Purpose in Life and Conscientiousness Protect Against the Development of Suicidal Ideation in U.S. Military Veterans With PTSD and MDD: Results From the National Health and Resilience in Veterans Study.

Background:Although several studies have examined risk factors for suicidal ideation among veterans, little is known about risk and protective factors for suicidal ideation in high-risk veteran samples. Thus, this study examined a broad range of risk and protective factors associated with the development of suicidal ideation in a high-risk sample of U.S. veterans who screened positive for current posttraumatic stress disorder (PTSD) and/or major depressive disorder (MDD). Methods:Data were analyzed from the National Health and Resilience in Veterans Study, a nationally representative, prospective cohort study of U.S. veterans. Veterans completed self-report measures to screen for PTSD and MDD and to assess for risk and protective factors. The sample included 222 veterans with PTSD and/or MDD who did not endorse suicidal ideation at baseline and completed at least one assessment over a seven-year follow-up period. A multivariable binary logistic regression analysis was conducted to examine baseline factors associated with incident suicidal ideation. Results:Nearly one in three (27.1%) of veterans with PTSD and/or MDD developed suicidal ideation over the seven-year follow-up period. Non-Caucasian race and lower scores on measures of purpose in life, conscientiousness, and frequency of religious service attendance were independently associated with incident suicidal ideation. Lower purpose in life (52.3%) and conscientiousness (33.2%) explained the vast majority of variance in incident suicidal ideation. Conclusion:Nearly 30% of veterans with PTSD and/or MDD who did not endorse suicidal ideation at baseline developed suicidal ideation over a seven-year period. Prevention and treatment efforts designed to bolster purpose in life and conscientiousness may help mitigate risk for suicidal ideation in this high-risk population

A Deep Search For Faint Galaxies Associated With Very Low-redshift C IV Absorbers: III. The Mass- and Environment-dependent Circumgalactic Medium

Using Hubble Space Telescope Cosmic Origins Spectrograph observations of 89 QSO sightlines through the Sloan Digital Sky Survey footprint, we study the relationships between C IV absorption systems and the properties of nearby galaxies as well as large-scale environment. To maintain sensitivity to very faint galaxies, we restrict our sample to 0.0015 < z < 0.015, which defines a complete galaxy survey to L > 0.01 L* or stellar mass log M_* > 8 Msun. We report two principal findings. First, for galaxies with impact parameter rho < 1 rvir, C IV detection strongly depends on the luminosity/stellar mass of the nearby galaxy. C IV is preferentially associated with galaxies with log M_* > 9.5 Msun; lower mass galaxies rarely exhibit significant C IV absorption (covering fraction f = 9 +12-6% for 11 galaxies with log M_* < 9.5 Msun). Second, C IV detection within the log M_* > 9.5 Msun population depends on environment. Using a fixed-aperture environmental density metric for galaxies with rho < 160 kpc at z < 0.055, we find that 57+/-12% (8/14) of galaxies in low-density regions (regions with fewer than seven L > 0.15 L* galaxies within 1.5 Mpc) have affiliated C IV absorption; however, none (0/7) of the galaxies in denser regions show C IV. Similarly, the C IV detection rate is lower for galaxies residing in groups with dark-matter halo masses of log Mhalo > 12.5 Msun. In contrast to C IV, H I is pervasive in the CGM without regard to mass or environment. These results indicate that C IV absorbers with log N(C IV) > 13.5 cm^-2 trace the halos of log M_* > 9.5 Msun galaxies but also reflect larger scale environmental conditions.Comment: 26 pages, 13 figures. ApJ, in pres

CGM2^2 ++ CASBaH: The Mass Dependence of H~I Lyα\alpha-Galaxy Clustering and the Extent of the CGM

We combine datasets from the CGM$^{2}$ and CASBaH surveys to model a transition point, $R_{\rm cross}$, between circumgalactic and intergalactic media (CGM and IGM, respectively). In total, our data consist of 7244 galaxies at z < 0.5 with precisely measured spectroscopic redshifts, all having impact parameters of 0.01 - 20 comoving Mpc from 28 QSO sightlines with high-resolution UV spectra that cover H I Ly$\alpha$. Our best-fitting model is an exclusionary two-component model that combines a 3D absorber-galaxy cross correlation function with a simple Gaussian profile at inner radii to represent the CGM. By design, this model gives rise to a determination of $R_{\rm cross}$ as a function of galaxy stellar mass, which can be interpreted as the boundary between the CGM and IGM. For galaxies with $10^8 \leq M_{\star}/M_{\odot} \leq 10^{10.5}$, we find that $R_{\rm cross}(M_{\star}) \approx 2 \pm 0.6 R_{\rm vir}$. Additionally, we find excellent agreement between $R_{\rm cross}(M_{\star})$ and the theoretically-determined splashback radius for galaxies in this mass range. Overall, our results favor models of galaxy evolution at z < 0.5 that distribute $T \approx 10^{4}$K gas to distances beyond the virial radius.Comment: Submitted to ApJ, 17 pages, 8 figure

