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Background: Accurate diagnosis and staging are crucial to ensure uniform allocation to the optimal treatment methods for non-small cell lung cancer (NSCLC) patients, but may differ among multidisciplinary tumor boards (MDTs). Discordance between clinical and pathologic TNM stage is particularly important for patients with locally advanced NSCLC (stage IIIA) because it may influence their chance of allocation to curative-intent treatment. We therefore aimed to study agreement on staging and treatment to gain insight into MDT decision-making. Research Question: What is the level of agreement on clinical staging and treatment recommendations among MDTs in stage IIIA NSCLC patients? Study Design and Methods: Eleven MDTs each evaluated the same 10 pathologic stage IIIA NSCLC patients in their weekly meeting (n = 110). Patients were selected purposively for their challenging nature. All MDTs received exactly the same clinical information and images per patient. We tested agreement in cT stage, cN stage, cM stage (TNM 8th edition), and treatment proposal among MDTs using Randolph's free-marginal multirater kappa. Results: Considerable variation among the MDTs was seen in T staging (κ, 0.55 [95% CI, 0.34-0.75]), N staging (κ, 0.59 [95% CI, 0.35-0.83]), overall TNM staging (κ, 0.53 [95% CI, 0.35-0.72]), and treatment recommendations (κ, 0.44 [95% CI, 0.32-0.56]). Most variation in T stage was seen in patients with suspicion of invasion of surrounding structures, which influenced such treatment recommendations as induction therapy and type. For N stage, distinction between N1 and N2 disease was an important source of discordance among MDTs. Variation occurred between 2 patients even regarding M stage. A wide range of additional diagnostics was proposed by the MDTs. Interpretation: This study demonstrated high variation in staging and treatment of patients with stage IIIA NSCLC among MDTs in different hospitals. Although some variation may be unavoidable in these challenging patients, we should strive for more uniformity.

International audience; This paper enacts a dialogue between planning literature on polycentric urban regions (PUR) and port geography literature on multi-port gateways. The main proposition is that polycentric systems are the emergent outcome of the interactions between three dimensions of polycentricity: morphological, functional and institutional. The focus is on the Dutch–Belgian Amsterdam–Rotterdam–Antwerp (ARA)port–industrial region: one of the world’s largest concentrations of oil refining and petrochemical activity. The central question is to what extent is the ARA region a polycentric system and what explains this observed polycentricity? Our analyses demonstrate a high degree of morphological and functional polycentricity with each of the constituent (firms located in) ports connected through flows and specialization in processing and trading oil (products). However, this is not the intended result of formalized spatial planning, nor did the ARA ever became a frame of reference among planning agencies. Rather, it is the result of self-organization in the oil industry that has culminated in the emergence of the ARA as an internationally recognized spot market, later institutionally formalized in delivery contracts (oil futures) traded on international commodity exchanges. We conclude that polycentric systems could be understood as emergent systems that obtained generative capacities, inturn influencing its different constituting dimensions.

Background Although most newly presenting patients with pulmonary hypertension ( PH ) have elevated pulmonary artery wedge pressure, identification of so‐called postcapillary PH can be challenging. A noninvasive tool predicting elevated pulmonary artery wedge pressure in patients with incident PH may help avoid unnecessary invasive diagnostic procedures. Methods and Results A combination of clinical data, ECG, and echocardiographic parameters was used to refine a previously developed left heart failure risk score in a retrospective cohort of pre‐ and postcapillary PH patients. This updated score (renamed the OPTICS risk score) was externally validated in a prospective cohort of patients from 12 Dutch nonreferral centers the OPTICS network. Using the updated OPTICS risk score, the presence of postcapillary PH could be predicted on the basis of body mass index ≥30, diabetes mellitus, atrial fibrillation, dyslipidemia, history of valvular surgery, sum of SV 1 (deflection in V1 in millimeters) and RV 6 (deflection in V6 in millimeters) on ECG, and left atrial dilation. The external validation cohort included 81 postcapillary PH patients and 66 precapillary PH patients. Using a predefined cutoff of >104, the OPTICS score had 100% specificity for postcapillary PH (sensitivity, 22%). In addition, we investigated whether a high probability of heart failure with preserved ejection fraction, assessed by the H 2 FPEF score (obesity, atrial fibrillation, age >60 yrs, ≥2 antihypertensives, E/e' >9, and pulmonary artery systolic pressure by echo >35 mmHg), similarly predicted the presence of elevated pulmonary artery wedge pressure. High probability of heart failure with preserved ejection fraction (H 2 FPEF score ≥6) was less specific for postcapillary PH . Conclusions In a community setting, the OPTICS risk score can predict elevated pulmonary artery wedge pressure in PH patients without clear signs of left‐sided heart disease. The OPTICS risk score may be used to tailor the decision to perform invasive diagnostic testing.

