| 1. |
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| 2. |
- van Rheenen, W, et al.
(författare)
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Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
- 2021
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53:12, s. 1636-
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
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| 3. |
- Grazian, A., et al.
(författare)
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Lyman continuum escape fraction of faint galaxies at z similar to 3.3 in the CANDELS/GOODS-North, EGS, and COSMOS fields with LBC
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 602
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Tidskriftsartikel (refereegranskat)abstract
- Context. The reionization of the Universe is one of the most important topics of present-day astrophysical research. The most plausible candidates for the reionization process are star-forming galaxies, which according to the predictions of the majority of the theoretical and semi-analytical models should dominate the H I ionizing background at z greater than or similar to 3. Aims. We measure the Lyman continuum escape fraction, which is one of the key parameters used to compute the contribution of star-forming galaxies to the UV background. It provides the ratio between the photons produced at lambda <= 912 angstrom rest-frame and those that are able to reach the inter-galactic medium, i.e. that are not absorbed by the neutral hydrogen or by the dust of the galaxy's inter-stellar medium. Methods. We used ultra-deep U-band imaging (U = 30.2 mag at 1 sigma) from Large Binocular Camera at the Large Binocular Telescope (LBC/LBT) in the CANDELS/GOODS-North field and deep imaging in the COSMOS and EGS fields in order to estimate the Lyman continuum escape fraction of 69 star-forming galaxies with secure spectroscopic redshifts at 3.27 <= z <= 3.40 to faint magnitude limits (L = 0.2L*, or equivalently M-1500 similar to -19). The narrow redshift range implies that the LBC U-band filter exclusively samples the lambda <= 912 angstrom rest-frame wavelengths. Results. We measured through stacks a stringent upper limit (<1.7% at 1 sigma) for the relative escape fraction of H I ionizing photons from bright galaxies (L > L*), while for the faint population (L = 0.2L*) the limit to the escape fraction is less than or similar to 10%. We computed the contribution of star-forming galaxies to the observed UV background at z similar to 3 and find that it is not sufficient to keep the Universe ionized at these redshifts unless their escape fraction increases significantly (>= 10%) at low luminosities (M-1500 >= -19). Conclusions. We compare our results on the Lyman continuum escape fraction of high-z galaxies with recent estimates in the literature, and discuss future prospects to shed light on the end of the Dark Ages. In the future, strong gravitational lensing will be fundamental in order to measure the Lyman continuum escape fraction down to faint magnitudes (M-1500 similar to -16) that are inaccessible with the present instrumentation on blank fields. These results will be important in order to quantify the role of faint galaxies to the reionization budget.
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| 4. |
- Gong, J., et al.
(författare)
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Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium
- 2023
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:8, s. 3365-3378
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionSex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. MethodsA total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models. ResultsIncident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. DiscussionDementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.
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| 5. |
- Peters, Ruth, et al.
(författare)
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An investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis.
- 2020
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Ingår i: Neurology. - 1526-632X. ; 94:3
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data.To identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data.Over 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age.Our findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals.The review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454.
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| 6. |
- Feldmeier, John J., et al.
(författare)
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SEARCHING FOR NEUTRAL HYDROGEN HALOS AROUND z similar to 2.1 AND z similar to 3.1 Ly alpha EMITTING GALAXIES
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 776:2, s. 75-
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Tidskriftsartikel (refereegranskat)abstract
- We search for evidence of diffuse Ly alpha emission from extended neutral hydrogen surrounding Ly alpha emitting galaxies (LAEs) using deep narrow-band images of the Extended Chandra Deep Field South. By stacking the profiles of 187 LAEs at z = 2.06, 241 LAEs at z = 3.10, and 179 LAEs at z = 3.12, and carefully performing low-surface brightness photometry, we obtain mean surface brightness maps that reach 9.9, 8.7, and 6.2 x 10(-19) erg cm(-2) s(-1) arcsec(-2) in the emission line. We undertake a thorough investigation of systematic uncertainties in our surface brightness measurements and find that our limits are 5-10 times larger than would be expected from Poisson background fluctuations; these uncertainties are often underestimated in the literature. At z similar to 3.1, we find evidence for extended halos with small-scale lengths of 5-8 kpc in some but not all of our sub-samples. We demonstrate that sub-samples of LAEs with low equivalent widths and brighter continuum magnitudes are more likely to possess such halos. At z similar to 2.1, we find no evidence of extended Ly alpha emission down to our detection limits. Through Monte-Carlo simulations, we also show that we would have detected large diffuse LAE halos if they were present in our data sets. We compare these findings to other measurements in the literature and discuss possible instrumental and astrophysical reasons for the discrepancies.
