Uterine leiomyomata (UL) are the most common neoplasms of the female reproductive tract and primary cause for hysterectomy, leading to considerable morbidity and high economic burden. Here we conduct ...a GWAS meta-analysis in 35,474 cases and 267,505 female controls of European ancestry, identifying eight novel genome-wide significant (P < 5 × 10
) loci, in addition to confirming 21 previously reported loci, including multiple independent signals at 10 loci. Phenotypic stratification of UL by heavy menstrual bleeding in 3409 cases and 199,171 female controls reveals genome-wide significant associations at three of the 29 UL loci: 5p15.33 (TERT), 5q35.2 (FGFR4) and 11q22.3 (ATM). Four loci identified in the meta-analysis are also associated with endometriosis risk; an epidemiological meta-analysis across 402,868 women suggests at least a doubling of risk for UL diagnosis among those with a history of endometriosis. These findings increase our understanding of genetic contribution and biology underlying UL development, and suggest overlapping genetic origins with endometriosis.
We present a high-resolution spectroscopic analysis of 62 red giants in the Milky Way globular cluster (GC) NGC 5286. We have determined abundances of representative light proton-capture, α, Fe-peak ...and neutron-capture element groups, and combined them with photometry of multiple sequences observed along the colour–magnitude diagram. Our principal results are: (i) a broad, bimodal distribution in s-process element abundance ratios, with two main groups, the s-poor and s-rich groups; (ii) substantial star-to-star Fe variations, with the s-rich stars having higher Fe, e.g.
$\langle \mathrm{Fe/H}\rangle _{s{\hbox{-}\rm rich}} - \langle \mathrm{Fe/H}\rangle _{s{\hbox{-}\rm poor}}$
∼ 0.2 dex; and (iii) the presence of O–Na–Al (anti)correlations in both stellar groups. We have defined a new photometric index, c
BVI
= (B − V) − (V − I), to maximize the separation in the colour–magnitude diagram between the two stellar groups with different Fe and s-element content, and this index is not significantly affected by variations in light elements (such as the O–Na anticorrelation). The variations in the overall metallicity present in NGC 5286 add this object to the class of anomalous GCs. Furthermore, the chemical abundance pattern of NGC 5286 resembles that observed in some of the anomalous GCs, e.g. M 22, NGC 1851, M 2, and the more extreme ω Centauri, that also show internal variations in s-elements, and in light elements within stars with different Fe and s-elements content. In view of the common variations in s-elements, we propose the term s-Fe-anomalous GCs to describe this sub-class of objects. The similarities in chemical abundance ratios between these objects strongly suggest similar formation and evolution histories, possibly associated with an origin in tidally disrupted dwarf satellites.
ABSTRACT
In this work, we combine spectroscopic information from the SkyMapper survey for Extremely Metal-Poor stars and astrometry from Gaia DR2 to investigate the kinematics of a sample of 475 ...stars with a metallicity range of $-6.5 \le \rm Fe/H \le -2.05$ dex. Exploiting the action map, we identify 16 and 40 stars dynamically consistent with the Gaia Sausage and Gaia Sequoia accretion events, respectively. The most metal poor of these candidates have metallicities of $\rm Fe/H=-3.31\, \mathrm{ and }\, -3.74$, respectively, helping to define the low-metallicity tail of the progenitors involved in the accretion events. We also find, consistent with other studies, that ∼21 per cent of the sample have orbits that remain confined to within 3 kpc of the Galactic plane, that is, |Zmax| ≤ 3 kpc. Of particular interest is a subsample (∼11 per cent of the total) of low |Zmax| stars with low eccentricities and prograde motions. The lowest metallicity of these stars has Fe/H = –4.30 and the subsample is best interpreted as the very low-metallicity tail of the metal-weak thick disc population. The low |Zmax|, low eccentricity stars with retrograde orbits are likely accreted, while the low |Zmax|, high eccentricity pro- and retrograde stars are plausibly associated with the Gaia Sausage system. We find that a small fraction of our sample (∼4 per cent of the total) is likely escaping from the Galaxy, and postulate that these stars have gained energy from gravitational interactions that occur when infalling dwarf galaxies are tidally disrupted.
