SwePub - search: WFRF:(Evans Aaron S.)

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1.	Mahajan, Anubha, et al. (author) Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation 2022 In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572 Journal article (peer-reviewed)abstract We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
2.	Kanoni, Stavroula, et al. (author) Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis. 2022 In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1 Journal article (peer-reviewed)abstract Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
3.	Tobias, Deirdre K, et al. (author) Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine 2023 In: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457 Research review (peer-reviewed)abstract Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
4.	Beal, Jacob, et al. (author) Robust estimation of bacterial cell count from optical density 2020 In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1 Journal article (peer-reviewed)abstract Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
5.	Lai, Thomas, et al. (author) GOALS-JWST: Small Neutral Grains and Enhanced 3.3 μm PAH Emission in the Seyfert Galaxy NGC 7469 2023 In: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 957:2 Journal article (peer-reviewed)abstract We present James Webb Space Telescope (JWST) Near Infrared Spectrograph (NIRSpec) integral field spectroscopy of the nearby luminous infrared galaxy NGC 7469. We take advantage of the high spatial/spectral resolution and wavelength coverage of JWST/NIRSpec to study the 3.3 μm neutral polycyclic aromatic hydrocarbon (PAH) grain emission on ∼200 pc scales. A clear change in the average grain properties between the star-forming ring and the central AGN is found. Regions in the vicinity of the AGN, with [Ne iii]/[Ne ii] > 0.25, tend to have larger grain sizes and lower aliphatic-to-aromatic (3.4/3.3) ratios, indicating that smaller grains are preferentially removed by photodestruction in the vicinity of the AGN. PAH emission at the nucleus is weak and shows a low 11.3/3.3 PAH ratio. We find an overall suppression of the total PAH emission relative to the ionized gas in the central 1 kpc region of the AGN in NGC 7469 compared to what has been observed with Spitzer on 3 kpc scales. However, the fractional 3.3 μm-to-total PAH power is enhanced in the starburst ring, possibly due to a variety of physical effects on subkiloparsec scales, including recurrent fluorescence of small grains or multiple photon absorption by large grains. Finally, the IFU data show that while the 3.3 μm PAH-derived star formation rate (SFR) in the ring is 27% higher than that inferred from the [Ne ii] and [Ne iii] emission lines, the integrated SFR derived from the 3.3 μm feature would be underestimated by a factor of 2 due to the deficit of PAHs around the AGN, as might occur if a composite system like NGC 7469 were to be observed at high redshift.
6.	Armus, Lee, et al. (author) GOALS-JWST: Mid-infrared Spectroscopy of the Nucleus of NGC 7469 2023 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 942:2 Journal article (peer-reviewed)abstract We present mid-infrared spectroscopic observations of the nucleus of the nearby Seyfert galaxy NGC 7469 taken with the MIRI instrument on the James Webb Space Telescope (JWST) as part of Directors Discretionary Time Early Release Science program 1328. The high-resolution nuclear spectrum contains 19 emission lines covering a wide range of ionization. The high-ionization lines show broad, blueshifted emission reaching velocities up to 1700 km s−1 and FWHM ranging from ∼500 to 1100 km s−1. The width of the broad emission and the broad-to-narrow line flux ratios correlate with ionization potential. The results suggest a decelerating, stratified, AGN-driven outflow emerging from the nucleus. The estimated mass outflow rate is 1-2 orders of magnitude larger than the current black hole accretion rate needed to power the AGN. Eight pure rotational H2 emission lines are detected with intrinsic widths ranging from FWHM ∼125 to 330 km s−1. We estimate a total mass of warm H2 gas of ∼1.2 × 107 M ⊙ in the central 100 pc. The PAH features are extremely weak in the nuclear spectrum, but a 6.2 μm PAH feature with an equivalent width of ∼0.07 μm and a flux of 2.7 × 10−17 W m−2 is detected. The spectrum is steeply rising in the mid-infrared, with a silicate strength of ∼0.02, significantly smaller than seen in most PG QSOs but comparable to other Seyfert 1s. These early MIRI mid-infrared IFU data highlight the power of JWST to probe the multiphase interstellar media surrounding actively accreting supermassive black holes.