Context. Metastatic lung cancer is an incurable disease that results in a high burden of symptoms, a poor quality of life, and an expected prognosis of less than one year after diagnosis. Treatment shortly before death may result in potential burdensome and inappropriate hospital admissions and hospital deaths. Dying at home is, at a population level, considered a quality for good end-of-life care.Objectives. We examined what percentage of patients with metastatic lung cancer died inside the hospital and if hospital death, or other characteristics of the patient, oncologist or health care, were associated with treatment in the last month of life.Methods. This retrospective cohort study evaluated the medical records of 1322 patients with metastatic lung cancer who received care at one of 10 hospitals across The Netherlands and died between 1/6/2013 and 31/7/2015. Demographic and clinical characteristics were obtained from the medical records.Results. In total, 18% of the patients died during a hospital admission. This percentage was higher for patients who received chemotherapy (42%) or targeted therapy with tyrosine kinase inhibitors (25%) in the last month of life. Patients younger than 60 years of age, patients who received chemotherapy in the last month of life, and patients in whom tyrosine kinase inhibitors were started in the last month of life were more likely to die inside the hospital.Conclusion. In The Netherlands, fewer than one in five patients with metastatic lung cancer died in the hospital and in-hospital death was associated with the relatively late use of chemotherapy or targeted therapy. Careful selection of patients for disease-modifying therapy might enhance the opportunity for patients to die at their preferred place. (C) 2019 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Exclusion of pulmonary hypertension secondary to left-sided heart disease (left heart failure (LHF)) is pivotal in the diagnosis of pulmonary arterial hypertension (PAH). In case of doubt, invasive measurements are recommended. The aim of the present study was to investigate whether it is possible to diagnose LHF using noninvasive parameters in a population suspected of PAH.300 PAH and 80 LHF patients attended our pulmonary hypertension clinic before August 2010, and were used to build the predictive model. 79 PAH and 55 LHF patients attended our clinic from August 2010, and were used for prospective validation.A medical history of left heart disease, S deflection in V1 plus R deflection in V6 in millimetres on ECG, and left atrial dilation or left valvular heart disease that is worse than mild on echocardiography were independent predictors of LHF. The derived risk score system showed good predictive characteristics: R2=0.66 and area under the curve 0.93. In patients with a risk score ≥72, there is 100% certainty that the cause of pulmonary hypertension is LHF. Using this risk score system, the number of right heart catheterisations in LHF may be reduced by 20%.In a population referred under suspicion of PAH, a predictive model incorporating medical history, ECG and echocardiography data can diagnose LHF noninvasively in a substantial percentage of cases.

This paper deals with path dependence in seaport governance. A central notion in this respect is lock-in. Economic geographers have recently started to reconsider the deterministic perspective on lock-in and developed the concept of institutional plasticity. Such plasticity is the result of actions of actors to purposefully 'recombine and convert or reinterpret institutions for their new objectives or transfer institutions to different contexts' (Strambach, 2010). This concept is applied to seaports, where so far, path dependence and lock-in have not been studied in detail. Our main conclusion is that a process of institutional stretching takes place when port authorities see a need to develop new capabilities and activities. In this process new layers are added to existing arrangements, gradually leading to a formalised governance reform but without breaking out of the existing path of development. (c) 2012 Elsevier Ltd. All rights reserved.

