Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same region.

The ninth 48hr game making challenge (2015)

The 48 hour game making challenge has been running since 2007. In recent years, we have not only been running a 'game jam' for the local community but we have also been exploring the way in which the event itself and the place of the event has the potential to create its own stories. The 2015 challenge is part of a series of data collection opportunities focussed on the game jam itself and the meaning making that the participants engage in about the event. We are continuing the data collection commenced in 2012: "Game jams are the creative festivals of the game development community and a game jam is very much an event or performance; its stories are those of subjective experience. Participants return year after year and recount personal stories from previous challenges; arrival in the 48hr location typically inspires instances of individual memory and narration more in keeping with those of a music festival or an oft frequented holiday destination. Since its inception, the 48hr has been heavily documented, from the photo-blogging of our first jam and the twitter streams of more recent events to more formal interviews and documentaries (see Anderson, 2012). We have even had our own moments of Gonzo journalism with an on-site press room one year and an ‘embedded’ journalist another year (Keogh, 2011). In the last two years of the 48hr we have started to explore ways and means to collect more abstract data during the event, that is, empirical data about movement and activity. The intent behind this form of data collection was to explore graphic and computer generated visualisations of the event, not for the purpose of formal analysis but in the service of further story telling." [exerpt from truna aka j.turner, Thomas & Owen, 2013) See: truna aka j.turner, Thomas & Owen (2013) Living the indie life: mapping creative teams in a 48 hour game jam and playing with data, Proceedings of the 9th Australasian Conference on Interactive Entertainment, IE'2013, September 30 - October 01 2013, Melbourne, VIC, Australia

Disease mapping using Bayesian hierarchical models

description and analysis of geographically indexed health data with respect to demographic, environmental, behavioural, socioeconomic, genetic, and infectious risk factors (Elliott andWartenberg 2004). Disease maps can be useful for estimating relative risk; ecological analyses, incorporating area and/or individual-level covariates; or cluster analyses (Lawson 2009). As aggregated data are often more readily available, one common method of mapping disease is to aggregate the counts of disease at some geographical areal level, and present them as choropleth maps (Devesa et al. 1999; Population Health Division 2006). Therefore, this chapter will focus exclusively on methods appropriate for areal data...

Multidisciplinary review of teaching and assessing competency attainment by non-medical prescribers

Background Prescribing is a complex task, requiring specific knowledge and skills, and the execution of effective, context-specific clinical reasoning. Systematic reviews indicate medical prescribing errors have a median rate of 7% [IQR 2%-14%] of medication orders [1-3]. For podiatrists pursuing prescribing rights, a clear need exists to ensure practitioners develop a well-defined set of prescribing skills, which will contribute to competent, safe and appropriate practice. Aim To investigate the methods employed to teach and assess the principles of effective prescribing in the undergraduate podiatry program and compare and contrast these findings with four other non-medical professions who undertake prescribing after training at Queensland University of Technology. Method The NPS National Prescribing Competency Standards were employed as the prescribing standard. A curriculum mapping exercise was undertaken to determine whether the prescribing principles articulated in the competency standards were addressed by each profession. Results A range of methods are currently utilised to teach prescribing across disciplines. Application of prescribing competencies to the context of each profession appears to influence the teaching methods used. Most competencies were taught using a multimodal format, including interactive lectures, self-directed learning, tutorial sessions and clinical placement. In particular clinical training was identified as the most consistent form of educating safe prescribers across all five disciplines. Assessment of prescribing competency utilised multiple techniques including written and oral examinations and research tasks, case studies, objective structured clinical examination exercises and the assessment of clinical practice. Effective and reliable assessment of prescribing undertaken by students in diverse settings remains challenging e.g. that occurring in the clinical practice environment. Conclusion Recommendations were made to refine curricula and to promote efficient cross-discipline teaching by staff from the disciplines of podiatry, pharmacy, nurse practitioner, optometry and paramedic science. Students now experience a sophisticated level of multidisciplinary learning in the clinical setting which integrates the expertise and skills of experience prescribers combined with innovative information technology platforms (CCTV and live patient assessments). Further work is required to establish a practical, effective approach to the assessment of prescribing competence especially between the university and clinical settings.

