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1.
  • Eron, Joseph J., et al. (author)
  • Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1
  • 2019
  • In: Antiviral Research. - : Elsevier BV. - 0166-3542 .- 1872-9096. ; 170
  • Journal article (peer-reviewed)abstract
    • © 2019 The Authors Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52–96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF.
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3.
  • Dunham, I, et al. (author)
  • The DNA sequence of human chromosome 22
  • 1999
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 402:6761, s. 489-495
  • Journal article (peer-reviewed)
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4.
  • In ’t Veld, Sjors G.J.G., et al. (author)
  • Detection and localization of early- and late-stage cancers using platelet RNA
  • 2022
  • In: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
  • Journal article (peer-reviewed)abstract
    • Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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5.
  • Su, Zhan, et al. (author)
  • Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
  • 2012
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
  • Journal article (peer-reviewed)abstract
    • Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
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6.
  • Liu, Wei, et al. (author)
  • Serial Femtosecond Crystallography of G Protein-Coupled Receptors
  • 2013
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 342:6165, s. 1521-1524
  • Journal article (peer-reviewed)abstract
    • X-ray crystallography of G protein-coupled receptors and other membrane proteins is hampered by difficulties associated with growing sufficiently large crystals that withstand radiation damage and yield high-resolution data at synchrotron sources. We used an x-ray free-electron laser (XFEL) with individual 50-femtosecond-duration x-ray pulses to minimize radiation damage and obtained a high-resolution room-temperature structure of a human serotonin receptor using sub-10-micrometer microcrystals grown in a membrane mimetic matrix known as lipidic cubic phase. Compared with the structure solved by using traditional microcrystallography from cryo-cooled crystals of about two orders of magnitude larger volume, the room-temperature XFEL structure displays a distinct distribution of thermal motions and conformations of residues that likely more accurately represent the receptor structure and dynamics in a cellular environment.
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7.
  • Shaw, Bronwen E., et al. (author)
  • Analysis of the Effect of Race, Socioeconomic Status, and Center Size on Unrelated National Marrow Donor Program Donor Outcomes : Donor Toxicities Are More Common at Low-Volume Bone Marrow Collection Centers
  • 2015
  • In: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 21:10, s. 1830-1838
  • Journal article (peer-reviewed)abstract
    • Previous studies have shown that risks of collection-related pain and symptoms are associated with sex, body mass index, and age in unrelated donors undergoing collection at National Marrow Donor Program centers. We hypothesized that other important factors (race, socioeconomic status [SES], and number of procedures at the collection center) might affect symptoms in donors. We assessed outcomes in 2726 bone marrow (BM) and 6768 peripheral blood stem cell (PBSC) donors collected between 2004 and 2009. Pain/symptoms are reported as maximum levels over mobilization and collection (PBSC) or within 2 days of collection (BM) and at 1 week after collection. For PBSC donors, race and center volumes were not associated with differences in pain/symptoms at any time. PBSC donors with high SES levels reported higher maximum symptom levels 1 week after donation (P = .017). For BM donors, black males reported significantly higher levels of pain (OR, 1.90; CI, 1.14 to 3.19; P = .015). No differences were noted by SES group. BM donors from low-volume centers reported more toxicity (OR, 2.09; CI, 1.26 to 3.46; P = .006). In conclusion, race and SES have a minimal effect on donation-associated symptoms. However, donors from centers performing <= 1 BM collection every 2 months have more symptoms after BM donation. Approaches should be developed by registries and low-volume centers to address this issue.
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8.
  • Tsilidis, Konstantinos K., et al. (author)
  • Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent : a Mendelian randomization study
  • 2021
  • In: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 113:6, s. 1490-1502
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.OBJECTIVES: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). METHODS: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.RESULTS: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.CONCLUSIONS: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
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9.
  • Unsalan, Ozan, et al. (author)
  • The Sariçiçek howardite fall in Turkey : Source crater of HED meteorites on Vesta and impact risk of Vestoids
  • 2019
  • In: Meteoritics and Planetary Science. - Hoboken : John Wiley & Sons. - 1086-9379 .- 1945-5100. ; 54:5, s. 953-1008
  • Journal article (peer-reviewed)abstract
    • The Sariçiçek howardite meteorite shower consisting of 343 documented stones occurred on September 2, 2015 in Turkey and is the first documented howardite fall. Cosmogenic isotopes show that Sariçiçek experienced a complex cosmic‐ray exposure history, exposed during ~12–14 Ma in a regolith near the surface of a parent asteroid, and that an ~1 m sized meteoroid was launched by an impact 22 ± 2 Ma ago to Earth (as did one‐third of all HED meteorites). SIMS dating of zircon and baddeleyite yielded 4550.4 ± 2.5 Ma and 4553 ± 8.8 Ma crystallization ages for the basaltic magma clasts. The apatite U‐Pb age of 4525 ± 17 Ma, K‐Ar age of ~3.9 Ga, and the U,Th‐He ages of 1.8 ± 0.7 and 2.6 ± 0.3 Ga are interpreted to represent thermal metamorphic and impact‐related resetting ages, respectively. Petrographic; geochemical; and O‐, Cr‐, and Ti‐isotopic studies confirm that Sariçiçek belongs to the normal clan of HED meteorites. Petrographic observations and analysis of organic material indicate a small portion of carbonaceous chondrite material in the Sariçiçek regolith and organic contamination of the meteorite after a few days on soil. Video observations of the fall show an atmospheric entry at 17.3 ± 0.8 km s−1 from NW; fragmentations at 37, 33, 31, and 27 km altitude; and provide a pre‐atmospheric orbit that is the first dynamical link between the normal HED meteorite clan and the inner Main Belt. Spectral data indicate the similarity of Sariçiçek with the Vesta asteroid family (V‐class) spectra, a group of asteroids stretching to delivery resonances, which includes (4) Vesta. Dynamical modeling of meteoroid delivery to Earth shows that the complete disruption of a ~1 km sized Vesta family asteroid or a ~10 km sized impact crater on Vesta is required to provide sufficient meteoroids ≤4 m in size to account for the influx of meteorites from this HED clan. The 16.7 km diameter Antionia impact crater on Vesta was formed on terrain of the same age as given by the 4He retention age of Sariçiçek. Lunar scaling for crater production to crater counts of its ejecta blanket show it was formed ~22 Ma ago.
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10.
  • Auffret, Alistair G., et al. (author)
  • HistMapR : Rapid digitization of historical land-use maps in R
  • 2017
  • In: Methods in Ecology and Evolution. - 2041-210X. ; 8:11, s. 1453-1457
  • Journal article (peer-reviewed)abstract
    • Habitat destruction and degradation represent serious threats to biodiversity, and quantification of land-use change over time is important for understanding the consequences of these changes to organisms and ecosystem service provision. Comparing land use between maps from different time periods allows estimation of the magnitude of habitat change in an area. However, digitizing historical maps manually is time-consuming and analyses of change are usually carried out at small spatial extents or at low resolutions. HistMapR contains a number of functions that can be used to semi-automatically digitize historical land use according to a map's colours, as defined by the RGB bands of the raster image. We test the method on different historical land-use map series and compare results to manual digitizations. Digitization is fast, and agreement with manually digitized maps of around 80-90% meets common targets for image classification. We hope that the ability to quickly classify large areas of historical land use will promote the inclusion of land-use change into analyses of biodiversity, species distributions and ecosystem services.
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11.
