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1.
  • Chumak, A. V., et al. (författare)
  • Advances in Magnetics Roadmap on Spin-Wave Computing
  • 2022
  • Ingår i: IEEE Transactions on Magnetics. - 0018-9464. ; 58:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Magnonics addresses the physical properties of spin waves and utilizes them for data processing. Scalability down to atomic dimensions, operation in the GHz-to-THz frequency range, utilization of nonlinear and nonreciprocal phenomena, and compatibility with CMOS are just a few of many advantages offered by magnons. Although magnonics is still primarily positioned in the academic domain, the scientific and technological challenges of the field are being extensively investigated, and many proof-of-concept prototypes have already been realized in laboratories. This roadmap is a product of the collective work of many authors that covers versatile spin-wave computing approaches, conceptual building blocks, and underlying physical phenomena. In particular, the roadmap discusses the computation operations with Boolean digital data, unconventional approaches like neuromorphic computing, and the progress towards magnon-based quantum computing. The article is organized as a collection of sub-sections grouped into seven large thematic sections. Each sub-section is prepared by one or a group of authors and concludes with a brief description of current challenges and the outlook of further development for each research direction. Author
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2.
  • Birney, Ewan, et al. (författare)
  • Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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3.
  • Sutton, M. A., et al. (författare)
  • Towards a climate-dependent paradigm of ammonia emission and deposition
  • 2013
  • Ingår i: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 1471-2970 .- 0962-8436. ; 368:1621
  • Tidskriftsartikel (refereegranskat)abstract
    • Existing descriptions of bi-directional ammonia (NH3) land-atmosphere exchange incorporate temperature and moisture controls, and are beginning to be used in regional chemical transport models. However, such models have typically applied simpler emission factors to upscale the main NH3 emission terms. While this approach has successfully simulated the main spatial patterns on local to global scales, it fails to address the environment-and climate-dependence of emissions. To handle these issues, we outline the basis for a new modelling paradigm where both NH3 emissions and deposition are calculated online according to diurnal, seasonal and spatial differences in meteorology. We show how measurements reveal a strong, but complex pattern of climatic dependence, which is increasingly being characterized using ground-based NH3 monitoring and satellite observations, while advances in process-based modelling are illustrated for agricultural and natural sources, including a global application for seabird colonies. A future architecture for NH3 emission-deposition modelling is proposed that integrates the spatio-temporal interactions, and provides the necessary foundation to assess the consequences of climate change. Based on available measurements, a first empirical estimate suggests that 5 degrees C warming would increase emissions by 42 per cent (28-67%). Together with increased anthropogenic activity, global NH3 emissions may increase from 65 (45-85) Tg N in 2008 to reach 132 (89-179) Tg by 2100.
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4.
  • Cherifi-Hertel, S., et al. (författare)
  • Non-Ising and chiral ferroelectric domain walls revealed by nonlinear optical microscopy
  • 2017
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • The properties of ferroelectric domain walls can significantly differ from those of their parent material. Elucidating their internal structure is essential for the design of advanced devices exploiting nanoscale ferroicity and such localized functional properties. Here, we probe the internal structure of 180° ferroelectric domain walls in lead zirconate titanate (PZT) thin films and lithium tantalate bulk crystals by means of second-harmonic generation microscopy. In both systems, we detect a pronounced second-harmonic signal at the walls. Local polarimetry analysis of this signal combined with numerical modelling reveals the existence of a planar polarization within the walls, with Néel and Bloch-like configurations in PZT and lithium tantalate, respectively. Moreover, we find domain wall chirality reversal at line defects crossing lithium tantalate crystals. Our results demonstrate a clear deviation from the ideal Ising configuration that is traditionally expected in uniaxial ferroelectrics, corroborating recent theoretical predictions of a more complex, often chiral structure.
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  • Kronast, F., et al. (författare)
  • Element-specific magnetic hysteresis of individual 18 nm Fe nanocubes
  • 2011
  • Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 11:4, s. 1710-1715
  • Tidskriftsartikel (refereegranskat)abstract
    • Correlating the electronic structure and magnetic response with the morphology and crystal structure of the same single ferromagnetic nanoparticle has been up to now an unresolved challenge. Here, we present measurements of the element-specific electronic structure and magnetic response as a function of magnetic field amplitude and orientation for chemically synthesized single Fe nanocubes with 18 nm edge length. Magnetic states and interactions of monomers, dimers, and trimers are analyzed by X-ray photoemission electron microscopy for different particle arrangements. The element-specific electronic structure can be probed and correlated with the changes of magnetic properties. This approach opens new possibilities for a deeper understanding of the collective response of magnetic nanohybrids in multifunctional materials and in nanomagnetic colloidal suspensions used in biomedical and engineering technologies. © 2011 American Chemical Society.
