To what extent and in what manner do Chinese and Indian contract research organisation learn and upgrade with the unbundling the global pharmaceutical R&D value chain?

The paper applies the GVC framework to analyse the organisational and geographical reconfiguration of the global R&D function of leading US and European pharmaceutical MNCs. Though pharmaceutical MNCs have been outsourcing clinical trial activities since the mid-1990s, the outsourcing of discovery research tasks is a phenomenon of the 2000s (Ramirez 2013). Moreover, in the context of a crisis of R&D productivity and increasing pressure from shareholders, a number of US and European pharmaceutical MNCs are breaking up their R&D function in an attempt to increase flexibility and reduce risk as well as costs and are thereby restructuring the global architecture of their R&D function. This break-up, or unbundling (Sako 2006), of the R&D function is particularly interesting given the prevalence of market failure in innovation (Howells et al 2008), the non-modular nature of the R&D process in this industry (Pisano 2006) and the strategic important of this activity to the core competence and long-term competitive advantage of firms in this sector. The focus of this paper is on the outsourcing of R&D activities to Chinese and Indian independently-owned contract research organisations (CROs) and the way these firms are becoming integrated as service providers into the global R&D function (or R&D value chain) of pharmaceutical MNCs. Above all the paper is concerned with the development of capabilities of CROs from these two countries and the dynamics of upgrading in GVCs in knowledge-intensive functions. The paper therefore discusses the role of both knowledge flows within global pharmaceutical R&D value chains as well as national innovation systems on the development of capabilities of Chinese and Indian CROs. Our analysis is based on data from semi-structured interviews collected from senior R&D managers from a sample of ten US and European pharmaceutical MNCs and owners and senior R&D managers from five Chinese and five Indian CROs who are providing research services to MNCs in this industry. We discuss the emergence of R&D outsourcing in this industry and the nature and mechanisms of knowledge flows within R&D value chains. The embeddedness of CROS in the national innovation systems of their home countries is also discussed.

2-D R-matrix propagation: A large scale electron scattering simulation dominated by the multiplication of dynamically changing matrices

We examine the computational aspects of propagating a global R-matrix, R, across sub-regions in a 2-D plane. This problem originates in the large scale simulation of electron collisions with atoms and ions at intermediate energies. The propagation is dominated by matrix multiplications which are complicated because of the dynamic nature of R, which changes the designations of its rows and columns and grows in size as the propagation proceeds. The use of PBLAS to solve this problem on distributed memory HPC machines is the main focus of the paper.

Estimativa da irradiação solar global com partição mensal e sazonal para a região de Cascavel - PR

No presente trabalho, mostram-se equações de estimativa da irradiação solar global (R G), por meio do modelo de Angstrom, com partições sazonal e mensal para a região de Cascavel - PR. Os dados experimentais foram cedidos pelo IAPAR, coletados na sua estação meteorológica localizada na COODETEC/Cascavel - PR, no período de 1983 a 1998. Dos 16 anos de dados, 12 anos foram utilizados para cálculo dos coeficientes (a e b) e quatro anos para a validação das equações. Os coeficientes de determinação encontrados foram superiores a 80% para as duas partições. O mínimo da R G é superestimado e o máximo é subestimado quando comparados com o mínimo e o máximo para dados reais, sendo esses encontrados no solstício de inverno e equinócio de primavera, respectivamente. A variação sazonal e mensal do coeficiente a foi menor (0,16 a 0,19 e 0,14 a 0,21) e do coeficiente b maior (0,34 a 0,43 e 0,32 a 0,44). As maiores variações dos erros médios diários ocorreram no equinócio de primavera (-19,45% a 27,28%) e as menores no equinócio de outono (-11,32% a 10,61%). O ajuste mais eficaz das equações foi encontrado para a partição mensal.