  • Baggen, Jim, et al. (author)
  • Role of enhanced receptor engagement in the evolution of a pandemic acute hemorrhagic conjunctivitis virus
  • 2018
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:2, s. 397-402
  • Journal article (peer-reviewed)abstract
    • Acute hemorrhagic conjunctivitis (AHC) is a painful, contagious eye disease, with millions of cases in the last decades. Coxsackievirus A24 (CV-A24) was not originally associated with human disease, but in 1970 a pathogenic "variant" (CV-A24v) emerged, which is now the main cause of AHC. Initially, this variant circulated only in Southeast Asia, but it later spread worldwide, accounting for numerous AHC outbreaks and two pandemics. While both CV-A24 variant and nonvariant strains still circulate in humans, only variant strains cause AHC for reasons that are yet unknown. Since receptors are important determinants of viral tropism, we set out to map the CV-A24 receptor repertoire and establish whether changes in receptor preference have led to the increased pathogenicity and rapid spread of CV-A24v. Here, we identify ICAM-1 as an essential receptor for both AHC-causing and non-AHC strains. We provide a high-resolution cryo-EM structure of a virus-ICAM-1 complex, which revealed critical ICAM-1-binding residues. These data could help identify a possible conserved mode of receptor engagement among ICAM-1-binding enteroviruses and rhinoviruses. Moreover, we identify a single capsid substitution that has been adopted by all pandemic CV-A24v strains and we reveal that this adaptation enhances the capacity of CV-A24v to bind sialic acid. Our data elucidate the CV-A24v receptor repertoire and point to a role of enhanced receptor engagement in the adaptation to the eye, possibly enabling pandemic spread.
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12.
  • Gerkin, Richard C., et al. (author)
  • Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms
  • 2021
  • In: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 46
  • Journal article (peer-reviewed)abstract
    • In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0–100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19−; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19− groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: −82.5 ± 27.2 points; C19−: −59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0–10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.
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13.
  • Hooftman, Danny A. P., et al. (author)
  • Could green infrastructure supplement ecosystem service provision from semi-natural grasslands?
  • 2023
  • In: Journal of Environmental Management. - Stockholm : Elsevier BV. - 0301-4797 .- 1095-8630. ; 328
  • Journal article (peer-reviewed)abstract
    • Ancient semi-natural grasslands in Europe are important for ecosystem service (ES) provision. Often, the surrounding matrix contains ‘Grassland Green Infrastructure’ (GGI) that contain grassland species which have the potential to supplement grassland ES provision across the landscape. Here we investigate the potential for GGI to deliver a set of complementary ES, driven by plant composition.We surveyed 36 landscapes across three European countries comprising core grasslands and their surrounding GGI. We calculated community-level values of plant species characteristics to provide indicators for four ES: nature conservation value, pollination, carbon storage and aesthetic appeal.Inferred ES delivery for GGI was substantially lower than in core grasslands for conservation, pollination and aesthetic appeal indicators, but not for carbon storage. These differences were driven by the GGI having 17% fewer plant species, and compositional differences, with 61% of species unique to the core grasslands. In addition, connectivity to the core, the amount of GGI and inferred seed dispersal distances by livestock, were strongly positively correlated with conservation value, pollination and aesthetic indicators. All ES indicators showed similar responses to the GGI spatial structure and distance to the core, suggesting robust effects of these drivers on ES. We projected that improved landscape-wide delivery of nature conservation value and pollination could be achieved through targeted GGI management. Reductions in the distances seeds would need to disperse, more GGI, along with a diversification of the GGI elements, were predicted to enhance service credits.We conclude that for vegetation-related ES, species surveys can be employed to assess potential ES delivery. Creating and enhancing GGI is a useful landscape management strategy to supplement the ES delivered by ancient grasslands.
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14.
  • Jacobs, Alan M., et al. (author)
  • The Qualitative Transparency Deliberations : Insights and Implications
  • 2021
  • In: Perspectives on Politics. - 1537-5927 .- 1541-0986. ; 19:1, s. 171-208
  • Journal article (peer-reviewed)abstract
    • In recent years, a variety of efforts have been made in political science to enable, encourage, or require scholars to be more open and explicit about the bases of their empirical claims and, in turn, make those claims more readily evaluable by others. While qualitative scholars have long taken an interest in making their research open, reflexive, and systematic, the recent push for overarching transparency norms and requirements has provoked serious concern within qualitative research communities and raised fundamental questions about the meaning, value, costs, and intellectual relevance of transparency for qualitative inquiry. In this Perspectives Reflection, we crystallize the central findings of a three-year deliberative process-the Qualitative Transparency Deliberations (QTD)-involving hundreds of political scientists in a broad discussion of these issues. Following an overview of the process and the key insights that emerged, we present summaries of the QTD Working Groups' final reports. Drawing on a series of public, online conversations that unfolded at www.qualtd.net, the reports unpack transparency's promise, practicalities, risks, and limitations in relation to different qualitative methodologies, forms of evidence, and research contexts. Taken as a whole, these reports-the full versions of which can be found in the Supplementary Materials-offer practical guidance to scholars designing and implementing qualitative research, and to editors, reviewers, and funders seeking to develop criteria of evaluation that are appropriate-as understood by relevant research communities-to the forms of inquiry being assessed. We dedicate this Reflection to the memory of our coauthor and QTD working group leader Kendra Koivu.(1)
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15.
  • Odom, Karan J., et al. (author)
  • Sex role similarity and sexual selection predict male and female song elaboration and dimorphism in fairy-wrens
  • 2021
  • In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 11:24, s. 17901-17919
  • Journal article (peer-reviewed)abstract
    • Historically, bird song complexity was thought to evolve primarily through sexual selection on males; yet, in many species, both sexes sing and selection pressure on both sexes may be broader. Previous research suggests competition for mates and resources during short, synchronous breeding seasons leads to more elaborate male songs at high, temperate latitudes. Furthermore, we expect male-female song structure and elaboration to be more similar at lower, tropical latitudes, where longer breeding seasons and year-round territoriality yield similar social selection pressures in both sexes. However, studies seldom take both types of selective pressures and sexes into account. We examined song in both sexes in 15 populations of nine-fairy-wren species (Maluridae), a Southern Hemisphere clade with female song. We compared song elaboration (in both sexes) and sexual song dimorphism to latitude and life-history variables tied to sexual and social selection pressures and sex roles. Our results suggest that song elaboration evolved in part due to sexual competition in males: male songs were longer than female songs in populations with low male survival and less male provisioning. Also, female songs evolved independently of male songs: female songs were slower paced than male songs, although only in less synchronously breeding populations. We also found male and female songs were more similar when parental care was more equal and when male survival was high, which provides strong evidence that sex role similarity correlates with male-female song similarity. Contrary to Northern Hemisphere latitudinal patterns, male and female songs were more similar at higher, temperate latitudes. These results suggest that selection on song can be sex specific, with male song elaboration favored in contexts with stronger sexual selection. At the same time, selection pressures associated with sex role similarity appear to favor sex role similarity in song structure.
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16.
  • Plue, Jan, et al. (author)
  • Green infrastructure can promote plant functional connectivity in a grassland species around fragmented semi-natural grasslands in NW-Europe
  • 2022
  • In: Ecography. - : Wiley. - 0906-7590 .- 1600-0587. ; 2022:10
  • Journal article (peer-reviewed)abstract
    • Species may benefit from green infrastructure, i.e. the network of natural and anthropogenic habitat remnants in human-dominated landscapes, if it helps isolated populations in remaining habitat patches to be functionally connected. The importance of green infrastructure is therefore increasingly emphasized in conservation policy to counter biodiversity loss. However, there is limited evidence, particularly in plants, that green infrastructure promotes functional connectivity, i.e. supports the colonization of habitat patches across a landscape. We applied landscape genetics to test whether the green infrastructure supports structural and functional connectivity in the grassland perennial Galium verum, in 35 landscapes in Belgium, Germany and Sweden. We used multivariate genetic clustering techniques, nestedness analyses and conditional inference trees to examine landscape-scale patterns in genetic diversity and structure of plant populations in the green infrastructure surrounding semi-natural grasslands. Inferred functional connectivity explained genetic variation better than structural connectivity, yielding positive effects on genetic variation. The road verge network, a major structural component of the green infrastructure and its functional connectivity, most effectively explained genetic diversity and composition in G. verum. Galium verum ramets occupying the surrounding landscape proved to be genetic subsets of focal grassland populations, shaping a nested landscape population genetic structure with focal grasslands, particularly ancient ones, harbouring unique genetic diversity. This nested pattern weakened as road network density increased, suggesting road verge networks enable high landscape occupancy by increased habitat availability and facilitates gene flow into the surrounding landscape. Our study proposes that green infrastructure can promote functional connectivity, providing that a plant species can survive outside of core habitat patches. As this often excludes habitat specialist species, conservation practice and policy should primarily focus on ancient, managed semi-natural grasslands. These grasslands both harbour unique genetic diversity and act as primary gene and propagule sources for the surrounding landscape, highlighting their conservation value.
