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1.
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2.
  • Kalman, L. V., et al. (författare)
  • Pharmacogenetic allele nomenclature: International workgroup recommendations for test result reporting
  • 2016
  • Ingår i: Clinical Pharmacology and Therapeutics. - : WILEY-BLACKWELL. - 0009-9236 .- 1532-6535. ; 99:2, s. 172-185
  • Tidskriftsartikel (refereegranskat)abstract
    • This article provides nomenclature recommendations developed by an international workgroup to increase transparency and standardization of pharmacogenetic (PGx) result reporting. Presently, sequence variants identified by PGx tests are described using different nomenclature systems. In addition, PGx analysis may detect different sets of variants for each gene, which can affect interpretation of results. This practice has caused confusion and may thereby impede the adoption of clinical PGx testing. Standardization is critical to move PGx forward.
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3.
  • Obst, Matthias, 1974, et al. (författare)
  • A Marine Biodiversity Observation Network for Genetic Monitoring of Hard-Bottom Communities (ARMS-MBON)
  • 2020
  • Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Marine hard-bottom communities are undergoing severe change under the influence of multiple drivers, notably climate change, extraction of natural resources, pollution and eutrophication, habitat degradation, and invasive species. Monitoring marine biodiversity in such habitats is, however, challenging as it typically involves expensive, non-standardized, and often destructive sampling methods that limit its scalability. Differences in monitoring approaches furthermore hinders inter-comparison among monitoring programs. Here, we announce a Marine Biodiversity Observation Network (MBON) consisting of Autonomous Reef Monitoring Structures (ARMS) with the aim to assess the status and changes in benthic fauna with genomic-based methods, notably DNA metabarcoding, in combination with image-based identifications. This article presents the results of a 30-month pilot phase in which we established an operational and geographically expansive ARMS-MBON. The network currently consists of 20 observatories distributed across European coastal waters and the polar regions, in which 134 ARMS have been deployed to date. Sampling takes place annually, either as short-term deployments during the summer or as long-term deployments starting in spring. The pilot phase was used to establish a common set of standards for field sampling, genetic analysis, data management, and legal compliance, which are presented here. We also tested the potential of ARMS for combining genetic and image-based identification methods in comparative studies of benthic diversity, as well as for detecting non-indigenous species. Results show that ARMS are suitable for monitoring hard-bottom environments as they provide genetic data that can be continuously enriched, re-analyzed, and integrated with conventional data to document benthic community composition and detect non-indigenous species. Finally, we provide guidelines to expand the network and present a sustainability plan as part of the European Marine Biological Resource Centre (www.embrc.eu).
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4.
  • Andrade, S. C. S., et al. (författare)
  • Disentangling ribbon worm relationships: multi-locus analysis supports traditional classification of the phylum Nemertea
  • 2012
  • Ingår i: Cladistics. - : Wiley. - 0748-3007. ; 28:2, s. 141-159
  • Tidskriftsartikel (refereegranskat)abstract
    • The phylogenetic relationships of selected members of the phylum Nemertea are explored by means of six markers amplified from the genomic DNA of freshly collected specimens (the nuclear 18S rRNA and 28S rRNA genes, histones H3 and H4, and the mitochondrial genes 16S rRNA and cytochrome c oxidase subunit I). These include all previous markers and regions used in earlier phylogenetic analyses of nemerteans, therefore acting as a scaffold to which one could pinpoint any previously published study. Our results, based on analyses of static and dynamic homology concepts under probabilistic and parsimony frameworks, agree in the non-monophyly of Palaeonemertea and in the monophyly of Heteronemerta and Hoplonemertea. The position of Hubrechtella and the Pilidiophora hypothesis are, however, sensitive to analytical method, as is the monophyly of the non-hubrechtiid palaeonemerteans. Our results are, however, consistent with the main division of Hoplonemertea into Polystilifera and Monostilifera, the last named being divided into Cratenemertea and Distromatonemertea, as well as into the main division of Heteronemertea into Baseodiscus and the remaining species. The study also continues to highlight the deficient taxonomy at the family and generic level within Nemertea and sheds light on the areas of the tree that require further refinement.
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5.
  • Bachmann, L., et al. (författare)
  • The role of systematics for understanding ecosystem functions: Proceedings of the Zoologica Scripta Symposium, Oslo, Norway, 25 August 2022
  • 2023
  • Ingår i: Zoologica Scripta. - : Wiley. - 0300-3256 .- 1463-6409. ; 52:3, s. 187-214
  • Tidskriftsartikel (refereegranskat)abstract
    • On 25 August 2022, the Zoologica Scripta - An International Journal of Systematic Zoology and the Norwegian Academy of Sciences and Letters arranged a symposium entitled 'The role of systematics for understanding ecosystem functions' in the Academy's premises in Oslo, Norway. The symposium aimed at offering a forum for exploring and discussing trends and future developments in the field of systematics. Eleven international experts contributed expertise on various issues related to global challenges, such as biodiversity assessments, databases, cutting-edge analysis tools, and the consequences of the taxonomic impediment. Here, we compiled a multi-author proceedings paper of the symposium contributions that are arranged in chapters and presents the content and the key conclusions of the majority of the presentations.
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6.
  • Brodowski, W, et al. (författare)
  • Exclusive measurement of pp -> pp pi(+)pi(-) at CELSIUS
  • 2000
  • Ingår i: ACTA PHYSICA POLONICA B. - : ACTA PHYSICA POLONICA B, JAGELLONIAN UNIV, INST PHYSICS. - 0587-4254. ; 31:10-11, s. 2295-2298
  • Tidskriftsartikel (refereegranskat)abstract
    • With the PROMICE/WASA detector setup at CELSIUS the reaction pp --> NN pi pi has been measured in the energy range from 650 to 775 MeV. These data constitute the first exclusive high-statistics measurements on a pure hydrogen target, supplying both differ
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7.
