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- Street, D., et al.
(author)
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Progression of atypical parkinsonian syndromes: PROSPECT-M-UK study implications for clinical trials
- 2023
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In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 146:8, s. 3232-3242
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Journal article (peer-reviewed)abstract
- Street et al. compare candidate clinical trial end points in progressive supranuclear palsy, multiple system atrophy, corticobasal syndrome and related disorders. Neuroimaging metrics generally enable lower sample sizes than cognitive and functional measures, although optimal outcome measures vary by disease and subtype. The advent of clinical trials of disease-modifying agents for neurodegenerative disease highlights the need for evidence-based end point selection. Here we report the longitudinal PROSPECT-M-UK study of progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), multiple system atrophy (MSA) and related disorders, to compare candidate clinical trial end points. In this multicentre UK study, participants were assessed with serial questionnaires, motor examination, neuropsychiatric and MRI assessments at baseline, 6 and 12 months. Participants were classified by diagnosis at baseline and study end, into Richardson syndrome, PSP-subcortical (PSP-parkinsonism and progressive gait freezing subtypes), PSP-cortical (PSP-frontal, PSP-speech and language and PSP-CBS subtypes), MSA-parkinsonism, MSA-cerebellar, CBS with and without evidence of Alzheimer's disease pathology and indeterminate syndromes. We calculated annual rate of change, with linear mixed modelling and sample sizes for clinical trials of disease-modifying agents, according to group and assessment type. Two hundred forty-three people were recruited [117 PSP, 68 CBS, 42 MSA and 16 indeterminate; 138 (56.8%) male; age at recruitment 68.7 +/- 8.61 years]. One hundred and fifty-nine completed the 6-month assessment (82 PSP, 27 CBS, 40 MSA and 10 indeterminate) and 153 completed the 12-month assessment (80 PSP, 29 CBS, 35 MSA and nine indeterminate). Questionnaire, motor examination, neuropsychiatric and neuroimaging measures declined in all groups, with differences in longitudinal change between groups. Neuroimaging metrics would enable lower sample sizes to achieve equivalent power for clinical trials than cognitive and functional measures, often achieving N < 100 required for 1-year two-arm trials (with 80% power to detect 50% slowing). However, optimal outcome measures were disease-specific. In conclusion, phenotypic variance within PSP, CBS and MSA is a major challenge to clinical trial design. Our findings provide an evidence base for selection of clinical trial end points, from potential functional, cognitive, clinical or neuroimaging measures of disease progression.
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- Gould, A., et al.
(author)
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MOA-2010-BLG-523:" Failed Planet"= RS CVn Star
- 2013
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In: Astrophysical Journal. - 0004-637X. ; 763:2
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Journal article (peer-reviewed)abstract
- The Galactic bulge source MOA-2010-BLG-523S exhibited short-term deviations from a standard microlensing light curve near the peak of an A(max) similar to 265 high-magnification microlensing event. The deviations originally seemed consistent with expectations for a planetary companion to the principal lens. We combine long-term photometric monitoring with a previously published high-resolution spectrum taken near peak to demonstrate that this is an RS CVn variable, so that planetary microlensing is not required to explain the light-curve deviations. This is the first spectroscopically confirmed RS CVn star discovered in the Galactic bulge.
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- Callaway, EM, et al.
(author)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Journal article (peer-reviewed)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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- Ryu, Y. -H., et al.
