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1.
  • Allentoft, Morten E., et al. (författare)
  • Population genomics of post-glacial western Eurasia
  • 2024
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
  • Tidskriftsartikel (refereegranskat)abstract
    • Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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2.
  • Elberling, Bo, et al. (författare)
  • Soil and Plant Community Characteristics and Dynamics at Zackenberg
  • 2008
  • Ingår i: High-arctic ecosystem dynamics in a changing climate - Ten years of monitoring and research at Zackenberg Research Station, Northeast Greenland (Advances in Ecological Research). - 0065-2504. - 9780123736659 ; 40, s. 223-248
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • Arctic soils hold large amounts of nutrients in the weatherable minerals and the soil organic matter, which slowly decompose. The decomposition processes release nutrients to the plant-available nutrient pool as well as greenhouse gases to the atmosphere. Changes in climatic conditions, for example, changes in the distribution of snow, water balance and the length of the growing season, are likely to affect the complex interactions between plants, abiotic and biotic soil processes as well as the composition of soil micro- and macro-fauna and thereby the overall decomposition rates. These interactions, in turn, will influence soil-plant functioning and vegetation composition in the short as well as in the long term. In this chapter, we report on soils and. plant communities and their distribution patterns in the valley Zackenbergdalen and focus on the detailed investigations within five dominating plant communities. These five communities are located along an ecological gradient in the landscape and are closely related to differences in water availability. They are therefore indirectly formed as a result of the distribution of landforms, redistribution of snow and drainage conditions. Each of the plant communities is closely related to specific nutrient levels and degree of soil development including soil element accumulation and translocation, for example, organic carbon. Results presented here show that different parts of the landscape have responded quite differently to the same overall climate changes the last 10 years and thus, most likely in the future too. Fens represent the wettest sites holding large reactive buried carbon stocks. A warmer climate will cause a permafrost degradation, which most likely will result in anoxic decomposition and increasing methane emissions. However, the net gas emissions at fen sites are sensitive to long-term changes in the water table level. Indeed, increasing maximum active layer depth at fen sites has been recorded together with a decreasing water level at Zackenberg. This is in line with the first signs of increasing extension of grasslands at the expense of fens. In contrast, the most exposed and dry areas have less soil carbon, and decomposition processes are periodically water limited. Here, an increase in air temperatures may increase active layer depth more than at fen sites, but water availability will be critical in determining nutrient cycling and plant production. Field manipulation experiments of increasing temperature, water supply and nutrient addition show that soil-plant interactions are sensitive to these variables. However, additional plant-specific investigations are needed before net effects of climate changes on different landscape and plant communities can be integrated in a landscape context and used to assess the net ecosystem effect of future climate scenarios.
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3.
  • Nielsen, Frederik Knud, et al. (författare)
  • Mixture effects of 3 mechanistically different steroidogenic disruptors (prochloraz, genistein, and ketoconazole) in the H295R cell assay
  • 2015
  • Ingår i: International journal of toxicology. - 1091-5818 .- 1092-874X. ; 34:6, s. 534-542
  • Tidskriftsartikel (refereegranskat)abstract
    • Mixture effects of 3 model endocrine disruptors, prochloraz, ketoconazole, and genistein, on steroidogenesis were tested in the adrenocortical H295R cell line. Seven key steroid hormones (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone, and 17β-estradiol) were analyzed using gas chromatography and tandem mass spectrometry (GC-MS/MS) to investigate the effects throughout the steroidogenic pathway. Current modeling approaches often rely on models assuming compounds acting independently and that the individual effects in some way can be summarized to predict a mixture effect. In H295R cells with an intact steroidogenic pathway, such assumptions may not be feasible. The purpose of this study was therefore to evaluate whether effects of a mixture with differing modes of action followed or deviated from additivity (concentration addition) and whether the H295R cell line was suitable for evaluating mixture toxicity of endocrine disruptors with different modes of action. The compounds were chosen because they interfere with steroidogenesis in different ways. They all individually decrease the concentrations of the main sex steroids downstream but exert different effects upstream in the steroidogenic pathway. Throughout the study, we observed lowest observed effect concentrations of mixtures at levels 2 to 10 times higher than the predicted EC50, strongly indicating antagonistic effects. The results demonstrate that chemical analysis combined with the H295R cell assay is a useful tool also for studying how mixtures of endocrine disruptors with differing modes of action interfere with the steroidogenic pathway and that existing models like concentration addition are insufficient in such cases. Furthermore, for end points where compounds exert opposite effects, no relevant models are available.
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4.
  • Nielsen, Frederik Knud, et al. (författare)
  • Mixture effects of 3 mechanistically different steroidogenic disruptors (prochloraz, genistein, and ketoconazole) in the H295R cell assay
  • 2015
  • Ingår i: International Journal of Toxicology. - : SAGE Publications Inc.. - 1091-5818 .- 1092-874X. ; 34:6, s. 534-542
  • Tidskriftsartikel (refereegranskat)abstract
    • Mixture effects of 3 model endocrine disruptors, prochloraz, ketoconazole, and genistein, on steroidogenesis were tested in the adrenocortical H295R cell line. Seven key steroid hormones (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone, and 17β-estradiol) were analyzed using gas chromatography and tandem mass spectrometry (GC-MS/MS) to investigate the effects throughout the steroidogenic pathway. Current modeling approaches often rely on models assuming compounds acting independently and that the individual effects in some way can be summarized to predict a mixture effect. In H295R cells with an intact steroidogenic pathway, such assumptions may not be feasible. The purpose of this study was therefore to evaluate whether effects of a mixture with differing modes of action followed or deviated from additivity (concentration addition) and whether the H295R cell line was suitable for evaluating mixture toxicity of endocrine disruptors with different modes of action. Thecompounds were chosen because they interfere with steroidogenesis in different ways. They all individually decrease the concentrations of the main sex steroids downstream but exert different effects upstream in the steroidogenic pathway. Throughout the study, we observed lowest observed effect concentrations of mixtures at levels 2 to 10 times higher than the predicted EC50, strongly indicating antagonistic effects. The results demonstrate that chemical analysis combined with the H295R cell assay is a useful tool also for studying how mixtures of endocrine disruptors with differing modes of action interfere with the steroidogenic pathway and that existing models like concentration addition are insufficient in such cases. Furthermore, for end points where compounds exert opposite effects, no relevant models are available.
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5.
  • Riise, Eili N., et al. (författare)
  • Concentrated exposure and response prevention for adolescents with obsessive-compulsive disorder : An effectiveness study
  • 2016
  • Ingår i: Journal of Obsessive-Compulsive and Related Disorders. - : Elsevier BV. - 2211-3649 .- 2211-3657. ; 11, s. 13-21
  • Tidskriftsartikel (refereegranskat)abstract
    • This study evaluated the effectiveness of a concentrated exposure and response prevention (ERP) treatment for adolescents with obsessive-compulsive disorder (OCD). Twenty-two adolescents with OCD (range 11–17 years) received therapist-assisted ERP during four consecutive days, followed by a three week period of self-administered ERP. Treatment was delivered to 2–3 patients and their parents simultaneously at an outpatient clinic for child and adolescent psychiatry as part of standard health care. OCD-symptoms were assessed at pre-treatment, post-treatment, 3- and 6-month follow-up. The results demonstrated that patients had significant reduction in OCD-symptoms from pre- to post-treatment and the gains were maintained at follow-up. 91% (n=20) were classified as responders at post-treatment, and 77% (n=17) at six-month follow-up. Remission rates were 73% (n=16) at post-treatment and 68% (n=15) at six-month follow-up. OCD-related impairment and symptoms of anxiety and depression were significantly reduced at post-treatment and follow-up. The results suggest that concentrated ERP is a promising treatment for adolescents with OCD.
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6.
