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1.
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2.
  • Klionsky, Daniel J., et al. (author)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Research review (peer-reviewed)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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3.
  • Beal, Jacob, et al. (author)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Journal article (peer-reviewed)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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4.
  • Mahajan, Anubha, et al. (author)
  • Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
  • 2022
  • In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
  • Journal article (peer-reviewed)abstract
    • We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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5.
  • Marouli, Eirini, et al. (author)
  • Rare and low-frequency coding variants alter human adult height
  • 2017
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
  • Journal article (peer-reviewed)abstract
    • Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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6.
  • Turcot, Valerie, et al. (author)
  • Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
  • 2018
  • In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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7.
  • Abelev, Betty, et al. (author)
  • Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
  • 2013
  • In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
  • Journal article (peer-reviewed)abstract
    • Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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8.
  • Abelev, Betty, et al. (author)
  • Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
  • 2012
  • In: Journal of High Energy Physics. - 1029-8479. ; :11
  • Journal article (peer-reviewed)abstract
    • The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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9.
  • Abelev, Betty, et al. (author)
  • Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
  • 2012
  • In: Journal of High Energy Physics. - 1029-8479. ; :7
  • Journal article (peer-reviewed)abstract
    • We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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11.
  • Bangsbo, Jens, et al. (author)
  • The Copenhagen Consensus Conference 2016 : children, youth, and physical activity in schools and during leisure time
  • 2016
  • In: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 50:19, s. 1177-1178
  • Journal article (other academic/artistic)abstract
    • From 4 to 7 April 2016, 24 researchers from 8 countries and from a variety of academic disciplines gathered in Snekkersten, Denmark, to reach evidence-based consensus about physical activity in children and youth, that is, individuals between 6 and 18 years. Physical activity is an overarching term that consists of many structured and unstructured forms within school and out-of-school-time contexts, including organised sport, physical education, outdoor recreation, motor skill development programmes, recess, and active transportation such as biking and walking. This consensus statement presents the accord on the effects of physical activity on children's and youth's fitness, health, cognitive functioning, engagement, motivation, psychological well-being and social inclusion, as well as presenting educational and physical activity implementation strategies. The consensus was obtained through an iterative process that began with presentation of the state-of-the art in each domain followed by plenary and group discussions. Ultimately, Consensus Conference participants reached agreement on the 21-item consensus statement.
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13.
  • Cirgic, Emina, 1978, et al. (author)
  • A cost-minimization analysis of large overjet reduction with two removable functional appliances based on a randomized controlled trial.
  • 2018
  • In: European journal of orthodontics. - : Oxford University Press (OUP). - 1460-2210 .- 0141-5387. ; 40:4, s. 437-443
  • Journal article (peer-reviewed)abstract
    • The purpose of this study was to assess and relate the societal costs of reducing large overjet with a prefabricated functional appliance (PFA), or a slightly modified Andresen activator (AA), using a cost-minimization analysis (CMA).A multicentre, prospective, randomized clinical trial was conducted with patients from 12 general dental practices. Ninety-seven patients with an Angle Class II, division 1 malocclusion, and an overjet of ≥6 mm were randomly allocated by lottery to treatment with either a PFA or an AA. The PFA and AA groups consisted of 57 and 40 subjects, respectively. Blinding was not performed. Duration of treatment, number of scheduled/unscheduled appointments, and retreatment were registered. Direct and indirect costs were analysed with reference to intention-to-treat (ITT), successful (S), and unsuccessful (US) outcomes. Societal costs were described as the total of direct and indirect costs, not including retreatments.Treatment with a PFA or an AA.The direct and societal costs were significantly lower for the PFA than for the AA group. The number of visits was lower in the PFA group, when ITT was considered, and for the US cases as well. No difference in retreatment rate could be seen between the groups.Costs depend on local factors and thus should not be generalized to other settings.No harms were detected during the study.The success rate of the both appliances was low. However, the PFA was the preferred approach for reduction of a large overjet in mixed dentition, since it minimized costs and there were no difference in clinical outcomes between PFA and AA.This trial was registered at 'FoU i Sverige' (http://www.fou.nu/is/sverige), registration number: 97131.The protocol was not published before trial commencement.
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14.
