Identification of targets of tumor suppressor microRNA-34a using a reporter library system

miRNAs play critical roles in various biological processes by targeting specific mRNAs. Current approaches to identifying miRNA targets are insufficient for elucidation of a miRNA regulatory network. Here, we created a cell-based screening system using a luciferase reporter library composed of 4,891 full-length cDNAs, each of which was integrated into the 3′ UTR of a luciferase gene. Using this reporter library system, we conducted a screening for targets of miR-34a, a tumor-suppressor miRNA. We identified both previously characterized and previously uncharacterized targets. miR-34a overexpression in MDA-MB-231 breast cancer cells repressed the expression of these previously unrecognized targets. Among these targets, GFRA3 is crucial for MDA-MB-231 cell growth, and its expression correlated with the overall survival of patients with breast cancer. Furthermore, GFRA3 was found to be directly regulated by miR-34a via its coding region. These data show that this system is useful for elucidating miRNA functions and networks

From peripheral region to escalator region in Europe: young Baltic graduates in London

This paper examines recent migration from three little-studied European Union (EU) countries, the Baltic states, focusing on early-career graduates who move to London. It looks at how these young migrants explain the reasons for their move, their work and living experiences in London, and their plans for the future, based on 78 interviews with individual migrants. A key objective of this paper is to rejuvenate the core–periphery structural framework through the theoretical lens of London as an ‘escalator’ region for career development. We add a necessary nuance on how the time dimension is crucial in understanding how an escalator region functions – both in terms of macro-events such as EU enlargement or economic crisis, and for life-course events such as career advancement or family formation. Our findings indicate that these educated young adults from the EU’s north-eastern periphery migrate for a combination of economic, career, lifestyle and personal-development reasons. They are ambivalent about their futures and when, and whether, they will return-migrate

A randomised controlled trial to assess the effectiveness of a single session of nurse administered massage for short term relief of chronic non-malignant pain

Background: Massage is increasingly used to manage chronic pain but its benefit has not been clearly established. The aim of the study is to determine the effectiveness of a single session of nurse-administered massage for the short term relief of chronic non-malignant pain and anxiety. Methods: A randomised controlled trial design was used, in which the patients were assigned to a massage or control group. The massage group received a 15 minute manual massage and the control group a 15 minute visit to talk about their pain. Adult patients attending a pain relief unit with a diagnosis of chronic pain whose pain was described as moderate or severe were eligible for the study. An observer blind to the patients' treatment group carried out assessments immediately before (baseline), after treatment and 1, 2, 3 and 4 hours later. Pain was assessed using 100 mm visual analogue scale and the McGill Pain Questionnaire. Pain Relief was assessed using a five point verbal rating scale. Anxiety was assessed with the Spielberger short form State-Trait Anxiety Inventory. Results: 101 patients were randomised and evaluated, 50 in the massage and 51 in the control group. There were no statistically significant differences between the groups at baseline interview. Patients in the massage but not the control group had significantly less pain compared to baseline immediately after and one hour post treatment. 95% confidence interval for the difference in mean pain reduction at one hour post treatment between the massage and control groups is 5.47 mm to 24.70 mm. Patients in the massage but not the control group had a statistically significant reduction in anxiety compared to baseline immediately after and at 1 hour post treatment. Conclusion: Massage is effective in the short term for chronic pain of moderate to severe intensity

Evaluating the successful implementation of evidence into practice using the PARiHS framework : theoretical and practical challenges

Background The PARiHS framework (Promoting Action on Research Implementation in Health Services) has proved to be a useful practical and conceptual heuristic for many researchers and practitioners in framing their research or knowledge translation endeavours. However, as a conceptual framework it still remains untested and therefore its contribution to the overall development and testing of theory in the field of implementation science is largely unquantified. Discussion This being the case, the paper provides an integrated summary of our conceptual and theoretical thinking so far and introduces a typology (derived from social policy analysis) used to distinguish between the terms conceptual framework, theory and model – important definitional and conceptual issues in trying to refine theoretical and methodological approaches to knowledge translation. Secondly, the paper describes the next phase of our work, in particular concentrating on the conceptual thinking and mapping that has led to the generation of the hypothesis that the PARiHS framework is best utilised as a two-stage process: as a preliminary (diagnostic and evaluative) measure of the elements and sub-elements of evidence (E) and context (C), and then using the aggregated data from these measures to determine the most appropriate facilitation method. The exact nature of the intervention is thus determined by the specific actors in the specific context at a specific time and place. In the process of refining this next phase of our work, we have had to consider the wider issues around the use of theories to inform and shape our research activity; the ongoing challenges of developing robust and sensitive measures; facilitation as an intervention for getting research into practice; and finally to note how the current debates around evidence into practice are adopting wider notions that fit innovations more generally. Summary The paper concludes by suggesting that the future direction of the work on the PARiHS framework is to develop a two-stage diagnostic and evaluative approach, where the intervention is shaped and moulded by the information gathered about the specific situation and from participating stakeholders. In order to expedite the generation of new evidence and testing of emerging theories, we suggest the formation of an international research implementation science collaborative that can systematically collect and analyse experiences of using and testing the PARiHS framework and similar conceptual and theoretical approaches. We also recommend further refinement of the definitions around conceptual framework, theory, and model, suggesting a wider discussion that embraces multiple epistemological and ontological perspectives

A pragmatic cluster randomised trial evaluating three implementation interventions