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17.
  • Stannard, Kimberley A., et al. (author)
  • Galectin inhibitory disaccharides promote tumour immunity in a breast cancer model
  • 2010
  • In: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 299:2, s. 95-110
  • Journal article (peer-reviewed)abstract
    • High level galectin-1 expression results in cancer cell evasion of the immune response, increased tumour survival and aggressive metastases. Using a galectin-1 polyclonal antibody, high levels of galectin-1 protein were shown to be expressed by breast cancer cells established from FVB/N MMTV-c-neu mice as well as by the B16F10 melanoma cell line. In mixed lymphocyte cultures using tumour cells as antigenic stimulators, addition of recombinant galectin-1 dose-dependently inhibited lymphocyte production. Disaccharides were identified that inhibited galectin-1 function and increased growth and activation of CD8+ CTL's killing cancer cells. X-ray crystallographic structures of human galectin-1 in complex with inhibitory disaccharides revealed their mode of binding. Combining galectin-blocking carbohydrates as adjuvants with vaccine immunotherapy in vivo to promote immune responses significantly decreased tumour progression and improved the outcomes for tumour challenged mice. This is the first report showing that suitably selected galectin-1 blocking disaccharides will act as adjuvants promoting vaccine stimulated immune responses against tumours in vivo.
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18.
  • Traveset, Anna, et al. (author)
  • Effect of green infrastructure on restoration of pollination networks and plant performance in semi-natural dry grasslands across Europe
  • 2024
  • In: Journal of Applied Ecology. - 0021-8901 .- 1365-2664.
  • Journal article (peer-reviewed)abstract
    • Agricultural intensification, afforestation and land abandonment are major drivers of biodiversity loss in semi-natural grasslands across Europe. Reversing these losses requires the reinstatement of plant–animal interactions such as pollination. Here we assessed the differences in species composition and patterns of plant-pollinator interactions in ancient and restored grasslands and how these patterns are influenced by landscape connectivity, across three European regions (Belgium, Germany and Sweden).We evaluated the differences in pollinator community assemblage, abundance and interaction network structure between 24 ancient and restored grasslands. We then assessed the effect of surrounding landscape functional connectivity (i.e. green infrastructure, GI) on these variables and tested possible consequences on the reproduction of two model plants, Lotus corniculatus and Salvia pratensis.Neither pollinator richness nor species composition differed between ancient and restored grasslands. A high turnover of interactions across grasslands was detected but was mainly due to replacement of pollinator and plant species. The impact of grassland restoration was consistent across various pollinator functional groups, whereas the surrounding GI had differential effects. Notably, bees, butterflies, beetles, and dipterans (excluding hoverflies) exhibited the most significant responses to GI variations. Interestingly, networks in restored grasslands were more specialised (i.e. less functionally redundant) than in ancient ones and also showed a higher number of insect visits to habitat-generalist plant species. Landscape connectivity had a similar effect, with habitat-specialist plant species receiving fewer visits at higher GI values.Fruit set in S. pratensis and L. corniculatus was unaffected by grassland type or GI. However, the fruit set in the specialist S. pratensis increased with the number of pollinator visits, indicating a positive correlation between pollinator activity and reproductive success in this particular species.Synthesis and applications. Our findings provide evidence of the necessity to enhance ecosystem functions while avoiding biotic homogenisation. Restoration programs should aim at increasing landscape connectivity which influences plant communities, pollinator assemblages and their interaction patterns. To avoid generalist species taking over from specialists in restored grasslands, we suggest reinforcing the presence of specialist species in the latter, for instance by means of introductions, as well as increasing the connectivity to source populations.
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19.
  • Wright, Shane C., et al. (author)
  • GLP-1R signaling neighborhoods associate with the susceptibility to adverse drug reactions of incretin mimetics
  • 2023
  • In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
  • Journal article (peer-reviewed)abstract
    • G protein-coupled receptors are important drug targets that engage and activate signaling transducers in multiple cellular compartments. Delineating therapeutic signaling from signaling associated with adverse events is an important step towards rational drug design. The glucagon-like peptide-1 receptor (GLP-1R) is a validated target for the treatment of diabetes and obesity, but drugs that target this receptor are a frequent cause of adverse events. Using recently developed biosensors, we explored the ability of GLP-1R to activate 15 pathways in 4 cellular compartments and demonstrate that modifications aimed at improving the therapeutic potential of GLP-1R agonists greatly influence compound efficacy, potency, and safety in a pathway- and compartment-selective manner. These findings, together with comparative structure analysis, time-lapse microscopy, and phosphoproteomics, reveal unique signaling signatures for GLP-1R agonists at the level of receptor conformation, functional selectivity, and location bias, thus associating signaling neighborhoods with functionally distinct cellular outcomes and clinical consequences. Agonists of the glucagon-like peptide-1 receptor are used to treat diabetes and obesity. Here, Wright et al. investigate the subcellular location of the receptor's signaling events and uncover associations between signaling profiles and adverse drug reactions.
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20.
  • Allen-Philbey, Kimberley, et al. (author)
  • Subcutaneous cladribine to treat multiple sclerosis : experience in 208 patients
  • 2021
  • In: Therapeutic Advances in Neurological Disorders. - : SAGE Publications. - 1756-2856 .- 1756-2864. ; 14
  • Journal article (peer-reviewed)abstract
    • Objective: To report on safety and effectiveness of subcutaneous cladribine (Litak®) in multiple sclerosis (MS) patients. Methods: Litak® was offered to MS-patients irrespective of disease course. Litak® 10 mg was administered for 3–4 days during week 1. Based on lymphocyte count at week 4, patients received another 0–3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts. Results: In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17–72) years and EDSS 0–8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data (n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data (n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months. Conclusions: Litak® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage.
  •  
21.
  • Bouckaert, Kimberley P, et al. (author)
  • Critical evaluation of folate data in European and international databases : recommendations for standardization in international nutritional studies.
  • 2011
  • In: Molecular Nutrition & Food Research. - : Wiley. - 1613-4125 .- 1613-4133. ; 55:1, s. 166-180
  • Journal article (peer-reviewed)abstract
    • SCOPE: The objective was to perform an inventory and critical evaluation of folate data in selected European and international databases. The ultimate aim was to establish guidelines for compiling standardized folate databases for international nutritional studies.METHODS AND RESULTS: An ad hoc questionnaire was prepared to critically compare and evaluate folate data completeness, quantification, terminologies, and documentation of 18 European and international databases, and national fortification regulations. Selected countries participated in the European Prospective Investigation into Nutrition and Cancer project and European Food Information Resource Network (EuroFIR). Folate completeness was generally high. "Total folate" was the most common terminology and microbiological assay was the most frequently reported quantification method. There is a lack of comparability within and between databases due to a lack of value documentation, the use of generic or non-appropriate terminologies, folate value conversions, and/or lack of identification of synthetic folic acid.CONCLUSION: Full value documentation and the use of EuroFIR component identifiers and/or INFOODS tagnames for total folate ("FOL") and synthetic folic acid ("FOLAC"), with the additional use of individual folates, will increase comparability between databases. For now, the standardized microbiological assay for total folate and HPLC for synthetic folic acid are the recommended quantification methods.
