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| 2. |
- Lambert, J-C, et al.
(författare)
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Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease
- 2013
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 18:4, s. 461-470
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Tidskriftsartikel (refereegranskat)abstract
- Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n = 2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case-control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43-1.96); P=1.1 x 10(-10)). We finally searched for association between SNPs within the FRMD4A locus and A beta plasma concentrations in three independent non-demented populations (n = 2579). We reported that polymorphisms were associated with plasma A beta 42/A beta 40 ratio (best signal, P=5.4 x 10(-7)). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD.
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| 3. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 4. |
- La Tessa, C., et al.
(författare)
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Out-of-field dose studies with an anthropomorphic phantom : Comparison of X-rays and particle therapy treatments
- 2012
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 105:1, s. 133-138
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Characterization of the out-of-field dose profile following irradiation of the target with a 3D treatment plan delivered with modern techniques. Methods: An anthropomorphic RANDO phantom was irradiated with a treatment plan designed for a simulated 5×2×5cm 3 tumor volume located in the center of the head. The experiment was repeated with all most common radiation treatment types (photons, protons and carbon ions) and delivery techniques (Intensity Modulated Radiation Therapy, passive modulation and spot scanning). The measurements were performed with active diamond detector and passive thermoluminescence (TLD) detectors to investigate the out-of-field dose both inside and outside the phantom. Results: The highest out-of-field dose values both on the surface and inside the phantom were measured during the treatment with 25 MV photons. In the proximity of the Planned Target Volume (PTV), the lowest lateral dose profile was observed for passively modulated protons mainly because of the presence of the collimator in combination with the chosen volume shape. In the far out-of-field region (above 100 mm from the PTV), passively modulated ions were characterized by a less pronounced dose fall-off in comparison with scanned beams. Overall, the treatment with scanned carbon ions delivered the lowest dose outside the target volume. Conclusions: For the selected PTV, the use of the collimator in proton therapy drastically reduced the dose deposited by ions or photons nearby the tumor. Scanning modulation represents the optimal technique for achieving the highest dose reduction far-out-of-field.
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| 6. |
- Gustafsson, Katarina, 1980, et al.
(författare)
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PHITS simulations of the Matroshka experiment
- 2010
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Ingår i: Advances in Space Research. - : Elsevier BV. - 1879-1948 .- 0273-1177. ; 46:10, s. 1266-1272
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Tidskriftsartikel (refereegranskat)abstract
- The radiation environment in space is very different from the one encountered on Earth. In addition to the sparsely ionizing radiation, there are particles of different Z with energies ranging from keV up to hundreds of GeV which can cause severe damage to both electronics and humans. It is therefore important to understand the interactions of these highly ionizing particles with different materials such as the hull of space vehicles, human organs and electronics. We have used the Particle and Heavy-Ion Transport code System (PHITS), which is a three-dimensional Monte Carlo code able to calculate interactions and transport of particles and heavy ions with energies up to 100 GeV/nucleon in most matter. PHITS is developed and maintained by a collaboration between RIST (Research Organization for Information Science & Technology), JAEA (Japan Atomic Energy Agency), KEK (High Energy Accelerator Research Organization), Japan and Chalmers University of Technology, Sweden. For the purpose of examining the applicability of PHITS to the shielding design we have simulated the ESA facility Matroshka (MTR) designed and lead by the German Aerospace Center (DLR). Preliminary results are presented and discussed in this paper.
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| 7. |
- Kim, Myung-Hee Y., et al.
