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1.
  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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  • De Leoz, M. L. A., et al. (författare)
  • NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods
  • 2020
  • Ingår i: Molecular & Cellular Proteomics. - 1535-9476. ; 19:1, s. 11-30
  • Tidskriftsartikel (refereegranskat)abstract
    • A broad-based interlaboratory study of glycosylation profiles of a reference and modified IgG antibody involving 103 reports from 76 laboratories. Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.
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12.
  • Menkveld, Albert J., et al. (författare)
  • Nonstandard Errors
  • 2024
  • Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
  • Tidskriftsartikel (refereegranskat)abstract
    • In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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13.
  • Niang, S., et al. (författare)
  • Accumulation of Positrons from a LINAC Based Source
  • 2020
  • Ingår i: Acta Physica Polonica. A. - 0587-4246 .- 1898-794X. ; 137:2, s. 164-166
  • Tidskriftsartikel (refereegranskat)abstract
    • The GBAR experiment aims to measure the gravitational acceleration of antihydrogen (H) over bar. It will use (H) over bar (+) ions formed by the interaction of antiprotons with a dense positronium cloud, which will require about 1010 positrons to produce one (H) over bar (+). We present the first results on the positron accumulation, reaching 3.8 +/- 0.4x10(8) e(+) collected in 560 s.
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14.
  • Charlton, M., et al. (författare)
  • Positron production using a 9 MeV electron linac for the GBAR experiment
  • 2021
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 985
  • Tidskriftsartikel (refereegranskat)abstract
    • For the GBAR (Gravitational Behaviour of Antihydrogen at Rest) experiment at CERN's Antiproton Decelerator (AD) facility we have constructed a source of slow positrons, which uses a low-energy electron linear accelerator (linac). The driver linac produces electrons of 9 MeV kinetic energy that create positrons from bremsstrahlung-induced pair production. Staying below 10 MeV ensures no persistent radioactive activation in the target zone and that the radiation level outside the biological shield is safe for public access. An annealed tungsten-mesh assembly placed directly behind the target acts as a positron moderator. The system produces 5 x 10(7) slow positrons per second, a performance demonstrating that a low-energy electron linac is a superior choice over positron-emitting radioactive sources for high positron flux.
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15.
  • Husson, A., et al. (författare)
  • A pulsed high-voltage decelerator system to deliver low-energy antiprotons
  • 2021
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 1002
  • Tidskriftsartikel (refereegranskat)abstract
    • The GBAR (Gravitational Behavior of Antihydrogen at Rest) experiment at CERN requires efficient deceleration of 100 keV antiprotons provided by the new ELENA synchrotron ring to synthesize antihydrogen. This is accomplished using electrostatic deceleration optics and a drift tube that is designed to switch from -99 kV to ground when the antiproton bunch is inside – essentially a charged particle “elevator” – producing a 1 keV pulse. We describe the simulation, design, construction and successful testing of the decelerator device at -92 kV on-line with antiprotons from ELENA.
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16.
  • Kim, B. H., et al. (författare)
  • Development of a PbWO4 Detector for Single-Shot Positron Annihilation Lifetime Spectroscopy at the GBAR Experiment
  • 2020
  • Ingår i: Acta Physica Polonica. A. - 0587-4246 .- 1898-794X. ; 137:2, s. 122-125
  • Tidskriftsartikel (refereegranskat)abstract
    • We have developed a PbWO4 (PWO) detector with a large dynamic range to measure the intensity of a positron beam and the absolute density of the ortho-positronium (o-Ps) cloud it creates. A simulation study shows that a setup based on such detectors may be used to determine the angular distribution of the emission and reflection of o-Ps to reduce part of the uncertainties of the measurement. These will allow to improve the precision in the measurement of the cross-section for the (anti)hydrogen formation by (anti)proton-positronium charge exchange and to optimize the yield of antihydrogen ion which is an essential parameter in the GBAR experiment.
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17.
