| 1. |
- Went, M, et al.
(författare)
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Author Correction: Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 213-
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Tidskriftsartikel (refereegranskat)abstract
- The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, in the original HTML version of this Article, the order of authors within the author list was incorrect. The PRACTICAL consortium was incorrectly listed after Richard S. Houlston and should have been listed after Nora Pashayan. This error has been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.
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| 2. |
- Went, M, et al.
(författare)
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Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3707-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.
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| 3. |
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| 5. |
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| 6. |
- Mitchell, Jonathan S., et al.
(författare)
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Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P = 1.31 x 10(-8)), 6q21 (rs9372120, P = 9.09 x 10(-15)), 7q36.1 (rs7781265, P = 9.71 x 10(-9)), 8q24.21 (rs1948915, P = 4.20 x 10(-11)), 9p21.3 (rs2811710, P = 1.72 x 10(-13)), 10p12.1 (rs2790457, P = 1.77 x 10(-8)), 16q23.1 (rs7193541, P = 5.00 x 10(-12)) and 20q13.13 (rs6066835, P = 1.36 x 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.
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| 7. |
- Ali, Mina, et al.
(författare)
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The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 1649-
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Tidskriftsartikel (refereegranskat)abstract
- Recently, we identified ELL2 as a susceptibility gene for multiple myeloma (MM). To understand its mechanism of action, we performed expression quantitative trait locus analysis in CD138+ plasma cells from 1630 MM patients from four populations. We show that the MM risk allele lowers ELL2 expression in these cells (Pcombined = 2.5 × 10−27; βcombined = −0.24 SD), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause–effect relationship. Our results provide mechanistic insight into MM predisposition.
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| 8. |
- Balogh, Johanna, et al.
(författare)
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Phospholipase C and cAMP-dependent positive inotropic effects of ATP in mouse cardiomyocytes via P2Y(11)-like receptors.
- 2005
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Ingår i: Journal of Molecular and Cellular Cardiology. - : Elsevier BV. - 1095-8584 .- 0022-2828. ; 39:2, s. 223-230
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Tidskriftsartikel (refereegranskat)abstract
- ATP is released as a cotransmitter together with catecholamines from sympathetic nerves. In the heart ATP has been shown to cause a pronounced positive inotropic effect and may also act in synergy with β-adrenergic agonists to augment cardiomyocyte contractility. The aim of the present study was to investigate the inotropic effects mediated by purinergic P2 receptors using isolated mouse cardiomyocytes. Stable adenine nucleotide analogs were used and the agonist rank order for adenine nucleotide stimulation of the mouse cardiomyocytes was AR-C67085 > ATPγS > 2-MeSATP >>> 2-MeSADP = 0, that fits the agonist profile of the P2Y11 receptor. ATPγS induced a positive inotropic response in single mouse cardiomyocytes. The response was similar to that for the β1 receptor agonist isoproterenol. The most potent response was obtained using AR-C67085, a P2Y11 receptor agonist. This agonist also potentiated contractions in isolated trabecular preparations. The adenylyl cyclase blocker (SQ22563) and phospholipase C (PLC) blocker (U73122) demonstrated that both pathways were required for the inotropic response of AR-C67085. A cAMP enzyme immunoassay confirmed that AR-C67085 increased cAMP in the cardiomyocytes. These findings are in agreement with the P2Y11 receptor, coupled both to activation of IP3 and cAMP, being a major receptor for ATP induced inotropy. Analyzing cardiomyocytes from desmin deficient mice, Des–/–, with a congenital cardiomyopathy, we found a lower sensitivity to AR-C67085, suggesting a down-regulation of P2Y11 receptor function in heart failure. The prominent action of the P2Y11 receptor in controling cardiomyocyte contractility and possible alterations in its function during cardiomyopathy may suggest this receptor as a potential therapeutic target. It is possible that agonists for the P2Y11 receptor could be used to improve cardiac output in patients with circulatory shock and that P2Y11 receptor antagonist could be beneficial in patients with congestive heart failure (CHF).
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| 10. |
- Fridlund, Bengt, et al.
