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Sökning: WFRF:(Kirchner J.) > (2015-2019)

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  • Valassi, E., et al. (författare)
  • High mortality within 90 days of diagnosis in patients with Cushing's syndrome: results from the ERCUSYN registry
  • 2019
  • Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 181:5, s. 461-472
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Patients with Cushing's syndrome (CS) have increased mortality. The aim of this study was to evaluate the causes and time of death in a large cohort of patients with CS and to establish factors associated with increased mortality. Methods: In this cohort study, we analyzed 1564 patients included in the European Registry on CS (ERCUSYN); 1045 (67%) had pituitary-dependent CS, 385 (25%) adrenal-dependent CS, 89 (5%) had an ectopic source and 45 (3%) other causes. The median (IQR) overall follow-up time in ERCUSYN was 2.7 (1.2-5.5) years. Results: Forty-nine patients had died at the time of the analysis; 23 (47%) with pituitary-dependent CS, 6 (12%) with adrenal-dependent CS, 18 (37%) with ectopic CS and two (4%) with CS due to other causes. Of 42 patients whose cause of death was known, 15 (36%) died due to progression of the underlying disease, 13 (31%) due to infections, 7 (17%) due to cardiovascular or cerebrovascular disease and 2 due to pulmonary embolism. The commonest cause of death in patients with pituitary-dependent CS and adrenal-dependent CS were infectious diseases (n = 8) and progression of the underlying tumor (n = 10) in patients with ectopic CS. Patients who had died were older and more often males, and had more frequently muscle weakness, diabetes mellitus and ectopic CS, compared to survivors. Of 49 deceased patients, 22 (45%) died within 90 days from start of treatment and 5 (10%) before any treatment was given. The commonest cause of deaths in these 27 patients were infections (n = 10; 37%). In a regression analysis, age, ectopic CS and active disease were independently associated with overall death before and within 90 days from the start of treatment. Conclusion: Mortality rate was highest in patients with ectopic CS. Infectious diseases the commonest cause of death soon after diagnosis, emphasizing the need for careful vigilance at that time, especially in patients presenting with concomitant diabetes mellitus.
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  • Wain, Louise V, et al. (författare)
  • Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
  • 2017
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:3, s. 416-425
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.
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  • Gottselig, N., et al. (författare)
  • Elemental Composition of Natural Nanoparticles and Fine Colloids in European Forest Stream Waters and Their Role as Phosphorus Carriers
  • 2017
  • Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 31:10, s. 1592-1607
  • Tidskriftsartikel (refereegranskat)abstract
    • Biogeochemical cycling of elements largely occurs in dissolved state, but many elements may also be bound to natural nanoparticles (NNP, 1-100 nm) and fine colloids (100-450 nm). We examined the hypothesis that the size and composition of stream water NNP and colloids vary systematically across Europe. To test this hypothesis, 96 stream water samples were simultaneously collected in 26 forested headwater catchments along two transects across Europe. Three size fractions (~1-20 nm, >20-60 nm, and >60 nm) of NNP and fine colloids were identified with Field Flow Fractionation coupled to inductively coupled plasma mass spectrometry and an organic carbon detector. The results showed that NNP and fine colloids constituted between 2 ± 5% (Si) and 53 ± 21% (Fe; mean ± SD) of total element concentrations, indicating a substantial contribution of particles to element transport in these European streams, especially for P and Fe. The particulate contents of Fe, Al, and organic C were correlated to their total element concentrations, but those of particulate Si, Mn, P, and Ca were not. The fine colloidal fractions >60 nm were dominated by clay minerals across all sites. The resulting element patterns of NNP <60 nm changed from North to South Europe from Fe- to Ca-dominated particles, along with associated changes in acidity, forest type, and dominant lithology.
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  • Müller, T D, et al. (författare)
  • Ghrelin.
  • 2015
  • Ingår i: Molecular metabolism. - : Elsevier BV. - 2212-8778. ; 4:6, s. 437-60
  • Tidskriftsartikel (refereegranskat)abstract
    • The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism.
