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- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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- Young, William J., et al.
(författare)
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Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
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- Auner, H W., et al.
(författare)
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Reduced intensity-conditioned allogeneic stem cell transplantation for multiple myeloma relapsing or progressing after autologous transplantation: a study by the European Group for Blood and Marrow Transplantation
- 2013
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Ingår i: Bone Marrow Transplantation. - : Nature Publishing Group: Open Access Hybrid Model Option B. - 0268-3369 .- 1476-5365. ; 48:11, s. 1395-1400
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Tidskriftsartikel (refereegranskat)abstract
- Outcomes and prognostic factors of reduced intensity-conditioned allo-SCT (RIC allo-SCT) for multiple myeloma (MM) relapsing or progressing after prior autologous (auto)-SCT are not well defined. We performed an analysis of 413 MM patients who received a related or unrelated RIC allo-SCT for the treatment of relapse/progression after prior auto-SCT. Median age at RIC allo-SCT was 54.1 years, and 44.6% of patients had undergone two or more prior auto-SCTs. Median OS and PFS from the time of RIC allo-SCT for the entire population were 24.7 and 9.6 months, respectively. Cumulative non-relapse mortality (NRM) at 1 year was 21.5%. In multivariate analysis, CMV seronegativity of both patient and donor was associated with significantly better PFS, OS and NRM. Patient-donor gender mismatch was associated with better PFS, fewer than two prior auto-SCT was associated with better OS, and shorter time from the first auto-SCT to the RIC allo-SCT was associated with lower NRM. The results of this study identify patient and donor CMV seronegativity as the key prognostic factor for outcome after RIC allo-SCT for MM relapsing or progressing after prior auto-SCT.
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- Styrud, J, et al.
(författare)
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Appendectomy versus antibiotic treatment in acute appendicitis. A prospective multicenter randomized controlled trial
- 2006
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 30:6, s. 1033-1037
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Tidskriftsartikel (refereegranskat)abstract
- Background Appendectomy has been the treatment for acute appendicitis for over 120 years. Antibiotic treatment has occasionally been used in small uncontrolled studies, instead of operation, but this alternative has never before been tried in a multicenter randomized trial. Patients and Methods Male patients, 18–50 years of age, admitted to six different hospitals in Sweden between 1996 and 1999 were enrolled in the study. No women were enrolled by decision of the local ethics committee. If appendectomy was planned, patients were asked to participate, and those who agreed were randomized either to surgery or to antibiotic therapy. Patients randomized to surgery were operated on with open surgery or laparoscopically. Those randomized to antibiotic therapy were treated intravenously for 2 days, followed by oral treatment for 10 days. If symptoms did not resolve within 24 hours, an appendectomy was performed. Participants were monitored at the end of 1 week, 6 weeks, and 1 year. Results During the study period 252 men participated, 124 in the surgery group and 128 in the antibiotic group. The frequency of appendicitis was 97% in the surgery group and 5% had a perforated appendix. The complication rate was 14% in the surgery group. In the antibiotic group 86% improved without surgery; 18 patients were operated on within 24 hours, and the diagnosis of acute appendicitis was confirmed in all but one patient, and he was suffering from terminal ileitis. There were seven patients (5%) with a perforated appendix in this group. The rate of recurrence of symptoms of appendicitis among the 111 patients treated with antibiotics was 14% during the 1-year follow-up. Conclusions Acute nonperforated appendicitis can be treated successfully with antibiotics. However, there is a risk of recurrence in cases of acute appendicitis, and this risk should be compared with the risk of complications after appendectomy.
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| 16. |
- Zwickl, Craig M., et al.
