| 1. |
- Allentoft, Morten E., et al.
(author)
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Population genomics of post-glacial western Eurasia
- 2024
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In: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Journal article (peer-reviewed)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 2. |
- Ballesteros, Soledad, et al.
(author)
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A randomized controlled trial of brain training with non-action video games in older adults : results of the 3-month follow-up
- 2015
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In: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 7
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Journal article (peer-reviewed)abstract
- This randomized controlled study (ClinicalTrials.gov NCT02007616)investigated the maintenance of training effects of 20 1-hr non-action video gametraining sessions with selected games from a commercial package on several agedecliningcognitive functions and subjective wellbeing after a 3-month no-contactperiod. Two groups of cognitively normal older adults participated in both the posttraining(posttest) and the present follow-up study, the experimental group who receivedtraining and the control group who attended several meetings with the research teamduring the study but did not receive training. Groups were similar at baseline ondemographics, vocabulary, global cognition, and depression status. Significant improvements in the trained group, and no variation in the control group had been previously found at posttest, in processing speed, attention and visual recognition memory, as well as in two dimensions of subjective wellbeing. In the current study, improvement from baseline to 3 months follow-up was found only in wellbeing (Affection and Assertivity dimensions) in the trained group whereas there was no change in the control group. Previous significant improvements in processing speed, attentionand spatial memory become nonsignificant after the 3-month interval. Training olderadults with non-action video games enhanced aspects of cognition just after training butthis effect disappeared after a 3-month no-contact follow-up period. Cognitive plasticitycan be induced in older adults by training, but to maintain the benefits periodic boosting sessions would be necessary.
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| 3. |
- Ballesteros, Soledad, et al.
(author)
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Brain training with non-action video games enhances aspects of cognition in older adults : a randomized controlled trial
- 2014
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In: Frontiers in Aging Neuroscience. - : Frontiers Media S.A.. - 1663-4365. ; 6
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Journal article (peer-reviewed)abstract
- Age-related cognitive and brain declines can result in functional deterioration in many cognitive domains, dependency, and dementia. A major goal of aging research is to investigate methods that help to maintain brain health, cognition, independent living and wellbeing in older adults. This randomized controlled study investigated the effects of 20 1-hr non-action video game training sessions with games selected from a commercially available package (Lumosity) on a series of age-declined cognitive functions and subjective wellbeing. Two groups of healthy older adults participated in the study, the experimental group who received the training and the control group who attended two meetings with the research team along the study. Groups were similar at baseline on demographics, vocabulary, global cognition, and depression status. All participants were assessed individually before and after the intervention, or a similar period of time, using neuropsychological tests and laboratory tasks to investigate possible transfer effects. The results showed significant improvements in the trained group, and no variation in the control group, in processing speed (choice reaction time), attention (reduction of distraction and increase of alertness), immediate and delayed visual recognition memory, as well as a trend to improve in Affection and Assertivity, two dimensions of the Wellbeing Scale. Visuospatial working memory (WM) and executive control (shifting strategy) did not improve. Overall, the current results support the idea that training healthy older adults with non-action video games will enhance some cognitive abilities but not others.
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| 4. |
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| 5. |
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| 6. |
- Coca-Prieto, Inmaculada, et al.
(author)
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Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis
- 2009
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In: BMC Gastroenterology. - 1471-230X. ; 9, s. 46-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. METHODS: Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases) and 31 patients with severe hypertriglyceridaemia (controls) were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. RESULTS: Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS). CONCLUSION: Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during childhood.
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| 7. |
- Gomez-Piqueras, Pedro, et al.
(author)
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Psychometric Analysis and Effectiveness of the Psychological Readiness of Injured Athlete to Return to Sport (PRIA-RS) Questionnaire on Injured Soccer Players
- 2020
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In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 17:5
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Journal article (peer-reviewed)abstract
- The decision-making process about when an athlete may safely return to training and competition after an injury is a difficult decision. Safe return to training and competition is characterised by physical and psychological readiness to return to the sport. The objectives of this study are (1) to assess the measurement properties of the Psychological Readiness of Injured Athlete to Return to Sport questionnaire (PRIA-RS), and (2) to analyse the effectiveness which the PRIA-RS questionnaire possesses when applied during four consecutive seasons on professional soccer players. One hundred and nine male soccer players from the Albacete Soccer Club (Spain) were involved during four consecutive seasons for the current study: 2012-2013, 2013-2014, 2014-2015 and 2015-2016. Psychometric analysis (validity, reliability, internal consistency and effectiveness) and external psychometric analysis (evaluating measures of patient-reported outcomes (EMPRO)) were confirmed and supported. The main results of the study reveal that the psychometric properties of this questionnaire are optimum for their application in a professional sports context.