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  • Blösch, Günter, et al. (författare)
  • Twenty-three unsolved problems in hydrology (UPH) - a community perspective
  • 2019
  • Ingår i: Hydrological Sciences Journal. - : Informa UK Limited. - 0262-6667 .- 2150-3435. ; 64:10, s. 1141-1158
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.
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  • Gusarova, Viktoria, et al. (författare)
  • Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes
  • 2018
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85-0.92, p = 6.3 × 10-10), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49-0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D.
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  • Harpold, A. A., et al. (författare)
  • Laser vision : lidar as a transformative tool to advance critical zone science
  • 2015
  • Ingår i: Hydrology and Earth System Sciences. - : Copernicus GmbH. - 1027-5606 .- 1607-7938. ; 19:6, s. 2881-2897
  • Tidskriftsartikel (refereegranskat)abstract
    • Observation and quantification of the Earth's surface is undergoing a revolutionary change due to the increased spatial resolution and extent afforded by light detection and ranging (lidar) technology. As a consequence, lidar-derived information has led to fundamental discoveries within the individual disciplines of geomorphology, hydrology, and ecology. These disciplines form the cornerstones of critical zone (CZ) science, where researchers study how interactions among the geosphere, hydrosphere, and biosphere shape and maintain the 'zone of life', which extends from the top of unweathered bedrock to the top of the vegetation canopy. Fundamental to CZ science is the development of transdisciplinary theories and tools that transcend disciplines and inform other's work, capture new levels of complexity, and create new intellectual outcomes and spaces. Researchers are just beginning to use lidar data sets to answer synergistic, transdisciplinary questions in CZ science, such as how CZ processes co-evolve over long timescales and interact over shorter timescales to create thresholds, shifts in states and fluxes of water, energy, and carbon. The objective of this review is to elucidate the transformative potential of lidar for CZ science to simultaneously allow for quantification of topographic, vegetative, and hydrological processes. A review of 147 peer-reviewed lidar studies highlights a lack of lidar applications for CZ studies as 38 % of the studies were focused in geomorphology, 18 % in hydrology, 32 % in ecology, and the remaining 12 % had an interdisciplinary focus. A handful of exemplar transdisciplinary studies demonstrate lidar data sets that are well-integrated with other observations can lead to fundamental advances in CZ science, such as identification of feedbacks between hydrological and ecological processes over hillslope scales and the synergistic co-evolution of landscape-scale CZ structure due to interactions amongst carbon, energy, and water cycles. We propose that using lidar to its full potential will require numerous advances, including new and more powerful open-source processing tools, exploiting new lidar acquisition technologies, and improved integration with physically based models and complementary in situ and remote-sensing observations. We provide a 5-year vision that advocates for the expanded use of lidar data sets and highlights subsequent potential to advance the state of CZ science.
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  • Schmidt, Amand F., et al. (författare)
  • PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study
  • 2017
  • Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 5:2, s. 97-105
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects of PCSK9 inhibitors on diabetes risk. Methods In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA 1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. Findings Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0.09 mmol/L, 95% CI 0.02 to 0.15), bodyweight (1.03 kg, 0.24 to 1.82), waist-to-hip ratio (0.006, 0.003 to 0.010), and an odds ratio for type diabetes of 1.29 (1.11 to 1.50). Based on the collected data, we did not identify associations with HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -0.09 to 0.30). Interpretation PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefi ts of PCSK9 inhibitor treatment, as was previously done for statins.
