NT-ProBNP levels in saliva and its clinical relevance to heart failure

Background: Current blood based diagnostic assays to detect heart failure (HF) have large intra-individual and inter-individual variations which have made it difficult to determine whether the changes in the analyte levels reflect an actual change in disease activity. Human saliva mirrors the body's health and well being and similar to 20% of proteins that are present in blood are also found in saliva. Saliva has numerous advantages over blood as a diagnostic fluid which allows for a non-invasive, simple, and safe sample collection. The aim of our study was to develop an immunoassay to detect NT-proBNP in saliva and to determine if there is a correlation with blood levels. Methods: Saliva samples were collected from healthy volunteers (n = 40) who had no underlying heart conditions and HF patients (n = 45) at rest. Samples were stored at -80 degrees C until analysis. A customised homogeneous sandwich AlphaLISA((R)) immunoassay was used to quantify NT-proBNP levels in saliva. Results: Our NT-proBNP immunoassay was validated against a commercial Roche assay on plasma samples collected from HF patients (n = 37) and the correlation was r(2) = 0.78 (p<0.01, y = 1.705 x +1910.8). The median salivary NT-proBNP levels in the healthy and HF participants were <16 pg/mL and 76.8 pg/mL, respectively. The salivary NT-proBNP immunoassay showed a clinical sensitivity of 82.2% and specificity of 100%, positive predictive value of 100% and negative predictive value of 83.3%, with an overall diagnostic accuracy of 90.6%. Conclusion: We have firstly demonstrated that NT-proBNP can be detected in saliva and that the levels were higher in heart failure patients compared with healthy control subjects. Further studies will be needed to demonstrate the clinical relevance of salivary NT-proBNP in unselected, previously undiagnosed populations.

Circulating fragments of N-Terminal Pro-B-Type Natriuretic Peptides in plasma of heart failure patients

BACKGROUND: The use of nonstandardized N-terminal pro-B-type natriuretic peptide (NT-proBNP) assays can contribute to the misdiagnosis of heart failure (HF). Moreover, there is yet to be established a common consensus regarding the circulating forms of NT-proBNP being used in current assays. We aimed to characterize and quantify the various forms of NT-proBNP in the circulation of HF patients. METHODS: Plasma samples were collected from HF patients (n = 20) at rest and stored at -80 degrees C. NT-proBNP was enriched from HF patient plasma by use of immunoprecipitation followed by mass spectrometric analysis. Customized homogeneous sandwich AlphaLISA (R) immunoassays were developed and validated to quantify 6 fragments of NT-proBNP. RESULTS: Mass spectrometry identified the presence of several N- and C-terminally processed forms of circulating NT-proBNP, with physiological proteolysis between Pro2-Leu3, Leu3-Gly4, Pro6-Gly7, and Pro75-Arg76. Consistent with this result, AlphaLISA immunoassays demonstrated that antibodies targeting the extreme N or C termini measured a low apparent concentration of circulating NT-proBNP. The apparent circulating NT-proBNP concentration was increased with antibodies targeting nonglycosylated and nonterminal epitopes (P < 0.05). CONCLUSIONS: In plasma collected from HF patients, immunoreactive NT-proBNP was present as multiple N- and C-terminally truncated fragments of the full length NT-proBNP molecule. Immunodetection of NT-proBNP was significantly improved with the use of antibodies that did not target these terminal regions. These findings support the development of a next generation NT-proBNP assay targeting nonterminal epitopes as well as avoiding the central glycosylated region of this molecule. (c) 2013 American Association for Clinical Chemistry

A rapid and cost-effective method of producing recombinant proBNP and NT-proBNP variants in Escherichia coli for immunoassay of heart failure

The measurements of plasma natriuretic peptides (NT-proBNP, proBNP and BNP) are used to diagnose heart failure but these are expensive to produce. We describe a rapid, cheap and facile production of proteins for immunoassays of heart failure. DNA encoding N-terminally His-tagged NT-proBNP and proBNP were cloned into the pJexpress404 vector. ProBNP and NT-proBNP peptides were expressed in Escherichia coli, purified and refolded in vitro. The analytical performance of these peptides were comparable with commercial analytes (NT-proBNP EC50 for the recombinant is 2.6 ng/ml and for the commercial material is 5.3 ng/ml) and the EC50 for recombinant and commercial proBNP, are 3.6 and 5.7 ng/ml respectively). Total yield of purified refolded NT-proBNP peptide was 1.75 mg/l and proBNP was 0.088 mg/l. This approach may also be useful in expressing other protein analytes for immunoassay applications. To develop a cost effective protein expression method in E. coli to obtain high yields of NT-proBNP (1.75 mg/l) and proBNP (0.088 mg/l) peptides for immunoassay use.