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| 8. |
- Heili-Frades, Sarah, et al.
(author)
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Continuous monitoring of intrinsic PEEP based on expired CO2 kinetics : an experimental validation study
- 2019
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In: Critical Care. - : BMC. - 1364-8535 .- 1466-609X. ; 23
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Journal article (peer-reviewed)abstract
- Background Quantification of intrinsic PEEP (PEEPi) has important implications for patients subjected to invasive mechanical ventilation. A new non-invasive breath-by-breath method (etCO(2)D) for determination of PEEPi is evaluated. MethodsIn 12 mechanically ventilated pigs, dynamic hyperinflation was induced by interposing a resistance in the endotracheal tube. Airway pressure, flow, and exhaled CO2 were measured at the airway opening. Combining different I:E ratios, respiratory rates, and tidal volumes, 52 different levels of PEEPi (range 1.8-11.7cmH(2)O; mean 8.450.32cmH(2)O) were studied. The etCO(2)D is based on the detection of the end-tidal dilution of the capnogram. This is measured at the airway opening by means of a CO2 sensor in which a 2-mm leak is added to the sensing chamber. This allows to detect a capnogram dilution with fresh air when the pressure coming from the ventilator exceeds the PEEPi. This method was compared with the occlusion method. Results The etCO(2)D method detected PEEPi step changes of 0.2cmH(2)O. Reference and etCO(2)D PEEPi presented a good correlation (R-2 0.80, P<0.0001) and good agreement, bias -0.26, and limits of agreement +/- 1.96 SD (2.23, -2.74) (P<0.0001). Conclusions The etCO(2)D method is a promising accurate simple way of continuously measure and monitor PEEPi. Its clinical validity needs, however, to be confirmed in clinical studies and in conditions with heterogeneous lung diseases.
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| 9. |
- Hidalgo, D., et al.
(author)
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Three planets transiting the evolved star EPIC 249893012: a hot 8.8-Mearth super-Earth and two warm 14.7 and 10.2-Mearth sub-Neptunes
- 2020
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 636
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Journal article (peer-reviewed)abstract
- We report the discovery of a new planetary system with three transiting planets, one super-Earth and two sub-Neptunes, that orbit EPIC 249893012, a G8 IV-V evolved star (M⋆ = 1.05 ± 0.05 M☉, R⋆ = 1.71 ± 0.04 R☉, Teff = 5430 ± 85 K). The star is just leaving the main sequence. We combined K2 photometry with IRCS adaptive-optics imaging and HARPS, HARPS-N, and CARMENES high-precision radial velocity measurements to confirm the planetary system, determine the stellar parameters, and measure radii, masses, and densities of the three planets. With an orbital period of 3.5949-0.0007+0.0007days, a mass of 8.75-1.08+1.09 M⊕, and a radius of 1.95-0.08+0.09 R⊕, the inner planet b is compatible with nickel-iron core and a silicate mantle (ρb = 6.39-1.04+1.19 g cm-3). Planets c and d with orbital periods of 15.624-0.001+0.001 and 35.747-0.005+0.005 days, respectively, have masses and radii of 14.67-1.89+1,84 M⊕ and 3.67-0.14+0.17 R⊕ and 10.18-2.42+2.46 M⊕ and 3.94-0.12+0.13 R⊕, respectively, yielding a mean density of 1.62-0.29+0.30 and 0.91-0.23+0.25 g cm-3, respectively. The radius of planet b lies in the transition region between rocky and gaseous planets, but its density is consistent with a rocky composition. Its semimajor axis and the corresponding photoevaporation levels to which the planet has been exposed might explain its measured density today. In contrast, the densities and semimajor axes of planets c and d suggest a very thick atmosphere. The singularity of this system, which orbits a slightly evolved star that is just leaving the main sequence, makes it a good candidate for a deeper study from a dynamical point of view.
