A computational framework for complex disease stratification from multiple large-scale datasets.

BACKGROUND: Multilevel data integration is becoming a major area of research in systems biology. Within this area, multi-'omics datasets on complex diseases are becoming more readily available and there is a need to set standards and good practices for integrated analysis of biological, clinical and environmental data. We present a framework to plan and generate single and multi-'omics signatures of disease states. METHODS: The framework is divided into four major steps: dataset subsetting, feature filtering, 'omics-based clustering and biomarker identification. RESULTS: We illustrate the usefulness of this framework by identifying potential patient clusters based on integrated multi-'omics signatures in a publicly available ovarian cystadenocarcinoma dataset. The analysis generated a higher number of stable and clinically relevant clusters than previously reported, and enabled the generation of predictive models of patient outcomes. CONCLUSIONS: This framework will help health researchers plan and perform multi-'omics big data analyses to generate hypotheses and make sense of their rich, diverse and ever growing datasets, to enable implementation of translational P4 medicine

5-FU-induced cardiac toxicity - an underestimated problem in radiooncology?

Background 5-Fluorouracil (5-FU) is an antimetabolite, which is frequently used as chemotherapeutic agent for combined chemoradiotherapy. The purpose of this study was to present the clinical course of three patients who developed severe cardiac toxicity by 5-FU and to give a review of the literature on the cardiotoxic potential of 5-FU. Results Cardiotoxicity is a rare, but relevant side effect of fluoropyrimidines. It comprehends a wide spectrum of side effects, from electrocardiogram changes (69% of cardiac events) to myocardial infarction (22%) and cardiogenic shock (1%). In this case series three patients with cardiotoxic events during chemoradiotherapy including 5-FU, the reaction's characteristics and their influence on further therapy are described. Two of the patients could not be treated with 5-FU any more because they had developed a myocardial ischemia, which was most likely caused by fluorouracil. Another patient, who complained about typical angina pectoris during 5-FU-infusion and had a new left anterior hemiblock, was reexposed with prophylactic administration of nitrendipine. Conclusion Cardiotoxicity caused by 5-FU is an underestimated problem in radiooncology. Especially patients without history of cardiac disease are often treated as out-patients and therefore without cardiac monitoring. Consequently asymptomatic and symptomatic cardiac events may be overlooked. The benefit of prophylactic agents remains unclear, so close cardiac monitoring is the most established method to prevent manifest cardiotoxic events

Ongoing and Emerging Questions in Water Erosion Studies

51 Pags.- 9 Figs. The definitive version is available at: http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1099-145XSoil erosion is a threat to food security, especially in regions where the area of arable land is shrinking dramatically because of soil degradation. Research on soil erosion expanded progressively throughout the 20th centu\ry, although a number of unresolved problems persist despite this issue being crucial for the environment and the welfare of society. Some basic unresolved issues, including the absence of a universally accepted definition of soil erosion and disagreement about how to measure it have contributed to a degree of scientific stagnation. Accurate prediction of the response of soils to disturbance is hampered by the dependence of the erosion process on the spatial scale involved, the time lag between the disturbance and the erosion response and the short periods for which data are typically available. We argue that devoting increased attention to the following environmental, demographic, political and societal issues will reinvigorate progress in the field. (i) The relationships between on-site and off-site consequences of soil erosion need to be elucidated if the economic and environmental costs are to be adequately assessed. (ii) Effective measures for soil conservation need to focus on spatial patterns of plant cover that reduce sediment connectivity, and most importantly on the relationships between hillslopes and sediment transfer in eroded channels. (iii) The scientific community must be able to identify early warning signs of critical transitions, if irreversible soil degradation is to be prevented. (iv) Consensus needs to be reached concerning the contribution of soil erosion to the carbon cycle. (v) The consequences of climate change on erosion and sediment transport should be investigated in depth. (vi) The general society needs to perceive soil erosion as a critical matter requiring an urgent response.This research was supported by the projects ESPAS (CGL2015-65569-R) and INDICA (CGL2011-27753-C02-01 and 02) (MINECO/FEDER). The research groups on “Geomorphology and Global Change” and “Climate, Water, Global Change and Natural Systems” were financed by the Aragón Government and the European Social Fund (ESF). E. Nadal-Romero was the recipient of a “Ramón y Cajal” postdoctoral contract (Spanish Ministry of Economy and Competitiveness). The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement no 603498 (RECARE project).Peer reviewe