| 1. |
- Eckerström, Carl, et al.
(författare)
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High white matter lesion load is associated with hippocampal atrophy in mild cognitive impairment.
- 2011
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 31:2, s. 132-8
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Tidskriftsartikel (refereegranskat)abstract
- Mild cognitive impairment (MCI) is a heterogeneous condition suggested as a prodromal state of Alzheimer's disease (AD) and subcortical vascular dementia (SVD). Recent findings suggest that white matter lesions (WML) may be associated with hippocampal atrophy. The objective of the study was to examine hippocampal and WML volumes in MCI patients and to examine if WML were linked to hippocampal atrophy.
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| 2. |
- Eckerström, Carl, et al.
(författare)
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Multimodal Prediction of Dementia with up to 10 Years Follow Up: The Gothenburg MCI Study
- 2015
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 44:1, s. 205-214
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neuropsychological tests, CSF A beta(42,) T-tau, P-tau181, hippocampal volume, and white matter lesions have been shown to predict conversion to dementia in patients with mild cognitive impairment (MCI). Objective: To examine the predictive value of combinations of these markers and to examine if the absence of pathological markers provides a lasting reduction of conversion rates. Methods: The Gothenburg MCI study is a clinically based study. Seventy-three MCI patients were included in the present sub-study and followed for a maximum of ten years. Thirty-four patients converted to dementia (18 to AD) and 39 remained stable. At inclusion, patients were classified into positive or negative risk groups according to results from neuropsychological testing (Rey auditory verbal learning test, Boston naming test, Trail making test B), CSF biomarkers (amyloid beta(42), T-tau, and P-tau181) and MRI scans (hippocampal volume, white matter lesions). Results: Trail making test B (TMT-B) was the best single predictor for the prediction of dementia (AUC 0.89, HR 25), and T-tau was the best predictor ofAD(AUC 0.97, HR 41). The combination of hippocampal volume and TMT-Bwas the best combination for the prediction of dementia (HR 25), and the combination of hippocampal volume and T-tau was the best combination for the prediction of AD (HR 37). Conclusion: Neuropsychological tests, CSF markers, and hippocampal volume predicted conversion from MCI to AD and general dementia. The absence of pathological markers provided a long-time protection from dementia.
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| 3. |
- Eckerström, Carl, et al.
(författare)
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Similar pattern of atrophy in early- and late-onset Alzheimer's disease
- 2018
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 10, s. 253-259
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Previous research on structural changes in early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) have reported inconsistent findings. Methods: In the present substudy of the Gothenburg MCI study, 1.5 T scans were used to estimate lobar and hippocampal volumes using FreeSurfer. Study participants (N = 145) included 63 patients with AD, (24 patients with EOAD [aged ≤65 years], 39 patients with LOAD [aged >65 years]), 25 healthy controls aged ≤65 years, and 57 healthy controls aged >65 years. Results: Hippocampal atrophy is the most prominent feature of both EOAD and LOAD compared with controls. Direct comparison between EOAD and LOAD showed that the differences between the groups did not remain after correcting for age. Discussion: Structurally, EOAD and LOAD does not seem to be different nosological entities. The difference in brain volumes between the groups compared with controls is likely due to age-related atrophy. © 2018 The Authors
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| 4. |
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| 5. |
- Klasson, Anders, et al.
(författare)
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Design for lateral stability of slender timber beams considering slip in the lateral bracing system
- 2018
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Ingår i: Structures. - : Elsevier BV. - 2352-0124. ; 16, s. 157-163
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigates the significance of potential slip in the bracings of simply supported slender timber members. Three bracing configurations are considered. The first case is that of a timber beam braced at one point at mid-span, the second one braced at two points and the third one braced at three points. Possible slip in the bracing members can for example be due to joint deformation, initial crookedness of purlins and slack (or relaxation) of cables in the stabilizing bay (catenary action). In this study, it is shown that slip in the bracing system can result in a reduced load-bearing capacity (due to larger beam stresses) of the beams. Also, the greater the slip, the greater lateral deflections and consequent bracing forces of the braced member. A simplified approach, using a larger initial geometrical imperfection, to account for potential slip in bracings is also evaluated. This approach is found to work reasonably well in terms of stresses and bracing forces, but underestimates the lateral displacements.
