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1.
  • Hibar, D. P., et al. (författare)
  • Cortical abnormalities in bipolar disorder: An MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group
  • 2018
  • Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:4, s. 932-942
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d='0.293; P=1.71 × 10 '21), left fusiform gyrus (d='0.288; P=8.25 × 10 '21) and left rostral middle frontal cortex (d='0.276; P=2.99 × 10 '19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD. © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
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  • Ekman, Sten, et al. (författare)
  • Design inspired innovation for rural India
  • 2011
  • Ingår i: ICED 11 - 18th International Conference on Engineering Design - Impacting Society Through Engineering Design. - 9781904670223 ; , s. 120-129
  • Konferensbidrag (refereegranskat)abstract
    • The need for reducing poverty and to develop the standard of living in rural areas around the world is enormous. Ideas for new approaches have to be created, developed and implemented. Design thinking and methods combined with innovation in practice and management - as Design Inspired Innovation - could be such a concept to provide for rural people to empower themselves and improve their living conditions. On the other hand it is important to learn from the sustainable lifestyle practices being followed in rural villages and extrapolate them to the urban setting. The purpose of this paper is to discuss an initiative between Swedish and Indian researchers, MBA students and their networks. It is based on appropriate design research methodology, ethnographic design research and innovation science. Experiences from initial empirical studies show that master students gathering data in the field (focusing in the areas such as ICT, banking & finance, health care, entrepreneurship, energy and agribusiness), analyzing and interpreting the data together with researchers can get new insights of opportunities in innovation and entrepreneurship at the 'bottom of the pyramid'.
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  • Hibar, D. P., et al. (författare)
  • Subcortical volumetric abnormalities in bipolar disorder
  • 2016
  • Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:12, s. 1710-1716
  • Tidskriftsartikel (refereegranskat)abstract
    • Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10 -7) and thalamus (d=-0.148; P=4.27 × 10 -3) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10 -5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons. © 2016 Macmillan Publishers Limited, part of Springer Nature.
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  • Aad, G., et al. (författare)
  • Measurement of the charge asymmetry in top-quark pair production in association with a photon with the ATLAS experiment
  • 2023
  • Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 843
  • Tidskriftsartikel (refereegranskat)abstract
    • A measurement of the charge asymmetry in top-quark pair (tt¯) production in association with a photon is presented. The measurement is performed in the single-lepton tt¯ decay channel using proton–proton collision data collected with the ATLAS detector at the Large Hadron Collider at CERN at a centre-of-mass-energy of 13 TeV during the years 2015–2018, corresponding to an integrated luminosity of 139 fb−1. The charge asymmetry is obtained from the distribution of the difference of the absolute rapidities of the top quark and antiquark using a profile likelihood unfolding approach. It is measured to be AC=−0.003±0.029 in agreement with the Standard Model expectation. © 2023 The Author(s)
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  • Albrecht, F., et al. (författare)
  • Unraveling Parkinson's disease heterogeneity using subtypes based on multimodal data
  • 2022
  • Ingår i: Parkinsonism and Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 102, s. 19-29
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Parkinson's disease (PD) is a clinically and neuroanatomically heterogeneous neurodegenerative disease characterized by different subtypes. To this date, no studies have used multimodal data that combines clinical, motor, cognitive and neuroimaging assessments to identify these subtypes, which may provide complementary, clinically relevant information. To address this limitation, we subtyped participants with mild-moderate PD based on a rich, multimodal dataset of clinical, cognitive, motor, and neuroimaging variables. Methods: Cross-sectional data from 95 PD participants from our randomized EXPANd (EXercise in PArkinson's disease and Neuroplasticity) controlled trial were included. Participants were subtyped using clinical, motor, and cognitive assessments as well as structural and resting-state MRI data. Subtyping was done by random forest clustering. We extracted information about the subtypes by inspecting their neuroimaging profiles and descriptive statistics. Results: Our multimodal subtyping analysis yielded three PD subtypes: a motor-cognitive subtype characterized by widespread alterations in brain structure and function as well as impairment in motor and cognitive abilities; a cognitive dominant subtype mainly impaired in cognitive function that showed frontoparietal structural and functional changes; and a motor dominant subtype impaired in motor variables without any brain alterations. Motor variables were most important for the subtyping, followed by gray matter volume in the right medial postcentral gyrus. Conclusions: Three distinct PD subtypes were identified in our multimodal dataset. The most important features to subtype PD participants were motor variables in addition to structural MRI in the sensorimotor region. These findings have the potential to improve our understanding of PD heterogeneity, which in turn can lead to personalized interventions and rehabilitation.
