| 1. |
- Allentoft, Morten E., et al.
(författare)
-
100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
-
Tidskriftsartikel (refereegranskat)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
|
|
| 2. |
- Allentoft, Morten E., et al.
(författare)
-
Population genomics of post-glacial western Eurasia
- 2024
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
-
Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
|
|
| 3. |
- Holm, Niels R, et al.
(författare)
-
OCT or Angiography Guidance for PCI in Complex Bifurcation Lesions.
- 2023
-
Ingår i: The New England journal of medicine. - 1533-4406. ; 389:16, s. 1477-1487
-
Tidskriftsartikel (refereegranskat)abstract
- Imaging-guided percutaneous coronary intervention (PCI) is associated with better clinical outcomes than angiography-guided PCI. Whether routine optical coherence tomography (OCT) guidance in PCI of lesions involving coronary-artery branch points (bifurcations) improves clinical outcomes as compared with angiographic guidance is uncertain.We conducted a multicenter, randomized, open-label trial at 38 centers in Europe. Patients with a clinical indication for PCI and a complex bifurcation lesion identified by means of coronary angiography were randomly assigned in a 1:1 ratio to OCT-guided PCI or angiography-guided PCI. The primary end point was a composite of major adverse cardiac events (MACE), defined as death from a cardiac cause, target-lesion myocardial infarction, or ischemia-driven target-lesion revascularization at a median follow-up of 2 years.We assigned 1201 patients to OCT-guided PCI (600 patients) or angiography-guided PCI (601 patients). A total of 111 patients (18.5%) in the OCT-guided PCI group and 116 (19.3%) in the angiography-guided PCI group had a bifurcation lesion involving the left main coronary artery. At 2 years, a primary end-point event had occurred in 59 patients (10.1%) in the OCT-guided PCI group and in 83 patients (14.1%) in the angiography-guided PCI group (hazard ratio, 0.70; 95% confidence interval, 0.50 to 0.98; P=0.035). Procedure-related complications occurred in 41 patients (6.8%) in the OCT-guided PCI group and 34 patients (5.7%) in the angiography-guided PCI group.Among patients with complex coronary-artery bifurcation lesions, OCT-guided PCI was associated with a lower incidence of MACE at 2 years than angiography-guided PCI. (Funded by Abbott Vascular and others; OCTOBER ClinicalTrials.gov number, NCT03171311.).
|
|
| 4. |
- Mahajan, Anubha, et al.
(författare)
-
Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
-
Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
|
|
| 5. |
- Pečnerová, Patrícia, et al.
(författare)
-
Population genomics of the muskox' resilience in the near absence of genetic variation
- 2024
-
Ingår i: Molecular Ecology. - 0962-1083 .- 1365-294X. ; 33:2
-
Tidskriftsartikel (refereegranskat)abstract
- Genomic studies of species threatened by extinction are providing crucial information about evolutionary mechanisms and genetic consequences of population declines and bottlenecks. However, to understand how species avoid the extinction vortex, insights can be drawn by studying species that thrive despite past declines. Here, we studied the population genomics of the muskox (Ovibos moschatus), an Ice Age relict that was at the brink of extinction for thousands of years at the end of the Pleistocene yet appears to be thriving today. We analysed 108 whole genomes, including present-day individuals representing the current native range of both muskox subspecies, the white-faced and the barren-ground muskox (O. moschatus wardi and O. moschatus moschatus) and a ~21,000-year-old ancient individual from Siberia. We found that the muskox' demographic history was profoundly shaped by past climate changes and post-glacial re-colonizations. In particular, the white-faced muskox has the lowest genome-wide heterozygosity recorded in an ungulate. Yet, there is no evidence of inbreeding depression in native muskox populations. We hypothesize that this can be explained by the effect of long-term gradual population declines that allowed for purging of strongly deleterious mutations. This study provides insights into how species with a history of population bottlenecks, small population sizes and low genetic diversity survive against all odds.
|
|
| 6. |
- Persson, Christian, 1960-, et al.
(författare)
-
New Business Forms in e-Business and Media – e-Media
- 2009
-
Ingår i: Iarigai 2009.
-
Konferensbidrag (refereegranskat)abstract
- It has been the scope of this study to create new service forms and business models for the border area between e-Business and Media (e-Media). The project was carried out by a Nordic consortium consisting of five research organisations and eight companies with financial support from the Nordic Innovation Centre (NICe). The study first analyses the structural changes in the media and allied industries, i.e. content creation and advertising. Thereafter, a framework for innovations in e-Media is built up, together with a variety of business models. The framework is used to identify new, innovative service embryos for the e-Media sector. Finally eight new services are developed in industrial case studies. The project has been carried out by a consortium consisting of five Nordic research organisations, which have relations to e-Business and the media sector, together with eight industrial partners from the media sector, software companies, and service providers. The outcome of the project is an extensive description of innovation methods and business models for Nordic companies working in the media or e-Business sector or offering services over the net. The report also gives eight examples of more or less successfully exploited e-Media pilot cases.
|
|
| 7. |
- Raghavan, Maanasa, et al.
(författare)
-
The genetic prehistory of the New World Arctic
- 2014
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 345:6200, s. 1020-
-
Tidskriftsartikel (refereegranskat)abstract
- The New World Arctic, the last region of the Americas to be populated by humans, has a relatively well-researched archaeology, but an understanding of its genetic history is lacking. We present genome-wide sequence data from ancient and present-day humans from Greenland, Arctic Canada, Alaska, Aleutian Islands, and Siberia. We show that Paleo-Eskimos (similar to 3000 BCE to 1300 CE) represent a migration pulse into the Americas independent of both Native American and Inuit expansions. Furthermore, the genetic continuity characterizing the Paleo-Eskimo period was interrupted by the arrival of a new population, representing the ancestors of present-day Inuit, with evidence of past gene flow between these lineages. Despite periodic abandonment of major Arctic regions, a single Paleo-Eskimo metapopulation likely survived in near-isolation for more than 4000 years, only to vanish around 700 years ago.
|
|
| 8. |
|
|
| 9. |
- Rasmussen, Rune, et al.
