| 1. |
- Benisty, S, et al.
(författare)
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Location of lacunar infarcts correlates with cognition in a sample of non-disabled subjects with age-related white-matter changes: the LADIS study.
- 2009
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 80:5, s. 478-83
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: In cerebral small vessel disease, white-matter hyperintensities (WMH) and lacunes are both related to cognition. Still, their respective contribution in older people remains unclear. The purpose of this study is to assess the topographic distribution of lacunes and determine whether it has an impact on cognitive functions in a sample of non-disabled patients with age-related white-matter changes. METHODS: Data were drawn from the baseline evaluation of the LADIS (Leucoaraioisis and Disability study) cohort of non-disabled subjects beyond 65 years of age. The neuropsychological evaluation was based on the Mini Mental Status Examination (MMSE), a modified Alzheimer Diseases Assessment Scale for global cognitive functions, and compound Z scores for memory, executive functions, speed and motor control. WMH were rated according to the Fazekas scale; the number of lacunes was assessed in the following areas: lobar white matter, putamen/pallidum, thalamus, caudate nucleus, internal/external capsule, infratentorial areas. An analysis of covariance was performed after adjustment for possible confounders. RESULTS: Among 633 subjects, 47% had at least one lacune (31% at least one within basal ganglia). The presence of lacunes in the thalamus was associated with lower scores of MMSE (beta = -0.61; p = 0.043), and worse compound scores for speed and motor control (beta = -0.25; p = 0.006), executive functions (beta = -0.19; p = 0.022) independently of the cognitive impact of WMH. There was also a significant negative association between the presence of lacunes in putamen/pallidum and the memory compound Z score (beta = -0.13; p = 0.038). By contrast, no significant negative association was found between cognitive parameters and the presence of lacunes in internal capsule, lobar white matter and caudate nucleus. CONCLUSION: In non-disabled elderly subjects with leucoaraisosis, the location of lacunes within subcortical grey matter is a determinant of cognitive impairment, independently of the extent of WMH.
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| 2. |
- Sjölander, Annica, 1969, et al.
(författare)
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The PPAR-alpha gene in Alzheimer's disease: lack of replication of earlier association.
- 2009
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 30:4, s. 666-8
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a single nucleotide polymorphism (SNP, rs1800206) in the peroxisome proliferator-activated receptor alpha (PPAR-alpha) gene has been proposed to be associated with Alzheimer's disease (AD). To verify this finding, we analyzed the PPAR-alpha SNP in 461 patients with AD and 1395 controls. In subgroups, PPAR-alpha gene data could be investigated in relation to biochemical and neuropathological markers for AD. We found no significant differences in genotype or allele distributions between AD patients and controls. None of the PPAR-alpha gene variants influenced markers for AD.
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| 3. |
- Curtin, W. A., et al.
(författare)
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Multi-scale plasticity modeling : Coupled discrete dislocation and continuum crystal plasticity
- 2008
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Ingår i: Advances in Heterogeneous Material Mechanics 2008 - 2nd International Conference on Heterogeneous Material Mechanics, ICHMM 2008. - 9781932078800 ; , s. 320-320
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Konferensbidrag (refereegranskat)abstract
- A hierarchical multiscale model that couples a region of material described by discrete dislocation plasticity1 to a surrounding region described by conventional crystal plasticity is presented. The coupled model captures size-dependent plasticity phenomena, such as dislocation structuring and formation of geometrically necessary dislocations, that can occur at the micron scale while also capturing the plastic flow, and associated energy dissipation, at much larger scales where size-dependent effects are minimal. The key to the model is the treatment of the interface between the discrete and continuum regions, where continuity of tractions and displacements is maintained in an average sense and the flow of burgers vector via "passing" of discrete dislocations is managed. The model is validated through uniaxial plane-strain tension tests which show that the coupled model deforms similarly to both single-scale models. The multiscale model is then applied to study crack growth, where both near-tip dislocation structures and far-field plastic dissipation are crucial to the overall toughening. Results show that the toughening is nearly independent of the size of the discrete dislocation plasticity region around the crack tip down to 5um, simultaneously validating the model and identifying the lengths scales over which size dependence plays a role in this problem. The multiscale model reduces the computational burden of discrete dislocation plasticity modeling substantially with little or no loss of fidelity in the predictions of material behavior, thereby greatly extending the range of discrete dislocation modeling. Future work will combine this method with the Coupled Atomistic/Discrete-Dislocation2 model developed by one of the co-authors, leading to a true atom-to-continuum multiscale model for metallic materials.
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| 4. |
- Dyrby, Tim B, et al.
(författare)
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Segmentation of age-related white matter changes in a clinical multi-center study.
