| 1. |
- Momozawa, Y, et al.
(författare)
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IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2427-
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Tidskriftsartikel (refereegranskat)abstract
- GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.
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| 2. |
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| 3. |
- van Wesemael, Tineke J., et al.
(författare)
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Smoking is associated with the concurrent presence of multiple autoantibodies in rheumatoid arthritis rather than with anti-citrullinated protein antibodies per se : A multicenter cohort study
- 2016
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The contribution of smoking to rheumatoid arthritis (RA) is hypothesized to be mediated through formation of anti-citrullinated protein antibodies (ACPA). In RA, however, autoantibodies such as ACPA, rheumatoid factor (RF), and anti-carbamylated protein antibodies (anti-CarP) often occur together, and it is thus unclear whether smoking is specifically associated with some autoantibodies rather than others. We therefore investigated whether smoking is only associated with ACPA or with the presence of multiple RA-related autoantibodies. Methods: A population-based Japanese cohort (n = 9575) was used to investigate the association of smoking with RF and anti-cyclic citrullinated peptide antibodies (anti-CCP2) in individuals without RA. Furthermore, RA patients fulfilling the 1987 criteria from three early arthritis cohorts from the Netherlands (n = 678), the United Kingdom (n = 761), and Sweden (n = 795) were used. Data on smoking, RF, anti-CCP2, and anti-CarP were available. A total score of autoantibodies was calculated, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by logistic regression. Results: In the population-based non-RA cohort, no association was found between smoking and one autoantibody (RF or anti-CCP2), but smoking was associated with double-autoantibody positivity (OR 2.95, 95% CI 1.32-6.58). In RA patients, there was no association between smoking and the presence of one autoantibody (OR 0.99, 95% CI 0.78-1.26), but smoking was associated with double-autoantibody positivity (OR 1.32, 95% CI 1.04-1.68) and triple-autoantibody positivity (OR 2.05, 95% CI 1.53-2.73). Conclusions: Smoking is associated with the concurrent presence of multiple RA-associated autoantibodies rather than just ACPA. This indicates that smoking is a risk factor for breaking tolerance to multiple autoantigens in RA.
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| 7. |
- Kissel, Theresa, et al.
(författare)
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IgG Anti–Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter : A Cross-Sectional Study Encompassing ~1,500 Samples
- 2022
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Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 74:7, s. 1147-1158
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti–citrullinated protein antibodies (ACPAs). A notable feature of IgG ACPA is the abundant expression of N-linked glycans in the variable domain. However, the presence of ACPA variable domain glycosylation (VDG) across disease stages, and its response to therapy, are poorly described. To understand its dynamics, we investigated the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages.Methods: Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. Additionally, we measured VDG in 234 samples from patients with RA who did or did not achieve long-term drug-free remission (DFR) during up to 16 years follow-up.Results: IgG ACPA VDG significantly increased (P < 0.0001) toward disease onset and was associated with ACPA levels and epitope spreading prior to diagnosis. A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). In patients in whom DFR was later achieved, IgG ACPA VDG was already reduced at the time of RA onset.Conclusion: The abundance of IgG ACPA VDG increases toward RA onset and correlates with maturation of the ACPA response. While IgG ACPA VDG levels are fairly stable in established disease, a lower degree of VDG at RA onset correlates with DFR. Although the underlying biologic mechanisms remain elusive, our data support the concept that VDG relates to an expansion of the ACPA response in the pre-disease phase and contributes to disease development.
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| 15. |
- Verheul, Marije K., et al.