(författare)
-
The effects of continuous prostacyclin infusion on regional blood flow and cerebral vasospasm following subarachnoid haemorrhage: study protocol for a randomised controlled trial
- 2012
-
Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Background: One of the main causes of mortality and morbidity following subarachnoid haemorrhage (SAH) is the development of cerebral vasospasm, a frequent complication arising in the weeks after the initial bleeding. Despite extensive research, to date no effective treatment of vasospasm exists. Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation. In vitro models have shown a relaxing effect of prostacyclin after induced contraction in cerebral arteries, and a recent pilot trial showed a positive effect on cerebral vasospasm in a clinical setting. No randomised, clinical trials have been conducted, investigating the possible pharmacodynamic effects of prostacyclin on the human brain following SAH. Methods: This trial is a single-centre, randomised, placebo-controlled, parallel group, blinded, clinical, pilot trial. A total of 90 patients with SAH will be randomised to one of three intervention arms: epoprostenol 1 ng/kg/min, epoprostenol 2 ng/kg/min or placebo in addition to standard treatment. Trial medication will start day 5 after SAH and continue to day 10. The primary outcome measure is changes in regional cerebral blood flow from baseline in the arterial territories of the anterior cerebral artery, medial cerebral artery and the posterior cerebral artery, measured by CT perfusion scan. The secondary outcomes will be vasospasm measured by CT angiography, ischaemic parameters measured by brain microdialysis, flow velocities in the medial cerebral artery, clinical parameters and outcome (Glasgow Outcome Scale) at 3 months.
|
|
| 10. |
- Svensson, Emma, et al.
(författare)
-
The Effect of Botulinum Toxin Type A Injections on Stricture Formation, Leakage Rates, Esophageal Elongation, and Anastomotic Healing Following Primary Anastomosis in a Long- and Short-Gap Esophageal Atresia Model : A Protocol for a Randomized, Controlled, Blinded Trial in Pigs
- 2021
-
Ingår i: International Journal of Surgery Protocols. - : IJS Press. - 2468-3574. ; 25:1, s. 171-177
-
Tidskriftsartikel (refereegranskat)abstract
- Background:Esophageal atresia (EA) is a congenital malformation affecting 1:3000-4500 newborns. Approximately 15% have a long-gap EA (LGEA), in which case a primary anastomosis is often impossible to achieve. To create continuity of the esophagus patients instead have to undergo lengthening procedures or organ interpositions; methods associated with high morbidity and poor functional outcomes. Esophageal injections of Botulinum Toxin Type A (BTX-A) could enable primary anastomosis and mitigate stricture formation through decreased tissue tension.Methods and Analysis:In this randomized controlled blinded animal trial, 24 pigs are divided into a long- or short-gap EA group (LGEA and SGEA, respectively) and randomized to receive BTX-A or isotonic saline injections. In the LGEA group, injections are given endoscopically in the esophageal musculature. After seven days, a 3 cm esophageal resection and primary anastomosis is performed. In the SGEA group, a 1 cm esophageal resection and primary anastomosis is performed, followed by intraoperative injections of BTX-A or isotonic saline. After 14 days, stricture formation, presence of leakage, and esophageal compliance is assessed using endoscopic and manometric techniques, and in vivo and ex vivo contrast radiography. Tissue elongation is evaluated in a stretch-tension test, and the esophagus is assessed histologically to evaluate anastomotic healing.Ethics and Dissemination:The study complies with the ARRIVE guidelines for animal studies and has been approved by the Danish Animal Experimentation Council. Results will be published in peer-reviewed journals and presented at national and international conferences.
|
|
| 11. |
- Appel, Peter W.Uitterdijk, et al.
(författare)
-
Unusual features caused by lightning impact in West Greenland
- 2006
-
Ingår i: Geological Magazine. - : Cambridge University Press. - 0016-7568 .- 1469-5081. ; 143:5, s. 737-741
-
Tidskriftsartikel (refereegranskat)abstract
- Two lightning impacts are described from an area near the Inland Ice in West Greenland. The first lightning blasted an outcrop of metacherts. It subsequently split into two branches, which traversed rock outcrops and boulders, leaving behind two white almost straight lines, 30 m and 14 m long, respectively, where all lichens and plants were burned away. On the white lines the upper few millimetres of the traversed boulders were melted to a glass which subsequently peeled off by thermal expansion to leave a rough surface. Magnetic investigation of an amphibolite boulder found on the white line showed that a strong electric current indeed traversed the boulder. A few years later a second lightning impacted on a mountaintop close to the first impact. The second lightning left a trail on the rock surface covered by a thin layer of glass. The glass displays spectacular colours ranging from metallic blue to red, yellow and green.
|
|
| 12. |
- Bache, Iben, et al.
(författare)
-
An excess of chromosome 1 breakpoints in male infertility.
- 2004
-
Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 12:12, s. 993-1000
-
Tidskriftsartikel (refereegranskat)abstract
- In a search for potential infertility loci, which might be revealed by clustering of chromosomal breakpoints, we compiled 464 infertile males with a balanced rearrangement from Mendelian Cytogenetics Network database (MCNdb) and compared their karyotypes with those of a Danish nation-wide cohort. We excluded Robertsonian translocations, rearrangements involving sex chromosomes and common variants. We identified 10 autosomal bands, five of which were on chromosome 1, with a large excess of breakpoints in the infertility group. Some of these could potentially harbour a male-specific infertility locus. However, a general excess of breakpoints almost everywhere on chromosome 1 was observed among the infertile males: 26.5 versus 14.5% in the cohort. This excess was observed both for translocation and inversion carriers, especially pericentric inversions, both for published and unpublished cases, and was significantly associated with azoospermia. The largest number of breakpoints was reported in 1q21; FISH mapping of four of these breakpoints revealed that they did not involve the same region at the molecular level. We suggest that chromosome 1 harbours a critical domain whose integrity is essential for male fertility.
|
|
| 13. |
- Basu, Neil, et al.
