338 resultados para Miettinen, Tarmo
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According to what Robert Koch termed the etiological standpoint, illnesses are best understood and controlled by focusing on their causes, including in their definitions and, thus, in the construction of their taxonomies. In some ways flawed, this standpoint has been misunderstood and misapplied. A taxonomy based solely on etiology was an unrealistic dream in the context of 'the bacteriological revolution', and it also is unrealistic in the present context of 'the genetic revolution.' We argue that the illnesses in a taxonomy of them are in some cases best defined directly in terms of their respective somatic anomalies, in some others indirectly by the unique and universal etiology of that anomaly (left unspecified) in a 'deeper' somatic anomaly, and in yet others as a combination of these; and when the somatic anomaly for direct definition remains unknown, it is to be defined indirectly by the clinical syndrome that is its patient-relevant manifestation, possibly in conjunction with a somatic cause. We note, also, that these taxonomic issues have no material bearing on epidemiologists' etiologic research for the knowledge base of community-level preventive medicine.
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The receptor tyrosine kinase Tie2, and its activating ligand Angiopoietin-1 (Ang1), are required for vascular remodelling and vessel integrity, whereas Ang2 may counteract these functions. However, it is not known how Tie2 transduces these different signals. Here, we show that Ang1 induces unique Tie2 complexes in mobile and confluent endothelial cells. Matrix-bound Ang1 induced cell adhesion, motility and Tie2 activation in cell-matrix contacts that became translocated to the trailing edge in migrating endothelial cells. In contrast, in contacting cells Ang1 induced Tie2 translocation to cell-cell contacts and the formation of homotypic Tie2-Tie2 trans-associated complexes that included the vascular endothelial phosphotyrosine phosphatase, leading to inhibition of paracellular permeability. Distinct signalling proteins were preferentially activated by Tie2 in the cell-matrix and cell-cell contacts, where Ang2 inhibited Ang1-induced Tie2 activation. This novel type of cellular microenvironment-dependent receptor tyrosine kinase activation may explain some of the effects of angiopoietins in angiogenesis and vessel stabilization.
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This paper presents an overview of the Mobile Data Challenge (MDC), a large-scale research initiative aimed at generating innovations around smartphone-based research, as well as community-based evaluation of mobile data analysis methodologies. First, we review the Lausanne Data Collection Campaign (LDCC), an initiative to collect unique longitudinal smartphone dataset for the MDC. Then, we introduce the Open and Dedicated Tracks of the MDC, describe the specific datasets used in each of them, discuss the key design and implementation aspects introduced in order to generate privacy-preserving and scientifically relevant mobile data resources for wider use by the research community, and summarize the main research trends found among the 100+ challenge submissions. We finalize by discussing the main lessons learned from the participation of several hundred researchers worldwide in the MDC Tracks.
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OBJECTIVES This study sought to determine whether high intestinal cholesterol absorption represents a cardiovascular risk factor and to link ABCG8 and ABO variants to cardiovascular disease (CVD). BACKGROUND Plant sterol-enriched functional foods are widely used for cholesterol lowering. Their regular intake yields a 2-fold increase in circulating plant sterol levels that equally represent markers of cholesterol absorption. Variants in ABCG8 and ABO have been associated with circulating plant sterol levels and CVD, thereby suggesting atherogenic effects of plant sterols or of cholesterol uptake. METHODS The cholestanol-to-cholesterol ratio (CR) was used as an estimate of cholesterol absorption because it is independent of plant sterols. First, we investigated the associations of 6 single nucleotide polymorphisms in ABCG8 and ABO with CR in the LURIC (LUdwisghafen RIsk and Cardiovascular health study) and the YFS (Young Finns Study) cohorts. Second, we conducted a systematic review and meta-analysis to investigate whether CR might be related to CVD. RESULTS In LURIC, the minor alleles of rs4245791 and rs4299376 and the major alleles of rs41360247, rs6576629, and rs4953023 of the ABCG8 gene and the minor allele of rs657152 of the ABO gene were significantly associated with higher CR. Consistent results were obtained for rs4245791, rs4299376, rs6576629, and rs4953023 in YFS. The meta-analysis, including 6 studies and 4,362 individuals, found that CR was significantly increased in individuals with CVD. CONCLUSIONS High cholesterol absorption is associated with risk alleles in ABCG8 and ABO and with CVD. Harm caused by elevated cholesterol absorption rather than by plant sterols may therefore mediate the relationships of ABCG8 and ABO variants with CVD.
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This study describes detailed partitioning of phytomass carbon (C) and soil organic carbon (SOC) for four study areas in discontinuous permafrost terrain, Northeast European Russia. The mean aboveground phytomass C storage is 0.7 kg C/m**2. Estimated landscape SOC storage in the four areas varies between 34.5 and 47.0 kg C/m**2 with LCC (land cover classification) upscaling and 32.5-49.0 kg C/m**2 with soil map upscaling. A nested upscaling approach using a Landsat thematic mapper land cover classification for the surrounding region provides estimates within 5 ± 5% of the local high-resolution estimates. Permafrost peat plateaus hold the majority of total and frozen SOC, especially in the more southern study areas. Burying of SOC through cryoturbation of O- or A-horizons contributes between 1% and 16% (mean 5%) of total landscape SOC. The effect of active layer deepening and thermokarst expansion on SOC remobilization is modeled for one of the four areas. The active layer thickness dynamics from 1980 to 2099 is modeled using a transient spatially distributed permafrost model and lateral expansion of peat plateau thermokarst lakes is simulated using geographic information system analyses. Active layer deepening is expected to increase the proportion of SOC affected by seasonal thawing from 29% to 58%. A lateral expansion of 30 m would increase the amount of SOC stored in thermokarst lakes/fens from 2% to 22% of all SOC. By the end of this century, active layer deepening will likely affect more SOC than thermokarst expansion, but the SOC stores vulnerable to thermokarst are less decomposed.
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Objectives: To investigate whether baseline serum cholestanol:cholesterol ratio, which is negatively related to cholesterol synthesis, could predict reduction of coronary events in the Scandinavian simvastatin survival study.
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In this paper we propose a new identification method based on the residual white noise autoregressive criterion (Pukkila et al. , 1990) to select the order of VARMA structures. Results from extensive simulation experiments based on different model structures with varying number of observations and number of component series are used to demonstrate the performance of this new procedure. We also use economic and business data to compare the model structures selected by this order selection method with those identified in other published studies.
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Biological wastewater treatment is a complex, multivariate process, in which a number of physical and biological processes occur simultaneously. In this study, principal component analysis (PCA) and parallel factor analysis (PARAFAC) were used to profile and characterise Lagoon 115E, a multistage biological lagoon treatment system at Melbourne Water's Western Treatment Plant (WTP) in Melbourne, Australia. In this study, the objective was to increase our understanding of the multivariate processes taking place in the lagoon. The data used in the study span a 7-year period during which samples were collected as often as weekly from the ponds of Lagoon 115E and subjected to analysis. The resulting database, involving 19 chemical and physical variables, was studied using the multivariate data analysis methods PCA and PARAFAC. With these methods, alterations in the state of the wastewater due to intrinsic and extrinsic factors could be discerned. The methods were effective in illustrating and visually representing the complex purification stages and cyclic changes occurring along the lagoon system. The two methods proved complementary, with each having its own beneficial features. (C) 2003 Elsevier B.V. All rights reserved.