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Sökning: WFRF:(Stephan Elisabeth)

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1.
  • Kassemeyer, Stephan, et al. (författare)
  • Femtosecond free-electron laser x-ray diffraction data sets for algorithm development
  • 2012
  • Ingår i: Optics Express. - 1094-4087. ; 20:4, s. 4149-4158
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe femtosecond X-ray diffraction data sets of viruses and nanoparticles collected at the Linac Coherent Light Source. The data establish the first large benchmark data sets for coherent diffraction methods freely available to the public, to bolster the development of algorithms that are essential for developing this novel approach as a useful imaging technique. Applications are 2D reconstructions, orientation classification and finally 3D imaging by assembling 2D patterns into a 3D diffraction volume.
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2.
  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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3.
  • Lu, Yingchang, et al. (författare)
  • New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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4.
  • Miehlke, Stephan, et al. (författare)
  • European guidelines on microscopic colitis : United European Gastroenterology (UEG) and European Microscopic Colitis Group (EMCG) statements and recommendations
  • 2021
  • Ingår i: United European Gastroenterology journal. - : Sage Publications. - 2050-6406 .- 2050-6414. ; 9:1, s. 13-37
  • Forskningsöversikt (refereegranskat)abstract
    • Introduction: Microscopic colitis is a chronic inflammatory bowel disease characterised by normal or almost normal endoscopic appearance of the colon, chronic watery, non-bloody diarrhoea and distinct histological abnormalities, which identify three histological subtypes, the collagenous colitis, the lymphocytic colitis and the incomplete microscopic colitis. With ongoing uncertainties and new developments in the clinical management of microscopic colitis, there is a need for evidence-based guidelines to improve the medical care of patients suffering from this disorder.Methods: Guidelines were developed by members from the European Microscopic Colitis Group and United European Gastroenterology in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists, pathologists and basic scientists, and voted upon using the Delphi method.Results: These guidelines provide information on epidemiology and risk factors of microscopic colitis, as well as evidence-based statements and recommendations on diagnostic criteria and treatment options, including oral budesonide, bile acid binders, immunomodulators and biologics. Recommendations on the clinical management of microscopic colitis are provided based on evidence, expert opinion and best clinical practice.Conclusion: These guidelines may support clinicians worldwide to improve the clinical management of patients with microscopic colitis.
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5.
  • Speliotes, Elizabeth K., et al. (författare)
  • Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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6.
  • Watson, Hunna J., et al. (författare)
  • Common Genetic Variation and Age of Onset of Anorexia Nervosa
  • 2022
  • Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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7.
  • Zabana, Yamile, et al. (författare)
  • Pathogenesis Of Microscopic Colitis : A Systematic Review
  • 2022
  • Ingår i: Journal of Crohn's & Colitis. - Oxford, United Kingdom : Elsevier. - 1873-9946 .- 1876-4479. ; 16:1, s. 143-161
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Whereas the exact aetiology of microscopic colitis [MC] remains unknown, a dysregulated immune response to luminal factors or medications is the most accepted pathogenesis hypothesis.Methods: We conducted a systematic review of the pathogenesis of MC. We applied the Joanna Briggs Institute methodologies and the PRISMA statement for the reporting of systematic reviews [PROSPERO Trial Identifier: CRD42020145008]. Populations, Exposure of interest, and Outcome [PEO] questions were used to explore the following topics in MC: 1] intestinal luminal factors; 2] autoimmunity; 3] innate immunity; 4] adaptive immunity; 5] extracellular matrix; 6] genetic risk factors; and 7] mechanism of diarrhoea. A search was done in PubMed, Embase, and Web of Science up to February 2020. A narrative description was performed explaining the findings for each aspect of MC aetiopathogenesis.Results: Thirty-eight documents provided evidence for PEO1, 100 for PEO2, 72 for PEO3 and 4, 38 for PEO5, 20 for PEO6, and 23 for PEO7. The majority of documents were cohorts, case reports, and case series, with a few case-control and some experimental studies. Consistency among data provided by different studies was considered to support pathogenetic hypotheses. MC is a multifactorial disease believed to involve innate and adaptive immune responses to luminal factors, genetic risk, autoimmunity, and extracellular matrix alterations, all contributing by varied mechanisms to watery diarrhoea.Conclusions: This is the first systematic review on the aetiology of MC supporting the notion that MC is a multifactorial disease. However, high-profile studies are lacking, and most evidence derives from small heterogeneous studies.
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8.
  • Ahrens, Maryon, et al. (författare)
  • Multi-messenger Observations of a Binary Neutron Star Merger
  • 2017
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 848:2
  • Tidskriftsartikel (refereegranskat)abstract
    • On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of similar to 1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg(2) at a luminosity distance of 40(-8)(+8) Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 M-circle dot. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at similar to 40 Mpc) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over similar to 10 days. Following early non-detections, X-ray and radio emission were discovered at the transient's position similar to 9 and similar to 16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta.
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9.
  • Archambault, Alexi N., et al. (författare)
  • Cumulative Burden of Colorectal Cancer Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer
  • 2020
  • Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:5, s. 1274-1286.e12
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 x 10(-5)). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings.CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
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10.