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8.
  • Garte, S, et al. (författare)
  • Metabolic gene polymorphism frequencies in control populations
  • 2001
  • Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1055-9965. ; 10:12, s. 1239-1248
  • Tidskriftsartikel (refereegranskat)
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9.
  • Huezo-Diaz, P, et al. (författare)
  • CYP2C19 genotype predicts steady state escitalopram concentration in GENDEP
  • 2012
  • Ingår i: Journal of psychopharmacology (Oxford, England). - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 26:3, s. 398-407
  • Tidskriftsartikel (refereegranskat)abstract
    • In vitro work shows CYP2C19 and CYP2D6 contribute to the metabolism of escitalopram to its primary metabolite, N-desmethylescitalopram. We report the effect of CYP2C19 and CYP2D6 genotypes on steady state morning concentrations of escitalopram and N-desmethylescitalopram and the ratio of this metabolite to the parent drug in 196 adult patients with depression in GENDEP, a clinical pharmacogenomic trial. Subjects who had one CYP2D6 allele associated with intermediate metabolizer phenotype and one associated with poor metabolizer (i.e. IM/PM genotypic category) had a higher mean logarithm escitalopram concentration than CYP2D6 extensive metabolizers (EMs) ( p = 0.004). Older age was also associated with higher concentrations of escitalopram. Covarying for CYP2D6 and age, we found those homozygous for the CYP2C19*17 allele associated with ultrarapid metabolizer (UM) phenotype had a significantly lower mean escitalopram concentration (2-fold, p = 0.0001) and a higher mean metabolic ratio ( p = 0.0003) than EMs, while those homozygous for alleles conferring the PM phenotype had a higher mean escitalopram concentration than EMs (1.55-fold, p = 0.008). There was a significant overall association between CYP2C19 genotypic category and escitalopram concentration ( p = 0.0003; p = 0.0012 Bonferroni corrected). In conclusion, we have demonstrated an association between CYP2C19 genotype, including the CYP2C19*17 allele, and steady state escitalopram concentration.
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10.
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11.
  • van der Wouden, C. H., et al. (författare)
  • Implementing Pharmacogenomics in Europe : Design and Implementation Strategy of the Ubiquitous Pharmacogenomics Consortium
  • 2017
  • Ingår i: Clinical Pharmacology and Therapeutics. - : WILEY. - 0009-9236 .- 1532-6535. ; 101:3, s. 341-358
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite scientific and clinical advances in the field of pharmacogenomics (PGx), application into routine care remains limited. Opportunely, several implementation studies and programs have been initiated over recent years. This article presents an overview of these studies and identifies current research gaps. Importantly, one such gap is the undetermined collective clinical utility of implementing a panel of PGx-markers into routine care, because the evidence base is currently limited to specific, individual drug-gene pairs. The Ubiquitous Pharmacogenomics (U-PGx) Consortium, which has been funded by the European Commission's Horizon-2020 program, aims to address this unmet need. In a prospective, block-randomized, controlled clinical study (PREemptive Pharmacogenomic testing for prevention of Adverse drug REactions [PREPARE]), pre-emptive genotyping of a panel of clinically relevant PGx-markers, for which guidelines are available, will be implemented across healthcare institutions in seven European countries. The impact on patient outcomes and cost-effectiveness will be investigated. The program is unique in its multicenter, multigene, multidrug, multi-ethnic, and multi-healthcare system approach.
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12.
  • Wein, Marc N., et al. (författare)
  • SIKs control osteocyte responses to parathyroid hormone
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Parathyroid hormone (PTH) activates receptors on osteocytes to orchestrate bone formation and resorption. Here we show that PTH inhibition of SOST (sclerostin), a WNT antagonist, requires HDAC4 and HDAC5, whereas PTH stimulation of RANKL, a stimulator of bone resorption, requires CRTC2. Salt inducible kinases (SIKs) control subcellular localization of HDAC4/5 and CRTC2. PTH regulates both HDAC4/5 and CRTC2 localization via phosphorylation and inhibition of SIK2. Like PTH, new small molecule SIK inhibitors cause decreased phosphorylation and increased nuclear translocation of HDAC4/5 and CRTC2. SIK inhibition mimics many of the effects of PTH in osteocytes as assessed by RNA-seq in cultured osteocytes and following in vivo administration. Once daily treatment with the small molecule SIK inhibitor YKL-05-099 increases bone formation and bone mass. Therefore, a major arm of PTH signalling in osteocytes involves SIK inhibition, and small molecule SIK inhibitors may be applied therapeutically to mimic skeletal effects of PTH.
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13.
  • Andel, B., et al. (författare)
  • β -delayed fission of isomers in Bi 188
  • 2020
  • Ingår i: Physical Review C. - 2469-9985. ; 102:1
  • Tidskriftsartikel (refereegranskat)abstract
    • β-delayed fission (βDF) decay of a low-spin (ls) and a high-spin (hs) isomer in Bi188 was studied at the ISOLDE facility at CERN. Isomer-selective laser ionization and time gating were employed to investigate each isomer separately and their βDF partial half-lives were determined: T1/2p,βDF(188Bihs)=5.6(8)×103 s and T1/2p,βDF(188Bils)=1.7(6)×103 s. This work is the first βDF study of two states in one isotope and allows the spin dependence of low-energy fission to be explored. The fission fragment mass distribution of a daughter nuclide Pb188, following the β decay of the high-spin isomer, was deduced and indicates a mixture of symmetric and asymmetric fission modes. Experimental results were compared with self-consistent mean-field calculations based on the finite-range Gogny D1M interaction. To reproduce the measured T1/2p,βDF(188Bihs), the calculated fission barrier of Pb188 had to be reduced by ≈30%. After this reduction, the measured T1/2p,βDF(188Bils) was in agreement with calculations for a few possible configurations for Bils188. Theoretical βDF probabilities for these configurations were found to be lower by a factor of 4-9 than the βDF probability of Bihs188. The fission fragment mass distribution of Pb188 was compared to the scission-point model SPY and the calculations based on the finite-range liquid-drop model. The first observation of βDF for Bi190 is also reported. © 2020 authors. Published by the American Physical Society. Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.