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  • Axelsson, John, et al. (författare)
  • Effects of Sustained Sleep Restriction on Mitogen-Stimulated Cytokines, Chemokines and T Helper 1/T Helper 2 Balance in Humans
  • 2013
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Recent studies suggest that acute sleep deprivation disrupts cellular immune responses by shifting T helper (Th) cell activity towards a Th2 cytokine profile. Since little is known about more long-term effects, we investigated how five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1- and Th2 cytokine secretion. Methods: Nine healthy males participated in an experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00 - 07.00 h) followed by 5 days with restricted sleep (03.00 - 07.00 h). On the second baseline day and on the fifth day with restricted sleep, samples were drawn every third hour for determination of cytokines/chemokines (tumor necrosis factor alpha (TNF-alpha), interleukin (IL) -1 beta, IL-2, IL-4 and monocyte chemoattractant protein-1 (MCP-1)) after in vitro stimulation of whole blood samples with the mitogen phytohemagglutinin (PHA). Also leukocyte numbers, mononuclear cells and cortisol were analysed. Results: 5-days of sleep restriction affected PHA-induced immune responses in several ways. There was a general decrease of IL-2 production (p<.05). A shift in Th1/Th2 cytokine balance was also evident, as determined by a decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown. Two significant interactions showed that restricted sleep resulted in increased TNF-alpha and MCP-1 in the late evening and early night hours (p's<.05). In addition, all variables varied across the 24 h day. Conclusions: 5-days of sleep restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL-4 ratio) which is similar to the effects of acute sleep deprivation and psychological stress. This may have implications for people suffering from conditions characterized by excessive Th2 activity like in allergic disease, such as asthma, for whom restricted sleep could have negative consequences. BAS AK, 1991, IMMUNOLOGICAL REVIEWS, V123, P5
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  • Bergenholtz, Gunnar, 1939, et al. (författare)
  • Sveriges ledande position inom odontologisk forskning hotas
  • 2003
  • Ingår i: Tandläkartidn. ; 9, s. 60-61
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Nationella samordningsgruppens aktiviteter syftar till att: - identifiera forskningsmiljöer som kan stärkas genom nationell koordinering - sammanföra yngre forskare från olika forskningsmiljöer - sammanföra etablerade forskare men yngre forskare - stimulera till forskningssamarbete på ett nationellt plan
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  • Borge, C. R., et al. (författare)
  • Effects of guided deep breathing on breathlessness and the breathing pattern in chronic obstructive pulmonary disease: A double-blind randomized control study
  • 2015
  • Ingår i: Patient Education and Counseling. - : Elsevier BV. - 0738-3991 .- 1873-5134. ; 98:2, s. 182-190
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To investigate whether guided deep breathing using a device improves breathlessness, quality of life, and breathing pattern in moderate and severe stage of chronic obstructive pulmonary disease (COPD). METHODS: In total, 150 patients participated in a double-blind randomized controlled trial in a four-week intervention and a four-month follow-up. Participants were randomized into a guided deep breathing group (GDBG), music listening group (MLG), or sitting still group (SSG). The patients' symptom score using the St George's Respiratory Questionnaire (SGRQ), and a Global Rating Change scale (GRC) was applied to measure breathlessness as primary outcome. The activity score and impact score of SRGQ, and breathing pattern were secondary outcomes. RESULTS: Positive effects of the GDBG were detected in GRC scale in breathlessness at four weeks (p=0.03) with remaining effect compared to MLG (p=0.04), but not to SSG at four months follow-up. GDBG showed positive effect for respiratory rate (p<0.001) at four weeks follow-up. A positive significant change (p<0.05-0.01) was found in all groups of SGRQ symptom score. CONCLUSION: GDBG had a beneficial effect on respiratory pattern and breathlessness. MLG and SSG also yielded significant improvements. PRACTICE IMPLICATIONS: Guided deep breathing may be used as a self-management procedure.