(författare)
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Triple positivity for anti–citrullinated protein autoantibodies, rheumatoid factor, and anti–carbamylated protein antibodies conferring high specificity for rheumatoid arthritis : implications for very early identification of at‐risk individuals
- 2018
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Ingår i: Arthritis & Rheumatology. - Hoboken : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 70:11, s. 1721-1731
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In rheumatoid arthritis(RA), the autoantibodies anti-citrullinated protein antibodies(ACPA) and rheumatoid factor(RF) are commonly used to aid RA diagnosis. Although these autoantibodies are mainly found in RA, their specificity is not optimal. It is therefore difficult to identify RA patients, especially in very early disease, based on the presence of ACPA and RF alone. Also, anti-carbamylated protein(anti-CarP) antibodies have diagnostic and prognostic value as the presence of anti-CarP antibodies associates with joint damage in RA patients and with future RA development in arthralgia patients. Therefore, we aimed to investigate the value of combined antibody testing in relation to prediction and diagnosis of (early) RA.METHODS: A literature search resulted in twelve studies, consisting of RA patients, pre-RA individuals, disease controls, healthy first-degree relatives of RA patients or healthy controls, in which data on RF, ACPA and anti-CarP antibody-status was available. Random effects meta-analyses were carried out for several antibody combinations.RESULTS: The individual antibodies are highly prevalent in RA(34%-80%) compared to the control groups, but are also present in non-RA controls(0%-23%). To classify most people correctly as RA or non-RA, the combination of ACPA and/or RF often performs well(specificity:65-100, sensitivity:59-88). However, triple positivity for ACPA, RF and anti-CarP antibodies results in a higher specificity(98-100) (accompanied by a lower sensitivity(11-39)).CONCLUSIONS: As the rheumatology field is moving towards very early identification of RA and possible screening for individuals at maximum risk in populations with a low pre-test probability, triple positivity provides interesting information on individuals at risk to develop RA.
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| 16. |
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| 17. |
- Derksen, V. F A M, et al.
(författare)
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Rheumatoid arthritis phenotype at presentation differs depending on the number of autoantibodies present
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76, s. 716-720
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Tidskriftsartikel (refereegranskat)abstract
- Objectives In rheumatoid arthritis (RA), seropositive and seronegative disease may be two entities with different underlying pathophysiological mechanisms, long-term outcomes and disease presentations. However, the effect of the conjoint presence of multiple autoantibodies, as proxy for a more pronounced humoral autoimmune response, on clinical phenotype remains unclear. Therefore, this study investigates the association between the number of autoantibodies and initial clinical presentation in two independent cohorts of patients with early RA. Methods Autoantibody status (rheumatoid factor, anticitrullinated protein antibodies and anticarbamylated protein antibodies) was determined at baseline in the Leiden Early Arthritis Cohort (n=828) and the Swedish BARFOT (Better Anti-Rheumatic Farmaco-Therapy, n=802) study. The association between the number of autoantibodies and baseline clinical characteristics was investigated using univariable and multivariable ordinal regression. Results In both cohorts, the following independent associations were found in multivariable analysis: patients with a higher number of RA-associated antibodies were younger, more often smokers, had a longer symptom duration and a higher erythrocyte sedimentation rate at presentation compared with patients with few autoantibodies. Conclusions The number of autoantibodies, reflecting the breadth of the humoral autoimmune response, is associated with the clinical presentation of RA. Predisease pathophysiology is thus reflected by the initial clinical phenotype.
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| 24. |
- Amkreutz, J. A. M. P., et al.
