| 1. |
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| 2. |
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| 3. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 4. |
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| 5. |
- Kondo, Y., et al.
(författare)
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First observation of 28 O
- 2023
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 620:7976, s. 965-970
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Tidskriftsartikel (refereegranskat)abstract
- Subjecting a physical system to extreme conditions is one of the means often used to obtain a better understanding and deeper insight into its organization and structure. In the case of the atomic nucleus, one such approach is to investigate isotopes that have very different neutron-to-proton (N/Z) ratios than in stable nuclei. Light, neutron-rich isotopes exhibit the most asymmetric N/Z ratios and those lying beyond the limits of binding, which undergo spontaneous neutron emission and exist only as very short-lived resonances (about 10−21s), provide the most stringent tests of modern nuclear-structure theories. Here we report on the first observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively. The 28O nucleus is of particular interest as, with the Z = 8 and N = 20 magic numbers1,2, it is expected in the standard shell-model picture of nuclear structure to be one of a relatively small number of so-called ‘doubly magic’ nuclei. Both 27O and 28O were found to exist as narrow, low-lying resonances and their decay energies are compared here to the results of sophisticated theoretical modelling, including a large-scale shell-model calculation and a newly developed statistical approach. In both cases, the underlying nuclear interactions were derived from effective field theories of quantum chromodynamics. Finally, it is shown that the cross-section for the production of 28O from a 29F beam is consistent with it not exhibiting a closed N = 20 shell structure.
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| 6. |
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| 7. |
- Wang, H., et al.
(författare)
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Intruder configurations in 29 Ne at the transition into the island of inversion: Detailed structure study of 28 Ne
- 2023
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 843
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Tidskriftsartikel (refereegranskat)abstract
- Detailed γ-ray spectroscopy of the exotic neon isotope 28Ne has been performed for the first time using the one-neutron removal reaction from 29Ne on a liquid hydrogen target at 240 MeV/nucleon. Based on an analysis of parallel momentum distributions, a level scheme with spin-parity assignments has been constructed for 28Ne and the negative-parity states are identified for the first time. The measured partial cross sections and momentum distributions reveal a significant intruder p-wave strength providing evidence of the breakdown of the N=20 and N=28 shell gaps. Only a weak, possible f-wave strength was observed to bound final states. Large-scale shell-model calculations with different effective interactions do not reproduce the large p-wave and small f-wave strength observed experimentally, indicating an ongoing challenge for a complete theoretical description of the transition into the island of inversion along the Ne isotopic chain.
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| 8. |
- Holl, Matthias, 1986, et al.
(författare)
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Border of the island of inversion: Unbound states in Ne-29
- 2022
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Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 105:3
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Tidskriftsartikel (refereegranskat)abstract
- The nucleus Ne-29 is situated at the border of the island of inversion. Despite significant efforts, no bound low-lying intruder f(7/2) state, which would place Ne-29 firmly inside the island of inversion, has yet been observed. Here, the first investigation of unbound states of Ne-29 is reported. The states were populated in Ne-30(p, pn) and Na-30(p, 2p) reactions at a beam energy of around 230 MeV/nucleon, and analyzed in terms of their resonance properties, partial cross sections, and momentum distributions. The momentum distributions are compared to calculations using the eikonal, direct reaction model, allowing assignments for the observed states. The lowest lying resonance at an excitation energy of 1.48(4) MeV shows clear signs of a significant l = 3 component, giving first evidence for f(7/2) single particle strength in Ne-29. The excitation energies and strengths of the observed states are compared to shell-model calculations using the SDPF-U-MIX interaction.
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| 9. |
- Revel, A., et al.
