Mass, Spectroscopy, and Two-Neutron Decay of

The structure and decay of the most neutron-rich beryllium isotope, ^{16}Be, has been investigated following proton knockout from a high-energy ^{17}B beam. Two relatively narrow resonances were observed for the first time, with energies of 0.84(3) and 2.15(5) MeV above the two-neutron decay threshold and widths of 0.32(8) and 0.95(15) MeV, respectively. These were assigned to be the ground (J^{π}=0^{+}) and first excited (2^{+}) state, with E_{x}=1.31(6) MeV. The mass excess of ^{16}Be was thus deduced to be 56.93(13) MeV, some 0.5 MeV more bound than the only previous measurement. Both states were observed to decay by direct two-neutron emission. Calculations incorporating the evolution of the wave function during the decay as a genuine three-body process reproduced the principal characteristics of the neutron-neutron energy spectra for both levels, indicating that the ground state exhibits a strong spatially compact dineutron component, while the 2^{+} level presents a far more diffuse neutron-neutron distribution.

Multiple Mechanisms in Proton-Induced Nucleon Removal at ∼100 MeV/Nucleon.

We report on the first proton-induced single proton- and neutron-removal reactions from the neutron-deficient ^{14}O nucleus with large Fermi-surface asymmetry S_{n}-S_{p}=18.6 MeV at ∼100 MeV/nucleon, a widely used energy regime for rare-isotope studies. The measured inclusive cross sections and parallel momentum distributions of the ^{13}N and ^{13}O residues are compared to the state-of-the-art reaction models, with nuclear structure inputs from many-body shell-model calculations. Our results provide the first quantitative contributions of multiple reaction mechanisms including the quasifree knockout, inelastic scattering, and nucleon transfer processes. It is shown that the inelastic scattering and nucleon transfer, usually neglected at such energy regime, contribute about 50% and 30% to the loosely bound proton and deeply bound neutron removal, respectively. These multiple reaction mechanisms should be considered in analyses of inclusive one-nucleon removal cross sections measured at intermediate energies for quantitative investigation of single-particle strengths and correlations in atomic nuclei.

Validation of the

The cluster structure of the neutron-rich isotope ^{10}Be has been probed via the (p,pα) reaction at 150 MeV/nucleon in inverse kinematics and in quasifree conditions. The populated states of ^{6}He residues were investigated through missing mass spectroscopy. The triple differential cross section for the ground-state transition was extracted for quasifree angle pairs (θ_{p},θ_{α}) and compared to distorted-wave impulse approximation reaction calculations performed in a microscopic framework using successively the Tohsaki-Horiuchi-Schuck-Röpke product wave function and the wave function deduced from antisymmetrized molecular dynamics calculations. The remarkable agreement between calculated and measured cross sections in both shape and magnitude validates the molecular structure description of the ^{10}Be ground-state, configured as an α-α core with two valence neutrons occupying π-type molecular orbitals.

Initiating home spirometry for children during the COVID-19 pandemic - A practical guide.

The COVID-19 pandemic has led to a rapid escalation in use of home monitoring and video consultations in children with a variety of chronic respiratory conditions. Our department set up a home spirometry service from scratch once it became evident that we needed to keep patients away from hospital clinics whenever possible. We faced a number of challenges but now have around 400 children using home spirometers. There are a number of portable spirometers available, some with online platforms. The technology, particularly the software/apps interface, has been improved by the companies in response to issues that have arisen. We believe the use of home monitoring is here to stay.

Assessment of structural chromosomal instability phenotypes as biomarkers of carboplatin response in triple negative breast cancer: the TNT trial.

