| 1. |
- Pulit, S. L., et al.
(författare)
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Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
- 2018
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Ingår i: Neurology-Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 2376-7839. ; 4:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.
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| 2. |
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| 3. |
- Nolte, I. M., et al.
(författare)
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Genetic loci associated with heart rate variability and their effects on cardiac disease risk
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74 < r(g) < -0.55) and blood pressure (-0.35 < r(g) < -0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.
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| 4. |
- Armesto, N., et al.
(författare)
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Heavy-ion collisions at the LHC-Last call for predictions
- 2008
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 35:5, s. 054001-
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Forskningsöversikt (refereegranskat)abstract
- This writeup is a compilation of the predictions for the forthcoming Heavy Ion Program at the Large Hadron Collider, as presented at the CERN Theory Institute 'Heavy Ion Collisions at the LHC - Last Call for Predictions', held from 14th May to 10th June 2007.
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| 5. |
- Fernandez, J. L. Abelleira, et al.
(författare)
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A Large Hadron Electron Collider at CERN
- 2012
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 39:7
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Tidskriftsartikel (refereegranskat)
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| 6. |
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| 7. |
- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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| 8. |
- Bass, Gary Alan, 1979-, et al.
(författare)
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Techniques for mesoappendix transection and appendix resection: insights from the ESTES SnapAppy study
- 2023
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Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer Science and Business Media LLC. - 1863-9933 .- 1615-3146 .- 1863-9941. ; 49, s. 17-32
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Surgically managed appendicitis exhibits great heterogeneity in techniques for mesoappendix transection and appendix amputation from its base. It is unclear whether a particular surgical technique provides outcome benefit or reduces complications. Material and methods: We undertook a pre-specified subgroup analysis of all patients who underwent laparoscopic appendectomy at index admission during SnapAppy (ClinicalTrials.gov Registration: NCT04365491). We collected routine, anonymized observational data regarding surgical technique, patient demographics and indices of disease severity, without change to clinical care pathway or usual surgeon preference. Outcome measures of interest were the incidence of complications, unplanned reoperation, readmission, admission to the ICU, death, hospital length of stay, and procedure duration. We used Poisson regression models with robust standard errors to calculate incident rate ratios (IRRs) and 95% confidence intervals (CIs). Results: Three-thousand seven hundred sixty-eight consecutive adult patients, included from 71 centers in 14 countries, were followed up from date of admission for 90days. The mesoappendix was divided hemostatically using electrocautery in 1564(69.4%) and an energy device in 688(30.5%). The appendix was amputated by division of its base between looped ligatures in 1379(37.0%), with a stapler in 1421(38.1%) and between clips in 929(24.9%). The technique for securely dividing the appendix at its base in acutely inflamed (AAST Grade 1) appendicitis was equally divided between division between looped ligatures, clips and stapled transection. However, the technique used differed in complicated appendicitis (AAST Grade 2 +) compared with uncomplicated (Grade 1), with a shift toward transection of the appendix base by stapler (58% vs. 38%; p < 0.001). While no statistical difference in outcomes could be detected between different techniques for division of appendix base, decreased risk of any [adjusted IRR (95% CI): 0.58 (0.41–0.82), p = 0.002] and severe [adjusted IRR (95% CI): 0.33 (0.11–0.96), p = 0.045] complications could be detected when using energy devices. Conclusions: Safe mesoappendix transection and appendix resection are accomplished using heterogeneous techniques. Technique selection for both mesoappendix transection and appendix resection correlates with AAST grade. Higher grade led to more ultrasonic tissue transection and stapled appendix resection. Higher AAST appendicitis grade also correlated with infection-related complication occurrence. Despite the overall well-tolerated heterogeneity of approaches to acute appendicitis, increasing disease acuity or complexity appears to encourage homogeneity of intraoperative surgical technique toward advanced adjuncts.
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| 9. |
- Forssten, Maximilian Peter, 1996-, et al.
