Flexible selection of a single treatment incorporating short-term endpoint information in a phase II/III clinical trial

Seamless phase II/III clinical trials in which an experimental treatment is selected at an interim analysis have been the focus of much recent research interest. Many of the methods proposed are based on the group sequential approach. This paper considers designs of this type in which the treatment selection can be based on short-term endpoint information for more patients than have primary endpoint data available. We show that in such a case, the familywise type I error rate may be inflated if previously proposed group sequential methods are used and the treatment selection rule is not specified in advance. A method is proposed to avoid this inflation by considering the treatment selection that maximises the conditional error given the data available at the interim analysis. A simulation study is reported that illustrates the type I error rate inflation and compares the power of the new approach with two other methods: a combination testing approach and a group sequential method that does not use the short-term endpoint data, both of which also strongly control the type I error rate. The new method is also illustrated through application to a study in Alzheimer's disease. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Verbal short‐term memory performance in pupils with Down Syndrome

Research has shown that verbal short‐term memory span is shorter in individuals with Down syndrome than in typically developing individuals of equivalent mental age, but little attention has been given to variations within or across groups. Differences in the environment and in particular educational experiences may play a part in the relative ease or difficulty with which children remember verbal material. This article explores the performance of 26 Egyptian pupils with Down syndrome and 26 Egyptian typically developing children on two verbal short‐term memory tests: digit recall and non‐word repetition tasks. The findings of the study revealed that typically developing children showed superior performance on these tasks to that of pupils with Down syndrome, whose performance was both lower and revealed a narrower range of attainment. Comparisons with the performance of children with Down syndrome in this study suggested that not only did the children with Down syndrome perform more poorly than the typically developing children, their profile also appeared worse than the results of studies of children with a similar mental age with Down syndrome carried out in western countries. The results from this study suggested that, while deficits in verbal short‐term memory in Down syndrome may well be universal, it is important to recognise that performances may vary as a consequence of culture and educational experiences. The significance of these findings is explored with reference to approaches to education and how these are conceptualised in relation to children with disabilities.

The potential of 1 h refractivity changes from an operational C-band magnetron-based radar for numerical weather prediction validation and data assimilation

Refractivity changes (ΔN) derived from radar ground clutter returns serve as a proxy for near-surface humidity changes (1 N unit ≡ 1% relative humidity at 20 °C). Previous studies have indicated that better humidity observations should improve forecasts of convection initiation. A preliminary assessment of the potential of refractivity retrievals from an operational magnetron-based C-band radar is presented. The increased phase noise at shorter wavelengths, exacerbated by the unknown position of the target within the 300 m gate, make it difficult to obtain absolute refractivity values, so we consider the information in 1 h changes. These have been derived to a range of 30 km with a spatial resolution of ∼4 km; the consistency of the individual estimates (within each 4 km × 4 km area) indicates that ΔN errors are about 1 N unit, in agreement with in situ observations. Measurements from an instrumented tower on summer days show that the 1 h refractivity changes up to a height of 100 m remain well correlated with near-surface values. The analysis of refractivity as represented in the operational Met Office Unified Model at 1.5, 4 and 12 km grid lengths demonstrates that, as model resolution increases, the spatial scales of the refractivity structures improve. It is shown that the magnitude of refractivity changes is progressively underestimated at larger grid lengths during summer. However, the daily time series of 1 h refractivity changes reveal that, whereas the radar-derived values are very well correlated with the in situ observations, the high-resolution model runs have little skill in getting the right values of ΔN in the right place at the right time. This suggests that the assimilation of these radar refractivity observations could benefit forecasts of the initiation of convection.

Controlled trial of the short- and long-term effect of psychological treatment of post-partum depression 2. Impact on the mother-child relationship and child outcome

Background: Postnatal depression is associated with adverse child cognitive and socio-emotional outcome. It is not known whether psychological treatment affects the quality of the mother-child relationship and child outcome. Aims: To evaluate the effect of three psychological treatments on the mother-child relationship and child outcome. Method: Women with post-partum depression (n=193) were assigned randomly to routine primary care, non-directive counselling, cognitive-behavioural therapy or psychodynamic therapy The women and their children, were assessed at 43, [8 and 60 months post-partum. Results: Indications of a positive benefit were limited. All three treatments had a significant benefit on maternal reports of early difficulties in relationships with the infants, counselling gave better infant emotional and behaviour ratings at 18 months and more sensitive early mother-infant interactions. The treatments had no significant impact on maternal management of early infant behaviour problems, security of infant-mother attachment. Infant cognitive development or any child outcome at 5 years. Conclusions: Early intervention was of short-term benefit to the mother-child relationship and infant behaviour problems. More-prolonged intervention may be needed. Health visitors could deliver this.

