| 1. |
- Huyghe, Jeroen R, et al.
(författare)
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Genetic architectures of proximal and distal colorectal cancer are partly distinct
- 2021
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:7, s. 1325-1334
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Tidskriftsartikel (refereegranskat)abstract
- Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.Results: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
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| 2. |
- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 3. |
- Currie, Thayne, et al.
(författare)
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SCExAO/CHARIS Direct Imaging Discovery of a 20 au Separation, Low-mass Ratio Brown Dwarf Companion to an Accelerating Sun-like Star
- 2020
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 904:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the direct imaging discovery of a substellar companion to the nearby Sun-like star, HD 33632 Aa, at a projected separation of similar to 20 au, obtained with SCExAO/CHARIS integral field spectroscopy complemented by Keck/NIRC2 thermal infrared imaging. The companion, HD 33632 Ab, induces a 10.5 sigma astrometric acceleration on the star as detected with the Gaia and Hipparcos satellites. SCExAO/CHARIS JHK (1.1-2.4 mu m) spectra and Keck/NIRC2 L-p (3.78 mu m) photometry are best matched by a field L/T transition object: an older, higher-gravity, and less dusty counterpart to HR 8799 cde. Combining our astrometry with Gaia/Hipparcos data and archival Lick Observatory radial velocities, we measure a dynamical mass of 46.4 8 M-J and an eccentricity of e < 0.46 at 95% confidence. HD 33632 Ab's mass and mass ratio (4.0% 0.7%) are comparable to the low-mass brown dwarf GJ 758 B and intermediate between the more massive brown dwarf HD 19467 B and the (near-)planet-mass companions to HR 2562 and GJ 504. Using Gaia to select for direct imaging observations with the newest extreme adaptive optics systems can reveal substellar or even planet-mass companions on solar system-like scales at an increased frequency compared to blind surveys.
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| 4. |
- Yang, Yi, et al.
(författare)
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High-resolution Near-infrared Polarimetry and Submillimeter Imaging of FS Tau A : Possible Streamers in Misaligned Circumbinary Disk System
- 2020
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 889:2
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed the young (2.8 Myr-old) binary system FS Tau A using near-infrared (H-band) high -contrast polarimetry data from Subaru/HiCIAO and submillimeter CO (J = 2-1) line emission data from Atacama Large Millimeter/submillimeter Array (ALMA). Both the near-infrared and submillimeter observations reveal several clear structures extending to similar to 240 au from the stars. Based on these observations at different wavelengths, we report the following discoveries. One arm-like structure detected in the near-infrared band initially extends from the south of the binary with a subsequent turn to the northeast, corresponding to two bar-like structures detected in ALMA observations with an local standard of rest kinematic (LSRK) velocity of 1.19-5.64 km s(-1). Another feature detected in the near-infrared band extends initially from the north of the binary, relating to an arm-like structure detected in ALMA observations with an LSRK velocity of 8.17-16.43 km s(-1). From their shapes and velocities, we suggest that these structures can mostly be explained by two streamers that connect the outer circumbinary disk and the central binary components. These discoveries will be helpful for understanding the evolution of streamers and circumstellar disks in young binary systems.
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| 5. |
- Gervais, Nicole J., et al.
(författare)
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Scene memory and hippocampal volume in middle-aged women with early hormone loss
- 2022
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Ingår i: Neurobiology of Aging. - : ELSEVIER SCIENCE INC. - 0197-4580 .- 1558-1497. ; 117, s. 97-106
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Tidskriftsartikel (refereegranskat)abstract
- The present study explored whether early midlife bilateral salpingo-oophorectomy (BSO), a female specific risk factor for dementia, is associated with reduced medial temporal lobe structure and function. Younger middle-aged women with the BRCA1/2 mutation and a BSO prior to spontaneous menopause (SM) were recruited. We determined the performance of women with BSO not taking estradiol-based hormone therapy ( n = 18) on a task measuring object and scene recognition and quantified medial temporal lobe subregion volumes using manually segmented high-resolution T2-weighted MRI scans. Comparisons were made to those with BSO taking estradiol-based hormone therapy ( n = 20), age-matched premenopausal controls ( n = 28), and older women in SM not taking hormone therapy matched for duration of hormone deprivation ( n = 17). Reduced hippocampal integrity specific to the BSO group not taking hormone therapy was observed, reflected by significantly smaller dentate gyrus/CA2/CA3 volumes and lower scene recognition memory performance. These findings show that hippocampal subfield volume may be useful for identifying early midlife changes in women at elevated risk for dementia.
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| 6. |
- Mayama, Satoshi, et al.
(författare)
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Subaru Near-infrared Imaging Polarimetry of Misaligned Disks around the SR 24 Hierarchical Triple System
- 2020
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 159:1
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Tidskriftsartikel (refereegranskat)abstract
- The SR 24 multistar system hosts both circumprimary and circumsecondary disks, which are strongly misaligned with each other. The circumsecondary disk is circumbinary in nature. Interestingly, both disks are interacting, and they possibly rotate in opposite directions. To investigate the nature of this unique twin disk system, we present 01 resolution near-infrared polarized intensity images of the circumstellar structures around SR 24, obtained with HiCIAO mounted on the Subaru 8.2 m telescope. Both the circumprimary disk and the circumsecondary disk are resolved and have elongated features. While the position angle of the major axis and radius of the near-IR (NIR) polarization disk around SR 24S are 55° and 137 au, respectively, those around SR 24N are 110° and 34 au, respectively. With regard to overall morphology, the circumprimary disk around SR 24S shows strong asymmetry, whereas the circumsecondary disk around SR 24N shows relatively strong symmetry. Our NIR observations confirm the previous claim that the circumprimary and circumsecondary disks are misaligned from each other. Both the circumprimary and circumsecondary disks show similar structures in 12CO observations in terms of its size and elongation direction. This consistency is because both NIR and 12CO are tracing surface layers of the flared disks. As the radius of the polarization disk around SR 24N is roughly consistent with the size of the outer Roche lobe, it is natural to interpret the polarization disk around SR 24N as a circumbinary disk surrounding the SR 24Nb–Nc system.
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