Intracardiac thrombus formation after the Fontan operation

AbstractObjectives: Intracardiac thrombus formation is suspected to be a specific sequela after the Fontan operation and is difficult to determine by means of routine transthoracic echocardiography. The aim of our study was to evaluate the occurrence of intracardiac thrombi in the different types of Fontan modifications and to identify predisposing risk factors. Methods: We evaluated 52 patients who had undergone a Fontan-type operation and were free of symptoms regarding thrombosis as determined by transesophageal echocardiography. Results: In 17 (33%) patients thrombus formation could be found without clinical evidence of thromboembolic complications. Neither underlying morphologic disease nor age at operation, type of Fontan operation, sex, follow-up interval, arrhythmias, or laboratory or hemodynamic findings could be identified as predisposing risk factors. Conclusion: In patients having had a Fontan operation with inadequate or without anticoagulation medication, we would recommend routine transesophageal echocardiography to exclude eventual thrombi. Because of the high incidence of thrombi, we suggest oral anticoagulation therapy in all patients. (J Thorac Cardiovasc Surg 2000;119:745-52

The Future of Sovereign Borrowing in Europe

In March 2013 around 130 participants from academia, banking and finance, governments and central banking gathered at the premises of the OeNB in Vienna for a conference jointly organized by the European Money and Finance Forum SUERF, the OeNB and the Austrian Society for Bank Research to discuss “The Future of Sovereign Borrowing.” The financial, economic and sovereign debt crisis has fundamentally changed the rules of the game in sovereign debt markets, particularly in the euro area, but also beyond its borders. Sovereign bonds are no longer widely perceived as ‘risk-free’ assets. Even the sovereign bonds of safe-haven countries have come under close scrutiny or lost some of their prime ratings. Yet crisis countries have seen dramatic downgrades of their sovereign debt ratings so that they face soaring risk spreads and unsustainably high financing costs (or even a loss of access to bond market financing), pushing them towards shorter financing or forcing them to rely on financial support from other countries and the international community or massive intervention by central banks

New Paradigms in Banking, Financial Markets and Regulation?

On May 11-12, 2011, SUERF, the Belgian Financial Forum, the Brussels Finance Institute and the Centre for European Policy Studies (CEPS) jointly organised the 29th SUERF Colloquium New paradigms in money and finance? The papers included in this SUERF Study are based on contributions to the Colloquium. The 2008-11 financial crisis has demonstrated unsatisfactory performance in financial institutions and in financial regulation and supervision all over the world. The contributors to the present volume look with critical eyes on financial theories, supervisory structures, (mis)pricing of risk and distorted incentives, risk management models and procedures, conflicts of interest and bank strategies. Their perspectives are quite different, but they share the ambition of finding improved analytical, organizational or managerial approaches so that decisionmakers have a better chance of showing good performance in the future. In essence, they are looking for new paradigms in banking, financial markets and regulation

Large-scale validation of miRNAs by disease association, evolutionary conservation and pathway activity.

The validation of microRNAs (miRNAs) identified by next generation sequencing involves amplification-free and hybridization-based detection of transcripts as criteria for confirming valid miRNAs. Since respective validation is frequently not performed, miRNA repositories likely still contain a substantial fraction of false positive candidates while true miRNAs are not stored in the repositories yet. Especially if downstream analyses are performed with these candidates (e.g. target or pathway prediction), the results may be misleading. In the present study, we evaluated 558 mature miRNAs from miRBase and 1,709 miRNA candidates from next generation sequencing experiments by amplification-free hybridization and investigated their distributions in patients with various disease conditions. Notably, the most significant miRNAs in diseases are often not contained in the miRBase. However, these candidates are evolutionary highly conserved. From the expression patterns, target gene and pathway analyses and evolutionary conservation analyses, we were able to shed light on the complexity of miRNAs in humans. Our data also highlight that a more thorough validation of miRNAs identified by next generation sequencing is required. The results are available in miRCarta ( https://mircarta.cs.uni-saarland.de )

A comprehensive and comparative phenotypic analysis of the collaborative founder strains identifies new and known phenotypes

The collaborative cross (CC) is a large panel of mouse-inbred lines derived from eight founder strains (NOD/ShiLtJ, NZO/HILtJ, A/J, C57BL/6J, 129S1/SvImJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ). Here, we performed a comprehensive and comparative phenotyping screening to identify phenotypic differences and similarities between the eight founder strains. In total, more than 300 parameters including allergy, behavior, cardiovascular, clinical blood chemistry, dysmorphology, bone and cartilage, energy metabolism, eye and vision, immunology, lung function, neurology, nociception, and pathology were analyzed;in most traits from sixteen females and sixteen males. We identified over 270 parameters that were significantly different between strains. This study highlights the value of the founder and CC strains for phenotype-genotype associations of many genetic traits that are highly relevant to human diseases. All data described here are publicly available from the mouse phenome database for analyses and downloads

A comprehensive and comparative phenotypic analysis of the collaborative founder strains identifies new and known phenotypes.

The collaborative cross (CC) is a large panel of mouse-inbred lines derived from eight founder strains (NOD/ShiLtJ, NZO/HILtJ, A/J, C57BL/6J, 129S1/SvImJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ). Here, we performed a comprehensive and comparative phenotyping screening to identify phenotypic differences and similarities between the eight founder strains. In total, more than 300 parameters including allergy, behavior, cardiovascular, clinical blood chemistry, dysmorphology, bone and cartilage, energy metabolism, eye and vision, immunology, lung function, neurology, nociception, and pathology were analyzed; in most traits from sixteen females and sixteen males. We identified over 270 parameters that were significantly different between strains. This study highlights the value of the founder and CC strains for phenotype-genotype associations of many genetic traits that are highly relevant to human diseases. All data described here are publicly available from the mouse phenome database for analyses and downloads

Systems medicine and integrated care to combat chronic noncommunicable diseases

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems

Controlling complexity: the clinical relevance of mouse complex genetics.

Experimental animal models are essential to obtain basic knowledge of the underlying biological mechanisms in human diseases. Here, we review major contributions to biomedical research and discoveries that were obtained in the mouse model by using forward genetics approaches and that provided key insights into the biology of human diseases and paved the way for the development of novel therapeutic approaches

Understanding complexity in neurodegenerative diseases

Healthy functioning is an emergent property of the network of interacting biomolecules that comprise an organism. It follows that disease (a network shift that causes malfunction) is also an emergent property, emerging from a perturbation of the network. On the one hand, the biomolecular network of every individual is unique and this is evident when similar disease-producing agents cause different individual pathologies. Consequently, a personalized model and approach for every patient may be required for therapies to become effective across mankind. On the other hand, diverse combinations of internal and external perturbation factors may cause a similar shift in network functioning. We offer this as an explanation for the multi-factorial nature of most diseases: they are "systems biology diseases," or "network diseases." Here we use neurodegenerative diseases, like Parkinson's disease (PD), as an example to show that due to the inherent complexity of these networks, it is difficult to understand multi-factorial diseases with simply our "naked brain." When describing interactions between biomolecules through mathematical equations and integrating those equations into a mathematical model, we try to reconstruct the emergent properties of the system in silico. The reconstruction of emergence from interactions between huge numbers of macromolecules is one of the aims of systems biology. Systems biology approaches enable us to break through the limitation of the human brain to perceive the extraordinarily large number of interactions, but this also means that we delegate the understanding of reality to the computer. We no longer recognize all those essences in the system's design crucial for important physiological behavior (the so-called "design principles" of the system). In this paper we review evidence that by using more abstract approaches and by experimenting in silico, one may still be able to discover and understand the design principles that govern behavioral emergence