| 1. |
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| 2. |
- Nelson, G., et al.
(author)
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QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy
- 2021
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In: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 284:1, s. 56-73
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Journal article (peer-reviewed)abstract
- A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility. In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper (1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; (2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers and observers of such; (3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics.
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| 3. |
- Valassi, E., et al.
(author)
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High mortality within 90 days of diagnosis in patients with Cushing's syndrome: results from the ERCUSYN registry
- 2019
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In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 181:5, s. 461-472
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Journal article (peer-reviewed)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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| 9. |
- Wain, Louise V, et al.
(author)
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Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
- 2017
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:3, s. 416-425
-
Journal article (peer-reviewed)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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| 10. |
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| 11. |
- Gottselig, N., et al.
(author)
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Elemental Composition of Natural Nanoparticles and Fine Colloids in European Forest Stream Waters and Their Role as Phosphorus Carriers
- 2017
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In: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 31:10, s. 1592-1607
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Journal article (peer-reviewed)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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| 12. |
- Müller, T D, et al.
(author)
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Ghrelin.
- 2015
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In: Molecular metabolism. - : Elsevier BV. - 2212-8778. ; 4:6, s. 437-60
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Journal article (peer-reviewed)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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| 13. |
- Blösch, Günter, et al.
(author)
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Twenty-three unsolved problems in hydrology (UPH) - a community perspective
- 2019
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In: Hydrological Sciences Journal. - : Informa UK Limited. - 0262-6667 .- 2150-3435. ; 64:10, s. 1141-1158
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Journal article (peer-reviewed)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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| 14. |
- Gusarova, Viktoria, et al.
(author)
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Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9, s. 1-11
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Journal article (peer-reviewed)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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| 15. |
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| 16. |
- Harpold, A. A., et al.
(author)
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Laser vision : lidar as a transformative tool to advance critical zone science
- 2015
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In: Hydrology and Earth System Sciences. - : Copernicus GmbH. - 1027-5606 .- 1607-7938. ; 19:6, s. 2881-2897
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Journal article (peer-reviewed)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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| 17. |
- McDonnell, J.J., et al.
(author)
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How old is streamwater? : Open questions in catchment transit time conceptualization, modelling and analysis
- 2010
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In: Hydrological Processes. - : John Wiley & Sons. - 0885-6087 .- 1099-1085. ; 24:12, s. 1745-1754
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Journal article (peer-reviewed)abstract
- The time water spends travelling subsurface through a catchment to the stream network (i.e. the catchment water transit time) fundamentally describes the storage, flow pathway heterogeneity and sources of water in a catchment. The distribution of transit times reflects how catchments retain and release water and solutes that in turn set biogeochemical conditions and affect contamination release or persistence. Thus, quan- tifying the transit time distribution provides an important constraint on biogeochemical processes and catchment sensitivity to anthropogenic inputs, contamination and land-use change. Although the assumptions and limitations of past and present transit time modelling approaches have been recently reviewed (McGuire and McDonnell, 2006), there remain many fundamental research challenges for understanding how transit time can be used to quantify catchment flow processes and aid in the development and testing of rainfall–runoff models. In this Commen- tary study, we summarize what we think are the open research questions in transit time research. These thoughts come from a 3-day workshop in January 2009 at the International Atomic Energy Agency in Vienna. We attempt to lay out a roadmap for this work for the hydrological commu- nity over the next 10 years. We do this by first defining what we mean (qualitatively and quantitatively) by transit time and then organize our vision around needs in transit time theory, needs in field studies of tran- sit time and needs in rainfall – runoff modelling. Our goal in presenting this material is to encourage widespread use of transit time information in process studies to provide new insights to catchment function and to inform the structural development and testing of hydrologic models.
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| 18. |
- Dangtip, S, et al.
(author)
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A facility for measurements of nuclear cross sections for fast neutron cancer therapy
- 2000
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In: NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT. - : ELSEVIER SCIENCE BV. - 0168-9002. ; 452:3, s. 484-504
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Journal article (peer-reviewed)abstract
- A facility for measurements of neutron-induced double-differential light-ion production cross-sections, for application within. e.g.. fast neutron cancer therapy, is described. The central detection elements are three-detector telescopes consisting of two
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| 19. |
- Finan, B, et al.
(author)
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Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans
- 2013
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In: Science translational medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 5:209, s. 209ra151-
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Journal article (peer-reviewed)abstract
- Compared to best-in-class GLP-1 mono-agonists, unimolecular co-agonists of GLP-1 and GIP with optimized pharmacokinetics enhance glycemic and metabolic benefits in mammals.
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| 20. |
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| 21. |
- Mohammed Taha, Hiba, et al.
(author)
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The NORMAN Suspect List Exchange (NORMAN-SLE) : facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry
- 2022
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In: Environmental Sciences Europe. - : Springer. - 2190-4707 .- 2190-4715. ; 34:1
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Journal article (peer-reviewed)abstract
- Background: The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for “suspect screening” lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide.Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https://zenodo.org/communities/norman-sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA’s CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101).Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the “one substance, one assessment” approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-network.com/nds/SLE/).