- 2008
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119. ; 41:2, s. 335-45
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Tidskriftsartikel (refereegranskat)abstract
- Age-related white matter changes (WMC) are thought to be a marker of vascular pathology, and have been associated with motor and cognitive deficits. In the present study, an optimized artificial neural network was used as an automatic segmentation method to produce probabilistic maps of WMC in a clinical multi-center study. The neural network uses information from T1- and T2-weighted and fluid attenuation inversion recovery (FLAIR) magnetic resonance (MR) scans, neighboring voxels and spatial location. Generalizability of the neural network was optimized by including the Optimal Brain Damage (OBD) pruning method in the training stage. Six optimized neural networks were produced to investigate the impact of different input information on WMC segmentation. The automatic segmentation method was applied to MR scans of 362 non-demented elderly subjects from 11 centers in the European multi-center study Leukoaraiosis And Disability (LADIS). Semi-manually delineated WMC were used for validating the segmentation produced by the neural networks. The neural network segmentation demonstrated high consistency between subjects and centers, making it a promising technique for large studies. For WMC volumes less than 10 ml, an increasing discrepancy between semi-manual and neural network segmentation was observed using the similarity index (SI) measure. The use of all three image modalities significantly improved cross-center generalizability compared to neural networks using the FLAIR image only. Expert knowledge not available to the neural networks was a minor source of discrepancy, while variation in MR scan quality constituted the largest source of error.
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| 5. |
- Gouw, Alida A, et al.
(författare)
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Progression of white matter hyperintensities and incidence of new lacunes over a 3-year period: the Leukoaraiosis and Disability study.
- 2008
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Ingår i: Stroke; a journal of cerebral circulation. - 1524-4628. ; 39:5, s. 1414-20
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: We studied the natural course of white matter hyperintensities (WMH) and lacunes, the main MRI representatives of small vessel disease, over time and evaluated possible predictors for their development. METHODS: Baseline and repeat MRI (3-year follow-up) were collected within the multicenter, multinational Leukoaraiosis and Disability study (n=396). Baseline WMH were scored on MRI by the Fazekas scale and the Scheltens scale. WMH progression was assessed using the modified Rotterdam Progression scale (absence/presence of progression in 9 brain regions). Baseline and new lacunes were counted per region. WMH and lacunes at baseline and vascular risk factors were evaluated as predictors of WMH progression and new lacunes. RESULTS: WMH progressed (mean+/-SD=1.9+/-1.8) mostly in the subcortical white matter, where WMH was also most prevalent at baseline. The majority of new lacunes, which were found in 19% of the subjects (maximum=9), also appeared in the subcortical white matter, mainly of the frontal lobes, whereas most baseline lacunes were located in the basal ganglia. Baseline WMH and lacunes predicted both WMH progression and new lacunes. Furthermore, previous stroke, diabetes, and blood glucose were risk factors for WMH progression. Male sex, hypertension, systolic blood pressure, previous stroke, body mass index, high-density lipoprotein, and triglyceride levels were risk factors for new lacunes. CONCLUSIONS: WMH and lacunes progressed over time, predominantly in the subcortical white matter. Progression was observed especially in subjects with considerable WMH and lacunes at baseline. Moreover, the presence of vascular risk factors at baseline predicted WMH progression and new lacunes over a 3-year period.
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| 6. |
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| 7. |
- Lindholm Dahlstrand, Åsa, 1964-, et al.
(författare)
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Internal venturing : Sponsored corporate spin-offs in Sweden
- 2007
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Ingår i: International Business Geography. - London : Routledge. - 9780415429191 - 0415429196 - 9780203939208 ; , s. 97-116
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Quite a number of earlier studies have found that the majority of new technology-based firms are spin-offs from existing organizations, usually established in the geographical neighborhood of the parent (Dorfman 1983; Roberts 1991; Saxenian 1994; Sternberg 1996; Keeble 1997; Lindholm Dahlstrand 1997, 2001; Lindholm Dahlstrand and Dahlander 2003). Since established corporations are responsible for a large amount of R&D in many industrialized regions and countries, they are also likely to play a key role in evolving new technologies and future growth. However, even though knowledge-intensive organizations such as large technology-based corporations and universities are often found as sources of technological innovations, they have frequently demonstrated difficulties in realizing or exploiting the full value of such innovations (Abernathy and Utterback 1978; Pavitt 1991; Bower and Christensen 1995; Rivette and Kline 2000). Reasons for this may be: a financial, e.g. they cannot find the capital to explore further; b organizational, e.g. the present organization is not suitable for exploitation; or c related to opportunity recognition, i.e. the established firm cannot see an underlying opportunity that may be appropriated with its resource-base.
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| 8. |
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| 9. |
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| 10. |
- Ryberg, C, et al.
(författare)
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White matter changes contribute to corpus callosum atrophy in the elderly: the LADIS study.
- 2008
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Ingår i: AJNR. American journal of neuroradiology. - 1936-959X. ; 29:8, s. 1498-504
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: The corpus callosum (CC) is the most important structure involved in the transmission of interhemispheric information. The aim of this study was to investigate the potential correlation between regional age-related white matter changes (ARWMC) and atrophy of CC in elderly subjects. MATERIALS AND METHODS: In 578 subjects with ARWMC from the Leukoaraiosis And DISability (LADIS) study, the cross-sectional area of the CC was automatically segmented on the normalized midsagittal MR imaging section and subdivided into 5 regions. The ARWMC volumes were measured quantitatively by using a semiautomated technique and segmented into 6 brain regions. RESULTS: Significant correlation between the area of the rostrum and splenium regions of the CC and the ARWMC load in most brain regions was identified. This correlation persisted after correction for global atrophy. CONCLUSION: Increasing loads of ARWMC volume were significantly correlated with atrophy of the CC and its subregions in nondisabled elderly subjects with leukoaraiosis. However, the pattern of correlation between CC subregions and ARWMC was not specifically related to the topographic location of ARWMC. The results suggest that ARWMC may lead to a gradual loss of CC tissue.
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