7.	Bianchin, Marina, et al. (author) GOALS-JWST: Gas Dynamics and Excitation in NGC 7469 Revealed by NIRSpec 2024 In: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 965:2 Journal article (peer-reviewed)abstract We present new JWST NIRSpec integral field spectroscopy (IFS) data for the luminous infrared galaxy NGC 7469, a nearby (70.6 Mpc) active galaxy with a Seyfert 1.5 nucleus that drives a highly ionized gas outflow and a prominent nuclear star-forming ring. Using the superb sensitivity and high spatial resolution of the JWST instrument NIRSpec IFS, we investigate the role of the Seyfert nucleus in the excitation and dynamics of the circumnuclear gas. Our analysis focuses on the [Fe ii], H2, and hydrogen recombination lines that trace the radiation/shocked-excited molecular and ionized interstellar medium around the active galactic nucleus (AGN). We investigate gas excitation through H2/Brγ and [Fe ii]/Paβ emission line ratios and find that photoionization by the AGN dominates within the central 300 pc of the galaxy except in a small region that shows signatures of shock-heated gas; these shock-heated regions are likely associated with a compact radio jet. In addition, the velocity field and velocity dispersion maps reveal complex gas kinematics. Rotation is the dominant feature, but we also identify noncircular motions consistent with gas inflows as traced by the velocity residuals and the spiral pattern in the Paα velocity dispersion map. The inflow is 2 orders of magnitude higher than the AGN accretion rate. The compact nuclear radio jet has enough power to drive the highly ionized outflow. This scenario suggests that the inflow and outflow are in a self-regulating feeding-feedback process, with a contribution from the radio jet helping to drive the outflow.
8.	Bohn, Thomas, et al. (author) GOALS-JWST: NIRCam and MIRI Imaging of the Circumnuclear Starburst Ring in NGC 7469 2023 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 942:2 Journal article (peer-reviewed)abstract We present James Webb Space Telescope (JWST) imaging of NGC 7469 with the Near-Infrared Camera and the Mid-InfraRed Instrument. NGC 7469 is a nearby, z = 0.01627, luminous infrared galaxy that hosts both a Seyfert Type-1.5 nucleus and a circumnuclear starburst ring with a radius of ∼0.5 kpc. The new near-infrared (NIR) JWST imaging reveals 66 star-forming regions, 37 of which were not detected by Hubble Space Telescope (HST) observations. Twenty-eight of the 37 sources have very red NIR colors that indicate obscurations up to A v ∼ 7 and a contribution of at least 25% from hot dust emission to the 4.4 μm band. Their NIR colors are also consistent with young (<5 Myr) stellar populations and more than half of them are coincident with the mid-infrared (MIR) emission peaks. These younger, dusty star-forming regions account for ∼6% and ∼17% of the total 1.5 and 4.4 μm luminosity of the starburst ring, respectively. Thanks to JWST, we find a significant number of young dusty sources that were previously unseen due to dust extinction. The newly identified 28 young sources are a significant increase compared to the number of HST-detected young sources (4-5). This makes the total percentage of the young population rise from ∼15% to 48%. These results illustrate the effectiveness of JWST in identifying and characterizing previously hidden star formation in the densest star-forming environments around active galactic nuclei (AGN).
9.	Evans, Aaron S., et al. (author) GOALS-JWST: Hidden Star Formation and Extended PAH Emission in the Luminous Infrared Galaxy VV 114 2022 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 940:1 Journal article (peer-reviewed)abstract James Webb Space Telescope (JWST) Mid-Infrared Instrument (MIRI) images of the luminous infrared (IR) galaxy VV 114 are presented. This redshift ∼0.020 merger has a western component (VV 114W) rich in optical star clusters and an eastern component (VV 114E) hosting a luminous mid-IR nucleus hidden at UV and optical wavelengths by dust lanes. With MIRI, the VV 114E nucleus resolves primarily into bright NE and SW cores separated by 630 pc. This nucleus comprises 45% of the 15 μm light of VV 114, with the NE and SW cores having IR luminosities, L IR(8 − 1000 μm) ∼ 8 ± 0.8 × 1010 L ⊙ and ∼ 5 ± 0.5 × 1010 L ⊙, respectively, and IR densities, ΣIR ≳ 2 ± 0.2 × 1013 L ⊙ kpc−2 and ≳ 7 ± 0.7 × 1012 L ⊙ kpc−2, respectively—in the range of ΣIR for the Orion star-forming core and the nuclei of Arp 220. The NE core, previously speculated to have an active galactic nucleus (AGN), has starburst-like mid-IR colors. In contrast, the VV 114E SW core has AGN-like colors. Approximately 40 star-forming knots with L IR ∼ 0.02-5 × 1010 L ⊙ are identified, 28% of which have no optical counterpart. Finally, diffuse emission accounts for 40%-60% of the mid-IR emission. Mostly notably, filamentary polycyclic aromatic hydrocarbon (PAH) emission stochastically excited by UV and optical photons accounts for half of the 7.7 μm light of VV 114. This study illustrates the ability of JWST to detect obscured compact activity and distributed PAH emission in the most extreme starburst galaxies in the local universe.
