Changing perspectives on the internationalization of R&D and innovation by multinational enterprises: a review of the literature

Internationalization of R&D and innovation by Multinational Enterprises (MNEs) has undergone a gradual and comprehensive change in perspective over the past 50 years. From sporadic works in the late 1950s and in the 1960s, it became a systematically analysed topic in the 1970s, starting with pioneering reports and “foundation texts”. Our review unfolds the theoretical and empirical evolution of the literature from dyadic interpretations of centralization versus decentralization of R&D by MNEs to more comprehensive frameworks, wherein established MNEs from Advanced Economies still play a pivotal role, but new players and places also emerge in the global generation and diffusion of knowledge. Hence views of R&D internationalization increasingly rely on concepts, ideas and methods from IB and other related disciplines such as industrial organization, international economics and economic geography. Two main findings are highlighted. First, scholarly research pays an increasing attention to the network-like characteristics of international R&D activities. Second, different streams of literature have emphasized the role of location- specific factors in R&D internationalization. The increasing emphasis on these aspects has created new research opportunities in some key areas, including inter alia: cross-border knowledge sourcing strategies, changes in the geography of R&D and innovation, and the international fragmentation of production and R&D activities

Supervivencia global a largo plazo en el cáncer de pulmón. Análisis de una serie de 610 pacientes no seleccionados

Introducción y objetivos: Muchos estudios sobre la supervivencia en el cáncer de pulmón se refieren a subgrupos de pacientes seleccionados por diferentes criterios que suelen influir favorablemente en la estimación del pronóstico. El objetivo de este trabajo es conocer la supervivencia global de los pacientes diagnosticados en nuestro medio. Pacientes y métodos: De 694 pacientes diagnosticados de cáncer de pulmón en nuestro centro en el período 1991-1998, se incluyó en el estudio a 610 (88%) con datos de supervivencia. Se analizaron la edad, el sexo, la estirpe histológica, estadios, tumor, nódulos, metástasis (TNM), tratamiento aplicado bienio diagnóstico y su relación con la supervivencia. Resultados: Se incluyó en el estudio a 596 varones y a 14 mujeres, con una mediana de edad de 67 años. En cuanto a la estirpe del cáncer de pulmón, 141 eran microcíticos, 447 no microcíticos y 22 de otra estirpe. Se operó a 118 pacientes (19,3%). El 6,4% de los casos de cáncer de pulmón microcítico y el 40,5% de los no microcíticos recibieron sólo tratamiento sintomático. Éste fue más frecuente en mayores de 70 años (52,5%) y menos habitual durante el último bienio (1997-1998; 19%). La supervivencia a los 5 años del grupo total fue del 7,9% (del 2,8% para los microcíticos y del 9,4% para los no microcíticos). Los mayores de 70 años tuvieron peor supervivencia. Hubo diferencias significativas entre los sucesivos estadios TNM clínico, salvo entre IIIA y IIIB. Los diagnosticados en el período 1997-1998 tuvieron mejor supervivencia (un 40,8% al año y un 11,2% a los 5 años). Conclusiones: La supervivencia observada, similar a la de otros países europeos, es pobre porque la tasa de resecciones quirúrgicas es baja dado el alto porcentaje de estadios avanzado

Critical COPD respiratory illness is linked to increased transcriptomic activity of neutrophil proteases genes

Abstract Background Gene expression profiling (GEP) in cells obtained from peripheral blood has shown that this is a very useful approach for biomarker discovery and for studying molecular pathogenesis of prevalent diseases. While there is limited literature available on gene expression markers associated with Chronic Obstructive Pulmonary Disease (COPD), the transcriptomic picture associated with critical respiratory illness in this disease is not known at the present moment. Findings By using Agilent microarray chips, we have profiled gene expression signatures in the whole blood of 28 COPD patients hospitalized with different degrees of respiratory compromise.12 of them needed of admission to the ICU, whilst 16 were admitted to the Respiratory Medicine Service. GeneSpring GX 11.0 software was used for performing statistical comparisons of transcript levels between ICU and non-ICU patients. Ingenuity pathway analysis 8.5 (IPA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to select, annotate and visualize genes by function and pathway (gene ontology). T-test showed evidence of 1501 genes differentially expressed between ICU and non-ICU patients. IPA and KEGG analysis of the most representative biological functions revealed that ICU patients had increased levels of neutrophil gene transcripts, being [cathepsin G (CTSG)], [elastase, neutrophil expressed (ELANE)], [proteinase 3 (PRTN3)], [myeloperoxidase (MPO)], [cathepsin D (CTSD)], [defensin, alpha 3, neutrophil-specific (DEFA3)], azurocidin 1 (AZU1)], and [bactericidal/permeability-increasing protein (BPI)] the most representative ones. Proteins codified by these genes form part of the azurophilic granules of neutrophils and are involved in both antimicrobial defence and tissue damage. This “neutrophil signature” was paralleled by the necessity of advanced respiratory and vital support, and the presence of bacterial infection. Conclusion Study of transcriptomic signatures in blood suggests an essential role of neutrophil proteases in COPD patients with critical respiratory illness. Measurement and modulation of the expression of these genes could present an option for clinical monitoring and treatment of severe COPD exacerbations.</p