(författare)
-
EULAR points to consider in the development of classification and diagnostic criteria in systemic vasculitis
- 2010
-
Ingår i: Annals of the Rheumatic Diseases. - London, UK : BMJ. - 1468-2060 .- 0003-4967. ; 69:10, s. 1744-1750
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives The systemic vasculitides are multiorgan diseases where early diagnosis and treatment can significantly improve outcomes. Robust nomenclature reduces diagnostic delay. However, key aspects of current nomenclature are widely perceived to be out of date, these include disease definitions, classification and diagnostic criteria. Therefore, the aim of the present work was to identify deficiencies and provide contemporary points to consider for the development of future definitions and criteria in systemic vasculitis. Methods The expert panel identified areas of concern within existing definitions/criteria. Consequently, a systematic literature review was undertaken looking to address these deficiencies and produce 'points to consider' in accordance with standardised European League Against Rheumatism (EULAR) operating procedures. In the absence of evidence, expert consensus was used. Results There was unanimous consensus for re-evaluating existing definitions and developing new criteria. A total of 17 points to consider were proposed, covering 6 main areas: biopsy, laboratory testing, diagnostic radiology, nosology, definitions and research agenda. Suggestions to improve and expand current definitions were described including the incorporation of anti-neutrophil cytoplasm antibody and aetiological factors, where known. The importance of biopsy in diagnosis and exclusion of mimics was highlighted, while equally emphasising its problems. Thus, the role of alternative diagnostic tools such as MRI, ultrasound and surrogate markers were also discussed. Finally, structures to develop future criteria were considered. Conclusions Limitations in current classification criteria and definitions for vasculitis have been identified and suggestions provided for improvement. Additionally it is proposed that, in combination with the updated evidence, these should form the basis of future attempts to develop and validate revised criteria and definitions of vasculitis.
|
|
| 14. |
- Bengtsson, Jan, 1949, et al.
(författare)
-
Filosofilexikonet
- 1988
-
Bok (övrigt vetenskapligt/konstnärligt)
|
|
| 15. |
- Bengtsson, Jan, 1949, et al.
(författare)
-
Filosofilexikonet
- 1991
-
Bok (övrigt vetenskapligt/konstnärligt)
|
|
| 16. |
- Bengtsson, Jan, 1949, et al.
(författare)
-
Filosofilexikonet
- 1995
-
Bok (övrigt vetenskapligt/konstnärligt)
|
|
| 17. |
- Bengtsson, Jan, 1949, et al.
(författare)
-
Filosofilexikonet
- 1997
-
Bok (övrigt vetenskapligt/konstnärligt)
|
|
| 18. |
- Bentham, James, et al.
(författare)
-
A century of trends in adult human height
- 2016
-
Ingår i: eLIFE. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
|
|
| 19. |
- Bentham, James, et al.
(författare)
-
A century of trends in adult human height
- 2016
-
Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
|
|
| 20. |
- Bomholt, Tobias, et al.
(författare)
-
The Accuracy of Hemoglobin A1c and Fructosamine Evaluated by Long-Term Continuous Glucose Monitoring in Patients with Type 2 Diabetes Undergoing Hemodialysis
- 2022
-
Ingår i: Blood Purification. - : S. Karger. - 0253-5068 .- 1421-9735. ; 51:7, s. 608-616
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The accuracy of hemoglobin A1c (HbA1c) as a glycemic marker in patients with type 2 diabetes (T2D) receiving hemodialysis (HD) remains unknown. To assess accuracy, we compared HbA1c and fructosamine levels with interstitial glucose measured by continuous glucose monitoring (CGM) in patients with T2D receiving HD.METHODS: Thirty patients in the HD group and 36 patients in the control group (T2D and an estimated glomerular filtration rate >60 mL/min/1.73 m2) completed the study period of 17 weeks. CGM (Ipro2®, Medtronic) was performed 5 times for periods of up to 7 days (with 4-week intervals) during a 16-week period. HbA1c (mmol/mol), the estimated mean plasma glucose from HbA1c (eMPGA1c [mmol/L]) and fructosamine (μmol/L) was measured at week 17 and compared with mean sensor glucose levels from CGM.FINDINGS: In the HD group, mean sensor glucose was 1.4 mmol/L (95% confidence interval [CI]: 1.0-1.8) higher than the eMPGA1c, whereas the difference for controls was 0.1 mmol/L (95% CI: -0.1-[0.4]; p < 0.001). Adjusted for mean sensor glucose, HbA1c was lower in the HD group (-7.3 mmol/mol, 95% CI: -10.0-[-4.7]) than in the control group (p < 0.001), with no difference detected for fructosamine (p = 0.64).DISCUSSION: HbA1c evaluated by CGM underestimates plasma glucose levels in patients receiving HD. The underestimation represents a clinical challenge in optimizing glycemic control in the HD population. Fructosamine is unaffected by the factors affecting HbA1c and appears to be more accurate for glycemic monitoring. CGM or fructosamine could thus complement HbA1c in obtaining more accurate glycemic control in this patient group.
|
|
| 21. |
|
|
| 22. |
- Dahl, Michael, et al.
(författare)
-
Can a central blood volume deficit be detected by systolic pressure variation during spontaneous breathing?
- 2016
-
Ingår i: BMC Anesthesiology. - : Springer Science and Business Media LLC. - 1471-2253 .- 1471-2253. ; 16
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Whether during spontaneous breathing arterial pressure variations (APV) can detect a volume deficit is not established. We hypothesized that amplification of intra-thoracic pressure oscillations by breathing through resistors would enhance APV to allow identification of a reduced cardiac output (CO). This study tested that hypothesis in healthy volunteers exposed to central hypovolemia by head-up tilt. Methods: Thirteen healthy volunteers were exposed to central hypovolemia by 45 degrees head-up tilt while breathing through a facemask with 7.5 cmH(2)O inspiratory and/or expiratory resistors. A brachial arterial catheter was used to measure blood pressure and thus systolic pressure variation (SPV), pulse pressure variation and stroke volume variation. Pulse contour analysis determined stroke volume (SV) and CO and we evaluated whether APV could detect a 10 % decrease in CO. Results: During head-up tilt SV decreased form 91 (+/- 46) to 55 (+/- 24) mL (mean +/- SD) and CO from 5.8 (+/- 2.9) to 4.0 (+/- 1.8) L/min (p < 0.05), while heart rate increased (65 (+/- 11) to 75 (+/- 13) bpm; P < 0.05). Systolic pressure decreased from 127 (+/- 14) to 121 (+/- 13) mmHg during head-up tilt, while SPV tended to increase (from 21 (+/- 15)% to 30 (+/- 13) %). Yet during head-up tilt, a SPV >= 37 % predicted a decrease in CO >= 10 % with a sensitivity and specificity of 78 % and 100 %, respectively. Conclusion: In spontaneously breathing healthy volunteers combined inspiratory and expiratory resistors enhance SPV during head-up tilted induced central hypovolemia and allow identifying a 10 % reduction in CO. Applying inspiratory and expiratory resistors might detect a fluid deficit in spontaneously breathing patients.
|
|
| 23. |
- de Groot, Kirsten, et al.