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7.
  • Kvitne, K. E., et al. (författare)
  • Correlations between 4 beta-hydroxycholesterol and hepatic and intestinal CYP3A4: protein expression, microsomal ex vivo activity, and in vivo activity in patients with a wide body weight range
  • 2022
  • Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 78:8, s. 1289-1299
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Variability in cytochrome P450 3A4 (CYP3A4) metabolism is mainly caused by non-genetic factors, hence providing a need for accurate phenotype biomarkers. Although 4 beta-hydroxycholesterol (4 beta OHC) is a promising endogenous CYP3A4 biomarker, additional investigations are required to evaluate its ability to predict CYP3A4 activity. This study investigated the correlations between 4 beta OHC concentrations and hepatic and intestinal CYP3A4 protein expression and ex vivo microsomal activity in paired liver and jejunum samples, as well as in vivo CYP3A4 phenotyping (midazolam) in patients with a wide body weight range. Methods The patients (n = 96; 78 with obesity and 18 normal or overweight individuals) were included from the COCKTAIL-study (NCT02386917). Plasma samples for analysis of 4 beta OHC and midazolam concentrations, and liver (n = 56) and jejunal (n = 38) biopsies were obtained. The biopsies for determination of CYP3A4 protein concentration and microsomal activity were obtained during gastric bypass or cholecystectomy. In vivo CYP3A4 phenotyping was performed using semi-simultaneous oral (1.5 mg) and intravenous (1.0 mg) midazolam. Results 4 beta OHC concentrations were positively correlated with hepatic microsomal CYP3A4 activity (rho = 0.53, p < 0.001), and hepatic CYP3A4 concentrations (rho = 0.30, p = 0.027), but not with intestinal CYP3A4 concentrations (rho = 0.18, p = 0.28) or intestinal microsomal CYP3A4 activity (rho = 0.15, p = 0.53). 4 beta OHC concentrations correlated weakly with midazolam absolute bioavailability (rho = - 0.23, p = 0.027) and apparent oral clearance (rho = 0.28, p = 0.008), but not with systemic clearance (rho = - 0.03, p = 0.81). Conclusion These findings suggest that 4 beta OHC concentrations reflect hepatic, but not intestinal, CYP3A4 activity. Further studies should investigate the potential value of 4 beta OHC as an endogenous biomarker for individual dose requirements of intravenously administered CYP3A4 substrate drugs.
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8.
  • Kvitne, K. E., et al. (författare)
  • Impact of type 2 diabetes on in vivo activities and protein expressions of cytochrome P450 in patients with obesity
  • 2022
  • Ingår i: Clinical and Translational Science. - : Wiley. - 1752-8054 .- 1752-8062. ; 15:11, s. 2685-2696
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have not accounted for the close link between type 2 diabetes mellitus (T2DM) and obesity when investigating the impact of T2DM on cytochrome P450 (CYP) activities. The aim was to investigate the effect of T2DM on in vivo activities and protein expressions of CYP2C19, CYP3A, CYP1A2, and CYP2C9 in patients with obesity. A total of 99 patients from the COCKTAIL study (NCT02386917) were included in this cross-sectional analysis; 29 with T2DM and obesity (T2DM-obesity), 53 with obesity without T2DM (obesity), and 17 controls without T2DM and obesity (controls). CYP activities were assessed after the administration of a cocktail of probe drugs including omeprazole (CYP2C19), midazolam (CYP3A), caffeine (CYP1A2), and losartan (CYP2C9). Jejunal and liver biopsies were also obtained to determine protein concentrations of the respective CYPs. CYP2C19 activity and jejunal CYP2C19 concentration were 63% (−0.39 [95% CI: −0.82, −0.09]) and 40% (−0.09 fmol/μg protein [95% CI: −0.18, −0.003]) lower in T2DM-obesity compared with the obesity group, respectively. By contrast, there were no differences in the in vivo activities and protein concentrations of CYP3A, CYP1A2, and CYP2C9. Multivariable regression analyses also indicated that T2DM was associated with interindividual variability in CYP2C19 activity, but not CYP3A, CYP1A2, and CYP2C9 activities. The findings indicate that T2DM has a significant downregulating impact on CYP2C19 activity, but not on CYP3A, CYP1A2, and CYP2C9 activities and protein concentrations in patients with obesity. Hence, the effect of T2DM seems to be isoform-specific. © 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
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9.