Background Implementation research is concerned with bridging the gap between evidence and practice through the study of methods to promote the uptake of research into routine practice. Good quality evidence has been summarised into guideline recommendations to show that peri-operative fasting times could be considerably shorter than patients currently experience. The objective of this trial was to evaluate the effectiveness of three strategies for the implementation of recommendations about peri-operative fasting. Methods A pragmatic cluster randomised trial underpinned by the PARIHS framework was conducted during 2006 to 2009 with a national sample of UK hospitals using time series with mixed methods process evaluation and cost analysis. Hospitals were randomised to one of three interventions: standard dissemination (SD) of a guideline package, SD plus a web-based resource championed by an opinion leader, and SD plus plan-do-study-act (PDSA). The primary outcome was duration of fluid fast prior to induction of anaesthesia. Secondary outcomes included duration of food fast, patients' experiences, and stakeholders' experiences of implementation, including influences. ANOVA was used to test differences over time and interventions. Results Nineteen acute NHS hospitals participated. Across timepoints, 3,505 duration of fasting observations were recorded. No significant effect of the interventions was observed for either fluid or food fasting times. The effect size was 0.33 for the web-based intervention compared to SD alone for the change in fluid fasting and was 0.12 for PDSA compared to SD alone. The process evaluation showed different types of impact, including changes to practices, policies, and attitudes. A rich picture of the implementation challenges emerged, including inter-professional tensions and a lack of clarity for decision-making authority and responsibility. Conclusions This was a large, complex study and one of the first national randomised controlled trials conducted within acute care in implementation research. The evidence base for fasting practice was accepted by those participating in this study and the messages from it simple; however, implementation and practical challenges influenced the interventions' impact. A set of conditions for implementation emerges from the findings of this study, which are presented as theoretically transferable propositions that have international relevance. Trial registration ISRCTN18046709 - Peri-operative Implementation Study Evaluation (POISE

FIRE (facilitating implementation of research evidence) : a study protocol

Research evidence underpins best practice, but is not always used in healthcare. The Promoting Action on Research Implementation in Health Services (PARIHS) framework suggests that the nature of evidence, the context in which it is used, and whether those trying to use evidence are helped (or facilitated) affect the use of evidence. Urinary incontinence has a major effect on quality of life of older people, has a high prevalence, and is a key priority within European health and social care policy. Improving continence care has the potential to improve the quality of life for older people and reduce the costs associated with providing incontinence aids

Government size, composition of public expenditure, and economic development

This paper analyzes the effects of government size and of the composition of public expenditure on economic development. Using the system-GMM estimator for linear dynamic panel data models, on a sample covering up to 156 countries and 5-year periods from 1980 to 2010, we find that government size as a percentage of GDP has a quadratic (inverted U-shaped) effect on the growth rate of the Human Development Index (HDI). This effect is especially pronounced in developed and high income countries. We also find that the composition of public expenditure affects development, with the share of five subcomponents exhibiting non-linear relationships with HDI growth.COMPETE, QREN, FEDER, Fundação para a Ciência e a Tecnologia (FCT

Virtual Outcrops in a Pocket: The Smartphone as a Fully Equipped Photogrammetric Data Acquisition Tool

Since the advent of affordable consumer-grade cameras over a century ago, photographic images have been the standard medium for capturing and visualizing outcrop-scale geological features. Despite the ubiquity of raster image data capture in routine fieldwork, the development of close-range 3D remote-sensing techniques has led to a paradigm shift in the representation and analysis of rock exposures from two- to three-dimensional forms. The use of geological 3D surface reconstructions in routine fieldwork has, however, been limited by the portability, associated learning curve, and/or expense of tools required for data capture, visualization, and analysis. Smartphones are rapidly becoming a viable alternative to conventional 3D close-range remote-sensing data capture and visualization platforms, providing a catalyst for the general uptake of 3D outcrop technologies by the geological community, which were up until relatively recently the purview of a relatively small number of geospatial specialists. Indeed, the continuous improvement of smartphone cameras, coupled with their integration with global navigation satellite system (GNSS) and inertial sensors provides 3D reconstructions with comparable accuracy to survey-grade systems. These developments have already led many field geologists to replace reflex cameras, as well as dedicated handheld GNSS receivers and compass clinometers, with smartphones, which offer the equivalent functionality within a single compact platform. Here we demonstrate that through the use of a smartphone and a portable gimbal stabilizer, we can readily generate and register high-quality 3D scans of outcropping geological structures, with the workflow exemplified using a mirror of a seismically active fault. The scan is conducted with minimal effort over the course of a few minutes with limited equipment, thus being representative of a routine situation for a field geologist

How to summarise and report written qualitative data from patients: a method for use in cancer support care

Goals of work: Determination of key themes to aid the analysis of qualitative data collected at three cancer support centres in England, using the Measure Yourself Concerns and Wellbeing (MYCaW) questionnaire. Patients and methods: People with cancer who use complementary therapies experience and value a wide range of treatment effects, yet tools are urgently required to quantitatively measure these outcomes. MYCAW is an individualised questionnaire used in cancer support centres providing complementary therapies, scoring 'concerns or problems' and 'wellbeing' and collects qualitative data about other major events in a patient's life and what has been most important to the patient. Content analysis on 782 MYCaW questionnaires from people at these cancer support centres was carried out. The "concerns", "other things going on in their life" and "important aspects of centre" were thematically categorised, externally validated by a focus group and the inter-rater reliability calculated. Main results: Clinical information from a cancer patient's perspective was collected that is not measured on standard quality of life questionnaires; furthermore some themes acknowledge the multifaceted aspects of CAM provision, rather than information only relating to the therapeutic intervention. Categories for qualitative MYCaW analysis have been established providing a tool for future research and/or service delivery improvement within cancer support centres such as these. Conclusions: The established themes provide a framework to aid analysis of qualitative aspects of complementary therapy care for people with cancer, improving our understanding of how the patient’s cancer experience can be aided by complementary therapies in specialized cancer centres