| 21. |
- Jung, Christian, et al.
(författare)
-
A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
-
Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
|
|
| 22. |
- Kottyan, Leah C., et al.
(författare)
-
The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share.
- 2015
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:2, s. 582-596
-
Tidskriftsartikel (refereegranskat)abstract
- Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögrens syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.
|
|
| 23. |
- Kristiansen, Kristian, 1948, et al.
(författare)
-
Re-theorising mobility and the formation of culture and language among the Corded Ware Culture in Europe
- 2017
-
Ingår i: Antiquity. - : Antiquity Publications. - 0003-598X .- 1745-1744. ; 91:356, s. 334-347
-
Tidskriftsartikel (refereegranskat)abstract
- Copyright © 2017 Antiquity Publications Ltd.Recent genetic, isotopic and linguistic research has dramatically changed our understanding of how the Corded Ware Culture in Europe was formed. Here the authors explain it in terms of local adaptations and interactions between migrant Yamnaya people from the Pontic-Caspian steppe and indigenous North European Neolithic cultures. The original herding economy of the Yamnaya migrants gradually gave way to new practices of crop cultivation, which led to the adoption of new words for those crops. The result of this hybridisation process was the formation of a new material culture, the Corded Ware Culture, and of a new dialect, Proto-Germanic. Despite a degree of hostility between expanding Corded Ware groups and indigenous Neolithic groups, stable isotope data suggest that exogamy provided a mechanism facilitating their integration. This article should be read in conjunction with that by Heyd (2017, in this issue).
|
|
| 24. |
|
|
| 25. |
- Li, He, et al.
(författare)
-
Identification of a Sjögren's syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons
- 2017
-
Ingår i: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 13:6
-
Tidskriftsartikel (refereegranskat)abstract
- Sjogren's syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL) analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study. Multiple cis-eQTLs were associated with transcript levels of 2'-5'-oligoadenylate synthetase 1 (OAS1) peaking at rs10774671 (PeQTL = 6.05 x 10(-14)). Association of rs10774671 with SS susceptibility was identified and confirmed through meta-analysis of two independent cohorts (P-meta = 2.59 x 10(-9); odds ratio = 0.75; 95% confidence interval = 0.66-0.86). The risk allele of rs10774671 shifts splicing of OAS1 from production of the p46 isoform to multiple alternative transcripts, including p42, p48, and p44. We found that the isoforms were differentially expressed within each genotype in controls and patients with and without autoantibodies. Furthermore, our results showed that the three alternatively spliced isoforms lacked translational response to type I IFN stimulation. The p48 and p44 isoforms also had impaired protein expression governed by the 3' end of the transcripts. The SS risk allele of rs10774671 has been shown by others to be associated with reduced OAS1 enzymatic activity and ability to clear viral infections, as well as reduced responsiveness to IFN treatment. Our results establish OAS1 as a risk locus for SS and support a potential role for defective viral clearance due to altered IFN response as a genetic pathophysiological basis of this complex autoimmune disease.
|
|
| 26. |
|
|
| 27. |
- Meyer, H.F., et al.
(författare)
-
Overview of physics studies on ASDEX Upgrade
- 2019
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
-
Forskningsöversikt (refereegranskat)abstract
- The ASDEX Upgrade (AUG) programme, jointly run with the EUROfusion MST1 task force, continues to significantly enhance the physics base of ITER and DEMO. Here, the full tungsten wall is a key asset for extrapolating to future devices. The high overall heating power, flexible heating mix and comprehensive diagnostic set allows studies ranging from mimicking the scrape-off-layer and divertor conditions of ITER and DEMO at high density to fully non-inductive operation (q 95 = 5.5, ) at low density. Higher installed electron cyclotron resonance heating power 6 MW, new diagnostics and improved analysis techniques have further enhanced the capabilities of AUG. Stable high-density H-modes with MW m-1 with fully detached strike-points have been demonstrated. The ballooning instability close to the separatrix has been identified as a potential cause leading to the H-mode density limit and is also found to play an important role for the access to small edge-localized modes (ELMs). Density limit disruptions have been successfully avoided using a path-oriented approach to disruption handling and progress has been made in understanding the dissipation and avoidance of runaway electron beams. ELM suppression with resonant magnetic perturbations is now routinely achieved reaching transiently . This gives new insight into the field penetration physics, in particular with respect to plasma flows. Modelling agrees well with plasma response measurements and a helically localised ballooning structure observed prior to the ELM is evidence for the changed edge stability due to the magnetic perturbations. The impact of 3D perturbations on heat load patterns and fast-ion losses have been further elaborated. Progress has also been made in understanding the ELM cycle itself. Here, new fast measurements of and E r allow for inter ELM transport analysis confirming that E r is dominated by the diamagnetic term even for fast timescales. New analysis techniques allow detailed comparison of the ELM crash and are in good agreement with nonlinear MHD modelling. The observation of accelerated ions during the ELM crash can be seen as evidence for the reconnection during the ELM. As type-I ELMs (even mitigated) are likely not a viable operational regime in DEMO studies of 'natural' no ELM regimes have been extended. Stable I-modes up to have been characterised using -feedback. Core physics has been advanced by more detailed characterisation of the turbulence with new measurements such as the eddy tilt angle - measured for the first time - or the cross-phase angle of and fluctuations. These new data put strong constraints on gyro-kinetic turbulence modelling. In addition, carefully executed studies in different main species (H, D and He) and with different heating mixes highlight the importance of the collisional energy exchange for interpreting energy confinement. A new regime with a hollow profile now gives access to regimes mimicking aspects of burning plasma conditions and lead to nonlinear interactions of energetic particle modes despite the sub-Alfvénic beam energy. This will help to validate the fast-ion codes for predicting ITER and DEMO.
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
- Rascovan, Nicolas, et al.
(författare)
-
Emergence and Spread of Basal Lineages of Yersinia pestis during the Neolithic Decline
- 2019
-
Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 176:1, s. 295-305
-
Tidskriftsartikel (refereegranskat)abstract
- Between 5,000 and 6,000 years ago, many Neolithic societies declined throughout western Eurasia due to a combination of factors that are still largely debated. Here, we report the discovery and genome reconstruction of Yersinia pestis, the etiological agent of plague, in Neolithic farmers in Sweden, pre-dating and basal to all modern and ancient known strains of this pathogen. We investigated the history of this strain by combining phylogenetic and molecular clock analyses of the bacterial genome, detailed archaeological information, and genomic analyses from infected individuals and hundreds of ancient human samples across Eurasia. These analyses revealed that multiple and independent lineages of Y. pestis branched and expanded across Eurasia during the Neolithic decline, spreading most likely through early trade networks rather than massive human migrations. Our results are consistent with the existence of a prehistoric plague pandemic that likely contributed to the decay of Neolithic populations in Europe.
|
|
