We discuss Greenland Ice Sheet (GrIS) surface mass balance (SMB) differences between the updated polar version of the RACMO climate model (RACMO2.3) and the previous version (RACMO2.1). Among other ...revisions, the updated model includes an adjusted rainfall-to-snowfall conversion that produces exclusively snowfall under freezing conditions; this especially favours snowfall in summer. Summer snowfall in the ablation zone of the GrIS has a pronounced effect on melt rates, affecting modelled GrIS SMB in two ways. By covering relatively dark ice with highly reflective fresh snow, these summer snowfalls have the potential to locally reduce melt rates in the ablation zone of the GrIS through the snow-albedo-melt feedback. At larger scales, SMB changes are driven by differences in orographic precipitation following a shift in large-scale circulation, in combination with enhanced moisture to precipitation conversion for warm to moderately cold conditions. A detailed comparison of model output with observations from automatic weather stations, ice cores and ablation stakes shows that the model update generally improves the simulated SMB-elevation gradient as well as the representation of the surface energy balance, although significant biases remain.
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 present-day 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.
Protein bodies (PBs) are particles consisting of insoluble, aggregated proteins with potential as a vaccine formulation. PBs can contain high concentrations of antigen, are stable and relatively ...resistant to proteases, release antigen slowly and are cost-effective to manufacture. Yet, the capacity of PBs to provoke immune responses and protection in the upper respiratory tract, a major entry route of respiratory pathogens, is largely unknown.
In this study, we vaccinated mice intranasally with PBs comprising antigens from Streptococcus pneumoniae and evaluated the level of protection against nasopharyngeal colonization. PBs composed of the α-helical domain of pneumococcal surface protein A (PspAα) provided superior protection against colonization with S. pneumoniae compared to soluble PspAα. Immunization with soluble protein or PBs induced differences in antibody binding to pneumococci as well as a highly distinct antigen-specific nasal cytokine profile upon in vivo stimulation with inactivated S. pneumoniae. Moreover, immunization with PBs composed of conserved putative pneumococcal antigens reduced colonization by S. pneumoniae in mice, both as a single- and as a multi-antigen formulation.
In conclusion, PBs represent a vaccine formulation that elicits strong mucosal immune responses and protection. The versatility of this platform offers opportunities for development of next-generation vaccine formulations.
Variation in the incidence rate in epidemiological studies on amyotrophic lateral sclerosis (ALS) may be due to a small population size and under ascertainment of patients. The previously reported ...incidence decline in the elderly and a decrease in the male:female ratio in postmenopausal age groups have yet to be confirmed.
ALS epidemiology in a large population based register in The Netherlands was studied between 1 January 2006 and 31 December 2009, and applied capture-recapture methodology in separate age and gender groups to adjust for the number of unobserved patients.
1217 incident patients were observed, and a capture-recapture incidence of 2.77 per 100 000 person-years (95% CI 2.63 to 2.91). Prevalence on 31 December 2008 was 10.32 per 100 000 individuals (95% CI 9.78 to 10.86). The incident cohort had a higher median age at onset (63.0 vs 58.1 years) and more bulbar onset patients (30.0% vs 19.1%) compared with the prevalent cohort. Incidence and prevalence peaked in the 70-74 year age group followed by a rapid decline in older age. The male:female ratio in the premenopausal age group (1.91, 95% CI 1.32 to 2.79) was not significantly higher than that in the postmenopausal age group (1.50, 95% CI 1.34 to 1.67).
The marked difference in patient characteristics between incident and prevalent cohorts underscores the importance of including incident patients when studying susceptibility or disease modifying factors in ALS. The incidence decline in the elderly may suggest that ALS is not merely the result of ageing. Absence of a significant postmenopausal drop in the male:female ratio suggests that the protective role of female sex hormones in ALS is limited.
Analyses of remote sensing data, surface observations and output from a regional atmosphere model point to new records in 2010 for surface melt and albedo, runoff, the number of days when bare ice is ...exposed and surface mass balance of the Greenland ice sheet, especially over its west and southwest regions. Early melt onset in spring, triggered by above-normal near-surface air temperatures, contributed to accelerated snowpack metamorphism and premature bare ice exposure, rapidly reducing the surface albedo. Warm conditions persisted through summer, with the positive albedo feedback mechanism being a major contributor to large negative surface mass balance anomalies. Summer snowfall was below average. This helped to maintain low albedo through the 2010 melting season, which also lasted longer than usual.
The second phase of the Global Land‐Atmosphere Coupling Experiment (GLACE‐2) is aimed at quantifying, with a suite of long‐range forecast systems, the degree to which realistic land surface ...initialization contributes to the skill of subseasonal precipitation and air temperature forecasts. Results, which focus here on North America, show significant contributions to temperature prediction skill out to two months across large portions of the continent. For precipitation forecasts, contributions to skill are much weaker but are still significant out to 45 days in some locations. Skill levels increase markedly when calculations are conditioned on the magnitude of the initial soil moisture anomaly.
