| 11. |
- Abdalla, H., et al.
(author)
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H.E.S.S. Follow-up Observations of Binary Black Hole Coalescence Events during the Second and Third Gravitational-wave Observing Runs of Advanced LIGO and Advanced Virgo
- 2021
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In: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 923:1
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Journal article (peer-reviewed)abstract
- We report on the observations of four well-localized binary black hole (BBH) mergers by the High Energy Stereoscopic System (H.E.S.S.) during the second and third observing runs of Advanced LIGO and Advanced Virgo, O2 and O3. H.E.S.S. can observe 20 deg(2) of the sky at a time and follows up gravitational-wave (GW) events by "tiling" localization regions to maximize the covered localization probability. During O2 and O3, H.E.S.S. observed large portions of the localization regions, between 35% and 75%, for four BBH mergers (GW170814, GW190512_180714, GW190728_064510, and S200224ca). For these four GW events, we find no significant signal from a pointlike source in any of the observations, and we set upper limits on the very high energy (>100 GeV) gamma-ray emission. The 1-10 TeV isotropic luminosity of these GW events is below 10(45) erg s(-1) at the times of the H.E.S.S. observations, around the level of the low-luminosity GRB 190829A. Assuming no changes are made to how follow-up observations are conducted, H.E.S.S. can expect to observe over 60 GW events per year in the fourth GW observing run, O4, of which eight would be observable with minimal latency.
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| 12. |
- Bousquet, Jean, et al.
(author)
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ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
- 2021
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
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Research review (peer-reviewed)abstract
- Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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| 13. |
- Singleton, Ellen, et al.
(author)
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Heterogeneous distribution of tau pathology in the behavioural variant of Alzheimer's disease
- 2021
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In: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 92:8, s. 872-880
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Journal article (peer-reviewed)abstract
- Objective: The clinical phenotype of the rare behavioural variant of Alzheimer's disease (bvAD) is insufficiently understood. Given the strong clinico-anatomical correlations of tau pathology in AD, we investigated the distribution of tau deposits in bvAD, in-vivo and ex-vivo, using positron emission tomography (PET) and postmortem examination. Methods: For the tau PET study, seven amyloid-β positive bvAD patients underwent [18F]flortaucipir or [18F]RO948 PET. We converted tau PET uptake values into standardised (W-)scores, adjusting for age, sex and mini mental state examination in a 'typical' memory-predominant AD (n=205) group. W-scores were computed within entorhinal, temporoparietal, medial and lateral prefrontal, insular and whole-brain regions-of-interest, frontal-to-entorhinal and frontal-to-parietal ratios and within intrinsic functional connectivity network templates. For the postmortem study, the percentage of AT8 (tau)-positive area in hippocampus CA1, temporal, parietal, frontal and insular cortices were compared between autopsy-confirmed patients with bvAD (n=8) and typical AD (tAD;n=7). Results: Individual regional W-scores ≥1.96 (corresponding to p<0.05) were observed in three cases, that is, case #5: medial prefrontal cortex (W=2.13) and anterior default mode network (W=3.79), case #2: lateral prefrontal cortex (W=2.79) and salience network (W=2.77), and case #7: frontal-to-entorhinal ratio (W=2.04). The remaining four cases fell within the normal distributions of the tAD group. Postmortem AT8 staining indicated no group-level regional differences in phosphorylated tau levels between bvAD and tAD (all p>0.05). Conclusions: Both in-vivo and ex-vivo, patients with bvAD showed heterogeneous distributions of tau pathology. Since key regions involved in behavioural regulation were not consistently disproportionally affected by tau pathology, other factors are more likely driving the clinical phenotype in bvAD.
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| 14. |
- Wisse, Laura E.M., et al.