  • Cirgic, Emina, 1978, et al. (author)
  • Adolescents' experiences of using removable functional appliances
  • 2015
  • In: Orthodontics & Craniofacial Research. - : Wiley. - 1601-6335. ; 18:3, s. 165-174
  • Journal article (peer-reviewed)abstract
    • Structured Abstract ObjectivesThe aim of this qualitative study was to explore and describe adolescents experiences of treatment with removable functional appliances. Setting and sample populationPublic Dental Service, Gothenburg, Sweden. Material and methodsIndividual interviews focusing on adolescents' experiences of using a removable functional appliance were held with 21 adolescents (12 girls and nine boys). The mean age of the participants was 13.2years (range 11-15, SD 1.25) at the interview occasion. Interviews were transcribed verbatim and analysed according to a qualitative research approach, phenomenography. ResultsOutcomes of data analysis emerged in five categories with totally 12 subcategories that describe the adolescents' various conceptions of the treatment. The adolescent's experiences of using removable functional appliance appeared to have a large variation, comprising of the individual approach, feelings and strategies, the dentist role and receiving external support. ConclusionParticipants developed their own strategies of measurement to see improvement. An active involvement of the adolescents' in the treatment seems to be needed, supported by the dentist at coming appointments, using overjet measurement as a tool for motivation. Furthermore, efforts should be made by clinicians to listen and understand adolescents' needs and requirement before the treatment start.
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15.
  • Cirgic, Emina, 1978, et al. (author)
  • Treatment of large overjet in Angle Class II: division 1 malocclusion with Andresen activators versus prefabricated functional appliances-a multicenter, randomized, controlled trial
  • 2016
  • In: European Journal of Orthodontics. - : Oxford University Press (OUP). - 0141-5387 .- 1460-2210. ; 38:5, s. 516-524
  • Journal article (peer-reviewed)abstract
    • The purpose of this study was to compare the clinical effectiveness in reducing large overjet between a prefabricated functional appliance (PFA) and a slightly modified Andresen activator (AA). A multicentre, prospective randomized clinical trial was conducted with patients from 12 general dental practices. One hundred and five patients with an Angle Class II, division 1 malocclusion and an overjet of a parts per thousand yen6mm were eligible for the study. Eight patients were excluded due to various reasons and the sample consisted thus of 97 subjects (44 girls, 53 boys) with a mean age of 10.3 years. The study was designed as intention to treat and the patients were randomly allocated by lottery to treatment with either a PFA or an AA. The PFA and AA group consisted of 57 subjects (28 girls, 29 boys) and 40 subjects (16 girls, 24 boys), respectively. Overjet, overbite, lip seal, and sagittal molar relationship were recorded before, at the end of treatment and 1-year post-treatment. Blinding was not performed. The endpoint of treatment was set to overjet a parts per thousand currency sign3mm and after this a 6 months retention period followed. No significant difference was found in overjet, overbite, sagittal relation, and lip seal between the two groups for the total observation period. The treatment of 40 (70 per cent) patients with PFA and 21 (53 per cent) with AA were considered unsuccessful mainly due to poor compliance. No cephalometric records were taken as only patient-centred clinical outcome were used as an indicator for treatment success. The criteria of reduction of overjet to as low as 3mm could have affected the success rate. No difference in effectiveness could be shown between PFAs and AAs in correcting overjet, overbite, sagittal molar relation, and lip seal. The success rate in treatment with both appliances is, however, low. This trial was registered in "FoU i Sverige" (), registration number: 97131.
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16.
  • Farzaneh, Farokh, et al. (author)
  • von Langenbeck procedures at 14 months or Wardill at 18 months for primary repair of cleft palate in adult Swedish patients with bilateral complete cleft lip and palate: A study of facial growth.
  • 2009
  • In: Scandinavian journal of plastic and reconstructive surgery and hand surgery / Nordisk plastikkirurgisk forening [and] Nordisk klubb for handkirurgi. - : Informa UK Limited. - 1651-2073 .- 0284-4311. ; 43:4, s. 214-24
  • Journal article (peer-reviewed)abstract
    • We compared facial growth in patients with bilateral complete cleft lip and palate (BCLP) in whom the palate had been repaired by the von Langenbeck procedure at the age of 14 months (L-14), or by the Wardill procedure at 18 months (W-18). A total of 151 unaffected subjects were used as a reference group. Thirty-six adult patients, 26 in the L-14 group, and 10 in the W-18 group, were investigated clinically and with lateral skull radiography, and they also filled out a questionnaire about their dental condition. Multiple linear regression was used to analyse the effect of surgical strategy, sex, and the presence of a velopharyngeal flap on several dependent variables indicating sagittal and vertical jaw relations, and inclination of incisors. The BCLP group was characterised by a pre-normal basal relation (ss-n-sm), retroclined upper (ILs/NL) and lower (ILi/ML) incisors, maxillary retrognathism (s-n-ss) in men, larger maxillary plane angle (NSL/NL) in women, larger mandibular plane (NSL/ML) and intermaxillary vertical relation (NL/ML) in men, and smaller anterior facial height (n-gn) and upper anterior facial height (n-sp). In the BCLP group, differences in outcomes could be explained only by sex. The sagittal jaw base relation (ss-n-sm) was significantly smaller in men than in women, whereas the total anterior facial height (n-gn) was greater in men. Lateral crossbite was found in about 75% of patients. About 70% were satisfied with their dental condition. The choice of surgical strategy had no significant influence on the variables measured on facial morphology.
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17.