  • Smedby, Karin Ekström, et al. (författare)
  • Ultraviolet radiation exposure and risk of malignant lymphomas
  • 2005
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 97:3, s. 199-209
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The incidence of malignant lymphomas has been increasing rapidly, but the causes of these malignancies remain poorly understood. One hypothesis holds that exposure to ultraviolet (UV) radiation increases lymphoma risk. We tested this hypothesis in a population-based case-control study in Denmark and Sweden. METHODS: A total of 3740 patients diagnosed between October 1, 1999, and August 30, 2002, with incident malignant lymphomas, including non-Hodgkin lymphoma, chronic lymphocytic leukemia, and Hodgkin lymphoma, and 3187 population controls provided detailed information on history of UV exposure and skin cancer and information on other possible risk factors for lymphomas. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by logistic regression. Statistical tests were two-sided. RESULTS: Multivariable-adjusted analyses revealed consistent, statistically significant negative associations between various measures of UV light exposure and risk of non-Hodgkin lymphoma. A high frequency of sun bathing and sunburns at age 20 years and 5-10 years before the interview and sun vacations abroad were associated with 30%-40% reduced risks of non-Hodgkin lymphoma (e.g., for sunbathing four times a week or more at age 20 versus never sunbathing, OR = 0.7, 95% CI = 0.6 to 0.9; for two or more sunburns a year at age 20 versus no sunburns, OR = 0.6, 95% CI = 0.5 to 0.8). These inverse associations increased in strength with increasing levels of exposure (all P(trend)< or =.01). Similar, albeit weaker, associations were observed for Hodgkin lymphoma. There were no clear differences among non-Hodgkin lymphoma subtypes, although associations were stronger for B-cell than for T-cell lymphomas. A history of skin cancer was associated with a doubling in risks of both non-Hodgkin and Hodgkin lymphoma. CONCLUSIONS: A history of high UV exposure was associated with reduced risk of non-Hodgkin lymphoma. The positive association between skin cancer and malignant lymphomas is, therefore, unlikely to be mediated by UV exposure.
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8.
  • Allentoft, Morten E., et al. (författare)
  • 100 ancient genomes show repeated population turnovers in Neolithic Denmark
  • 2024
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
  • Tidskriftsartikel (refereegranskat)abstract
    • Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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9.
  • Ameen, Carly, et al. (författare)
  • Specialized sledge dogs accompanied Inuit dispersal across the North American Arctic
  • 2019
  • Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 286:1916
  • Tidskriftsartikel (refereegranskat)abstract
    • Domestic dogs have been central to life in the North American Arctic for millennia. The ancestors of the Inuit were the first to introduce the widespread usage of dog sledge transportation technology to the Americas, but whether the Inuit adopted local Palaeo-Inuit dogs or introduced a new dog population to the region remains unknown. To test these hypotheses, we generated mitochondrial DNA and geometric morphometric data of skull and dental elements from a total of 922 North American Arctic dogs and wolves spanning over 4500 years. Our analyses revealed that dogs from Inuit sites dating from 2000 BP possess morphological and genetic signatures that distinguish them from earlier Palaeo-Inuit dogs, and identified a novel mitochondrial clade in eastern Siberia and Alaska. The genetic legacy of these Inuit dogs survives today in modern Arctic sledge dogs despite phenotypic differences between archaeological and modern Arctic dogs. Together, our data reveal that Inuit dogs derive from a secondary pre-contact migration of dogs distinct from Palaeo-Inuit dogs, and probably aided the Inuit expansion across the North American Arctic beginning around 1000 BP.
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10.
  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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11.
  • Bechshoft, Thea, et al. (författare)
  • Developing a new research tool for use in free-ranging cetaceans : recovering cortisol from harbour porpoise skin
  • 2015
  • Ingår i: Conservation Physiology. - 2051-1434. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • We developed a chemical analytical procedure for sampling, extracting and determining epidermal skin cortisol concentrations (SCCs) in the harbour porpoise (Phocoena phocoena) using gas chromatography–tandem mass spectrometry. In brief, this involved a pressurized liquid extraction with a two-step solid-phase clean-up. A derivatization step was conducted prior to detection. To evaluate the new assay, cortisol was analysed in three different sample types obtained from four harbour porpoises: skin plates, dorsal fin skin plugs (with and without lidocaine) and epidermal scrapes. Skin cortisol concentrations could be measured using the new assay in the majority of the tested skin samples down to a minimal sample size of 49 mg dry weight (dw). Water content ranged from 10 to 46% in the plug samples, which had SCCs from 2.1 to 77.7 ng/g dw. Epidermal scrape samples had the highest water content (83–87%) and lower SCCs (0.6–15 ng/g dw), while the skin plates had intermediate water contents (60–66%) and SCCs of 2.6–13.0 ng/g dw. SCC was slightly higher in plugs with lidocaine than without (average values of 41 and 33 ng/g dw, respectively). Substantial within-individual variations in cortisol concentrations are also common in other matrices such as blood and hair. Some important factors behind this variation could be e.g. the animal's sex, age, body condition, reproductive stage, and the body region sampled, as well as season, moulting cycles and water temperature. Clearly, more research into SCCs is required. The findings described here represent the first critical steps towards using epidermal skin cell samples to assess chronic stress levels in cetaceans and the development of a widely applicable health-assessment tool in these species.
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12.
  • Bechshoft, Thea, et al. (författare)
  • Developing a new research tool for use in free-ranging cetaceans : recovering cortisol from harbour porpoise skin
  • 2015
  • Ingår i: Conservation Physiology. - : Oxford University Press. - 2051-1434. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • We developed a chemical analytical procedure for sampling, extracting and determining epidermal skin cortisol concentrations (SCCs) in the harbour porpoise (Phocoena phocoena) using gas chromatography–tandem mass spectrometry. In brief, this involved a pressurized liquid extraction with a two-step solid-phase clean-up. A derivatization step was conducted prior to detection. To evaluate the new assay, cortisol was analysed in three different sample types obtained from four harbour porpoises: skin plates, dorsal fin skin plugs (with and without lidocaine) and epidermal scrapes. Skin cortisol concentrations could be measured using the new assay in the majority of the tested skin samples down to a minimal sample size of 49 mg dry weight (dw). Water content ranged from 10 to 46% in the plug samples, which had SCCs from 2.1 to 77.7 ng/g dw. Epidermal scrape samples had the highest water content (83–87%) and lower SCCs (0.6–15 ng/g dw), while the skin plates had intermediate water contents (60–66%) and SCCs of 2.6–13.0 ng/g dw. SCC was slightly higher in plugs with lidocaine than without (average values of 41 and 33 ng/g dw, respectively). Substantial within-individual variations in cortisol concentrations are also common in other matrices such as blood and hair. Some important factors behind this variation could be e.g. the animal's sex, age, body condition, reproductive stage, and the body region sampled, as well as season, moulting cycles and water temperature. Clearly, more research into SCCs is required. The findings described here represent the first critical steps towards using epidermal skin cell samples to assess chronic stress levels in cetaceans and the development of a widely applicable health-assessment tool in these species.
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13.
  • Bekoe, Samuel Oppong, et al. (författare)
  • Detection and quantification of antibiotic residues in urine samples of healthy individuals from rural and urban communities in Ghana using a validated SPE-LC-MS/MS method
  • 2020
  • Ingår i: SN APPLIED SCIENCES. - 2523-3963. ; 2:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of unregulated and inappropriate dispensing, and use of antibiotics remains significant in the development of antimicrobial resistance in infectious disease endemic regions of developing countries. The exposure to antibiotics from unfamiliar and unsuspecting sources such as drinking water and food, and adulterated herbal medicines remains a cause for concern. A sensitive SPE-LC-MS/MS method was developed and validated for the quantification and qualification of 12 antibiotics, including amoxicillin, clavulanic acid, metronidazole, ampicillin, cefuroxime, tetracycline, ceftriaxone, sulphamethoxazole, trimethoprim, ciprofloxacin, benzylpenicillin, and erythromycin, in the urine of healthy volunteers. The method was linear (r(2) > 0.98) within the concentration range 50-5000 ngmL(-1) for all the analytes. Instrument precision of 8-27% and 4-21% at 100 and 1000 ngmL(-1) levels were demonstrated. High mean recoveries between 71 and 125% with minimal variations were obtained for all compounds in the accuracy study. Limits of detection and quantification ranged between 70.3-271.0 ngmL(-1) and 213-821 ngmL(-1) respectively. The validated method successfully detected and quantified 9 of the 12 analytes, with the exception of clavulanic acid, cefuroxime, and benzylpenicillin. Most of the samples contained one analyte (52, 86.7%), with a handful containing two (7, 11.7%) and three analytes (1, 1.7%). Ciprofloxacin was the modal analyte detected (17, 24.6%), with amoxicillin and trimethoprim recording the average lowest (22.76 x 10(3) ngmL(-1)) and highest concentrations (255.47 x 10(3) ngmL(-1)) respectively. The developed method is a useful tool for non-invasive monitoring of consumption and the irrational use of antibiotics in microbial resistant-prone regions of the world.