  • Bader, Erik, et al. (författare)
  • Identification of proliferative and mature beta-cells in the islets of Langerhans
  • 2016
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 535:7612, s. 430-
  • Tidskriftsartikel (refereegranskat)abstract
    • Insulin-dependent diabetes is a complex multifactorial disorder characterized by loss or dysfunction of beta-cells. Pancreatic beta-cells differ in size, glucose responsiveness, insulin secretion and precursor cell potential(1-5); understanding the mechanisms that underlie this functional heterogeneity might make it possible to develop new regenerative approaches. Here we show that Fltp (also known as Flattop and Cfap126), a Wnt/planar cell polarity (PCP) effector and reporter gene(6), acts as a marker gene that subdivides endocrine cells into two subpopulations and distinguishes proliferation-competent from mature beta-cells with distinct molecular, physiological and ultrastructural features. Genetic lineage tracing revealed that endocrine subpopulations from Fltp-negative and -positive lineages react differently to physiological and pathological changes. The expression of Fltp increases when endocrine cells cluster together to form polarized and mature 3D islet mini-organs(7-9). We show that 3D architecture and Wnt/PCP ligands are sufficient to trigger beta-cell maturation. By contrast, the Wnt/PCP effector Fltp is not necessary for beta-cell development, proliferation or maturation. We conclude that 3D architecture and Wnt/PCP signalling underlie functional beta-cell heterogeneity and induce beta-cell maturation. The identification of Fltp as a marker for endocrine subpopulations sheds light on the molecular underpinnings of islet cell heterogeneity and plasticity and might enable targeting of endocrine subpopulations for the regeneration of functional beta-cell mass in diabetic patients.
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11.
  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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12.
  • Betker, Marie, et al. (författare)
  • Sprayed Hybrid Cellulose Nanofibril-Silver Nanowire Transparent Electrodes for Organic Electronic Applications
  • 2023
  • Ingår i: ACS Applied Nano Materials. - : American Chemical Society (ACS). - 2574-0970. ; 6:14, s. 13677-13688
  • Tidskriftsartikel (refereegranskat)abstract
    • In times of climate change and resource scarcity, researchers are aiming to find sustainable alternatives to synthetic polymers for the fabrication of biodegradable, eco-friendly, and, at the same time, high-performance materials. Nanocomposites have the ability to combine several favorable properties of different materials in a single device. Here, we evaluate the suitability of two kinds of inks containing silver nanowires for the fast, facile, and industrial-relevant fabrication of two different types of cellulose-based silver nanowire electrodes via layer-by-layer spray deposition only. The Type I electrode has a layered structure, which is composed of a network of silver nanowires sprayed on top of a cellulose nanofibrils layer, while the Type II electrode consists of a homogeneous mixture of silver nanowires and cellulose nanofibrils. A correlation between the surface structure, conductivity, and transparency of both types of electrodes is established. We use the Haacke figure of merit for transparent electrode materials to demonstrate the favorable influence of cellulose nanofibrils in the spray ink by identifying Type II as the electrode with the lowest sheet resistance (minimum 5 ± 0.04 Ω/sq), while at the same time having a lower surface roughness and shorter fabrication time than Type I. Finally, we prove the mechanical stability of the Type II electrode by bending tests and its long-time stability under ambient conditions. The results demonstrate that the mixed spray ink of silver nanowires and cellulose nanofibrils is perfectly suitable for the fast fabrication of highly conductive organic nanoelectronics on an industrial scale.
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13.
  • Borgehammar, Stephan, et al. (författare)
  • Liturgical Representations of Saint Birgitta : The Versified Offices by Birgerus Gregorii and Nicolaus Hermanni
  • 2021. - 1
  • Ingår i: Swedish Students at the University of Paris in the Middle Ages, I : Origin, Studies, Carriers, Achievements - Origin, Studies, Carriers, Achievements. - 1103-7989. - 9789188568793 ; 28, s. 620-647
  • Bokkapitel (refereegranskat)abstract
    • Slutsatsen av denna undersökning är att Birger Gregersson has skrivit ett skickligt utformat, något pompöst officium som förmedlar en bild av Birgitta som ett helt och hållet universellt helgon och samtidigt en utsökt prydnad för sitt eget land. Nils Hermansson har å sin sida givit oss en Birgitta som i sitt liv och sin undervisning är en trogen dotter till Jungfru Maria och en kyrkolärare. Nils Hermansson avsåg möjligen att hans officium skulle användas inom birgittinorden medan Birger Gregersson skrev sitt för allmänt bruk i Sverige. I praktiken kom de att användas i olika stift i Norden och deras beståndsdelar kom ofta att blandas. I vilken mån de båda författarna hade glädje av sin utbildning vid universitetet i Paris när de skrev sina officier förblir en öppen fråga.
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14.
  • Bülck, Cynthia, et al. (författare)
  • Proteolytic processing of galectin-3 by meprin metalloproteases is crucial for host-microbiome homeostasis
  • 2023
  • Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 9:13
  • Tidskriftsartikel (refereegranskat)abstract
    • The metalloproteases meprin α and meprin β are highly expressed in the healthy gut but significantly decreased in inflammatory bowel disease, implicating a protective role in mucosal homeostasis. In the colon, meprin α and meprin β form covalently linked heterodimers tethering meprin α to the plasma membrane, therefore presenting dual proteolytic activity in a unique enzyme complex. To unravel its function, we applied N-terminomics and identified galectin-3 as the major intestinal substrate for meprin α/β heterodimers. Galectin-3-deficient and meprin α/β double knockout mice show similar alterations in their microbiome in comparison to wild-type mice. We further demonstrate that meprin α/β heterodimers differentially process galectin-3 upon bacterial infection, in germ-free, conventionally housed (specific pathogen-free), or wildling mice, which in turn regulates the bacterial agglutination properties of galectin-3. Thus, the constitutive cleavage of galectin-3 by meprin α/β heterodimers may play a key role in colon host-microbiome homeostasis.
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15.