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| 10. |
- Hurtado, Pilar, et al.
(author)
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Contrasting Environmental Drivers Determine Biodiversity Patterns in Epiphytic Lichen Communities along a European Gradient
- 2020
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In: Microorganisms. - : MDPI. - 2076-2607. ; 8:12
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Journal article (peer-reviewed)abstract
- Assessing the ecological impacts of environmental change on biological communities requires knowledge of the factors driving the spatial patterns of the three diversity facets along extensive environmental gradients. We quantified the taxonomic (TD), functional (FD), and phylogenetic diversity (PD) of lichen epiphytic communities in 23 beech forests along Europe to examine their response to environmental variation (climate, habitat quality, spatial predictors) at a continental geographic scale. We selected six traits related to the climatic conditions in forest ecosystems, the water-use strategy and the nutrient uptake, and we built a phylogenetic tree based on four molecular markers. FD and climate determined TD and PD, with spatial variables also affecting PD. The three diversity facets were primarily shaped by distinct critical predictors, with the temperature diurnal range affecting FD and PD, and precipitation of the wettest month determining TD. Our results emphasize the value of FD for explaining part of TD and PD variation in lichen communities at a broad geographic scale, while highlighting that these diversity facets provide complementary information about the communities' response under changing environmental conditions. Furthermore, traits such as growth form, photobiont type, and reproductive strategy mediated the response of lichen communities to abiotic factors emerging as useful indicators of macroclimatic variations.
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| 11. |
- Insausti, Ricardo, et al.
(author)
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Ex vivo, in situ perfusion protocol for human brain fixation compatible with microscopy, MRI techniques, and anatomical studies
- 2023
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In: Frontiers in Neuroanatomy. - : Frontiers Media SA. - 1662-5129. ; 17
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Journal article (peer-reviewed)abstract
- We present a method for human brain fixation based on simultaneous perfusion of 4% paraformaldehyde through carotids after a flush with saline. The left carotid cannula is used to perfuse the body with 10% formalin, to allow further use of the body for anatomical research or teaching. The aim of our method is to develop a vascular fixation protocol for the human brain, by adapting protocols that are commonly used in experimental animal studies. We show that a variety of histological procedures can be carried out (cyto- and myeloarchitectonics, histochemistry, immunohistochemistry, intracellular cell injection, and electron microscopy). In addition, ex vivo, ex situ high-resolution MRI (9.4T) can be obtained in the same specimens. This procedure resulted in similar morphological features to those obtained by intravascular perfusion in experimental animals, provided that the postmortem interval was under 10 h for several of the techniques used and under 4 h in the case of intracellular injections and electron microscopy. The use of intravascular fixation of the brain inside the skull provides a fixed whole human brain, perfectly fitted to the skull, with negligible deformation compared to conventional techniques. Given this characteristic of ex vivo, in situ fixation, this procedure can probably be considered the most suitable one available for ex vivo MRI scans of the brain. We describe the compatibility of the method proposed for intravascular fixation of the human brain and fixation of the donor’s body for anatomical purposes. Thus, body donor programs can provide human brain tissue, while the remainder of the body can also be fixed for anatomical studies. Therefore, this method of human brain fixation through the carotid system optimizes the procurement of human brain tissue, allowing a greater understanding of human neurological diseases, while benefiting anatomy departments by making the remainder of the body available for teaching purposes.
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| 12. |
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| 13. |
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| 14. |
- Lam, Kristine W. F., et al.
