EVERSUN: A phase 2 trial of alternating sunitinib and everolimus as first-line therapy for advanced renal cell carcinoma

Background We hypothesised that alternating inhibitors of the vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin pathways would delay the development of resistance in advanced renal cell carcinoma (aRCC). Patients and methods A single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of 12-week cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end point was proportion alive and progression-free at 6 months (PFS6m). The secondary end points were feasibility, tumour response, overall survival (OS), and adverse events (AEs). The correlative objective was to assess biomarkers and correlate with clinical outcome. Results We recruited 55 eligible participants from September 2010 to August 2012. Demographics: mean age 61, 71% male, favourable risk 16%, intermediate risk 84%. Cycle 2 commenced within 14 weeks for 80% of participants; 64% received ≥22 weeks of alternating therapy; 78% received ≥22 weeks of any treatment. PFS6m was 29/55 (53%; 95% confidence interval [CI] 40% to 66%). Tumour response rate was 7/55 (13%; 95% CI 4% to 22%, all partial responses). After median follow-up of 20 months, 47 of 55 (86%) had progressed with a median progression-free survival of 8 months (95% CI 5–10), and 30 of 55 (55%) had died with a median OS of 17 months (95% CI 12–undefined). AEs were consistent with those expected for each single agent. No convincing prognostic biomarkers were identified. Conclusions The EVERSUN regimen was feasible and safe, but its activity did not meet pre-specified values to warrant further research. This supports the current approach of continuing anti-VEGF therapy until progression or prohibitive toxicity before changing treatment.

RNASeqBrowser: A genome browser for simultaneous visualization of raw strand specific RNAseq reads and UCSC genome browser custom tracks

Background Strand specific RNAseq data is now more common in RNAseq projects. Visualizing RNAseq data has become an important matter in Analysis of sequencing data. The most widely used visualization tool is the UCSC genome browser that introduced the custom track concept that enabled researchers to simultaneously visualize gene expression at a particular locus from multiple experiments. Our objective of the software tool is to provide friendly interface for visualization of RNAseq datasets. Results This paper introduces a visualization tool (RNASeqBrowser) that incorporates and extends the functionality of the UCSC genome browser. For example, RNASeqBrowser simultaneously displays read coverage, SNPs, InDels and raw read tracks with other BED and wiggle tracks -- all being dynamically built from the BAM file. Paired reads are also connected in the browser to enable easier identification of novel exon/intron borders and chimaeric transcripts. Strand specific RNAseq data is also supported by RNASeqBrowser that displays reads above (positive strand transcript) or below (negative strand transcripts) a central line. Finally, RNASeqBrowser was designed for ease of use for users with few bioinformatic skills, and incorporates the features of many genome browsers into one platform. Conclusions The features of RNASeqBrowser: (1) RNASeqBrowser integrates UCSC genome browser and NGS visualization tools such as IGV. It extends the functionality of the UCSC genome browser by adding several new types of tracks to show NGS data such as individual raw reads, SNPs and InDels. (2) RNASeqBrowser can dynamically generate RNA secondary structure. It is useful for identifying non-coding RNA such as miRNA. (3) Overlaying NGS wiggle data is helpful in displaying differential expression and is simple to implement in RNASeqBrowser. (4) NGS data accumulates a lot of raw reads. Thus, RNASeqBrowser collapses exact duplicate reads to reduce visualization space. Normal PC’s can show many windows of NGS individual raw reads without much delay. (5) Multiple popup windows of individual raw reads provide users with more viewing space. This avoids existing approaches (such as IGV) which squeeze all raw reads into one window. This will be helpful for visualizing multiple datasets simultaneously. RNASeqBrowser and its manual are freely available at http://www.australianprostatecentre.org/research/software/rnaseqbrowser webcite or http://sourceforge.net/projects/rnaseqbrowser/ webcite

Identification of genetic variants contributing to the migraine phenotype in different Australian populations

This project aimed to identify novel genetic risk variants associated with migraine in the Norfolk Island population. Statistical analysis and bioinformatics approaches such as polygenic modeling and gene clustering methods were carried out to explore genotypic and expression data from high-throughput techniques. This project had a particular focus on hormonal genes and other genetic variants and identified a modest effect size on the migraine phenotype.