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14.
  • Benhamou, S, et al. (författare)
  • Meta- and pooled analyses of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk
  • 2002
  • Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 23:8, s. 1343-1350
  • Tidskriftsartikel (refereegranskat)abstract
    • Susceptibility to lung cancer may in part be attributable to inter-individual variability in metabolic activation or detoxification of tobacco carcinogens. The glutathione S-transferase M1 (GSTM1) genetic polymorphism has been extensively studied in this context; two recent meta-analyses of case-control studies suggested an association between GSTM1 deletion and lung cancer. At least 15 studies have been published after these overviews. We undertook a new meta-analysis to summarize the results of 43 published case-control studies including >18 000 individuals. A slight excess of risk of lung cancer for individuals with the GSTM1 null genotype was found (odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.07-1.27). No evidence of publication bias was found (P = 0.4), however, it is not easy to estimate the extent of such bias and we cannot rule out some degree of publication bias in our results. A pooled analysis of the original data of about 9500 subjects involved in 21 case-control studies from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC) data set was performed to assess the role of GSTM1 genotype as a modifier of the effect of smoking on lung cancer risk with adequate power. Analyses revealed no evidence of increased risk of lung cancer among carriers of the GSTM1 null genotype (age-, gender- and center-adjusted OR = 1.08, 95% CI 0.98-1.18) and no evidence of interaction between GSTM1 genotype and either smoking status or cumulative tobacco consumption.
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15.
  • Carlson, R. F., et al. (författare)
  • A method for measuring light ion reaction cross-sections
  • 2005
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 547:2-3, s. 541-554
  • Tidskriftsartikel (refereegranskat)abstract
    • An experimental procedure for measuring reaction cross-sections of light ions in the energy range 20 50 MeV/nucleon, using a modified attenuation technique, is described. The detection method incorporates a forward detector that simultaneously measures the reaction cross-sections for five different sizes of the solid angle in steps from 99.1% to 99.8% of the total solid angle. The final reaction cross-section values are obtained by extrapolation to the full solid angle.
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16.
  • Cerutti, P. O., et al. (författare)
  • The socioeconomic and environmental impacts of wood energy value chains in Sub-Saharan Africa : A systematic map protocol
  • 2015
  • Ingår i: Environmental Evidence. - : Springer Science and Business Media LLC. - 2047-2382. ; 4:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The vast majority of households in Sub-Saharan Africa (SSA) depend on wood energy - comprising firewood and charcoal - for their daily energetic needs. Such consumption trends are expected to remain a common feature of SSA's wood energy production and supply chains, at least in the short- to medium-terms. Notwithstanding its importance, wood energy generally has low priority in SSA national policies. However, the use of wood energy is often considered a key driver of unsustainable management and negative environmental consequences in the humid and dry forests. To date, unsystematic assessments of the socio-economic and environmental consequences of wood energy use have underplayed its significance, thus further hampering policy debates. Therefore, a more balanced approach which considers both demand and supply dynamics is needed. This systematic map aims at providing a comprehensive approach to understanding the role and impacts of wood energy across all regions and aspects in SSA. Methods: The objective of this systematic map is to collate evidence from studies of environmental and socio-economic impacts of wood energy value chains, by considering both demand and supply within SSA. The map questions are framed using a Populations, Exposure, Comparators and Outcomes (PECO) approach. We name the supply and demand of wood energy as the "exposure," composed of wood energy production, harvesting, processing, and consumption. The populations of interest include both the actors involved in these activities and the forest sites where these activities occur. The comparator is defined as those cases where the same wood energy activities occur with i) available/accessible alternative energy sources, ii) regulatory frameworks that govern the sector and iii) alternative technologies for efficient use. The outcomes of interest encompass both socioeconomic and environmental impacts that can affect more than the populations named above. For instance, in addition to the direct socioeconomic impacts felt by participants in the wood energy value chain, forest dwellers may experience livelihood changes due to forest degradation caused by external harvesters. Moreover, intensified deforestation in one area may concurrently lead to forest regeneration in another.
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19.
  • Perry, G. W., et al. (författare)
  • Spatiotemporally resolved electrodynamic properties of a Sun-aligned arc over Resolute Bay
  • 2015
  • Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 120:11, s. 9977-9987
  • Tidskriftsartikel (refereegranskat)abstract
    • Common volume measurements by the Resolute Bay Incoherent Scatter Radar-North (RISR-N) and Optical Mesosphere and Thermosphere Imagers (OMTI) have been used to clarify the electrodynamic structure of a Sun-aligned arc in the polar cap. The plasma parameters of the dusk-to-dawn drifting arc and surrounding ionosphere are extracted using the volumetric imaging capabilities of RISR-N. Multipoint line-of-sight RISR-N measurements of the plasma drift are inverted to construct a time sequence of the electric field and field-aligned current system of the arc. Evidence of dramatic electrodynamic and plasma structuring of the polar cap ionosphere due to the arc is described. One notable feature of the arc is a meridionally extended plasma density depletion on its leading edge, located partially within a downward field-aligned current region. The depletion is determined to be a by-product of enhanced chemical recombination operating on a time scale of 15 min. A similarly shaped electric field structure of over 100 mV/m and line-of-sight ion temperatures nearing 3000 K were collocated with the depletion.
