Objectives:To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders.Methods:751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007–8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005–7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed.Results:A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases.Conclusions:Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.

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Video-based media spaces are designed to support casual interaction between intimate collaborators. Yet transmitting video is fraught with privacy concerns. Some researchers suggest that the video stream be 'filtered' to mask out potentially sensitive information. While a variety of filtering techniques exist, they have not been evaluated for how well they safeguard privacy.In this paper, we analyze how a blur and a pixelize video filter might impact both awareness and privacy in a media space. Each filter is considered at nine different levels of fidelity, ranging from heavily applied filter levels that mask almost all information, to lightly applied filters that reveal almost everything. We examined how well observers of several filtered video scenes extract particular awareness cues: the number of actors; their posture (moving, standing, seated); their gender; the visible objects (basic to detailed); and how available people look (their busyness, seriousness and approachability). We also examined the privacypreserving potential of each filter level in the context of common workplace activities. Our results suggest that the blur filter, and to a lesser extent the pixelize filter, have a level suitable for providing awareness information while safeguarding privacy.

Given that health-care for patients in the UK is free at the point of delivery, we postulate that in our cohort genetic factors rather than socio-economic status are likely to be more significant in causing renal failure. However, there may be cultural and other reasons for this, which requires further study.

This paper considers the problem of designing an observer for a linear system subject to unknown inputs. This problem has been extensively studied in the literature with respect to both linear and nonlinear (sliding mode) observers. Necessary and sufficient conditions to enable a linear unknown input observer to be designed have been established for many years. One way to express these conditions is that the transfer function matrix between the unknown input and the measured output must be minimum phase and relative degree one. Identical conditions must be met in order to design a 'classical' sliding mode observer for the same problem. This paper shows how the relative degree condition can be weakened if a classical sliding mode observer is combined with sliding mode exact differentiators to essentially generate additional independent output signals from the available measurements. A practical example dedicated to actuator fault detection and identification of a winding machine demonstrates the efficacy of the approach.

Patients with rheumatoid arthritis (RA) receive highly targeted biologic therapies without previous knowledge of target expression levels in the diseased tissue. Approximately 40% of patients do not respond to individual biologic therapies and 5–20% are refractory to all. In a biopsy-based, precision-medicine, randomized clinical trial in RA (R4RA; n = 164), patients with low/absent synovial B cell molecular signature had a lower response to rituximab (anti-CD20 monoclonal antibody) compared with that to tocilizumab (anti-IL6R monoclonal antibody) although the exact mechanisms of response/nonresponse remain to be established. Here, in-depth histological/molecular analyses of R4RA synovial biopsies identify humoral immune response gene signatures associated with response to rituximab and tocilizumab, and a stromal/fibroblast signature in patients refractory to all medications. Post-treatment changes in synovial gene expression and cell infiltration highlighted divergent effects of rituximab and tocilizumab relating to differing response/nonresponse mechanisms. Using ten-by-tenfold nested cross-validation, we developed machine learning algorithms predictive of response to rituximab (area under the curve (AUC) = 0.74), tocilizumab (AUC = 0.68) and, notably, multidrug resistance (AUC = 0.69). This study supports the notion that disease endotypes, driven by diverse molecular pathology pathways in the diseased tissue, determine diverse clinical and treatment–response phenotypes. It also highlights the importance of integration of molecular pathology signatures into clinical algorithms to optimize the future use of existing medications and inform the development of new drugs for refractory patients.

Large numbers of individuals with a clinical diagnosis of RA identified from a large primary care database are not receiving DMARDs. This work suggests that many individuals with RA have not been treated appropriately and this may have major long-term consequences on joint damage and general health.

These considerations represent the first international consensus on the conduct of interventional studies following acute knee joint trauma.