(author)
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It Takes Two Planets in Resonance to Tango around K2-146
- 2020
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In: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 159:3
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Journal article (peer-reviewed)abstract
- K2-146 is a cool, 0.358M dwarf that was found to host a mini-Neptune with a 2.67 day period. The planet exhibited strong transit timing variations (TTVs) of greater than 30 minutes, indicative of the presence of an additional object in the system. Here we report the discovery of the previously undetected outer planet in the system, K2-146 c, using additional photometric data. K2-146 c was found to have a grazing transit geometry and a 3.97 day period. The outer planet was only significantly detected in the latter K2 campaigns presumably because of precession of its orbital plane. The TTVs of K2-146 b and c were measured using observations spanning a baseline of almost 1200 days. We found strong anti -correlation in the TTVs, suggesting the two planets are gravitationally interacting. Our TTV and transit model analyses revealed that K2-146 b has a radius of 2.25 0.10 Re and a mass of 5.6 0.7 Me, whereas K2-146 c has a radius of 2.591 Re and a mass of 7.1 0.9 Me. The inner and outer planets likely have moderate eccentricities of e = 0.14 0.07 and 0.16 0.07, respectively. Long-term numerical integrations of the two -planet orbital solution show that it can be dynamically stable for at least 2 Myr. We show that the resonance angles of the planet pair are librating, which may be an indication that K2-146 b and c are in a 3:2 mean motion resonance. The orbital architecture of the system points to a possible convergent migration origin.
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| 15. |
- Nowak, Grzegorz, et al.
(author)
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K2-280 b - a low density warm sub-Saturn around a mildly evolved star
- 2020
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 497:4, s. 4423-4435
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Journal article (peer-reviewed)abstract
- We present an independent discovery and detailed characterization of K2-280 b, a transiting low density warm sub-Saturn in a 19.9-d moderately eccentric orbit (e = 0.35(-0.04)(+0.05)) from K2 campaign 7. A joint analysis of high precision HARPS, HARPS-N, and FIES radial velocity measurements and K2 photometric data indicates that K2-280 b has a radius of R-b = 7.50 +/- 0.44 R-circle plus and a mass of M-b = 37.1 +/- 5.6 M-circle plus, yielding a mean density of rho(b) = 0.48(-0.10)(+0.13) g cm(-3). The host star is a mildly evolved G7 star with an effective temperature of T-eff = 5500 +/- 100 K, a surface gravity of log g(star) = 4.21 +/- 0.05 (cgs), and an iron abundance of [Fe/H] = 0.33 +/- 0.08 dex, and with an inferred mass of M-star = 1.03 +/- 0.03 M-circle dot and a radius of R-star = 1.28 +/- 0.07 R-circle dot. We discuss the importance of K2-280 b for testing formation scenarios of sub-Saturn planets and the current sample of this intriguing group of planets that are absent in the Solar system.
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| 16. |
- Persson, Carina, 1964, et al.
(author)
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Greening of the brown-dwarf desert EPIC 212036875b: a 51 M-J object in a 5-day orbit around an F7V star
- 2019
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 628
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Journal article (peer-reviewed)abstract
- Context. Although more than 2000 brown dwarfs have been detected to date, mainly from direct imaging, their characterisation is difficult due to their faintness and model-dependent results. In the case of transiting brown dwarfs, however, it is possible to make direct high-precision observations. Aims. Our aim is to investigate the nature and formation of brown dwarfs by adding a new well-characterised object, in terms of its mass, radius and bulk density, to the currently small sample of less than 20 transiting brown dwarfs. Methods. One brown dwarf candidate was found by the KESPRINT consortium when searching for exoplanets in the K2 space mission Campaign 16 field. We combined the K2 photometric data with a series of multicolour photometric observations, imaging, and radial velocity measurements to rule out false positive scenarios and to determine the fundamental properties of the system. Results. We report the discovery and characterisation of a transiting brown dwarf in a 5.17-day eccentric orbit around the slightly evolved F7V star EPIC 212036875. We find a stellar mass of 1.15 +/- 0.08 M-circle dot, a stellar radius of 1.41 +/- 0.05 R-circle dot, and an age of 5.1 +/- 0.9 Gyr. The mass and radius of the companion brown dwarf are 51 +/- 2 M-J and 0.83 +/- 0.03 R-J, respectively, corresponding to a mean density of 108(-13)(+15) g cm(-3). Conclusions. EPIC 212036875 b is a rare object that resides in the brown-dwarf desert. In the mass-density diagram for planets, brown dwarfs, and stars, we find that all giant planets and brown dwarfs follow the same trend from similar to 0.3 M-J to the turn-over to hydrogen burning stars at similar to 73 M-J. EPIC 212036875 b falls close to the theoretical model for mature H/He dominated objects in this diagram as determined by interior structure models. We argue that EPIC 212036875 b formed via gravitational disc instabilities in the outer part of the disc, followed by a quick migration. Orbital tidal circularisation may have started early in its history for a brief period when the brown dwarf's radius was larger. The lack of spin-orbit synchronisation points to a weak stellar dissipation parameter (Q(star)' greater than or similar to 10(8)), which implies a circularisation timescale of greater than or similar to 23 Gyr, or suggests an interaction between the magnetic and tidal forces of the star and the brown dwarf.
