Investigating the Potential and Pitfalls of EV-Encapsulated MicroRNAs as Circulating Biomarkers of Breast Cancer

Extracellular vesicles (EVs) shuttle microRNA (miRNA) throughout the circulation and are believed to represent a fingerprint of the releasing cell. We isolated and characterized serum EVs of breast tumour-bearing animals, breast cancer (BC) patients, and healthy controls. EVs were characterized using transmission electron microscopy (TEM), protein quantification, western blotting, and nanoparticle tracking analysis (NTA). Absolute quantitative (AQ)-PCR was employed to analyse EV-miR-451a expression. Isolated EVs had the appropriate morphology and size. Patient sera contained significantly more EVs than did healthy controls. In tumour-bearing animals, a correlation between serum EV number and tumour burden was observed. There was no significant relationship between EV protein yield and EV quantity determined by NTA, highlighting the requirement for direct quantification. Using AQ-PCR to relate miRNA copy number to EV yield, a significant increase in miRNA-451a copies/EV was detected in BC patient sera, suggesting potential as a novel biomarker of breast cancer

Encouraging serendipity in research: designing technologies to support connection-making

Mobile applications have the ability to present information to users that is influenced by their surroundings, activities and interests. Such applications have the potential to influence the likelihood of individuals experiencing ‘serendipity’, through a combination of information, context, insight and activity. This study reports the deployment of a system that sends push text suggestions to users throughout the day, where the content of those messages is informed by users’ experience and interests. We investigated the responses to and interactions with messages that varied in format and relevance, and which were received at different times throughout the day. Sixteen participants were asked to use a mobile diary application to record their experiences and thoughts regarding information that was received over a period of five consecutive days. Results suggest that participants’ perception of the received suggestions was influenced by the relevance of the suggestion to their interests, but that there were also positive attitudes towards seemingly irrelevant information. Qualitative data indicates that participants, if in an appropriate time and place, are willing to accept and act upon push suggestions as long as the number of suggestions that they receive is not overwhelming. This study contributes towards an understanding of how mobile users make connections with new information, furthering our understanding of how serendipitous connections and insightful thinking could be accommodated using technology

Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer.

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.BCAC is funded by Cancer Research UK (C1287/A10118, C1287/A12014) and by the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). Genotyping on the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710, C8197/A16565), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program and the Ministry of Economic Development, Innovation and Export Trade of Quebec, grant PSR-SIIRI-701. Combination of the GWAS data was supported in part by the US National Institutes of Health (NIH) Cancer Post-Cancer GWAS initiative, grant 1 U19 CA148065-01 (DRIVE, part of the GAME-ON initiative). For a full description of funding and acknowledgments, see the Supplementary Note.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.324

Home and Online Management and Evaluation of Blood Pressure (HOME BP) using a digital intervention in poorly controlled hypertension: randomised controlled trial

Objective: The HOME BP (Home and Online Management and Evaluation of Blood Pressure) trial aimed to test a digital intervention for hypertension management in primary care by combining self-monitoring of blood pressure with guided self-management. Design: Unmasked randomised controlled trial with automated ascertainment of primary endpoint. Setting: 76 general practices in the United Kingdom. Participants: 622 people with treated but poorly controlled hypertension (&gt;140/90 mm Hg) and access to the internet. Interventions: Participants were randomised by using a minimisation algorithm to self-monitoring of blood pressure with a digital intervention (305 participants) or usual care (routine hypertension care, with appointments and drug changes made at the discretion of the general practitioner; 317 participants). The digital intervention provided feedback of blood pressure results to patients and professionals with optional lifestyle advice and motivational support. Target blood pressure for hypertension, diabetes, and people aged 80 or older followed UK national guidelines. Main outcome measures: The primary outcome was the difference in systolic blood pressure (mean of second and third readings) after one year, adjusted for baseline blood pressure, blood pressure target, age, and practice, with multiple imputation for missing values. Results: After one year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean blood pressure dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic blood pressure of −3.4 mm Hg (95% confidence interval −6.1 to −0.8 mm Hg) and a mean difference in diastolic blood pressure of −0.5 mm Hg (−1.9 to 0.9 mm Hg). Results were comparable in the complete case analysis and adverse effects were similar between groups. Within trial costs showed an incremental cost effectiveness ratio of £11 ($15, €12; 95% confidence interval £6 to £29) per mm Hg reduction. Conclusions: The HOME BP digital intervention for the management of hypertension by using self-monitored blood pressure led to better control of systolic blood pressure after one year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded. Trial registration: ISRCTN13790648

Comparing areas of commonality and distinction between the national practice models of Meitheal and Signs of Safety

In this report, a characterisation is provided on the central elements/principles that are contained within the Meitheal and the Child and Family Support Networks and Signs of Safety practice models. Both represent two distinctive national practice models within Tusla s service delivery system of Family Support and Child Protection. In the case of Meitheal, this model functions as part of Tusla s Programme for Prevention, Partnership and Family Support. While the Signs of Safety practice model is operating within the confines of Tusla s Child Protection and Welfare Strategy. Therefore, our primary emphasis in this context is to highlight areas: of alignment/overlap; where there are distinctions; and how both practice models complement each other.non-peer-reviewe

The Stage and the City: Narrative, Identity and Place in Dermot Bolger's The Ballymun Trilogy (2004-2008)

Located two miles from Dublin Airport, Ballymun was built (1966–9) to accommodate people displaced from the inner-city slums dramatised in Sean O'Casey's Dublin Trilogy. ‘The Stage and the City’ draws on the author's research project at Trinity College Dublin, on Theatre and Urban Regeneration. Specifically, it situates Dermot Bolger's The Ballymun Trilogy – From These Green Heights (2004), The Townlands of Brazil (2006) and The Consequences of Lightning (2008) – in relation to theories of globalisation and the global city, and the use of culture in urban regeneration programmes. The article exposes the problems that The Ballymun Trilogy poses for sociological and aesthetic categorisations. The genesis of the fictional world in actual, local experiences raises questions of ownership of narrative content, and of empowerment in acts of performance. The Ballymun Trilogy was produced in the axis Arts and Community Resource Centre, a local community initiative that has become the flagship building of the regeneration project. The article describes and analyses the axis Theatre as a platform on which a heavily stigmatised urban community is enabled to articulate itself. In short, the plays of The Ballymun Trilogy validate the often traumatic struggles of the community of Ballymun, and also raise questions for how we understand contemporary community theatre, and the potential of cultural work in contexts emerging in global cities

The Power of Conferences

The Power of Conferences: Stories of serendipity, innovation and driving social change asks ten notable Australians to reflect on the role that conferences have played in their personal and professional achievements. Through their stories the power of conferences is revealed, providing evidence of a deep and lasting impact on the development and success of Australian luminaries and their communities. This book arose from a long term collaboration with Business Events Sydney