A candidate gene association study for growth performance in an improved Giant Freshwater Prawn (Macrobrachium rosenbergii) culture line

A candidate gene approach using type I single nucleotide polymorphism (SNP) markers can provide an effective method for detecting genes and gene regions that underlie phenotypic variation in adaptively significant traits. In the absence of available genomic data resources, transcriptomes were recently generated in Macrobrachium rosenbergii to identify candidate genes and markers potentially associated with growth. The characterisation of 47 candidate loci by ABI re-sequencing of four cultured and eight wild samples revealed 342 putative SNPs. Among these, 28 SNPs were selected in 23 growth-related candidate genes to genotype in 200 animals selected for improved growth performance in an experimental GFP culture line in Vietnam. The associations between SNP markers and individual growth performance were then examined. For additive and dominant effects, a total of three exonic SNPs in glycogen phosphorylase (additive), heat shock protein 90 (additive and dominant) and peroxidasin (additive), and a total of six intronic SNPs in ankyrin repeats-like protein (additive and dominant), rolling pebbles (dominant), transforming growth factor-β induced precursor (dominant), and UTP-glucose-1-phosphate uridylyltransferase 2 (dominant) genes showed significant associations with the estimated breeding values in the experimental animals (P =0.001−0.031). Individually, they explained 2.6−4.8 % of the genetic variance (R2=0.026−0.048). This is the first large set of SNP markers reported for M. rosenbergii and will be useful for confirmation of associations in other samples or culture lines as well as having applications in marker-assisted selection in future breeding programs.

Effectiveness of on-line resources to enhance student learning and engagement

BACKGROUND For engineering graduates to be work-ready with marketable skills they must not only be well-versed with engineering science and its applications, but also able to adapt to using commercial software that is widely used in engineering practice. Hydrological/hydraulic modelling is one aspect of engineering practice which demands the ability to apply fundamentals into design and construction using software. The user manuals for such software are usually tailored for the experienced engineer but not for undergraduates who typically are novices to concepts of modelling and software tools. As the focus of a course such as Advanced Water Engineering is on the wider aspects of engineering application of hydrological and hydraulic concepts, it is ineffective for the lecturers to direct the students to user manuals as students have neither the time nor the desire to sift through numerous pages in a manual. An alternative and efficient way to demonstrate the use of the software is enabling students to develop a model to simulate real-world scenario using the tools of the software and directing them to make informed decisions based on outcomes. PURPOSE Past experience of the lecturer showed that the resources available for the students left a knowledge gap leading to numerous student queries outside contact hours. The purpose of this study is to assess how effective purpose-built video resources can be in supplementing the traditional learning resources to enhance student learning. APPROACH Short-length animated video clips comprising guided step-by-step instructions were prepared using screen capture software to capture screen activity and later edited to focus on specific features using pop-up annotations; Vocal narration was purposely excluded to avoid disturbances due to noise and allow different learning paces of individual students. The video clips were made available to the students alongside the traditional resources/approaches such as in-class demonstrations, guideline notes, and tips for efficient and error-free procedural descriptions. The number of queries the lecturer received from the student cohort outside the lecture times was recorded. An anonymous survey to assess the usefulness and adequacy of the courseware was conducted. OUTCOMES While a significant decline in the number of student queries was noted, an overwhelming majority of the survey respondents confirmed the usefulness of the purpose-developed courseware. CONCLUSIONS/RECOMMENDATIONS/SUMMARY The survey and lecturer’s experience indicated that animated demonstration video clips illustrating the various steps involved in developing hydrologic and hydraulic models and simulating design scenarios is an effective supplement for traditional learning resources. Among the many advantages of the custom-made video clips as a learning resource are that they (1) highlight the aspects that are important to undergraduate learning but not available in the software manuals as the latter are designed for more mature users/learners; (2) provide short, to-the point communication in a step-by-step manner; (3) allow students flexibility to self-learn at their own pace; (4) enhance student learning; and (5) enable time savings for the lecturer in the long term by avoiding queries of a repetitive nature. It is expected that these newly developed resources will be improved to incorporate students’ suggestions before being offered to future cohorts of students. The concept can also be expanded to other relevant courses where animated demonstrations of key modelling steps are beneficial to student learning.