(författare)
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Association Between Bone Mineral Density and Autoantibodies in Patients With Rheumatoid Arthritis
- 2021
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Ingår i: Arthritis and Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 73:6, s. 921-930
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Autoantibodies, such as anti–citrullinated protein antibodies (ACPAs), have been described as inducing bone loss in rheumatoid arthritis (RA), which can also be reflected by bone mineral density (BMD). We therefore examined the association between osteoporosis and autoantibodies in two independent RA cohorts. Methods: Dual x-ray absorptiometry (DXA) of the lumbar spine and left hip was performed in 408 Dutch patients with early RA during 5 years of follow-up and in 198 Swedish patients with early RA during 10 years of follow-up. The longitudinal effect of ACPAs and other autoantibodies on several BMD measures was assessed using generalized estimating equations. Results: In the Dutch cohort, significantly lower BMD at baseline was observed in ACPA-positive patients compared to ACPA-negative patients, with an estimated marginal mean BMD in the left hip of 0.92 g/cm2 (95% confidence interval [95% CI] 0.91–0.93) versus 0.95 g/cm2 (95% CI 0.93–0.97) (P = 0.01). In line with this, significantly lower Z scores at baseline were noted in the ACPA-positive group compared to the ACPA-negative group (estimated marginal mean Z score in the left hip of 0.18 [95% CI 0.08–0.29] versus 0.48 [95% CI 0.33–0.63]) (P < 0.01). However, despite clear differences at baseline, ACPA positivity was not associated with greater decrease in absolute BMD or Z scores over time. Furthermore, there was no association between BMD and higher levels of ACPAs or other autoantibodies (rheumatoid factor and anti–carbamylated protein antibodies). In the Swedish cohort, ACPA-positive patients tended to have a higher prevalence of osteopenia at baseline (P = 0.04), but again, ACPA positivity was not associated with an increased prevalence of osteopenia or osteoporosis over time. Conclusion: The presence of ACPAs is associated with significantly lower BMD at baseline, but not with greater BMD loss over time in treated RA patients. These results suggest that ACPAs alone do not appear to contribute to bone loss after disease onset when disease activity is well-managed. © 2020 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
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| 26. |
- Jayne, David R. W., et al.
(författare)
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Randomized trial of plasma exchange or high-dosage Methylprednisolone as adjunctive therapy for severe renal vasculitis
- 2007
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673. ; 18:7, s. 2180-2188
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Tidskriftsartikel (refereegranskat)abstract
- Systemic vasculitis associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA) is the most frequent cause of rapidly progressive glomerulonephritis. Renal failure at presentation carries an increased risk for ESRD and death despite immunosuppressive therapy. This study investigated whether the addition of plasma exchange was more effective than intravenous methylprednisolone in the achievement of renal recovery in those who presented with a serum creatinine > 500 mu mol/L (5.8 mg/dl). A total of 137 patients with a new diagnosis of ANCA-associated systemic vasculitis confirmed by renal biopsy and serum creatinine > 500 mu mol/L (5.8 mg/dl) were randomly assigned to receive seven plasma exchanges (n = 70) or 3000 mg of intravenous methylprednisolone (n = 67). Both groups received oral cyclophosphamide and oral prednisolone. The primary end point was dialysis independence at 3 mo. Secondary end points included renal and patient survival at 1 yr and severe adverse event rates. At 3 mo, 33 (49%) of 67 after intravenous methylprednisolone compared with 48 (69%) or 70 after plasma exchange were alive and independent of dialysis (95% confidence interval for the difference 18 to 35%; P = 0.02). As compared with intravenous methylprednisolone, plasma exchange was associated with a reduction in risk for progression to ESRD of 24% (95% confidence interval 6.1 to 41%), from 43 to 19%, at 12 mo. Patient survival and severe adverse event rates at 1 yr were 51 (76%) of 67 and 32 of 67 (48%) in the intravenous methylprednisolone group and 51 (73%) of 70 and 35 of (50%) 70 in the plasma exchange group, respectively. Plasma exchange increased the rate of renal recovery in ANCA-associated systemic vasculitis that presented with renal failure when compared with intravenous methylprednisolone. Patient survival and severe adverse event rates were similar in both groups.
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| 30. |
- Lynch, Kate D, et al.
(författare)
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Effects of Vedolizumab in Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Diseases.
