| 1. |
- Veres, P., et al.
(författare)
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Observation of inverse Compton emission from a long gamma-ray burst
- 2019
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 575:7783, s. 459-
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Tidskriftsartikel (refereegranskat)abstract
- Long-duration gamma-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectron volt-to-mega electronvoltband, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission(1,2). Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands(1-6). The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock(7-9). Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C(10,11). Here we report multifrequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 x 10(-6) to 10(12) electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs.
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| 2. |
- Goldstein, A., et al.
(författare)
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Fermi Observations of the LIGO Event GW170104
- 2017
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Ingår i: Astrophysical Journal Letters. - : IOP PUBLISHING LTD. - 2041-8205 .- 2041-8213. ; 846:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the Fermi Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) observations of the LIGO binary black hole merger (BBH) event GW170104. No candidate electromagnetic counterpart was detected by either GBM or LAT. A detailed analysis of the GBM and LAT data over timescales from seconds to days covering the Laser Interferometer Gravitational-wave Observatory (LIGO) localization region is presented. The resulting flux upper bound from the GBM is (5.2-9.4). x. 10(-7) erg cm(-2) s(-1) in the 10-1000 keV range and from the LAT is (0.2-90). x. 10(-9) erg cm(-2) s(-1) in the 0.1-1 GeV range. We also describe the improvements to our automated pipelines and analysis techniques for searching for and characterizing the potential electromagnetic counterparts for future gravitational-wave events from Advanced LIGO/Virgo.
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| 3. |
- Startin, C. M., et al.
(författare)
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Plasma biomarkers for amyloid, tau, and cytokines in Down syndrome and sporadic Alzheimer's disease
- 2019
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Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDown syndrome (DS), caused by chromosome 21 trisomy, is associated with an ultra-high risk of dementia due to Alzheimer's disease (AD), driven by amyloid precursor protein (APP) gene triplication. Understanding relevant molecular differences between those with DS, those with sporadic AD (sAD) without DS, and controls will aid in understanding AD development in DS. We explored group differences in plasma concentrations of amyloid- peptides and tau (as their accumulation is a characteristic feature of AD) and cytokines (as the inflammatory response has been implicated in AD development, and immune dysfunction is common in DS).MethodsWe used ultrasensitive assays to compare plasma concentrations of the amyloid- peptides A(40) and A(42), total tau (t-tau), and the cytokines IL1, IL10, IL6, and TNF between adults with DS (n=31), adults with sAD (n=27), and controls age-matched to the group with DS (n=27), and explored relationships between molecular concentrations and with age within each group. In the group with DS, we also explored relationships with neurofilament light (NfL) concentration, due to its potential use as a biomarker for AD in DS.ResultsA(40), A(42), and IL1 concentrations were higher in DS, with a higher A(42)/A(40) ratio in controls. The group with DS showed moderate positive associations between concentrations of t-tau and both A(42) and IL1. Only NfL concentration in the group with DS showed a significant positive association with age.ConclusionsConcentrations of A(40) and A(42) were much higher in adults with DS than in other groups, reflecting APP gene triplication, while no difference in the A(42)/A(40) ratio between those with DS and sAD may indicate similar processing and deposition of A(40) and A(42) in these groups. Higher concentrations of IL1 in DS may reflect an increased vulnerability to infections and/or an increased prevalence of autoimmune disorders, while the positive association between IL1 and t-tau in DS may indicate IL1 is associated with neurodegeneration. Finally, NfL concentration may be the most suitable biomarker for dementia progression in DS. The identification of such a biomarker is important to improve the detection of dementia and monitor its progression, and for designing clinical intervention studies.
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| 4. |
- Ahumada, Tomas, et al.
(författare)
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In Search of Short Gamma-Ray Burst Optical Counterparts with the Zwicky Transient Facility
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 932:1
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Tidskriftsartikel (refereegranskat)abstract
- The Fermi Gamma-ray Burst Monitor (GBM) triggers on-board in response to ∼40 short gamma-ray bursts (SGRBs) per year; however, their large localization regions have made the search for optical counterparts a challenging endeavour. We have developed and executed an extensive program with the wide field of view of the Zwicky Transient Facility (ZTF) camera, mounted on the Palomar 48 inch Oschin telescope (P48), to perform target-of-opportunity (ToO) observations on 10 Fermi-GBM SGRBs during 2018 and 2020–2021. Bridging the large sky areas with small field-of-view optical telescopes in order to track the evolution of potential candidates, we look for the elusive SGRB afterglows and kilonovae (KNe) associated with these high-energy events. No counterpart has yet been found, even though more than 10 ground-based telescopes, part of the Global Relay of Observatories Watching Transients Happen (GROWTH) network, have taken part in these efforts. The candidate selection procedure and the follow-up strategy have shown that ZTF is an efficient instrument for searching for poorly localized SGRBs, retrieving a reasonable number of candidates to follow up and showing promising capabilities as the community approaches the multi-messenger era. Based on the median limiting magnitude of ZTF, our searches would have been able to retrieve a GW170817-like event up to ∼200 Mpc and SGRB afterglows to z = 0.16 or 0.4, depending on the assumed underlying energy model. Future ToOs will expand the horizon to z = 0.2 and 0.7, respectively.