Absorptive capacity and the benefits from global reservoirs of knowledge:evidence from a linked China-OECD dataset

This paper investigates the role of absorptive capacity in the diffusion of global technology with sector and firm heterogeneity. We construct the FDI-intensity weighted global R&D stock for each industry and link it to Chinese firm-level panel data relating to 53,981 firms over the period 2001-2005. Non-parametric frontier analysis is employed to explore how absorptive capacity affects technical change and catch-up in the presence of global knowledge spillovers. We find that R&D activities and training at individual firms serve as an effective source of absorptive capability. The contribution of absorptive capacity varies according to the type of FDI and the extent of openness.

Consequences of Corymbia (Myrtaceae) hybridisation on leaf-oil profiles

The present study examines patterns of heritability of plant secondary metabolites following hybridisation among three genetically homogeneous taxa of spotted gum (Corymbia henryi (S.T.Blake) K.D.Hill & L.A.S.Johnson, C. citriodora subsp. variegata (F.Muell.) K.D.Hill & L.A.S.Johnson and C. citriodora (Hook.) K.D.Hill & L.A.S.Johnson subsp. citriodora (section Maculatae), and their congener C. torelliana (F.Muell.) K.D.Hill & L.A.S.Johnson (section Torellianae)). Hexane extracts of leaves of all four parent taxa were statistically distinguishable (ANOSIM: global R = 0.976, P = 0.008). Hybridisation patterns varied among the taxa studied, with the hybrid formed with C. citriodora subsp. variegata showing an intermediate extractive profile between its parents, whereas the profiles of the other two hybrids were dominated by that of C. torelliana. These different patterns in plant secondary-metabolite inheritance may have implications for a range of plant-insect interactions.

Plantations, not farmlands, cause biotic homogenisation of ground-active beetles in South-Eastern Australia

Following landscape change, species invasions and extinctions may lead to biotic homogenisation, resulting in increased taxonomic and functional similarity between previously distinct biotas. Biotic homogenisation is more likely to occur in landscapes where the matrix contrasts strongly with native vegetation patches. To test this, we examined the distribution of ground-active beetles in a landscape of remnant Eucalyptus open woodland patches where large areas of lower contrast matrix (farmland) are being transformed to high-contrast pine plantations in south-eastern Australia. We sampled beetles from 30 sites including six replicates of five categories; (1) remnants adjacent to farmland, (2) remnants adjacent to plantation, (3) farmland, (4) plantation, and, (5) remnants between pine plantation and farmland. Community composition in the pine matrix was similar to native patches embedded in pine (ANOSIM, Global R=. 0.49, P<. 0.000), which we suggest is due to biotic homogenisation. Remnant patches with edges of both farmland and pine plantation did not represent an intermediate community composition between patches surrounded by either matrix type, but rather a unique habitat with unique species. Farmland supported the greatest number of individuals (. F=. 9.049, df. =. 25, P<. 0.000) and species (. F=. 5.875, df. =. 25, P=. 0.002), even compared to native remnant patches. Our results suggest that matrix transformations can reduce species richness and homogenise within-patch populations. This may increase the risk of species declines in fragmented landscapes where plantations are not only replacing native vegetation patches, but also other matrix types that may better support biodiversity. Our findings are particularly concerning given expanding plantation establishment worldwide.

Correlação entre torque, equlíbrio e função do joelho após reconstrução do LCA

Background: Several studies emphasize the importance of assessing the knee function after anterior cruciate ligament (ACL) reconstruction. The influence of several variables on the function of these patients has been analyzed, but there is no consensus in the science literature. Purpose: To evaluate the correlation between the torque and balance on the knee function after ACL reconstruction. Methods: 23 males patients with ACL reconstruction were tested. The procedures of the study included analysis of concentric peak torque at 60o/s and 180o/s of quadriceps femoris and hamstring muscle with a isokinetic dynamometer. The balance in single-limb stance was measured with stabilometry. The functional performance were performed by two hop tests. To estimate the subjective function of the patients was applied Lysholm Knee Scoring Scale and a Global Rating scale. Results: The analysis of data showed a moderate positive correlation between knee extensor torque and functional performance tests (r= 0,48; p=0,02). A moderate negative correlation was found between the two variables of the stabilometry center of pressure and average speed of centre of pressure and the Global Rating scale (r = -0.4, p = 0,04 and r = -0,49, p = 0 ,02, respectively). No correlation was found between peak torque and balance in single-limb stance. Conclusion: The results of the present study suggest that knee extensor strength and postural balance have some influence on knee function in patients after ACL reconstruction