  • Castellani, Carlo, et al. (författare)
  • Benchmarks for Cystic Fibrosis carrier screening: A European consensus document
  • 2010
  • Ingår i: Journal of Cystic Fibrosis. - : Elsevier BV. - 1873-5010 .- 1569-1993. ; 9:3, s. 165-178
  • Forskningsöversikt (refereegranskat)abstract
    • This paper presents an overview of the conclusions from an international conference convened to address current issues related to the provision of Cystic Fibrosis carrier screening within Europe. Consensus was not aimed at stating whether such a programme should be implemented. Instead the focus was to provide a framework for countries and agencies who are considering or planning its establishment. The general principles and target population of Cystic Fibrosis carrier screening, advantages and disadvantages, health economics, monitoring and future evaluative and research directions were covered. A range of screening strategies have been assessed and compared: pre-conceptional and prenatal screening; individual and couple screening; sequential and simultaneous sampling or testing. Furthermore, technical issues were examined with respect to the choice of the panel of mutations, its detection rate, sensitivity, management of intermediate 'at-risk' couples, screening approach to different populations and ethnic minorities, and assurance of laboratory quality control. The consensus statement also aims to establish the benchmarks for communicating with health care providers, the general public and potential and actual participants before and after the genetic test. (C) 2010 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
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16.
  • Christiansson, Elisabeth (författare)
  • Kyrklig och social reform : motiveringar till diakoni 1845-1965
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The main purpose of this dissertation is to see how proponents of diaconia justified the establishment of three Swedish diaconal institutions: Diaconissanstalten 1851 (The Institution for Deaconesses, Stockholm, now Ersta diakonissällskap/Ersta Association for Diaconal Work), Stockholms Stadsmission 1853 (The Stockholm City Mission) and Svenska Diakonanstalten 1898 (The Swedish institution for Deacons, first in Gävle, from 1905 in Stockholm, now Stiftelsen Stora Sköndal/The Stora Sköndal Foundation). Included is also a study of how diaconal work was justified in Sweden in the post-war period, a time when religious neutrality within health care and education was high on the political agenda. An additional purpose is to discuss how these justifications are related to the modern discourse of social work. The primary source material consists of journals that voiced the opinions of the aforementioned diaconal institutions, Parliamentary records and newspaper articles. This material is culled for justificatory arguments. The set of justifications found in each setting is discussed from three angles: theology, ideology and gender roles. The dissertation shows that justifications for diaconal institutions have varied over time, but that all the initiatives have reformism in common. Diaconal institutions are vindicated as projects for social and ecclesial improvement and not merely as instruments for the material or spiritual well-being of individuals. This reformist stance contrasts with how responsibility for one's neighbour was justified in pre-industrial Sweden: as a duty performed within a static society. Reformism in diaconia is in this dissertation looked upon as an early example of modernisation. The justifications of diaconal work found in the source material are the following. In the 1850s diaconal work was justified theologically as a means of revival and evangelism. The ideological stance of its proponents was social conservative. Female diaconia was propagated because women were regarded as particularly apt for nursing and caring. Around the year 1900 diaconal work was mainly a question of reinforcing the Church of Sweden as the spiritual and moral foundation of Swedish society. Ideologically, diaconia (both male and female) was still social conservative. The justification of male diaconia was that supposedly male characteristics could be made useful in a lay ministry at the service of the Church of Sweden. In post-war Sweden the basis for justifications shifted to social liberalism and a theology of stewardship.
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17.
  • Docherty, Anna R, et al. (författare)
  • GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
  • 2023
  • Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
  • Tidskriftsartikel (refereegranskat)abstract
    • Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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18.
  • Edelbro, Catrin, et al. (författare)
  • European initiative on CDIO in raw material programmes
  • 2017
  • Ingår i: Proceedings of the 13th International CDIO Conference in Calgary. - Calgary.
  • Konferensbidrag (refereegranskat)abstract
    • One of five Knowledge and Innovation Communities (KICs), was launched in Europe in 2014and has its focus on exploration, extraction, mineral processing, metallurgy, recycling andmaterial substitution of raw materials. To reach the vision, where the European Union’sindustrial strength is based on a cost-efficient, secure, sustainable supply and use of rawmaterials, a new generation of skilled people entering industry, universities and researchneeds to be developed. Today’s technical MSc graduates in raw materials and especiallyprimary resources (i.e. exploration, extraction, mining and mineral processing and metallurgy)best suits large companies where they often act as specialists and experts. For small tomedium enterprises as well as for our future engineers other skills than technical arenecessary. As a part of the KIC Raw Materials, the education project “The implementation ofCDIO in raw material programmes” started in 2016. The project focuses, during 2016-2017,on (WP1) faculty- and (WP2) pilot case development. There are no academic institutes inEurope that have yet applied CDIO for primary resource related MSc programmes. Thispaper describes an education project within the KIC Raw material and presents key outputswith implementing CDIO in mining and metallurgy related programmes.
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19.
  • Frantz, Laurent A. F., et al. (författare)
  • Ancient pigs reveal a near-complete genomic turnover following their introduction to Europe
  • 2019
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:35, s. 17231-17238
  • Tidskriftsartikel (refereegranskat)abstract
    • Archaeological evidence indicates that pig domestication had begun by similar to 10,500 y before the present ( BP) in the Near East, and mitochondrial DNA ( mtDNA) suggests that pigs arrived in Europe alongside farmers similar to 8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.
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20.