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20.
  • Roghanian, Ali, et al. (författare)
  • Antagonistic Human FcγRIIB (CD32B) Antibodies Have Anti-Tumor Activity and Overcome Resistance to Antibody Therapy In Vivo.
  • 2015
  • Ingår i: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 27:4, s. 473-488
  • Tidskriftsartikel (refereegranskat)abstract
    • Therapeutic antibodies have transformed cancer therapy, unlocking mechanisms of action by engaging the immune system. Unfortunately, cures rarely occur and patients display intrinsic or acquired resistance. Here, we demonstrate the therapeutic potential of targeting human (h) FcγRIIB (CD32B), a receptor implicated in immune cell desensitization and tumor cell resistance. FcγRIIB-blocking antibodies prevented internalization of the CD20-specific antibody rituximab, thereby maximizing cell surface accessibility and immune effector cell mediated antitumor activity. In hFcγRIIB-transgenic (Tg) mice, FcγRIIB-blocking antibodies effectively deleted target cells in combination with rituximab, and other therapeutic antibodies, from resistance-prone stromal compartments. Similar efficacy was seen in primary human tumor xenografts, including with cells from patients with relapsed/refractory disease. These data support the further development of hFcγRIIB antibodies for clinical assessment.
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21.
  • Sarteau, A. C., et al. (författare)
  • Changes to care delivery at nine international pediatric diabetes clinics in response to the COVID-19 global pandemic
  • 2021
  • Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 22:3, s. 463-468
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Pediatric diabetes clinics around the world rapidly adapted care in response to COVID-19. We explored provider perceptions of care delivery adaptations and challenges for providers and patients across nine international pediatric diabetes clinics. Methods Providers in a quality improvement collaborative completed a questionnaire about clinic adaptations, including roles, care delivery methods, and provider and patient concerns and challenges. We employed a rapid analysis to identify main themes. Results Providers described adaptations within multiple domains of care delivery, including provider roles and workload, clinical encounter and team meeting format, care delivery platforms, self-management technology education, and patient-provider data sharing. Providers reported concerns about potential negative impacts on patients from COVID-19 and the clinical adaptations it required, including fears related to telemedicine efficacy, blood glucose and insulin pump/pen data sharing, and delayed care-seeking. Particular concern was expressed about already vulnerable patients. Simultaneously, providers reported 'silver linings' of adaptations that they perceived as having potential to inform care and self-management recommendations going forward, including time-saving clinic processes, telemedicine, lifestyle changes compelled by COVID-19, and improvements to family and clinic staff literacy around data sharing. Conclusions Providers across diverse clinical settings reported care delivery adaptations in response to COVID-19-particularly telemedicine processes-created challenges and opportunities to improve care quality and patient health. To develop quality care during COVID-19, providers emphasized the importance of generating evidence about which in-person or telemedicine processes were most beneficial for specific care scenarios, and incorporating the unique care needs of the most vulnerable patients.
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22.
  • Sibbritt, D, et al. (författare)
  • What is the healthcare utilisation and out-of-pocket expenditure associated with osteoarthritis? A cross-sectional study
  • 2022
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:3, s. e055468-
  • Tidskriftsartikel (refereegranskat)abstract
    • To examine the use and out-of-pocket expenses resulting from consultations, products and practices across conventional, self-care, and complementary medicine (CM) treatments for osteoarthritis (OA) among Australian women.Design, setting and participantsA cross-sectional survey of 800 women from the 45 and Up Study who had reported a clinical diagnosis of OA.Outcome measuresWomen’s use of conventional, CM and self-prescribed treatments for OA and the associated out-of-pocket cost.ResultsCompleted questionnaires were returned by 403 women (50.4%). Their average time since the first diagnosis of OA was 15.4 years, and self-rated severity of OA was 5.1 (out of 10) over the past 12 months. During the previous year, 67.0% of the women consulted a doctor, 39.2% consulted an allied health practitioner and 34.7% consulted a CM practitioner for their OA. Some women (19%) consulted with practitioner(s) from all three practitioner groups, 27% consulted with practitioner(s) from two of the three practitioner groups, while 6% consulted with a CM practitioner only. Women with a greater time since diagnosis had more consultations, as did women who rated their OA as more severe. Women’s average combined out-of-pocket expenditure for OA-related healthcare consultations, prescription medications, products, and practices was $673 per annum. Extrapolated to all Australian women with OA, aged 50 years and over, the total out-of-pocket expenditure for this condition is estimated to be $873 million per annum.ConclusionsAustralian women with OA use a range of conventional and CM consultations, self-care, products and practices to manage their condition, incurring significant out-of-pocket expenses. Given the high individual and societal burden of OA, there is a need for further research into the concurrent use of different healthcare resources with a view to providing safe, cost-effective management of OA across the healthcare system and the wider community.
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23.