(författare)
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Essentials of Nursing Care in Randomized Controlled Trials of Nurse-Led Interventions in Somatic Care : A Systematic Review
- 2014
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Ingår i: Open Journal of Nursing. - Irvine : Scientific Research Publishing. - 2162-5336 .- 2162-5344. ; 4:3, s. 181-197
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Forskningsöversikt (refereegranskat)abstract
- Background: Nursing practice has to contribute to evidence pointing out why there is a need for more nurse-designed randomized control trials (RCTs) focusing on evidence-based practice (EBP). How far this EBP has progressed in different health aspects is usually established by systematic reviews of RCTs. Nurse-led RCTs exist but no study has addressed the essentials of nursing care. Aim: The aim was therefore to determine the essentials of nurses’ interventions by means of nurse-led RCTs in somatic care focusing on the stated context, goals, content, strategies as well as the nurse’s role related to effectiveness. Methods: A systematic review was realized according to Cochrane review assumptions to identify, appraise and synthesize all empirical evidence meeting pre-specified eligibility criteria. The PRISMA statement guided the data extraction process (n = 55) from PubMed and CINAHL. Results: Of the RCTs in somatic care, 71% showed a positive effectiveness of nurse-led interventions, of which the nurse had a significant role with regard to being the main responsible in 67% of the studies. Also, 47% of the RCTs presented a theoretical standpoint related to the nurse-led interventions and most prominent were international evidence-based guidelines. Goals were found to have either a patient-centered or a professional-centered ambition. Strategies were based on patient-directed initiatives, nurse-patient-directed initiatives or nurse-directed initiatives, while contents were built upon either a patient-nurse interaction or a nursing management plan. Conclusions: This review underlines the necessity of a holistic view of a person, as nurse-led RCTs comprising a patient-centered ambition, patient-directed initiative and patient-nurse interaction plan showed beneficial nursing care effectiveness, particularly if theory-based. In a nurse-led RCT, a basic theoretical perspective is advantageous as well as to elucidate the role of the nurse in relation to the estimated effects.
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| 11. |
- Jonsson, Stefan, et al.
(författare)
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Identification of sequence variants influencing immunoglobulin levels
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 49:8, s. 1182-1191
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Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulins are the effector molecules of the adaptive humoral immune system. In a genome-wide association study of 19,219 individuals, we found 38 new variants and replicated 5 known variants associating with IgA, IgG or IgM levels or with composite immunoglobulin traits, accounted for by 32 loci. Variants at these loci also affect the risk of autoimmune diseases and blood malignancies and influence blood cell development. Notable associations include a rare variant at RUNX3 decreasing IgA levels by shifting isoform proportions (rs188468174[C>T]: P = 8.3 × 10(-55), β = -0.90 s.d.), a rare in-frame deletion in FCGR2B abolishing IgG binding to the encoded receptor (p.Asn106del: P = 4.2 × 10(-8), β = 1.03 s.d.), four IGH locus variants influencing class switching, and ten new associations with the HLA region. Our results provide new insight into the regulation of humoral immunity.
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| 14. |
- Rönnblad, E, et al.
(författare)
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[Elbow injuries in children]
- 2016
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Ingår i: Lakartidningen. - 1652-7518. ; 113
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Tidskriftsartikel (refereegranskat)
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| 15. |
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| 16. |
- Strandberg, Karin, et al.
(författare)
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Fyra nya instrument för analys av blodgaser testade: Behändiga kassetter skall ge bättre användarvänlighet
- 2000
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Ingår i: Läkartidningen. - : Swedish Medical Association. - 0023-7205 .- 1652-7518. ; 97:7, s. 698-701
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Tidskriftsartikel (refereegranskat)abstract
- An entirely new type of blood gas analyser has made its way into the marketplace, to be used, for example, in emergency rooms, intensive care units, ambulances, and bedside with quarantined patients in infectious diseases units. The instruments reviewed here employ new miniaturised analysis circuitry, integrated into the cassette on which the blood sample is applied. These instruments are designed for use by care-givers without specific laboratory training. Four point-of-care blood gas analysers are tested: OPTI 1 (AVL), I-STAT (HP), IRMA (Infiniti) och ABL 70 (Radiometer).
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| 17. |
- Thorin, M. H., et al.
