Do motor vehicle crashes arise from single or multiple unique risk processes? An inquiry into crash causes and modelling

Crashes at any particular transport network location consist of a chain of events arising from a multitude of potential causes and/or contributing factors whose nature is likely to reflect geometric characteristics of the road, spatial effects of the surrounding environment, and human behavioural factors. It is postulated that these potential contributing factors do not arise from the same underlying risk process, and thus should be explicitly modelled and understood. The state of the practice in road safety network management applies a safety performance function that represents a single risk process to explain crash variability across network sites. This study aims to elucidate the importance of differentiating among various underlying risk processes contributing to the observed crash count at any particular network location. To demonstrate the principle of this theoretical and corresponding methodological approach, the study explores engineering (e.g. segment length, speed limit) and unobserved spatial factors (e.g. climatic factors, presence of schools) as two explicit sources of crash contributing factors. A Bayesian Latent Class (BLC) analysis is used to explore these two sources and to incorporate prior information about their contribution to crash occurrence. The methodology is applied to the state controlled roads in Queensland, Australia and the results are compared with the traditional Negative Binomial (NB) model. A comparison of goodness of fit measures indicates that the model with a double risk process outperforms the single risk process NB model, and thus indicating the need for further research to capture all the three crash generation processes into the SPFs.

Single nucleotide polymorphisms in clinics: Fantasy or reality for cancer?

Single nucleotide polymorphisms (SNPs) have been classically used for dissecting various human complex disorders using candidate gene studies. During the last decade, large scale SNP analysis i.e. genome-wide association studies (GWAS) have provided an agnostic approach to identify possible genetic loci associated with heterogeneous disease such as cancer susceptibility, prognosis of survival or drug response. Further, the advent of new technologies, including microarray based genotyping as well as high throughput next generation sequencing has opened new avenues for SNPs to be used in clinical practice. It is speculated that the utility of SNPs to understand the mechanisms, biology of variable drug response and ultimately treatment individualization based on the individual’s genome composition will be indispensable in the near future. In the current review, we discuss the advantages and disadvantages of the clinical utility of genetic variants in disease risk-prediction, prognosis, clinical outcome and pharmacogenomics. The lessons and challenges for the utility of SNP based biomarkers are also discussed, including the need for additional functional validation studies.

Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes

Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We report a genome-wide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in two cohorts including 1,783 Scottish individuals and 1,113 individuals from the UK Prospective Diabetes Study. In a combined meta-analysis, we identified a SNP, rs11212617, associated with treatment success (n = 3,920, P = 2.9 P×-9, odds ratio = 1.35, 95% CI 1.22-1.49) at a locus containing ATM, the ataxia telangiectasia mutated gene. In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMP-activated protein kinase in response to metformin. We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin. © 2011 Nature America, Inc. All rights reserved.

Crystal structures of the endoplasmic reticulum aminopeptidase-1 (ERAP1) reveal the molecular basis for N-terminal peptide trimming

Endoplasmatic reticulum aminopeptidase 1 (ERAP1) is a multifunctional enzyme involved in trimming of peptides to an optimal length for presentation by major histocompatibility complex (MHC) class I molecules. Polymorphisms in ERAP1 have been associated with chronic inflammatory diseases, including ankylosing spondylitis (AS) and psoriasis, and subsequent in vitro enzyme studies suggest distinct catalytic properties of ERAP1 variants. To understand structure-activity relationships of this enzyme we determined crystal structures in open and closed states of human ERAP1, which provide the first snapshots along a catalytic path. ERAP1 is a zinc-metallopeptidase with typical H-E-X-X-H-(X)18-E zinc binding and G-A-M-E-N motifs characteristic for members of the gluzincin protease family. The structures reveal extensive domain movements, including an active site closure as well as three different open conformations, thus providing insights into the catalytic cycle. A K 528R mutant strongly associated with AS in GWAS studies shows significantly altered peptide processing characteristics, which are possibly related to impaired interdomain interactions.

Improving factory performance using an integrated sugar factory model

A whole of factory model of a raw sugar factory was developed in SysCAD software to assess and improve factory operations. The integrated sugar factory model ‘Sugar-SysCAD’ includes individual models for milling, heating and clarification, evaporation, crystallisation, steam cycle, sugar dryer and process and injection water circuits. These individual unit operation models can be either used as standalone models to optimise the unit operation or in the integrated mode to provide more accurate prediction of the effects of changes in any part of the process on the outputs of the whole factory process. Using the integrated sugar factory model, the effect of specific process operations can be understood and practical solutions can be determined to address process problems. The paper presents two factory scenarios to show the capabilities of the whole of factory model.

QUT’s research data storage solutions: A launchpad for research journeys

This poster presents key features of how QUT’s integrated research data storage and management services work with researchers through their own individual or team research life cycle. By understanding the characteristics of research data, and the long-term need to store this data, QUT has provided resources and tools that support QUT’s goal of being a research intensive institute. Key to successful delivery and operation has been the focus upon researchers’ individual needs and the collaboration between providers, in particular, Information Technology Services, High Performance Computing and Research Support, and QUT Library. QUT’s Research Data Storage service provides all QUT researchers (staff and Higher Degree Research students (HDRs)) with a secure data repository throughout the research data lifecycle. Three distinct storage areas provide for raw research data to be acquired, project data to be worked on, and published data to be archived. Since the service was launched in late 2014, it has provided research project teams from all QUT faculties with acquisition, working or archival data space. Feedback indicates that the storage suits the unique needs of researchers and their data. As part of the workflow to establish storage space for researchers, Research Support Specialists and Research Data Librarians consult with researchers and HDRs to identify data storage requirements for projects and individual researchers, and to select and implement the most suitable data storage services and facilities. While research can be a journey into the unknown[1], a plan can help navigate through the uncertainty. Intertwined in the storage provision is QUT’s Research Data Management Planning tool. Launched in March 2015, it has already attracted 273 QUT staff and 352 HDR student registrations, and over 620 plans have been created (2/10/2015). Developed in collaboration with Office of Research Ethics and Integrity (OREI), uptake of the plan has exceeded expectations.

