Guidance for the preparation of neurological management guidelines by EFNS scientific task forces - revised recommendations 2012

This paper is meant to provide guidance to anyone wishing to write a neurological guideline for diagnosis or treatment, and is directed at the Scientist Panels and task forces of the European Federation of Neurological Societies (EFNS). It substitutes the previous guidance paper from 2004. It contains several new aspects: the guidance is now based on a change of the grading system for evidence and for the resulting recommendations, and has adopted The Grading of Recommendations, Assessment, Development and Evaluation system (GRADE). The process of grading the quality of evidence and strength of recommendations can now be improved and made more transparent. The task forces embarking on the development of a guideline must now make clearer and more transparent choices about outcomes considered most relevant when searching the literature and evaluating their findings. Thus, the outcomes chosen will be more critical, more patient-oriented and easier to translate into simple recommendations. This paper also provides updated practical recommendations for planning a guideline task force within the framework of the EFNS. Finally, this paper hopes to find the approval also by the relevant bodies of our future organization, the European Academy of Neurology.

Pancreatic carcinoma, pancreatitis, and healthy controls: metabolite models in a three-class diagnostic dilemma

Metabolomics as one of the most rapidly growing technologies in the "-omics" field denotes the comprehensive analysis of low molecular-weight compounds and their pathways. Cancer-specific alterations of the metabolome can be detected by high-throughput mass-spectrometric metabolite profiling and serve as a considerable source of new markers for the early differentiation of malignant diseases as well as their distinction from benign states. However, a comprehensive framework for the statistical evaluation of marker panels in a multi-class setting has not yet been established. We collected serum samples of 40 pancreatic carcinoma patients, 40 controls, and 23 pancreatitis patients according to standard protocols and generated amino acid profiles by routine mass-spectrometry. In an intrinsic three-class bioinformatic approach we compared these profiles, evaluated their selectivity and computed multi-marker panels combined with the conventional tumor marker CA 19-9. Additionally, we tested for non-inferiority and superiority to determine the diagnostic surplus value of our multi-metabolite marker panels. Compared to CA 19-9 alone, the combined amino acid-based metabolite panel had a superior selectivity for the discrimination of healthy controls, pancreatitis, and pancreatic carcinoma patients [Formula: see text] We combined highly standardized samples, a three-class study design, a high-throughput mass-spectrometric technique, and a comprehensive bioinformatic framework to identify metabolite panels selective for all three groups in a single approach. Our results suggest that metabolomic profiling necessitates appropriate evaluation strategies and-despite all its current limitations-can deliver marker panels with high selectivity even in multi-class settings.

The Work and Workshop of the Master of the Rajhrad Altarpiece

The main aim of this project was to verify the possibility raised in the publication of new archival data in 1980 that the group of panel paintings attributed to the Master of the Rajhrad Altarpiece and his workshop were not created before 1420, as earlier academic opinion held, but in fact only around 1450. It included a detailed analysis of the 21 panels forming the group, including infrared reflectography research. This helped identify the highly personal underdrawing style of the "Rajhrad Master" as common to all the panels in the group, proving that they really form a coherent whole. Questions of the painter's education and the nature of Bohemian society around 1450 were also considered, as. Bartlova felt these had been neglected in earlier studies. She concludes that the Master studied in Prague in the late 1430s and then continued studying in Vienna and Munich from 1440. The new dating of the group of panels connected with this anonymous master and his workshop throws new light on Bohemian artistic production during the late Hussite period (c.1430-c.1470). It was generally thought that artistic activity moved out of Prague after the outbreak of the Hussite wars in the 1420s, but this research revealed considerable activity there throughout the period. Numerous painters listed in the Book of the Prague Painters' Guild for this period can now be linked with extant panels, although most of these have survived outside Prague, principally in South Bohemia. These findings have broad implications for studies of Bohemian art in this period.