  • Farzaneh, Farokh, et al. (author)
  • von Langenbeck procedures at 8 months or Wardill at 18 months for primary repair of cleft palate in adult Swedish patients with unilateral complete cleft lip and palate: A study of facial growth.
  • 2008
  • In: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Informa UK Limited. - 1651-2073 .- 0284-4311. ; 42:2, s. 67-76
  • Journal article (peer-reviewed)abstract
    • The purpose of this study was to compare facial growth in patients with unilateral complete cleft lip and palate (UCLP) in whom the palate was repaired with the von Langenbeck procedure at 8 months (L-8), or the Wardill procedure at 18 months (W-18). A total of 151 unaffected subjects were used as a reference series. Sixty-one adult patients, 34 in the L-8 group and 27 in the W-18 group, were investigated clinically and with lateral skull radiography and also filled out a questionnaire about their dental condition. Multiple linear regression was used to analyse the effects of the surgical strategy, sex, and the presence of a velopharyngeal flap on several dependent variables indicating sagittal jaw relations, vertical jaw relations, and inclination of incisors. The UCLP group was characterised by a short (n-sp) and retrusive maxilla (s-n-ss) and a retrusive mandible for women (s-n-sm), larger maxillary inclination (NSL/NL), more retroclined lower incisors (IL(I)/ML), shorter upper facial heights (n-sp) and normal total face height (n-gn) than the reference group. In the UCLP group there were significant differences between men and women in mandibular prognathism (s-n-sm), maxillary/mandibular relations (ss-n-sm), maxillary inclination (NSL/NL), total anterior facial height (n-gn), and upper anterior facial height (n-sp). Lateral crossbite was found in 20% of the UCLP group. The prevalence was similar in the L-8 and W-18 groups. Almost 80% of the patients in the UCLP group considered that their dental condition was good. The choice of surgical strategy had no significant influence on the variables measured on facial morphology.
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18.
  • Gjerde, Kjetil, et al. (author)
  • On the suitability of carbon nanotube forests as non-stick surfaces for nanomanipulation
  • 2008
  • In: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-6848 .- 1744-683X. ; 4:3, s. 392-399
  • Journal article (peer-reviewed)abstract
    • A carbon nanotube forest provides a unique non-stick surface for nanomanipulation, as the nanostructuring of the surface allows micro- and nanoscale objects to be easily removed after first being deposited via a liquid dispersion. A common problem for smooth surfaces is the strong initial stiction caused by adhesion forces after deposition onto the surface. In this work, carbon nanotube forests fabricated by plasma-enhanced chemical vapour deposition are compared to structures with a similar morphology, silicon nanograss, defined by anisotropic reactive ion-etching. While manipulation experiments with latex microbeads on structured as well as smooth surfaces ( gold, silicon, silicon dioxide, Teflon, diamond-like carbon) showed a very low initial stiction for both carbon nanotube forests and silicon nanograss, a homogeneous distribution of particles was significantly easier to achieve on the carbon nanotube forests. Contact-angle measurements during gradual evaporation revealed that the silicon nanograss was superhydrophic with no contact-line pinning, while carbon nanotube forests in contrast showed strong contact-line pinning, as confirmed by environmental scanning electron microscopy of microdroplets. As a consequence, latex microbeads dispersed on the surface from an aqueous solution distributed evenly on carbon nanotube forests, but formed large agglomerates after evaporation on silicon nanograss. Lateral manipulation of latex microbeads with a microcantilever was found to be easier on carbon nanotube forests and silicon nanograss compared to smooth diamond-like carbon, due to a substantially lower initial stiction force on surfaces with nanoscale roughness. Nanomanipulation of bismuth nanowires, carbon nanotubes and organic nanofibres was demonstrated on carbon nanotube forests using a sharp tungsten tip. We find that the reason for the remarkable suitability of carbon nanotube forests as a non-stick surface for nanomanipulation is indeed the strong contact-line pinning in combination with the nanostructured surface, which allows homogeneous dispersion and easy manipulation of individual particles.
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19.