  • Kvitne, K. E., et al. (författare)
  • Short- and long-term effects of body weight, calorie restriction and gastric bypass on CYP1A2, CYP2C19 and CYP2C9 activity
  • 2022
  • Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 88:9, s. 4121-4133
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim Roux-en-Y gastric bypass (RYGB) may influence drug disposition due to surgery-induced gastrointestinal alterations and/or subsequent weight loss. The objective was to compare short- and long-term effects of RYGB and diet on the metabolic ratios of paraxanthine/caffeine (cytochrome P450 [CYP] 1A2 activity), 5-hydroxyomeprazole/omeprazole (CYP2C19 activity) and losartan/losartan carboxylic acid (CYP2C9 activity), and cross-sectionally compare these CYP-activities with normal-to-overweight controls. Methods This trial included patients with severe obesity preparing for RYGB (n = 40) or diet-induced (n = 41) weight loss, and controls (n = 18). Both weight loss groups underwent a 3-week low-energy diet (<1200 kcal/day, weeks 0-3) followed by a 6-week very-low-energy diet or RYGB (both <800 kcal/day, weeks 3-9). Follow-up time was 2 years, with four pharmacokinetic investigations. Results Mean +/- SD weight loss from baseline was similar in the RYGB-group (13 +/- 2.4%) and the diet group (10.5 +/- 3.9%) at week 9, but differed at year 2 (RYGB -30 +/- 6.9%, diet -3.1 +/- 6.3%). From weeks 0 to 3, mean (95% confidence interval [CI]) CYP2C19 activity similarly increased in both groups (RYGB 43% [16, 55], diet 48% [22, 60]). Mean CYP2C19 activity increased by 30% (2.6, 43) after RYGB (weeks 3-9), but not in the diet-group (between-group difference -0.30 [-0.63, 0.03]). CYP2C19 activity remained elevated in the RYGB group at year 2. Baseline CYP2C19 activity was 2.7-fold higher in controls compared with patients with obesity, whereas no difference was observed in CYP1A2 and CYP2C9 activities. Conclusion Our findings suggest that CYP2C19 activity is lower in patients with obesity and increases following weight loss. This may be clinically relevant for drug dosing. No clinically significant effect on CYP1A2 and CYP2C9 activities was observed.
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10.
  • Martin, D. D., et al. (författare)
  • The Use of Bone Age in Clinical Practice - Part 1
  • 2011
  • Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 76:1, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • This review examines the role of skeletal maturity ('bone age', BA) assessment in clinical practice. BA is mainly used in children with the following conditions: short stature (addressed in part 1 of this review), tall stature, early or late puberty, and congenital adrenal hyperplasia (all addressed in part 2). Various manual and automatic methods of BA assessment have been developed. Healthy tall children tend to have advanced BA and healthy short children tend to have delayed BA in comparison to chronological age. Growth hormone (GH) treatment of children with GH deficiency leads to a catch-up in BA that is usually appropriate for the height of the child. Response to GH is dependent on BA delay in young children with idiopathic short stature, and GH dosage appears to affect BA acceleration. In chronic renal failure, BA is delayed until puberty but then increases due to increased sensitivity of the growth plate to sex steroids, thus further impairing adult height. The assessment of BA provides an important contribution to the diagnostic workup and management of children with short stature.
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11.
