A population of luminous accreting black holes with hidden mergers

Major galaxy mergers are thought to play an important part in fuelling the growth of supermassive black holes. However, observational support for this hypothesis is mixed, with some studies showing a correlation between merging galaxies and luminous quasars and others showing no such association. Recent observations have shown that a black hole is likely to become heavily obscured behind merger-driven gas and dust, even in the early stages of the merger, when the galaxies are well separated (5 to 40 kiloparsecs). Merger simulations further suggest that such obscuration and black-hole accretion peaks in the final merger stage, when the two galactic nuclei are closely separated (less than 3 kiloparsecs). Resolving this final stage requires a combination of high-spatial-resolution infrared imaging and high-sensitivity hard-X-ray observations to detect highly obscured sources. However, large numbers of obscured luminous accreting supermassive black holes have been recently detected nearby (distances below 250 megaparsecs) in X-ray observations. Here we report high-resolution infrared observations of hard-X-ray-selected black holes and the discovery of obscured nuclear mergers, the parent populations of supermassive-black-hole mergers. We find that obscured luminous black holes (bolometric luminosity higher than 2x10^44 ergs per second) show a significant (P<0.001) excess of late-stage nuclear mergers (17.6 per cent) compared to a sample of inactive galaxies with matching stellar masses and star formation rates (1.1 per cent), in agreement with theoretical predictions. Using hydrodynamic simulations, we confirm that the excess of nuclear mergers is indeed strongest for gas-rich major-merger hosts of obscured luminous black holes in this final stage.Comment: To appear in the 8 November 2018 issue of Nature. This is the authors' version of the wor

Impact of combined 18F-FDG PET/CT in head and neck tumours

To compare the interobserver agreement and degree of confidence in anatomical localisation of lesions using 2-[fluorine-18]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) and 18F-FDG PET alone in patients with head and neck tumours. A prospective study of 24 patients (16 male, eight female, median age 59 years) with head and neck tumours was undertaken. 18F-FDG PET/CT was performed for staging purposes. 2D images were acquired over the head and neck area using a GE Discovery LS™ PET/CT scanner. 18F-FDG PET images were interpreted by three independent observers. The observers were asked to localise abnormal 18F-FDG activity to an anatomical territory and score the degree of confidence in localisation on a scale from 1 to 3 (1=exact region unknown; 2=probable; 3=definite). For all 18F-FDG-avid lesions, standardised uptake values (SUVs) were also calculated. After 3 weeks, the same exercise was carried out using 18F-FDG PET/CT images, where CT and fused volume data were made available to observers. The degree of interobserver agreement was measured in both instances. A total of six primary lesions with abnormal 18F-FDG uptake (SUV range 7.2–22) were identified on 18F-FDG PET alone and on 18F-FDG PET/CT. In all, 15 nonprimary tumour sites were identified with 18F-FDG PET only (SUV range 4.5–11.7), while 17 were identified on 18F-FDG PET/CT. Using 18F-FDG PET only, correct localisation was documented in three of six primary lesions, while 18F-FDG PET/CT correctly identified all primary sites. In nonprimary tumour sites, 18F-FDG PET/CT improved the degree of confidence in anatomical localisation by 51%. Interobserver agreement in assigning primary and nonprimary lesions to anatomical territories was moderate using 18F-FDG PET alone (kappa coefficients of 0.45 and 0.54, respectively), but almost perfect with 18F-FDG PET/CT (kappa coefficients of 0.90 and 0.93, respectively). We conclude that 18F-FDG PET/CT significantly increases interobserver agreement and confidence in disease localisation of 18F-FDG-avid lesions in patients with head and neck cancers

PHANGS-JWST First Results: Mapping the 3.3 μm Polycyclic Aromatic Hydrocarbon Vibrational Band in Nearby Galaxies with NIRCam Medium Bands