(författare)
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Surgical management of acute appendicitis during the European COVID-19 second wave: safe and effective
- 2023
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Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer Science and Business Media LLC. - 1863-9933 .- 1615-3146 .- 1863-9941. ; 49, s. 57-67
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The COVID-19 (SARS-CoV-2) pandemic drove acute care surgeons to pivot from long established practice patterns. Early safety concerns regarding increased postoperative complication risk in those with active COVID infection promoted antibiotic-driven non-operative therapy for select conditions ahead of an evidence-base. Our study assesses whether active or recent SARS-CoV-2 positivity increases hospital length of stay (LOS) or postoperative complications following appendectomy. Methods: Data were derived from the prospective multi-institutional observational SnapAppy cohort study. This preplanned data analysis assessed consecutive patients aged ≥ 15years who underwent appendectomy for appendicitis (November 2020–May 2021). Patients were categorized based on SARS-CoV-2 seropositivity: no infection, active infection, and prior infection. Appendectomy method, LOS, and complications were abstracted. The association between SARS-CoV-2 seropositivity and complications was determined using Poisson regression, while the association with LOS was calculated using a quantile regression model. Results: Appendectomy for acute appendicitis was performed in 4047 patients during the second and third European COVID waves. The majority were SARS-CoV-2 uninfected (3861, 95.4%), while 70 (1.7%) were acutely SARS-CoV-2 positive, and 116 (2.8%) reported prior SARS-CoV-2 infection. After confounder adjustment, there was no statistically significant association between SARS-CoV-2 seropositivity and LOS, any complication, or severe complications. Conclusion: During sequential SARS-CoV-2 infection waves, neither active nor prior SARS-CoV-2 infection was associated with prolonged hospital LOS or postoperative complication. Despite early concerns regarding postoperative safety and outcome during active SARS-CoV-2 infection, no such association was noted for those with appendicitis who underwent operative management.
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| 10. |
- Loley, C, et al.
(författare)
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No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis
- 2016
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 35278-
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, genome-wide association studies have identified 58 independent risk loci for coronary artery disease (CAD) on the autosome. However, due to the sex-specific data structure of the X chromosome, it has been excluded from most of these analyses. While females have 2 copies of chromosome X, males have only one. Also, one of the female X chromosomes may be inactivated. Therefore, special test statistics and quality control procedures are required. Thus, little is known about the role of X-chromosomal variants in CAD. To fill this gap, we conducted a comprehensive X-chromosome-wide meta-analysis including more than 43,000 CAD cases and 58,000 controls from 35 international study cohorts. For quality control, sex-specific filters were used to adequately take the special structure of X-chromosomal data into account. For single study analyses, several logistic regression models were calculated allowing for inactivation of one female X-chromosome, adjusting for sex and investigating interactions between sex and genetic variants. Then, meta-analyses including all 35 studies were conducted using random effects models. None of the investigated models revealed genome-wide significant associations for any variant. Although we analyzed the largest-to-date sample, currently available methods were not able to detect any associations of X-chromosomal variants with CAD.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Nieminen, P., et al.
(författare)
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gamma-ray spectroscopy of Bi-191,Bi-193
- 2004
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 69:6, s. 064326-
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Tidskriftsartikel (refereegranskat)abstract
- Prompt and delayed gamma rays from Bi-191,Bi-193 have been identified using the recoil-decay tagging, isomer tagging, and recoil gating techniques, resulting in extensive level schemes for both nuclei. Excitation energies of the isomeric 13/2(+) states have been established and oblate strongly coupled bands built on them have been observed. The nearly spherical 9/2(-) ground-state bands appear to be crossed by more oblate-deformed low-lying structures. The properties of the bands feeding the 1/2(+) intruder states indicate some structural change between Bi-193 and Bi-191. The deformation associated with each of these states has been extracted from total Routhian surface calculations which also reveal the development of prolate minima with decreasing neutron number. B(M1)/B(E2) ratios have been measured for the observed strongly coupled bands in order to resolve the intrinsic excitations. The observed quasiparticle structures in Bi-193 and high-spin isomers both in Bi-193 and Bi-191 are interpreted based on the coupling of the odd proton to the even-even Pb core.
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| 15. |
- Van De Vel, K., et al.
(författare)
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In-beam gamma-ray spectroscopy of Po-190 : First observation of a low-lying prolate band in Po isotopes
- 2003
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 17:2, s. 167-171
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Tidskriftsartikel (refereegranskat)abstract
- Gamma rays from excited states of Po-190 have been observed using I the Jurosphere Ge-detector array coupled to the RITU gas-filled separator. They were associated with a collective band which from spin 4h onwards resembles the prolate rotational bands known in the isotones Pb-188 and Hg-186. This indicates that in Po-190 the prolate configuration becomes yrast above I = 2h. The experimental results are interpreted in a two-band mixing calculation and are in agreement with a-decay data and potential energy surface calculations.
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| 16. |
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| 17. |
- Leinonen, V, et al.
(författare)
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Positron emission tomography with [18F]flutemetamol and [11C]PiB for in vivo detection of cerebral cortical amyloid in normal pressure hydrocephalus patients.