- 2020
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Ingår i: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. - : Elsevier BV. - 1542-7714. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Gut-homing lymphocytes that express the integrin α4β7 and CCR9 might contribute to development of primary sclerosing cholangitis (PSC). Vedolizumab, which blocks the integrin α4β7, is used to treat patients with inflammatory bowel diseases (IBD), but there are few data on its efficacy in patients with PSC. We investigated the effects of vedolizumab in a large international cohort of patients with PSC and IBD.We collected data from European and North American centers participating in the International PSC Study Group from patients with PSC and IBD who received at least 3 doses of vedolizumab (n= 102; median vedolizumab treatment duration, 412 days). Demographic and clinical data were collected from baseline and during the follow-up period (until liver transplantation, death, or 56 days after the final vedolizumab infusion). We analyzed overall changes in biochemical features of liver and proportions of patients with reductions in serum levels of alkaline phosphatase (ALP) of 20% or more, from baseline through last follow-up evaluation. Other endpoints included response of IBD to treatment (improved, unchanged, or worsened, judged by the treating clinician, as well as endoscopic score) and liver-related outcomes.In the entire cohort, the median serum level of ALP increased from 1.54-fold the upper limit of normal at baseline to 1.64-fold the upper limit of normal at the last follow-up examination (P= .018); serum levels of transaminases and bilirubin also increased by a small amount between baseline and the last follow-up examination. Serum levels of ALP decreased by 20% or more in 21 patients (20.6%); only the presence of cirrhosis (odds ratio, 4.48; P= .019) was independently associated with this outcome. Of patients with available endoscopic data, 56.8% had a response of IBD to treatment. Liver-related events occurred in 21 patients (20.6%), including bacterial cholangitis, cirrhosis decompensation, or transplantation.In an analysis of patients with PSC and IBD in an international study group, we found no evidence for a biochemical response to vedolizumab, although serum level of ALP decreased by 20% or more in a subset of patients. Vedolizumab appears to be well tolerated and the overall response of IBD was the same as expected for patients without PSC.
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| 31. |
- Muchaxo, R E A, et al.
(författare)
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Association between upper-limb isometric strength and handcycling performance in elite athletes
- 2022
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Ingår i: Sports Biomechanics. - : Taylor & Francis. - 1476-3141 .- 1752-6116.
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the association among isometric upper-limb strength of handcyclists and sport-specific performance outcomes. At two international events, 62 athletes were tested on upper-limb strength, measured with an isometric-strength setup and with Manual Muscle Test (MMT). Horizontal force (F-z), effectiveness, rate of development, variability, and asymmetries were calculated for upper-limb pull and push. Performance measures were mean (POmean) and peak (POpeak) 20-s sprint power output and average time-trial velocity (TTvelocity). Regression models were conducted to investigate which pull and push strength variables associated strongest with performance measures. Additional regression analyses were conducted with an MMT sum score as predictor. Push and pull F-z showed the strongest associations with all outcomes. Combined push and pull F-z explained (p < .001) 80-81% of variance of POmean and POpeak. For TTvelocity, only push F-z was included in the model explaining 29% of the variance (p < .001). MMT models revealed weaker associations with sprint PO (R-2 = .38-.40, p < .001) and TTvelocity (R-2 = .18, p = 0.001). The findings confirmed the relevance of upper-limb strength on handcycling performance and the significance of ratio-scaled strength measures. Isometric strength outcomes are adequate sport-specific indicators of impairment in handcycling classification, but future research should corroborate this notion and its potential to discriminate between sports classes.
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| 32. |
- Muchaxo, Rafael E A, et al.
(författare)
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Do Handcycling Time-Trial Velocities Achieved by Para-Cycling Athletes Vary Across Handcycling Classes?