Exogenous gonadotropins have little impact on follicular but considerable effect on serum cytokine concentrations – a comparison between Natural Cycle and stimulated IVF using a multiplexed assay platform

Introduction: Throughout follicular growth and subsequent corpus luteum formation the leukocyte number increases and follicular vascularisation changes. These processes are enhanced under exogenous stimulation with gonadotropins. Cytokines released by leukocytes contribute to further recruitment and vascularisation of the follicle, and they play an important role in regulating ovarian steroidogenesis by influencing theca and granulosa–lutein cell function. Changes in cytokine and vascular endothelial growth factor (VEGF) concentrations in the ovary as a consequence of gonadotropin stimulation may negatively influence oocyte quality. In this project we have compared the intrafollicular production of inflammatory cytokines and growth factors between natural IVF cycles (NC) and classical, gonadotropin-stimulated IVF cycles (gsIVF). Material and Methods: Serum on the day of oocyte retrieval and follicular fluid (FF) were collected in 37 NC and 39 gsIVF cycles. Thirteen women within this population underwent one NC and one gsIVF cycle each. A total of 14 cytokines from Bio-Plex panels I and II were determined in matched serum and FF samples using Luminex xMAP technology on the Bio-Plex(R) platform, using the serum protocol. Results: Tumour necrosis factor-alpha, RANTES, eotaxin and interferon-gamma-induced protein-10 levels were lower in FF than in serum, and thus not further investigated. Interleukin (IL)-6, -8, -10, -15, -18, monocyte chemotactic protein-1 (MCP-1), VEGF and leukaemia inhibitory factor (LIF) showed higher median concentrations in FF than in serum, indicating possible ovarian production. Moreover, most of these showed higher evels in the gsIVF than in the NC groups in the serum, but not in the follicular fluid. IL-8 was reduced in gsIVF cycles. Conclusion: The fact that serum but not FF levels of the studied cytokines were higher in the stimulated than in the natural cycles can be attributed to the increased number of active follicles present after controlled ovarian stimulation.

Drug eluting and bare metal stents in people with and without diabetes: collaborative network meta-analysis

Objective To compare the effectiveness and safety of three types of stents (sirolimus eluting, paclitaxel eluting, and bare metal) in people with and without diabetes mellitus. Design Collaborative network meta-analysis. Data sources Electronic databases (Medline, Embase, the Cochrane Central Register of Controlled Trials), relevant websites, reference lists, conference abstracts, reviews, book chapters, and proceedings of advisory panels for the US Food and Drug Administration. Manufacturers and trialists provided additional data. Review methods Network meta-analysis with a mixed treatment comparison method to combine direct within trial comparisons between stents with indirect evidence from other trials while maintaining randomisation. Overall mortality was the primary safety end point, target lesion revascularisation the effectiveness end point. Results 35 trials in 3852 people with diabetes and 10 947 people without diabetes contributed to the analyses. Inconsistency of the network was substantial for overall mortality in people with diabetes and seemed to be related to the duration of dual antiplatelet therapy (P value for interaction 0.02). Restricting the analysis to trials with a duration of dual antiplatelet therapy of six months or more, inconsistency was reduced considerably and hazard ratios for overall mortality were near one for all comparisons in people with diabetes: sirolimus eluting stents compared with bare metal stents 0.88 (95% credibility interval 0.55 to 1.30), paclitaxel eluting stents compared with bare metal stents 0.91 (0.60 to 1.38), and sirolimus eluting stents compared with paclitaxel eluting stents 0.95 (0.63 to 1.43). In people without diabetes, hazard ratios were unaffected by the restriction. Both drug eluting stents were associated with a decrease in revascularisation rates compared with bare metal stents in people both with and without diabetes. Conclusion In trials that specified a duration of dual antiplatelet therapy of six months or more after stent implantation, drug eluting stents seemed safe and effective in people both with and without diabetes.

