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| 2. |
- Lockhart, Samuel N, et al.
(författare)
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Amyloid and Tau PET Demonstrate Region-Specific Associations in Normal Older People.
- 2017
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Ingår i: NeuroImage. - : Elsevier BV. - 1095-9572 .- 1053-8119. ; 150, s. 191-199
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Tidskriftsartikel (refereegranskat)abstract
- β-amyloid (Aβ) and tau pathology become increasingly prevalent with age, however, the spatial relationship between the two pathologies remains unknown. We examined local (same region) and non-local (different region) associations between these 2 aggregated proteins in 46 normal older adults using [(18)F]AV-1451 (for tau) and [(11)C]PiB (for Aβ) positron emission tomography (PET) and 1.5T magnetic resonance imaging (MRI) images. While local voxelwise analyses showed associations between PiB and AV-1451 tracer largely in the temporal lobes, k-means clustering revealed that some of these associations were driven by regions with low tracer retention. We followed this up with a whole-brain region-by-region (local and non-local) partial correlational analysis. We calculated each participant's mean AV-1451 and PiB uptake values within 87 regions of interest (ROI). Pairwise ROI analysis demonstrated many positive PiB-AV-1451 associations. Importantly, strong positive partial correlations (controlling for age, sex, and global gray matter fraction, p < .01) were identified between PiB in multiple regions of association cortex and AV-1451 in temporal cortical ROIs. There were also less frequent and weaker positive associations of regional PiB with frontoparietal AV-1451 uptake. Particularly in temporal lobe ROIs, AV-1451 uptake was strongly predicted by PiB across multiple ROI locations. These data indicate that Aβ and tau pathology show significant local and non-local regional associations among cognitively normal elderly, with increased PiB uptake throughout the cortex correlating with increased temporal lobe AV-1451 uptake. The spatial relationship between Aβ and tau accumulation does not appear to be specific to Aβ location, suggesting a regional vulnerability of temporal brain regions to tau accumulation regardless of where Aβ accumulates.
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| 4. |
- Ossenkoppele, R., et al.
(författare)
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Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease
- 2016
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 139, s. 1551-1567
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Tidskriftsartikel (refereegranskat)abstract
- The PET tracer [F-18]-AV-1451 allows visualization of tau pathology in living subjects. Ossenkoppele et al. employ the tracer in patients with distinct Alzheimer's disease variants to investigate correlates of tau deposition. Pathological aggregation of tau, but not amyloid-beta, is linked to patterns of neurodegeneration and clinical manifestations of Alzheimer's disease.See Sarazin et al. (doi:10.1093/brain/aww041) for a scientific commentary on this article. The PET tracer [F-18]-AV-1451 allows visualization of tau pathology in living subjects. Ossenkoppele et al. employ the tracer in patients with distinct Alzheimer's disease variants to investigate correlates of tau deposition. Pathological aggregation of tau, but not amyloid-beta, is linked to patterns of neurodegeneration and clinical manifestations of Alzheimer's disease.The advent of the positron emission tomography tracer F-18-AV1451 provides the unique opportunity to visualize the regional distribution of tau pathology in the living human brain. In this study, we tested the hypothesis that tau pathology is closely linked to symptomatology and patterns of glucose hypometabolism in Alzheimer's disease, in contrast to the more diffuse distribution of amyloid-beta pathology. We included 20 patients meeting criteria for probable Alzheimer's disease dementia or mild cognitive impairment due to Alzheimer's disease, presenting with a variety of clinical phenotypes, and 15 amyloid-beta-negative cognitively normal individuals, who underwent F-18-AV1451 (tau), C-11-PiB (amyloid-beta) and F-18-FDG (glucose metabolism) positron emission tomography, apolipoprotein E (APOE) genotyping and neuropsychological testing. Voxel-wise contrasts against controls (at P < 0.05 family-wise error corrected) showed that F-18-AV1451 and F-18-FDG patterns in patients with posterior cortical atrophy ('visual variant of Alzheimer's disease', n = 7) specifically targeted the clinically affected posterior brain regions, while C-11-PiB bound diffusely throughout the neocortex. Patients with an amnestic-predominant presentation (n = 5) showed highest F-18-AV1451 retention in medial temporal and lateral temporoparietal regions. Patients with logopenic variant primary progressive aphasia ('language variant of Alzheimer's disease', n = 5) demonstrated asymmetric left greater than right hemisphere F-18-AV1451 uptake in three of five patients. Across 30 FreeSurfer-defined regions of interest in 16 Alzheimer's disease patients with all three positron emission tomography scans available, there was a strong negative association between F-18-AV1451 and F-18-FDG uptake (Pearson's r = -0.49 +/- 0.07, P < 0.001) and less pronounced positive associations between C-11-PiB and F-18-FDG (Pearson's r = 0.16 +/- 0.09, P < 0.001) and F-18-AV1451 and C-11-PiB (Pearson's r = 0.18 +/- 0.09, P < 0.001). Voxel-wise linear regressions thresholded at P < 0.05 (uncorrected) showed that, across all patients, younger age was associated with greater F-18-AV1451 uptake in wide regions of the neocortex, while older age was associated with increased F-18-AV1451 in the medial temporal lobe. APOE I mu 4 carriers showed greater temporal and parietal F-18-AV1451 uptake than non-carriers. Finally, worse performance on domain-specific neuropsychological tests was associated with greater F-18-AV1451 uptake in key regions implicated in memory (medial temporal lobes), visuospatial function (occipital, right temporoparietal cortex) and language (left > right temporoparietal cortex). In conclusion, tau imaging-contrary to amyloid-beta imaging-shows a strong regional association with clinical and anatomical heterogeneity in Alzheimer's disease. Although preliminary, these results are consistent with and expand upon findings from post-mortem, animal and cerebrospinal fluid studies, and suggest that the pathological aggregation of tau is closely linked to patterns of neurodegeneration and clinical manifestations of Alzheimer's disease.