(author)
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Hippocampal subfield volumetry from structural isotropic 1 mm3 MRI scans : A note of caution
- 2021
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In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 42:2, s. 539-550
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Journal article (peer-reviewed)abstract
- Spurred by availability of automatic segmentation software, in vivo MRI investigations of human hippocampal subfield volumes have proliferated in the recent years. However, a majority of these studies apply automatic segmentation to MRI scans with approximately 1 × 1 × 1 mm3 resolution, a resolution at which the internal structure of the hippocampus can rarely be visualized. Many of these studies have reported contradictory and often neurobiologically surprising results pertaining to the involvement of hippocampal subfields in normal brain function, aging, and disease. In this commentary, we first outline our concerns regarding the utility and validity of subfield segmentation on 1 × 1 × 1 mm3 MRI for volumetric studies, regardless of how images are segmented (i.e., manually or automatically). This image resolution is generally insufficient for visualizing the internal structure of the hippocampus, particularly the stratum radiatum lacunosum moleculare, which is crucial for valid and reliable subfield segmentation. Second, we discuss the fact that automatic methods that are employed most frequently to obtain hippocampal subfield volumes from 1 × 1 × 1 mm3 MRI have not been validated against manual segmentation on such images. For these reasons, we caution against using volumetric measurements of hippocampal subfields obtained from 1 × 1 × 1 mm3 images.
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| 15. |
- Haugaard-Kedström, Linda M., et al.
(author)
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A High-Affinity Peptide Ligand Targeting Syntenin Inhibits Glioblastoma
- 2021
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 64:3, s. 1423-1434
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Journal article (peer-reviewed)abstract
- Despite the recent advances in cancer therapeutics, highly aggressive cancer forms, such as glioblastoma (GBM), still have very low survival rates. The intracellular scaffold protein syntenin, comprising two postsynaptic density protein-95/discslarge/zona occludens-1 (PDZ) domains, has emerged as a novel therapeutic target in highly malignant phenotypes including GBM. Here, we report the development of a novel, highly potent, and metabolically stable peptide inhibitor of syntenin, KSL-128114, which binds the PDZ1 domain of syntenin with nanomolar affinity. KSL-128114 is resistant toward degradation in human plasma and mouse hepatic microsomes and displays a global PDZ domain selectivity for syntenin. An X-ray crystal structure reveals that KSL128114 interacts with syntenin PDZ1 in an extended noncanonical binding mode. Treatment with KSL-128114 shows an inhibitory effect on primary GBM cell viability and significantly extends survival time in a patient-derived xenograft mouse model. Thus, KSL-128114 is a novel promising candidate with therapeutic potential for highly aggressive tumors, such as GBM.
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| 16. |
- Jiang, Qiang, et al.
(author)
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Origin of geochemically heterogeneous mid-ocean ridge basalts from the Macquarie Ridge Complex, SW Pacific
- 2021
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In: Lithos. - : Elsevier. - 0024-4937 .- 1872-6143. ; 380-381
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Journal article (peer-reviewed)abstract
- The Macquarie Ridge Complex (MRC), located at the Australian–Pacific plate boundary south of New Zealand, is a rugged bathymetric ridge comprising a series of submarine seamounts and Macquarie Island, the only subaerial portion of the complex. Mid-ocean ridge basalts (MORBs) from Macquarie Island show various enrichments in incompatible elements with compositions ranging from typical normal MORB to enriched MORB. However, these basalts have isotopic compositions trending towards a high μ-like (μ = 238U/204Pb; HIMU) mantle component, which is unusual for MORB-type rocks. The origin of this mantle signature is not understood, and it is unclear whether this isotopic signature is characteristic of the entire MRC or unique to Macquarie Island. Here we report new major and trace element abundances, and Sr, Nd, and Pb isotopes for samples from the MRC seamounts and from new sampling sites on Macquarie Island. The geochemical and isotopic data show that the entire MRC comprises normal to enriched MORB. Mixing modelling indicates that the heterogeneous isotopic signatures of the MRC basalts are not derived from contamination of the nearby Balleny mantle plume but have affinities with that of the Cenozoic Zealandia intraplate HIMU-like basalts. We propose that the heterogeneous geochemical signatures of the MRC basalts are derived from amphibole-bearing garnet pyroxenite veins, which is supported by the rare earth element partial melting modelling and strong correlations between Nd and Pb isotopic ratios vs La/Sm. We posit that the pyroxenite veins were generated in the oceanic lithospheric mantle, which was metasomatised by hydrous and carbonatitic fluids/melts derived either from delaminated, metasomatised Zealandia subcontinental lithosphere mantle, or from subducted material in the asthenosphere. The subducted material could be derived from ancient and/or recent subduction along the former east Gondwana margin.