  • Gillberg, Christopher, 1950, et al. (författare)
  • Autism Under Age 3 Years: A Clinical Study of 28 Cases Referred for Autistic Symptoms in Infancy
  • 1990
  • Ingår i: Journal of Child Psychology and Psychiatry and Allied Disciplines. - : Wiley. - 0021-9630 .- 1469-7610. ; 31:6, s. 921-934
  • Tidskriftsartikel (refereegranskat)abstract
    • Twenty-eight children referred with a preliminary diagnosis of autistic disorder under age 3 yrs were extensively examined from the neuropsychiatric point of view and followed up for several months to several years. A diagnosis of autistic disorder was confirmed in 75% of the cases. A variety of associated medical conditions was identified. It was concluded that autism can be diagnosed in a substantial proportion of cases before age 3 yrs and that the neurobiological background is similar to that seen in older autistic children.
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21.
  • Giunta, Riccardo E, et al. (författare)
  • ESPRAS Survey on Breast Reconstruction in Europe. : ESPRAS Umfrage zur Brustrekonstruktion in Europa.
  • 2021
  • Ingår i: Handchirurgie, Mikrochirurgie, plastische Chirurgie : Organ der Deutschsprachigen Arbeitsgemeinschaft fur Handchirurgie : Organ der Deutschsprachigen Arbeitsgemeinschaft fur Mikrochirurgie der Peripheren Nerven und Gefasse : Organ der V.... - : Georg Thieme Verlag KG. - 1439-3980. ; 53:4, s. 340-348
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Leadership Forum (ELF) of the European Society of Plastic, Reconstructive and Aesthetic Surgery (ESPRAS) previously identified the need for harmonisation of breast reconstruction standards in Europe, in order to strengthen the role of plastic surgeons. This study aims to survey the status, current trends and potential regional differences in the practice of breast reconstruction in Europe, with emphasis on equity and access.A largescale web-based questionnaire was sent to consultant plastic and reconstructive surgeons, who are experienced in breast reconstruction and with understanding of the national situation in their country. Suitable participants were identified via the Executive Committee (ExCo) of ESPRAS and national delegates of ESPRAS. The results were evaluated and related to evidence-based literature.A total of 33 participants from 29 European countries participated in this study. Overall, the incidence of breast reconstruction was reported to be relatively low across Europe, comparable to other large geographic regions, such as North America. Equity of provision and access to breast reconstruction was distributed evenly within Europe, with geographic regions potentially affecting the type of reconstruction offered. Standard practices with regard to radiotherapy differed between countries and a clear demand for European guidelines on breast reconstruction was reported.This study identified distinct lack of consistency in international practice patterns across European countries and a strong demand for consistent European guidance. Large-scale and multi-centre European clinical trials are required to further elucidate the presented areas of interest and to define European standard operating procedures.
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22.
  • Herbert, Juan Herrera, et al. (författare)
  • Implementation of CDIO Initiative In New European Education Programs in Raw Materials
  • 2017
  • Ingår i: EDULEARN17 Proceedings. - 2340-1117. - 9788469737774 ; , s. 6518-6526
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • EIT Raw Materials, one of the six Knowledge and Innovation Communities (KICs) initiated by the EIT (European Institute of Innovation and Technology) and funded by the European Commission, has the mission to boost competitiveness, growth and attractiveness of the European raw materials sector via radical innovation and guided entrepreneurship. It aims to significantly enhance innovation in the raw materials sector by the sharing of knowledge, information and expertise. This must generate a significant impact on European competitiveness and employment by driving and fostering innovation and empowering students, entrepreneurs and education partners driving toward the circular economy.To reach the vision, where the European Union’s industrial strength is based on a cost-efficient, secure, sustainable supply and use of raw materials, a new generation of skilled people entering industry, universities and research needs to be developed. Today’s technical MSc graduates in raw materials and especially primary resources (i.e. exploration, extraction, mining and mineral processing and metallurgy) meet the technical standards required by the raw materials industry across the full raw materials value chain and best suits large companies where they often act as specialists and experts. For small to medium enterprises as well as for our future engineers, other skills than technical are necessary.EIT Raw Materials will educate people that will have an intra- and entrepreneurial mind-set and will be able to develop their functions in new working environments, fostering the entrepreneurial and innovation skills, knowledge and attitudes needed for the entre- and intrapreneurs of tomorrowThe CDIO™ INITIATIVE is an innovative educational framework for producing the next generation of engineers. The framework provides students with an education stressing engineering fundamentals set in the context of Conceiving — Designing — Implementing — Operating (CDIO) real-world systems and products. There are no academic institutes in Europe that have yet applied CDIO for primary resource related MSc programs. Within the KIC EIT Raw Materials Academy, the overarching brand of all the KIC’s education activities are created in order to stimulate education activities and foster new ways of learning and teaching; an approved education project is focusing on the implementation of the CDIO methodology in primary resources linked programs. The project started in 2016 and focuses on faculty and pilot case development and the contributing partners are from academia, industry and research institutes. This project focuses on faculty development for an active and experimental learning by teaching the “technical” faculty through CDIO linked courses (entrepreneurship, business, etc.), communicative workshops, inspiration lectures and by involving the “business and entrepreneurial” faculty in exploration, mining, mineral processing and metallurgy related issues also through curriculum and pilot cases developed together with the industry.This paper describes how this education project is being developed within the EIT Raw Materials and will give an overview of the needed skillset of future engineers demanded in the Raw Materials primary sector. It presents key outputs about already developed and implemented activities in mining engineering and metallurgy related programs.
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23.