  • Nordeide Kuiper, I., et al. (författare)
  • Lifelong exposure to air pollution and greenness in relation to asthma, rhinitis and lung function in adulthood
  • 2021
  • Ingår i: Environmental International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 146
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To investigate if air pollution and greenness exposure from birth till adulthood affects adult asthma, rhinitis and lung function. Methods: We analysed data from 3428 participants (mean age 28) in the RHINESSA study in Norway and Sweden. Individual mean annual residential exposures to nitrogen dioxide (NO2), particulate matter (PM10 and PM2.5), black carbon (BC), ozone (O3) and greenness (normalized difference vegetation index (NDVI)) were averaged across susceptibility windows (0–10 years, 10–18 years, lifetime, adulthood (year before study participation)) and analysed in relation to physician diagnosed asthma (ever/allergic/non-allergic), asthma attack last 12 months, current rhinitis and low lung function (lower limit of normal (LLN), z-scores of forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC below 1.64). We performed logistic regression for asthma attack, rhinitis and LLN lung function (clustered with family and study centre), and conditional logistic regression with a matched case-control design for ever/allergic/non-allergic asthma. Multivariable models were adjusted for parental asthma and education. Results: Childhood, adolescence and adult exposure to NO2, PM10 and O3 were associated with an increased risk of asthma attacks (ORs between 1.29 and 2.25), but not with physician diagnosed asthma. For rhinitis, adulthood exposures seemed to be most important. Childhood and adolescence exposures to PM2.5 and O3 were associated with lower lung function, in particular FEV1 (range ORs 2.65 to 4.21). No associations between NDVI and asthma or rhinitis were revealed, but increased NDVI was associated with lower FEV1 and FVC in all susceptibility windows (range ORs 1.39 to 1.74). Conclusions: Air pollution exposures in childhood, adolescence and adulthood were associated with increased risk of asthma attacks, rhinitis and low lung function in adulthood. Greenness was not associated with asthma or rhinitis, but was a risk factor for low lung function. © 2020 The Authors
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  • Alonzo, Frederic, et al. (författare)
  • Modelling the propagation of effects of chronic exposure to ionising radiation from individuals to populations
  • 2008
  • Ingår i: Journal of Environmental Radioactivity. - : Elsevier BV. - 0265-931X .- 1879-1700. ; 99:9, s. 1464-1473
  • Tidskriftsartikel (refereegranskat)abstract
    • This study evaluated the potential effect of ionising radiation on population growth using simple population models and parameter values derived from chronic exposure experiments in two invertebrate species with contrasting life-history strategies. In the earthworm Eisenia fetida, models predicted increasing delay in population growth with increasing gamma dose rate (up to 0.6 generation times at 11 mGy h(-1)). Population extinction was predicted at 43 mGy h(-1). In the microcrustacean Daphnia magna, models predicted increasing delay in population growth with increasing alpha dose rate (up to 0.8 generation times at 15.0 mGy h(-1)), only after two successive generations were exposed. The study examined population effects of changes in different individual endpoints (including survival, number of offspring produced and time to first reproduction). Models showed that the two species did not respond equally to equivalent levels of change, the fast growing daphnids being more susceptible to reduction in fecundity or delay in reproduction than the slow growing earthworms. This suggested that susceptibility of a population to ionising radiation cannot be considered independent of the species' life history.
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14.
  • Braasch, Ingo, et al. (författare)
  • The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons
  • 2016
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:4, s. 427-437
  • Tidskriftsartikel (refereegranskat)abstract
    • To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences.
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  • Gulbinas, V, et al. (författare)
  • Exciton diffusion and relaxation in methyl-substituted polyparaphenylene polymer films
  • 2007
  • Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 127:14
  • Tidskriftsartikel (refereegranskat)abstract
    • Exciton diffusion in ladder-type methyl-substituted polyparaphenylene film and solution was investigated by means of femtosecond pump-probe spectroscopy using a combined approach, analyzing exciton-exciton annihilation, and transient absorption depolarization properties. We show that the different views on the exciton dynamics offered by anisotropy decay and annihilation are required in order to obtain a correct picture of the energy transfer dynamics. Comparison of the exciton diffusion coefficient and exciton diffusion radius obtained for polymer film with the two techniques reveals that there is substantial short-range order in the film. Also in isolated chains there is considerable amount of order, as revealed from only partial anisotropy decay, which shows that only a small fraction of the excitons move to differently oriented polymer segments. It is further concluded that interchain energy transfer is faster than intrachain transfer, mainly as a result of shorter interchain distances between chromophoric units.
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21.