  •  
22.
  • Congdon, Jenna V., et al. (author)
  • Hear them roar: A comparison of black-capped chickadee (Poecile atricapillus) and human (Homo sapiens) perception of arousal in vocalizations across all classes of terrestrial vertebrates
  • 2019
  • In: Journal of Comparative Psychology. - : American Psychological Association (APA). - 1939-2087 .- 0735-7036.
  • Journal article (peer-reviewed)abstract
    • Recently, evidence for acoustic universals in vocal communication was found by demonstrating that humans can identify levels of arousal in vocalizations produced by species across three biological classes (Filippi et al., 2017). Here, we extend this work by testing whether two vocal learning species, humans and chickadees, can discriminate vocalizations of high and low arousal using operant discrimination go/no-go tasks. Stimuli included vocalizations from nine species: giant panda, American alligator, common raven, hourglass treefrog, African elephant, Barbary macaque, domestic pig, black-capped chickadee, and human. Subjects were trained to respond to high or low arousal vocalizations, then tested with additional high and low arousal vocalizations produced by each species. Chickadees (Experiment 1) and humans (Experiment 2) learned to discriminate between high and low arousal stimuli and significantly transferred the discrimination to additional panda, human, and chickadee vocalizations. Finally, we conducted discriminant function analyses using four acoustic measures, finding evidence suggesting that fundamental frequency played a role in responding during the task. However, these analyses also suggest roles for other acoustic factors as well as familiarity. In sum, the results from these studies provide evidence that chickadees and humans are capable of perceiving arousal in vocalizations produced by multiple species.
  •  
23.
  • Declerck, Steven A. J., et al. (author)
  • Rapid adaptation of herbivore consumers to nutrient limitation : eco-evolutionary feedbacks to population demography and resource control
  • 2015
  • In: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 18:6, s. 553-562
  • Journal article (peer-reviewed)abstract
    • Humans alter biogeochemical cycles of essential elements such as phosphorus (P). Prediction of ecosystem consequences of altered elemental cycles requires integration of ecology, evolutionary biology and the framework of ecological stoichiometry. We studied micro-evolutionary responses of a herbivorous rotifer to P-limited food and the potential consequences for its population demography and for ecosystem properties. We subjected field-derived, replicate rotifer populations to P-deficient and P-replete algal food, and studied adaptation in common garden transplant experiments after 103 and 209days of selection. When fed P-limited food, populations with a P-limitation selection history suffered 37% lower mortality, reached twice the steady state biomass, and reduced algae by 40% compared to populations with a P-replete selection history. Adaptation involved no change in rotifer elemental composition but reduced investment in sex. This study demonstrates potentially strong eco-evolutionary feedbacks from shifting elemental balances to ecosystem properties, including grazing pressure and the ratio of grazer:producer biomass.
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24.
  • Fagerholm, Per, et al. (author)
  • Stable corneal regeneration four years after implantation of a cell-free recombinant human collagen scaffold
  • 2014
  • In: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 35:8, s. 2420-2427
  • Journal article (peer-reviewed)abstract
    • We developed cell-free implants, comprising carbodiimide crosslinked recombinant human collagen (RHC), to enable corneal regeneration by endogenous cell recruitment, to address the worldwide shortage of donor corneas. Patients were grafted with RHC implants. Over four years, the regenerated neo-corneas were stably integrated without rejection, without the long immunosuppression regime needed by donor cornea patients. There was no recruitment of inflammatory dendritic cells into the implant area, whereas, even with immunosuppression, donor cornea recipients showed dendritic cell migration into the central cornea and a rejection episode was observed. Regeneration as evidenced by continued nerve and stromal cell repopulation occurred over the four years to approximate the micro-architecture of healthy corneas. Histopathology of a regenerated, clear cornea from a regrafted patient showed normal corneal architecture. Donor human cornea grafted eyes had abnormally tortuous nerves and stromal cell death was found. Implanted patients had a 4-year average corrected visual acuity of 20/54 and gained more than 5 Snellen lines of vision on an eye chart. The visual acuity can be improved with more robust materials for better shape retention. Nevertheless, these RHC implants can achieve stable regeneration and therefore, represent a potentially safe alternative to donor organ transplantation.
  •  
25.
  • Fry, Ellen L., et al. (author)
  • Vegetation type, not the legacy of warming, modifies the response of microbial functional genes and greenhouse gas fluxes to drought in Oro-Arctic and alpine regions
  • 2023
  • In: FEMS microbiology ecology. - 1574-6941. ; 99:12
  • Journal article (peer-reviewed)abstract
    • Climate warming and summer droughts alter soil microbial activity, affecting greenhouse gas (GHG) emissions in Arctic and alpine regions. However, the long-term effects of warming, and implications for future microbial resilience, are poorly understood. Using one alpine and three Arctic soils subjected to in situ long-term experimental warming, we simulated drought in laboratory incubations to test how microbial functional-gene abundance affects fluxes in three GHGs: carbon dioxide, methane, and nitrous oxide. We found that responses of functional gene abundances to drought and warming are strongly associated with vegetation type and soil carbon. Our sites ranged from a wet, forb dominated, soil carbon-rich systems to a drier, soil carbon-poor alpine site. Resilience of functional gene abundances, and in turn methane and carbon dioxide fluxes, was lower in the wetter, carbon-rich systems. However, we did not detect an effect of drought or warming on nitrous oxide fluxes. All gene-GHG relationships were modified by vegetation type, with stronger effects being observed in wetter, forb-rich soils. These results suggest that impacts of warming and drought on GHG emissions are linked to a complex set of microbial gene abundances and may be habitat-specific.
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26.
  • Grenn, Francis P., et al. (author)
  • The Parkinson's Disease Genome-Wide Association Study Locus Browser
  • 2020
  • In: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257.
  • Journal article (peer-reviewed)abstract
    • Background: Parkinson's disease (PD) is a neurodegenerative disease with an often complex component identifiable by genome-wide association studies. The most recent large-scale PD genome-wide association studies have identified more than 90 independent risk variants for PD risk and progression across more than 80 genomic regions. One major challenge in current genomics is the identification of the causal gene(s) and variant(s) at each genome-wide association study locus. The objective of the current study was to create a tool that would display data for relevant PD risk loci and provide guidance with the prioritization of causal genes and potential mechanisms at each locus. Methods: We included all significant genome-wide signals from multiple recent PD genome-wide association studies including themost recent PD risk genome-wide association study, age-at-onset genome-wide association study, progression genome-wide association study, and Asian population PD risk genome-wide association study. We gathered data for all genes 1 Mb up and downstream of each variant to allow users to assess which gene(s) are most associated with the variant of interest based on a set of self-ranked criteria. Multiple databases were queried for each gene to collect additional causal data. Results: We created a PD genome-wide association study browser tool (https://pdgenetics.shinyapps.io/GWASBrowser/) to assist the PD research community with the prioritization of genes for follow-up functional studies to identify potential therapeutic targets. Conclusions: Our PD genome-wide association study browser tool provides users with a useful method of identifying potential causal genes at all known PD risk loci from large-scale PD genome-wide association studies. We plan to update this tool with new relevant data as sample sizes increase and new PD risk loci are discovered.
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27.
