Characteristics and Outcomes of Patients with Vasoplegic Versus Tissue Dysoxic Septic Shock

Background: The current consensus definition of septic shock requires hypotension after adequate fluid challenge or vasopressor requirement. Some patients with septic shock present with hypotension and hyperlactatemia greater than 2 mmol/L (tissue dysoxic shock), whereas others have hypotension alone with normal lactate (vasoplegic shock). Objective: The objective of this study was to determine differences in outcomes of patients with tissue dysoxic versus vasoplegic septic shock. Methods: This was a secondary analysis of a large, multicenter randomized controlled trial. Inclusion criteria were suspected infection, two or more systemic inflammatory response criteria, and systolic blood pressure less than 90 mmHg after a fluid bolus. Patients were categorized by presence of vasoplegic or tissue dysoxic shock. Demographics and Sequential Organ Failure Assessment scores were evaluated between the groups. The primary outcome was in-hospital mortality. Results: A total of 247 patients were included, 90 patients with vasoplegic shock and 157 with tissue dysoxic shock. There were no significant differences in age, race, or sex between the vasoplegic and tissue dysoxic shock groups. The group with vasoplegic shock had a lower initial Sequential Organ Failure Assessment score than did the group with tissue dysoxic shock (5.5 vs. 7.0 points; P = 0.0002). The primary outcome of in-hospital mortality occurred in 8 (9%) of 90 patients with vasoplegic shock compared with 41 (26%) of 157 in the group with tissue dysoxic shock (proportion difference, 17%; 95% confidence interval, 7%–26%; P < 0.0001; log-rank test P = 0.02). After adjusting for confounders, tissue dysoxic shock remained an independent predictor of in-hospital mortality. Conclusions: In this analysis of patients with septic shock, we found a significant difference in in-hospital mortality between patients with vasoplegic versus tissue dysoxic septic shock. These findings suggest a need to consider these differences when designing future studies of septic shock therapies

Group metacognitive therapy for repetitive negative thinking in primary and non-primary generalized anxiety disorder: An effectiveness trial

Background Generalized anxiety disorder (GAD) is a common and highly comorbid anxiety disorder characterized by repetitive negative thinking (RNT). Treatment trials tend to exclude individuals with non-primary GAD, despite this being a common presentation in real world clinics. RNT is also associated with multiple emotional disorders, suggesting that it should be targeted regardless of the primary disorder. This study evaluated the acceptability and effectiveness of brief group metacognitive therapy (MCT) for primary or non-primary GAD within a community clinic. Methods Patients referred to a specialist community clinic attended six, two-hour weekly sessions plus a one-month follow-up (N=52). Measures of metacognitive beliefs, RNT, symptoms, positive and negative affect, and quality of life were completed at the first, last, and follow-up sessions. Results Attrition was low and large intent-to-treat effects were observed on most outcomes, particularly for negative metacognitive beliefs and RNT. Treatment gains increased further to follow-up. Benchmarking comparisons demonstrated that outcomes compared favorably to longer disorder-specific protocols for primary GAD. Limitations No control group or independent assessment of protocol adherence. Conclusions Brief metacognitive therapy is an acceptable and powerful treatment for patients with primary or non-primary GAD

EPOCHS VII: Discovery of high redshift (6.5<z<126.5 < z < 12) AGN candidates in JWST ERO and PEARLS data