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| 7. |
- Guaita, Lucia, et al.
(författare)
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The Lyman alpha reference sample IV. Morphology at low and high redshift
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 576
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Tidskriftsartikel (refereegranskat)abstract
- Context. The transport of Ly alpha photons in galaxies is a complex process and the conditions under which Ly alpha photons manage to escape from certain galaxies is still under investigation. The Lyman alpha reference sample (LARS) is a sample of 14 local star-forming galaxies, designed to study Ly alpha in detail and relate it to rest-frame UV and optical emission. Aims. With the aim of identifying rest-frame UV and optical properties, which are typical of Ly alpha emitters (LAEs, galaxies with EW(Ly alpha) > 20 angstrom) at both low and high redshift, we investigated the morphological properties of the LARS galaxies, in particular the ones that exhibit intense Ly alpha radiation. Methods. We measured sizes and morphological parameters in the continuum, Ly alpha, and Ha images. We studied morphology by using the Gini coefficient vs. M20 and asymmetry vs. concentration diagrams. We then simulated LARS galaxies at z similar to 2 and 5.7, performing the same morphological measurements. We also investigated the detectability of LARS galaxies in current deep field observations. The subsample of LAEs within LARS (LARS-LAEs) was stacked to provide a comparison to stacking studies performed at high redshift. Results. LARS galaxies have continuum size, stellar mass, and rest-frame absolute magnitude typical of Lyman break analogues in the local Universe and also similar to 2 < z < 3 star-forming galaxies and massive LAEs. LARS optical morphology is consistent with the one of merging systems, and irregular or starburst galaxies. For the first time we quantify the morphology in Ly alpha images: even if a variety of intrinsic conditions of the interstellar medium can favour the escape of Ly alpha photons, LARS-LAEs appear small in the continuum, and their Ly alpha is compact. LARS galaxies tend to be more extended in Ly alpha than in the rest-frame UV. It means that Ly alpha photons escape by forming haloes around HII regions of LARS galaxies. Conclusions. The stack of LARS-LAE Ly alpha images is peaked in the centre, indicating that the conditions, which make a galaxy an LAE, tend to produce a concentrated surface brightness profile. On the other hand, the stack of all LARS galaxies is shallower and more extended. This can be caused by the variety of dust and HI amount and distribution, which produces a more complex, patchy, and extended profile, like the one observed for Lyman break galaxies that can contribute to the stack. We cannot identify a single morphological property that controls whether a galaxy emits a net positive Ly alpha flux. However, the LARS-LAEs have continuum properties consistent with merging systems.
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| 8. |
- Oh, D. J., et al.
(författare)
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Parental history of dementia and the risk of dementia: A cross-sectional analysis of a global collaborative study
- 2023
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Ingår i: Psychiatry and Clinical Neurosciences. - 1323-1316 .- 1440-1819. ; 77:8, s. 449-456
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Tidskriftsartikel (refereegranskat)abstract
- Background: Parental history of dementia appears to increase the risk of dementia, but there have been inconsistent results. We aimed to investigate whether the association between parental history of dementia and the risk of dementia are different by dementia subtypes and sex of parent and offspring. Methods: For this cross-sectional study, we harmonized and pooled data for 17,194 older adults from nine population-based cohorts of eight countries. These studies conducted face-to-face diagnostic interviews, physical and neurological examinations, and neuropsychological assessments to diagnose dementia. We investigated the associations of maternal and paternal history of dementia with the risk of dementia and its subtypes in offspring. Results: The mean age of the participants was 72.8 +/- 7.9 years and 59.2% were female. Parental history of dementia was associated with higher risk of dementia (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.15-1.86) and Alzheimer's disease (AD) (OR = 1.72, 95% CI = 1.31-2.26), but not with the risk of non-AD. This was largely driven by maternal history of dementia, which was associated with the risk of dementia (OR = 1.51, 95% CI = 1.15-1.97) and AD (OR = 1.80, 95% CI = 1.33-2.43) whereas paternal history of dementia was not. These results remained significant when males and females were analyzed separately (OR = 2.14, 95% CI = 1.28-3.55 in males; OR = 1.68, 95% CI = 1.16-2.44 for females). Conclusions: Maternal history of dementia was associated with the risk of dementia and AD in both males and females. Maternal history of dementia may be a useful marker for identifying individuals at higher risk of AD and stratifying the risk for AD in clinical trials.