The forthcoming Surface Water and Ocean Topography (SWOT) satellite mission will provide global measurements of the free surface of large rivers, providing new opportunities for remote ...sensing‐derived estimates of river discharge in gaged and ungaged basins. SWOT discharge algorithms have been developed and benchmarked using synthetic data but remain untested on real‐world swath altimetry observations. We present the first discharge estimates from AirSWOT, a SWOT‐like airborne Ka‐band radar, using 6 days of measurements over a 40‐km segment of the Willamette River in Oregon, USA. The three evaluated discharge algorithms estimated discharge with normalized root‐mean‐square errors of 10–31% when compared with in situ gage data but were sensitive to an initial estimate of mean annual discharge. Our results show that these discharge algorithms provide reliable discharge estimates on remotely sensed data at SWOT‐like spatial scales while highlighting the need for further algorithm sensitivity tests.
Plain Language Summary
River discharge is a key element of the water cycle, but river gaging networks have significant gaps at the global scale. In 2021, the Surface Water and Ocean Topography (SWOT) mission will be launched to collect high‐accuracy measurements of the world's surface waters, including all global rivers wider than 100 m. In anticipation of SWOT, methods to estimate discharge from its measurements have been developed but have yet to be tested on real‐world data at the spatial scales and accuracies expected of SWOT. We test three such discharge algorithms on data collected by AirSWOT, an airborne variant of SWOT, as it flew over the Willamette River in Oregon, USA. We show that river discharge can be estimated by these algorithms with encouraging accuracy (10–31%) using only airborne measurements and a model‐derived estimate of the mean annual discharge. We stress the need for further testing of these algorithms to determine their sensitivities to the initial estimate of flow and the hydraulic character of the river reach but suggest that these results are encouraging for future global‐scale deployment of SWOT discharge algorithms.
Key Points
River discharge is estimated using solely swath altimetry for the first time
Three discharge algorithms which have been developed and tested on in‐situ or synthetic datasets yield normalized errors of 10–31 %
Algorithm accuracies are encouraging for the forthcoming SWOT satellite mission but show a strong dependence on prior information
NGC 1851 is surrounded by a stellar component that extends more than 10 times beyond the tidal radius. Although the nature of this stellar structure is not known, it has been suggested to be a sparse ...halo of stars or associated with a stellar stream. We analyse the nature of this intriguing stellar component surrounding NGC 1851 by investigating its radial velocities and chemical composition, in particular in comparison with those of the central cluster analysed in a homogeneous manner. In total we observed 23 stars in the halo with radial velocities consistent with NGC 1851, and for 15 of them we infer Fe/H abundances. Our results show that (i) stars dynamically linked to NGC 1851 are present at least up to ∼2.5 tidal radii, supporting the presence of a halo of stars surrounding the cluster; (ii) apart from the NGC 1851 radial velocity-like stars, our observed velocity distribution agrees with that expected from Galactic models, suggesting that no other substructure (such as a stream) at different radial velocities is present in our field; (iii) the chemical abundances for the s-process elements Sr and Ba are consistent with the s-normal stars observed in NGC 1851; (iv) all halo stars have metallicities, and abundances for the other studied elements Ca, Mg and Cr, consistent with those exhibited by the cluster. The complexity of the whole NGC 1851 cluster+halo system may agree with the scenario of a tidally disrupted dwarf galaxy in which NGC 1851 was originally embedded.
We report on a strictly differential line-by-line analysis of high-quality UVES spectra of bright giants in the metal-poor globular cluster NGC 6752. We achieved high precision differential chemical ...abundance measurements for Fe, Na, Si, Ca, Ti, Cr, Ni, Zn, Y, Zr, Ba, La, Ce, Pr, Nd, Sm, Eu and Dy with uncertainties as low as ∼0.01 dex (∼2 per cent). We obtained the following main results. (1) The observed abundance dispersions are a factor of ∼2 larger than the average measurement uncertainty. (2) There are positive correlations, of high statistical significance, between all elements and Na. (3) For any pair of elements, there are positive correlations of high statistical significance, although the amplitudes of the abundance variations are small. Removing abundance trends with effective temperature and/or using a different pair of reference stars does not alter these results. These abundance variations and correlations may reflect a combination of (a) He abundance variations and (b) inhomogeneous chemical evolution in the pre- or protocluster environment. Regarding the former, the current constraints on ΔY from photometry likely preclude He as being the sole explanation. Regarding the latter, the nucleosynthetic source(s) must have synthesized Na, α, Fe-peak and neutron-capture elements and in constant amounts for species heavier than Si; no individual object can achieve such nucleosynthesis. We speculate that other, if not all, globular clusters may exhibit comparable abundance variations and correlations to NGC 6752 if subjected to a similarly precise analysis.