Implementation of an interactive relational graphics database

The benefits that accrue from the use of design database include (i) reduced costs of preparing data for application programs and of producing the final specification, and (ii) possibility of later usage of data stored in the database for other applications related to Computer Aided Engineering (CAE). An INTEractive Relational GRAphics Database (INTERGRAD) based on relational models has been developed to create, store, retrieve and update the data related to two dimensional drawings. INTERGRAD provides two languages, Picture Definition Language (PDL) and Picture Manipulation Language (PML). The software package has been implemented on a PDP 11/35 system under the RSX-11M version 3.1 operating system and uses the graphics facility consisting of a VT-11 graphics terminal, the DECgraphic 11 software and an input device, a lightpen.

Applications of pedigree-based genome mapping in wheat and barley breeding programs.

The aim of the pedigree-based genome mapping project is to investigate and develop systems for implementing marker assisted selection to improve the efficiency of selection and increase the rate of genetic gain in breeding programs. Pedigree-based whole genome marker application provides a vehicle for incorporating marker technologies into applied breeding programs by bridging the gap between marker-trait association and marker implementation. We report on the development of protocols for implementation of pedigree-based whole genome marker analysis in breeding programs within the Australian northern winter cereals region. Examples of applications from the Queensland DPI&F wheat and barley breeding programs are provided, commenting on the use of microsatellites and other types of molecular markers for routine genomic analysis, the integration of genotypic, phenotypic and pedigree information for targeted wheat and barley lines, the genomic impacts of strong selection pressure in case study pedigrees, and directions for future pedigree-based marker development and analysis.

Effect of an interactive therapeutic robotic animal on engagement, mood states, agitation and psychotropic drug use in people with dementia: A cluster-randomised controlled trial protocol

Introduction: Apathy, agitated behaviours, loneliness and depression are common consequences of dementia. This trial aims to evaluate the effect of a robotic animal on behavioural and psychological symptoms of dementia in people with dementia living in long-term aged care. Methods and analysis: A cluster-randomised controlled trial with three treatment groups: PARO (robotic animal), Plush-Toy (non-robotic PARO) or Usual Care (Control). The nursing home sites are Australian Government approved and accredited facilities of 60 or more beds. The sites are located in South-East Queensland, Australia. A sample of 380 adults with a diagnosis of dementia, aged 60 years or older living in one of the participating facilities will be recruited. The intervention consists of three individual 15 min non-facilitated sessions with PARO or Plush- Toy per week, for a period of 10 weeks. The primary outcomes of interest are improvement in agitation, mood states and engagement. Secondary outcomes include sleep duration, step count, change in psychotropic medication use, change in treatment costs, and staff and family perceptions of PARO or Plush-Toy. Video data will be analysed using Noldus XT Pocket Observer; descriptive statistics will be used for participants’ demographics and outcome measures; cluster and individual level analyses to test all hypotheses and Generalised Linear Models for cluster level and Generalised Estimation Equations and/or Multi-level Modeling for individual level data. Ethics and dissemination: The study participants or their proxy will provide written informed consent. The Griffith University Human Research Ethics Committee has approved the study (NRS/03/14/HREC). The results of the study will provide evidence of the efficacy of a robotic animal as a psychosocial treatment for the behavioural and psychological symptoms of dementia. Findings will be presented at local and international conference meetings and published in peer-reviewed journals.

Mapping species differences for adventitious rooting in a Corymbia torelliana x Corymbia citriodora subspecies variegata hybrid

Quantitative trait loci (QTL) detection was carried out for adventitious rooting and associated propagation traits in a second-generation outbred Corymbia torelliana x Corymbia citriodora subspecies variegata hybrid family (n=186). The parental species of this cross are divergent in their capacity to develop roots adventitiously on stem cuttings and their propensity to form lignotubers. For the ten traits studied, there was one or two QTL detected, with some QTL explaining large amounts of phenotypic variation (e.g. 66% for one QTL for percentage rooting), suggesting that major effects influence rooting in this cross. Collocation of QTL for many strongly genetically correlated rooting traits to a single region on linkage group 12 suggested pleiotropy. A three locus model was most parsimonious for linkage group 12, however, as differences in QTL position and lower genetic correlations suggested separate loci for each of the traits of shoot production and root initiation. Species differences were thought to be the major source of phenotypic variation for some rooting rate and root quality traits because of the major QTL effects and up to 59-fold larger homospecific deviations (attributed to species differences) relative to heterospecific deviations (attributed to standing variation within species) evident at some QTL for these traits. A large homospecific/heterospecific ratio at major QTL suggested that the gene action evident in one cross may be indicative of gene action more broadly in hybrids between these species for some traits.