10.	Inami, H., et al. (author) GOALS-JWST: Unveiling Dusty Compact Sources in the Merging Galaxy IIZw096 2022 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 940:1 Journal article (peer-reviewed)abstract We have used the Mid-InfraRed Instrument (MIRI) on the James Webb Space Telescope (JWST) to obtain the first spatially resolved, mid-infrared images of IIZw096, a merging luminous infrared galaxy (LIRG) at z = 0.036. Previous observations with the Spitzer Space Telescope suggested that the vast majority of the total IR luminosity (L IR) of the system originated from a small region outside of the two merging nuclei. New observations with JWST/MIRI now allow an accurate measurement of the location and luminosity density of the source that is responsible for the bulk of the IR emission. We estimate that 40%-70% of the IR bolometric luminosity, or 3-5 × 1011 L ⊙, arises from a source no larger than 175 pc in radius, suggesting a luminosity density of at least 3-5 × 1012 L ⊙ kpc−2. In addition, we detect 11 other star-forming sources, five of which were previously unknown. The MIRI F1500W/F560W colors of most of these sources, including the source responsible for the bulk of the far-IR emission, are much redder than the nuclei of local LIRGs. These observations reveal the power of JWST to disentangle the complex regions at the hearts of merging, dusty galaxies.
11.	Lai, Thomas, et al. (author) GOALS-JWST: Tracing AGN Feedback on the Star-forming Interstellar Medium in NGC 7469 2022 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 941:2 Journal article (peer-reviewed)abstract We present James Webb Space Telescope (JWST) Mid-Infrared Instrument (MIRI) integral-field spectroscopy of the nearby merging, luminous infrared galaxy, NGC 7469. This galaxy hosts a Seyfert type-1.5 nucleus, a highly ionized outflow, and a bright, circumnuclear star-forming ring, making it an ideal target to study active galactic nucleus (AGN) feedback in the local universe. We take advantage of the high spatial/spectral resolution of JWST/ MIRI to isolate the star-forming regions surrounding the central active nucleus and study the properties of the dust and warm molecular gas on ∼100 pc scales. The starburst ring exhibits prominent polycyclic aromatic hydrocarbon (PAH) emission, with grain sizes and ionization states varying by only ∼30%, and a total star formation rate of 10–30 Me yr−1 derived from fine structure and recombination emission lines. Using pure rotational lines of H2 we detect 1.2 × 107 Me of warm molecular gas at a temperature higher than 200 K in the ring. All PAH bands get significantly weaker toward the central source, where larger and possibly more ionized grains dominate the emission, likely the result of the ionizing radiation and/or the fast wind emerging from the AGN. The small grains and warm molecular gas in the bright regions of the ring however display properties consistent with normal star-forming regions. These observations highlight the power of JWST to probe the inner regions of dusty, rapidly evolving galaxies for signatures of feedback and inform models that seek to explain the coevolution of supermassive black holes and their hosts.
12.	Linden, S. T., et al. (author) GOALS-JWST: Revealing the Buried Star Clusters in the Luminous Infrared Galaxy VV 114 2023 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 944:2 Journal article (peer-reviewed)abstract We present the results of a James Webb Space Telescope NIRCam investigation into the young massive star cluster (YMC) population in the luminous infrared galaxy VV 114. We identify 374 compact YMC candidates with signal-to-noise ratios ≥ 3, 5, and 5 at F150W, F200W, and F356W, respectively. A direct comparison with our HST cluster catalog reveals that ∼20% of these sources are undetected at optical wavelengths. Based on yggdrasil stellar population models, we identify 17 YMC candidates in our JWST imaging alone with F150W - F200W and F200W - F356W colors suggesting they are all very young, dusty (A V = 5-15), and massive (105.8 < M ⊙ < 106.1). The discovery of these “hidden” sources, many of which are found in the “overlap” region between the two nuclei, quadruples the number of t < 3 Myr clusters and nearly doubles the number of t < 6 Myr clusters detected in VV 114. Now extending the cluster age distribution ( dN / d τ ∝ τ γ ) to the youngest ages, we find a slope of γ = −1.30 ± 0.39 for 106 < τ(yr) < 107, which is consistent with the previously determined value from 107 < τ(yr) < 108.5, and confirms that VV 114 has a steep age distribution slope for all massive star clusters across the entire range of cluster ages observed. Finally, the consistency between our JWST- and HST-derived age distribution slopes indicates that the balance between cluster formation and destruction has not been significantly altered in VV 114 over the last 0.5 Gyr.