  • Holm-Waters, Susanna, et al. (författare)
  • Preclinical Pharmacology of 2-(3-Fluoro-5-Methanesulfonyl-phenoxy)Ethyl (Propyl)amine (IRL790), a Novel Dopamine Transmission Modulator for the Treatment of Motor and Psychiatric Complications in Parkinson Disease
  • 2020
  • Ingår i: Journal of Pharmacology and Experimental Therapeutics. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0022-3565 .- 1521-0103. ; 374:1, s. 113-125
  • Tidskriftsartikel (refereegranskat)abstract
    • IRL790 ([2-(3-fluoro-5-methanesulfonylphenoxy)ethyl](propyl)amine, mesdopetam) is a novel compound in development for the clinical management of motor and psychiatric disabilities in Parkinson disease. The discovery of IRL790 was made applying a systems pharmacology approach based on in vivo response profiling. The chemical design idea was to develop a new type of DA D3/D2 receptor type antagonist built on agonist rather than antagonist structural motifs. We hypothesized that such a dopamine antagonist with physicochemical properties similar to agonists would exert antidyskinetic and antipsychotic effects in states of dysregulated dopaminergic signaling while having little negative impact on physiologic dopamine transmission and, hence, minimal liability for side effects related to dopamine-dependent functions. At the level of in vivo pharmacology, IRL790 displays balancing effects on aberrant motor phenotypes, reducing L-DOPA-induced dyskinesias in the rodent 6-hydroxydopamine lesion model and reducing psychostimulant-induced locomotor hyperactivity elicited by pretreatment with either d-amphetamine or dizocilpine, without negatively impacting normal motor performance. Thus, IRL790 has the ability to normalize the behavioral phenotype in hyperdopaminergic as well as hypoglutamatergic states. Neurochemical and immediate early gene (IEG) response profiles suggest modulation of DA neurotransmission, with some features, such as increased DA metabolites and extracellular DA, shared by atypical antipsychotics and others, such as increased frontal cortex IEGs, unique to IRL790. IRL790 also increases extracellular levels of acetylcholine in the prefrontal cortex and ventral hippocampus. At the receptor level, IRL790 appears to act as a preferential DA D3 receptor antagonist. Computational docking studies support preferential affinity at D3 receptors with an agonist-like binding mode. SIGNIFICANCE STATEMENT This paper reports preclinical pharmacology along with molecular modeling results on IRL790, a novel compound in clinical development for the treatment of motor and psychiatric complications in advanced Parkinson disease. IRL790 is active in models of perturbed dopaminergic and glutamatergic signaling, including rodent 6-hydroxydopamine L-DOPA-induced dyskinesias and psychostimulant-induced hyperactivity, in a dose range that does not impair normal behavior. This effect profile is attributed to interactions at dopamine D2/D3 receptors, with a 6- to 8-fold preference for the D3 subtype.
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24.
  • Kehoe, Laura, et al. (författare)
  • Make EU trade with Brazil sustainable
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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25.
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26.
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27.
  • Lembrechts, Jonas J., et al. (författare)
  • Global maps of soil temperature
  • 2022
  • Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:9, s. 3110-3144
  • Tidskriftsartikel (refereegranskat)abstract
    • Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0–5 and 5–15cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean=3.0±2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6±2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (−0.7±2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications.
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28.
  • Lorenzen, Eline D., et al. (författare)
  • Species-specific responses of Late Quaternary megafauna to climate and humans
  • 2011
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 479:7373, s. 359-364
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.
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29.
  • Längin, Matthias, et al. (författare)
  • Xenografts Show Signs of Concentric Hypertrophy and Dynamic Left Ventricular Outflow Tract Obstruction after Orthotopic Pig-to-baboon Heart Transplantation
  • 2023
  • Ingår i: Transplantation. - 0041-1337. ; 107:12, s. 328-338
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Orthotopic cardiac xenotransplantation has seen substantial advancement in the last years and the initiation of a clinical pilot study is close. However, donor organ overgrowth has been a major hurdle for preclinical experiments, resulting in loss of function and the decease of the recipient. A better understanding of the pathogenesis of organ overgrowth after xenotransplantation is necessary before clinical application. Methods. Hearts from genetically modified (GGTA1-KO, hCD46/hTBM transgenic) juvenile pigs were orthotopically transplanted into male baboons. Group I (control, n = 3) received immunosuppression based on costimulation blockade, group II (growth inhibition, n = 9) was additionally treated with mechanistic target of rapamycin inhibitor, antihypertensive medication, and fast corticoid tapering. Thyroid hormones and insulin-like growth factor 1 were measured before transplantation and before euthanasia, left ventricular (LV) growth was assessed by echocardiography, and hemodynamic data were recorded via a wireless implant. Results. Insulin-like growth factor 1 was higher in baboons than in donor piglets but dropped to porcine levels at the end of the experiments in group I. LV mass increase was 10-fold faster in group I than in group II. This increase was caused by nonphysiological LV wall enlargement. Additionally, pressure gradients between LV and the ascending aorta developed, and signs of dynamic left ventricular outflow tract (LVOT) obstruction appeared. Conclusions. After orthotopic xenotransplantation in baboon recipients, untreated porcine hearts showed rapidly progressing concentric hypertrophy with dynamic LVOT obstruction, mimicking hypertrophic obstructive cardiomyopathy in humans. Antihypertensive and antiproliferative drugs reduced growth rate and inhibited LVOT obstruction, thereby preventing loss of function.
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30.
  • Mansoor, Rashid, et al. (författare)
  • Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data
  • 2022
  • Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPlasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia.MethodsIndividual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7.ResultsA total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39-3.05], p < 0.001).ConclusionsIn patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery.
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31.
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32.
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33.
