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1.	Kotecha, Dipak, et al. (författare) Impact of Renal Impairment on Beta-Blocker Efficacy in PatientsWithHeartFailure. 2019 Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 1558-3597 .- 0735-1097. ; 74:23, s. 2893-2904 Tidskriftsartikel (refereegranskat)abstract Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy.This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR).Analysis of 16,740 individual patients with left ventricular ejection fraction<50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm.Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73m2; 4,584 patients (27.4%) had eGFR 45 to 59ml/min/1.73m2, and 2,286 (13.7%) 30 to 44ml/min/1.73m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10ml/min/1.73m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p<0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59ml/min/1.73m2 (95%CI: 0.62 to 0.86; p<0.001) and 0.71 for eGFR 30 to 44ml/min/1.73m2 (95%CI: 0.58 to 0.87; p=0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal functionon follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR<30ml/min/1.73m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR.Patients with heart failure, left ventricular ejection fraction<50% and sinus rhythm should receivebeta-blocker therapy even with moderate or moderately severe renal dysfunction.
2.	Bhatt, Deepak L., et al. (författare) Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study 2019 Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 42:5, s. 498-505 Tidskriftsartikel (refereegranskat)abstract In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients >= 50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of >= 50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.
3.	Hibar, Derrek P., et al. (författare) Novel genetic loci associated with hippocampal volume 2017 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8 Tidskriftsartikel (refereegranskat)abstract The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
4.	Hijazi, Ziad, et al. (författare) Combining High Sensitivity Troponin I and T Measurements Improves Prediction of Long-Term Clinical Outcomes in Patients With Atrial Fibrillation - An Aristotle Substudy 2013 Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 128:22 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
5.	Hijazi, Ziad, et al. (författare) Comparison of Cardiac Troponins I and T Measured with High-Sensitivity Methods for Evaluation of Prognosis in Atrial Fibrillation : An ARISTOTLE Substudy 2015 Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 61:2, s. 368-378 Tidskriftsartikel (refereegranskat)abstract BACKGROUND:Although cardiac troponin is associated with outcomes in atrial fibrillation (AF), the complementary prognostic information provided by cardiac troponin I (cTnI) and cTnT is unknown. This study investigated the distribution, determinants, and prognostic value of cTnI and cTnT concentrations in patients with AF.METHODS:At the time of randomization, we analyzed cTnI and cTnT concentrations of 14 806 AF patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial using high-sensitivity assays. Correlations (Spearman), determinants (multiple analysis of variance), and outcomes (adjusted Cox models and c-statistics) were investigated.RESULTS:Concentrations of cTnI and cTnT were correlated (r = 0.70) and measurable in most participants [cTnI 98.5% (median 5.4 ng/L, ≥99th percentile in 9.2%) and cTnT 93.5% (median 10.9 ng/L, ≥99th percentile in 34.4%)]. Renal impairment was the most important factor affecting the concentrations of both troponins. cTnI increase was more associated with heart failure, vascular disease, and persistent/permanent AF, and cTnT with age, male sex, and diabetes. Over a median 1.9 years of follow-up, patients with both troponins above the median had significantly higher risk for stroke/systemic embolism [hazard ratio (HR) 1.72 (95% CI 1.31-2.27)], cardiac death [3.14 (2.35-4.20)], and myocardial infarction [2.99 (1.78-5.03)] than those with both troponins below median (all P < 0.005). Intermediate risks were observed when only 1 troponin was above the median. When combined with clinical information, each marker provided similar prognostication and had comparable c-statistics.CONCLUSIONS:cTnI and cTnT concentrations are moderately correlated and measurable in plasma of most AF patients. The risk of stroke and cardiovascular events is highest when both troponins are above median concentrations. Each troponin provides comparable prognostic information when combined with clinical risk factors.
6.	Hijazi, Ziad, et al. (författare) High-Sensitivity Troponin I for Risk Assessment in Patients With Atrial Fibrillation Insights From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial 2014 Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 129:6, s. 625-634 Tidskriftsartikel (refereegranskat)abstract Background High-sensitivity troponin-I (hs-TnI) measurement improves risk assessment for cardiovascular events in many clinical settings, but the added value in atrial fibrillation patients has not been described. Methods and Results At randomization, hs-TnI was analyzed in 14 821 atrial fibrillation patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial comparing apixaban with warfarin. The associations between hs-TnI concentrations and clinical outcomes were evaluated by using adjusted Cox analysis. The hs-TnI assay detected troponin (1.3 ng/L) in 98.5% patients, 50% had levels >5.4, 25% had levels >10.1, and 9.2% had levels 23 ng/L (the 99th percentile in healthy individuals). During a median of 1.9 years follow-up, annual rates of stroke or systemic embolism ranged from 0.76% in the lowest hs-TnI quartile to 2.26% in the highest quartile (>10.1 ng/L). In multivariable analysis, hs-TnI was significantly associated with stroke or systemic embolism, adjusted hazard ratio 1.98 (1.42-2.78), P=0.0007. hs-TnI was also significantly associated with cardiac death; annual rates ranged from 0.40% to 4.24%, hazard ratio 4.52 (3.05-6.70), P<0.0001, in the corresponding groups, and for major bleeding hazard ratio 1.44 (1.11-1.86), P=0.0250. Adding hs-TnI levels to the CHA(2)DS(2)VASc score improved c-statistics from 0.629 to 0.653 for stroke or systemic embolism, and from 0.591 to 0.731 for cardiac death. There were no significant interactions with study treatment. Conclusions Troponin-I is detected in 98.5% and elevated in 9.2% of atrial fibrillation patients. The hs-TnI level is independently associated with a raised risk of stroke, cardiac death, and major bleeding and improves risk stratification beyond the CHA(2)DS(2)VASc score. The benefits of apixaban in comparison with warfarin are consistent regardless of hs-TnI levels.
