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Sökning: WFRF:(Westman Eric)

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  • Adams, Hieab H. H., et al. (författare)
  • Novel genetic loci underlying human intracranial volume identified through genome-wide association
  • 2016
  • Ingår i: Nature Neuroscience. - 1097-6256 .- 1546-1726. ; 19:12, s. 1569-1582
  • Tidskriftsartikel (refereegranskat)abstract
    • Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.
  • Adelmann, Kent, et al. (författare)
  • Att bygga broar - kulturella, språkliga och mediala möten
  • 2010
  • Samlingsverk (redaktörskap) (övrigt vetenskapligt)abstract
    • Sjunde nationella konferensen i svenska med didaktisk inriktning samt Första nordiska konferensen i modersmålsdidaktik hölls i Malmö 18-20 november 2009 under temat Att bygga broar – kulturella, språkliga och mediala möten. Här presenteras artiklar från de fyra plenarföreläsarna samt elva av sektionsföredragen. Texterna är på svenska, danska, norska och engelska och griper i enlighet med temat in i språk- och litteraturdidaktiska ögonblick över nära nog hela forskningsfältet i svenska med didaktisk inriktning.
  • Aguilar, Carlos, et al. (författare)
  • Automated CT-based segmentation and quantification of total intracranial volume
  • 2015
  • Ingår i: European Radiology. - 0938-7994. ; 25:11, s. 3151-3160
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To develop an algorithm to segment and obtain an estimate of total intracranial volume (tICV) from computed tomography (CT) images.MATERIALS AND METHODS: Thirty-six CT examinations from 18 patients were included. Ten patients were examined twice the same day and eight patients twice six months apart (these patients also underwent MRI). The algorithm combines morphological operations, intensity thresholding and mixture modelling. The method was validated against manual delineation and its robustness assessed from repeated imaging examinations. Using automated MRI software, the comparability with MRI was investigated. Volumes were compared based on average relative volume differences and their magnitudes; agreement was shown by a Bland-Altman analysis graph.RESULTS: We observed good agreement between our algorithm and manual delineation of a trained radiologist: the Pearson's correlation coefficient was r = 0.94, tICVml[manual] = 1.05 × tICVml[automated] - 33.78 (R(2) = 0.88). Bland-Altman analysis showed a bias of 31 mL and a standard deviation of 30 mL over a range of 1265 to 1526 mL.CONCLUSIONS: tICV measurements derived from CT using our proposed algorithm have shown to be reliable and consistent compared to manual delineation. However, it appears difficult to directly compare tICV measures between CT and MRI.KEY POINTS: • Automated estimation of tICV is in good agreement with manual tracing. • Consistent tICV estimations from repeated measurements demonstrate the robustness of the algorithm. • Automatically segmented volumes seem less variable than those from manual tracing. • Unbiased and automated tlCV estimation is possible from CT.
  • B. Pereira, Joana, 1982-, et al. (författare)
  • Amyloid network topology characterizes the progression of Alzheimer's disease during the predementia stages
  • 2018
  • Ingår i: Cerebral Cortex. - Oxford University Press. - 1047-3211. ; 28:1, s. 340-349
  • Tidskriftsartikel (refereegranskat)abstract
    • There is increasing evidence showing that the accumulation of the amyloid-β (Aβ) peptide into extracellular plaques is a central event in Alzheimer's disease (AD). These abnormalities can be detected as lowered levels of Aβ42 in the cerebrospinal fluid (CSF) and are followed by increased amyloid burden on positron emission tomography (PET) several years before the onset of dementia. The aim of this study was to assess amyloid network topology in nondemented individuals with early stage Aβ accumulation, defined as abnormal CSF Aβ42 levels and normal Florbetapir PET (CSF+/PET-), and more advanced Aβ accumulation, defined as both abnormal CSF Aβ42 and Florbetapir PET (CSF+/PET+). The amyloid networks were built using correlations in the mean 18F-florbetapir PET values between 72 brain regions and analyzed using graph theory analyses. Our findings showed an association between early amyloid stages and increased covariance as well as shorter paths between several brain areas that overlapped with the default-mode network (DMN). Moreover, we found that individuals with more advanced amyloid accumulation showedmore widespread changes in brain regions both within and outside the DMN. These findings suggest that amyloid network topology could potentially be used to assess disease progression in the predementia stages of AD.
  • Borgström, Eric, 1982-, et al. (författare)
  • Skrivbegreppet i Lgr11 En studie av grundskolans ämnesplan i svenska
  • 2017
  • Ingår i: Språk och Norm. Language and Norms : Rapport från ASLA:s symposium, Uppsala universitet 21-22 april 2016. Papers from the ASLA Symposium at Uppsala University 21-22 April, 2016. - Uppsala, Sweden : ASLA: Svenska föreningen för tillämpad språkvetenskap. - 978-91-87884-26-9 ; s. 26-36
  • Bokkapitel (övrigt vetenskapligt)
  • Borgström, Eric, et al. (författare)
  • Skrivbegreppet i Lgr11 En studie av grundskolans ämnesplan i svenska
  • 2017
  • Ingår i: Språk och norm : Rapport från ASLA:s symposium, Uppsala universitet 21-22 april 2016. - Uppsala : ASLA: Svenska föreningen för tillämpad språkvetenskap. - 978-91-87884-26-9 ; s. 28-36
  • Bokkapitel (övrigt vetenskapligt)
  • Brinkmalm, Gunnar, et al. (författare)
  • An online nano-LC-ESI-FTICR-MS method for comprehensive characterization of endogenous fragments from amyloid β and amyloid precursor protein in human and cat cerebrospinal fluid.