  • Helsen, Kenny, et al. (author)
  • Impact of an invasive alien plant on litter decomposition along a latitudinal gradient
  • 2018
  • In: Ecosphere. - : Wiley. - 2150-8925 .- 2150-8925. ; 9:1
  • Journal article (peer-reviewed)abstract
    • Invasive alien plant effects on ecosystem functions are often difficult to predict across environmental gradients due to the context-dependent interactions between the invader and the recipient communities. Adopting a functional trait-based framework could provide more mechanistic predictions for invasive species' impacts. In this study, we contrast litter decomposition rates among communities with and without the invasive plant Impatiens glandulifera in five regions along a 1600 km long latitudinal gradient in Europe. Across this gradient, four functional traits, namely leaf dry matter content (LDMC), specific leaf area (SLA), stem-specific density (SSD), and plant height, are correlated to rates of litter decomposition of standardized rooibos (labile), green tea (recalcitrant), and I. glandulifera litter. Our results show that both invaded and non-invaded plant communities had a higher expression of acquisitive traits (low LDMC and SSD, high SLA) with increasing temperature along the latitudinal gradient, partly explaining the variation in decomposition rates along the gradient. At the same time, invasion shifted community trait composition toward more acquisitive traits across the latitudinal gradient. These trait changes partly explained the increased litter decomposition rates of the labile litter fraction of rooibos and I. glandulifera litter in invaded communities, a shift that was most evident in the warmer study regions. Plant available nitrogen was lower in invaded communities, likely due to high nutrient uptake by I. glandulifera. Meanwhile, the coldest study region was characterized by a reversed effect of invasion on decomposition rates. Here, community traits related to low litter quality and potential allelopathic effects of the invader resulted in reduced litter decomposition rates, suggesting a threshold temperature at which invader effects on litter decomposition turn positive. This study therefore illustrates how functional trait changes toward acquisitive traits can help explain invader-induced changes in ecosystem functions such as increased litter decomposition.
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28.
  • Helsen, Kenny, et al. (author)
  • No genetic erosion after five generations for Impatiens glandulifera populationsacross the invaded range in Europe
  • 2019
  • In: BMC Genetics. - : BioMed Central. - 1471-2156. ; 20
  • Journal article (peer-reviewed)abstract
    • Background: The observation that many alien species become invasive despite low genetic diversity has long been considered the ‘genetic paradox’ in invasion biology. This paradox is often resolved through the temporal buildup genetic diversity through multiple introduction events. These temporal dynamics in genetic diversity are especially important for annual invasive plants that lack a persistent seed bank, for which population persistence is strongly dependent on consecutive seed ‘re-establishment’ in each growing season. Theory predicts that the number of seeds during re-establishment, and the levels of among-population gene flow can strongly affect recolonization dynamics, resulting in either an erosion or build-up of population genetic diversity through time. This study focuses on temporal changes in the population genetic structure of the annual invasive plant Impatiens glandulifera across Europe. We resampled 13 populations in 6 regions along a 1600 km long latitudinal gradient from northern France to central Norway after 5 years, and assessed population genetic diversity with 9 microsatellite markers.Results: Our study suggests sufficiently high numbers of genetically diverse founders during population re- establishment, which prevent the erosion of local genetic diversity. We furthermore observe that I. glanduliferaexperiences significant among-population gene flow, gradually resulting in higher genetic diversity and lower overall genetic differentiation through time. Nonetheless, moderate founder effects concerning population genetic composition (allele frequencies) were evident, especially for smaller populations.Despite the initially low genetic diversity, this species seems to be successful at persisting across its invaded range, and will likely continue to build up higher genetic diversity at the local scale.
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29.
  • Hooftman, Danny, et al. (author)
  • Dispersal limitation, eutrophication and propagule pressure constrain the conservation value of Grassland Green Infrastructure
  • 2021
  • In: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 258
  • Journal article (peer-reviewed)abstract
    • Semi-natural grasslands harbour many of Europe's species of conservation interest. Although larger grasslands are the focus of most conservation activity, many grassland fragments are scattered across landscapes –in small patches or along linear elements– which can form Grassland Green Infrastructure (GGI). GGI has the potential to enhance landscape diversity by creating functioning metacommunities comprising of large semi-natural grasslands and these surrounding fragments. While often highlighted in conservation policy, little is known about the biodiversity supported by green infrastructure itself and thus its conservation potential.To address this issue, we contrasted plant communities in 36 ‘core’ grassland sites across three European countries with communities in the surrounding GGI. We related compositional differences to amount and type of GGI habitat (patches or linear), and the distances for seed dispersal by livestock from core sites. We found substantial differences between the GGI and the core sites, with a mean 54% species turn-over. These differences indicated filtering of stress tolerant species characteristic of low nutrient conditions, and semi-natural grassland specialists. Species with poorer dispersal abilities declined strongly with increasing distances from the core sites. The many additional species in the GGI, not found in the core sites, were predominantly those with a competitive strategy and high seed dispersal ability.We conclude that the biodiversity-supporting role of GGI across Europe is severely constrained by eutrophication, dispersal limitation and external propagule pressure. Actions to improve the quality of GGI might include enhancing dispersal by livestock combined with more type-diversification and less intensively used grassland habitats.
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30.
  • Jonsson, Magnus, et al. (author)
  • Nationwide Outcome Analysis of Primary Carotid Endarterectomy in Symptomatic Patients Depending on Closure Technique and Patch Type
  • 2023
  • In: European Journal of Vascular and Endovascular Surgery. - : Saunders Elsevier. - 1078-5884 .- 1532-2165. ; 65:4, s. 467-473
  • Journal article (peer-reviewed)abstract
    • Objective: Current European guidelines recommend both eversion carotid endarterectomy (CEA) and conventional CEA with routine patch closure, rather than routine primary closure. Polyester and polytetrafluoroethylene (PTFE) have been used as patch material for a long time. More recently, bovine pericardium has been used; however, there are few studies comparing long term results between bovine pericardium and other patch types. The aim of this study was to investigate the short and long term results after CEA depending on surgical technique and patch material.Methods: A registry based study on all primary CEAs (n = 9 205) performed for symptomatic carotid artery stenosis in Sweden from July 2008 to December 2019, cross linked with data from the Swedish stroke registry, Riksstroke, and chart review for evaluation of any events occurring during follow up. The primary endpoint was ipsilateral stroke < 30 days. Secondary endpoints included re-operations due to neck haematoma and < 30 day ipsilateral stroke, > 30 day ipsilateral stroke, all stroke > 30 days, and all cause mortality.Results: 2 495 patients underwent eversion CEA and 6 710 conventional CEA for symptomatic carotid stenosis. The most commonly used patch material was Dacron (n = 3 921), followed by PTFE (n = 588) and bovine pericardium (n = 413). A total of 1 788 patients underwent conventional CEA with primary closure. Two hundred and seventy-three patients (3.0%) had a stroke < 30 days. Primary closure was associated with an increased risk of ipsilateral stroke and stroke or death <30 days: odds ratio 1.7 (95% confidence interval [CI] 1.2 -2.4, p = .002); and 1.5 (95% CI 1.2 -2.0), respectively. During follow up (median 4.2 years), 592 patients had any form of stroke and 1 492 died. There was no significant difference in long term risk of ipsilateral stroke, all stroke, or death depending on surgical technique or patch material.Conclusion: There was an increased risk of ipsilateral stroke < 30 days in patients operated on with primary closure compared with eversion CEA and patch angioplasty. There was no difference between primary closure, different patch types, or eversion after the peri-operative phase.
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31.