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| 6. |
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| 7. |
- Klasson, Anna, et al.
(författare)
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Positive MRI Enhancement in THP-1 Cells with Gd2O3 Nanoparticles
- 2008
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Ingår i: Contrast Media and Molecular Imaging. - : Wiley. - 1555-4309 .- 1555-4317. ; 3:3, s. 106-111
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Tidskriftsartikel (refereegranskat)abstract
- There is a demand for more efficient and tissue-specific MRI contrast agents and recent developments involve the design of substances useful as molecular markers and magnetic tracers. In this study, nanoparticles of gadolinium oxide (Gd2O3) have been investigated for cell labeling and capacity to generate a positive contrast. THP-1, a monocytic cell line that is phagocytic, was used and results were compared with relaxivity of particles in cell culture medium (RPMI 1640). The results showed that Gd2O3-labeled cells have shorter T1 and T2 relaxation times compared with untreated cells. A prominent difference in signal intensity was observed, indicating that Gd2O3 nanoparticles can be used as a positive contrast agent for cell labeling. The r1 for cell samples was 4.1 and 3.6 s-1 mm-1 for cell culture medium. The r2 was 17.4 and 12.9 s-1 mm-1, respectively. For r1, there was no significant difference in relaxivity between particles in cells compared to particles in cell culture medium, (pr1 = 0.36), but r2 was significantly different for the two different series (pr2 = 0.02). Viability results indicate that THP-1 cells endure treatment with Gd2O3 nanoparticles for an extended period of time and it is therefore concluded that results in this study are based on viable cells.
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| 8. |
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| 9. |
- Klasson, Anders, et al.
(författare)
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Slender Roof Structures - Failure Reviews and a Qualitative Survey of Experienced Structural Engineers
- 2018
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Ingår i: Structures. - : Elsevier BV. - 2352-0124. ; 15, s. 174-183
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Tidskriftsartikel (refereegranskat)abstract
- Many slender roof structures have collapsed due to snow loading and instability. Although accurate stability calculations can be performed using theoretical models, these calculations may not always reflect the behaviour of real structures as a result of the uncertainties relating to e.g. loading, material behaviour, geometry, initial imperfections and the actual boundary conditions of the structure. As a result, the approach to stability design requires subjective decisions by the structural engineer concerning loading and modelling assumptions. This paper investigates the significance of these types of decisions made by structural engineers in designing slender roof structures. This investigation is based on a review of previous failure studies together with a survey of 17 experienced structural engineers. The results of this investigation indicate that most structural failures are a result of human errors; thus, a suitable strategy for avoiding errors is through quality control and design checking. Moreover, a significant discrepancy was observed concerning design assumptions made by the engineers in the study. Some of these assumptions, e.g. a non-conservative choice of the buckling length of a beam, have a significant negative impact to structural safety. It is therefore recommended that the structural engineers involved in the design of a structure have adequate experience and a holistic mindset. Another recommendation is that both drawings and design calculations are thoroughly reviewed before construction. Also, temporary bracing to be used during construction should be included in design. Finally, it is important that the communication between different partners in the design of a structure is satisfying.
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| 10. |
- Klasson, Anders, et al.
(författare)
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Slender steel columns : How they are affected by imperfections and bracing stiffness
- 2016
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Ingår i: Structures. - : Elsevier BV. - 2352-0124. ; 8, s. 35-43
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Tidskriftsartikel (refereegranskat)abstract
- Finite-element programs can be used for designing columns and their bracing systems. It is well known, however, that the output obtained from such programs is highly dependent upon the input (such as imperfections and stiffness properties). In the present study, the effects of imperfections on the predicted strength and stiffness requirements of steel columns and of their bracing systems are investigated. Two different systems are analyzed: 1) a braced non-sway column and 2) a braced sway column. It was found that a poor choice of the shape of the initial imperfections can provide unrealistic results in terms of both the buckling load on the columns and the predicted reactions of the bracings. It was also found that superimposing different imperfection shapes can contribute to obtaining realistic and trustworthy results. Furthermore, it was shown that the shapes of the initial imperfections that lead to the lowest buckling load and those that result in the strongest bracing forces, are generally not the same.
