EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to—or adding—another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies

Replication Data for: Characterizing bedforms in shallow seas as an integrative predictor of seafloor stability and the occurrence of macrozoobenthic species

This dataset contains all data and scripts required to replicate the results in the paper and consists of three zipped folders. Each folder contains a script folder with the necessary R-scripts as well as a data folder that contains all data necessary to replicate the results. These include raw single-beam data of the Marsdiep tidal basin and GIS layers of bathymetry and bathymetric instability used in the paper, and R-scripts used to calculate Terrain Ruggedness Index from single-beam data and scripts used for the analysis

Dataset for: Benthic primary producers are key to sustain the Wadden Sea food web: Stable carbon isotope analysis at landscape scale

Coastal food webs can be supported by local benthic or pelagic primary producers and by the import of organic matter. Distinguishing between these energy sources is essential for our understanding of ecosystem functioning. However, the relative contribution of these components to the food web at the landscape scale is often unclear, as many studies lack good taxonomic and spatial resolution across large areas. Here, using stable carbon isotopes, we report on the primary carbon sources for consumers and their spatial variability across one of the world's largest intertidal ecosystems (Dutch Wadden Sea; 1460 km2 intertidal surface area), at an exceptionally high taxonomic (178 species) and spatial resolution (9,165 samples from 839 locations). Species composition and biomass data were collected during a spatially comprehensive monitoring campaign (Synoptic Intertidal Benthic Survey, SIBES) between June and October of 2008–2012 (Bijleveld et al. 2012, Compton et al. 2013). This sampling program covers the entire intertidal of the Dutch Wadden Sea and consists of gridded samples taken at 500 m intervals and additional random samples (~4,500 samples per year). As samples were collected from June to September, sampling was conducted haphazardly in geographic space over these six weeks to ensure that there was no temporal bias in the sampling and thus in our estimates

Amino acid data supporting: Compound- specific stable isotope analysis of amino acid nitrogen reveals detrital support of microphytobenthos in the Dutch Wadden Sea benthic food web

Nitrogen stable isotope values for amino acid measurements for glutamic acid and phenylalanine for the Dutch Wadden Sea food web. 28 species measured with reasonable replication for a total of 339 individuals measured. Related dataset: https://doi.org/10.4121/2121311

First field-based evidence that the seagrass-lucinid mutualism can mitigate sulfide stress in seagrasses

Seagrass meadows form vital ecological components of coastal zones worldwide, but are rapidly declining. Large-scale seagrass diebacks have been related to accumulation of toxic sulfide in the sediment, a phenomenon predicted to occur more frequently in the near future due to ongoing global warming and increasing organic loading of coastal systems worldwide. Recently, a facultative mutualism between seagrasses and lucinid bivalves with endosymbiotic sulfide-consuming gill bacteria was discovered that may prevent toxic sulfide accumulation in seagrass sediments. Yet, direct field-based evidence for the importance of this mutualism in alleviating sulfide stress in seagrasses is currently lacking, as well as how its role may change when sediment sulfide levels increase due to environmental change. Here, we investigated the sulfide detoxification function of this seagrass-lucinid mutualism and its resilience to organic-loading induced sulfide stress in a temperate lagoon system (Thau lagoon, France), using a correlative field survey and a full factorial field experiment. The field survey revealed a strong positive correlation between seagrass above-ground biomass and lucinid densities, and pore water sulfide concentrations close to zero at all sites. Furthermore, the field experiment revealed that addition of organic matter (starch mixed with sucrose) increased sedimentary sulfide intrusion into seagrass (Zostera noltei) leaves (a proxy for sulfide stress), while experimentally enhanced lucinid densities reduced sulfide intrusion, regardless of addition of organic matter. Moreover, addition of organic matter reduced seagrass rhizome biomass and increased pore water sulfide levels, lucinid tissue sulfur content, lucinid condition (expressed as flesh/shell dry weight ratio), and total lucinid biomass, while enhancement of lucinid densities reduced lucinid condition. These results provide the first field-based evidence that lucinid bivalves and their sulfide-oxidizing gill symbionts mitigate sulfide stress in seagrasses, and suggests that the dependence of seagrass on this seagrass-lucinid mutualism will increase under conditions of enhanced sediment sulfide production, as predicted for the near future. Therefore, we suggest that awareness of the ecological importance of the seagrass-lucinid mutualism may be instrumental for designing new measures for improving long-term restoration success and seagrass resilience to global change

Bulk carbon and nitrogen stable isotope data supporting: Compound- specific stable isotope analysis of amino acid nitrogen reveals detrital support of microphytobenthos in the Dutch Wadden Sea benthic food web

Bulk carbon and nitrogen values resulting from the 2010-2014 SIBES samplings from the Dutch Wadden Sea. 28 species sampled with reasonable replication and end member measurements for microphytobenthos and water particulate organic matter. Related dataset: https://doi.org/10.4121/2120747