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- Wang, Li-San, et al.
(författare)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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- Crary, John F., et al.
(författare)
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Primary age-related tauopathy (PART) : a common pathology associated with human aging
- 2014
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 128:6, s. 755-766
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Tidskriftsartikel (refereegranskat)abstract
- We recommend a new term, "primary age-related tauopathy" (PART), to describe a pathology that is commonly observed in the brains of aged individuals. Many autopsy studies have reported brains with neurofibrillary tangles (NFTs) that are indistinguishable from those of Alzheimer's disease (AD), in the absence of amyloid (A beta) plaques. For these "NFT+/A beta-aEuroe brains, for which formal criteria for AD neuropathologic changes are not met, the NFTs are mostly restricted to structures in the medial temporal lobe, basal forebrain, brainstem, and olfactory areas (bulb and cortex). Symptoms in persons with PART usually range from normal to amnestic cognitive changes, with only a minority exhibiting profound impairment. Because cognitive impairment is often mild, existing clinicopathologic designations, such as "tangle-only dementia" and "tangle-predominant senile dementia", are imprecise and not appropriate for most subjects. PART is almost universally detectable at autopsy among elderly individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time. Improved biomarkers and tau imaging may enable diagnosis of PART in clinical settings in the future. Indeed, recent studies have identified a common biomarker profile consisting of temporal lobe atrophy and tauopathy without evidence of A beta accumulation. For both researchers and clinicians, a revised nomenclature will raise awareness of this extremely common pathologic change while providing a conceptual foundation for future studies. Prior reports that have elucidated features of the pathologic entity we refer to as PART are discussed, and working neuropathological diagnostic criteria are proposed.
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- Nelson, Peter T., et al.
(författare)
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Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status : A Review of the Literature
- 2012
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Ingår i: Journal of Neuropathology and Experimental Neurology. - 0022-3069 .- 1554-6578. ; 71:5, s. 362-381
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Forskningsöversikt (refereegranskat)abstract
- Clinicopathologic correlation studies are critically important for the field of Alzheimer disease (AD) research. Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations. Many sources of data variability can weaken the apparent correlation between cognitive status and AD neuropathologic changes. Indeed, most persons in advanced old age have significant non-AD brain lesions that may alter cognition independently of AD. Worldwide research efforts have evaluated thousands of human subjects to assess the causes of cognitive impairment in the elderly, and these studies have been interpreted in different ways. We review the literature focusing on the correlation of AD neuropathologic changes (i.e. beta-amyloid plaques and neurofibrillary tangles) with cognitive impairment. We discuss the various patterns of brain changes that have been observed in elderly individuals to provide a perspective for understanding AD clinicopathologic correlation and conclude that evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of AA plaques and neurofibrillary tangles. Although AA plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles.
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- Van Deerlin, Vivian M, et al.
(författare)
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Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 234-239
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.
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- Aronsson, S., et al.
(författare)
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A live mindset in Live Virtual Constructive simulations : a spin-up for future LVC air combat training
- 2022
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Ingår i: The Journal of Defence Modeling and Simulation. - : SAGE Publications. - 1548-5129 .- 1557-380X.
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Tidskriftsartikel (refereegranskat)abstract
- Combining Live, Virtual, and Constructive (LVC) aircraft in the same training scenario holds promise for developing and enhancing fighter pilot training. The simulator study reported here builds on joint pilot-researcher co-design work of beyond visual range LVC training (LVC-T) scenarios to provide training value to pilots in both Live and Virtual aircraft. One fourship of pilots simulated Live entities by acting under peacetime restrictions, while other pilots acted as during regular Virtual training. The objective was to investigate pilots’ reflections on the implications of LVC-T and on the methodology used to provide hands-on experience of a plausible LVC-T scenario. The purpose is to inform the design and use of future LVC in air combat training from the perspective of training value. Results indicate that pilots are positive toward the LVC scenario design, especially the dynamics that a large-scale scenario brings to training of decision making. They indicate a high degree of presence, the need for specific regulations to enforce flight safety, and that restrictions put on the simulated Live entities had implications for the other pilots. In addition to regular Live (L) and simulator (V + C) training, LVC-T may enhance pilots’ repertoires and decision-making patterns.
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- Herrera, I., et al.
(författare)
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Applying resilience concepts in crisis management and critical infrastructures-the DARWIN project
- 2017
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Ingår i: RISK, RELIABILITY AND SAFETY: INNOVATING THEORY AND PRACTICE. - : CRC PRESS. - 9781315374987 - 9781138029972 ; , s. 2137-2144
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Konferensbidrag (refereegranskat)abstract
- Recent crises and disasters, both natural and man-made have led to the conclusion that there is a need for a resilient approach to preparing for and dealing with such events is needed. In this context, the DARWIN project aims to improve response to expected and unexpected crises affecting critical infrastructures and social structures by developing management guidelines on resilience concepts and innovative training modules for crisis management. The guidelines will cover essential resilience abilities of stakeholders to anticipate, monitor, respond, adapt, learn and evolve, to ensure efficient operation in face of crises. This paper uses a selection of resilience concepts to illustrate how resilience management guidelines can be used to understand and improve crises management. The application of the concepts to this specific case is an experiment to guide further work. This experiment shows that resilience guidelines should enable discovery on how multiple actors operate in a flexible manner and adapt in rapidly changing environment. Further work, needs to specify a set of guidelines co-developed and tested with end-users.
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