  • Arzoumanian, Doris, et al. (författare)
  • Dust polarized emission observations of NGC 6334: BISTRO reveals the details of the complex but organized magnetic field structure of the high-mass star-forming hub-filament network
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 647
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Molecular filaments and hubs have received special attention recently thanks to new studies showing their key role in star formation. While the (column) density and velocity structures of both filaments and hubs have been carefully studied, their magnetic field (B-field) properties have yet to be characterized. Consequently, the role of B-fields in the formation and evolution of hub-filament systems is not well constrained. Aims. We aim to understand the role of the B-field and its interplay with turbulence and gravity in the dynamical evolution of the NGC 6334 filament network that harbours cluster-forming hubs and high-mass star formation. Methods. We present new observations of the dust polarized emission at 850 μm toward the 2 pc × 10 pc map of NGC 6334 at a spatial resolution of 0.09 pc obtained with the James Clerk Maxwell Telescope (JCMT) as part of the B-field In STar-forming Region Observations (BISTRO) survey. We study the distribution and dispersion of the polarized intensity (PI), the polarization fraction (PF), and the plane-of-The-sky B-field angle (χB_POS) toward the whole region, along the 10 pc-long ridge and along the sub-filaments connected to the ridge and the hubs. We derived the power spectra of the intensity and χBPOS along the ridge crest and compared them with the results obtained from simulated filaments. Results. The observations span 3 orders of magnitude in Stokes I and PI and 2 orders of magnitude in PF (from 0.2 to 20%). A large scatter in PI and PF is observed for a given value of I. Our analyses show a complex B-field structure when observed over the whole region ( 10 pc); however, at smaller scales (1 pc), χBPOS varies coherently along the crests of the filament network. The observed power spectrum of χBPOS can be well represented with a power law function with a slope of-1.33 ± 0.23, which is 20% shallower than that of I. We find that this result is compatible with the properties of simulated filaments and may indicate the physical processes at play in the formation and evolution of star-forming filaments. Along the sub-filaments, χBPOS rotates frombeing mostly perpendicular or randomly oriented with respect to the crests to mostly parallel as the sub-filaments merge with the ridge and hubs. This variation of the B-field structure along the sub-filaments may be tracing local velocity flows of infalling matter in the ridge and hubs. Our analysis also suggests a variation in the energy balance along the crests of these sub-filaments, from magnetically critical or supercritical at their far ends to magnetically subcritical near the ridge and hubs. We also detect an increase in PF toward the high-column density (NH2 â 1023 cm-2) star cluster-forming hubs. These latter large PF values may be explained by the increase in grain alignment efficiency due to stellar radiation from the newborn stars, combined with an ordered B-field structure. Conclusions. These observational results reveal for the first time the characteristics of the small-scale (down to 0.1 pc) B-field structure of a 10 pc-long hub-filament system. Our analyses show variations in the polarization properties along the sub-filaments that may be tracing the evolution of their physical properties during their interaction with the ridge and hubs. We also detect an impact of feedback from young high-mass stars on the local B-field structure and the polarization properties, which could put constraints on possible models for dust grain alignment and provide important hints as to the interplay between the star formation activity and interstellar B-fields.
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  • Blumer, P., et al. (författare)
  • Positron accumulation in the GBAR experiment
  • 2022
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 1040
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a description of the GBAR positron (e+) trapping apparatus, which consists of a three stage Buffer Gas Trap (BGT) followed by a High Field Penning Trap (HFT), and discuss its performance. The overall goal of the GBAR experiment is to measure the acceleration of the neutral antihydrogen (H¯) atom in the terrestrial gravitational field by neutralising a positive antihydrogen ion (H¯+), which has been cooled to a low temperature, and observing the subsequent H¯ annihilation following free fall. To produce one H¯+ ion, about 1010 positrons, efficiently converted into positronium (Ps), together with about 107 antiprotons (p¯), are required. The positrons, produced from an electron linac-based system, are accumulated first in the BGT whereafter they are stacked in the ultra-high vacuum HFT, where we have been able to trap 1.4(2) × 109 positrons in 1100 s.
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20.
  • Adrich, P., et al. (författare)
  • Production of antihydrogen atoms by 6 keV antiprotons through a positronium cloud
  • 2023
  • Ingår i: European Physical Journal C. - : Springer Nature. - 1434-6044 .- 1434-6052. ; 83:11
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the first production of an antihydrogen beam by charge exchange of 6.1 keV antiprotons with a cloud of positronium in the GBAR experiment at CERN. The 100 keV antiproton beam delivered by the AD/ELENA facility was further decelerated with a pulsed drift tube. A 9 MeV electron beam from a linear accelerator produced a low energy positron beam. The positrons were accumulated in a set of two Penning-Malmberg traps. The positronium target cloud resulted from the conversion of the positrons extracted from the traps. The antiproton beam was steered onto this positronium cloud to produce the antiatoms. We observe an excess over background indicating antihydrogen production with a significance of 3-4 standard deviations.