(författare)
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Comparison of Martian surface ionizing radiation measurements from MSL-RAD with Badhwar-O'Neill 2011/HZETRN model calculations
- 2014
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Ingår i: Journal of Geophysical Research - Planets. - 2169-9097 .- 2169-9100. ; 119:6, s. 1311-1321
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Tidskriftsartikel (refereegranskat)abstract
- Dose rate measurements from Mars Science Laboratory-radiation assessment detector (MSL-RAD) for 300 sols on Mars are compared to simulation results using the Badhwar-O'Neill 2011 galactic cosmic ray (GCR) environment model and the high-charge and energy transport (HZETRN) code. For the nuclear interactions of primary GCR through Mars atmosphere and Curiosity rover, the quantum multiple scattering theory of nuclear fragmentation is used. Daily atmospheric pressure is measured at Gale Crater by the MSL Rover Environmental Monitoring Station. Particles impinging on top of the Martian atmosphere reach RAD after traversing varying depths of atmosphere that depend on the slant angles, and the model accounts for shielding of the RAD “E” detector (used for dosimetry) by the rest of the instrument. Simulation of average dose rate is in good agreement with RAD measurements for the first 200 sols and reproduces the observed variation of surface dose rate with changing heliospheric conditions and atmospheric pressure. Model results agree less well between sols 200 and 300 due to subtleties in the changing heliospheric conditions. It also suggests that the average contributions of albedo particles (charge number Z < 3) from Martian regolith comprise about 10% and 42% of the average daily point dose and dose equivalent, respectively. Neutron contributions to tissue-averaged effective doses will be reduced compared to point dose equivalent estimates because a large portion of the neutron point dose is due to low-energy neutrons with energies.
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| 8. |
- Puchalska, Monika, 1977, et al.
(författare)
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NUNDO: a numerical model of a human torso phantom and its application to effective dose equivalent calculations for astronauts at the ISS
- 2014
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Ingår i: Radiation and Environmental Biophysics. - : Springer Science and Business Media LLC. - 1432-2099 .- 0301-634X. ; 53:4, s. 719-727
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Tidskriftsartikel (refereegranskat)abstract
- The health effects of cosmic radiation on astronauts need to be precisely quantified and controlled. This task is important not only in perspective of the increasing human presence at the International Space Station (ISS), but also for the preparation of safe human missions beyond low earth orbit. From a radiation protection point of view, the baseline quantity for radiation risk assessment in space is the effective dose equivalent. The present work reports the first successful attempt of the experimental determination of the effective dose equivalent in space, both for extra-vehicular activity (EVA) and intra-vehicular activity (IVA). This was achieved using the anthropomorphic torso phantom RANDO(A (R)) equipped with more than 6,000 passive thermoluminescent detectors and plastic nuclear track detectors, which have been exposed to cosmic radiation inside the European Space Agency MATROSHKA facility both outside and inside the ISS. In order to calculate the effective dose equivalent, a numerical model of the RANDO(A (R)) phantom, based on computer tomography scans of the actual phantom, was developed. It was found that the effective dose equivalent rate during an EVA approaches 700 mu Sv/d, while during an IVA about 20 % lower values were observed. It is shown that the individual dose based on a personal dosimeter reading for an astronaut during IVA results in an overestimate of the effective dose equivalent of about 15 %, whereas under an EVA conditions the overestimate is more than 200 %. A personal dosemeter can therefore deliver quite good exposure records during IVA, but may overestimate the effective dose equivalent received during an EVA considerably.
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| 9. |
- Rafkin, Scot C.R., et al.
(författare)
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Diurnal variations of energetic particle radiation at the surface of Mars as observed by the Mars Science Laboratory Radiation Assessment Detector
- 2014
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Ingår i: Journal of Geophysical Research - Planets. - 2169-9097 .- 2169-9100. ; 119:6, s. 1345-1358
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Tidskriftsartikel (refereegranskat)abstract
- The Radiation Assessment Detector onboard the Mars Science Laboratory rover Curiosity is detecting the energetic particle radiation at the surface of Mars. Data collected over the first 350 Martian days of the nominal surface mission show a pronounced diurnal cycle in both the total dose rate and the neutral particle count rate. The diurnal variations detected by the Radiation Assessment Detector were neither anticipated nor previously considered in the literature. These cyclic variations in dose rate and count rate are shown to be the result of changes in atmospheric column mass driven by the atmospheric thermal tide that is characterized through pressure measurements obtained by the Rover Environmental Monitoring Station, also onboard the rover. In addition to bulk changes in the radiation environment, changes in atmospheric shielding forced by the thermal tide are shown to disproportionately affect heavy ions compared to H and He nuclei.
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