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221.
  • Stougaard Pedersen, Birgitte, et al. (författare)
  • To Move, to Touch, to Listen : Multisensory Aspects of the Digital Reading Condition
  • 2021
  • Ingår i: Poetics today. - : Duke University Press. - 0333-5372 .- 1527-5507. ; 42:2, s. 281-300
  • Tidskriftsartikel (refereegranskat)abstract
    • The article discusses modes of reading that emerge from reading situationsthat involve literary digital interfaces and digital audiobooks. Building onanalyses of sensorial characteristics of the act of reading a digital audiobook and aliterary digital app, respectively, the article presents and defines the concept of multisensoryreading. This concept emphasizes the literary work’s material and performative features, as well as the experienced reading situation. The authors explore how the digital literary interface changes reading situations and argue that newreading habits create a need to renegotiate what it means to read in a digital age.In particular, sensory aspects can be understood as integrally involved in what theyterm the digital reading condition.
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222.
  • Stray-Pedersen, Asbjorg, et al. (författare)
  • Primary immunodeficiency diseases : Genomic approaches delineate heterogeneous Mendelian disorders
  • 2017
  • Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 139:1, s. 232-245
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/ 110) and management was directly altered in nearly a quarter (26/ 110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.
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223.
  • Tolbod, Lars P., et al. (författare)
  • Non-invasive quantification of tumor blood flow in prostate cancer using O-15-H2O PET/CT
  • 2018
  • Ingår i: American Journal of Nuclear Medicine and Molecular Imaging. - : E-CENTURY PUBLISHING CORP. - 2160-8407. ; 8:5, s. 292-302
  • Tidskriftsartikel (refereegranskat)abstract
    • Tumor blood flow (TBF) measurements in prostate cancer (PCa) provide an integrative index of tumor growth, which could be important for primary diagnosis and therapy response evaluation. O-15-water PET is the noninvasive gold standard but is technically demanding. The aim of this study was to compare the accuracy of three different non-invasive strategies with an invasively measured arterial input function (BSIF): Using image-derived input functions (IDIF) from either 1) a separate heart scan or 2) the pelvic scan or 3) a populations-based input function (PBIF). Nine patients with biopsy-verified PCa scheduled for prostatectomy were included. All patients were characterized with serum levels of PSA (s-PSA), multiparametric magnetic resonance imaging (mpMRl) and post-surgical histopathology Gleason Grade. Dynamic O-15-water was performed of the heart and the pelvic area 15 minutes apart. TBF estimated from both wash-in (K-1) and wash-out (k(2)) constants was calculated using a one-compartmental model. Results: Mean (range) s PSA was 12 (3-27) ng/mL, Gleason Grade Group was 2.9 (1-5), k(2) was 0.44 (0.007-1.2), and K-1 was 0.24 (0.07-0.55) mL,/mL/min. k(2) (BSIF)correlated with s-PSA (r=0.86, P<0.01) and Gleason Grade Group (rho=0.78, P=0.01). BSIF, heart-IDIF and PBIF provided near-identical k(2) and K-1 (r>0.95, P<0.001) with slopes near unity. The correlations of BSIF and pelvic-IDIF rate constants were good (r>0.95, P<0.001), but individual errors high. In conclusion, non-invasive protocols for O-15-water PET with IDIF or PBIF accurately measures perfusion in prostate cancer and might be useful for evaluation of tumor aggressiveness and treatment response.
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224.
  • Turcot, Valerie, et al. (författare)
  • Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
  • 2018
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
  • Tidskriftsartikel (refereegranskat)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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225.
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226.
  • Vogelezang, Suzanne, et al. (författare)
  • Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.
  • 2020
  • Ingår i: PLoS genetics. - 1553-7404. ; 16:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
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227.
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228.