7.	Hijazi, Ziad, et al. (författare) High Sensitivity Troponin T and Risk Stratification in Patients with Atrial Fibrillation during Treatment with Apixaban or Warfarin 2014 Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 63:1, s. 52-61 Tidskriftsartikel (refereegranskat)abstract ObjectivesThe aim of this study was to evaluate the prognostic value of high-sensitivity troponin T (hs-TnT) in addition to clinical risk factors and the CHA2DS2VASc (congestive heart failure, hypertension, 75 years of age and older, diabetes mellitus, previous stroke or transient ischemic attack, vascular disease, 65 to 74 years of age, female) risk score in patients with atrial fibrillation (AF).BackgroundThe level of troponin is a powerful predictor of cardiovascular events and mortality.MethodsA total of 14,897 patients with AF were randomized to treatment with apixaban or warfarin in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial. The associations between baseline hs-TnT levels and outcomes were evaluated using adjusted Cox regression models.ResultsLevels of hs-TnT were measurable in 93.5% of patients; 75% had levels >7.5 ng/l, 50% had levels >11.0 ng/l, and 25% had levels >16.7 ng/l. During a median 1.9-year period, the annual rates of stroke or systemic embolism ranged from 0.87% in the lowest hs-TnT quartile to 2.13% in the highest hs-TnT quartile (adjusted hazard ratio [HR]: 1.94; 95% confidence interval [CI]: 1.35 to 2.78; p = 0.0010). The annual rates in the corresponding groups ranged from 0.46% to 4.24% (adjusted HR: 4.31; 95% CI: 2.91 to 6.37; p < 0.0001) for cardiac death and from 1.26% to 4.21% (adjusted HR: 1.91; 95% CI: 1.43 to 2.56; p = 0.0001) for major bleeding. Adding hs-TnT levels to the CHA2DS2VASc score improved the C statistic from 0.620 to 0.635 for stroke or systemic embolism (p = 0.0226), from 0.592 to 0.711 for cardiac death (p < 0.0001), and from 0.591 to 0.629 for major bleeding (p < 0.0001). Apixaban reduced rates of stroke, mortality, and bleeding regardless of the hs-TnT level.ConclusionsLevels of hs-TnT are often elevated in patients with AF. The hs-TnT level is independently associated with an increased risk of stroke, cardiac death, and major bleeding and improves risk stratification beyond the CHA2DS2VASc risk score. The benefits of apixaban as compared with warfarin are consistent regardless of the hs-TnT level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE];
8.	Horikoshi, Momoko, et al. (författare) New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism. 2013 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1 Tidskriftsartikel (refereegranskat)abstract Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
9.	Rafati, Nima, et al. (författare) Large Deletions at the SHOX Locus in the Pseudoautosomal Region Are Associated with Skeletal Atavism in Shetland Ponies 2016 Ingår i: G3. - : Oxford University Press (OUP). - 2160-1836. ; 6:7, s. 2213-2223 Tidskriftsartikel (refereegranskat)abstract Skeletal atavism in Shetland ponies is a heritable disorder characterized by abnormal growth of the ulna and fibula that extend the carpal and tarsal joints, respectively. This causes abnormal skeletal structure and impaired movements, and affected foals are usually killed. In order to identify the causal mutation we subjected six confirmed Swedish cases and a DNA pool consisting of 21 control individuals to whole genome resequencing. We screened for polymorphisms where the cases and the control pool were fixed for opposite alleles and observed this signature for only 25 SNPs, most of which were scattered on genome assembly unassigned scaffolds. Read depth analysis at these loci revealed homozygosity or compound heterozygosity for two partially overlapping large deletions in the pseudoautosomal region (PAR) of chromosome X/Y in cases but not in the control pool. One of these deletions removes the entire coding region of the SHOX gene and both deletions remove parts of the CRLF2 gene located downstream of SHOX. The horse reference assembly of the PAR is highly fragmented, and in order to characterize this region we sequenced bacterial artificial chromosome (BAC) clones by single-molecule real-time (SMRT) sequencing technology. This considerably improved the assembly and enabled size estimations of the two deletions to 1602180 kb and 60280 kb, respectively. Complete association between the presence of these deletions and disease status was verified in eight other affected horses. The result of the present study is consistent with previous studies in humans showing crucial importance of SHOX for normal skeletal development.
10.	Siriwardena, Ajith K., et al. (författare) Standards for reporting on surgery for chronic pancreatitis : a report from the International Study Group for Pancreatic Surgery (ISGPS) 2020 Ingår i: Surgery (United States). - : Elsevier BV. - 0039-6060. ; 168:1, s. 101-105 Tidskriftsartikel (refereegranskat)abstract Background: The International Study Group for Pancreatic Surgery provides globally accepted definitions for reporting of complications after pancreatic surgery. This International Study Group for Pancreatic Surgery project aims to provide a standardized framework for reporting of the results of operative treatment for chronic pancreatitis. Methods: An International Study Group for Pancreatic Surgery project circulation list was created with pre-existing and new members and including gastroenterologists in addition to surgeons. A computerized search of the literature was undertaken for articles reporting the operative treatment of chronic pancreatitis. The results of the literature search were presented at the first face-to-face meeting of this International Study Group for Pancreatic Surgery project group. A document outlining proposed reporting standards was produced by discussion during an initial meeting of the International Study Group for Pancreatic Surgery. An electronic questionnaire was then sent to all current members of the International Study Group for Pancreatic Surgery. Responses were collated and further discussed at international meetings in North America, Europe, and at the International Association of Pancreatology World Congress in 2019. A final consensus document was produced by integration of multiple iterations. Results: The International Study Group for Pancreatic Surgery consensus standards for reporting of surgery in chronic pancreatitis recommends 4 core domains and the necessary variables needed for reporting of results: clinical baseline before operation; the morphology of the diseased gland; a new, standardized, operative terminology; and a minimum outcome dataset. The 4 domains combine to give a comprehensive framework for reports. Conclusion: Adoption of the 4 domains of the International Study Group for Pancreatic Surgery reporting standards for surgery for chronic pancreatitis will facilitate comparison of results between centers and help to improve the care for patients with this debilitating disease.
11.	Ademuyiwa, Adesoji O., et al. (författare) Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries 2016 Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4 Tidskriftsartikel (refereegranskat)abstract Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
12.	Alexander, C, et al. (författare) Molecular imprinting science and technology: a survey of the literature for the years up to and including 2003 2006 Ingår i: Journal of molecular recognition. ; 19:2, s. 106-180 Tidskriftsartikel (refereegranskat)
13.	Ali, Alaa M. G., et al. (författare) Alcohol Consumption and Survival after a Breast Cancer Diagnosis: A Literature-Based Meta-analysis and Collaborative Analysis of Data for 29,239 Cases 2014 Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 23:6, s. 934-945 Tidskriftsartikel (refereegranskat)abstract Background: Evidence for an association of alcohol consumption with prognosis after a diagnosis of breast cancer has been inconsistent. We have reviewed and summarized the published evidence and evaluated the association using individual patient data from multiple case cohorts. Methods: A MEDLINE search to identify studies published up to January 2013 was performed. We combined published estimates of survival time for "moderate drinkers" versus nondrinkers. An analysis of individual participant data using Cox regression was carried out using data from 11 case cohorts. Results: We identified 11 published studies suitable for inclusion in the meta-analysis. Moderate postdiagnosis alcohol consumption was not associated with overall survival [HR, 0.95; 95% confidence interval (CI), 0.85-1.05], but there was some evidence of better survival associated with prediagnosis consumption (HR, 0.80; 95% CI, 0.73-0.88). Individual data on alcohol consumption for 29,239 cases with 4,839 deaths were available from the 11 case cohorts, all of which had data on estrogen receptor (ER) status. For women with ER-positive disease, there was little evidence that pre-or postdiagnosis alcohol consumption is associated with breast cancer-specific mortality, with some evidence of a negative association with all-cause mortality. On the basis of a single study, moderate postdiagnosis alcohol intake was associated with a small reduction in breast cancer-specific mortality for women with ER-negative disease. There was no association with prediagnosis intake for women with ER-negative disease. Conclusion: There was little evidence that pre- or post-diagnosis alcohol consumption is associated with breast cancer-specific mortality for women with ER-positive disease. There was weak evidence that moderate post-diagnosis alcohol intake is associated with a small reduction in breast cancer-specific mortality in ER-negative disease. Impact: Considering the totality of the evidence, moderate postdiagnosis alcohol consumption is unlikely to have a major adverse effect on the survival of women with breast cancer. (C) 2014 AACR.