- 2020
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Ingår i: Adapted Physical Activity Quarterly. - : Human Kinetics. - 0736-5829 .- 1543-2777. ; 37:4, s. 461-480
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Tidskriftsartikel (refereegranskat)abstract
- The classification system for handcycling groups athletes into five hierarchical classes, based on how much their impairment affects performance. Athletes in class H5, with the least impairments, compete in a kneeling position, while athletes in classes H1 to H4 compete in a recumbent position. This study investigated the average time-trial velocity of athletes in different classes. A total of 1,807 results from 353 athletes who competed at 20 international competitions (2014-2018) were analyzed. Multilevel regression was performed to analyze differences in average velocities between adjacent pairs of classes, while correcting for gender, age, and event distance. The average velocity of adjacent classes was significantly different (p < .01), with higher classes being faster, except for H4 and H5. However, the effect size of the differences between H3 and H4 was smaller (d = 0.12). Hence, results indicated a need for research in evaluating and developing evidence-based classification in handcycling, yielding a class structure with meaningful performance differences between adjacent classes.
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| 33. |
- Muchaxo, Rafael E. A., et al.
(författare)
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The impact of lower-limb function on upper-limb pull and push strength in elite handcycling athletes
- 2023
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Ingår i: Sports Biomechanics. - : Taylor & Francis. - 1476-3141 .- 1752-6116.
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the impact of performing a closed kinetic chain with the lower limbs on isometric upper-limb pull and push strength. Sixty-two elite handcyclists were assessed with the Manual Muscle Test and allocated to groups with partial to normal (LLF) or no lower-limb (no-LLF) function. Both groups performed upper-limb strength measurements under two kinetic-chain conditions. During the closed-chain condition, the lower limbs were attached to two footrests, providing horizontal and vertical support. During the open-chain condition, the footrests were removed and the limbs were supported vertically by a horizontal plate. Repeated-measures ANOVA were conducted to investigate main effects (open vs. closed chain, LLF vs. no-LLF) and their interaction. During pull, LLF performed better (p < 0.001, +11%) by pushing against the footrests. However, this increase in pulling strength during a closed-chain condition was not observed in the no-LLF. Therefore, findings suggest an advantage for the least impaired athletes by being able to perform lower-limb closed chains during pulling. Handcyclists with LLF can maximise pulling performance by adjusting the footrests. The classification system should consider the implications of these findings on the allocation of athletes with different levels of LLF and/or on the equipment regulation.
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| 34. |
- Reinisch, W., et al.
(författare)
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The management of iron deficiency in inflammatory bowel disease - an online tool developed by the RAND/UCLA appropriateness method
- 2013
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Ingår i: Alimentary pharmacology & therapeutics. - : Wiley. - 0269-2813. ; 38:9, s. 1109-1118
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIron deficiency is a common and undertreated problem in inflammatory bowel disease (IBD). AimTo develop an online tool to support treatment choice at the patient-specific level. MethodsUsing the RAND/UCLA Appropriateness Method (RUAM), a European expert panel assessed the appropriateness of treatment regimens for a variety of clinical scenarios in patients with non-anaemic iron deficiency (NAID) and iron deficiency anaemia (IDA). Treatment options included adjustment of IBD medication only, oral iron supplementation, high-/low-dose intravenous (IV) regimens, IV iron plus erythropoietin-stimulating agent (ESA), and blood transfusion. The panel process consisted of two individual rating rounds (1148 treatment indications; 9-point scale) and three plenary discussion meetings. ResultsThe panel reached agreement on 71% of treatment indications. No treatment' was never considered appropriate, and repeat treatment after previous failure was generally discouraged. For 98% of scenarios, at least one treatment was appropriate. Adjustment of IBD medication was deemed appropriate in all patients with active disease. Use of oral iron was mainly considered an option in NAID and mildly anaemic patients without disease activity. IV regimens were often judged appropriate, with high-dose IV iron being the preferred option in 77% of IDA scenarios. Blood transfusion and IV+ESA were indicated in exceptional cases only. ConclusionsThe RUAM revealed high agreement amongst experts on the management of iron deficiency in patients with IBD. High-dose IV iron was more often considered appropriate than other options. To facilitate dissemination of the recommendations, panel outcomes were embedded in an online tool, accessible via http://ferroscope.com/.