  • Mattsson, Niklas, 1979, et al. (författare)
  • The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers.
  • 2011
  • Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 7:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program.
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34.
  • Mullins, Niamh, et al. (författare)
  • Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
  • 2022
  • Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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35.
  • Mullins, Niamh, et al. (författare)
  • GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores
  • 2019
  • Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 176:8, s. 651-660
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium.Methods: The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders.Results: Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%).Conclusions: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.
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36.
  • Muscaritoli, Maurizio, et al. (författare)
  • ESPEN practical guideline : Clinical Nutrition in cancer
  • 2021
  • Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 40:5, s. 2898-2913
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: This practical guideline is based on the current scientific ESPEN guidelines on nutrition in cancer patients. Methods: ESPEN guidelines have been shortened and transformed into flow charts for easier use in clinical practice. The practical guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with cancer. Results: A total of 43 recommendations are presented with short commentaries for the nutritional and metabolic management of patients with neoplastic diseases. The disease-related recommendations are preceded by general recommendations on the diagnostics of nutritional status in cancer patients. Conclusion: This practical guideline gives guidance to health care providers involved in the management of cancer patients to offer optimal nutritional care.
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37.
  • Nass, Karol, et al. (författare)
  • Indications of radiation damage in ferredoxin microcrystals using high-intensity X-FEL beams
  • 2015
  • Ingår i: Journal of Synchrotron Radiation. - 0909-0495 .- 1600-5775. ; 22:2, s. 225-238
  • Tidskriftsartikel (refereegranskat)abstract
    • Proteins that contain metal cofactors are expected to be highly radiation sensitive since the degree of X-ray absorption correlates with the presence of high-atomic-number elements and X-ray energy. To explore the effects of local damage in serial femtosecond crystallography (SFX), Clostridium ferredoxin was used as a model system. The protein contains two [4Fe–4S] clusters that serve as sensitive probes for radiation-induced electronic and structural changes. High-dose room-temperature SFX datasets were collected at the Linac Coherent Light Source of ferredoxin microcrystals. Difference electron density maps calculated from high-dose SFX and synchrotron data show peaks at the iron positions of the clusters, indicative of decrease of atomic scattering factors due to ionization. The electron density of the two [4Fe–4S] clusters differs in the FEL data, but not in the synchrotron data. Since the clusters differ in their detailed architecture, this observation is suggestive of an influence of the molecular bonding and geometry on the atomic displacement dynamics following initial photoionization. The experiments are complemented by plasma code calculations.
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38.
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39.
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40.
  • Pomp, Stephan, et al. (författare)
  • A Medley with over ten years of (mostly) light-ion production measurements at The Svedberg Laboratory
  • 2010
  • Ingår i: EFNUDAT. - : EDP Sciences. - 9782759805853 ; , s. 07013-
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Over the past years an experimental programme has been run at the neutron beam of The Svedberg Laboratory with the aim to study light-ion production induced by 96 and 175 MeV neutrons for a wide variety of targets. The measurements have been conducted using the Medley facility which allows measurement of p, d, t, He-3 and alpha production at fixed angles (from 20 to 160 degrees in steps of 20 degrees) over a wide dynamic range. An overview of the results obtained at the now finished campaign at 96 MeV will be given. Since 2007 we have been running at 175 MeV with C, O, Si, Fe, Bi and U as target material. Preliminary results from these measurements will be shown and compared to model calculations with Talys-1.2. We also summarize the Medley measurements of elastic np and nd scattering and of angular distributions of fission fragments.
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41.
  • Ried, Janina S., et al. (författare)
  • A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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42.
  • Rieder, Stephan R., et al. (författare)
  • Dynamic modelling of the long term behaviour of cadmium, lead and mercury in Swiss forest soils using CHUM-AM
  • 2014
  • Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 468, s. 864-876
  • Tidskriftsartikel (refereegranskat)abstract
    • The applicability of the dynamic soil model CHUM-AM was tested to simulate concentrations of Cd, Pb and Hg in five Swiss forest soils. Soil cores of up to 50 cm depth were sampled and separated into two defined soil layers. Soil leachates were collected below the litter by zero-tension lysimeters and at 15 and 50 cm soil depths by tension lysimeters over two years. The concentrations of Cd, Pb and Hg in the solid phase and soil solution were measured by ICP-MS (Cd, Pb) or CV-AFS (Hg). Measured metal concentrations were compared with modelled concentrations using CHUM-AM. Additionally we ran the model with three different deposition scenarios (current deposition; maximum acceptable deposition according to the Swiss ordinance on Air Pollution Control; critical loads according to CLRTAP) to predict metal concentrations in the soils for the next 1000 years. Assuming current loads concentrations of Cd and Pb showed varying trends (increasing/decreasing) between the soils. Soils rich in organic carbon or with a high pH value showed increasing trends in Cd and Pb concentrations whereas the concentrations in the other soils decreased. In contrast Hg concentrations are predicted to further increase in all soils. Critical limits for Pb and Hg will partly be exceeded by current loads or by the critical loads proposed by the CLRTAP but the critical limits for Cd will rarely be reached within the next 1000 years. In contrast, maximal acceptable deposition will partly lead to concentrations above the critical limits for Pb in soils within the next 400 years, whereas the acceptable deposition of Cd will not lead to concentrations above the proposed critical limits. In conclusion the CHUM-AM model is able to accurately simulate heavy metal (Cd, Pb and Hg) concentrations in Swiss forest soils of various soil properties.
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43.