13.	Middha, Pooja K., et al. (author) A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry 2023 In: Breast Cancer Research. - : BioMed Central (BMC). - 1465-5411 .- 1465-542X. ; 25:1 Journal article (peer-reviewed)abstract Background Genome-wide studies of gene-environment interactions (GxE) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide GxE analysis of similar to 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 x 10(-5) prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94). Conclusions Overall, the contribution of GxE interactions to the heritability of breast cancer is very small. At the population level, multiplicative GxE interactions do not make an important contribution to risk prediction in breast cancer.
14.	Rich, Jeffrey A., et al. (author) GOALS-JWST: Pulling Back the Curtain on the AGN and Star Formation in VV 114 2023 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 944:2 Journal article (peer-reviewed)abstract We present results from the James Webb Space Telescope Director’s Discretionary Time Early Release Science program 1328 targeting the nearby, luminous infrared galaxy, VV 114. We use the MIRI and NIRSpec instruments to obtain integral-field spectroscopy of the heavily obscured eastern nucleus (V114E) and surrounding regions. The spatially resolved, high-resolution spectra reveal the physical conditions in the gas and dust over a projected area of 2-3 kpc that includes the two brightest IR sources, the NE and SW cores. Our observations show for the first time spectroscopic evidence that the SW core hosts an active galactic nucleus as evidenced by its very low 6.2 μm and 3.3 μm polycyclic aromatic hydrocarbon equivalent widths (0.12 and 0.017 μm, respectively) and mid- and near-IR colors. Our observations of the NE core show signs of deeply embedded star formation including absorption features due to aliphatic hydrocarbons, large quantities of amorphous silicates, as well as HCN due to cool gas along the line of sight. We detect elevated [Fe ii]/Pfα consistent with extended shocks coincident with enhanced emission from warm H2, far from the IR-bright cores and clumps. We also identify broadening and multiple kinematic components in both H2 and fine structure lines caused by outflows and previously identified tidal features.
15.	Vivian, U., et al. (author) GOALS-JWST: Resolving the Circumnuclear Gas Dynamics in NGC 7469 in the Mid-infrared 2022 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 940:1 Journal article (peer-reviewed)abstract The nearby, luminous infrared galaxy NGC 7469 hosts a Seyfert nucleus with a circumnuclear star-forming ring and is thus the ideal local laboratory for investigating the starburst-AGN (active galactic nucleus) connection in detail. We present integral-field observations of the central 1.3 kpc region in NGC 7469 obtained with the JWST Mid-InfraRed Instrument. Molecular and ionized gas distributions and kinematics at a resolution of ∼100 pc over the 4.9-7.6 μm region are examined to study the gas dynamics influenced by the central AGN. The low-ionization [Fe ii] λ5.34 μm and [Ar ii] λ6.99 μm lines are bright on the nucleus and in the starburst ring, as opposed to H2 S(5) λ6.91 μm, which is strongly peaked at the center and surrounding ISM. The high-ionization [Mg v] line is resolved and shows a broad, blueshifted component associated with the outflow. It has a nearly face-on geometry that is strongly peaked on the nucleus, where it reaches a maximum velocity of −650 km s−1, and extends about 400 pc to the east. Regions of enhanced velocity dispersion in H2 and [Fe ii] ∼ 180 pc from the AGN that also show high L(H2)/L(PAH) and L([Fe ii])/L(Pfα) ratios to the W and N of the nucleus pinpoint regions where the ionized outflow is depositing energy, via shocks, into the dense interstellar medium between the nucleus and the starburst ring. These resolved mid-infrared observations of the nuclear gas dynamics demonstrate the power of JWST and its high-sensitivity integral-field spectroscopic capability to resolve feedback processes around supermassive black holes in the dusty cores of nearby luminous infrared galaxies.