(författare)
-
Pulse Versus Daily Oral Cyclophosphamide for Induction of Remission in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis A Randomized Trial
- 2009
-
Ingår i: Annals of Internal Medicine. - 0003-4819. ; 150:10, s. 3-670
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Current therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis are limited by toxicity. Objective: To compare pulse cyclophosphamide with daily oral cyclophosphamide for induction of remission. Design: Randomized, controlled trial. Random assignments were computer-generated; allocation was concealed by faxing centralized treatment assignment to providers at the time of enrollment. Patients, investigators, and assessors of outcomes were not blinded to assignment. Setting: 42 centers in 12 European countries. Patients: 149 patients who had newly diagnosed generalized ANCA-associated vasculitis with renal involvement but not immediately life-threatening disease. Intervention: Pulse cyclophosphamide, 15 mg/kg every 2 to 3 weeks (76 patients), or daily oral cyclophosphamide, 2 mg/kg per day (73 patients), plus prednisolone. Measurement: Time to remission (primary outcome); change in renal function, adverse events, and cumulative dose of cyclophosphamide (secondary outcomes). Results: Groups did not differ in time to remission (hazard ratio, 1.098 [95% CI, 0.78 to 1.55]; P = 0.59) or proportion of patients who achieved remission at 9 months (88.1% vs. 87.7%). Thirteen patients in the pulse group and 6 in the daily oral group achieved remission by 9 months and subsequently had relapse. Absolute cumulative cyclophosphamide dose in the daily oral group was greater than that in the pulse group (15.9 g [interquartile range, 11 to 22.5 g] vs. 8.2 g [interquartile range, 5.95 to 10.55 g]; P < 0.001). The pulse group had a lower rate of leukopenia (hazard ratio, 0.41 [CI, 0.23 to 0.71]). Limitations: The study was not powered to detect a difference in relapse rates between the 2 groups. Duration of follow-up was limited. Conclusion: The pulse cyclophosphamide regimen induced remission of ANCA-associated vasculitis as well as the daily oral regimen at a reduced cumulative cyclophosphamide dose and caused fewer cases of leukopenia. Primary Funding Source: The European Union.
|
|
| 24. |
- de Leeuw, Evelyne, et al.
(författare)
-
Healthy Cities Phase V evaluation: further synthesizing realism.
- 2015
-
Ingår i: Health Promotion International. - : Oxford University Press (OUP). - 1460-2245 .- 0957-4824. ; 30, s. 118-125
-
Tidskriftsartikel (refereegranskat)abstract
- In this article we reflect on the quality of a realist synthesis paradigm applied to the evaluation of Phase V of the WHO European Healthy Cities Network. The programmatic application of this approach has led to very high response rates and a wealth of important data. All articles in this Supplement report that cities in the network move from small-scale, time-limited projects predominantly focused on health lifestyles to the significant inclusion of policies and programmes on systems and values for good health governance. The evaluation team felt that, due to time and resource limitations, it was unable to fully exploit the potential of realist synthesis. In particular, the synthetic integration of different strategic foci of Phase V designation areas did not come to full fruition. We recommend better and more sustained integration of realist synthesis in the practice of Healthy Cities in future Phases.
|
|
| 25. |
|
|
| 26. |
- Dominguez, Mev, et al.
(författare)
-
Functional implications of the p.Cys680Arg mutation in the MLH1 mismatch repair protein.
- 2014
-
Ingår i: Molecular Genetics & Genomic Medicine. - : Wiley. - 2324-9269. ; 2:4, s. 352-355
-
Tidskriftsartikel (refereegranskat)abstract
- In clinical genetic diagnostics, it is difficult to predict whether genetic mutations that do not greatly alter the primary sequence of the encoded protein causing unknown functional effects on cognate proteins lead to development of disease. Here, we report the clinical identification of c.2038 T>C missense mutation in exon 18 of the human MLH1 gene and biochemically characterization of the p.Cys680Arg mutant MLH1 protein to implicate it in the pathogenicity of the Lynch syndrome (LS). We show that the mutation is deficient in DNA mismatch repair and, therefore, contributing to LS in the carriers.
|
|
| 27. |
- Eek, Frida, et al.
(författare)
-
Differences in socioeconomic and gender inequalities in tobacco smoking in Denmark and Sweden; a cross sectional comparison of the equity effect of different public health policies
- 2010
-
Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Denmark and Sweden are considered to be countries of rather similar socio-political type, but public health policies and smoking habits differ considerably between the two neighbours. A study comparing mechanisms behind socioeconomic inequalities in tobacco smoking, could yield information regarding the impact of health policy and -promotion in the two countries. Methods: Cross-sectional comparisons of socioeconomic and gender differences in smoking behaviour among 6 995 Danish and 13 604 Swedish persons aged 18-80 years. Results: The prevalence of smoking was higher in Denmark compared to Sweden. The total attributable fraction (TAF) of low education regarding daily smoking was 36% for Danish men and 35% for Danish women, and 32% and 46%, respectively, for Swedish men and women. TAF of low education regarding continued smoking were 16.2% and 15.8% for Danish men and women, and 11.0% and 18.8% for Swedish men and women, respectively The main finding of the study was that the socioeconomic patterning of smoking, based on level of education and expressed as the relative contribution to the total burden of smoking exposure, was rather different in Sweden and Denmark. Moreover, these differences were modified by gender and age. As a general pattern, socioeconomic differences in Sweden tended to contribute more to the total burden of this habit among women, especially in the younger age groups. In men, the patterns were much more similar between the two countries. Regarding continued smoking/unsuccessful quitting, the patterns were similar for women, but somewhat different for men. Here we found that socioeconomic differences contributed more to overall continued smoking in Danish men, especially in the middle-age and older age strata. Conclusion: The results imply that Swedish anti-smoking policy and/or implemented measures have been less effective in a health equity perspective among the younger generation of women, but more effective among men, compared to Danish policy implementation. The results also raises the more general issue regarding the possible need for a trade-off principle between overall population efficacy versus equity efficacy of anti-tobacco, as well as general public health policies and intervention strategies.
|
|
| 28. |
- Erdbrügger, Uta, et al.
