Fine-mapping the HOXB region detects common variants tagging a rare coding allele : evidence for synthetic association in prostate cancer

The HOXB13 gene has been implicated in prostate cancer (PrCa) susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, P = 2.62×10(-14)). Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (G84E, rs138213197), which has been identified recently as a moderate penetrance PrCa susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility.

The social foundations of risk

Ulrich Beck's argument about risk society emphasises, among other things, the pervasiveness of risk. As a feature of the human condition in the contemporary, globalised, world that distinguishes the present from the past, risk is widespread across society and affects all social strata. While Beck has gestured towards the irregular distribution of contemporary risks, nonetheless he has suggested that traditional structural entities – class and wealth – no longer provide the key interpretive frameworks for the calculation of susceptibility. In short, the tentacles of risk are long and almost no one is out of reach. Yet, while the risk society thesis has generated a large theoretical literature, there is very little in the way of research that marries theorising to original data collection. This paper represents an attempt to address this gap by using empirical data to investigate whether risk is more textured than Beck's account suggests. Focusing on health as a domain of risk, the paper uses data from a national sample survey of the Australian electorate to investigate the extent to which social divisions structure perceptions of risk within the general population. The findings suggest that various aspects of social stratification, such as income, occupation and education, do indeed play a role in shaping perceptions of risk.

Institutional investors, risk/return and corporate governance : practical lessons from the Global Financial Crisis

The global grown in institutional investors means that firms can no longer ignore their influence in capital markets. However, not all institutional investors have the same motives to influence the firms they invest in. Institution investors' ability to influence management depends on the size of their investment and whether they have any business relations with the firm. Using a sample of Australian firms from 2006 to 2008, our empirical results show that the proportion of a company's shares held by institutional investors is positively associated with firm governance ratings, risk and profitability. This study shows that a positive association between risk and return is associated with large active institutional ownership, which we interpret as shareholders with sufficient power to pressure management to increase short-term profits.

Responsible reconstruction : The architect's role

This paper investigates the role of the architect in post-disaster reconstruction and questions their ability to facilitate per- manent building solutions. There is an ever-increasing population of refugees and internally displaced persons due to disasters and conflicts who have a basic need for shelter. To date, housing solutions for such people has tended to focus on short-term, temporary shelter solutions that have been largely unsuccessful. This increasing demand for shelter has led to an emerging group of architects skilled in post-disaster reconstruction. These architects acknowledge that shelter is critical to survival, but believe architects should focus on rebuilding in a manner that is quick, durable but permanent. They believe that an architect skilled in post-disaster reconstruction can produce solutions that meet the requirement of the emergency phase, through to semi-permanent and even permanent homes, without wasting time and money on interim shelters. Case Study Research was used to examine and evaluate the assistance provided by Emergency Architects Australia (EAA) to the Kei Gold community in the Solomon Islands after the 2007 earthquake and tsunami. The results indicate that an architect’s response to a disaster must go beyond providing temporary shelter; they must create permanent building solutions that respond to the site and the culture while servicing the needs of the communi- ty. The vernacular reconstruction methods implemented by EAA in Kei Gold Village have been successful in develop- ing permanent housing solutions. Further research and development is required to gain a broader understanding of the role of the architect in disasters of varying scales and typologies.

Australian health and safety inspectors’ perceptions and actions in relation to changed work arrangements

Extensive international research points to an association between changed work arrangements, especially those commonly labelled as contingent work, with adverse occupational health and safety (OHS) outcomes. Research also indicates these work arrangements have weakened or bypassed existing OHS and workers’ compensation regulatory regimes. However, there has been little if any research into how OHS inspectors perceive these issues and how they address them during workplace visits or investigations. Between 2003 and 2007 research was undertaken that entailed detailed documentary and statistical analysis, extended interviews with 170 regulatory managers and inspectors, and observational data collected while accompanying inspectors on 118 ‘typical’ workplace visits. Key findings are that inspectors responsible for a range of industries see altered work arrangements as a serious challenge, especially labour hire (agency work) and subcontracting. Though the law imposes clear obligations, inspectors identified misunderstanding/blameshifting and poor compliance amongst parties to these arrangements. The complexity of these work arrangements also posed logistical challenges to inspectorates.

