Immunophenotyping of acute leukemia and lymphoproliferative disorders: a consensus proposal of the European LeukemiaNet Work Package 10

The European LeukemiaNet (ELN), workpackage 10 (WP10) was designed to deal with diagnosis matters using morphology and immunophenotyping. This group aimed at establishing a consensus on the required reagents for proper immunophenotyping of acute leukemia and lymphoproliferative disorders. Animated discussions within WP10, together with the application of the Delphi method of proposals circulation, quickly led to post-consensual immunophenotyping panels for disorders on the ELN website. In this report, we established a comprehensive description of these panels, both mandatory and complementary, for both types of clinical conditions. The reason for using each marker, sustained by relevant literature information, is provided in detail. With the constant development of immunophenotyping techniques in flow cytometry and related software, this work aims at providing useful guidelines to perform the most pertinent exploration at diagnosis and for follow-up, with the best cost benefit in diseases, the treatment of which has a strong impact on health systems.

A Trustability Metric for Code Search based on Developer Karma

The promise of search-driven development is that developers will save time and resources by reusing external code in their local projects. To efficiently integrate this code, users must be able to trust it, thus trustability of code search results is just as important as their relevance. In this paper, we introduce a trustability metric to help users assess the quality of code search results and therefore ease the cost-benefit analysis they undertake trying to find suitable integration candidates. The proposed trustability metric incorporates both user votes and cross-project activity of developers to calculate a "karma" value for each developer. Through the karma value of all its developers a project is ranked on a trustability scale. We present JBENDER, a proof-of-concept code search engine which implements our trustability metric and we discuss preliminary results from an evaluation of the prototype.

Surveillance and simulation of bovine spongiform encephalopathy and scrapie in small ruminants in Switzerland

BACKGROUND: After bovine spongiform encephalopathy (BSE) emerged in European cattle livestock in 1986 a fundamental question was whether the agent established also in the small ruminants' population. In Switzerland transmissible spongiform encephalopathies (TSEs) in small ruminants have been monitored since 1990. While in the most recent TSE cases a BSE infection could be excluded, for historical cases techniques to discriminate scrapie from BSE had not been available at the time of diagnosis and thus their status remained unclear. We herein applied state-of-the-art techniques to retrospectively classify these animals and to re-analyze the affected flocks for secondary cases. These results were the basis for models, simulating the course of TSEs over a period of 70 years. The aim was to come to a statistically based overall assessment of the TSE situation in the domestic small ruminant population in Switzerland. RESULTS: In sum 16 TSE cases were identified in small ruminants in Switzerland since 1981, of which eight were atypical and six were classical scrapie. In two animals retrospective analysis did not allow any further classification due to the lack of appropriate tissue samples. We found no evidence for an infection with the BSE agent in the cases under investigation. In none of the affected flocks, secondary cases were identified. A Bayesian prevalence calculation resulted in most likely estimates of one case of BSE, five cases of classical scrapie and 21 cases of atypical scrapie per 100'000 small ruminants. According to our models none of the TSEs is considered to cause a broader epidemic in Switzerland. In a closed population, they are rather expected to fade out in the next decades or, in case of a sporadic origin, may remain at a very low level. CONCLUSIONS: In summary, these data indicate that despite a significant epidemic of BSE in cattle, there is no evidence that BSE established in the small ruminant population in Switzerland. Classical and atypical scrapie both occur at a very low level and are not expected to escalate into an epidemic. In this situation the extent of TSE surveillance in small ruminants requires reevaluation based on cost-benefit analysis.

Towards dynamics in flood risk assessment

As a consequence of flood impacts, communities inhabiting mountain areas are increasingly affected by considerable damage to infrastructure and property. The design of effective flood risk mitigation strategies and their subsequent implementation is crucial for a sustainable development in mountain areas. The assessment of the dynamic evolution of flood risk is the pillar of any subsequent planning process that is targeted at a reduction of the expected adverse consequences of the hazard impact. Given these premises, firstly, a comprehensive method to derive flood hazard process scenarios for well-defined areas at risk is presented. Secondly, conceptualisations of a static and dynamic flood risk assessment are provided. These are based on formal schemes to compute the risk mitigation performance of devised mitigation strategies within the framework of economic cost-benefit analysis. In this context, techniques suitable to quantify the expected losses induced by the identified flood impacts are provided.