  • Hansen, Henry H., et al. (author)
  • Projecting fish community responses to dam removal – Data-limited modeling
  • 2023
  • In: Ecological Indicators. - : Elsevier. - 1470-160X .- 1872-7034. ; 154
  • Journal article (peer-reviewed)abstract
    • Modeling fish community responses to dam removal is an emerging field of study as dam removals become more common, but uncertainties concerning recovery time and community stability remain. In Europe, an EU-wide biodiversity strategy plans to restore around 25,000 km of rivers to free-flowing status, which emphasizes the importance of being able to predict fish community responses after dam removal. We developed a multi-species size spectrum model for a fish community in the Mörrum River in Sweden to identify possible outcomes after a dam was removed in 2020. Electrofishing monitoring before the dam removal was used to calibrate the model. We projected multiple scenarios into the future to explore patterns of community stability, individual species responses, and recovery time while varying parameters related to dam removal mortality, base resource rate change, and maximum recruitment change. We created 30 hypothetical scenarios using an abrupt change perspective (parameters are step-based) and 30 scenarios using a gradual change perspective (parameters are smooth). In both perspectives, dam removal mortality and a decreasing resource rate reduced community biomass and delayed recovery time compared to pre-dam removal conditions. Our results demonstrate that recovery from a dam removal scenario is not necessarily a benefit for all species. In scenarios where dam removal practices or dam failures cause high mortality events and sustained impacts on base trophic level resources, recovery of pre-removal biomass may take decades, while community stability may be unstable for twice that time-period. Our study shows that size spectrum models can be applied to dam removal scenarios to explore potential recovery outcomes, particularly from a risk avoidance perspective. A benefit of using such an approach is the relatively low data requirements needed to perform projections (e.g., present species, fish growth rates, relative fish abundance). Implementing this model in other river systems, particularly at the reach scale, can help river restoration and management assess tradeoffs associated with different habitat restoration approaches prior to committing to a dam removal plan.
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20.
  • Hansen, Ken, 1954, et al. (author)
  • Evidensbaserad ortodonti
  • 2007
  • In: Aktuell Nordisk Odontologi 2007. ; , s. 187-204
  • Book chapter (other academic/artistic)
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21.
  • Heid, Iris M, et al. (author)
  • Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
  • 2010
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
  • Journal article (peer-reviewed)abstract
    • Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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24.
  • Horikoshi, Momoko, et al. (author)
  • New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
  • 2013
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1
  • Journal article (peer-reviewed)abstract
    • Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
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25.
  • Justice, Anne E., et al. (author)
  • Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
  • 2019
  • In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
  • Journal article (peer-reviewed)abstract
    • Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
  •  
26.
  • Kanoni, Stavroula, et al. (author)
  • Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
  • 2022
  • In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
  • Journal article (peer-reviewed)abstract
    • Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
  •  
27.
  • Kato, Norihiro, et al. (author)
  • Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
  • 2015
  • In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
  • Journal article (peer-reviewed)abstract
    • We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
  •  
28.
  • Klionsky, Daniel J., et al. (author)
  • Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
  • 2008
  • In: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
  • Research review (peer-reviewed)abstract
    • Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
  •  
29.
  • Kraja, Aldi T., et al. (author)
  • New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475000 Individuals
  • 2017
  • In: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1942-325X .- 1942-3268. ; 10:5
  • Journal article (peer-reviewed)abstract
    • Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.Methods and Results - Here, we augment the sample with 140886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, approximate to 475000), and the other in the subset of individuals of European descent (approximate to 423000). Twenty-one SNVs were genome-wide significant (P<5x10(-8) ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.
  •  
30.
  • Lefmann, Kim, et al. (author)
  • Simulation of a suite of generic long-pulse neutron instruments to optimize the time structure of the European Spallation Source
  • 2013
  • In: Review of Scientific Instruments. - : AIP Publishing. - 1089-7623 .- 0034-6748. ; 84:5
  • Journal article (peer-reviewed)abstract
    • We here describe the result of simulations of 15 generic neutron instruments for the long-pulsed European Spallation Source. All instruments have been simulated for 20 different settings of the source time structure, corresponding to pulse lengths between 1 ms and 2 ms; and repetition frequencies between 10 Hz and 25 Hz. The relative change in performance with time structure is given for each instrument, and an unweighted average is calculated. The performance of the instrument suite is proportional to (a) the peak flux and (b) the duty cycle to a power of approximately 0.3. This information is an important input to determining the best accelerator parameters. In addition, we find that in our simple guide systems, most neutrons reaching the sample originate from the central 3-5 cm of the moderator. This result can be used as an input in later optimization of the moderator design. We discuss the relevance and validity of defining a single figure-of-merit for a full facility and compare with evaluations of the individual instrument classes. (C) 2013 AIP Publishing LLC.
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31.
  • Lindskog Stokland, Birgitta, 1959, et al. (author)
  • Changes in molar position with missing opposed and/or adjacent tooth: a 12-year study in women
  • 2012
  • In: Journal of Oral Rehabilitation. - 0305-182X. ; 39:2, s. 136-43
  • Journal article (peer-reviewed)abstract
    • Summary The aim of this study was to radiographically analyse long-term changes in (i) overeruption of unopposed molars and (ii) tipping of molars with a mesial edentulous space, and whether there is an interaction between the two events. A further aim was to analyse if loss of alveolar bone height might influence overeruption and tipping. The sample consisted of panoramic radiographs taken at an interval of 12years of 292 subjects from a prospective population study of women. The panoramic radiographs were scanned and analysed. Changes in tipping, overeruption and alveolar bone height of molars and control teeth were measured. The results showed that unopposed molars were more commonly found in the upper jaw and that unopposed molars showed 4·9 times higher risk of overeruption of ≥2mm (95% CI 1·5-15·3) than opposed molars during the 12-year observation period. The average overeruption for the unopposed molars was 4·5% (s.d. 7·6), which corresponds to approximately 0·9mm. The degree of overeruption increased with decreased bone support. Molars with a mesial edentulous space were most prevalent in the lower jaw, but neither an edentulous space nor alveolar bone level/bone level change were found to have a significant effect on tipping of the molars. The average mesial tipping was 0·8° (s.d. 5·6). In conclusion, unopposed molars showed a significantly increased risk for overeruption. Molars facing a mesial edentulous space showed a low risk for mesial tipping, but a significant interaction between overeruption and tipping was identified.