Design studio terrains: Mapping the learning landscapes of Australian architectural education

It has been nearly 25 years since the problems associated with passive learning in large undergraduate classes were first established by McDermott (1991). STEM education, for example North Carolina State University’s SCALE-UP project, has subsequently been influenced by some unique aspects of design studio education. While there are now many institutions applying SCALE-UP or similar approaches to enable lively interaction, enhanced learning, increased student engagement, and to teach many different content areas to classes of all sizes, nearly all of these have remained in the STEM fields (Beichner, 2008). Architectural education, although originally at the forefront of this field, has arguably been left behind. Architectural practice is undergoing significant change, globally. Access to new technology and the development of specialised architectural documentation software has scaffolded new building procurement methods and allowed consultant teams to work more collaboratively, efficiently and even across different time zones. Up until recently, the spatial arrangements, pedagogical approaches, and project work outcomes in the architectural design studio, have not been dissimilar to its inception. It is not possible to keep operating architectural design studios the same way that they have for the past two hundred years, with this new injection of high-end technology and personal mobile Wi-Fi enabled devices. Employing a grounded theory methodology, this study reviews the current provision of architectural design learning terrains across a range of tertiary institutions, in Australia. Some suggestions are provided for how these spaces could be modified to address the changing nature of the profession, and implications for how these changes may impact the design of future SCALE-UP type spaces outside of the discipline of architecture, are also explored.

Confirmation of QTL mapping and marker validation for partial seedling resistance to crown rot in wheat line '2-49'

We have tested the efficacy of putative microsatellite single sequence repeat (SSR) markers, previously identified in a 2-49 (Gluyas Early/Gala) × Janz doubled haploid wheat (Triticum aestivum) population, as being linked to partial seedling resistance to crown rot disease caused by Fusarium pseudograminearum. The quantitative trait loci (QTLs) delineated by these markers have been tested for linkage to resistance in an independent Gluyas Early × Janz doubled haploid population. The presence of a major QTL on chromosome 1DL (QCr.usq-1D1) and a minor QTL on chromosome 2BS (QCr.usq-2B1) was confirmed. However, a putative minor QTL on chromosome 2A was not confirmed. The QTL on 1D was inherited from Gluyas Early, a direct parent of 2-49, whereas the 2B QTL was inherited from Janz. Three other putative QTLs identified in 2-49 × Janz (on 1AL, 4BL, and 7BS) were inherited by 2-49 from Gala and were not able to be confirmed in this study. The screening of SSR markers on a small sample of elite wheat genotypes indicated that not all of the most tightly linked SSR markers flanking the major QTLs on 1D and 1A were polymorphic in all backgrounds, indicating the need for additional flanking markers when backcrossing into some elite pedigrees. Comparison of SSR haplotypes with those of other genotypes exhibiting partial crown rot resistance suggests that additional, novel sources of crown rot resistance are available.

High resolution genetic and physical mapping of the I-3 region of tomato chromosome 7 reveals almost continuous microsynteny with grape chromosome 12 but interspersed microsynteny with duplications on Arabidopsis chromosomes 1, 2 and 3

The tomato I-3 gene introgressed from the Lycopersicon pennellii accession LA716 confers resistance to race 3 of the fusarium wilt pathogen Fusarium oxysporum f. sp. lycopersici. We have improved the high-resolution map of the I-3 region of tomato chromosome 7 with the development and mapping of 31 new PCR-based markers. Recombinants recovered from L. esculentum cv. M82 × IL7-2 F2 and (IL7-2 × IL7-4) × M82 TC1F2 mapping populations, together with recombinants recovered from a previous M82 × IL7-3 F2 mapping population, were used to position these markers. A significantly higher recombination frequency was observed in the (IL7-2 × IL7-4) × M82 TC1F2 mapping population based on a reconstituted L. pennellii chromosome 7 compared to the other two mapping populations based on smaller segments of L. pennellii chromosome 7. A BAC contig consisting of L. esculentum cv. Heinz 1706 BACs covering the I-3 region has also been established. The new high-resolution map places the I-3 gene within a 0.38 cM interval between the molecular markers RGA332 and bP23/gPT with an estimated physical size of 50-60 kb. The I-3 region was found to display almost continuous microsynteny with grape chromosome 12 but interspersed microsynteny with Arabidopsis thaliana chromosomes 1, 2 and 3. An S-receptor-like kinase gene family present in the I-3 region of tomato chromosome 7 was found to be present in the microsyntenous region of grape chromosome 12 but was absent altogether from the A. thaliana genome.

