Phenotypes of childhood asthma: are they real?

It has been suggested that there are several distinct phenotypes of childhood asthma or childhood wheezing. Here, we review the research relating to these phenotypes, with a focus on the methods used to define and validate them. Childhood wheezing disorders manifest themselves in a range of observable (phenotypic) features such as lung function, bronchial responsiveness, atopy and a highly variable time course (prognosis). The underlying causes are not sufficiently understood to define disease entities based on aetiology. Nevertheless, there is a need for a classification that would (i) facilitate research into aetiology and pathophysiology, (ii) allow targeted treatment and preventive measures and (iii) improve the prediction of long-term outcome. Classical attempts to define phenotypes have been one-dimensional, relying on few or single features such as triggers (exclusive viral wheeze vs. multiple trigger wheeze) or time course (early transient wheeze, persistent and late onset wheeze). These definitions are simple but essentially subjective. Recently, a multi-dimensional approach has been adopted. This approach is based on a wide range of features and relies on multivariate methods such as cluster or latent class analysis. Phenotypes identified in this manner are more complex but arguably more objective. Although phenotypes have an undisputed standing in current research on childhood asthma and wheezing, there is confusion about the meaning of the term 'phenotype' causing much circular debate. If phenotypes are meant to represent 'real' underlying disease entities rather than superficial features, there is a need for validation and harmonization of definitions. The multi-dimensional approach allows validation by replication across different populations and may contribute to a more reliable classification of childhood wheezing disorders and to improved precision of research relying on phenotype recognition, particularly in genetics. Ultimately, the underlying pathophysiology and aetiology will need to be understood to properly characterize the diseases causing recurrent wheeze in children.

Robust estimates of climate-induced hydrological change in a temperate mountainous region

A sustainable water resources management depends on sound information about the impacts of climate change. This information is, however, not easily derived because natural runoff variability interferes with the climate change signal. This study presents a procedure that leads to robust estimates of magnitude and Time Of Emergence (TOE) of climate-induced hydrological change that also account for the natural variability contained in the time series. Firstly, natural variability of 189 mesoscale catchments in Switzerland is sampled for 10 ENSEMBLES scenarios for the control (1984–2005) and two scenario periods (near future: 2025–2046, far future: 2074–2095) applying a bootstrap procedure. Then, the sampling distributions of mean monthly runoff are tested for significant differences with the Wilcoxon-Mann–Whitney test and for effect size with Cliff’s delta d. Finally, the TOE of a climate change induced hydrological change is determined when at least eight out of the ten hydrological projections significantly differ from natural variability. The results show that the TOE occurs in the near future period except for high-elevated catchments in late summer. The significant hydrological projections in the near future correspond, however, to only minor runoff changes. In the far future, hydrological change is statistically significant and runoff changes are substantial. Temperature change is the most important factor determining hydrological change in this mountainous region. Therefore, hydrological change depends strongly on a catchment’s mean elevation. Considering that the hydrological changes are predicted to be robust in the near future highlights the importance of accounting for these changes in water resources planning.

First intercomparison study on the analysis of oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) and nitrogen heterocyclic polycyclic aromatic compounds (N-PACs) in contaminated soil

Oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) and nitrogen heterocyclic polycyclic aromatic compounds (N-PACs) are toxic, highly leachable and often abundant at sites that are also contaminated with PAHs. However, due to lack of regulations and standardized methods for their analysis, they are seldom included in monitoring and risk-assessment programs. This intercomparison study constitutes an important step in the harmonization of the analytical methods currently used, and may also be considered a first step towards the certification of reference materials for these compounds. The results showed that the participants were able to determine oxy-PAHs with accuracy similar to PAHs, with average determined mass fractions agreeing well with the known levels in a spiked soil and acceptable inter- and intra-laboratory precisions for all soils analyzed. For the N-PACs, the results were less satisfactory, and have to be improved by using analytical methods more specifically optimized for these compounds.