Simulação do saldo de radiação na Serra da Mantiqueira

A influência do desmatamento da Mata Atlântica sobre o microclima da Serra da Mantiqueira ainda não é totalmente compreendida. Para conhecer as consequências do desmatamento sobre o clima serrano é necessário realizar estudos sobre o balanço de radiação na superfície. A falta de dados possibilita conjugar imagens de satélite com dados meteorológicos em um Sistema de Informação Geográfica na determinação do balanço de radiação. O presente estudo teve por objetivo avaliar o modelo MTCLIM em dias de céu claro ou nublado para simular o balanço de radiação na Serra da Mantiqueira, divisa entre os estados de São Paulo, Minas Gerais e Rio de Janeiro, Brasil. Imagens diárias, semanais e dezesseis dias do sensor MODIS disponíveis em 2003 foram utilizadas em rotinas específicas do MTCLIM. Alvos específicos foram selecionados para avaliar o comportamento do balanço de radiação. Observou-se que o balanço de radiação acompanhou a topografia local e é influenciado pelo tipo de uso da terra. Conclui-se que a temperatura da superfície contribui para aumentar a temperatura do ar implicando em diminuição do balanço de radiação sobre pastagem. O modelo MTCLIM demonstrou boa correlação para a temperatura do ar (R² = 0,82) e para a radiação solar global (R² = 0,71).

Anticancer drug screening from images of zebrafish embryogenesis

During the previous 10 years, global R&D expenditure in the pharmaceuticals and biotechnology sector has steadily increased, without a corresponding increase in output of new medicines. To address this situation, the biopharmaceutical industry's greatest need is to predict the failures at the earliest possible stage of the drug development process. A major key to reducing failures in drug screenings is the development and use of preclinical models that are more predictive of efficacy and safety in clinical trials. Further, relevant animal models are needed to allow a wider testing of novel hypotheses. Key to this is the developing, refining, and validating of complex animal models that directly link therapeutic targets to the phenotype of disease, allowing earlier prediction of human response to medicines and identification of safety biomarkers. Morehover, well-designed animal studies are essential to bridge the gap between test in cell cultures and people. Zebrafish is emerging, complementary to other models, as a powerful system for cancer studies and drugs discovery. We aim to investigate this research area designing a new preclinical cancer model based on the in vivo imaging of zebrafish embryogenesis. Technological advances in imaging have made it feasible to acquire nondestructive in vivo images of fluorescently labeled structures, such as cell nuclei and membranes, throughout early Zebrafishsh embryogenesis. This In vivo image-based investigation provides measurements for a large number of features at cellular level and events including nuclei movements, cells counting, and mitosis detection, thereby enabling the estimation of more significant parameters such as proliferation rate, highly relevant for investigating anticancer drug effects. In this work, we designed a standardized procedure for accessing drug activity at the cellular level in live zebrafish embryos. The procedure includes methodologies and tools that combine imaging and fully automated measurements of embryonic cell proliferation rate. We achieved proliferation rate estimation through the automatic classification and density measurement of epithelial enveloping layer and deep layer cells. Automatic embryonic cells classification provides the bases to measure the variability of relevant parameters, such as cell density, in different classes of cells and is finalized to the estimation of efficacy and selectivity of anticancer drugs. Through these methodologies we were able to evaluate and to measure in vivo the therapeutic potential and overall toxicity of Dbait and Irinotecan anticancer molecules. Results achieved on these anticancer molecules are presented and discussed; furthermore, extensive accuracy measurements are provided to investigate the robustness of the proposed procedure. Altogether, these observations indicate that zebrafish embryo can be a useful and cost-effective alternative to some mammalian models for the preclinical test of anticancer drugs and it might also provides, in the near future, opportunities to accelerate the process of drug discovery.