Exhibits

The Finnish American Heritage Center at Finlandia University recently installed three exhibits. They include a photographic exhibit titled “Rural Reflections: Finnish American Buildings and Landscapes in Michigan’s Copper Country”; a historic photography exhibit named “People, Place and Time: Michigan’s Copper Country Through the Lens of J.W. Nara”; and a pair of lithographs acquired by the National Park Service which were on either side of the Italian Hall stage the night of the infamous Christmas Eve tragedy 100 years ago. The “Rural Reflections” exhibit documents the built environment that Finnish immigrants and their descendants created in Michigan's Copper Country from the 1880s through the 1930s. Although much of this heritage has been lost with the passage of time, the district yet holds one of the largest concentrations of rural Finnish buildings and cultural landscapes in North America. The Nara exhibit, funded in part by descendants Robert and Ruth Nara of Bootjack Michigan, works from historical photographs held at the Michigan Tech Archives. Interpretive panels highlight the people, places, and times that J.W. Nara experienced during his lifetime and include material on urban life, farming, and the 1913 Michigan copper miners’ strike. The lithographs are a recent and unique acquisition for the Keweenaw National Historical Park, and will be on protected display at the FAHC. One of the panels shows the Italian royal family and was produced in 1908, while the other, produced in 1905, is of the five founders of the modern Italian state. For more information about the exhibits at the Finnish American Heritage Center, call (906) 487-7302.

Exhibits

The Finnish American Heritage Center at Finlandia University recently installed three exhibits. They include a photographic exhibit titled “Rural Reflections: Finnish American Buildings and Landscapes in Michigan’s Copper Country”; a historic photography exhibit named “People, Place and Time: Michigan’s Copper Country Through the Lens of J.W. Nara”; and a pair of lithographs acquired by the National Park Service which were on either side of the Italian Hall stage the night of the infamous Christmas Eve tragedy 100 years ago. The “Rural Reflections” exhibit documents the built environment that Finnish immigrants and their descendants created in Michigan's Copper Country from the 1880s through the 1930s. Although much of this heritage has been lost with the passage of time, the district yet holds one of the largest concentrations of rural Finnish buildings and cultural landscapes in North America. The Nara exhibit, funded in part by descendants Robert and Ruth Nara of Bootjack Michigan, works from historical photographs held at the Michigan Tech Archives. Interpretive panels highlight the people, places, and times that J.W. Nara experienced during his lifetime and include material on urban life, farming, and the 1913 Michigan copper miners’ strike. The lithographs are a recent and unique acquisition for the Keweenaw National Historical Park, and will be on protected display at the FAHC. One of the panels shows the Italian royal family and was produced in 1908, while the other, produced in 1905, is of the five founders of the modern Italian state. For more information about the exhibits at the Finnish American Heritage Center, call (906) 487-7302.

Exhibits

The Finnish American Heritage Center at Finlandia University recently installed three exhibits. They include a photographic exhibit titled “Rural Reflections: Finnish American Buildings and Landscapes in Michigan’s Copper Country”; a historic photography exhibit named “People, Place and Time: Michigan’s Copper Country Through the Lens of J.W. Nara”; and a pair of lithographs acquired by the National Park Service which were on either side of the Italian Hall stage the night of the infamous Christmas Eve tragedy 100 years ago. The “Rural Reflections” exhibit documents the built environment that Finnish immigrants and their descendants created in Michigan's Copper Country from the 1880s through the 1930s. Although much of this heritage has been lost with the passage of time, the district yet holds one of the largest concentrations of rural Finnish buildings and cultural landscapes in North America. The Nara exhibit, funded in part by descendants Robert and Ruth Nara of Bootjack Michigan, works from historical photographs held at the Michigan Tech Archives. Interpretive panels highlight the people, places, and times that J.W. Nara experienced during his lifetime and include material on urban life, farming, and the 1913 Michigan copper miners’ strike. The lithographs are a recent and unique acquisition for the Keweenaw National Historical Park, and will be on protected display at the FAHC. One of the panels shows the Italian royal family and was produced in 1908, while the other, produced in 1905, is of the five founders of the modern Italian state. For more information about the exhibits at the Finnish American Heritage Center, call (906) 487-7302.