BACKGROUND: In the TNT trial of triple negative breast cancer (NCT00532727), germline BRCA1/2 mutations were present in 28% of carboplatin responders. We assessed quantitative measures of structural chromosomal instability (CIN) to identify a wider patient subgroup within TNT with preferential benefit from carboplatin over docetaxel. PATIENTS AND METHODS: Copy number aberrations (CNAs) were established from 135 formalin-fixed paraffin-embedded primary carcinomas using Illumina OmniExpress SNP-arrays. Seven published [allelic imbalanced CNA (AiCNA); allelic balanced CNA (AbCNA); copy number neutral loss of heterozygosity (CnLOH); number of telomeric allelic imbalances (NtAI); BRCA1-like status; percentage of genome altered (PGA); homologous recombination deficiency (HRD) scores] and two novel [Shannon diversity index (SI); high-level amplifications (HLAMP)] CIN-measurements were derived. HLAMP was defined based on the presence of at least one of the top 5% amplified cytobands located on 1q, 8q and 10p. Continuous CIN-measurements were divided into tertiles. All nine CIN-measurements were used to analyse objective response rate (ORR) and progression-free survival (PFS). RESULTS: Patients with tumours without HLAMP had a numerically higher ORR and significantly longer PFS in the carboplatin (C) than in the docetaxel (D) arm [56% (C) versus 29% (D), PHLAMP,quiet = 0.085; PFS 6.1 months (C) versus 4.1 months (D), Pinteraction/HLAMP = 0.047]. In the carboplatin arm, patients with tumours showing intermediate telomeric NtAI and AiCNA had higher ORR [54% (C) versus 20% (D), PNtAI,intermediate = 0.03; 62% (C) versus 33% (D), PAiCNA,intermediate = 0.076]. Patients with high AiCNA and PGA had shorter PFS in the carboplatin arm [3.4 months (high) versus 5.7 months (low/intermediate); and 3.8 months (high) versus 5.6 months (low/intermediate), respectively; Pinteraction/AiCNA = 0.027, Padj.interaction/AiCNA = 0.125 and Pinteraction/PGA = 0.053, Padj.interaction/PGA = 0.176], whilst no difference was observed in the docetaxel arm. CONCLUSIONS: Patients with tumours lacking HLAMP and demonstrating intermediate CIN-measurements formed a subgroup benefitting from carboplatin relative to docetaxel treatment within the TNT trial. This suggests a complex and paradoxical relationship between the extent of genomic instability in primary tumours and treatment response in the metastatic setting.

Quasifree Neutron Knockout Reaction Reveals a Small s-Orbital Component in the Borromean Nucleus

A kinematically complete quasifree (p,pn) experiment in inverse kinematics was performed to study the structure of the Borromean nucleus ^{17}B, which had long been considered to have a neutron halo. By analyzing the momentum distributions and exclusive cross sections, we obtained the spectroscopic factors for 1s_{1/2} and 0d_{5/2} orbitals, and a surprisingly small percentage of 9(2)% was determined for 1s_{1/2}. Our finding of such a small 1s_{1/2} component and the halo features reported in prior experiments can be explained by the deformed relativistic Hartree-Bogoliubov theory in continuum, revealing a definite but not dominant neutron halo in ^{17}B. The present work gives the smallest s- or p-orbital component among known nuclei exhibiting halo features and implies that the dominant occupation of s or p orbitals is not a prerequisite for the occurrence of a neutron halo.

Surface Localization of the Dineutron in

The formation of a dineutron in the ^{11}Li nucleus is found to be localized to the surface region. The experiment measured the intrinsic momentum of the struck neutron in ^{11}Li via the (p,pn) knockout reaction at 246 MeV/nucleon. The correlation angle between the two neutrons is, for the first time, measured as a function of the intrinsic neutron momentum. A comparison with reaction calculations reveals the localization of the dineutron at r∼3.6 fm. The results also support the density dependence of dineutron formation as deduced from Hartree-Fock-Bogoliubov calculations for nuclear matter.

Extending the Southern Shore of the Island of Inversion to

Detailed spectroscopy of the neutron-unbound nucleus ^{28}F has been performed for the first time following proton/neutron removal from ^{29}Ne/^{29}F beams at energies around 230 MeV/nucleon. The invariant-mass spectra were reconstructed for both the ^{27}F^{(*)}+n and ^{26}F^{(*)}+2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the ^{28}F ground state, with S_{n}(^{28}F)=-199(6) keV, while analysis of the 2n decay channel allowed a considerably improved S_{n}(^{27}F)=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 ^{28}F. Importantly, in the case of the ground state, the reconstructed ^{27}F+n momentum distribution following neutron removal from ^{29}F indicates that it arises mainly from the 1p_{3/2} neutron intruder configuration. This demonstrates that the island of inversion around N=20 includes ^{28}F, and most probably ^{29}F, and suggests that ^{28}O is not doubly magic.

Halo Structure of the Neutron-Dripline Nucleus

The heaviest bound isotope of boron ^{19}B has been investigated using exclusive measurements of its Coulomb dissociation, into ^{17}B and two neutrons, in collisions with Pb at 220 MeV/nucleon. Enhanced electric dipole (E1) strength is observed just above the two-neutron decay threshold with an integrated E1 strength of B(E1)=1.64±0.06(stat)±0.12(sys) e^{2} fm^{2} for relative energies below 6 MeV. This feature, known as a soft E1 excitation, provides the first firm evidence that ^{19}B has a prominent two-neutron halo. Three-body calculations that reproduce the energy spectrum indicate that the valence neutrons have a significant s-wave configuration and exhibit a dineutronlike correlation.

Iatrogenic endometriosis harbors somatic cancer-driver mutations.

