A comparison of methods for treatment selection in seamless phase II/III clinical trials incorporating information on short-term endpoints

In an adaptive seamless phase II/III clinical trial interim analysis data are used for treatment selection, enabling resources to be focussed on comparison of more effective treatment(s) with a control. In this paper we compare two methods recently proposed to enable use of short-term endpoint data for decision-making at the interim analysis. The comparison focusses on the power and the probability of correctly identifying the most promising treatment. We show that the choice of method depends on how well short-term data predict the best treatment, which may be measured by the correlation between treatment effects on short-term and long-term endpoints

Seasonal Variability In The Ionosphere Of Uranus

Infrared ground-based observations using IRTF, UKIRT, and Keck II of Uranus have been analyzed as to identify the long-term behavior of the H-3(+) ionosphere. Between 1992 and 2008 there are 11 individual observing runs, each recording emission from the H-3(+) Q branch emission around 4 mu m through the telluric L' atmospheric window. The column-averaged rotational H-3(+) temperature ranges between 715 K in 1992 and 534 K in 2008, with the linear fit to all the run-averaged temperatures decreasing by 8 K year(-1). The temperature follows the fractional illumination curve of the planet, declining from solstice (1985) to equinox (2007). Variations in H-3(+) column density do not appear to be correlated to either solar cycle phase or season. The radiative cooling by H-3(+) is similar to 10 times larger than the ultraviolet solar energy being injected to the atmosphere. Despite the fact that the solar flux alone is incapable of heating the atmosphere to the observed temperatures, the geometry with respect to the Sun remains an important driver in determining the thermospheric temperature. Therefore, the energy source that heats the thermosphere must be linked to solar mechanisms. We suggest that this may be in the form of conductivity created by solar ionization of atmospheric neutrals and/or seasonally dependent magnetospherically driven current systems.STFC PP/E/000983/1, ST/G0022223/1RCUKGemini ObservatoryNational Aeronautics and Space Administration (NASA) NXX08A043G, NNX08AE38AAstronom

Magnetic reconnection near the planet as a possible driver of Jupiter's mysterious polar auroras

Auroral emissions have been extensively observed at the Earth, Jupiter, and Saturn. These planets all have appreciable atmospheres and strong magnetic fields, and their auroras predominantly originate from a region encircling each magnetic pole. However, Jupiter’s auroras poleward of these “main” emissions are brighter and more dynamic, and the drivers responsible for much of these mysterious polar auroras have eluded identification to date. We propose that part of the solution may stem from Jupiter’s stronger magnetic field. We model large-scale Alfvénic perturbations propagating through the polar magnetosphere towards Jupiter, showing that the resulting <0.1° deflections of the magnetic field closest to the planet could trigger magnetic reconnection as near as ∼0.2 Jupiter radii above the cloud tops. At Earth and Saturn this physics should be negligible, but reconnection electric field strengths above Jupiter’s poles can approach ∼1 V m-1, typical of the solar corona. We suggest this near-planet reconnection could generate beams of high-energy electrons capable of explaining some of Jupiter’s polar auroras

To add or not to add a new treatment arm to a multiarm study: A decision-theoretic framework.

Multiarm clinical trials, which compare several experimental treatments against control, are frequently recommended due to their efficiency gain. In practise, all potential treatments may not be ready to be tested in a phase II/III trial at the same time. It has become appealing to allow new treatment arms to be added into on-going clinical trials using a "platform" trial approach. To the best of our knowledge, many aspects of when to add arms to an existing trial have not been explored in the literature. Most works on adding arm(s) assume that a new arm is opened whenever a new treatment becomes available. This strategy may prolong the overall duration of a study or cause reduction in marginal power for each hypothesis if the adaptation is not well accommodated. Within a two-stage trial setting, we propose a decision-theoretic framework to investigate when to add or not to add a new treatment arm based on the observed stage one treatment responses. To account for different prospect of multiarm studies, we define utility in two different ways; one for a trial that aims to maximise the number of rejected hypotheses; the other for a trial that would declare a success when at least one hypothesis is rejected from the study. Our framework shows that it is not always optimal to add a new treatment arm to an existing trial. We illustrate a case study by considering a completed trial on knee osteoarthritis