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  • Schijven, Dick, et al. (författare)
  • Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
  • 2023
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:14
  • Tidskriftsartikel (refereegranskat)abstract
    • Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
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  • Park, J, et al. (författare)
  • Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?
  • 2021
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:10
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
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  • Eshmvminov, D., et al. (författare)
  • FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review
  • 2023
  • Ingår i: Annals of Surgical Oncology. - 1068-9265. ; 30:7, s. 4417-4428
  • Forskningsöversikt (refereegranskat)abstract
    • BackgroundPancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC.MethodsWe performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based.ResultsA total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC.ConclusionsIn patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.
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  • Kawahara, R., et al. (författare)
  • Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis
  • 2021
  • Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 18, s. 1304-1316
  • Tidskriftsartikel (refereegranskat)abstract
    • Glycoproteomics is a powerful yet analytically challenging research tool. Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. Although the results were variable, several high-performance glycoproteomics informatics strategies were identified. Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics. This analysis presents the results of a community-based evaluation of existing software for large-scale glycopeptide data analysis.
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25.
  • Doi, Yasuo, et al. (författare)
  • The JCMT BISTRO Survey: Magnetic Fields Associated with a Network of Filaments in NGC 1333
  • 2020
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 899:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present new observations of the active star formation region NGC 1333 in the Perseus molecular cloud complex from the James Clerk Maxwell Telescope B-Fields In Star-forming Region Observations (BISTRO) survey with the POL-2 instrument. The BISTRO data cover the entire NGC 1333 complex (∼1.5 pc ? 2 pc) at 0.02 pc resolution and spatially resolve the polarized emission from individual filamentary structures for the first time. The inferred magnetic field structure is complex as a whole, with each individual filament aligned at different position angles relative to the local field orientation. We combine the BISTRO data with low- and high- resolution data derived from Planck and interferometers to study the multiscale magnetic field structure in this region. The magnetic field morphology drastically changes below a scale of ∼1 pc and remains continuous from the scales of filaments (∼0.1 pc) to that of protostellar envelopes (∼0.005 pc or ∼1000 au). Finally, we construct simple models in which we assume that the magnetic field is always perpendicular to the long axis of the filaments. We demonstrate that the observed variation of the relative orientation between the filament axes and the magnetic field angles are well reproduced by this model, taking into account the projection effects of the magnetic field and filaments relative to the plane of the sky. These projection effects may explain the apparent complexity of the magnetic field structure observed at the resolution of BISTRO data toward the filament network.
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  • Eswaraiah, Chakali, et al. (författare)
  • The JCMT BISTRO Survey: Revealing the Diverse Magnetic Field Morphologies in Taurus Dense Cores with Sensitive Submillimeter Polarimetry
  • 2021
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 912:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We have obtained sensitive dust continuum polarization observations at 850 μm in the B213 region of Taurus using POL-2 on SCUBA-2 at the James Clerk Maxwell Telescope as part of the B-fields in STar-forming Region Observations (BISTRO) survey. These observations allow us to probe magnetic field (B-field) at high spatial resolution (∼2000 au or ∼0.01 pc at 140 pc) in two protostellar cores (K04166 and K04169) and one prestellar core (Miz-8b) that lie within the B213 filament. Using the Davis-Chandrasekhar-Fermi method, we estimate the B-field strengths in K04166, K04169, and Miz-8b to be 38 ± 14, 44 ± 16, and 12 ± 5 μG, respectively. These cores show distinct mean B-field orientations. The B-field in K04166 is well ordered and aligned parallel to the orientations of the core minor axis, outflows, core rotation axis, and large-scale uniform B-field, in accordance with magnetically regulated star formation via ambipolar diffusion taking place in K04166. The B-field in K04169 is found to be ordered but oriented nearly perpendicular to the core minor axis and large-scale B-field and not well correlated with other axes. In contrast, Miz-8b exhibits a disordered B-field that shows no preferred alignment with the core minor axis or large-scale field. We found that only one core, K04166, retains a memory of the large-scale uniform B-field. The other two cores, K04169 and Miz-8b, are decoupled from the large-scale field. Such a complex B-field configuration could be caused by gas inflow onto the filament, even in the presence of a substantial magnetic flux.
