Nebenwirkungsraten von Opioiden unter äquianalgetischen Dosen im Rahmen intravenöser patientenkontrollierter Analgesie - eine systematische Übersicht und Netzwerkmetaanalyse

Nebenwirkungen während einer Opioidtherapie gehören zur klinischen Praxis und beeinträchtigen nicht nur die Qualität der Schmerztherapie sondern auch die Genesung des Patienten. Eine individuelle, auf das jeweilige Nebenwirkungsprofil und die Bedürfnisse des Patienten abgestimmte Opioidwahl kann die Schmerztherapie optimieren und den Heilungsprozess fördern. Ziel dieser Arbeit war, den Einfluss der Opioidwahl unter äquianalgetischen Bedingungen im Rahmen der intravenösen patientenkontrollierten Analgesie auf das Auftreten der häufigsten Nebenwirkungen zu untersuchen. Hierfür wurden die elektronischen Datenbanken Medline, Embase, Cochrane Library und Web of Science auf randomisierte, kontrollierte Studien durchsucht. Nach Entwicklung und Durchführung einer strukturierten Literaturrecherche wurden insgesamt 168 Studien durch zwei unabhängige Untersucher gelesen und bewertet. Mit der Erstellung einer systematischen Übersichtsarbeit und Netzwerk-Metaanalyse wurden Daten zu 17 unterschiedlichen Opioiden und ihren Nebenwirkungsprofilen verglichen und zusammengefasst. 63 Studien erfüllten die Einschlusskriterien, aus denen Daten zu 5063 Patienten im Alter von 18 bis 90 Jahren extrahiert werden konnten. Primärer Endpunkt dieser Arbeit waren alle opioidinduzierten Nebenwirkungen unter äquianalgetischer Dosierung. Die Nebenwirkungen Übelkeit und Erbrechen, Juckreiz, Sedierung und Atemdepression wurden am häufigsten berichtet. Sekundäre Endpunkte waren die Zufriedenheit der Patienten, die PCA Pumpeneinstellungen sowie der absolute Opioidkonsum. Mit einem relativen Risiko von 1,37 [1,05; 1,80] weist Buprenorphin eine signifikant höhere Rate für Übelkeit und Erbrechen auf, wohingegen Fentanyl mit einem Risiko von 0,82 [0,67; 1,00] weniger Übelkeit und Erbrechen hervorzurufen scheint. Bei den relativen Risiken für Juckreiz scheinen vor allem Nalbuphin mit 0,07 [0,01; 0,60] und Pethidin/Meperidin mit 0,47 [0,25; 0,87] einen kleinen Vorteil zu zeigen. In der mit Scores bewerteten Sedierung weisen Oxymorphon mit -1,40[-2,41; -0,39], Fentanyl mit -1,57 [-2,91; -0,23] und Pethidin/Meperidin mit -1,70[-2,77; -0,62] die statistisch signifikant niedrigsten Raten auf. Aus den in dieser Arbeit extrahierten Daten lassen sich keine Vorteile einer Substanz für die Inzidenz von Atemdepression herleiten. Bei den visuellen Analogskalen für Zufriedenheit erreichen Pethidin/Meperidin mit 0,59 [0,18; 1,00], Fentanyl mit 0,96 [0,39; 1,52], Remifentanil mit 1,80 [1,12; 2,48], Alfentanil mit 1,95 [1,06; 2,85] und Oxycodon mit 2,00 [1,18; 2,82] Mittelwertabweichung, die statistisch signifikant größten Zufriedenheitswerte. Die aus den eingeschlossenen Studien evaluierten analgetischen Potenzen zeigten mehrheitlich Abweichungen über zehn Prozent zu den aktuell gängigen Literaturwerten. Nach Durchschau aller Ergebnisse scheinen vor allem die Opioide Fentanyl und Pethidin/Meperidin unter äquianalgetischen Dosierungen die verträglichsten Nebenwirkungsprofile aufzuweisen. Beide Substanzen können nach Ausschluss individueller Kontraindikationen für die intravenöse postoperative Schmerztherapie empfohlen werden. Die Tendenzen der Nebenwirkungsprofile dieser Arbeit sollten bei der individuellen Schmerztherapie und der Suche nach einer optimalen Substanz für den Patienten berücksichtigt werden

