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Objectives To delineate the impact of peripheral musculoskeletal manifestations on stratification of disease phenotype and outcome in new-onset spondyloarthritis (SpA), using a prospective observational nationwide inception cohort, the BelGian Inflammatory Arthritis and spoNdylitis cohorT (Be-Giant). Methods Newly diagnosed adult SpA patients, fulfilling the Assessment of SpondyloArthritis International Society (ASAS) criteria for axial or peripheral SpA, were included in Be-Giant and prospectively followed every six months. Peripheral involvement (defined as arthritis, enthesitis and/or dactylitis) was determined in relation to clinically similar patient subsets at baseline and disease activity patterns during two-year follow-up, identified through K-means cluster analysis and latent class growth analysis. Results From November 2010 to March 2020, 367 patients were enrolled in Be-Giant, of whom 162 (44%) had peripheral manifestations. Two patient clusters [A, axial predominant (n  = 248) and B, peripheral predominant (n  = 119)] were identified at diagnosis. Longitudinal analysis (n  = 115) revealed two trajectories of disease activity in each cluster: one with persistently high disease activity over time ('High'), the other rapidly evolving to low disease activity ('Low'). In cluster A patients, peripheral manifestations predisposed to the 'High' trajectory [odds ratio (OR) = 2.0, 95% CI: 1.3, 3.1, P  = 0.001], despite more rapid initiation of biologics compared with patients without peripheral manifestations (hazard ratio (HR)  = 2.1, 95% CI: 1.0, 4.4, P  = 0.04 – Cox proportional-hazards model). Conclusion Peripheral musculoskeletal manifestations are major determinants of phenotypical diversity in new-onset SpA. Intriguingly, stratification of axial SpA according to concomitant peripheral involvement identified an endotype with an unfavorable outcome despite more prompt therapeutic intensification with biologics. These observations justify an endotype-tailored approach beyond current ASAS/EULAR management recommendations. [ABSTRACT FROM AUTHOR]

• The complex structure of dsDNA challenges the development and standardization of anti-dsDNA antibody assays. • Performance characteristics of assays to detect anti-dsDNA antibodies differ between methods and assays. • Automated assays for anti-dsDNA antibodies are increasingly introduced in clinical laboratories. • It is important to be aware of the performance characteristics (sensitivity / specificity) of the assay used in clinical practice. • Defining test result interval-specific likelihood ratios may help with the interpretation of anti-dsDNA antibodies in a diagnostic context. Antibodies to dsDNA are an important laboratory parameter for diagnosis, monitoring and classification of systemic lupus erythematosus (SLE). In clinical laboratories, several techniques are used to detect and quantify anti-dsDNA antibodies. Each technique has its advantages and disadvantages regarding sensitivity, specificity, avidity and assay procedure. Assays differ with respect to the antigen source (native versus synthetic versus molecular biological) used and the way the antigen is presented (e.g. in solution, covalently linked to a solid phase,...). Consequently, correlation between assays can be poor and standardization of anti-dsDNA antibody tests is challenging. We here provide an overview of the currently available anti-dsDNA tests frequently used in clinical laboratories [ Crithidia luciliae immunofluorescence test (CLIFT), Enzyme linked immune sorbent assay (ELISA), fluoroenzyme immunoassay (FEIA), chemiluminisence immunoassay (CIA), multiplexed bead-based assays and Farr-RIA] and their performance characteristics. From this literature study, we concluded that performance characteristics differ between assays. Often, a combination of techniques is necessary for the best result interpretation. [ABSTRACT FROM AUTHOR]

The Thwaites Eastern Ice Shelf (TEIS) buttresses the eastern grounded portion of Thwaites Glacier through contact with a pinning point at its seaward limit. Loss of this ice shelf will promote further acceleration of Thwaites Glacier. Understanding the dynamic controls and structural integrity of the TEIS is therefore important to estimating Thwaites' future sea-level contribution. We present a ∼ 20-year record of change on the TEIS that reveals the dynamic controls governing the ice shelf's past behaviour and ongoing evolution. We derived ice velocities from MODIS and Sentinel-1 image data using feature tracking and speckle tracking, respectively, and we combined these records with ITS_LIVE and GOLIVE velocity products from Landsat-7 and Landsat-8. In addition, we estimated surface lowering and basal melt rates using the Reference Elevation Model of Antarctica (REMA) DEM in comparison to ICESat and ICESat-2 altimetry. Early in the record, TEIS flow dynamics were strongly controlled by the neighbouring Thwaites Western Ice Tongue (TWIT). Flow patterns on the TEIS changed following the disintegration of the TWIT around 2008, with a new divergence in ice flow developing around the pinning point at its seaward limit. Simultaneously, the TEIS developed new rifting that extends from the shear zone upstream of the ice rise and increased strain concentration within this shear zone. As these horizontal changes occurred, sustained thinning driven by basal melt reduced ice thickness, particularly near the grounding line and in the shear zone area upstream of the pinning point. This evidence of weakening at a rapid pace suggests that the TEIS is likely to fully destabilize in the next few decades, leading to further acceleration of Thwaites Glacier. [ABSTRACT FROM AUTHOR]

We use reanalysis data and satellite remote sensing of cloud properties to examine how meteorological conditions alter the surface energy balance to cause surface melt that is detectable in satellite passive microwave imagery over West Antarctica. This analysis can detect each of the three primary mechanisms for inducing surface melt at a specific location: thermal blanketing involving sensible heat flux and/or longwave heating by optically thick cloud cover, all-wave radiative enhancement by optically thin cloud cover, and föhn winds. We examine case studies over Pine Island and Thwaites glaciers, which are of interest for ice shelf and ice sheet stability, and over Siple Dome, which is more readily accessible for field work. During January 2015 over Siple Dome we identified a melt event whose origin is an all-wave radiative enhancement by optically thin clouds. During December 2011 over Pine Island and Thwaites glaciers, we identified a melt event caused mainly by thermal blanketing from optically thick clouds. Over Siple Dome, those same 2011 synoptic conditions yielded a thermal-blanketing-driven melt event that was initiated by an impulse of sensible heat flux and then prolonged by cloud longwave heating. The December 2011 synoptic conditions also generated föhn winds at a location on the Ross Ice Shelf adjacent to the Transantarctic Mountains, and we analyze this case with additional support from automatic weather station data. In contrast, a late-summer thermal blanketing period over Pine Island and Thwaites glaciers during February 2013 showed surface melt initiated by cloud longwave heating and then prolonged by enhanced sensible heat flux. One limitation thus far with this type of analysis involves uncertainties in the cloud optical properties. Nevertheless, with improvements this type of analysis can enable quantitative prediction of atmospheric stress on the vulnerable Antarctic ice shelves in a steadily warming climate. [ABSTRACT FROM AUTHOR]

The Greenland Ice Sheet (GrIS) rapid mass loss is primarily driven by an increase in meltwater runoff, which highlights the importance of understanding the formation, evolution, and impact of meltwater features on the ice sheet. Buried lakes are meltwater features that contain liquid water and exist under layers of snow, firn, and/or ice. These lakes are invisible in optical imagery, challenging the analysis of their evolution and implication for larger GrIS dynamics and mass change. Here, we present a method that uses a convolutional neural network, a deep learning method, to automatically detect buried lakes across the GrIS. For the years 2018 and 2019 (which represent low- and high-melt years, respectively), we compare total areal extent of both buried and surface lakes across six regions, and we use a regional climate model to explain the spatial and temporal differences. We find that the total buried lake extent after the 2019 melt season is 56 % larger than after the 2018 melt season across the entire ice sheet. Northern Greenland has the largest increase in buried lake extent after the 2019 melt season, which we attribute to late-summer surface melt and high autumn temperatures. We also provide evidence that different processes are responsible for buried lake formation in different regions of the ice sheet. For example, in southwest Greenland, buried lakes often appear on the surface during the previous melt season, indicating that these meltwater features form when surface lakes partially freeze and become insulated as snowfall buries them. Conversely, in southeast Greenland, most buried lakes never appear on the surface, indicating that these features may form due to downward percolation of meltwater and/or subsurface penetration of shortwave radiation. We provide support for these processes via the use of a physics-based snow model. This study provides additional perspective on the potential role of meltwater on GrIS dynamics and mass loss. [ABSTRACT FROM AUTHOR]

