| 1. |
- Mullins, N., et al.
(författare)
-
Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
- 2021
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53, s. 817-829
-
Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
|
|
| 2. |
|
|
| 3. |
- Jonsson, Lina, 1982, et al.
(författare)
-
Characterisation of age and polarity at onset in bipolar disorder
- 2021
-
Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 219:6, s. 659-669
-
Tidskriftsartikel (refereegranskat)abstract
- Background Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. Aims To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics. Method Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts. Results Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (beta = -0.34 years, s.e. = 0.08), major depression (beta = -0.34 years, s.e. = 0.08), schizophrenia (beta = -0.39 years, s.e. = 0.08), and educational attainment (beta = -0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO. Conclusions AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
|
|
| 4. |
- Jia, X. M., et al.
(författare)
-
Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder
- 2021
-
Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26:9, s. 5239-5250
-
Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3-2.8, one-sided p = 6.0 x 10(-4)), this enrichment did not replicate in an additional 9,929 BD cases and 14,018 controls (OR = 0.9, one-side p = 0.70). Although BD shares common variant heritability with schizophrenia, in the BSC sample we did not observe a significant enrichment of P-LP variants in SCZ GWAS genes, in two classes of neuronal synaptic genes (RBFOX2 and FMRP) associated with SCZ or in loss-of-function intolerant genes. In this study, the largest analysis of exonic variation in BD, individuals with BD do not carry a replicable enrichment of rare P-LP variants across the exome or in any of several groups of genes with biologic plausibility. Moreover, despite a strong shared susceptibility between BD and SCZ through common genetic variation, we do not observe an association between BD risk and rare P-LP coding variants in genes known to modulate risk for SCZ.
|
|
| 5. |
- Rystedt, J. M.L., et al.
(författare)
-
Routine versus selective intraoperative cholangiography during cholecystectomy: systematic review, meta-analysis and health economic model analysis of iatrogenic bile duct injury
- 2021
-
Ingår i: BJS open. - Oxford : Oxford University Press (OUP). - 2474-9842. ; 5:2
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Bile duct injury (BDI) is a severe complication following cholecystectomy. Early recognition and treatment of BDI has been shown to reduce costs and improve patients' quality of life. The aim of this study was to assess the effect and cost-effectiveness of routine versus selective intraoperative cholangiography (IOC) in cholecystectomy. Methods: A systematic review and meta-analysis, combined with a health economic model analysis in the Swedish setting, was performed. Costs per quality-adjusted life-year (QALY) for routine versus selective IOC during cholecystectomy for different scenarios were calculated. Results: In this meta-analysis, eight studies with more than 2 million patients subjected to cholecystectomy and 9000 BDIs were included. The rate of BDI was estimated to 0.36 per cent when IOC was performed routinely, compared with to 0.53 per cent when used selectively, indicating an increased risk for BDI of 43 per cent when IOC was used selectively (odds ratio 1.43, 95 per cent c.i. 1.22 to 1.67). The model analysis estimated that seven injuries were avoided annually by routine IOC in Sweden, a population of 10 million. Over a 10-year period, 33 QALYs would be gained at an approximate net cost of (sic)808 000 , at a cost per QALY of about (sic)24 900. Conclusion: Routine IOC during cholecystectomy reduces the risk of BDI compared with the selective strategy and is a potentially cost-effective intervention.
|
|
| 6. |
- Adolfsson, J., et al.
(författare)
-
QCD challenges from pp to A–A collisions
- 2020
-
Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 56:11
-
Forskningsöversikt (refereegranskat)abstract
- This paper is a write-up of the ideas that were presented, developed and discussed at the third International Workshop on QCD Challenges from pp to A–A, which took place in August 2019 in Lund, Sweden (Workshop link: https://indico.lucas.lu.se/event/1214/). The goal of the workshop was to focus on some of the open questions in the field and try to come up with concrete suggestions for how to make progress on both the experimental and theoretical sides. The paper gives a brief introduction to each topic and then summarizes the primary results.
|
|
| 7. |
- Moser, O., et al.
