Genome-wide association study identifies a possible susceptibility locus for endometrial cancer

Background: Genome-wide association studies (GWAS) have identified more than 100 genetic loci for various cancers. However, only one is for endometrial cancer. Methods: We conducted a three-stage GWAS including 8,492 endometrial cancer cases and 16,596 controls. After analyzing 585,963 single-nucleotide polymorphisms (SNP) in 832 cases and 2,682 controls (stage I) from the Shanghai Endometrial Cancer Genetics Study, we selected the top 106 SNPs for in silico replication among 1,265 cases and 5,190 controls from the Australian/British Endometrial Cancer GWAS (stage II). Nine SNPs showed results consistent in direction with stage I with P < 0.1. These nine SNPs were investigated among 459 cases and 558 controls (stage IIIa) and six SNPs showed a direction of association consistent with stages I and II. These six SNPs, plus two additional SNPs selected on the basis of linkage disequilibrium and P values in stage II, were investigated among 5,936 cases and 8,166 controls from an additional 11 studies (stage IIIb). Results: SNP rs1202524, near the CAPN9 gene on chromosome 1q42.2, showed a consistent association with endometrial cancer risk across all three stages, with ORs of 1.09 [95% confidence interval (CI), 1.03–1.16] for the A/G genotype and 1.17 (95% CI, 1.05–1.30) for the G/G genotype (P = 1.6 × 10−4 in combined analyses of all samples). The association was stronger when limited to the endometrioid subtype, with ORs (95% CI) of 1.11 (1.04–1.18) and 1.21 (1.08–1.35), respectively (P = 2.4 × 10−5). Conclusions: Chromosome 1q42.2 may host an endometrial cancer susceptibility locus. Impact: This study identified a potential genetic locus for endometrial cancer risk

A novel representation of bioacoustic events for content-based search in field audio data

Bioacoustic data can provide an important base for environmental monitoring. To explore a large amount of field recordings collected, an automated similarity search algorithm is presented in this paper. A region of an audio defined by frequency and time bounds is provided by a user; the content of the region is used to construct a query. In the retrieving process, our algorithm will automatically scan through recordings to search for similar regions. In detail, we present a feature extraction approach based on the visual content of vocalisations – in this case ridges, and develop a generic regional representation of vocalisations for indexing. Our feature extraction method works best for bird vocalisations showing ridge characteristics. The regional representation method allows the content of an arbitrary region of a continuous recording to be described in a compressed format.

Synthesis and evaluation of resveratrol-based nitroxides as potential treatments for hypertension

The synthesis and evaluation of novel resveratrol-based nitroxides have been explored for the potential treatment of hypertension. New methodology for the direct aryl iodination of isoindoline and isoindoline nitroxide using periodic acid and potassium iodide in concentrated sulphuric acid was developed. Diiodinated tetramethyl and tetraethyl isoindolines and a tetramethyl isoindoline nitroxide were prepared in excellent yields (70 – 82%). A diiodinated tetraethyl isoindoline nitroxide was generated from the corresponding nitroxide in modest yield (37%) alongside iodinated nitrones. The mono-iodinated species were also generated in modest yields (34 – 48%). Incorporation of the nitroxide unit into the structure of resveratrol was achieved using palladium-catalysed Heck coupling. Use of the previously prepared iodo products 5-iodo-1,1,3,3-tetramethylisoindolin-2-yloyl 18 and 5,6-diiodo-1,1,3,3-tetramethylisoindolin-2-yloyl 22 gave resveratrol nitroxides 12 and 13 in yields of 50% (optimized) and 1.6% respectively. Preliminary evaluation of the resveratrol analogue 12 as a treatment for hypertension was undertaken in the DOCA-salt rat model. A reduction in systolic blood pressure as well as alleviation of ventricular hypertrophy was observed. A larger study involving the DOCA salt rats is currently in progress.