(författare)
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Principles and procedures for assessment of acute toxicity incorporating in silico methods
- 2022
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Ingår i: COMPUTATIONAL TOXICOLOGY. - : Elsevier. - 2468-1113. ; 24
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Tidskriftsartikel (refereegranskat)abstract
- Acute toxicity in silico models are being used to support an increasing number of application areas including (1) product research and development, (2) product approval and registration as well as (3) the transport, storage and handling of chemicals. The adoption of such models is being hindered, in part, because of a lack of guidance describing how to perform and document an in silico analysis. To address this issue, a framework for an acute toxicity hazard assessment is proposed. This framework combines results from different sources including in silico methods and in vitro or in vivo experiments. In silico methods that can assist the prediction of in vivo outcomes (i.e., LD50) are analyzed concluding that predictions obtained using in silico approaches are now well-suited for reliably supporting assessment of LD50- based acute toxicity for the purpose of the Globally Harmonized System (GHS) classification. A general overview is provided of the endpoints from in vitro studies commonly evaluated for predicting acute toxicity (e.g., cytotoxicity/cytolethality as well as assays targeting specific mechanisms). The increased understanding of pathways and key triggering mechanisms underlying toxicity and the increased availability of in vitro data allow for a shift away from assessments solely based on endpoints such as LD50, to mechanism-based endpoints that can be accurately assessed in vitro or by using in silico prediction models. This paper also highlights the importance of an expert review of all available information using weight-of-evidence considerations and illustrates, using a series of diverse practical use cases, how in silico approaches support the assessment of acute toxicity.
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| 17. |
- Ahlberg, Anders, et al.
(författare)
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Onshore climate change during the late triassic marine inundation of the Central European Basin
- 2002
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Ingår i: Terra Nova: the European journal of geosciences. - : Wiley. - 0954-4879. ; 14:4, s. 241-248
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Tidskriftsartikel (refereegranskat)abstract
- Sedimentological, pedological and palynological evidence reveal radically increasing onshore humidity during the Rhaetian marine invasion of central Europe along the north-eastern margin of the Central European Basin (southern Sweden). Pre-Rhaetian aridity favoured the formation of Carnian redbeds with calcrete, which were succeeded by Norian hematite-cemented conglomerates, arkoses, arkosic wackestones, and smectititic mudstones deposited on braidplains and in lakes. Superimposed autochthonous coals and gleysols indicate the Rhaetian onset of year-round humidity. Chemically mature sandstones, kaolinitic mudstones and luvisols also formed at this time, influenced by a permanent vegetation cover which lowered soil pH and strongly intensified chemical weathering. The Rhaetian deposits accumulated in floodplain lakes repeatedly subjected to sediment infill, plant colonization and palaeosol development. The humidity shift resembles that contemporaneously recorded in the North Sea region.
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- Ahlberg, Charlotte, et al.
(författare)
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Self-organization of fibers in a suspension between two counter-rotating discs
- 2009
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Ingår i: Proceedings of the ASME Fluids Engineering Division Summer Conference 2009. - NEW YORK : AMER SOC MECHANICAL ENGINEERS. - 9780791843727 ; , s. 585-592
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Konferensbidrag (refereegranskat)abstract
- The behavior of fibers suspended in a flow between two flat counter-rotating discs has been studied experimentally. Captured images of the fibers in the flow were analyzed by steerable filters, to extract positions and orientations of the fibers. Experiments were performed for gaps between the discs of less than one fiber length, and for equal absolute values of the angular velocities for the discs. The length-to-diameter ratio of the fibers was approximately 14. During certain conditions, the fibers organized themselves in a distinct manner, which we will denote as fiber trains, in which three or more fibers are aligned next to each other, at the same radial position, with a short fiber-to-fiber distance. The direction of the individual fibers is radial and the direction of the whole train is tangential. Trains containing more than 60 fibers have been observed and are quite impressing.
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| 22. |
- Ahlberg, Erik, et al.
(författare)
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"Vi klimatforskare stödjer Greta och skolungdomarna"
- 2019
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Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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| 29. |
- Ahlberg, M., et al.