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| 5. |
- Alic, I., et al.
(författare)
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Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26:10, s. 5766-5788
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Tidskriftsartikel (refereegranskat)abstract
- A population of more than six million people worldwide at high risk of Alzheimer's disease (AD) are those with Down Syndrome (DS, caused by trisomy 21 (T21)), 70% of whom develop dementia during lifetime, caused by an extra copy of beta-amyloid-(A beta)-precursor-protein gene. We report AD-like pathology in cerebral organoids grown in vitro from non-invasively sampled strands of hair from 71% of DS donors. The pathology consisted of extracellular diffuse and fibrillar A beta deposits, hyperphosphorylated/pathologically conformed Tau, and premature neuronal loss. Presence/absence of AD-like pathology was donor-specific (reproducible between individual organoids/iPSC lines/experiments). Pathology could be triggered in pathology-negative T21 organoids by CRISPR/Cas9-mediated elimination of the third copy of chromosome 21 gene BACE2, but prevented by combined chemical beta and gamma-secretase inhibition. We found that T21 organoids secrete increased proportions of A beta-preventing (A beta 1-19) and A beta-degradation products (A beta 1-20 and A beta 1-34). We show these profiles mirror in cerebrospinal fluid of people with DS. We demonstrate that this protective mechanism is mediated by BACE2-trisomy and cross-inhibited by clinically trialled BACE1 inhibitors. Combined, our data prove the physiological role of BACE2 as a dose-sensitive AD-suppressor gene, potentially explaining the dementia delay in similar to 30% of people with DS. We also show that DS cerebral organoids could be explored as pre-morbid AD-risk population detector and a system for hypothesis-free drug screens as well as identification of natural suppressor genes for neurodegenerative diseases.
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| 6. |
- Gerotziafas, GT, et al.
(författare)
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Guidance for the Management of Patients with Vascular Disease or Cardiovascular Risk Factors and COVID-19: Position Paper from VAS-European Independent Foundation in Angiology/Vascular Medicine
- 2020
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Ingår i: Thrombosis and haemostasis. - : Georg Thieme Verlag KG. - 2567-689X .- 0340-6245. ; 120:12, s. 1597-1628
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age. The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19. VAS recommends (1) a COVID-19-oriented primary health care network for patients with VD-CVR for identification of patients with VD-CVR in the community and patients' education for disease symptoms, use of eHealth technology, adherence to the antithrombotic and vascular regulating treatments, and (2) close medical follow-up for efficacious control of VD progression and prompt application of physical and social distancing measures in case of new epidemic waves. For patients with VD-CVR who receive home treatment for COVID-19, VAS recommends assessment for (1) disease worsening risk and prioritized hospitalization of those at high risk and (2) VTE risk assessment and thromboprophylaxis with rivaroxaban, betrixaban, or low-molecular-weight heparin (LMWH) for those at high risk. For hospitalized patients with VD-CVR and COVID-19, VAS recommends (1) routine thromboprophylaxis with weight-adjusted intermediate doses of LMWH (unless contraindication); (2) LMWH as the drug of choice over unfractionated heparin or direct oral anticoagulants for the treatment of VTE or hypercoagulability; (3) careful evaluation of the risk for disease worsening and prompt application of targeted antiviral or convalescence treatments; (4) monitoring of D-dimer for optimization of the antithrombotic treatment; and (5) evaluation of the risk of VTE before hospital discharge using the IMPROVE-D-dimer score and prolonged post-discharge thromboprophylaxis with rivaroxaban, betrixaban, or LMWH.
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| 10. |
- Strydom, A., et al.
(författare)
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Neurofilament light as a blood biomarker for neurodegeneration in Down syndrome
- 2018
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Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 10, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Down syndrome (DS) may be considered a genetic form of Alzheimer's disease (AD) due to universal development of AD neuropathology, but diagnosis and treatment trials are hampered by a lack of reliable blood biomarkers. A potential biomarker is neurofilament light (NF-L), due to its association with axonal damage in neurodegenerative conditions. Methods: We measured blood NF-L concentrations in 100 adults with DS using Simoa NF-light® assays, and we examined relationships with age as well as cross-sectional and longitudinal dementia diagnosis. Results: NF-L concentrations increased with age (Spearman's rho = 0.789, p < 0.001), with a steep increase after age 40, and they were predictive of dementia status (p = 0.022 adjusting for age, sex, and APOE4), but they showed no relationship with long-standing epilepsy or premorbid ability. Baseline NF-L concentrations were associated with longitudinal dementia status. Conclusions: NF-L is a biomarker for neurodegeneration in DS with potential for use in future clinical trials to prevent or delay dementia.
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