DArT markers: Diversity analyses and mapping in Sorghum bicolor

The sequential nature of gel-based marker systems entails low throughput and high costs per assay. Commonly used marker systems such as SSR and SNP are also dependent on sequence information. These limitations result in high cost per data point and significantly limit the capacity of breeding programs to obtain sufficient return on investment to justify the routine use of marker-assisted breeding for many traits and particularly quantitative traits. Diversity Arrays Technology (DArT™) is a cost effective hybridisation-based marker technology that offers a high multiplexing level while being independent of sequence information. This technology offers sorghum breeding programs an alternative approach to whole-genome profiling. We report on the development, application, mapping and utility of DArT™ markers for sorghum germplasm. Results: A genotyping array was developed representing approximately 12,000 genomic clones using PstI+BanII complexity with a subset of clones obtained through the suppression subtractive hybridisation (SSH) method. The genotyping array was used to analyse a diverse set of sorghum genotypes and screening a Recombinant Inbred Lines (RIL) mapping population. Over 500 markers detected variation among 90 accessions used in a diversity analysis. Cluster analysis discriminated well between all 90 genotypes. To confirm that the sorghum DArT markers behave in a Mendelian manner, we constructed a genetic linkage map for a cross between R931945-2-2 and IS 8525 integrating DArT and other marker types. In total, 596 markers could be placed on the integrated linkage map, which spanned 1431.6 cM. The genetic linkage map had an average marker density of 1/2.39 cM, with an average DArT marker density of 1/3.9 cM. Conclusion: We have successfully developed DArT markers for Sorghum bicolor and have demonstrated that DArT provides high quality markers that can be used for diversity analyses and to construct medium-density genetic linkage maps. The high number of DArT markers generated in a single assay not only provides a precise estimate of genetic relationships among genotypes, but also their even distribution over the genome offers real advantages for a range of molecular breeding and genomics applications.

Mapping and characterisation of the inter-reefal benthic assemblages of the Torres Strait

A comprehensive survey of the benthic assemblages of the Torres Strait was conducted in order to provide critical baseline information for regional marine planning, assessing the environmental sustainability of fisheries and understanding the ecosystems of the region. Over 150 sites throughout the region were sampled with a modified prawn trawl, towed underwater video, pipe dredge and epibenthic sled. This manuscript provides a broad overview of the activities undertaken and data collected. Two thousand three hundred and seventy-two different nominal species were sampled by the trawl and sled, only 728 by both gears. The towed video was not able to provide the same level of taxonomic resolution of epibenthic taxa, but was particularly useful in areas where the seabed was too rough to be sampled. Data from the trawl, sled and video were combined to characterise the epibenthic assemblages of the region. Data from the towed video was also used to provide a characterisation of the inter-reefal benthic habitats, which was then analysed in combination with physical covariate data to examine relationships between the two. Levels of mud and gravel in the sediments, trawling effort and seabed current stress were the covariates most significantly correlated with the nature of the seabed habitats.

Mapping quantitative trait loci for resistance to Pratylenchus thornei from synthetic hexaploid wheat in the International Triticeae Mapping Initiative (ITMI) population

Root-lesion nematode (Pratylenchus thornei) is a serious pathogen of wheat in many countries. The International Triticeae Mapping Initiative (ITMI) population of recombinant inbred lines (RILs) was assessed for resistance to P. thornei to determine the chromosome locations of the resistance genes. The ITMI population is derived from a cross between the resistant synthetic hexaploid wheat W-7984 and a susceptible bread wheat cultivar Opata 85. Two years of phenotypic data for resistance to P. thornei were obtained in replicated glasshouse trials. Quantitative trait locus (QTL) analysis was performed using available segregation and map data for 114 RILs. A QTL on chromosome 6DS showed consistent effects for reduced nematode numbers (partial resistance) across years and accounted for 11% and 23% of the phenotypic variation. A second QTL for P. thornei resistance on chromosome 2BS accounted for an additional 19% and 5%. Restriction fragment length polymorphism (RFLP) and simple sequence repeat (SSR) markers associated with the QTLs are physically located in regions rich in major genes at the distal ends of the short chromosome arms of 6D and 2B. SSR markers with potential for marker-assisted selection of P. thornei resistance effective in different genetic backgrounds have been identified.

Isolation, characterization and mapping of temperature-sensitive mutants of mycobacteriophage I3

Eighteen temperature-sensitive mutants of mycobacteriophage I3 have been isolated and partially characterized. All the mutants were defective in vegetative replication. Based on temperature shift experiments with the temperature sensitive mutants, the thermosensitive phase of the phage development period has been characterized for each mutant. The genes have been mapped by recombination analysis. The early, continuous and middle genes seem to cluster on the genetic map