Label-free isolation of a prostate cancer cell among blood cells and the single-cell measurement of drug accumulation using an integrated microfluidic chip

Circulating tumor cells (CTCs) are found in the blood of patients with cancer. Although these cells are rare, they can provide useful information for chemotherapy. However, isolation of these rare cells from blood is technically challenging because they are small in numbers. An integrated microfluidic chip, dubbed as CTC chip, was designed and fabricated for conducting tumor cell isolation. As CTCs usually show multidrug resistance (MDR), the effect of MDR inhibitors on chemotherapeutic drug accumulation in the isolated single tumor cell is measured. As a model of CTC isolation, human prostate tumor cells were mixed with mouse blood cells and the labelfree isolation of the tumor cells was conducted based on cell size difference. The major advantages of the CTC chip are the ability for fast cell isolation, followed by multiple rounds of single-cell measurements, suggesting a potential assay for detecting the drug responses based on the liquid biopsy of cancer patients.

Characteristics of road factors in multi and single vehicle motorcycle crashes in Queensland

Motorcyclists were involved in 6.4% of all police-reported crashes and 12.5% of all fatal crashes in Queensland during 2004-2011. Of these crashes, 43% were single-vehicle (SV) and 57% were multi-vehicle (MV). The overall reduction in motorcycle crashes in this period masked different trends: single-vehicle crashes increased while MV motorcycle crashes decreased. However, little research has been undertaken to understand the similarities and differences between SV and MV motorcycle crashes in Queensland and the factors underlying these diverging trends. The descriptive analyses and regression model developed here confirm international research findings regarding the greater role of road infrastructure factors in SV crashes. In particular, road geometric factors such as horizontal and vertical alignment and road surface factors such as sealed/unsealed and wet/dry were more important in SV than MV crashes.

A framing analysis on Nepalese media portrayal of disaster events using news frames and PPRR cycle

This study seeks to understand the prevailing status of Nepalese media portrayal of natural disasters and develop a disaster management framework to improve the effectiveness and efficiency of news production through the continuum of prevention, preparedness, response and recovery (PPRR) phases of disaster management. The study is currently under progress. It is being undertaken in three phases. In phase-1, a qualitative content analysis is conducted. The news contents are categorized in frames as proposed in the 'Framing theory' and pre-defined frames. However, researcher has looked at the theories of the Press, linking to social responsibility theory as it is regarded as the major obligation of the media towards the society. Thereafter, the contents are categorized as per PPRR cycle. In Phase-2, based on the findings of content analysis, 12 in-depth interviews with journalists, disaster managers and community leaders are conducted. In phase-3, based on the findings of content analysis and in-depth interviews, a framework for effective media management of disaster are developed using thematic analysis. As the study is currently under progress hence, findings from the pilot study are elucidated. The response phase of disasters is most commonly reported in Nepal. There is relatively low coverage of preparedness and prevention. Furthermore, the responsibility frame in the news is most prevalent following human interest. Economic consequences and conflict frames are also used while reporting and vulnerability assessment has been used as an additional frame. The outcomes of this study are multifaceted: At the micro-level people will be benefited as it will enable a reduction in the loss of human lives and property through effective dissemination of information in news and other mode of media. They will be ‘well prepared for', 'able to prevent', 'respond to' and 'recover from' any natural disasters. At the meso level the media industry will be benefited and have their own 'disaster management model of news production' as an effective disaster reporting tool which will improve in media's editorial judgment and priority. At the macro-level it will assist government and other agencies to develop appropriate policies and strategies for better management of natural disasters.

Determination of the effect of JO146, a CtHtrA inhibitor, on the chlamydial developmental cycle and persistence

The role of Chlamydia trachomatis HtrA (CtHtrA) for the growth and pathogenesis of this organism is presented. Inhibition of CtHtrA led to loss of infectious progeny in Chlamydia, particularly during heat stress or recovery from penicillin persistence. Isolation of CtHtrA inhibitor resistant mutants identified positive selection for mutants in fatty acid related pathways. Importantly, HtrA inhibition was effective against clinical isolates of C. trachomatis. Thus the findings combined indicate that CtHtrA is an important chlamydial growth factor that has the potential to be targeted for the development of anti-chlamydial drugs in the future.

Single 2×1 domain orientation on Si(001) surfaces using aperiodic Bi line arrays

Studies of Bi heteroepitaxy on Si(001) have shown that lines grow to lengths of up to 500nm if the substrate is heated to above the Bi desorption temperature (500°C) during or after Bi deposition. Unlike many other nanoline systems, the lines formed by this nonequilibrium growth process have no detectable width dispersion. Although much attention has been given to the atomic geometery of the line, in this paper, we focus on how the lines can be used to create a majority 2×1 domain orientation. It is demonstrated that the Bi lines can be used to produce a single-domain orientation on Si(001) if the lines are grown on Si(001) surfaces with a regular distribution of single height steps. This is a compelling example of how a nanoscale motif can be used to modify mesoscopic surface structure on Si(001).