Jacobs W., van Rietbergen T., Atzema O., van Grunsven L. and van Dongen F. The impact of multinational enterprises (MNEs) on knowledge-intensive business services (KIBS) start-ups: empirical evidence from the Dutch Randstad, Regional Studies. This paper focuses on the impact of multinational enterprises (MNEs) on the level of entrepreneurship in knowledge-intensive business services (KIBS) in metropolitan regions. Large globalizing metropolitan regions or world cities' are generally considered prime office locations for MNEs and KIBS alike. Certain locations in these metropolitan regions or world cities provide multifarious benefits of being co-agglomerated. Yet the impact of local MNEs, whether domestic or foreign, on successful local entrepreneurship in related KIBS has hardly been conceptually or empirically addressed in the literature. This paper presents evidence from the Dutch Randstad based on a questionnaire given to 2,000 KIBS firms founded in 2001-08 and supported by interviews with major international KIBS. The main conclusion is that MNEs in KIBS firms spawn successful entrepreneurship in KIBS. Implications for regional development policy are also addressed. Jacobs W., van Rietbergen T., Atzema O., van Grunsven L. and van Dongen F. ????(MNE)??????????(KIBS)????????????????(Randstad)????,????????????(MNE) ????????????????(KIBS)???????????????,?????????? ???,? MNE ? KIBS ???????????????????????????,???????????????????????????,???????????? MNE,????? KIBS ???????????????,?????????????????????2001??2008???KIBS??????????,?????????KIBS??????,??????????(Randstad)???????????KIBS ??? MNE,??? KIBS ????????????????????????? Jacobs W., van Rietbergen T., Atzema O., van Grunsven L. et van Dongen F., L'impact des entreprises multinationales sur les services aux entreprises en demarrage a forte intensite de connaissance: des preuves empiriques provenant de la Randstad neerlandaise, Regional Studies. Cet article porte sur l'impact des entreprises multinationales (a savoir, les MNE) sur l'esprit d'entreprise des services aux entreprises a forte densite de connaissances (a savoir les KIBS) dans les regions metropolitaines. En regle generale, on considere les grandes regions metropolitaines mondialisees, autrement dit les grandes villes du monde', comme des emplacements de premier ordre pour les bureaux des MNE et des KIBS, tous les deux. Certains emplacements dans ces regions metropolitaines ou dans ces grandes villes du monde offrent de nombreux avantages de co-agglomeration. Toujours est-il que, dans la documentation, on n'a guere aborde d'un point de vue conceptuel ou empirique l'impact des MNE locales, soit nationales, soit internationales, sur l'esprit d'entreprise reussi des KIBS apparentes. Cet article presente des resultats provenant de la Randstad neerlandaise fondes sur une questionnaire aupres de 2000 KIBS etablis entre 2001 et 2008 completee par des interviews aupres d'importants KIBS internationaux. La principale conclusion est la suivante: les MNE parmi les KIBS donnent naissance a un esprit d'entreprise reussi dans les KIBS. On aborde aussi les consequences pour la politique d'amenagement du territoire. Jacobs W., van Rietbergen T., Atzema O., van Grunsven L. und van Dongen F. Auswirkung von multinationalen Unternehmen auf Firmengrundungen im Bereich der wissensintensiven Geschaftsdienste: Belege aus der niederlandischen Randstad, Regional Studies. Im Mittelpunkt dieses Beitrags stehen die Auswirkungen von multinationalen Unternehmen auf den Umfang des Unternehmertums in wissensintensiven Geschaftsdiensten in Metropolitanregionen. Gro ss e globalisierende Metropolitanregionen oder Weltstadte' gelten generell als erstklassige Standorte fur gewerbliche Immobilien fur multinationale Unternehmen und wissensintensive Geschaftsdienste. Bestimmte Standorte in diesen Metropolitanregionen oder Weltstadten bieten aufgrund ihres gemeinsamen Ballungsraums vielfaltige Vorteile. Allerdings wurde die Auswirkung von lokalen multinationalen Unternehmen (egal ob im in- oder auslandischen Besitz) auf erfolgreiches lokales Unternehmertum in zugehorigen wissensintensiven Geschaftsdiensten in der Literatur bisher noch kaum konzeptuell oder empirisch untersucht. In diesem Beitrag stellen wir Belege der niederlandischen Randstad vor, die mithilfe eines Fragebogens erfasst wurden, der an 2000 im Zeitraum von 2001 bis 2008 gegrundete Firmen fur wissensintensive Geschaftsdienste ausgegeben und durch Interviews mit wichtigen internationalen Firmen fur wissensintensive Geschaftsdienste erganzt wurde. Die wichtigste Schlussfolgerung lautet, dass multinationale Unternehmen im Bereich der wissensintensiven Geschaftsdienste erfolgreiches Unternehmertum fur wissensintensive Geschaftsdienste hervorbringen. Ebenso werden die Konsequenzen fur die Regionalentwicklung erortert. Jacobs W., van Rietbergen T., Atzema O., van Grunsven L. y van Dongen F. El impacto de las empresas multinacionales en la creacion de empresas para servicios a empresas intensivos en conocimiento (SEIC): evidencia empirica de Randstad en los Paises Bajos, Regional Studies. Este articulo trata sobre el impacto de las empresas multinacionales en el nivel de interes empresarial de los servicios a empresas intensivos en conocimiento (SEIC) en regiones metropolitanas. Las grandes regiones metropolitanas globalizadas o ciudades del mundo' se consideran en general lugares principales de inmuebles de uso comercial para empresas multinacionales y SEIC. Determinados lugares en estas regiones metropolitanas o ciudades del mundo ofrecen diversos beneficios gracias a su aglomeracion conjunta. Sin embargo, el impacto de las empresas multinacionales locales, ya sean nacionales o extranjeras, en el exito del empresariado local en los SEIC relacionados apenas se ha abordado desde un punto de vista conceptual o empirico en la bibliografia. En este articulo presentamos datos de la region neerlandesa Randstad a partir de un cuestionario que se entrego a 2.000 empresas de SEIC fundadas entre 2001 y 2008, junto con entrevistas a las principales empresas de SEIC internacionales. La principal conclusion es que las empresas multinacionales en los servicios a empresas intensivos en conocimiento generan exito empresarial en estos servicios. Tambien explicamos las implicaciones para la politica de desarrollo regional.