  • Gulbinas, V, et al. (författare)
  • Nonlinear exciton relaxation in ladder-type poly (para-phenylene)
  • 2007
  • Ingår i: Molecular Crystals and Liquid Crystals. - : Informa UK Limited. - 1543-5318 .- 1542-1406 .- 1563-5287. ; 467, s. 47-57
  • Tidskriftsartikel (refereegranskat)abstract
    • Nonlinear exciton relaxation processes, exciton-exciton annihilation, and amplified spontaneous emission were investigated in thin films of ladder-type poly(para-phenylene) under excitation by femtosecond light pulses. Both processes become apparent at similar excitation intensities, however their properties are very different. They cause different exciton relaxation kinetics and their intensity dependences are different.
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22.
  • Hertel, Jens K., et al. (författare)
  • FTO, Type 2 Diabetes, and Weight Gain Throughout Adult Life A Meta-Analysis of 41,504 Subjects From the Scandinavian HUNT, MDC, and MPP Studies
  • 2011
  • Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 60:5, s. 1637-1644
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE-FTO is the most important polygene identified for obesity. We aimed to investigate whether a variant in FTO affects type 2 diabetes risk entirely through its effect on BMI and how FTO) influences BMI across adult life span. RESEARCH DESIGN AND METHODS-Through regression models, we assessed the relationship between the FTO single nucleotide polymorphisms rs9939609, type 2 diabetes, and BMI across life span in subjects from the Norwegian population-based HUNT study using cross-sectional and longitudinal perspectives. For replication and meta-analysis, we used data from the Malmo Diet and Cancer (MDC) and Malmo Preventive Project (MPP) cohorts, comprising a total sample of 41,504 Scandinavians. RESULTS-The meta-analysis revealed a highly significant association for rs9939609 with both type 2 diabetes (OR 1.13; P = 4.5 x 10(-8)) and the risk to develop incident type 2 diabetes (OR 1.16; P = 3.2 x 10(-8)). The associations remained also after correction for BMI and other anthropometric measures. Furthermore, we confirmed the strong effect on BMI (0.28 kg/m(2) per risk allele; P = 2.0 x 10(-26), with no heterogeneity between different age-groups. We found no differences in change of BMI over time according to rs9939609 risk alleles, neither overall (Delta BMI = 0.0 [-0.05, 0.05]) nor in any individual age stratum, indicating no further weight gain attributable to FTO genotype in adults. CONCLUSIONS-We have identified that a variant in FTO alters type 2 diabetes risk partly independent of its observed effect on BMI. The additional weight gain as a result of the FTO risk variant seems to occur before adulthood, and the BMI difference remains stable thereafter. Diabetes 60:1637-1644, 2011
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23.
  • Hertel, J K, et al. (författare)
  • Genetic analysis of recently identified type 2 diabetes loci in 1,638 unselected patients with type 2 diabetes and 1,858 control participants from a Norwegian population-based cohort (the HUNT study)
  • 2008
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 51:6, s. 971-977
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis Recent genome-wide association studies performed in selected patients and control participants have provided strong support for several new type 2 diabetes susceptibility loci. To get a better estimation of the true risk conferred by these novel loci, we tested a completely unselected population of type 2 diabetes patients from a Norwegian health survey (the HUNT study). Methods We genotyped single nucleotide polymorphisms (SNPs) in PKN2, IGFBP2, FLJ39370 (also known as C4ORF32), CDKAL1, SLC30A8, CDKN2B, HHEX and FTO using a Norwegian population-based sample of 1,638 patients with type 2 diabetes and 1,858 non-diabetic control participants (the HUNT Study), for all of whom data on BMI, WHR, cholesterol and triacylglycerol levels were available. We used diabetes, measures of obesity and lipid values as phenotypes in case-control and quantitative association study designs. Results We replicated the association with type 2 diabetes for rs10811661 in the vicinity of CDKN2B (OR 1.20, 95% CI: 1.06-1.37, p=0.004), rs9939609 in FTO (OR 1.14, 95% CI: 1.04-1.25, p=0.006) and rs13266634 in SLC30A8 (OR 1.20, 95% CI: 1.09-1.33, p=3.9x10(-4)). We found borderline significant association for the IGFBP2 SNP rs4402960 (OR 1.10, 95% CI: 0.99-1.22). Results for the HHEX SNP (rs1111875) and the CDKAL1 SNP (rs7756992) were non-significant, but the magnitude of effect was similar to previous estimates. We found no support for an association with the less consistently replicated FLJ39370 or PKN2 SNPs. In agreement with previous studies, FTO was most strongly associated with BMI (p=8.4x10(-4)). Conclusions/interpretation Our data show that SNPs near IGFBP2, CDKAL1, SLC30A8, CDKN2B, HHEX and FTO are also associated with diabetes in non-selected patients with type 2 diabetes.
