Integrated genomic characterization of endometrial carcinoma

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

On the time spent preparing grant proposals : an observational study of Australian researchers

Objective: To estimate the time spent by the researchers for preparing grant proposals, and to examine whether spending more time increase the chances of success. Design: Observational study. Setting: The National Health and Medical Research Council (NHMRC) of Australia. Participants: Researchers who submitted one or more NHMRC Project Grant proposals in March 2012. Main outcome measures: Total researcher time spent preparing proposals; funding success as predicted by the time spent. Results: The NHMRC received 3727 proposals of which 3570 were reviewed and 731 (21%) were funded. Among our 285 participants who submitted 632 proposals, 21% were successful. Preparing a new proposal took an average of 38 working days of researcher time and a resubmitted proposal took 28 working days, an overall average of 34 days per proposal. An estimated 550 working years of researchers' time (95% CI 513 to 589) was spent preparing the 3727 proposals, which translates into annual salary costs of AU$66 million. More time spent preparing a proposal did not increase the chances of success for the lead researcher (prevalence ratio (PR) of success for 10 day increase=0.91, 95% credible interval 0.78 to 1.04) or other researchers (PR=0.89, 95% CI 0.67 to 1.17). Conclusions: Considerable time is spent preparing NHMRC Project Grant proposals. As success rates are historically 20–25%, much of this time has no immediate benefit to either the researcher or society, and there are large opportunity costs in lost research output. The application process could be shortened so that only information relevant for peer review, not administration, is collected. This would have little impact on the quality of peer review and the time saved could be reinvested into research.

A new first-order decision-making model for the procurement of public sector infrastructure: Procedures and Testing

Given global demand for new infrastructure, governments face substantial challenges in funding new infrastructure and delivering Value for Money (VfM). As part of the background to this challenge, a critique is given of current practice in the selection of the approach to procure major public sector infrastructure in Australia and which is akin to the Multi-Attribute Utility Approach (MAUA). To contribute towards addressing the key weaknesses of MAUA, a new first-order procurement decision-making model is presented. The model addresses the make-or-buy decision (risk allocation); the bundling decision (property rights incentives), as well as the exchange relationship decision (relational to arms-length exchange) in its novel approach to articulating a procurement strategy designed to yield superior VfM across the whole life of the asset. The aim of this paper is report on the development of this decisionmaking model in terms of the procedural tasks to be followed and the method being used to test the model. The planned approach to testing the model uses a sample of 87 Australian major infrastructure projects in the sum of AUD32 billion and deploys a key proxy for VfM comprising expressions of interest, as an indicator of competition.

Multi-criteria ranking and source apportionment of airborne particulate matter

Particulate matter research is essential because of the well known significant adverse effects of aerosol particles on human health and the environment. In particular, identification of the origin or sources of particulate matter emissions is of paramount importance in assisting efforts to control and reduce air pollution in the atmosphere. This thesis aims to: identify the sources of particulate matter; compare pollution conditions at urban, rural and roadside receptor sites; combine information about the sources with meteorological conditions at the sites to locate the emission sources; compare sources based on particle size or mass; and ultimately, provide the basis for control and reduction in particulate matter concentrations in the atmosphere. To achieve these objectives, data was obtained from assorted local and international receptor sites over long sampling periods. The samples were analysed using Ion Beam Analysis and Scanning Mobility Particle Sizer methods to measure the particle mass with chemical composition and the particle size distribution, respectively. Advanced data analysis techniques were employed to derive information from large, complex data sets. Multi-Criteria Decision Making (MCDM), a ranking method, drew on data variability to examine the overall trends, and provided the rank ordering of the sites and years that sampling was conducted. Coupled with the receptor model Positive Matrix Factorisation (PMF), the pollution emission sources were identified and meaningful information pertinent to the prioritisation of control and reduction strategies was obtained. This thesis is presented in the thesis by publication format. It includes four refereed papers which together demonstrate a novel combination of data analysis techniques that enabled particulate matter sources to be identified and sampling site/year ranked. The strength of this source identification process was corroborated when the analysis procedure was expanded to encompass multiple receptor sites. Initially applied to identify the contributing sources at roadside and suburban sites in Brisbane, the technique was subsequently applied to three receptor sites (roadside, urban and rural) located in Hong Kong. The comparable results from these international and national sites over several sampling periods indicated similarities in source contributions between receptor site-types, irrespective of global location and suggested the need to apply these methods to air pollution investigations worldwide. Furthermore, an investigation into particle size distribution data was conducted to deduce the sources of aerosol emissions based on particle size and elemental composition. Considering the adverse effects on human health caused by small-sized particles, knowledge of particle size distribution and their elemental composition provides a different perspective on the pollution problem. This thesis clearly illustrates that the application of an innovative combination of advanced data interpretation methods to identify particulate matter sources and rank sampling sites/years provides the basis for the prioritisation of future air pollution control measures. Moreover, this study contributes significantly to knowledge based on chemical composition of airborne particulate matter in Brisbane, Australia and on the identity and plausible locations of the contributing sources. Such novel source apportionment and ranking procedures are ultimately applicable to environmental investigations worldwide.