Within research on world cities, much attention has been paid to advanced producer services (APS) and their role within both global urban hierarchies and network formation between cities. What is largely ignored is that these APS provide services to firms operating in a range of different sectors. Does sector-specific specialisation of advanced producer services influence the economic geography of corporate networks between cities? If so, what factors might explain this geographical pattern? This paper investigates these theoretical questions by empirically focusing on those advanced producer services related to the port and maritime sector. The empirical results show that the location of AMPS is correlated with maritime localisation economies, expressed in the presence of shipowners and port-related industry as well as APS in general, but not by throughput flows of ports. Based upon the findings, policy recommendations are addressed. © 2010 Urban Studies Journal Limited.

An earlier version of this paper can be found as GaWC Research Bulletin 298 (http://www.lut.ac.uk/gawc/rb/rb298.html) and the paper was published in the following book: Derudder B. and Witlox F. (Eds.) (2010) Commodity Chains and World Cities, Wiley-VCH.; International audience; This paper analyses the location patterns of firms that provide specialized advanced producer services (APS) to international commodity chains that move through seaports. Such activities can take place in world cities or in port cities. The analysis of APS location patterns in port cities provides a good opportunity to integrate the study of world cities into the framework of global production networks. Based upon our empirical findings, we conclude that while port-related APS activities predominantly follow the world city hierarchy, a number of port cities stand out because they act as nodes in global commodity flows and as centres of advanced services related to shipping and port activities. Based upon these empirical findings we address future avenues of research

