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Background: Despite the well-known negative prognostic value of the V600EBRAF mutation in patients with metastatic colorectal cancer (mCRC), its outcome is quite heterogeneous, and the basis for this prognostic heterogeneity should be better defined. Methods: Two large retrospective series of V600EBRAF-mutated mCRC from 22 institutions served as an exploratory and validation set to develop a prognostic score. The model was internally and externally validated. Results: A total of 395 V600EBRAF-mutated mCRCs were included in the exploratory set. Performance status, CA19.9, lactate dehydrogenase, neutrophil/lymphocyte ratio, grading and liver, lung and nodal involvement emerged as independent prognostic factors for overall survival (OS). Two different scoring systems were built: a ‘complete’ score (0–16) including all significant covariates and a ‘simplified’ score (0–9), based only on clinicopathological covariates, and excluding laboratory values. Adopting the complete score, proportions of patients with a low (0–4), intermediate (5–8) and high (9–16) score were 44.7%, 42.6% and 12.6%, respectively. The median OS was 29.6, 15.5 (hazard ratio [HR] for intermediate vs low risk: 2.16, 95% confidence interval [CI]: 1.44–3.22, p < .001) and 6.6 months (HR for high vs low risk: 4.72, 95% CI: 2.72–8.20, p < .001). Similar results were observed also after adjusting for the type of first-line treatment and adopting the simplified score. The simplified prognostic score derived from the exploratory set was then applied to the validation set for external confirmation. Conclusions: These scoring systems are based on easy-to-collect data and defined specific subgroups with relevant differences in their life expectancy. These tools could be useful in clinical practice, would allow better stratification of patients in clinical trials and may be adopted for proper adjustments in exploratory translational analyses.

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Contains fulltext : 179673.pdf (Publisher’s version ) (Closed access) This chapter assesses the state of play in Europeanization research, focusing on the impact of European integration on national policies and administrations. After dissecting the concept of Europeanization, it sketches this literature’s guiding question: how to account for differential domestic impacts of European integration. It then describes how much Europeanization research has shifted away from a top down focus on institutional misfits to creative strategic use of EU inputs by domestic stakeholders. Furthermore, it establishes a marked pluralization of policy-oriented research, which now encompasses a great variety of policy sectors, (member) states and EU inputs. In the realm of administrative adaptation, similarly, Europeanization research has clearly gone beyond the initial focus on national coordination systems, to encompass EU-induced changes in administrative structures and individual attitudes.

The third sector is one of the main partners for European governments in policy development and implementation. However, the relationship has often been a delicate one, touching on issues of autonomy and legitimacy. In this chapter, we give an overview of different theoretical reasons for and types of collaboration between the third sector and the state. We also describe the different traditions of collaboration that have emerged across Europe. Finally, we discuss the risks associated with this kind of relationship.

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Contains fulltext : 179684.pdf (Publisher’s version ) (Closed access) Policy evaluations are increasingly considered a taken-for-granted prerequisite for a well-performing public sector. In this chapter, we address the question whether this view reflects the actual situation concerning evaluation capacity and culture in Europe. First, we reflect on the history of policy evaluation in Europe, by distinguishing between two ‘waves of evaluation’: the countries in Northwestern Europe that have conducted evaluations since the 1960s and the countries in the rest of Europe for which evaluation is a more recent phenomenon. Next, to illustrate the two waves of evaluation, we zoom in on three political systems that represent the national, regional and international level in Europe: the United Kingdom (UK), Flanders (Belgium) and the EU. For each system, we map evaluation culture and capacity by analysing six indicators. The chapter concludes with a reflection on current trends in evaluation research and possibilities for future research.

