Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation

A role for WNT signalling in gastric carcinogenesis has been suggested due to two major observations. First, patients with germline mutations in adenomatous polyposis coli (APC) are susceptible to stomach polyps and second, in gastric cancer, WNT activation confers a poor prognosis. However, the functional significance of deregulated WNT signalling in gastric homoeostasis and cancer is still unclear. In this study we have addressed this by investigating the immediate effects of WNT signalling activation within the stomach epithelium. We have specifically activated the WNT signalling pathway within the mouse adult gastric epithelium via deletion of either glycogen synthase kinase 3 (GSK3) or APC or via expression of a constitutively active β-catenin protein. WNT pathway deregulation dramatically affects stomach homoeostasis at very short latencies. In the corpus, there is rapid loss of parietal cells with fundic gland polyp (FGP) formation and adenomatous change, which are similar to those observed in familial adenomatous polyposis. In the antrum, adenomas occur from 4 days post-WNT activation. Taken together, these data show a pivotal role for WNT signalling in gastric homoeostasis, FGP formation and adenomagenesis. Loss of the parietal cell population and corresponding FGP formation, an early event in gastric carcinogenesis, as well as antral adenoma formation are immediate effects of nuclear β-catenin translocation and WNT target gene expression. Furthermore, our inducible murine model will permit a better understanding of the molecular changes required to drive tumourigenesis in the stomach

How to achieve synergy between medical education and cognitive neuroscience? An exercise on prior knowledge in understanding

A major challenge in contemporary research is how to connect medical education and cognitive neuroscience and achieve synergy between these domains. Based on this starting point we discuss how this may result in a common language about learning, more educationally focused scientific inquiry, and multidisciplinary research projects. As the topic of prior knowledge in understanding plays a strategic role in both medical education and cognitive neuroscience it is used as a central element in our discussion. A critical condition for the acquisition of new knowledge is the existence of prior knowledge, which can be built in a mental model or schema. Formation of schemas is a central event in student-centered active learning, by which mental models are constructed and reconstructed. These theoretical considerations from cognitive psychology foster scientific discussions that may lead to salient issues and questions for research with cognitive neuroscience. Cognitive neuroscience attempts to understand how knowledge, insight and experience are established in the brain and to clarify their neural correlates. Recently, evidence has been obtained that new information processed by the hippocampus can be consolidated into a stable, neocortical network more rapidly if this new information fits readily into a schema. Opportunities for medical education and medical education research can be created in a fruitful dialogue within an educational multidisciplinary platform. In this synergetic setting many questions can be raised by educational scholars interested in evidence-based education that may be highly relevant for integrative research and the further development of medical education

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Interrelationship among and repeatability of seven stability indices estimated from commercial cotton (Gossypium hirsutum L.) variety evaluation trials in three Mediterranean countries

Multi-environment trial data are required, to obtain variety stability performance parameters as selection tools for effective cultivar evaluation. The interrelationship among seven stability parameters and their association with mean yield, along with the repeatability of these parameters across consecutive years was the objective of this study. Cottonseed yield data of 31 cotton cultivars, proprietary of Delta and Pine Land Co and other companies, evaluated in 20 locations over the 1999-2005 year period in Greece, Spain and Turkey were used for combined analysis of variance in four datasets. Across locations in a single evaluation year (dataset A), across locations in each of two single consecutive evaluation year (dataset B), across locations and two consecutive years (dataset C) and across locations and three consecutive years (dataset D). For each dataset, cultivar phenotypic variance (sigma(2)(p)) was appropriately partitioned in its components and the h(2) and sigma(2)(ge) component estimated. Furthermore, following the appropriate stability analysis b(i); sd(i)(2), sigma(2)(i); YS(i) and AMMI1 along with the GGE Biplot distance (GGED) and instability (GGEIN) parameters were obtained. The interrelationship among the parameters and their association with mean yield based on Spearman rank correlation was studied in each of the seven single evaluation years (dataset A). Rank correlation coefficients were also used as estimates of the repeatability of these stability parameters across consecutive year combinations (dataset B, C and D). The parameters GGED and YS(i) were consistently highly correlated with each other and mean yield in five out of seven single evaluation years. The data provided evidence that single year evaluation across locations might be sufficient to reliably rank cotton cultivars, based on mean yield along with GGED and YS(i). Combined analysis across two consecutive years (dataset C) was more effective as compared to single year evaluation. GGED was relatively more repeatable than YS(i) and mean yield in single (dataset B) and 2-year comparisons (dataset C). Although GGED is an index depended and proportional to yield, provides a superior way to integrate mean performance and stability into a single measure, which can be assessed visually on biplots. Regarding the other stability parameters, the results were contradicting and of low repeatability across single years and two consecutive years. Cultivar evaluation combined across locations in 3 years did not improve the repeatability of cultivar variance effects but resulted in very high repeatability of GGED, YS(i) and mean yield

Resource tangibility and foreign firms’ corporate political strategies in emerging economies: evidence from India

Foreign firms operating in emerging economies are increasingly exploiting and becoming dependent on locally existing intangible resources such as intellectual skills, technological know-how and reputation. Political strategies are used to absorb the external constraints associated with this external dependence. Little is known about the different types of political strategies used by foreign firms in emerging economies and the factors that determine this choice. We draw on Resource Dependence theory to argue that this choice will be influenced by the degree to which foreign firms depend on tangible vs. intangible resources. Using a sample of 105 foreign subsidiaries in India, we find that foreign firms that depend on local intangible resources are more likely to use information-based political strategies, but less likely to provide direct financial incentives to policymakers; whereas firms that depend on local tangibles are less likely to use information-based strategies. Foreign firms that depend on both tangible and intangible resources are more likely to use the constituency building strategy. Our findings enhance our understanding of the factors affecting foreign firms’ political strategy in emerging economies