14.	Andersson, Anders, 1980-, et al. (författare) Estimating effort and catch of a recreational trolling fishery in one of Europe’s largest lakes Annan publikation (övrigt vetenskapligt/konstnärligt)
15.	Andersson, Anders, 1980-, et al. (författare) Recreational trolling effort and catch of Atlantic salmon and brown trout in Vänern, the EU's largest lake 2020 Ingår i: Fisheries Research. - : Elsevier. - 0165-7836 .- 1872-6763. ; 227 Tidskriftsartikel (refereegranskat)abstract Recreational fishing has grown substantially worldwide; for some recreational fisheries both catch and economic value now exceeds that of commercial fisheries. Monitoring of recreational fisheries effort and catch is therefore important for sustainable fisheries management. We developed and implemented an angler survey to estimate effort and catch for the recreational trolling fishery for landlocked Atlantic salmon (Salmo salar) and brown trout (S. trutta) in Lake Vänern, Sweden. Major challenges were the large spatial scale and dispersed fishing effort, a lack of revenue from fishing licence sales, and a lack of catch reporting requirements. We developed a complemented roving/mail-in survey to estimate effort and catch during the main fishing periods, spring and fall, 2014. Instantaneous counts from major access sites were used for effort estimates, and mail-in surveys were used for catch rates. Our results show that Vänern supports a salmon and trout fishery of some 28.7 ± 3.3 tonnes per year. Fishing effort was higher in the spring than in the fall, and there were seasonal differences in catch rates for trout but not for salmon. Estimates show that the recreational trolling fishery now harvests more salmon and trout annually than do the commercial and subsistence fisheries combined. This highlights the importance of continuing an angler survey program for Vänern as a key element for sustainable fisheries management, and can serve as a model for other recreational fisheries at large spatial scales.
16.	Andersson, John Åke, et al. (författare) Sweden's Economic Relationships with Uganda 2016 Rapport (övrigt vetenskapligt/konstnärligt)abstract This explorative study aims to map commercial and other economic relations between Sweden and Uganda during the years 2000-2014. In addition, we will discuss whether and how these relations may be related to Swedish bilateral aid.
17.	Andersson, Lars Gustaf, et al. (författare) Spaces of becoming: the Stockholm Film Workshop as a transnational site of film production 2018 Ingår i: Transnational Cinema at the Borders : Borderscapes and the Cinematic Imaginary - Borderscapes and the Cinematic Imaginary. - 9781138091108 ; , s. 40-51 Bokkapitel (refereegranskat)abstract An account of the Stockholm Film Workshop (1973 - 2001) and how it became a site of film production by immigrant filmworkers, primarily from Latin America and Greece.
18.	Aulin, Julia, et al. (författare) Serial measurement of interleukin-6 and risk of mortality in anticoagulated patients with atrial fibrillation : Insights from ARISTOTLE and RE-LY trials. 2020 Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 18:9, s. 2287-2295 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The inflammatory biomarker interleukin-6 (IL-6) is associated with mortality in atrial fibrillation (AF).OBJECTIVE: To investigate if repeated IL-6 measurements improve the prognostication for stroke or systemic embolism, major bleeding, and mortality in anticoagulated patients with AF.METHODS: IL-6 levels by ELISA were measured at study entry and at 2 months in 4830 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial with 1.8 years median follow-up. In the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, IL-6 was measured at study entry, 3, 6, and 12 months in 2559 patients with 2.0 years median follow-up. Associations between a second IL-6 measurement and outcomes, adjusted for baseline IL-6, clinical variables, and other cardiovascular biomarkers, were analyzed by Cox regression.RESULTS: Median IL-6 levels were 2.0 ng/L (interquartile range [IQR] 1.30-3.20) and 2.10 ng/L (IQR 1.40-3.40) at the two time-points in ARISTOTLE, and, in RE-LY, 2.5 ng/L (IQR 1.6-4.3), 2.5 ng/L (IQR 1.6-4.2), 2.4 ng/L (IQR 1.6, 3.9), and 2.4 ng/L (IQR 1.5, 3.9), respectively. IL-6 was associated with mortality; hazard ratios per 50% higher IL-6 at 2 or 3 months, respectively, were 1.32 (95% confidence interval, 1.23-1.41; P < .0001) in ARISTOTLE, and 1.11 (1.01-1.22, P = .0290) in RE-LY; with improved C index from 0.74 to 0.76 in ARISTOTLE, but not in the smaller RE-LY cohort. There were no consistent associations with second IL-6 and stroke or systemic embolism, or major bleeding.CONCLUSIONS: Persistent systemic inflammatory activity, assessed by repeated IL-6 measurements, is associated with mortality independent of established clinical risk factors and other strong cardiovascular biomarkers in anticoagulated patients with AF.
19.	Bombarda, F., et al. (författare) Runaway electron beam control 2019 Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1 Tidskriftsartikel (refereegranskat)
20.	Chapman, Henry N, et al. (författare) Femtosecond X-ray protein nanocrystallography. 2011 Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 470:7332, s. 73-7 Tidskriftsartikel (refereegranskat)abstract X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (∼200nm to 2μm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.
21.	De Caterina, Raffaele, et al. (författare) History of bleeding and outcomes with apixaban versus warfarin in patients with atrial fibrillation in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial 2016 Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 175, s. 175-183 Tidskriftsartikel (refereegranskat)abstract Aims History of bleeding strongly influences decisions for anticoagulation in atrial fibrillation (AF). We analyzed outcomes in relation to history of bleeding and randomization in ARISTOTLE trial patients. Methods and results The on-treatment safety population included 18,140 patients receiving at least 1 dose of study drug (apixaban) or warfarin. Centrally adjudicated outcomes in relation to bleeding history were analyzed using a Cox proportional hazards model adjusted for randomized treatment and established risk factors. Efficacy end points were analyzed on the randomized (intention to treat) population. A bleeding history was reported at baseline in 3,033 patients (16.7%), who more often were male, with a history of prior stroke/transient ischemic attack/systemic embolism and diabetes; higher CHADS2 scores, age, and body weight; and lower creatinine clearance and mean systolic blood pressure. Major (but not intracranial) bleeding occurred more frequently in patients with versus without a history of bleeding (adjusted hazard ratio 1.35, 95% CI 1.14-1.61). There were no significant interactions between bleeding history and treatment for stroke/systemic embolism, hemorrhagic stroke, death, or major bleeding, with fewer outcomes with apixaban versus warfarin for all of these outcomes independent of the presence/absence of a bleeding history. Conclusion In patients with AF in a randomized clinical trial of oral anticoagulants, a history of bleeding is associated with several risk factors for stroke and portends a higher risk of major-but not intracranial-bleeding, during anticoagulation. However, the beneficial effects of apixaban over warfarin for stroke, hemorrhagic stroke, death, or major bleeding remains consistent regardless of history of bleeding.
