A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease

Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS including 5953 cases of aggressive PrCa and 11 463 controls (men without PrCa). We computed association tests for approximately 2.6 million SNPs and followed up the most significant SNPs by genotyping 49 121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa [odds ratio = 1.12 (95% confidence interval 1.03-1.21), P = 1.4 × 10(-8)]. This report describes a genetic variant which is associated with aggressive PrCa, which is a type of PrCa associated with a poorer prognosis.

General order conditions for stochastic Runge-Kutta methods for both commuting and non-commuting stochastic ordinary differential equation systems

In many modeling situations in which parameter values can only be estimated or are subject to noise, the appropriate mathematical representation is a stochastic ordinary differential equation (SODE). However, unlike the deterministic case in which there are suites of sophisticated numerical methods, numerical methods for SODEs are much less sophisticated. Until a recent paper by K. Burrage and P.M. Burrage (1996), the highest strong order of a stochastic Runge-Kutta method was one. But K. Burrage and P.M. Burrage (1996) showed that by including additional random variable terms representing approximations to the higher order Stratonovich (or Ito) integrals, higher order methods could be constructed. However, this analysis applied only to the one Wiener process case. In this paper, it will be shown that in the multiple Wiener process case all known stochastic Runge-Kutta methods can suffer a severe order reduction if there is non-commutativity between the functions associated with the Wiener processes. Importantly, however, it is also suggested how this order can be repaired if certain commutator operators are included in the Runge-Kutta formulation. (C) 1998 Elsevier Science B.V. and IMACS. All rights reserved.

Sustainable infrastructure operations : a review of assessment schemes and decision support

Infrastructure forms a vital component in supporting today’s way of life and has a significant role or impact on economic, environmental and social outcomes of the region around it. The design, construction and operation of such assets are a multi-billion dollar industry in Australia alone. Another issue that will play a major role in our way life is that of climate change and the greater concept of sustainability. With limited resources and a changing natural world it is necessary for infrastructure to be developed and maintained in a manner that is sustainable. In order to achieve infrastructure sustainability in operations it is necessary for there to be: a sustainability assessment scheme that provides a scientifically sound and realistic approach to measuring an assets level of sustainability; and, systems and tools to support the making of decisions that result in sustainable outcomes by providing feedback in a timely manner. Having these in place will then help drive the consideration of sustainability during the decision making process for infrastructure operations and maintenance. In this paper we provide two main contributions; a comparison and review of sustainability assessment schemes for infrastructure and their suitability for use in the operations phase; and, a review of decision support systems/tools in the area of infrastructure sustainability in operations. For this paper, sustainability covers not just the environment, but also finance/economic and societal/community aspects as well. This is often referred to as the Triple Bottom Line and forms one of the three dimensions of corporate sustainability [Stapledon, 2004].

Continuous and non-intrusive identity verification in real-time environments based on free-text keystroke dynamics

Internet services are important part of daily activities for most of us. These services come with sophisticated authentication requirements which may not be handled by average Internet users. The management of secure passwords for example creates an extra overhead which is often neglected due to usability reasons. Furthermore, password-based approaches are applicable only for initial logins and do not protect against unlocked workstation attacks. In this paper, we provide a non-intrusive identity verification scheme based on behavior biometrics where keystroke dynamics based-on free-text is used continuously for verifying the identity of a user in real-time. We improved existing keystroke dynamics based verification schemes in four aspects. First, we improve the scalability where we use a constant number of users instead of whole user space to verify the identity of target user. Second, we provide an adaptive user model which enables our solution to take the change of user behavior into consideration in verification decision. Next, we identify a new distance measure which enables us to verify identity of a user with shorter text. Fourth, we decrease the number of false results. Our solution is evaluated on a data set which we have collected from users while they were interacting with their mail-boxes during their daily activities.

Parent and adolescent perceptions of family functioning : a comparison of clinic and non-clinic families

In this paper two studies are reported which compare (a) the perceptions of family functioning held by clinic and non-clinic adolescents, and (b) the perceptions of family functioning held by adolescents and their mothers in clinic and non-clinic families. In Study 1, matched group of clinic and non-clinic adolescents were compared on their responses to a 30-item scale (ICPS) designed to measure three factors of family functioning: Intimacy (high vs. low), Parenting Style (democratic vs. controlled) and Conflict (high vs. low). Clinic and non-clinic adolescents were also compared on their responses to a multi-dimensional measure of adolescent self-concept. Although there was little difference between the two groups of adolescents in terms of their perceptions of family functioning, there were strong relationships between the self-concept variables and the family functioning variables. In Study 2, comparisons were made between the perceptions of family functioning held by mothers and adolescents for both clinical and non-clinic families. There were no differences between the two groups of adolescents in terms of their perceptions of family functioning, although there were clear differences between the two groups of mothers. In addition, clinic adolescents and their mothers did not differ in their perceptions of the family, whereas adolescents in the non-clinic group saw their families significantly as less intimate and more conflicted than did their mothers.

