| 2571. |
- Nichols, Emma, et al.
(författare)
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Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
- 2019
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:1, s. 88-106
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Tidskriftsartikel (refereegranskat)abstract
- Background: The number of individuals living with dementia is increasing, negatively affecting families, communities, and health-care systems around the world. A successful response to these challenges requires an accurate understanding of the dementia disease burden. We aimed to present the first detailed analysis of the global prevalence, mortality, and overall burden of dementia as captured by the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, and highlight the most important messages for clinicians and neurologists.Methods: GBD 2016 obtained data on dementia from vital registration systems, published scientific literature and surveys, and data from health-service encounters on deaths, excess mortality, prevalence, and incidence from 195 countries and territories from 1990 to 2016, through systematic review and additional data-seeking efforts. To correct for differences in cause of death coding across time and locations, we modelled mortality due to dementia using prevalence data and estimates of excess mortality derived from countries that were most likely to code deaths to dementia relative to prevalence. Data were analysed by standardised methods to estimate deaths, prevalence, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs; computed as the sum of YLLs and YLDs), and the fractions of these metrics that were attributable to four risk factors that met GBD criteria for assessment (high body-mass index [BMI], high fasting plasma glucose, smoking, and a diet high in sugarsweetened beverages).Findings: In 2016, the global number of individuals who lived with dementia was 43.8 million (95% uncertainty interval [UI] 3 7. 8-51.0), increased from 20.2 million (17. 4-23 5) in 1990. This increase of 117% (95% UI 114-121) contrasted with a minor increase in age-standardised prevalence of 1.7% (1.0-2.4), from 701 cases (95% UI 602-815) per 100 000 population in 1990 to 712 cases (614-828) per 100 000 population in 2016. More women than men had dementia in 2016 (27.0 million, 95% UI 23 .3-31. 4, vs 16.8 million, 14.4-19.6), and dementia was the fifth leading cause of death globally, accounting for 2.4 million (95% UI 2.1-2.8) deaths. Overall, 28.8 million (95% UI 24. 5-34. 0) DALYs were attributed to dementia; 6.4 million (95% UI 3 .4-10. 5) of these could be attributed to the modifiable GBD risk factors of high BMI, high fasting plasma glucose, smoking, and a high intake of sugar-sweetened beverages.Interpretation: The global number of people living with dementia more than doubled from 1990 to 2016, mainly due to increases in population ageing and growth. Although differences in coding for causes of death and the heterogeneity in case-ascertainment methods constitute major challenges to the estimation of the burden of dementia, future analyses should improve on the methods for the correction of these biases. Until breakthroughs are made in prevention or curative treatment, dementia will constitute an increasing challenge to health-care systems worldwide.
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| 2572. |
- Nie, Jin, et al.
(författare)
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Influence of geometric parameters of passenger car's front-end structure on the head dynamic response and injury risk of pedestrian
- 2014
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Ingår i: Qiche Gongcheng/Automotive Engineering. - 1000-680X. ; 36:12, s. 1473-1482
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Tidskriftsartikel (refereegranskat)abstract
- The AIS 3+ injury risks of pedestrians in their collisions with different passenger cars are studied by in-depth analysis on accident data, and the effects of the front-end structure of passenger car on pedestrian injuries and their causative factors are investigated by simulation analysis. With 128 makes of passenger cars from the market in China as samples, the main geometric dimensions of front-end structure of sedans, SUVs and minivans are compared. Based on detailed pedestrian accident data, the distribution and severity of injuries in all kinds of car-pedestrian accidents are statistically analyzed, and the relationship between vehicle impact speed and pedestrian casualty risks are determined. The pedestrian head impact conditions of different makes of cars are compared at different impact speeds of 20, 40 and 60 km/h respectively with multi-body dynamics models. The results show that the front-end geometric shape of passenger cars has obvious influence on the dynamics response and injury risk of pedestrians' head. The findings from the study could provide certain theoretical basis for better developing the pedestrian protection measures for different types of passenger cars.
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| 2573. |
- Niessen, Peter, et al.