16.	Buiten, Victorine A., et al. (author) GOALS-JWST: Mid-infrared Molecular Gas Excitation Probes the Local Conditions of Nuclear Star Clusters and the Active Galactic Nucleus in the LIRG VV 114 2024 In: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 966:2 Journal article (peer-reviewed)abstract The enormous increase in mid-IR sensitivity and spatial and spectral resolution provided by the JWST spectrographs enables, for the first time, detailed extragalactic studies of molecular vibrational bands. This opens an entirely new window for the study of the molecular interstellar medium in luminous infrared galaxies (LIRGs). We present a detailed analysis of rovibrational bands of gas-phase CO, H2O, C2H2, and HCN toward the heavily obscured eastern nucleus of the LIRG VV 114, as observed by NIRSpec and the medium resolution spectrograph on the Mid-InfraRed Instrument (MIRI MRS). Spectra extracted from apertures of 130 pc in radius show a clear dichotomy between the obscured active galactic nucleus (AGN) and two intense starburst regions. We detect the 2.3 μm CO bandheads, characteristic of cool stellar atmospheres, in the star-forming regions, but not toward the AGN. Surprisingly, at 4.7 μm, we find highly excited CO (T ex ≈ 700-800 K out to at least rotational level J = 27) toward the star-forming regions, but only cooler gas (T ex ≈ 200 K) toward the AGN. We conclude that only mid-infrared pumping through the rovibrational lines can account for the equilibrium conditions found for CO and H2O in the deeply embedded starbursts. Here, the CO bands probe regions with an intense local radiation field inside dusty young massive star clusters or near the most massive young stars. The lack of high-excitation molecular gas toward the AGN is attributed to geometric dilution of the intense radiation from the bright point source. An overview of the relevant excitation and radiative transfer physics is provided in an appendix.
17.	Gallagher III, J. S., et al. (author) An Imaging and Spectroscopic Exploration of the Dusty Compact Obscured Nucleus Galaxy Zw 049.057 2024 In: Astrophysical Journal, Supplement Series. - 1538-4365 .- 0067-0049. ; 274:1 Journal article (peer-reviewed)abstract Zw 049.057 is a moderate-mass, dusty, early-type galaxy that hosts a powerful compact obscured nucleus (CON, L FIR,CON ≥ 1011 L ⊙). The resolution of the Hubble Space Telescope enabled measurements of the stellar light distribution and characterization of dust features. Zw 049.057 is inclined with a prominent three-zone disk; the R ≈ 1 kpc star-forming inner dusty disk contains molecular gas, a main disk with less dust and an older stellar population, and a newly detected outer stellar region at R > 6 kpc with circular isophotes. Previously unknown polar dust lanes are signatures of a past minor merger that could have warped the outer disk to near face-on. Dust transmission measurements provide lower limit gas mass estimates for dust features. An extended region with moderate optical depth and M ≥ 2 × 108 M ⊙ obscures the central 2 kpc. Optical spectra show strong interstellar Na D absorption with a constant velocity across the main disk, likely arising in this extraplanar medium. Opacity measurements of the two linear dust features, pillars, give a total mass of ≥106 M ⊙, flow rates of ≥2 M ⊙ yr−1, and few Myr flow times. Dust pillars are associated with the CON and are visible signs of its role in driving large-scale feedback. Our assessments of feedback processes suggest gas recycling sustains the CON. However, radiation pressure driven mass loss and efficient star formation must be avoided for the active galactic nucleus to retain sufficient gas over its lifespan to produce substantial mass growth of the central black hole.