  •  
32.
  • Lindskog Stokland, Birgitta, 1959, et al. (author)
  • Molar position associated with a missing opposed and/or adjacent tooth: a follow up study in women
  • 2013
  • In: Swedish Dental Journal. - 0347-9994. ; 37:2, s. 97-105
  • Journal article (peer-reviewed)abstract
    • The purpose of the study was to assess (i) the degree of overeruption of molars lacking opposed teeth and (ii) the inclination of molars with a mesial edentulous space and also to study (iii) changes during a 12 year period. The subject sample originated from the prospective population study of women in Gothenburg, Sweden where scanned panoramic radiographs taken with an interval of 12 years were analysed. Tipping as well as overeruption were scored on the two images according to a five-level scale. Sixty-seven subjects fulfilled the inclusion criteria at baseline and were referred to as "the non-extraction group". Further 35 subjects had lost the opposed and/or the adjacent tooth/teeth during the 12-year follow-up period: "the extraction-group". These groups were studied separately and a comparison between these groups was performed. The prevalence of molars tipped more than 15 degrees at baseline was 17.1 % in the upper jaw and 44.3 % in the lower jaw, in the non-extraction group. At baseline overeruption was seen in 25 % of the unopposed upper molars and none of lower molars in the non-extraction group. The prevalence of tipping and overeruption was statistical significant less in the extraction group (P<0.01), than in the non-extraction group at baseline, but at follow-up no statistical significant group differences existed. -The prevalence of tipped molars facing a mesial edentulous space and overerupted unopposed molars increased in adults during the 12-year period but the changes were small. -Overeruption and tipping is most pronounced immediately after extractions.
  •  
33.
  • Lindskog Stokland, Birgitta, 1959, et al. (author)
  • Orthodontic tooth movement into edentulous ridge areas--a case series.
  • 2013
  • In: European journal of orthodontics. - : Oxford University Press (OUP). - 1460-2210 .- 0141-5387. ; 35:3, s. 277-285
  • Journal article (peer-reviewed)abstract
    • The aim of this case series was to analyse dimensional alterations of the alveolar ridge and tooth-supporting structures, as well as root resorption, following orthodontic tooth movement into edentulous areas with reduced ridge dimensions. The study involved six subjects (30-70 years) with 10 edentulous jaw areas in the premolar regions. Clinical and radiographic examinations and 3D measurements on scanned study casts were performed at baseline, at retention, and after 1 year of (i) the edentulous area into which the tooth was moved and (ii) the established edentulous area from which the tooth was moved. The orthodontic tooth movement into an edentulous area resulted in most individuals in only minor dimensional alterations of the periodontal tissues. With regard to the width of the alveolar process, the results indicated a decreased width in the newly established edentulous area, whereas in the area into which the tooth had been moved, the width increased. In all cases, the moved tooth showed lateral root resorption on its pressure side at the level of the bone crest at time of retention, but signs of repair were noticed at the 1-year follow-up. Within the limitations of the study, it can be concluded that orthodontic tooth movement results in dimensional alterations of the edentulous ridge and that lateral root resorption is an inevitable side-effect.
  •  
34.
  • Lu, Yingchang, et al. (author)
  • New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
  • 2016
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Journal article (peer-reviewed)abstract
    • To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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35.
  • Lund, Henrik, 1975, et al. (author)
  • Apical root resorption during orthodontic treatment: A prospective study using cone beam CT
  • 2012
  • In: The Angle Orthodontist. - : The Angle Orthodontist (EH Angle Education & Research Foundation). - 0003-3219 .- 1945-7103. ; 82:3, s. 480-487
  • Journal article (peer-reviewed)abstract
    • Abstract Objective: To investigate the incidence and severity of root resorption during orthodontic treatment by means of cone beam computed tomography (CBCT) and to explore factors affecting orthodontically induced inflammatory root resorption (OIIRR). Materials and Methods: CBCT examinations were performed on 152 patients with Class I malocclusion. All roots from incisors to first molars were assessed on two or three occasions. Results: At treatment end, 94% of patients had ≥1 root with shortening >1 mm, and 6.6% had ≥1 tooth where it exceeded 4 mm. Among teeth, 56.3% of upper lateral incisors had root shortening >1 mm. Of upper incisors and the palatal root of upper premolars, 2.6% showed root shortenings >4 mm. Slanted surface resorptions of buccal and palatal surfaces were found in 15.1% of upper central and 11.5% of lateral incisors. Monthly root shortening was greater after 6-month control than before. Upper jaw teeth and anterior teeth were significantly associated with the degree of root shortening. Gender, root length at baseline, and treatment duration were not. Conclusion: Practically all patients and up to 91% of all teeth showed some degree of root shortening, but few patients and teeth had root shortenings >4 mm. Slanted root resorption was found on root surfaces that could be evaluated only by a tomographic technique. A CBCT technique can provide more valid and accurate information about root resorption.
