The presence of a patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions; however, the subject remains controversial and no official statements have been published. This interdisciplinary paper, prepared with involvement of eight European scientific societies, aims to review the available trial evidence and to define the principles needed to guide decision making in patients with PFO. In order to guarantee a strict process, position statements were developed with the use of a modified grading of recommendations assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements of particular management options were weighed and graded according to predefined scales. Despite being based often on limited and non-randomised data, while waiting for more conclusive evidence, it was possible to conclude on a number of position statements regarding a rational general approach to PFO management and to specific considerations regarding left circulation thromboembolism. For some therapeutic aspects, it was possible to express stricter position statements based on randomised trials. This position paper provides the first largely shared, interdisciplinary approach for a rational PFO management based on the best available evidence.

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These recommendations were developed based on a synthesis of international guidelines, supporting evidence, and expert consensus considering the Canadian healthcare context with the intention of promoting best practices and improving healthcare delivery for persons with RA.

Tuning compiler optimizations for rapidly evolving hardware makes porting and extending an optimizing compiler for each new platform extremely challenging. Iterative optimization is a popular approach to adapting programs to a new architecture automatically using feedback-directed compilation. However, the large number of evaluations required for each program has prevented iterative compilation from widespread take-up in production compilers. Machine learning has been proposed to tune optimizations across programs systematically but is currently limited to a few transformations, long training phases and critically lacks publicly released, stable tools.Our approach is to develop a modular, extensible, self-tuning optimization infrastructure to automatically learn the best optimizations across multiple programs and architectures based on the correlation between program features, run-time behavior and optimizations. In this paper we describe Milepost GCC, the first publicly-available open-source machine learning-based compiler. It consists of an Interactive Compilation Interface (ICI) and plugins to extract program features and exchange optimization data with the cTuning.org open public repository. It automatically adapts the internal optimization heuristic at function-level granularity to improve execution time, code size and compilation time of a new program on a given architecture. Part of the Milepost technology together with low-level ICI-inspired plugin framework is now included in the mainline GCC.We developed machine learning plugins based on probabilistic and transductive approaches to predict good combinations of optimizations. Our preliminary experimental results show that it is possible to automatically reduce the execution time of individual MiBench programs, some by more than a factor of 2, while also improving compilation 1 INRIA Saclay, France (HiPEAC member) · 2 University of Versailles Saint Quentin en Yvelines, France · 3 IBM Haifa, Israel (HiPEAC member) · 4 CAPS Entreprise, France (HiPEAC member) · 5 ARC International, UK · 6 University of Edinburgh, UK (HiPEAC member) · 2 time and code size. On average we are able to reduce the execution time of the MiBench benchmark suite by 11% for the ARC reconfigurable processor. We also present a realistic multi-objective optimization scenario for Berkeley DB library using Milepost GCC and improve execution time by approximately 17%, while reducing compilation time and code size by 12% and 7% respectively on Intel Xeon processor.

ABSTRACT. Objective. The Canadian Rheumatology Association (CRA) has developed recommendations for the pharmacological management of rheumatoid arthritis (RA) with traditional and biologic disease-modifying antirheumatic drugs (DMARD) in 2 parts. Part II, focusing on specific safety aspects of treatment with traditional and biologic DMARD in patients with RA, is reported here. Methods. Key questions were identified a priori based on results of a national needs-assessment survey. A systematic review of all clinical practice guidelines and consensus statements regarding treatment with traditional and biologic DMARD in patients with RA published between January 2000 and June 2010 was performed in Medline, Embase, and CINAHL databases, and was supplemented with a "grey literature" search including relevant public health guidelines. Systematic reviews of postmarketing surveillance and RA registry studies were performed to update included guideline literature reviews as appropriate. Guideline quality was independently assessed by 2 reviewers. Guideline characteristics, recommendations, and supporting evidence from observational studies and randomized trials were synthesized into evidence tables. The working group voted on recommendations using a modified Delphi technique.Results. Thirteen recommendations addressing perioperative care, screening for latent tuberculosis infection prior to the initiation of biologic DMARD, optimal vaccination practices, and treatment of RA patients with active or a history of malignancy were developed for rheumatologists, other primary prescribers of RA drug therapies, and RA patients. Conclusion. These recommendations were developed based on a synthesis of international RA and public health guidelines, supporting evidence, and expert consensus in the context of the Canadian health system. They are intended to help promote best practices and improve healthcare delivery for persons with RA. (First Release June 15 2012; J Rheumatol 2012;39:1583-602; doi:10.3899 Recommendations provided here are intended to be read in conjunction with the Canadian Rheumatology Association Recommendations for the Pharmacological Management of Rheumatoid Arthritis. These recommendations address specific safety questions that were identified a priori and are not intended to cover all safety aspects concerning treatment with traditional and biologic disease modifying antirheumatic drugs (DMARD).Traditional and biologic DMARD have greatly enhanced the care of persons with rheumatoid arthritis (RA); however, potential risks associated with their use need be considered. The Canadian Rheumatology Association (CRA) has developed recommendations for the pharmacological management of RA with traditional and biologic DMARD in 2 parts. Part I described the development process of CRA recommendations in detail and included 5 overarching RA care principles along with 26 treatment recommendations 1 . Part II, reported here, focuses on specific safety aspects of treatment with traditional and biologic DMARD in patients with ...