  • Yan, Ping, et al. (författare)
  • 3D magnetotelluric modelling of the Alnö alkaline and carbonatite ring complex, central Sweden
  • 2016
  • Ingår i: Tectonophysics. - 0040-1951 .- 1879-3266. ; 679, s. 218-234
  • Tidskriftsartikel (refereegranskat)abstract
    • Thirty-four broadband magnetotelluric stations were deployed across the Alno alkaline and carbonatite ring intrusion in central Sweden. The measurements were designed such that both 2D models along existing seismic profiles and a 3D model can be constructed. Alno Island and surrounding areas are densely populated and industrialized and in order to reduce the effect of noise, the remote reference technique was utilized in time series processing. Strike and dimensionality analyses together with the induction arrows show that there is no homogeneous regional strike direction in this area. Therefore, only the determinant of the impedance tensor was used for 2D inversion whereas all elements of the impedance tensor were used for 3D inversion. Representative rock samples were collected from existing outcrops and their resistivities were measured in the laboratory to facilitate interpretation of the inversion models. The results from these measurements show that coarse grained (sovite, white color) and fine-grained (dark color) carbonatites are the most conductive and resistive rock types, respectively. In accordance with the interpretation of the reflection seismic images, the 2D and 3D resistivity models depict the caldera-related ring-type fault system and updoming faulted and fractured systems as major 10-500 Omega m conductors, extending down to about 3 km depth. A central similar to 4000 Omega m resistive unit at about 3 km depth appears to correspond to a solidified fossil magma chamber as speculated from the reflection seismic data and earlier field geological studies.
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229.
  • Yan, Ping, 1987- (författare)
  • Inversion of Magnetotelluric Data Constrained by Borehole Logs and Reflection Seismic Sections
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • This thesis presents two new algorithms for doing constrained Magnetotelluric (MT) inversion based on an existing Occam 2D inversion program. The first algorithm includes borehole resistivity logs as prior information to constrain resistivity directly in the vicinity of boreholes. The second algorithm uses reflection seismic data as prior constraints to transfer structural information from seismic images to 2D resistivity models. These two algorithms are efficient (proved through tests of synthetic examples) and widely applicable. In this thesis, they have been successfully applied to the COSC (Collisional Orogeny in the Scandinavian Caledonides) MT data.The COSC project aims to study the mountain belt dynamics in central Sweden by drilling two 2.5 km deep boreholes. MT data were collected to locate the main décollement that separates the overlying Caledonian allochthons and the underlying Precambrian basement, as the main décollement is associated with very conductive Alum shale. The previous interpretation based on part of the COSC seismic profile (CSP) was that the main décollement was located along a reflection with depth of 4.5 km underneath Åre and ~3 km underneath Mörsil, in central Jämtland.The MT resistivity model reveals a very conductive layer in the central and western parts of the profile, the top of which coincides with the first seismic reflection. This means that the first conductive alum shale layer occurs at less than 1 km depth, supporting a new interpretation of the main décollement at shallower depth. In a re-interpretation of the CSP data based on the MT model, the main décollement occurs a few hundred metres below the top of the conductor and is coincident with a laterally continuous seismic reflection. Further, the overlying seismic reflections resemble imbricated alum shale of the Lower Allochthon. MT inversion using seismic constraints from CSP gives further support to the new interpretation.Moreover, MT investigations were conducted in the Alnö alkaline and carbonatite ring-intrusion complex in Sweden. 2D and 3D resistivity models inverted from MT data together with resistivity and porosity laboratory measurements delineate a fossil magma chamber as a resistive anomaly surrounded by electrically conductive up-doming and ring-shaped faults and fractures.
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230.
  • Zetterberg, Henrik, 1973, et al. (författare)
  • Intra-individual stability of CSF biomarkers for Alzheimer's disease over two years
  • 2007
  • Ingår i: Journal of Alzheimer's disease : JAD. - 1387-2877. ; 12:3, s. 255-60
  • Tidskriftsartikel (refereegranskat)abstract
    • This study examines the intra-individual stability of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) over 2 years in 83 patients with mild cognitive impairment (MCI) and 17 cognitively healthy control individuals. All participants underwent clinical and neuropsychological evaluation and lumbar puncture at baseline and after 2 years at a university hospital memory clinic. CSF was analyzed for total tau (T-tau), phospho-tau(181) (P-tau(181)) and amyloid-beta(1-42) (Abeta(1-42)). During the 2-year observational time, 12 MCI patients progressed to AD and 3 progressed to vascular dementia, while 68 remained stable. Baseline T-tau and P-tau(181) levels were elevated in the MCI-AD group as compared to the stable MCI patients and the control group (p<0.01), while baseline Abeta(1-42) levels were lower (p<0.001). Stable MCI patients were biochemically indistinguishable from controls. The biomarker levels at baseline and after 2 years showed Pearson R values between 0.81 and 0.91 (p<0.001) and coefficients of variation of 7.2 to 8.7%. In conclusion, intra-individual biomarker levels are remarkably stable over 2 years. Thus, even minor biochemical changes induced by treatment against AD should be detectable using these biomarkers, which bodes well for their usefulness as surrogate markers for drug efficacy in clinical trials.
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