Intercomparison of stratospheric ozone profiles for the assessment of the upgraded GROMOS radiometer at Bern

Since November 1994, the GROund-based Millimeter-wave Ozone Spectrometer (GROMOS) measures stratospheric and lower mesospheric ozone in Bern, Switzerland (47.95° N, 7.44° E). GROMOS is part of the Network for the Detection of Atmospheric Composition Change (NDACC). In July 2009, a Fast-Fourier-Transform spectrometer (FFTS) has been added as backend to GROMOS. The new FFTS and the original filter bench (FB) measured parallel for over two years. In October 2011, the FB has been turned off and the FFTS is now used to continue the ozone time series. For a consolidated ozone time series in the frame of NDACC, the quality of the stratospheric ozone profiles obtained with the FFTS has to be assessed. The FFTS results from July 2009 to December 2011 are compared to ozone profiles retrieved by the FB. FFTS and FB of the GROMOS microwave radiometer agree within 5% above 20 hPa. A later harmonization of both time series will be realized by taking the FFTS as benchmark for the FB. Ozone profiles from the FFTS are also compared to coinciding lidar measurements from the Observatoire Haute Provence (OHP), France. For the time period studied a maximum mean difference (lidar – GROMOS FFTS) of +3.8% at 3.1 hPa and a minimum mean difference of +1.4% at 8 hPa is found. Further, intercomparisons with ozone profiles from other independent instruments are performed: satellite measurements include MIPAS onboard ENVISAT, SABER onboard TIMED, MLS onboard EOS Aura and ACE-FTS onboard SCISAT-1. Additionally, ozonesondes launched from Payerne, Switzerland, are used in the lower stratosphere. Mean relative differences of GROMOS FFTS and these independent instruments are less than 10% between 50 and 0.1 hPa.

Comparability of Outcome Frameworks in Medical Education: Implications for framework development

Background: The demand for international harmonization in medical education increases with the growing mobility of students and health professionals. Many medical societies and governmental offices have issued outcome frameworks (OF), which describe aims and contents of medical education based on competencies. These national standards affect the development of curricula as well as assessment and licensing procedures. Comparing OF and identifying factors that limit their comparability may thus foster international harmonization of medical education. Summary of Work: We conducted a systematic search for national OF in MedLine, EmBase and the internet. We included all OF in German or English that resulted from a national consensus process and were published or endorsed by a national society or governmental body. We extracted information in five predetermined categories: history of origin, audience, formal structure, medical schooling system and key terms. Summary of Results: Out of 1816 results, 13 OF were included into further analyses. OF reference each other, often without addressing existing differences (e.g. in target audiences). The two most cited OF are “CanMEDs” and “Scottish Doctor”. OF differ especially in their level of detail as well as in the underlying educational system. Discussion and Conclusions: Based on our results we propose a two-step blueprint for OF, that may help to establish comparability for internationally aligned key features – so-called “core competencies” – while at the same time allowing for necessary regional adaptations in terms of “secondary competencies”. Take-home messages: Considerable differences in at least five categories of OF currently hinder the comparability of outcome frameworks.

Does published orthodontic research account for clustering effects during statistical data analysis?

In orthodontics, multiple site observations within patients or multiple observations collected at consecutive time points are often encountered. Clustered designs require larger sample sizes compared to individual randomized trials and special statistical analyses that account for the fact that observations within clusters are correlated. It is the purpose of this study to assess to what degree clustering effects are considered during design and data analysis in the three major orthodontic journals. The contents of the most recent 24 issues of the American Journal of Orthodontics and Dentofacial Orthopedics (AJODO), Angle Orthodontist (AO), and European Journal of Orthodontics (EJO) from December 2010 backwards were hand searched. Articles with clustering effects and whether the authors accounted for clustering effects were identified. Additionally, information was collected on: involvement of a statistician, single or multicenter study, number of authors in the publication, geographical area, and statistical significance. From the 1584 articles, after exclusions, 1062 were assessed for clustering effects from which 250 (23.5 per cent) were considered to have clustering effects in the design (kappa = 0.92, 95 per cent CI: 0.67-0.99 for inter rater agreement). From the studies with clustering effects only, 63 (25.20 per cent) had indicated accounting for clustering effects. There was evidence that the studies published in the AO have higher odds of accounting for clustering effects [AO versus AJODO: odds ratio (OR) = 2.17, 95 per cent confidence interval (CI): 1.06-4.43, P = 0.03; EJO versus AJODO: OR = 1.90, 95 per cent CI: 0.84-4.24, non-significant; and EJO versus AO: OR = 1.15, 95 per cent CI: 0.57-2.33, non-significant). The results of this study indicate that only about a quarter of the studies with clustering effects account for this in statistical data analysis.

