Monitoring treatment fidelity in a randomised controlled trial of a complex intervention.

Aim. This paper is a report of a study to describe how treatment fidelity is being enhanced and monitored, using a model from the National Institutes of Health Behavior Change Consortium. Background. The objective of treatment fidelity is to minimize errors in interpreting research trial outcomes, and to ascribe those outcomes directly to the intervention at hand. Treatment fidelity procedures are included in trials of complex interventions to account for inferences made from study outcomes. Monitoring treatment fidelity can help improve study design, maximize reliability of results, increase statistical power, determine whether theory-based interventions are responsible for observed changes, and inform the research dissemination process. Methods. Treatment fidelity recommendations from the Behavior Change Consortium were applied to the SPHERE study (Secondary Prevention of Heart DiseasE in GeneRal PracticE), a randomized controlled trial of a complex intervention. Procedures to enhance and monitor intervention implementation included standardizing training sessions, observing intervention consultations, structuring patient recall systems, and using written practice and patient care plans. The research nurse plays an important role in monitoring intervention implementation. Findings. Several methods of applying treatment fidelity procedures to monitoring interventions are possible. The procedure used may be determined by availability of appropriate personnel, fiscal constraints, or time limits. Complex interventions are not straightforward and necessitate a monitoring process at trial stage. Conclusion. The Behavior Change Consortium’s model of treatment fidelity is useful for structuring a system to monitor the implementation of a complex intervention, and helps to increase the reliability and validity of evaluation findings.

METAMORPHOSE European Doctoral Programs on Metamaterials - State-of-the-art

A new European Doctoral Program on Metamaterials has been initiated by the European Union (EU) Network of Excellence METAMORPHOSE. So far, twenty European academic institutions have established a consortium that operates a geographically distributed doctoral school in the emerging and multidisciplinary field of metamaterials.

WASP-10b: a 3M(J), gas-giant planet transiting a late-type K star

We report the discovery of WASP-10b, a new transiting extrasolar planet (ESP) discovered by the Wide Angle Search for Planets ( WASP) Consortium and confirmed using Nordic Optical Telescope FIbre-fed Echelle Spectrograph and SOPHIE radial velocity data. A 3.09-d period, 29 mmag transit depth and 2.36 h duration are derived for WASP-10b using WASP and high-precision photometric observations. Simultaneous fitting to the photometric and radial velocity data using a Markov Chain Monte Carlo procedure leads to a planet radius of 1.28R(J), a mass of 2.96M(J) and eccentricity of approximate to 0.06. WASP-10b is one of the more massive transiting ESPs, and we compare its characteristics to the current sample of transiting ESP, where there is currently little information for masses greater than approximate to 2M(J) and non-zero eccentricities. WASP-10's host star, GSC 2752-00114 (USNO-B1.0 1214-0586164) is among the fainter stars in the WASP sample, with V = 12.7 and a spectral type of K5. This result shows promise for future late-type dwarf star surveys.

Creative Activism: a pedagogical and research tool

Environmental activism has a long history in protest, addressing issues of degradation and segregation that threaten existing ecologies, social and built fabrics. Environmental activism is traditionally understood as a reaction, chiefly by groups of people, against a perceived external threat. In the 60’s and 70’s, an activist stance began to emerge in the work of some artists and architects, who used creative methods such as performances, happenings, temporary spatial interventions etc to convey their political/aesthetic messages. Some of this work engaged directly with communities but predominantly it was the production of one individual working ‘outside’ society. However such actions demonstrated not only the power of the visual in conveying a political message but also the potential of conceptual creative approaches to reveal alternative values and hidden potentials. This marked a shift from activism as protestation towards an activism of reconceptualisation. Recently, activist groups have developed a more politically informed process. Whilst their ‘tools’ may resemble work from the 60’s and 70’s , their methodologies are non-traditional, ’rhizomatic’, pedagogical and fluid; working alongside, rather than against, the established power and funding structures. Such creative processes build new, often unexpected, stakeholder networks; offer neutral spaces in which contentious issues can be faced; and create better understanding of values and identities. They can also lead to permanent improvements and development in the physical fabric. This paper will discuss a pedagogical example of activism in architectural education. The event (www.fourdaysontheoutside.com) is in its fifth year of existence and as such has revealed a value and impulse beyond its learning and teaching value. The paper will discuss how the event contributes to the university’s outreach programme and how its structure acts as a seedbed for potential research projects and partnerships. UK Universities talk extensively about applied research but have few actual strategies by which to generate it. Fourdaysontheoutside offers some potential ways forward.