Earth system/ice‐sheet coupling is an area of recent, major Earth System Model (ESM) development. This work occurs at the intersection of glaciology and climate science and is motivated by a need for robust projections of sea‐level rise. The Community Ice Sheet Model version 2 (CISM2) is the newest component model of the Community Earth System Model version 2 (CESM2). This study describes the coupling and novel capabilities of the model, including: (1) an advanced energy‐balance‐based surface mass balance calculation in the land component with downscaling via elevation classes; (2) a closed freshwater budget from ice sheet to the ocean from surface runoff, basal melting, and ice discharge; (3) dynamic land surface types; and (4) dynamic atmospheric topography. The Earth system/ice‐sheet coupling is demonstrated in a simulation with an evolving Greenland Ice Sheet (GrIS) under an idealized high CO2 scenario. The model simulates a large expansion of ablation areas (where surface ablation exceeds snow accumulation) and a large increase in surface runoff. This results in an elevated freshwater flux to the ocean, as well as thinning of the ice sheet and area retreat. These GrIS changes result in reduced Greenland surface albedo, changes in the sign and magnitude of sensible and latent heat fluxes, and modified surface roughness and overall ice sheet topography. Representation of these couplings between climate and ice sheets is key for the simulation of ice and climate interactions. Plain Language Summary: Ice sheets are glaciers of continental size. At present, the Greenland and Antarctic ice sheets are losing mass at an accelerated rate in response to atmospheric and ocean warming and are becoming major contributors to sea‐level rise. Former ice sheets are key to understanding past climate changes that can inform us about the dynamics of the Earth system. This study presents the coupling and utility of the Community Earth System Model version 2 (CESM2) with the Community Ice Sheet Model version 2 (CISM2). CISM2 calculates ice velocities, internal temperatures, and the dynamical evolution of the ice sheet. CESM simulates ice melt rates through an advanced calculation that accounts for snow compaction and the reflection of solar radiation from the surface. Melt water and ice discharge fluxes from the ice sheet are communicated to the ocean model. The land and atmospheric models of CESM2 react to changes in the extent, elevation, and roughness of ice sheets. As such, CESM2‐CISM2 can be used to study the sensitivity of ice sheets to Earth system changes, and vice versa. Coupling to the Antarctic Ice Sheet is not included in the current version, but is planned for future versions. Key Points: We present a bi‐directionally coupled ice sheet and Earth system model including advanced representation of surface snow/ice processesThe surface mass balance is calculated in the land component with an energy balance scheme and downscaled to the ice‐sheet component via elevation classesIce sheet meltwater and solid discharge are passed to the ocean component; changes in ice sheet area and topography to land and atmosphere [ABSTRACT FROM AUTHOR]

Estimates of snow and firn density are required for satellite-altimetry-based retrievals of ice sheet mass balance that rely on volume-to-mass conversions. Therefore, biases and errors in presently used density models confound assessments of ice sheet mass balance and by extension ice sheet contribution to sea level rise. Despite this importance, most contemporary firn densification models rely on simplified semi-empirical methods, which are partially reflected by significant modeled density errors when compared to observations. In this study, we present a new drifting-snow compaction scheme that we have implemented into SNOWPACK, a physics-based land surface snow model. We show that our new scheme improves existing versions of SNOWPACK by increasing simulated near-surface (defined as the top 10 m) density to be more in line with observations (near-surface bias reduction from - 44.9 to - 5.4 kgm-3). Furthermore, we demonstrate high-quality simulation of near-surface Antarctic snow and firn density at 122 observed density profiles across the Antarctic ice sheet, as indicated by reduced model biases throughout most of the near-surface firn column when compared to two semi-empirical firn densification models (SNOWPACK mean bias=-9.7 kgm-3 , IMAU-FDM mean bias=-32.5 kgm-3 , GSFC-FDM mean bias=15.5 kgm-3). Notably, our analysis is restricted to the near surface where firn density is most variable due to accumulation and compaction variability driven by synoptic weather and seasonal climate variability. Additionally, the GSFC-FDM exhibits lower mean density bias from 7–10 m (SNOWPACK bias=-22.5 kgm-3 , GSFC-FDM bias=10.6 kgm-3) and throughout the entire near surface at high-accumulation sites (SNOWPACK bias=-31.4 kgm-3 , GSFC-FDM bias=-4.7 kgm-3). However, we found that the performance of SNOWPACK did not degrade when applied to sites that were not included in the calibration of semi-empirical models. This suggests that SNOWPACK may possibly better represent firn properties in locations without extensive observations and under future climate scenarios, when firn properties are expected to diverge from their present state. [ABSTRACT FROM AUTHOR]

Objectives: In systemic sclerosis, baseline extent of radiological involvement is an important outcome predictor and baseline absence of radiological involvement suggests a more favourable prognosis. As current predictive models are based on cohorts with variable disease duration, we aim to assess disease dynamics in early disease. Methods: Patients were included from the prospective longitudinal Belgian Systemic Sclerosis Cohort. We included patients with a disease duration < = 36 months at baseline with available baseline thoracic high-resolution computed tomography (HRCT) images and longitudinal pulmonary function test (PFT) results until 42 months of follow-up. Results: Fifty-two patients were included; 50% were male and 44% suffered from diffuse cutaneous systemic sclerosis. A total of 46% carried anti-topoisomerase 1 antibodies. The mean disease duration at baseline visit was 11 months. At baseline visit, 40.4% (21/52) patients had HRCT abnormalities. Patients with abnormal HRCT findings more frequently suffered from diffuse cutaneous systemic sclerosis (p < 0.05) and less frequently carried anti-centromere antibodies (p < 0.05). Patients without CT abnormalities at baseline had a shorter disease duration (9 ± 7 months versus 14 ± 12 months). After 42 months, 8/52 patients, including 3 patients with normal HRCT findings at baseline, died due to SSc-related manifestations. Progression of lung fibrosis occurred in 16 patients at month 42, including 7 patients with normal CT at baseline. No clear predictors of progression could be identified. Conclusion: In early SSc patients, the disease dynamics differ from the large published cohorts. Progressive lung fibrosis and mortality can also occur in patients without radiological abnormalities at baseline. Key Points • Disease dynamics in early SSc differ from more established SSc. • In early SSc, progressive pulmonary fibrosis can occur in patients without CT abnormalities at baseline. • In early SSc, more stringent pulmonary follow-up is warranted both in lcSSc and dcSSc. [ABSTRACT FROM AUTHOR]

Ice cores are an important record of the past surface mass balance (SMB) of ice sheets, with SMB mitigating the ice sheets' sea level impact over the recent decades. For the Antarctic Ice Sheet (AIS), SMB is dominated by large-scale atmospheric circulation, which collects warm moist air from further north and releases it in the form of snow as widespread accumulation or focused atmospheric rivers on the continent. This suggests that the snow deposited at the surface of the AIS should record strongly coupled SMB and surface air temperature (SAT) variations. Ice cores use δ18O as a proxy for SAT as they do not record SAT directly. Here, using isotope-enabled global climate models and the RACMO2.3 regional climate model, we calculate positive SMB–SAT and SMB– δ18O annual correlations over ∼90 % of the AIS. The high spatial resolution of the RACMO2.3 model allows us to highlight a number of areas where SMB and SAT are not correlated, and we show that wind-driven processes acting locally, such as foehn and katabatic effects, can overwhelm the large-scale atmospheric contribution in SMB and SAT responsible for the positive SMB–SAT annual correlations. We focus in particular on Dronning Maud Land, East Antarctica, where the ice promontories clearly show these wind-induced effects. However, using the PAGES2k ice core compilations of SMB and δ18O of and , we obtain a weak annual correlation, on the order of 0.1, between SMB and δ18O over the past ∼150 years. We obtain an equivalently weak annual correlation between ice core SMB and the SAT reconstruction of over the past ∼50 years, although the ice core sites are not spatially co-located with the areas displaying a low SMB–SAT annual correlation in the models. To resolve the discrepancy between the measured and modeled signals, we show that averaging the ice core records in close spatial proximity increases their SMB–SAT annual correlation. This increase shows that the weak measured annual correlation partly results from random noise present in the ice core records, but the change is not large enough to match the annual correlation calculated in the models. Our results thus indicate a positive correlation between SAT and SMB in models and ice core reconstructions but with a weaker value in observations that may be due to missing processes in models or some systematic biases in ice core data that are not removed by a simple average. [ABSTRACT FROM AUTHOR]