  • Smits, KM, et al. (författare)
  • Association of metabolic gene polymorphisms with tobacco consumption in healthy controls
  • 2004
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 110:2, s. 266-270
  • Tidskriftsartikel (refereegranskat)abstract
    • Polymorphisms in genes that encode for metabolic enzymes have been associated with variations in enzyme activity between individuals. Such variations could be associated with differences in individual exposure to carcinogens that are metabolized by these genes. In this study, we examine the association between polymorphisms in several metabolic genes and the consumption of tobacco in a large sample of healthy individuals. The database of the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens was used. All the individuals who were controls from the case-control studies included in the data set with information on smoking habits and on genetic polymorphisms were selected (n = 20,938). Sufficient information was available on the following genes that are involved in the metabolism of tobacco smoke constituents: CYPIAI, GSTMI, GSTTI, NAT2 and GSTPI. None of the tested genes was clearly associated with smoking behavior. Information on smoking dose, available for a subset of subjects, showed no effect of metabolic gene polymorphisms on the amount of smoking. No association between polymorphisms in the genes studied and tobacco consumption was observed; therefore, no effect of these genes on smoking behavior should be expected.
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24.
  • Sundberg, J., et al. (författare)
  • A Versatile Dinucleating Ligand Containing Sulfonamide Groups
  • 2014
  • Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 53:6, s. 2873-2882
  • Tidskriftsartikel (refereegranskat)abstract
    • Copper, iron, and gallium coordination chemistries of the new pentadentate bis-sulfonamide ligand 2,6-bis(N-2-pyridylmethylsulfonamido)-4-methylphenol (psmpH(3)) were investigated. PsmpH(3) is capable of varying degrees of deprotonation, and notably, complexes containing the fully trideprotonated ligand can be prepared in aqueous solutions using only divalent metal ions. Two of the copper(II) complexes, [Cu-2(psmp)(OH)] and [Cu-2(psmp)(OAc)(2)](-), demonstrate the anticipated 1:2 ligand/metal stoichiometry and show that the dimetallic binding site created for exogenous ligands possesses high inherent flexibility since additional one- and three-atom bridging ligands bridge the two copper(11) ions in each complex, respectively. This gives rise to a difference of 0.4 angstrom in the Cu center dot center dot center dot Cu distances. Complexes with 2:3 and 2:1 ligand/metal stoithiometries for the divalent and trivalent metal ions, respectively, were observed in [Cu-3(psmp)(2)(H2O)] and [M(psmpH)(psmpH(2))], where M = Ga-III, Fe-III. The deprotonated tridentate N-2-pyridylsulfonylmethylphenolato moieties chelate the metal ions in a meridional fashion, whereas in [Cu-3(psmp)(2)(H2O)] the rare mu(2)-N-sulfonarnido bridging coordination mode is observed. In the bis-ligand mononuclear complexes, one picolyl arm of each ligand is protonated and uncoordinated. Magnetic susceptibility measurements on the doubly and triply bridged dicopper(II) complexes indicate strong and medium strength antiferromagnetic coupling interactions, with J = 234 cm(-1) and 115 cm(-1) for [Cu-2(psmp)(OH)] and [Cu-2(psmp)(OAc)(2)](-), respectively (in H-HDvV = ... +JS(1)S(2) convention). The trinudear [Cu-3(psmp)(2)(H2O)], in which the central copper ion is linked to two flanking copper atoms by two mu(2)-N-sulfonamido bridges and two phenoxide bridges shows an overall magnetic behavior of antiferromagnetic coupling. This is corroborated computationally by broken-symmetry densityfunctional theory, which for isotropic modeling of the coupling predicts an antiferromagnetic coupling strength of J = 70.5 cm(-1).
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25.
  • Sundberg, J., et al. (författare)
  • Accessing iron amides from dimesityliron
  • 2015
  • Ingår i: Journal of Organometallic Chemistry. - : Elsevier BV. - 0022-328X. ; 786, s. 40-47
  • Tidskriftsartikel (refereegranskat)abstract
    • A new phase of dimesityliron has been crystallized from diethylether; the crystal structure shows a dinuclear complex with co-crystallized solvent. Crystalline [Fe-2(mes)(2)(mu(2)-mes)(2)]center dot Et2O is a convenient starting material and reacts with di(2-pyridyl) amine to yield rare iron di(2-pyridyl) amido complexes. Crystal structures of air-sensitive [Fe-2(mes)(2)(dpa)(2)], [Fe-2(dpa)(3)Cl] and [Fe-4(dpa)(6)O] were determined. [Fe-4(dpa)(6)O] is known, and the dinuclear complexes [Fe-2(mes)(2)(dpa)(2)] and [Fe-2(dpa)(3)Cl] represent only the second and third reports of homometallic iron dpa(-) complexes. Long Fe. Fe distances of 3.043(1) and 3.104(2) angstrom in [Fe-2(mes)(2)(dpa)(2)] and [Fe-2(dpa)(3)Cl], respectively, and very unsymmetrically coordinated amido groups, indicate that the iron atoms are not involved in M-M bonding. This fact, and the relatively low coordination numbers of the high spin Fe(II) atoms are consistent with sensitivity of these compounds towards O-2. DFT calculations were employed to rationalize the formation of the unusual architectures displayed by the dpa(-) complexes of iron. (C) 2015 Elsevier B.V. All rights reserved.
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27.
  • Andersson-Gunneras, S., et al. (författare)
  • Biosynthesis of cellulose-enriched tension wood in Populus : global analysis of transcripts and metabolites identifies biochemical and developmental regulators in secondary wall biosynthesis
  • 2006
  • Ingår i: The Plant Journal. - Malden : Wiley-Blackwell. - 0960-7412 .- 1365-313X. ; 45:2, s. 144-165
  • Tidskriftsartikel (refereegranskat)abstract
    • Stems and branches of angiosperm trees form tension wood (TW) when exposed to a gravitational stimulus. One of the main characteristics of TW, which distinguishes it from normal wood, is the formation of fibers with a thick inner gelatinous cell wall layer mainly composed of crystalline cellulose. Hence TW is enriched in cellulose, and deficient in lignin and hemicelluloses. An expressed sequence tag library made from TW-forming tissues in Populus tremula (L.) x tremuloides (Michx.) and data from transcript profiling using microarray and metabolite analysis were obtained during TW formation in Populus tremula (L.) in two growing seasons. The data were examined with the aim of identifying the genes responsible for the change in carbon
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28.