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  • Schmidt, Amand F., et al. (författare)
  • Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
  • 2019
  • Ingår i: BMC Cardiovascular Disorders. - : BMC. - 1471-2261 .- 1471-2261. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
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  • Weismuller, T. J., et al. (författare)
  • Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis
  • 2017
  • Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 152:8
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. METHODS: We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. RESULTS: Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time to event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n = 594); patients of advanced age at diagnosis had an increased incidence compared with younger patients (incidence rate: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21-30 years old, 9.0 per 100 patient-years for patients 31-40 years old, 14.0 per 100 patient-years for patients 4150 years old, 15.2 per 100 patient-years for patients 51-60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn's disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; P <.001 and HR, 0.90; P =.03, respectively) and malignancy (HR, 0.68; P =.008 and HR, 0.77; P =.004, respectively). Small-duct PSC was associated with a lower risk of LTD or malignancy compared with classic PSC (HR, 0.30 and HR, 0.15, respectively; both P <.001). Female sex was also associated with a lower risk of LTD or malignancy (HR, 0.88; P =.002 and HR, 0.68; P <.001, respectively). In multivariable analyses assessing the primary endpoint, small-duct PSC characterized a low-risk phenotype in both sexes (adjusted HR for men, 0.23; P <.001 and adjusted HR for women, 0.48; P =.003). Conversely, patients with ulcerative colitis had an increased risk of liver disease progression compared with patients with Crohn's disease (HR, 1.56; P <.001) or no IBD (HR, 1.15; P =.002). CONCLUSIONS: In an analysis of data from individual patients with PSC worldwide, we found significant variation in clinical course associated with age at diagnosis, sex, and ductal and IBD subtypes. The survival estimates provided might be used to estimate risk levels for patients with PSC and select patients for clinical trials.
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  • Kirchner, Nina, et al. (författare)
  • Shallow ice approximation, second order shallow ice approximation, and full Stokes models : A discussion of their roles in palaeo-ice sheet modelling and development
  • 2016
  • Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 147, s. 136-147
  • Tidskriftsartikel (refereegranskat)abstract
    • Full Stokes ice sheet models provide the most accurate description of ice sheet flow, and can therefore be used to reduce existing uncertainties in predicting the contribution of ice sheets to future sea level rise on centennial time-scales. The level of accuracy at which millennial time-scale palaeo-ice sheet simulations resolve ice sheet flow lags the standards set by Full Stokes models, especially, when Shallow Ice Approximation (SIA) models are used. Most models used in paleo-ice sheet modeling were developed at a time when computer power was very limited, and rely on several assumptions. At the time there was no means of verifying the assumptions by other than mathematical arguments. However, with the computer power and refined Full Stokes models available today, it is possible to test these assumptions numerically. In this paper, we review (Ahlkrona et al., 2013a) where such tests were performed and inaccuracies in commonly used arguments were found. We also summarize (Ahlkrona et al., 2013b) where the implications of the inaccurate assumptions are analyzed for two paleo-models - the SIA and the SOSIA. We review these works without resorting to mathematical detail, in order to make them accessible to a wider audience with a general interest in palaeo-ice sheet modelling. Specifically, we discuss two implications of relevance for palaeo-ice sheet modelling. First, classical SIA models are less accurate than assumed in their original derivation. Secondly, and contrary to previous recommendations, the SOSIA model is ruled out as a practicable tool for palaeo-ice sheet simulations. We conclude with an outlook concerning the new Ice Sheet Coupled Approximation Level (ISCAL) method presented in Ahlkrona et al. (2016), that has the potential to match the accuracy standards of full Stokes model on palaeo-timescales of tens of thousands of years, and to become an alternative to hybrid models currently used in palaeo-ice sheet modelling. The method is applied to an ice sheet covering Svalbard.