18.	Heyer, Mark, et al. (author) The Dense Gas Mass Fraction and the Relationship to Star Formation in M51 2022 In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 930:2 Journal article (peer-reviewed)abstract Observations of 12CO J = 1 – 0 and HCN J = 1 – 0 emission from NGC 5194 (M51) made with the 50 m Large Millimeter Telescope and the SEQUOIA focal plane array are presented. Using the HCN-to-CO ratio, we examine the dense gas mass fraction over a range of environmental conditions within the galaxy. Within the disk, the dense gas mass fraction varies along the spiral arms but the average value over all spiral arms is comparable to the mean value of interarm regions. We suggest that the near-constant dense gas mass fraction throughout the disk arises from a population of density-stratified, self-gravitating molecular clouds and the required density threshold to detect each spectral line. The measured dense gas fraction significantly increases in the central bulge in response to the effective pressure, Pe, from the weight of the stellar and gas components. This pressure modifies the dynamical state of the molecular cloud population and, possibly, the HCN-emitting regions in the central bulge from self-gravitating to diffuse configurations in which Pe is greater than the gravitational energy density of individual clouds. Diffuse molecular clouds comprise a significant fraction of the molecular gas mass in the central bulge, which may account for the measured sublinear relationships between the surface densities of the star formation rate and molecular and dense gas.
19.	Hohenschurz-Schmidt, David, et al. (author) Recommendations for the development, implementation, and reporting of control interventions in efficacy and mechanistic trials of physical, psychological, and self-management therapies : the CoPPS Statement 2023 In: BMJ. British Medical Journal. - : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 381, s. e072108- Journal article (peer-reviewed)abstract Control interventions (often called "sham," "placebo," or "attention controls") are essential for studying the efficacy or mechanism of physical, psychological, and self-management interventions in clinical trials. This article presents core recommendations for designing, conducting, and reporting control interventions to establish a quality standard in non-pharmacological intervention research. A framework of additional considerations supports researchers' decision making in this context. We also provide a reporting checklist for control interventions to enhance research transparency, usefulness, and rigour.
20.	Jung, Dooseok Escher, et al. (author) Universal Upper End of the Stellar Initial Mass Function in the Young and Compact LEGUS Clusters 2023 In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 954:2 Journal article (peer-reviewed)abstract We investigate the variation in the upper end of the stellar initial mass function (uIMF) in 375 young and compact star clusters in five nearby galaxies within ∼5 Mpc. All the young stellar clusters (YSCs) in the sample have ages ≲ 4 Myr and masses above 500 M⊙, according to standard stellar models. The YSC catalogs were produced from Hubble Space Telescope images obtained as part of the Legacy ExtraGalactic UV Survey (LEGUS) Hubble treasury program. They are used here to test whether the uIMF is universal or changes as a function of the cluster's stellar mass. We perform this test by measuring the Hα luminosity of the star clusters as a proxy for their ionizing photon rate, and charting its trend as a function of cluster mass. Large cluster numbers allow us to mitigate the stochastic sampling of the uIMF. The advantage of our approach relative to previous similar attempts is the use of cluster catalogs that have been selected independently of the presence of Hα emission, thus removing a potential sample bias. We find that the uIMF, as traced by the Hα emission, shows no dependence on cluster mass, suggesting that the maximum stellar mass that can be produced in star clusters is universal, in agreement with previous findings.
21.	Kapoor, Pooja Middha, et al. (author) Combined associations of a polygenic risk score and classical risk factors with breast cancer risk 2021 In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337 Journal article (peer-reviewed)abstract We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
22.	Yang, Xin, et al. (author) Cancer risks associated with germline PALB2 pathogenic variants : An international study of 524 families 2020 In: Journal of Clinical Oncology. - 0732-183X. ; 38:7, s. 674-685 Journal article (peer-reviewed)abstract PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 3 1022). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.
23.	Bell, Taylor, et al. (author) Nightside clouds and disequilibrium chemistry on the hot Jupiter WASP-43b 2024 In: Nature Astronomy. - 2397-3366. ; 8:7, s. 879-898 Journal article (peer-reviewed)abstract Hot Jupiters are among the best-studied exoplanets, but it is still poorly understood how their chemical composition and cloud properties vary with longitude. Theoretical models predict that clouds may condense on the nightside and that molecular abundances can be driven out of equilibrium by zonal winds. Here we report a phase-resolved emission spectrum of the hot Jupiter WASP-43b measured from 5 μm to 12 μm with the JWST’s Mid-Infrared Instrument. The spectra reveal a large day–night temperature contrast (with average brightness temperatures of 1,524 ± 35 K and 863 ± 23 K, respectively) and evidence for water absorption at all orbital phases. Comparisons with three-dimensional atmospheric models show that both the phase-curve shape and emission spectra strongly suggest the presence of nightside clouds that become optically thick to thermal emission at pressures greater than ~100 mbar. The dayside is consistent with a cloudless atmosphere above the mid-infrared photosphere. Contrary to expectations from equilibrium chemistry but consistent with disequilibrium kinetics models, methane is not detected on the nightside (2σ upper limit of 1–6 ppm, depending on model assumptions). Our results provide strong evidence that the atmosphere of WASP-43b is shaped by disequilibrium processes and provide new insights into the properties of the planet’s nightside clouds. However, the remaining discrepancies between our observations and our predictive atmospheric models emphasize the importance of further exploring the effects of clouds and disequilibrium chemistry in numerical models.