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| 22. |
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| 23. |
- Schmidt, Amand F., et al.
(author)
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PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study
- 2017
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In: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 5:2, s. 97-105
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Journal article (peer-reviewed)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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| 24. |
- Schmidt, Amand F., et al.
(author)
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Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
- 2019
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In: BMC Cardiovascular Disorders. - : BMC. - 1471-2261 .- 1471-2261. ; 19:1
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Journal article (peer-reviewed)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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| 25. |
- Weismuller, T. J., et al.
(author)
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Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis
- 2017
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In: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 152:8
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Journal article (peer-reviewed)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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| 26. |
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| 27. |
- Applegate, Patrick J., et al.
(author)
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An assessment of key model parametric uncertainties in projections of Greenland ice sheet behavior
- 2012
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In: The Cryosphere. - : Copernicus GmbH. - 1994-0416 .- 1994-0424. ; 6:3, s. 589-606
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Journal article (peer-reviewed)abstract
- Lack of knowledge about the values of ice sheet model input parameters introduces substantial uncertainty into projections of Greenland Ice Sheet contributions to future sea level rise. Computer models of ice sheet behavior provide one of several means of estimating future sea level rise due to mass loss from ice sheets. Such models have many input parameters whose values are not well known. Recent studies have investigated the effects of these parameters on model output, but the range of potential future sea level increases due to model parametric uncertainty has not been characterized. Here, we demonstrate that this range is large, using a 100-member perturbed-physics ensemble with the SICOPOLIS ice sheet model. Each model run is spun up over 125 000 yr using geological forcings and subsequently driven into the future using an asymptotically increasing air temperature anomaly curve. All modeled ice sheets lose mass after 2005 AD. Parameters controlling surface melt dominate the model response to temperature change. After culling the ensemble to include only members that give reasonable ice volumes in 2005 AD, the range of projected sea level rise values in 2100 AD is similar to 40 % or more of the median. Data on past ice sheet behavior can help reduce this uncertainty, but none of our ensemble members produces a reasonable ice volume change during the mid-Holocene, relative to the present. This problem suggests that the model's exponential relation between temperature and precipitation does not hold during the Holocene, or that the central-Greenland temperature forcing curve used to drive the model is not representative of conditions around the ice margin at this time (among other possibilities). Our simulations also lack certain observed physical processes that may tend to enhance the real ice sheet's response. Regardless, this work has implications for other studies that use ice sheet models to project or hindcast the behavior of the Greenland Ice Sheet.
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| 28. |
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| 29. |
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| 30. |
- Ernakovich, J. G., et al.
(author)
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Is A Common Goal A False Hope in Convergence Research? : Opportunities and Challenges of International Convergence Research to Address Arctic Change
- 2021
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In: Earth's Future. - : American Geophysical Union (AGU). - 2328-4277. ; 9:5
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Journal article (peer-reviewed)abstract
- The Arctic faces multiple pressures including climate change, shifting demographics, human health risks, social justice imbalances, governance issues, and expanding resource extraction. A convergence of academic disciplines—such as natural and social sciences, engineering and technology, health and medicine—and international perspectives is required to meaningfully contribute to solving the challenges of Arctic peoples and ecosystems. However, successfully carrying out convergent, international research and education remains a challenge. Here, lessons from the planning phase of a convergence research project concerned with the health of Arctic waters developed by the Arctic Science IntegrAtion Quest (ASIAQ) are discussed. We discuss our perspective on the challenges, as well as strategies for success, in convergence research as gained from the ASIAQ project which assembled an international consortium of researchers from disparate disciplines representing six universities from four countries (Sweden, Japan, Russia, and the United States) during 2018–2020.
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| 31. |
- Gadea, A, et al.
(author)
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Hindered E4 decay of the 12(+) yrast trap in Fe-52
- 2005
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 619:1-2, s. 88-94
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Journal article (peer-reviewed)abstract
- The gamma decay of the 12(+) yrast trap in Fe-52 has been measured for the first time. The two E4 gamma-branches to the 8(+) states are hindered with respect to other B(E4) reduced transition probabilities measured in the f(7/2) shell. The interpretation of the data is given in the full pf shell model framework, comparing the results obtained with different residual interactions. It is shown that measurements of hexadecapole transition probabilities constitute a powerful tool in discriminating the correct configuration of the involved wavefunctions.
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| 32. |
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| 33. |
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| 35. |
- Kirchner, Nina, et al.
(author)
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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
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In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 147, s. 136-147
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Journal article (peer-reviewed)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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| 36. |
- Kirchner, Nina, et al.
(author)
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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
-
In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 135, s. 103-114
-
Research review (peer-reviewed)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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| 37. |
- Kirchner, Nina, et al.