(författare)
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Recent results from the amanda experiment
- 2003
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Ingår i: Proceedings of 38th Rencontres de Moriond on Electroweak Interactions and Unified Theories 15-22 Mar 2003. Les Arcs, France.
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Konferensbidrag (refereegranskat)abstract
- AMANDA (Antarctic Muon And Neutrino Detector Array) is a neutrino telescope built under the southern polar icecap and its scope is to explore the possibility to detect high energy cosmic neutrinos. This should generate insight into the powerful celestial objects where acceleration mechanisms can bring up to 10 20 eV. We describe the achievements and results from the AMANDA-B10 prototype and the preliminary results from the current AMANDA-II detector which show dramatic increase in sensitivity.
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| 2574. |
- Nilsson, C. L., et al.
(författare)
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Chromosome 19 Annotations with Disease Speciation: A First Report from the Global Research Consortium
- 2013
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:1, s. 134-149
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Tidskriftsartikel (refereegranskat)abstract
- A first research development progress report of the Chromosome 19 Consortium with members from Sweden, Norway, Spain, United States, China and India, a part of the Chromosome-centric Human Proteome Project (C-HPP) global initiative, is presented (http://www.c-hpp.org). From the chromosome 19 peptide-targeted library constituting 6159 peptides, a pilot study was conducted using a subset with 125 isotope-labeled peptides. We applied an annotation strategy with triple quadrupole, ESI-Qtrap, and MALDI mass spectrometry platforms, comparing the quality of data within and in between these instrumental set-ups. LC–MS conditions were outlined by multiplex assay developments, followed by MRM assay developments. SRM was applied to biobank samples, quantifying kallikrein 3 (prostate specific antigen) in plasma from prostate cancer patients. The antibody production has been initiated for more than 1200 genes from the entire chromosome 19, and the progress developments are presented. We developed a dedicated transcript microarray to serve as the mRNA identifier by screening cancer cell lines. NAPPA protein arrays were built to align with the transcript data with the Chromosome 19 NAPPA chip, dedicated to 90 proteins, as the first development delivery. We have introduced an IT-infrastructure utilizing a LIMS system that serves as the key interface for the research teams to share and explore data generated within the project. The cross-site data repository will form the basis for sample processing, including biological samples as well as patient samples from national Biobanks.
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| 2575. |
- Nitschke, S., et al.
(författare)
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Glycogen synthase downregulation rescues the amylopectinosis of murine RBCK1 deficiency
- 2022
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:7, s. 2361-2377
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Tidskriftsartikel (refereegranskat)abstract
- Longer glucan chains tend to precipitate. Glycogen, by far the largest mammalian glucan and the largest molecule in the cytosol with up to 55 000 glucoses, does not, due to a highly regularly branched spherical structure that allows it to be perfused with cytosol. Aberrant construction of glycogen leads it to precipitate, accumulate into polyglucosan bodies that resemble plant starch amylopectin and cause disease. This pathology, amylopectinosis, is caused by mutations in a series of single genes whose functions are under active study toward understanding the mechanisms of proper glycogen construction. Concurrently, we are characterizing the physicochemical particularities of glycogen and polyglucosans associated with each gene. These genes include GBE1, EPM2A and EPM2B, which respectively encode the glycogen branching enzyme, the glycogen phosphatase laforin and the laforin-interacting E3 ubiquitin ligase malin, for which an unequivocal function is not yet known. Mutations in GBE1 cause a motor neuron disease (adult polyglucosan body disease), and mutations in EPM2A or EPM2B a fatal progressive myoclonus epilepsy (Lafora disease). RBCK1 deficiency causes an amylopectinosis with fatal skeletal and cardiac myopathy (polyglucosan body myopathy 1, OMIM# 615895). RBCK1 is a component of the linear ubiquitin chain assembly complex, with unique functions including generating linear ubiquitin chains and ubiquitinating hydroxyl (versus canonical amine) residues, including of glycogen. In a mouse model we now show (i) that the amylopectinosis of RBCK1 deficiency, like in adult polyglucosan body disease and Lafora disease, affects the brain; (ii) that RBCK1 deficiency glycogen, like in adult polyglucosan body disease and Lafora disease, has overlong branches; (iii) that unlike adult polyglucosan body disease but like Lafora disease, RBCK1 deficiency glycogen is hyperphosphorylated; and finally (iv) that unlike laforin-deficient Lafora disease but like malin-deficient Lafora disease, RBCK1 deficiency's glycogen hyperphosphorylation is limited to precipitated polyglucosans. In summary, the fundamental glycogen pathology of RBCK1 deficiency recapitulates that of malin-deficient Lafora disease. Additionally, we uncover sex and genetic background effects in RBCK1 deficiency on organ-and brain-region specific amylopectinoses, and in the brain on consequent neuroinflammation and behavioural deficits. Finally, we exploit the portion of the basic glycogen pathology that is common to adult polyglucosan body disease, both forms of Lafora disease and RBCK1 deficiency, namely overlong branches, to show that a unified approach based on downregulating glycogen synthase, the enzyme that elongates glycogen branches, can rescue all four diseases.