Seawater carbonate chemistry and Strongylocentrotus purpuratus body length and gene expression pattern changes during experiments, 2011

Extensive use of fossil fuels is leading to increasing CO2 concentrations in the atmosphere and causes changes in the carbonate chemistry of the oceans which represents a major sink for anthropogenic CO2. As a result, the oceans' surface pH is expected to decrease by ca. 0.4 units by the year 2100, a major change with potentially negative consequences for some marine species. Because of their carbonate skeleton, sea urchins and their larval stages are regarded as likely to be one of the more sensitive taxa. In order to investigate sensitivity of pre-feeding (2 days post-fertilization) and feeding (4 and 7 days post-fertilization) pluteus larvae, we raised Strongylocentrotus purpuratus embryos in control (pH 8.1 and pCO2 41 Pa e.g. 399 µatm) and CO2 acidified seawater with pH of 7.7 (pCO2 134 Pa e.g. 1318 µatm) and investigated growth, calcification and survival. At three time points (day 2, day 4 and day 7 post-fertilization), we measured the expression of 26 representative genes important for metabolism, calcification and ion regulation using RT-qPCR. After one week of development, we observed a significant difference in growth. Maximum differences in size were detected at day 4 (ca. 10 % reduction in body length). A comparison of gene expression patterns using PCA and ANOSIM clearly distinguished between the different age groups (Two way ANOSIM: Global R = 1) while acidification effects were less pronounced (Global R = 0.518). Significant differences in gene expression patterns (ANOSIM R = 0.938, SIMPER: 4.3% difference) were also detected at day 4 leading to the hypothesis that differences between CO2 treatments could reflect patterns of expression seen in control experiments of a younger larva and thus a developmental artifact rather than a direct CO2 effect. We found an up regulation of metabolic genes (between 10 to 20% in ATP-synthase, citrate synthase, pyruvate kinase and thiolase at day 4) and down regulation of calcification related genes (between 23 and 36% in msp130, SM30B, SM50 at day 4). Ion regulation was mainly impacted by up regulation of Na+/K+-ATPase at day 4 (15%) and down regulation of NHE3 at day 4 (45%). We conclude that in studies in which a stressor induces an alteration in the speed of development, it is crucial to employ experimental designs with a high time resolution in order to correct for developmental artifacts. This helps prevent misinterpretation of stressor effects on organism physiology.