Understanding causal relationships between the built and social environment, health and associated behaviours and risk factors

Introduction: Built environment interventions designed to reduce non-communicable diseases and health inequity, complement urban planning agendas focused on creating more ‘liveable’, compact, pedestrian-friendly, less automobile dependent and more socially inclusive cities.However, what constitutes a ‘liveable’ community is not well defined. Moreover, there appears to be a gap between the concept and delivery of ‘liveable’ communities. The recently funded NHMRC Centre of Research Excellence (CRE) in Healthy Liveable Communities established in early 2014, has defined ‘liveability’ from a social determinants of health perspective. Using purpose-designed multilevel longitudinal data sets, it addresses five themes that address key evidence-base gaps for building healthy and liveable communities. The CRE in Healthy Liveable Communities seeks to generate and exchange new knowledge about: 1) measurement of policy-relevant built environment features associated with leading non-communicable disease risk factors (physical activity, obesity) and health outcomes (cardiovascular disease, diabetes) and mental health; 2) causal relationships and thresholds for built environment interventions using data from longitudinal studies and natural experiments; 3) thresholds for built environment interventions; 4) economic benefits of built environment interventions designed to influence health and wellbeing outcomes; and 5) factors, tools, and interventions that facilitate the translation of research into policy and practice. This evidence is critical to inform future policy and practice in health, land use, and transport planning. Moreover, to ensure policy-relevance and facilitate research translation, the CRE in Healthy Liveable Communities builds upon ongoing, and has established new, multi-sector collaborations with national and state policy-makers and practitioners. The symposium will commence with a brief introduction to embed the research within an Australian health and urban planning context, as well as providing an overall outline of the CRE in Healthy Liveable Communities, its structure and team. Next, an overview of the five research themes will be presented. Following these presentations, the Discussant will consider the implications of the research and opportunities for translation and knowledge exchange. Theme 2 will establish whether and to what extent the neighbourhood environment (built and social) is causally related to physical and mental health and associated behaviours and risk factors. In particular, research conducted as part of this theme will use data from large-scale, longitudinal-multilevel studies (HABITAT, RESIDE, AusDiab) to examine relationships that meet causality criteria via statistical methods such as longitudinal mixed-effect and fixed-effect models, multilevel and structural equation models; analyse data on residential preferences to investigate confounding due to neighbourhood self-selection and to use measurement and analysis tools such as propensity score matching and ‘within-person’ change modelling to address confounding; analyse data about individual-level factors that might confound, mediate or modify relationships between the neighbourhood environment and health and well-being (e.g., psychosocial factors, knowledge, perceptions, attitudes, functional status), and; analyse data on both objective neighbourhood characteristics and residents’ perceptions of these objective features to more accurately assess the relative contribution of objective and perceptual factors to outcomes such as health and well-being, physical activity, active transport, obesity, and sedentary behaviour. At the completion of the Theme 2, we will have demonstrated and applied statistical methods appropriate for determining causality and generated evidence about causal relationships between the neighbourhood environment, health, and related outcomes. This will provide planners and policy makers with a more robust (valid and reliable) basis on which to design healthy communities.

Institutional investors, risk/return and corporate governance : practical lessons from the Global Financial Crisis

The global grown in institutional investors means that firms can no longer ignore their influence in capital markets. However, not all institutional investors have the same motives to influence the firms they invest in. Institution investors' ability to influence management depends on the size of their investment and whether they have any business relations with the firm. Using a sample of Australian firms from 2006 to 2008, our empirical results show that the proportion of a company's shares held by institutional investors is positively associated with firm governance ratings, risk and profitability. This study shows that a positive association between risk and return is associated with large active institutional ownership, which we interpret as shareholders with sufficient power to pressure management to increase short-term profits.