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| 17. |
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| 18. |
- Ravikumar, Sadhana, et al.
(author)
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Ex vivo MRI atlas of the human medial temporal lobe : characterizing neurodegeneration due to tau pathology
- 2021
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In: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 9:1
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Journal article (peer-reviewed)abstract
- Tau neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer’s disease (AD). To elucidate patterns of structural change in the MTL specifically associated with tau pathology, we compared high-resolution ex vivo MRI scans of human postmortem MTL specimens with histology-based pathological assessments of the MTL. MTL specimens were obtained from twenty-nine brain donors, including patients with AD, other dementias, and individuals with no known history of neurological disease. Ex vivo MRI scans were combined using a customized groupwise diffeomorphic registration approach to construct a 3D probabilistic atlas that captures the anatomical variability of the MTL. Using serial histology imaging in eleven specimens, we labelled the MTL subregions in the atlas based on cytoarchitecture. Leveraging the atlas and neuropathological ratings of tau and TAR DNA-binding protein 43 (TDP-43) pathology severity, morphometric analysis was performed to correlate regional MTL thickness with the severity of tau pathology, after correcting for age and TDP-43 pathology. We found significant correlations between tau pathology and thickness in the entorhinal cortex (ERC) and stratum radiatum lacunosum moleculare (SRLM). When focusing on cases with low levels of TDP-43 pathology, we found strong associations between tau pathology and thickness in the ERC, SRLM and the subiculum/cornu ammonis 1 (CA1) subfields of the hippocampus, consistent with early Braak stages.
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| 19. |
- Ravikumar, Sadhana, et al.
(author)
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Improved Segmentation of Deep Sulci in Cortical Gray Matter Using a Deep Learning Framework Incorporating Laplace’s Equation
- 2023
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In: Information Processing in Medical Imaging - 28th International Conference, IPMI 2023, Proceedings. - 1611-3349 .- 0302-9743. - 9783031340475 ; 13939 LNCS, s. 692-704
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Conference paper (peer-reviewed)abstract
- When developing tools for automated cortical segmentation, the ability to produce topologically correct segmentations is important in order to compute geometrically valid morphometry measures. In practice, accurate cortical segmentation is challenged by image artifacts and the highly convoluted anatomy of the cortex itself. To address this, we propose a novel deep learning-based cortical segmentation method in which prior knowledge about the geometry of the cortex is incorporated into the network during the training process. We design a loss function which uses the theory of Laplace’s equation applied to the cortex to locally penalize unresolved boundaries between tightly folded sulci. Using an ex vivo MRI dataset of human medial temporal lobe specimens, we demonstrate that our approach outperforms baseline segmentation networks, both quantitatively and qualitatively.
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| 20. |
- Ravikumar, Sadhana, et al.
(author)
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Postmortem imaging reveals patterns of medial temporal lobe vulnerability to tau pathology in Alzheimer’s disease
- 2024
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In: Nature Communications. - 2041-1723. ; 15:1
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Journal article (peer-reviewed)abstract
- Our current understanding of the spread and neurodegenerative effects of tau neurofibrillary tangles (NFTs) within the medial temporal lobe (MTL) during the early stages of Alzheimer’s Disease (AD) is limited by the presence of confounding non-AD pathologies and the two-dimensional (2-D) nature of conventional histology studies. Here, we combine ex vivo MRI and serial histological imaging from 25 human MTL specimens to present a detailed, 3-D characterization of quantitative NFT burden measures in the space of a high-resolution, ex vivo atlas with cytoarchitecturally-defined subregion labels, that can be used to inform future in vivo neuroimaging studies. Average maps show a clear anterior to poster gradient in NFT distribution and a precise, spatial pattern with highest levels of NFTs found not just within the transentorhinal region but also the cornu ammonis (CA1) subfield. Additionally, we identify granular MTL regions where measures of neurodegeneration are likely to be linked to NFTs specifically, and thus potentially more sensitive as early AD biomarkers.