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  • Kirchner, Nina, et al. (författare)
  • Shallow ice approximation, second order shallow ice approximation, and full Stokes models : A discussion of their roles in palaeo-ice sheet modelling and development
  • 2016
  • Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 135, s. 103-114
  • Forskningsöversikt (refereegranskat)abstract
    • Full Stokes ice sheet models provide the most accurate description of ice sheet flow, and can therefore be used to reduce existing uncertainties in predicting the contribution of ice sheets to future sea level rise on centennial time-scales. The level of accuracy at which millennial time-scale palaeo-ice sheet simulations resolve ice sheet flow lags the standards set by Full Stokes models, especially, when Shallow Ice Approximation (SIA) models are used. Most models used in paleo-ice sheet modeling were developed at a time when computer power was very limited, and rely on several assumptions. At the time there was no means of verifying the assumptions by other than mathematical arguments. However, with the computer power and refined Full Stokes models available today, it is possible to test these assumptions numerically. In this paper, we review (Ahlkrona et al., 2013a) where such tests were performed and inaccuracies in commonly used arguments were found. We also summarize (Ahlkrona et al., 2013b) where the implications of the inaccurate assumptions are analyzed for two paleo-models - the SIA and the SOSIA. We review these works without resorting to mathematical detail, in order to make them accessible to a wider audience with a general interest in palaeo-ice sheet modelling. Specifically, we discuss two implications of relevance for palaeo-ice sheet modelling. First, classical SIA models are less accurate than assumed in their original derivation. Secondly, and contrary to previous recommendations, the SOSIA model is ruled out as a practicable tool for palaeo-ice sheet simulations. We conclude with an outlook concerning the new Ice Sheet Coupled Approximation Level (ISCAL) method presented in Ahlkrona et al. (2016), that has the potential to match the accuracy standards of full Stokes model on palaeo-timescales of tens of thousands of years, and to become an alternative to hybrid models currently used in palaeo-ice sheet modelling. The method is applied to an ice sheet covering Svalbard.
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  • Stokes, Chris R., et al. (författare)
  • On the reconstruction of palaeo-ice sheets : Recent advances and future challenges
  • 2015
  • Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 125, s. 15-49
  • Forskningsöversikt (refereegranskat)abstract
    • Reconstructing the growth and decay of palaeo-ice sheets is critical to understanding mechanisms of global climate change and associated sea-level fluctuations in the past, present and future. The significance of palaeo-ice sheets is further underlined by the broad range of disciplines concerned with reconstructing their behaviour, many of which have undergone a rapid expansion since the 1980s. In particular, there has been a major increase in the size and qualitative diversity of empirical data used to reconstruct and date ice sheets, and major improvements in our ability to simulate their dynamics in numerical ice sheet models. These developments have made it increasingly necessary to forge interdisciplinary links between sub-disciplines and to link numerical modelling with observations and dating of proxy records. The aim of this paper is to evaluate recent developments in the methods used to reconstruct ice sheets and outline some key challenges that remain, with an emphasis on how future work might integrate terrestrial and marine evidence together with numerical modelling. Our focus is on pan-ice sheet reconstructions of the last deglaciation, but regional case studies are used to illustrate methodological achievements, challenges and opportunities. Whilst various disciplines have made important progress in our understanding of ice-sheet dynamics, it is clear that data-model integration remains under-used, and that uncertainties remain poorly quantified in both empirically-based and numerical ice-Sheet reconstructions. The representation of past climate will continue to be the largest source of uncertainty for numerical modelling. As such, palaeo-observations are critical to constrain and validate modelling. State-of-the-art numerical models will continue to improve both in model resolution and in the breadth of inclusion of relevant processes, thereby enabling more accurate and more direct comparison with the increasing range of palaeo-observations. Thus, the capability is developing to use all relevant palaeo-records to more strongly constrain deglacial (and to a lesser extent pre-LGM) ice sheet evolution. In working towards that goal, the accurate representation of uncertainties is required for both constraint data and model outputs. Close cooperation between modelling and data-gathering communities is essential to ensure this capability is realised and continues to progress.
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  • Clayton, Aled, et al. (författare)
  • Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017
  • 2018
  • Ingår i: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 7
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. This report summarises the presentations and activities of the ISEV Workshop on extracellular vesicle biomarkers held in Birmingham, UK during December 2017. Among the key messages was broad agreement about the importance of biospecimen science. Much greater attention needs to be paid towards the provenance of collected samples. The workshop also highlighted clear gaps in our knowledge about pre-analytical factors that alter extracellular vesicles (EVs). The future utility of certified standards for credentialing of instruments and software, to analyse EV and for tracking the influence of isolation steps on the structure and content of EVs were also discussed. Several example studies were presented, demonstrating the potential utility for EVs in disease diagnosis, prognosis, longitudinal serial testing and stratification of patients. The conclusion of the workshop was that more effort focused on pre-analytical issues and benchmarking of isolation methods is needed to strengthen collaborations and advance more effective biomarkers.