(författare)
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Smoking, smoking cessation, and fracture risk in elderly women followed for 10 years
- 2016
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Ingår i: Osteoporosis International. - Stockholm : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 27:1, s. 249-255
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Tidskriftsartikel (refereegranskat)abstract
- Summary: This study examines the impact of smoking and smoking cessation on fracture risk in 75-year-old women followed for 10 years. Smoking increased fracture risk, especially for vertebral fractures. Smoking cessation decreased the risk for vertebral fractures but not for other fracture types. Introduction: The purpose of this study was to examine effects of smoking and smoking cessation on fracture risk. Methods: This prospective observational population-based study followed 1033 women during 10 years from age 75. Data regarding smoking were collected at age 75. Hazard ratios (HRs) and 95 % confidence intervals for fracture were calculated using competing risks proportional hazards regression. Results: Both former smokers and current smokers had an increased risk for any fracture (HR 1.30; 1.03–1.66, and HR 1.32; 1.01–1.73, respectively) and any osteoporotic fracture (hip, proximal humerus, distal radius, vertebra) (HR 1.31; 1.01–1.70 and HR 1.49; 1.11–1.98, respectively) compared to non-smokers. Former smokers had an increased risk for proximal humerus fractures (HR 2.23; 1.35–3.70), and current smokers had an increased risk for vertebral fractures (HR 2.30; 1.57–3.38) compared to non-smokers. After adjustment for weight, previous fractures, alcohol habits, bone mineral density (BMD), use of corticoids, vitamin D, bisphosphonates, and previous falls, former smokers had an increased risk for proximal humerus fracture (HR 2.07; 1.19–3.57) and current smokers had an increased risk for osteoporotic (HR 1.47; 1.05–2.05) and vertebral fractures (HR 2.50; 1.58–3.95) compared to non-smokers. Former smokers had a decreased risk for vertebral fractures, but not for other types of fractures, compared to current smokers. Conclusions: Smoking increased the risk for fracture among elderly women, especially vertebral fractures. Smoking cessation decreased the risk for vertebral fractures but not for other types of fractures.
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| 18. |
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| 19. |
- Wihlborg, A., et al.
(författare)
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Fracture predictive ability of physical performance tests and history of falls in elderly women: a 10-year prospective study
- 2015
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 26:8, s. 2101-2109
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Tidskriftsartikel (refereegranskat)abstract
- A Summary In a large cohort of elderly women followed for 10 years, we found that balance, gait speed, and self-reported history of fall independently predicted fracture. These clinical risk factors are easily evaluated and therefore advantageous in a clinical setting. They would improve fracture risk assessment and thereby also fracture prevention. Introduction The aim of this study was to identify additional risk factors for osteoporosis-related fracture by investigating the fracture predictive ability of physical performance tests and self-reported history of falls. Methods In the population-based Osteoporosis Prospective Risk Assessment study (OPRA), 1044 women were recruited at the age of 75 and followed for 10 years. At inclusion, knee extension force, standing balance, gait speed, and bone mineral density (BMD) were examined. Falls the year before investigation was assessed by questionnaire. Cox proportional hazards regression analysis was used to determine fracture hazard ratios (HR) with BMD, history of fracture, BMI, smoking habits, bisphosphonate, vitamin D, glucocorticoid, and alcohol use as covariates. Continuous variables were standardized and HR shown for each standard deviation change. Results Of all women, 427 (41 %) sustained at least one fracture during the 10-year follow-up. Failing the balance test had an HR of 1.98 (1.18-3.32) for hip fracture. Each standard deviation decrease in gait speed was associated with an HR of 1.37 (1.14-1.64) for hip fracture. Previous fall had an HR of 1.30 (1.03-1.65) for any fracture; 1.39 (1.08-1.79) for any osteoporosis-related fracture; and 1.60 (1.03-2.48) for distal forearm fracture. Knee extension force did not show fracture predictability. Conclusion The balance test, gait speed test, and self-reported history of fall all hold independent fracture predictability. Consideration of these clinical risk factors for fracture would improve the fracture risk assessment and subsequently also fracture prevention.
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| 24. |
- Wiklund, Daniel, 1970, et al.
(författare)
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A friction model evaluated with results from a bending-under-tension test
- 2009
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Ingår i: Tribology International. - : Elsevier BV. - 0301-679X .- 1879-2464. ; 42:10, s. 1448-1452
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Tidskriftsartikel (refereegranskat)abstract
- The friction in stamping is an important process parameter to control the flow of material in the tool. Consequently, it is also an important parameter in the design process of new stamping tools when numerical simulations of the forming operations are performed. In this work an advanced friction model is evaluated. which considers properties of surface topography, lubricant, sheet material, and process parameters such as sliding speed and pressure. The evaluation is made by comparing theoretical results with experimental ones obtained in a bending-under-tension friction test. The results show conformance in behaviour between the friction model and the experimental work. Furthermore, a model, which considers the influence of bulk plastic strains on the real area of contact, is investigated. The developed model predicts that the effective hardness of a surface is reduced by the presence of underlying plastic flow. it is found that when the strain rates are increased, the Stribeck curve becomes flatter and mixed lubrication is introduced at lower Hersey values. The friction model clearly shows the potential of improving the FE simulations of sheet metal forming operations, in comparison to the use of the classical Coulomb's friction model.
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