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| 17. |
- Jiang, Qiang, et al.
(author)
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Timing of Seafloor Spreading Cessation at the Macquarie Ridge Complex (SW Pacific) and Implications for Upper Mantle Heterogeneity
- 2021
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In: Geochemistry Geophysics Geosystems. - : American Geophysical Union (AGU). - 1525-2027. ; 22:1
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Journal article (peer-reviewed)abstract
- The Macquarie Ridge Complex (MRC) on the Australia‐Pacific plate boundary south of New Zealand is an extinct mid‐ocean ridge that has experienced a complex tectonic history and produced highly heterogeneous mid‐ocean ridge basalts (MORBs). When and how seafloor spreading ceased along the proto‐Macquarie mid‐ocean ridge remain elusive, and it is unclear how the mantle source of MORBs is affected by the gradual cessation of seafloor spreading at mid‐ocean ridges. To constrain the tectonic evolution of the MRC, the mantle source variations for MORBs at dying mid‐ocean ridges, and the mechanisms of mantle enrichment and asthenospheric heterogeneities, we report 11 pyroxene, plagioclase, basaltic glass, groundmass, and sericite 40Ar/39Ar and one zircon U‐Pb ages for the MRC MORBs. Our data reveal that basalts from the MRC seamounts were erupted between 25.9 and 1.6 Ma and Macquarie Island at ∼10 Ma. Combined age and plate reconstruction results reveal that the cessation of seafloor spreading at the MRC generally propagated from south to north along the ridge. Basalts produced by the then dying Macquarie mid‐ocean ridge at different times on different seamounts/island show a large variation in isotopic compositions and there is no clear correlation between ages and isotopic ratios. The heterogeneity of mantle source for MORBs from the proto‐Macquarie mid‐ocean ridge suggests that the upper asthenospheric mantle is heterogeneous, and such heterogeneity becomes most obvious at dying mid‐ocean ridges where the degrees of partial melting are low and a large range of melt compositions are produced.
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| 18. |
- Leuzy, Antoine, et al.
(author)
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A multicenter comparison of [18F]flortaucipir, [18F]RO948, and [18F]MK6240 tau PET tracers to detect a common target ROI for differential diagnosis
- 2021
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 48:7, s. 2295-2305
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Journal article (peer-reviewed)abstract
- Purpose: This study aims to determine whether comparable target regions of interest (ROIs) and cut-offs can be used across [18F]flortaucipir, [18F]RO948, and [18F]MK6240 tau positron emission tomography (PET) tracers for differential diagnosis of Alzheimer’s disease (AD) dementia vs either cognitively unimpaired (CU) individuals or non-AD neurodegenerative diseases. Methods: A total of 1755 participants underwent tau PET using either [18F]flortaucipir (n = 975), [18F]RO948 (n = 493), or [18F]MK6240 (n = 287). SUVR values were calculated across four theory-driven ROIs and several tracer-specific data-driven (hierarchical clustering) regions of interest (ROIs). Diagnostic performance and cut-offs for ROIs were determined using receiver operating characteristic analyses and the Youden index, respectively. Results: Comparable diagnostic performance (area under the receiver operating characteristic curve [AUC]) was observed between theory- and data-driven ROIs. The theory-defined temporal meta-ROI generally performed very well for all three tracers (AUCs: 0.926–0.996). An SUVR value of approximately 1.35 was a common threshold when using this ROI. Conclusion: The temporal meta-ROI can be used for differential diagnosis of dementia patients with [18F]flortaucipir, [18F]RO948, and [18F]MK6240 tau PET with high accuracy, and that using very similar cut-offs of around 1.35 SUVR. This ROI/SUVR cut-off can also be applied across tracers to define tau positivity.
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