22.	Dima, Danai, et al. (författare) Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3-90 years. 2022 Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 452-469 Tidskriftsartikel (refereegranskat)abstract Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
23.	Dupont, Chris L., et al. (författare) Functional Tradeoffs Underpin Salinity-Driven Divergence in Microbial Community Composition 2014 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2, s. e89549- Tidskriftsartikel (refereegranskat)abstract Bacterial community composition and functional potential change subtly across gradients in the surface ocean. In contrast, while there are significant phylogenetic divergences between communities from freshwater and marine habitats, the underlying mechanisms to this phylogenetic structuring yet remain unknown. We hypothesized that the functional potential of natural bacterial communities is linked to this striking divide between microbiomes. To test this hypothesis, metagenomic sequencing of microbial communities along a 1,800 km transect in the Baltic Sea area, encompassing a continuous natural salinity gradient from limnic to fully marine conditions, was explored. Multivariate statistical analyses showed that salinity is the main determinant of dramatic changes in microbial community composition, but also of large scale changes in core metabolic functions of bacteria. Strikingly, genetically and metabolically different pathways for key metabolic processes, such as respiration, biosynthesis of quinones and isoprenoids, glycolysis and osmolyte transport, were differentially abundant at high and low salinities. These shifts in functional capacities were observed at multiple taxonomic levels and within dominant bacterial phyla, while bacteria, such as SAR11, were able to adapt to the entire salinity gradient. We propose that the large differences in central metabolism required at high and low salinities dictate the striking divide between freshwater and marine microbiomes, and that the ability to inhabit different salinity regimes evolved early during bacterial phylogenetic differentiation. These findings significantly advance our understanding of microbial distributions and stress the need to incorporate salinity in future climate change models that predict increased levels of precipitation and a reduction in salinity.
24.	Ekeberg, Tomas, 1983-, et al. (författare) Three-dimensional structure determination with an X-ray laser Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Three-dimensional structure determination of a non-crystalline virus has been achieved from a set of randomly oriented continuous diffraction patterns captured with an X-ray laser. Intense, ultra-short X-ray pulses intercepted a beam of single mimivirus particles, producing single particle X-ray diffraction patterns that are assembled into a three-dimensional amplitude distribution based on statistical consistency. Phases are directly retrieved from the assembled Fourier distribution to synthesize a three-dimensional image. The resulting electron density reveals a pseudo-icosahedral asymmetric virion structure with a compartmentalized interior, within which the DNA genome occupies only about a fifth of the volume enclosed by the capsid. Additional electron microscopy data indicate the genome has a chromatin-like fiber structure that has not previously been observed in a virus.
25.	Fazey, Ioan, et al. (författare) Transforming knowledge systems for life on Earth : Visions of future systems and how to get there 2020 Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70 Tidskriftsartikel (refereegranskat)abstract Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
26.	Frangou, Sophia, et al. (författare) Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years 2022 Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 431-451 Tidskriftsartikel (refereegranskat)abstract Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
27.	Hambäck, Peter A., et al. (författare) Insekter och spindlar i anlagda våtmarker : Intressanta fynd från en systematisk undersökning i Uppland och södra Halland 2022 Ingår i: Entomologisk tidskrift. - 0013-886X. ; 143:1-2, s. 47-66 Tidskriftsartikel (refereegranskat)abstract Wetland area has decreased dramatically compared with preindustrial times, and in manyagricultural areas almost all wetlands have been drained to gain cropland. The trend hasin recent years been reversed because society has realized the many benefits of wetlandfunctions, such as for nutrient retention and flood control. In this study we inventoried 75 wetlands in Uppland and Halland for insects and spiders with Malaise traps, pitfall traps andsuction sampling. Most included wetlands are constructed, because the main purpose was toexamine if these wetlands also can be good for arthropod diversity, but we also included somemore natural wetlands as comparison. In total, we identified more than 25,000 individualsof more than 900 species of Coleoptera, Araneae, Diptera and Heteroptera. We found onenew species for Sweden, Hilara manicata Meigen 1822, and 37 new regional records. Alarge number of species found are considered threatened or else rare. Some wetlands closeto Mälaren were particularly interesting, with three species (Hypsosinga heri (Hahn 1831),Rhaphium antennatum (Charlier 1835) and Bagous robustus Brisout de Barneville 1863)that have no records nearby during recent times. These and other species found in the studyshow that constructed wetlands can provide good habitats for arthropod biodiversity andrare species, particularly if wetland shores are grazed and trampled by cattle.
28.	Hantke, Max F., et al. (författare) A data set from flash X-ray imaging of carboxysomes 2016 Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 3 Tidskriftsartikel (refereegranskat)abstract Ultra-intense femtosecond X-ray pulses from X-ray lasers permit structural studies on single particles and biomolecules without crystals. We present a large data set on inherently heterogeneous, polyhedral carboxysome particles. Carboxysomes are cell organelles that vary in size and facilitate up to 40% of Earth’s carbon fixation by cyanobacteria and certain proteobacteria. Variation in size hinders crystallization. Carboxysomes appear icosahedral in the electron microscope. A protein shell encapsulates a large number of Rubisco molecules in paracrystalline arrays inside the organelle. We used carboxysomes with a mean diameter of 115±26 nm from Halothiobacillus neapolitanus. A new aerosol sample-injector allowed us to record 70,000 low-noise diffraction patterns in 12 min. Every diffraction pattern is a unique structure measurement and high-throughput imaging allows sampling the space of structural variability. The different structures can be separated and phased directly from the diffraction data and open a way for accurate, high-throughput studies on structures and structural heterogeneity in biology and elsewhere.