Contains fulltext : 131853.pdf (Publisher’s version ) (Closed access) Strategic coupling refers to the process of matching local assets with global network demands. Although the concept has benefited from an increase in relational thinking, several critical issues remain unresolved. In this article, we identify and discuss three such issues – the characteristics of the entities involved in strategic coupling, the way in which the ‘local’ is conceptualized in the context of ‘global’ positioning, and the understanding of strategic action. To address these issues, we use Cox’s notion of ‘spaces of dependence and engagement’ in combination with Ball’s concept of the ‘structure of provision’. The case of the port of Rotterdam demonstrates the value of our perspective in elucidating the process of ‘strategic coupling’ within global networks of containerized traffic. 19 p.

Port research is not a new field of interest for human geographers, evidenced by numerous conceptual models and empirical cases of port evolution and development in the literature. However, several critical questions remain unanswered, notably the exact position of port geography as a subdiscipline within human geography in the past, present and future. Based on a pluralistic approach, the paper analyzes the changing waves and development of port geography as a sub-discipline of human geography, with a special focus on whether port geography has experienced a paradigm shift and, if so, when, why, and how. Also, through analyzing the major terrains of port geography research from the macro perspective, it brings a new lease of life to port geography in this rapidly changing world.

Pulmonary arterial hypertension is a progressive disease of the pulmonary vasculature, ultimately leading to right heart failure and death. Current treatment is aimed at targeting three different pathways: the prostacyclin, endothelin and nitric oxide pathways. These therapies improve functional class, increase exercise capacity and improve haemodynamics. In addition, data from a meta-analysis provide compelling evidence of improved survival. Despite these treatments, the outcome is still grim and the cause of death is inevitable – right ventricular failure. One explanation for this paradox of haemodynamic benefit and still worse outcome is that the right ventricle does not benefit from a modest reduction in pulmonary vascular resistance. This article describes the physiological concepts that might underlie this paradox. Based on these concepts, we argue that not only a significant reduction in pulmonary vascular resistance, but also a significant reduction in pulmonary artery pressure is required to save the right ventricle. Haemodynamic data from clinical trials hold the promise that these haemodynamic requirements might be met if upfront combination therapy is used.

How do seaports evolve in relation to each other? Recent studies in port economics and transport geography focused on how supply chain integration has structurally changed the competitive landscape in which individual ports and port actors operate. Port regionalization has been addressed as the corresponding new phase in the spatial and functional evolution of port systems. However, these studies lack theoretical foundations that allow us to empirically assess both the role of the institutional context and of strategic agency in the competitive (spatial and functional) evolution of regional (integrated) port systems. The paper presents a theoretical framework to analyze and understand the co- evolution of seaports in a regional context by making use of the concept of windows of opportunity. The empirical part will unravel the role of seaport-based co-evolution in the processes aimed at positioning market players and ports on the container scene in the Rhine-Scheldt Delta.

Despite ongoing transformations in the maritime transportation industry and the rise of global supply chain systems, most of the world’s important container ports remain urban. Ports continue to occupy urban spaces, are embedded in localized knowledge systems, draw on urban labour markets and infrastructure and are subject to local politics and policy concerns. We identify contemporary geographic theories which help us understand the often increasingly urban attachment of core economic activities despite globalization. We explore how these theories may apply to port studies, highlighting both how they have been used by maritime scholars to this point and also why further development and application are warranted. We argue that a central concern of these geographic theories is the articulation of place- and sector-specific processes operating at a variety of spatial scales. This is in contrast to most maritime studies which continue to be dominated by perspectives which emphasize the global logic of the transportation industry and the analysis of space in generalized and abstract terms. We conclude that a re-appreciation in maritime studies of urban economic processes, informed by geographical theory, will provide policy-makers and others with more understanding of why deep connections between ports and urban places still matter.