24.	Sakamoto, Kazushi, et al. (author) Deeply Buried Nuclei in the Infrared-luminous Galaxies NGC 4418 and Arp 220. I. ALMA Observations at lambda=1.4-0.4 mm and Continuum Analysis 2021 In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 923:2 Journal article (peer-reviewed)abstract We observed with Atacama Large Millimeter/submillimeter Array three deeply buried nuclei in two galaxies, NGC 4418 and Arp 220, at similar to 0.'' 2 resolution over a total bandwidth of 67 GHz in f(rest) = 215-697 GHz. Here we (1) introduce our program, (2) describe our data reduction method for wide-band, high-resolution imaging spectroscopy, (3) analyze in visibilities the compact nuclei with line forests, (4) develop a continuum-based estimation method of dust opacity and gas column density in heavily obscured nuclei, which uses the buried galactic nuclei (BGN) model and is sensitive to log (NH2/cm(-2)) similar to 25-26 at lambda similar to 1 mm, and (5) present the continuum data and diagnosis of our targets. The three continuum nuclei have major-axis FWHMs of similar to 0.'' 1-0.'' 3 (20-140 pc) aligned to their rotating nuclear disks of molecular gas. However, each nucleus is described better with two or three concentric components than with a single Gaussian. The innermost cores have sizes of 0.'' 05-0.'' 10 (8-40 pc), peak brightness temperatures of similar to 100-500 K at 350 GHz, and more fractional flux at lower frequencies. The intermediate components correspond to the nuclear disks. They have axial ratios of approximate to 0.5 and hence inclinations greater than or similar to 60 degrees. The outermost elements include the bipolar outflow from Arp 220W. We estimate 1 mm dust opacity of tau(d, 1 mm )approximate to 2.2, 1.2, and less than or similar to 0.4, respectively, for NGC 4418, Arp 220W, and Arp 220E. The first two correspond to log(N-H/cm(2)) similar to 26 for conventional dust-opacity laws, and hence the nuclei are highly Compton thick.
25.	Sakamoto, Kazushi, et al. (author) Deeply Buried Nuclei in the Infrared-luminous Galaxies NGC 4418 and Arp 220. II. Line Forests at lambda=1.4-0.4 mm and Circumnuclear Gas Observed with ALMA 2021 In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 923:2 Journal article (peer-reviewed)abstract We present the line observations in our Atacama Millimeter-Submillimeter Array imaging spectral scan toward three deeply buried nuclei in NGC 4418 and Arp 220. We cover 67 GHz in f (rest) = 215-697 GHz at about 0.'' 2 (30, 80 pc) resolution. All the nuclei show dense line forests; we report our initial line identification using 55 species. The line velocities generally indicate gas rotation around each nucleus, tracing nuclear disks of similar to 100 pc in size. We confirmed the counter-rotation of the nuclear disks in Arp 220 and that of the nuclear disk and the galactic disk in NGC 4418. While the brightest lines exceed 100 K, most of the major lines and many C-13 isotopologues show absorption against even brighter continuum cores of the nuclei. The lines with higher upper-level energies, including those from vibrationally excited molecules, tend to arise from smaller areas, indicating radially varying conditions in these nuclei. The outflows from the two Arp 220 nuclei cause blueshifted line absorption below the continuum level. The absorption mostly has small spatial offsets from the continuum peaks to indicate the outflow orientations. The bipolar outflow from the western nucleus is also imaged in multiple emission lines, showing the extent of similar to 1 '' (400 pc). Redshifted line absorption against the nucleus of NGC 4418 indicates either an inward gas motion or a small collimated outflow slanted to the nuclear disk. We also resolved some previous confusions due to line blending and misidentification.
26.	Young, William J., et al. (author) Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways 2022 In: Nature Communications. - : Springer Nature. - 2041-1723. ; 13 Journal article (peer-reviewed)abstract The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.

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