[Swiss Research Agenda for Nursing (SRAN): the development of an agenda for clinical nursing research in Switzerland]

In many Anglo-Saxon and North European countries nursing research agendas have been developed to address priorities in nursing research in accordance with a nationally defined health policy. In Switzerland, due to lack of a nationwide governmental health policy, co-ordination of nursing research so far was scarce. The "Swiss Research Agenda for Nursing (SRAN)" project developed an agenda for clinical nursing research between 2005 and 2007. Based on literature reviews, expert panels and a national survey a project team formulated an agenda which passed a consensus conference. The agenda recommends aspects that should lead research and defines seven research priorities for nursing in Switzerland for the time between 2007 and 2017. Nursing research should prioritize to investigate 1) the effectiveness of nursing interventions; 2) the influences of service adaptations in a changing health care system; 3) the phenomena in patients requiring nursing care; 4) the influence of the work environment on the quality of nursing care; 5) the functioning of family and social systems; 6) varieties of life circumstances and their integration; and 7) the implementation of ethical principles in nursing. Written in German and French, the Swiss Research Agenda for Nursing for the first time formulates priorities for nursing research in Switzerland and can be used for strategic discussions. As a next step, the development of an action plan to enhance nursing research will take place in Switzerland.

Sustainability study of nanomaterials including societal and occupational implications

In recent years there has been a tremendous amount of research in the area of nanotechnology. History tells us that the commercialization of technologies will always be accompanied by both positive and negative effects for society and the environment. Products containing nanomaterials are already available in the market, and yet there is still not much information regarding the potential negative effects that these products may cause. The work presented in this dissertation describes a holistic approach to address different dimensions of nanotechnology sustainability. Life cycle analysis (LCA) was used to study the potential usage of polyethylene filled with nanomaterials to manufacture automobile body panels. Results showed that the nanocomposite does not provide an environmental benefit over traditional steel panels. A new methodology based on design of experiments (DOE) techniques, coupled with LCA, was implemented to investigate the impact of inventory uncertainties. Results showed that data variability does not have a significant effect on the prediction of the environmental impacts. Material profiles for input materials did have a highly significant effect on the overall impact. Energy consumption and material characterization were identified as two mainstreams where additional research is needed in order to predict the overall impact of nanomaterials more effectively. A study was undertaken to gain insights into the behavior of small particles in contact with a surface exposed to air flow to determine particle lift-off from the surface. A mapping strategy was implemented that allows for the identification of conditions for particle liftoff based on particle size and separation distance from the wall. Main results showed that particles smaller than 0:1mm will not become airborne under shear flow unless the separation distance is greater than 15 nm. Results may be used to minimize exposure to airborne materials. Societal implications that may occur in the workplace were researched. This research task explored different topics including health, ethics, and worker perception with the aim of identifying the base knowledge available in the literature. Recommendations are given for different scenarios to describe how workers and employers could minimize the unwanted effects of nanotechnology production.

Analysis of independent microarray datasets of renal biopsies identifies a robust transcript signature of acute allograft rejection

Transcriptomics could contribute significantly to the early and specific diagnosis of rejection episodes by defining 'molecular Banff' signatures. Recently, the description of pathogenesis-based transcript sets offered a new opportunity for objective and quantitative diagnosis. Generating high-quality transcript panels is thus critical to define high-performance diagnostic classifier. In this study, a comparative analysis was performed across four different microarray datasets of heterogeneous sample collections from two published clinical datasets and two own datasets including biopsies for clinical indication, and samples from nonhuman primates. We characterized a common transcriptional profile of 70 genes, defined as acute rejection transcript set (ARTS). ARTS expression is significantly up-regulated in all AR samples as compared with stable allografts or healthy kidneys, and strongly correlates with the severity of Banff AR types. Similarly, ARTS were tested as a classifier in a large collection of 143 independent biopsies recently published by the University of Alberta. Results demonstrate that the 'in silico' approach applied in this study is able to identify a robust and reliable molecular signature for AR, supporting a specific and sensitive molecular diagnostic approach for renal transplant monitoring.