The chapter reviews the evolution of the state of the art of research in public administration and management in Europe since WWII. It argues that a pan-European community has developed, flanking and in many respects integrating the distinct national communities that characterised the field till the 1970s/1980s. After a bibliographical review of the main themes that catalyse the interest of PA scholars, it focuses on the most researched theme in Europe, namely public management reform. The ways in which the topic has been studied before, during and after the NPM ideological wave are examined by looking into country clusters across Europe: Germanic, Anglo-Saxon, Southern European, Nordic European, and Central-Eastern European. Concluding points include the theoretical importance of context in European research, and the profile of the European scholar.

One of the key features of public administration in Europe is that multiple languages are in use, both in the public and academic debates. Language shapes thought, debate and hence also research. To find out which problems researchers run into when they want to convey results of their research and the debates on public administration to academics and practitioners in other countries, we have asked a number of scholars to describe how several key concepts in public administration and public management are translated into their native language and which problems they encounter when doing so. Their contributions make up for the largest part of this chapter, preceded by a short analysis and commentary on some of the common problems and lessons that should be drawn.

Negotiation is ubiquitous in the public sector, from policy formation to budget allocation or the coordination of public–private partnerships. The focus on negotiations has nevertheless been somewhat limited in public administration research, but in neighboring disciplines such as behavioral economics and social psychology, negotiations have been studied extensively. This chapter aims at filling this gap.This chapter discusses negotiations by focusing on the individual negotiator. I focus on what a negotiation is and who negotiates in the public sector by discussing some substantive examples. Distributive and integrative negotiations are discerned and are accompanied by some public sector illustrations. Specific attention is given to public sector distinctiveness in context and its workers and its potential consequences for negotiations.

Autonomy and control are important dynamics in each advisory system. Autonomy is important because it ensures independent and critical advice and allows advisors to ‘speak truth to power’ (Wildavsky 1989; Pielke 2010). At the same time, government control is also an important aspect (Van Twist et al. 2015; Craft and Halligan 2015; Halligan 1995) to assure that advices are on-topic, on-time, in the right format, and relevant for government decision-making,- and policymaking processes. This paper describes the trade-off the Netherlands, Sweden, and the United Kingdom make with regard to the level of ‘autonomy’ and ‘control’ of their policy advisory bodies. We make a distinction between legal, economic, and operational means (Kunneke 1991) through which autonomy is stimulated or control is exercised on a managerial and policy (primary processes) level of policy advisory bodies.

This chapter identifies how electronic public service delivery has diffused in various public sector organizations in Europe. Three, in practice intertwined, sources of influence are identified: opportunity (the seemingly inevitable and autonomous impact of technologies), inscription of normative structures (the materialization of abstract ideas and rhetoric in specific types of information and communication technologies) and enthusiasms (the sometimes overstated beliefs, held by various stakeholders, that technology is the answer to all kinds of questions). The way these sources of influences work out in practice is demonstrated by discussing the diffusion of a specific type of electronic government, that is personalized electronic service delivery, in ten Dutch municipalities. The chapter is ended with reflections and directions for future research.

Many empirical studies of European public administration and public management are case studies. In light of a trend towards more quantitative research and the rise of behavioural public administration, this chapter makes an argument for the continuity of case study research, as it is often better equipped to deal with macro-level phenomena and processes. This chapter then ventures into the practice of case study research by European scholars, providing information concerning the nature of 103 case studies published by Governance and Public Administration in 2001, 2006, 2010 and 2015. Based on this review and recent developments in case study methodology, we provide some suggestions for case study designs, including theoretically informed case selection, competitive theory testing and more sensitivity to “time” and its various manifestations.

Mechanisms of acquired resistance to trastuzumab-based treatment in gastric cancer are largely unknown. In this study, we analyzed 22 pairs of tumor samples taken at baseline and post-progression in patients receiving chemotherapy and trastuzumab for advanced HER2-positive [immunohistochemistry (IHC) 3+ or 2+ with in-situ hybridization (ISH) amplification] gastric or gastroesophageal cancers. Strict clinical criteria for defining acquired trastuzumab resistance were adopted. Loss of HER2 positivity and loss of HER2 over-expression were defined as post-trastuzumab IHC score