We present a reconstruction of historical (1950–2014) surface mass balance (SMB) of the Greenland ice sheet (GrIS) using a high-resolution regional climate model (RACMO2; ∼11 km) to dynamically downscale the climate of the Community Earth System Model version 2 (CESM2; ∼111 km). After further statistical downscaling to 1 km spatial resolution, evaluation using in situ SMB measurements and remotely sensed GrIS mass change shows good agreement. Comparison with an ensemble of previously conducted RACMO2 simulations forced by climate reanalysis demonstrates that the current product realistically represents the long-term average and variability of individual SMB components and captures the recent increase in meltwater runoff that accelerated GrIS mass loss. This means that, for the first time, climate forcing from an Earth system model (CESM2), which assimilates no observations, can be used without additional corrections to reconstruct the historical GrIS SMB and its recent decline that initiated mass loss in the 1990s. This paves the way for attribution studies of future GrIS mass loss projections and contribution to sea level rise. [ABSTRACT FROM AUTHOR]

Improving our knowledge of the temporal and spatial variability of the Antarctic Ice Sheet (AIS) surface mass balance (SMB) is crucial to reduce the uncertainties of past, present, and future Antarctic contributions to sea level rise. An examination of the surface air temperature–SMB relationship in model simulations demonstrates a strong link between the two. Reconstructions based on ice cores display a weaker relationship, indicating a model–data discrepancy that may be due to model biases or to the non-climatic noise present in the records. We find that, on the regional scale, the modeled relationship between surface air temperature and SMB is often stronger than between temperature and δ18O. This suggests that SMB data can be used to reconstruct past surface air temperature. Using this finding, we assimilate isotope-enabled SMB and δ18O model output with ice core observations to generate a new surface air temperature reconstruction. Although an independent evaluation of the skill is difficult because of the short observational time series, this new reconstruction outperforms the previous reconstructions for the continental-mean temperature that were based on δ18O alone. The improvement is most significant for the East Antarctic region, where the uncertainties are particularly large. Finally, using the same data assimilation method as for the surface air temperature reconstruction, we provide a spatial SMB reconstruction for the AIS over the last 2 centuries, showing large variability in SMB trends at a regional scale, with an increase (0.82 Gt yr -2) in West Antarctica over 1957–2000 and a decrease in East Antarctica during the same period (-0.13 Gt yr -2). As expected, this is consistent with the recent reconstruction used as a constraint in the data assimilation. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) affects the upper gastrointestinal (GI) system in 90% of patients. High-resolution manometry (HRM) assesses esophageal dysmotility, but its role in diagnosis and follow-up remains unclear. The objectives of this systematic review were to investigate the role of HRM in the assessment of SSc-associated upper GI involvement and to evaluate the correlation between HRM abnormalities and clinical characteristics and the effects of therapeutic interventions on HRM findings. Fifteen articles were included. Most (11/15) studies were of very good or good quality. Most studies assessed correlations between esophageal symptoms and esophageal dysmotility. Two studies assessed the effectiveness of buspirone and reported HRM findings. Studies assessing upper GI symptoms using validated questionnaires, such as the University of California Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 or Gastrointestinal Symptoms Severity Index score, found an association between absent contractility on HRM and upper GI symptoms, but even asymptomatic patients often have esophageal body dysmotility on HRM. Esophageal dysmotility positively correlates with the presence of interstitial lung disease on high-resolution computed tomography and reduced diffusion capacity (< 0.8 of predicted value). Trials investigating the effect of buspirone demonstrate both increased lower esophageal sphincter resting pressure and reduced upper GI symptoms. Most studies report on limited patient numbers and retrospective data. Potential bias was minimized using quality appraisal. HRM findings correlate to upper GI symptoms when assessed by validated questionnaires and can detect response to therapy in buspirone trials. Esophageal body dysmotility on HRM positively correlates with the presence of interstitial lung disease. Key Points: • Esophageal body dysmotility on HRM correlates with presence of ILD. • HRM findings seem to correspond to clinical symptom alleviation in interventional trials, but data are still limited. • At present HRM, a procedure with a high negative burden to the patient, offers little to no role in the therapeutic strategy. [ABSTRACT FROM AUTHOR]

In this study, the resolution dependence of the simulated Greenland ice sheet surface mass balance (GrIS SMB) in the variable-resolution Community Earth System Model (VR-CESM) is investigated. Coupled atmosphere–land simulations are performed on two regionally refined grids over Greenland at 0.5 ∘ (∼55 km) and 0.25 ∘ (∼28 km), maintaining a quasi-uniform resolution of 1 ∘ (∼111 km) over the rest of the globe. On the refined grids, the SMB in the accumulation zone is significantly improved compared to airborne radar and in situ observations, with a general wetting (more snowfall) at the margins and a drying (less snowfall) in the interior GrIS. Total GrIS precipitation decreases with resolution, which is in line with best-available regional climate model results. In the ablation zone, CESM starts developing a positive SMB bias with increased resolution in some basins, notably in the east and the north. The mismatch in ablation is linked to changes in cloud cover in VR-CESM, and a reduced effectiveness of the elevation classes subgrid parametrization in CESM. Overall, our pilot study introduces VR-CESM as a new tool in the cryospheric sciences, which could be used to dynamically downscale SMB in scenario simulations and to force dynamical ice sheet models through the CESM coupling framework. [ABSTRACT FROM AUTHOR]

Surface meltwater ponding has been implicated as a major driver for recent ice shelf collapse as well as the speedup of tributary glaciers in the northeast Antarctic Peninsula. Surface melt on the NAP is impacted by the strength and frequency of westerly winds, which result in sporadic foehn flow. We estimate changes in the frequency of foehn flow and the associated impact on snow melt, density, and the percolation depth of meltwater over the period 1982–2017 using a regional climate model and passive microwave data. The first of two methods extracts spatial patterns of melt occurrence using empirical orthogonal function analysis. The second method applies the Foehn Index, introduced here to capture foehn occurrence over the full study domain. Both methods show substantial foehn‐induced melt late in the melt season since 2015, resulting in compounded densification of the near‐surface snow, with potential implications for future ice shelf stability. Plain Language Summary: Surface melt and the ponding of water on the surface has been linked to recent ice shelf collapse in the northeast Antarctic Peninsula, which includes the Larsen C ice shelf, one of the regions in Antarctica that is most vulnerable to a changing climate. Melt can be caused either by high temperatures or by foehn winds, that is, a hot, dry wind on the downwind side of a mountain range. To determine when foehn winds occurred from 1982 to 2017, and how much surface melt they produced, we use two methods. The first method finds recurring patterns of melt on the northeast Antarctic Peninsula from both satellite observations and models and determines which patterns are produced by foehn conditions. The second method uses simulated atmospheric conditions to determine when and over how much surface area foehn conditions occur and then calculates the melt produced at the same time. Both methods find high levels of foehn‐induced melt after the summer melt season occurring since 2015, resulting in high‐density snow near the surface in regions where foehn winds are common. If similar conditions persist into the future, late‐season and autumn melt could have substantial ramifications for the health of the Larsen C ice shelf. Key Points: A long‐term record of foehn‐induced melt is calculated from a regional climate model via two methodsWe introduce the Foehn Index which captures foehn intensity over space and timeLate‐season foehn‐induced melt between 2015 and 2017 produced compounded densification in the upper snowpack resulting in increasing runoff [ABSTRACT FROM AUTHOR]