"Contextualidad" científica y "convertibilidad" filosófica. La respuesta de la Scienza nuova a la crisis epistemológica de la primera modernidad

Hay toda una serie de preguntas que giran en torno a la problemática interna misma de la Scienza Nuova, y que sólo un “nuevo” concepto de ciencia –vinculado a la crítica de Vico a la formación de sistemas característica de la temprana Modernidad– las consigue responder de manera efectiva, bosquejando una nueva idea “orgánica” entre saber especulativo-teórico y saber orientado a los estados de cosas.There is a whole series of questions that revolves around the core problem of the Scienza Nuova: only a “new” concept of science –linked to Vico’s criticism of the formation of systems, characteristic of the early modernity– is able to respond to these questions in an effective manner, sketching a new “organic” idea between speculative-theoretical knowledge and knowledge directed to the state of things

Analytical characterization of camel meat and milk fat

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.The aim of this study was to characterize the fat composition of camel milk fat and camel hump fat and thereby assist in the technological development of camel milk and meat based products. The latter is of major interest in parts of Africa where the camel resides in large numbers. A combination of silver-ion and reversed phase HPLC enables the isolation of triglycerides according to their saturation class and carbon number. Subjection of the isolated triglycerides to enzymatic splitting with lipase and subsequent analysis of the free fatty acids generated enables a positional analysis of the main triglyceride components and thus a characterization of the fat. The analytical techniques employed may equally well be applied to other fats or oils to allow their characterization

Quantifying alternative splicing from paired-end RNA-sequencing data

RNA-sequencing has revolutionized biomedical research and, in particular, our ability to study gene alternative splicing. The problem has important implications for human health, as alternative splicing may be involved in malfunctions at the cellular level and multiple diseases. However, the high-dimensional nature of the data and the existence of experimental biases pose serious data analysis challenges. We find that the standard data summaries used to study alternative splicing are severely limited, as they ignore a substantial amount of valuable information. Current data analysis methods are based on such summaries and are hence suboptimal. Further, they have limited flexibility in accounting for technical biases. We propose novel data summaries and a Bayesian modeling framework that overcome these limitations and determine biases in a nonparametric, highly flexible manner. These summaries adapt naturally to the rapid improvements in sequencing technology. We provide efficient point estimates and uncertainty assessments. The approach allows to study alternative splicing patterns for individual samples and can also be the basis for downstream analyses. We found a severalfold improvement in estimation mean square error compared popular approaches in simulations, and substantially higher consistency between replicates in experimental data. Our findings indicate the need for adjusting the routine summarization and analysis of alternative splicing RNA-seq studies. We provide a software implementation in the R package casper.Comment: Published in at http://dx.doi.org/10.1214/13-AOAS687 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org). With correction

Business Models in the Data Economy: A Case Study from the Business Partner Data Domain

Data management seems to experience a renaissance today. One particular trend in the so-called data economy has been the emergence of business models based on the provision of high-quality data. In this context, the paper examines business models of business partner data providers. The paper explores as to how and why these business models differ. Based on a study of six cases, the paper identifies three different business model patterns. A resource-based view is taken to explore the details of these patterns. Furthermore, the paper develops a set of propositions that help understand why the different business models evolved and how they may develop in the future. Finally, the paper discusses the ongoing market transformation process indicating a shift from traditional value chains toward value networks - a change which, if it is sustainable, would seriously threaten the business models of well-established data providers, such as Dun & Bradstreet, for example

Tracking Dark Energy with the ISW effect: short and long-term predictions

We present an analysis of the constraining power of future measurements of the Integrated Sachs-Wolfe (ISW) effect on models of the equation of state of dark energy as a function of redshift, w(z). To achieve this, we employ a new parameterization of w, which utilizes the mean value of w(z) () as an explicit parameter. This helps to separate the information contained in the estimation of the distance to the last scattering surface (from the CMB) from the information contained in the ISW effect. We then use Fisher analysis to forecast the expected uncertainties in the measured parameters from future ISW observations for two models of dark energy with very different time evolution properties. For example, we demonstrate that the cross-correlation of Planck CMB data and LSST galaxy catalogs will provide competitive constraints on w(z), compared to a SNAP-like SNe project, for models of dark energy with a rapidly changing equation of state (e.g. 'Kink' models). Our work confirms that, while SNe measurements are more suitable for constraining variations in w(z) at low redshift, the ISW effect can provide important independent constraints on w(z) at high z.Comment: 15 pages, 17 figures. Added discussion, references, 2 new figures. Minor errors fixed in the calculation. The predicted ISW constraints on w(z) are slightly tighter. Matches the version accepted to PR