Association study of MTHFD1 coding polymorphisms R134K and R653Q with migraine susceptibility

Objective There is evidence that folate metabolism has a role in migraine pathophysiology, particularly in the migraine with aura subtype. In this study we investigate whether two non-synonymous single nucleotide polymorphisms (SNPs), rs1950902 (C401T; R134K) and rs2236225 (G1958A; R653Q), in MTHDF1 are associated with migraine in an Australian case-control population. Background Increased plasma levels of homocysteine (HCy), one of the metabolites produced in the folate pathway, has been found to be a risk factor for migraine. There is also a genetic link, as a common polymorphism (C667T) that reduces the catalytic activity of MTHFR, the enzyme that catalyses the formation of HCy, is associated with an increase in risk of the migraine with aura (MA) subtype. MTHFD1 is a crucial multifunctional enzyme that catalyses three separate reactions of the folate pathway and therefore variants in MTHFD1 may also influence migraine susceptibility. Methods The R134K and R653Q variants in MTHFD1 were genotyped in an Australian cohort of 520 unrelated migraineurs (162 were diagnosed with migraine without aura [MO] and 358 with MA) and 520 matched controls. Data were analysed for association with migraine and for interaction with the MTHFR C667T polymorphism. Results We find no significant differences in genotype or allele frequencies for either SNP between migraineurs and controls, or when either MO or MA cases were compared to controls. In addition these MTHFD1 polymorphisms did not appear to influence the risk of MA conferred by the MTHFR 667T allele. Conclusions We find no evidence for association of the MTHFD1 R134K and R653Q polymorphisms with migraine in our Australian case-control population. However, as folate metabolism appears to be important in migraine, particularly with respect to the aura component, future studies using high throughput methods to expand the number of SNPs in folate-related genes genotyped and investigation of interactions between SNPs may be justified.

Corneal changes following short-term miniscleral contact lens wear

Purpose To examine the influence of short-term miniscleral contact lens wear on corneal shape, thickness and anterior surface aberrations. Methods Scheimpflug imaging was captured before, immediately following and 3 hours after a short period (3 hours) of miniscleral contact lens wear for 10 young (mean 27 ± 5 years), healthy participants. Natural diurnal variations were considered by measuring baseline diurnal changes obtained on a separate control day without contact lens wear. Results Small but significant anterior corneal flattening was observed immediately following lens removal (overall mean 0.02 ± 0.03 mm, p < 0.001) which returned to baseline levels three hours after lens removal. During the three hour recovery period significant corneal thinning (-13.4 ± 10.5 μm) and posterior surface flattening (0.03 ± 0.02 mm) were also observed (both p < 0.01). The magnitude of posterior corneal flattening during recovery correlated with the amount of corneal thinning (r = 0.69, p = 0.03). Central corneal clearance (maximum tear reservoir depth) was not associated with corneal swelling following lens removal (r = -0.24, p > 0.05). An increase in lower-order corneal astigmatism Z(2,2) was also observed following lens wear (mean -0.144 ± 0.075 μm, p = 0.02). Conclusions Flattening of the anterior corneal surface was observed immediately following lens wear, while ‘rebound’ thinning and flattening of the posterior surface was evident following the recovery period. Modern miniscleral contact lenses that vault the cornea may slightly influence corneal shape and power but do not induce clinically significant corneal oedema during short-term wear.

Association hierarchy mining and its application for network traffic characterisation

This thesis presents an association rule mining approach, association hierarchy mining (AHM). Different to the traditional two-step bottom-up rule mining, AHM adopts one-step top-down rule mining strategy to improve the efficiency and effectiveness of mining association rules from datasets. The thesis also presents a novel approach to evaluate the quality of knowledge discovered by AHM, which focuses on evaluating information difference between the discovered knowledge and the original datasets. Experiments performed on the real application, characterizing network traffic behaviour, have shown that AHM achieves encouraging performance.

