updated strategic directions for strengthening nursing and midwifery services (SDNM) for the period 2011–2015. Complementing and building on the 2002–2008 SDNM, it seeks to provide policymakers, practitioners and other stakeholders at every level with a flexible framework for broad-based, collaborative action to enhance the capacity of nurses and midwives to contribute to: * universal coverage * people-centred health care * policies affecting their practice and working conditions, and the * scaling up of national health systems to meet global goals and targets. The SDNM for 2011–2015 draws on several key World Health Assembly resolutions, and are underpinned by the associated global policy recommendations and codes of practice. (1,2) After two years of extensive research and consultation, a SDNM task force was developed, and a consensus on a range of specific activities revolving around 13 objectives in five interrelated key results areas (KRAs), was achieved: n health system and service strengthening n policy and practice * education, training and career development * workforce management and * partnership. Stakeholders, although free to prioritize certain parts of the framework to meet their own particular needs, are encouraged to adhere to the cornerstone of collaborative action, namely the common goal enshrined in the core SDNM 2011–2015 vision statement: improved health outcomes for individuals, families and communities through the provision of competent, culturally sensitive, evidence-based nursing and midwifery services.

Note on similarity solutions for viscous flow over an impermeable and non-linearly (quadratic) stretching sheet

Similarity solutions for flow over an impermeable, non-linearly (quadratic) stretching sheet were studied recently by Raptis and Perdikis (Int. J. Non-linear Mech. 41 (2006) 527–529) using a stream function of the form ψ=αxf(η)+βx2g(η). A fundamental error in their problem formulation is pointed out. On correction, it is shown that similarity solutions do not exist for this choice of ψ

The use of speech and lip modalities for robust speaker verification under adverse conditions

Investigates the use of lip information, in conjunction with speech information, for robust speaker verification in the presence of background noise. We have previously shown (Int. Conf. on Acoustics, Speech and Signal Proc., vol. 6, pp. 3693-3696, May 1998) that features extracted from a speaker's moving lips hold speaker dependencies which are complementary with speech features. We demonstrate that the fusion of lip and speech information allows for a highly robust speaker verification system which outperforms either subsystem individually. We present a new technique for determining the weighting to be applied to each modality so as to optimize the performance of the fused system. Given a correct weighting, lip information is shown to be highly effective for reducing the false acceptance and false rejection error rates in the presence of background noise

Implementation of ICD-11... perspectives from the Australian Bureau of Statistics

As the development of ICD-11 progresses, the Australian Bureau of Statistics is beginning to consider what will be required to successfully implement the new version of the classification. This paper will present early thoughts on the following: building understanding amongst the user community of upcoming changes and the implications of those changes; the need for training of coders and data users; development of analytical methods and conduct of comparability studies; processes to test, accept and implement new or updated coding software; assessment of coding quality; changes to data analyses and reporting processes; updates to regular publications; and assessing the resources required for successful implementation.

Experiences in training ICD-10 trainers

The National Centre for Health Information Research & Training (formerly NCCH Brisbane) has been conducting an annual introductory ICD-10 coding program in Brisbane for seven years. In 2008, the Centre introduced a new initiative, inviting potential trainers to participate in a one week train the trainer workshop prior to the regular coder training. The new trainers are provided with the opportunity to practice their new skills with the support and assistance of the NCHIRT trainers during the subsequent introductory program. This paper will report on the results of a survey of participants of these programs about their experiences conducting training courses in their own countries. The train the trainer program as a means to create a cadre of trainers to support the implementation of ICD-11 will be explored.

The rise of co-creative consumers : user experience sharing behaviour in online communities