We present maps of the 3.3 mu m polycyclic aromatic hydrocarbon (PAH) emission feature in NGC 628, NGC 1365, and NGC 7496 as observed with the Near-Infrared Camera imager on JWST from the PHANGS-JWST Cycle 1 Treasury project. We create maps that isolate the 3.3 mu m PAH feature in the F335M filter (F335M(PAH)) using combinations of the F300M and F360M filters for removal of starlight continuum. This continuum removal is complicated by contamination of the F360M by PAH emission and variations in the stellar spectral energy distribution slopes between 3.0 and 3.6 mu m. We modify the empirical prescription from Lai et al. to remove the starlight continuum in our highly resolved galaxies, which have a range of starlight- and PAH-dominated lines of sight. Analyzing radially binned profiles of the F335M(PAH) emission, we find that between 5% and 65% of the F335M intensity comes from the 3.3 mu m feature within the inner 0.5 r (25) of our targets. This percentage systematically varies from galaxy to galaxy and shows radial trends within the galaxies related to each galaxy's distribution of stellar mass, interstellar medium, and star formation. The 3.3 mu m emission is well correlated with the 11.3 mu m PAH feature traced with the MIRI F1130W filter, as is expected, since both features arise from C-H vibrational modes. The average F335M(PAH)/F1130W ratio agrees with the predictions of recent models by Draine et al. for PAHs with size and charge distributions shifted toward larger grains with normal or higher ionization

Characterization of Particles in Protein Solutions: Reaching the Limits of Current Technologies

Recent publications have emphasized the lack of characterization methods available for protein particles in a size range comprised between 0.1 and 10 μm and the potential risk of immunogenicity associated with such particles. In the present paper, we have investigated the performance of light obscuration, flow microscopy, and Coulter counter instruments for particle counting and sizing in protein formulations. We focused on particles 2–10 μm in diameter and studied the effect of silicon oil droplets originating from the barrel of pre-filled syringes, as well as the effect of high protein concentrations (up to 150 mg/ml) on the accuracy of particle characterization. Silicon oil was demonstrated to contribute significantly to the particle counts observed in pre-filled syringes. Inconsistent results were observed between different protein concentrations in the range 7.5–150 mg/ml for particles <10 μm studied by optical techniques (light obscuration and flow microscopy). However, the Coulter counter measurements were consistent across the same studied concentration range but required sufficient solution conductivity from the formulation buffer or excipients. Our results show that currently available technologies, while allowing comparisons between samples of a given protein at a fixed concentration, may be unable to measure particle numbers accurately in a variety of protein formulations, e.g., at high concentration in sugar-based formulations

Linking stellar populations to H II regions across nearby galaxies I. Constraining pre-supernova feedback from young clusters in NGC 1672

Context. Stellar feedback is one of the fundamental factors regulating the evolution of galaxies. However, we still do not have access to strong observational constraints on the relative importance of the different feedback mechanisms (e.g. radiation, ionised gas pressure, stellar winds) in driving Ha II region evolution and molecular cloud disruption. To quantify and compare the different feedback mechanisms, the size of an Ha II region is crucial, whereas samples of well-resolved Ha II regions are scarce. Aims. We constrain the relative importance of the various feedback mechanisms from young massive star populations by resolving Ha II regions across the disk of the nearby star-forming galaxy NGC 1672. Methods. We combined measurements of ionised gas nebular lines obtained by PHANGS-MUSE, with high-resolution (PSF FWHM ∼ 0.1 ∼10 pc) imaging from Hubble Space Telescope (HST) in both the narrow-band Hα and broad-band (NUV, U, B, V, I) filters. We identified a sample of 40 isolated, compact Ha II regions in the HST Hα image. We measured the sizes of these Ha II regions, which were previously unresolved in seeing-limited ground-based observations. In addition, we identified the ionisation source(s) for each Ha II region from catalogues produced as part of the PHANGS-HST survey. In doing so, we were able to link young stellar populations with the properties of their surrounding Ha II regions. Results. The HST observations allowed us to resolve all 40 regions, with radii between 5 and 40 pc. The Ha II regions investigated here are mildly dominated by thermal or wind pressure, yet their elevation above the radiation pressure is within the expected uncertainty range. We see that radiation pressure provides a substantially higher contribution to the total pressure than previously found in the literature over similar size scales. In general, we find higher pressures within more compact Ha II regions, which is driven by the inherent size scaling relations of each pressure term, albeit with significant scatter introduced by the variation in the stellar population properties (e.g. luminosity, mass, age, metallicity). Conclusions. For nearby galaxies, the combination of MUSE/VLT observations with stellar population and resolved Hα observations from HST provides a promising approach that could yield the statistics required to map out how the importance of different stellar feedback mechanisms evolve over the lifetime of a Ha II region

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Spatio-Temporal Dependence of the Signaling Response in Immune-Receptor Trafficking Networks Regulated by Cell Density: A Theoretical Model