  • 2012
  • Ingår i: Journal of mass spectrometry : JMS. - 1096-9888. ; 47:5, s. 591-603
  • Tidskriftsartikel (refereegranskat)abstract
    • Amyloid precursor protein (APP) is the precursor protein to amyloid β (Aβ), the main constituent of senile plaques in Alzheimer's disease (AD). Endogenous Aβ peptides reflect the APP processing, and greater knowledge of different APP degradation pathways is important to understand the mechanism underlying AD pathology. When one analyzes longer Aβ peptides by low-energy collision-induced dissociation tandem mass spectrometry (MS/MS), mainly long b-fragments are observed, limiting the possibility to determine variations such as amino acid variants or post-translational modifications (PTMs) within the N-terminal half of the peptide. However, by using electron capture dissociation (ECD), we obtained a more comprehensive sequence coverage for several APP/Aβ peptide species, thus enabling a deeper characterization of possible variants and PTMs. Abnormal APP/Aβ processing has also been described in the lysosomal storage disease Niemann-Pick type C and the major large animal used for studying this disease is cat. By ECD MS/MS, a substitution of Asp7 → Glu in cat Aβ was identified. Further, sialylated core 1 like O-glycans at Tyr10, recently discovered in human Aβ (a previously unknown glycosylation type), were identified also in cat cerebrospinal fluid (CSF). It is therefore likely that this unusual type of glycosylation is common for (at least) species belonging to the magnorder Boreoeutheria. We here describe a detailed characterization of endogenous APP/Aβ peptide species in CSF by using an online top-down MS-based method.
  • Brusini, Irene, et al. (författare)
  • Shape Information Improves the Cross-Cohort Performance of Deep Learning-Based Segmentation of the Hippocampus
  • 2020
  • Ingår i: Frontiers in Neuroscience. - Frontiers Media S.A.. - 1662-4548 .- 1662-453X. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Performing an accurate segmentation of the hippocampus from brain magnetic resonance images is a crucial task in neuroimaging research, since its structural integrity is strongly related to several neurodegenerative disorders, including Alzheimer's disease (AD). Some automatic segmentation tools are already being used, but, in recent years, new deep learning (DL)-based methods have been proven to be much more accurate in various medical image segmentation tasks. In this work, we propose a DL-based hippocampus segmentation framework that embeds statistical shape of the hippocampus as context information into the deep neural network (DNN). The inclusion of shape information is achieved with three main steps: (1) a U-Net-based segmentation, (2) a shape model estimation, and (3) a second U-Net-based segmentation which uses both the original input data and the fitted shape model. The trained DL architectures were tested on image data of three diagnostic groups [AD patients, subjects with mild cognitive impairment (MCI) and controls] from two cohorts (ADNI and AddNeuroMed). Both intra-cohort validation and cross-cohort validation were performed and compared with the conventional U-net architecture and some variations with other types of context information (i.e., autocontext and tissue-class context). Our results suggest that adding shape information can improve the segmentation accuracy in cross-cohort validation, i.e., when DNNs are trained on one cohort and applied to another. However, no significant benefit is observed in intra-cohort validation, i.e., training and testing DNNs on images from the same cohort. Moreover, compared to other types of context information, the use of shape context was shown to be the most successful in increasing the accuracy, while keeping the computational time in the order of a few minutes.
  • Budhiraja, Meenal, et al. (författare)
  • Cortical structure abnormalities in females with conduct disorder prior to age 15
  • 2019
  • Ingår i: Psychiatry Research : Neuroimaging. - Elsevier. - 0925-4927. ; 289, s. 37-44
  • Tidskriftsartikel (refereegranskat)abstract
    • Among females, conduct disorder (CD) before age 15 is associated with multiple adverse outcomes in adulthood. The few existing structural neuroimaging studies of females with CD report abnormalities of gray matter volumes. The present study compared cortical thickness and surface area of young women with childhood/adolescent CD and healthy women to determine whether cortical abnormalities were present in adulthood and whether they were related to prior CD. Structural brain images from 31 women with CD and 25 healthy women were analyzed using FreeSurfer. Group differences between cortical thickness and surface area were assessed using cluster-wise corrections with Monte Carlo simulations. Women with prior CD, relative to healthy women, showed: (1) reduced cortical thickness in left fusiform gyrus extending up to entorhinal cortex and lingual gyrus; (2) reduced surface area in right superior parietal cortex; (3) increased surface area in left superior temporal gyrus, and right precentral gyrus. These differences remained significant after adjusting for past comorbid disorders, current symptoms of anxiety and depression, current substance use as well as maltreatment. The study suggests that among females, CD prior to age 15 is associated with cortical structure abnormalities in brain regions involved in emotion processing and social interaction.
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