Development of criteria and procedures for the evaluation of the European Action Plan for Organic Agriculture

This final report provides a synthesis of the results of the EU-funded ORGAP project, with the title “European Action Plan of Organic Food and Farming - Development of criteria and procedures for the evaluation of the EU Action Plan for Organic Agriculture”. This project started in May 2005 and was completed in April 2008. The overall objective of this project was to give scientific support to the implementation of the EU Organic Action Plan (EUOAP) by the development of an evaluation toolbox. In the project 10 partners from 9 countries (CH, UK, DE, IT, DK, SI, CZ, NL, ES) participated, as well as the European umbrella organisation of the Organic Agricultural Movements (IFOAM EU Regional group), ensuring a broad stakeholder consultation process and dissemination all over Europe. Chapter 1 describes the background and the objectives, structure and the outcome of the ORGAP Project. It shows that since the late 1980s, organic farming development in the European Union (EU) has been stimulated mainly by two factors, one related to strong consumer demand, supported by the EU regulation defining organic food, and the other to policy support for the provision of public goods. Responding to concerns that area payments as ‘supply-push’ measures can impact negatively on the markets for organic products, policy-makers have started to take a more integrated approach to policy using the ‘action plan’ mechanism. Action plans can be found in most EU member states. At national level, action plans provide a mechanism to ensure a balanced policy mix, reflecting different aims and the various supply-push and demand-pull policy instruments available, tailored to local conditions. In 2004 the European Commission launched the European Action Plan for Organic Food and Farming. The plan contained 21 action points, which relate to the following areas: • Consumer information and promotion campaigns; • Improved research, market intelligence and statistical data collection; • Full utilisation of the rural development programme and other existing options to support organic farming; • Improving the transparency, scope and implementation of the regulation defining organic farming In the meantime, the European Commission has started to implemented most of the actions. In chapter 2 a brief history about organic action plan development is given, in particular about the European as well as national organic action plan for organic food and farming. The European Action Plan for Organic Food and Farming (EC 2004) is the result of a three-year process of developing the Action Plan, starting in 2001. This process led to: a Commission staff paper exploring the options for an action plan in 2001; the establishment of an independent expert working group in 2002, a public internet consultation on specific options in February 2003; a European Parliament hearing on the action plan options in June 2003; and a public hearing on the action plan options in January 2004. In June 2004 the action plan was decided by the EU Council in June 2004, following significant internal debate within the Commission and the EU Parliament. The involvement of stakeholders in the development of the EUOAP was mainly in the explorative phases involving identification of organic sector development needs and possible solution phase. The actual action plan was prepared after the public hearing in January 2004, so that stakeholders were not able to comment on the action plan document or the balance of individual actual action points. During the subsequent implementation phase, primary responsibility also rests with the EU Commission, with input from the EU Council, EU Parliament and member-state government representatives, with only limited input from other stakeholder groups. The European Commission has started to implement the actions of the European Organic Action Plan, many of which have been achieved or are at an advanced stage of completion. The most significant initiatives are the publication of the new Council regulation (EC) 834/2004 on organic production and labelling of organic products and the consumer information campaign. The development of national organic action plans started in Europe in 1995 when Denmark introduced its first organic action plan. Denmark thus acted as a forerunner and pioneer in this field. Nowadays, most EU Member States have organic action plans for organic food and farming. Of those that don’t, some have plans in preparation. Under the framework of the ORGAP Project, six national (CZ, DK, DE, IT, NL, SI) and two regional (Andalucia (AND), England (ENG) action plans for organic food and farming were com-pared. As a consequence of the very different situation in the eight case-study countries, the action plans studied vary in their scope. The English and the Dutch action plans represent market-driven and demand-led approaches with a clear focus on market development measures. The German Federal Organic Farming Scheme on the other hand puts a distinct emphasis on informational policy instruments to strengthen the organic sector through consumer information as well as through research and development. Finally, the Andalusian, Czech, Danish, Italian and the Slovenian action plans represent quite broad approaches integrating a broad portfolio of measures targeted to supply and market development as well as to information and research. Apart from the Andalusian Action Plan, all other action plans studied include quantitative tar-gets. Most typically targets for organic adoption are set (CZ, DK, NL, SI and DE). However, the Dutch and Slovenian action plans include a combination of targets addressing the share of nationally produced organic products, the domestic organic market share in general, organic sales per capita and the