We present an analysis of a sample of robust high redshift galaxies selected photometrically from the `blank' fields of the Prime Extragalactic Areas for Reionization Science (PEARLS) survey and Early Release Observations (ERO) data of the James Webb Space Telescope (JWST) with the aim of selecting candidate high redshift active galactic nuclei (AGN). Sources were identified from the parent sample using a threefold selection procedure, which includes spectral energy distribution (SED) fitting to identify sources that are best fitted by AGN SED templates, a further selection based on the relative performance of AGN and non-AGN models, and finally morphological fitting to identify compact sources of emission, resulting in a purity-oriented procedure. Using this procedure, we identify a sample of nine AGN candidates at $6.5 < z < 12$, from which we constrain their physical properties as well as measure a lower bound on the AGN fraction in this redshift range of $5 \pm 1$\%. As this is an extreme lower limit due to our focus on purity and our SEDs being calibrated for unobscured Type 1 AGN, this demonstrates that AGN are perhaps quite common at this early epoch. The rest-frame UV colors of our candidate objects suggest that these systems are potentially candidate obese black hole galaxies (OBG), or AGN with very little galaxy component. We also investigate emission from our sample sources from fields overlapping with Chandra and VLA surveys, allowing us to place X-ray and 3 GHz radio detection limits on our candidates. Of note is a $z = 11.9$ candidate source exhibiting an abrupt morphological shift in the reddest band as compared to the bluer bands, indicating a potential merger or an unusually strong outflow.Comment: Submitted to MNRAS, 12 pages, 11 figures, typos correcte

JWST's PEARLS: TN J1338-1942 -- I. Extreme jet triggered star-formation in a z=4.11 luminous radio galaxy

We present the first JWST observations of the z = 4.11 luminous radio galaxy TN J1338–1942, obtained as part of the ‘Prime Extragalactic Areas for Reionization and Lensing Science’ (‘PEARLS’) project. Our NIRCam observations, designed to probe the key rest-frame optical continuum and emission line features at this redshift, enable resolved spectral energy distribution modelling that incorporates both a range of stellar population assumptions and radiative shock models. With an estimated stellar mass of log10(M/M) ∼ 10.9, TN J1338–1942 is confirmed to be one of the most massive galaxies known at this epoch. Our observations also reveal extremely high equivalent-width nebular emission coincident with the luminous AGN jets that is best fit by radiative shocks surrounded by extensive recent star formation. We estimate the total star-formation rate (SFR) could be as high as ∼ 1600 M yr−1 , with the SFR that we attribute to the jet induced burst conservatively 500 M yr−1. The mass-weighted age of the star-formation, tmass < 4 Myr, is consistent with the likely age of the jets responsible for the triggered activity and significantly younger than that measured in the core of the host galaxy. The extreme scale of the potential jet-triggered star-formation activity indicates the potential importance of positive AGN feedback in the earliest stages of massive galaxy formation, with our observations also illustrating the extraordinary prospects for detailed studies of high-redshift galaxies with JWST.KJD acknowledges funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement number 892117 (HIZRAD) and support from the STFC through an Ernest Rutherford Fellowship (grant number ST/W003120/1). RAW, SHC, and RAJ acknowledge support from NASA JWST Interdisciplinary Scientist grants NAG5-12460, NNX14AN10G, and 80NSSC18K0200 from GSFC. Work by CJC acknowledges support from the European Research Council (ERC) Advanced Investigator Grant EPOCHS (788113). BLF thanks the Berkeley Center for Theoretical Physics for their hospitality during the writing of this paper. MAM acknowledges the support of a National Research Council of Canada Plaskett Fellowship, and the Australian Research Council center of Excellence for All Sky Astrophysics in 3 Dimensions (ASTRO 3D), through project number CE17010001. CNAW acknowledges funding from the JWST/NIRCam contract NASS-0215 to the University of Arizona. TAH is supported by an appointment to the NASA Postdoctoral Program (NPP) at NASA Goddard Space Flight Center, administered by Oak Ridge Associated Universities under contract with NASA.Peer reviewe