Robust control algorithm for grid-interfaced three-phase inverters with high-bandwidth LCL filter

The paper introduces the design of robust current and voltage control algorithms for a grid-connected three-phase inverter which is interfaced to the grid through a high-bandwidth three-phase LCL filter. The algorithms are based on the state feedback control which have been designed in a systematic approach and improved by using oversampling to deal with the issues arising due to the high-bandwidth filter. An adaptive loop delay compensation method has also been adopted to minimize the adverse effects of loop delay in digital controller and to increase the robustness of the control algorithm in the presence of parameter variations. Simulation results are presented to validate the effectiveness of the proposed algorithm.

The role of conflict in determining consensus on quality in Wikipedia articles

This paper presents research that investigated the role of conflict in the editorial process of the online encyclopedia, Wikipedia. The study used a grounded approach to analyzing 147 conversations about quality from the archived history of the Wikipedia article 'Australia'. It found that conflict in Wikipedia is a generative friction, regulated by references to policy as part of a coordinated effort within the community to improve the quality of articles.

Through the eyes of the mentor : framing expectations within preservice teacher and mentor relationships

Mentoring relationships during pre-service education are a significant relationship through which emerging teachers negotiate their teacher identity (Iancu-Haddad & Oplatka, 2009; Hudson, 2010). It is therefore important to understand how mentor teachers frame their expectations. This paper explores mentoring relationships established within a Queensland partnership program funded through the Federal Government’s Improving Teacher Quality National Partnership Agreement (DEEWR, 2011). Within the broader policy context, these mentoring relationships were seen as an important space for pre-service teachers to experience cultural induction into Education Queensland schooling, and be advocates for quality teaching (Willis, Bahr, Bannah, & Welch, 2012). Interview and survey data from 14 teacher mentors were analysed using a dialectic constant comparison approach (Dick 2007). Three significant themes were identified. Mentor teachers’ understanding of their roles positioned pre-service teachers as either novices or alternatively as colleagues, and these had implications for the opportunities for learning that were then made available to the pre-service teachers. The mentor teacher’s beliefs about teaching as a practical craft, and how the mentor teachers judged a pre-service teacher’s “enthusiasm” were also analysed. Understanding the factors that guide teacher mentor approaches may inform future designs of mentoring and preservice teacher preparation programs.

Gait parameters associated with hallux valgus : a systematic review

Background Hallux valgus (HV) has been linked to functional disability and increased falls risk in older adults. However, specific gait alterations in individuals with HV are unclear. This systematic review investigated gait parameters associated with HV in otherwise healthy adults. Methods Electronic databases (Medline, Embase, CINAHL) were searched to October 2011, including cross-sectional studies with clearly defined HV and non-HV comparison groups. Two investigators independently rated studies for methodological quality. Effect sizes (95% confidence intervals (CI)) were calculated as standardized mean differences (SMD) for continuous data and risk ratios (RR) for dichotomous data. Results Nine studies included a total of 589 participants. Three plantar pressure studies reported increased hallux loading (SMD 0.56 to 1.78) and medial forefoot loading (SMD 0.62 to 1.21), while one study found reduced first metatarsal loading (SMD −0.61, CI −1.19 to −0.03) in HV participants. HV participants demonstrated less ankle and rearfoot motion during terminal stance (SMD −0.81 to −0.63) and increased intrinsic muscle activity (RR 1.6, 1.1 to 2.2). Most studies reported no differences in spatio-temporal parameters; however, one study found reduced speed (SMD −0.73, -1.25 to −0.20), step length (SMD −0.66 to −0.59) and less stable gait patterns (SMD −0.86 to −0.78) in older adults with HV. Conclusions HV impacts on particular gait parameters, and further understanding of potentially modifiable factors is important for prevention and management of HV. Cause and effect relationships cannot be inferred from cross-sectional studies, thus prospective studies are warranted to elucidate the relationship between HV and functional disability.