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| 2576. |
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| 2577. |
- Niu, X. R., et al.
(författare)
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Elevation-Dependent Warming Over the Tibetan Plateau From an Ensemble of CORDEX-EA Regional Climate Simulations
- 2021
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Ingår i: Journal of Geophysical Research-Atmospheres. - : American Geophysical Union (AGU). - 2169-897X .- 2169-8996. ; 126:9
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Tidskriftsartikel (refereegranskat)abstract
- Under the Coordinated Regional Climate Downscaling Experiments-East Asia (CORDEX-EA-II), the outputs from two regional climate models (RCMs) driven by four global climate models (GCMs) are used to investigate the characteristics and possible mechanisms of the projected elevation-dependent warming (EDW) over the Tibetan Plateau (TP) under the Representative Concentration Pathway emission scenario 8.5 (RCP8.5). Results show that widespread warming over the TP is projected with considerable disagreements in warming intensity and the maximum warming center among RCMs. The largest spread in the surface air temperature (T-as) projections is found above 5,000 m, indicating that a large uncertainty exists over the higher elevations. A marked EDW signal over the TP is simulated under the RCP 8.5 by the multi-RCM ensemble mean for all seasons, particularly in autumn. Based on the analysis of the surface energy budget, it is found that the surface albedo feedback (SAF) is the primary contributor to EDW and acts as the main source of uncertainty in EDW projections among RCMs. The downward longwave radiation (DLW) is found to be the dominant factor in regulating T-as change over the TP, and its contribution to EDW is model-dependent. Furthermore, the structure and magnitude of projected EDW are sensitive to the RCM physics and driving GCM, as they can alter the projections of snow cover and albedo, which modulate the simulated SAF and its effect on EDW. Additionally, RegCM4 shows a higher sensitivity to the anthropogenic greenhouse forcing than WRF, evidenced by the larger temperature projections and stronger EDW signal in RegCM4.
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| 2578. |
- Nolan, P. L., et al.
(författare)
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Fermi large area telescope second source catalog
- 2012
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 199:2, s. 31-
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Tidskriftsartikel (refereegranskat)abstract
- We present the second catalog of high-energy gamma-ray sources detected by the Large Area Telescope (LAT), the primary science instrument on the Fermi Gamma-ray Space Telescope (Fermi), derived from data taken during the first 24 months of the science phase of the mission, which began on 2008 August 4. Source detection is based on the average flux over the 24 month period. The second Fermi-LAT catalog (2FGL) includes source location regions, defined in terms of elliptical fits to the 95% confidence regions and spectral fits in terms of power-law, exponentially cutoff power-law, or log-normal forms. Also included are flux measurements in five energy bands and light curves on monthly intervals for each source. Twelve sources in the catalog are modeled as spatially extended. We provide a detailed comparison of the results from this catalog with those from the first Fermi-LAT catalog (1FGL). Although the diffuse Galactic and isotropic models used in the 2FGL analysis are improved compared to the 1FGL catalog, we attach caution flags to 162 of the sources to indicate possible confusion with residual imperfections in the diffuse model. The 2FGL catalog contains 1873 sources detected and characterized in the 100 MeV to 100 GeV range of which we consider 127 as being firmly identified and 1171 as being reliably associated with counterparts of known or likely gamma-ray-producing source classes.