The association between the measurement of adherence to anti-diabetes medicine and the HbA1c

BACKGROUND: Adherence to medicines is important in subjects with diabetes, as nonadherence is associated with an increased risk of morbidity and mortality. However, it is not clear whether there is an association between adherence to medicines and glycaemic control, as not all studies have shown this. One of the reasons for this discrepancy may be that, although there is a standard measure of glycaemic control i.e. HbA1c, there is no standard measure of adherence to medicines. Adherence to medicines can be measured either qualitatively by Morisky or non-Morisky methods or quantitatively using the medicines possession ratio (MPR). AIMS OF THE REVIEW: The aims of this literature review are (1) to determine whether there is an association between adherence to anti-diabetes medicines and glycaemic control, and (2) whether any such association is dependent on how adherence is measured. Methods A literature search of Medline, CINAHL and the Internet (Google) was undertaken with search terms; 'diabetes' with 'adherence' (or compliance, concordance, persistence, continuation) with 'HbA1c' (or glycaemic control). RESULTS: Twenty-three studies were included; 10 qualitative and 12 quantitative studies, and one study using both methods. For the qualitative methods measurements of adherence to anti-diabetes medicines (non-Morisky and Morisky), eight out of ten studies show an association with HbA1c. Nine of ten studies using the quantitative MPR, and two studies using MPR for insulin only, have also shown an association between adherence to anti-diabetes medicines and HbA1c. However, the one study that used both Morisky and MPR did not show an association. Three of the four studies that did not show a relationship, did not use a range of HbA1c values in their regression analysis. The other study that did not show a relationship was specifically in a low income population. CONCLUSIONS: Most studies show an association between adherence to anti-diabetes medicines and HbA1c levels, and this seems to be independent of method used to measure adherence. However, to show an association it is necessary to have a range of HbA1c values. Also, the association is not always apparent in low income populations.

Australian Library and Information Association Course Accreditation Review 2013

This report has been prepared for the Australian Library and Information Association (ALIA) in response to the request to undertake a literature review and environmental scan to inform discussions of the issues associated with professional accreditation. ALIA is the peak body which develops and monitors the professional standards that ensure the high quality of graduates entering the library and information services (LIS) profession in Australia. The report presents a themed discussion of the issues identified in the literature review and environmental scan to build a full picture of the role of course accreditation in LIS education. This is set against developments in the wider context of quality assurance in Australian tertiary education, to analyse the implications of this changing environment for ALIA’s accreditation policies and ractices.

Short-data recursive HMM parameter estimation for rapid vision-based aircraft heading estimation

Rapid recursive estimation of hidden Markov Model (HMM) parameters is important in applications that place an emphasis on the early availability of reasonable estimates (e.g. for change detection) rather than the provision of longer-term asymptotic properties (such as convergence, convergence rate, and consistency). In the context of vision- based aircraft (image-plane) heading estimation, this paper suggests and evaluates the short-data estimation properties of 3 recursive HMM parameter estimation techniques (a recursive maximum likelihood estimator, an online EM HMM estimator, and a relative entropy based estimator). On both simulated and real data, our studies illustrate the feasibility of rapid recursive heading estimation, but also demonstrate the need for careful step-size design of HMM recursive estimation techniques when these techniques are intended for use in applications where short-data behaviour is paramount.

