Spatial clusters of suicide in Australia

Background: Understanding the spatial distribution of suicide can inform the planning, implementation and evaluation of suicide prevention activity. This study explored spatial clusters of suicide in Australia, and investigated likely socio-demographic determinants of these clusters. Methods: National suicide and population data at a statistical local area (SLA) level were obtained from the Australian Bureau of Statistics for the period of 1999 to 2003. Standardised mortality ratios (SMR) were calculated at the SLA level, and Geographic Information System (GIS) techniques were applied to investigate the geographical distribution of suicides and detect clusters of high risk in Australia. Results: Male suicide incidence was relatively high in the northeast of Australia, and parts of the east coast, central and southeast inland, compared with the national average. Among the total male population and males aged 15 to 34, Mornington Shire had the whole or a part of primary high risk cluster for suicide, followed by the Bathurst-Melville area, one of the secondary clusters in the north coastal area of the Northern Territory. Other secondary clusters changed with the selection of cluster radius and age group. For males aged 35 to 54 years, only one cluster in the east of the country was identified. There was only one significant female suicide cluster near Melbourne while other SLAs had very few female suicide cases and were not identified as clusters. Male suicide clusters had a higher proportion of Indigenous population and lower median socio-economic index for area (SEIFA) than the national average, but their shapes changed with selection of maximum cluster radii setting. Conclusion: This study found high suicide risk clusters at the SLA level in Australia, which appeared to be associated with lower median socio-economic status and higher proportion of Indigenous population. Future suicide prevention programs should focus on these high risk areas.

Seed-based biclustering of gene expression data

Background Accumulated biological research outcomes show that biological functions do not depend on individual genes, but on complex gene networks. Microarray data are widely used to cluster genes according to their expression levels across experimental conditions. However, functionally related genes generally do not show coherent expression across all conditions since any given cellular process is active only under a subset of conditions. Biclustering finds gene clusters that have similar expression levels across a subset of conditions. This paper proposes a seed-based algorithm that identifies coherent genes in an exhaustive, but efficient manner. Methods In order to find the biclusters in a gene expression dataset, we exhaustively select combinations of genes and conditions as seeds to create candidate bicluster tables. The tables have two columns: (a) a gene set, and (b) the conditions on which the gene set have dissimilar expression levels to the seed. First, the genes with less than the maximum number of dissimilar conditions are identified and a table of these genes is created. Second, the rows that have the same dissimilar conditions are grouped together. Third, the table is sorted in ascending order based on the number of dissimilar conditions. Finally, beginning with the first row of the table, a test is run repeatedly to determine whether the cardinality of the gene set in the row is greater than the minimum threshold number of genes in a bicluster. If so, a bicluster is outputted and the corresponding row is removed from the table. Repeating this process, all biclusters in the table are systematically identified until the table becomes empty. Conclusions This paper presents a novel biclustering algorithm for the identification of additive biclusters. Since it involves exhaustively testing combinations of genes and conditions, the additive biclusters can be found more readily.

Iterative development of MobileMums : a physical activity intervention for women with young children.

Background To describe the iterative development process and final version of ‘MobileMums’: a physical activity intervention for women with young children (<5 years) delivered primarily via mobile telephone (mHealth) short messaging service (SMS). Methods MobileMums development followed the five steps outlined in the mHealth development and evaluation framework: 1) conceptualization (critique of literature and theory); 2) formative research (focus groups, n= 48); 3) pre-testing (qualitative pilot of intervention components, n= 12); 4) pilot testing (pilot RCT, n= 88); and, 5) qualitative evaluation of the refined intervention (n= 6). Results Key findings identified throughout the development process that shaped the MobileMums program were the need for: behaviour change techniques to be grounded in Social Cognitive Theory; tailored SMS content; two-way SMS interaction; rapport between SMS sender and recipient; an automated software platform to generate and send SMS; and, flexibility in location of a face-to-face delivered component. Conclusions The final version of MobileMums is flexible and adaptive to individual participant’s physical activity goals, expectations and environment. MobileMums is being evaluated in a community-based randomised controlled efficacy trial (ACTRN12611000481976).