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| 11. |
- Klasson, Anders, et al.
(författare)
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The effects on the bracing stiffness of timber structures of the stiffness of its members
- 2019
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Ingår i: Structures. - : Elsevier BV. - 2352-0124. ; 19, s. 41-47
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The design of slender structures is often associated with a number of assumptions made by engineers in checking on the stability of the structure. Not seldom, these assumptions are rather uncertain. In the present paper the effects of the stiffness of different members on the bracing stiffness of timber structures is studied. Both full-scale laboratory testing and FE-modelling are employed here in the investigation. In particular, two different bracing approaches are analysed, those of (1) cross bracing (wind trusses) and (2) diaphragm action (through use of steel sheeting) in the plane of the roof. In addition, the effects of the connections and the number of fasteners used in the structure are evaluated. The stiffness of the connections is obtained by means of an FE-updating approach, i.e. that the relevant parts included in the FE-model are calibrated to ensure that the FE-results match the laboratory results. The findings obtained indicated, (1) that the connections can have a significant effect on the stiffness of the bracing systems, (2) that the cross bracings close to the mid-span of the structure are less effective than those close to the supports, (3) that the lateral stiffness obtained using a diaphragm approach is closely related to the number of fasteners between the steel sheet and the timber parts in the roof that are employed, and (4) that the two different bracing approaches used provide about the same lateral stiffness of the roof. Finally, it should be emphasized that FE-models can markedly overestimate the stiffness of timber structures. If the connections are not modelled accurately, the engineers involved are advised to seek safe sided assumptions regarding them.
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| 12. |
- Klasson, Niklas, et al.
(författare)
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Delineation of two intracranial areas and the perpendicular intracranial width is sufficient for intracranial volume estimation
- 2018
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Ingår i: Insights into Imaging. - : Springer Science and Business Media LLC. - 1869-4101. ; 9:1, s. 25-34
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim of the present study is to determine if the delineation of one or two optimally chosen intracranial areas (ICA) is enough to achieve adequate estimates of intracranial volume (ICV) in magnetic resonance imaging. MethodsThe correlations of 62 fully delineated ICVs with four types of ICV estimates were calculated. The estimate types were: (1) a single midsagittal ICA, (2) single ICA multiplied by the intracranial width perpendicular to the ICA, (3) sum of two ICAs multiplied by the perpendicular intracranial width and (4) shape-preserving piecewise cubic interpolation using two ICAs. For methods 2-4, the fully delineated ICVs were randomly separated into an evaluation and a validation set of equal size. Method 1 was validated against all of the fully delineated ICVs. Result Estimates from method 1 had a Pearson correlation of 0.904 with fully delineated ICV. For method 2, the correlation was 0.986 when delineating the sagittal ICA at 31% of the sagittal intracranial width. For methods 3 and 4, the correlations were both 0.997 when delineating the sagittal ICAs at 17.5 and 64% and at 12 and 64% respectively. conclusions Delineation of two specific intracranial areas is sufficient for intracranial volume estimation. Delineation of two specific intracranial areas is sufficient for intracranial volume estimation. The estimates had a Pearson correlation of 0.997 with intracranial volume.
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| 13. |
- Klasson, Niklas, et al.