(författare)
-
Higher levels of SDMA and not ADMA are associated with poorer survival of trial patients with systemic ANCA-associated vasculitis
- 2018
-
Ingår i: European journal of rheumatology. - : AVES. - 2147-9720 .- 2148-4279. ; 5:3, s. 153-159
-
Tidskriftsartikel (refereegranskat)abstract
- Endothelial dysfunction, increased cardiovascular events (CVE), and accelerated atherosclerosis have been described in patients with small vessel vasculitis and collagen vascular disease. Identifying predictors of cardiovascular risk will help to optimize short- and long-term care of patients with vasculitis. The present study investigates the predictive role of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) and its stereoisomer symmetric dimethylarginine (SDMA) for cardiovascular risk, all-cause mortality, and renal function in patients with anti-neutrophil-cytoplasmic antibodies-associated small vessel vasculitis (AASV) subjected to standardized treatment regimens in four European Vasculitis Study Group trials representing all stages of renal disease.
|
|
| 29. |
- Faurschou, Mikkel, et al.
(författare)
-
Brief Report: Long-term outcome of a randomized clinical trial comparing methotrexate to cyclophosphamide for remission induction in early systemic antineutrophil cytoplasmic antibody-associated vasculitis
- 2012
-
Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 64:10, s. 3472-3477
-
Tidskriftsartikel (refereegranskat)abstract
- Objective The NORAM (Nonrenal Wegener's Granulomatosis Treated Alternatively with Methotrexate [MTX]) trial demonstrated that MTX can replace cyclophosphamide (CYC) as remission-inducing treatment for patients with newly diagnosed early systemic antineutrophil cytoplasmic antibodyassociated vasculitis. Duration of relapse-free survival was longer among CYC-treated patients than among MTX-treated patients during short-term followup. The aim of the present study was to describe the long-term outcome in patients enrolled in the randomized clinical trial. Methods Outcome questionnaires were sent to investigators who had recruited patients for the NORAM trial. Patients treated with MTX for induction of remission (n = 49) were compared to CYC-treated patients (n = 46) with respect to immunosuppressive therapy during followup, relapse-free survival, mortality, and occurrence of other clinical events. Results The median duration of followup was 6 years (range 0.110.8 years). One patient developed end-stage renal disease, and 11 died. The number of patients affected by serious infection, malignancy, or severe organ failure did not differ between treatment groups, and no difference in survival rate was observed. The duration of corticosteroid therapy was longer in the MTX group during the 18 months of the trial (P = 0.005). During subsequent followup, patients who were in the MTX group in the NORAM trial received corticosteroids, CYC, and other immunosuppressive agents (azathioprine, MTX, and/or mycophenolate mofetil) for longer periods than those who were in the CYC group (P = 0.004, P = 0.037, and P = 0.031, respectively). The cumulative relapse-free survival tended to be lower in the MTX group (P = 0.056). Conclusion In the NORAM cohort, no difference in occurrence of major adverse events was observed between treatment groups during long-term followup. However, first-line treatment with MTX was associated with less effective disease control than CYC-based induction therapy.
|
|
| 30. |
|
|
| 31. |
- Flossmann, Oliver, et al.
(författare)
-
Development of comprehensive disease assessment in systemic vasculitis
- 2007
-
Ingår i: Annals of the Rheumatic Diseases. - : Oxford University Press (OUP). - 1468-2060. ; 66:3, s. 283-292
-
Tidskriftsartikel (refereegranskat)abstract
- The systemic vasculitides are multisystem disorders with considerable mortality and morbidity and frequent relapses. In the absence of reliable serological markers, accurate clinical tools are required to assess disease activity and damage for treatment decisions, and for the performance of clinical trials. This article reviews and summarises the development and use of disease assessment tools for determining activity and damage in systemic vasculitis and reports ongoing initiatives for further development of disease assessment tools. A literature search was conducted using PubMed and reference lists for vasculitis, assessment, clinical trials, outcome and prognosis. The findings indicate that comprehensive disease assessment in vasculitis requires documentation of disease activity, chronic irreversible damage and impairment of function.
|
|
| 32. |
- Flossmann, Oliver, et al.
(författare)
-
Long-term patient survival in ANCA-associated vasculitis
- 2011
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:3, s. 488-494
-
Tidskriftsartikel (refereegranskat)abstract
- Background Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain. Objective To describe the long-term patient survival and possible prognostic factors at presentation in an international, multicentre, prospectively recruited representative patient cohort who were treated according to strictly defined protocols at presentation and included the full spectrum of ANCA-associated vasculitis disease. Methods Outcome data were collected for 535 patients who had been recruited at the time of diagnosis to four randomised controlled trials between 1995 and 2002. Trial eligibility was defined by disease severity and extent, covered the spectrum of severity of ANCA-associated vasculitis and used consistent diagnostic criteria. Demographic, clinical and laboratory parameters at trial entry were tested as potential prognostic factors in multivariable models. Results The median duration of follow-up was 5.2 years and 133 (25%) deaths were recorded. Compared with an age-and sex-matched general population there was a mortality ratio of 2.6 (95% CI 2.2 to 3.1). Main causes of death within the first year were infection (48%) and active vasculitis (19%). After the first year the major causes of death were cardiovascular disease (26%), malignancy (22%) and infection (20%). Multivariable analysis showed an estimated glomerular filtration rate <15 ml/min, advancing age, higher Birmingham Vasculitis Activity Score, lower haemoglobin and higher white cell count were significant negative prognostic factors for patient survival. Conclusion Patients with ANCA-associated vasculitis treated with conventional regimens are at increased risk of death compared with an age-and sex-matched population.
|
|
| 33. |
|
|
| 34. |
- Göçeroǧlu, Arda, et al.
(författare)
-
ANCA-associated glomerulonephritis : Risk factors for renal relapse
- 2016
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:12
-
Tidskriftsartikel (refereegranskat)abstract
- Relapse in ANCA-associated vasculitis (AAV) has been studied previously, but there are few studies on renal relapse in particular. Identifying patients at high risk of renal relapse may aid in optimizing clinical management. We investigated which clinical and histological parameters are risk factors for renal relapse in ANCA-associated glomerulonephritis (AAGN). Patients (n = 174) were newly diagnosed and had mild±moderate or severe renal involvement. Data were derived from two trials of the European Vasculitis Society: MEPEX and CYCAZAREM. The Cox regression model was used to identify parameters increasing the instantaneous risk (= rate) of renal relapse (useful for instant clinical decisions). For identifying predictors of renal relapse during follow-up, we used Fine & Gray's regression model. Competing events were end-stage renal failure and death. The cumulative incidence of renal relapse at 5 years was 9.5% (95% CI: 4.8±14.3%). In the Cox model, sclerotic class AAGN increased the instantaneous risk of renal relapse. In Fine & Gray's model, the absence of interstitial infiltrates at diagnosis was predictive for renal relapse. In this study we used two different models to identify possible relationships between clinical and histopathological parameters at time of diagnosis of AAV with the risk of experiencing renal relapse. Sclerotic class AAGN increased the instantaneous risk of renal relapse. This association is most likely due to the high proportion of sclerosed glomeruli reducing the compensatory capacity. The absence of interstitial infiltrates increased the risk of renal relapse which is a warning sign that patients with a relatively benign onset of disease may also be prone to renal relapse. Renal relapses occurring in patients with sclerotic class AAGN and renal relapses occurring in patients without interstitial infiltrates were mutually exclusive, which may indicate that they are essentially different.
|
|
| 35. |
- Halvorsen, Thomas, et al.