miRDeep*: an integrated application tool for miRNA identification from RNA sequencing data

miRDeep and its varieties are widely used to quantify known and novel micro RNA (miRNA) from small RNA sequencing (RNAseq). This article describes miRDeep*, our integrated miRNA identification tool, which is modeled off miRDeep, but the precision of detecting novel miRNAs is improved by introducing new strategies to identify precursor miRNAs. miRDeep* has a user-friendly graphic interface and accepts raw data in FastQ and Sequence Alignment Map (SAM) or the binary equivalent (BAM) format. Known and novel miRNA expression levels, as measured by the number of reads, are displayed in an interface, which shows each RNAseq read relative to the pre-miRNA hairpin. The secondary pre-miRNA structure and read locations for each predicted miRNA are shown and kept in a separate figure file. Moreover, the target genes of known and novel miRNAs are predicted using the TargetScan algorithm, and the targets are ranked according to the confidence score. miRDeep* is an integrated standalone application where sequence alignment, pre-miRNA secondary structure calculation and graphical display are purely Java coded. This application tool can be executed using a normal personal computer with 1.5 GB of memory. Further, we show that miRDeep* outperformed existing miRNA prediction tools using our LNCaP and other small RNAseq datasets. miRDeep* is freely available online at http://www.australianprostatecentre.org/research/software/mirdeep-star

Fine-mapping identifies multiple prostate cancer risk loci on 5p15 some associating with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease.

Referral patterns and proximity to palliative care inpatient services by level of socio-economic disadvantage : a national study using spatial analysis

Background: A range of health outcomes at a population level are related to differences in levels of social disadvantage. Understanding the impact of any such differences in palliative care is important. The aim of this study was to assess, by level of socio-economic disadvantage, referral patterns to specialist palliative care and proximity to inpatient services. Methods: All inpatient and community palliative care services nationally were geocoded (using postcode) to one nationally standardised measure of socio-economic deprivation – Socio-Economic Index for Areas (SEIFA; 2006 census data). Referral to palliative care services and characteristics of referrals were described through data collected routinely at clinical encounters. Inpatient location was measured from each person’s home postcode, and stratified by socio-economic disadvantage. Results: This study covered July – December 2009 with data from 10,064 patients. People from the highest SEIFA group (least disadvantaged) were significantly less likely to be referred to a specialist palliative care service, likely to be referred closer to death and to have more episodes of inpatient care for longer time. Physical proximity of a person’s home to inpatient care showed a gradient with increasing distance by decreasing levels of socio-economic advantage. Conclusion: These data suggest that a simple relationship of low socioeconomic status and poor access to a referral-based specialty such as palliative care does not exist. Different patterns of referral and hence different patterns of care emerge.

What can grassroots leadership teach us about school leadership

This paper explores grassroots leadership, an under-researched and often side-lined approach to leadership that operates outside of formal bureaucratic structures. The paper’s central purpose is the claim that an understanding of grassroots leadership and tactics used by grassroots leaders provides valuable insights for the study of school leadership. In this paper, we present and discuss an original model of grassroots leadership based on the argument that this under-researched area can further our understanding of school leadership. Drawing upon the limited literature in the field, we present a model consisting of two approaches to change (i.e. conflict and consensus) and two categories of change (i.e. reform and refinement) and then provide illustrations of how the model works in practice. We make the argument that the model has much merit for conceptualizing school leadership, and this is illustrated by applying the model to formal bureaucratic leadership within school contexts. Given the current climate in education where business and management language is pervasive within leadership-preparation programs, we argue that it is timely for university academics, who are responsible for preparing school leaders to consider broadening their approach by exposing school leaders to a variety of change-based strategies and tactics used by grassroots leaders.