Magellanic System Stars Identified in the SMACS J0723.3-7327 JWST ERO Images

We identify 68 distant stars in JWST/NIRCam ERO images of the field of galaxy cluster SMACS J0723.3-7327 (SMACS 0723). Given the relatively small ($\sim$$10^{\circ}$) angular separation between SMACS 0723 and the Large Magellanic Cloud, it is likely that these stars are associated with the LMC outskirts or Leading Arm. This is further bolstered by a spectral energy distribution analysis, which suggests an excess of stars at a physical distance of $40-100$ kpc, consistent with being associated with or located behind the Magellanic system. In particular, we find that the overall surface density of stars brighter than 27.0 mag in the field of SMACS 0723 is $\sim$2.3 times that of stars in a blank field with similar galactic latitude (the North Ecliptic Pole Time Domain Field), and that the density of stars in the SMACS 0723 field with SED-derived distances consistent with the Magellanic system is $\sim$7.3 times larger than that of the blank field. The candidate stars at these distances are consistent with a stellar population at the same distance modulus with [Fe/H] $= -1.0$ and an age of $\sim$$5.0$ Gyr. On the assumption that all of the 68 stars are associated with the LMC, then the stellar density of the LMC at the location of the SMACS 0723 field is $\sim$$710$ stars kpc$^{-3}$, which helps trace the density of stars in the LMC outskirts.Comment: Submitted to ApJ, comments welcom

JWST's PEARLS: a new lens model for ACT-CL J0102−-4915, "EL Gordo'', and the first red supergiant star at cosmological distances discovered by JWST

The first JWST data on the massive colliding cluster El Gordo confirm 23 known families of multiply lensed images and identify 8 new members of these families. Based on these families, which have been confirmed spectroscopically by MUSE, we derived an initial lens model. This model guided the identification of 37 additional families of multiply lensed galaxies, among which 28 are entirely new systems, and 9 were previously known. The initial lens model determined geometric redshifts for the 37 new systems. The geometric redshifts agree reasonably well with spectroscopic or photometric redshifts when those are available. The geometric redshifts enable two additional models that include all 60 families of multiply lensed galaxies spanning a redshift range $2<z<6$. The derived dark-matter distribution confirms the double-peak configuration of mass found by earlier work with the southern and northern clumps having similar masses. We confirm that El Gordo is the most massive known cluster at $z>0.8$ and has an estimated virial mass close the maximum mass allowed by standard cosmological models. The JWST images also reveal the presence of small-mass perturbers that produce small lensing distortions. The smallest of these is consistent with being a dwarf galaxy at $z=0.87$ and has an estimated mass of $3.8\times10^9$~\Msol, making it the smallest substructure found at $z>0.5$. The JWST images also show several candidate caustic-crossing events. One of them is detected at high significance at the expected position of the critical curve and is likely a red supergiant star at $z=2.1878$. This would be the first red supergiant found at cosmological distances. The cluster lensing should magnify background objects at $z>6$, making more of them visible than in blank fields of similar size, but there appears to be a deficiency of such objects.Comment: 27 pages, 21 figure

JWST's PEARLS: Mothra, a new kaiju star at z=2.091 extremely magnified by MACS0416, and implications for dark matter models

We report the discovery of Mothra, an extremely magnified monster star, likely a binary system of two supergiant stars, in one of the strongly lensed galaxies behind the galaxy cluster MACS0416. The star is in a galaxy with spectroscopic redshift $z=2.091$ in a portion of the galaxy that is parsecs away from the cluster caustic. The binary star is observed only on the side of the critical curve with negative parity but has been detectable for at least eight years, implying the presence of a small lensing perturber. Microlenses alone cannot explain the earlier observations of this object made with the Hubble Space Telescope. A larger perturber with a mass of at least $10^4$\,\Msun\ offers a more satisfactory explanation. Based on the lack of perturbation on other nearby sources in the same arc, the maximum mass of the perturber is $M< 2.5\times10^6$\,\Msun, making it the smallest substructure constrained by lensing above redshift 0.3. The existence of this millilens is fully consistent with the expectations from the standard cold dark matter model. On the other hand, the existence of such small substructure in a cluster environment has implications for other dark matter models. In particular, warm dark matter models with particle masses below 8.7\,keV are excluded by our observations. Similarly, axion dark matter models are consistent with the observations only if the axion mass is in the range $0.5\times10^{-22}\, {\rm eV} < m_a < 5\times10^{-22}\, {\rm eV}$.Comment: 26 pages and 27 figure

A search for high-redshift direct collapse black hole candidates in the PEARLS north ecliptic pole field