  • Kapás, Rozália E., 1988- (author)
  • Grassland restoration : Connectivity, plant community change and cows
  • 2023
  • Doctoral thesis (other academic/artistic)abstract
    • The ecological significance of semi-natural grasslands is high because these habitats provide a home for a diverse flora and fauna and support a range of associated ecosystem services. Due to large-scale land-use changes the extent of grassland habitat has declined. Hence, restoration efforts to mitigate grassland losses are now being prioritized across the globe and there is an increasing need to understand the drivers behind the recovery of degraded habitats. Since many restoration initiatives rely on spontaneous dispersal of plant species from sources at both local- and landscape-scales, community assembly is influenced by a range of factors which interact both over time and across spatial scales. Given this complexity over the scales, gaps remain in our understanding of how post-restoration management can be designed to facilitate the effective dispersal and establishment of target species in restored grasslands.In this thesis, I examined colonization patterns in Swedish grasslands by comparing plant communities in both ancient and restored grasslands and under contrasting management regimes. At small spatial scales and over the short-term following restoration, I investigated species recruitment sources and their relative contribution to colonization and regeneration. At larger temporal and spatial scales, I examined how the composition of vegetation and seed bank communities is determined by local environmental factors together with distance to species pool and presence of grazing livestock.I found that species mostly colonized spatially from local species sources through seed rain. The seed bank contributed to species colonization to a greater extent in ancient grasslands than in restored grasslands. Management through livestock grazing and shorter distance to species pool were positively associated with the number of species found in grasslands. Grazing livestock facilitated target species establishment into restored sites and the differences between ancient and restored grassland communities were smaller when grazing was active, highlighting that ancient sites can provide a source of colonizing species for restored sites. I found that plant species associated with former land-use declined immediately following restoration, while the occurrence of target species generally increased. However, there was a high initial stochasticity in the establishment of the target species and communities in restored grasslands were still distinct from continuously managed sites even after several decades.These results demonstrate that species presence in nearby ancient grasslands and potential dispersal from the local seed sources drives species colonization in restored and ancient grasslands. Livestock grazing was shown to be an important driver of grassland recovery, either by mediating spatial dispersal of seeds or improving site conditions for establishment. Target species are able to accumulate in the vegetation and seed bank over the long-term, as restored grasslands age. This accumulation will ensure an increasing resilience of grassland communities against future disturbances or changes in the climate. However this depends upon active management, for example by implementing management plans which include continued livestock grazing, and upon conserving remaining ancient grasslands as hotspots for biodiversity within the wider landscape.
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32.
  • Kapás, Rozália E., 1988-, et al. (author)
  • Grassland species colonization of a restored grassland on a former forest varies in short-term success but is facilitated by greater functional connectivity
  • 2024
  • In: Nordic Journal of Botany. - : Wiley. - 0107-055X .- 1756-1051. ; 2024:4
  • Journal article (peer-reviewed)abstract
    • In recent years, restoration on former grassland sites has been widely encouraged globally, aiming to address the historical loss of 90% of ancient species-rich grasslands, and to mitigate the associated threat to grassland biodiversity. The objective of our study was to investigate on a small-scale how plant species spontaneously colonize restored grasslands. We inventoried 275 permanent plots twice (in 2019 and 2021) in a restored grassland, following the removal of a conifer plantation. Species richness and vegetation cover in surveyed plots were dependent on grazing activity and distance to adjacent grassland. Plant species associated with forest habitats declined, while the occurrence of generalist species together with a few grassland specialists generally increased. However, not all grassland specialists gained occurrence and the colonization pattern was not consistent over time, possibly due to the lack of continuous seed arrival and low livestock activity and hence lack of disturbance. These results suggest that successful colonization of plant species benefits from links to species-rich sites adjacent to the restoration target, with spatial dispersal and improved conditions for species establishment being key to species occurrence. Both dispersal and establishment potential are likely facilitated through the presence of grazing livestock with access to both species-rich grasslands and restoration targets. However, the shift towards a more typical grassland community takes place gradually, with vulnerable populations of early colonizing grassland species prone to local extinction in short-term. As a result, continued functional connectivity provided by grazing animals is necessary to improve the diversity of the restored site and ensure the establishment of grassland specialists and to maintain the plant community composition.
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33.
  • Kimberley, Adam, et al. (author)
  • Unbalanced species losses and gains lead to non-linear trajectories as grasslands become forests
  • 2019
  • In: Journal of Vegetation Science. - : Wiley. - 1100-9233 .- 1654-1103. ; 30:6, s. 1089-1098
  • Journal article (peer-reviewed)abstract
    • Questions Rates of plant community shifts after environmental changes depend on how quickly affected species are gained and lost. Understanding how the balance between extinction and colonisation varies over time, and how it is influenced by local and landscape factors, is essential to understanding overall change trajectories. Investigating change requires data at several time steps over sufficient periods, and the paucity of such data represents an important knowledge gap. We ask: (a) how variation over time in the rates of species' extinction and species' colonization controls the trajectory of biodiversity change in abandoned semi-natural grasslands? and (b) can landscape composition and habitat history modify change trajectories by acting independently on groups within plant communities? Location Sweden, Stockholm Archipelago. Methods We use data on plant composition, management history and landscape context in former grasslands, abandoned at different points since 1901, in a space-for-time analysis, comparing rates of grassland species loss and forest species establishment and investigating resulting biodiversity trajectories. Results Grassland species declined steeply in recently abandoned habitats before levelling off, while the accumulation of forest species was linear, with no plateau reached even at the longest time since abandonment. Hence, we observed a trough in biodiversity, with an initial decline in overall species richness followed by a partial recovery. Only forest species gain was enhanced by nearby habitat availability. Conclusions Information on community compositional changes over short time periods may be misleading about the extent and even direction of ongoing biodiversity gains and losses. Moreover, the non-linear changes observed suggest thresholds in time, after which succession to the forest community accelerates and the ability to manage a return to the grassland community diminishes. Accounting for the combined influence of landscape composition and history is key to fully understanding community shifts over time.
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34.
  • Kozak Ljunggren, Monika, et al. (author)
  • Effect of Surgical Technique on Corneal Implant Performance.
  • 2014
  • In: Translational Vision Science & Technology. - : Association for Research in Vision and Ophthalmology (ARVO). - 2164-2591. ; 3:2
  • Journal article (peer-reviewed)abstract
    • PURPOSE: Our aim was to determine the effect of a surgical technique on biomaterial implant performance, specifically graft retention.METHODS: Twelve mini pigs were implanted with cell-free, 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) cross-linked recombinant human collagen type III (RHCIII) hydrogels as substitutes for donor corneal allografts using overlying sutures with or without human amniotic membrane (HAM) versus interrupted sutures with HAM. The effects of the retention method were compared as well as the effects of collagen concentration (13.7% to 15% RHCIII).RESULTS: All implanted corneas showed initial haze that cleared with time, resulting in corneas with optical clarity matching those of untreated controls. Biochemical analysis showed that by 12 months post operation, the initial RHCIII implants had been completely remodeled, as type I collagen, was the major collagenous protein detected, whereas no RHCIII could be detected. Histological analysis showed all implanted corneas exhibited regeneration of epithelial and stromal layers as well as nerves, along with touch sensitivity and tear production. Most neovascularization was seen in corneas stabilized by interrupted sutures.CONCLUSIONS: This showed that the surgical technique used does have a significant effect on the overall performance of corneal implants, overlying sutures caused less vascularization than interrupted sutures.TRANSLATIONAL RELEVANCE: Understanding the significance of the suturing technique can aid the selection of the most appropriate procedure when implanting artificial corneal substitutes. The same degree of regeneration, despite a higher collagen content indicates that future material development can progress toward stronger, more resistant implants.
  •  
35.