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| 9. |
- Amanullah, Rahman, et al.
(författare)
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Diversity in extinction laws of Type Ia supernovae measured between 0.2 and 2 μm
- 2015
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 453:3, s. 3300-3328
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Tidskriftsartikel (refereegranskat)abstract
- We present ultraviolet (UV) observations of six nearby Type Ia supernovae (SNe Ia) obtained with the Hubble Space Telescope, three of which were also observed in the near-IR (NIR) with Wide-Field Camera 3. UV observations with the Swift satellite, as well as ground-based optical and NIR data provide complementary information. The combined data set covers the wavelength range 0.2-2 mu m. By also including archival data of SN 2014J, we analyse a sample spanning observed colour excesses up to E(B - V) = 1.4 mag. We study the wavelength-dependent extinction of each individual SN and find a diversity of reddening laws when characterized by the total-to-selective extinction R-V. In particular, we note that for the two SNe with E(B - V) greater than or similar to 1 mag, for which the colour excess is dominated by dust extinction, we find R-V = 1.4 +/- 0.1 and R-V = 2.8 +/- 0.1. Adding UV photometry reduces the uncertainty of fitted R-V by similar to 50 per cent allowing us to also measure R-V of individual low-extinction objects which point to a similar diversity, currently not accounted for in the analyses when SNe Ia are used for studying the expansion history of the Universe.
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| 10. |
- Berry, Michael, et al.
(författare)
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STACKED REST-FRAME ULTRAVIOLET SPECTRA OF Ly alpha-EMITTING AND CONTINUUM-SELECTED GALAXIES AT 2 < z < 3.5
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 749:1, s. 4-
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Tidskriftsartikel (refereegranskat)abstract
- We present properties of individual and composite rest-UV spectra of continuum-and narrowband-selected star-forming galaxies (SFGs) at a redshift of 2 < z < 3.5 discovered by the MUSYC collaboration in the Extended Chandra Deep Field-South. Among our sample of 81 UV-bright SFGs, 59 have R < 25.5, of which 32 have rest-frame equivalent widths of W-Ly alpha > 20 angstrom, the canonical limit to be classified as an Ly alpha-emitting galaxy. We divide our data set into subsamples based on properties that we are able to measure for each individual galaxy: Ly alpha equivalent width, rest-frame UV colors, and redshift. Among our subsample of galaxies with R < 25.5, those with rest frame W-Ly alpha > 20 angstrom have bluer UV continua, weaker low-ionization interstellar absorption lines, weaker C IV absorption, and stronger Si II* nebular emission than those with W-Ly alpha < 20 angstrom. We measure a velocity offset of Delta nu similar to 600 km s(-1) between Ly alpha emission and low-ionization absorption, which does not vary substantially among any of our subsamples. We find that the interstellar component, as opposed to the stellar component, dominates the high-ionization absorption line profiles. We find that the low-and high-ionization Si ionization states have similar kinematic properties, yet the low-ionization absorption is correlated with Ly alpha emission and the high-ionization absorption is not. These trends are consistent with outflowing neutral gas being in the form of neutral clouds embedded in ionized gas as previously suggested by Steidel et al. Moreover, our galaxies with bluer UV colors have stronger Ly alpha emission, weaker low-ionization absorption, and more prominent nebular emission line profiles. From a redshift of 2.7 < z < 3.5 to 2.0 < z < 2.7, our subsample of galaxies with W-Ly alpha < 20 angstrom shows no significant evolution in their physical properties or the nature of their outflows. Among our data set, UV-bright galaxies with W-Ly alpha > 20 angstrom exhibit weaker Ly alpha emission at lower redshifts, although we caution that this could be caused by spectroscopic confirmation of low Ly alpha equivalent width galaxies being harder at z similar to 3 than z similar to 2.
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