Clinical endpoint adjudication in a contemporary all-comers coronary stent investigation: methodology and external validation

Globalisation in coronary stent research calls for harmonization of clinical endpoint definitions and event adjudication. Little has been published about the various processes used for event adjudication or their impact on outcome reporting.

Executive compensation and executive incentive problems: an empirical analysis

The question of whether the design of the corporate executive pay package reflects an attempt to reduce agency costs between shareholders an managers is adressed. The components of senior executive pay are found to vary systematically across firms in a manner that cannot easily be explained by tax effects, and which would indicate that individual elements of pay are aimed at controlling for limited horizon and risk exposure problems. Managerial decisions and the structure of managerial pay therefore appear to be interrelated.

Merger decisions and executive stock ownership in acquiring firms

This study supports the proposition that managerial welfare affects merger decisions. The abnormal stock returns experienced by bidder firms, from the time of the announcement of a merger bid through the stockholder approval date, are positively relaterd to the percentage of own-company stock held by the senior management of the bidder. The results suggest that substantial amounts of own-company share ownership help align the interests of stockholders and management.

Wildlife health investigations: needs, challenges and recommendations.

In a fast changing world with growing concerns about biodiversity loss and an increasing number of animal and human diseases emerging from wildlife, the need for effective wildlife health investigations including both surveillance and research is now widely recognized. However, procedures applicable to and knowledge acquired from studies related to domestic animal and human health can be on partly extrapolated to wildlife. This article identifies requirements and challenges inherent in wildlife health investigations, reviews important definitions and novel health investigation methods, and proposes tools and strategies for effective wildlife health surveillance programs. Impediments to wildlife health investigations are largely related to zoological, behavioral and ecological characteristics of wildlife populations and to limited access to investigation materials. These concerns should not be viewed as insurmountable but it is imperative that they are considered in study design, data analysis and result interpretation. It is particularly crucial to remember that health surveillance does not begin in the laboratory but in the fields. In this context, participatory approaches and mutual respect are essential. Furthermore, interdisciplinarity and open minds are necessary because a wide range of tools and knowledge from different fields need to be integrated in wildlife health surveillance and research. The identification of factors contributing to disease emergence requires the comparison of health and ecological data over time and among geographical regions. Finally, there is a need for the development and validation of diagnostic tests for wildlife species and for data on free-ranging population densities. Training of health professionals in wildlife diseases should also be improved. Overall, the article particularly emphasizes five needs of wildlife health investigations: communication and collaboration; use of synergies and triangulation approaches; investments for the long term; systematic collection of metadata; and harmonization of definitions and methods.

Ophthalmic epidemiology in Europe: the "European Eye Epidemiology" (E3) consortium.

The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case-control, cases only, randomized trials), providing ophthalmological data on approximately 170,000 European participants. The aim of the consortium is to promote and sustain collaboration and sharing of data and knowledge in the field of ophthalmic epidemiology in Europe, with particular focus on the harmonization of methods for future research, estimation and projection of frequency and impact of visual outcomes in European populations (including temporal trends and European subregions), identification of risk factors and pathways for eye diseases (lifestyle, vascular and metabolic factors, genetics, epigenetics and biomarkers) and development and validation of prediction models for eye diseases. Coordinating these existing data will allow a detailed study of the risk factors and consequences of eye diseases and visual impairment, including study of international geographical variation which is not possible in individual studies. It is expected that collaborative work on these existing data will provide additional knowledge, despite the fact that the risk factors and the methods for collecting them differ somewhat among the participating studies. Most studies also include biobanks of various biological samples, which will enable identification of biomarkers to detect and predict occurrence and progression of eye diseases. This article outlines the rationale of the consortium, its design and presents a summary of the methodology.