| 1. |
- Zhou, XP, et al.
(författare)
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Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
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| 2. |
- Adam, A, et al.
(författare)
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Abstracts from Hydrocephalus 2016.
- 2017
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Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 14:Suppl 1
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Jakosky, B. M., et al.
(författare)
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The Mars Atmosphere and Volatile Evolution (MAVEN) Mission
- 2015
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Ingår i: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 195:1-4, s. 3-48
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Forskningsöversikt (refereegranskat)abstract
- The MAVEN spacecraft launched in November 2013, arrived at Mars in September 2014, and completed commissioning and began its one-Earth-year primary science mission in November 2014. The orbiter's science objectives are to explore the interactions of the Sun and the solar wind with the Mars magnetosphere and upper atmosphere, to determine the structure of the upper atmosphere and ionosphere and the processes controlling it, to determine the escape rates from the upper atmosphere to space at the present epoch, and to measure properties that allow us to extrapolate these escape rates into the past to determine the total loss of atmospheric gas to space through time. These results will allow us to determine the importance of loss to space in changing the Mars climate and atmosphere through time, thereby providing important boundary conditions on the history of the habitability of Mars. The MAVEN spacecraft contains eight science instruments (with nine sensors) that measure the energy and particle input from the Sun into the Mars upper atmosphere, the response of the upper atmosphere to that input, and the resulting escape of gas to space. In addition, it contains an Electra relay that will allow it to relay commands and data between spacecraft on the surface and Earth.
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| 4. |
- Abdul-Rahim, A. H., et al.
(författare)
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Risk of stroke in chronic heart failure patients with preserved ejection fraction, but without atrial fibrillation: analysis of the CHARM-Preserved and I-Preserve trials
- 2017
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 38:10, s. 742-750
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Tidskriftsartikel (refereegranskat)abstract
- Aims The incidence and predictors of stroke in patients with heart failure and preserved ejection fraction (HF-PEF), but without atrial fibrillation (AF), are unknown. We described the incidence of stroke in HF-PEF patients with and without AF and predictors of stroke in those without AF. Methods and results We pooled data from the CHARM-Preserved and I-Preserve trials. Using Cox regression, we derived a model for stroke in patients without AF in this cohort and compared its performance with a published model in heart failure patients with reduced ejection fraction (HF-REF)-predictive variables: age, body mass index, New York Heart Association class, history of stroke, and insulin-treated diabetes. The two stroke models were compared and Kaplan-Meier curves for stroke estimated. The risk model was validated in a third HF-PEF trial. Of the 6701 patients, 4676 did not have AF. Stroke occurred in 124 (6.1%) with AF and in 171 (3.7%) without AF (rates 1.80 and 1.00 per 100 patient-years, respectively). There was no difference in performance of the stroke model derived in the HF-PEF cohort and the published HF-REF model (c-index 0.71, 95% confidence interval 0.57-0.84 vs. 0.73, 0.59-0.85, respectively) as the predictive variables overlapped. The model performed well in the validation cohort (0.86, 0.62-0.99). The rate of stroke in patients in the upper third of risk approximated to that in patients with AF (1.60 and 1.80 per 100 patient-years, respectively). Conclusions A small number of clinical variables identify a subset of patients with HF-PEF, but without AF, at elevated risk of stroke.
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| 5. |
- Maire, A-L, et al.
(författare)
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Hint of curvature in the orbital motion of the exoplanet 51 Eridani b using 3 yr of VLT/SPHERE monitoring
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 624
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Tidskriftsartikel (refereegranskat)abstract
- Context. The 51 Eridani system harbors a complex architecture with its primary star forming a hierarchical system with the binary GJ 3305AB at a projected separation of 2000 au, a giant planet orbiting the primary star at 13 au, and a low-mass debris disk around the primary star with possible cold and warm components inferred from the spectral energy distribution. Aims. We aim to better constrain the orbital parameters of the known giant planet. Methods. We monitored the system over three years from 2015 to 2018 with the Spectro-Polarimetric High-contrast Exoplanet REsearch (SPHERE) instrument at the Very Large Telescope (VET). Results. We measure an orbital motion for the planet of similar to 130 mas with a slightly decreasing separation (similar to 10 mas) and find a hint of curvature. This potential curvature is further supported at 3 sigma significance when including literature Gemini Planet Imager (GPI) astrometry corrected for calibration systematics. Fits of the SPHERE and GPI data using three complementary approaches provide broadly similar results. The data suggest an orbital period of 32(-9)(+17) yr (i.e., 12(-2)(+4), au in semi-major axis), an inclination of 133(-7)(+1)(4) deg, an eccentricity of 0.45(-0.15)(+0.10), and an argument of periastron passage of 87(-30)(+34) deg [mod 180 degrees]. The time at periastron passage and the longitude of node exhibit bimodal distributions because we do not yet detect whether the planet is accelerating or decelerating along its orbit. Given the inclinations of the orbit and of the stellar rotation axis (134-144 degrees), we infer alignment or misalignment within 18 degrees for the star-planet spin-orbit. Further astrometric monitoring in the next 3-4 yr is required to confirm at a higher significance the curvature in the motion of the planet, determine if the planet is accelerating or decelerating on its orbit, and further constrain its orbital parameters and the star-planet spin-orbit.