Controlled trial of the short- and long-term effect of psychological treatment of post-partum depression - 1. Impact on maternal mood!

Background: Psychological interventions for postnatal depression can be beneficial in the short term but their longer-term impact is unknown, Aims To evaluate the long-term effect on maternal mood of three psychological treatments in relation to routine primary care. Method: Women with post-partum depression (n=193)were assigned randomly to one of four conditions: routine primary care, non-directive counselling, cognitive-behavioural therapy or psychodynamic therapy. They were assessed immediately after the treatment phase (at 4.5 months) and at 18 and 60 months post-partum. Results: Compared with the control, ail three treatments had a significant impact at 4.5 months on maternal mood (Edinburgh Postnatal Depression Scale, EPDS). Only psychodynamic therapy produced a rate of reduction in depression (Structured Clinical interview for DSM III-R) significantly superior to that of the control. The benefit of treatment was no longer apparent by 9 months postpartum, treatment did not reduce subsequent episodes of post-partum depression. Conclusions: Psychological intervention for post-partum depression improves maternal mood (EPDS) in the short term. However, this benefit is not superior to spontaneous remission in the long term.

Facing the future: energy performance certificates and commercial property

Purpose – The paper aims to present the findings of a “situation review” of the Energy Performance of Buildings Directive (EPBD), focusing on energy performance certificates (EPCs) to highlight areas of specific importance for the UK property investment community. The paper is based on research commissioned by the Investment Property Forum (IPF) and funded through the IPF Research Programme (2006-2009). Design/methodology/approach – Interviews were undertaken with experts from the fields of property investment and building engineering. The interviews were undertaken with to identify: the current knowledge of EPCs in the property investment sector; key issues with practical implementation of the legislation; and perceptions of the potential impacts of legislation, particularly in relation to value stakeholder and behaviour. Findings – The paper finds that, although the regulations have been published, there is still a need for clarification in the marketplace with regard to some of the detail of regulations and the certification process. The following areas are of most concern to property investors: costs of surveys; potential difficulties with the process; and a shortage of assessors. With respect to these impacts it is becoming clear that investors who have not yet started considering the EPBD and its requirements within their strategy are likely to face difficulties in the short term. The most significant value-related impacts of EPBD are expected to be value differentiation of properties and “price chipping” against the rental or capital value of the property, where an occupier or potential purchaser will use the recommendations contained within an EPC to force a reduction in value. The latter is expected to emerge in the short term, whereas the former is expected to be realised over the medium to long term. Both these impacts have potentially significant implications for property investment holdings and also future investment behaviour.

Sources of variation in the ampicillin-resistant Escherichia coli concentration in the feces of organic broiler chickens

Currently, there are limited published data for the population dynamics of antimicrobial-resistant commensal bacteria. This study was designed to evaluate both the proportions of the Escherichia coli populations that are resistant to ampicillin at the level of the individual chicken on commercial broiler farms and the feasibility of obtaining repeated measures of fecal E. coli concentrations. Short-term temporal variation in the concentration of fecal E. coli was investigated, and a preliminary assessment was made of potential factors involved in the shedding of high numbers of ampicillin-resistant E. coli by growing birds in the absence of the use of antimicrobial drugs. Multilevel linear regression modeling revealed that the largest component of random variation in log-transformed fecal E. coli concentrations was seen between sampling occasions for individual birds. The incorporation of fixed effects into the model demonstrated that the older, heavier birds in the study were significantly more likely (P = 0.0003) to shed higher numbers of ampicillin-resistant E. coli. This association between increasing weight and high shedding was not seen for the total fecal E. coli population (P = 0.71). This implies that, in the absence of the administration of antimicrobial drugs, the proportion of fecal E. coli that was resistant to ampicillin increased as the birds grew. This study has shown that it is possible to collect quantitative microbiological data on broiler farms and that such data could make valuable contributions to risk assessments concerning the transfer of resistant bacteria between animal and human populations.