Research data finder : an institutional metadata repository

QUT’s new metadata repository (data registry), Research Data Finder, has been designed to promote the visibility and discoverability of QUT research datasets. Funded by the Australian National Data Service (ANDS), it will provide a qualitative snapshot of research data outputs created or collected by members of the QUT research community that are available via open or mediated access. As a fully integrated metadata repository Research Data Finder aligns with institutional sources of truth, such as QUT’s research administrative system, ResearchMaster, as well as QUT’s Academic Profiles system to provide high quality data descriptions that increase awareness of, and access to, shareable research data. In addition, the repository and its workflows are designed to foster smoother data management practices, enhance opportunities for collaboration and research, promote cross-disciplinary research and maximize existing research datasets. The metadata schema used in Research Data Finder is the Registry Interchange Format - Collections and Services (RIF-CS), developed by ANDS in 2009. This comprehensive schema is potentially complex for researchers; unlike metadata for publications, which are often made publicly available with the official publication, metadata for datasets are not typically available and need to be created. Research Data Finder uses a hybrid self-deposit and mediated deposit system. In addition to automated ingests from ResearchMaster (research project information) and Academic Profiles system (researcher information), shareable data is identified at a number of key “trigger points” in the research cycle. These include: research grant proposals; ethics applications; Data Management Plans; Liaison Librarian data interviews; and thesis submissions. These ingested records can be supplemented with related metadata including links to related publications, such as those in QUT ePrints. Records deposited in Research Data Finder are harvested by ANDS and made available to a national and international audience via Research Data Australia, ANDS’ discovery service for Australian research data. Researcher and research group metadata records are also harvested by the National Library of Australia (NLA) and these records are then published in Trove (the NLA’s digital information portal). By contributing records to the national infrastructure, QUT data will become more visible. Within Australia and internationally, many funding bodies have already mandated the open access of publications produced from publicly funded research projects, such as those supported by the Australian Research Council (ARC), or the National Health and Medical Research Council (NHMRC). QUT will be well placed to respond to the rapidly evolving climate of research data management. This project is supported by the Australian National Data Service (ANDS). ANDS is supported by the Australian Government through the National Collaborative Research Infrastructure Strategy Program and the Education Investment Fund (EIF) Super Science Initiative.

Design minds : an online design education platform for non-designers to enact cultural change

Education in the 21st century demands a model for understanding a new culture of learning in the face of rapid change, open access data and geographical diversity. Teachers no longer need to provide the latest information because students themselves are taking an active role in peer collectives to help create it. This paper examines, through an Australian case study entitled ‘Design Minds’, the development of an online design education platform as a key initiative to enact a government priority for state-wide cultural change through design-based curriculum. Utilising digital technology to create a supportive community, ‘Design Minds’ recognises that interdisciplinary learning fostered through engagement will empower future citizens to think, innovate, and discover. This paper details the participatory design process undertaken with multiple stakeholders to create the platform. It also outlines a proposed research agenda for future measurement of its value in creating a new learning culture, supporting regional and remote communities, and revitalising frontline services. It is anticipated this research will inform ongoing development of the online platform, and future design education and research programs in K-12 schools in Australia.

Cryo-electron tomography of Marburg Virus particles and their morphogenesis within infected cells

Several major human pathogens, including the filoviruses, paramyxoviruses, and rhabdoviruses, package their single-stranded RNA genomes within helical nucleocapsids, which bud through the plasma membrane of the infected cell to release enveloped virions. The virions are often heterogeneous in shape, which makes it difficult to study their structure and assembly mechanisms. We have applied cryo-electron tomography and sub-tomogram averaging methods to derive structures of Marburg virus, a highly pathogenic filovirus, both after release and during assembly within infected cells. The data demonstrate the potential of cryo-electron tomography methods to derive detailed structural information for intermediate steps in biological pathways within intact cells. We describe the location and arrangement of the viral proteins within the virion. We show that the N-terminal domain of the nucleoprotein contains the minimal assembly determinants for a helical nucleocapsid with variable number of proteins per turn. Lobes protruding from alternate interfaces between each nucleoprotein are formed by the C-terminal domain of the nucleoprotein, together with viral proteins VP24 and VP35. Each nucleoprotein packages six RNA bases. The nucleocapsid interacts in an unusual, flexible "Velcro-like" manner with the viral matrix protein VP40. Determination of the structures of assembly intermediates showed that the nucleocapsid has a defined orientation during transport and budding. Together the data show striking architectural homology between the nucleocapsid helix of rhabdoviruses and filoviruses, but unexpected, fundamental differences in the mechanisms by which the nucleocapsids are then assembled together with matrix proteins and initiate membrane envelopment to release infectious virions, suggesting that the viruses have evolved different solutions to these conserved assembly steps.