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27.
  • Koenig, Julian, et al. (författare)
  • Cortical thickness and resting-state cardiac function across the lifespan : A cross-sectional pooled mega-analysis
  • 2021
  • Ingår i: Psychophysiology. - : Wiley. - 0048-5772 .- 1469-8986 .- 1540-5958. ; 58:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12–87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS—or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.
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28.
  • Kim, KH, et al. (författare)
  • Clonal hematopoiesis in the donor does not adversely affect long-term outcomes following allogeneic hematopoietic stem cell transplantation: result from a 13-year follow-up
  • 2023
  • Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 108:7, s. 1817-1826
  • Tidskriftsartikel (refereegranskat)abstract
    • Donor clonal hematopoiesis may be transferred to the recipient through allogeneic hematopoietic stem cell transplantation (HCT), but the potential for adverse long-term impact on transplant outcomes remains unknown. A total of 744 samples from 372 recipients who received HCT and the corresponding donors were included. Bar-coded error-corrected sequencing using a modified molecular inversion probe capture protocol was performed, which targeted 34 genes covering mutations involved in clonal hematopoiesis with indeterminate potential (CHIP) and other AML-related mutations. A total of 30 mutations were detected from 25 donors (6.7%): the most frequently mutated gene was TET2 (n=7, 28%), followed by DNMT3A (n=4, 16%), SMC3 (n=3, 12%) and SF3B1 (n=3, 12%). With a median follow-up duration of 13 years among survivors, the presence of CHIP in the donor was not associated with recipient overall survival (p=0.969), relapse incidence (p=0.600) or non-relapse mortality (p=0.570). Donor CHIP did not impair neutrophil (p=0.460) or platelet (p=0.250) engraftment, the rates of acute (p=0.490), or chronic graft-vs-host disease (p=0.220). No significant difference was noted for secondary malignancy following HCT between the two groups. The present study suggests that the presence of CHIP in allogeneic stem donors does not adversely affect transplant outcomes after HCT. Accordingly, further study is warranted to reach a clearer conclusion on whether molecular profiling to determine the presence of CHIP mutations is necessary for the pre-transplant evaluation of donors prior to stem cell donation.
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29.
  • Kim, KH, et al. (författare)
  • Clonal hematopoiesis in the donor does not adversely affect long-term outcomes following allogeneic hematopoietic stem cell transplantation: result from a 13-year follow-up
  • 2023
  • Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 108:7, s. 1817-1826
  • Tidskriftsartikel (refereegranskat)abstract
    • Donor clonal hematopoiesis may be transferred to the recipient through allogeneic hematopoietic stem cell transplantation (HCT), but the potential for adverse long-term impact on transplant outcomes remains unknown. A total of 744 samples from 372 recipients who received HCT and the corresponding donors were included. Bar-coded error-corrected sequencing using a modified molecular inversion probe capture protocol was performed, which targeted 34 genes covering mutations involved in clonal hematopoiesis with indeterminate potential (CHIP) and other AML-related mutations. A total of 30 mutations were detected from 25 donors (6.7%): the most frequently mutated gene was TET2 (n=7, 28%), followed by DNMT3A (n=4, 16%), SMC3 (n=3, 12%) and SF3B1 (n=3, 12%). With a median follow-up duration of 13 years among survivors, the presence of CHIP in the donor was not associated with recipient overall survival (p=0.969), relapse incidence (p=0.600) or non-relapse mortality (p=0.570). Donor CHIP did not impair neutrophil (p=0.460) or platelet (p=0.250) engraftment, the rates of acute (p=0.490), or chronic graft-vs-host disease (p=0.220). No significant difference was noted for secondary malignancy following HCT between the two groups. The present study suggests that the presence of CHIP in allogeneic stem donors does not adversely affect transplant outcomes after HCT. Accordingly, further study is warranted to reach a clearer conclusion on whether molecular profiling to determine the presence of CHIP mutations is necessary for the pre-transplant evaluation of donors prior to stem cell donation.
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30.