Analysis of risk management disclosures by Australian publicly listed companies

In the aftermath of the global financial crisis, effective risk management (RM) and its communication to stakeholders are now considered essential components in corporate governance. However, despite the importance of RM communication, it is still unclear how and to what extent disclosures in financial reports can achieve effective communication of RM activities. The situation is hampered by the paucity of international RM Research that captures institution differences in corporate governance standards. The Australian setting provides an ideal environment in which to examine RM communication because the Australian Securities Exchange (ASX) has since 2007 recommended RM disclosures under its principle-based governance rules. The recommendations are contained in Principle 7 of the Corporate Governance Principles and recommendations (ASX CGPR). Accordingly, to assess the effectiveness of the AXS's RM governance principle, this study examines the nature and extent of RM disclosures reported by major ASX-listed firms. Using a mixed method approach (thematic content analysis and a series of regression analysis) we find widespread divergence in disclosure practices and low conformance with the Principle 7 recommendations. Certain corporate governance mechanisms appear to influence some categories of RM dislcosure but equity risk has surprisingly little explanatory power. These results suggest that the RM disclosures practices observed in the Australian setting may not be meeting the objectives of regulators and the needs of stakeholders.

The value of tail risk hedging in defined contribution plans: What does history tell us

Hedging against tail events in equity markets has been forcefully advocated in the aftermath of recent global financial crisis. Whether this is beneficial to long horizon investors like employees enrolled in defined contribution (DC) plans, however, has been subject to criticism. We conduct historical simulation since 1928 to examine the effectiveness of active and passive tail risk hedging using out of money put options for hypothetical equity portfolios of DC plan participants with 20 years to retirement. Our findings show that the cost of tail hedging exceeds the benefits for a majority of the plan participants during the sample period. However, for a significant number of simulations, hedging result in superior outcomes relative to an unhedged position. Active tail hedging is more effective when employees confront several panic-driven periods characterized by short and sharp market swings in the equity markets over the investment horizon. Passive hedging, on the other hand, proves beneficial when they encounter an extremely rare event like the Great Depression as equity markets go into deep and prolonged decline.

Faster parameter estimation using risk-sensitive filters

In this paper, we propose a risk-sensitive approach to parameter estimation for hidden Markov models (HMMs). The parameter estimation approach considered exploits estimation of various functions of the state, based on model estimates. We propose certain practical suboptimal risk-sensitive filters to estimate the various functions of the state during transients, rather than optimal risk-neutral filters as in earlier studies. The estimates are asymptotically optimal, if asymptotically risk neutral, and can give significantly improved transient performance, which is a very desirable objective for certain engineering applications. To demonstrate the improvement in estimation simulation studies are presented that compare parameter estimation based on risk-sensitive filters with estimation based on risk-neutral filters.

The relationship between 'reasonably practicable'and risk management regulation

This paper examines two concepts which are central to contemporary standard setting in occupational health and safety (OHS) regulation, and explores the differences and similarities between these concepts – the notion of ‘reasonably practicable’ which qualifies the ‘general duties’ and some other provisions in the Australian OHS standards, and the risk management requirements typically found in OHS regulations and approved codes of practice (advisory standards in Queensland).

Outsourcing risk -the regulation of occupational health and safety where subcontractors are employed

The subcontracting out of production tasks and services is not a new phenomenon, but from the late 1970s, and more especially over the last 15years, the practice-now frequently referred to as outsourcing-has grown substantially across a range of industries in most industrialized countries.Recent surveys undertaken in the United States,Europe,and Australia have all identified a rapid increase in outsourcing/subcontracting, especially amongst large private and public sector organizations. The Second Australian Workplace Industrial Relations Survey found that the number of contractors, agency workers, outworkers, and volunteers had increased by almost 40% in the last 5 years to 1997 with contracting out more common in the public sector than the private sector. Outsourcing has become a major tool by which large organizations have sought to increase competitiveness/cut costs, bypass regulatory controls, and secure more flexible employment arrangements.