Cell signaling processes involve receptor trafficking through highly connected networks of interacting components. The binding of surface receptors to their specific ligands is a key factor for the control and triggering of signaling pathways. In most experimental systems, ligand concentration and cell density vary within a wide range of values. Dependence of the signal response on cell density is related with the extracellular volume available per cell. This dependence has previously been studied using non-spatial models which assume that signaling components are well mixed and uniformly distributed in a single compartment. In this paper, a mathematical model that shows the influence exerted by cell density on the spatio-temporal evolution of ligands, cell surface receptors, and intracellular signaling molecules is developed. To this end, partial differential equations were used to model ligand and receptor trafficking dynamics through the different domains of the whole system. This enabled us to analyze several interesting features involved with these systems, namely: a) how the perturbation caused by the signaling response propagates through the system; b) receptor internalization dynamics and how cell density affects the robustness of dose-response curves upon variation of the binding affinity; and c) that enhanced correlations between ligand input and system response are obtained under conditions that result in larger perturbations of the equilibrium . Finally, the results are compared with those obtained by considering that the above components are well mixed in a single compartment

PHANGS-JWST First Results: Dust-embedded Star Clusters in NGC 7496 Selected via 3.3 μm PAH Emission

The earliest stages of star formation occur enshrouded in dust and are not observable in the optical. Here we leverage the extraordinary new high-resolution infrared imaging from JWST to begin the study of dust-embedded star clusters in nearby galaxies throughout the Local Volume. We present a technique for identifying dust-embedded clusters in NGC 7496 (18.7 Mpc), the first galaxy to be observed by the PHANGS-JWST Cycle 1 Treasury Survey. We select sources that have strong 3.3 mu m PAH emission based on a F300M - F335M color excess and identify 67 candidate embedded clusters. Only eight of these are found in the PHANGS-HST optically selected cluster catalog, and all are young (six have SED fit ages of similar to 1 Myr). We find that this sample of embedded cluster candidates may significantly increase the census of young clusters in NGC 7496 from the PHANGS-HST catalog; the number of clusters younger than similar to 2 Myr could be increased by a factor of 2. Candidates are preferentially located in dust lanes and are coincident with the peaks in the PHANGS-ALMA CO (2-1) maps. We take a first look at concentration indices, luminosity functions, SEDs spanning from 2700 angstrom to 21 mu m, and stellar masses (estimated to be between similar to 10(4) and 10(5) M (circle dot)). The methods tested here provide a basis for future work to derive accurate constraints on the physical properties of embedded clusters, characterize the completeness of cluster samples, and expand analysis to all 19 galaxies in the PHANGS-JWST sample, which will enable basic unsolved problems in star formation and cluster evolution to be addressed

PHANGS-JWST First Results: Tracing the Diffuse Interstellar Medium with JWST Imaging of Polycyclic Aromatic Hydrocarbon Emission in Nearby Galaxies

JWST observations of polycyclic aromatic hydrocarbon (PAH) emission provide some of the deepest and highest resolution views of the cold interstellar medium (ISM) in nearby galaxies. If PAHs are well mixed with the atomic and molecular gas and illuminated by the average diffuse interstellar radiation field, PAH emission may provide an approximately linear, high-resolution, high-sensitivity tracer of diffuse gas surface density. We present a pilot study that explores using PAH emission in this way based on Mid-Infrared Instrument observations of IC 5332, NGC 628, NGC 1365, and NGC 7496 from the Physics at High Angular resolution in Nearby GalaxieS-JWST Treasury. Using scaling relationships calibrated in Leroy et al., scaled F1130W provides 10-40 pc resolution and 3σ sensitivity of Σgas ∼ 2 M ⊙ pc−2. We characterize the surface densities of structures seen at &lt;7 M ⊙ pc−2 in our targets, where we expect the gas to be H i-dominated. We highlight the existence of filaments, interarm emission, and holes in the diffuse ISM at these low surface densities. Below ∼10 M ⊙ pc−2 for NGC 628, NGC 1365, and NGC 7496 the gas distribution shows a “Swiss cheese”-like topology due to holes and bubbles pervading the relatively smooth distribution of the diffuse ISM. Comparing to recent galaxy simulations, we observe similar topology for the low-surface-density gas, though with notable variations between simulations with different setups and resolution. Such a comparison of high-resolution, low-surface-density gas with simulations is not possible with existing atomic and molecular gas maps, highlighting the unique power of JWST maps of PAH emission