  • Papawassiliou, Wassilios, 1991-, et al. (författare)
  • Detection of Weyl fermions and the metal to Weyl-semimetal phase transition in WTe2via broadband high resolution NMR
  • 2022
  • Ingår i: Physical Review Research. - 2643-1564. ; 4:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Weyl fermions (WFs) in the type-II Weyl semimetal (WSM) WTe2 are difficult to resolve experimentally because the Weyl bands disperse in an extremely narrow region of the (E−k) space. Here, by using DFT-assisted high-resolution 125Te solid-state nuclear magnetic resonance (ssNMR) in the temperature range 50–700 K, we succeeded in detecting low energy WF excitations and monitoring their evolution with temperature. Remarkably, WFs are observed to emerge at T∼120 K, while at lower temperatures WTe2 behaves as a trivial metal. This intriguing phenomenon is induced by the rapid raise of the Fermi level upon heating, which crosses the Weyl bands only for T>120 K. The abrupt change of the NMR parameters at this temperature is signature of a topological Lifshitz transition instead of a cursive energy-bands crossing.
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31.
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32.
  • Hwang, Jihye, et al. (författare)
  • The JCMT BISTRO Survey: A Spiral Magnetic Field in a Hub-filament Structure, Monoceros R2
  • 2022
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 941:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present and analyze observations of polarized dust emission at 850 μm toward the central 1 × 1 pc hub-filament structure of Monoceros R2 (Mon R2). The data are obtained with SCUBA-2/POL-2 on the James Clerk Maxwell Telescope (JCMT) as part of the B-fields in Star-forming Region Observations survey. The orientations of the magnetic field follow the spiral structure of Mon R2, which are well described by an axisymmetric magnetic field model. We estimate the turbulent component of the magnetic field using the angle difference between our observations and the best-fit model of the underlying large-scale mean magnetic field. This estimate is used to calculate the magnetic field strength using the Davis–Chandrasekhar–Fermi method, for which we also obtain the distribution of volume density and velocity dispersion using a column density map derived from Herschel data and the C18O (J = 3 - 2) data taken with HARP on the JCMT, respectively. We make maps of magnetic field strengths and mass-to-flux ratios, finding that magnetic field strengths vary from 0.02 to 3.64 mG with a mean value of 1.0 ± 0.06 mG, and the mean critical mass-to-flux ratio is 0.47 ± 0.02. Additionally, the mean Alfvén Mach number is 0.35 ± 0.01. This suggests that, in Mon R2, the magnetic fields provide resistance against large-scale gravitational collapse, and the magnetic pressure exceeds the turbulent pressure. We also investigate the properties of each filament in Mon R2. Most of the filaments are aligned along the magnetic field direction and are magnetically subcritical.
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33.
  • Le Guen, Yann, et al. (författare)
  • Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes.
  • 2023
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 1091-6490 .- 0027-8424. ; 120:36
  • Tidskriftsartikel (refereegranskat)abstract
    • Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
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34.
  • Simonsen, C Z, et al. (författare)
  • Patients Requiring Conversion to General Anesthesia during Endovascular Therapy Have Worse Outcomes: A Post Hoc Analysis of Data from the SAGA Collaboration.
  • 2020
  • Ingår i: AJNR. American journal of neuroradiology. - 1936-959X. ; 41:12, s. 2298-2302
  • Tidskriftsartikel (refereegranskat)abstract
    • Endovascular therapy for acute ischemic stroke is often performed with the patient under conscious sedation. Emergent conversion from conscious sedation to general anesthesia is sometimes necessary. The aim of this study was to assess the functional outcome in converted patients compared with patients who remained in conscious sedation and to identify predictors associated with the risk of conversion.Data from 368 patients, included in 3 trials randomizing between conscious sedation and general anesthesia before endovascular therapy (SIESTA, ANSTROKE, and GOLIATH) constituted the study cohort. Twenty-one (11%) of 185 patients randomized to conscious sedation were emergently converted to general anesthesia.Absence of hyperlipidemia seemed to be the strongest predictor of conversion to general anesthesia, albeit a weak predictor (area under curve = 0.62). Sex, hypertension, diabetes, smoking status, atrial fibrillation, blood pressure, size of the infarct, and level and side of the occlusion were not significantly associated with conversion to general anesthesia. Neither age (mean age, 71.3 ± 13.8 years for conscious sedation versus 71.6 ± 12.3 years for converters, P=.58) nor severity of stroke (mean NIHSS score, 17 ± 4 versus 18 ± 4, respectively, P=.27) were significantly different between converters and those who tolerated conscious sedation. The converters had significantly worse outcome with a common odds ratio of 2.67 (P=.015) for a shift toward a higher mRS score compared with the patients remaining in the conscious sedation group.Patients undergoing conversion had significantly worse outcome compared with patients remaining in conscious sedation. No factor was identified that predicted conversion from conscious sedation to general anesthesia.
