| 1. |
- 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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| 2. |
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| 3. |
- Aad, G., et al.
(författare)
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The ATLAS Simulation Infrastructure
- 2010
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 823-874
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Tidskriftsartikel (refereegranskat)abstract
- The simulation software for the ATLAS Experiment at the Large Hadron Collider is being used for large-scale production of events on the LHC Computing Grid. This simulation requires many components, from the generators that simulate particle collisions, through packages simulating the response of the various detectors and triggers. All of these components come together under the ATLAS simulation infrastructure. In this paper, that infrastructure is discussed, including that supporting the detector description, interfacing the event generation, and combining the GEANT4 simulation of the response of the individual detectors. Also described are the tools allowing the software validation, performance testing, and the validation of the simulated output against known physics processes.
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| 4. |
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| 5. |
- Bardizbanyan, Alen, 1986, et al.
(författare)
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Improving Data Access Efficiency by Using a Tagless Access Buffer (TAB)
- 2013
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Ingår i: Proceedings of the 2013 IEEE/ACM International Symposium on Code Generation and Optimization, CGO 2013. - 9781467355254 ; , s. 269-279
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Konferensbidrag (refereegranskat)abstract
- The need for energy efficiency continues to grow for many classes of processors, including those for which performance remains vital. Data cache is crucial for good performance, but it also represents a significant portion of the processor's energy expenditure. We describe the implementation and use of a tagless access buffer (TAB) that greatly improves data access energy efficiency while slightly improving performance. The compiler recognizes memory reference patterns within loops and allocates these references to a TAB. This combined hardware/software approach reduces energy usage by (1) replacing many level-one data cache (L1D) accesses with accesses to the smaller, more power-efficient TAB; (2) removing the need to perform tag checks or data translation lookaside buffer (DTLB) lookups for TAB accesses; and (3) reducing DTLB lookups when transferring data between the L1D and the TAB. Accesses to the TAB occur earlier in the pipeline, and data lines are prefetched from lower memory levels, which result in asmall performance improvement. In addition, we can avoid many unnecessary block transfers between other memory hierarchy levels by characterizing how data in the TAB are used. With a combined size equal to that of a conventional 32-entry register file, a four-entry TAB eliminates 40% of L1D accesses and 42% of DTLB accesses, on average. This configuration reduces data-access related energy by 35% while simultaneously decreasing execution time by 3%.
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| 6. |
- 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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| 7. |
- Footman, Katharine, et al.
(författare)
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Smoking cessation and desire to stop smoking in nine countries of the former soviet union
- 2013
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Ingår i: Nicotine & tobacco research. - : Oxford University Press (OUP). - 1462-2203 .- 1469-994X. ; 15:9, s. 1628-1633
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Smoking rates and corresponding levels of premature mortality from smoking-related diseases in the former Soviet Union (fSU) are among the highest in the world. To reduce this health burden, greater focus on smoking cessation is needed, but little is currently known about rates and characteristics of cessation in the fSU. Methods: Nationally representative household survey data from a cross-sectional study of 18,000 respondents in Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia, and Ukraine were analyzed to describe patterns of desire and action taken to stop smoking, quit ratios (former ever-smokers as a percent of ever-smokers, without a specified recall period), and help used to stop smoking. Multivariate logistic regression was used to analyze characteristics associated with smoking cessation and desire to stop smoking. Results: Quit ratios varied from 10.5% in Azerbaijan to 37.6% in Belarus. About 67.2% of respondents expressed a desire to quit, and 64.9% had taken action and tried to stop. The use of help to quit was extremely low (12.6%). Characteristics associated with cessation included being female, over 60, with higher education, poorer health, lower alcohol dependency, higher knowledge of tobacco's health effects, and support for tobacco control. Characteristics associated with desire to stop smoking among current smokers included younger age, poorer health, greater knowledge of tobacco's health effects, and support for tobacco control. Conclusions: Quit ratios are low in the fSU but there is widespread desire to stop smoking. Stronger tobacco control and cessation support are urgently required to reduce smoking prevalence and associated premature mortality.
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| 8. |
- Gallagher, Michael D., et al.
(författare)
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TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions
- 2014
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 127:3, s. 407-418
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Tidskriftsartikel (refereegranskat)abstract
- Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14), with the major allele correlated with later age at death (p = 0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that the major allele associates with later age at death (p = 0.016), as well as later age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease.
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| 9. |
- 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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| 10. |
- Roberts, Bayard, et al.
(författare)
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Changes in Smoking Prevalence in 8 Countries of the Former Soviet Union Between 2001 and 2010
- 2012
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Ingår i: American Journal of Public Health. - 0090-0036 .- 1541-0048. ; 102:7, s. 1320-1328
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. We sought to present new data on smoking prevalence in 8 countries, analyze prevalence changes between 2001 and 2010, and examine trend variance by age, location, education level, and household economic status. Methods. We conducted cross-sectional household surveys in 2010 in Armenia, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia, and Ukraine. We compared smoking prevalence with a related 2001 study for the different countries and population subgroups, and also calculated the adjusted prevalence rate ratios of smoking. Results. All-age 2010 smoking prevalence among men ranged from 39% (Moldova) to 59% (Armenia), and among women from 2% (Armenia) to 16% (Russia). There was a significantly lower smoking prevalence among men in 2010 compared with 2001 in Belarus, Kazakhstan, Kyrgyzstan, and Russia, but not for women in any country. For all countries combined, there was a significantly lower smoking prevalence in 2010 than in 2001 for men aged 18 to 39 years and men with a good or average economic situation. Conclusions. Smoking prevalence appears to have stabilized and may be declining in younger groups, but remains extremely high among men, especially those in lower socioeconomic groups. (Am J Public Health. 2012;102:1320-1328. doi:10.2105/AJPH.2011.300547)
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