Sex discrimination and non-random sampling in the Australian labour market

Historically a significant gap between male and female wages has existed in the Australian labour market. Indeed this wage differential was institutionalised in the 1912 arbitration decision which determined that the basic female wage would be set at between 54 and 66 per cent of the male wage. More recently however, the 1969 and 1972 Equal Pay Cases determined that male/female wage relativities should be based upon the premise of equal pay for work of equal value. It is important to note that the mere observation that average wages differ between males and females is not sine qua non evidence of sex discrimination. Economists restrict the definition of wage discrimination to cases where two distinct groups receive different average remuneration for reasons unrelated to differences in productivity characteristics. This paper extends previous studies of wage discrimination in Australia (Chapman and Mulvey, 1986; Haig, 1982) by correcting the estimated male/female wage differential for the existence of non-random sampling. Previous Australian estimates of male/female human capital basedwage specifications together with estimates of the corresponding wage differential all suffer from a failure to address this issue. If the sample of females observed to be working does not represent a random sample then the estimates of the male/female wage differential will be both biased and inconsistent.

A microscopic simulation model to estimate Bus Rapid Transit (BRT) station service capacity with mixed stopping and non-stopping bus operation

Bus Rapid Transit (BRT) station is the interface between passenger and service. The station is crucial to line operation as it is typically the only location where buses can pass each other. Congestion may occur here when buses maneuvering into and out of the platform lane interfere with bus flow, or when a queue of buses forms upstream of the platform lane blocking the passing lane. However, some systems include operation where express buses pass the critical station, resulting in a proportion of non stopping buses. It is important to understand the operation of the critical busway station under this type of operation, as it affects busway line capacity. This study uses micro simulation to treat the BRT station operation and to analyze the relationship between station Limit state bus capacity (B_ls), Total Bus Capacity (B_ttl). First, the simulation model is developed for Limit state scenario and then a mathematical model is defined, calibrated for a specified range of controlled scenarios of mean and coefficient of variation of dwell time. Thereafter, the proposed B_ls model is extended to consider non stopping buses and B_ttlmodel is defined. The proposed models provides better understanding to the BRT line capacity and is useful for transit authorities for designing better BRT operation.

Comparing cooperative and non-cooperative crash risk assessment

Cooperative Systems provide, through the multiplication of information sources over the road, a lot of potential to improve the assessment of the road risk describing a particular driving situation. In this paper, we compare the performance of a cooperative risk assessment approach against a non-cooperative approach; we used an advanced simulation framework, allowing for accurate and detailed, close-to-reality simulations. Risk is estimated, in both cases, with combinations of indicators based on the TTC. For the non-cooperative approach, vehicles are equipped only with an AAC-like forward-facing ranging sensor. On the other hand, for the cooperative approach, vehicles share information through 802.11p IVC and create an augmented map representing their environment; risk indicators are then extracted from this map. Our system shows that the cooperative risk assessment provides a systematic increase of forward warning to most of the vehicles involved in a freeway emergency braking scenario, compared to a non-cooperative system.

A systematic review of the literature comparing the practices of dispensing and non-dispensing doctors

Objectives: Some doctors perform the dual roles of prescribing and dispensing pharmaceuticals. The dispensing doctors (DDs) role may give rise to prescribing behaviours that vary from those of non-DDs. The aim of this review was to systematically and comparatively appraise the research evidence related to the practices of DDs. Methods: A systematic search of bibliographic databases and reference lists from selected papers were the sources of the data. Inclusion criteria were papers published in English, between 1970 and 2008 that provided quantitative data comparing the practices of DDs and non-DDs. At least two of the authors abstracted data from all eligible papers using a purpose-made data extraction form. Results: Twenty-one papers were included in this review. Evidence indicated that DDs prescribed more pharmaceutical items and less often generically than non-DDs. There was limited evidence to suggest that DDs prescribed less judiciously and were associated with poor dispensing standards. Patient convenience and access to pharmaceuticals were main reasons for doctors to dispense. Conclusion: DDs can fill an important gap in the provision of pharmaceuticals for their patients especially where health workforce shortages exist. There was evidence the dispensing role influenced prescribing. Patient convenience should be balanced against scarce medical resources, being utilised for dispensing.