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| 35. |
- Van Der Woude, Auke M., et al.
(författare)
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Near-real-time CO2 fluxes from CarbonTracker Europe for high-resolution atmospheric modeling
- 2023
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 15:2, s. 579-605
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Tidskriftsartikel (refereegranskat)abstract
- We present the CarbonTracker Europe High-Resolution (CTE-HR) system that estimates carbon dioxide (CO2) exchange over Europe at high resolution (0.1 × 0.2° ) and in near real time (about 2 months' latency). It includes a dynamic anthropogenic emission model, which uses easily available statistics on economic activity, energy use, and weather to generate anthropogenic emissions with dynamic time profiles at high spatial and temporal resolution (0.1×0.2° hourly). Hourly net ecosystem productivity (NEP) calculated by the Simple Biosphere model Version 4 (SiB4) is driven by meteorology from the European Centre for Medium-Range Weather Forecasts (ECMWF) Reanalysis 5th Generation (ERA5) dataset. This NEP is downscaled to 0.1×0.2° using the high-resolution Coordination of Information on the Environment (CORINE) land-cover map and combined with the Global Fire Assimilation System (GFAS) fire emissions to create terrestrial carbon fluxes. Ocean CO2 fluxes are included in our product, based on Jena CarboScope ocean CO2 fluxes, which are downscaled using wind speed and temperature. Jointly, these flux estimates enable modeling of atmospheric CO2 mole fractions over Europe. We assess the skill of the CTE-HR CO2 fluxes (a) to reproduce observed anomalies in biospheric fluxes and atmospheric CO2 mole fractions during the 2018 European drought, (b) to capture the reduction of anthropogenic emissions due to COVID-19 lockdowns, (c) to match mole fraction observations at Integrated Carbon Observation System (ICOS) sites across Europe after atmospheric transport with the Transport Model, version 5 (TM5) and the Stochastic Time-Inverted Lagrangian Transport (STILT), driven by ECMWF-IFS, and (d) to capture the magnitude and variability of measured CO2 fluxes in the city center of Amsterdam (the Netherlands). We show that CTE-HR fluxes reproduce large-scale flux anomalies reported in previous studies for both biospheric fluxes (drought of 2018) and anthropogenic emissions (COVID-19 pandemic in 2020). After applying transport of emitted CO2, the CTE-HR fluxes have lower median root mean square errors (RMSEs) relative to mole fraction observations than fluxes from a non-informed flux estimate, in which biosphere fluxes are scaled to match the global growth rate of CO2 (poor person's inversion). RMSEs are close to those of the reanalysis with the CTE data assimilation system. This is encouraging given that CTE-HR fluxes did not profit from the weekly assimilation of CO2 observations as in CTE. We furthermore compare CO2 concentration observations at the Dutch Lutjewad coastal tower with high-resolution STILT transport to show that the high-resolution fluxes manifest variability due to different emission sectors in summer and winter. Interestingly, in periods where synoptic-scale transport variability dominates CO2 concentration variations, the CTE-HR fluxes perform similarly to low-resolution fluxes (5-10× coarsened). The remaining 10 % of the simulated CO2 mole fraction differs by >2 ppm between the low-resolution and high-resolution flux representation and is clearly associated with coherent structures ("plumes") originating from emission hotspots such as power plants. We therefore note that the added resolution of our product will matter most for very specific locations and times when used for atmospheric CO2 modeling. Finally, in a densely populated region like the Amsterdam city center, our modeled fluxes underestimate the magnitude of measured eddy covariance fluxes but capture their substantial diurnal variations in summertime and wintertime well. We conclude that our product is a promising tool for modeling the European carbon budget at a high resolution in near real time. The fluxes are freely available from the ICOS Carbon Portal (CC-BY-4.0) to be used for near-real-time monitoring and modeling, for example, as an a priori flux product in a CO2 data assimilation system. The data are available at 10.18160/20Z1-AYJ2 .
