| 61. |
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| 62. |
- Shu, Xiang, et al.
(författare)
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Associations of obesity and circulating insulin and glucose with breast cancer risk : a Mendelian randomization analysis
- 2019
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Ingår i: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 48:3, s. 795-806
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Tidskriftsartikel (refereegranskat)abstract
- Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
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| 63. |
- Solano, Emilia R., et al.
(författare)
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Axisymmetric oscillations at L-H transitions in JET : M-mode
- 2017
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 57:2
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Tidskriftsartikel (refereegranskat)abstract
- L to H transition studies at JET have revealed an n = 0, m = 1 magnetic oscillation starting immediately at the L to H transition (called M-mode for brevity). While the magnetic oscillation is present a weak ELM-less H-mode regime is obtained, with a clear increase of density and a weak electron temperature pedestal. It is an intermediate state between L and H-mode. In ICRH heated plasmas or low density NBI plasmas the magnetic mode and the pedestal can remain steady (with small oscillations) for the duration of the heating phase, of order 10 s or more. The axisymmetric magnetic oscillation has period similar to 0.5-2 ms, and poloidal mode number m = 1: it looks like a pedestal localised up/down oscillation, although it is clearly a natural oscillation of the plasma, not driven by the position control system. Electron cyclotron emission, interferometry, reflectometry and fast Li beam measurements locate the mode in the pedestal region. Da, fast infrared camera and Langmuir probe measurements show that the mode modulates heat and particle fluxes to the target. The mode frequency appears to scale with the poloidal Alfven velocity, and not with sound speed (i.e. it is not a geodesic acoustic mode). A heuristic model is proposed for the frequency scaling of the mode. We discuss the relationship between the M-mode and other related observations near the L-H transition.
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| 64. |
- Akiyama, Kazunori, et al.
(författare)
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First Sagittarius A * Event Horizon Telescope Results. I. The Shadow of the Supermassive Black Hole in the Center of the Milky Way
- 2022
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the first Event Horizon Telescope (EHT) observations of Sagittarius A* (Sgr A*), the Galactic center source associated with a supermassive black hole. These observations were conducted in 2017 using a global interferometric array of eight telescopes operating at a wavelength of λ = 1.3 mm. The EHT data resolve a compact emission region with intrahour variability. A variety of imaging and modeling analyses all support an image that is dominated by a bright, thick ring with a diameter of 51.8 ± 2.3 μas (68% credible interval). The ring has modest azimuthal brightness asymmetry and a comparatively dim interior. Using a large suite of numerical simulations, we demonstrate that the EHT images of Sgr A* are consistent with the expected appearance of a Kerr black hole with mass ∼4 × 106 M☉, which is inferred to exist at this location based on previous infrared observations of individual stellar orbits, as well as maser proper-motion studies. Our model comparisons disfavor scenarios where the black hole is viewed at high inclination (i > 50°), as well as nonspinning black holes and those with retrograde accretion disks. Our results provide direct evidence for the presence of a supermassive black hole at the center of the Milky Way, and for the first time we connect the predictions from dynamical measurements of stellar orbits on scales of 103-105 gravitational radii to event-horizon-scale images and variability. Furthermore, a comparison with the EHT results for the supermassive black hole M87* shows consistency with the predictions of general relativity spanning over three orders of magnitude in central mass.
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| 65. |
- Brezinsek, S., et al.