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14.
  • Bekoe, Samuel Oppong, et al. (författare)
  • Detection and quantification of antibiotic residues in urine samples of healthy individuals from rural and urban communities in Ghana using a validated SPE-LC-MS/MS method
  • 2020
  • Ingår i: SN APPLIED SCIENCES. - : Springer Science and Business Media LLC. - 2523-3963 .- 2523-3971. ; 2:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of unregulated and inappropriate dispensing, and use of antibiotics remains significant in the development of antimicrobial resistance in infectious disease endemic regions of developing countries. The exposure to antibiotics from unfamiliar and unsuspecting sources such as drinking water and food, and adulterated herbal medicines remains a cause for concern. A sensitive SPE-LC-MS/MS method was developed and validated for the quantification and qualification of 12 antibiotics, including amoxicillin, clavulanic acid, metronidazole, ampicillin, cefuroxime, tetracycline, ceftriaxone, sulphamethoxazole, trimethoprim, ciprofloxacin, benzylpenicillin, and erythromycin, in the urine of healthy volunteers. The method was linear (r(2) > 0.98) within the concentration range 50-5000 ngmL(-1) for all the analytes. Instrument precision of 8-27% and 4-21% at 100 and 1000 ngmL(-1) levels were demonstrated. High mean recoveries between 71 and 125% with minimal variations were obtained for all compounds in the accuracy study. Limits of detection and quantification ranged between 70.3-271.0 ngmL(-1) and 213-821 ngmL(-1) respectively. The validated method successfully detected and quantified 9 of the 12 analytes, with the exception of clavulanic acid, cefuroxime, and benzylpenicillin. Most of the samples contained one analyte (52, 86.7%), with a handful containing two (7, 11.7%) and three analytes (1, 1.7%). Ciprofloxacin was the modal analyte detected (17, 24.6%), with amoxicillin and trimethoprim recording the average lowest (22.76 x 10(3) ngmL(-1)) and highest concentrations (255.47 x 10(3) ngmL(-1)) respectively. The developed method is a useful tool for non-invasive monitoring of consumption and the irrational use of antibiotics in microbial resistant-prone regions of the world.
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16.
  • Casas, Monica Escolà, et al. (författare)
  • Analytical sample preparation strategies for the determination of antimalarial drugs in human whole blood, plasma and urine
  • 2014
  • Ingår i: Journal of chromatography. B. - 1570-0232 .- 1873-376X. ; 962, s. 109-131
  • Tidskriftsartikel (refereegranskat)abstract
    • Antimalarial drugs commonly referred to as antimalarials, include a variety of compounds with different physicochemical properties. There is a lack of information on antimalarial distribution in the body over time after administration, e.g. the drug concentrations in whole blood, plasma, and urine, which must be improved in order to advance curing the parasitic disease malaria. A key problem also lies in that pharmacokinetic studies not always are performed in patient groups that may benefit most of the treatment such as children, pregnancy and lower-weight ethnic populations. Here we review the available sample preparation strategies combined with liquid chromatographic (LC) analysis to determine antimalarials in whole blood, plasma and urine published over the last decade. Sample preparation can be done by protein precipitation, solid-phase extraction, liquid-liquid extraction or dilution. After LC separation, the preferred detection tool is tandem mass spectrometry (MS/MS) but other detection methods have been used e.g. UV, fluorescence and electrochemical detection. Major trends for sample preparation of the different groups of antimalarials for each matrix and its detection have been summarized. Finally, the main problems that the researchers have dealt with are highlighted. This information will aid analytical chemists in the development of novel methods for determining existing antimalarials and upcoming new drugs
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17.
  • Casas, Monica Escolà, et al. (författare)
  • Analytical sample preparation strategies for the determination of antimalarial drugs in human whole blood, plasma and urine
  • 2014
  • Ingår i: Journal of chromatography. B. - : Elsevier BV. - 1570-0232. ; 962, s. 109-131
  • Tidskriftsartikel (refereegranskat)abstract
    • Antimalarial drugs commonly referred to as antimalarials, include a variety of compounds with different physicochemical properties. There is a lack of information on antimalarial distribution in the body over time after administration, e.g. the drug concentrations in whole blood, plasma, and urine, which must be improved in order to advance curing the parasitic disease malaria. A key problem also lies in that pharmacokinetic studies not always are performed in patient groups that may benefit most of the treatment such as children, pregnancy and lower-weight ethnic populations. Here we review the available sample preparation strategies combined with liquid chromatographic (LC) analysis to determine antimalarials in whole blood, plasma and urine published over the last decade. Sample preparation can be done by protein precipitation, solid-phase extraction, liquid-liquid extraction or dilution. After LC separation, the preferred detection tool is tandem mass spectrometry (MS/MS) but other detection methods have been used e.g. UV, fluorescence and electrochemical detection. Major trends for sample preparation of the different groups of antimalarials for each matrix and its detection have been summarized. Finally, the main problems that the researchers have dealt with are highlighted. This information will aid analytical chemists in the development of novel methods for determining existing antimalarials and upcoming new drugs
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18.
  • Clausen, Bettina Hjelm, et al. (författare)
  • Cell therapy centered on IL-1Ra is neuroprotective in experimental stroke.
  • 2016
  • Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 131:5, s. 91-775
  • Tidskriftsartikel (refereegranskat)abstract
    • Cell-based therapies are emerging as new promising treatments in stroke. However, their functional mechanism and therapeutic potential during early infarct maturation has so far received little attention. Here, we asked if cell-based delivery of the interleukin-1 receptor antagonist (IL-1Ra), a known neuroprotectant in stroke, can promote neuroprotection, by modulating the detrimental inflammatory response in the tissue at risk. We show by the use of IL-1Ra-overexpressing and IL-1Ra-deficient mice that IL-1Ra is neuroprotective in stroke. Characterization of the cellular and spatiotemporal production of IL-1Ra and IL-1α/β identifies microglia, not infiltrating leukocytes, as the major sources of IL-1Ra after experimental stroke, and shows IL-1Ra and IL-1β to be produced by segregated subsets of microglia with a small proportion of these cells co-expressing IL-1α. Reconstitution of whole body irradiated mice with IL-1Ra-producing bone marrow cells is associated with neuroprotection and recruitment of IL-1Ra-producing leukocytes after stroke. Neuroprotection is also achieved by therapeutic injection of IL-1Ra-producing bone marrow cells 30 min after stroke onset, additionally improving the functional outcome in two different stroke models. The IL-1Ra-producing bone marrow cells increase the number of IL-1Ra-producing microglia, reduce the availability of IL-1β, and modulate mitogen-activated protein kinase (MAPK) signaling in the ischemic cortex. The importance of these results is underlined by demonstration of IL-1Ra-producing cells in the human cortex early after ischemic stroke. Taken together, our results attribute distinct neuroprotective or neurotoxic functions to segregated subsets of microglia and suggest that treatment strategies increasing the production of IL-1Ra by infiltrating leukocytes or microglia may also be neuroprotective if applied early after stroke onset in patients.
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19.
  • Engert, Andreas, et al. (författare)
  • The European Hematology Association Roadmap for European Hematology Research : a consensus document
  • 2016
  • Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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22.
  • Fjellgaard Mikalsen, Ragni, et al. (författare)
  • Extinguishing smoldering fires in wood pellets through cooling
  • 2017
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Extinguishing smoldering fires is a severe challenge for fire brigades, and has proven to be difficult even on the lab scale. In this study, the influence of a closed water cooling loop located within the fuel bed was investigated experimentally. Increasing the cooling led to a system less prone to intense combustion at an early stage, and eventually to complete extinguishment of self-sustained smoldering fires. Extinguishment was obtained in half of the cases with maximum cooling. Extinguishment occurred soon after smoldering had been established, giving a significant reduction in fuel consumption compared to the self-sustained smoldering fires that continued to complete burn-out.
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23.
  • Fjellgaard Mikalsen, Ragni, et al. (författare)
  • Extinguishing Smoldering Fires in Wood Pellets with Water Cooling : An Experimental Study
  • 2019
  • Ingår i: Fire technology. - : Springer Science and Business Media LLC. - 0015-2684 .- 1572-8099. ; 25:1, s. 257-284
  • Tidskriftsartikel (refereegranskat)abstract
    • Smoldering fires in stored or transported solid biofuels are very difficult to extinguish. The current study has explored heat extraction from the combustion zone as a method for extinguishing such flameless fires. Heat extraction from the sample was made feasible using water flowing through a metal pipe located inside the sample. The fuel container was a steel cylinder with insulated side walls, open at the top and heated from below. Wood pellets (1.25 kg, 1.8 l) was used as fuel. Results from small-scale experiments provide proof-of-concept of cooling as a new extinguishing method for smoldering fires. During self-sustained smoldering with heat production in the range 0 W to 60 W, the heat loss to the cooling unit was in the range 5 W to 20 W. There were only marginal differences between non-extinguished and extinguished cases. Up-scaling is discussed, cooling could be feasible for preventing smoldering fires in silos.
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24.
  • Fjellgaard Mikalsen, Ragni (författare)
  • Fighting flameless fires : Initiating and extinguishing self-sustainedsmoldering fires in wood pellets
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Smoldering fires represent domestic, environmental and industrial hazards. This flameless form of combustion is more easily initiated than flaming, and is also more persistent and difficult to extinguish. The growing demand for non-fossil fuels has increased the use of solid biofuels such as biomass. This represents a safety challenge, as biomass self-ignition can cause smoldering fires, flaming fires or explosions.Smoldering and extinguishment in granular biomass was studied experimentally. The set-up consisted of a cylindrical fuel container of steel with thermally insulated side walls. The container was closed at the bottom, open at the top and heated from below by a hot surface. Two types of wood pellets were used as fuel, with 0.75-1.5 kg samples.Logistic regression was used to determine the transition region between non-smoldering and self-sustained smoldering experiments, and to determine the influence of parameters. Duration of external heating was most important for initiation of smoldering. Sample height was also significant, while the type of wood pellet was near-significant and fuel container height was not.The susceptibility of smoldering to changes in air supply was studied. With a small gap at the bottom of the fuel bed, the increased air flow in the same direction as the initial smoldering front (forward air flow) caused a significantly more intense combustion compared to the normal set-up with opposed air flow.Heat extraction from the combustion was studied using a water-cooled copper pipe. Challenges with direct fuel-water contact (fuel swelling, water channeling and runoff) were thus avoided. Smoldering was extinguished in 7 of 15 cases where heat extraction was in the same range as the heat production from combustion. This is the first experimental proof-of-concept of cooling as an extinguishment method for smoldering fires.Marginal differences in heating and cooling separated smoldering from extinguished cases; the fuel bed was at a heating-cooling balance point. Lower cooling levels did not lead to extinguishment, but cooling caused more predictable smoldering, possibly delaying the most intense combustion. Also observed at the balance point were pulsating temperatures; a form of long-lived (hours), macroscopic synchronization not previously observed in smoldering fires.For practical applications, cooling could be feasible for prevention of temperature escalation from self-heating in industrial storage units. This study provides a first step towards improved fuel storage safety for biomass. 
  •  
25.
  • Fjellgaard Mikalsen, Ragni, et al. (författare)
  • Smoldering combustion- from pulsations to extinguishment
  • 2017
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Smoldering is known as a slow, but unpredictable form of combustion. In this study we have looked at how smoldering is affected by water cooling of the fuel bed without direct contact between fuel and water flow. The study is a part of the EMRIS project, and its findings have possible implications for preventing and suppressing fires in industrial storage units.
  •  
26.
  •  
27.
  • Hagen, Kristen, et al. (författare)
  • Does Concentrated Exposure Treatment for Obsessive-Compulsive Disorder Improve Insomnia Symptoms? : Results From a Randomized Controlled Trial
  • 2021
  • Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Insomnia is a substantial problem in patients with obsessive-compulsive disorder (OCD). There is, however, a lack of studies investigating changes in concurrent symptoms of insomnia in OCD after concentrated treatment. A recent randomized controlled trial randomized participants to the Bergen 4-day treatment (B4DT, n = 16), or 12 weeks of unguided self-help (SH, n = 16), or waitlist (WL, n = 16). Patients from the SH- and WL-group who wanted further treatment after the 12 weeks were then offered the B4DT (total of 42 patients treated with the B4DT). There were no significant differences in symptoms of insomnia between the conditions at post-treatment, but a significant moderate improvement at 3-month follow-up for patients who received the B4DT. Insomnia was not associated with OCD-treatment outcome, and change in symptoms of insomnia was mainly related to changes in depressive symptoms. The main conclusion is that concentrated exposure treatment is effective irrespective of comorbid insomnia, and that insomnia problems are moderately reduced following treatment.
  •  
28.
  • Hansen, Bjarne H, et al. (författare)
  • The Scandinavian Sarcoma Group Skeletal Metastasis Registry Functional outcome and pain after surgery for bone metastases in the pelvis and extremities
  • 2009
  • Ingår i: ACTA ORTHOPAEDICA. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 80, s. 85-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Few authors have investigated function and pain after surgical treatment of patients with bone metastases. In 1999 the Scandinavian Sarcoma Group (SSG) initiated the Skeletal Metastasis Registry as a multi-centric, prospective study to provide a scientific basis for recommendations of treatment. Patients and methods We have analyzed function and pain in 530 patients (mean age 65 yr) operated on (599 operations) for non-spinal skeletal metastases at 9 SSG centres. 7% were operated for more than 1 metastasis. Carcinoma of the breast, prostate, kidney, and lung were the dominating sites for primary tumors. Results 25% of the patients died within 6 weeks after operation. 11% of the patients had complications. 6% had reoperation. In patients surviving more than 1 year the reoperation rate was 12%. 92% of the patients had no, light or moderate pain from metastasis at 6 weeks (first control) and 6 months follow-up. Patients using opioids were reduced from 40% preoperative to 30% at 6 months after surgery. In patients with metastases in pelvis or lower extremity 79% were walking with or without crutches, 6 weeks and 88%, 6 months after surgery. More patients with metastases; in proximal femur were mobile at 6 weeks and 6 months when treated with prosthetic replacement compared to internal fixation. Interpretation Palliative surgery for bone metastases improves function and reduce pain. Mobility is improved by surgery in patients with metastases in the pelvis or lower extremity. Prosthetic replacement seems to do better than internal fixation for metastases in the proximal femur. We need to analyze function and pain earlier than 6 weeks postoperative to investigate the benefit of surgery in patients with short time survival.
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29.
  • Hansen, Bjarne R. S., et al. (författare)
  • Hydrogen Storage Capacity Loss in a LiBH4-Al Composite
  • 2013
  • Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 117:15, s. 7423-7432
  • Tidskriftsartikel (refereegranskat)abstract
    • A detailed investigation of the decomposition reactions and decay in the hydrogen storage capacity during repeated hydrogen release and uptake cycles for the reactive composite LiBH4-Al (2:3) is presented. Furthermore, the influence of a titanium boride, TiB2, additive is investigated. The study combines information from multiple techniques: in situ synchrotron radiation powder X-ray diffraction, Sieverts measurements, simultaneous thermogravimetric analysis, differential scanning calorimetry and mass spectroscopy, solid-state magic-angle spinning nuclear magnetic resonance (MAS NMR), and Raman spectroscopy. The decomposition of LiBH4-Al results in the formation of LiAl, AlB2, and Li2B12H12 via several reactions and intermediate compounds. The TiB2 additive appears to have a limited effect on the decomposition pathway of the samples, but seems to facilitate formation of intermediate species at lower temperatures compared to the sample without additive. Solid solutions of LixAl1-xB2 or Al1-xB2 are observed during decomposition and from Rietveld refinement the composition of the solid solution is estimated to be Li0.22Al0.78B2. The intercalation of Li in the AlB2 structure is further investigated by B-11 and Al-27 MAS NMR spectra of the LiH-AlB2 and AlB2 samples (presented in Supporting Information). Hydrogen release and uptake for LiBH4-Al reveals a significant loss in the hydrogen storage capacity, that is, after four cycles a capacity of about 45% remains, and after 10 cycles, the capacity is degraded to approximately 15% of the theoretically available hydrogen content. This capacity loss may be due to the formation of Li2B12H12, as observed by B-11 MAS NMR and Raman spectroscopy. Formation of Li2B12H12 has previously been observed during the decomposition of LiBH4, but it has not been reported earlier in the LiBH4-Al (2:3) system.
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30.
  • Hansen, Bjarne, et al. (författare)
  • The Bergen 4-Day OCD Treatment Delivered in a Group Setting : 12-Month Follow-Up
  • 2018
  • Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • The Bergen 4-day concentrated exposure treatment (cET) for obsessive-compulsive disorder (OCD) has proven highly acceptable; with practically no drop-out and a 6 month remission rate of nearly 70%. The aim of the present study was to evaluate long term gains of the approach, and to compare the results to findings from our recent meta-analysis. Sixty-nine of 95 patients consecutively referred to an outpatient clinic in the specialist health care, were offered the Bergen 4-day treatment. Among the 65 who initiated treatment, 60.0% were classified with severe to extreme OCD. None of the patients dropped-out during treatment. Independent Yale-Brown Obsessive-Compulsive Scale interviews were conducted post-treatment, and at 3- and 12-month follow-up. Using the international consensus criteria, 83.1% responded to treatment at 12-month follow-up, and 67.7% of patients were classified as recovered. Significant changes were also seen in depression, as measured by Patient Health Questionnaire-9, and in generalized anxiety, as measured by Generalized Anxiety Disorder-7 scale. A total of 89% of the patients rated the treatment as very good and 100% would recommend the treatment to a friend. Compared to results in a recent meta-analysis, the Bergen 4-day treatment is favorable in respect to attrition, response and 12-month recovery. In sum the Bergen 4-day treatment is a feasible way to deliver treatment for OCD, and the effects are stable at 12-month follow-up. Implications for dissemination are discussed.
  •  
31.
  • Hansen, Bjarne, et al. (författare)
  • The Bergen 4-Day Treatment for Panic Disorder : A Pilot Study
  • 2018
  • Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • The current article reports on the findings from a pilot treatment study on panic disorder (PD) with or without agoraphobia. Consecutively referred patients were included and treated with the Bergen 4-day treatment format. Twenty-nine patients were included, primarily from unsuccessful treatment courses in the Norwegian specialist mental health care system, either ongoing or previously. Prior to treatment, only 34% were able to work but at 3-month follow-up 93% were able to do so. The proportion achieving reliable change on the panic severity measure was 76% post-treatment and 90% at follow-up. The remission rate was 72% at both assessments. These effects are significantly higher than those reported for six standard CBT studies in the literature using the same primary outcome measure (Panic Disorder Severity Scale). It is concluded that the Bergen 4-day treatment is a promising treatment approach for PD, and a randomized controlled trial is warranted.
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32.
  • Hansen, Bjarne, et al. (författare)
  • The Bergen 4-day treatment for OCD : four years follow-up of concentrated ERP in a clinical mental health setting
  • 2019
  • Ingår i: Cognitive Behaviour Therapy. - : Informa UK Limited. - 1650-6073 .- 1651-2316. ; 48:2, s. 89-105
  • Tidskriftsartikel (refereegranskat)abstract
    • There are few long-term follow-up studies on psychological treatment of anxiety disorders carried out in clinical mental health settings, so called effectiveness studies. The present paper presents a four year follow-up of patients with obsessive-compulsive disorder treated by the Bergen 4-day treatment (B4DT), a concentrated form of exposure and response prevention (ERP). A total of 77 obsessive–compulsive disorder (OCD) patients received treatment during four consecutive days and were assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) pre, post, and at follow-ups after 3 and 6 months, and 4 years post-treatment. The Y-BOCS mean score changed from 25.9 at pre- to 10.0 post-treatment and 9.9 at long-term follow-up. The proportion fulfilling the strict international consensus criteria for remission was 73% at post-treatment and 69% at follow-up. When taking declining rate, attrition rate, remission, relapse, and further improvement during the follow-up period into account, 72% were recovered on a long-term basis. A comparison with previously published effectiveness studies of ERP indicated that the 4-day treatment yielded significantly higher proportions of remission at post-treatment and recovery at follow-up, as well as within-group effect size on the Y-BOCS. The implications of these results are discussed.
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33.
  • Harris, Alison J. T., 1982-, et al. (författare)
  • Archives of human-dog relationships : Genetic and stable isotope analysis of Arctic fur clothing
  • 2020
  • Ingår i: Journal of Anthropological Archaeology. - : Elsevier BV. - 0278-4165 .- 1090-2686. ; 59
  • Tidskriftsartikel (refereegranskat)abstract
    • Among Indigenous populations of the Arctic, domestic dogs (Canislupus familiaris) were social actors aiding in traction and subsistence activities. Less commonly, dogs fulfilled a fur-bearing role in both the North American and Siberian Arctic. Examples of garments featuring dog skins were collected during the 19th-20th centuries and are now curated by the National Museum of Denmark. We sequenced the mitochondrial genomes of macroscopically identified dog skin garments. We conducted stable carbon and nitrogen isotope ratio analysis of the dog furs and of fur samples from contemporaneous pelts of Arctic (C. lupus arctos) and grey (C. lupus) wolves. Despite the presence of biocides used to protect the fur clothing during storage, we extracted well-preserved DNA using a minimally-invasive sampling protocol. Unexpectedly, the mtDNA genomes of one-third of the samples were consistent with wild taxa, rather than domestic dogs. The strong marine component in the diets of North American dogs distinguished them from Greenland and Canadian wolves, but Siberian dogs consumed diets that were isotopically similar to wild species. We found that dog provisioning practices were variable across the Siberian and North American Arctic, but in all cases, involved considerable human labor.
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34.
  • Havnen, Audun, et al. (författare)
  • Concentrated ERP Delivered in a Group Setting : A Replication Study
  • 2017
  • Ingår i: Behavioural and Cognitive Psychotherapy. - 1352-4658 .- 1469-1833. ; 45:5, s. 530-536
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In a previous effectiveness study (Havnen et al., 2014), 35 obsessive compulsive disorder (OCD) patients underwent Concentrated Exposure Treatment (cET), which is a newly developed group treatment format delivered over four consecutive days. Aims: The primary aims of the present study were to evaluate the treatment results for a new sample of OCD patients receiving the cET treatment approach and to replicate the effectiveness study described in Havnen et al. (2014). Method: Forty-two OCD patients underwent cET treatment. Treatment was delivered by different therapists than in Havnen et al. (2014), except for two groups led by the developers of the treatment. Assessments of OCD symptom severity, treatment satisfaction, and occupational impairment were included. Results: The results showed a significant reduction in Yale-Brown Obsessive Compulsive Scale scores from pre-treatment to post-treatment, which was maintained at 6-month follow-up. At post-treatment, 74% of the sample was remitted; at 6-month follow-up, 60% were recovered. The sample showed a very high degree of overall treatment satisfaction. The results from the present study were statistically compared with those obtained in the previous study. The analyses showed that the study samples had comparable demographic data and equal application of treatment. The outcome of the present and original study did not differ significantly on primary and secondary outcome measures. Conclusions: This study shows that cET was successfully replicated in a new patient sample treated by different therapists than the original study. The results indicate that cET is well accepted by the patients, and the potential for dissemination is discussed.
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35.
  • Havnen, Audun, et al. (författare)
  • Concentrated ERP delivered in a group setting : An effectiveness study
  • 2014
  • Ingår i: Journal of Obsessive-Compulsive and Related Disorders. - : Elsevier BV. - 2211-3649 .- 2211-3657. ; 3:4, s. 319-324
  • Tidskriftsartikel (refereegranskat)abstract
    • The aims of the present study were to evaluate the acceptability and long term gains of a highly concentrated exposure and response prevention (ERP) for obsessive compulsive disorder (OCD). Treatment was individually tailored and delivered in a group format over four consecutive days in an outpatient OCD treatment unit, part of the ordinary specialist health care. A total of 35 patients accepted the offer of treatment; 23 of the patients were classified with severe to extreme OCD, and 74% of the sample had previously received treatment for their OCD (20% of these with ERP). The results showed that more than 90% of the patients expressed a high degree of satisfaction with the concentrated ERP. At six months follow-up 27 (77%) were classified as recovered and a significant improvement was seen in depressive symptoms as well. The majority of the sample also showed improvement with regard to employment status 12 months after treatment. The results indicate that this highly concentrated treatment may be a feasible format of delivering ERP.
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36.
  • Kvale, Gerd, et al. (författare)
  • Effect of D-Cycloserine on the Effect of Concentrated Exposure and Response Prevention in Difficult-to-Treat Obsessive-Compulsive Disorder : A Randomized Clinical Trial
  • 2020
  • Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 3:8
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE: Evidence is lacking for viable treatment options for patients with difficult-to-treat obsessive-compulsive disorder (OCD). It has been suggested that D-cycloserine (DCS) could potentiate the effect of exposure and response prevention (ERP) treatment, but the hypothesis has not been tested among patients with difficult-to-treat OCD.OBJECTIVE: To evaluate whether DCS potentiates the effect of concentrated ERP among patients with difficult-to-treat OCD.DESIGN, SETTING, AND PARTICIPANTS: The study was a randomized placebo-controlled triple-masked study with a 12-month follow-up. Participants were adult outpatients with difficult-to-treat OCD. A total of 220 potential participants were referred, of whom 36 did not meet inclusion criteria and 21 declined to participate. Patients had either relapsed after (n = 100) or not responded to (n = 63) previous ERP treatment. A total of 9 specialized OCD teams within the public health care system in Norway participated, giving national coverage. An expert team of therapists from the coordinating site delivered treatment. Inclusion of patients started in January 2016 and ended in August 2017. Data analysis was conducted February to September 2019.INTERVENTIONS: All patients received individual, concentrated ERP treatment delivered during 4 consecutive days in a group setting (the Bergen 4-day treatment format) combined with 100 mg DCS, 250 mg DCS, or placebo.MAIN OUTCOMES AND MEASURES: Change in symptoms of OCD and change in diagnostic status. Secondary outcomes measures included self-reported symptoms of OCD, anxiety, depression, and quality of life.RESULTS: The total sample of 163 patients had a mean (SD) age of 34.5 (10.9) years, and most were women (117 [71.8%]). They had experienced OCD for a mean (SD) of 16.2 (10.2) years. A total of 65 patients (39.9%) were randomized to receive 100 mg DCS, 67 (41.1%) to 250 mg of DCS, and 31 (19.0%) to placebo. Overall, 91 (56.5%) achieved remission at posttreatment, while 70 (47.9%) did so at the 12-month follow-up. There was no significant difference in remission rates among groups. There was a significant reduction in symptoms at 12 months, and within-group effect sizes ranged from 3.01 (95% CI, 2.38-3.63) for the group receiving 250 mg DCS to 3.49 (95% CI, 2.78-4.18) for the group receiving 100 mg DCS (all P < .001). However, there was no significant effect of treatment group compared with placebo in obsessive-compulsive symptoms (250 mg group at posttreatment: d = 0.33; 95% CI, -0.10 to 0.76; 100 mg group at posttreatment: d = 0.36; 95% CI, -0.08 to 0.79), symptoms of depression and anxiety (eg, Patient Health Questionnaire-9 score among 250 mg group at 12-month follow-up: d = 0.30; 95% CI, -0.17 to 0.76; Generalized Anxiety Disorder-7 score among 100 mg group at 12-month follow-up: d = 0.27; 95% CI, -0.19 to 0.73), and well-being (250 mg group: d = 0.10; 95% CI, -0.42 to 0.63; 100 mg group: d = 0.34; 95% CI, -0.19 to 0.86). No serious adverse effects were reported.CONCLUSIONS AND RELEVANCE: In this study, DCS did not potentiate ERP treatment effect, but concentrated ERP treatment was associated with improvement. This randomized clinical trial evaluates whether D-cycloserine potentiates the effect of concentrated exposure and response prevention among patients with difficult-to-treat obsessive-compulsive disorder.
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37.
  • Kvale, Gerd, et al. (författare)
  • Successfully treating 90 patients with obsessive compulsive disorder in eight days : the Bergen 4-day treatment
  • 2018
  • Ingår i: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 18
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Oslo University Hospital, Norway, had by autumn 2016, accumulated a waiting list of 101 patients with obsessive-compulsive disorder (OCD) who had a legal right to receive treatment by a specialized OCD team. In this challenging situation, the Bergen OCD-team suggested to solve the problem by offering all patients an option for the rapid Bergen 4-day treatment (B4DT). The B4DT is an individual treatment delivered during four consecutive days in a group of six patients with the same number of therapists. The approach has previously shown a post-treatment response rate of 90% and a 3-month remission rate of 70%. Methods: Ninety-seven of the wait-list patients were available for the scheduled time slots, and 90 received the 4-day format during 8 days (45 patients each week). The therapists were recruited from 22 different specialized OCD-teams from all over Norway, and 44 (68%) had not previously delivered the 4-day format. Results: Post-treatment; 91.1% of the patients were classified as responders, and 72.2% were in remission. At 3-month follow-up; 84.4 were classified as responders and the remission rate was 67.7%. Oslo University Hospital now offers the 4-day treatment as standard treatment for OCD. Conclusions: We conclude that the B4DT is an acceptable and potentially effective OCD-treatment.
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38.
  • Launes, Gunvor, et al. (författare)
  • A Randomized Controlled Trial of Concentrated ERP, Self-Help and Waiting List for Obsessive- Compulsive Disorder : The Bergen 4-Day Treatment
  • 2019
  • Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The Bergen 4-day treatment (B4DT) is a concentrated exposure-based treatment for patients with Obsessive-Compulsive Disorder (OCD) delivered during four consecutive days. The B4DT has in a number of effectiveness studies demonstrated promising results as approximately 90% of patients gain reliable clinical change post-treatment and nearly 70% are recovered on a long-term basis.Methods: The current study is the first randomized controlled trial evaluating the effects of the B4DT. Forty-eight patients diagnosed with OCD were randomized to B4DT, self-help (SH), or waiting list (WL) with 16 patients in each condition. All participants randomized to the B4DT underwent the treatment without any attrition.Results: The B4DT yielded significantly better effects than control conditions on measures of OCD, depression, and generalized anxiety. The response rate (≥35% reduction of the individual patient’s pre-treatment Y-BOCS score) was 93.8% in B4DT, 12.5% in SH and 0% in WL, while remission rate (response criterion is fulfilled and the post-treatment Y-BOCS score is ≤12 points) was 62.5%, 6.3%, and 0%, respectively. Furthermore, patients who had received the B4DT, showed improved work- and social functioning. None of the patients treated with B4DT showed signs of deterioration. In comparison, one patient in the SH condition was in remission, and one showed significant clinical improvement, whereas the remaining showed no change.Conclusion: The results indicate that the B4DT is an effective treatment for patients suffering from OCD.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02886780.
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39.
  • Launes, Gunvor, et al. (författare)
  • The Bergen 4-Day Treatment (B4DT) for Obsessive-Compulsive Disorder : Outcomes for Patients Treated After Initial Waiting List or Self-Help Intervention
  • 2020
  • Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • The Bergen 4-day treatment (B4DT) for obsessive-compulsive disorder (OCD) was recently tested in a randomized controlled trial, where the results showed that the B4DT was more effective than a self-help intervention (SH) and a waiting list condition (WL). Patients in the SH and WL condition still in need of treatment after the first intervention (N = 26; 13 from each condition) were offered the B4DT. None of the patients declined participation, and there were no dropouts. At post-treatment 59.5% were in remission, 31.0% had treatment response, and 9.5% showed no change. At 3-month follow-up 71.4% were in remission, 19.0% had treatment response, and 9.5% showed no change. There were also significant improvement in self-reported symptoms of OCD, generalized anxiety symptoms, and depressive symptoms. The results are in line with what we previously have found for the B4DT in a number of effectiveness studies. In addition, the results indicate that the patients who previously had received an unsuccessful SH intervention and patients who had first been in a WL condition, profited as much as patients who had received the B4DT as the initial intervention. Implications for clinical guidelines and for dissemination of the B4DT are discussed.
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40.
  • Launes, Gunvor, et al. (författare)
  • The Bergen 4-Day Treatment for Obsessive-Compulsive Disorder : Does It Work in a New Clinical Setting?
  • 2019
  • Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Sorlandet Hospital in Norway has a history of offering patients with obsessive-compulsive disorder (OCD) cognitive behavior group therapy using 12 weekly sessions of 2.5 h each. A previous evaluation of this treatment has shown that 51.9% did not respond at post-treatment. Recently, a highly concentrated group-treatment format, the Bergen 4-day treatment (B4DT), has been shown to help more than 90% of patients with OCD post-treatment. Based on these positive results, it was decided to explore whether the B4DT could be a feasible format for delivering ERP at another clinic. Thirty-five consecutively recruited patients were included in the current pilot study, and assessed at pre-treatment, post-treatment, and 3-month follow-up. Treatment response rate (35% reduction in OCD-symptom score) was 94% at post-treatment, and 80% at follow-up. Seventy-four percent were in remission at post-treatment and 68% at followup. Only one patient dropped out of treatment. The patients were highly satisfied with the treatment content and format. The results indicate that the 4-day treatment could successfully be implemented at a new clinic.
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41.
  • Malmström, Annika, et al. (författare)
  • Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial
  • 2017
  • Ingår i: Acta Oncologica. - : TAYLOR & FRANCIS LTD. - 0284-186X .- 1651-226X. ; 56:12, s. 1776-1785
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: A pilot study of temozolomide (TMZ) given before radiotherapy (RT) for anaplastic astrocytoma (AA) and glioblastoma (GBM) resulted in prolonged survival compared to historical controls receiving RT alone. We therefore investigated neoadjuvant TMZ (NeoTMZ) in a randomized trial. During enrollment, concomitant and adjuvant radio-chemotherapy with TMZ became standard treatment. The trial was amended to include concurrent TMZ.Patients and methods: Patients, after surgery for GBM or AA, age 60 years and performance status (PS) 0-2, were randomized to either 2-3 cycles of TMZ, 200mg/m(2) days 1-5 every 28 days, followed by RT 60Gy in 30 fractions or RT only. Patients without progressive disease after two TMZ cycles, received the third cycle. From March 2005, TMZ 75mg/m(2) was administered daily concomitant with RT. TMZ was recommended first-line treatment at progression. Primary endpoint was overall survival and secondary safety.Results: The study closed prematurely after enrolling 144 patients, 103 with GBM and 41 with AA. Median age was 53 years (range 24-60) and 89 (62%) were male. PS was 0-1 for 133 (92%) patients, 53 (37%) had complete surgical resection and 18 (12%) biopsy. Ninety-two (64%) received TMZ concomitant with RT. Seventy-two (50%) were randomized to neoadjuvant treatment. For the overall study population survival was 20.3 months for RT and 17.7 months for NeoTMZ (p=.76), this not reaching the primary objective. For the preplanned subgroup analysis, we found that NeoTMZ AA patients had a median survival of 95.1 months compared to 35.2 months for RT (p=.022). For patients with GBM, no difference in survival was observed (p=.10). MGMT and IDH status affected outcome.Conclusions: No advantage of NeoTMZ was noted for the overall study population or subgroup of GBM, while NeoTMZ resulted in 5 years longer median survival for patients diagnosed as AA.
  •  
42.
  • Mataix-Cols, David, et al. (författare)
  • Nordic OCD & Related Disorders Consortium : Rationale, design, and methods.
  • 2020
  • Ingår i: American Journal of Medical Genetics Part B. - : Wiley. - 1552-4841 .- 1552-485X. ; 183:1, s. 38-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder, yet its etiology is unknown and treatment outcomes could be improved if biological targets could be identified. Unfortunately, genetic findings for OCD are lagging behind other psychiatric disorders. Thus, there is a pressing need to understand the causal mechanisms implicated in OCD in order to improve clinical outcomes and to reduce morbidity and societal costs. Specifically, there is a need for a large-scale, etiologically informative genetic study integrating genetic and environmental factors that presumably interact to cause the condition. The Nordic countries provide fertile ground for such a study, given their detailed population registers, national healthcare systems and active specialist clinics for OCD. We thus formed the Nordic OCD and Related Disorders Consortium (NORDiC, www.crowleylab.org/nordic), and with the support of NIMH and the Swedish Research Council, have begun to collect a large, richly phenotyped and genotyped sample of OCD cases. Our specific aims are geared toward answering a number of key questions regarding the biology, etiology, and treatment of OCD. This article describes and discusses the rationale, design, and methodology of NORDiC, including details on clinical measures and planned genomic analyses.
  •  
43.
  • Miskinyte, Giedre, et al. (författare)
  • Direct conversion of human fibroblasts to functional excitatory cortical neurons integrating into human neural networks
  • 2017
  • Ingår i: Stem Cell Research and Therapy. - : Springer Science and Business Media LLC. - 1757-6512. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Human fibroblasts can be directly converted to several subtypes of neurons, but cortical projection neurons have not been generated. Methods: Here we screened for transcription factor combinations that could potentially convert human fibroblasts to functional excitatory cortical neurons. The induced cortical (iCtx) cells were analyzed for cortical neuronal identity using immunocytochemistry, single-cell quantitative polymerase chain reaction (qPCR), electrophysiology, and their ability to integrate into human neural networks in vitro and ex vivo using electrophysiology and rabies virus tracing. Results: We show that a combination of three transcription factors, BRN2, MYT1L, and FEZF2, have the ability to directly convert human fibroblasts to functional excitatory cortical neurons. The conversion efficiency was increased to about 16% by treatment with small molecules and microRNAs. The iCtx cells exhibited electrophysiological properties of functional neurons, had pyramidal-like cell morphology, and expressed key cortical projection neuronal markers. Single-cell analysis of iCtx cells revealed a complex gene expression profile, a subpopulation of them displaying a molecular signature closely resembling that of human fetal primary cortical neurons. The iCtx cells received synaptic inputs from co-cultured human fetal primary cortical neurons, contained spines, and expressed the postsynaptic excitatory scaffold protein PSD95. When transplanted ex vivo to organotypic cultures of adult human cerebral cortex, the iCtx cells exhibited morphological and electrophysiological properties of mature neurons, integrated structurally into the cortical tissue, and received synaptic inputs from adult human neurons. Conclusions: Our findings indicate that functional excitatory cortical neurons, generated here for the first time by direct conversion of human somatic cells, have the capacity for synaptic integration into adult human cortex.
  •  
44.
  • Nordahl, Håkon, et al. (författare)
  • Sleep disturbances in treatment-seeking OCD-patients : Changes after concentrated exposure treatment
  • 2018
  • Ingår i: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 59:2, s. 186-191
  • Tidskriftsartikel (refereegranskat)abstract
    • Research indicates that patients with Obsessive Compulsive Disorder (OCD) frequently suffer from comorbid sleep difficulties, and that these difficulties often are not clinically recognized and diagnosed. There has been limited research investigating if comorbid sleep difficulties impair treatment outcome for OCD and if the sleep difficulties change following OCD-treatment. Thirty-six patients with obsessive compulsive disorder underwent concentrated exposure treatment delivered in a group over four consecutive days and were assessed with measures of OCD, depressive symptoms and sleep disturbance at three different time points (pre, post and 6 months follow-up). The sample was characterized by a high degree of comorbidity with other psychiatric disorders. At pre-treatment nearly 70% of the patients reported sleep difficulties indicative of primary insomnia. The results showed that patients had large reductions of OCD-symptoms as well as significant improvements in sleep disturbance assessed after treatment, and that these improvements were maintained at follow-up. Sleep disturbance did not impair treatment outcome, on the contrary patients with higher degree of sleep disturbance at pre-treatment had better outcome on OCD-symptoms after treatment. The results indicated that the majority of the OCD sample suffered from sleep disturbances and that these sleep disturbances were significantly reduced following adequate treatment of OCD without specific sleep interventions. However, a proportion of the patients suffered from residual symptoms of insomnia after treatment.
  •  
45.
  • Oppong Bekoe, Samuel, et al. (författare)
  • Determination of thirteen antibiotics in drug products : a new LC-MS/MS tool for screening drug product quality
  • 2014
  • Ingår i: Analytical Methods. - 1759-9660 .- 1759-9679. ; 6, s. 5847-5855
  • Tidskriftsartikel (refereegranskat)abstract
    • Poor quality antibiotic medicines in circulation in Sub-Saharan Africa continue to be a burden. Pharmaceutical trade in substandard and counterfeit medicines is on the rise. The chemical quality of antibiotics dispensed in health facilities and recognised drug outlets in Ghana, when compromised, could be a major drawback to efforts made in fighting antibiotic resistance globally. To improve on antibiotic drug quality monitoring, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology, which is capable of quantifying thirteen antibiotics in drug products, was developed and validated in present work. The methodology was applied to various drug products including tablets, capsules, suspensions, syrups, intravenous and injection solutions as well as ear and eye droplets used as essential medicines in a Sub-Saharan country, Ghana.
  •  
46.
  • Oppong Bekoe, Samuel, et al. (författare)
  • Determination of thirteen antibiotics in drug products : a new LC-MS/MS tool for screening drug product quality
  • 2014
  • Ingår i: Analytical Methods. - : Royal Society of Chemistry. - 1759-9660 .- 1759-9679. ; 6, s. 5847-5855
  • Tidskriftsartikel (refereegranskat)abstract
    • Poor quality antibiotic medicines in circulation in Sub-Saharan Africa continue to be a burden. Pharmaceutical trade in substandard and counterfeit medicines is on the rise. The chemical quality of antibiotics dispensed in health facilities and recognised drug outlets in Ghana, when compromised, could be a major drawback to efforts made in fighting antibiotic resistance globally. To improve on antibiotic drug quality monitoring, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology, which is capable of quantifying thirteen antibiotics in drug products, was developed and validated in present work. The methodology was applied to various drug products including tablets, capsules, suspensions, syrups, intravenous and injection solutions as well as ear and eye droplets used as essential medicines in a Sub-Saharan country, Ghana.
  •  
47.
  • Raghavan, Maanasa, et al. (författare)
  • The genetic prehistory of the New World Arctic
  • 2014
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 345:6200, s. 1020-
  • Tidskriftsartikel (refereegranskat)abstract
    • The New World Arctic, the last region of the Americas to be populated by humans, has a relatively well-researched archaeology, but an understanding of its genetic history is lacking. We present genome-wide sequence data from ancient and present-day humans from Greenland, Arctic Canada, Alaska, Aleutian Islands, and Siberia. We show that Paleo-Eskimos (similar to 3000 BCE to 1300 CE) represent a migration pulse into the Americas independent of both Native American and Inuit expansions. Furthermore, the genetic continuity characterizing the Paleo-Eskimo period was interrupted by the arrival of a new population, representing the ancestors of present-day Inuit, with evidence of past gene flow between these lineages. Despite periodic abandonment of major Arctic regions, a single Paleo-Eskimo metapopulation likely survived in near-isolation for more than 4000 years, only to vanish around 700 years ago.
  •  
48.
  • Rasmussen, Morten, et al. (författare)
  • Ancient human genome sequence of an extinct Palaeo-Eskimo
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 463:7282, s. 757-762
  • Tidskriftsartikel (refereegranskat)abstract
    • We report here the genome sequence of an ancient human. Obtained from ∼4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average depth of 20×, we recover 79% of the diploid genome, an amount close to the practical limit of current sequencing technologies. We identify 353,151 high-confidence single-nucleotide polymorphisms (SNPs), of which 6.8% have not been reported previously. We estimate raw read contamination to be no higher than 0.8%. We use functional SNP assessment to assign possible phenotypic characteristics of the individual that belonged to a culture whose location has yielded only trace human remains. We compare the high-confidence SNPs to those of contemporary populations to find the populations most closely related to the individual. This provides evidence for a migration from Siberia into the New World some 5,500 years ago, independent of that giving rise to the modern Native Americans and Inuit.
  •  
49.
  • Ratasvuori, Maire, et al. (författare)
  • Prognostic role of en-bloc resection and late onset of bone metastasis in patients with bone-seeking carcinomas of the kidney, breast, lung, and prostate: SSG study on 672 operated skeletal metastases
  • 2014
  • Ingår i: Journal of Surgical Oncology. - : Wiley-Blackwell. - 0022-4790 .- 1096-9098. ; 110:4, s. 360-365
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Objectives In metastatic disease, decisions regarding potential surgery require reliable data about the patients survival. In this study, we evaluated different prognostic factors and their impact in four common primary tumors causing bone metastases. Methods Data were acquired from the Scandinavian Sarcoma Group (SSG) metastasis registry. The patients underwent surgery between July 1999 and July 2009. This study included breast, prostate, lung, and kidney cancer cases, with a total of 672 operated non-spinal metastases. Differences in prognostic factors were evaluated using the Kaplan-Meier method with long-rank test. Cox regression multivariate analysis was performed to identify statistically independent prognostic factors. Results Significant factors affecting survival were the presence of organ metastases, overall heath status, and disease load. In kidney cancer, en bloc resection of solitary metastases was associated with a significant fourfold longer survival compared to intralesional surgery. Preoperative radiotherapy was associated with higher complication and reoperation rates. Conclusions This data summary is important tool for clinicians to evaluate survival and choose treatment options for patients suffering from metastatic bone disease. J. Surg. Oncol. 2014; 110:360-365.
  •  
50.
  • Riise, Eili N., et al. (författare)
  • Concentrated exposure and response prevention for adolescents with obsessive-compulsive disorder : A replication study
  • 2018
  • Ingår i: Journal of Obsessive-Compulsive and Related Disorders. - : Elsevier BV. - 2211-3649 .- 2211-3657. ; 19, s. 15-22
  • Tidskriftsartikel (refereegranskat)abstract
    • A previous effectiveness study (Riise et al., 2016) demonstrated promising findings from a 4-day concentrated exposure and response prevention (ERP) treatment, the Bergen 4-day treatment (B4DT), for adolescents with obsessive-compulsive disorder (OCD). The present study investigated whether the results reported in the original study were replicated in a new sample of adolescents. Forty-one referred patients aged 11–18 underwent treatment at an outpatient clinic, as part of public health care. Treatment was delivered to 2–4 patients and their parents simultaneously, during four consecutive days, followed by a three-week period of self-administered ERP. Obsessive-compulsive symptoms were assessed at pre-treatment, post-treatment, 3- and 6-month follow-up. The results demonstrated significant reductions in OCD-symptoms. Remission was achieved by 33 patients (80%) at post-treatment, and 30 (73%) at follow-up. At post-treatment or follow-up there were no significant differences between the present sample and the sample in Riise et al. (2016) on OCD-severity or on rates of response or remission. The results demonstrate that the treatment was successfully replicated in a new sample and adds further support to the efficacy of the B4DT. Findings suggest that a concentrated treatment format with prolonged sessions might be a viable option to improve treatment outcomes of ERP.
  •  
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