Double-strand breaks and the concept of short- and long-term epigenetic memory

Double-strand breaks represent an extremely cytolethal form of DNA damage and thus pose a serious threat to the preservation of genetic and epigenetic information. Though it is well-known that double-strand breaks such as those generated by ionising radiation are among the principal causative factors behind mutations, chromosomal aberrations, genetic instability and carcino-genesis, significantly less is known about the epigenetic consequences of double-strand break formation and repair for carcinogenesis. Double-strand break repair is a highly coordinated process that requires the unravelling of the compacted chromatin structure to facilitate repair machinery access and then restoration of the original undamaged chromatin state. Recent experimental findings have pointed to a potential mechanism for double-strand break-induced epigenetic silencing. This review will discuss some of the key epigenetic regulatory processes involved in double-strand break (DSB) repair and how incomplete or incorrect restoration of chromatin structure can leave a DSB-induced epigenetic memory of damage with potentially pathological repercussions

Cerebellar grey matter deficits in first-episode schizophrenia mapped using cortical pattern matching

Cerebellar dysfunction has been proposed to lead to “cognitive dysmetria” in schizophrenia via the cortico-cerebellar-thalamic-cortical circuit, contributing to a range of cognitive and clinical symptoms of the disorder. Here we investigated total cerebellar grey and white matter volumes and cerebellar regional grey matter abnormalities in 13 remitted first-episode schizophrenia patients with less than 2 years’ duration of illness. Patient data were compared to 13 pair-wise age, gender, and handedness-matched healthy volunteers using cortical pattern averaging on high-resolution magnetic resonance images. Total cerebellar volume and total grey matter volumes in first-episode schizophrenia patients did not differ from healthy control subjects, but total cerebellar white matter was increased and total grey to white matter ratios were reduced in patients. Four clusters of cerebellar grey matter reduction were identified: (i) in superior vermis; (ii) in the left lobuli VI; (iii) in right-inferior lobule IX, extending into left lobule IX; and (iv) bilaterally in the areas of lobuli III, peduncle and left flocculus. Grey matter deficits were particularly prominent in right lobuli III and IX, left flocculus and bilateral pedunculi. These cerebellar areas have been implicated in attention control, emotional regulation, social functioning, initiation of smooth pursuit eye movements, eye-blink conditioning, language processing, verbal memory, executive function and the processing of spatial and emotional information. Consistent with common clinical, cognitive, and pathophysiological signs of established illness, our findings demonstrate cerebellar pathology as early as in first-episode schizophrenia.

Examining the neural correlates of choice behavior in a gambling task using steady state topography

The present study investigated the behavioral and neuropsychological characteristics of decision-making behavior during a gambling task as well as how these characteristics may relate to the Somatic Marker Hypothesis and the Frequency of Gain model. The applicability to intertemporal choice was also discussed. Patterns of card selection during a computerized interpretation of the Iowa Gambling Task were assessed for 10 men and 10 women. Steady State Topography was employed to assess cortical processing throughout this task. Results supported the hypothesis that patterns of card selection were in line with both theories. As hypothesized, these 2 patterns of card selection were also associated with distinct patterns of cortical activity, suggesting that intertemporal choice may involve the recruitment of right dorsolateral prefrontal cortex for somatic labeling, left fusiform gyrus for object representations, and the left dorsolateral prefrontal cortex for an analysis of the associated frequency of gain or loss. It is suggested that processes contributing to intertemporal choice may include inhibition of negatively valenced options, guiding decisions away from those options, as well as computations favoring frequently rewarded options.

Old mastheads and new media : newspapers striving to adapt in Australia and South-east Asia