Examining the influence of participant performance factors on contractor satisfaction : a structural equation model

Participant performance is critical to the success of projects. At the same time, enhancing the satisfaction of participants not only helps in problem solving but also improves their motivation and cooperation. However, previous research related to participant satisfaction is primarily concerned with clients and customers and relatively little attention has been paid to contractors. This paper investigates how the performance of project participants affects contractor project satisfaction in terms of the client's clarity of objectives (OC) and promptness of payments (PP), designer carefulness (DC), construction risk management (RM), the effectiveness their contribution (EW) and mutual respect and trust (RT). With 125 valid responses from contractors in Malaysia, a contractor satisfaction model is developed based on structural equation modelling. The results demonstrate the necessity for dividing abstract satisfaction into two dimensions, comprising economic-related satisfaction (ES) and production-related satisfaction (PS), with DC, OC, PP and RM having significant effects on ES, while DC, OC, EW and RM influence PS. In addition, the model tests the indirect effects of these performance variables on ES and PS. In particular, OC indirectly affects ES and PS through mediation of RM and DC respectively. The results also provide opportunities for improving contractor satisfaction and supplementing the contractor selection criteria for clients.

Wasted efforts : centuries wasted on unsuccessful grant applications : new study

New Australian research has found scientists spent the equivalent of 550 working years applying for grants from the country's largest health and medical research grants scheme in 2012, and that around 75% of this time was spent on unsuccessful applications. The Queensland University of Technology (QUT) study also found that spending more time on a funding proposal did not equate to a greater chance of success.

Beat-mixing Rock music: Rock and electronic dance music merge to create the Manarays

This research introduces the proposition that Electronic Dance Music’s beat-mixing function could be implemented to create immediacy in other musical genres. The inclusion of rhythmic sections at the beginning and end of each musical work created a ‘DJ friendly’ environment. The term used in this thesis to refer to the application of beat-mixing in Rock music is ‘ClubRock’. Collaboration between a number of DJs and Rock music professionals applied the process of beat-mixing to blend Rock tracks to produce a continuous ClubRock set. The DJ technique of beat-mixing Rock music transformed static renditions into a fluid creative work. The hybridisation of the two genres, EDM and Rock, resulted in a contribution to Rock music compositional approaches and the production of a unique Rock album; Manarays—Get Lucky.

Humans, ‘things’ and space : costing hospital infection control interventions

Background: Previous attempts at costing infection control programmes have tended to focus on accounting costs rather than economic costs. For studies using economic costs, estimates tend to be quite crude and probably underestimate the true cost. One of the largest costs of any intervention is staff time, but this cost is difficult to quantify and has been largely ignored in previous attempts. Aim: To design and evaluate the costs of hospital-based infection control interventions or programmes. This article also discusses several issues to consider when costing interventions, and suggests strategies for overcoming these issues. Methods: Previous literature and techniques in both health economics and psychology are reviewed and synthesized. Findings: This article provides a set of generic, transferable costing guidelines. Key principles such as definition of study scope and focus on large costs, as well as pitfalls (e.g. overconfidence and uncertainty), are discussed. Conclusion: These new guidelines can be used by hospital staff and other researchers to cost their infection control programmes and interventions more accurately.

