| 1. |
- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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| 2. |
- Amiri, M., et al.
(författare)
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Periodic activity from a fast radio burst source
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582:7812, s. 351-355
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Tidskriftsartikel (refereegranskat)abstract
- Fast radio bursts (FRBs) are bright, millisecond-duration radio transients originating from sources at extragalactic distances1, the origin of which is unknown. Some FRB sources emit repeat bursts, ruling out cataclysmic origins for those events2–4. Despite searches for periodicity in repeat burst arrival times on timescales from milliseconds to many days2,5–7, these bursts have hitherto been observed to appear sporadically and—although clustered8—without a regular pattern. Here we report observations of a 16.35 ± 0.15 day periodicity (or possibly a higher-frequency alias of that periodicity) from the repeating FRB 180916.J0158+65 detected by the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst Project4,9. In 38 bursts recorded from 16 September 2018 to 4 February 2020 utc, we find that all bursts arrive in a five-day phase window, and 50 per cent of the bursts arrive in a 0.6-day phase window. Our results suggest a mechanism for periodic modulation either of the burst emission itself or through external amplification or absorption, and disfavour models invoking purely sporadic processes.
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| 3. |
- Marcote, B., et al.
(författare)
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A repeating fast radio burst source localized to a nearby spiral galaxy
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 577:7789, s. 190-194
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Tidskriftsartikel (refereegranskat)abstract
- Fast radio bursts (FRBs) are brief, bright, extragalactic radio flashes1,2. Their physical origin remains unknown, but dozens of possible models have been postulated3. Some FRB sources exhibit repeat bursts4–7. Although over a hundred FRB sources have been discovered8, only four have been localized and associated with a host galaxy9–12, and just one of these four is known to emit repeating FRBs9. The properties of the host galaxies, and the local environments of FRBs, could provide important clues about their physical origins. The first known repeating FRB, however, was localized to a low-metallicity, irregular dwarf galaxy, and the apparently non-repeating sources were localized to higher-metallicity, massive elliptical or star-forming galaxies, suggesting that perhaps the repeating and apparently non-repeating sources could have distinct physical origins. Here we report the precise localization of a second repeating FRB source6, FRB 180916.J0158+65, to a star-forming region in a nearby (redshift 0.0337 ± 0.0002) massive spiral galaxy, whose properties and proximity distinguish it from all known hosts. The lack of both a comparably luminous persistent radio counterpart and a high Faraday rotation measure6 further distinguish the local environment of FRB 180916.J0158+65 from that of the single previously localized repeating FRB source, FRB 121102. This suggests that repeating FRBs may have a wide range of luminosities, and originate from diverse host galaxies and local environments.
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| 4. |
- Scholz, P., et al.
(författare)
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Simultaneous X-Ray and Radio Observations of the Repeating Fast Radio Burst FRB similar to 180916.J0158+65
- 2020
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 901:2
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Tidskriftsartikel (refereegranskat)abstract
- We report on simultaneous radio and X-ray observations of the repeating fast radio burst source FRB 180916.J0158+65 using the Canadian Hydrogen Intensity Mapping Experiment (CHIME), Effelsberg, and Deep Space Network (DSS-14 and DSS-63) radio telescopes and the Chandra X-ray Observatory. During 33 ks of Chandra observations, we detect no radio bursts in overlapping Effelsberg or Deep Space Network observations and a single burst during CHIME/FRB source transits. We detect no X-ray events in excess of the background during the Chandra observations. These non-detections imply a 5 sigma limit of <5 x 10(-10)erg cm(-2)for the 0.5-10 keV fluence of prompt emission at the time of the radio burst and 1.3 x 10(-9)erg cm(-2)at any time during the Chandra observations. Given the host-galaxy redshift of FRB 180916.J0158+65 (z similar to 0.034), these correspond to energy limits of <1.6 x 10(45)erg and <4 x 10(45)erg, respectively. We also place a 5 sigma limit of <8 x 10(-15)erg s(-1) cm(-2)on the 0.5-10 keV absorbed flux of a persistent source at the location of FRB 180916.J0158+65. This corresponds to a luminosity limit of <2 x 10(40)erg s(-1). Using an archival set of radio bursts from FRB 180916.J0158+65, we search for prompt gamma-ray emission in Fermi/GBM data but find no significant gamma-ray bursts, thereby placing a limit of 9 x 10(-9)erg cm(-2)on the 10-100 keV fluence. We also search Fermi/LAT data for periodic modulation of the gamma-ray brightness at the 16.35 days period of radio burst activity and detect no significant modulation. We compare these deep limits to the predictions of various fast radio burst models, but conclude that similar X-ray constraints on a closer fast radio burst source would be needed to strongly constrain theory.
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| 5. |
- Kirsten, Franz, 1983, et al.