Enhancing IEEE 802.11 Energy Efficiency for Continuous Media Applications

This paper proposes the Optimized Power save Algorithm for continuous Media Applications (OPAMA) to improve end-user device energy efficiency. OPAMA enhances the standard legacy Power Save Mode (PSM) of IEEE 802.11 by taking into consideration application specific requirements combined with data aggregation techniques. By establishing a balanced cost/benefit tradeoff between performance and energy consumption, OPAMA is able to improve energy efficiency, while keeping the end-user experience at a desired level. OPAMA was assessed in the OMNeT++ simulator using real traces of variable bitrate video streaming applications. The results showed the capability to enhance energy efficiency, achieving savings up to 44% when compared with the IEEE 802.11 legacy PSM.

Bildungsexpansion und Bildungsbeteiligung. Oder: warum immer mehr Schulpflichtige das Gymnasium besuchen

Die vorliegende Untersuchung ist ein Beitrag, die Frage zu klären, warum in der westdeutschen Nachkriegszeit immer mehr Schulpflichtige nach Abschluss der Grundschule das Gymnasium besuchen. Ausgehend von einem entscheidungstheoretischen Modell der subjektiven Werterwartung werden Mechanismen der elterlichen Bildungsentscheidung aufgezeigt. Dabei wird davon ausgegangen, dass sowohl zunehmende Bildungsmotivationen als auch Veränderungen in der subjektiven Bewertung von Kosten und Nutzen für eine höhere Bildung wichtige Voraussetzungen für die zunehmende Bildungsbeteiligung, aber auch Folgen der Bildungsexpansion waren. Die empirischen Analysen für drei Zeitpunkte in den 60er, 70er und 80er Jahren bestätigen diese Annahmen weitgehend. Ebenso wurde empirisch belegt, welch wichtige Rolle neben den Bildungsintentionen von Eltern und dem vorhergehenden Bildungsverlauf ihrer Kinder auch strukturelle Momente der Bildungsexpansion und ihre Eigendynamik beim tatsächlichen Bildungsübergang spielen. Schließlich gibt es Hinweise dafür, dass die Persistenz klassenspezifischer Bildungsungleichheiten auf einer konstanten Balance von Nutzen und Kosten zwischen den sozialen Klassen basiert.

Tools for better SLM knowledge management and informed decision-making in addressing land degradation at different scales: the WOCAT–LADA–DESIRE methodology

Desertification research conventionally focuses on the problem – that is, degradation – while neglecting the appraisal of successful conservation practices. Based on the premise that Sustainable Land Management (SLM) experiences are not sufficiently or comprehensively documented, evaluated, and shared, the World Overview of Conservation Approaches and Technologies (WOCAT) initiative (www.wocat.net), in collaboration with FAO’s Land Degradation Assessment in Drylands (LADA) project (www.fao.org/nr/lada/) and the EU’s DESIRE project (http://www.desire-project.eu/), has developed standardised tools and methods for compiling and evaluating the biophysical and socio-economic knowledge available about SLM. The tools allow SLM specialists to share their knowledge and assess the impact of SLM at the local, national, and global levels. As a whole, the WOCAT–LADA–DESIRE methodology comprises tools for documenting, self-evaluating, and assessing the impact of SLM practices, as well as for knowledge sharing and decision support in the field, at the planning level, and in scaling up identified good practices. SLM depends on flexibility and responsiveness to changing complex ecological and socioeconomic causes of land degradation. The WOCAT tools are designed to reflect and capture this capacity of SLM. In order to take account of new challenges and meet emerging needs of WOCAT users, the tools are constantly further developed and adapted. Recent enhancements include tools for improved data analysis (impact and cost/benefit), cross-scale mapping, climate change adaptation and disaster risk management, and easier reporting on SLM best practices to UNCCD and other national and international partners. Moreover, WOCAT has begun to give land users a voice by backing conventional documentation with video clips straight from the field. To promote the scaling up of SLM, WOCAT works with key institutions and partners at the local and national level, for example advisory services and implementation projects. Keywords: Sustainable Land Management (SLM), knowledge management, decision-making, WOCAT–LADA–DESIRE methodology.

Effect of comprehensive cardiac rehabilitation after heart valve surgery (CopenHeartVR): study protocol for a randomised clinical trial