Direct-collapse black holes (DCBHs) of mass $\sim 10^4$-$10^5 M_\odot$ that form in HI-cooling halos in the early Universe are promising progenitors of the $\gtrsim 10^9 M_\odot$ supermassive black holes that fuel the observed $z \gtrsim 7$ quasars. Efficient accretion of the surrounding gas onto such DCBH seeds may render them sufficiently bright for detection with the James Webb Space Telescope (JWST) up to $z\approx 15$. Additionally, the very steep and red spectral slope predicted across the $\approx 1$-5 $\mu$m wavelength range of the JWST/NIRSpec instrument during their initial growth phase should make them photometrically identifiable up to very high redshifts. Here, we present a search for such DCBH candidates across the 34 arcmin$^{2}$ in the first two spokes of the JWST cycle-1 "Prime Extragalactic Areas for Reionization and Lensing Science" (PEARLS) survey of the North Ecliptic Pole Time Domain Field (NEP), covering 8 NIRCam filters down to a maximum depth of $\sim$ 29 AB mag. We identify three objects with spectral energy distributions consistent with the Pacucci et al. (2016) DCBH models. However, we also note that even with data in 8 NIRCam filters, objects of this type remain degenerate with dusty galaxies and obscured active galactic nuclei over a wide range of redshifts. Follow-up spectroscopy would be required to pin down the nature of these objects, and two of our DCBH candidates are sufficiently bright to make this practical. Based on our sample of DCBH candidates and assumptions on the typical duration of the DCBH steep-slope state, we set a conservative upper limit of $\approx 7\times 10^{-4}$ comoving Mpc$^{-3}$ (cMpc$^{-3}$) on the comoving density of host halos capable of hosting DCBHs with spectral energy distributions similar to the Pacucci et al. (2016) models at $z\approx 6$-13.Comment: 10 pages, 6 figures, 1 table, submitted to A&

Sex-specific regulation of chemokine Cxcl5/6 controls neutrophil recruitment and tissue injury in acute inflammatory states

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Barts and The London Trustees Studentship (SM), Marie Curie fellowships (MB, JD), Arthritis Research UK career development fellowship (JW), William Harvey Research Foundation grant (JW/RSS), Kidney Research UK fellowship (NSAP), Barts and The London Vacation Scholarship (ISN), Wellcome Trust senior fellowship (DWG), and a Wellcome Trust career development fellowship (RSS). This work forms part of the research themes contributing to the translational research portfolio of Barts and The London Cardiovascular Biomedical Research Unit, which is supported and funded by National Institute for Health Researc

Can computer-aided diagnosis assist in the identification of prostate cancer on prostate MRI? a multi-center, multi-reader investigation.

For prostate cancer detection on prostate multiparametric MRI (mpMRI), the Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) and computer-aided diagnosis (CAD) systems aim to widely improve standardization across radiologists and centers. Our goal was to evaluate CAD assistance in prostate cancer detection compared with conventional mpMRI interpretation in a diverse dataset acquired from five institutions tested by nine readers of varying experience levels, in total representing 14 globally spread institutions. Index lesion sensitivities of mpMRI-alone were 79% (whole prostate (WP)), 84% (peripheral zone (PZ)), 71% (transition zone (TZ)), similar to CAD at 76% (WP, p=0.39), 77% (PZ, p=0.07), 79% (TZ, p=0.15). Greatest CAD benefit was in TZ for moderately-experienced readers at PI-RADSv2 <3 (84% vs mpMRI-alone 67%, p=0.055). Detection agreement was unchanged but CAD-assisted read times improved (4.6 vs 3.4 minutes, p<0.001). At PI-RADSv2 ≥ 3, CAD improved patient-level specificity (72%) compared to mpMRI-alone (45%, p<0.001). PI-RADSv2 and CAD-assisted mpMRI interpretations have similar sensitivities across multiple sites and readers while CAD has potential to improve specificity and moderately-experienced radiologists' detection of more difficult tumors in the center of the gland. The multi-institutional evidence provided is essential to future prostate MRI and CAD development