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| 5. |
- Wu, Han-Chun, et al.
(författare)
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Large positive in-plane magnetoresistance induced by localized states at nanodomain boundaries in graphene
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Graphene supports long spin lifetimes and long diffusion lengths at room temperature, making it highly promising for spintronics. However, making graphene magnetic remains a principal challenge despite the many proposed solutions. Among these, graphene with zig-zag edges and ripples are the most promising candidates, as zig-zag edges are predicted to host spin-polarized electronic states, and spin-orbit coupling can be induced by ripples. Here we investigate the magnetoresistance of graphene grown on technologically relevant SiC/Si(001) wafers, where inherent nanodomain boundaries sandwich zig-zag structures between adjacent ripples of large curvature. Localized states at the nanodomain boundaries result in an unprecedented positive in-plane magnetoresistance with a strong temperature dependence. Our work may offer a tantalizing way to add the spin degree of freedom to graphene.
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| 6. |
- Wu, Han-Chun, et al.
(författare)
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Transport Gap Opening and High On-Off Current Ratio in Trilayer Graphene with Self-Aligned Nanodomain Boundaries.
- 2015
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 9:9, s. 8967-8975
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Tidskriftsartikel (refereegranskat)abstract
- Trilayer graphene exhibits exceptional electronic properties that are of interest both for fundamental science and for technological applications. The ability to achieve a high on-off current ratio is the central question in this field. Here, we propose a simple method to achieve a current on-off ratio of 10(4) by opening a transport gap in Bernal-stacked trilayer graphene. We synthesized Bernal-stacked trilayer graphene with self-aligned periodic nanodomain boundaries (NBs) on the technologically relevant vicinal cubic-SiC(001) substrate and performed electrical measurements. Our low-temperature transport measurements clearly demonstrate that the self-aligned periodic NBs can induce a charge transport gap greater than 1.3 eV. More remarkably, the transport gap of ∼0.4 eV persists even at 100 K. Our results show the feasibility of creating new electronic nanostructures with high on-off current ratios using graphene on cubic-SiC.
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| 8. |
- Al-Janabi, Hareth, et al.
(författare)
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Development of a self-report measure of capability wellbeing for adults : the ICECAP-A.
- 2012
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Ingår i: Quality of Life Research. - : Springer Science and Business Media LLC. - 0962-9343 .- 1573-2649. ; 21:1, s. 167-76
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The benefits of health and social care are not confined to patient health alone and therefore broader measures of wellbeing may be useful for economic evaluation. This paper reports the development of a simple measure of capability wellbeing for adults (ICECAP-A).METHODS: In-depth, informant-led, interviews to identify the attributes of capability wellbeing were conducted with 36 adults in the UK. Eighteen semi-structured, repeat interviews were carried out to develop a capability-based descriptive system for the measure. Informants were purposively selected to ensure variation in socio-economic status, age, sex, ethnicity and health. Data analysis was carried out inductively and iteratively alongside interviews, and findings were used to shape the questions in later interviews.RESULTS: Five over-arching attributes of capability wellbeing were identified for the measure: "stability", "attachment", "achievement", "autonomy" and "enjoyment". One item, with four response categories, was developed for each attribute for the ICECAP-A descriptive system.CONCLUSIONS: The ICECAP-A capability measure represents a departure from traditional health economics outcome measures, by treating health status as an influence over broader attributes of capability wellbeing. Further work is required to value and validate the attributes and test the sensitivity of the ICECAP-A to healthcare interventions.
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| 9. |
- Al-Janabi, Hareth, et al.
(författare)
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What do people value when they provide unpaid care for an older person? A meta-ethnography with interview follow-up.
- 2008
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Ingår i: Social Science and Medicine. - : Elsevier BV. - 0277-9536 .- 1873-5347. ; 67:1, s. 111-21
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Tidskriftsartikel (refereegranskat)abstract
- Government policies to shift care into the community and demographic changes mean that unpaid (informal) carers will increasingly be relied on to deliver care, particularly to older people. As a result, careful consideration needs to be given to informal care in economic evaluations. Current methods for economic evaluations may neglect important aspects of informal care. This paper reports the development of a simple measure of the caring experience for use in economic evaluations. A meta-ethnography was used to reduce qualitative research to six conceptual attributes of caring. Sixteen semi-structured interviews were then conducted with carers of older people, to check the attributes and develop them into the measure. Six attributes of the caring experience comprise the final measure: getting on, organisational assistance, social support, activities, control, and fulfilment. The final measure (the Carer Experience Scale) focuses on the process of providing care, rather than health outcomes from caring. Arguably this provides a more direct assessment of carers' welfare. Following work to test and scale the measure, it may offer a promising way of incorporating the impact on carers in economic evaluations.
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