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| 6. |
- Noguchi, S, et al.
(författare)
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FANTOM5 CAGE profiles of human and mouse samples
- 2017
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Ingår i: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4, s. 170112-
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Tidskriftsartikel (refereegranskat)abstract
- In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
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| 7. |
- Samland, M., et al.
(författare)
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Spectral and atmospheric characterization of 51 Eridani b using VLT/SPHERE
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 603
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Tidskriftsartikel (refereegranskat)abstract
- Context. 51 Eridani b is an exoplanet around a young (20 Myr) nearby (29.4 pc) F0-type star, which was recently discovered by direct imaging. It is one of the closest direct imaging planets in angular and physical separation (similar to 0.5 '', similar to 13 au) and is well suited for spectroscopic analysis using integral field spectrographs. Aims. We aim to refine the atmospheric properties of the known giant planet and to constrain the architecture of the system further by searching for additional companions. Methods. We used the extreme adaptive optics instrument SPHERE at the Very Large Telescope (VLT) to obtain simultaneous dual-band imaging with IRDIS and integral field spectra with IFS, extending the spectral coverage of the planet to the complete Y-to H-band range and providing additional photometry in the K12-bands (2.11, 2.25 mu m). The object is compared to other known cool and peculiar dwarfs. The posterior probability distributions for parameters of cloudy and clear atmospheric models are explored using MCMC. We verified our methods by determining atmospheric parameters for the two benchmark brown dwarfs Gl 570D and HD 3651B. We used archival VLT-NACO (L') Sparse Aperture Masking data to probe the innermost region for additional companions. Results. We present the first spectrophotometric measurements in the Y and K bands for the planet and revise its J-band flux to values 40% fainter than previous measurements. Cloudy models with uniform cloud coverage provide a good match to the data. We derive the temperature, radius, surface gravity, metallicity, and cloud sedimentation parameter f(sed). We find that the atmosphere is highly super-solar ([Fe/H] = 1.0 +/- 0.1 dex), and the low f(sed) = 1.26(-0.29)(+0.36) value is indicative of a vertically extended, optically thick cloud cover with small sized particles. The model radius and surface gravity estimates suggest higher planetary masses of M-gravity = 9.1(-3.3)(+4.9) M-J. The evolutionary model only provides a lower mass limit of > 2 M-J (for pure hot-start). The cold-start model cannot explain the luminosity of the planet. The SPHERE and NACO/SAM detection limits probe the 51 Eri system at solar system scales and exclude brown-dwarf companions more massive than 20 M-J beyond separations of similar to 2.5 au and giant planets more massive than 2 M-J beyond 9 au.
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| 8. |
- Shen, L., et al.
