Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era

A comparative prospective study of dynamic variable angle hip screw and Gamma nail in intertrochanteric hip fractures.

PURPOSE: To compare the results between a variable angle dynamic screw-plate(DMS) and the Gamma nail in the treatment of intertrochanteric hip fractures. METHODS: A comparative prospective study of 142 patients (AO/OTA Type 31-A1; A2; A3 and B2) treated by variable angle dynamic screw-plate (DMS Group = 71) or by intramedullary nailing (Gamma Nail Group = 71). RESULTS: At the 12-month follow-up, we did not find any statistically significant difference, intraoperatively, radiographically, or clinically, between the two groups of patients, except for shortening. In 12 patients in the DMS group (17%) and in one patient in the Gamma nail group, there was shortening of the operated leg between 1 cm and 3 cm (p = 0.02). In all instances, shortening occurred in patients who sustained A.O. type fractures 31A2. 2 and 3 (19 patients), which are unstable and comminuted. CONCLUSIONS: The DMS allows effective management of intertrochanteric fractures of the femur. Surgeons should consider choosing surgical treatment according to the type of intertrochanteric fracture. In less comminuted fractures, a compression hip screw may be a faster and safer surgical solution. In comminuted fractures, surgical difficulties may increase in parallel to fracture complexity

The Case for a Principled Approach to Law and Economics: Efficiency Analysis and General Principles of EU Law

Arche which in Ancient Greek means beginning or principle shows the common lineage between the study of principles and the beginning of a study: the enquiry into the nature of things starts, and should start, from the deciphering of the principles, be they of things or of law. This is also true for the general principles of law regarding the study of any legal order, and particularly of the EU legal order. Specifically, I shall demonstrate in this essay that the social influence those principles may have is to coherently formalise the EU judicial reasoning by the promotion of a notion of economic desirability when these principles are invoked. In other words, I shall argue that the principle of economic efficiency underpins each of the general principles of EU law analysed in this essay. For, the general principles of EU law as construed and interpreted by the EU judges are imbued with consequentialism rather moralism, with an analogical and practical reasoning rather than abstract reasoning, with an inductive rather than an deductive approach – in short, these principles are founded with pragmatism rather than with legalism. Indeed, the analysis of the general principles of EU law understood in their legal abstraction is neither relevant nor conclusive for a better understanding of the EU judicial reasoning. These principles are a mere conceptualisation of the EU judicial review in order to trim down the legal outcomes preferred in terms of the social consequences they (are supposed to) generate. This conceptualisation allows for an a posteriori legal justification to a legal outcome decided a priori. In sharp contrast to Wechsler’s argument that general principles of law encapsulate “what surely are the main qualities of law, its generality and its neutrality”, one can agree with Holmes who said, regarding the Common law judge, that judges “decide the case first and determines the principles afterwards”. Accordingly, after having delved into the plea that vouches for a more principled economic analysis of EU law (but also more generally of any legal orders) thatwould take place beyond the Dworkin-Posner dichotomy (1) and (2), I shall empirically scrutinize, through a casuistic analysis of the ECJ jurisprudence, the validity of the proposed approach of efficiency analysis of three general principles of EU law (3). I close the essay with some concluding remarks (4)