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35.
  • Thurner, Lorenz, et al. (författare)
  • Lymphocyte predominant cells detect Moraxella catarrhalis-derived antigens in nodular lymphocyte-predominant Hodgkin lymphoma
  • 2020
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma of B-cell origin with frequent expression of functional B-cell receptors (BCRs). Here we report that expression cloning followed by antigen screening identifies DNA-directed RNA polymerase beta' (RpoC) from Moraxella catarrhalis as frequent antigen of BCRs of IgD(+) LP cells. Patients show predominance of HLA-DRB1*04/07 and the IgVH genes encode extraordinarily long CDR3s. High-titer, light-chain-restricted anti-RpoC IgG1/kappa -type serum-antibodies are additionally found in these patients. RpoC and MID/hag, a superantigen co-expressed by Moraxella catarrhalis that is known to activate IgD(+) B cells by binding to the Fc domain of IgD, have additive activation effects on the BCR, the NF-kappa B pathway and the proliferation of IgD(+) DEV cells expressing RpoC-specific BCRs. This suggests an additive antigenic and superantigenic stimulation of B cells with RpoC-specific IgD(+) BCRs under conditions of a permissive MHC-II haplotype as a model of NLPHL lymphomagenesis, implying future treatment strategies. Nodular lymphocyte-predominant Hodgkin lymphoma with IgD+ lymphocyte-predominant (LP) cells is a rare clinical distinct lymphoma subset of B-cell origin. Here the authors show that antigens expressed by Moraxella catarrhalis are recognized by B cell receptors of IgD+ LP cells, suggesting the contribution of chronic antigen stimulation to lymphomagenesis.
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36.
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37.
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38.
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39.
  • Pasquini, Luca, et al. (författare)
  • Magnesium- and intermetallic alloys-based hydrides for energy storage : modelling, synthesis and properties
  • 2022
  • Ingår i: Progress in Energy. - : Institute of Physics Publishing (IOPP). - 2516-1083. ; 4:3
  • Forskningsöversikt (refereegranskat)abstract
    • Hydrides based on magnesium and intermetallic compounds provide a viable solution to the challenge of energy storage from renewable sources, thanks to their ability to absorb and desorb hydrogen in a reversible way with a proper tuning of pressure and temperature conditions. Therefore, they are expected to play an important role in the clean energy transition and in the deployment of hydrogen as an efficient energy vector. This review, by experts of Task 40 'Energy Storage and Conversion based on Hydrogen' of the Hydrogen Technology Collaboration Programme of the International Energy Agency, reports on the latest activities of the working group 'Magnesium- and Intermetallic alloys-based Hydrides for Energy Storage'. The following topics are covered by the review: multiscale modelling of hydrides and hydrogen sorption mechanisms; synthesis and processing techniques; catalysts for hydrogen sorption in Mg; Mg-based nanostructures and new compounds; hydrides based on intermetallic TiFe alloys, high entropy alloys, Laves phases, and Pd-containing alloys. Finally, an outlook is presented on current worldwide investments and future research directions for hydrogen-based energy storage.
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40.