(author)
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OGLE-2016-BLG-1190Lb : The First Spitzer Bulge Planet Lies Near the Planet/Brown-dwarf Boundary
- 2018
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In: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 155:1
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Journal article (peer-reviewed)abstract
- We report the discovery of OGLE-2016-BLG-1190Lb, which is likely to be the first Spitzer microlensing planet in the Galactic bulge/ bar, an assignation that can be confirmed by two epochs of high-resolution imaging of the combined source-lens baseline object. The planet's mass, M-p = 13.4 +/- 0.9 M-J, places it right at the deuteriumburning limit, i. e., the conventional boundary between planets and brown dwarfs. Its existence raises the question of whether such objects are really planets (formed within the disks of their hosts) or failed stars (lowmass objects formed by gas fragmentation). This question may ultimately be addressed by comparing disk and bulge/bar planets, which is a goal of the Spitzer microlens program. The host is a G dwarf, M-host = 0.89. +/- 0.07 M-circle dot, and the planet has a semimajor axis a similar to 2.0 au. We use Kepler K2 Campaign 9 microlensing data to break the lens-mass degeneracy that generically impacts parallax solutions from Earth-Spitzer observations alone, which is the first successful application of this approach. The microlensing data, derived primarily from near-continuous, ultradense survey observations from OGLE, MOA, and three KMTNet telescopes, contain more orbital information than for any previous microlensing planet, but not quite enough to accurately specify the full orbit. However, these data do permit the first rigorous test of microlensing orbital-motion measurements, which are typically derived from data taken over < 1% of an orbital period.
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- Bianco, Federica B., et al.
(author)
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Optimization of the Observing Cadence for the Rubin Observatory Legacy Survey of Space and Time : A Pioneering Process of Community-focused Experimental Design
- 2022
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In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 258:1
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Journal article (peer-reviewed)abstract
- Vera C. Rubin Observatory is a ground-based astronomical facility under construction, a joint project of the National Science Foundation and the U.S. Department of Energy, designed to conduct a multipurpose 10 yr optical survey of the Southern Hemisphere sky: the Legacy Survey of Space and Time. Significant flexibility in survey strategy remains within the constraints imposed by the core science goals of probing dark energy and dark matter, cataloging the solar system, exploring the transient optical sky, and mapping the Milky Way. The survey's massive data throughput will be transformational for many other astrophysics domains and Rubin's data access policy sets the stage for a huge community of potential users. To ensure that the survey science potential is maximized while serving as broad a community as possible, Rubin Observatory has involved the scientific community at large in the process of setting and refining the details of the observing strategy. The motivation, history, and decision-making process of this strategy optimization are detailed in this paper, giving context to the science-driven proposals and recommendations for the survey strategy included in this Focus Issue.
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- Jaimes, R. Figuera, et al.
(author)
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Many new variable stars discovered in the core of the globular cluster NGC 6715 (M54) with EMCCD observations
- 2016
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 592
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Journal article (peer-reviewed)abstract
- Context. We show the benefits of using electron-multiplying CCDs and the shift-and-add technique as a tool to minimise the effects of atmospheric turbulence, such as blending between stars in crowded fields, and to avoid saturated stars in the fields observed. We intend to complete, or improve on, the census of the variable star population in globular cluster NGC 6715. Aims. Our aim is to obtain high-precision time-series photometry of the very crowded central region of this stellar system via the collection of better angular resolution images than has been previously achieved with conventional CCDs on ground-based telescopes. Methods. Observations were carried out using the Danish 1.54-m telescope at the ESO La Silla observatory in Chile. The telescope is equipped with an electron-multiplying CCD that enables short-exposure-time images to be obtained (ten images per second) that were stacked using the shift-and-add technique to produce the normal-exposure-time images (minutes). The high precision photometry was performed via difference image analysis employing the DanDIA pipeline. We attempted automatic detection of variable stars in the field. Results. We statistically analysed the light curves of 1405 stars in the crowded central region of NGC 6715 to automatically identify the variable stars present in this cluster. We found light curves for 17 previously known variable stars near the edges of our reference image (16 RR Lyrae and 1 semi-regular) and we discovered 67 new variables (30 RR Lyrae, 21 irregular (long-period type), 3 semi-regular, 1 W Virginis, 1 eclipsing binary, and 11 unclassified). Photometric measurements for these stars are available in electronic form through the Strasbourg Astronomical Data Centre.
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