The EEAS' diplomatic dreams and the reality of European and international law

The aim of this paper is to confront the diplomatic ambitions of the European External Action Service (EEAS) with the reality of EU and international law. Treaty provisions as well as policy documents and statements of EU officials reveal a development in the direction of a strengthened role for the EU itself as a diplomatic actor. The findings underline a continued tension between the EU’s diplomatic ambitions and EU and international law as it stands. In relation to the EU’s internal structures, there is no doubt that in the new EU institutional landscape dividing lines remain firmly in place. Yet, the working arrangements do point to ‘holistic’ thinking implying cooperation and reciprocity. In addition the paper argues that the EU’s ambitions sit uncomfortably with traditional state-centred international diplomatic law. Extensive diplomatic activity of the EU depends on the acceptance by the willingness of third states to accept the EU as a diplomatic actor

Leaders Address Inequity Through a Framework of International-Mindedness

This paper offers school leaders and scholar practitioners twin frameworks of international-mindedness and cultural proficiency as a means to addressing persistent education gaps. International-mindedness is a global perspective framework and cultural proficiency is an equity-focused framework. These complementary frameworks are grounded in the educational policies and practices found in the International Baccalaureate (IB) programs. In an era focused on closing achievement gaps, students from diverse backgrounds have opportunities to engage in topics and dispositions in IB that connect to their prior knowledge and experiences through a new lens and global perspective. Once viewed as an elitist high school program, the IB is now offered in an increasing number of public schools as a school wide initiative to support the needs of all students, including language learners and students from low socio-economic backgrounds. Teachers and school leaders in IB schools teach human similarities and differences through a local and global perspective to better prepare and engage all students in the knowledge and skills they will need in the changing world of the 21st century. To realize this expanded goal of access and achievement for all students, school leaders and educators must also understand the complementary conceptual frameworks of cultural proficiency and international-mindedness. The authors recommend that by aligning the frameworks of international-mindedness and cultural proficiency, students of all demographic groups and their teachers become aware of a wider world, respect and value diversity, understand how the world works, participate both locally and globally, and may be motivated to take action as engaged citizens

Transforming towards sustainable health and wellbeing systems:Eight guiding principles based on the experiences of nine Dutch Population Health Management initiatives

Introduction Population Health Management initiatives are increasingly introduced, aiming to develop towards sustainable health and wellbeing systems. Yet, little is known about which strategies to implement during this development. This study provides insights into which strategies are used, why, and when, based on the experiences of nine Dutch Population Health Management initiatives. Methods The realist evaluation approach was used to gain an understanding of the relationships between context, mechanisms and outcomes when Population Health Management strategies were implemented. Data were retrieved from three interview rounds (n = 207) in 2014, 2016 and 2017. Data was clustered into guiding principles, underpinned with strategy-context-mechanism-outcome configurations. Results The Dutch initiatives experienced different developments, varying between immediate large-scale collaborations with eventual relapse, and incremental growth towards cross-sector collaboration. Eight guiding principles for development towards health and wellbeing systems were identified, focusing on: 1. Shared commitment for a Population Health Management-vision; 2. Mutual understanding and trust; 3. Accountability; 4. Aligning politics and policy; 5. Financial incentives; 6. A learning cycle based on a data-infrastructure; 7. Community input and involvement; and 8. Stakeholder representation and leadership. Conclusion Development towards a sustainable health and wellbeing system is complex and time-consuming. Its success not only depends on the implementation of all eight guiding principles, but is also influenced by applying the right strategies at the right moment in the development

Text-mining assisted regulatory annotation

Text-mining technologies can be integrated with genome annotation systems, increasing the availability of annotated cis-regulatory data

What’s in a Realist Configuration? Deciding Which Causal Configurations to Use, How, and Why