29.	Hantke, Max F., et al. (författare) High-throughput imaging of heterogeneous cell organelles with an X-ray laser 2014 Ingår i: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 8:12, s. 943-949 Tidskriftsartikel (refereegranskat)abstract We overcome two of the most daunting challenges in single-particle diffractive imaging: collecting many high-quality diffraction patterns on a small amount of sample and separating components from mixed samples. We demonstrate this on carboxysomes, which are polyhedral cell organelles that vary in size and facilitate up to 40% of Earth's carbon fixation. A new aerosol sample-injector allowed us to record 70,000 low-noise diffraction patterns in 12 min with the Linac Coherent Light Source running at 120 Hz. We separate different structures directly from the diffraction data and show that the size distribution is preserved during sample delivery. We automate phase retrieval and avoid reconstruction artefacts caused by missing modes. We attain the highest-resolution reconstructions on the smallest single biological objects imaged with an X-ray laser to date. These advances lay the foundations for accurate, high-throughput structure determination by flash-diffractive imaging and offer a means to study structure and structural heterogeneity in biology and elsewhere.
30.	Hedström, Brita, et al. (författare) Visby Innerstad : En användningsplan 1973 Rapport (populärvet., debatt m.m.)abstract Sedan lång tid föreligger i stort sett enighet om att bevara innerstadens bebyggelse och att anpassa eventuella nytillskott till det redan bestående. Med den inställningen har förändringsprocessen både dämpats och mildrats men ändå inte bragts att avstanna. Förändringar sker ständigt om det också huvudsakligen i smått: de många synbart så anspråkslösa byggnadsåtgärderna adderar efterhand ihop sig till något större och mer genomgripande. Långsamt, nästan omärkligt, ändrar innerstaden sitt ansikte.Ändå är det inte själva husen som förändrats mest utan användningen av dem. Ur funktionell synpunkt har 1950 - och 60-talen har varit något av en omstörtning i innerstadens historia: den har förlorat nästan hälften av de boende, en stor del av detaljhandeln och praktiskt taget helt sin gamla roll som skolcentrum. I gengäld har ytterstaden vuxit ut till ett sammanhängande kilometerbrett bälte. Till stor del av denna funktionella förändring en följd av beslutet att bevara innerstadens bebyggelse. Vad som inte fått plats inom den gamla ramen har etablerats utandör den.Föreliggande arbete vill ge en översiktlig bild av förändringsförloppen, sedda i ett långt tidsperspektiv men med tonvikt på dagsläget. Bebyggelsen tas upp till utförlig granskning men också användningen av den. Det är just samspelet mellan husen och de funtkioner, de fyller, som kan sägas utgöra bokens huvudtema. I de flesta fall är detta sammanhang hus-användning alldeles konfliktfritt och föranleder därför inte heller någon diskussion. Vad som behandlas är de relativt få problematiska fallen, hus som borde rustas upp för att fylla sin uppgift, hus som är olämpligt nyttjade eller inte använda alls. En serie sådana fall tas upp till systematisk genomgång; samtidigt berörs också de trafik - och miljömässiga konsekvenserna. Bokens syfte är alltså klart: den ger ett underlag av fakta för arbetet med att jämka samman byggnader och användningsformer. I den meningen kan skriften kallas en anvädningsplan för Visby innanför murarna.Arkitekturskolanas arbete har bedrivitis parallellt med den kommunala Innerstadskommitténs verksamhet. Något organiserat samarbete har inte förekommit med de informella kontakterna har varit både täta och goda. Att likheterna mellan Innerstadskommittén och Arkitekturskolans slutsatser blivit så pass stora, kan tillskrivas en gemensam helhetssyn.En av Arkitekturskolans elever, arkitekt Lars-Ingvar Larsson, har tidigare självständigt genomfört en undersökning av förändringar i innerstaden 1945-70- Denna studie publicerats separat och bör uppfattas som ett komplement till den hör föreliggande.Förutom de i innehållsförteckningen nämnda har ytterligare några aktivt medverkat i arbetet. Studiet av trafikfrågorna i innerstaden, i hamnen och öster om ringmuren leddes av Åke Claesson, I fältstudier och diskussioner medverkande Göran Månsson.Arkitekturskolan har fått god hjälp av ett antal initierade personer i Visby. Särskild tacksamhet är vi skyldiga byggnadsnämnden ordförande Henning Jacobson, kommunalrådet C B Stenström, stadsarkitekten Måns Hagbergm f. länsbostadsdorektören Åke Malmberg och landsantikvarien Gunnar Svahnström. I boken publiceringskostnaderna har ekonomiskt bidrag lämnats av Gotlands kommun och Riksantikvarieämbetet.Boken har redigerats av Sture Balgård och Ann Mari Westerlind med hjälp av Henrik O Andersson, Bo Ek, Göran Lindahl, Fredrik von Platen, John Sjöström Gunnar Westerlind och Hans Wetterfors.Skeppsholmen, Stockholm, sommaren 1973.Arkitekturskolans lärare och elever.
31.	Hijazi, Ziad, et al. (författare) Biomarkers of inflammation and risk of cardiovascular events in anticoagulated patients with atrial fibrillation 2016 Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 102:7, s. 508-517 Tidskriftsartikel (refereegranskat)abstract Objective: Atrial fibrillation (AF) is a risk factor for stroke and mortality and the prothrombotic state has been linked to inflammation. In this study we evaluated the relationship between inflammatory biomarkers at baseline and future risk of cardiovascular events in the Apixaban for Reduction In Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.Methods: The ARISTOTLE trial randomised 18 201 patients with AF to apixaban or warfarin. Interleukin 6 (IL-6) and C reactive protein (CRP) were analysed in plasma obtained at randomisation from 14 954 participants, and median follow-up was 1.9 years. Association between quartile groups of IL-6 and CRP and outcomes were analysed by Cox regression adjusted for clinical risk factors and other cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C).Results: The IL-6 median level was 2.3 ng/L (IQR 1.5-3.9), median CRP level was 2.2 mg/L (1.0-4.8). IL-6 and CRP were significantly associated with all-cause mortality independent of clinical risk factors and other biomarkers (HR (95% CI) 1.93 (1.57 to 2.37) and 1.49 (1.24 to 1.79), respectively, Q4 vs Q1). IL-6 was associated with myocardial infarction, cardiovascular mortality, and major bleeding beyond clinical risk factors but not in the presence of cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C). Neither inflammatory biomarker was associated with stroke/systemic embolism. Risk prediction for stroke, death and major bleeding was not improved by IL-6 or CRP when added to clinical risk factors and the other cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C).Conclusions: In patients with AF on anticoagulation, after accounting for clinical risk factors and other biomarkers, biomarkers of inflammation were significantly associated with an increased risk of mortality. However, there were no associations with the risk of stroke or major bleeding.