Morphological Properties of z~0.5 Absorption-Selected Galaxies: The Role of Galaxy Inclination

We have used GIM2D to quantify the morphological properties of 40 intermediate redshift MgII absorption-selected galaxies (0.03<Wr(2796)<2.9 Ang), imaged with WFPC-2/HST, and compared them to the halo gas properties measured form HIRES/Keck and UVES/VLT quasar spectra. We find that as the quasar-galaxy separation, D, increases the MgII equivalent decreases with large scatter, implying that D is not the only physical parameter affecting the distribution and quantity of halo gas. Our main result shows that inclination correlates with MgII absorption properties after normalizing out the relationship (and scatter) between the absorption properties and D. We find a 4.3 sigma correlation between Wr(2796) and galaxy inclination, normalized by impact parameter, i/D. Other measures of absorption optical depth also correlate with i/D at greater than 3.2 sigma significance. Overall, this result suggests that MgII gas has a co-planer geometry, not necessarily disk-like, that is coupled to the galaxy inclination. It is plausible that the absorbing gas arises from tidal streams, satellites, filaments, etc., which tend to have somewhat co-planer distributions. This result does not support a picture in which MgII absorbers with Wr(2796)<1A are predominantly produced by star-formation driven winds. We further find that; (1) MgII host galaxies have quantitatively similar bulge and disk scale length distribution to field galaxies at similar redshifts and have a mean disk and bulge scale length of 3.8kpc and 2.5kpc, respectively; (2) Galaxy color and luminosity do not correlate strongly with absorption properties, implying a lack of a connection between host galaxy star formation rates and absorption strength; (3) Parameters such as scale lengths and bulge-to-total ratios do not significantly correlate with the absorption parameters, suggesting that the absorption is independent of galaxy size or mass.Comment: 21 pages, 7 figures, 7 tables. Accepted for publication in MNRAS. Revised v3 updates Table 5 columns 8 and 11. ArXiv copy includes full version of Fig. 1 (additional 6 pages

Differential In Vitro Effects of Intravenous versus Oral Formulations of Silibinin on the HCV Life Cycle and Inflammation

Silymarin prevents liver disease in many experimental rodent models, and is the most popular botanical medicine consumed by patients with hepatitis C. Silibinin is a major component of silymarin, consisting of the flavonolignans silybin A and silybin B, which are insoluble in aqueous solution. A chemically modified and soluble version of silibinin, SIL, has been shown to potently reduce hepatitis C virus (HCV) RNA levels in vivo when administered intravenously. Silymarin and silibinin inhibit HCV infection in cell culture by targeting multiple steps in the virus lifecycle. We tested the hepatoprotective profiles of SIL and silibinin in assays that measure antiviral and anti-inflammatory functions. Both mixtures inhibited fusion of HCV pseudoparticles (HCVpp) with fluorescent liposomes in a dose-dependent fashion. SIL inhibited 5 clinical genotype 1b isolates of NS5B RNA dependent RNA polymerase (RdRp) activity better than silibinin, with IC50 values of 40–85 µM. The enhanced activity of SIL may have been in part due to inhibition of NS5B binding to RNA templates. However, inhibition of the RdRps by both mixtures plateaued at 43–73%, suggesting that the products are poor overall inhibitors of RdRp. Silibinin did not inhibit HCV replication in subgenomic genotype 1b or 2a replicon cell lines, but it did inhibit JFH-1 infection. In contrast, SIL inhibited 1b but not 2a subgenomic replicons and also inhibited JFH-1 infection. Both mixtures inhibited production of progeny virus particles. Silibinin but not SIL inhibited NF-κB- and IFN-B-dependent transcription in Huh7 cells. However, both mixtures inhibited T cell proliferation to similar degrees. These data underscore the differences and similarities between the intravenous and oral formulations of silibinin, which could influence the clinical effects of this mixture on patients with chronic liver diseases

Understanding the circumgalactic medium is critical for understanding galaxy evolution

Galaxies evolve under the influence of gas flows between their interstellar medium and their surrounding gaseous halos known as the circumgalactic medium (CGM). The CGM is a major reservoir of galactic baryons and metals, and plays a key role in the long cycles of accretion, feedback, and recycling of gas that drive star formation. In order to fully understand the physical processes at work within galaxies, it is therefore essential to have a firm understanding of the composition, structure, kinematics, thermodynamics, and evolution of the CGM. In this white paper we outline connections between the CGM and galactic star formation histories, internal kinematics, chemical evolution, quenching, satellite evolution, dark matter halo occupation, and the reionization of the larger-scale intergalactic medium in light of the advances that will be made on these topics in the 2020s. We argue that, in the next decade, fundamental progress on all of these major issues depends critically on improved empirical characterization and theoretical understanding of the CGM. In particular, we discuss how future advances in spatially-resolved CGM observations at high spectral resolution, broader characterization of the CGM across galaxy mass and redshift, and expected breakthroughs in cosmological hydrodynamic simulations will help resolve these major problems in galaxy evolution.Comment: Astro2020 Decadal Science White Pape

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology