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  • Stacey, Simon N, et al. (author)
  • A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.
  • 2011
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:11, s. 1098-103
  • Journal article (peer-reviewed)abstract
    • To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).
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  • Sigmundsson, F., et al. (author)
  • Segmented lateral dyke growth in a rifting event at Bardarbunga volcanic system, Iceland
  • 2015
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 517:7533
  • Journal article (peer-reviewed)abstract
    • Crust at many divergent plate boundaries forms primarily by the injection of vertical sheet-like dykes, some tens of kilometres long(1). Previous models of rifting events indicate either lateral dyke growth away from a feeding source, with propagation rates decreasing as the dyke lengthens(2-4), or magma flowing vertically into dykes from an underlying source(5,6), with the role of topography on the evolution of lateral dykes not clear. Here we show how a recent segmented dyke intrusion in the Bardarbunga volcanic system grew laterally for more than 45 kilometres at a variable rate, with topography influencing the direction of propagation. Barriers at the ends of each segment were overcome by the build-up of pressure in the dyke end; then a new segment formed and dyke lengthening temporarily peaked. The dyke evolution, which occurred primarily over 14 days, was revealed by propagating seismicity, ground deformation mapped by Global Positioning System(GPS), interferometric analysis of satellite radar images (InSAR), and graben formation. The strike of the dyke segments varies from an initially radial direction away from the Bardarbunga caldera, towards alignment with that expected from regional stress at the distal end. A model minimizing the combined strain and gravitational potential energy explains the propagation path. Dyke opening and seismicity focused at the most distal segment at any given time, and were simultaneous with magma source deflation and slow collapse at the Bardarbunga caldera, accompanied by a series of magnitude M > 5 earthquakes. Dyke growth was slowed down by an effusive fissure eruption near the end of the dyke. Lateral dyke growth with segment barrier breaking by pressure build-up in the dyke distal end explains how focused upwelling of magma under central volcanoes is effectively redistributed over long distances to create new upper crust at divergent plate boundaries.
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  • Geirsson, H., et al. (author)
  • Overview of results from continuous GPS observations in Iceland from 1995 to 2010
  • 2010
  • In: Jökull. - 0449-0576. ; 60:1, s. 1-21
  • Journal article (peer-reviewed)abstract
    • Iceland is a natural laboratory for a variety of processes associated with crustal deformation, such as earthquakes, magmatic events, tectonic plate motions, and glacial load changes. Continuous GPS (CGPS) measurements started in Iceland in 1995, and since then data from the network have helped to shed light on many different active deformation processes. The number of CGPS sites in Iceland tripled during 2006–2008, as a result of an international collaborative effort coordinated by Icelandic scientists. By early 2010 the number of CGPS stations in Iceland had reached 64, located primarily around and within the North- American–Eurasian plate boundary zone. Since its initiation, the CGPS network has played an important role in monitoring volcanoes and seismogenic areas, most notably during the 2009–2010 Eyjafjallajökull volcano unrest. Plate spreading of up to 2 cm per year usually dominates the horizontal motion observed at the CGPS sites, while uplift is observed at many of the stations due to recent retreat of the Icelandic ice caps. Co-seismic and post-seismic deformation of the largest earthquakes in 2000 and 2008 in the South Iceland Seismic Zone were captured by the network, and high-rate (1 Hz) CGPS observations helped to identify two magnitude 6 mainshocks in 2008 that were separated in time by only 2–3 seconds. The CGPS network has thus enabled us to monitor deformation occurring over days to months caused by migration of magma or fluids, post-seismic transients, rapid deformation caused by earthquakes and eruptions, as well as the long term plate spreading signal.
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  • Ran, Ylva, et al. (author)
  • Environmental assessment of diets: overview and guidance on indicator choice
  • 2024
  • In: The Lancet Planetary Health. - : ELSEVIER SCI LTD. - 2542-5196. ; 8:3, s. e172-e187
  • Research review (peer-reviewed)abstract
    • Comprehensive but interpretable assessment of the environmental performance of diets involves choosing a set of appropriate indicators. Current knowledge and data gaps on the origin of dietary foodstuffs restrict use of indicators relying on site-specific information. This Personal View summarises commonly used indicators for assessing the environmental performance of diets, briefly outlines their benefits and drawbacks, and provides recommendations on indicator choices for actors across multiple fields involved in activities that include the environmental assessment of diets. We then provide recommendations on indicator choices for actors across multiple fields involved in activities that use environmental assessments, such as health and nutrition experts, policy makers, decision makers, and private-sector and public-sector sustainability officers. We recommend that environmental assessment of diets should include indicators for at least the five following areas: climate change, biosphere integrity, blue water consumption, novel entities, and impacts on natural resources (especially wild fish stocks), to capture important environmental trade-offs. If more indicators can be handled in the assessment, indicators to capture impacts related to land use quantity and quality and green water consumption should be used. For ambitious assessments, indicators related to biogeochemical flows, stratospheric ozone depletion, and energy use can be added.
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  • Sigmundsson, F., et al. (author)
  • Intrusion triggering of the 2010 Eyjafjallajökull explosive eruption
  • 2010
  • In: Nature. ; 468:7322, s. 426-430
  • Journal article (peer-reviewed)abstract
    • Gradual inflation of magma chambers often precedes eruptions at highly active volcanoes. During such eruptions, rapid deflation occurs as magma flows out and pressure is reduced1–3. Less is known about the deformation style at moderately active volcanoes, such as Eyjafjallajo¨kull, Iceland, where an explosive summit eruption of trachyandesite beginning on 14 April 2010 caused exceptional disruption to air traffic, closing airspace over much of Europe for days. This eruption was preceded by an effusive flank eruption of basalt from 20 March to 12 April 2010. The 2010 eruptions are the culmination of 18 years of intermittent volcanic unrest4–9. Here we show that deformation associated with the eruptions was unusual because it did not relate to pressure changes within a single magma chamber. Deformation was rapid before the first eruption (.5mm per day after 4 March), but negligible during it. Lack of distinct co-eruptive deflation indicates that the net volume of magma drained from shallow depth during this eruption was small; rather, magma flowed from considerable depth. Before the eruption, a 0.05km3 magmatic intrusion grew over a period of three months, in a temporally and spatially complex manner, as revealed by GPS (Global Positioning System) geodetic measurements and interferometric analysis of satellite radar images. The second eruption occurred within the ice-capped caldera of the volcano, with explosivity amplified by magma–ice interaction. Gradual contraction of a source, distinct from the pre-eruptive inflation sources, is evident from geodetic data. Eyjafjallajo¨kull’s behaviour can be attributed to its off-rift setting with a ‘cold’ subsurface structure and limited magma at shallow depth, as may be typical for moderately active volcanoes. Clear signs of volcanic unrest signals over years to weeks may indicate reawakening of such volcanoes, whereas immediate short-term eruption precursors may be subtle and difficult to detect.
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  • von Horn, H, et al. (author)
  • GH is a regulator of IGF2 promoter-specific transcription in human liver
  • 2002
  • In: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 172:3, s. 457-465
  • Journal article (peer-reviewed)abstract
    • The regulation of the insulin-like growth factor-II gene (IGF2) is complex and involves the usage of four promoters resulting in different 5' untranslated regions, but with a common translated product. The IGF2 gene product is a mitogenic and survival factor that has been suggested to be important for a normal fetal development and cancer. In this paper we present evidence suggesting that the human IGF2 gene is regulated by GH, and that this regulation occurs in a promoter-specific way. Three lines of evidence support this finding. First, in vivo data from patients treated with GH (one injection or daily injections for 5 consecutive days) showed an increase in the IGF2 P2 promoter derived transcript after acute treatment, and of the P4 promoter transcript after short-term treatment while the P1 promoter derived transcript did not show any significant change. Secondly, isolated human liver cells treated with GH for 2 h displayed an upregulation of the P2 promoter derived transcript. Thirdly, employing transfection experiments in GH-receptor positive CHO cells with P2 and P4 promoter-luciferase constructs, an upregulation by GH was evident, while a P1 promoter construct was unresponsive. We suggest that GH may be a physiological regulator of IGF2 in humans.
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  • Ahlström, Aisling, 1976, et al. (author)
  • A double-blind randomized controlled trial investigating a time-lapse algorithm for selecting Day 5 blastocysts for transfer
  • 2022
  • In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 37:4, s. 708-717
  • Journal article (peer-reviewed)abstract
    • STUDY QUESTION Can use of a commercially available time-lapse algorithm for Day 5 blastocyst selection improve pregnancy rates compared with morphology alone? SUMMARY ANSWER The use of a time-lapse selection model to choose blastocysts for fresh single embryo transfer on Day 5 did not improve ongoing pregnancy rate compared to morphology alone. WHAT IS KNOWN ALREADY Evidence from time-lapse monitoring suggests correlations between timing of key developmental events and embryo viability. No good quality evidence exists to support improved pregnancy rates following time-lapse selection. STUDY DESIGN, SIZE, DURATION A prospective multicenter randomized controlled trial including 776 randomized patients was performed between 2018 and 2021. Patients with at least two good quality blastocysts on Day 5 were allocated by a computer randomization program in a proportion of 1:1 into either the control group, whereby single blastocysts were selected for transfer by morphology alone, or the intervention group whereby final selection was decided by a commercially available time-lapse model. The embryologists at the time of blastocyst morphological scoring were blinded to which study group the patients would be randomized, and the physician and patients were blind to which group they were allocated until after the primary outcome was known. The primary outcome was number of ongoing pregnancies in the two groups. PARTICIPANTS/MATERIALS, SETTING, METHODS From 10 Nordic IVF clinics, 776 patients with a minimum of two good quality blastocysts on Day 5 (D5) were randomized into one of the two study groups. A commercial time-lapse model decided the final selection of blastocysts for 387 patients in the intervention (time-lapse) group, and blastocysts with the highest morphological score were transferred for 389 patients in the control group. Only single embryo transfers in fresh cycles were performed. MAIN RESULTS AND THE ROLE OF CHANCE In the full analysis set, the ongoing pregnancy rate for the time-lapse group was 47.4% (175/369) and 48.1% (181/376) in the control group. No statistically significant difference was found between the two groups: mean difference -0.7% (95% CI -8.2, 6.7, P = 0.90). Pregnancy rate (60.2% versus 59.0%, mean difference 1.1%, 95% CI -6.2, 8.4, P = 0.81) and early pregnancy loss (21.2% versus 18.5%, mean difference 2.7%, 95% CI -5.2, 10.6, P = 0.55) were the same for the time-lapse and the control group. Subgroup analyses showed that patient and treatment characteristics did not significantly affect the commercial time-lapse model D5 performance. In the time-lapse group, the choice of best blastocyst changed on 42% of occasions (154/369, 95% CI 36.9, 47.2) after the algorithm was applied, and this rate was similar for most treatment clinics. LIMITATIONS, REASONS FOR CAUTION During 2020, the patient recruitment rate slowed down at participating clinics owing to coronavirus disease-19 restrictions, so the target sample size was not achieved as planned and it was decided to stop the trial prematurely. The study only investigated embryo selection at the blastocyst stage on D5 in fresh IVF transfer cycles. In addition, only blastocysts of good morphological quality were considered for transfer, limiting the number of embryos for selection in both groups: also, it could be argued that this manual preselection of blastocysts limits the theoretical selection power of time-lapse, as well as restricting the results mainly to a good prognosis patient group. Most patients were aimed for blastocyst stage transfer when a minimum of five zygotes were available for extended culture. Finally, the primary clinical outcome evaluated was pregnancy to only 6-8 weeks. WIDER IMPLICATIONS OF THE FINDINGS The study suggests that time-lapse selection with a commercially available time-lapse model does not increase chance of ongoing pregnancy after single blastocyst transfer on Day 5 compared to morphology alone. STUDY FUNDING/COMPETING INTEREST(S) The study was financed by a grant from the Swedish state under the ALF-agreement between the Swedish government and the county councils (ALFGBG-723141). Vitrolife supported the study with embryo culture dishes and culture media. During the study period, T.H. changed his employment from Livio AB to Vitrolife AB. All other authors have no conflicts of interests to disclose. DATE OF FIRST PATIENT'S ENROLMENT 11 June 2018.
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  • Andersson, L-O, et al. (author)
  • A new neutron beam facility
  • 2004
  • In: Proc. of the 9th European Particle Accelerator Conference.
  • Conference paper (peer-reviewed)
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  • Bill-Axelson, Anna, et al. (author)
  • Radical prostatectomy versus watchful waiting in localized prostate cancer : the Scandinavian prostate cancer group-4 randomized trial
  • 2008
  • In: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:16, s. 1144-1154
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up.METHODS: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided.RESULTS: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001).CONCLUSION: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery. 
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  • Brewington, Seth, et al. (author)
  • Islands of change vs. islands of disaster : Managing pigs and birds in the Anthropocene of the North Atlantic
  • 2015
  • In: The Holocene. - : Sage Publications. - 0959-6836 .- 1477-0911. ; 25:10, s. 1676-1684
  • Journal article (peer-reviewed)abstract
    • The offshore islands of the North Atlantic were among some of the last settled places on earth, with humans reaching the Faroes and Iceland in the late Iron Age and Viking period. While older accounts emphasizing deforestation and soil erosion have presented this story of island colonization as yet another social–ecological disaster, recent archaeological and paleoenvironmental research combined with environmental history, environmental humanities, and bioscience is providing a more complex understanding of long-term human ecodynamics in these northern islands. An ongoing interdisciplinary investigation of the management of domestic pigs and wild bird populations in Faroes and Iceland is presented as an example of sustained resource management using local and traditional knowledge to create structures for successful wild fowl management on the millennial scale.
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  • Døssing, Arne, et al. (author)
  • On the origin of the Amerasia Basin and the High Arctic Large Igneous Province-Results of new aeromagnetic data
  • 2013
  • In: Earth and Planetary Science Letters. - : Elsevier BV. - 0012-821X .- 1385-013X. ; 363, s. 219-230
  • Journal article (peer-reviewed)abstract
    • The history of the 2.5 million km2 Amerasia Basin (sensu lato) is in many ways the least known in the global tectonic system. Radically different hypotheses proposed to explain its origin are supported only by inconclusive and/or indirect observations and several outstanding issues on the origin of the Basin remain unaddressed. The difficulty lies in the geodynamic evolution and signature of the Basin being overprinted by excess volcanism of the Alpha-Mendeleev Ridge complex, part of the High Arctic Large Igneous Province (HALIP) and one of the largest (>1 million km2) and most intense magmatic and magnetic complexes on Earth. Here, we present the results of a 550,000km2 aerogeophysical survey over the poorly explored Lomonosov Ridge (near Greenland) and adjoining Amerasia and Eurasia Basins that provides the first direct evidence for consistent linear magnetic features between the Alpha and Lomonosov Ridges, enabling the tectonic origin of both the Amerasia Basin and the HALIP to be constrained. A landward Lower Cretaceous ( ~ 138 - 125(120) Ma) giant dyke swarm (minimum 350×800km2) and tentative oceanward Barremian (or alternatively lower Valanginian-Barremian) seafloor spreading anomalies are revealed. Prior to Cenozoic opening of the Eurasia Basin the giant dyke swarm stretched from Franz Josef Land to the southern Alpha Ridge and possibly further to Queen Elisabeth Islands, Canada. The swarm points towards a 250-km-wide donut-shaped anomaly on the southern Alpha Ridge, which we propose was the centre of the HALIP mantle plume, suggesting that pronounced intrusive activity, associated with an Alpha Ridge mantle plume, took place well before the Late Cretaceous Superchron and caused continental breakup in the northern Amerasia Basin. Our results imply that at least the southern Alpha Ridge as well as large parts of the area between the Lomonosov and southern Alpha Ridges are highly attenuated continental crust formed by poly-phase breakup with LIP volcanic addition. Significantly, our results are consistent with an early ( ~ pre-120 Ma) overall continental scale rotational opening of the Amerasia Basin in which the Eurasian continental margin is rifted from the Canadian-southern Alpha Ridge margin about one or more poles in the Mackenzie Delta (Alaska). The findings provide a key to resolving Arctic plate reconstructions and LIPs in the Mesozoic.
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  • Einarsson, E, et al. (author)
  • Phase-contrast enhanced synchrotron micro-tomography of human meniscus tissue
  • 2022
  • In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 30:9, s. 1222-1233
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To investigate the feasibility of synchrotron radiation-based phase contrast enhanced micro-computed tomography (SR-PhC-μCT) for imaging of human meniscus. Quantitative parameters related to fiber orientation and crimping were evaluated as potential markers of tissue degeneration.DESIGN: Human meniscus specimens from 10 deceased donors were prepared using different preparation schemes: fresh frozen and thawed before imaging or fixed and paraffin-embedded. The samples were imaged using SR-PhC-μCT with an isotropic voxel size of 1.625 μm. Image quality was evaluated by visual inspection and spatial resolution. Fiber voxels were defined using a grey level threshold and a structure tensor analysis was applied to estimate collagen fiber orientation. The area at half maximum (FAHM) was calculated from angle histograms to quantify orientation distribution. Crimping period was calculated from the power spectrum of image profiles of crimped fibers. Parameters were compared to degenerative stage as evaluated by Pauli histopathological scoring.RESULTS: Image quality was similar between frozen and embedded samples and spatial resolutions ranged from 5.1 to 5.8 μm. Fiber structure, including crimping, was clearly visible in the images. Fibers appeared to be less organized closer to the tip of the meniscus. Fiber density might decrease slightly with degeneration. FAHM and crimping period did not show any clear association with histopathological scoring.CONCLUSION: SR-PhC-μCT is a feasible technique for high-resolution 3D imaging of fresh frozen meniscus tissue. Further work is needed to establish quantitative parameters that relate to tissue degeneration, but this imaging technique is promising for future studies of meniscus structure and biomechanical response.
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  • Einarsson, Emma, et al. (author)
  • Relating MR relaxation times of ex vivo meniscus to tissue degeneration through comparison with histopathology
  • 2020
  • In: Osteoarthritis and Cartilage Open. - : Elsevier BV. - 2665-9131. ; 2:2
  • Journal article (peer-reviewed)abstract
    • Background: Quantitative magnetic resonance imaging (MRI), e.g. relaxation parameter mapping, may be sensitive to structural and compositional tissue changes, and could potentially be used to non-invasively detect and monitor early meniscus degeneration related to knee osteoarthritis. Objective: To investigate MR relaxation times as potential biomarkers for meniscus degeneration through comparisons with histopathology. Methods: We measured MR relaxation parameters in the posterior horn of 40 menisci (medial and lateral) at a wide range of degenerative stages. T1, T2 and T2∗ were mapped using standard and ultrashort echo time sequences at 9.4 T and compared to gold standard histology using Pauli's histopathological scoring system, including assessment of surface integrity, collagen organization, cellularity and Safranin-O staining. Results: All three relaxation times increased with total Pauli score (mean difference per score (95% CI) for T2∗: 0.62 (0.37, 0.86), T2: 0.83 (0.53, 1.1) and T1: 24.7 (16.5, 32.8) ms/score). Clear associations were seen with scores of surface integrity (mean difference per score for T2∗: 3.0 (1.8, 4.2), T2: 4.0 (2.5, 5.5) and T1: 116 (75.6, 156) ms/score) and collagen organization (mean difference between highest and lowest score for T2∗: 5.3 (1.6, 8.9), T2: 6.1 (1.7, 11) and T1: 204 (75.9, 332) ms). The results were less clear for the remaining histopathological measures. Conclusions: MR relaxation times T1, T2 and T2∗ of ex vivo human menisci are associated with histologically verified degenerative processes, in particular related to surface integrity and collagen organization. If confirmed in vivo, MR relaxation times may thus be potential biomarkers for meniscus degeneration.
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  • Einarsson, H., et al. (author)
  • Inhibition of bacterial growth by Maillard reaction products
  • 1983
  • In: Journal of Agricultural and Food Chemistry. - 0021-8561 .- 1520-5118. ; 31:5, s. 1043-1047
  • Journal article (peer-reviewed)abstract
    • Maillard reaction products (MRP) were obtained by refluxing solutions containing either arginine and xylose (AX) or histidine and glucose (HG). The solutions were tested either unfractionated or partly purified by dialysis through a Spectra/Por (R)-6 membrane with a molecular weight cutoff at 1000. The bacteria tested were both pathogenic and spoilage bacteria frequently found in food. The effects of the AX and HG added were assessed on the basis of the growth curves and the MIC (minimum inhibitory concentration) values recorded. The MIC values obtained show that the inhibitory effect of MRP is dependent on the type of MRP and type of bacteria used. As can be seen from the growth curves, the lag phase of the growth was prolonged with increased concentrations of MRP. The results of the dialysis show that the high molecular weight fraction (Mr ?1000) was more inhibitory than the low molecular weight fraction (Mr ?1000) when tested with Bacillus subtilis, Escherichia coli, and Staphylococcus aureus. The MRP used in this study have in other studies been shown to possess a high antioxidative effect. © 1983 American Chemical Society.
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  • Einarsson, H., et al. (author)
  • Inhibitory mechanisms of Maillard reaction products.
  • 1988
  • In: Microbios. - 0026-2633. ; 53:214, s. 27-36
  • Journal article (peer-reviewed)abstract
    • In order to determine the inhibitory mechanism of antibacterial Maillard reaction products (MRP), heated mixtures containing arginine and xylose (AX) or histidine and glucose (HG) were studied for their mutagenic effect, using the Salmonella mutagenic test system ('Ames test'), with regard to their effect on the uptake of serine, glucose and oxygen and for their effect on iron solubility. It was found that the MRPs tested had little or no mutagenic effect, while an inhibitory effect on the uptake of serine, glucose and oxygen was observed. The MRPs also had an effect on the solubility of iron in nutrient broth and in phosphate buffer. While the AX mixture reduced the solubility of iron it was increased by the HG mixture. The reduction of iron solubility in the presence of the AX mixture was much greater at pH 8 than at pH 5. The present data suggest that the antibacterial effect of the MRPs tested is primarily due to the interaction between MRPs and iron, resulting in reduced oxygen uptake.
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  • Källmark, H., et al. (author)
  • Serologic immunogenicity and safety of herpes zoster subunit vaccine in patients with rheumatoid arthritis receiving Janus kinase inhibitors
  • 2023
  • In: Rheumatology. - 1462-0324.
  • Journal article (peer-reviewed)abstract
    • Objective Patients with RA treated with Janus kinase inhibitors (JAKis) are at increased risk of herpes zoster (HZ). The objective of this study was to investigate the serological immunogenicity and safety of the HZ subunit (HZ/su) vaccine in RA patients treated with JAKi, for which little is known.Methods RA patients treated with JAKi (n = 82) at the Department of Rheumatology, Skane University Hospital, Lund and Malmo, Sweden, and healthy controls (n = 51) received two doses of the HZ/su vaccine (Shingrix). Vaccine-specific antibody responses were analysed using indirect ELISA. Post-vaccination antibody levels were compared between patients and controls using analysis of covariance. Potential predictors for vaccine response were investigated using a multivariable linear regression analysis. Self-reported adverse events (AEs) and changes in RA disease activity were analysed.Results Following vaccination, vaccine-specific antibody levels increased significantly in both patients and controls (P < 0.0001). A total of 80.5% of patients and 98.0% of controls achieved a >= 4-fold increase in antibody levels. Post-vaccination antibody levels were lower in patients than controls [ratio 0.44 (95% CI 0.31, 0.63)] and lower in patients receiving JAKi + methotrexate than JAKi monotherapy [ratio 0.43 (95% CI 0.24, 0.79)]. AEs, mostly mild/moderate, were common. One patient developed HZ and six patients (6.5%) had increased RA disease activity following vaccination.Conclusion The HZ/su vaccine was serologically immunogenic in most RA patients treated with JAKi. Moreover, the vaccine had an acceptable safety profile. These results support recommendations for use of the HZ/su vaccine in this vulnerable population.Trial registration ClinicalTrials.gov (https://clinicaltrials.gov), NCT03886038.
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  • Marteinsson, Viggo Thor, et al. (author)
  • Microbial communities in the subglacial waters of the Vatnajokull ice cap, Iceland
  • 2013
  • In: The Isme Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 7:2, s. 427-437
  • Journal article (peer-reviewed)abstract
    • Subglacial lakes beneath the Vatnajokull ice cap in Iceland host endemic communities of microorganisms adapted to cold, dark and nutrient-poor waters, but the mechanisms by which these microbes disseminate under the ice and colonize these lakes are unknown. We present new data on this subglacial microbiome generated from samples of two subglacial lakes, a subglacial flood and a lake that was formerly subglacial but now partly exposed to the atmosphere. These data include parallel 16S rRNA gene amplicon libraries constructed using novel primers that span the v3-v5 and v4-v6 hypervariable regions. Archaea were not detected in either subglacial lake, and the communities are dominated by only five bacterial taxa. Our paired libraries are highly concordant for the most abundant taxa, but estimates of diversity (abundance-based coverage estimator) in the v4-v6 libraries are 3-8 times higher than in corresponding v3-v5 libraries. The dominant taxa are closely related to cultivated anaerobes and microaerobes, and may occupy unique metabolic niches in a chemoautolithotrophic ecosystem. The populations of the major taxa in the subglacial lakes are indistinguishable (>99% sequence identity), despite separation by 6 km and an ice divide; one taxon is ubiquitous in our Vatnajokull samples. We propose that the glacial bed is connected through an aquifer in the underlying permeable basalt, and these subglacial lakes are colonized from a deeper, subterranean microbiome. The ISME Journal (2013) 7, 427-437; doi:10.1038/ismej.2012.97; published online 13 September 2012
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  • Meisl, Christina J., et al. (author)
  • Nomograms including the UBC (R) Rapid test to detect primary bladder cancer based on a multicentre dataset
  • 2022
  • In: BJU International. - : John Wiley & Sons. - 1464-4096 .- 1464-410X. ; 130:6, s. 754-763
  • Journal article (peer-reviewed)abstract
    • Objectives To evaluate the clinical utility of the urinary bladder cancer antigen test UBC (R) Rapid for the diagnosis of bladder cancer (BC) and to develop and validate nomograms to identify patients at high risk of primary BC. Patients and Methods Data from 1787 patients from 13 participating centres, who were tested between 2012 and 2020, including 763 patients with BC, were analysed. Urine samples were analysed with the UBC (R) Rapid test. The nomograms were developed using data from 320 patients and externally validated using data from 274 patients. The diagnostic accuracy of the UBC (R) Rapid test was evaluated using receiver-operating characteristic curve analysis. Brier scores and calibration curves were chosen for the validation. Biopsy-proven BC was predicted using multivariate logistic regression. Results The sensitivity, specificity, and area under the curve for the UBC (R) Rapid test were 46.4%, 75.5% and 0.61 (95% confidence interval [CI] 0.58-0.64) for low-grade (LG) BC, and 70.5%, 75.5% and 0.73 (95% CI 0.70-0.76) for high-grade (HG) BC, respectively. Age, UBC (R) Rapid test results, smoking status and haematuria were identified as independent predictors of primary BC. After external validation, nomograms based on these predictors resulted in areas under the curve of 0.79 (95% CI 0.72-0.87) and 0.95 (95% CI: 0.92-0.98) for predicting LG-BC and HG-BC, respectively, showing excellent calibration associated with a higher net benefit than the UBC (R) Rapid test alone for low and medium risk levels in decision curve analysis. The R Shiny app allows the results to be explored interactively and can be accessed at www.blucab-index. net. Conclusion The UBC (R) Rapid test alone has limited clinical utility for predicting the presence of BC. However, its combined use with BC risk factors including age, smoking status and haematuria provides a fast, highly accurate and non-invasive tool for screening patients for primary LG-BC and especially primary HG-BC.
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42.
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43.
  • Mueller, M., et al. (author)
  • Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity
  • 2015
  • In: Journal of Hepatology. - 0168-8278. ; 62:6, s. 1398-1404
  • Journal article (peer-reviewed)abstract
    • Background & Aims: Bile acids (BAs) are major regulators of hepatic BA and lipid metabolism but their mechanisms of action in non-alcoholic fatty liver disease (NAFLD) are still poorly understood. Here we aimed to explore the molecular and biochemical mechanisms of ursodeoxycholic acid (UDCA) in modulating the cross-talk between liver and visceral white adipose tissue (vWAT) regarding BA and cholesterol metabolism and fatty acid/lipid partitioning in morbidly obese NAFLD patients. Methods: In this randomized controlled pharmacodynamic study, we analyzed serum, liver and vWAT samples from 40 well-matched morbidly obese patients receiving UDCA (20 mg/ kg/day) or no treatment three weeks prior to bariatric surgery. Results: Short term UDCA administration stimulated BA synthesis by reducing circulating fibroblast growth factor 19 and farnesoid X receptor (FXR) activation, resulting in cholesterol 7 alpha-hydroxylase induction mirrored by elevated C4 and 7 alpha-hydroxycholesterol. Enhanced BA formation depleted hepatic and LDL-cholesterol with subsequent activation of the key enzyme of cholesterol synthesis 3-hydroxy-3-methylglutaryl-CoA reductase. Blunted FXR anti-lipogenic effects induced lipogenic stearoyl-CoA desaturase (SCD) in the liver, thereby increasing hepatic triglyceride content. In addition, induced SCD activity in vWAT shifted vWAT lipid metabolism towards generation of less toxic and more lipogenic monounsaturated fatty acids such as oleic acid. Conclusion: These data demonstrate that by exerting FXR-antagonistic effects, UDCA treatment in NAFLD patients strongly impacts on cholesterol and BA synthesis and induces neutral lipid accumulation in both liver and vWAT. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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44.
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46.
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47.
  • Ran, Ylva, et al. (author)
  • Environmental assessment of diets: overview and guidance on indicator choice
  • 2024
  • In: The Lancet Planetary Health. - : Elsevier BV. - 2542-5196. ; 8:3, s. e172-e187
  • Research review (peer-reviewed)abstract
    • Comprehensive but interpretable assessment of the environmental performance of diets involves choosing a set of appropriate indicators. Current knowledge and data gaps on the origin of dietary foodstuffs restrict use of indicators relying on site-specific information. This Personal View summarises commonly used indicators for assessing the environmental performance of diets, briefly outlines their benefits and drawbacks, and provides recommendations on indicator choices for actors across multiple fields involved in activities that include the environmental assessment of diets. We then provide recommendations on indicator choices for actors across multiple fields involved in activities that use environmental assessments, such as health and nutrition experts, policy makers, decision makers, and private-sector and public-sector sustainability officers. We recommend that environmental assessment of diets should include indicators for at least the five following areas: climate change, biosphere integrity, blue water consumption, novel entities, and impacts on natural resources (especially wild fish stocks), to capture important environmental trade-offs. If more indicators can be handled in the assessment, indicators to capture impacts related to land use quantity and quality and green water consumption should be used. For ambitious assessments, indicators related to biogeochemical flows, stratospheric ozone depletion, and energy use can be added.
  •  
48.
  • Ran, Ylva, et al. (author)
  • Environmental assessment of diets: overview and guidance on indicator choice
  • 2024
  • In: The Lancet Planetary Health. - 2542-5196. ; 8:3, s. e172-e187
  • Journal article (peer-reviewed)abstract
    • Comprehensive but interpretable assessment of the environmental performance of diets involves choosing a set of appropriate indicators. Current knowledge and data gaps on the origin of dietary foodstuffs restrict use of indicators relying on site-specific information.This Personal View summarises commonly used indicators for assessing the environmental performance of diets, briefly outlines their benefits and drawbacks, and provides recommendations on indicator choices for actors across multiple fields involved in activities that include the environmental assessment of diets.We then provide recommendations on indicator choices for actors across multiple fields involved in activities that use environmental assessments, such as health and nutrition experts, policy makers, decision makers, and private-sector and public-sector sustainability officers. We recommend that environmental assessment of diets should include indicators for at least the five following areas: climate change, biosphere integrity, blue water consumption, novel entities, and impacts on natural resources (especially wild fish stocks), to capture important environmental trade-offs.If more indicators can be handled in the assessment, indicators to capture impacts related to land use quantity and quality and green water consumption should be used. For ambitious assessments, indicators related to biogeochemical flows, stratospheric ozone depletion, and energy use can be added.
  •  
49.
  • Ran, Ylva, et al. (author)
  • Environmental assessment of diets: overview and guidance on indicator choice
  • 2024
  • In: The Lancet Planetary Health. - : ELSEVIER SCI LTD. - 2542-5196. ; 8:3, s. e172-e187
  • Journal article (peer-reviewed)abstract
    • Comprehensive but interpretable assessment of the environmental performance of diets involves choosing a set of appropriate indicators. Current knowledge and data gaps on the origin of dietary foodstuffs restrict use of indicators relying on site-specific information. This Personal View summarises commonly used indicators for assessing the environmental performance of diets, briefly outlines their benefits and drawbacks, and provides recommendations on indicator choices for actors across multiple fields involved in activities that include the environmental assessment of diets. We then provide recommendations on indicator choices for actors across multiple fields involved in activities that use environmental assessments, such as health and nutrition experts, policy makers, decision makers, and privatesector and public-sector sustainability officers. We recommend that environmental assessment of diets should include indicators for at least the five following areas: climate change, biosphere integrity, blue water consump tion, novel entities, and impacts on natural resources (especially wild fish stocks), to capture important environ mental trade-offs. If more indicators can be handled in the assessment, indicators to capture impacts related to land use quantity and quality and green water consumption should be used. For ambitious assessments, indicators related to biogeochemical flows, stratospheric ozone depletion, and energy use can be added.
  •  
50.
  • Rodríguez-Varela, Ricardo, et al. (author)
  • The genetic history of Scandinavia from the Roman Iron Age to the present
  • 2023
  • In: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 186:1, s. 32-46
  • Journal article (peer-reviewed)abstract
    • We investigate a 2,000-year genetic transect through Scandinavia spanning the Iron Age to the present, based on 48 new and 249 published ancient genomes and genotypes from 16,638 modern individuals. We find regional variation in the timing and magnitude of gene flow from three sources: the eastern Baltic, the British-Irish Isles, and southern Europe. British-Irish ancestry was widespread in Scandinavia from the Viking period, whereas eastern Baltic ancestry is more localized to Gotland and central Sweden. In some regions, a drop in current levels of external ancestry suggests that ancient immigrants contributed proportionately less to the modern Scandinavian gene pool than indicated by the ancestry of genomes from the Viking and Medieval periods. Finally, we show that a north-south genetic cline that characterizes modern Scandinavians is mainly due to the differential levels of Uralic ancestry and that this cline existed in the Viking Age and possibly earlier.
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