(författare)
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Estimated intracranial volume from FreeSurfer is biased by total brain volume
- 2018
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Ingår i: European Radiology Experimental. - : Springer Science and Business Media LLC. - 2509-9280. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Background Estimated intracranial volume (eTIV) from FreeSurfer is not segmentation-based but calculated from the alignment of the input magnetic resonance (MR) images to the MNI305 brain atlas, an approach that could lead to a bias by total brain volume. If eTIV is unbiased, variance beyond that explained by intracranial volume should be random. Our null hypothesis was that no correlation would remain between eTIV and total brain volume when controlling for intracranial volume. Methods eTIV and total brain volume for 62 participants were calculated on 1.5-T, T1-weighted MR images using FreeSurfer (version 6.0.0). Manual delineations of the intracranial volume were also made for the same images. To evaluate the null hypothesis, the partial correlation between eTIV and total brain volume was calculated when controlling for intracranial volume. Results The partial correlation between eTIV and total brain volume when controlling for intracranial volume was 0.355 (p=0.026). The null hypothesis was rejected. Conclusion eTIV from FreeSurfer is biased by total brain volume.
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| 14. |
- Klasson, Niklas, et al.
(författare)
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Valid and efficient manual estimates of intracranial volume from magnetic resonance images
- 2015
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Ingår i: BMC Medical Imaging. - : Springer Science and Business Media LLC. - 1471-2342. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Manual segmentations of the whole intracranial vault in high-resolution magnetic resonance images are often regarded as very time-consuming. Therefore it is common to only segment a few linearly spaced intracranial areas to estimate the whole volume. The purpose of the present study was to evaluate how the validity of intracranial volume estimates is affected by the chosen interpolation method, orientation of the intracranial areas and the linear spacing between them. Methods: Intracranial volumes were manually segmented on 62 participants from the Gothenburg MCI study using 1.5 T, T-1-weighted magnetic resonance images. Estimates of the intracranial volumes were then derived using subsamples of linearly spaced coronal, sagittal or transversal intracranial areas from the same volumes. The subsamples of intracranial areas were interpolated into volume estimates by three different interpolation methods. The linear spacing between the intracranial areas ranged from 2 to 50 mm and the validity of the estimates was determined by comparison with the entire intracranial volumes. Results: A progressive decrease in intra-class correlation and an increase in percentage error could be seen with increased linear spacing between intracranial areas. With small linear spacing (<= 15 mm), orientation of the intracranial areas and interpolation method had negligible effects on the validity. With larger linear spacing, the best validity was achieved using cubic spline interpolation with either coronal or sagittal intracranial areas. Even at a linear spacing of 50 mm, cubic spline interpolation on either coronal or sagittal intracranial areas had a mean absolute agreement intra-class correlation with the entire intracranial volumes above 0.97. Conclusion: Cubic spline interpolation in combination with linearly spaced sagittal or coronal intracranial areas overall resulted in the most valid and robust estimates of intracranial volume. Using this method, valid ICV estimates could be obtained in less than five minutes per patient.
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| 15. |
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| 16. |
- Olsson, Erik, 1960, et al.
(författare)
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White Matter Lesion Assessment in Patients with Cognitive Impairment and Healthy Controls: Reliability Comparisons between Visual Rating, a Manual, and an Automatic Volumetrical MRI Method-The Gothenburg MCI Study.
- 2013
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Ingår i: Journal of aging research. - : Hindawi Limited. - 2090-2204 .- 2090-2212. ; 2013
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Tidskriftsartikel (refereegranskat)abstract
- Age-related white matter lesions (WML) are a risk factor for stroke, cognitive decline, and dementia. Different requirements are imposed on methods for the assessment of WML in clinical settings and for research purposes, but reliability analysis is of major importance. In this study, WML assessment with three different methods was evaluated. In the Gothenburg mild cognitive impairment study, MRI scans from 152 participants were used to assess WML with the Fazekas visual rating scale on T2 images, a manual volumetric method on FLAIR images, and FreeSurfer volumetry on T1 images. Reliability was acceptable for all three methods. For low WML volumes (2/3 of the patients), reliability was overall lower and nonsignificant for the manual volumetric method. Unreliability in the assessment of patients with low WML with manual volumetry may mainly be due to intensity variation in the FLAIR sequence used; hence, intensity standardization and normalization methods must be used for more accurate assessments. The FreeSurfer segmentations resulted in smaller WML volumes than the volumes acquired with the manual method and showed deviations from visible hypointensities in the T1 images, which quite likely reduces validity.