(författare)
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Erosion, screening, and migration of tungsten in the JET divertor
- 2019
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Ingår i: Nuclear Fusion. - : IOP PUBLISHING LTD. - 0029-5515 .- 1741-4326. ; 59:9
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Tidskriftsartikel (refereegranskat)abstract
- The erosion of tungsten (W), induced by the bombardment of plasma and impurity particles, determines the lifetime of plasma-facing components as well as impacting on plasma performance by the influx of W into the confined region. The screening of W by the divertor and the transport of W in the plasma determines largely the W content in the plasma core, but the W source strength itself has a vital impact on this process. The JET tokamak experiment provides access to a large set of W erosion-determining parameters and permits a detailed description of the W source in the divertor closest to the ITER one: (i) effective sputtering yields and fluxes as function of impact energy of intrinsic (Be, C) and extrinsic (Ne, N) impurities as well as hydrogenic isotopes (H, D) are determined and predictions for the tritium (T) isotope are made. This includes the quantification of intra- and inter-edge localised mode (ELM) contributions to the total W source in H-mode plasmas which vary owing to the complex flux compositions and energy distributions in the corresponding phases. The sputtering threshold behaviour and the spectroscopic composition analysis provides an insight in the dominating species and plasma phases causing W erosion. (ii) The interplay between the net and gross W erosion source is discussed considering (prompt) re-deposition, thus, the immediate return of W ions back to the surface due to their large Larmor radius, and surface roughness, thus, the difference between smooth bulk-W and rough W-coating components used in the JET divertor. Both effects impact on the balance equation of local W erosion and deposition. (iii) Post-mortem analysis reveals the net erosion/deposition pattern and the W migration paths over long periods of plasma operation identifying the net W transport to remote areas. This W transport is related to the divertor plasma regime, e.g. attached operation with high impact energies of impinging particles or detached operation, as well as to the applied magnetic configuration in the divertor, e.g. close divertor with good geometrical screening of W or open divertor configuration with poor screening. JET equipped with the ITER-like wall (ILW) provided unique access to the net W erosion rate within a series of 151 subsequent H-mode discharges (magnetic field: B-t = 2.0 T, plasma current: I-p = 2.0 MA, auxiliary power P-aux = 12 MW) in one magnetic configuration accumulating 900 s of plasma with particle fluences in the range of 5-6 x 10(26) D(+ )m(-2) in the semi-detached inner and attached outer divertor leg. The comparison of W spectroscopy in the intra-ELM and inter-ELM phases with post-mortem analysis of W marker tiles provides a set of gross and net W erosion values at the outer target plate. ERO code simulations are applied to both divertor leg conditions and reproduce the erosion/deposition pattern as well as confirm the high experimentally observed prompt W re-deposition factors of more than 95% in the intra- and inter-ELM phase of the unseeded deuterium H-mode plasma. Conclusions to the expected divertor conditions in ITER as well as to the JET operation in the DT plasma mixture are drawn on basis of this unique benchmark experiment.
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| 66. |
- Coignard, J, et al.
(författare)
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A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1078-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
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| 67. |
- Dixon-Suen, Suzanne C, et al.
(författare)
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Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
- 2022
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Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.METHODS: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.RESULTS: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).CONCLUSION: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
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| 68. |
- Litaudon, X., et al.
(författare)
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14 MeV calibration of JET neutron detectors-phase 1: Calibration and characterization of the neutron source
- 2018
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:2
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Tidskriftsartikel (refereegranskat)abstract
- In view of the planned DT operations at JET, a calibration of the JET neutron monitors at 14 MeV neutron energy is needed using a 14 MeV neutron generator deployed inside the vacuum vessel by the JET remote handling system. The target accuracy of this calibration is 10% as also required by ITER, where a precise neutron yield measurement is important, e.g. for tritium accountancy. To achieve this accuracy, the 14 MeV neutron generator selected as the calibration source has been fully characterised and calibrated prior to the in-vessel calibration of the JET monitors. This paper describes the measurements performed using different types of neutron detectors, spectrometers, calibrated long counters and activation foils which allowed us to obtain the neutron emission rate and the anisotropy of the neutron generator, i.e.The neutron flux and energy spectrum dependence on emission angle, and to derive the absolute emission rate in 4π sr. The use of high resolution diamond spectrometers made it possible to resolve the complex features of the neutron energy spectra resulting from the mixed D/T beam ions reacting with the D/T nuclei present in the neutron generator target. As the neutron generator is not a stable neutron source, several monitoring detectors were attached to it by means of an ad hoc mechanical structure to continuously monitor the neutron emission rate during the in-vessel calibration. These monitoring detectors, two diamond diodes and activation foils, have been calibrated in terms of neutrons/counts within ± 5% total uncertainty. A neutron source routine has been developed, able to produce the neutron spectra resulting from all possible reactions occurring with the D/T ions in the beam impinging on the Ti D/T target. The neutron energy spectra calculated by combining the source routine with a MCNP model of the neutron generator have been validated by the measurements. These numerical tools will be key in analysing the results from the in-vessel calibration and to derive the response of the JET neutron detectors to DT plasma neutrons starting from the response to the generator neutrons, and taking into account all the calibration circumstances.
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| 69. |
- Willadsen, E., et al.