(författare)
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Extending the Southern Shore of the Island of Inversion to F-28
- 2020
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Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 124:15
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Tidskriftsartikel (refereegranskat)abstract
- Detailed spectroscopy of the neutron-unbound nucleus F-28 has been performed for the first time following proton/neutron removal from Ne-29/F-29 beams at energies around 230 MeV=nucleon. The invariant-mass spectra were reconstructed for both the F-27((*)) + n and F-26((*)) + 2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the F-28 ground state, with S-n(F-28) = -199(6) keV, while analysis of the 2n decay channel allowed a considerably improved S-n(F-27) = 1620(60) keV to be deduced. Comparison with shell-model predictions and eikonal-model reaction calculations have allowed spin-parity assignments to be proposed for some of the lower-lying levels of F-28. Importantly, in the case of the ground state, the reconstructed F-27 + n momentum distribution following neutron removal from F-29 indicates that it arises mainly from the 1p(3/2) neutron intruder configuration. This demonstrates that the island of inversion around N = 20 includes F-28, and most probably F-29, and suggests that O-28 is not doubly magic.
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| 10. |
- Wasserman, D, et al.
(författare)
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Compulsory admissions of patients with mental disorders: State of the art on ethical and legislative aspects in 40 European countries
- 2020
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Ingår i: European psychiatry : the journal of the Association of European Psychiatrists. - : Royal College of Psychiatrists. - 1778-3585. ; 63:1, s. e82-
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Tidskriftsartikel (refereegranskat)abstract
- Background.Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care.Methods.The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions.Results.We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures.Conclusions.We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.
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| 11. |
- Boillos, J. M., et al.
(författare)
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Isotopic cross sections of fragmentation residues produced by light projectiles on carbon near
- 2022
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Ingår i: Physical Review C. - 2469-9993 .- 2469-9985. ; 105:1
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Tidskriftsartikel (refereegranskat)abstract
- We measured 135 cross sections of residual nuclei produced in fragmentation reactions of C12, N14, and O13−16,20,22 projectiles impinging on a carbon target at kinetic energies of near 400A MeV, most of them for the first time, with the RB3/LAND setup at the GSI facility in Darmstadt (Germany). The use of this state-of-the-art experimental setup in combination with the inverse kinematics technique gave the full identification in atomic and mass numbers of fragmentation residues with a high precision. The cross sections of these residues were determined with uncertainties below 20% for most of the cases. These data are compared to other previous measurements with stable isotopes and are also used to benchmark different model calculations.
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| 12. |
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| 13. |
- Eijsbouts, C., et al.
(författare)
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Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders
- 2021
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53:11, s. 1543-1552
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Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS. © 2021, The Author(s).
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| 14. |
- Atar, L., et al.
(författare)
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Quasifree (p, 2p) Reactions on Oxygen Isotopes: Observation of Isospin Independence of the Reduced Single-Particle Strength
- 2018
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Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 120:5
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Tidskriftsartikel (refereegranskat)abstract
- Quasifree one-proton knockout reactions have been employed in inverse kinematics for a systematic study of the structure of stable and exotic oxygen isotopes at the R3B/LAND setup with incident beam energies in the range of 300-450 MeV/u. The oxygen isotopic chain offers a large variation of separation energies that allows for a quantitative understanding of single-particle strength with changing isospin asymmetry. Quasifree knockout reactions provide a complementary approach to intermediate-energy one-nucleon removal reactions. Inclusive cross sections for quasifree knockout reactions of the type OA(p,2p)NA-1 have been determined and compared to calculations based on the eikonal reaction theory. The reduction factors for the single-particle strength with respect to the independent-particle model were obtained and compared to state-of-the-art ab initio predictions. The results do not show any significant dependence on proton-neutron asymmetry.
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| 15. |
- Duer, M., et al.
(författare)
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Observation of a correlated free four-neutron system
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 606:7915
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Tidskriftsartikel (refereegranskat)abstract
- A long-standing question in nuclear physics is whether chargeless nuclear systems can exist. To our knowledge, only neutron stars represent near-pure neutron systems, where neutrons are squeezed together by the gravitational force to very high densities. The experimental search for isolated multi-neutron systems has been an ongoing quest for several decades(1), with a particular focus on the four-neutron system called the tetraneutron, resulting in only a few indications of its existence so far(2-4), leaving the tetraneutron an elusive nuclear system for six decades. Here we report on the observation of a resonance-like structure near threshold in the four-neutron system that is consistent with a quasi-bound tetraneutron state existing for a very short time. The measured energy and width of this state provide a key benchmark for our understanding of the nuclear force. The use of an experimental approach based on a knockout reaction at large momentum transfer with a radioactive high-energy He-8 beam was key.