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  • Floriancic, Marius G., et al. (författare)
  • Spatial variability in specific discharge and streamwater chemistry during low flows : Results from snapshot sampling campaigns in eleven Swiss catchments
  • 2019
  • Ingår i: Hydrological Processes. - : Wiley. - 0885-6087 .- 1099-1085. ; 33:22, s. 2847-2866
  • Tidskriftsartikel (refereegranskat)abstract
    • Catchments consist of distinct landforms that affect the storage and release of subsurface water. Certain landforms may be the main contributors to streamflow during extended dry periods, and these may vary for different catchments in a given region. We present a unique dataset from snapshot field campaigns during low-flow conditions in 11 catchments across Switzerland to illustrate this. The catchments differed in size (10 to 110 km(2)), varied from predominantly agricultural lowlands to Alpine areas, and covered a range of physical characteristics. During each snapshot campaign, we jointly measured streamflow and collected water samples for the analysis of major ions and stable water isotopes. For every sampling location (basin), we determined several landscape characteristics from national geo-datasets, including drainage area, elevation, slope, flowpath length, dominant land use, and geological and geomorphological characteristics, such as the lithology and fraction of quaternary deposits. The results demonstrate very large spatial variability in specific low-flow discharge and water chemistry: Neighboring sampling locations could differ significantly in their specific discharge, isotopic composition, and ion concentrations, indicating that different sources contribute to streamflow during extended dry periods. However, none of the landscape characteristics that we analysed could explain the spatial variability in specific discharge or streamwater chemistry in multiple catchments. This suggests that local features determine the spatial differences in discharge and water chemistry during low-flow conditions and that this variability cannot be assessed a priori from available geodata and statistical relations to landscape characteristics. The results furthermore suggest that measurements at the catchment outlet during low-flow conditions do not reflect the heterogeneity of the different source areas in the catchment that contribute to streamflow.
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24.
  • How, Penelope, et al. (författare)
  • Calving controlled by melt-under-cutting : detailed calving styles revealed through time-lapse observations
  • 2019
  • Ingår i: Annals of Glaciology. - : Cambridge University Press (CUP). - 0260-3055 .- 1727-5644. ; 60:78, s. 20-31
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a highly detailed study of calving dynamics at Tunabreen, a tidewater glacier in Svalbard. A time-lapse camera was trained on the terminus and programmed to capture images every 3 seconds over a 28-hour period in August 2015, producing a highly detailed record of 34 117 images from which 358 individual calving events were distinguished. Calving activity is characterised by frequent events (12.8 events h(-1)) that are small relative to the spectrum of calving events observed, demonstrating the prevalence of small-scale calving mechanisms. Five calving styles were observed, with a high proportion of calving events (82%) originating at, or above, the waterline. The tidal cycle plays a key role in the timing of calving events, with 68% occurring on the falling limb of the tide. Calving activity is concentrated where meltwater plumes surface at the glacier front, and a similar to 5 m undercut at the base of the glacier suggests that meltwater plumes encourage melt-under-cutting. We conclude that frontal ablation at Tunabreen may be paced by submarine melt rates, as suggested from similar observations at glaciers in Svalbard and Alaska. Using submarine melt rate to calculate frontal ablation would greatly simplify estimations of tidewater glacier losses in prognostic models.
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25.