development of tourist farms. The English action plan target was defined in terms of the proportion of the organic market for indigenous products supplied by domestic producers. To conclude, the case study action plans vary with regard to the development process, targets, objectives and the emphasis of measures on certain areas. This is due to quite different political and socio-economic framework conditions for organic farming in these countries. The comparison revealed that the weaknesses identified in the status quo analyses have only partly been translated to the targets and measures included in the action plan documents. This is on the one side a result of the national priority and budget setting and on the other side on the interdependency between EU policies and national policies. However, as all action plans were developed together with stakeholders, the composition of the stakeholder groups and the power of the initiating actor are crucial to the target and priority setting. In chapter 3 the authors write about organic action plans – what we know and do not know. This includes success factors, stakeholder involvement, coherence and consistency issues and the how to evaluate organic action plans with ORGAPET. What makes a successful action plan? This question is much more difficult to answer than it looks at first sight. Many other economic, social and policy developments influence the organic sector and often instances occur which have not been foreseen when a certain action plan was devised. Because of this a simple measurement of the state of a specific objective might be too simplistic. Under certain circumstances an organic action plan could already be regarded as a success if the measures contribute substantially to a development in the right direction. The point of reference would be here: What would have happened if the organic action plan would have not been in place? The second point to keep in mind in judging the success of an organic action plan is to be aware of the fact that such action plans are often not complete in a sense that they fully include all political measures directly relevant for organic farming. In such cases it is important to keep in mind and to analyse the broader policy and market environment relevant to organic farming in order to judge success of the action plan. Organic farming policies can of course only be successful if they are successfully implemented and need sufficient care and knowledge with respect to the often numerously legal conditions outside the specific organic farming area that influence implementation. It also means that a clear mission of implementation agencies and qualified and motivated personal involved are a key to successful organic policies and to successful organic action plans. Is the concept of an organic action plan an outdate concept? Some policy makers believe that it has been a fashion and its time is over. The authors of this report are convinced that any at-tempt to unify elements that influence organic farming and organic farming policies and to bring policies into an integrated, coherent framework will still be necessary and welcome in the future. Whether such attempts in the future will be called organic action plans is a different issue. Currently some key challenges include the question whether the general trend in agricultural prices has actually been reversed. If agricultural prices which tended to decrease in real terms throughout the 20th century are actually moving upwards due to factors such as increased demand for agricultural products, climate change and a possible slowdown of technological progress. Such general developments will also influence the development of organic farming and the development of suitable measures to support it. Some of the implications of a higher price level for conventional agriculture and a higher volatility of prices both in the conventional and organic markets might challenge the continuation of the traditional per hectare organic support policies. If climate change is actually perceived as the key challenge for decades to come then effects with respect to mitigate climate change of organic farming and with respect to the adaptive capacity of organic farming are quite important for any policy justification in support of organic farming. And finally, there is the productivity issue. If the actually demand for food stuff is increasing rapidly throughout the world then the obvious limitations of organic farming in this respect reported from industrial countries become more serious. In that context research and development supporting increasing productivity in organic farming might become much more important than in the past. It is clear that just looking at the originally envisaged targets and objectives might not be sufficient to judge whether or not an action plan has been successful. One key argument going be-yond clear targets and well balanced measures is that embedding action plan development in the wider policy area seems to be absolutely essential to be successful. However, there are a number of other issues to be dealt with which are also quite important prerequisites for successful organic action plans such as stakeholder involvement, coherence and consistency of action plans and an evaluation monitoring capacity. Stakeholder involvement may be understood and carried out in quite different ways including the provision of information, providing opportunities to comment on proposals, and empowering stakeholders to make their own choices. When preparing the toolbox aimed for evaluating the European Organic Action Plan in the OR-GAP project, attempts were made to involve both organic and mixed stakeholders in various steps in eight different national/regional settings and with different methods. These experiences form the background for recommending stakeholders with a