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| 36. |
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| 37. |
- Kraaijenbrink, Cassandra, et al.
(författare)
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Steering Does Affect Biophysical Responses in Asynchronous, but Not Synchronous Submaximal Handcycle Ergometry in Able-Bodied Men.
- 2021
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Ingår i: Frontiers in Sports and Active Living. - : Frontiers Media S.A.. - 2624-9367. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Real-life daily handcycling requires combined propulsion and steering to control the front wheel. Today, the handcycle cranks are mostly mounted synchronously unlike the early handcycle generations. Alternatively, arm cycle ergometers do not require steering and the cranks are mostly positioned asynchronously. The current study aims to evaluate the effects of combining propulsion and steering requirements on synchronous and asynchronous submaximal handcycle ergometry. We hypothesize that asynchronous handcycling with steering results in the mechanically least efficient condition, due to compensation for unwanted rotations that are not seen in synchronous handcycling, regardless of steering. Sixteen able-bodied male novices volunteered in this lab-based experiment. The set-up consisted of a handcycle ergometer with 3D force sensors at each crank that also allows "natural" steering. Four submaximal steady-state (60 rpm, ~35 W) exercise conditions were presented in a counterbalanced order: synchronous with a fixed steering axis, synchronous with steering, asynchronous with a fixed axis and asynchronous with steering. All participants practiced 3 × 4 mins with 30 mins rest in between every condition. Finally, they did handcycle for 4 mins in each of the four conditions, interspaced with 10 mins rest, while metabolic outcomes, kinetics and kinematics of the ergometer were recorded. The additional steering component did not influence velocity, torque and power production during synchronous handcycling and therefore resulted in an equal metabolically efficient handcycling configuration compared to the fixed condition. Contrarily, asynchronous handcycling with steering requirements showed a reduced mechanical efficiency, as velocity around the steering axis increased and torque and power production were less effective. Based on the torque production around the crank and steering axes, neuromuscular compensation strategies seem necessary to prevent steering movements in the asynchronous mode. To practice or test real-life daily synchronous handcycling, a synchronous crank set-up of the ergometer is advised, as exercise performance in terms of mechanical efficiency, metabolic strain, and torque production is independent of steering requirements in that mode. Asynchronous handcycling or arm ergometry demands a different handcycle technique in terms of torque production and results in higher metabolic responses than synchronous handcycling, making it unsuitable for testing.
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| 38. |
- Muchaxo, Rafael, et al.
(författare)
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A Role for Trunk Function in Elite Recumbent Handcycling Performance?
- 2021
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Ingår i: Journal of Sports Sciences. - : Taylor & Francis. - 0264-0414 .- 1466-447X. ; 39:20, s. 2312-2321
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Tidskriftsartikel (refereegranskat)abstract
- Handcycling classification considers trunk function, but there is limited scientific evidence of trunk involvement in recumbent performance. This study investigated the association between trunk function and recumbent handcycling performance of athletes without upper-limb impairments (H3-H4 sport classes). The study was divided into two parts. First, 528 time-trial results from 81 handcyclists with spinal cord injury (SCI) were obtained between 2014 and 2020. Average time-trial velocity was used as performance measure and SCI level as trunk function determinant. Multilevel regression analysis was performed to analyse differences in performance among SCI groups while correcting for lesion completeness, sex, and age. Second, in 26 handcyclists, standardised trunk flexion strength was measured with a handheld dynamometer. Peak and mean power-output from a sprint test and time-trial average velocity were used as performance measures. Spearman correlations were conducted to investigate the association between trunk strength and performance. Results showed that the different SCI groups did not exhibit significant differences in performance. Furthermore, trunk flexion strength and performance exhibited non-significant weak to moderate correlations (for time-trial speed: rs = 0.36; p = 0.07). Results of both analyses suggest that trunk flexion strength does not seem to significantly impact recumbent handcycling performance in athletes without upper-limb impairments.
