| 41. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Tidskriftsartikel (refereegranskat)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 42. |
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| 44. |
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| 45. |
- Herland, Anna, et al.
(författare)
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Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips
- 2020
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Ingår i: Nature Biomedical Engineering. - : Springer Science and Business Media LLC. - 2157-846X. ; 4:4, s. 421-436
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of drug pharmacokinetics (PKs) and pharmacodynamics (PDs) performed in animals are often not predictive of drug PKs and PDs in humans, and in vitro PK and PD modelling does not provide quantitative PK parameters. Here, we show that physiological PK modelling of first-pass drug absorption, metabolism and excretion in humans—using computationally scaled data from multiple fluidically linked two-channel organ chips—predicts PK parameters for orally administered nicotine (using gut, liver and kidney chips) and for intravenously injected cisplatin (using coupled bone marrow, liver and kidney chips). The chips are linked through sequential robotic liquid transfers of a common blood substitute by their endothelium-lined channels (as reported by Novak et al. in an associated Article) and share an arteriovenous fluid-mixing reservoir. We also show that predictions of cisplatin PDs match previously reported patient data. The quantitative in-vitro-to-in-vivo translation of PK and PD parameters and the prediction of drug absorption, distribution, metabolism, excretion and toxicity through fluidically coupled organ chips may improve the design of drug-administration regimens for phase-I clinical trials.
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| 46. |
- Marcouille, O., et al.
(författare)
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Production of high energy photons with in vacuum wigglers : From SOLEIL wiggler to MAXIV wiggler
- 2019
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Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
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Konferensbidrag (refereegranskat)abstract
- Small gap wigglers become more and more attractive to produce high photon fluxes in the hard X-ray photon range. They use magnet blocks of high magnetization which resists much better to heating (baking, synchrotron radiation) than in the past, produce high magnetic field with numerous periods and are very compact. They also are a very good alternative to superconducting technology which requires special infrastructure, heavy maintenance and is not running cost free. SOLEIL, operating presently at 2.75 GeV has designed and built an in-vacuum wiggler of 38 periods of 50 mm producing 2.1 T at a minimum gap of 5.5 mm to delivered photon beam between 20 keV and 50 keV. Already in operation, further improvements are presently in progress to push photons towards higher energy, in particular thanks to the operation at lower gap (4.5 mm). MAX IV and SOLEIL, in the frame of collaboration, ave built an upgraded version of the existing SOLEIL wiggler with the target to extend the spectral range at high energy (above 50 keV) but also at low energy (4 keV) with the same insertion device. The design of the existing magnetic system has been modified to reach 2.4 T at a minimum gap of 4.2 mm and includes taper operation to avoid undulator structure in the radiated spectrum at low energy.
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| 47. |
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| 49. |
- Guillaume, E., et al.
(författare)
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Electron Rephasing in a Laser-Wakefield Accelerator
- 2015
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 115:15
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Tidskriftsartikel (refereegranskat)abstract
- An important limit for energy gain in laser-plasma wakefield accelerators is the dephasing length, after which the electron beam reaches the decelerating region of the wakefield and starts to decelerate. Here, we propose to manipulate the phase of the electron beam in the wakefield, in order to bring the beam back into the accelerating region, hence increasing the final beam energy. This rephasing is operated by placing an upward density step in the beam path. In a first experiment, we demonstrate the principle of this technique using a large energy spread electron beam. Then, we show that it can be used to increase the energy of monoenergetic electron beams by more than 50%.
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| 50. |
- Hodge, J. A., et al.
(författare)
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ALMA Reveals Potential Evidence for Spiral Arms, Bars, and Rings in High-redshift Submillimeter Galaxies
- 2019
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 876:2
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Tidskriftsartikel (refereegranskat)abstract
- We present subkiloparsec-scale mapping of the 870 mu m ALMA continuum emission in six luminous (LIR similar to 5 x 10(12 )L(circle dot)) submillimeter galaxies (SMGs) from the ALESS survey of the Extended Chandra Deep Field South. Our high-fidelity 0 ''.07-resolution imaging (similar to 500 pc) reveals robust evidence for structures with deconvolved sizes of less than or similar to 0.5-1 kpc embedded within (dominant) exponential dust disks. The large-scale morphologies of the structures within some of the galaxies show clear curvature and/or clump-like structures bracketing elongated nuclear emission, suggestive of bars, star-forming rings, and spiral arms. In this interpretation, the ratio of the "ring" and "bar" radii (1.9 +/- 0.3) agrees with that measured for such features in local galaxies. These potential spiral/ring/bar structures would be consistent with the idea of tidal disturbances, with their detailed properties implying flat inner rotation curves and Toomre-unstable disks (Q < 1). The inferred one-dimensional velocity dispersions (sigma(r) less than or similar to 70-160 km s(-1)) are marginally consistent with the limits implied if the sizes of the largest structures are comparable to the Jeans length. We create maps of the star formation rate density (Sigma(SFR)) on similar to 500 pc scales and show that the SMGs are able to sustain a given (galaxy-averaged) E-SFR over much larger physical scales than local (ultra)luminous infrared galaxies. However, on 500 pc scales, they do not exceed the Eddington limit set by radiation pressure on dust. If confirmed by kinematics, the potential presence of nonaxisymmetric structures would provide a means for net angular momentum loss and efficient star formation, helping to explain the very high star formation rates measured in SMGs.
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