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| 21. |
- Ravikumar, Sadhana, et al.
(author)
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Unfolding the Medial Temporal Lobe Cortex to Characterize Neurodegeneration Due to Alzheimer’s Disease Pathology Using Ex vivo Imaging
- 2021
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In: Machine Learning in Clinical Neuroimaging - 4th International Workshop, MLCN 2021, Held in Conjunction with MICCAI 2021, Proceedings. - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. - 9783030875855 ; 13001 LNCS, s. 3-12
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Conference paper (peer-reviewed)abstract
- Neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer’s Disease (AD). In this work, we investigate the relationship between MTL morphometry features derived from high-resolution ex vivo imaging and histology-based measures of NFT pathology using a topological unfolding framework applied to a dataset of 18 human postmortem MTL specimens. The MTL has a complex 3D topography and exhibits a high degree of inter-subject variability in cortical folding patterns which poses a significant challenge for volumetric registration methods typically used during MRI template construction. By unfolding the MTL cortex, the proposed framework explicitly accounts for the sheet-like geometry of the MTL cortex and provides a two-dimensional reference coordinate space which can be used to implicitly register cortical folding patterns across specimens based on distance along the cortex despite large anatomical variability. Leveraging this framework in a subset of 15 specimens, we characterize the associations between NFTs and morphological features such as cortical thickness and surface curvature and identify regions in the MTL where patterns of atrophy are strongly correlated with NFT pathology.
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| 22. |
- Roh, Hyung S., et al.
(author)
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Integrating Color Deconvolution Thresholding and Weakly Supervised Learning for Automated Segmentation of Neurofibrillary Tangle and Neuropil Threads
- 2023
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In: Medical Imaging 2023 : Digital and Computational Pathology - Digital and Computational Pathology. - 1605-7422. - 9781510660472 ; 12471
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Conference paper (peer-reviewed)abstract
- Abnormally phosphorylated tau proteins are known to be a major indicator of Alzheimer's Disease (AD) with strong association with memory loss and cognitive decline. Automated generation of pixel-wise accurate neurofibrillary tangles (NFTs) and neuropil threads (NTs) segmentation is a challenging task, due to lack of ground truth segmentation data of these abnormal tau pathology. This problem is most prominent in the case of segmenting NTs, where the small threadlike morphology makes pixel-wise labeling a laborious task and unrealistic for large-scale studies. Lack of ground truth data poses a significant limitation for many learning-based methods to generate accurate segmentations of NFTs and NTs. This work presents an automated pipeline for pixel level segmentation of NFTs and NTs that does not rely on ground truth segmentation data. The pipeline is composed of four main steps: (1) color deconvolution is used to separate histopathology images into staining channels (DAB, Hematoxylin, and Eosin), (2) Otsu's thresholding is used on the DAB stain channel to generate pixel level segmentation of abnormal tau proteins staining, (3) a weakly-supervised learning paradigm (WildCat), using only global descriptors of images, is used to generate density maps of potential regions of NFTs and NTs, and (4) density maps and segmentations are then integrated using connected component analysis to localize NFTs and NTs in the detected tau segmentations. Our results show high global classification accuracy for NFTs (Acc:0.96) and NTs (Acc:0.91), and statistically significant distinctions when evaluating the percent area occupied of the detected NTs relative to expert ratings of NTs severity. Qualitative assessment of the NFTs and NTs results showed accurate pixel-level segmentations of the NFTs, while modest performance for NTs.
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| 23. |
- Sadaghiani, Shokufeh, et al.