32.	Hijazi, Ziad, et al. (författare) N-Terminal Pro-B-Type Natriuretic Peptide for Risk Assessment in Patients With Atrial Fibrillation : Insights from the ARISTOTLE trial 2013 Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 61:22, s. 2274-2284 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE:This study sought to assess the prognostic value of N-terminal pro–B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial, and the treatment effect of apixaban according to NT-proBNP levels.BACKGROUND:Natriuretic peptides are associated with mortality and cardiovascular events in several cardiac diseases.METHODS:In the ARISTOTLE trial, 18,201 patients with AF were randomized to apixaban or warfarin. Plasma samples at randomization were available from 14,892 patients. The association between NT-proBNP concentrations and clinical outcomes was evaluated using Cox proportional hazard models, after adjusting for established cardiovascular risk factors.RESULTS:Quartiles of NT-proBNP were Q1:≤363, Q2:364-713, Q3:714-1250 and Q4:>1250 ng/L. During 1.8 years the annual rates of stroke or systemic embolism ranged from 0.74% in the bottom NT-proBNP quartile to 2.21% in the top quartile, adjusted hazard ratio (HR) 2.35 (95% CI 1.62-3.40, p<0.0001. Annual rates of cardiac death ranged from 0.86% in Q1 to 4.14% in Q4, adjusted HR 2.50 (1.81-3.45), p<0.0001. Adding NT-proBNP levels to the CHA2DS2VASc score improved C-statistics from 0.62 to 0.65 (p=0.0009) for stroke or systemic embolism and from 0.59 to 0.69 for cardiac death (p<0.0001). Apixaban reduced stroke, mortality, and bleeding regardless of the NT-proBNP level.CONCLUSIONS:NT-proBNP levels are often elevated in AF and independently associated with an increased risk of stroke and mortality. NT-proBNP improves risk stratification beyond the CHA2DS2VASc score and might be a novel tool for improved stroke prediction in AF. The efficacy of apixaban compared with warfarin is independent of the NT-proBNP level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE].
33.	Hillier, Ladeana W, et al. (författare) Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution 2004 Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716 Tidskriftsartikel (refereegranskat)abstract We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
34.	Horowitz, John D., et al. (författare) Asymmetric and Symmetric Dimethylarginine Predict Outcomes in Patients With Atrial Fibrillation : An ARISTOTLE Substudy 2018 Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 72:7, s. 721-733 Tidskriftsartikel (refereegranskat)abstract BACKGROUND There is little mechanistic information on factors predisposing atrial fibrillation (AF) patients to thromboembolism or bleeding, but generation of nitric oxide (NO) might theoretically contribute to both. OBJECTIVES The authors tested the hypothesis that plasma levels of the methylated arginine derivatives asymmetric and symmetric dimethylarginine (ADMA/SDMA), which inhibit NO generation, might be associated with outcomes in AF. METHODS Plasma samples were obtained from 5,004 patients with AF at randomization to warfarin or apixaban in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. ADMA and SDMA concentrations were measured by high-performance liquid chromatography. Relationships to clinical characteristics were evaluated by multivariable analyses. Associations with major outcomes, during a median of 1.9 years follow-up, were evaluated by adjusted Cox proportional hazards models. RESULTS Both ADMA and SDMA plasma concentrations at study entry increased significantly with patients' age, female sex, renal impairment, permanent AF, or congestive heart failure. ADMA and SDMA increased (p < 0.001) with both increased CHA2DS2-VASc and HAS-BLED scores, but decreased in the presence of diabetes. On multivariable analysis adjusting for established risk factors and treatment, tertile groups of ADMA concentrations were significantly associated with stroke/systemic embolism (p = 0.034), and death (p < 0.0001), whereas tertile groups of SDMA were associated with major bleeding and death (p < 0.001 for both). Incorporating ADMA and SDMA into CHA2DS2-VASc or HAS-BLED predictive models improved C-indices for those outcomes. Neither ADMA nor SDMA predicted differential responses to warfarin or apixaban. CONCLUSIONS In anticoagulated patients with AF, elevated ADMA levels are weakly associated with thromboembolic events, elevated SDMA levels with bleeding events and both are strongly associated with increased mortality. These findings suggest that disturbances of NO function modulate both thrombotic and hemorrhagic risk in anticoagulated patients with AF. (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]; NCT00412984)
35.	Krebs, Frederik C, et al. (författare) A round robin study of flexible large-area roll-to-roll processed polymer solar cell modules 2009 Ingår i: SOLAR ENERGY MATERIALS AND SOLAR CELLS. - : Elsevier BV. - 0927-0248. ; 93:11, s. 1968-1977 Tidskriftsartikel (refereegranskat)abstract A round robin for the performance of roll-to-roll coated flexible large-area polymer solar-cell modules involving 18 different laboratories in Northern America, Europe and Middle East is presented. The study involved the performance measurement of the devices at one location (Riso DTU) followed by transportation to a participating laboratory for performance measurement and return to the starting location (Riso DTU) for re-measurement of the performance. It was found possible to package polymer solar-cell modules using a flexible plastic barrier material in such a manner that degradation of the devices played a relatively small role in the experiment that has taken place over 4 months. The method of transportation followed both air-mail and surface-mail paths.
36.	Latz, Meike, et al. (författare) Short- and long-read metabarcoding of the eukaryotic rRNA operon : Evaluation of primers and comparison to shotgun metagenomics sequencing 2022 Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 22:6, s. 2304-2318 Tidskriftsartikel (refereegranskat)abstract High-throughput sequencing-based analysis of microbial diversity has evolved vastly over the last decade. Currently, the go-to method for studying microbial eukaryotes is short-read metabarcoding of variable regions of the 18S rRNA gene with <500 bp amplicons. However, there is a growing interest in applying long-read sequencing of amplicons covering the rRNA operon for improving taxonomic resolution. For both methods, the choice of primers is crucial. It determines if community members are covered, if they can be identified at a satisfactory taxonomic level, and if the obtained community profile is representative. Here, we designed new primers targeting 18S and 28S rRNA based on 177,934 and 21,072 database sequences, respectively. The primers were evaluated in silico along with published primers on reference sequence databases and marine metagenomics data sets. We further evaluated a subset of the primers for short- and long-read sequencing on environmental samples in vitro and compared the obtained community profile with primer-unbiased metagenomic sequencing. Of the short-read pairs, a new V6-V8 pair and the V4_Balzano pair used with a simplified PCR protocol provided good results in silico and in vitro. Fewer differences were observed between the long-read primer pairs. The long-read amplicons and ITS1 alone provided higher taxonomic resolution than V4. Together, our results represent a reference and guide for selection of robust primers for research on and environmental monitoring of microbial eukaryotes.