(författare)
-
Inducible laryngeal obstruction : an official joint European Respiratory Society and European Laryngological Society statement
- 2017
-
Ingår i: European Respiratory Journal. - : EUROPEAN RESPIRATORY SOC JOURNALS LTD. - 0903-1936 .- 1399-3003. ; 50:3
-
Tidskriftsartikel (refereegranskat)abstract
- Inducible laryngeal obstruction (ILO) describes an inappropriate, transient, reversible narrowing of the larynx in response to external triggers. ILO is an important cause of a variety of respiratory symptoms and can mimic asthma. Current understanding of ILO has been hampered by imprecise nomenclature and variable approaches to assessment and management. A task force of the European Respiratory Society (ERS) and European Laryngological Society (ELS) was thus set up to address this, and to identify research priorities. A literature search identified relevant articles published until June 2016, using all identifiable terms for ILO, although including only articles using laryngoscopy. In total, 172 out of 252 articles met the inclusion criteria, summarised in sections on diagnostic approach, aetiology, comorbidities, epidemiology and treatment. The consensus taxonomy published by ERS, ELS and the American College of Chest Physicians (ACCP) in 2015 is used throughout this statement. We highlight the high prevalence of ILO and the clinical impact for those affected. Despite recent advances, most aspects of this condition unfortunately remain incompletely understood, precluding firm guidance. Specifically, validated diagnostic and treatment algorithms are yet to be established, and no randomised control studies were identified in this search; hence we also make recommendations for future research.
|
|
| 36. |
- Harper, Lorraine, et al.
(författare)
-
Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up
- 2012
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 71:6, s. 955-960
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction The previously reported randomised controlled trial of a consensus regimen of pulse cyclophosphamide suggested that it was as effective as a daily oral (DO) cyclophosphamide for remission induction of antineutrophil cytoplasm autoantibodies-associated systemic vasculitis when both were combined with the same glucocorticoid protocol (CYCLOPS study (Randomised trial of daily oral versus pulse Cyclophosphamide as therapy for ANCA-associated Systemic Vasculitis published de groot K, harper L et al Ann Int Med 2009)). The study had limited power to detect a difference in relapse. This study describes the long-term outcomes of patients in the CYCLOPS study. Methods Long-term outcomes were ascertained retrospectively from 148 patients previously recruited to the CYCLOPS Trial. Data on survival, relapse, immunosuppressive treatment, cancer incidence, bone fractures, thromboembolic disease and cardiovascular morbidity were collected from physician records retrospectively. All patients were analysed according to the group to which they were randomised. Results Median duration of follow-up was 4.3 years (IQR, 2.95-5.44 years). There was no difference in survival between the two limbs (p=0.92). Fifteen (20.8%) DO and 30 (39.5%) pulse patients had at least one relapse. The risk of relapse was significantly lower in the DO limb than the pulse limb (HR=0.50, 95% CI 0.26 to 0.93; p=0.029). Despite the increased risk of relapse in pulse-treated patients, there was no difference in renal function at study end (p=0.82). There were no differences in adverse events between the treatment limbs. Discussion Pulse cyclophosphamide is associated with a higher relapse risk than DO cyclophosphamide. However, this is not associated with increased mortality or long-term morbidity. Although the study was retrospective, data was returned in 90% of patients from the original trial.
|
|
| 37. |
|
|
| 38. |
- Hudson, Lawrence N, et al.
(författare)
-
The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
-
Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
-
Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
|
|
| 39. |
- Idris, Berlian I., et al.
(författare)
-
Higher smoking prevalence in urban compared to non-urban areas: Time trends in six, European countries
- 2007
-
Ingår i: Health and Place. - : Elsevier BV. - 1873-2054 .- 1353-8292. ; 13:3, s. 702-712
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated differences in smoking prevalence between urban and non-urban area of residence in six Western European countries (Sweden, Finland, Denmark, Germany, Italy and Spain), and smoking prevalence trends over the period 1985-2000. In most countries, smoking prevalence was highest in urban areas, and increased with urbanization. Urban/non-urban inequalities were most pronounced among individuals with low education levels, and also among females. There were no significant differences in annual rate of change in smoking prevalence between non-urban and urban areas. (c) 2006 Elsevier Ltd. All rights reserved.
|
|
| 40. |
- Jayne, David, et al.
(författare)
-
A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies
- 2003
-
Ingår i: New England Journal of Medicine. - 0028-4793. ; 349:1, s. 36-44
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The primary systemic vasculitides usually associated with autoantibodies to neutrophil cytoplasmic antigens include Wegener's granulomatosis and microscopic polyangiitis. We investigated whether exposure to cyclophosphamide in patients with generalized vasculitis could be reduced by substitution of azathioprine at remission. METHODS: We studied patients with a new diagnosis of generalized vasculitis and a serum creatinine concentration of 5.7 mg per deciliter (500 micromol per liter) or less. All patients received at least three months of therapy with oral cyclophosphamide and prednisolone. After remission, patients were randomly assigned to continued cyclophosphamide therapy (1.5 mg per kilogram of body weight per day) or a substitute regimen of azathioprine (2 mg per kilogram per day). Both groups continued to receive prednisolone and were followed for 18 months from study entry. Relapse was the primary end point. RESULTS: Of 155 patients studied, 144 (93 percent) entered remission and were randomly assigned to azathioprine (71 patients) or continued cyclophosphamide (73 patients). There were eight deaths (5 percent), seven of them during the first three months. Eleven relapses occurred in the azathioprine group (15.5 percent), and 10 occurred in the cyclophosphamide group (13.7 percent, P=0.65). Severe adverse events occurred in 15 patients during the induction phase (10 percent), in 8 patients in the azathioprine group during the remission phase (11 percent), and in 7 patients in the cyclophosphamide group during the remission phase (10 percent, P=0.94 for the comparison between groups during the remission phase). The relapse rate was lower among the patients with microscopic polyangiitis than among those with Wegener's granulomatosis (P=0.03). CONCLUSIONS: In patients with generalized vasculitis, the withdrawal of cyclophosphamide and the substitution of azathioprine after remission did not increase the rate of relapse. Thus, the duration of exposure to cyclophosphamide may be safely reduced.
|
|
| 41. |
- Jayne, David R. W., et al.