Successful strategy making in Bupa not-for-profit provident: a case study and interview with Mr Ray King, chief executive of Bupa

Purpose – The focus of extant strategy literature is on for-profit organisations and within these group public organisations. There are other forms of organisations and following the deep recession of 2008 there is greater interest in other forms of organisation. In this case study and interview the aim is to examine strategy, strategic decisions and strategic management of a not-for-profit provident. Design/methodology/approach – The paper draws on documentary evidence and a semi-structured interview with Ray King, chief executive of Bupa. The perspective of CEO is key in strategy and such perspectives are relatively rarer. Findings – Bupa invests its surplus to provide better healthcare. Free from the pressures of quarterly reporting and shareholders it can pursue long-term value creation for members rather than short-term surpluses. Research limitations/implications – The case study and interview offers a unique insight into strategy-making within a successful mutual provident that has grown organically and externally becoming an international leader in health insurance. Originality/value – This case study sheds light on strategy-making within a not-for-profit provident that has diversified and grown significantly over the past six decades. Furthermore, very few case studies offer insight into the thinking of a chief executive who has successfully managed a business in a turbulent environment.

Evaluation of boundary-layer type in a weather forecast model utilising long-term Doppler lidar observations

Many studies evaluating model boundary-layer schemes focus either on near-surface parameters or on short-term observational campaigns. This reflects the observational datasets that are widely available for use in model evaluation. In this paper we show how surface and long-term Doppler lidar observations, combined in a way to match model representation of the boundary layer as closely as possible, can be used to evaluate the skill of boundary-layer forecasts. We use a 2-year observational dataset from a rural site in the UK to evaluate a climatology of boundary layer type forecast by the UK Met Office Unified Model. In addition, we demonstrate the use of a binary skill score (Symmetric Extremal Dependence Index) to investigate the dependence of forecast skill on season, horizontal resolution and forecast leadtime. A clear diurnal and seasonal cycle can be seen in the climatology of both the model and observations, with the main discrepancies being the model overpredicting cumulus capped and decoupled stratocumulus capped boundary-layers and underpredicting well mixed boundary-layers. Using the SEDI skill score the model is most skillful at predicting the surface stability. The skill of the model in predicting cumulus capped and stratocumulus capped stable boundary layer forecasts is low but greater than a 24 hr persistence forecast. In contrast, the prediction of decoupled boundary-layers and boundary-layers with multiple cloud layers is lower than persistence. This process based evaluation approach has the potential to be applied to other boundary-layer parameterisation schemes with similar decision structures.

Long term changes in EUV and X-ray emissions from the solar corona and chromosphere as measured by the response of the Earth’s ionosphere during total solar eclipses from 1932 to 1999

Measurements of the ionospheric E region during total solar eclipses in the period 1932-1999 have been used to investigate the fraction of Extreme Ultra Violet and soft X-ray radiation, phi, that is emitted from the limb corona and chromosphere. The relative apparent sizes of the Moon and the Sun are different for each eclipse, and techniques are presented which correct the measurements and, therefore, allow direct comparisons between different eclipses. The results show that the fraction of ionising radiation emitted by the limb corona has a clear solar cycle variation and that the underlying trend shows this fraction has been increasing since 1932. Data from the SOHO spacecraft are used to study the effects of short-term variability and it is shown that the observed long-term rise in phi has a negligible probability of being a chance occurrence.

Advancing polar prediction capabilities on daily to seasonal time scales

It is argued that existing polar prediction systems do not yet meet users’ needs; and possible ways forward in advancing prediction capacity in polar regions and beyond are outlined. The polar regions have been attracting more and more attention in recent years, fuelled by the perceptible impacts of anthropogenic climate change. Polar climate change provides new opportunities, such as shorter shipping routes between Europe and East Asia, but also new risks such as the potential for industrial accidents or emergencies in ice-covered seas. Here, it is argued that environmental prediction systems for the polar regions are less developed than elsewhere. There are many reasons for this situation, including the polar regions being (historically) lower priority, with less in situ observations, and with numerous local physical processes that are less well-represented by models. By contrasting the relative importance of different physical processes in polar and lower latitudes, the need for a dedicated polar prediction effort is illustrated. Research priorities are identified that will help to advance environmental polar prediction capabilities. Examples include an improvement of the polar observing system; the use of coupled atmosphere-sea ice-ocean models, even for short-term prediction; and insight into polar-lower latitude linkages and their role for forecasting. Given the enormity of some of the challenges ahead, in a harsh and remote environment such as the polar regions, it is argued that rapid progress will only be possible with a coordinated international effort. More specifically, it is proposed to hold a Year of Polar Prediction (YOPP) from mid-2017 to mid-2019 in which the international research and operational forecasting community will work together with stakeholders in a period of intensive observing, modelling, prediction, verification, user-engagement and educational activities.