(författare)
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A repeating fast radio burst source in a globular cluster
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 602:7898, s. 585-589
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Tidskriftsartikel (refereegranskat)abstract
- Fast radio bursts (FRBs) are flashes of unknown physical origin1. The majority of FRBs have been seen only once, although some are known to generate multiple flashes2,3. Many models invoke magnetically powered neutron stars (magnetars) as the source of the emission4,5. Recently, the discovery6 of another repeater (FRB 20200120E) was announced, in the direction of the nearby galaxy M81, with four potential counterparts at other wavelengths6. Here we report observations that localized the FRB to a globular cluster associated with M81, where it is 2 parsecs away from the optical centre of the cluster. Globular clusters host old stellar populations, challenging FRB models that invoke young magnetars formed in a core-collapse supernova. We propose instead that FRB 20200120E originates from a highly magnetized neutron star formed either through the accretion-induced collapse of a white dwarf, or the merger of compact stars in a binary system7. Compact binaries are efficiently formed inside globular clusters, so a model invoking them could also be responsible for the observed bursts.
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| 6. |
- Ferrari, A., et al.
(författare)
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Adolescents and young adults (AYA) with cancer : a position paper from the AYA Working Group of the European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOPE)
- 2021
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 6:2
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Forskningsöversikt (refereegranskat)abstract
- It is well recognised that adolescents and young adults (AYA) with cancer have inequitable access to oncology services that provide expert cancer care and consider their unique needs. Subsequently, survival gains in this patient population have improved only modestly compared with older adults and children with cancer. In 2015, the European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOPE) established the joint Cancer in AYA Working Group in order to increase awareness among adult and paediatric oncology communities, enhance knowledge on specific issues in AYA and ultimately improve the standard of care for AYA with cancer across Europe. This manuscript reflects the position of this working group regarding current AYA cancer care, the challenges to be addressed and possible solutions. Key challenges include the lack of specific biological understanding of AYA cancers, the lack of access to specialised centres with age-appropriate multidisciplinary care and the lack of available clinical trials with novel therapeutics. Key recommendations include diversifying interprofessional cooperation in AYA care and specific measures to improve trial accrual, including centralising care where that is the best means to achieve trial accrual. This defines a common vision that can lead to improved outcomes for AYA with cancer in Europe.
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| 7. |
- Nimmo, K., et al.
(författare)
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Burst timescales and luminosities as links between young pulsars and fast radio bursts
- 2022
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Ingår i: Nature Astronomy. - : Springer Science and Business Media LLC. - 2397-3366. ; 6:3, s. 393-401
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Tidskriftsartikel (refereegranskat)abstract
- Fast radio bursts (FRBs) are extragalactic radio flashes of unknown physical origin. Their high luminosities and short durations require extreme energy densities, such as those found in the vicinity of neutron stars and black holes. Studying the burst intensities and polarimetric properties on a wide range of timescales, from milliseconds down to nanoseconds, is key to understanding the emission mechanism. However, high-time-resolution studies of FRBs are limited by their unpredictable activity levels, available instrumentation and temporal broadening in the intervening ionized medium. Here we show that the repeating FRB 20200120E can produce isolated shots of emission as short as about 60 nanoseconds in duration, with brightness temperatures as high as 3 × 1041 K (excluding relativistic effects), comparable with ‘nano-shots’ from the Crab pulsar. Comparing both the range of timescales and luminosities, we find that FRB 20200120E observationally bridges the gap between known Galactic young pulsars and magnetars and the much more distant extragalactic FRBs. This suggests a common magnetically powered emission mechanism spanning many orders of magnitude in timescale and luminosity. In this Article, we probe a relatively unexplored region of the short-duration transient phase space; we highlight that there probably exists a population of ultrafast radio transients at nanosecond to microsecond timescales, which current FRB searches are insensitive to.
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| 8. |
- Pleunis, Z., et al.
(författare)
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LOFAR Detection of 110-188MHz emission and frequency-dependent activity from FRB20180916B
- 2021
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
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Tidskriftsartikel (refereegranskat)abstract
- The object FRB 20180916B is a well-studied repeating fast radio burst source. Its proximity (∼150 Mpc), along with detailed studies of the bursts, has revealed many clues about its nature, including a 16.3 day periodicity in its activity. Here we report on the detection of 18 bursts using LOFAR at 110-188 MHz, by far the lowest-frequency detections of any FRB to date. Some bursts are seen down to the lowest observed frequency of 110 MHz, suggesting that their spectra extend even lower. These observations provide an order-of-magnitude stronger constraint on the optical depth due to freëCfree absorption in the source's local environment. The absence of circular polarization and nearly flat polarization angle curves are consistent with burst properties seen at 300-1700 MHz. Compared with higher frequencies, the larger burst widths (∼40-160 ms at 150 MHz) and lower linear polarization fractions are likely due to scattering. We find ∼2-3 rad m variations in the Faraday rotation measure that may be correlated with the activity cycle of the source. We compare the LOFAR burst arrival times to those of 38 previously published and 22 newly detected bursts from the uGMRT (200-450 MHz) and CHIME/FRB (400-800 MHz). Simultaneous observations show five CHIME/FRB bursts when no emission is detected by LOFAR. We find that the burst activity is systematically delayed toward lower frequencies by about 3 days from 600 to 150 MHz. We discuss these results in the context of a model in which FRB 20180916B is an interacting binary system featuring a neutron star and high-mass stellar companion.
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