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- 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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| 5. |
- 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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- 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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- 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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