STUDY QUESTION: Does incisional endometriosis (IE) harbor somatic cancer-driver mutations? SUMMARY ANSWER: We found that approximately one-quarter of IE cases harbor somatic-cancer mutations, which commonly affect components of the MAPK/RAS or PI3K-Akt-mTor signaling pathways. WHAT IS KNOWN ALREADY: Despite the classification of endometriosis as a benign gynecological disease, it shares key features with cancers such as resistance to apoptosis and stimulation of angiogenesis and is well-established as the precursor of clear cell and endometrioid ovarian carcinomas. Our group has recently shown that deep infiltrating endometriosis (DE), a form of endometriosis that rarely undergoes malignant transformation, harbors recurrent somatic mutations. STUDY DESIGN, SIZE, DURATION: In a retrospective study comparing iatrogenically induced and endogenously occurring forms of endometriosis unlikely to progress to cancer, we examined endometriosis specimens from 40 women with IE and 36 women with DE. Specimens were collected between 2004 and 2017 from five hospital sites in either Canada, Germany or the Netherlands. IE and DE cohorts were age-matched and all women presented with histologically typical endometriosis without known history of malignancy. PARTICIPANTS/MATERIALS, SETTING, METHODS: Archival tissue specimens containing endometriotic lesions were macrodissected and/or laser-capture microdissected to enrich endometriotic stroma and epithelium and a hypersensitive cancer hotspot sequencing panel was used to assess for presence of somatic mutations. Mutations were subsequently validated using droplet digital PCR. PTEN and ARID1A immunohistochemistry (IHC) were performed as surrogates for somatic events resulting in functional loss of respective proteins. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, we detected somatic cancer-driver events in 11 of 40 (27.5%) IE cases and 13 of 36 (36.1%) DE cases, including hotspot mutations in KRAS, ERBB2, PIK3CA and CTNNB1. Heterogeneous PTEN loss occurred at similar rates in IE and DE (7/40 vs 5/36, respectively), whereas ARID1A loss only occurred in a single case of DE. While rates of detectable somatic cancer-driver events between IE and DE are not statistically significant (P > 0.05), KRAS activating mutations were more prevalent in DE. LIMITATIONS, REASONS FOR CAUTION: Detection of somatic cancer-driver events were limited to hotspots analyzed in our panel-based sequencing assay and loss of protein expression by IHC from archival tissue. Whole genome or exome sequencing, or epigenetic analysis may uncover additional somatic alterations. Moreover, because of the descriptive nature of this study, the functional roles of identified mutations within the context of endometriosis remain unclear and causality cannot be established. WIDER IMPLICATIONS OF THE FINDINGS: The alterations we report may be important in driving the growth and survival of endometriosis in ectopic regions of the body. Given the frequency of mutation in surgically displaced endometrium (IE), examination of similar somatic events in eutopic endometrium, as well as clinically annotated cases of other forms of endometriosis, in particular endometriomas that are most commonly linked to malignancy, is warranted. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by a Canadian Cancer Society Impact Grant [701603, PI Huntsman], Canadian Institutes of Health Research Transitional Open Operating Grant [MOP-142273, PI Yong], the Canadian Institutes of Health Research Foundation Grant [FDN-154290, PI Huntsman], the Canadian Institutes of Health Research Project Grant [PJT-156084, PIs Yong and Anglesio], and the Janet D. Cottrelle Foundation through the BC Cancer Foundation [PI Huntsman]. D.G. Huntsman is a co-founder and shareholder of Contextual Genomics Inc., a for profit company that provides clinical reporting to assist in cancer patient treatment. R. Aguirre-Hernandez, J. Khattra and L.M. Prentice have a patent MOLECULAR QUALITY ASSURANCE METHODS FOR USE IN SEQUENCING pending and are current (or former) employees of Contextual Genomics Inc. The remaining authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

First Observation of

The most neutron-rich boron isotopes ^{20}B and ^{21}B have been observed for the first time following proton removal from ^{22}N and ^{22}C at energies around 230 MeV/nucleon. Both nuclei were found to exist as resonances which were detected through their decay into ^{19}B and one or two neutrons. Two-proton removal from ^{22}N populated a prominent resonancelike structure in ^{20}B at around 2.5 MeV above the one-neutron decay threshold, which is interpreted as arising from the closely spaced 1^{-},2^{-} ground-state doublet predicted by the shell model. In the case of proton removal from ^{22}C, the ^{19}B plus one- and two-neutron channels were consistent with the population of a resonance in ^{21}B 2.47±0.19 MeV above the two-neutron decay threshold, which is found to exhibit direct two-neutron decay. The ground-state mass excesses determined for ^{20,21}B are found to be in agreement with mass surface extrapolations derived within the latest atomic-mass evaluations.