Abstract Antarctic blue ice zones, the most productive locations for meteorite recovery on Earth, contain old ice that is easily accessible and available in large quantities. However, the mechanisms behind these meteorite traps remain a topic of ongoing debate. Here, we propose an interdisciplinary approach to improve our understanding of a meteorite trap in Dronning Maud Land (East Antarctica) on the Nansen blue ice field meteorite trap (2600–3100 m above sea level), where more than half of the Asuka meteorites have been collected. Based on 185 surface blue ice samples, one of the largest observed spatial patterns in oxygen isotopic variation to date is found. Relying on meteorites for which the terrestrial ages are determined using 14C and 36Cl, this surface ice is interpreted to date from the Last Interglacial up to the present-day. By combining state-of-the-art satellite derived surface velocities, surface mass balance modelling and ice flow modelling, we estimate that about 75–85% of the meteorites found on the ice field were supplied by ice flow after entering the ice sheet in an accumulation area of a few hundred square kilometres located south (upstream) of the ice field. Less than 0.4 new meteorites per year are supplied to the ice field through ice flow, suggesting that the hundreds of meteorites found 25 years after the first visit to this ice field mostly represent meteorites that were previously not found, rather than newly supplied meteorites. By combining these findings, the infall rate of meteorites from space is estimated, which is in line with values from the literature, but situated at the higher end of the range. A comparison of the oxygen isotopic variation of the surface blue ice to that of the European Project for Ice Coring in Antarctica (EPICA), Dronning Maud Land (EDML) ice core (located 750 km to the west, at the same elevation), suggests that the regional changes in topography have been relatively limited since the Last Interglacial, supporting theories of an overall stable East Antarctic Ice Sheet (EAIS) over this time period. [ABSTRACT FROM AUTHOR]

The Antarctic ice sheet mass balance is a major component of the sea level budget and results from the difference of two fluxes of a similar magnitude: ice flow discharging in the ocean and net snow accumulation on the ice sheet surface, i.e. the surface mass balance (SMB). Separately modelling ice dynamics and SMB is the only way to project future trends. In addition, mass balance studies frequently use regional climate models (RCMs) outputs as an alternative to observed fields because SMB observations are particularly scarce on the ice sheet. Here we evaluate new simulations of the polar RCM MAR forced by three reanalyses, ERA-Interim, JRA-55, and MERRA-2, for the period 1979–2015, and we compare MAR results to the last outputs of the RCM RACMO2 forced by ERA-Interim. We show that MAR and RACMO2 perform similarly well in simulating coast-to-plateau SMB gradients, and we find no significant differences in their simulated SMB when integrated over the ice sheet or its major basins. More importantly, we outline and quantify missing or underestimated processes in both RCMs. Along stake transects, we show that both models accumulate too much snow on crests, and not enough snow in valleys, as a result of drifting snow transport fluxes not included in MAR and probably underestimated in RACMO2 by a factor of 3. Our results tend to confirm that drifting snow transport and sublimation fluxes are much larger than previous model-based estimates and need to be better resolved and constrained in climate models. Sublimation of precipitating particles in low-level atmospheric layers is responsible for the significantly lower snowfall rates in MAR than in RACMO2 in katabatic channels at the ice sheet margins. Atmospheric sublimation in MAR represents 363 Gt yr-1 over the grounded ice sheet for the year 2015, which is 16 % of the simulated snowfall loaded at the ground. This estimate is consistent with a recent study based on precipitation radar observations and is more than twice as much as simulated in RACMO2 because of different time residence of precipitating particles in the atmosphere. The remaining spatial differences in snowfall between MAR and RACMO2 are attributed to differences in advection of precipitation with snowfall particles being likely advected too far inland in MAR. [ABSTRACT FROM AUTHOR]

ObjectiveMultiple spliceosome components are known autoantigens in systemic sclerosis (SSc). Here we aim to identify new and characterize rare anti-spliceosomal autoantibodies in patients with SSc without known autoantibody specificity. MethodsSera that precipitated spliceosome subcomplexes, as detected by immunoprecipitation-mass spectrometry (IP-MS), were identified from a database of 106 patients with SSc without known autoantibody specificity. New autoantibody specificities were confirmed with immunoprecipitation-western blot. The IP-MS pattern of new anti-spliceosomal autoantibodies was compared with anti-U1 RNP-positive sera of patients with different systemic autoimmune rheumatic diseases and anti-SmD-positive sera of patients with systemic lupus erythematosus (n = 24). ResultsThe NineTeen Complex (NTC) was identified and confirmed as new spliceosomal autoantigen in one patient with SSc. U5 RNP, as well as additional splicing factors, were precipitated by the serum of another patient with SSc. The IP-MS patterns of anti-NTC and anti-U5 RNP autoantibodies were distinct from those of anti-U1 RNP- and anti-SmD-positive sera. Furthermore, there was no difference in IP-MS patterns between a limited number of anti-U1 RNP-positive sera of patients with different systemic autoimmune rheumatic diseases. ConclusionAnti-NTC autoantibodies are a new anti-spliceosomal autoantibody specificity, here first identified in a patient with SSc. Anti-U5 RNP autoantibodies are a distinct but rare anti-spliceosomal autoantibody specificity. All major spliceosomal subcomplexes have now been described as target of autoantibodies in systemic autoimmune diseases. [Display omitted] • Autoantibodies against the NineTeen Complex are identified in a patient with systemic sclerosis. • Anti-U5 RNP autoantibodies are rare but distinct anti-spliceosomal autoantibodies. • All major spliceosomal subcomplexes have now been identified as autoantigen in systemic autoimmune rheumatic diseases. [ABSTRACT FROM AUTHOR]

Objective: To determine the link between extraarticular manifestations (EAMs) and baseline characteristics in patients with axial spondyloarthritis (SpA), and to define their potentially differential prognostic value in 2 large, independent Belgian axial SpA cohorts with distinct recruitment periods. Methods: Information on demographic and clinical characteristics and extraarticular manifestations (EAMs) was obtained from patients with axial SpA originating from the (Be)Giant (Belgian Inflammatory Arthritis and Spondylitis) cohort, which includes consecutive axial SpA patients whose data have been collected since 2010, and from the ASPECT (Ankylosing Spondylitis Patients Epidemiological Cross‐sectional Trial) cohort, a Belgian registry of cross‐sectional data collected between February 2004 and February 2005 from consecutive patients with ankylosing spondylitis (AS) or probable AS. Results: Among the 1,250 Belgian patients studied, disease duration was associated with risk of developing inflammatory bowel disease (IBD), with an increase in risk by 20% per 10 years of disease duration (relative risk [RR] 1.2, P = 0.026), and associated with risk of developing acute anterior uveitis, with an increase in risk by 30% per 10 years of disease duration (RR 1.3, P < 0.001). In the subgroup of 171 newly diagnosed patients with prospective follow‐up data, higher mean C‐reactive protein levels over time were demonstrated in those with acute anterior uveitis or IBD compared to those without EAMs or those with psoriasis alone (each P = 0.01). Conclusion: The risk of developing acute anterior uveitis or IBD, but not psoriasis, in patients with axial SpA seems to increase with disease duration and appears to be linked to a higher cumulative exposure to inflammation, thus providing a possible explanation for the differential structural progression observed in those with axial SpA. [ABSTRACT FROM AUTHOR]

Increasing evidence supports a relation of some occupational exposures to systemic sclerosis pathogenesis. We aimed to evaluate occupational exposure and clinical characteristics in male patients with systemic sclerosis followed in two Belgian academic hospitals. One hundred and three male patients, included in the Belgian Systemic Sclerosis Cohort, were identified. An expert in occupational medicine reviewed the occupational history and allocated the patients to one of the following groups: probable exposure to crystalline silica, probable exposure to solvents, probable exposure to other toxins, or no suspected occupational exposure. Clinical characteristics were extracted from the Belgian Systemic Sclerosis Cohort database. Sufficient data were available for 96/103 patients. Most of these male patients (70/96, 72.9%) had a history of occupational exposure, 55 patients were likely exposed to crystalline silica, 11 patients to solvents, 2 patients to both silica and solvents, and 2 patients to asbestos. Only 26 patients had no suspected occupational exposure (27.1%). We noticed a significant difference in smoking status between exposed and non-exposed patients, with the highest percentage of ever smokers in the group with solvent exposure (p = 0.011). We found no significant differences in disease phenotype between exposed and non-exposed patients. However, we noted a trend to a higher prevalence of anti-Scl70 antibodies, cardiac dysfunction, and higher disease activity score in patients with occupational exposure. We observed a strikingly high prevalence of occupational exposure to both silica and solvents in male systemic sclerosis patients. Occupational exposure to silica or solvents is highly prevalent in male systemic sclerosis patients. [ABSTRACT FROM AUTHOR]