  • Lindgren, Jessica, 1971-, et al. (author)
  • The complexity of forest borders determines the understory vegetation
  • 2018
  • In: Applied Vegetation Science. - : Wiley. - 1402-2001 .- 1654-109X. ; 21:1, s. 85-93
  • Journal article (peer-reviewed)abstract
    • Questions: What are the most important drivers of plant species richness (γ-diversity) and species turnover (β-diversity) in the field layer of a forest edge? Does the tree and shrub species richness structure and complexity affect the richness of forest and grassland specialist species?Location: South-eastern Sweden.Methods: We sampled 50 forest edges with different levels of structural complexity in agricultural landscapes. In each border we recorded trees, shrubs and herb layer species in a 50 m transect parallel with the forest. We investigated species composition and species turnover in relationship to the proportions of gaps the border, the diversity of trees and shrubs and distance to semi-natural grasslands.Results: Total plant species richness in the field layer was mainly explained by the proportion of gaps to areas with full canopy cover, and tree diversity. Increasing number of gaps promoted higher diversity of grassland specialist species within the field layer, resulting in open forest borders with the highest overall species richness. Gaps did however have a negative impact on forest species richness. Conversely, increasing forest species richness was positively related to tree diversity but number of grassland specialist species was negatively affected by tree diversity.Conclusions: Managing forest borders, and therefore increasing the area of semi-open habitats in fragmented agricultural landscapes, gives future opportunities to create a network of suitable habitats for both grassland and deciduous forest specialist species. Such measures therefore have the potential to increase functional connectivity and support dispersal of species in homogeneous forest/agriculture landscapes.
  •  
36.
  • Liu, Wenguang, et al. (author)
  • Recombinant human collagen for tissue engineered corneal substitutes
  • 2008
  • In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 29:9, s. 1147-1158
  • Journal article (peer-reviewed)abstract
    • We successfully fabricated transparent, robust hydrogels as corneal substitutes from concentrated recombinant human type I and type III collagen solutions crosslinked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). White light transmission through these gels is comparable or superior to that of human corneas. Hydrogels from both type I and type III collagens supported in vitro epithelium and nerve over-growth. While both these biocompatible hydrogels have adequate tensile strength and elasticity for surgical manipulation, type III collagen hydrogels tended to be mechanically superior. Twelve-month post-implantation results of type I recombinant collagen-based corneal substitutes into mini-pigs showed retention of optical clarity, along with regeneration of corneal cells, nerves and tear film. For clinical use, implants based on fully characterized, recombinant human collagen eliminate the risk of pathogen transfer or xenogeneic immuno-responses posed by animal collagens. © 2007 Elsevier Ltd. All rights reserved.
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37.
  • Merrett, Kimberley, et al. (author)
  • Synthetic neoglycopolymer-recombinant human collagen hybrids as biomimetic crosslinking agents in corneal tissue engineering
  • 2009
  • In: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 30:29, s. 5403-5408
  • Journal article (peer-reviewed)abstract
    • Saturated neoglycopolymers, prepared via tandem ROMP-hydrogenation (ROMP = ring-opening metathesis polymerization) of carbohydrate-functionalized norbornenes, are investigated as novel collagen crosslinking agents in corneal tissue engineering. The neoglycopolymers were incorporated into recombinant human collagen type III (RHC III) as collagen crosslinking agents and glycosaminoglycan (GAG) mimics. The purely synthetic nature of these composites is designed to reduce susceptibility to immunological and allergic reactions, and to circumvent the transmission of animal infectious diseases. The collagen-neoglycopolymer biomaterials exhibit higher stability to collagenase-induced biodegradation than the control materials, composites of RHC III crosslinked using EDC/NHS (EDC = 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide; NHS = N-hydroxysuccinimide). Even at this proof of concept stage, the thermal stability, enzymatic resistance, and permeability of the neoglycopolymer hydrogels are comparable or superior to those of these fully optimized control materials, which have successfully been tested clinically. Tensile strength is adequate for transplantation, but lower than that of the optimized control materials.
  •  
38.
  • Merrett, Kimberley, et al. (author)
  • Tissue-engineered recombinant human collagen-based corneal substitutes for implantation : Performance of type I versus type III collagen
  • 2008
  • In: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 49:9, s. 3887-3894
  • Journal article (peer-reviewed)abstract
    • PURPOSE. To compare the efficacies of recombinant human collagens types I and III as corneal substitutes for implantation. METHODS. Recombinant human collagen (13.7%) type I or III was thoroughly mixed with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide. The final homogenous solution was either molded into sheets for in vitro studies or into implants with the appropriate corneal dimensions for transplantation into minipigs. Animals with implants were observed for up to 12 months after surgery. Clinical examinations of the cornea included detailed slit lamp biomicroscopy, in vivo confocal microscopy, and fundus examination. Histopathologic examinations were also performed on corneas harvested after 12 months. RESULTS. Both cross-linked recombinant collagens had refractive indices of 1.35, with optical clarity similar to that in human corneas. Their chemical and mechanical properties were similar, although RHC-III implants showed superior optical clarity. Implants into pig corneas over 12 months show comparably stable integration, with regeneration of corneal cells, tear film, and nerves. Optical clarity was also maintained in both implants, as evidenced by fundus examination. CONCLUSIONS. Both RHC-I and -III implants can be safely and stably integrated into host corneas. The simple cross-linking methodology and recombinant source of materials makes them potentially safe and effective future corneal matrix substitutes.
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39.
  • Mesher, David, et al. (author)
  • Population-level effects of human papillomavirus vaccination programs on infections with nonvaccine genotypes
  • 2016
  • In: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 22:10, s. 1732-1740
  • Journal article (peer-reviewed)abstract
    • We analyzed human papillomavirus (HPV) prevalences during prevaccination and postvaccination periods to consider possible changes in nonvaccine HPV genotypes after introduction of vaccines that confer protection against 2 high-risk types, HPV16 and HPV18. Our meta-analysis included 9 studies with data for 13,886 girls and women ≤19 years of age and 23,340 women 20–24 years of age. We found evidence of cross-protection for HPV31 among the younger age group after vaccine introduction but little evidence for reductions of HPV33 and HPV45. For the group this same age group, we also found slight increases in 2 nonvaccine high-risk HPV types (HPV39 and HPV52) and in 2 possible high-risk types (HPV53 and HPV73). However, results between age groups and vaccines used were inconsistent, and the increases had possible alternative explanations; consequently, these data provided no clear evidence for type replacement. Continued monitoring of these HPV genotypes is important.
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40.
  • Plue, Jan, et al. (author)
  • Functional rather than structural connectivity explains grassland plant diversity patterns following landscape scale habitat loss
  • 2020
  • In: Landscape Ecology. - 0921-2973 .- 1572-9761.
  • Journal article (peer-reviewed)abstract
    • Context Functional connectivity is vital for plant species dispersal, but little is known about how habitat loss and the presence of green infrastructure interact to affect both functional and structural connectivity, and the impacts of each on species groups. Objectives We investigate how changes in the spatial configuration of species-rich grasslands and related green infrastructure such as road verges, hedgerows and forest borders in three European countries have influenced landscape connectivity, and the effects on grassland plant biodiversity. Methods We mapped past and present land use for 36 landscapes in Belgium, Germany and Sweden, to estimate connectivity based on simple habitat spatial configuration (structural connectivity) and accounting for effective dispersal and establishment (functional connectivity) around focal grasslands. We used the resulting measures of landscape change to interpret patterns in plant communities. Results Increased presence of landscape connecting elements could not compensate for large scale losses of grassland area resulting in substantial declines in structural and functional connectivity. Generalist species were negatively affected by connectivity, and responded most strongly to structural connectivity, while functional connectivity determined the occurrence of grassland specialists in focal grasslands. Restored patches had more generalist species, and a lower density of grassland specialist species than ancient patches. Conclusions Protecting both species rich grasslands and dispersal pathways within landscapes is essential for maintaining grassland biodiversity. Our results show that increases in green infrastructure have not been sufficient to offset loss of semi-natural habitat, and that landscape links must be functionally effective in order to contribute to grassland diversity.