Determinants of contractor satisfaction

Performance in the construction industry is increasingly scrutinized as a result of the delays, cost overruns and poor quality of the industry’s products and services. Increasingly, disputes, conflicts and mismatches of objectives among participants are contributory factors. Performance measurement approaches have been developed to overcome these problems. However, these approaches focus primarily on objective measures to the exclusion of subjective measures, particularly those concerning contractor satisfaction (Co-S). The contractor satisfaction model (CoSMo) developed here is intended to rectify the situation. Data derived from a questionnaire survey of 75 large contractors in Malaysia in respect of a key project are analysed to identify participant factors and their strength of relationship with Co-S dimensions. The results are presented in the form of eight regression equations. The outcome is a tool for use by project participants to provide a better understanding of how they, and the project, affect contractor satisfaction. The developed model sheds some light on a hitherto unknown aspect of construction management in providing an increased awareness of the importance of major Malaysian construction contractors’ needs in the execution of successful projects.

Spatiotemporal model or time series model for assessing city-wide temperature effects on mortality?

Most studies examining the temperature–mortality association in a city used temperatures from one site or the average from a network of sites. This may cause measurement error as temperature varies across a city due to effects such as urban heat islands. We examined whether spatiotemporal models using spatially resolved temperatures produced different associations between temperature and mortality compared with time series models that used non-spatial temperatures. We obtained daily mortality data in 163 areas across Brisbane city, Australia from 2000 to 2004. We used ordinary kriging to interpolate spatial temperature variation across the city based on 19 monitoring sites. We used a spatiotemporal model to examine the impact of spatially resolved temperatures on mortality. Also, we used a time series model to examine non-spatial temperatures using a single site and the average temperature from three sites. We used squared Pearson scaled residuals to compare model fit. We found that kriged temperatures were consistent with observed temperatures. Spatiotemporal models using kriged temperature data yielded slightly better model fit than time series models using a single site or the average of three sites' data. Despite this better fit, spatiotemporal and time series models produced similar associations between temperature and mortality. In conclusion, time series models using non-spatial temperatures were equally good at estimating the city-wide association between temperature and mortality as spatiotemporal models.

A randomised, controlled clinical trial comparing chlorhexidine gel and low-dose fluoride toothpaste to prevent early childhood caries

Objectives This randomised, controlled trial compared the effectiveness of 0.12% chlorhexidine (CHX) gel and 304% fluoride toothpaste to prevent early childhood caries (ECC) in a birth cohort by 24 months. Methods The participants were randomised to receive either (i) twice daily toothbrushing with toothpaste and once daily 0.12% CHX gel (n = 110) or (ii) twice daily toothbrushing with toothpaste only (study controls) (n = 89). The primary outcome measured was caries incidence and the secondary outcome was percentage of children with mutans streptococci (MS). All mothers were contacted by telephone at 6, 12, and 18 months. At 24 months, all children were examined at a community dental clinic. Results At 24 months, the caries prevalence was 5% (3/61) in the CHX and 7% (4/58) in the controls (P = 0.7). There were no differences in percentages of MS-positive children between the CHX and control groups (54%vs 53%). Only 20% applied the CHX gel once daily and 80% less than once daily. Conclusions Toothbrushing using 304% fluoride toothpaste with or without the application of chlorhexidine gel (0.12%) reduces ECC from 23% found in the general community to 5–7%. The lack of effect with chlorhexidine is likely to be due to low compliance.

Temperature sensitivity in Indigenous Australians

"To the Editor: Indigenous people face challenges that may make them more sensitive to extreme temperatures. These include poor health, inadequate infrastructure, and poverty.1 Few studies have examined the effects of extreme temperatures on Indigenous people2 or have considered the possible role of body mass in sensitivity to extreme temperatures..."