  •  
36.
  •  
37.
  • Makedonas, Dimitrios, et al. (author)
  • Root resorption diagnosed with cone beam computed tomography after 6 months and at the end of orthodontic treatment with fixed appliances
  • 2013
  • In: Angle orthodontist. - : The Angle Orthodontist (EH Angle Education & Research Foundation). - 0003-3219 .- 1945-7103. ; 83:3, s. 389-393
  • Journal article (peer-reviewed)abstract
    • Objective: To investigate the prevalence of orthodontically induced root resorption after treatment and the correlation with resorption found after 6 months of treatment. Materials and Methods: One hundred fifty-six patients (11-18 years) treated with fixed appliances and extraction of four premolars were examined with cone beam computed tomography before treatment, after 6 months of treatment (n = 97), and at the end of active treatment. The Malmgren Index was used to describe the degree of root resorption. Results: Severe root resorption (>2 mm, score 3) was found in 25.6% of the patients at the end of treatment. Extreme root resorption was found in one patient. Root resorption was seen more frequently in the maxillary incisor region. There was no correlation between the severity of root resorption after 6 months and the amount observed at the end of treatment. Furthermore, no correlation was seen between treatment duration and the severity of root resorption. Conclusions: Clinically significant resorption was diagnosed in 25.6% of the patients, but no correlations, either with the resorption seen after 6 months or with the length of treatment, were found. Radiographic examination after 3 to 6 months of orthodontic treatment is too early and will not reduce the number of patients who will have teeth with severe root resorption.
  •  
38.
  • Makedonas, Dimitrios, et al. (author)
  • Root resorption diagnosed with cone beam computed tomography after 6 months of orthodontic treatment with fixed appliance and the relation to risk factors
  • 2012
  • In: The Angle Orthodontist. - : The Angle Orthodontist (EH Angle Education & Research Foundation). - 0003-3219 .- 1945-7103. ; 82:2, s. 196-201
  • Journal article (peer-reviewed)abstract
    • Abstract Objectives: To investigate root resorption after 6 months of active orthodontic treatment and its relation to possible risk factors. Materials and Methods: Ninety-seven patients (10-18 years) with a Class I malocclusion and crowding treated with fixed appliance and premolar extractions were examined with cone beam computed tomography before and after 6 months of active treatment. The exposure covered all teeth from first molar to first molar in both jaws. The Malmgren index was used to evaluate the degree of root resorption. Irregular root contour (score 1) was seen in most teeth already before active treatment, and therefore resorptions were registered only as score 2 (<2 mm, minor resorption) or higher. Results: Minor root resorption was noted in 10% of the patients and severe root resorption, >2 mm (score 3) was found in four patients. Root resorption was more frequently seen in the upper jaw, especially the incisors. There was no statistically significant correlation of root resorption with any of the selected risk factors. Conclusions: After 6 months of treatment, clinically significant resorption was diagnosed in 4% of the patients, ie, in 96% of the patients the radiographic examination did not reveal any significant information. The selected risk factors did not have any impact on the amount of resorption after 6 months of active treatment.
  •  
39.
  • Mattsson Granlund, Christina M, et al. (author)
  • Frequency of errors and pathology in panoramic images of young orthodontic patients.
  • 2012
  • In: European journal of orthodontics. - : Oxford University Press (OUP). - 1460-2210 .- 0141-5387. ; 34:4, s. 452-457
  • Journal article (peer-reviewed)abstract
    • The aims of this study were to evaluate the frequency of errors in panoramic radiographs in young orthodontic patients, to register pathologic and abnormal conditions, and to compare these findings with the patient's record. A total of 1287 panoramic radiographs of children and adolescents (530 boys and 757 girls; mean age 14.2 years) were analyzed. The radiographs were obtained of patients referred for orthodontic treatment during a 1 year period. Four observers evaluated the radiographs for 10 common errors, pathologies, and/or anomalies. Cohen's kappa was used for the calculations of inter- and intraobserver variability. Five of the errors were divided into clinically relevant or not clinically relevant errors, i.e. errors influencing diagnosis. Only those pathological findings with a possible influence on orthodontic treatment were compared with the patient's record. Of the 1287 radiographs, 96 per cent had errors. The number of errors in each image varied between 1 and 5, and in 24 per cent of these images, the errors could be of importance for clinical decision making. The most common error was that the tongue was not in contact with the hard palate. Pathologies or anomalies were found in 558 patients and a total of 1221 findings were recorded. Findings of possible relevance for orthodontic treatment were 63, and 12 of those were registered in the patient records. Pathological findings outside the dental arches were low and could be an argument for minimizing the radiation field.