  • Kirchner, Nina, et al. (författare)
  • GRANTSISM : An Excel™ ice sheet model for use in introductory Earth science courses
  • 2018
  • Ingår i: Journal of Geoscience education. - : Informa UK Limited. - 1089-9995 .- 2158-1428. ; 66:2, s. 109-120
  • Tidskriftsartikel (refereegranskat)abstract
    • GRANTISM (GReenland and ANTarctic Ice Sheet Model) is an educational ExcelTM model introduced by Pattyn (2006). Here, GRANTISM is amended to simulate the Svalbard-Barents-Sea Ice Sheet during the Last Glacial Maximum, an analogue for the contemporary West Antarctic Ice Sheet. A new name, “GRANTSISM,” is suggested; the added S represents Svalbard. GRANTSISM introduces students of bachelor’s or master’s programs in Earth sciences (first or second cycle program in the Bologna system for higher education), but with little or no background in numerical modeling, to basic ice sheet modeling. GRANTSISM provides hands-on learning experiences related to ice sheet dynamics in response to climate forcing, and fosters understanding of processes and feedbacks. GRANTSISM was successfully used in noncompulsory courses in which students have been able to reproduce paleo-ice sheet evolution scenarios discussed here as examples. Students progressed further by designing, developing, and analyzing their own modeling scenarios. Here, we describe GRANTSISM and report on how learning activities with GRANTSISM were assessed by students who had no prior experience in ice sheet modeling. The response rate for a noncompulsory survey of the learning activity was less than 40%. A subsequent control experiment with a compulsory survey, however, showed the same patterns of answers, so the student response is considered representative. First, GRANTSISM is concluded to be a highly attractive tool to introduce learners with an interest in ice sheet behavior to ice sheet modeling. Second, it triggers an interest for more in-depth learning experiences related to numerical ice sheet modeling.  
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26.
  • Seiler, Ruedi, et al. (författare)
  • Insensitivity of Tree-Ring Growth to Temperature and Precipitation Sharpens the Puzzle of Enhanced Pre-Eruption NDVI on Mt. Etna (Italy)
  • 2017
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • On Mt. Etna (Italy), an enhanced Normalized Difference in Vegetation Index (NDVI) signature was detected in the summers of 2001 and 2002 along a distinct line where, in November 2002, a flank eruption subsequently occurred. These observations suggest that preeruptive volcanic activity may have enhanced photosynthesis along the future eruptive fissure. If a direct relation between NDVI and future volcanic eruptions could be established, it would provide a straightforward and low-cost method for early detection of upcoming eruptions. However, it is unclear if, or to what extent, the observed enhancement of NDVI can be attributed to volcanic activity prior to the subsequent eruption. We consequently aimed at determining whether an increase in ambient temperature or additional water availability owing to the rise of magma and degassing of water vapour prior to the eruption could have increased photosynthesis of Mt. Etna's trees. Using dendro-climatic analyses we quantified the sensitivity of tree ring widths to temperature and precipitation at high elevation stands on Mt. Etna. Our findings suggest that tree growth at high elevation on Mt. Etna is weakly influenced by climate, and that neither an increase in water availability nor an increase in temperature induced by pre-eruptive activity is a plausible mechanism for enhanced photosynthesis before the 2002/2003 flank eruption. Our findings thus imply that other, yet unknown, factors must be sought as causes of the pre-eruption enhancement of NDVI on Mt. Etna.
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27.
  • Tesi, Tommaso, et al. (författare)
  • Massive remobilization of permafrost carbon during post-glacial warming
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent hypotheses, based on atmospheric records and models, suggest that permafrost carbon (PF-C) accumulated during the last glaciation may have been an important source for the atmospheric CO2 rise during post-glacial warming. However, direct physical indications for such PF-C release have so far been absent. Here we use the Laptev Sea (Arctic Ocean) as an archive to investigate PF-C destabilization during the last glacial–interglacial period. Our results show evidence for massive supply of PF-C from Siberian soils as a result of severe active layer deepening in response to the warming. Thawing of PF-C must also have brought about an enhanced organic matter respiration and, thus, these findings suggest that PF-C may indeed have been an important source of CO2 across the extensive permafrost domain. The results challenge current paradigms on the post-glacial CO2 rise and, at the same time, serve as a harbinger for possible consequences of the present-day warming of PF-C soils.
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28.
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29.
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