Abstract: Ice sheet response to forced changes—such as that from anthropogenic climate forcing—is closely regulated by two‐way interactions with other components of the Earth system. These interactions encompass the ice sheet response to Earth system forcing, the Earth system response to ice sheet change, and feedbacks resulting from coupled ice sheet/Earth system evolution. Motivated by the impact of Antarctic and Greenland ice sheet change on future sea level rise, here we review the state of knowledge of ice sheet/Earth system interactions and feedbacks. We also describe emerging observation and model‐based methods that can improve understanding of ice sheet/Earth system interactions and feedbacks. We particularly focus on the development of Earth system models that incorporate current understanding of Earth system processes, ice dynamics, and ice sheet/Earth system couplings. Such models will be critical tools for projecting future sea level rise from anthropogenically forced ice sheet mass loss. [ABSTRACT FROM AUTHOR]

Background: The advice of a dynamic multidisciplinary discussion (MDD) is believed to be important in the diagnosis of interstitial lung diseases (ILDs). However, to what extent MDD diagnoses differ from the preliminary diagnoses before formal workup and MDD (preMDD diagnoses) is still insufficiently studied.Methods: We compared preMDD and MDD diagnoses in patients discussed at the Leuven University Hospitals MDDs between January 2005 and December 2015.Results: Of 938 consecutive patients discussed in an MDD, 755 (80.5%) received a specific diagnosis. From the 183 patients with unclassifiable ILD, 150 patients (16.0%) received suggestions concerning further investigations to establish a definite diagnosis. In 191 patients (41.9% of patients with a preMDD diagnosis), the MDD changed the diagnosis. In 384 patients (79.5% of patients without preMDD diagnosis), MDD provided a diagnosis when the referring physician did not. MDD diagnosis showed a trend toward better prognostic discrimination between idiopathic pulmonary fibrosis and other ILDs compared with preMDD diagnosis (Harrell C-index, 0.666 vs 0.631; P = .08), which was particularly clear in patients with discordant MDD and preMDD diagnoses (hazard ratio, 2.68 vs 0.84; P = .012 vs .768).Conclusions: The MDD provided a definite diagnosis in 80.5% of presented cases, suggesting further investigations in almost all others. Given the high number of patients without preMDD diagnosis, the rate of change in preMDD diagnoses (41.9% of patients with a preMDD diagnosis) probably is an underestimation. The better prognostic discrimination among ILDs by using MDD indicates the added value of MDD in ILD. [ABSTRACT FROM AUTHOR]

We evaluate modelled Antarctic ice sheet (AIS) near-surface climate, surface mass balance (SMB) and surface energy balance (SEB) from the updated polar version of the regional atmospheric climate model, RACMO2 (1979-2016). The updated model, referred to as RACMO2.3p2, incorporates upper-air relaxation, a revised topography, tuned parameters in the cloud scheme to generate more precipitation towards the AIS interior and modified snow properties reducing drifting snow sublimation and increasing surface snowmelt. Comparisons of RACMO2 model output with several independent observational data show that the existing biases in AIS temperature, radiative fluxes and SMB components are further reduced with respect to the previous model version. The model-integrated annual average SMB for the ice sheet including ice shelves (minus the Antarctic Peninsula, AP) now amounts to 2229 Gt with an interannual variability of 109 Gt y-1. The largest improvement is found in modelled surface snowmelt, which now compares well with satellite and weather station observations. For the high-resolution (~5.5 km) AP simulation, results remain comparable to earlier studies. The updated model provides a new, high-resolution data set of the contemporary near-surface climate and SMB of the AIS; this model version will be used for future climate scenario projections in a forthcoming study. [ABSTRACT FROM AUTHOR]

We evaluate modelled Greenland ice sheet (GrIS) near-surface climate, surface energy balance (SEB) and surface mass balance (SMB) from the updated regional climate model RACMO2 (1958-2016). The new model version, referred to as RACMO2.3p2, incorporates updated glacier outlines, topography and ice albedo fields. Parameters in the cloud scheme governing the conversion of cloud condensate into precipitation have been tuned to correct inland snowfall underestimation: snow properties are modified to reduce drifting snow and melt production in the ice sheet percolation zone. The ice albedo prescribed in the updated model is lower at the ice sheet margins, increasing ice melt locally. RACMO2.3p2 shows good agreement compared to in situ meteorological data and point SEB/SMB measurements, and better resolves the spatial patterns and temporal variability of SMB compared with the previous model version, notably in the north-east, south-east and along the K-transect in south-western Greenland. This new model version provides updated, high-resolution gridded fields of the GrIS presentday climate and SMB, and will be used for projections of the GrIS climate and SMB in response to a future climate scenario in a forthcoming study. [ABSTRACT FROM AUTHOR]

In up to 20% of patients with systemic sclerosis (SSc) no known autoantibody specificity can be identified. Recently discovered autoantigens, such as telomeric repeat binding factor 1 (TERF1), as well as established autoantigens, like RuvBL1/2, are associated with telomere and telomerase biology. We aimed to identify new telomere- and telomerase-associated autoantigens in patients with SSc without known autoantibody specificity. Unlabelled protein immunoprecipitation combined with gel-free liquid chromatography-tandem mass spectrometry (IP-MS) was performed with sera of 106 patients with SSc from two tertiary referral centres that had a nuclear pattern on HEp-2 indirect immunofluorescence without previously identified autoantibody. Telomere- or telomerase-associated proteins or protein complexes precipitated by individual sera were identified. Candidate autoantigens were confirmed through immunoprecipitation-western blot (IP-WB). A custom Luminex xMAP assay for 5 proteins was evaluated with sera from persons with SSc (n = 467), other systemic autoimmune rheumatic diseases (n = 923), non-rheumatic disease controls (n = 187) and healthy controls (n = 199). Eight telomere- and telomerase-associated autoantigens were identified in a total of 11 index patients, including the THO complex (n = 3, all with interstitial lung disease and two with cardiac involvement), telomeric repeat-binding factor 2 (TERF2, n = 1), homeobox-containing protein 1 (HMBOX1, n = 2), regulator of chromosome condensation 1 (RCC1, n = 1), nucleolar and coiled-body phosphoprotein 1 (NOLC1, n = 1), dyskerin (DKC1, n = 1), probable 28S rRNA (cytosine(4447)-C(5))-methyltransferase (NOP2, n = 1) and nuclear valosin-containing protein-like (NVL, n = 2). A Luminex xMAP assay for THO complex subunit 1 (THOC1), TERF2, NOLC1, NOP2 and NVL revealed high reactivity in all index patients, but also in other patients with SSc and disease controls. However, the reactivity by xMAP assay in these other patients was not confirmed by IP-WB. IP-MS revealed key telomere- and telomerase-associated proteins and protein complexes as autoantigens in patients with SSc. • Eight new telomere- and telomerase-associated autoantigens are identified in systemic sclerosis (SSc). • The new autoantigens are known to associate with multiple known SSc autoantigens. • Telomere and telomerase biology could represent an autoantigen hub in SSc. • The new immunoprecipitation-mass spectrometry approach can reduce the seronegative gap in SSc and other autoimmune diseases significantly. [ABSTRACT FROM AUTHOR]