Cell migration and proliferation on homogeneous and non-homogeneous domains : modelling on the scale of individuals and populations

Cell migration is a behaviour critical to many key biological effects, including wound healing, cancerous cell invasion and morphogenesis, the development of an organism from an embryo. However, given that each of these situations is distinctly different and cells are extremely complicated biological objects, interest lies in more basic experiments which seek to remove conflating factors and present a less complex environment within which cell migration can be experimentally examined. These include in vitro studies like the scratch assay or circle migration assay, and ex vivo studies like the colonisation of the hindgut by neural crest cells. The reduced complexity of these experiments also makes them much more enticing as problems to mathematically model, like done here. The primary goal of the mathematical models used in this thesis is to shed light on which cellular behaviours work to generate the travelling waves of invasion observed in these experiments, and to explore how variations in these behaviours can potentially predict differences in this invasive pattern which are experimentally observed when cell types or chemical environment are changed. Relevant literature has already identified the difficulty of distinguishing between these behaviours when using traditional mathematical biology techniques operating on a macroscopic scale, and so here a sophisticated individual-cell-level model, an extension of the Cellular Potts Model (CPM), is been constructed and used to model a scratch assay experiment. This model includes a novel mechanism for dealing with cell proliferations that allowed for the differing properties of quiescent and proliferative cells to be implemented into their behaviour. This model is considered both for its predictive power and used to make comparisons with the travelling waves which result in more traditional macroscopic simulations. These comparisons demonstrate a surprising amount of agreement between the two modelling frameworks, and suggest further novel modifications to the CPM that would allow it to better model cell migration. Considerations of the model’s behaviour are used to argue that the dominant effect governing cell migration (random motility or signal-driven taxis) likely depends on the sort of invasion demonstrated by cells, as easily seen by microscopic photography. Additionally, a scratch assay simulated on a non-homogeneous domain consisting of a ’fast’ and ’slow’ region is also used to further differentiate between these different potential cell motility behaviours. A heterogeneous domain is a novel situation which has not been considered mathematically in this context, nor has it been constructed experimentally to the best of the candidate’s knowledge. Thus this problem serves as a thought experiment used to test the conclusions arising from the simulations on homogeneous domains, and to suggest what might be observed should this non-homogeneous assay situation be experimentally realised. Non-intuitive cell invasion patterns are predicted for diffusely-invading cells which respond to a cell-consumed signal or nutrient, contrasted with rather expected behaviour in the case of random-motility-driven invasion. The potential experimental observation of these behaviours is demonstrated by the individual-cell-level model used in this thesis, which does agree with the PDE model in predicting these unexpected invasion patterns. In the interest of examining such a case of a non-homogeneous domain experimentally, some brief suggestion is made as to how this could be achieved.

Study protocol : establishing good relationships between patients and health care providers while providing cardiac care. Exploring how patient-clinician engagement contributes to health disparities between indigenous and non-indigenous Australians in South Australia

Abstract Background: Studies that compare Indigenous Australian and non-Indigenous patients who experience a cardiac event or chest pain are inconclusive about the reasons for the differences in-hospital and survival rates. The advances in diagnostic accuracy, medication and specialised workforce has contributed to a lower case fatality and lengthen survival rates however this is not evident in the Indigenous Australian population. A possible driver contributing to this disparity may be the impact of patient-clinician interface during key interactions during the health care process. Methods/Design: This study will apply an Indigenous framework to describe the interaction between Indigenous patients and clinicians during the continuum of cardiac health care, i.e. from acute admission, secondary and rehabilitative care. Adopting an Indigenous framework is more aligned with Indigenous realities, knowledge, intellects, histories and experiences. A triple layered designed focus group will be employed to discuss patient-clinician engagement. Focus groups will be arranged by geographic clusters i.e. metropolitan and a regional centre. Patient informants will be identified by Indigenous status (i.e. Indigenous and non-Indigenous) and the focus groups will be convened separately. The health care provider focus groups will be convened on an organisational basis i.e. state health providers and Aboriginal Community Controlled Health Services. Yarning will be used as a research method to facilitate discussion. Yarning is in congruence with the oral traditions that are still a reality in day-to-day Indigenous lives. Discussion: This study is nestled in a larger research program that explores the drivers to the disparity of care and health outcomes for Indigenous and non-Indigenous Australians who experience an acute cardiac admission. A focus on health status, risk factors and clinical interventions may camouflage critical issues within a patient-clinician exchange. This approach may provide a way forward to reduce the appalling health disadvantage experienced within the Indigenous Australian communities. Keywords: Patient-clinician engagement, Qualitative, Cardiovascular disease, Focus groups, Indigenous

Postpartum care for Aboriginal and non-Aboriginal women with Gestational Diabetes Mellitus across urban, rural and remote locations : a protocol for a cohort linkage study