(författare)
-
Randomized trial of plasma exchange or high-dosage Methylprednisolone as adjunctive therapy for severe renal vasculitis
- 2007
-
Ingår i: Journal of the American Society of Nephrology. - 1046-6673. ; 18:7, s. 2180-2188
-
Tidskriftsartikel (refereegranskat)abstract
- Systemic vasculitis associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA) is the most frequent cause of rapidly progressive glomerulonephritis. Renal failure at presentation carries an increased risk for ESRD and death despite immunosuppressive therapy. This study investigated whether the addition of plasma exchange was more effective than intravenous methylprednisolone in the achievement of renal recovery in those who presented with a serum creatinine > 500 mu mol/L (5.8 mg/dl). A total of 137 patients with a new diagnosis of ANCA-associated systemic vasculitis confirmed by renal biopsy and serum creatinine > 500 mu mol/L (5.8 mg/dl) were randomly assigned to receive seven plasma exchanges (n = 70) or 3000 mg of intravenous methylprednisolone (n = 67). Both groups received oral cyclophosphamide and oral prednisolone. The primary end point was dialysis independence at 3 mo. Secondary end points included renal and patient survival at 1 yr and severe adverse event rates. At 3 mo, 33 (49%) of 67 after intravenous methylprednisolone compared with 48 (69%) or 70 after plasma exchange were alive and independent of dialysis (95% confidence interval for the difference 18 to 35%; P = 0.02). As compared with intravenous methylprednisolone, plasma exchange was associated with a reduction in risk for progression to ESRD of 24% (95% confidence interval 6.1 to 41%), from 43 to 19%, at 12 mo. Patient survival and severe adverse event rates at 1 yr were 51 (76%) of 67 and 32 of 67 (48%) in the intravenous methylprednisolone group and 51 (73%) of 70 and 35 of (50%) 70 in the plasma exchange group, respectively. Plasma exchange increased the rate of renal recovery in ANCA-associated systemic vasculitis that presented with renal failure when compared with intravenous methylprednisolone. Patient survival and severe adverse event rates were similar in both groups.
|
|
| 42. |
- Kilpeläinen, Tuomas O, et al.
(författare)
-
Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
|
|
| 43. |
|
|
| 44. |
- Kotilainen, Aarno T., et al.
(författare)
-
Echoes from the Past : A Healthy Baltic Sea Requires More Effort
- 2014
-
Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 43:1, s. 60-68
-
Tidskriftsartikel (refereegranskat)abstract
- Integrated sediment multiproxy studies and modeling were used to reconstruct past changes in the Baltic Sea ecosystem. Results of natural changes over the past 6000 years in the Baltic Sea ecosystem suggest that forecasted climate warming might enhance environmental problems of the Baltic Sea. Integrated modeling and sediment proxy studies reveal increased sea surface temperatures and expanded seafloor anoxia (in deep basins) during earlier natural warm climate phases, such as the Medieval Climate Anomaly. Under future IPCC scenarios of global warming, there is likely no improvement of bottom water conditions in the Baltic Sea. Thus, the measures already designed to produce a healthier Baltic Sea are insufficient in the long term. The interactions between climate change and anthropogenic impacts on the Baltic Sea should be considered in management, implementation of policy strategies in the Baltic Sea environmental issues, and adaptation to future climate change.
|
|
| 45. |
- Kristiansen, Kristian, 1948, et al.
(författare)
-
Re-theorising mobility and the formation of culture and language among the Corded Ware Culture in Europe
- 2017
-
Ingår i: Antiquity. - : Antiquity Publications. - 0003-598X .- 1745-1744. ; 91:356, s. 334-347
-
Tidskriftsartikel (refereegranskat)abstract
- Copyright © 2017 Antiquity Publications Ltd.Recent genetic, isotopic and linguistic research has dramatically changed our understanding of how the Corded Ware Culture in Europe was formed. Here the authors explain it in terms of local adaptations and interactions between migrant Yamnaya people from the Pontic-Caspian steppe and indigenous North European Neolithic cultures. The original herding economy of the Yamnaya migrants gradually gave way to new practices of crop cultivation, which led to the adoption of new words for those crops. The result of this hybridisation process was the formation of a new material culture, the Corded Ware Culture, and of a new dialect, Proto-Germanic. Despite a degree of hostility between expanding Corded Ware groups and indigenous Neolithic groups, stable isotope data suggest that exogamy provided a mechanism facilitating their integration. This article should be read in conjunction with that by Heyd (2017, in this issue).
|
|
| 46. |
- Mahr, Alfred, et al.
(författare)
-
Revisiting the classification of clinical phenotypes of anti-neutrophil cytoplasmic antibody-associated vasculitis: a cluster analysis
- 2013
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 72:6, s. 1003-1010
-
Tidskriftsartikel (refereegranskat)abstract
- Background Granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic polyangiitis (MPA) are subgroups of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) defined historically by clinical and histological features. GPA and MPA are heterogeneous entities with overlapping phenotypes. To identify novel subgroupings, cluster analysis was used to explore the phenotypic spectrum of AAV. Methods This study used a dataset of patients newly diagnosed as having GPA and MPA enrolled in five clinical trials. One cluster model included nine clinical baseline variables as input variables, and a second cluster model additionally included ANCA specificities. The clustering process involved multiple correspondence analyses followed by hierarchical ascendant cluster analysis. The clinical relevance of the generated clusters was analysed by their summary characteristics and outcomes. Results The analyses involved data for 673 subjects: 396 (59%) with GPA and 277 (41%) with MPA. Both cluster models resulted in five partially redundant clusters of subjects, and the model including ANCA resulted in more pertinent separations. These clusters were named 'renal AAV with proteinase 3 (PR3)-ANCA' (40% of subjects), 'renal AAV without PR3-ANCA' (32%) and 'non-renal AAV' (12%), 'cardiovascular AAV' (9%) and 'gastrointestinal AAV' (7%). The five clusters had distinct death and relapse rates. On the basis of 4 variables, 651 subjects (97%) could be accurately allocated to 1 of the 5 classes. Conclusions This analysis suggests that AAV encompasses five classes associated with different outcomes. As compared with the traditional GPA-MPA separation, this classification system may better reflect the phenotypic spectrum of AAV.
|
|
| 47. |
- Margaryan, Ashot, et al.