Background Heart valve diseases are common with an estimated prevalence of 2.5% in the Western world. The number is rising due to an ageing population. Once symptomatic, heart valve diseases are potentially lethal, and heavily influence daily living and quality of life. Surgical treatment, either valve replacement or repair, remains the treatment of choice. However, post surgery, the transition to daily living may become a physical, mental and social challenge. We hypothesise that a comprehensive cardiac rehabilitation programme can improve physical capacity and self-assessed mental health and reduce hospitalisation and healthcare costs after heart valve surgery. Methods A randomised clinical trial, CopenHeartVR, aims to investigate whether cardiac rehabilitation in addition to usual care is superior to treatment as usual after heart valve surgery. The trial will randomly allocate 210 patients, 1:1 intervention to control group, using central randomisation, and blinded outcome assessment and statistical analyses. The intervention consists of 12 weeks of physical exercise, and a psycho-educational intervention comprising five consultations. Primary outcome is peak oxygen uptake (VO2 peak) measured by cardiopulmonary exercise testing with ventilatory gas analysis. Secondary outcome is self-assessed mental health measured by the standardised questionnaire Short Form 36. Also, long-term healthcare utilisation and mortality as well as biochemistry, echocardiography and cost-benefit will be assessed. A mixed-method design is used to evaluate qualitative and quantitative findings encompassing a survey-based study before the trial and a qualitative pre- and post-intervention study. Discussion The study is approved by the local regional Research Ethics Committee (H-1-2011-157), and the Danish Data Protection Agency (j.nr. 2007-58-0015).

Effectiveness of non-conventional methods for accelerated orthodontic tooth movement: a systematic review and meta-analysis.

OBJECTIVES To assess the available evidence on the effectiveness of accelerated orthodontic tooth movement through surgical and non-surgical approaches in orthodontic patients. METHODS Randomized controlled trials and controlled clinical trials were identified through electronic and hand searches (last update: March 2014). Orthognathic surgery, distraction osteogenesis, and pharmacological approaches were excluded. Risk of bias was assessed using the Cochrane risk of bias tool. RESULTS Eighteen trials involving 354 participants were included for qualitative and quantitative synthesis. Eight trials reported on low-intensity laser, one on photobiomodulation, one on pulsed electromagnetic fields, seven on corticotomy, and one on interseptal bone reduction. Two studies on corticotomy and two on low-intensity laser, which had low or unclear risk of bias, were mathematically combined using the random effects model. Higher canine retraction rate was evident with corticotomy during the first month of therapy (WMD=0.73; 95% CI: 0.28, 1.19, p<0.01) and with low-intensity laser (WMD=0.42mm/month; 95% CI: 0.26, 0.57, p<0.001) in a period longer than 3 months. The quality of evidence supporting the interventions is moderate for laser therapy and low for corticotomy intervention. CONCLUSIONS There is some evidence that low laser therapy and corticotomy are effective, whereas the evidence is weak for interseptal bone reduction and very weak for photobiomodulation and pulsed electromagnetic fields. Overall, the results should be interpreted with caution given the small number, quality, and heterogeneity of the included studies. Further research is required in this field with additional attention to application protocols, adverse effects, and cost-benefit analysis. CLINICAL SIGNIFICANCE From the qualitative and quantitative synthesis of the studies, it could be concluded that there is some evidence that low laser therapy and corticotomy are associated with accelerated orthodontic tooth movement, while further investigation is required before routine application.

A Research Roadmap for Complementary and Alternative Medicine – What We Need to Know by 2020