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| 2579. |
- Nookuea, Worrada, et al.
(författare)
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Viscosity Data of Aqueous MDEA-[Bmim][BF4] Solutions Within Carbon Capture Operating Conditions
- 2017
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Ingår i: 8th International Conference on Applied Energy, ICAE2016, 8-11 October 2016, Beijing, China. - : Elsevier. ; 105, s. 4581-4586
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Konferensbidrag (refereegranskat)abstract
- Post-combustion capture with chemical absorption shows higher potential for commercial scale application compared with other technologies. To capture CO2 from the industrial and power plant's flue gases, aqueous alkanolamine solutions are widely used. However, several drawbacks from utilizing the aqueous alkanolamines such as MEA still need to be solved. For example, alkanolamine solutions require intensive energy for regeneration and cause severe corrosion to the equipment though they have high reactivity in capturing CO2. Ionic liquids have been of interest in the recent development of chemical absorption according to their unique characteristics including wide liquid range, negligible volatility and thermal stability. However, due to their high price, high viscosity and low absorption capacity compared to alkanolamines, ionic liquids are still non-desirable for industrial applications. One possible solution to improve the performance of ionic liquids is to use mixtures of ionic liquids and alkanolamines. For a better understanding of the absorption using the mixture of aqueous alkanolamines and ionic liquids, the knowledge of thermo-physical properties of the solutions, especially the viscosity and density are of importance. This paper reports the measured viscosity of MDEA-[Bmim][BF4] aqueous mixtures at various temperatures and concentrations. It was found that the viscosity increase with an increase in [Bmim][BF4] concentration, but decrease with an increase in temperature. Moreover, the impact of temperature on the viscosity is more significant at low temperature range.
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| 2580. |
- Ny, Lars, 1967, et al.
(författare)
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BRAF mutational status as a prognostic marker for survival in malignant melanoma: a systematic review and meta-analysis.
- 2020
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 59:7, s. 833-844
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Tidskriftsartikel (refereegranskat)abstract
- Background: The analysis of the BRAF mutational status has been established as a standard procedure during diagnosis of advanced malignant melanoma due to the fact that BRAF inhibitors constitute a cornerstone in the treatment of metastatic disease. However, the general impact of BRAF mutational status on survival remains unclear. Our study aimed to assess the underlying prognostic significance of BRAF mutant versus wild type (WT) malignant melanoma on overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS).Material and methods: A systematic literature search in EMBASE, Medline and Cochrane CENTRAL was performed. Studies were included if they reported survival outcomes for BRAF mutant versus WT patients as hazard ratios (HR) or in Kaplan-Meier (KM) curves. Random-effects meta-analysis models were used to pool HRs across the studies.Results: Data from 52 studies, representing 7519 patients, were pooled for analysis of OS. The presence of a BRAF mutation was statistically significantly associated with a reduced OS (HR [95% confidence interval (CI)]: 1.23 [1.09-1.38]), however, with substantial heterogeneity between the studies (I2: 58.0%). Meta-regression and sensitivity analyses showed that age, sex and BRAF mutation testing method did not have a significant effect on the OS HR. BRAF mutant melanoma showed comparable effect on DFS to non-BRAF mutant melanoma in stage I-III melanoma (combined HR: 1.16, 95% CI: 0.92-1.46), and on PFS in stage III-IV (HR: 0.98 (95% CI: 0.68-1.40)).Conclusion: Although there was substantial heterogeneity between the studies, the overall results demonstrated a poorer prognosis and OS in patients harbouring BRAF mutations. Future studies should take this into account when evaluating epidemiological data and treatment effects of new interventions in patients with malignant melanoma.
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