School-based intervention to reduce anxiety in children: study protocol for a randomized controlled trial (PACES)

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Emotional problems such as anxiety and low mood in children are common, impair everyday functioning and increase the risk of severe mental health disorders in adulthood. Relatively few children with emotional health problems are identified and referred for treatment indicating the need to investigate preventive approaches. METHODS/DESIGN: The study is designed to be a pragmatic cluster randomized controlled trial evaluating the effectiveness of an efficacious school-based cognitive behavior therapy (CBT) prevention program (FRIENDS) on symptoms of anxiety and low mood in children 9 to 10 years of age. The unit of allocation is schools which are assigned to one of three conditions: school-led FRIENDS, health-led FRIENDS or treatment as usual. Assessments will be undertaken at baseline, 6 months and 12 months. The primary outcome measure is change on the Revised Child Anxiety and Depression Scale. Secondary outcome measures assess changes in self-esteem, worries, bullying and life satisfaction. An economic evaluation will be undertaken. DISCUSSION: As of September 2011, 41 schools have been recruited and randomized. Final 12-month assessments are scheduled to be completed by May 2013. TRIAL REGISTRATION: ISRCTN23563048.The project is funded by the NIHR Public Health Research Programme (09/3000/03

Cassini observations of ion and electron beams at Saturn and their relationship to infrared auroral arcs

We present Cassini Visual and Infrared Mapping Spectrometer observations of infrared auroral emissions from the noon sector of Saturn's ionosphere revealing multiple intense auroral arcs separated by dark regions poleward of the main oval. The arcs are interpreted as the ionospheric signatures of bursts of reconnection occurring at the dayside magnetopause. The auroral arcs were associated with upward field-aligned currents, the magnetic signatures of which were detected by Cassini at high planetary latitudes. Magnetic field and particle observations in the adjacent downward current regions showed upward bursts of 100–360 keV light ions in addition to energetic (hundreds of keV) electrons, which may have been scattered from upward accelerated beams carrying the downward currents. Broadband, upward propagating whistler waves were detected simultaneously with the ion beams. The acceleration of the light ions from low altitudes is attributed to wave-particle interactions in the downward current regions. Energetic (600 keV) oxygen ions were also detected, suggesting the presence of ambient oxygen at altitudes within the acceleration region. These simultaneous in situ and remote observations reveal the highly energetic magnetospheric dynamics driving some of Saturn's unusual auroral features. This is the first in situ identification of transient reconnection events at regions magnetically conjugate to Saturn's magnetopause

The prevention of anxiety in children through school-based interventions: study protocol for a 24-month follow-up of the PACES project

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Anxiety in children is common and incapacitating and increases the risk of mental health disorders in adulthood. Although effective interventions are available, few children are identified and referred for specialist treatment. Alternative approaches in which prevention programmes are delivered in school appear promising. However, comparatively little is known about the best intervention leader (health care-led vs. school-led), long-term effects or the primary preventive value of such programmes. METHODS/DESIGN: Preventing Anxiety in Children through Education in Schools, or PACES, is a pragmatic cluster randomised controlled trial evaluating the effectiveness of a cognitive-behavioural therapy prevention programme (FRIENDS) on symptoms of anxiety and low mood in 9- to 10-year-old children. Forty-one schools were randomly assigned to one of three conditions: school-led FRIENDS, health care-led FRIENDS or treatment as usual. Assessments were undertaken at baseline, 6 months and 12 months, with the primary outcome measure being the Revised Child Anxiety and Depression Scale score at 12 months. Secondary outcome measures are changes in self-esteem, worries, bullying and life satisfaction. DISCUSSION: This protocol summarises the procedure for the 24-month follow-up of this cohort. The study will determine the medium-term effectiveness of an anxiety prevention programme delivered in schools. TRIAL REGISTRATION: ISRCTN23563048.The project is funded by the NIHR Public Health Research Programme (09/3000/03