Nucleus

The unbound nucleus ^{26}O has been investigated using invariant-mass spectroscopy following one-proton removal reaction from a ^{27}F beam at 201 MeV/nucleon. The decay products, ^{24}O and two neutrons, were detected in coincidence using the newly commissioned SAMURAI spectrometer at the RIKEN Radioactive Isotope Beam Factory. The ^{26}O ground-state resonance was found to lie only 18±3(stat)±4(syst) keV above threshold. In addition, a higher lying level, which is most likely the first 2^{+} state, was observed for the first time at 1.28_{-0.08}^{+0.11} MeV above threshold. Comparison with theoretical predictions suggests that three-nucleon forces, pf-shell intruder configurations, and the continuum are key elements to understanding the structure of the most neutron-rich oxygen isotopes beyond the drip line.

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium.

BACKGROUND: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. METHODS: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. RESULTS: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. CONCLUSION: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.

Observation of a p-wave one-neutron halo configuration in (37)Mg.

Cross sections of 1n-removal reactions from the neutron-rich nucleus (37)Mg on C and Pb targets and the parallel momentum distributions of the (37)Mg residues from the C target have been measured at 240 MeV/nucleon. A combined analysis of these distinct nuclear- and Coulomb-dominated reaction data shows that the (37)Mg ground state has a small 1n separation energy of 0.22(-0.09)(+0.12) MeV and an appreciable p-wave neutron single-particle strength. These results confirm that (37)Mg lies near the edge of the "island of inversion" and has a sizable p-wave neutron halo component, the heaviest such system identified to date.

Deformation-driven p-wave halos at the drip line: 31Ne.

The halo structure of 31Ne is studied using 1n-removal reactions on C and Pb targets at 230 MeV/nucleon. A combined analysis of the cross sections of these nuclear and Coulomb dominated reactions that feed directly the 30Ne ground-state reveals 31Ne to have a small neutron separation energy, 0.15(-0.10)(+0.16) MeV, and spin-parity 3/2-. Consistency of the data with reaction and large-scale shell-model calculations identifies 31Ne as deformed and having a significant p-wave halo component, suggesting that halos are more frequent occurrences at the neutron drip line.

Genome-wide association study of osteochondrosis in the tarsocrural joint of Dutch Warmblood horses identifies susceptibility loci on chromosomes 3 and 10.

Equine osteochondrosis is a developmental joint disease that is a significant source of morbidity affecting multiple breeds of horse. The genetic variants underlying osteochondrosis susceptibility have not been established. Here, we describe the results of a genome-wide association study of osteochondrosis using 90 cases and 111 controls from a population of Dutch Warmblood horses. We report putative associations between osteochondrosis and loci on chromosome 3 (BIEC2-808543; P = 5.03 × 10(-7) ) and chromosome 10 (BIEC2-121323; P = 2.62 × 10(-7) ).

Direct mass measurements of 19B, 22C, 29F, 31Ne, 34Na and other light exotic nuclei.

We report on direct time-of-flight based mass measurements of 16 light neutron-rich nuclei. These include the first determination of the masses of the Borromean drip-line nuclei (19)B, (22)C, and (29)F as well as that of (34)Na. In addition, the most precise determinations to date for (23)N and (31)Ne are reported. Coupled with recent interaction cross-section measurements, the present results support the occurrence of a two-neutron halo in (22)C, with a dominant ν2s(1/2)(2) configuration, and a single-neutron halo in (31)Ne with the valence neutron occupying predominantly the 2p(3/2) orbital. Despite a very low two-neutron separation energy the development of a halo in (19)B is hindered by the 1d(5/2)(2) character of the valence neutrons.

N = 16 spherical shell closure in 24O.

The unbound excited states of the neutron drip-line isotope 24O have been investigated via the 24O(p,p')23O + n reaction in inverse kinematics at a beam energy of 62 MeV/nucleon. The decay energy spectrum of 24O* was reconstructed from the momenta of 23O and the neutron. The spin parity of the first excited state, observed at E(x) = 4.65±0.14 MeV, was determined to be J(π) = 2+ from the angular distribution of the cross section. Higher-lying states were also observed. The quadrupole transition parameter ß2 of the 2(1)+ state was deduced, for the first time, to be 0.15±0.04. The relatively high excitation energy and small ß2 value are indicative of the N = 16 shell closure in 24O.

Migration of nuclear shell gaps studied in the d(24Ne,pγ)25Ne reaction.

The transfer of neutrons onto 24Ne has been measured using a reaccelerated radioactive beam of 24Ne to study the (d,p) reaction in inverse kinematics. The unusual raising of the first 3/2+ level in 25Ne and its significance in terms of the migration of the neutron magic number from N=20 to N=16 is put on a firm footing by confirmation of this state's identity. The raised 3/2+ level is observed simultaneously with the intruder negative parity 7/2- and 3/2- levels, providing evidence for the reduction in the N=20 gap. The coincident gamma-ray decays allowed the assignment of spins as well as the transferred orbital angular momentum. The excitation energy of the 3/2+ state shows that the established USD shell model breaks down well within the sd model space and requires a revised treatment of the proton-neutron monopole interaction.