(author)
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Associations of phosphorylated tau pathology with whole-hemisphere ex vivo morphometry in 7 tesla MRI
- 2023
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In: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:6, s. 2355-2364
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Journal article (peer-reviewed)abstract
- Introduction: Neurodegenerative disorders are associated with different pathologies that often co-occur but cannot be measured specifically with in vivo methods. Methods: Thirty-three brain hemispheres from donors with an Alzheimer's disease (AD) spectrum diagnosis underwent T2-weighted magnetic resonance imaging (MRI). Gray matter thickness was paired with histopathology from the closest anatomic region in the contralateral hemisphere. Results: Partial Spearman correlation of phosphorylated tau and cortical thickness with TAR DNA-binding protein 43 (TDP-43) and α-synuclein scores, age, sex, and postmortem interval as covariates showed significant relationships in entorhinal and primary visual cortices, temporal pole, and insular and posterior cingulate gyri. Linear models including Braak stages, TDP-43 and α-synuclein scores, age, sex, and postmortem interval showed significant correlation between Braak stage and thickness in the parahippocampal gyrus, entorhinal cortex, and Broadman area 35. Conclusion: We demonstrated an association of measures of AD pathology with tissue loss in several AD regions despite a limited range of pathology in these cases. Highlights: Neurodegenerative disorders are associated with co-occurring pathologies that cannot be measured specifically with in vivo methods. Identification of the topographic patterns of these pathologies in structural magnetic resonance imaging (MRI) may provide probabilistic biomarkers. We demonstrated the correlation of the specific patterns of tissue loss from ex vivo brain MRI with underlying pathologies detected in postmortem brain hemispheres in patients with Alzheimer's disease (AD) spectrum disorders. The results provide insight into the interpretation of in vivo structural MRI studies in patients with AD spectrum disorders.
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| 24. |
- Subjak, Jan, et al.
(author)
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TOI-503: The First Known Brown-dwarf Am-star Binary from the TESS Mission
- 2020
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In: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 159:4
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Journal article (peer-reviewed)abstract
- We report the discovery of an intermediate-mass transiting brown dwarf (BD), TOI-503b, from the TESS mission. TOI-503b is the first BD discovered by TESS, and it has circular orbit around a metallic-line A-type star with a period of P.=.3.6772.+/-.0.0001 days. The light curve from TESS indicates that TOI-503b transits its host star in a grazing manner, which limits the precision with which we measure the BD's radius ( = R 1.34+ R b 0.150.26 J). We obtained highresolution spectroscopic observations with the FIES, Ondr.ejov, PARAS, Tautenburg, and TRES spectrographs, and measured the mass of TOI-503b to be Mb.=.53.7.+/-.1.2 MJ. The host star has a mass of Ma.=.1.80.+/-.0.06Me, a radius of Ra.=.1.70.+/-.0.05Re, an effective temperature of Teff.=.7650.+/-.160 K, and a relatively high metallicity of 0.61.+/-.0.07 dex. We used stellar isochrones to derive the age of the system to be 180 Myr, which places its age between that of RIK 72b (a 10 Myr old BD in the Upper Scorpius stellar association) and AD 3116b (a 600 Myr old BD in the Praesepe cluster). Given the difficulty in measuring the tidal interactions between BDs and their host stars, we cannot precisely say whether this BD formed in situ or has had its orbit circularized by its host star over the relatively short age of the system. Instead, we offer an examination of plausible values for the tidal quality factor for the star and BD. TOI-503b joins a growing number of known short-period, intermediate-mass BDs orbiting mainsequence stars, and is the second such BD known to transit an A star, after HATS-70b. With the growth in the population in this regime, the driest region in the BD desert (35-55MJ sin i) is reforesting.
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| 25. |
- Surányi, Balázs, et al.
(author)
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Syntax-prosody mapping, topic-comment structure and stress-focus correspondence in Hungarian
- 2012
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In: Prosody and Meaning. - : DE GRUYTER. - 1861-4167. - 9783110261790 - 9783110260076 ; 25, s. 35-71
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Book chapter (peer-reviewed)abstract
- This paper investigates the basic prosodic structure of Hungarian and its inter-action with information structure, in particular the following two aspects: the prosodic realization of the topic-comment partition, and the resolution of conflicts that may potentially arise between the basic algorithms of the syntax-prosody mapping on the one hand, and the prosodic requirement of the focus constituent to contain nuclear stress (stress-focus correspondence) on the other . We report the results of a production experiment in which we examined sen-tences where the semantic focus constituent is not in the position of the de-fault nuclear stress and is unable to be placed there by a syntactic transforma-tion . Regarding the topic-comment partition, our data reveals that there is a systematic prosodic difference between the two parts of a sentence in terms of pitch accent type: H*L is the default accent within the comment, while topic phrases are realized with a variety of pitch accents, but not with H*L . With re-spect to the conflict between the syntax-prosody mapping and the stress-focus correspondence, we found three resolution strategies: (i) adjusting the location of the topic-comment partition by avoiding the (default) comment accent H*L in pre-focal positions; (ii) extending the F0-register of the narrowly focused element while keeping the default prosodic phrasing intact; and (iii) making no changes (in compliance to the requirement of stress-focus correspondence) . Finally, we discuss several possible theoretical analyses that may derive these effects .