Vorinostat/SAHA-induced apoptosis in malignant mesothelioma is FLIP/caspase 8-dependent and HR23B-independent

Introduction: Malignant pleural mesothelioma (MPM) is a rapidly fatal malignancy that is increasing in incidence. The caspase 8 inhibitor FLIP is an anti-apoptotic protein over-expressed in several cancer types including MPM. The histone deacetylase (HDAC) inhibitor Vorinostat (SAHA) is currently being evaluated in relapsed mesothelioma. We examined the roles of FLIP and caspase 8 in regulating SAHA-induced apoptosis in MPM. Methods: The mechanism of SAHA-induced apoptosis was assessed in 7 MPM cell lines and in a multicellular spheroid model. SiRNA and overexpression approaches were used, and cell death was assessed by flow cytometry, Western blotting and clonogenic assays. Results: RNAi-mediated FLIP silencing resulted in caspase 8-dependent apoptosis in MPM cell line models. SAHA potently down-regulated FLIP protein expression in all 7 MPM cell lines and in a multicellular spheroid model of MPM. In 6/7 MPM cell lines, SAHA treatment resulted in significant levels of apoptosis induction. Moreover, this apoptosis was caspase 8-dependent in all six sensitive cell lines. SAHA-induced apoptosis was also inhibited by stable FLIP overexpression. In contrast, down-regulation of HR23B, a candidate predictive biomarker for HDAC inhibitors, significantly inhibited SAHA-induced apoptosis in only 1/6 SAHA-sensitive MPM cell lines. Analysis of MPM patient samples demonstrated significant inter-patient variations in FLIP and caspase 8 expressions. In addition, SAHA enhanced cisplatin-induced apoptosis in a FLIP-dependent manner. Conclusions: These results indicate that FLIP is a major target for SAHA in MPM and identifies FLIP, caspase 8 and associated signalling molecules as candidate biomarkers for SAHA in this disease. © 2011 Elsevier Ltd. All rights reserved.

Computer security incidents against Australian businesses : predictors of victimisation

Drawing on data from the Australian Business Assessment of Computer User Security (ABACUS) survey, this paper examines a range of factors that may influence businesses’ likelihood of being victimised by a computer security incident. It has been suggested that factors including business size, industry sector, level of outsourcing, expenditure on computer security functions and types of computer security tools and/or policies used may influence the probability of particular businesses experiencing such incidents. This paper uses probability modelling to test whether this is the case for the 4,000 businesses that responded to the ABACUS survey. It was found that the industry sector that a business belonged to, and business expenditure on computer security, were not related to businesses’ likelihood of detecting computer security incidents. Instead, the number of employees that a business has and whether computer security functions were outsourced were found to be key indicators of businesses’ likelihood of detecting incidents. Some of the implications of these findings are considered in this paper.

Child complainants and the court process in Australia

In recent years, it has been recognised that child complainants in the criminal justice system can experience difficulties over and above those of other complainants and that children can experience the court process as extremely traumatising. This can be exacerbated if children are complainants in child sexual offence matters and if they have to give evidence against a family member. This paper has three primary aims. First, it outlines the major factors that contribute to making court processes harrowing for child complainants. Second, it outlines some of the main initiatives that have been introduced to address these factors. Finally, it weighs up the evidence about initiatives designed to assist child complainants and concludes that such initiatives have had only limited practical impact for child complainants in the criminal justice system. The limited impact is attributed to the need to balance the rights of the accused with consideration for the complainant, a failure to translate legislative changes into practice, the impact of judicial discretion and/or a focus on protecting child complainants at the expense of increasing convictions.