  • ANDRADE, S.C.S, et al. (författare)
  • A transcriptomic approach to ribbon worm systematics (Nemertea): resolving the Pilidiophora problem.
  • 2014
  • Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 31:12, s. 3206-3215
  • Tidskriftsartikel (refereegranskat)abstract
    • Resolving the deep relationships of ancient animal lineages has proven difficult using standard Sanger-sequencing approaches with a handful of markers. We thus reassess the relatively well-studied phylogeny of the phylum Nemertea (ribbon worms)—for which the targeted gene approaches had resolved many clades but had left key phylogenetic gaps—by using a phylogenomic approach using Illumina-based de novo assembled transcriptomes and automatic orthology prediction methods. The analysis of a concatenated data set of 2,779 genes (411,138 amino acids) with about 78% gene occupancy and a reduced version with 95% gene occupancy, under evolutionary models accounting or not for site-specific amino acid replacement patterns results in a well-supported phylogeny that recovers all major accepted nemertean clades with the monophyly of Heteronemertea, Hoplonemertea, Monostilifera, being well supported. Significantly, all the ambiguous patterns inferred from Sanger-based approaches were resolved, namely the monophyly of Palaeonemertea and Pilidiophora. By testing for possible conflict in the analyzed supermatrix, we observed that concatenation was the best solution, and the results of the analyses should settle prior debates on nemertean phylogeny. The study highlights the importance, feasibility, and completeness of Illumina-based phylogenomic data matrices.
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29.
  • Bell, CC, et al. (författare)
  • Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease
  • 2016
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 25187-
  • Tidskriftsartikel (refereegranskat)abstract
    • Liver biology and function, drug-induced liver injury (DILI) and liver diseases are difficult to study using current in vitro models such as primary human hepatocyte (PHH) monolayer cultures, as their rapid de-differentiation restricts their usefulness substantially. Thus, we have developed and extensively characterized an easily scalable 3D PHH spheroid system in chemically-defined, serum-free conditions. Using whole proteome analyses, we found that PHH spheroids cultured this way were similar to the liver in vivo and even retained their inter-individual variability. Furthermore, PHH spheroids remained phenotypically stable and retained morphology, viability and hepatocyte-specific functions for culture periods of at least 5 weeks. We show that under chronic exposure, the sensitivity of the hepatocytes drastically increased and toxicity of a set of hepatotoxins was detected at clinically relevant concentrations. An interesting example was the chronic toxicity of fialuridine for which hepatotoxicity was mimicked after repeated-dosing in the PHH spheroid model, not possible to detect using previous in vitro systems. Additionally, we provide proof-of-principle that PHH spheroids can reflect liver pathologies such as cholestasis, steatosis and viral hepatitis. Combined, our results demonstrate that the PHH spheroid system presented here constitutes a versatile and promising in vitro system to study liver function, liver diseases, drug targets and long-term DILI.
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30.
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31.
  • Brandberg, H, et al. (författare)
  • A prospective cohort study of self-reported computerised medical history taking for acute chest pain: protocol of the CLEOS-Chest Pain Danderyd Study (CLEOS-CPDS)
  • 2020
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 10:1, s. e031871-
  • Tidskriftsartikel (refereegranskat)abstract
    • Management of acute chest pain focuses on diagnosis or safe rule-out of an acute coronary syndrome (ACS). We aim to determine the additional value of self-reported computerised history taking (CHT).Methods and analysisProspective cohort study design with self-reported, medical histories collected by a CHT programme (Clinical Expert Operating System, CLEOS) using a tablet. Women and men presenting with acute chest pain to the emergency department at Danderyd University Hospital (Stockholm, Sweden) are eligible. CHT will be compared with standard history taking for completeness of data required to calculate ACS risk scores such as History, ECG, Age, Risk factors and Troponin (HEART), Global Registry of Acute Coronary Events (GRACE), and Thrombolysis in Myocardial Infarction (TIMI). Clinical outcomes will be extracted from hospital electronic health records and national registries. The CLEOS-Chest Pain Danderyd Study project includes (1) a feasibility study of CHT, (2) a validation study of CHT as compared with standard history taking, (3) a paired diagnostic accuracy study using data from CHT and established risk scores, (4) a clinical utility study to evaluate the impact of CHT on the management of chest pain and the use of resources, and (5) data mining, aiming to generate an improved risk score for ACS. Primary outcomes will be analysed after 1000 patients, but to allow for subgroup analysis, the study intends to recruit 2000 or more patients. This ongoing project may lead to new and more effective ways for collecting thorough, accurate medical histories with important implications for clinical practice.Ethics and disseminationThis study has been reviewed and approved by the Stockholm Regional Ethical Committee (now Swedish Ethical Review Authority). Results will be published, regardless of the outcome, in peer-reviewed international scientific journals.Trial registration numberThis study is registered athttps://www.clinicaltrials.gov(unique identifier:NCT03439449).
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32.
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33.
