Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Space and Fluidity: Student learning in supervision in social work field placements in Hong Kong

Social work students consider fieldwork placements as one of the most significant experiences in their learning for practice. Supervision in fieldwork placements is central to facilitating student field learning. The scholarship of student learning in supervision is weighted towards field educators’ and academics’ reflections on aspects of field teaching and learning. Although more research studies have surfaced in recent years, studies that specifically examine students’ learning experience from students’ perspectives are under-represented. The unique features of organizing and supervising social work fieldwork placements in Hong Kong provide an excellent site to understand student learning in supervision. In Hong Kong, university employed field supervisors undertake the majority of student supervision. This arrangement supports the direct role of the university in specifying the requirements and structure of supervision and its responsibility for facilitating student learning. This exploratory qualitative study examines the experience of learning in supervision from students’ perspectives. A sample of twelve social work students undertaking their final fieldwork placement in Hong Kong took part in this study. Students were paired up and each pair participated in a series of three inquiry sessions conducted at the early, middle and late stage of placement. The multiple inquiry approach provides numerous opportunities for students to articulate and construct their learning experiences over the course of their placement. The transcripts of the inquiry sessions were analysed thematically. The significance of the thesis is both conceptual and applied. The findings support the conceptualisation of supervision as a learning space, a fruitful base from which to explore important themes underpinning students’ experience of learning in supervision. Amongst these the notions of fluidity and active engagement are especially relevant. The findings suggest students’ approach to learning is fluid. They are constantly responding, reacting and adapting to their learning situation and supervision context. The findings indicate students in a placement context have deep learning aspirations or are able to develop deep learning goals. The non-static nature of students’ learning aspirations emphasises the need to sustain, support and harness students’ deep learning: a process that is vital to professional learning. The importance of active engagement in the learning process suggests a way of being in this supervision space. The findings highlight the role participants play in shaping the quality of the supervision space and harnessing the potential that this space offers. The study discusses what active engagement means in the context of supervision. The findings of the thesis have particular relevance for social work educators involved in the facilitation of student field learning and for staff in educational institutions involved in the organization of fieldwork placements. A student-informed understanding of learning in supervision challenges and extends existing ways of structuring supervision and facilitating learning in supervision. The thesis discusses the essential elements of a supervision space that supports student learning and the need for a de-cluttered space for learning to occur. Given the crucial role students and field supervisors play in this undertaking, the implications for building the capacities of both to engage are also highlighted. This means the training of field supervisors involves developing a strong educational philosophy based on a sound understanding of the nature of learning and practice and an appreciation of the supervision space. It also means helping students firstly examine their epistemology about practice and learning and secondly translate that into coherent approaches to engaging in learning in supervision. The thesis adds to the current scholarship on field education from students’ perspectives and extends the knowledge on supervisory practices in the facilitation of student learning in supervision and on placement

Gender and role identity as moderators in the relationship between work and family demands and life outcomes.

Through a survey of Singaporeans in full-time paid employment, this study aims to explore some of the relationships between the work and family demands experienced by Singaporeans on one hand, and their work and life outcomes on the other. At the same time, it examines the influence of self- identity and gender in moderating those relationships.Master of Business Administratio

Effects of phase-locked acoustic stimulation during a nap on EEG spectra and declarative memory consolidation

AbstractObjectivesAcoustic stimulation synchronized to slow waves (SWs) can enhance these sleep features and facilitate memory consolidation during nocturnal sleep. Here, we investigated whether a similar benefit could be accrued following stimulation during an afternoon nap. We also evaluated the event-related dynamics of associated EEG spectral changes and their correlation with memory performance.MethodsSixteen healthy young adults (mean age: 22 ± 1.4 years; nine males) were studied under two conditions: stimulation (STIM) and no stimulation (SHAM), in counter-balanced order. In the STIM condition, acoustic stimulation was delivered using blocks of five tones, each phase-locked to the SW up-state during a 90-min nap opportunity. In the SHAM condition, these time points were marked, but tones were not presented. Prior to the nap, participants learned 40 semantically related word pairs and immediate recall was tested. A delayed recall test was administered 45 min after awakening.ResultsCompared to the SHAM condition, acoustic stimulation increased SW amplitude, theta, and fast spindle activity and attenuated the forgetting of word pairs (p values < 0.05).ConclusionPhase-locked acoustic stimulation can promote sleep-dependent declarative memory during a daytime nap. This can be achieved by stimulation in Stage 2 and SWS without a requirement for high-amplitude slow wave detection

Correction to: Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci (Nature Genetics, (2018), 50, 7, (928-936), 10.1038/s41588-018-0142-8)

In the version of this article initially published, the name of author Manuela Gago-Dominguez was misspelled as Manuela Gago Dominguez. The error has been corrected in the HTML and PDF version of the article