Development of a bi-material representative volume element using damaged homogenisation approach

Most civil engineering structures are formed using a number of materials that are bonded to each other with their surface-to-surface interaction playing key role on the overall response of the structure. Unfortunately these interactions are extremely variable; simplified and extremely detailed models trialed to date prove quite complex. Models that assume perfect interaction, on the other hand, predict unsafe behavior. In this paper a damage mechanics based interaction between two materials of different softening properties is developed using homogenisation approach. This paper describes the process of developing a bi-material representative volume element (RVE) using damaged homogenisation approach. The novelty in this paper is the development of non-local transient damage identification algorithm. Numerical examples prove the stability of the approach for a simplified RVE and encourage application to other shapes of RVEs.

Dynamic load sharing in heavy vehicle suspensions - further analysis of the equalisation effects of larger air lines

This paper provides details on comparative testing of axle-to-chassis forces of two heavy vehicles (HVs) based on an experimental programme carried out in 2007. Dynamic forces at the air springs were measured against speed and roughness values for the test roads used. One goal of that programme was to determine whether dynamic axle-to-chassis forces could be reduced by using larger-than-standard diameter longitudinal air lines. This paper presents a portion of the methodology, analysis and results from that programme. Two analytical techniques and their results are presented. The first uses correlation coefficients of the forces between air springs and the second is a student’s t-test. These were used to determine the causality surrounding improved dynamic load sharing between heavy vehicle air springs with larger air lines installed longitudinally compared with the standard sized air lines installed on the majority of air-sprung heavy vehicles.

Moderation practices in a faculty of education : the four discourse model

Moderation of student assessment is a critical component of teaching and learning in contemporary universities. In Australia, moderation is mandated through university policies and through the new national university accreditation authority, Tertiary Education Quality and Standards Agency which began operations in late January 2012 (TEQSA, 2012). The TEQSA requirement to declare details of moderation and any other arrangements used to support consistency and reliability of assessment and grading across each subject in the course of study is a radical step intended to move toward heightened accountability and greater transparency in the tertiary sector as well as entrenching evidence-based practice in the management of Australian academic programs. In light of this reform, the purpose of this project was to investigate and analyse current moderation practices operating within a faculty of education at a large urban university in Queensland, Australia. This qualitative study involved interviews with the unit coordinators (n=21) and tutors (n=8) of core undergraduate education units and graduate diploma units within the faculty. Four distinct discourses of moderation that academics drew on to discuss their practices were identified in the study. These were: equity, justification, community building, and accountability. These discourses, together with recommendations for changes to moderation practices are discussed in this paper.

A single copy of a virus-derived transgene encoding hairpin RNA gives immunity to barley yellow dwarf virus

Barley yellow dwarf virus-PAV (BYDV-PAV) is the most serious and widespread virus of cereals worldwide. Natural resistance genes against this luteovirus give inadequate control, and previous attempts to introduce synthetic resistance into cereals have produced variable results. In an attempt to generate barley with protection against BYDV-PAV, plants were transformed with a transgene designed to produce hairpin (hp)RNA containing BYDV-PAV sequences. From 25 independent barley lines transformed with the BYDV-PAV hpRNA construct, nine lines showed extreme resistance to the virus and the majority of these contained a single transgene. In the progeny of two independent transgenic lines, inheritance of a single transgene consistently correlated with protection against BYDV-PAV. This protection was rated as immunity because the virus could not be detected in the challenged plants by ELISA nor recovered by aphid feeding experiments. In the field, BYDV-PAV is sometimes associated with the related luteovirus Cereal yellow dwarf virus-RPV (CYDV-RPV). When the transgenic plants were challenged with BYDV-PAV and CYDV-RPV together, the plants were susceptible to CYDV-RPV but immune to BYDV-PAV. This shows that the immunity is virus-specific and not broken down by the presence of CYDV. It suggests that CYDV-RPV does not encode a silencing-suppressor gene or that its product does not protect BYDV-PAV against the plant's RNAi-like defence mechanism. Either way, our results indicate that the BYDV-PAV immunity will be robust in the field and is potentially useful in minimizing losses in cereal production worldwide.