OHS inspectors and psychosocial risk factors: Evidence from Australia

Legislation giving prominence to psychosocial risk factors at work has changed the role of government occupational health and safety (OHS) inspectors in many countries. Yet little is known about how inspectorates have responded to these changes. Between 2003 and 2007 an Australian study was undertaken on OHS standards, entailing detailed documentary analysis, interviews with 36 inspectorate managers and 89 inspectors, and observations made when researchers accompanied inspectors on 120 typical workplace visits. Our study found that general duty provisions in OHS legislation clearly incorporated psychosocial hazards and inspectorates had introduced guidance material, pursued campaigns and increased interventions in this area. However, the regulatory framework remained narrow (focused on bullying/harassment, occupational violence and work stress) and workplace visits revealed psychosocial hazards as a marginal area of inspectorate activity. These findings were reinforced in interviews. While aware of psychosocial hazards inspectors often saw the issue as problematic due to limited training, resourcing constraints, deficiencies in regulation and fears of victimisation amongst workers. In order to address these problems a number of changes are required that recognize the distinctiveness of psychosocial hazards including their ‘invisibility’. Notable here are revisions to regulation (both general duty provisions and specific codes), the development of comprehensive guidance and assessment tools to be used by inspectors, greater use of procedural enforcement, and enhanced inspectorate resourcing and training. There is also a need to recognize complex inter-linkages between psychosocial hazards and the industrial relations context.

Flood victim’s heartbreak : ‘don’t be complacent about the risk’

"No one had higher stakes in the findings of the Queensland Floods Commission of Inquiry than Grantham father Matthew Keep, whose mother, mother-in-law and baby daughter, Jessica, died at Grantham that terrible day in January. For seven months he has read every statement, submission, running log, disaster management plan and media article available. As he has comforted his grieving wife, Stacy, helped care for his two young children Madison, 5, and Jacob, 4, who amazingly survived the flood, and welcomed a new baby into the family, Matthew has searched for answers for himself and his community. Why were authorities not able to warn people in seven towns in Toowoomba and the Lockyer Valley that the worst flash flooding in at least a century was about to strike, killing 22 people? How could such a sudden and catastrophic flood claim three members of his family within minutes?"

Prevalence of malnutrition, obesity and nutritional risk of Australian paediatric inpatients: A national one-day snapshot

Aim Low prevalence rates of malnutrition at 2.5% to 4% have previously been reported in two tertiary paediatric Australian hospitals. The current study is the first to measure the prevalence of malnutrition, obesity and nutritional risk of paediatric inpatients in multiple hospitals throughout Australia. Methods Malnutrition, obesity and nutritional risk prevalence were investigated in 832 and 570 paediatric inpatients, respectively, in eight tertiary paediatric hospitals and eight regional hospitals across Australia on a single day. Malnutrition and obesity prevalence was determined using z-scores and body mass index (BMI) percentiles. High nutritional risk was determined as a Paediatric Yorkhill Malnutrition Score of 2 or more. Results The prevalence rates of malnourished, wasted, stunted, overweight and obese paediatric patients were 15%, 13.8%, 11.9%, 8.8% and 9.9%, respectively. Patients who identified as Aboriginal and Torres Strait Islander were more likely to have lower height-for-age z-scores (P < 0.01); however, BMI and weight-for-age z-scores were not significantly different. Children who were younger, from regional hospitals or with a primary diagnosis of cardiac disease or cystic fibrosis had significantly lower anthropometric z-scores (P = 0.05). Forty-four per cent of patients were identified as at high nutritional risk and requiring further nutritional assessment. Conclusions The prevalence of malnutrition and nutritional risk of Australian paediatric inpatients on a given day was much higher when compared with the healthy population. In contrast, the proportion of overweight and obese patients was less.

Activity patterns of preschool-aged children at risk for obesity

BACKGROUND Although the prevalence of obesity in young children highlights the importance of early interventions to promote physical activity (PA), there are limited data on activity patterns in this age group. The purpose of this study is to describe activity patterns in preschool-aged children and explore differences by weight status. METHODS Analyses use baseline data from Healthy Homes/Healthy Kids- Preschool, a pilot obesity prevention trial of preschool-aged children overweight or at risk for overweight. A modified parent-reported version of the previous-day PA recall was used to summarize types of activity. Accelerometry was used to summarize daily and hourly activity patterns. RESULTS "Playing with toys" accounted for the largest proportion of a child's previous day, followed by "meals and snacks", and "chores". Accelerometry-measured daily time spent in sedentary behavior, light PA, and moderate-to-vigorous PA (MVPA) was 412, 247, and 69 minutes, respectively. Percent of hourly time spent in MVPA ranged from 3% to 13%, peaking in the late morning and evening hours. There were no statistically significant MVPA differences by weight status. CONCLUSIONS This study extends our understanding of activity types, amounts, and patterns in preschool-age children and warrants further exploration of differences in physical activity patterns by weight status.