(författare)
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Time without PSA recurrence after radical prostatectomy as a predictor of prostate cancer death
- 2022
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 81:Suppl. 1, s. S286-S286
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction & Objectives: Although surveillance after radical prostatectomy routinely includes repeated Prostate Specific Antigen (PSA)-testing for many years, biochemical recurrence often occurs without further clinical progression. We therefore hypothesised that follow-up can be shortened for many patients without increasing the risk for prostate cancer death. We investigated the long-term probabilities of PSA recurrence, metastases and prostate cancer death in patients without biochemical recurrence 5 and 10 years after radical prostatectomy.Materials & Methods: Between 1989 and 1998, 14 urological centres in Scandinavia randomized patients to the Scandinavian Prostate Cancer Group study number 4 (SPCG-4) trial. Data was collected prospectively. All 306 patients from the SPCG-4 trial who underwent radical prostatectomy within 1 year from inclusion were eligible in our cohort. 4 patients were excluded due to surgery-related death (n=1) or salvage radiotherapy or hormonal treatment within 6 weeks from surgery (n=3). We stratified by Gleason score (≤3+4=7 or ≥4+3=7), pathological tumour stage (pT2 or ≥pT3), and negative or positive surgical margins. We analysed the cumulative incidences and absolute differences in metastatic disease and prostate cancer death.Results: We analysed 302 patients with complete follow-up during a median of 18 years. Median preoperative PSA was 9.8 ng/ml and median age at inclusion was 65 years. For patients without biochemical recurrence 5 years after radical prostatectomy the 20-year probability of biochemical recurrence was 25% among men with Gleason score ≤3+4=7 and 57% among men with Gleason score ≥4+3=7; the probabilities for metastases were 0.8% and 17%; and for prostate cancer death 0.8% and 12% respectively. The long-term probabilities were higher for pT≥3 vs. pT2 and for positive vs. negative surgical margins.Conclusions: Following radical prostatectomy, patients with Gleason score ≤3+4=7 without biochemical recurrence 5 years after radical prostatectomy had low risk of metastases and prostate cancer death independent of pT-stage and surgical margins. The risk of clinical progression decreased drastically the first 3 years after radical prostatectomy and after 10 years without biochemical recurrence, no patient was diagnosed with metastases or died from prostate cancer. Our study indicates that men with favourable histopathology without biochemical recurrence 5 years after radical prostatectomy can stop follow-up earlier than 10 years after radical prostatectomy while men with adverse pathology should continue with at least 10 years follow-up
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| 31. |
- Ahlberg, Rickard, 1970-, et al.
(författare)
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Real-life instability in ADHD from young to middle adulthood : a nationwide register-based study of social and occupational problems
- 2023
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Ingår i: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Studies using self-reports indicate that individuals with ADHD are at increased risk for functional impairments in social and occupational settings, but evidence around real-life instability remains limited. It is furthermore unclear if these functional impairments in ADHD differ across sex and across the adult lifespan.METHOD: A longitudinal observational cohort design of 3,448,440 individuals was used to study the associations between ADHD and residential moves, relational instability and job shifting using data from Swedish national registers. Data were stratified on sex and age (18-29 years, 30-39 years, and 40-52 years at start of follow up).RESULTS: 31,081 individuals (17,088 males; 13,993 females) in the total cohort had an ADHD-diagnosis. Individuals with ADHD had an increased incidence rate ratio (IRR) of residential moves (IRR 2.35 [95% CI, 2.32-2.37]), relational instability (IRR = 1.07 [95% CI, 1.06-1.08]) and job shifting (IRR = 1.03 [95% CI, 1.02-1.04]). These associations tended to increase with increasing age. The strongest associations were found in the oldest group (40-52 years at start of follow). Women with ADHD in all three age groups had a higher rate of relational instability compared to men with ADHD.CONCLUSION: Both men and women with a diagnosis of ADHD present with an increased risk of real-life instability in different domains and this behavioral pattern was not limited to young adulthood but also existed well into older adulthood. It is therefore important to have a lifespan perspective on ADHD for individuals, relatives, and the health care sector.
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| 33. |
- Álvaro, J. Javier, et al.
(författare)
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Global Cambrian trilobite palaeobiogeography assessed using parsimony analysis of endemicity
- 2013
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Ingår i: Early Palaeozoic Biogeography and Palaeogeography. - 0435-4052. - 9781862393738 ; Memoir 38:38, s. 273-296
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Bokkapitel (refereegranskat)abstract
- Palaeobiogeographical data on Cambrian trilobites obtained during the twentieth century are combined in this paper to evaluate palaeoceanographic links through c. 30 myr, once these arthropods biomineralized. Worldwide major tectonostratigraphic units are characterized at series intervals of Cambrian time and datasets of trilobite genera (629 for Cambrian Series 2, 965 for Cambrian Series 3, and 866 for the Furongian Series) are analysed using parsimony analysis of endemicity. Special attention is given to the biogeographical observations made in microcontinents and exotic terranes. The same is done for platform-basinal transects of well-known continental margins. The parsimony analysis of endemicity analysis resulted in distinct palaeogeographical area groupings among the tectonostratigraphic units. With these groupings, several palaeobiogeographical units are distinguished, which do not necessarily fit the previously proposed biogeographical realms and provinces. Their development and spatial distributions are broadly controlled by Cambrian palaeoclimates, palaeogeographical conditions (e.g. carbonate productivity and anoxic conditions) and ocean current circulation.
