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.

MIMO and SISO identification of radiation force terms for models of marine structures in waves

This paper presents a discussion on the use of MIMO and SISO techniques for identification of the radiation force terms in models for surface vessels. We compare and discuss two techniques recently proposed in literature for this application: time domain identification and frequency domain identification. We compare the methods in terms of estimates model order, accuracy of the fit, use of the available information, and ease of use and implementation.

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?"

2nd ESMO consensus conference on lung cancer : early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, earlystage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on early-stage disease. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

In vitro investigations on the effect of dermal fibroblasts on keratinocyte responses to ultraviolet B radiation

Exposure to ultraviolet radiation is closely linked to the development of skin cancers in humans. The ultraviolet B (UVB) radiation wavelength (280-320 nm), in particular, causes DNA damage in epidermal keratinocytes, which are linked to the generation of signature premalignant mutations. Interactions between dermal fibroblasts and keratinocytes play a role in epidermal repair and regeneration after UVB-induced damage. To investigate these processes, established two and three-dimensional culture models were utilized to study the impact of fibroblast-keratinocyte crosstalk during the acute UVB response. Using a coculture system it was observed that fibroblasts enhanced keratinocyte survival and the repair of cyclobutane pyrimidine dimers (CPDs) after UVB radiation exposure. These findings were also mirrored in irradiated human skin coculture models employed in this study. Fibroblast coculture was shown to play a role in the expression and activation of members of the apoptotic cascade, including caspase-3 and Bad. Interestingly, the expression and phosphorylation of p53, a key player in the regulation of keratinocyte cell fate postirradiation, was also shown to be influenced by fibroblast-produced factors. This study highlights the importance of synergistic interactions between fibroblasts and keratinocytes in maintaining a functional epidermis while promoting repair and regeneration following UVB radiation-induced damage.

Predicting the likelihood of non-healing : a venous leg ulcer risk assessment tool

This project developed, validated and tested reliability of a risk assessment tool to predict the risk of failure to heal of patients with venous leg ulcers within 24 weeks. The risk assessment tool will allow clinicians to be able to determine realistic outcomes for their patients, promote early healing and potentially avoid weeks of inappropriate therapy. The tool will also assist in addressing specific risk factors and guide decisions on early, alternative, tailored interventions.

Gliptins - do they increase cardiovascular risk or benefit?

INTRODUCTION: In 2008, the US FDA required all new glucose-lowering therapies to show cardiovascular safety, and this applies to the dipeptidyl peptidase-4 inhibitors ('gliptins'). AREAS COVERED: The cardiovascular safety trials of saxagliptin and alogliptin have recently been published and are the subject of this evaluation. EXPERT OPINION: The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus - Thrombolysis in Myocardial Infarction 53 trial and Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care were both multicentre, randomised, double-blind, placebo-controlled, Phase IV clinical trials. These trials showed that saxagliptin and alogliptin did not increase the primary end point, which was a composite of cardiovascular outcomes that did not include hospitalisations for heart failure. However, saxagliptin significantly increased hospitalisation for heart failure, which was a component of the secondary end point. The effect of alogliptin on hospitalisations for heart failure has not been reported. Neither agent improved cardiovascular outcomes. As there is no published evidence of improved outcomes with gliptins, it is unclear to us why these agents are so widely available for use. We suggest that the use of gliptins be restricted to Phase IV clinical trials until such time as cardiovascular safety and benefits/superiority are clearly established

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.

Clinical perceptions of radiation therapy undergraduate competency standards

Introduction The multifactorial nature of clinical skills development makes assessment of undergraduate radiation therapist competence level by clinical mentors challenging. A recent overhaul of the clinical assessment strategy at Queensland University of Technology has moved away from the high-stakes Observed Structured Clinical Examination (OSCE) to encompass a more continuous measure of competence. This quantitative study aimed to gather stakeholder evidence to inform development of standards by which to measure student competence for a range of levels of progression. Methods A simple anonymous questionnaire was distributed to all Queensland radiation therapists. The tool asked respondents to assign different levels of competency with a range of clinical tasks to different levels of student. All data were anonymous and was combined for analysis using Microsoft Excel. Results Feedback indicated good agreement with tasks that specified amount of direction required and this has been incorporated into the new clinical achievements record that the students need to have signed off. Additional puzzling findings suggested higher expectations with planning tasks than with treatment-based tasks. Conclusion The findings suggest that the amount of direction required by students is a valid indicator of their level and has been adopted into the clinical assessment scheme. Further work will build on this to further define standards of competency for undergraduates.

Evaluation of the efficacy of radiation-modifying compounds using γH2AX as a molecular marker of DNA double-strand breaks

Radiation therapy is a widely used therapeutic approach for cancer. To improve the efficacy of radiotherapy there is an intense interest in combining this modality with two broad classes of compounds, radiosensitizers and radioprotectors. These either enhance tumour-killing efficacy or mitigate damage to surrounding non-malignant tissue, respectively. Radiation exposure often results in the formation of DNA double-strand breaks, which are marked by the induction of H2AX phosphorylation to generate γH2AX. In addition to its essential role in DDR signalling and coordination of double-strand break repair, the ability to visualize and quantitate γH2AX foci using immunofluorescence microscopy techniques enables it to be exploited as an indicator of therapeutic efficacy in a range of cell types and tissues. This review will explore the emerging applicability of γH2AX as a marker for monitoring the effectiveness of radiation-modifying compounds.

Quantification of gammaH2AX foci in response to ionising radiation

DNA double-strand breaks (DSBs), which are induced by either endogenous metabolic processes or by exogenous sources, are one of the most critical DNA lesions with respect to survival and preservation of genomic integrity. An early response to the induction of DSBs is phosphorylation of the H2A histone variant, H2AX, at the serine-139 residue, in the highly conserved C-terminal SQEY motif, forming gammaH2AX(1). Following induction of DSBs, H2AX is rapidly phosphorylated by the phosphatidyl-inosito 3-kinase (PIKK) family of proteins, ataxia telangiectasia mutated (ATM), DNA-protein kinase catalytic subunit and ATM and RAD3-related (ATR)(2). Typically, only a few base-pairs (bp) are implicated in a DSB, however, there is significant signal amplification, given the importance of chromatin modifications in DNA damage signalling and repair. Phosphorylation of H2AX mediated predominantly by ATM spreads to adjacent areas of chromatin, affecting approximately 0.03% of total cellular H2AX per DSB(2,3). This corresponds to phosphorylation of approximately 2000 H2AX molecules spanning approximately 2 Mbp regions of chromatin surrounding the site of the DSB and results in the formation of discrete gammaH2AX foci which can be easily visualized and quantitated by immunofluorescence microscopy(2). The loss of gammaH2AX at DSB reflects repair, however, there is some controversy as to what defines complete repair of DSBs; it has been proposed that rejoining of both strands of DNA is adequate however, it has also been suggested that re-instatement of the original chromatin state of compaction is necessary(4-8). The disappearence of gammaH2AX involves at least in part, dephosphorylation by phosphatases, phosphatase 2A and phosphatase 4C(5,6). Further, removal of gammaH2AX by redistribution involving histone exchange with H2A.Z has been implicated(7,8). Importantly, the quantitative analysis of gammaH2AX foci has led to a wide range of applications in medical and nuclear research. Here, we demonstrate the most commonly used immunofluorescence method for evaluation of initial DNA damage by detection and quantitation of gammaH2AX foci in gamma-irradiated adherent human keratinocytes(9)