  • Roering, Joshua J., et al. (författare)
  • Quantifying erosion rates and weathering pathways that maximize soil organic carbon storage
  • 2023
  • Ingår i: Biogeochemistry. - : Springer Nature. - 0168-2563 .- 1573-515X. ; 164, s. 319-333
  • Tidskriftsartikel (refereegranskat)abstract
    • Primary minerals that enter soils through bedrock weathering and atmospheric deposition can generate poorly crystalline minerals (PCM) that preferentially associate with soil organic carbon (SOC). These associations hinder microbial decomposition and the release of CO2 from soils to the atmosphere, making them a critical geochemical control on terrestrial carbon abundance and persistence. Studies that explore these relationships are typically derived from soil chronosequences that experience negligible erosion and thus do not readily translate to eroding landscapes. Here, we propose a theoretical framework to estimate steady-state PCM density and stocks for hilly and mountainous settings by coupling geochemical and geomorphic mass balance equations that account for soil production from bedrock and dust, soil erosion, PCM formation from weathering, and the transformation of PCMs into crystalline phases. We calculate an optimal erosion rate for maximum PCM abundance that arises because PCMs are limited by insufficient weathering at faster erosion rates and loss via “ripening” into more crystalline forms at slower erosion rates. The optimal erosion rate for modeled hilltop soil is modulated by reaction rate constants that govern the efficiency of primary mineral weathering and PCM ripening. By comparing our analysis with global compilations of erosion and soil production rates derived from cosmogenic nuclides, we show that landscapes with slow-to-moderate erosion rates may be optimal for harboring abundant PCM stocks that can facilitate SOC sequestration and limit turnover. Given the growing array of erosion-topography metrics and the widespread availability of high-resolution topographic data, our framework demonstrates how weathering and critical zone processes can be coupled to inform landscape prioritization for persistent SOC storage potential across a broad range of spatial and temporal scales.
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41.
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42.
  • Tahani, Mehrnoosh, et al. (författare)
  • JCMT BISTRO Observations: Magnetic Field Morphology of Bubbles Associated with NGC 6334
  • 2023
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 944:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We study the Hii regions associated with the NGC 6334 molecular cloud observed in the submillimeter and taken as part of the B-fields In STar-forming Region Observations Survey. In particular, we investigate the polarization patterns and magnetic field morphologies associated with these Hii regions. Through polarization pattern and pressure calculation analyses, several of these bubbles indicate that the gas and magnetic field lines have been pushed away from the bubble, toward an almost tangential (to the bubble) magnetic field morphology. In the densest part of NGC 6334, where the magnetic field morphology is similar to an hourglass, the polarization observations do not exhibit observable impact from Hii regions. We detect two nested radial polarization patterns in a bubble to the south of NGC 6334 that correspond to the previously observed bipolar structure in this bubble. Finally, using the results of this study, we present steps (incorporating computer vision; circular Hough transform) that can be used in future studies to identify bubbles that have physically impacted magnetic field lines.
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43.
  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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44.
  • Ching, Tao-Chung, et al. (författare)
  • The JCMT BISTRO-2 Survey: Magnetic Fields of the Massive DR21 Filament
  • 2022
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 941:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present 850 mu m dust polarization observations of the massive DR21 filament from the B-fields In STar-forming Region Observations (BISTRO) survey, using the POL-2 polarimeter and the SCUBA-2 camera on the James Clerk Maxwell Telescope. We detect ordered magnetic fields perpendicular to the parsec-scale ridge of the DR21 main filament. In the subfilaments, the magnetic fields are mainly parallel to the filamentary structures and smoothly connect to the magnetic fields of the main filament. We compare the POL-2 and Planck dust polarization observations to study the magnetic field structures of the DR21 filament on 0.1-10 pc scales. The magnetic fields revealed in the Planck data are well-aligned with those of the POL-2 data, indicating a smooth variation of magnetic fields from large to small scales. The plane-of-sky magnetic field strengths derived from angular dispersion functions of dust polarization are 0.6-1.0 mG in the DR21 filament and similar to 0.1 mG in the surrounding ambient gas. The mass-to-flux ratios are found to be magnetically supercritical in the filament and slightly subcritical to nearly critical in the ambient gas. The alignment between column density structures and magnetic fields changes from random alignment in the low-density ambient gas probed by Planck to mostly perpendicular in the high-density main filament probed by James Clerk Maxwell Telescope. The magnetic field structures of the DR21 filament are in agreement with MHD simulations of a strongly magnetized medium, suggesting that magnetic fields play an important role in shaping the DR21 main filament and subfilaments.
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45.