WASP-21b: a hot-Saturn exoplanet transiting a thick disc star

We report the discovery of WASP-21b, a new transiting exoplanet discovered by the Wide Angle Search for Planets (WASP) Consortium and established and characterized with the FIES, SOPHIE, CORALIE and HARPS fiber-fed echelle spectrographs. A 4.3-d period, 1.1% transit depth and 3.4-h duration are derived for WASP-21b using SuperWASP-North and high precision photometric observations at the Liverpool Telescope. Simultaneous fitting to the photometric and radial velocity data with a Markov Chain Monte Carlo procedure leads to a planet in the mass regime of Saturn. With a radius of 1.07 RJup and mass of 0.30 MJup, WASP-21b has a density close to 0.24 ?Jup corresponding to the distribution peak at low density of transiting gaseous giant planets. With a host star metallicity [Fe/H] of -0.46, WASP-21b strengthens the correlation between planetary density and host star metallicity for the five known Saturn-like transiting planets. Furthermore there are clear indications that WASP-21b is the first transiting planet belonging to the thick disc.

Spin-orbit angle measurements for six southern transiting planets. New insights into the dynamical origins of hot Jupiters

Context. Several competing scenarios for planetary-system formation and evolution seek to explain how hot Jupiters came to be so close to their parent stars. Most planetary parameters evolve with time, making it hard to distinguish between models. The obliquity of an orbit with respect to the stellar rotation axis is thought to be more stable than other parameters such as eccentricity. Most planets, to date, appear aligned with the stellar rotation axis; the few misaligned planets so far detected are massive (> 2 MJ). Aims: Our goal is to measure the degree of alignment between planetary orbits and stellar spin axes, to search for potential correlations with eccentricity or other planetary parameters and to measure long term radial velocity variability indicating the presence of other bodies in the system. Methods: For transiting planets, the Rossiter-McLaughlin effect allows the measurement of the sky-projected angle ß between the stellar rotation axis and a planet's orbital axis. Using the HARPS spectrograph, we observed the Rossiter-McLaughlin effect for six transiting hot Jupiters found by the WASP consortium. We combine these with long term radial velocity measurements obtained with CORALIE. We used a combined analysis of photometry and radial velocities, fitting model parameters with the Markov Chain Monte Carlo method. After obtaining ß we attempt to statistically determine the distribution of the real spin-orbit angle ?. Results: We found that three of our targets have ß above 90°: WASP-2b: ß = 153°+11-15, WASP-15b: ß = 139.6°+5.2-4.3 and WASP-17b: ß = 148.5°+5.1-4.2; the other three (WASP-4b, WASP-5b and WASP-18b) have angles compatible with 0°. We find no dependence between the misaligned angle and planet mass nor with any other planetary parameter. All six orbits are close to circular, with only one firm detection of eccentricity e = 0.00848+0.00085-0.00095 in WASP-18b. No long-term radial acceleration was detected for any of the targets. Combining all previous 20 measurements of ß and our six and transforming them into a distribution of ? we find that between about 45 and 85% of hot Jupiters have ? > 30°. Conclusions: Most hot Jupiters are misaligned, with a large variety of spin-orbit angles. We find observations and predictions using the Kozai mechanism match well. If these observational facts are confirmed in the future, we may then conclude that most hot Jupiters are formed from a dynamical and tidal origin without the necessity to use type I or II migration. At present, standard disc migration cannot explain the observations without invoking at least another additional process.

Guidelines for the measurement of BCR-ABL1 transcripts in chronic myeloid leukaemia

Molecular testing for the BCR-ABL1 fusion gene by real time quantitative polymerase chain reaction (RT-qPCR) is the most sensitive routine approach for monitoring the response to therapy of patients with chronic myeloid leukaemia. In the context of tyrosine kinase inhibitor (TKI) therapy, the technique is most appropriate for patients who have achieved complete cytogenetic remission and can be used to define specific therapeutic milestones. To achieve this effectively, standardization of the laboratory procedures and the interpretation of results are essential. We present here consensus best practice guidelines for RT-qPCR testing, data interpretation and reporting that have been drawn up and agreed by a consortium of 21 testing laboratories in the United Kingdom and Ireland in accordance with the procedures of the UK Clinical Molecular Genetics Society.

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P = 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)).

Replication of EPHA1 and CD33 associations with late-onset Alzheimer’s disease: a multi-centre case-control study

A recently published genome-wide association study (GWAS) of late-onset Alzheimer's disease (LOAD) revealed genome-wide significant association of variants in or near MS4A4A, CD2AP, EPHA1 and CD33. Meta-analyses of this and a previously published GWAS revealed significant association at ABCA7 and MS4A, independent evidence for association of CD2AP, CD33 and EPHA1 and an opposing yet significant association of a variant near ARID5B. In this study, we genotyped five variants (in or near CD2AP, EPHA1, ARID5B, and CD33) in a large (2,634 LOAD, 4,201 controls), independent dataset comprising six case-control series from the USA and Europe. We performed meta-analyses of the association of these variants with LOAD and tested for association using logistic regression adjusted by age-at-diagnosis, gender, and APOE e4 dosage.