Background: Gestational diabetes mellitus (GDM) is increasing, along with obesity and type 2 diabetes (T2DM), with Aboriginal and Torres Strait Islander people* in Australia particularly affected. GDM causes serious complications in pregnancy, birth, and the longer term, for both women and their infants. Women diagnosed with GDM have an eightfold risk of developing T2DM after pregnancy, compared with women who have not had GDM. Indigenous women have an even higher risk, at a younger age, and progress more quickly from GDM to T2DM, compared to non-Indigenous women. If left undetected and untreated, T2DM can lead to heart disease, stroke, renal disease, kidney failure, amputations and blindness. A GDM diagnosis offers a ‘window of opportunity’ for diabetes health interventions and it is vital that acceptable and effective prevention, treatment, and post-pregnancy care are provided. Low rates of post-pregnancy screening for T2DM are reported among non-Aboriginal women in Australia and among Indigenous women in other countries, however data for Aboriginal women are scarce. Breastfeeding, a healthy diet, and exercise can also help to prevent T2DM, and together with T2DM screening are recommended elements of ‘post-pregnancy care’ for women with GDM, This paper describes methods for a data linkage study to investigate rates of post-pregnancy care among women with GDM. Methods/Design: This retrospective cohort includes all women who gave birth at Cairns Base Hospital in Far North Queensland, Australia, from 2004 to 2010, coded as having GDM in the Cairns Base Hospital Clinical Coding system. Data linkage is being conducted with the Queensland Perinatal Data Collection, and three laboratories. Hospital medical records are being reviewed to validate the accuracy of GDM case ascertainment, and gather information on breastfeeding and provision of dietary advice. Multiple logistic regression is being used to compare post-pregnancy care between Aboriginal and non-Aboriginal women, while adjusting for other factors may impact on post-pregnancy care. Survival analysis is being used to estimate the rates of progression from GDM to T2DM. Discussion: There are challenges to collecting post-pregnancy data for women with GDM. However, research is urgently needed to ensure adequate post-pregnancy care is provided for women with GDM in Australia.

Pre-crash and non-crash traffic flow trends analysis on motorways

Crashes that occur on motorways contribute to a significant proportion (40-50%) of non-recurrent motorway congestions. Hence, reducing the frequency of crashes assists in addressing congestion issues (Meyer, 2008). Crash likelihood estimation studies commonly focus on traffic conditions in a short time window around the time of a crash while longer-term pre-crash traffic flow trends are neglected. In this paper we will show, through data mining techniques that a relationship between pre-crash traffic flow patterns and crash occurrence on motorways exists. We will compare them with normal traffic trends and show this knowledge has the potential to improve the accuracy of existing models and opens the path for new development approaches. The data for the analysis was extracted from records collected between 2007 and 2009 on the Shibuya and Shinjuku lines of the Tokyo Metropolitan Expressway in Japan. The dataset includes a total of 824 rear-end and sideswipe crashes that have been matched with crashes corresponding to traffic flow data using an incident detection algorithm. Traffic trends (traffic speed time series) revealed that crashes can be clustered with regards to the dominant traffic patterns prior to the crash. Using the K-Means clustering method with Euclidean distance function allowed the crashes to be clustered. Then, normal situation data was extracted based on the time distribution of crashes and were clustered to compare with the “high risk” clusters. Five major trends have been found in the clustering results for both high risk and normal conditions. The study discovered traffic regimes had differences in the speed trends. Based on these findings, crash likelihood estimation models can be fine-tuned based on the monitored traffic conditions with a sliding window of 30 minutes to increase accuracy of the results and minimize false alarms.

Separable and non-separable discrete wavelet transform based texture features and image classification of breast thermograms

Highly sensitive infrared cameras can produce high-resolution diagnostic images of the temperature and vascular changes of breasts. Wavelet transform based features are suitable in extracting the texture difference information of these images due to their scale-space decomposition. The objective of this study is to investigate the potential of extracted features in differentiating between breast lesions by comparing the two corresponding pectoral regions of two breast thermograms. The pectoral regions of breastsare important because near 50% of all breast cancer is located in this region. In this study, the pectoral region of the left breast is selected. Then the corresponding pectoral region of the right breast is identified. Texture features based on the first and the second sets of statistics are extracted from wavelet decomposed images of the pectoral regions of two breast thermograms. Principal component analysis is used to reduce dimension and an Adaboost classifier to evaluate classification performance. A number of different wavelet features are compared and it is shown that complex non-separable 2D discrete wavelet transform features perform better than their real separable counterparts.

Angiogenesis and non-small cell lung cancer

Lung cancer is the commonest cause of cancer death in the western world. Recent evidence suggests that angiogenesis is related to poor prognosis in many solid tumours including non-small cell lung cancer. Angiogenesis is controlled by a complex interaction between growth and apoptotic factors, proteases and adhesion molecules. The angiogenic process may prove a target for novel therapies such as matrix metalloproteinase inhibitors, growth factor antisense RNA, growth factor receptor antagonists and naturally occurring antiangiogenic peptides. These agents may be used alone or in combination with traditional chemotherapy, radiotherapy and surgery. (C) 2000 Elsevier Science Ireland Ltd.