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24.
  • Hinton, T. G., et al. (författare)
  • An invitation to contribute to a strategic research agenda in radioecology
  • 2013
  • Ingår i: Journal of Environmental Radioactivity. - : Elsevier BV. - 0265-931X .- 1879-1700. ; 115, s. 73-82
  • Tidskriftsartikel (refereegranskat)abstract
    • With intentions of integrating a portion of their respective research efforts into a trans-national programme that will enhance radioecology, eight European organisations recently formed the European Radioecology ALLIANCE (www.er-alliance.org). The ALLIANCE is an Association open to other organisations throughout the world with similar interests in promoting radioecology. The ALLIANCE members recognised that their shared radioecological research could be enhanced by efficiently pooling resources among its partner organizations and prioritising group efforts along common themes of mutual interest. A major step in this prioritisation process was to develop a Strategic Research Agenda (SRA). An EC-funded Network of Excellence in Radioecology, called STAR (Strategy for Allied Radioecology), was formed, in part, to develop the SRA. This document is the first published draft of the SRA. The SRA outlines a suggested prioritisation of research topics in radioecology, with the goal of improving research efficiency and more rapidly advancing the science. It responds to the question: What topics, if critically addressed over the next 20 years, would significantly advance radioecology? The three Scientific Challenges presented within the SRA, with their 15 associated research lines, are a strategic vision of what radioecology can achieve in the future. Meeting these challenges will require a directed effort and collaboration with many organisations the world over. Addressing these challenges is important to the advancement of radioecology and in providing scientific knowledge to decision makers. Although the development of the draft SRA has largely been a European effort, the hope is that it will initiate an open dialogue within the international radioecology community and its stakeholders. This is an abbreviated document with the intention of introducing the SRA and inviting contributions from interested stakeholders. Critique and input for improving the SRA are welcomed via a link on the STAR website (www.star-radioecology.org).
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25.
  • Hjelmesaeth, J., et al. (författare)
  • Impact of body weight, low energy diet and gastric bypass on drug bioavailability, cardiovascular risk factors and metabolic biomarkers: protocol for an open, non-randomised, three-armed single centre study (COCKTAIL)
  • 2018
  • Ingår i: Bmj Open. - 2044-6055. ; 8:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Roux-en-Y gastric bypass (GBP) is associated with changes in cardiometabolic risk factors and bioavailability of drugs, but whether these changes are induced by calorie restriction, the weight loss or surgery per se, remains uncertain. The COCKTAIL study was designed to disentangle the short-term (6 weeks) metabolic and pharmacokinetic effects of GBP and a very low energy diet (VLED) by inducing a similar weight loss in the two groups. Methods and analysis This open, non-randomised, three-armed, single-centre study is performed at a tertiary care centre in Norway. It aims to compare the short-term (6 weeks) and long-term (2 years) effects of GBP and VLED on, first, bioavailability and pharmacokinetics (24 hours) of probe drugs and biomarkers and, second, their effects on metabolism, cardiometabolic risk factors and biomarkers. The primary outcomes will be measured as changes in: (1) all six probe drugs by absolute bioavailability area under the curve (AUC(oral)/AUC(iv)) of midazolam (CYP3A4 probe), systemic exposure (AUC(oral)) of digoxin and rosuvastatin and drug:metabolite ratios for omeprazole, losartan and caffeine, levels of endogenous CYP3A biomarkers and genotypic variation, changes in the expression and activity data of the drug-metabolising, drug transport and drug regulatory proteins in biopsies from various organs and (2) body composition, cardiometabolic risk factors and metabolic biomarkers. Ethics and dissemination The COCKTAIL protocol was reviewed and approved by the Regional Committee for Medical and Health Research Ethics (Ref: 2013/2379/REK serest A). The results will be disseminated to academic and health professional audiences and the public via presentations at conferences, publications in peer-reviewed journals and press releases and provided to all participants.
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