Identification of mechanism, PECARN risk factors and injury patterns in severe paediatric cervical spine injuries in Queensland

Introduction Canadian C spine rule and NEXUS criteria have identified risk factors for cervical spine injury in adults but not for children. PECARN has developed an 8 variable model for cervical spine injury in children. We sought to identify the mechanism, prevalence of PECARN risk factors, injury patterns, and management of severe Paediatric cervical spine injuries presenting to the major children’s hospitals in Brisbane, Australia. Methods This a retrospective study of the children with cervical spine injuries who presented directly or were referred to the major children’s hospitals in Brisbane over 5 years. Results There were 38 patients with 18 male and 20 female.The mean age was 8.6 years. They were divided into two groups according to their age, (Group 1 < =8 years had 18 (47%) patients, while group 2 (9-15 years) had 20 (53%) patients. Motor vehicle related injuries were the most common (61%) in Group 1 while it was sporting injuries (50%) in group 2. All patients in group 1 had upper cervical injury (C0-C2) while subaxial injuries were most common in group 2 (66.6%). 82% of the patients had 2 or more PECARN risk factors. 18 children (47%) had normal neurological assessment at presentation, 6 (16%) had radicular symptoms, 11 (29%) could not be assessed as they had already been intubated due to the severity of the injury, 3 (8%) had incomplete cord injury. 29 (69%) patients had normal neurological assessment at final follow up and 2 children died from their injuries. Conclusion Our study confirms that younger children sustain upper cervical injuries most commonly secondary to motor vehicle accidents, while the older sustain subaxial injuries from sporting activities. The significant prevalence of the PECARN risk factors among this cohort of patients have led to them being incorporated into a protocol at these hospitals used to assess patients with suspected cervical spinal injury.

Identification of major loci controlling clinical manifestations of ankylosing spondylitis

Objective. To identify genomic regions linked with determinants of age at symptom onset, disease activity, and functional impairment in ankylosing spondylitis (AS). Methods. A whole genome linkage scan was performed in 188 affected sibling pair families with 454 affected individuals. Traits assessed were age at symptom onset, disease activity assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and functional impairment assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI). Parametric and nonparametric quantitative linkage analysis was performed using parameters defined in a previous segregation study. Results. Heritabilities of the traits studied in this data set were as follows: BASDAI 0.49 (P = 0.0001, 95% confidence interval [95% CI] 0.23-0.75), BASFI 0.76 (P = 10-7, 95% CI 0.49-1.0), and age at symptom onset 0.33 (P = 0.005, 95% CI 0.04-0.62). No linkage was observed between the major histocompatibility complex (MHC) and any of the traits studied (logarithm of odds [LOD] score <1.0). "Significant" linkage (LOD score 4.0) was observed between a region on chromosome 18p and the BASDAI. Age at symptom onset showed "suggestive" linkage to chromosome 11p (LOD score 3.3). Maximum linkage with the BASFI was seen at chromosome 2q (LOD score 2.9). Conclusion. In contrast to the genetic determinants of susceptibility to AS, clinical manifestations of the disease measured by the BASDAI, BASFI, and age at symptom onset are largely determined by a small number of genes not encoded within the MHC.

Let's do it: A framework to investigate the affordances of experimental learning environments

BACKGROUND Experimental learning, traditionally conducted in on-campus laboratory venues, is the cornerstone of science and engineering education. In order to ensure that engineering graduates are exposed to ‘real-world’ situations and attain the necessary professional skill-sets, as mandated by course accreditation bodies such as Engineers Australia, face-to-face laboratory experimentation with real equipment has been an integral component of traditional engineering education. The online delivery of engineering coursework endeavours to mimic this with remote and simulated laboratory experimentation. To satisfy student and accreditation requirements, the common practice has been to offer equivalent remote and/or simulated laboratory experiments in lieu of the ones delivered, face-to face, on campus. The current implementations of both remote and simulated laboratories tend to be specified with a focus on technical characteristics, instead of pedagogical requirements. This work attempts to redress this situation by developing a framework for the investigation of the suitability of different experimental educational environments to deliver quality teaching and learning. PURPOSE For the tertiary education sector involved with technical or scientific training, a research framework capable of assessing the affordances of laboratory venues is an important aid during the planning, designing and evaluating stages of face-to-face and online (or cyber) environments that facilitate student experimentation. Providing quality experimental learning venues has been identified as one of the distance-education providers’ greatest challenges. DESIGN/METHOD The investigation draws on the expertise of staff at three Australian universities: Swinburne University of Technology (SUT), Curtin University (Curtin) and Queensland University of Technology (QUT). The aim was to analyse video recorded data, in order to identify the occurrences of kikan-shido (a Japanese term meaning ‘between desks instruction’ and over-the-shoulder learning and teaching (OTST/L) events, thereby ascertaining the pedagogical affordances in face-to-face laboratories. RESULTS These will be disseminated at a Master Class presentation at this conference. DISCUSSION Kikan-shido occurrences did reflect on the affordances of the venue. Unlike with other data collection methods, video recorded data and its analysis is repeatable. Participant bias is minimised or even eradicated and researcher bias tempered by enabling re-coding by others. CONCLUSIONS Framework facilitates the identification of experiential face-to-face learning venue affordances. Investigation will continue with on-line venues.