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| 26. |
- Wuestefeld, Anika, et al.
(author)
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Comparison of histological delineations of medial temporal lobe cortices by four independent neuroanatomy laboratories
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In: Hippocampus. - 1050-9631.
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Journal article (peer-reviewed)abstract
- The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and prone to the accumulation of certain neuropathologies such as Alzheimer's disease neurofibrillary tau tangles. The MTL cortex is composed of several subregions which differ in their functional and cytoarchitectonic features. As neuroanatomical schools rely on different cytoarchitectonic definitions of these subregions, it is unclear to what extent their delineations of MTL cortex subregions overlap. Here, we provide an overview of cytoarchitectonic definitions of the entorhinal and parahippocampal cortices as well as Brodmann areas (BA) 35 and 36, as provided by four neuroanatomists from different laboratories, aiming to identify the rationale for overlapping and diverging delineations. Nissl-stained series were acquired from the temporal lobes of three human specimens (two right and one left hemisphere). Slices (50 μm thick) were prepared perpendicular to the long axis of the hippocampus spanning the entire longitudinal extent of the MTL cortex. Four neuroanatomists annotated MTL cortex subregions on digitized slices spaced 5 mm apart (pixel size 0.4 μm at 20× magnification). Parcellations, terminology, and border placement were compared among neuroanatomists. Cytoarchitectonic features of each subregion are described in detail. Qualitative analysis of the annotations showed higher agreement in the definitions of the entorhinal cortex and BA35, while the definitions of BA36 and the parahippocampal cortex exhibited less overlap among neuroanatomists. The degree of overlap of cytoarchitectonic definitions was partially reflected in the neuroanatomists' agreement on the respective delineations. Lower agreement in annotations was observed in transitional zones between structures where seminal cytoarchitectonic features are expressed less saliently. The results highlight that definitions and parcellations of the MTL cortex differ among neuroanatomical schools and thereby increase understanding of why these differences may arise. This work sets a crucial foundation to further advance anatomically-informed neuroimaging research on the human MTL cortex.
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| 27. |
- Yushkevich, Paul A., et al.
(author)
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Three-dimensional mapping of neurofibrillary tangle burden in the human medial temporal lobe
- 2021
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In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 144:9, s. 2784-2797
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Journal article (peer-reviewed)abstract
- Tau protein neurofibrillary tangles are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer's disease and related dementias. Our knowledge of the pattern of neurofibrillary tangle progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in Alzheimer's disease, is based on conventional two-dimensional histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe specimens (age 75.3 ± 11.4 years, range 45 to 93) were used to construct three-dimensional quantitative maps of neurofibrillary tangle burden in the medial temporal lobe at individual and group levels. Group-level maps were obtained in the space of an in vivo brain template, and neurofibrillary tangles were measured in specific anatomical regions defined in this template. Three-dimensional maps of neurofibrillary tangle burden revealed significant variation along the anterior-posterior axis. While early neurofibrillary tangle pathology is thought to be confined to the transentorhinal region, we found similar levels of burden in this region and other medial temporal lobe subregions, including amygdala, temporopolar cortex, and subiculum/cornu ammonis 1 hippocampal subfields. Overall, the three-dimensional maps of neurofibrillary tangle burden presented here provide more complete information about the distribution of this neurodegenerative pathology in the region of the cortex where it first emerges in Alzheimer's disease, and may help inform the field about the patterns of pathology spread, as well as support development and validation of neuroimaging biomarkers.
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| 28. |
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