  • Diagnostics at the MAX IV 3 GeV storage ring during commissioning
  • 2016
  • Ingår i: Proceedings of the 5th International Beam Instrumentation Conference, IBIC 2016. - 9783954501779 ; , s. 1-5
  • Konferensbidrag (refereegranskat)abstract
    • The MAX IV 3 GeV storage ring based on a multibend achromat lattice allows for horizontal emittances from 330 pm rad down to 180 pm rad, depending on the number of insertion devices. The diagnostics used during commissioning will be described, with emphasis on the emittance diagnostics. This will involve two diagnostic beam lines to image the electron beam with infrared and ultraviolet synchrotron radiation from bending magnets, in order to determine also beam energy spread. The scheme for horizontal emittance measurements looks promising also for an order of magnitude lower emittance. Bunch lengthening with harmonic cavities is essential for the low emittance machine performance. We have used a radiation-based sampling technique to verify individual bunch distributions.
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34.
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35.
  • Finnveden, Göran, et al. (författare)
  • Developing and evaluating new policy instruments for sustainable waste management
  • 2012
  • Ingår i: International Journal of Environment and Sustainable Development (IJESD). - 1474-6778 .- 1478-7466. ; 11:1, s. 19-31
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this paper is to suggest a number of interesting policy instruments that can make the Swedish waste management system more sustainable. Approximately 60 suggestions for policy instruments were gathered through a number of workshops with stakeholders. These were further prioritised in a workshop with stakeholders and by the research team resulting in a list of 15 instruments: information to citizens and companies; tax on raw materials; weight-based waste collection fee; environmentally differentiated waste collection fee; waste minimisation in enterprises; 'Advertising brochures - yes, please!'; recycling certificates; developed collection systems; tax on incineration of waste from fossil fuels; tax on incineration of waste; including waste in green certificates for electricity production; tax on hazardous substances; labelling of goods with hazardous substances; improved control by authorities; differentiated VAT and ban on incineration of recyclable materials. Several policy instruments are needed that can complement each other.
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36.
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37.
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38.
  • Gitau, K. J., et al. (författare)
  • Factors influencing the adoption of biochar-producing gasifier cookstoves by households in rural Kenya
  • 2019
  • Ingår i: Energy for Sustainable Development. - : ELSEVIER. - 0973-0826 .- 2352-4669. ; 52, s. 63-71
  • Tidskriftsartikel (refereegranskat)abstract
    • Fuel wood is the main source of cooking and heating energy in developing countries. However, it is combusted in inefficient cookstoves, leading to more fuel use and human health problems resulting from exposure to smoke. Thus new, efficient cooking systems that can address some of these problems are required. This study examined gasifier cookstove use in Kwale County, Kenya, and factors influencing adoption. Gasifier stoves were issued for free to 50 households, which were surveyed after 2-3 months of use. The results showed that the stove was used by 96% of the households at varying frequencies, 40% of them used it almost every day with 4% switching to only using the new stove. All the users appreciated it because it saved fuel, produced less smoke, and produced charcoal to use for either cooking or soil amendment. Compared with the traditional three-stone open fire, the gasifier stove was reported to be easier to clean (98% of respondents), easier to adjust the heat (88%), easier to handle (58%), caused less exposure to heat (96%) and was cleaner for pots and the kitchen (98%). Another reported benefit of the gasifier stove was that it needed no tending (i.e., adjusting wood and blowing to keep the flames burning). The gasifier stove was mainly used to cook foods that required a short cooking time and many preferred to use it to cook dinner. However, the households encountered some challenges with using the gasifier stoves. For example, fuel preparation, reloading, and lighting were reported as challenges by 42%, 77% and 19%, respectively, of the 83% of households who reported challenges. These challenges could be overcome by improving stove design and by devising innovative ways of cutting fuel into small pieces. 2019 The Authors. Published by Elsevier Inc. on behalf of International Energy Initiative.
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39.
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40.
  • Greaves, Deborah, et al. (författare)
  • Environmental Impact Assessment : Gathering experiences from wave energy test centres in Europe
  • 2016
  • Ingår i: International Journal of Marine Energy. - : Elsevier BV. - 2214-1669. ; 14, s. 68-79
  • Tidskriftsartikel (refereegranskat)abstract
    • The wave energy industry is an emerging sector and a new user of maritime space that has potential to contribute significantly to the EU renewable energy goals. International and national regulatory frameworks necessitate Environmental Impact Assessments (EIA) that provide important data to inform development consent decisions. Here we have evaluated experience related to the assessment programmes at EU wave energy test centres combined with knowledge gained from EIA produced for other similar renewable energy developments. From this we have identified key receptors of concern, as well as the type and magnitude of impacts which may be expected. The key environmental receptors of concern for wave energy EIA include the physical environment (e.g. morphology, waves and current) and flora and fauna(1) as represented by marine mammals, seabirds, benthos, fish and shellfish. From a review of the EIAs performed at wave energy test centres, we identified several lessons regarding the wave energy EIA process. There is clear evidence that the receptors of primary interest are dependent on factors such as the local environmental characteristics, the presence/absence of protected species and the regulatory authority under which the EIA is performed. Furthermore, it is recommended that concerns relating to cumulative impacts, from an expanding level of wave energy development taking place in a background of growing utilisation of the marine environment, which are largely unknown at this early stage of the industry may be comprehensively addressed at the national level as part of a Strategic Environmental Assessment (EIA) and/or in Maritime Spatial Planning (MSP) and that it should be regularly reassessed.
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41.
  • Gunnarsson, B-M, et al. (författare)
  • The immigrant and the workplace
  • 2004
  • Ingår i: SS 15 (Sociolinguistics Symposium 15), Workshop, April, 1-4, Newcastle upon Tyne, UK.
  • Konferensbidrag (refereegranskat)
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42.