Identification of bacterial community composition in freshwater aquaculture system farming of Litopenaeus vannamei reveals distinct temperature-driven patterns

Change in temperature is often a major environmental factor in triggering waterborne disease outbreaks. Previous research has revealed temporal and spatial patterns of bacterial population in several aquatic ecosystems. To date, very little information is available on aquaculture environment. Here, we assessed environmental temperature effects on bacterial community composition in freshwater aquaculture system farming of Litopenaeus vannamei (FASFL). Water samples were collected over a one-year period, and aquatic bacteria were characterized by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and 16S rDNA pyrosequencing. Resulting DGGE fingerprints revealed a specific and dynamic bacterial population structure with considerable variation over the seasonal change, suggesting that environmental temperature was a key driver of bacterial population in the FASFL. Pyrosequencing data further demonstrated substantial difference in bacterial community composition between the water at higher (WHT) and at lower (WLT) temperatures in the FASFL. Actinobacteria, Proteobacteria and Bacteroidetes were the highest abundant phyla in the FASFL, however, a large number of unclassified bacteria contributed the most to the observed variation in phylogenetic diversity. The WHT harbored remarkably higher diversity and richness in bacterial composition at genus and species levels when compared to the WLT. Some potential pathogenenic species were identified in both WHT and WLT, providing data in support of aquatic animal health management in the aquaculture industry.

The koala immunological toolkit: Sequence identification and comparison of key markers of the koala (Phascolarctos cinereus) immune response

The koala (Phascolarctos cinereus) is an Australian marsupial that continues to experience significant population declines. Infectious diseases caused by pathogens such as Chlamydia are proposed to have a major role. Very few species-specific immunological reagents are available, severely hindering our ability to respond to the threat of infectious diseases in the koala. In this study, we utilise data from the sequencing of the koala transcriptome to identify key immunological markers of the koala adaptive immune response and cytokines known to be important in the host response to chlamydial infection in other species. This report describes the identification and preliminary sequence analysis of (1) T lymphocyte glycoprotein markers (CD4, CD8); (2) IL-4, a marker for the Th2 response; (3) cytokines such as IL-6, IL-12 and IL-1β, that have been shown to have a role in chlamydial clearance and pathology in other hosts; and (4) the sequences for the koala immunoglobulins, IgA, IgG, IgE and IgM. These sequences will enable the development of a range of immunological reagents for understanding the koala’s innate and adaptive immune responses, while also providing a resource that will enable continued investigations into the origin and evolution of the marsupial immune system.

VIP Barcoding: Composition vector-based software for rapid species identification based on DNA barcoding

Species identification based on short sequences of DNA markers, that is, DNA barcoding, has emerged as an integral part of modern taxonomy. However, software for the analysis of large and multilocus barcoding data sets is scarce. The Basic Local Alignment Search Tool (BLAST) is currently the fastest tool capable of handling large databases (e.g. >5000 sequences), but its accuracy is a concern and has been criticized for its local optimization. However, current more accurate software requires sequence alignment or complex calculations, which are time-consuming when dealing with large data sets during data preprocessing or during the search stage. Therefore, it is imperative to develop a practical program for both accurate and scalable species identification for DNA barcoding. In this context, we present VIP Barcoding: a user-friendly software in graphical user interface for rapid DNA barcoding. It adopts a hybrid, two-stage algorithm. First, an alignment-free composition vector (CV) method is utilized to reduce searching space by screening a reference database. The alignment-based K2P distance nearest-neighbour method is then employed to analyse the smaller data set generated in the first stage. In comparison with other software, we demonstrate that VIP Barcoding has (i) higher accuracy than Blastn and several alignment-free methods and (ii) higher scalability than alignment-based distance methods and character-based methods. These results suggest that this platform is able to deal with both large-scale and multilocus barcoding data with accuracy and can contribute to DNA barcoding for modern taxonomy. VIP Barcoding is free and available at http://msl.sls.cuhk.edu.hk/vipbarcoding/.