Objectives: To investigate if patients with early rheumatoid arthritis responding insufficiently to initial methotrexate (MTX) and bridging glucocorticoids (GCs) could benefit from early but temporary etanercept introduction as a second remission-induction attempt., Methods: CareRA2020 (NCT03649061) was a 2-year, open-label, multicentre, pragmatic randomised controlled trial. Treatment-naïve patients started MTX and GC bridging (COBRA-Slim: CS). Within a time window from week (W) 8 until W32, early insufficient responders (28-joint Disease Activity Score - C-reactive Protein (DAS28-CRP) >3.2 between W8 and W32 or ≥2.6 at W32) were randomised to a Standard-CS strategy (adding leflunomide first) or Bio-induction-CS strategy (adding etanercept for 24 weeks). Additional treatment adaptations followed the treat-to-target principle. Longitudinal disease activity (DAS28-CRP) over 104 weeks (primary outcome), achievement of DAS28-CRP <2.6 28 weeks after randomisation, and biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use at W104 were compared between randomisation groups., Results: Following CS treatment, 142 patients were early responders; 55 early insufficient responders received Standard-CS and 55 Bio-induction-CS. Superiority of Bio-induction-CS over Standard-CS could not be demonstrated (ß=-0.204, (95% CI -0.486 to 0.078), p=0.157) for the primary outcome. More patients on Bio-induction-CS achieved DAS28-CRP <2.6 at 28 weeks after randomisation (59% (95% CI 44% to 72%) vs 44% (95% CI 31% to 59%) in Standard-CS) and they were treated less frequently with b/tsDMARDs at W104 (19/55, 35%) compared with Standard-CS (29/55, 53%)., Conclusion: Half of the patients responded well to initial COBRA-Slim induction therapy. In early insufficient responders, adding etanercept for 6 months did not improve disease control over 104 weeks versus adding leflunomide first. However, temporary introduction of etanercept resulted in improved disease control early after randomisation and less patients on b/tsDMARDs at W104., Trial Registration Number: NCT03649061., Ctr Pilot Approval Belgium: S59474, EudraCT number: 2017-004054-41., Competing Interests: Competing interests: RJ received consulting fees from Novartis, Pfizer, Amgen, AbbVie; speakers fee from Novartis; support for meeting/travel from Fresenius Kabi; and participation on advisory board from AbbVie, Amgen, Novartis and Fresenius Kabi. KT received consulting fees and payment/honoraria for speakers/manuscript writing/education from Eli Lilly, AbbVie, Amgen, Novartis, Pfizer, Celgene, Otsuka, Celltrion, Galapagos, Viatris, UCB and Sandoz. JV received support for meeting/travel from UCB and Novartis. SA received support for meeting/travel from Eli Lilly, payment/honoraria for speakers/manuscript writing/education from Eli Lilly, and was member of Research Foundation – Flanders (FWO) expert panel. AD received consulting fees from Amgen, support for meeting/travel from Galapagos, Eli Lilly, Sanofi and UCB; participation on data safety monitoring board/advisory board from Agmen. MD reported a grant from Research Foundation – Flanders (FWO), and support for meeting/travel from AbbVie, Novartis, Galapagos and UCB. EDM reported a grant from Research Foundation – Flanders (FWO). RW received consulting fees from Galapagos, and payment/honoraria for speakers/manuscript writing/education from Galapagos and Celltrion. PV received institution grants from Pfizer, Galapagos; consulting fees from Galapagos, Sidekick Health, Pfizer and Boehringer Ingelheim; payment/honoraria for speakers/manuscript writing/education from Eli Lilly, Galapagos and Roularta; support for meeting/travel from AbbVie; participation on data safety monitoring board/advisory board from Eli Lilly, Galapagos, Pfizer, AbbVie, Celltrion and vice president of the Royal Belgian Society for Rheumatology. The remaining authors declared no disclosures., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Firn (compressed snow) covers approximately 90[Formula: see text] of the Greenland ice sheet (GrIS) and currently retains about half of rain and meltwater through refreezing, reducing runoff and subsequent mass loss. The loss of firn could mark a tipping point for sustained GrIS mass loss, since decades to centuries of cold summers would be required to rebuild the firn buffer. Here we estimate the warming required for GrIS firn to reach peak refreezing, using 51 climate simulations statistically downscaled to 1 km resolution, that project the long-term firn layer evolution under multiple emission scenarios (1850-2300). We predict that refreezing stabilises under low warming scenarios, whereas under extreme warming, refreezing could peak and permanently decline starting in southwest Greenland by 2100, and further expanding GrIS-wide in the early 22[Formula: see text] century. After passing this peak, the GrIS contribution to global sea level rise would increase over twenty-fold compared to the last three decades., (© 2022. The Author(s).)

Objectives: To delineate the impact of peripheral musculoskeletal manifestations on stratification of disease phenotype and outcome in new-onset spondyloarthritis (SpA), using a prospective observational nationwide inception cohort, the BelGian Inflammatory Arthritis and spoNdylitis cohorT (Be-Giant)., Methods: Newly diagnosed adult SpA patients, fulfilling the Assessment of SpondyloArthritis International Society (ASAS) criteria for axial or peripheral SpA, were included in Be-Giant and prospectively followed every six months. Peripheral involvement (defined as arthritis, enthesitis and/or dactylitis) was determined in relation to clinically similar patient subsets at baseline and disease activity patterns during two-year follow-up, identified through K-means cluster analysis and latent class growth analysis., Results: From November 2010 to March 2020, 367 patients were enrolled in Be-Giant, of whom 162 (44%) had peripheral manifestations. Two patient clusters [A, axial predominant (n = 248) and B, peripheral predominant (n = 119)] were identified at diagnosis. Longitudinal analysis (n = 115) revealed two trajectories of disease activity in each cluster: one with persistently high disease activity over time ('High'), the other rapidly evolving to low disease activity ('Low'). In cluster A patients, peripheral manifestations predisposed to the 'High' trajectory [odds ratio (OR) = 2.0, 95% CI: 1.3, 3.1, P = 0.001], despite more rapid initiation of biologics compared with patients without peripheral manifestations (hazard ratio (HR)  = 2.1, 95% CI: 1.0, 4.4, P = 0.04 - Cox proportional-hazards model)., Conclusion: Peripheral musculoskeletal manifestations are major determinants of phenotypical diversity in new-onset SpA. Intriguingly, stratification of axial SpA according to concomitant peripheral involvement identified an endotype with an unfavorable outcome despite more prompt therapeutic intensification with biologics. These observations justify an endotype-tailored approach beyond current ASAS/EULAR management recommendations., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The East Antarctic Ice Sheet contains the vast majority of Earth's glacier ice (about 52 metres sea-level equivalent), but is often viewed as less vulnerable to global warming than the West Antarctic or Greenland ice sheets. However, some regions of the East Antarctic Ice Sheet have lost mass over recent decades, prompting the need to re-evaluate its sensitivity to climate change. Here we review the response of the East Antarctic Ice Sheet to past warm periods, synthesize current observations of change and evaluate future projections. Some marine-based catchments that underwent notable mass loss during past warm periods are losing mass at present but most projections indicate increased accumulation across the East Antarctic Ice Sheet over the twenty-first century, keeping the ice sheet broadly in balance. Beyond 2100, high-emissions scenarios generate increased ice discharge and potentially several metres of sea-level rise within just a few centuries, but substantial mass loss could be averted if the Paris Agreement to limit warming below 2 degrees Celsius is satisfied., (© 2022. Springer Nature Limited.)

Competing Interests: Competing interests: WAW has received research grants from Roche, Boehringer-Ingelheim and Galapagos. VS has received research grants and support from Boehringer-Ingelheim and Janssen-Cilag, and research support from Accord Healthcare, UCB, and Celgene. XB was part of a scientific advisory committee for Inova Diagnostics and Thermo Fisher (outside the scope from the submitted work).

The Arctic is the region on Earth that is warming the fastest. At the same time, Arctic sea ice is reducing while the Greenland ice sheet (GrIS) is losing mass at an accelerated pace. Here, we study the seasonal impact of reduced Arctic sea ice on GrIS surface mass balance (SMB), using the Community Earth System Model version 2.1 (CESM2), which features an advanced, interactive calculation of SMB. Addressing the impact of sea-ice reductions on the GrIS SMB from observations is difficult due to the short observational records. Also, signals detected using transient climate simulations may be aliases of other forcings. Here, we analyze dedicated simulations from the Polar Amplification Model Intercomparison Project with reduced Arctic sea ice and compare them with preindustrial sea ice simulations while keeping all other forcings constant. In response to reduced sea ice, the GrIS SMB increases in winter due to increased precipitation, driven by the more humid atmosphere and increasing cyclones. In summer, surface melt increases due to a warmer, more humid atmosphere providing increased energy transfer to the surface through the sensible and latent heat fluxes, which triggers the melt-albedo feedback. Further, warming occurs throughout the entire troposphere over Baffin Bay. This deep warming results in regional enhancement of the 500 hPa geopotential heights over the Baffin Bay and Greenland, increasing blocking and heat advection over the GrIS' surface. This anomalous circulation pattern has been linked to recent increases in the surface melt of the GrIS., Supplementary Information: The online version contains supplementary material available at 10.1007/s00382-021-05897-4., (© The Author(s) 2021.)