- 2013
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 20:7, s. 1043-52
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: This study determined the correlation between uptake of the amyloid positron emission tomography (PET) imaging agent [(18) F]flutemetamol and amyloid-β measured by immunohistochemical and histochemical staining in a frontal cortical biopsy.METHODS: Fifteen patients with possible normal pressure hydrocephalus (NPH) and previous brain biopsy obtained during intracranial pressure monitoring underwent [18F]flutemetamol PET. Seven of these patients also underwent [11C] Pittsburgh compound B (PiB) PET. [18F]Flutemetamol and [11C]PiB uptake was quantified using standardized uptake value ratio (SUVR) with the cerebellar cortex as a reference region. Tissue amyloid-β was evaluated using the monoclonal antibody 4G8, Thioflavin-S and Bielschowsky silver stain.RESULTS: [18F]Flutemetamol and [11C]PiB SUVRs correlated with biopsy specimen amyloid-β levels contralateral (r = 0.86, P < 0.0001; r = 0.96, P = 0.0008) and ipsilateral (r = 0.82, P = 0.0002; r = 0.87, P = 0.01) to the biopsy site. Association between cortical composite [(18) F]flutemetamol SUVRs and [11C]PiB SUVRs was highly significant (r = 0.97, P = 0.0003).CONCLUSIONS: [18F]Flutemetamol detects brain amyloid-β in vivo with moderate to high sensitivity and high specificity. This agent, therefore, represents a valuable new tool to study and verify the presence of amyloid-β pathology, both in patients with possible NPH and among the wider population.
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| 18. |
- Van de Vel, K., et al.
(författare)
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Identification of low-lying proton-based intruder states in Pb189-193
- 2002
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 65:6
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Tidskriftsartikel (refereegranskat)abstract
- Low-lying proton-based intruder states have been observed in the odd-mass isotopes Pb-189,Pb-191,Pb-193 in experiments at the RITU gas-filled recoil separator. The identification has been performed by observing the fine structure in the alpha decay of the parent Po-193,Po-195,Po-197 nuclei in prompt coincidence with conversion electrons and gamma rays in the daughter lead isotopes. Along with the literature data these results establish a systematics of intruder states in the odd-mass lead isotopes from Pb-197 down to Pb-185. Interpretation of these states involves the coupling of the 1i(13/2) or 3p(3/2) odd neutron to the 0(+) state in the oblate minimum in the even-mass lead core. Conversion coefficients have been determined for some of the transitions, revealing mixing between the coexisting states. The experimental results are compared to potential energy surface calculations.
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| 19. |
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| 20. |
- Heikela, H., et al.
(författare)
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Hydroxysteroid (17 beta) dehydrogenase 12 is essential for metabolic homeostasis in adult mice
- 2020
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Ingår i: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 319:3
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Tidskriftsartikel (refereegranskat)abstract
- Hydroxysteroid 17 beta dehydrogenase 12 (HSD17B12) is suggested to be involved in the elongation of very long chain fatty acids. Previously. we have shown a pivotal role for the enzyme during mouse development. In the present study we generated a conditional Hsd17b12 knockout (HSD17B12cKO) mouse model by breeding mice homozygous for a floxed Hsd17b12 allele with mice expressing the tamoxifen-inducible Cre recombinase at the ROSA26 locus. Gene inactivation was induced by administering tamoxifen to adult mice. The gene inactivation led to a 20% loss of body weight within 6 days, associated with drastic reduction in both white (83% males, 75% females) and brown (65% males. 60% females) fat, likely due to markedly reduced food and water intake. Furthermore, the knockout mice showed sickness behavior and signs of liver toxicity. specifically microvesicular hepatic steatosis and increased serum alanine aminotransferase (4.6-fold in males, 7.7-fold in females). The hepatic changes were more pronounced in females than males. Proinflammatory cytokines, such as interleukin-6 (IL-6), IL-17, and granulocyte colony-stimulating factor, were increased in the HSD17B12cKO mice indicating an inflammatory response. Serum lipidomics study showed an increase in the amount of dihydroceramides, despite the dramatic overall loss of lipids. In line with the proposed role for HSD17B12 in fatty acid elongation, we observed accumulation of ceramides, dihydroceramides, hexosylceramides, and lactosylceramides with shorter than 18-carbon fatty acid side chains in the serum. The results indicate that HSD17B12 is essential for proper lipid homeostasis and HSD17B12 deficiency rapidly results in fatal systemic inflammation and lipolysis in adult mice.
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| 21. |
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| 22. |
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| 23. |
- Cheikh-el-Chabab, M. K., et al.
(författare)
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Using real-time simulation in company value chains and business models for value creation
- 2021
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Ingår i: Real-time Simulation for Sustainable Production: Enhancing User Experience and Creating Business Value. - : Routledge. - 9781000392180 - 9780367515164 - 9781003054214 ; , s. 177-195
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This chapter describes how incorporating real-time simulation in different value chain processes can affect business models and benefit various stakeholders. The primary objective is to explain how real-time simulation tools can increasingly represent real-world functionality in today’s businesses and emerging industries. Different value-chain activities are discussed, and examples are given of value creation based on real-time simulation, starting from product development and continuing through customer receipt.
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| 24. |
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| 25. |
- Motiani, P., et al.