37.	Lue, Tom F., et al. (författare) Summary of the recommendations on sexual dysfunctions in men 2004 Ingår i: Journal of Sexual Medicine. - : Oxford University Press (OUP). - 1743-6109 .- 1743-6095. ; 1:1, s. 6-23 Tidskriftsartikel (refereegranskat)abstract Introduction. There are few published guidelines for the management of sexual dysfunctions in men and women, despite the prevalence and lack of attention to these problems. Disorders of sexual function in men include erectile dysfunction, orgasm/ejaculation disorders, priapism, and Peyronie's disease. Aim. To provide evidence-based and expert-opinion consensus guidelines for the clinical management of men's sexual dysfunctions. Methods. An International Consultation in collaboration with major urological and sexual medicine societies assembled over 200 multidisciplinary experts from 60 countries into 17 consultation committees. Committee members established the scope and objectives for each chapter. Following intensive review of available data and publications, committees developed evidence-based guidelines in each area. Main Outcome Measure. New algorithms and guidelines for assessment and treatment of men's sexual dysfunction were developed. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of the medical literature, in addition to cultural and ethical considerations. Results. Recommendations and guidelines for men's sexual dysfunction are presented. These guidelines were developed as evidence-based, patient-centered, and multidisciplinary in focus. For the clinical assessment and diagnosis of ED, a basic evaluation was recommended for all patients, with optional and specialized testing reserved for special cases. A new treatment algorithm is proposed. This algorithm provides a clinically relevant guideline for managing ED in the large majority of men. New treatment guidelines and algorithms are provided for men's orgasm and ejaculation disorders, including premature ejaculation, retrograde and delayed ejaculation. Finally, expert opinion-based guidelines for the clinical management of priapism and Peyronie's disease are provided. Conclusions. Additional research is needed to validate and extend these guidelines. Nonetheless, this summary encompasses the recommendations concerning men's sexual dysfunctions presented at the 2nd International Consultation on Sexual Medicine in Paris, France, June 28-July 1, 2003.
38.	Orlando, Ludovic, et al. (författare) Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse 2013 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 499:7456, s. 74- Tidskriftsartikel (refereegranskat)abstract The rich fossil record of equids has made them a model for evolutionary processes(1). Here we present a 1.12-times coverage draft genome from a horse bone recovered from permafrost dated to approximately 560-780 thousand years before present (kyr BP)(2,3). Our data represent the oldest full genome sequence determined so far by almost an order of magnitude. For comparison, we sequenced the genome of a Late Pleistocene horse (43 kyr BP), and modern genomes of five domestic horse breeds (Equus ferus caballus), a Przewalski's horse (E. f. prze-walskii) and a donkey (E. asinus). Our analyses suggest that the Equus lineage giving rise to all contemporary horses, zebras and donkeys originated 4.0-4.5 million years before present (Myr BP), twice the conventionally accepted time to the most recent common ancestor of the genus Equus(4,5). We also find that horse population size fluctuated multiple times over the past 2 Myr, particularly during periods of severe climatic changes. We estimate that the Przewalski's and domestic horse populations diverged 38-72 kyr BP, and find no evidence of recent admixture between the domestic horse breeds and the Przewalski's horse investigated. This supports the contention that Przewalski's horses represent the last surviving wild horse population(6). We find similar levels of genetic variation among Przewalski's and domestic populations, indicating that the former are genetically viable and worthy of conservation efforts. We also find evidence for continuous selection on the immune system and olfaction throughout horse evolution. Finally, we identify 29 genomic regions among horse breeds that deviate from neutrality and show low levels of genetic variation compared to the Przewalski's horse. Such regions could correspond to loci selected early during domestication.
39.	Sampson, Joshua N., et al. (författare) Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types 2015 Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12 Tidskriftsartikel (refereegranskat)abstract Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
40.	Satizabal, Claudia L., et al. (författare) Genetic architecture of subcortical brain structures in 38,851 individuals 2019 Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624- Tidskriftsartikel (refereegranskat)abstract Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
41.	Seibert, M. Marvin, et al. (författare) Single mimivirus particles intercepted and imaged with an X-ray laser 2011 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 470:7332, s. 78-81 Tidskriftsartikel (refereegranskat)abstract X-ray lasers offer new capabilities in understanding the structure of biological systems, complex materials and matter under extreme conditions(1-4). Very short and extremely bright, coherent X-ray pulses can be used to outrun key damage processes and obtain a single diffraction pattern from a large macromolecule, a virus or a cell before the sample explodes and turns into plasma(1). The continuous diffraction pattern of non-crystalline objects permits oversampling and direct phase retrieval(2). Here we show that high-quality diffraction data can be obtained with a single X-ray pulse from a noncrystalline biological sample, a single mimivirus particle, which was injected into the pulsed beam of a hard-X-ray free-electron laser, the Linac Coherent Light Source(5). Calculations indicate that the energy deposited into the virus by the pulse heated the particle to over 100,000 K after the pulse had left the sample. The reconstructed exit wavefront (image) yielded 32-nm full-period resolution in a single exposure and showed no measurable damage. The reconstruction indicates inhomogeneous arrangement of dense material inside the virion. We expect that significantly higher resolutions will be achieved in such experiments with shorter and brighter photon pulses focused to a smaller area. The resolution in such experiments can be further extended for samples available in multiple identical copies.
42.	Seidler, Anna Lene, et al. (författare) Systematic review and network meta-analysis with individual participant data on cord management at preterm birth (iCOMP) : Study protocol 2020 Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:3 Forskningsöversikt (refereegranskat)abstract Introduction: Timing of cord clamping and other cord management strategies may improve outcomes at preterm birth. However, it is unclear whether benefits apply to all preterm subgroups. Previous and current trials compare various policies, including time-based or physiology-based deferred cord clamping, and cord milking. Individual participant data (IPD) enable exploration of different strategies within subgroups. Network meta-analysis (NMA) enables comparison and ranking of all available interventions using a combination of direct and indirect comparisons. Objectives: (1) To evaluate the effectiveness of cord management strategies for preterm infants on neonatal mortality and morbidity overall and for different participant characteristics using IPD meta-analysis. (2) To evaluate and rank the effect of different cord management strategies for preterm births on mortality and other key outcomes using NMA. Methods and analysis: Systematic searches of Medline, Embase, clinical trial registries, and other sources for all ongoing and completed randomised controlled trials comparing cord management strategies at preterm birth (before 37 weeks' gestation) have been completed up to 13 February 2019, but will be updated regularly to include additional trials. IPD will be sought for all trials; aggregate summary data will be included where IPD are unavailable. First, deferred clamping and cord milking will be compared with immediate clamping in pairwise IPD meta-analyses. The primary outcome will be death prior to hospital discharge. Effect differences will be explored for prespecified participant subgroups. Second, all identified cord management strategies will be compared and ranked in an IPD NMA for the primary outcome and the key secondary outcomes. Treatment effect differences by participant characteristics will be identified. Inconsistency and heterogeneity will be explored. Ethics and dissemination: Ethics approval for this project has been granted by the University of Sydney Human Research Ethics Committee (2018/886). Results will be relevant to clinicians, guideline developers and policy-makers, and will be disseminated via publications, presentations and media releases.