Health service pathways for patients with chronic leg ulcers : identifying effective pathways for facilitation of evidence based wound care

Background: Chronic leg ulcers cause long term ill-health for older adults and the condition places a significant burden on health service resources. Although evidence on effective management of the condition is available, a significant evidence-practice gap is known to exist, with many suggested reasons e.g. multiple care providers, costs of care and treatments. This study aimed to identify effective health service pathways of care which facilitated evidence-based management of chronic leg ulcers. Methods: A sample of 70 patients presenting with a lower limb leg or foot ulcer at specialist wound clinics in Queensland, Australia were recruited for an observational study and survey. Retrospective data were collected on demographics, health, medical history, treatments, costs and health service pathways in the previous 12 months. Prospective data were collected on health service pathways, pain, functional ability, quality of life, treatments, wound healing and recurrence outcomes for 24 weeks from admission. Results: Retrospective data indicated that evidence based guidelines were poorly implemented prior to admission to the study, e.g. only 31% of participants with a lower limb ulcer had an ABPI or duplex assessment in the previous 12 months. On average, participants accessed care 2–3 times/week for 17 weeks from multiple health service providers in the twelve months before admission to the study clinics. Following admission to specialist wound clinics, participants accessed care on average once per week for 12 weeks from a smaller range of providers. The median ulcer duration on admission to the study was 22 weeks (range 2–728 weeks). Following admission to wound clinics, implementation of key indicators of evidence based care increased (p<0.001) and Kaplan-Meier survival analysis found the median time to healing was 12 weeks (95% CI 9.3–14.7). Implementation of evidence based care was significantly related to improved healing outcomes (p<0.001). Conclusions: This study highlights the complexities involved in accessing expertise and evidence based wound care for adults with chronic leg or foot ulcers. Results demonstrate that access to wound management expertise can promote streamlined health services and evidence based wound care, leading to efficient use of health resources and improved health.

Paclitaxel resistance and multicellular spheroid formation are induced by kallikrein-related peptidase 4 in serous ovarian cancer cells in an ascites mimicking microenvironment

High tumor kallikrein-related-peptidase 4 (KLK4) levels are associated with a poor outcome for women with serous epithelial ovarian cancer (EOC), for which peritoneal dissemination and chemoresistance are key events. To determine the role of KLK4 in these events, we examined KLK4-transfected SKOV-3 and endogenous KLK4 expressing OVCA432 cells in 3-dimensional (3D) suspension culture to mimic the ascites microenvironment. KLK4-SKOV-3 cells formed multicellular aggregates (MCAs) as seen in ascites, as did SKOV-3 cells treated with active KLK4. MCA formation was reduced by treatment with a KLK4 blocking antibody or the selective active site KLK4 sunflower trypsin inhibitor (SFTI-FCQR). KLK4-MCAs formed larger cancer cell foci in mesothelial cell monolayers than those formed by vector and native SKOV-3 cells, suggesting KLK4-MCAs are highly invasive in the peritoneal microenvironment. A high level of KLK4 is expressed by ascitic EOC cells compared to matched primary tumor cells, further supporting its role in the ascitic microenvironment. Interestingly, KLK4 transfected SKOV-3 cells expressed high levels of the KLK4 substrate, urokinase plasminogen activator (uPA), particularly in 3D-suspension, and high levels of both KLK4 and uPA were observed in patient cells taken from ascites. Importantly, the KLK4-MCAs were paclitaxel resistant which was reversed by SFTI-FCQR and to a lesser degree by the general serine protease inhibitor, Aprotinin, suggesting that in addition to uPA, other as yet unidentified substrates of KLK4 must be involved. Nonetheless, these data suggest that KLK4 inhibition, in conjunction with paclitaxel, may improve the outcome for women with serous epithelial ovarian cancer and high KLK4 levels in their tumors.