The globular cluster 47 Tuc exhibits a complex sub-giant branch (SGB) with a faint-SGB comprising only about the 10 per cent of the cluster mass and a bright-SGB hosting at least two distinct ...populations. We present a spectroscopic analysis of 62 SGB stars including 21 faint-SGB stars. We thus provide the first chemical analysis of the intriguing faint-SGB population and compare its abundances with those of the dominant populations. We have inferred abundances of Fe, representative light elements C, N, Na, and Al, α elements Mg and Si for individual stars. Oxygen has been obtained by co-adding spectra of stars on different sequences. In addition, we have analysed 12 stars along the two main RGBs of 47 Tuc. Our principal results are (i) star-to-star variations in C/N/Na among RGB and bright-SGB stars; (ii) substantial N and Na enhancements for the minor population corresponding to the faint-SGB; (iii) no high enrichment in C+N+O for faint-SGB stars. Specifically, the C+N+O of the faint-SGB is a factor of 1.1 higher than the bright-SGB, which, considering random (±1.3) plus systematic errors (±0.3), means that their C+N+O is consistent within observational uncertainties. However, a small C+N+O enrichment for the faint-SGB, similar to what predicted on theoretical ground, cannot be excluded. The N and Na enrichment of the faint-SGB qualitatively agrees with this population possibly being He-enhanced, as suggested by theory. The iron abundance of the bright and faint-SGB is the same to a level of ∼0.10 dex, and no other significant difference for the analysed elements has been detected.
Radiotherapy of liver metastases is commonly being performed with photon-beam based stereotactic body radiation therapy (SBRT). The high risk for radiation-induced liver disease (RILD) is a limiting ...factor in these treatments. The use of proton-beam based SBRT could potentially improve the sparing of the healthy part of the liver. The aim of this study was to use estimations of normal tissue complication probability (NTCP) to identify liver-metastases patients that could benefit from being treated with intensity-modulated proton therapy (IMPT), based on the reduction of the risk for RILD.
Ten liver metastases patients, previously treated with photon-beam based SBRT, were retrospectively planned with IMPT. A CTV-based robust optimisation (accounting for setup and range uncertainties), combined with a PTV-based conventional optimisation, was performed. A robustness criterion was defined for the CTV (V
> 98% for at least 10 of the 12 simulated scenarios). The NTCP was estimated for different endpoints using the Lyman-Kutcher-Burman model. The ΔNTCP (NTCP
- NTCP
) for RILD was registered for each patient. The patients for which the NTCP (RILD) < 5% were also identified. A generic relative biological effectiveness of 1.1 was assumed for the proton beams.
For all patients, the objectives set for the PTV and the robustness criterion set for the CTV were fulfilled with the IMPT plans. An improved sparing of the healthy part of the liver, right kidney, lungs, spinal cord and the skin was achieved with the IMPT plans, compared to the SBRT plans. Mean liver doses larger than the threshold value of 32 Gy led to NTCP values for RILD exceeding 5% (7 patients with SBRT and 3 patients with the IMPT plans). ΔNTCP values (RILD) ranging between - 98% and - 17% (7 patients) and between 0 and 2% (3 patients), were calculated.
In this study, liver metastases patients that could benefit from being treated with IMPT, based on the NTCP reductions, were identified. The clinical implementation of such a model-based approach to select liver metastases patients to proton therapy needs to be made with caution while considering the uncertainties involved in the NTCP estimations.
Isocitrate dehydrogenase-1 (Idh1) is an important metabolic enzyme that produces NADPH by converting isocitrate to α-ketoglutarate. Idh1 is known to reduce reactive oxygen species (ROS) induced in ...cells by treatment with lipopolysaccharide (LPS) in vitro. Here, we used Idh1-deficient knockout (Idh1 KO) mice to investigate the role of Idh1 in antioxidant defense in vivo. Idh1 KO mice showed heightened susceptibility to death induced by LPS and exhibited increased serum levels of inflammatory cytokines such as tumor necrosis factor-α and interleukin-6. The serum of LPS-injected Idh1 KO mice also contained elevated levels of AST, a marker of inflammatory liver damage. Furthermore, after LPS injection, livers of Idh1 KO mice showed histological evidence of elevated oxidative DNA damage compared with livers of wild-type (WT) mice. Idh1 KO livers showed a faster and more pronounced oxidative stress than WT livers. In line with that, Idh1 KO hepatocytes showed higher ROS levels and an increase in the NADP(+)/NADPH ratio when compared with hepatocytes isolated from WT mice. These results suggest that Idh1 has a physiological function in protecting cells from oxidative stress by regulating the intracellular NADP(+)/NADPH ratio. Our findings suggest that stimulation of Idh1 activity may be an effective therapeutic strategy for reducing oxidative stress during inflammatory responses, including the early stages of septic shock.
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