The benefits of thermal clothing during winter in patients with heart failure : a pilot randomised controlled trial

Background Many Australian cities experience large winter increases in deaths and hospitalisations. Flu outbreaks are only part of the problem and inadequate protection from cold weather is a key independent risk factor. Better home insulation has been shown to improve health during winter, but no study has examined whether better personal insulation improves health. Data and Methods We ran a randomised controlled trial of thermal clothing versus usual care. Subjects with heart failure (a group vulnerable to cold) were recruited from a public hospital in Brisbane in winter and followed-up at the end of winter. Those randomised to the intervention received two thermal hats and tops and a digital thermometer. The primary outcome was the number of days in hospital, with secondary outcomes of General Practitioner (GP) visits and self-rated health. Results The mean number of days in hospital per 100 winter days was 2.5 in the intervention group and 1.8 in the usual care group, with a mean difference of 0.7 (95% CI: –1.5, 5.4). The intervention group had 0.2 fewer GP visits on average (95% CI: –0.8, 0.3), and a higher self-rated health, mean improvement –0.3 (95% CI: –0.9, 0.3). The thermal tops were generally well used, but even in cold temperatures the hats were only worn by 30% of subjects. Conclusions Thermal clothes are a cheap and simple intervention, but further work needs to be done on increasing compliance and confirming the health and economic benefits of providing thermals to at-risk groups.

Cost-effectiveness of a telephone-delivered education programme to prevent early childhood caries in a disadvantaged area : a cohort study

Objectives Early childhood caries is a highly destructive dental disease which is compounded by the need for young children to be treated under general anaesthesia. In Australia, there are long waiting periods for treatment at public hospitals. In this paper, we examined the costs and patient outcomes of a prevention programme for early childhood caries to assess its value for government services. Design Cost-effectiveness analysis using a Markov model. Setting Public dental patients in a low socioeconomic, socially disadvantaged area in the State of Queensland, Australia. Participants Children aged 6 months to 6 years received either a telephone prevention programme or usual care. Primary and secondary outcome measures A mathematical model was used to assess caries incidence and public dental treatment costs for a cohort of children. Healthcare costs, treatment probabilities and caries incidence were modelled from 6 months to 6 years of age based on trial data from mothers and their children who received either a telephone prevention programme or usual care. Sensitivity analyses were used to assess the robustness of the findings to uncertainty in the model estimates. Results By age 6 years, the telephone intervention programme had prevented an estimated 43 carious teeth and saved £69 984 in healthcare costs per 100 children. The results were sensitive to the cost of general anaesthesia (cost-savings range £36 043–£97 298) and the incidence of caries in the prevention group (cost-savings range £59 496–£83 368) and usual care (cost-savings range £46 833–£93 328), but there were cost savings in all scenarios. Conclusions A telephone intervention that aims to prevent early childhood caries is likely to generate considerable and immediate patient benefits and cost savings to the public dental health service in disadvantaged communities.

Optimal catalyst thickness in titanium dioxide fixed film reactors: Mathematical modelling and experimental validation

The use of immobilised TiO2 for the purification of polluted water streams introduces the necessity to evaluate the effect of mechanisms such as the transport of pollutants from the bulk of the liquid to the catalyst surface and the transport phenomena inside the porous film. Experimental results of the effects of film thickness on the observed reaction rate for both liquid-side and support-side illumination are here compared with the predictions of a one-dimensional mathematical model of the porous photocatalytic slab. Good agreement was observed between the experimentally obtained photodegradation of phenol and its by-products, and the corresponding model predictions. The results have confirmed that an optimal catalyst thickness exists and, for the films employed here, is 5 μm. Furthermore, the modelling results have highlighted the fact that porosity, together with the intrinsic reaction kinetics are the parameters controlling the photocatalytic activity of the film. The former by influencing transport phenomena and light absorption characteristics, the latter by naturally dictating the rate of reaction.