  • Karoly, Janik, et al. (författare)
  • The JCMT BISTRO Survey: Studying the Complex Magnetic Field of L43
  • 2023
  • Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 952:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present observations of polarized dust emission at 850 mu m from the L43 molecular cloud, which sits in the Ophiuchus cloud complex. The data were taken using SCUBA-2/POL-2 on the James Clerk Maxwell Telescope as a part of the BISTRO large program. L43 is a dense (N-H2 similar to 10(22) - 10(23) cm(-2)) complex molecular cloud with a submillimeter-bright starless core and two protostellar sources. There appears to be an evolutionary gradient along the isolated filament that L43 is embedded within, with the most evolved source closest to the Sco OB2 association. One of the protostars drives a CO outflow that has created a cavity to the southeast. We see a magnetic field that appears to be aligned with the cavity walls of the outflow, suggesting interaction with the outflow. We also find a magnetic field strength of up to similar to 160 +/- 30 mu G in the main starless core and up to similar to 90 +/- 40 mu G in the more diffuse, extended region. These field strengths give magnetically super- and subcritical values, respectively, and both are found to be roughly trans-Alfvenic. We also present a new method of data reduction for these denser but fainter objects like starless cores.
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46.
  • Kwon, Woojin, et al. (författare)
  • B-fields in Star-forming Region Observations (BISTRO): Magnetic Fields in the Filamentary Structures of Serpens Main
  • 2022
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 926:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present 850 mu m polarimetric observations toward the Serpens Main molecular cloud obtained using the POL-2 polarimeter on the James Clerk Maxwell Telescope as part of the B-fields In STar-forming Region Observations survey. These observations probe the magnetic field morphology of the Serpens Main molecular cloud on about 6000 au scales, which consists of cores and six filaments with different physical properties such as density and star formation activity. Using the histogram of relative orientation (HRO) technique, we find that magnetic fields are parallel to filaments in less-dense filamentary structures where NH2 < 0.93 x 10(22) cm(-2) (magnetic fields perpendicular to density gradients), while they are perpendicular to filaments (magnetic fields parallel to density gradients) in dense filamentary structures with star formation activity. Moreover, applying the HRO technique to denser core regions, we find that magnetic field orientations change to become perpendicular to density gradients again at NH2 approximate to 4.6 x 10(22) NH2 approximate to 16 x 10(22) cm(-2), magnetic fields change back to being parallel to density gradients once again, which can be understood to be due to magnetic fields being dragged in by infalling material. In addition, we estimate the magnetic field strengths of the filaments (B-POS = 60-300 mu G)) using the Davis-Chandrasekhar-Fermi method and discuss whether the filaments are gravitationally unstable based on magnetic field and turbulence energy densities.
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47.
  • Yoo, AJ, et al. (författare)
  • Benchmarking the Extent and Speed of Reperfusion: First Pass TICI 2c-3 Is a Preferred Endovascular Reperfusion Endpoint
  • 2021
  • Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 12, s. 669934-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose: End-of-procedure substantial reperfusion [modified Treatment in Cerebral Ischemia (mTICI) 2b-3], the leading endpoint for thrombectomy studies, has several limitations including a ceiling effect, with recent achieved rates of ~90%. We aimed to identify a more optimal definition of angiographic success along two dimensions: (1) the extent of tissue reperfusion, and (2) the speed of revascularization.Methods: Core-lab adjudicated TICI scores for the first three passes of EmboTrap and the final all-procedures result were analyzed in the ARISE II multicenter study. The clinical impact of extent of reperfusion and speed of reperfusion (first-pass vs. later-pass) were evaluated. Clinical outcomes included 90-day functional independence [modified Rankin Scale (mRS) 0–2], 90-day freedom-from-disability (mRS 0–1), and dramatic early improvement [24-h National Institutes of Health Stroke Scale (NIHSS) improvement ≥ 8 points].Results: Among 161 ARISE II subjects with ICA or MCA M1 occlusions, reperfusion results at procedure end showed substantial reperfusion in 149 (92.5%), excellent reperfusion in 121 (75.2%), and complete reperfusion in 79 (49.1%). Reperfusion rates on first pass were substantial in 81 (50.3%), excellent reperfusion in 62 (38.5%), and complete reperfusion in 44 (27.3%). First-pass excellent reperfusion (first-pass TICI 2c-3) had the greatest nominal predictive value for 90-day mRS 0–2 (sensitivity 58.5%, specificity 68.6%). There was a progressive worsening of outcomes with each additional pass required to achieve TICI 2c-3.Conclusions: First-pass excellent reperfusion (TICI 2c-3), reflecting rapid achievement of extensive reperfusion, is the technical revascularization endpoint that best predicted functional independence in this international multicenter trial and is an attractive candidate for a lead angiographic endpoint for future trials.Clinical Trial Registration:http://www.clinicaltrials.gov, identifier NCT02488915.
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