  • Hagman, H., et al. (författare)
  • A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer : the Nordic ACT2 trial
  • 2016
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:1, s. 140-147
  • Tidskriftsartikel (refereegranskat)abstract
    • Maintenance treatment (mt) with bevacizumab (bev) +/- erlotinib (erlo) has modest effect after induction chemotherapy in metastatic colorectal cancer (mCRC). We hypothesized the efficacy of erlo to be dependent on KRAS mutational status and investigated this by exploring mt strategies with bev +/- erlo and low-dose capecitabine (cap). Included patients had mCRC scheduled for first-line therapy, Eastern Cooperative Oncology Group (ECOG) 0-1 and no major comorbidities. Treatment with XELOX/FOLFOX or XELIRI/FOLFIRI + bev was given for 18 weeks. After induction, patients without progression were eligible for randomization to mt; KRAS wild-type (wt) patients were randomized to bev +/- erlo (arms wt-BE, N = 36 versus wt-B, N = 35), KRAS mutated (mut) patients were randomized to bev or metronomic cap (arms mut-B, N = 34 versus mut-C, N = 33). Primary end point was progression-free survival (PFS) rate (PFSr) at 3 months after start of mt. A pooled analysis of KRAS wt patients from the previous ACT study was performed. We included 233 patients. Median age was 64 years, 62% male, 68% ECOG 0, 52% with primary tumor in situ. A total of 138 patients started mt after randomization. PFSr was 64.7% versus 63.6% in wt-B versus wt-BE, P = 1.000; and 75% versus 66.7% in mut-B versus mut-C, P = 0.579, with no significant difference in median PFS and overall survival (OS). In the pooled cohort, median PFS was 3.7 months in wt-B (N = 64) and 5.7 months in wt-BE (N = 62) (hazard ratios 1.03, 95% confidence interval 0.70-1.50, P = 0.867). The frequency of any grade 3/4 toxicities during mt was: 28%/58%/18%/15% (wt-B/wt-BE/mut-B/mut-C). Addition of erlo to bev as mt in KRAS wt mCRC did not significantly improve PFS or OS, but it did increase toxicity. KRAS status does not seem to influence the outcome of treatment with erlotinib. Metronomic cap warrants further investigation in mt strategies, given our explorative results. NCT01229813.
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43.
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44.
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45.
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46.
  • Johnsson, A., et al. (författare)
  • A randomized phase III trial on maintenance treatment with bevacizumab alone or in combination with erlotinib after chemotherapy and bevacizumab in metastatic colorectal cancer : the Nordic ACT Trial
  • 2013
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 24:9, s. 2335-2341
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The main objective was to study the effect on progression-free survival (PFS) of adding erlotinib to bevacizumab as maintenance treatment following chemotherapy and bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC). Patients and methods: Patients with untreated mCRC received doublet chemotherapy + bevacizumab during 18 weeks and those without tumor progression were eligible for randomization to bevacizumab + erlotinib (arm A) or bevacizumab alone (arm B), until progression or unacceptable toxic effect. Results: Of the 249 patients enrolled, 80 started maintenance treatment in arm A and 79 in arm B. The rate of any grade 3/4 toxic effect was 53% in arm A and 13% in arm B. Median PFS was 5.7 months in arm A and 4.2 months in arm B (HR = 0.79; 95% confidence interval 0.55-1.12; P = 0.19). Overall survival (OS) from start of induction chemotherapy was 26.7 months in the randomized population, with no difference between the two arms. Conclusions: The addition of erlotinib to bevacizumab as maintenance treatment after first-line chemotherapy in mCRC did not improve PFS significantly. On-going clinical and translational studies focus on identifying subgroups of patients that may benefit from erlotinib in the maintenance setting.
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47.
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48.
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49.
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50.
  • Kjellberg, A, et al. (författare)
  • Hyperbaric oxygen for treatment of long COVID-19 syndrome (HOT-LoCO): protocol for a randomised, placebo-controlled, double-blind, phase II clinical trial
  • 2022
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:11, s. e061870-
  • Tidskriftsartikel (refereegranskat)abstract
    • Long COVID-19, where symptoms persist 12 weeks after the initial SARS-CoV-2-infection, is a substantial problem for individuals and society in the surge of the pandemic. Common symptoms are fatigue, postexertional malaise and cognitive dysfunction. There is currently no effective treatment and the underlying mechanisms are unknown, although several hypotheses exist, with chronic inflammation as a common denominator. In prospective studies, hyperbaric oxygen therapy (HBOT) has been suggested to be effective for the treatment of similar syndromes such as chronic fatigue syndrome and fibromyalgia. A case series has suggested positive effects of HBOT in long COVID-19. This randomised, placebo-controlled clinical trial will explore HBOT as a potential treatment for long COVID-19. The primary objective is to evaluate if HBOT improves health-related quality of life (HRQoL) for patients with long COVID-19 compared with placebo/sham. The main secondary objective is to evaluate whether HBOT improves endothelial function, objective physical performance and short-term HRQoL.Methods and analysisA randomised, placebo-controlled, double-blind, phase II clinical trial in 80 previously healthy subjects debilitated due to long COVID-19, with low HRQoL. Clinical data, HRQoL questionnaires, blood samples, objective tests and activity metre data will be collected at baseline. Subjects will be randomised to a maximum of 10 treatments with hyperbaric oxygen or sham treatment over 6 weeks. Assessments for safety and efficacy will be performed at 6, 13, 26 and 52 weeks, with the primary endpoint (physical domains in RAND 36-Item Health Survey) and main secondary endpoints defined at 13 weeks after baseline. Data will be reviewed by an independent data safety monitoring board.Ethics and disseminationThe trial is approved by the Swedish National Institutional Review Board (2021–02634) and the Swedish Medical Products Agency (5.1-2020-36673). Positive, negative and inconclusive results will be published in peer-reviewed scientific journals with open access.Trial registration numberNCT04842448.
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