This thesis examines consumer initiated value co-creation behaviour in the context of convergent mobile online services using a Service-Dominant logic (SD logic) theoretical framework. It focuses on non-reciprocal marketing phenomena such as open innovation and user generated content whereby new viable business models are derived and consumer roles and community become essential to the success of business. Attention to customers. roles and personalised experiences in value co-creation has been recognised in the literature (e.g., Prahalad & Ramaswamy, 2000; Prahalad, 2004; Prahalad & Ramaswamy, 2004). Similarly, in a subsequent iteration of their 2004 version of the foundations of SD logic, Vargo and Lusch (2006) replaced the concept of value co-production with value co-creation and suggested that a value co-creation mindset is essential to underpin the firm-customer value creation relationship. Much of this focus, however, has been limited to firm initiated value co-creation (e.g., B2B or B2C), while consumer initiated value creation, particularly consumer-to-consumer (C2C) has received little attention in the SD logic literature. While it is recognised that not every consumer wishes to make the effort to engage extensively in co-creation processes (MacDonald & Uncles, 2009), some consumers may not be satisfied with a standard product, instead they engage in the effort required for personalisation that potentially leads to greater value for themselves, and which may benefit not only the firm, but other consumers as well. Literature suggests that there are consumers who do, and as a result initiate such behaviour and expend effort to engage in co-creation activity (e.g., Gruen, Osmonbekov and Czaplewski, 2006; 2007 MacDonald & Uncles, 2009). In terms of consumers. engagement in value proposition (co-production) and value actualisation (co-creation), SD logic (Vargo & Lusch, 2004, 2008) provides a new lens that enables marketing scholars to transcend existing marketing theory and facilitates marketing practitioners to initiate service centric and value co-creation oriented marketing practices. Although the active role of the consumer is acknowledged in the SD logic oriented literature, we know little about how and why consumers participate in a value co-creation process (Payne, Storbacka, & Frow, 2008). Literature suggests that researchers should focus on areas such as C2C interaction (Gummesson 2007; Nicholls 2010) and consumer experience sharing and co-creation (Belk 2009; Prahalad & Ramaswamy 2004). In particular, this thesis seeks to better understand consumer initiated value co-creation, which is aligned with the notion that consumers can be resource integrators (Baron & Harris, 2008) and more. The reason for this focus is that consumers today are more empowered in both online and offline contexts (Füller, Mühlbacher, Matzler, & Jawecki, 2009; Sweeney, 2007). Active consumers take initiatives to engage and co-create solutions with other active actors in the market for their betterment of life (Ballantyne & Varey, 2006; Grönroos & Ravald, 2009). In terms of the organisation of the thesis, this thesis first takes a „zoom-out. (Vargo & Lusch, 2011) approach and develops the Experience Co-Creation (ECo) framework that is aligned with balanced centricity (Gummesson, 2008) and Actor-to-Actor worldview (Vargo & Lusch, 2011). This ECo framework is based on an extended „SD logic friendly lexicon. (Lusch & Vargo, 2006): value initiation and value initiator, value-in-experience, betterment centricity and betterment outcomes, and experience co-creation contexts derived from five gaps identified from the SD logic literature review. The framework is also designed to accommodate broader marketing phenomena (i.e., both reciprocal and non-reciprocal marketing phenomena). After zooming out and establishing the ECo framework, the thesis takes a zoom-in approach and places attention back on the value co-creation process. Owing to the scope of the current research, this thesis focuses specifically on non-reciprocal value co-creation phenomena initiated by consumers in online communities. Two emergent concepts: User Experience Sharing (UES) and Co-Creative Consumers are proposed grounded in the ECo framework. Together, these two theorised concepts shed light on the following two propositions: (1) User Experience Sharing derives value-in-experience as consumers make initiative efforts to participate in value co-creation, and (2) Co-Creative Consumers are value initiators who perform UES. Three research questions were identified underpinning the scope of this research: RQ1: What factors influence consumers to exhibit User Experience Sharing behaviour? RQ2: Why do Co-Creative Consumers participate in User Experience Sharing as part of value co-creation behaviour? RQ3: What are the characteristics of Co-Creative Consumers? To answer these research questions, two theoretical models were developed: the User Experience Sharing Behaviour Model (UESBM) grounded in the Theory of Planned Behaviour framework, and the Co-Creative Consumer Motivation Model (CCMM) grounded in the Motivation, Opportunity, Ability framework. The models use SD logic consistent constructs and draw upon multiple streams of literature including consumer education, consumer psychology and consumer behaviour, and organisational psychology and organisational behaviour. These constructs include User Experience Sharing with Other Consumers (UESC), User Experience Sharing with Firms (UESF), Enjoyment in Helping Others (EIHO), Consumer Empowerment (EMP), Consumer Competence (COMP), and Intention to Engage in User Experience Sharing (INT), Attitudes toward User Experience Sharing (ATT) and Subjective Norm (SN) in the UESBM, and User Experience Sharing (UES), Consumer Citizenship (CIT), Relating Needs of Self (RELS) and Relating Needs of Others (RELO), Newness (NEW), Mavenism (MAV), Use Innovativeness (UI), Personal Initiative (PIN) and Communality (COMU) in the CCMM. Many of these constructs are relatively new to marketing and require further empirical evidence for support. Two studies were conducted to underpin the corresponding research questions. Study One was conducted to calibrate and re-specify the proposed models. Study Two was a replica study to confirm the proposed models. In Study One, data were collected from a PC DIY online community. In Study Two, a majority of data were collected from Apple product online communities. The data were examined using structural equation modelling and cluster analysis. Considering the nature of the forums, the Study One data is considered to reflect some characteristics of Prosumers and the Study Two data is considered to reflect some characteristics of Innovators. The results drawn from two independent samples (N = 326 and N = 294) provide empirical support for the overall structure theorised in the research models. The results in both models show that Enjoyment in Helping Others and Consumer Competence in the UESBM, and Consumer Citizenship and Relating Needs in CCMM have significant impacts on UES. The consistent results appeared in both Study One and Study Two. The results also support the conceptualisation of Co-Creative Consumers and indicate Co-Creative Consumers are individuals who are able to relate the needs of themselves and others and feel a responsibility to share their valuable personal experiences. In general, the results shed light on "How and why consumers voluntarily participate in the value co-creation process?. The findings provide evidence to conceptualise User Experience Sharing behaviour as well as the Co-Creative Consumer using the lens of SD logic. This research is a pioneering study that incorporates and empirically tests SD logic consistent constructs to examine a particular area of the logic – that is consumer initiated value co-creation behaviour. This thesis also informs practitioners about how to facilitate and understand factors that engage with either firm or consumer initiated online communities.