purely organic and/or mixed portfolio to involve through group discussions in order to increase and optimize their analytical capacities and thereby their delivery of relevant information regarding the preconditions for implementing the EUOAP and for assessing its policy impacts. Parallel to this, relevant non-organic stake-holders could be involved on the basis of individual interviews or small group interviews. When deciding on which stakeholders to involve in any stage it is thus necessary to identify all stakeholders considered relevant to the issue and to clarify for each of them which perspective they represent in first priority. Therefore a general model for analysing stakeholder involvement in public policy on organic food and farming has been developed in the project. It includes a distinction of expertise involved in the three main perspectives of organic action plans realised in Europe up to now: the specific values defining organic food and farming; the market perspective as organic food in most plans is expected to develop in response to consumer demand; and a political recognition of the public goods delivered as a consequence of performing organic farming practices. With regard to each of these three perspectives, it is possible to specify expertise of stakeholders acting in the core or periphery of the perspective and to distinguish expertise of purely organic stakeholders and other stakeholders with a mixed or even non-organic expertise relevant for the development of policies in support of organic food and farming. The degree to which participatory methods realise their potential contribution depends critically on how carefully they are used and in what context. There is no one set of techniques to be mechanically applied in all contexts for all participants, but a diverse range of possible techniques which need to be flexibly adapted to particular situations and needs. Stakeholder involvement helps improving the information basis and the legitimacy of public policies. This is especially important on complex issues such as organic action plans, which involves actors with stakes in issues as different as the values of organic food and farming, the food market and the public goods of organic food and farming at one and the same time. Successful stakeholder involvement thus demands: careful preparations of which stakeholders to include at any stage of the policy process and of the methods used to promote participation; sufficient time for the stakeholder to react; this means at least 8-12 weeks of time for allowing substantial and broad participation, in particular in the case of involvement of farmers organisations, and good communication and transparency in each of the five stages of the policy process. Although this results in higher costs and more resources for those administrating the process, the outcome of such a process will improve the legitimacy and acceptability of the decisions and will facilitate very much the implementation (e.g. through public private partnerships). Such a more participative, transparent and time-balanced process helps to avoid unnecessary discussions and misunderstandings, which at the end might be more effective and cost-efficient. Project Synthesis For an evaluation of the internal and external coherence of the EU Organic Action Plan (OAP), the ORGAP project team generally made use of empirical methods and techniques suggested for analysing the synergy of programmes as well as their cross-impacts. A policy analysis of key synergies (positive and negative) was performed by means of a matrix of cross impacts as specified in the MEANS framework (EC, 1999). Two separate matrices were constructed: to appraise the internal coherence between the various measures of the EU Organic Action Plan; and to appraise the external coherence between the EUOAP and some national organic action plans. Experts involved in this evaluation process (Evaluation team) identified any synergy which may exist between pairs of measures or categories of measures. The effects of synergies or conflicts have been rated with the help of 2 electronic consultation rounds. After validation of these ratings, the calculation of the “synthetic” coefficient of synergy was performed, in order to evaluate the overall level of synergy/conflict within the European Organic Action Plan. The analysis suggests that Actions 9 (ensure integrity) and 10 (harmonisation of standards) are essential for the success of the EUOAP, given their synergetic effects. They in addition enter into synergy with many other actions. Interesting is also Action 13 (risked based-inspections) wit

Evolving Towards the Hypercycle: A Spatial Model of Molecular Evolution

We extend earlier cellular automata models of spatially extended hypercycles by including an explicit genetic component into the model. This allows us to study the sequence evolution of hypercyclically coupled molecular replicators in addition to considering their population dynamics and spatial organization. In line with previous models, that considered either spatial organization or sequence evolution alone, we find both temporal oscillations of the relative concentration of the species forming the hypercycles as well as the formation of spatial organisations including spiral waves. We also confirm the greatly increased robustness of the spatially extended hypercycle against various classes of parasites. We find the sequence evolution of each of the hypercyclically coupled populations proceeds (after an inital selection-dominated phase) in a drift-like manner that can be described by a diffusion process in sequence space. Kimura's theory of neutral evolution is therefore applicable on long time-scales despite the fact that the hypercycle exhibits extreme periodic changes in population sizes and that are governed solely by frequency-dependent selection