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| 17. |
- Repetto, Linda, et al.
(författare)
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Genetic mechanisms of 184 neuro-related proteins in human plasma.
- 2023
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Understanding the genetic basis of neuro-related proteins is essential for dissecting the disease etiology of neuropsychiatric disorders and other complex traits and diseases. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-related traits as well as complex diseases such as hypertension, high cholesterol, immune-related disorders, and psychiatric disorders. Integrating with established drug information, we validated 13 combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets for diseases and comorbidities. This consortium effort provides a large-scale proteogenomic resource for biomedical research.
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| 18. |
- Repetto, Linda, et al.
(författare)
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Unraveling Neuro-Proteogenomic Landscape and Therapeutic Implications for Human Behaviors and Psychiatric Disorders.
- 2023
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Ingår i: Nature Portfolio. - : Research Square Platform LLC.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioral traits and the disease etiology of neuropsychiatric disorders. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-related traits such as sleeping, smoking, feelings, alcohol intake, mental health, and psychiatric disorders. Integrating with established drug information, we validated 13 out of 13 matched combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets. This consortium effort provides a large-scale proteogenomic resource for biomedical research on human behaviors and other neuro-related phenotypes.
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| 19. |
- Schneider, Daniela I., et al.
(författare)
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More than fishing in the dark : PCR of a dispersed sequence produces simple but ultrasensitive Wolbachia detection
- 2014
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Ingår i: BMC Microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 14, s. 121-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Detecting intracellular bacterial symbionts can be challenging when they persist at very low densities. Wolbachia, a widespread bacterial endosymbiont of invertebrates, is particularly challenging. Although it persists at high titers in many species, in others its densities are far below the detection limit of classic end-point Polymerase Chain Reaction (PCR). These low-titer infections can be reliably detected by combining PCR with DNA hybridization, but less elaborate strategies based on end-point PCR alone have proven less sensitive or less general. Results: We introduce a multicopy PCR target that allows fast and reliable detection of A-supergroup Wolbachia -even at low infection titers -with standard end-point PCR. The target is a multicopy motif (designated ARM: A-supergroup repeat motif) discovered in the genome of wMel (the Wolbachia in Drosophila melanogaster). ARM is found in at least seven other Wolbachia A-supergroup strains infecting various Drosophila, the wasp Muscidifurax and the tsetse fly Glossina. We demonstrate that end-point PCR targeting ARM can reliably detect both high-and low-titer Wolbachia infections in Drosophila, Glossina and interspecific hybrids. Conclusions: Simple end-point PCR of ARM facilitates detection of low-titer Wolbachia A-supergroup infections. Detecting these infections previously required more elaborate procedures. Our ARM target seems to be a general feature of Wolbachia A-supergroup genomes, unlike other multicopy markers such as insertion sequences (IS).
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| 20. |
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| 21. |
- Valind, Anders, et al.
(författare)
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The fetal thymus has a unique genomic copy number profile resulting from physiological T cell receptor gene rearrangement
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Somatic mosaicism, the presence of genetically distinct cells within an organism, has been increasingly associated with human morbidity, ranging from being a cause of rare syndromes to a risk factor for common disorders such as malignancy and cardiovascular disease. Previous studies interrogating the normal prevalence of somatic mosaicism have focused on adults. We here present an estimate of the baseline frequency of somatic mosaic copy number variation (CNV) at the time around birth, by sampling eight different organs from a total of five fetuses and newborns. Overall we find a significantly lower frequency of organ specific (i.e. mosaic) CNVs as compared to adults (p = 0.003; Mann-Whitney U-test). The rate of somatic CNV in adults has been estimated to around 2.2 CNV per organ assayed. In contrast, after stringent filtering, we found no organ-private CNVs in fetuses or newborns with exception of the thymus. This organ exhibited a specific genome profile in the form of deletions resulting from polyclonal T-cell receptor rearrangements. This implies that somatic non-immune related CNVs, if present at birth, are typically confined to very small cell populations within organs.
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