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In this article, the 2009 European League Against Rheumatism (EULAR) recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated. The 2009 recommendations were on the management of primary small and medium vessel vasculitis. The 2015 update has been developed by an international task force representing EULAR, the European Renal Association and the European Vasculitis Society (EUVAS). The recommendations are based upon evidence from systematic literature reviews, as well as expert opinion where appropriate. The evidence presented was discussed and summarised by the experts in the course of a consensus-finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) determined. In addition to the voting by the task force members, the relevance of the recommendations was assessed by an online voting survey among members of EUVAS. Fifteen recommendations were developed, covering general aspects, such as attaining remission and the need for shared decision making between clinicians and patients. More specific items relate to starting immunosuppressive therapy in combination with glucocorticoids to induce remission, followed by a period of remission maintenance; for remission induction in life-threatening or organ-threatening AAV, cyclophosphamide and rituximab are considered to have similar efficacy; plasma exchange which is recommended, where licensed, in the setting of rapidly progressive renal failure or severe diffuse pulmonary haemorrhage. These recommendations are intended for use by healthcare professionals, doctors in specialist training, medical students, pharmaceutical industries and drug regulatory organisations.

Objectives:To develop European League Against Rheumatism (EULAR) recommendations for the management of small and medium vessel vasculitis.Methods:An expert group (consisting of 10 rheumatologists, 3 nephrologists, 2 immunologists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search using a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of small and medium vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion.Results:In all, 15 recommendations were made for the management of small and medium vessel vasculitis. The strength of recommendations was restricted by low quality of evidence and by EULAR standardised operating procedures.Conclusions:On the basis of evidence and expert consensus, recommendations have been made for the evaluation, investigation, treatment and monitoring of patients with small and medium vessel vasculitis for use in everyday clinical practice.

Objectives:To develop European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis.Methods:An expert group (10 rheumatologists, 3 nephrologists, 2 immunolgists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search through a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of large vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion.Results:Seven recommendations were made relating to the assessment, investigation and treatment of patients with large vessel vasculitis. The strength of recommendations was restricted by the low level of evidence and EULAR standardised operating procedures.Conclusions:On the basis of evidence and expert consensus, management recommendations for large vessel vasculitis have been formulated and are commended for use in everyday clinical practice.

We present a two-stage methodology called Positions and Covering (P&C) to solve the two-dimensional bin packing problem (2D-BPP). The objective of this classical combinatorial NP-hard problem is to pack a set of items (small rectangles) in the minimum number of bins (larger rectangles). The first stage is the key-point of the Positions and Covering, where for each item, it is generated in a pseudo-polynomial way a set of valid positions that indicate the possible ways of packing the item into the bin. In the second stage, a new set-covering formulation, strengthen with three sets of valid inequalities, is used to select the optimal non-overlapping configuration of items for each bin. Experimental results for the P&C method are presented and compared with some of the best algorithms in the literature for small and medium size instances. Furthermore, we are considering both cases of the 2D-BPP, with and without rotations of the items by 90°. To the best of our knowledge, this is one of the first exact approaches to obtain optimal solutions for the rotation case.

Treatment of giant-cell arteritis with tocilizumab, an interleukin-6 receptor alpha inhibitor, while prednisone was tapered over a 26-week period resulted in higher rates of sustained remission than prednisone tapering plus placebo and reduced the total prednisone dose.

Among participants with eosinophilic granulomatosis with polyangiitis, 32% had remission at weeks 36 and 48 when treated with mepolizumab, an anti–interleukin-5 monoclonal antibody, as compared with 3% of the participants in the placebo group. Eosinophilic granulomatosis with polyangiitis (formerly known as the Churg–Strauss syndrome) is characterized by asthma, sinusitis, pulmonary infiltrates, neuropathy, and eosinophilic vasculitis of one or more end-organs. 1 – 4 Eosinophils are thought to induce pathogenic effects in patients with eosinophilic granulomatosis with polyangiitis by means of tissue and vascular infiltration and inflammation through a variety of mediators. 5 , 6 Although systemic glucocorticoids form the cornerstone of treatment for eosinophilic granulomatosis with polyangiitis, 7 – 9 most patients remain dependent on glucocorticoid therapy, and relapses are common. 10 – 13 Furthermore, some patients do not have a sufficient response to glucocorticoids. Because recurrent relapses place the patient at . . .