Evaluación de persuasión coercitiva en contextos grupales

La persuasión coercitiva es un subtipo de persuasión, una modalidad de influencia caracterizada por la aplicación de estrategias abusivas. Su aplicación implica una agresión, en ocasiones sumamente sutil, que combina técnicas ambientales, emocionales, cognitivas y disociativas, alterando la capacidad crítica de quien la recibe y generando, habitualmente, importantes daños psicológicos y desajustes sociales. Los grupos coercitivos, entre ellos las sectas destructivas, se caracterizan por aplicar estas técnicas con una elevada reiteración, persistencia e intensidad. Estas técnicas suelen aplicarse de forma planificada y engañosa; su graduación dificulta que las personas que la reciben detecten la agresividad y el perjuicio que conllevan. Resulta necesario definir clara y objetivamente qué acciones, actitudes y estrategias resultan manipulativas y a partir de qué grado o intensidad podría considerarse que un determinado grupo aplica, sistemáticamente, persuasión coercitiva. Si es patente la escasez de instrumentos de medición del abuso psicológico en diferentes ámbitos (violencia en pareja, acoso laboral, acoso escolar, etc.), aún menor ha sido el desarrollo de herramientas que valoren la presencia de estrategias coercitivas o abusivas en contextos grupales. En tanto que la aplicación de estas estrategias puede derivar en graves consecuencias psicosociales, resulta necesario el desarrollo de instrumentos que puedan resultar de utilidad en contextos clínicos y forenses. El objetivo principal de esta tesis es desarrollar y validar nuevas herramientas de evaluación de persuasión coercitiva en contextos grupales, para lo que se llevaron a cabo dos estudios empíricos: 1) Validación de la Entrevista de Evaluación de Persuasión Coercitiva (EPC). Recoge una amplia gama de coerciones y abusos desarrollados en contextos grupales manipulativos, consta de 66 preguntas con dos secciones de evaluación. La principal, con 61 preguntas, recoge 17 técnicas de persuasión coercitiva, dentro de cuatro subtipos de persuasión coercitiva: ambiental, emocional, cognitiva y disociativa (Cuevas y Canto, 2006). Se emplearon dos procedimientos para examinar su validez de contenido, los cuales aportaron resultados positivos. En primer lugar, la proporción de acuerdo (pa = 0,87), que mostró una concordancia muy relevante entre los 191 evaluadores que participaron. El análisis ítem a ítem mostró la conveniencia de no eliminar ninguna de las preguntas. En segundo lugar, la kappa de Fleiss, que suprime el efecto atribuible al azar (k = 0,57; k = 0,61 si se obvia uno de los diez casos clínicos valorados), sugiere un acuerdo entre moderado y bueno. 2) Diseño y validación de la Escala de Detección de Persuasión Coercitiva (EDPC). A partir de la validación de la entrevista anterior se diseñó esta escala, en una versión inicial de 50 ítems. Se analizaron sus propiedades psicométricas, que fueron también satisfactorias. Su fiabilidad, como consistencia interna, fue examinada con el Alfa de Cronbach estandarizado, resultando ser muy alta para su versión de 50 ítems (α =0,93), y aún mejor para la versión final propuesta de 40 ítems (α =0,97). Se analizó la distribución de las puntuaciones, concluyendo la no normalidad de su distribución, así como su estructura interna factorial, concluyendo la presencia de un factor: persuasión coercitiva. En cuanto a su validez, se examinó la validez convergente con la escala de Abuso Psicológico Grupal (GPA, Chambers, Langone, Dole y Grice, 1994), que mide abuso psicológico; las correlaciones fueron muy elevadas y significativas (p<0,01), especialmente con respecto a su escala global (r = 0,77**). También se examinó su validez de criterio o predictiva con distintas herramientas de ajuste psicológico, correlacionando positivamente de forma elevada, o moderadamente, con algunas escalas o subescalas relacionadas con ideación paranoide, eventos vitales estresantes, cogniciones postraumáticas, etc. En definitiva, se valida la entrevista EPC y se diseña y valida una nueva escala, la EDPC. Dos herramientas que se validan en población española, con unas adecuadas propiedades psicométricas, que pueden resultar de gran utilidad en el ámbito clínico y forense, con objeto de valorar el control y la manipulación ejercidas en contextos grupales. Utilizar este tipo de herramienta resulta relevante para poder constatar la responsabilidad de los grupos coercitivos, facilitando relacionar los daños valorados en las víctimas, con las acciones concretas desarrolladas por grupos, o personas, que llevan a cabo comportamientos abusivos. Referencias Bibliográficas: Chambers, W.V., Langone, M.D., Dole, A.A.y Grice, J.W. (1994). The Group Psychological Abuse Scale: A Measure of the Varieties of Cultic Abuse. Cultic Studies Journal, 11, 88-117. Cuevas, J.M. y Canto, J.M. (2006). Sectas: cómo funcionan, cómo son sus líderes, efectos destructivos y cómo combatirlas. Málaga: Aljibe.