Introduction: Fatigue is a major determinant of impaired quality of life in primary Sjögren syndrome (pSS) patients. Effective therapeutic strategies are lacking., Objectives: To review the potential benefit of rituximab, a chimeric anti-CD20 antibody, in the treatment of fatigue in pSS., Methods: A systematic review on the effect of rituximab on fatigue-related outcome measures was conducted, retrieving evidence from CENTRAL (Cochrane Central Register of Controlled Trials), MEDLINE (via PubMed), EMBASE, and Scopus., Results: No benefit of rituximab over placebo on any fatigue-related outcome measure could be demonstrated in the included trials. Significant effects were only observed when compared with baseline, but not when compared with placebo., Conclusions: The use of rituximab for the treatment of pSS-related fatigue cannot be supported by the currently available evidence., Competing Interests: J.-B.V. has received support from the Fund Joël Hurlet and holds a Fellowship “Fonds Wetenschappelijk Onderzoek–Strategisch Basisonderzoek” numbered 180465/SW. The other authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC)., Methods: Pragmatic, prospective, cluster-randomised, controlled, open, 1-year trial (NCT03043846). 18 centres were randomised (1:1). Patients met Axial Spondylo Arthritis International Society (ASAS) criteria for axSpA, had an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2.1, received non-optimal treatment by non-steroidal anti-inflammatory drugs and were biologic-naive., Interventions: (1) TC/T2T : visits every 4 weeks and prespecified strategy based on treatment intensification until achieving target (ie, ASDAS <2.1); (2) UC: visits every 12 weeks and treatment at the rheumatologist's discretion., Main Outcome: Percentage of patients with a ≥30% improvement on the ASAS-Health Index (ASAS-HI). Other efficacy outcomes and adverse events were recorded. A health economic evaluation was performed., Statistical Analysis: Two-level mixed models were used to estimate efficacy outcomes. Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained for TC/T2T versus UC., Results: 160 patients were included (80/group). Mean (SD) age was 37.9 (11.0) years and disease duration was 3.7 (6.2) years; 51.2% were men. ASDAS at inclusion was 3.0 (0.7), and ASAS-HI was 8.6 (3.7). ASAS-HI improved by ≥30% in 47.3% of the TC/T2T arm and in 36.1% of those receiving UC (non-significant). All secondary efficacy outcomes were more frequent in the TC/T2T arm, although not all statistically significant. Safety was similar in both arms. From a societal perspective, TC/T2T resulted in an additional 0.04 QALY, and saved €472 compared with UC., Conclusion: TC/T2T was not significantly superior to UC for the primary outcome, while many secondary efficacy outcomes favoured it, had a similar safety profile and was favourable from a societal health economic perspective., Trial Registration Number: NCT03043846., Competing Interests: Competing interests: Dr van Tubergen reports grants and personal fees from Novartis, grants from Pfizer, grants from UCB, grants from Biogen, grants from AbbVie, outside the submitted work. Dr van der Heijde reports personal fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma, outside the submitted work; and Director of Imaging Rheumatology bv. Dr van Gaalen reports grants from Stichting vrienden van Sole Mio, grants from Stichting ASAS, grants and personal fees from Novartis, grants from UCB, personal fees from MSD, personal fees from AbbVie, personal fees from Bristol Myers Squibb, outside the submitted work. AB received a research grant to her department from AbbVie, consultation fees from Eli Lilly and Galapagos and a speakers fee from UCB, all paid to her department. Dr Van den Bosch reports personal fees from AbbVie, personal fees from Celgene, personal fees from Eli Lilly, personal fees from Galapagos, personal fees from Janssen, personal fees from Novartis, personal fees from Pfizer, personal fees from UCB, outside the submitted work. Dr Claudepierre reports personal fees from Roche Chugai, Novartis, Pfizer, MSD, grants from Roche Chugai, Novartis, Pfizer, UCB, MSD, AbbVie, Lilly, Celgene, Janssen, BMS, outside the submitted work. Dr Molto reports grants from UCB during the conduct of the study; personal fees from AbbVie, grants and personal fees from UCB, personal fees from BMS, grants and personal fees from Pfizer, grants and personal fees from MSD, personal fees from Novartis, personal fees from Gilead, personal fees from Lilly, outside the submitted work. Dr Gossec reports grants from Amgen, Lilly, Janssen, Pfizer, Sandoz, Sanofi, Galapagos, personal fees from AbbVie, Amgen, BMS, Biogen, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, outside the submitted work. Dr Dougados reports grants from UCB, during the conduct of the study; grants and personal fees from AbbVie, grants and personal fees from Pfizer, grants and personal fees from Lilly, grants and personal fees from Novartis, grants and personal fees from Roche, grants and personal fees from BMS, grants and personal fees from Merck, outside the submitted work. Dr Dernis, Dr Ruyssen-Witrand, Dr Lenaerts, Dr Lopez-Medina, Dr Sparsa, Dr Starmans-Kool, Dr C Webers, Dr Pouplin, Dr Soubrier and Dr Joos have nothing to declare., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Myositis-specific autoantibodies (MSAs) are thought to be mutually exclusive in patients with idiopathic inflammatory myopathies (IIM) based on studies with immunoprecipitation-based (IP) detection methods. Recently, detection of multiple MSAs in unique patients is increasingly reported, but the extent of this phenomenon remains unclear., Methods: At our centre, we reviewed results from two line immunoassays and one dot immunoassay in 145 IIM patients and 240 controls for the presence of multiple MSAs. Pubmed and Embase were systematically searched for articles mentioning detection of multiple MSAs in IIM patients, published until February 2019. We assessed the frequency, detection method, the precise combinations and clinical phenotypes of participants with multiple MSAs., Results: At our centre, detection of multiple MSAs occurred in 3.4-8.3% of patients with IIM, depending on the assay. However, no cases with full concordance across all three assays were identified. Forty-four articles reported detection of multiple MSAs, representing a total of 133 cases, including four patients with a connective tissue disease other than IIM and two healthy controls. In 101 cases all MSAs were detected using only one detection method: 40 cases with IP-based methods (most frequently used technique) and 61 cases with other assay types. In most cases the phenotype of patients with multiple MSAs matched the predicted presentation associated with one MSA and in few cases the phenotype matched with both MSAs., Conclusion: Detection of multiple MSAs in unique IIM patients is less rare than commonly accepted. Specificity issues of the commercially available multiplex immunoassays may, at least partly, explain the higher frequency compared to IP-based methods. 'True multiple MSA-positive' patients may exist, though they are most likely rare., Competing Interests: Declaration of Conflicts Interest None, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: SSc often leads to fibrotic cutaneous involvement of the face and reduced oral aperture, with impaired food intake and oral hygiene. Oral exercises can increase oral aperture but are often hampered by low adherence rates. The aim of this mixed method study was to explore the feasibility, patient satisfaction and effectiveness of two exercise programmes in SSc-associated microstomia., Methods: Adult patients suffering from SSc and microstomia (maximal oral aperture <40 mm) were randomized to two groups. Group A exercised with a jaw motion device (Therabite), whereas group B performed mouth-stretching exercises. Patients were expected to exercise for 10 min, three times per day for 3 months. Patients were evaluated at baseline, 3 months (period without intervention), 6 months (after 3 months of intervention) and 9 months (post-intervention). At month 6, semi-structured one-to-one interviews were conducted., Results: We included six women and three men, median age 60 years and median disease duration 8 years. At 6 months, all patients in group A ( n  = 4) and four in group B ( n  = 5) improved, with a median of 9 and 7 mm, respectively. The adherence ranged between 63.7 and 98.9% in group A and between 48.5 and 97.4% in group B. The interview revealed three themes: drivers, challenges and perceived improvement., Conclusion: Both interventions improved maximal oral aperture. The adherence to therapy was high, but none of the patients considered it feasible to continue practising three times per day. Future studies are needed in order to define feasible long-term exercise programmes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Surface mass balance (SMB) provides mass input to the surface of the Antarctic and Greenland Ice Sheets and therefore comprises an important control on ice sheet mass balance and resulting contribution to global sea level change. As ice sheet SMB varies highly across multiple scales of space (meters to hundreds of kilometers) and time (hourly to decadal), it is notoriously challenging to observe and represent in models. In addition, SMB consists of multiple components, all of which depend on complex interactions between the atmosphere and the snow/ice surface, large-scale atmospheric circulation and ocean conditions, and ice sheet topography. In this review, we present the state-of-the-art knowledge and recent advances in ice sheet SMB observations and models, highlight current shortcomings, and propose future directions. Novel observational methods allow mapping SMB across larger areas, longer time periods, and/or at very high (subdaily) temporal frequency. As a recent observational breakthrough, cosmic ray counters provide direct estimates of SMB, circumventing the need for accurate snow density observations upon which many other techniques rely. Regional atmospheric climate models have drastically improved their simulation of ice sheet SMB in the last decade, thanks to the inclusion or improved representation of essential processes (e.g., clouds, blowing snow, and snow albedo), and by enhancing horizontal resolution (5-30 km). Future modeling efforts are required in improving Earth system models to match regional atmospheric climate model performance in simulating ice sheet SMB, and in reinforcing the efforts in developing statistical and dynamic downscaling to represent smaller-scale SMB processes., (©2019. The Authors.)