Strategies to advance translational research into brain barriers

There is a paucity of therapies for most neurological disorders--from rare lysosomal storage diseases to major public health concerns such as stroke and Alzheimer's disease. Advances in the targeting of drugs to the CNS are essential for the future success of neurotherapeutics; however, the delivery of many potentially therapeutic and diagnostic compounds to specific areas of the brain is restricted by the blood-brain barrier, the blood-CSF barrier, or other specialised CNS barriers. These brain barriers are now recognised as a major obstacle to the treatment of most brain disorders. The challenge to deliver therapies to the CNS is formidable, and the solution will require concerted international efforts among academia, government, and industry. At a recent meeting of expert panels, essential and high-priority recommendations to propel brain barrier research forward in six topical areas were developed and these recommendations are presented here.

Einbeziehung der privaten Krankenvollversicherung in den Risikostrukturausgleich der gesetzlichen Krankenversicherung in Deutschland. Abschätzung der quantitativen Auswirkungen

Die Einbeziehung der privaten Krankenversicherung (PKV) in den Risikostrukturausgleich (RSA) der gesetzlichen Krankenversicherung (GKV) wird häufig diskutiert. In der vorliegenden Studie wird anhand einer quantitativen Analyse unter Verwendung der Daten des Sozioökonomischen Panels (SOEP) abgeschätzt, welche Transfersumme aus dem System der PKV in das System der GKV fließen würden, wenn ein übergreifender RSA eingerichtet würde. Die Summe läge bei 9,9 Mrd. Euro pro Jahr unter Annahme der Beitragsbemessungsgrenze des Jahres 2006. Einbezogen wurden dabei nur die Unterschiede auf der Einnahmenseite des RSA. Einschränkend muss gesehen werden, dass unklar bleibt, welche Krankenversicherungsunternehmen be- oder entlastet würden und über welches Verfahren die Transfersumme aufgebracht werden könnte.

Plurilingual Interpretation in WTO Panel and Appellate Body Reports

This article analyzes the extent to which the Appellate Body and WTO panels compare the authentic texts in their examination of the WTO Agreements and the extent to which the parties themselves do so in their arguments. The texts of the WTO Agreements are authentic in English, French and Spanish. Article 33 of the Vienna Convention on the Law of Treaties governs the interpretation of treaties authenticated in two or more languages. WTO practice diverges significantly from the rules set out in Article 33 and the travaux préparatoires of the International Law Commission. The terms of a plurilingual treaty are presumed to have the same meaning in each authentic text, which means that a treaty interpreter need not compare the authentic texts as a routine matter as a matter of law. Nevertheless, routine comparison of authentic texts would be good practice in the WTO context, since there are several discrepancies that could affect the interpretation of WTO provisions.

La philanthropie: alliée ou concurrente des politiques sociales étatiques (I, 1880-1945)

La philanthropie joue actuellement un rôle très important en Suisse. On estime que la moitié des personnes domiciliées en Suisse est active dans le champ d’action du bénévolat. Toutefois, cet objet d’études a longtemps été délaissé par les historiens. Ces deux panels viseront à rendre compte des recherches récentes en s’intéressant à la dimension comparative et transnationale de la philanthropie en Suisse de 1880 à nos jours. Deux dimensions seront privilégiées. D’une part, l’accent sera mis sur les rapports entre les associations philanthropiques privées et l’Etat social. Les études tendent le plus souvent à mettre l’accent sur l’opposition, dans le domaine social, entre activités de bienfaisance ou de bénévolat et les politiques publiques. Or, les relations entre ces deux pôles ne se résument pas à cette opposition et oscillent, selon les lieux et les périodes, entre coopération étroite et concurrence acharnée, à moins que ne s’instaure, comme cela semble le cas de la Suisse, une division du travail plus ou moins institutionnalisée. D’autre part, une attention toute particulière sera mise sur les jeux d’échelle. Les activités des associations philanthropiques couvrent des espaces géographiques très différents : certaines se concentrent sur un quartier urbain, d’autres se focalisent sur l’ensemble de la planète. Toutefois, nous postulons que cette spatialisation ne se confine pas à un antagonisme local/global. Bien au contraire, les différentes échelles – locale, nationale, globale ou transnationale – interagissent étroitement. Des contributions d’historiens étrangers permettront d’inscrire le cas suisse dans une perspective comparative.