(författare)
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Exercise training alters lipoprotein particles independent of brown adipose tissue metabolic activity
- 2019
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Ingår i: Obesity science & practice. - : WILEY. - 2055-2238. ; 5:3, s. 258-272
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Tidskriftsartikel (refereegranskat)abstract
- Introduction New strategies for weight loss and weight maintenance in humans are needed. Human brown adipose tissue (BAT) can stimulate energy expenditure and may be a potential therapeutic target for obesity and type 2 diabetes. However, whether exercise training is an efficient stimulus to activate and recruit BAT remains to be explored. This study aimed to evaluate whether regular exercise training affects cold-stimulated BAT metabolism and, if so, whether this was associated with changes in plasma metabolites. Methods Healthy sedentary men (n = 11; aged 31 [SD 7] years; body mass index 23 [0.9] kg m(-2); VO2 max 39 [7.6] mL min(-1) kg(-1)) participated in a 6-week exercise training intervention. Fasting BAT and neck muscle glucose uptake (GU) were measured using quantitative [F-18]fluorodeoxyglucose positron emission tomography-magnetic resonance imaging three times: (1) before training at room temperature and (2) before and (3) after the training period during cold stimulation. Cervico-thoracic BAT mass was measured using MRI signal fat fraction maps. Plasma metabolites were analysed using nuclear magnetic resonance spectroscopy. Results Cold exposure increased supraclavicular BAT GU by threefold (p < 0.001), energy expenditure by 59% (p < 0.001) and plasma fatty acids (p < 0.01). Exercise training had no effect on cold-induced GU in BAT or neck muscles. Training increased aerobic capacity (p = 0.01) and decreased visceral fat (p = 0.02) and cervico-thoracic BAT mass (p = 0.003). Additionally, training decreased very low-density lipoprotein particle size (p = 0.04), triglycerides within chylomicrons (p = 0.04) and small high-density lipoprotein (p = 0.04). Conclusions Although exercise training plays an important role for metabolic health, its beneficial effects on whole body metabolism through physiological adaptations seem to be independent of BAT activation in young, sedentary men.
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| 26. |
- Percival, Carl J., et al.
(författare)
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Regional and global impacts of Criegee intermediates on atmospheric sulphuric acid concentrations and first steps of aerosol formation
- 2013
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Ingår i: Faraday discussions. - : Royal Society of Chemistry (RSC). - 1359-6640 .- 1364-5498. ; 165, s. 45-73
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Tidskriftsartikel (refereegranskat)abstract
- Carbonyl oxides (Criegee intermediates), formed in the ozonolysis of alkenes, are key species in tropospheric oxidation of organic molecules and their decomposition provides a non-photolytic source of OH in the atmosphere (Johnson and Marston, Chem. Soc. Rev., 2008, 37, 699, Harrison et al., Sci. Total Environ., 2006, 360, 5, Gab et al., Nature, 1985, 316, 535, ref. 1-3). Recently it was shown that small Criegee intermediates, C.I.'s, react far more rapidly with SO2 than typically represented in tropospheric models, (Welz, Science, 2012, 335, 204, ref. 4) which suggested that carbonyl oxides could have a substantial influence on the atmospheric oxidation of SO2. Oxidation of SO2 is the main atmospheric source of sulphuric acid (H2SO4), which is a critical contributor to aerosol formation, although questions remain about the fundamental nucleation mechanism (Sipila et al., Science, 2010, 327, 1243, Metzger et al., Proc. Natl. Acad. Sci. U. S. A., 2010 107, 6646, Kirkby et al., Nature, 2011, 476, 429, ref. 5-7). Non-absorbing atmospheric aerosols, by scattering incoming solar radiation and acting as cloud condensation nuclei, have a cooling effect on climate (Intergovernmental Panel on Climate Change (IPCC), Climate Change 2007: The Physical Science Basis, Cambridge University Press, 2007, ref. 8). Here we explore the effect of the Criegees on atmospheric chemistry, and demonstrate that ozonolysis of alkenes via the reaction of Criegee intermediates potentially has a large impact on atmospheric sulphuric acid concentrations and consequently the first steps in aerosol production. Reactions of Criegee intermediates with SO2 will compete with and in places dominate over the reaction of OH with SO2 (the only other known gas-phase source of H2SO4) in many areas of the Earth's surface. In the case that the products of Criegee intermediate reactions predominantly result in H2SO4 formation, modelled particle nucleation rates can be substantially increased by the improved experimentally obtained estimates of the rate coefficients of Criegee intermediate reactions. Using both regional and global scale modelling, we show that this enhancement is likely to be highly variable spatially with local hot-spots in e. g. urban outflows. This conclusion is however contingent on a number of remaining uncertainties in Criegee intermediate chemistry.
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