Low vitamin B12 levels among newly-arrived refugees from Bhutan, Iran and Afghanistan : a multicentre Australian study

Background: Vitamin B12 deficiency is prevalent in many countries of origin of refugees. Using a threshold of 5% above which a prevalence of low Vitamin B12 is indicative of a population health problem, we hypothesised that Vitamin B12 deficiency exceeds this threshold among newly-arrived refugees resettling in Australia, and is higher among women due to their increased risk of food insecurity. This paper reports Vitamin B12 levels in a large cohort of newly arrived refugees in five Australian states and territories. Methods: In a cross-sectional descriptive study, we collected Vitamin B12, folate and haematological indices on all refugees(n = 916; response rate 94% of eligible population) who had been in Australia for less than one year, and attended one of the collaborating health services between July 2010 and July 2011. Results: 16.5% of participants had Vitamin B12 deficiency (,150 pmol/L). One-third of participants from Iran and Bhutan, and one-quarter of participants from Afghanistan had Vitamin B12 deficiency. Contrary to our hypothesis, low Vitamin B12 levels were more prevalent in males than females. A higher prevalence of low Vitamin B12 was also reported in older age groups in some countries. The sensitivity of macrocytosis in detecting Vitamin B12 deficiency was only 4.6%. Conclusion: Vitamin B12 deficiency is an important population health issue in newly-arrived refugees from many countries. All newly-arrived refugees should be tested for Vitamin B12 deficiency. Ongoing research should investigate causes,treatment, and ways to mitigate food insecurity, and the contribution of such measures to enhancing the health of the refugee communities.

Digital Copyright Exchange Feasibility Study : Response to the Hooper Consultation from the Big Innovation Centre

In this submission, we provide evidence for our view that copyright policy in the UK must encourage new digital business models which meet the changing needs of consumers and foster innovation in the UK both within, and beyond, the creative industries. We illustrate our arguments using evidence from the music industry. However, we believe that our key points on the relationship between the copyright system and innovative digital business models apply across the UK creative industries.

Socioeconomic inequalities in cardiovascular mortality and the role of childhood socioeconomic conditions and adulthood risk factors : a prospective cohort study with 17-years of follow up

Background The mechanisms underlying socioeconomic inequalities in mortality from cardiovascular diseases (CVD) are largely unknown. We studied the contribution of childhood socioeconomic conditions and adulthood risk factors to inequalities in CVD mortality in adulthood. Methods The prospective GLOBE study was carried out in the Netherlands, with baseline data from 1991, and linked with the cause of death register in 2007. At baseline, participants reported on adulthood socioeconomic position (SEP) (own educational level), childhood socioeconomic conditions (occupational level of respondent’s father), and a broad range of adulthood risk factors (health behaviours, material circumstances, psychosocial factors). This present study is based on 5,395 men and 6,306 women, and the data were analysed using Cox regression models and hazard ratios (HR). Results A low adulthood SEP was associated with increased CVD mortality for men (HR 1.84; 95% CI: 1.41-2.39) and women (HR 1.80; 95%CI: 1.04-3.10). Those with poorer childhood socioeconomic conditions were more likely to die from CVD in adulthood, but this reached statistical significance only among men with the poorest childhood socioeconomic circumstances. About half of the investigated adulthood risk factors showed significant associations with CVD mortality among both men and women, namely renting a house, experiencing financial problems, smoking, physical activity and marital status. Alcohol consumption and BMI showed a U-shaped relationship with CVD mortality among women, with the risk being significantly greater for both abstainers and heavy drinkers, and among women who were underweight or obese. Among men, being single or divorced and using sleep/anxiety drugs increased the risk of CVD mortality. In explanatory models, the largest contributor to adulthood CVD inequalities were material conditions for men (42%; 95% CI: −73 to −20) and behavioural factors for women (55%; 95% CI: -191 to −28). Simultaneous adjustment for adulthood risk factors and childhood socioeconomic conditions attenuated the HR for the lowest adulthood SEP to 1.34 (95% CI: 0.99-1.82) for men and 1.19 (95% CI: 0.65-2.15) for women. Conclusions Adulthood material, behavioural and psychosocial factors played a major role in the explanation of adulthood SEP inequalities in CVD mortality. Childhood socioeconomic circumstances made a modest contribution, mainly via their association with adulthood risk factors. Policies and interventions to reduce health inequalities are likely to be most effective when considering the influence of socioeconomic circumstances across the entire life course and in particular, poor material conditions and unhealthy behaviours in adulthood.