  •  
40.
  • Middeldorp, Christel M., et al. (author)
  • The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
  • 2019
  • In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
  • Journal article (peer-reviewed)abstract
    • The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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41.
  • Mohlin, Bengt, 1944, et al. (author)
  • TMD in relation to malocclusion and orthodontic treatment.
  • 2007
  • In: The Angle orthodontist. - : The E. H. Angle Education and Research Foundation. - 0003-3219 .- 1945-7103. ; 77:3, s. 542-8
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: The aim of this systematic literature review was to evaluate associations between different malocclusions, orthodontic treatment, and signs and symptoms of temporomandibular disorders (TMD). MATERIALS AND METHODS: This review was part of a project at the Swedish Council on Technology Assessment in Health Care focusing on malocclusion and orthodontic treatment from a health perspective. As a first step, the literature was searched in the Medline and Cochrane Library databases from 1966 to May 2003. A later update was made in January 2005. Human studies in English or in Scandinavian languages were included. RESULTS: Associations between certain malocclusions and TMD were found in some studies, whereas the majority of the reviewed articles failed to identify significant and clinically important associations. TMD could not be correlated to any specific type of malocclusion, and there was no support for the belief that orthodontic treatment may cause TMD. Obvious individual variations in signs and symptoms of TMD over time according to some longitudinal studies further emphasized the difficulty in establishing malocclusion as a significant risk factor for TMD. A considerable reduction in signs and symptoms of TMD between the teenage period and young adulthood has been shown in some recent longitudinal studies. CONCLUSIONS: Associations between specific types of malocclusions and development of significant signs and symptoms of TMD could not be verified. There is still a need for longitudinal studies.
  •  
42.
  • Naghavi, Mohsen, et al. (author)
  • Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
  • 2015
  • In: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
  • Journal article (peer-reviewed)abstract
    • Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
  •  
43.
  • Pancherz, Hans, et al. (author)
  • The mechanism of Class II correction in surgical orthodontic treatment of adult Class II, division 1 malocclusions.
  • 2004
  • In: The Angle orthodontist. - 0003-3219. ; 74:6, s. 800-9
  • Journal article (peer-reviewed)abstract
    • The purpose of this investigation was to assess the dentoskeletal effects and facial profile changes as well as the mechanism of Class II correction in adult Class II subjects treated by surgical mandibular advancement in combination with orthodontics. The subject material comprised 46 adults with a Class II, division 1 malocclusion treated by nonextraction with a mandibular sagittal split osteotomy as well as with pre- and postsurgical multibracket appliances. Lateral head films from before treatment and after treatment were analyzed. The results revealed the following statistically significant (P < .001) treatment changes: (1) the mandibular prognathism enhanced; (2) the sagittal interjaw base relationship improved; (3) the mandibular plane angle increased; (4) the lower anterior facial height increased; (5) the lower posterior facial height decreased; (6) the facial profile straightened; (7) the overjet and Class II molar relationship were corrected. Overjet reduction was accomplished by 63% skeletal and 37% dental changes. The Class II molar correction was accomplished by 81% skeletal 19% dental changes. In conclusion, it can be said that mandibular sagittal split osteotomy in combination with pre- and postsurgical orthodontics is an effective and consistent method for the correction of Class II, division 1 malocclusions and for the straightening of the facial profile. A negative effect of treatment counteracting Class II correction is an increase in the mandibular plane angle.
  •  
44.