  • Rodriguez-Palmero, Agusti, et al. (författare)
  • DLG4-related synaptopathy : a new rare brain disorder
  • 2021
  • Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600 .- 1530-0366. ; 23:5, s. 888-899
  • Tidskriftsartikel (refereegranskat)abstract
    • PurposePostsynaptic density protein-95 (PSD-95), encoded by DLG4, regulates excitatory synaptic function in the brain. Here we present the clinical and genetic features of 53 patients (42 previously unpublished) with DLG4 variants.MethodsThe clinical and genetic information were collected through GeneMatcher collaboration. All the individuals were investigated by local clinicians and the gene variants were identified by clinical exome/genome sequencing.ResultsThe clinical picture was predominated by early onset global developmental delay, intellectual disability, autism spectrum disorder, and attention deficit–hyperactivity disorder, all of which point to a brain disorder. Marfanoid habitus, which was previously suggested to be a characteristic feature of DLG4-related phenotypes, was found in only nine individuals and despite some overlapping features, a distinct facial dysmorphism could not be established. Of the 45 different DLG4 variants, 39 were predicted to lead to loss of protein function and the majority occurred de novo (four with unknown origin). The six missense variants identified were suggested to lead to structural or functional changes by protein modeling studies.ConclusionThe present study shows that clinical manifestations associated with DLG4 overlap with those found in other neurodevelopmental disorders of synaptic dysfunction; thus, we designate this group of disorders as DLG4-related synaptopathy.
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44.
  • Rutemark, Christian, et al. (författare)
  • Requirement for complement in antibody responses is not explained by the classic pathway activator IgM
  • 2011
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 108:43, s. 17589-17590
  • Tidskriftsartikel (refereegranskat)abstract
    • Animals lacking complement factors C1q, C2, C3, or C4 have severely impaired Ab responses, suggesting a major role for the classic pathway. The classic pathway is primarily initiated by antigen-Ab complexes. Therefore, its role for primary Ab responses seems paradoxical because only low amounts of specific Abs are present in naive animals. A possible explanation could be that the classic pathway is initiated by IgM from naive mice, binding with sufficient avidity to the antigen. To test this hypothesis, a knock-in mouse strain, Cμ13, with a point mutation in the gene encoding the third constant domain of the μ-heavy chain was constructed. These mice produce IgM in which proline in position 436 is substituted with serine, a mutation previously shown to abrogate the ability of mouse IgM to activate complement. Unexpectedly, the Ab response to sheep erythrocytes and keyhole limpet hemocyanin in Cμ13 mice was similar to that in WT mice. Thus, although secreted IgM and the classic pathway activation are both required for the normal primary Ab response, this does not require that IgM activate C. This led us to test Ab responses in animals lacking one of three other endogenous activators of the classic pathway: specific intracellular adhesion molecule-grabbing nonintegrin R1, serum amyloid P component, and C-reactive protein. Ab responses were also normal in these animals.
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45.
  • Rødland, Elisabeth S., et al. (författare)
  • Analytical challenges and possibilities for the quantification of tire-road wear particles
  • 2023
  • Ingår i: TrAC. Trends in analytical chemistry. - : Elsevier. - 0165-9936 .- 1879-3142. ; 165:August
  • Tidskriftsartikel (refereegranskat)abstract
    • As one of the largest sources of microplastic particle emissions, tire-road wear particle mixtures (TRWPs) pose a potentially high threat to various environmental compartments. Their heterogenous properties, from varying particle size, density, shape, texture, elemental and chemical composition, cause chal-lenging analytical workflows. Current analytical methods for TRWP can be summarized in two main groups: single-particle-based and bulk-based methods. Both groups include a large variation of methods, with different demands for sampling and sample pre-treatment, and different possible outputs. This review provides an overview of the current analytical methods used for TRWP studies and in particularly quantifications, with focus on methods that have been peer-reviewed and tested for environmental samples. The review presents current possibilities and limitations with the different analytical ap-proaches, as well as highlighting gaps in the current TRWP knowledge and information needed to move this research field forward.
  •  
46.
  • Tobiasson, Magnus, et al. (författare)
  • Patient-Specific Measurable Residual Disease Markers Predict Outcome in Patients With Myelodysplastic Syndrome and Related Diseases After Hematopoietic Stem-Cell Transplantation
  • 2024
  • Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 42:12, s. 1378-1390
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Clinical relapse is the major threat for patients with myelodysplastic syndrome (MDS) undergoing hematopoietic stem-cell transplantation (HSCT). Early detection of measurable residual disease (MRD) would enable preemptive treatment and potentially reduced relapse risk.METHODS: Patients with MDS planned for HSCT were enrolled in a prospective, observational study evaluating the association between MRD and clinical outcome. We collected bone marrow (BM) and peripheral blood samples until relapse, death, or end of study 24 months after HSCT. Patient-specific mutations were identified with targeted next-generation sequencing (NGS) panel and traced using droplet digital polymerase chain reaction (ddPCR).RESULTS: Of 266 included patients, estimated relapse-free survival (RFS) and overall survival (OS) rates 3 years after HSCT were 59% and 64%, respectively. MRD results were available for 221 patients. Relapse was preceded by positive BM MRD in 42/44 relapses with complete MRD data, by a median of 71 (23-283) days. Of 137 patients in continuous complete remission, 93 were consistently MRD-negative, 39 reverted from MRD+ to MRD-, and five were MRD+ at last sampling. Estimated 1 year-RFS after first positive MRD was 49%, 39%, and 30%, using cutoff levels of 0.1%, 0.3%, and 0.5%, respectively. In a multivariate Cox model, MRD (hazard ratio [HR], 7.99), WHO subgroup AML (HR, 4.87), TP53 multi-hit (HR, 2.38), NRAS (HR, 3.55), and acute GVHD grade III-IV (HR, 4.13) were associated with shorter RFS. MRD+ was also independently associated with shorter OS (HR, 2.65). In a subgroup analysis of 100 MRD+ patients, presence of chronic GVHD was associated with longer RFS (HR, 0.32).CONCLUSION: Assessment of individualized MRD using NGS + ddPCR is feasible and can be used for early detection of relapse. Positive MRD is associated with shorter RFS and OS (ClinicalTrials.gov identifier: NCT02872662).