43.	Sonderby, Ida E., et al. (författare) Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia 2020 Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602 Tidskriftsartikel (refereegranskat)abstract Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
44.	Stitziel, Nathan O., et al. (författare) Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease 2016 Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 374:12, s. 1134-1144 Tidskriftsartikel (refereegranskat)abstract BACKGROUND The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes. RESULTS We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P = 4.2x10(-10)) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P = 4.0x10(-8)), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P = 0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P = 0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P = 2.0x10(-4)) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P = 2.5x10(-7)). CONCLUSIONS We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease.
45.	Threadgold, Emma, et al. (författare) Biased Estimates of Environmental Impact in the Negative Footprint Illusion: The Nature of Individual Variation 2022 Ingår i: Frontiers in Psychology. - : Frontiers Media S.A.. - 1664-1078. ; 12 Tidskriftsartikel (refereegranskat)abstract People consistently act in ways that harm the environment, even when believing their actions are environmentally friendly. A case in point is a biased judgment termed the negative footprint illusion, which arises when people believe that the addition of “eco-friendly” items (e.g., environmentally certified houses) to conventional items (e.g., standard houses), reduces the total carbon footprint of the whole item-set, whereas the carbon footprint is, in fact, increased because eco-friendly items still contribute to the overall carbon footprint. Previous research suggests this illusion is the manifestation of an “averaging-bias.” We present two studies that explore whether people’s susceptibility to the negative footprint illusion is associated with individual differences in: (i) environment-specific reasoning dispositions measured in terms of compensatory green beliefs and environmental concerns; or (ii) general analytic reasoning dispositions measured in terms of actively open-minded thinking, avoidance of impulsivity and reflective reasoning (indexed using the Cognitive Reflection Test; CRT). A negative footprint illusion was demonstrated when participants rated the carbon footprint of conventional buildings combined with eco-friendly buildings (Study 1 and 2) and conventional cars combined with eco-friendly cars (Study 2). However, the illusion was not identified in participants’ ratings of the carbon footprint of apples (Study 1 and 2). In Studies 1 and 2, environment-specific dispositions were found to be unrelated to the negative footprint illusion. Regarding reflective thinking dispositions, reduced susceptibility to the negative footprint illusion was only associated with actively open-minded thinking measured on a 7-item scale (Study 1) and 17-item scale (Study 2). Our findings provide partial support for the existence of a negative footprint illusion and reveal a role of individual variation in reflective reasoning dispositions in accounting for a limited element of differential susceptibility to this illusion.
46.	van der Meer, Dennis, et al. (författare) Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition 2020 Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430 Tidskriftsartikel (refereegranskat)abstract Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
47.	Wallentin, Lars, et al. (författare) Growth Differentiation Factor 15, a Marker of Oxidative Stress and Inflammation, for Risk Assessment in Patients With Atrial Fibrillation : Insights From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial 2014 Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 130:21, s. 1847-1858 Tidskriftsartikel (refereegranskat)abstract Background-Growth differentiation factor 15 (GDF-15), high-sensitivity troponin, and N-terminal pro-brain natriuretic peptide levels are predictive of death and cardiovascular events in healthy elderly subjects, patients with acute coronary syndrome, and patients with heart failure. High-sensitivity troponin I and N-terminal pro-brain natriuretic peptide are also prognostic in patients with atrial fibrillation. We evaluated the prognostic value of GDF-15 alone and in addition to clinical characteristics and other biomarkers in patients with atrial fibrillation. Methods and Results-The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14 798 patients. Efficacy and safety outcomes during 1.9 years of follow-up were compared across quartiles of GDF-15 by use of Cox analyses adjusted for clinical characteristics, randomized treatment, and other biomarkers. The GDF-15 level showed a median of 1383 ng/L (interquartile range, 977-2052 ng/L). Annual rates of stroke or systemic embolism ranged from 0.9% to 2.03% (P<0.001); of major bleeding, from 1.22% to 4.53% (P<0.001); and of mortality, from 1.34% to 7.19% (P<0.001) in the lowest compared with the highest GDF-15 quartile. The prognostic information provided by GDF-15 was independent of clinical characteristics and clinical risk scores. Adjustment for the other cardiac biomarkers attenuated the prognostic value for stroke, whereas the prognostic value for mortality and major bleeding remained. Apixaban consistently reduced stroke, mortality, and bleeding, regardless of GDF-15 levels. Conclusions-GDF-15 is a risk factor for major bleeding, mortality, and stroke in atrial fibrillation. The prognostic value for major bleeding and death remained even in the presence of N-terminal pro-brain natriuretic peptide and high-sensitivity troponin I.
48.	Wong, Gane Ka-Shu, et al. (författare) A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms. 2004 Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 432:7018, s. 717-22 Tidskriftsartikel (refereegranskat)
49.	2018 Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:1 Forskningsöversikt (refereegranskat)
50.	Abuzeid, Nadir, et al. (författare) Antimycobacterial activity of selected medicinal plants traditionally used in Sudan to treat infectious diseases 2014 Ingår i: Journal of Ethnopharmacology. - : Elsevier. - 0378-8741 .- 1872-7573. ; 157, s. 134-139 Tidskriftsartikel (refereegranskat)abstract Ethnopharmacological relevance: The emergence of multidrug-resistant strains of Mycobacterium tuberculosis underscores the need for continuous development of new and efficient methods to determine the susceptibility of isolates of Mycobacterium tuberculosis in the search for novel antimycobacterial agents. Natural products constitute an important source of new drugs, and design and implementation of antimycobacterial susceptibility testing methods are necessary to evaluate the different extracts and compounds. In this study we have explored the antimycobacterial properties of 50 ethanolic extracts from different parts of 46 selected medicinal plants traditionally used in Sudan to treat infectious diseases. Materials and methods: Plants were harvested and ethanolic extracts were prepared. For selected extracts, fractionation with hydrophilic and hydrophobic solvents was undertaken. A luminometry-based assay was used for determination of mycobacterial growth in broth cultures and inside primary human macrophages in the presence or absence of plant extracts and fractions of extracts. Cytotoxicity was also assessed for active fractions of plant extracts. Results: Of the tested extracts, three exhibited a significant inhibitory effect on an avirulent strain of Mycobacterium tubercluosis (H37Ra) at the initial screening doses (125 and 6.25 mu g/ml). These were bark and leaf extracts of Khaya senegalensis and the leaf extract of Rosmarinus officinalis L. Further fractions of these plant extracts were prepared with n-hexane, chloroform, ethyl acetate, n-butanol, ethanol and water, and the activity of these extracts was retained in hydrophobic fractions. Cytotoxicity assays revealed that the chloroform fraction of Khaya senegalensis bark was non-toxic to human monocyte-derived macrophages and other cell types at the concentrations used and hence, further analysis, including assessment of IC50 and intracellular activity was done with this fraction. Conclusion: These results encourage further investigations to identify the active compound(s) within the chloroform fraction of Khaya senegalensis bark. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

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