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  • Casar Borota, Olivera, et al. (författare)
  • Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations
  • 2021
  • Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:4, s. 1183-1194
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs. Mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, regulating chromatin remodeling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumors. Objective: To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs. Design: We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumors lacking ATRX immunolabeling, mutational status of the ATRX gene was explored. Results: Nine of the 48 tumors (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18; 28%) than in those with APTs (4/30;13%). Lack of ATRX was most common in the corticotroph tumors, 7/22 (32%), versus tumors of the Pit-1 lineage, 2/24 (8%). Loss-of-function ATRX mutations were found in all 9 ATRX immunonegative cases: nonsense mutations (n = 4), frameshift deletions (n = 4), and large deletions affecting 22-28 of the 36 exons (n = 3). More than 1 ATRX gene defect was identified in 2 PCs. Conclusion: ATRX mutations occur in a subset of APTs and are more common in corticotroph tumors. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumors.
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17.
  • Cedres, N, et al. (författare)
  • Brain Atrophy Subtypes and the ATN Classification Scheme in Alzheimer's Disease
  • 2021
  • Ingår i: Neuro-degenerative diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 20:4, s. 153-164
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Introduction:</i></b> We investigated the association between atrophy subtypes of Alzheimer’s disease (AD), the ATN classification scheme, and key demographic and clinical factors in 2 cohorts with different source characteristics (a highly selective research-oriented cohort, the Alzheimer’s Disease Neuroimaging Initiative [ADNI]; and a naturalistic heterogeneous clinically oriented cohort, Karolinska Imaging Dementia Study [KIDS]). <b><i>Methods:</i></b> A total of 382 AD patients were included. Factorial analysis of mixed data was used to investigate associations between AD subtypes based on brain atrophy patterns, ATN profiles based on cerebrospinal fluid biomarkers, and age, sex, Mini Mental State Examination (MMSE), cerebrovascular disease (burden of white matter signal abnormalities, WMSAs), and <i>APOE</i> genotype. <b><i>Results:</i></b> Older patients with high WMSA burden, belonging to the typical AD subtype and showing A+T+N+ or A+T+N− profiles clustered together and were mainly from ADNI. Younger patients with low WMSA burden, limbic-predominant or minimal atrophy AD subtypes, and A+T−N− or A+T−N+ profiles clustered together and were mainly from KIDS. <i>APOE</i> ε4 carriers more frequently showed the A+T−N− and A+T+N− profiles. <b><i>Conclusions:</i></b> Our findings align with the recent framework for biological subtypes of AD: the combination of risk factors, protective factors, and brain pathologies determines belonging of AD patients to distinct subtypes.
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  • Cornell Kärnekull, Stina, et al. (författare)
  • Long-Term Memory for Odors : Influences of Familiarity and Identification Across 64 Days
  • 2015
  • Ingår i: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 40:4, s. 259-267
  • Tidskriftsartikel (refereegranskat)abstract
    • Few studies have investigated long-term odor recognition memory, although some early observations suggested that the forgetting rate of olfactory representations is slower than for other sensory modalities. This study investigated recognition memory across 64 days for high and low familiar odors and faces. Memory was assessed in 83 young participants at 4 occasions; immediate, 4, 16, and 64 days after encoding. The results indicated significant forgetting for odors and faces across the 64 days. The forgetting functions for the 2 modalities were not fundamentally different. Moreover, high familiar odors and faces were better remembered than low familiar ones, indicating an important role of semantic knowledge on recognition proficiency for both modalities. Although odor recognition was significantly better than chance at the 64 days testing, memory for the low familiar odors was relatively poor. Also, the results indicated that odor identification consistency across sessions, irrespective of accuracy, was positively related to successful recognition.
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  • Ekman, M J, et al. (författare)
  • 6-minute walk test before and after a weight reduction program in obese subjects.
