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| 2. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 3. |
- Barack, Leor, et al.
(författare)
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Black holes, gravitational waves and fundamental physics : a roadmap
- 2019
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Ingår i: Classical and quantum gravity. - : IOP Publishing. - 0264-9381 .- 1361-6382. ; 36:14
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Forskningsöversikt (refereegranskat)abstract
- The grand challenges of contemporary fundamental physics dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'.
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| 4. |
- Bergemann, Maria, et al.
(författare)
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The Gaia-ESO Survey : Hydrogen lines in red giants directly trace stellar mass
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 594
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Tidskriftsartikel (refereegranskat)abstract
- Red giant stars are perhaps the most important type of stars for Galactic and extra-galactic archaeology: they are luminous, occur in all stellar populations, and their surface temperatures allow precise abundance determinations for many different chemical elements. Yet, the full star formation and enrichment history of a galaxy can be traced directly only if two key observables can be determined for large stellar samples: age and chemical composition. While spectroscopy is a powerful method to analyse the detailed abundances of stars, stellar ages are the missing link in the chain, since they are not a direct observable. However, spectroscopy should be able to estimate stellar masses, which for red giants directly infer ages provided their chemical composition is known. Here we establish a new empirical relation between the shape of the hydrogen line in the observed spectra of red giants and stellar mass determined from asteroseismology. The relation allows determining stellar masses and ages with an accuracy of 10-15%. The method can be used with confidence for stars in the following range of stellar parameters: 4000 < T-eff < 5000 K, 0.5 < log g < 3.5, -2.0 < [ Fe/H] < 0.3, and luminosities log L/L-Sun < 2.5. Our analysis provides observational evidence that the H-alpha spectral characteristics of red giant stars are tightly correlated with their mass and therefore their age. We also show that the method samples well all stellar populations with ages above 1 Gyr. Targeting bright giants, the method allows obtaining simultaneous age and chemical abundance information far deeper than would be possible with asteroseismology, extending the possible survey volume to remote regions of the Milky Way and even to neighbouring galaxies such as Andromeda or the Magellanic Clouds even with current instrumentation, such as the VLT and Keck facilities.
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| 5. |
- Puri, Rishi, et al.
(författare)
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Transcatheter aortic valve implantation in patients with small aortic annuli using a 20 mm balloon-expanding valve
- 2017
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 103, s. 148-153
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Tidskriftsartikel (refereegranskat)abstract
- Background While transcatheter aortic valve implantation (TAVI) is established for treating highoperative risk surgical aortic valve replacement candidates, until recently the smallest transcatheter heart valve (THV) measured 23 mm, posing greater risk for annular rupture and THV failure in patients with aortic stenosis (AS) with small aortic annuli (=20 mm). Objectives In the setting of a multicentre registry, we report on the safety, efficacy and early clinical outcomes of the SAPIEN XT 20 mm balloon-expanding THV. Results Among TAVI 55 recipients (n=30 for native AS, n=25 for a valve-in-valve procedure (V-in-V)), median age and Society of Thoracic Surgeons score were 85 (81 to 87) years and 7.8 (4.7 to 12.4)%, respectively. Mean and minimum annular diameters were 19±1 and 17±2 mm, respectively, in native patients with AS, and 17±1 mm (internal diameter) in V-in-V recipients. Successful device implantation rate was 96%, with no procedural-related death. Overall in-hospital-30-day death, stroke and major bleeding rates were 5%, 2% and 9%, respectively. In native AS TAVI recipients, mean transaortic gradient decreased from 54±20 to 12±5 mm Hg ( p<0.001), and from 45±17 to 24±8 mm Hg (p<0.001) in V-in-V recipients. Severe prosthesis-patient mismatch (PPM) rates were 10% and 48% in native AS and V-in-V TAVI recipients, respectively ( p=0.03). Post-TAVI, the rate of moderate aortic regurgitation was 7% and 0% in native AS and V-in-V TAVI recipients, respectively. Conclusions TAVI with the 20 mm SAPIEN XT THV appears safe and technically feasible, with acceptable short-term clinical outcomes and low rates of severe PPM in those with native AS.
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