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| 39. |
- Nooijen, Carla F J, et al.
(författare)
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The relation between sprint power and road time trial performance in elite para-cyclists.
- 2021
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Ingår i: Journal of Science and Medicine in Sport. - : Elsevier. - 1440-2440 .- 1878-1861. ; 24:11, s. 1193-1198
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Whilst cycling performance has been studied extensively, very little is known about the performance of para-cyclists. This study assessed the relation between sprint power and road time trial performance in elite para-cyclists, and whether this relation differed based on impairment type and type of bike used.DESIGN: Cross-sectional.METHODS: During international para-cycling events, 168 athletes (88 bicycles, 17 tricycles, 56 recumbent handbikes and 7 kneeling handbikes) performed 20-s sport-specific sprint tests (mean power output (POmean) W), and their road time trial performance (average speed (km/h)) was taken from the official results. Multilevel regression models to assess the relation of sprint with time trial performance were composed for i. leg-cyclists: bicycle and tricycle and ii. arm-cyclists: recumbent- and kneeling handbike, adjusted for identified confounders. Furthermore, impairment type (categorized as i) muscle power/range of motion, ii) limb deficiency/leg length difference, and iii) coordination) and bike type were tested as effect modifiers.RESULTS: POmean ranged from 303 ± 12 W for recumbent handcyclists to 482 ± 156 W for bicyclists. POmean was significantly related to time trial performance, for both leg-cyclists (β = 0.010, SE = 0.003, p < 0.01) and arm-cyclists (β = 0.029; SE = 0.005, p < 0.01), and impairment type and bike type were not found to be effect modifiers.CONCLUSIONS: Sprint power was related to road time trial performance in all para-cyclists, with no differences found in this relation based on impairment type nor bike type. For those competing on a bicycle, tricycle, recumbent- or kneeling handbike, sprint tests might therefore be useful to predict or monitor time trial performance.
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- Stilma, W, et al.
(författare)
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Awake Proning as an Adjunctive Therapy for Refractory Hypoxemia in Non-Intubated Patients with COVID-19 Acute Respiratory Failure: Guidance from an International Group of Healthcare Workers
- 2021
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Ingår i: The American journal of tropical medicine and hygiene. - : American Society of Tropical Medicine and Hygiene. - 1476-1645 .- 0002-9637. ; 104:5, s. 1676-1686
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Tidskriftsartikel (refereegranskat)abstract
- Non-intubated patients with acute respiratory failure due to COVID-19 could benefit from awake proning. Awake proning is an attractive intervention in settings with limited resources, as it comes with no additional costs. However, awake proning remains poorly used probably because of unfamiliarity and uncertainties regarding potential benefits and practical application. To summarize evidence for benefit and to develop a set of pragmatic recommendations for awake proning in patients with COVID-19 pneumonia, focusing on settings where resources are limited, international healthcare professionals from high and low- and middle-income countries (LMICs) with known expertise in awake proning were invited to contribute expert advice. A growing number of observational studies describe the effects of awake proning in patients with COVID-19 pneumonia in whom hypoxemia is refractory to simple measures of supplementary oxygen. Awake proning improves oxygenation in most patients, usually within minutes, and reduces dyspnea and work of breathing. The effects are maintained for up to 1 hour after turning back to supine, and mostly disappear after 6–12 hours. In available studies, awake proning was not associated with a reduction in the rate of intubation for invasive ventilation. Awake proning comes with little complications if properly implemented and monitored. Pragmatic recommendations including indications and contraindications were formulated and adjusted for resource-limited settings. Awake proning, an adjunctive treatment for hypoxemia refractory to supplemental oxygen, seems safe in non-intubated patients with COVID-19 acute respiratory failure. We provide pragmatic recommendations including indications and contraindications for the use of awake proning in LMICs.
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