  • Pancherz, Hans, et al. (author)
  • Thirty-two-year follow-up study of Herbst therapy : a biometric dental cast analysis
  • 2014
  • In: American Journal of Orthodontics and Dentofacial Orthopedics. - : Elsevier. - 0889-5406 .- 1097-6752. ; 145:1, s. 15-27
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: The aim of this study was to analyze the very long-term effects of Herbst treatment on tooth position and occlusion. SUBJECTS: Fourteen patients from a sample of 22 with Class II Division 1 malocclusions consecutively treated with the banded Herbst appliance were reexamined 32 years after therapy. METHODS: Dental casts were analyzed from before (T1) and after (T2) treatment, and at 6 years (T3) and 32 years (T4) after treatment. RESULTS: Minor changes in maxillary and mandibular dental arch perimeters and arch widths were seen during treatment (T1-T2) and posttreatment (T2-T4). Mandibular incisor irregularity remained, on average, unchanged from T1 to T2 but increased continuously during the 32-year follow-up period (T2-T4). Class II molar and canine relationships were normalized in most patients from T1 to T2. During the early posttreatment period (T2-T3), there was a minor relapse; during the late posttreatment period (T3-T4), molar and canine relationships remained, on average, unchanged. Overjet and overbite were reduced to normal values in all subjects during treatment (T1-T2). After treatment (T2-T4), overjet remained, on average, unchanged, but overbite increased insignificantly. CONCLUSIONS: Thirty-two years after Herbst therapy, overall, acceptable long-term results were seen. Stability was found in 64% of the patients for sagittal molar relationships, in 14% for sagittal canine relationships, in 86% for overjet, and in 86% for overbite. A Class II relapse seemed to be caused by an unstable interdigitation of the occluding teeth, a persisting oral habit, or an insufficient retention regimen after treatment. Most posttreatment changes occurred during the first 6 years after treatment. After the age of 20 years, only minor changes were noted. Long-term posttreatment changes in maxillary and mandibular dental arch perimeters and widths as well as in mandibular incisor irregularity seemed to be independent of treatment and a result of physiologic dentoskeletal changes throughout adulthood.
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45.
  • Ried, Janina S., et al. (author)
  • A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
  • 2016
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Journal article (peer-reviewed)abstract
    • Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
  •  
46.
  •  
47.
  • Scott, Robert A, et al. (author)
  • No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels
  • 2012
  • In: Diabetes. - Alexandria, VA : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 61:5, s. 1291-1296
  • Journal article (peer-reviewed)abstract
    • Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.
  •  
48.
  • Speliotes, Elizabeth K., et al. (author)
  • Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
  • 2010
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
  • Journal article (peer-reviewed)abstract
    • Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
  •  
49.
  • Vendelbo Lind, Mads, 1988, et al. (author)
  • Higher intake of fish and fat is associated with lower plasma s-adenosylhomocysteine: a cross-sectional study
  • 2017
  • In: Nutrition Research. - : Elsevier BV. - 0271-5317 .- 1879-0739. ; 46, s. 78-87
  • Journal article (peer-reviewed)abstract
    • Several B-vitamins act as co-factors in one-carbon metabolism, a pathway that plays a central role in several chronic diseases. However, there is a lack of knowledge of how diet affects markers in one-carbon metabolism. The aim of this study was to explore dietary patterns and components associated with one-carbon metabolites. We hypothesized that intake of whole-grains and fish would be associated with lower Hcy, and higher SAM:SAH ratio due to their nutrient content. We assessed dietary information using a four-day dietary record in 118 men and women with features of the metabolic syndrome. In addition we assessed whole-blood fatty acid composition and plasma alkylresorcinols. Plasma s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH), homocysteine (Hcy) and vitamin B12 was included as one-carbon metabolism markers. We used principal component analysis (PCA) to explore dietary patterns and multiple linear regression models to examine associations between dietary factors and one-carbon metabolites. PCA separated subjects based on prudent and unhealthy dietary patterns, but the dietary pattern score was not related to the one-carbon metabolites. Whole grain intake was found to be inversely associated to plasma Hcy (?4.7% (?9.3; 0.0), P =.05) and total grain intake tended to be positively associated with SAM and SAH (2.4% (?0.5; 5.5), P =.08; 5.8% (?0.2; 12.1), P =.06, respectively, per SD increase in cereal intake). Fish intake was inversely associated with plasma Hcy and SAH concentrations (?5.4% (?9.7; ?0.8), P =.02 and ?7.0% (?12.1; ?1.5), P =.01, respectively) and positively associated with the SAM:SAH ratio (6.2% (1.6; 11.0), P =.008). In conclusion, intake and fish and whole-grain appear to be associated with a beneficial one-carbon metabolism profile. This indicates that dietary components could play a role in regulation of one-carbon metabolism with a potential impact on disease prevention.
  •  
50.
  • Villumsen Berling, Trine, et al. (author)
  • Nærområdet
  • 2023
  • Other publication (other academic/artistic)abstract
    • Abstract in DanishTiden efter den kolde krig er slut. Nu befinder vi os i tiden efter Ukraine-krigen. Hvor stårDanmark og Østersøregionen i et tænkt scenarie, hvor Rusland ikke længere er optaget afkrigen i Ukraine og i stedet reorienterer sig mod vest? I dette arbejdspapir rammesætter vinogle sandsynlige scenarier for Danmarks nærområde. Ved at konstatere, at en demokratiskomstilling af Rusland er usandsynlig på den mellemlange bane, og ved at se på terræn ogmilitære kapabiliteter i Østersøområdet og de udfordringer, de indebærer, lægger dennerapport de første spæde linjer ud for den gentænkning af Danmarks strategi, der ernødvendiggjort af det russiske opgør med tiden efter den kolde krig. Informationsrum,kritisk infrastruktur og de danske positioner i både EU og NATO er rapportenshovedstrenge.
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