The high Arctic is the fastest warming region on Earth, evidenced by extreme near-surface temperature increase in non-summer seasons, recent rapid sea ice decline and permafrost melting since the early 1990's. Understanding the impact of climate change on the sensitive Arctic ecosystem to climate change has so far been hampered by the lack of time-constrained, high-resolution records and by implicit climate data analyses. Here, we show evidence of sharp growth in freshwater green algae as well as distinct diatom assemblage changes since ~1995, retrieved from a high-Arctic (80 °N) lake sediment record on Barentsøya (Svalbard). The proxy record approaches an annual to biennial resolution. Combining remote sensing and in-situ climate data, we show that this ecological change is concurrent with, and is likely driven by, the atmospheric warming and a sharp decrease in the length of the sea ice covered period in the region, and throughout the Arctic. Moreover, this research demonstrates the value of palaeoclimate records in pristine environments for supporting and extending instrumental records. Our results reinforce and extend observations from other sites that the high Arctic has already undergone rapid ecological changes in response to on-going climate change, and will continue to do so in the future.

Objectives: Following results in open-label studies of rituximab in patients with systemic sclerosis, a Belgian three-centre initiative was launched to explore safety and efficacy of rituximab in early, diffuse cutaneous systemic sclerosis (dcSSc)., Methods: Open-label study of 17 patients with early dcSSc, treated with two courses of rituximab, at month 0 and 6. Clinical examination, lung function testing, echocardiography, disease activity score (DAS) and functional status were performed at baseline and over 24 months of follow-up., Results: Modified Rodnan skin score (MRSS) changed significantly over time, with a mean of 25.5 (standard deviation [SD] 6.0) at baseline to 12.6 (SD 5.1) at month 24 (Mixed Model Analysis [MMA] p < 0.0001), which is a decrease of 51% at month 24 vs. baseline. DAS showed significant decrease over the total study period, with a score of 4.1 (SD 1.7) at baseline to 1.5 (SD 1.8) at month 24 (MMA p < 0.0001). Additionally, this was significant at all time points vs. baseline, both for MRSS and DAS. Internal organ status remained clinically stable throughout the study period. No statistically significant differences compared to baseline were found at the follow-up time points. Seven serious adverse events took place, all except for one, considered unrelated to study medication., Conclusions: This is the first multicentre Belgian collaboration investigating potential efficacy of rituximab in early dcSSc. Rituximab appears to be safe and tolerable and it may have beneficial effects on skin involvement, on overall disease activity and on stabilization of internal organ status in early dcSSc.

Interstitial lung disease (ILD) can be either idiopathic, the result of exposure or may be associated with extrapulmonary diseases. Among the latter, connective tissue diseases (CTDs) make up the largest part. The identification, follow-up and treatment of CTD-associated ILD (CTD-ILD) are a challenge for every physician as ILD can occur before, during and after the diagnosis of CTD. Early detection of pulmonary involvement is an essential task for the treating rheumatologist and recognition of the underlying CTD can pose a challenge for the treating pulmonologist. Multidisciplinary engagement towards the patient is therefore indispensable for optimal clinical care. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 326-335) ., (Copyright: © 2017.)

Objectives: This study aimed to describe the epidemiology of ankylosing spondylitis (AS) in rheumatology practice at the beginning of the anti-TNF (tumour necrosis factor) era, and to evaluate the initiation of anti-TNF therapy in a clinical setting where prescription is regulated by the authority's imposed reimbursement criteria., Methods: Between February 2004 and February 2005, all Belgian rheumatologists in academic and non-academic outpatient settings were invited to register all AS patients who visited their practice. A random sample of these patients was further examined by an in-depth clinical profile. In a follow-up investigation, we recorded whether patients initiated anti-TNF therapy and compared this to their eligibility at baseline evaluation., Results: 89 rheumatologists participated and registered 2141 patients; 1023 patients were clinically evaluated. These 847 fulfilled the New York modified criteria for definite AS and 176 for probable AS. The profile of AS in rheumatology practice is characterised by longstanding and active disease with a high frequency of extra-articular manifestations and metrological and functional impairment. At a median of 2 months after the clinical evaluation, anti-TNF therapy was initiated in 263 of 603 (44%) evaluable patients with definite AS and in 22 of 138 (16%) evaluable patients with probable AS (total 38%). More than 85% of the patients who started anti-TNF therapy had an increased Bath Ankylosing Spondylitis Disease Activity Index despite previous NSAID (non-steroidal anti-inflammatory drug) use., Conclusions: Of a representative cohort of 1023 Belgian AS patients seen in daily rheumatology practice, about 40% commenced anti-TNF therapy. Decision factors to start anti-TNF therapy may include disease activity and severity.

The administration of recombinant human IGF-I complexed with its predominant binding protein IGF binding protein-3 (rhIGF-I/IGFBP-3) may allow the safe administration of higher doses of IGF-I than can be accomplished with rhIGF-I alone. The aim of this randomized, double-blind, placebo- controlled pilot study was to evaluate the short-term safety and musculoskeletal effects of rhIGF-I/IGFBP-3 in older women (aged 65-90 yr) with recent hip fracture. Within 72 h after the event, 30 patients received continuous administration of either placebo (n = 10), 0.5 mg/kg.d rhIGF-I/IGFBP-3 (n = 9), or 1 mg/kg.d rhIGF-I/IGFBP-3 (n = 11). Treatment was administered by sc infusion through a portable mini-pump for a total of 8 wk after hip fracture surgery, with patient follow-up to 6 months after surgery. Efficacy evaluations included a contralateral hip bone density determination, markers of bone turnover (including serum osteocalcin and urinary excretion of N-telopeptide), grip strength, and tests of functional ability. During the administration of rhIGF-I/IGFBP-3, mean serum levels of IGF-I significantly (P < 0.001) increased from 83 ng/ml to 289 ng/ml (0.5 mg/kg.d) and 393 ng/ml (1 mg/kg.d), respectively. Both doses were well tolerated, and no hypoglycemia or other therapy-induced side effects were observed. After an initial loss of hip bone density after hip fracture surgery, patients treated with 1 mg/kg.d rhIGF-I/IGFBP-3 regained a substantial portion of their femoral bone mass. At 6 months postfracture (4 months after the 2-month infusion), they showed a statistically not significant decrease from baseline in hip bone density (-2.6%, P = 0.53). Placebo-treated patients, on the other hand, failed to regain lost bone: at 6 months postfracture, bone density in the placebo group had declined by 6.1% (P = 0.04). Additionally, in patients treated with 1.0 mg/kg.d rhIGF-I/IGFBP-3, grip strength had increased from baseline by 11.4% by the end of the study (P = 0.04) whereas patients on placebo lost 11.6% from baseline (P = 0.16). This increase in muscle strength in the high-dose group was associated with a positive effect on functional recovery. We conclude that a 2-month infusion of rhIGF-I/IGFBP-3 in patients with recent hip fracture is feasible, safe, and well tolerated. Analyzing the effects on bone mass, muscle strength, and functional ability, we observed beneficial trends. In the context of a small exploratory study, these findings should be interpreted with caution, but they support the need for future trials to further assess the therapeutic potential of rhIGF-I/IGFBP-3 in elderly subjects with osteoporosis.