(författare)
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Inter-rater reliability in classification of canonical babbling status based on canonical babbling ratio in infants with isolated cleft palate randomised to Timing of Primary Surgery for Cleft Palate (TOPS)
- 2023
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Ingår i: Clinical Linguistics & Phonetics. - : Informa UK Limited. - 0269-9206 .- 1464-5076. ; 37:1, s. 77-98
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Tidskriftsartikel (refereegranskat)abstract
- Canonical babbling (CB) is commonly defined as present when at least 15% of all syllables produced are canonical, in other words a canonical babbling ratio (CBR) >= 0.15. However, there is limited knowledge about inter-rater reliability in classification of CB status based on CBR and inter-rater differences in assessment of CBR. We investigated inter-rater reliability of experienced Speech Language Therapists (SLTs) on: classification of CB status based on CBR >= 0.15, CBRs and the total number of syllables per infant used to calculate CBR. Each infant (n = 484) was video-recorded at a clinical site in play interaction with their parent as part of the randomised controlled trial Timing of Primary Surgery for Cleft Palate. Each recording was subsequently assessed by three independent SLTs, from a pool of 29 SLTs. They assessed the recordings in real time. The three assessing SLTs agreed in classification of CB status in 423 (87.4%) infants, with higher complete agreement for canonical (91%; 326/358) than non-canonical (77%; 97/126). The average difference in CBR and total number of syllables identified between the SLT assessments of each infant was 0.12 and 95, respectively. This study provided new evidence that one trained SLT can reliably classify CB status (CBR >= 0.15) in real time when there is clear distinction between the observed CBR and the boundary (0.15); however, when the observed CBR approaches the boundary multiple SLT assessments are beneficial. Thus, we recommend to include assessment of inter-rater reliability, if the purpose is to compare CBR and total syllable count across infants or studies.
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| 70. |
- Batistoni, P., et al.
(författare)
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14 MeV calibration of JET neutron detectors-phase 2 : in-vessel calibration
- 2018
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Ingår i: Nuclear Fusion. - : IOP PUBLISHING LTD. - 0029-5515 .- 1741-4326. ; 58:10
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Tidskriftsartikel (refereegranskat)abstract
- A new DT campaign (DTE2) is planned at JET in 2020 to minimize the risks of ITER operations. In view of DT operations, a calibration of the JET neutron monitors at 14 MeV neutron energy has been performed using a well calibrated 14 MeV neutron generator (NG) deployed, together with its power supply and control unit, inside the vacuum vessel by the JET remote handling system. The NG was equipped with two calibrated diamond detectors, which continuously monitored its neutron emission rate during the calibration, and activation foils which provided the time integrated yield. Cables embedded in the remote handling boom were used to power the neutron generator, the active detectors and pre-amplifier, and to transport the detectors' signal. The monitoring activation foils were retrieved at the end of each day for decay gamma-ray counting, and replaced by fresh ones. About 76 hours of irradiation, in 9 days, were needed with the neutron generator in 73 different poloidal and toroidal positions in order to calibrate the two neutron yield measuring systems available at JET, the U-235 fission chambers (KN1) and the inner activation system (KN2). The NG neutron emission rates provided by the monitoring detectors were in agreement within 3%. Neutronics calculations have been performed using MCNP code and a detailed model of JET to derive the response of the JET neutron detectors to DT plasma neutrons starting from the response to the NG neutrons, and taking into account the anisotropy of the neutron generator and all the calibration circumstances. These calculations have made use of a very detailed and validated geometrical description of the neutron generator and of the modified. MNCP neutron source subroutine producing neutron energy-angle distribution for the neutrons emitted by the NG. The KN1 calibration factor for a DT plasma has been determined with +/- 4.2%' experimental uncertainty. Corrections due to NG and remote handling effects and the plasma volume effect have been calculated by simulation modelling. The related additional uncertainties are difficult to estimate, however the results of the previous calibration in 2013 have demonstrated that such uncertainties due to modelling are globally <= +/- 3%. It has been found that the difference between KN1 response to DD neutrons and that to DT neutrons is within the uncertainties in the derived responses. KN2 has been calibrated using the Nb-93(n,2n)Nb-92m and Al-27(n,a)Na-24 activation reactions (energy thresholds 10 MeV and 5 MeV respectively). The total uncertainty on the calibration factors is +/- 6% for Nb-93(n,2n)Nb-92m and +/- 8% Al-27(n,a)Na-24 (1 sigma). The calibration factors of the two independent systems KN1 and KN2 will be validated during DT operations. The experience gained and the lessons learnt are presented and discussed in particular with regard to the 14 MeV neutron calibrations in ITER.
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