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| 42. |
- Borg, K, et al.
(författare)
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Welander distal myopathy--an overview
- 1998
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Ingår i: Neuromuscular disorders : NMD. - : Elsevier BV. - 0960-8966. ; 8:2, s. 115-118
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Tidskriftsartikel (refereegranskat)
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| 43. |
- Braglia, L., et al.
(författare)
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Understanding Solid-Gas Reaction Mechanisms by Operando Soft X-Ray Absorption Spectroscopy at Ambient Pressure
- 2020
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 124:26, s. 14202-14212
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Tidskriftsartikel (refereegranskat)abstract
- Ambient-pressure operando soft X-ray absorption spectroscopy (soft-XAS) was applied to study the reactivity of hydroxylated SnO(2 )nanoparticles toward reducing gases. H-2 was first used as a test case, showing that the gas phase and surface states can be simultaneously probed: Soft-XAS at the O K-edge gains sensitivity toward the gas phase, while at the Sn M-4,M-5-edges, tin surface states are explicitly probed. Results obtained by flowing hydrocarbons (CH4 and CH3CHCH2) unequivocally show that these gases react with surface hydroxyl groups to produce water without producing carbon oxides and release electrons that localize on Sn to eventually form SnO. The partially reduced SnO2-x layer at the surface of SnO2 is readily reoxidized to SnO2 by treating the sample with O-2 at mild temperatures (>200 degrees C), revealing the nature of "electron sponge" of tin oxide. The experiments, combined with DFT calculations, allowed devising of a mechanism for dissociative hydrocarbon adsorption on SnO2, involving direct reduction of Sn sites at the surface via cleavage of C-H bonds and the formation of methoxy- and/or methyl-tin species at the surface.
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| 44. |
- Calner, Mikael, et al.
(författare)
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The first record of Odontopleura ovata (Trilobita) from Scandinavia: part of a middle Silurian intercontinental shelly benthos mass occurrence
- 2006
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Ingår i: GFF. - 2000-0863. ; 128:1, s. 33-37
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Tidskriftsartikel (refereegranskat)abstract
- We report here, for the first time, the occurrence of the trilobite Odontopleura (Odontopleura) ovata Emmrich, 1839 from Scandinavia. The specimens came in light during a study of middle Silurian calcareous mudstone formed in offshore settings of the Baltic Basin (Grotlingbo-1 core, south-eastern Gotland). Intrabasinal correlation shows that the taxon had a brief mass occurrence during the latest dubius, parvus-nassa, and dubius-nassa graptolite chrons across the Baltic Shield and East European Platform without inhabiting the carbonate platforms that fringed the basin. The sudden appearance of O. ovata and an abundant brachiopod fauna in the core corresponds in time with a general shelly benthos mass occurrence in the earliest recovery phase of the middle Silurian global conodont and graptolite crisis (the Mulde Event) and correlates with a transgression and geographical expansion of the Baltic Basin.
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| 48. |
- Emilsson, Gustav, 1989, et al.
(författare)
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Polymer brushes in solid-state nanopores form an impenetrable entropic barrier for proteins
- 2018
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 10:10, s. 4663-4669
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Tidskriftsartikel (refereegranskat)abstract
- Polymer brushes are widely used to prevent the adsorption of proteins, but the mechanisms by which they operate have remained heavily debated for many decades. We show conclusive evidence that a polymer brush can be a remarkably strong kinetic barrier towards proteins by using poly(ethylene glycol) grafted to the sidewalls of pores in 30 nm thin gold films. Despite consisting of about 90% water, the free coils seal apertures up to 100 nm entirely with respect to serum protein translocation, as monitored label-free through the plasmonic activity of the nanopores. The conclusions are further supported by atomic force microscopy and fluorescence microscopy. A theoretical model indicates that the brush undergoes a morphology transition to a sealing state when the ratio between the extension and the radius of curvature is approximately 0.8. The brush-sealed pores represent a new type of ultrathin filter with potential applications in bioanalytical systems.
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