  •  
47.
  • Yoon, Chun Hong, et al. (författare)
  • Unsupervised classification of single-particle X-ray diffraction snapshots by spectral clustering
  • 2011
  • Ingår i: Optics Express. - 1094-4087. ; 19:17, s. 16542-16549
  • Tidskriftsartikel (refereegranskat)abstract
    • Single-particle experiments using X-ray Free Electron Lasers produce more than 10(5) snapshots per hour, consisting of an admixture of blank shots (no particle intercepted), and exposures of one or more particles. Experimental data sets also often contain unintentional contamination with different species. We present an unsupervised method able to sort experimental snapshots without recourse to templates, specific noise models, or user-directed learning. The results show 90% agreement with manual classification.
  •  
48.
  • Zalewski, Kamil, et al. (författare)
  • A call for new communication channels for gynecological oncology trainees : a survey on social media use and educational needs by the European network of young gynecological oncologists
  • 2017
  • Ingår i: International Journal of Gynecological Cancer. - 1048-891X .- 1525-1438. ; 27:3, s. 620-626
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The aim of the study was to assess patterns in the use of social media (SM) platforms and to identify the training needs among European gynecologic oncology trainees.METHODS: In 2014, a web-based survey was sent to 633 trainees from the European Network of Young Gynaecological Oncologists (ENYGO) database. The 14-item questionnaire (partially using a 1- to 5-point Likert scale) assessed respondents' use of SM and preference for workshop content and organization. Descriptive analysis was used to describe the mean scores reported for different items, and the internal reliability of the questionnaire was assessed by Cronbach α.RESULTS: In total, 170 ENYGO members (27%) responded to the survey. Of those, 91% said that they use SM platforms, mostly for private purposes. Twenty-three percent used SM professionally and 43% indicated that they would consider SM to be a clinical discussion forum. The respondents said that they would like updates on conferences and professional activities to be shared on SM platforms. Complication management, surgical anatomy, and state of the art in gynecologic oncology were identified as preferred workshops topics. The most frequently indicated hands-on workshops were laparoscopic techniques and surgical anatomy. Consultants attached a higher level of importance to palliative care education and communication training than trainees. The mean duration of the workshop preferred was 2 days.CONCLUSIONS: This report highlights the significance of ENYGO trainees' attachment to SM platforms. Most respondents expect ENYGO to use these online channels for promoting educational activities and other updates. Using SM for clinical discussion will require specific guidelines to secure professional and also consumer integrity. This survey confirms surgical management and the state of the art as important knowledge gaps, and ENYGO has tailored its activities according to these results. Future activities will further direct attention and resources to education in palliative care and molecular tumor biology.
  •  
49.
  • Zhai, Chenyang, et al. (författare)
  • Surface Etching of Polymeric Semiconductor Films Improves Environmental Stability of Transistors
  • 2021
  • Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 33:7, s. 2673-2682
  • Tidskriftsartikel (refereegranskat)abstract
    • Solution-processed polymeric semiconductor films are attracting wide interest for applications in flexible electronics, wherein environmental stability is still a big obstacle. In many polymeric thin-film electronic devices, vertical phase separation has been observed, which leads to film depth dependences of electronic properties. Here, a soft plasma-assisted surface etching method to improve the environmental stability and maintain the electronic properties of organic field-effect transistors (OFETs) is proposed, by which the unwanted thin-film surface (exposed to air) is selectively taken away upon soft plasma etching, and the layer beneath the surface (subsurface) is preserved without any damage to the subsurface's structure or electronic function. Investigation of frequently used polymeric semiconductors poly(3-hexylthiophene) and poly[4-(4,4-dihexadecyl-4H-cyclopenta[1,2-b:5,4b']dithiophen-2-yl)-alt [1,2,5]thiadiazolo[3,4-c]pyridine] shows that the crystallinity of the surface layer is higher than that of the subsurface layer. However, for p-type polymeric semiconductors, higher crystallinity usually leads to a lower ionization energy and higher doping concentration during exposure to air and thus a higher background conductivity, deteriorating the switching-off capability of the organic field-effect transistors (OFETs). Therefore, by removing this surface layer, the lifetime of OFETs in air is effectively increased by over 50%.
  •  
50.
  • Zicari, Roberto V., et al. (författare)
  • Co-design of a trustworthy AI system in healthcare : deep learning based skin lesion classifier
  • 2021
  • Ingår i: Frontiers in Human Dynamics. - : Frontiers Media S.A.. - 2673-2726. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper documents how an ethically aligned co-design methodology ensures trustworthiness in the early design phase of an artificial intelligence (AI) system component for healthcare. The system explains decisions made by deep learning networks analyzing images of skin lesions. The co-design of trustworthy AI developed here used a holistic approach rather than a static ethical checklist and required a multidisciplinary team of experts working with the AI designers and their managers. Ethical, legal, and technical issues potentially arising from the future use of the AI system were investigated. This paper is a first report on co-designing in the early design phase. Our results can also serve as guidance for other early-phase AI-similar tool developments.
  •  
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