Practical client puzzles in the standard model

Client puzzles are cryptographic problems that are neither easy nor hard to solve. Most puzzles are based on either number theoretic or hash inversions problems. Hash-based puzzles are very efficient but so far have been shown secure only in the random oracle model; number theoretic puzzles, while secure in the standard model, tend to be inefficient. In this paper, we solve the problem of constucting cryptographic puzzles that are secure int he standard model and are very efficient. We present an efficient number theoretic puzzle that satisfies the puzzle security definition of Chen et al. (ASIACRYPT 2009). To prove the security of our puzzle, we introduce a new variant of the interval discrete logarithm assumption which may be of independent interest, and show this new problem to be hard under reasonable assumptions. Our experimental results show that, for 512-bit modulus, the solution verification time of our proposed puzzle can be up to 50x and 89x faster than the Karame-Capkum puzzle and the Rivest et al.'s time-lock puzzle respectively. In particular, the solution verification tiem of our puzzle is only 1.4x slower than that of Chen et al.'s efficient hash based puzzle.

Reduced expression of retinoblastoma gene product (pRB) and high expression of p53 are associated with poor prognosis in ovarian cancer

Paraffin sections (n = 168, 27 benign, 16 low malignant potential [LMP] and 125 malignant tumours) from epithelial ovarian tumours were evaluated immunohistochemically for expression of retinoblastoma gene product (pRB) and p53 protein, and the relationship among pRB, p53 and cyclin-dependent kinase inhibitor 2 (CDKN2) gene product p16INK4A (p16) was analysed, following our previous study of p16. Forty-one percent of the benign, 50% of the LMP and most (71%) of the malignant tumours showed high pRB expression. High expression of pRB (>50% pRB-positive cells) significantly correlated with non-mucinous histological subtypes. Reduced pRB expression, substage and residual disease were significant predictors for poor prognosis in stage I patients. All the benign and most of the LMP (81%) tumours were in either the p53-negative or low p53-positive category, but nearly half of the malignant tumours had high p53 expression. High p53 accumulation was found in non-mucinous, high grade and late stage tumours. For well-differentiated carcinomas, high p53 expression was a predictor of poor prognosis. However, even though high p53 expression was not associated with histological subtype, stage or the presence of residual disease, high p53 expression was not an independent predictor when all clinical parameters were combined. For all ovarian cancers, a close correlation was found between high p53 and high p16 expression. The relationship between the expression of pRB and p16 depended on tumour stage. In stage I tumours, high pRB was associated with low p16 reactivity. On the other hand, most advanced tumours showed both high pRB and high p16 reactivity. Int. J. Cancer 74:407–415, 1997. © 1997 Wiley-Liss, Inc.