Screening of RE arranged during T ransfection ( RET ) gene mutations has been carried out in different series of sporadic medullary thyroid carcinomas (MTC). RET -positive tumours seem to be associated to a worse clinical outcome. However, the correlation between the type of RET mutation and the patients' clinicopathological data has not been evaluated yet. We analysed RET exons 5, 8, 10–16 in fifty-one sporadic MTC, and found somatic mutations in thirty-three (64.7%) tumours. Among the RET -positive cases, exon 16 was the most frequently affected (60.6%). Two novel somatic mutations (Cys630Gly, c.1881del18) were identified. MTC patients were divided into three groups: group 1, with mutations in RET exons 15 and 16; group 2, with other RET mutations; group 3, having no RET mutations. Group 1 had higher prevalence ( P =0.0051) and number of lymph node metastases ( P =0.0017), and presented more often multifocal tumours ( P =0.037) and persistent disease at last control ( P =0.0242) than group 2. Detectable serum calcitonin levels at last screening ( P =0.0119) and stage IV disease ( P =0.0145) were more frequent in group 1, than in the other groups. Our results suggest that, among the sporadic MTC, cases with RET mutations in exons 15 and 16 are associated with the worst prognosis. Cases with other RET mutations have the most indolent course, and those with no RET mutations have an intermediate risk.

Objective Functional hypothalamic amenorrhea (FHA) is one of the foremost manifestations in anorexia nervosa (AN), but a subset of patients have menses despite marked weight loss and underweight. The aim of our study was to investigate parameters potentially influencing FHA in AN. Design and methods In this observational retrospective study, we selected 114 female patients with AN who completed a 12 months semi-residential rehabilitation program and a subsequent 12 months outpatient follow-up. We divided our sample into three groups: “Group 0” patients who experienced FHA and recovered their menses, “Group 1” persistent FHA, “Group 2” never experienced FHA, and looked for clinical and hormonal correlations. Results At the enrollment, the BMI was higher in Group 2 than in Group 1 ( p  = 0.0202), but the last follow-up weight was higher in Group 1 ( p  < 0.0001) despite persistent amenorrhea. At logistic regression, the higher BMI at which patients experienced amenorrhea was the main prediction factor for persistent FHA. Notwithstanding comparable leptin levels at admission, they improved significantly at discharge only in Groups 0 and 2 ( p  = 0.0054 and p  = 0.0104, respectively). FT3 at admission was significantly higher in Group 2 than in Group 0 ( p  = 0.0249). Conclusions FHA does not correlate strictly with body weight variations in AN patients, indicating a multifactorial origin, likely including an individual predisposition. Higher FT3 levels identify patients who continue having menses at extremely low BMI. AN patients with persistent FHA constitute a subgroup in whom estroprogestins should be considered after significant weight recovery to prevent prolonged tissue hypoestrogenism.

Fluorescent dissolved organic matter (FDOM) in open surface waters (< 200 m) of the Atlantic, Pacific, and Indian oceans was analysed by excitation-emission matrix (EEM) spectroscopy and parallel factor analysis (PARAFAC). A four-component PARAFAC model was fit to the EEMs, which included two humic- (C1 and C2) and two amino acid-like (C3 and C4) components previously identified in ocean waters. Generalized-additive models (GAMs) were used to explore the environmental factors that drive the global distribution of these PARAFAC components. The explained variance for the humic-like components was substantially larger (> 70%) than for the amino acid-like components (< 35%). The environmental variables exhibiting the largest effect on the global distribution of C1 and C2 were apparent oxygen utilisation followed by chlorophyll a. Positive non-linear relationships between both predictor variables and the two humic-like PARAFAC components suggest that their distribution are biologically controlled. Compared with the dark ocean (> 200 m), the relationships of C1 and C2 with AOU indicate a higher C1/AOU and C2/AOU ratios of the humic-like substances in the dark ocean than in the surface ocean where a net effect of photobleaching is also detected. C3 (tryptophan-like) and C4 (tyrosine-like) variability was mostly dictated by salinity (S), by means of positive non-linear relationships, suggesting a primary physical control of their distributions at the global surface ocean scale that could be related to the changing evaporation-precipitation regime. Remarkably, bacterial biomass (BB) only contributed to explain a minor part of the variability of C1 and C4.

Flavin-containing monooxygenase from Methylophaga sp. (mFMO) was previously discovered to be a valuable biocatalyst used to convert small amines, such as trimethylamine, and various indoles. As FMOs are also known to act on sulfides, we explored mFMO and some mutants thereof for their ability to convert prochiral aromatic sulfides. We included a newly identified thermostable FMO obtained from the bacterium Nitrincola lacisaponensis (NiFMO). The FMOs were found to be active with most tested sulfides, forming chiral sulfoxides with moderate-to-high enantioselectivity. Each enzyme variant exhibited a different enantioselective behavior. This shows that small changes in the substrate binding pocket of mFMO influence selectivity, representing a tunable biocatalyst for enantioselective sulfoxidations.