25 years of knowledge creation processes in pharmaceutical contemporary trends

The pharmaceutical industry is knowledge and research-intensive. Due to technological, socio-political and organisational changes there has been a continuous evolution in the knowledge base utilized to achieve and maintain competitive advantages in this global industry. There is a gap in analysing the linkages and effects of those changes on knowledge creation processes associated with pharmaceutical R&D activities. Our paper looks to fill this gap. We built on an idiosyncratic research approach – the systematic literature review – and looked to unearth current trends affecting knowledge creation in international/global pharmaceutical R&D. We reviewed scientific papers published between 1980 and 2005. Key findings include promising trends in pharmaceutical innovation and human resource management, and their potential implications on current R&D practices within the pharmaceutical industry, from managerial and policy-making perspectives.

Conceptos y prácticas de la actividad física que se reproducen en las clases sociales: aproximación desde el enfoque determinantes/ determinación social de la salud

El concepto de actividad física es concebido de diferentes formas. Mostrando que existen varios factores que afectan de manera directa e indirecta la percepción que los sujetos construyen entorno a él, generando así una aproximación a diferentes definiciones de la actividad física desde varias perspectivas y dimensiones, donde predomina una noción netamente biológica. Este estudio pretende analizar, como desde las clases sociales se concibe la actividad física en sus conceptos y prácticas considerando los modelos de determinantes y determinación social para la salud. Con fin de comprender como los autores de la literatura científica conciben la actividad física y la relación con las clases sociales, desde una perspectiva teórica de los determinantes sociales de la salud y la teoría de la determinación social, se realizó una revisión documental y análisis de contenido de los conceptos y prácticas de la actividad física que se han considerado en los últimos 10 años. Para ello se seleccionaron las bases de datos PubMed y BVS (Biblioteca Virtual de Salud) por sus énfasis en publicaciones de salud mundialmente. Mostrando que la actividad física es concebida dominantemente desde una perspectiva biológica que ejerce una mirada reduccionista. Las relaciones entre actividad física y las clases sociales están claramente establecidas, sin embargo, estas relaciones pueden discrepar teniendo en cuenta el concepto de clase social, el contexto y la orientación de los autores y las poblaciones objetos de estudio. Obteniendo como resultado que los estudios documentados, revisados y analizados muestran una clara tendencia al modelo de determinantes; no obstante, algunos estudios en sus análisis se orientan hacia el modelo de determinación social. En cuanto al concepto de clases sociales los autores consideran una combinación de factores culturales y económicos sin atreverse a adoptar un concepto específico.

How innovation and R&D happen in the upstream oil & gas industry : insights from a global survey

Few would disagree that the upstream oil & gas industry has become more technology-intensive over the years. But how does innovation happen in the industry? Specifically, what ideas and inputs flow from which parts of the sector׳s value network, and where do these inputs go? And how do firms and organizations from different countries contribute differently to this process? This paper puts forward the results of a survey designed to shed light on these questions. Carried out in collaboration with the Society of Petroleum Engineers (SPE), the survey was sent to 469 executives and senior managers who played a significant role with regard to R&D and/or technology deployment in their respective business units. A total of 199 responses were received from a broad range of organizations and countries around the world. Several interesting themes and trends emerge from the results, including: (1) service companies tend to file considerably more patents per innovation than other types of organization; (2) over 63% of the deployed innovations reported in the survey originated in service companies; (3) neither universities nor government-led research organizations were considered to be valuable sources of new information and knowledge in the industry׳s R&D initiatives, and; (4) despite the increasing degree of globalization in the marketplace, the USA still plays an extremely dominant role in the industry׳s overall R&D and technology deployment activities. By providing a detailed and objective snapshot of how innovation happens in the upstream oil & gas sector, this paper provides a valuable foundation for future investigations and discussions aimed at improving how R&D and technology deployment are managed within the industry. The methodology did result in a coverage bias within the survey, however, and the limitations arising from this are explored.