(författare)
-
Glucose management for exercise using continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems in type 1 diabetes: position statement of the European Association for the Study of Diabetes (EASD) and of the International Society for Pediatric and Adolescent Diabetes (ISPAD) endorsed by JDRF and supported by the American Diabetes Association (ADA)
- 2020
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 63, s. 2501-2520
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin-dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (i.e. before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes.
|
|
| 8. |
- Acharya, S, et al.
(författare)
-
Constraining the Chiral Magnetic Effect with charge-dependent azimuthal correlations in Pb-Pb collisions at √sNN = 2.76 and 5.02 TeV
- 2020
-
Ingår i: Journal of High Energy Physics. - 1029-8479. ; 2020:9
-
Tidskriftsartikel (refereegranskat)abstract
- Systematic studies of charge-dependent two- and three-particle correlations in Pb-Pb collisions at sNN = 2.76 and 5.02 TeV used to probe the Chiral Magnetic Effect (CME) are presented. These measurements are performed for charged particles in the pseudorapidity (η) and transverse momentum (pT) ranges |η| < 0.8 and 0.2 < pT< 5 GeV/c. A significant charge-dependent signal that becomes more pronounced for peripheral collisions is reported for the CME-sensitive correlators γ1, 1 = 〈cos(φα + φβ − 2Ψ2)〉 and γ1, − 3 = 〈cos(φα − 3φβ + 2Ψ2)〉. The results are used to estimate the contribution of background effects, associated with local charge conservation coupled to anisotropic flow modulations, to measurements of the CME. A blast-wave parametrisation that incorporates local charge conservation tuned to reproduce the centrality dependent background effects is not able to fully describe the measured γ1,1. Finally, the charge and centrality dependence of mixed-harmonics three-particle correlations, of the form γ1, 2 = 〈cos(φα + 2φβ − 3Ψ3)〉, which are insensitive to the CME signal, verify again that background contributions dominate the measurement of γ1,1.
|
|
| 9. |
- Acharya, S., et al.
(författare)
-
First measurement of quarkonium polarization in nuclear collisions at the LHC
- 2021
-
Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 815
-
Tidskriftsartikel (refereegranskat)abstract
- The polarization of inclusive J/ψ and ϒ(1S) produced in Pb–Pb collisions at sNN=5.02 TeV at the LHC is measured with the ALICE detector. The study is carried out by reconstructing the quarkonium through its decay to muon pairs in the rapidity region 2.5
|
|
| 10. |
- Acharya, S., et al.
(författare)
-
Longitudinal and azimuthal evolution of two-particle transverse momentum correlations in Pb-Pb collisions at √sNN= 2.76 TeV
- 2020
-
Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693. ; 804
-
Tidskriftsartikel (refereegranskat)abstract
- This paper presents the first measurements of the charge independent (CI) and charge dependent (CD) two-particle transverse momentum correlators G2CI and G2CD in Pb–Pb collisions at √SNN=2.76 TeV by the ALICE collaboration. The two-particle transverse momentum correlator G2 was introduced as a measure of the momentum current transfer between neighboring system cells. The correlators are measured as a function of pair separation in pseudorapidity (Δη) and azimuth (Δφ) and as a function of collision centrality. From peripheral to central collisions, the correlator G2CI exhibits a longitudinal broadening while undergoing a monotonic azimuthal narrowing. By contrast, G2CD exhibits a narrowing along both dimensions. These features are not reproduced by models such as HIJING and AMPT. However, the observed narrowing of the correlators from peripheral to central collisions is expected to result from the stronger transverse flow profiles produced in more central collisions and the longitudinal broadening is predicted to be sensitive to momentum currents and the shear viscosity per unit of entropy density η/s of the matter produced in the collisions. The observed broadening is found to be consistent with the hypothesized lower bound of η/s and is in qualitative agreement with values obtained from anisotropic flow measurements.
|
|