Frequency response function based damage identification using principal component analysis and pattern recognition technique

Pattern recognition is a promising approach for the identification of structural damage using measured dynamic data. Much of the research on pattern recognition has employed artificial neural networks (ANNs) and genetic algorithms as systematic ways of matching pattern features. The selection of a damage-sensitive and noise-insensitive pattern feature is important for all structural damage identification methods. Accordingly, a neural networks-based damage detection method using frequency response function (FRF) data is presented in this paper. This method can effectively consider uncertainties of measured data from which training patterns are generated. The proposed method reduces the dimension of the initial FRF data and transforms it into new damage indices and employs an ANN method for the actual damage localization and quantification using recognized damage patterns from the algorithm. In civil engineering applications, the measurement of dynamic response under field conditions always contains noise components from environmental factors. In order to evaluate the performance of the proposed strategy with noise polluted data, noise contaminated measurements are also introduced to the proposed algorithm. ANNs with optimal architecture give minimum training and testing errors and provide precise damage detection results. In order to maximize damage detection results, the optimal architecture of ANN is identified by defining the number of hidden layers and the number of neurons per hidden layer by a trial and error method. In real testing, the number of measurement points and the measurement locations to obtain the structure response are critical for damage detection. Therefore, optimal sensor placement to improve damage identification is also investigated herein. A finite element model of a two storey framed structure is used to train the neural network. It shows accurate performance and gives low error with simulated and noise-contaminated data for single and multiple damage cases. As a result, the proposed method can be used for structural health monitoring and damage detection, particularly for cases where the measurement data is very large. Furthermore, it is suggested that an optimal ANN architecture can detect damage occurrence with good accuracy and can provide damage quantification with reasonable accuracy under varying levels of damage.

Moffatt vortices induced by the motion of a contact line

A recent hydrodynamic theory of liquid slippage on a solid substrate (Kirkinis & Davis, Phys. Rev. Lett., vol. 110, 2013, 234503) gives rise to a sequence of eddies (Moffatt vortices) that co-move with a moving contact line (CL) in a liquid wedge. The presence of these vortices is established through secular equations that depend on the dynamic contact angle α and capillary number Ca. The limiting case α→O is associated with the appearance of such vortices in a channel. The vortices are generated by the relative motion of the interfaces, which in turn is due to the motion of the CL. This effect has yet to be observed in experiment.

Controlling routine front line service workers: an Australian retail supermarket case

Food retail is known for its use of flexible labour and for the centralisation of functions at head office, resulting in a reduction of managerial autonomy at store level. This article employs a typology of controls developed from labour process scholarship to explore how retail managers negotiate the control of their predominantly part-time workforce. Using an Australian supermarket chain as a case, and mixed methods, the article demonstrates that supermarkets use a multiplicity of forms of control across their workforce. For front line service workers, the article identifies a new configuration of controls which intersects with employment status and acts differentially for checkout operators on different employment contracts.

Development and validation of a questionnaire to measure health professionals' attitudes toward identification of female victimes of domestic violence

Background Domestic violence against women is a major public health problem and violations of women’s human rights. Health professionals could play an important role in screening for the victims. From the evidence to date, it is unclear whether health professionals do play an active role in identification of the victims. Objectives To develop a reliable and valid instrument to measure health professionals’ attitude to identifying female victims of domestic violence. Methods A primary questionnaire was constructed in accordance with established guidelines using the Theory of Planned Behaviour Ajzen (1975) to develop an instrument to measure health professionals’ attitudes in identifying female victim of DV. An expert panel was used to establish content validity. Focus groups amongst a group of health professionals (N = 5) of the target population were performed to confirm face validity. A pilot study (N = 30 nurses and doctors) was undertaken to elicit the feasibility and reliability of the questionnaire. The questionnaire was also administered a second time after one week to check the stability of the tests. Results Feedbacks of the expert panel’s and group discussion confirmed that the questionnaire had the content and face validity. Cronbach’s alpha values for all the items were greater than 0.7. Strong correlations between the direct and indirect measures confirmed that the indirect measures were well constructed. High test-retest correlations confirmed that the measures were reliable in the sense of temporal stability. Significance This tool has the potential to be used by researchers in expanding the knowledge base in this important area.