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| 16. |
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| 17. |
- Heine, M., et al.
(författare)
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Determination of the neutron-capture rate of C-17 for r-process nucleosynthesis
- 2017
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Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 95:1, s. Article no 014613 -
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Tidskriftsartikel (refereegranskat)abstract
- With the (RB)-B-3-LAND setup at GSI we have measured exclusive relative-energy spectra of the Coulomb dissociation of C-18 at a projectile energy around 425A MeV on a lead target, which are needed to determine the radiative neutron-capture cross sections of C-17 into the ground state of C-18. Those data have been used to constrain theoretical calculations for transitions populating excited states in C-18. This allowed to derive the astrophysical cross section sigma(n gamma)*. accounting for the thermal population of C-17 target states in astrophysical scenarios. The experimentally verified capture rate is significantly lower than those of previously obtained Hauser-Feshbach estimations at temperatures T-9
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| 18. |
- Holl, M., et al.
(författare)
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Quasi-free neutron and proton knockout reactions from light nuclei in a wide neutron-to-proton asymmetry range
- 2019
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 795, s. 682-688
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Tidskriftsartikel (refereegranskat)abstract
- The quasi-free scattering reactions 11C(p,2p) and 10,11,12C(p,pn) have been studied in inverse kinematics at beam energies of 300–400 MeV/u at the R3B-LAND setup. The outgoing proton-proton and proton-neutron pairs were detected in coincidence with the reaction fragments in kinematically complete measurements. The efficiency to detect these pairs has been obtained from GEANT4 simulations which were tested using the 12C(p,2p) and 12C(p,pn) reactions. Experimental cross sections and momentum distributions have been obtained and compared to DWIA calculations based on eikonal theory. The new results reported here are combined with previously published cross sections for quasi-free scattering from oxygen and nitrogen isotopes and together they enable a systematic study of the reduction of single-particle strength compared to predictions of the shell model over a wide neutron-to-proton asymmetry range. The combined reduction factors show a weak or no dependence on isospin asymmetry, in contrast to the strong dependency reported in nucleon-removal reactions induced by nuclear targets at lower energies. However, the reduction factors for (p,2p) are found to be 'significantly smaller than for (p,pn) reactions for all investigated nuclei.
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| 19. |
- Kuhle, J., et al.
(författare)
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Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study
- 2015
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Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 21:8, s. 1013-1024
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.
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| 22. |
- Nannya, Y, et al.
(författare)
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Postazacitidine clone size predicts long-term outcome of patients with myelodysplastic syndromes and related myeloid neoplasms
- 2023
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Ingår i: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 7:14, s. 3624-3636
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Tidskriftsartikel (refereegranskat)abstract
- Azacitidine is a mainstay of therapy for MDS-related diseases. The purpose of our study is to elucidate the effect of gene mutations on hematological response and overall survival (OS), particularly focusing on their post-treatment clone size. We enrolled a total of 449 patients with MDS or related myeloid neoplasms. They were analyzed for gene mutations in pre- (n=449) and post- (n=289) treatment bone marrow samples using targeted-capture sequencing to assess the impact of gene mutations and their post-treatment clone size on treatment outcomes. In Cox proportional hazard modeling, multi-hit TP53 mutation (HR, 2.03; 95% CI, 1.42-2.91; P<.001), EZH2 mutation (HR, 1.71; 95% CI, 1.14-2.54; P=.009), and DDX41 mutations (HR, 0.33; 95% CI, 0.17-0.62; P<.001), together with age, high-risk karyotypes, low platelet, and high blast counts, independently predicted OS. Post-treatment clone size accounting for all drivers significantly correlated with International Working Group (IWG)-response (P<.001, trend test), except for that of DDX41-mutated clones, which did not predict IWG-response. Combined, IWG-response and post-treatment clone size further improved the prediction of the original model and even that of a recently proposed molecular prediction model, IPSS-M (c-index, 0.653 vs 0.688; P<.001, likelihood ratio test). In conclusion, evaluation of post-treatment clone size, together with pre-treatment mutational profile as well as IWG-response have a role in better prognostication of azacitidine-treated myelodysplasia patients.
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