As a key element in their response to new media forcing transformations in mass media and media use, newspapers have deployed various strategies to not only establish online and mobile products, and develop healthy business plans, but to set out to be dominant portals. Their response to change was the subject of an early investigation by one of the present authors (Keshvani 2000). That was part of a set of short studies inquiring into what impact new software applications and digital convergence might have on journalism practice (Tickle and Keshvani 2000), and also looking for demonstrations of the way that innovations, technologies and protocols then under development might produce a “wireless, streamlined electronic news production process (Tickle and Keshvani 2001).” The newspaper study compared the online products of The Age in Melbourne and the Straits Times in Singapore. It provided an audit of the Singapore and Australia Information and Communications Technology (ICT) climate concentrating on the state of development of carrier networks, as a determining factor in the potential strength of the two services with their respective markets. In the outcome, contrary to initial expectations, the early cable roll-out and extensive ‘wiring’ of the city in Singapore had not produced a level of uptake of Internet services as strong as that achieved in Melbourne by more ad hoc and varied strategies. By interpretation, while news websites and online content were at an early stage of development everywhere, and much the same as one another, no determining structural imbalance existed to separate these leading media participants in Australia and South-east Asia. The present research revisits that situation, by again studying the online editions of the two large newspapers in the original study, and one other, The Courier Mail, (recognising the diversification of types of product in this field, by including it as a representative of Newscorp, now a major participant). The inquiry works through the principle of comparison. It is an exercise in qualitative, empirical research that establishes a comparison between the situation in 2000 as described in the earlier work, and the situation in 2014, after a decade of intense development in digital technology affecting the media industries. It is in that sense a follow-up study on the earlier work, although this time giving emphasis to content and style of the actual products as experienced by their users. It compares the online and print editions of each of these three newspapers; then the three mastheads as print and online entities, among themselves; and finally it compares one against the other two, as representing a South-east Asian model and Australian models. This exercise is accompanied by a review of literature on the developments in ICT affecting media production and media organisations, to establish the changed context. The new study of the online editions is conducted as a systematic appraisal of the first level, or principal screens, of the three publications, over the course of six days (10-15.2.14 inclusive). For this, categories for analysis were made, through conducting a preliminary examination of the products over three days in the week before. That process identified significant elements of media production, such as: variegated sourcing of materials; randomness in the presentation of items; differential production values among media platforms considered, whether text, video or stills images; the occasional repurposing and repackaging of top news stories of the day and the presence of standard news values – once again drawn out of the trial ‘bundle’ of journalistic items. Reduced in this way the online artefacts become comparable with the companion print editions from the same days. The categories devised and then used in the appraisal of the online products have been adapted to print, to give the closest match of sets of variables. This device, to study the two sets of publications on like standards -- essentially production values and news values—has enabled the comparisons to be made. This comparing of the online and print editions of each of the three publications was set up as up the first step in the investigation. In recognition of the nature of the artefacts, as ones that carry very diverse information by subject and level of depth, and involve heavy creative investment in the formulation and presentation of the information; the assessment also includes an open section for interpreting and commenting on main points of comparison. This takes the form of a field for text, for the insertion of notes, in the table employed for summarising the features of each product, for each day. When the sets of comparisons as outlined above are noted, the process then becomes interpretative, guided by the notion of change. In the context of changing media technology and publication processes, what substantive alterations have taken place, in the overall effort of news organisations in the print and online fields since 2001; and in their print and online products separately? Have they diverged or continued along similar lines? The remaining task is to begin to make inferences from that. Will the examination of findings enforce the proposition that a review of the earlier study, and a forensic review of new models, does provide evidence of the character and content of change --especially change in journalistic products and practice? Will it permit an authoritative description on of the essentials of such change in products and practice? Will it permit generalisation, and provide a reliable base for discussion of the implications of change, and future prospects? Preliminary observations suggest a more dynamic and diversified product has been developed in Singapore, well themed, obviously sustained by public commitment and habituation to diversified online and mobile media services. The Australian products suggest a concentrated corporate and journalistic effort and deployment of resources, with a strong market focus, but less settled and ordered, and showing signs of limitations imposed by the delay in establishing a uniform, large broadband network. The scope of the study is limited. It is intended to test, and take advantage of the original study as evidentiary material from the early days of newspaper companies’ experimentation with online formats. Both are small studies. The key opportunity for discovery lies in the ‘time capsule’ factor; the availability of well-gathered and processed information on major newspaper company production, at the threshold of a transformational decade of change in their industry. The comparison stands to identify key changes. It should also be useful as a reference for further inquiries of the same kind that might be made, and for monitoring of the situation in regard to newspaper portals on line, into the future.