Background: The CAMbrella coordination action was funded within the Framework Programme 7. Its aim is to provide a research roadmap for clinical and epidemiological research for complementary and alternative medicine (CAM) that is appropriate for the health needs of European citizens and acceptable to their national research institutes and healthcare providers in both public and private sectors. One major issue in the European research agenda is the demographic change and its impact on health care. Our vision for 2020 is that there is an evidence base that enables European citizens to make informed decisions about CAM, both positive and negative. This roadmap proposes a strategic research agenda for the field of CAM designed to address future European health care challenges. This roadmap is based on the results of CAMbrella’s several work packages, literature reviews and expert discussions including a consensus meeting. Methods: We first conducted a systematic literature review on key issues in clinical and epidemiological research in CAM to identify the general concepts, methods and the strengths and weaknesses of current CAM research. These findings were discussed in a workshop (Castellaro, Italy, September 7–9th 2011) with international CAM experts and strategic and methodological recommendations were defined in order to improve the rigor and relevance of CAM research. These recommendations provide the basis for the research roadmap, which was subsequently discussed in a consensus conference (Järna, Sweden, May 9–11th 2012) with all CAMbrella members and the CAMbrella advisory board. The roadmap was revised after this discussion in CAMbrella Work Package (WP) 7 and finally approved by CAMbrella’s scientific steering committee on September 26th 2012. Results: Our main findings show that CAM is very heterogenous in terms of definitions and legal regulations between the European countries. In addition, citizens’ needs and attitudes towards CAM as well as the use and provision of CAM differ significantly between countries. In terms of research methodology, there was consensus that CAM researchers should make use of all the commonly accepted scientific research methods and employ those with utmost diligence combined in a mixed methods framework. Conclusions: We propose 6 core areas of research that should be investigated to achieve a robust knowledge base and to allow stakeholders to make informed decisions. These are: Research into the prevalence of CAM in Europe: Reviews show that we do not know enough about the circumstances in which CAM is used by Europeans. To enable a common European strategic approach, a clear picture of current use is of the utmost importance. Research into differences regarding citizens’ attitudes and needs towards CAM: Citizens are the driver for CAM utilization. Their needs and views on CAM are a key priority, and their interests must be investigated and addressed in future CAM research. Research into safety of CAM: Safety is a key issue for European citizens. CAM is considered safe, but reliable data is scarce although urgently needed in order to assess the risk and cost-benefit ratio of CAM. Research into the comparative effectiveness of CAM: Everybody needs to know in what situation CAM is a reasonable choice. Therefore, we recommend a clear emphasis on concurrent evaluation of the overall effectiveness of CAM as an additional or alternative treatment strategy in real-world settings. Research into effects of context and meaning: The impact of effects of context and meaning on the outcome of CAM treatments must be investigated; it is likely that they are significant. Research into different models of CAM health care integration: There are different models of CAM being integrated into conventional medicine throughout Europe, each with their respective strengths and limitations. These models should be described and concurrently evaluated; innovative models of CAM provision in health care systems should be one focus for CAM research. We also propose a methodological framework for CAM research. We consider that a framework of mixed methodological approaches is likely to yield the most useful information. In this model, all available research strategies including comparative effectiveness research utilising quantitative and qualitative methods should be considered to enable us to secure the greatest density of knowledge possible. Stakeholders, such as citizens, patients and providers, should be involved in every stage of developing the specific and relevant research questions, study design and the assurance of real-world relevance for the research. Furthermore, structural and sufficient financial support for research into CAM is needed to strengthen CAM research capacity if we wish to understand why it remains so popular within the EU. In order to consider employing CAM as part of the solution to the health care, health creation and self-care challenges we face by 2020, it is vital to obtain a robust picture of CAM use and reliable information about its cost, safety and effectiveness in real-world settings. We need to consider the availability, accessibility and affordability of CAM. We need to engage in research excellence and utilise comparative effectiveness approaches and mixed methods to obtain this data. Our recommendations are both strategic and methodological. They are presented for the consideration of researchers and funders while being designed to answer the important and implicit questions posed by EU citizens currently using CAM in apparently increasing numbers. We propose that the EU actively supports an EUwide strategic approach that facilitates the development of CAM research. This could be achieved in the first instance through funding a European CAM coordinating research office dedicated to foster systematic communication between EU governments, public, charitable and industry funders as well as researchers, citizens and other stakeholders. The aim of this office would be to coordinate research strategy developments and research funding opportunities, as well as to document and disseminate international research activities in this field. With the aim to develop sustainability as second step, a European Centre for CAM should be established that takes over the monitoring and further development of a coordinated research strategy for CAM, as well as it should have funds that can be awarded to foster high quality and robust independent research with a focus on citizens health needs and pan-European collaboration. We wish to establish a solid funding for CAM research to adequately inform health care and health creation decision-making throughout the EU. This centre would ensure that our vision of a common, strategic and scientifically rigorous approach to CAM research becomes our legacy and Europe’s reality. We are confident that our recommendations will serve these essential goals for EU citizens.

Long-term effectiveness of supported employment: 5-year follow-up of a randomized controlled trial

Objective The individual placement and support model of supported employment has been shown to be more effective than other vocational approaches in improving competitive work over 1-2 years in persons with severe mental illness. The authors evaluated the longer-term effects of the model compared with traditional vocational rehabilitation over 5 years. Method A randomized controlled trial compared supported employment to traditional vocational rehabilitation in 100 unemployed persons with severe mental illness. Competitive work and hospital admissions were tracked for 5 years, and interviews were conducted at 2 and 5 years to assess recovery attitudes and quality of life. A cost-benefit analysis compared program and total treatment costs to earnings from competitive employment. Results The beneficial effects of supported employment on work at 2 years were sustained over the 5-year follow-up period. Participants in supported employment were more likely to obtain competitive work than those in traditional vocational rehabilitation (65% compared with 33%), worked more hours and weeks, earned more wages, and had longer job tenures. Reliance on supported employment services for retaining competitive work decreased from 2 years to 5 years for participants in supported employment. Participants were also significantly less likely to be hospitalized, had fewer psychiatric hospital admissions, and spent fewer days in the hospital. The social return on investment was higher for supported employment participants, whether calculated as the ratio of work earnings to vocational program costs or of work earnings to total vocational program and mental health treatment costs. Conclusions The results demonstrate that the greater effectiveness of supported employment in improving competitive work outcomes is sustained beyond 2 years and suggest that supported employment programs contribute to reduced hospitalizations and produce a higher social return on investment.