  •  
41.
  • Rahlff, Janina, et al. (author)
  • Blue pigmentation of neustonic copepods benefits exploitation of a prey-rich niche at the air-sea boundary
  • 2018
  • In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8:1
  • Journal article (peer-reviewed)abstract
    • The sea-surface microlayer (SML) at the air-sea interface is a distinct, under-studied habitat compared to the subsurface and copepods, important components of ocean food webs, have developed key adaptations to exploit this niche. By using automated SML sampling, high-throughput sequencing and unmanned aerial vehicles, we report on the distribution and abundance of pontellid copepods in relation to the unique biophysicochemical signature of the SML. We found copepods in the SML even during high exposure to sun-derived ultraviolet radiation and their abundance was significantly correlated to increased algal biomass. We additionally investigated the significance of the pontellids’ blue pigmentation and found that the reflectance peak of the blue pigment matched the water-leaving spectral radiance of the ocean surface. This feature could reduce high visibility at the air-sea boundary and potentially provide camouflage of copepods from their predators.
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42.
  • Roth, Nina, 1984-, et al. (author)
  • Experimental warming outside the growing season and exclusion of grazing has a mild effect on upland grassland plant communities in the short term
  • 2023
  • In: Plant Ecology & Diversity. - 1755-0874 .- 1755-1668. ; 16:5-6, s. 189-201
  • Journal article (peer-reviewed)abstract
    • Background: Winters are expected to warm more than summers in central and northern Europe, with largely unknown effects on grassland plant communities.Aims: By studying the interactions between winter warming and summer grazing, we aimed to disentangle their effects and give recommendations for future grassland management.Methods: Our study area Upper Teesdale, England has winter temperatures close to 0°C and a well-studied vegetation, known for its arctic-alpine species growing at their climatic warm range limits. We set up a winter warming experiment using open top chambers (ca. +0.5°C) from mid-September until mid-May 2019 to 2022 and excluded sheep grazing during summer in a fully factorial design.Results: Graminoid biomass increased, and bryophyte biomass decreased with winter warming. There was little to no evidence that winter warming affected any of the other plant response variables we measured, neither did grazing nor the interaction between winter warming and grazing.Conclusions: Our experiment was relatively short in duration and treatments were realistic in magnitude, therefore the plant communities responded only slightly. Nevertheless, our data suggest a change towards more dominant vascular species and less bryophytes with winter warming, which might lead to lasting changes in the plant communities in the longer-term if not buffered by suitable grazing management.
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43.
  • Roth, Nina, et al. (author)
  • Floral resources in Swedish grasslands remain relatively stable under an experimental drought and are enhanced by soil amendments if regularly mown
  • 2023
  • In: Ecological Solutions and Evidence. - 2688-8319. ; 4:2
  • Journal article (peer-reviewed)abstract
    • One of the main reasons why insect pollinators are declining is a lack of floral resources. In agricultural landscapes, remaining seminatural grasslands play a key role for providing such resources. However, droughts pose an increasing threat to the abundance and continuity of flowers. Soil amendments are a novel management tool for Swedish grasslands aiming to increase carbon sequestration and soil water holding capacity. In this study, we examined how drought is affecting floral resources (i.e. floral units, nectar quantity and nectar continuity) in grasslands with different mowing regimes, and if soil amendments could mitigate potential negative drought effects.In summer 2019, we set up an experiment combining rain-out shelters (‘drought’), soil amendments (‘compost’) and different mowing regimes (‘mown’ vs. ‘abandoned’) in four extensively managed Swedish grasslands (48 plots, size 2 m2). Between May and August 2021, we counted the floral units nine times in each plot. We derived values for the nectar sugar production per floral unit from an existing database.We observed a decrease in floral units under drought in the mown, but not in the abandoned plots. Nectar quantity and continuity over the season were not significantly affected by drought across both mowing regimes—in the abandoned plots the nectar provision even extended slightly in duration (towards late summer). The compost treatment had positive effects on the floral units, nectar quantity and continuity (extending it towards early summer) in the mown, but not in the abandoned plots. The plant species in our study reacted differently to the treatments. Most of the nectar was provided by only few species (mainly Lathyrus pratensis, Vicia cracca and Anthriscus sylvestris).The results are species specific, thus other plant communities might respond differently. However, our experiment shows that nectar provision (based on database values) in grasslands with a native plant community and natural soil conditions remains relatively stable under drought. We also found that soil amendments increase floral resources in managed grasslands.
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44.
  •  
45.
  • Treat, Claire C., et al. (author)
  • Permafrost Carbon : Progress on Understanding Stocks and Fluxes Across Northern Terrestrial Ecosystems
  • 2024
  • In: Journal of Geophysical Research - Biogeosciences. - : American Geophysical Union (AGU). - 2169-8953 .- 2169-8961. ; 129:3
  • Journal article (peer-reviewed)abstract
    • Significant progress in permafrost carbon science made over the past decades include the identification of vast permafrost carbon stocks, the development of new pan-Arctic permafrost maps, an increase in terrestrial measurement sites for CO2 and methane fluxes, and important factors affecting carbon cycling, including vegetation changes, periods of soil freezing and thawing, wildfire, and other disturbance events. Process-based modeling studies now include key elements of permafrost carbon cycling and advances in statistical modeling and inverse modeling enhance understanding of permafrost region C budgets. By combining existing data syntheses and model outputs, the permafrost region is likely a wetland methane source and small terrestrial ecosystem CO2 sink with lower net CO2 uptake toward higher latitudes, excluding wildfire emissions. For 2002–2014, the strongest CO2 sink was located in western Canada (median: −52 g C m−2 y−1) and smallest sinks in Alaska, Canadian tundra, and Siberian tundra (medians: −5 to −9 g C m−2 y−1). Eurasian regions had the largest median wetland methane fluxes (16–18 g CH4 m−2 y−1). Quantifying the regional scale carbon balance remains challenging because of high spatial and temporal variability and relatively low density of observations. More accurate permafrost region carbon fluxes require: (a) the development of better maps characterizing wetlands and dynamics of vegetation and disturbances, including abrupt permafrost thaw; (b) the establishment of new year-round CO2 and methane flux sites in underrepresented areas; and (c) improved models that better represent important permafrost carbon cycle dynamics, including non-growing season emissions and disturbance effects.
  •  
46.
  • Van Orden, Kimberley, et al. (author)
  • Characteristics and Comorbid Symptoms of Older Adults Reporting Death Ideation
  • 2013
  • In: The American journal of geriatric psychiatry. - 1064-7481. ; 21:8, s. 803-810
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE:: To determine whether death ideation in late life is associated with markers of elevated risk for suicide, or reflects normal psychological processes in later life. DESIGN/SETTING:: Population-based cross-sectional study in Gothenburg, Sweden. PARTICIPANTS:: The sample consists of 345 men and women of age 85 years (born 1901-1902) and living in Gothenburg, Sweden. MAIN OUTCOME MEASURES:: The Paykel Scale measured the most severe level of suicidality over an individual's lifetime. Other key measures were severity of depression and anxiety and frequency of death/suicidal ideation over the previous month. RESULTS:: Latent class analysis revealed distinct groups of older adults who reported recent death ideation. Recent death ideation did not occur apart from other risk factors for suicide; instead individuals reporting recent death ideation also reported either 1) recent high levels of depression and anxiety, or 2) more distant histories of serious suicidal ideation (indicative of worst point severity of suicidal ideation)-both of which elevate risk for eventual suicide. CONCLUSIONS:: Our results indicate a heterogeneous presentation of older adults who report death ideation, with some presenting with acute distress and suicidal thoughts, and others presenting with low distress but histories of serious suicidal ideation. The presence of death ideation is associated with markers of increased risk for suicide, including "worst point" active suicidal ideation.
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