Antarctic Ice Sheet elevation changes, which are used to estimate changes in the mass of the interior regions, are caused by variations in the depth of the firn layer. We quantified the effects of ...temperature and accumulation variability on firn layer thickness by simulating the 1980-2004 Antarctic firn depth variability. For most of Antarctica, the magnitudes of firn depth changes were comparable to those of observed ice sheet elevation changes. The current satellite observational period (~15 years) is too short to neglect these fluctuations in firn depth when computing recent ice sheet mass changes. The amount of surface lowering in the Amundsen Sea Embayment revealed by satellite radar altimetry (1995-2003) was increased by including firn depth fluctuations, while a large area of the East Antarctic Ice Sheet slowly grew as a result of increased accumulation.
Interference from isomeric steroids is a potential cause of disparity between mass spectrometry-based 17-hydroxyprogesterone (17OHP) results. We aimed to assess the proficiency of mass spectrometry ...laboratories to report 17OHP in the presence of known isomeric steroids.
A series of five samples were prepared using a previously demonstrated commutable approach. These samples included a control (spiked to 15.0 nmol/L 17OHP) and four challenge samples further enriched with equimolar concentrations of 17OHP isomers (11α-hydroxyprogesterone, 11β-hydroxyprogesterone, 16α-hydroxyprogesterone or 21-hydroxyprogesterone). These samples were distributed to 38 participating laboratories that reported serum 17OHP results using mass spectrometry in two external quality assurance programs. The result for each challenge sample was compared to the control sample submitted by each participant.
Twenty-six laboratories (68 % of distribution) across three continents returned results. Twenty-five laboratories used liquid chromatography-tandem mass spectrometry (LC-MS/MS), and one used gas chromatography-tandem mass spectrometry to measure 17OHP. The all-method median of the control sample was 14.3 nmol/L, ranging from 12.4 to 17.6 nmol/L. One laboratory had results that approached the lower limit of tolerance (minus 17.7 % of the control sample), suggesting the isomeric steroid caused an irregular result.
Most participating laboratories demonstrated their ability to reliably measure 17OHP in the presence of the four clinically relevant isomeric steroids. The performance of the 12 (32 %) laboratories that did not engage in this activity remains unclear. We recommend that all laboratories offering LC-MS/MS analysis of 17OHP in serum, plasma, or dried bloodspots determine that the isomeric steroids are appropriately separated.
During the last interglacial period (Eemian, 130–115 kyr BP) eustatic global sea level likely peaked at > 6 m above the present-day level, but estimates of the contribution of the Greenland Ice Sheet ...vary widely. Here we use an asynchronously two-way-coupled regional climate–ice-sheet model, which includes physically realistic feedbacks between the changing ice sheet topography and climate forcing. Our simulation results in a contribution from the Greenland Ice Sheet to the Eemian sea level highstand between 1.2 and 3.5 m, with a most likely value of 2.1 m. Simulated Eemian ice loss in Greenland is dominated by the rapid retreat of the southwestern margin; two-thirds of the ice loss occurred south of 70° N. The southern dome survived the Eemian and remained connected to the central dome. Large-scale ice sheet retreat is prevented in areas with high accumulation. Our results broadly agree with ice-core-inferred elevation changes and marine records, but it does not match with the ice-core-derived temperature record from northern Greenland. During maximum Eemian summertime insolation, Greenland mass loss contributed ~ 0.5 m kyr−1 to sea level rise, 24% of the reconstructed total rate of sea level rise. Next to that, a difference of > 3 m remains between our maximum estimate of the Greenland contribution and the reconstructed minimum value of the global eustatic Eemian highstand. Hence, the Antarctic Ice Sheet must also have contributed significantly to this sea level highstand.
To perform a systematic literature review and meta-analysis on endothelial cell (EC) markers that are involved and dysregulated in systemic lupus erythematosus (SLE) in relation to disease activity, ...as EC dysregulation plays a major role in the development of premature atherosclerosis in SLE.
Search terms were entered into Embase, MEDLINE, Web of Science, Google Scholar and Cochrane. Inclusion criteria were 1) studies published after 2000 reporting measurements of EC markers in serum and/or plasma of SLE patients (diagnosed according to ACR/SLICC criteria), 2) English language peer reviewed articles, and 3) disease activity measurement. For meta-analysis calculations, the Meta-Essentials tool by Erasmus Research Institute and of Management (ERIM) was used. Only those EC markers, which were 1) reported in at least two articles and 2) reported a correlation coefficient (i.e. Spearman's rank or Pearson's) between the measured levels of the EC marker and disease activity were included. For meta-analyses, a fixed effect model was used.
From 2133 hits, 123 eligible articles were selected. The identified SLE-related endothelial markers were involved in EC activation, EC apoptosis, disturbed angiogenesis, defective vascular tone control, immune dysregulation and coagulopathy. Meta-analyses of primarily cross-sectional studies showed significant associations between marker levels and disease activity for the following endothelial markers: Pentraxin-3, Thrombomodulin, VEGF, VCAM-1, ICAM-1, IP-10 and MCP-1. Dysregulated EC markers without associations with disease activity were: Angiopoeitin-2, vWF, P-Selectin, TWEAK and E-Selectin.
We provide a complete literature overview for dysregulated EC markers in SLE comprising a wide range of different EC functions. SLE-induced EC marker dysregulation was seen with, but also without, association with disease activity. This study provides some clarity in the eminent complex field of EC markers as biomarkers for SLE. Longitudinal data on EC markers in SLE are now needed to guide us more in unravelling the pathophysiology of premature atherosclerosis and cardiovascular events in SLE patients.
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