(författare)
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Insulin treatment and clinical outcomes in patients with diabetes and heart failure with preserved ejection fraction
- 2019
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 21:8, s. 974-984
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Tidskriftsartikel (refereegranskat)abstract
- Aims Insulin causes sodium retention and hypoglycaemia and its use is associated with worse outcomes in heart failure (HF) with reduced ejection fraction. We have investigated whether this is also the case in HF with preserved ejection fraction (HFpEF). Methods and results We examined the association between diabetes/diabetes treatments and the risk of the primary composite of cardiovascular death or HF hospitalization, as well as other outcomes in adjusted analyses in CHARM-Preserved (left ventricular ejection fraction >= 45%), I-Preserve and TOPCAT (Americas) pooled. Of 8466 patients, 2653 (31%) had diabetes, including 979 (37%) receiving insulin. Patients receiving insulin were younger, had a higher body mass index, prevalence of ischaemic aetiology, N-terminal pro-B-type natriuretic peptide and use of diuretics, worse New York Heart Association class and signs and symptoms, and worse quality of life and renal function, compared to patients with diabetes not on insulin. Among the 1398 patients with echocardiographic data, insulin use was associated with higher left ventricular end-diastolic pressure and more diastolic dysfunction than in other participants. The primary outcome occurred at a rate of 6.3 per 100 patient-years in patients without diabetes, and 10.2 and 17.1 per 100 patient-years in diabetes patients without and with insulin use, respectively [fully adjusted hazard ratio (aHR) insulin-treated diabetes vs. other diabetes: 1.41, 95% confidence interval (CI) 1.23-1.63, P < 0.001]. The adjusted HR is 1.67 (95% CI 1.20-2.32, p = 0.002) for sudden death (insulin-treated diabetes vs. other diabetes). Conclusions Insulin use is associated with poor outcomes in HFpEF. Although we cannot conclude a causal association, the safety of insulin and alternative glucose-lowering treatments in HF needs to be evaluated in clinical trials.
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| 9. |
- Akiyama, E., et al.
(författare)
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DISCOVERY OF A DISK GAP CANDIDATE AT 20 AU IN TW HYDRAE
- 2015
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 802:2
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Tidskriftsartikel (refereegranskat)abstract
- We present a new Subaru/HiCIAO high-contrast H-band polarized intensity (PI) image of a nearby transitional disk associated with TW Hydrae. The scattered light from the disk was detected from 0 ''.2 to 1 ''.5 (11-81 AU) and the PI image shows a clear axisymmetric depression in PI at similar to 0 ''.4 (similar to 20 AU) from the central star, similar to the similar to 80 AU gap previously reported from Hubble Space Telescope images. The azimuthal PI profile also shows that the disk beyond 0 ''.2 is almost axisymmetric. We discuss two possible scenarios explaining the origin of the PI depression: (1) a gap structure may exist at similar to 20 AU from the central star because of a shallow slope seen in the PI profile, and (2) grain growth may be occurring in the inner region of the disk. Multi-band observations at near-infrared and millimeter/submillimeter wavelengths play a complementary role in investigating dust opacity and may help reveal the origin of the gap more precisely.
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| 10. |
- Bhatia, V., et al.
(författare)
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Beta-blocker Use and 30-day All-cause Readmission in Medicare Beneficiaries with Systolic Heart Failure
- 2015
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Ingår i: American Journal of Medicine. - : Elsevier BV. - 0002-9343. ; 128:7, s. 715-721
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Beta-blockers improve outcomes in patients with systolic heart failure. However, it is unknown whether their initial negative inotropic effect may increase 30-day all-cause readmission, a target outcome for Medicare cost reduction and financial penalty for hospitals under the Affordable Care Act. METHODS: Of the 3067 Medicare beneficiaries discharged alive from 106 Alabama hospitals (1998-2001) with a primary discharge diagnosis of heart failure and ejection fraction <45%, 2202 were not previously on beta-blocker therapy, of which 383 received new discharge prescriptions for beta-blockers. Propensity scores for beta-blocker use, estimated for each of the 2202 patients, were used to assemble a matched cohort of 380 pairs of patients receiving and not receiving beta-blockers who were balanced on 36 baseline characteristics (mean age 73 years, mean ejection fraction 27%, 45% women, 33% African American). RESULTS: Beta-blocker use was not associated with 30-day all-cause readmission (hazard ratio [HR] 0.87; 95% confidence interval [CI], 0.64-1.18) or heart failure readmission (HR 0.95; 95% CI, 0.57-1.58), but was significantly associated with lower 30-day all-cause mortality (HR 0.29; 95% CI, 0.12-0.73). During 4-year postdischarge, those in the beta-blocker group had lower mortality (HR 0.81; 95% CI, 0.67-0.98) and combined outcome of all-cause mortality or all-cause readmission (HR 0.87; 95% CI, 0.74-0.97), but not with all-cause readmission (HR 0.89; 95% CI, 0.76-1.04). CONCLUSIONS: Among hospitalized older patients with systolic heart failure, discharge prescription of beta-blockers was associated with lower 30-day all-cause mortality and 4-year combined death or readmission outcomes without higher 30-day readmission. Published by Elsevier Inc.
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