(författare)
-
Population genomics of the Viking world
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 585:7825, s. 390-396
-
Tidskriftsartikel (refereegranskat)abstract
- The maritime expansion of Scandinavian populations during the Viking Age (about ad750–1050) was a far-flung transformation in world history1,2. Here we sequenced the genomes of 442humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of this expansion. We find the Viking period involved gene flow into Scandinavia from the south and east. We observe genetic structure within Scandinavia, with diversity hotspots in the south and restricted gene flow within Scandinavia. We find evidence for a major influx of Danish ancestry into England; a Swedish influx into the Baltic; and Norwegian influx into Ireland, Iceland and Greenland. Additionally, we see substantial ancestry from elsewhere in Europe entering Scandinavia during the Viking Age. Our ancient DNA analysis also revealed that a Viking expedition included close family members. By comparing with modern populations, we find that pigmentation-associated loci have undergone strong population differentiation during the past millennium, and trace positively selected loci—including the lactase-persistence allele of LCT and alleles of ANKA that are associated with the immune response—in detail. We conclude that the Viking diaspora was characterized by substantial transregional engagement: distinct populations influenced the genomic makeup of different regions of Europe, and Scandinavia experienced increased contact with the rest of the continent.
|
|
| 48. |
- Morgan, Matthew David, et al.
(författare)
-
Negative anti-neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse
- 2017
-
Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Relapse of disease is frequent in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). It is unclear whether persistent ANCA when starting maintenance therapy increases the risk of relapse. We examined the association between ANCA status and relapse in two randomised controlled trials. Methods: ANCA-positive patients in two trials, CYCLOPS and IMPROVE, were switched from cyclophosphamide to maintenance therapy after achieving clinical remission. We classified patients as being either ANCA-positive or ANCA-negative at the time they started maintenance therapy. We compared the risk of relapse in ANCA-positive and ANCA-negative patients. Results: Of 252 patients included, 102 (40%) experienced at least one relapse during the follow-up period. At the time of the switch from induction to maintenance therapy, 111 were ANCA-positive, of whom 55 (50%) relapsed, compared to 141 patients who were ANCA-negative, of whom 47 (33%) relapsed. In multivariable time-to-event analysis, a reduced risk of relapse was associated with having become ANCA-negative at the time of switching to maintenance therapy (hazard ratio 0.63, 95% confidence interval 0.42-0.95; p=0.026). In addition, initial proteinase 3 (PR3)-ANCA, younger age, lower serum creatinine, pulsed cyclophosphamide for remission induction, and mycophenolate mofetil for remission maintenance were all associated with an increased risk of relapse. Conclusions: Becoming ANCA-negative before the switch to maintenance is associated with a reduced risk of relapse. Trial registration: CYCLOPS: ClinicalTrials.gov, NCT00430105. Registered retrospectively on 31 January 2007. IMPROVE: ClinicalTrials.gov, NCT00307645. Registered retrospectively on 27 March 2006.
|
|
| 49. |
- Nielsen, Karen Leth, et al.
(författare)
-
Escherichia coli causing recurrent urinary tract infections: Comparison to non-recurrent isolates and genomic adaptation in recurrent infections
- 2021
-
Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 9:7
-
Tidskriftsartikel (refereegranskat)abstract
- Recurrent urinary tract infection (rUTI) remains a major problem for many women and therefore the pursuit for genomic and phenotypic traits which could define rUTI has been ongoing. The present study applied a genomic approach to investigate recurrent urinary tract infections by comparative analyses of recurrent and non-recurrent Escherichia coli isolates from general practice. From whole-genome sequencing data, phylogenetic clustering and genomic traits were studied on a collection of isolates which caused recurrent infection compared to non-recurrent isolates. In addition, genomic variation between the 1st and following infection was studied on a subset of the isolates. Evidence of limited adaptation between the recurrent infections based on single nucleotide polymorphism analyses with a range of 0–13 non-synonymous single nucleotide polymorphisms (SNPs) between the paired isolates. This included an overrepresentation of SNPs in metabolism genes. We identified several genes which were more common in rUTI isolates, including nine fimbrial genes, however, not significantly after false-discovery rate. Finally, the results show that recurrent isolates of the present dataset are not distinctive by variation in the core genome, and thus, did not cluster distinct from non-rUTI isolates in a SNP phylogeny.
|
|
| 50. |
- Norlander, Katarina, et al.
(författare)
-
Comparison between two assessment methods for exercise-induced laryngeal obstructions
- 2016
-
Ingår i: European Archives of Oto-Rhino-Laryngology. - : Springer Science and Business Media LLC. - 0937-4477 .- 1434-4726. ; 273:2, s. 425-430
-
Tidskriftsartikel (refereegranskat)abstract
- Exercise-induced laryngeal obstructions (E-ILOs) are important differential diagnoses to exercise-induced asthma and are diagnosed by the continuous laryngoscopy exercise (CLE) test. There are two different methods for evaluating the severity of E-ILOs using recordings from the CLE test; the CLE score and EILOMEA. The aim of this study was to investigate the consistency between these methods. Using their respective method, the developers of each method evaluated 60 laryngoscopic recordings from patients with different subtypes and various levels of severity of E-ILOs. The CLE score evaluates glottic and supraglottic obstructions on a 4-grade scale. EILOMEA uses software to calculate the obstruction severity on continuous scales from a still frame of the larynx during maximal obstruction giving three parameters reflecting glottic and supraglottic obstruction. The means of the EILOMEA measures differed significantly for CLE score 1 vs. 2 and 2 vs. 3, but not for 0 vs. 1 for glottic as well as supraglottic obstructions. The EILOMEA method does not distinguish between CLE score 0 and 1, but otherwise the methods correlate. Since previous studies have suggested that only CLE scores of 2 and 3 reflect a severity of E-ILOs of clinical importance, this lack of the EILOMEA method is not crucial for a correct medical evaluation.
|
|