  • 2013
  • Ingår i: Obesity. - : Wiley. - 1930-739X .- 1930-7381. ; 21:3, s. 236-243
  • Tidskriftsartikel (refereegranskat)abstract
    • Weight loss and physical activity have shown favorable effects on risks associated with obesity. It is therefore of interest to evaluate exercise capacity and related co-morbidities in obese patients. We present data from obese subjects evaluated by the 6-minute walk test (6MWT) before and after a 7.3 (6.1-8.2) month weight reduction program. 251 subjects completed the test at baseline (BMI 40.6 [36.9-44.6] kg/m(2) ) and 129 (51.4 %) repeated the test after intervention (BMI 35.6 [31.2-38.5] kg/m(2) ). The six minute walking distance (6MWD) at baseline (535 [480-580] m) and at follow up (599 [522-640] m) correlated to several cardiovascular risk markers. Age, weight, height, resting heart rate, smoking status, fP-glucose and use of ß-blockers explained 43 % of the variance in predicted 6MWD at baseline. The effect of smoking status, fP-glucose, ß-blockers and resting heart rate lost significance at follow up. Presence of diabetes and the metabolic syndrome had a negative influence on 6MWD but did not affect the impact of intervention based on percentage increase in walking distance. Gender had no impact on 6MWD. Reported pain during the test was common but decreased after intervention (57.0 % vs. 28.7 %, p<0.001). In conclusion, the 6MWT may be used to evaluate intervention success beyond kilogram weight loss in obese subjects. We present formulas to predict 6MWD and the effect of weight loss on walking distance in clinical practice. Pain is a common problem which has to be considered when giving advice on exercise as a part of weight loss intervention.
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  • Ekman, U, et al. (författare)
  • The A/T/N biomarker scheme and patterns of brain atrophy assessed in mild cognitive impairment
  • 2018
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 8431-
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this study was to evaluate the A/T/N biomarker scheme in relation with brain atrophy patterns in individuals with mild cognitive impairment (MCI). Of the 154 participants with MCI, 74 progressed to AD within 36-months, and 80 remained stable. In addition, 101 cognitively healthy participants and 102 participants with AD were included. The A/T/N classification was assessed with cerebrospinal fluid markers. Each individual was rated as either positive (abnormal) or negative (normal) on each biomarker. Brain atrophy was assessed with visual ratings from magnetic resonance imaging. None of the individuals with MCI progressed to AD if they had a negative “A” biomarker in conjunction with minimal atrophy. In contrary, several individuals with MCI progressed to AD if they had a positive “A” biomarker in conjunction with minimal atrophy. Numerous individuals with MCI showed inconsistency in the neurodegeneration domain (“N”) regarding t-tau and atrophy. The assessment of the A/T/N classification scheme in addition with brain atrophy patterns in MCI, increases the knowledge of the clinical trajectories and the variability within the neurodegeneration domain. This emphasises that individuals with MCI display heterogeneous longitudinal patterns closely connected to their biomarker profiles, which could have important clinical implications.
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  • Ernberg, M, et al. (författare)
  • Examina och utbildning inom svensk odontologisk forskning
  • 2003
  • Ingår i: Tandläkartidn. ; 95:9, s. 54-59
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • En internationell utvärdering visade för några år sedan att Sverige riskerar att förlora sin position som världsledande nation inom odontologisk forskning. För att få en uppfattning om förändringarna inom forskarutbildningen och den postdoktorala meriteringen samlades data för 1990-2001 in från fakulteterna, Statistiska Centralbyrån samt Högskoleverket. Avsikten var att undersöka antalet forskarutbildade tandläkare, mångfalden bland doktoranderna och de som disputerat samt deras nuvarande anställningsform. Materialet jämfördes sedan med tidigare data. I medeltal avlade 25 personer per år doktorsexamen åren 1990-2001. Antalet har minskat under senare år. En majoritet av dem som avlade doktorsexamen hade odontologisk bakgrund. Relativt få har meriterat sig för en fortsatt akademisk karriär. 32 studerande påbörjade forskarutbildning åren 1991-2001. Andelen doktorander med annan akademisk grundexamen än odontologisk ökar. Sedan 1999 har forskningsvolymen minskat med motsvarande en hel fakultets forskningsvolym. Vi drar därför slutsatsen att kunskapsutvecklingen inom svensk odontologi riskerar att stagnera samt att fakulteternas behov av lärare till högre akademiska tjänster liksom folktandvårdens behov av handledare inom specialistutbildningen inte kommer att kunna tillgodoses i framtiden.
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