(author)
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Statistical modeling of a former Arctic Ocean ice shelf complex using Antarctic analogies
- 2013
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In: Journal of Geophysical Research: Earth Surface. - : American Geophysical Union (AGU). - 2169-9003. ; 118:2, s. 1105-1117
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Journal article (peer-reviewed)abstract
- Geophysical mapping and coring of the central Arctic Ocean seafloor provide evidence for repeated occurrences of ice sheet/ice shelf complexes during previous glacial periods. Several ridges and bathymetric highs shallower than present water depths of approximate to 1000m show signs of erosion from deep-drafting (armadas of) icebergs, which originated from thick outlet glaciers and ice shelves. Mapped glacigenic landforms and dates of cored sediments suggest that the largest ice shelf complex was confined to the Amerasian sector of the Arctic Ocean during Marine Isotope Stage (MIS) 6. However, the spatial extent of ice shelves can not be well reconstructed from occasional groundings on bathymetric highs. Therefore, we apply a statistical approach to provide independent support for an extensive MIS 6 ice shelf complex, which previously was inferred only from interpretation of geophysical and geological data. Specifically, we assess whether this ice shelf complex comprises a likely source of the deep-draft icebergs responsible for the mapped scour marks. The statistical modeling is based on exploiting relations between contemporary Antarctic ice shelves and their local physical environments and the assumption that Arctic Ocean MIS6 ice shelves scale similarly. Analyzing ice thickness data along the calving front of contemporary ice shelves, a peak over threshold method is applied to determine sources of deep-drafting icebergs in the Arctic Ocean MIS6 ice shelf complex. This approach is novel to modeling Arctic paleoglacial configurations. Predicted extreme calving front drafts match observed deep-draft iceberg scours if the ice shelf complex is sufficiently large.
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| 38. |
- Stokes, Chris R., et al.
(author)
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On the reconstruction of palaeo-ice sheets : Recent advances and future challenges
- 2015
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In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 125, s. 15-49
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Research review (peer-reviewed)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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| 39. |
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| 40. |
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| 41. |
- Blideanu, V., et al.
(author)
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Nucleon-induced reactions at intermediate energies : New data at 96 MeV and theoretical status
- 2004
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 70:1, s. 014607-
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Journal article (peer-reviewed)abstract
- Double-differential cross sections for light charged particle production (up to A=4) were measured in 96 MeV neutron-induced reactions, at the TSL Laboratory Cyclotron in Uppsala (Sweden). Measurements for three targets, Fe, Pb, and U, were performed using two independent devices, SCANDAL and MEDLEY. The data were recorded with low-energy thresholds and for a wide angular range (20°–160°). The normalization procedure used to extract the cross sections is based on the np elastic scattering reaction that we measured and for which we present experimental results. A good control of the systematic uncertainties affecting the results is achieved. Calculations using the exciton model are reported. Two different theoretical approaches proposed to improve its predictive power regarding the complex particle emission are tested. The capabilities of each approach is illustrated by comparison with the 96 MeV data that we measured, and with other experimental results available in the literature.
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| 42. |
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| 43. |
- Ciappina, M. F., et al.
(author)
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Double ionization of helium by ion impact analyzed using four-body Dalitz plots
- 2008
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In: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 77:6, s. 62706-
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Journal article (peer-reviewed)abstract
- We have performed experimental and theoretical studies of double ionization of helium by 6 MeV proton impact using a recently developed tool, four-particle Dalitz plots [Schulz , J. Phys. B 22, 3091 (2007)] which enable the representation of multiple differential cross sections as a function of all four fragments in a single spectrum without loss of any part of the total cross section. As a result, the relative importance of the various interactions between the fragments can be studied in great detail. Comparisons of experimental data with theoretical first-order calculations and simulations for the higher-order (TS-2) process show that elastic scattering between the heavy particles is surprisingly strong. For a large fraction of collision events, the final-state electron momenta are small compared to the momenta of the heavy particles. Our results suggest that an uncorrelated double ionization mechanism, involving two independent interactions of the projectile with both electrons, is significantly more important than previously expected for such fast collisions.
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| 44. |
- Clayton, Aled, et al.
(author)
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Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017
- 2018
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In: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 7
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Journal article (other academic/artistic)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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| 45. |
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| 46. |
- Duda, LC, et al.
(author)
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Polarized resonant inelastic X-ray scattering from single-crystal transition metal oxides
- 2000
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In: JOURNAL OF ELECTRON SPECTROSCOPY AND RELATED PHENOMENA. - : ELSEVIER SCIENCE BV. - 0368-2048. ; 110:1-3, s. 275-285
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Journal article (peer-reviewed)abstract
- Inelastic X-ray scattering of synchrotron radiation at core resonances has turned soft X-ray emission spectroscopy into a new tool for probing the electronic structure of transition metal (TM) oxides at high resolution. In contrast to ordinary fluorescenc
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| 47. |
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| 48. |
- Floriancic, Marius G., et al.
(author)
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Spatial variability in specific discharge and streamwater chemistry during low flows : Results from snapshot sampling campaigns in eleven Swiss catchments
- 2019
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In: Hydrological Processes. - : Wiley. - 0885-6087 .- 1099-1085. ; 33:22, s. 2847-2866
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Journal article (peer-reviewed)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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| 49. |
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| 50. |
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