Background: Realist studies represent an increasingly popular approach for exploring complex interventions’ successes and failures. The theory-driven approach seeks to explain “what works, how, why, in which contexts, for whom, and to what extent” using context–mechanism–outcome (CMO) configurations. When the approach was first developed, CMO configurations were the method for expressing causal explanations. Increasingly, realist studies have been conducted using different variations of the heuristic such as strategy–context–mechanism–outcome (SCMO) configurations or intervention–context–actor–mechanism–outcome (ICAMO) configurations. Researchers have highlighted a lack of methodological guidance regarding which additional explanatory factors can be included in configurations (e.g., strategies, interventions, actors). This article aims to clarify and further develop the concept of configurations by discussing how explanatory factors could be robustly added to the original CMO configuration as put forward by Pawson and Tilley. Comparing the use of different types of configurations: We draw on two of our own studies, one which formulated CMO configurations and one which formulated SCMO configurations, and on an evidence scan of realist studies. We explored the effects these different configurations had on studies’ findings and highlight why researchers chose CMOs or SCMOs. Finally, we provide recommendations regarding the use of configurations. These are as follows: Using additional explanatory factors is possible but consider the research scope to select the configuration appropriate for the study; Be transparent about the choice in configuration and include examples of configurations; Further studies about the use of additional explanatory factors are needed to better understand the effects on each step in the realist evaluation cycle; and New ways of disseminating realist findings are needed to balance transparency regarding the use of configurations. Conclusions: Adding explanatory factors is possible and can be insightful depending on the study’s scope and aims; however, any configuration type must adhere to the rule of generative causation

Saturable elimination of piperacillin in critically ill patients:implications for continuous infusion

The study aimed to evaluate saturation of piperacillin elimination in critically ill adult patients. Seventeen critically ill adult patients received continuous and intermittent infusion of piperacillin/tazobactam. Piperacillin plasma concentrations (n = 217) were analysed using population pharmacokinetic (PopPK) modelling. Post-hoc simulations were performed to evaluate the type I error rate associated with the study. Unseen data were used to validate the final model. The mean error (ME) and root mean square error (RMSE) were calculated as a measure of bias and imprecision, respectively. A PopPK model with parallel linear and non-linear elimination best fitted the data. The median and 95% confidence interval (CI) for the model parameters drug clearance (CL), volume of central compartment (V), volume of peripheral compartment (V-p) and intercompartmental clearance (Q) were 9 (7.69-11) L/h, 6.18 (4.93-11.2) L, 11.17 (7.26-12) L and 15.61 (12.66-23.8) L/h, respectively. The Michaelis-Menten constant (K-m) and the maximum elimination rate for Michaelis-Menten elimination (V-max) were estimated without population variability in the model to avoid overfitting and inflation of the type I error rate. The population estimates for K-m and V-max were 37.09 mg/L and 353.57 mg/h, respectively. The bias (ME) was -20.8 (95% CI -26.2 to -15.4) mg/L, whilst imprecision (RMSE) was 49.2 (95% CI 41.2-56) mg/L. In conclusion, piperacillin elimination is (partially) saturable. Moreover, the population estimate for K-m lies within the therapeutic window and therefore saturation of elimination should be accounted for when defining optimum dosing regimens for piperacillin in critically ill patients. (C) 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved

Endeavour update: a web resource for gene prioritization in multiple species

Endeavour (http://www.esat.kuleuven.be/endeavourweb; this web site is free and open to all users and there is no login requirement) is a web resource for the prioritization of candidate genes. Using a training set of genes known to be involved in a biological process of interest, our approach consists of (i) inferring several models (based on various genomic data sources), (ii) applying each model to the candidate genes to rank those candidates against the profile of the known genes and (iii) merging the several rankings into a global ranking of the candidate genes. In the present article, we describe the latest developments of Endeavour. First, we provide a web-based user interface, besides our Java client, to make Endeavour more universally accessible. Second, we support multiple species: in addition to Homo sapiens, we now provide gene prioritization for three major model organisms: Mus musculus, Rattus norvegicus and Caenorhabditis elegans. Third, Endeavour makes use of additional data sources and is now including numerous databases: ontologies and annotations, protein–protein interactions, cis-regulatory information, gene expression data sets, sequence information and text-mining data. We tested the novel version of Endeavour on 32 recent disease gene associations from the literature. Additionally, we describe a number of recent independent studies that made use of Endeavour to prioritize candidate genes for obesity and Type II diabetes, cleft lip and cleft palate, and pulmonary fibrosis