Origin of Sterile Neutrino Dark Matter Via Secret Neutrino Interactions with Vector Bosons

Secret neutrino interactions can play an essential role in the origin of dark matter. We present an anatomy of production mechanisms for sterile neutrino dark matter, a keV-scale gauge-singlet fermion that mixes with active neutrinos, in the presence of a new vector boson mediating secret interactions among active neutrinos. We identify three regimes of the vector boson’s mass and coupling where it makes a distinct impact on dark matter production through the dispersion relations and/or scattering rates. We also analyze models with gauged Lμ−Lτ and B−L numbers which have a similar dark matter cosmology but different vector boson phenomenology. We derive the parameter space in these models where the observed relic abundance is produced for sterile neutrino dark matter. They serve as a well-motivated target for the upcoming experimental searches

AGN's UV and X-ray luminosities in clumpy accretion flows

We consider the fuelling of the central massive black hole in Active Galactic Nuclei, through an inhomogeneous accretion flow. Performing simple analytical treatments, we show that shocks between elements (clumps) forming the accretion flow may account for the UV and X-ray emission in AGNs. In this picture, a cascade of shocks is expected, where optically thick shocks give rise to optical/UV emission, while optically thin shocks give rise to X-ray emission. The resulting blue bump temperature is found to be quite similar in different AGNs. We obtain that the ratio of X-ray luminosity to UV luminosity is smaller than unity, and that this ratio is smaller in massive objects compared to less massive sources. This is in agreement with the observed $L_{X}/L_{UV}$ ratio and suggests a possible interpretation of the $\alpha_{OX}-l_{UV}$ anticorrelation.Comment: 8 pages, 1 figure, accepted for publication in A&

Correlation of N2O and ozone in the Southern Polar vortex during the airborne Antarctic ozone experiment

In situ N20 mixing ratios, measured by an airborne laser spectrometer (ATLAS), have been used along with in situ ozone measurements to determine the correlation of N2O and ozone in the Antarctic stratosphere during the late austral winter. During the 1987 Airborne Antarctic Ozone Experiment (AAOE), N2O data were collected by a laser absorption spectrometer on board the ER-2 on five ferry flights between Ames Research Center (37 deg N) and Punta Arenas, Chile (53 deg S), and on twelve flights over Antarctica (53 S to 72 S). Of all the trace gas species measured by instruments on board the ER-2, only one showed a relationship to the N2O/O3 correlations in the vortex. With few exceptions, positive N20/O3 correlations coincided with total water mixing ratios of greater than 2.9 ppmv, and total water mixing ratios of less than 2.9 ppmv corresponded to negative correlations. The lower water mixing ratios, or dehydrated regions, are colocated with the negative correlations within the vortex, while the wetter regions always occur near the vortex edge

Jellyfish, Forage Fish, and the World's Major Fisherie

A majority of the world’s largest net-based fisheries target planktivorous forage fish that serve as a critical trophic link between the plankton and upper-level consumers such as large predatory fishes, seabirds, and marine mammals. Because the plankton production that drives forage fish also drives jellyfish production, these taxa often overlap in space, time, and diet in coastal ecosystems. This overlap likely leads to predatory and competitive interactions, as jellyfish are effective predators of fish early life stages and zooplankton. The trophic interplay between these groups is made more complex by the harvest of forage fish, which presumably releases jellyfish from competition and is hypothesized to lead to an increase in their production. To understand the role forage fish and jellyfish play as alternate energy transfer pathways in coastal ecosystems, we explore how functional group productivity is altered in three oceanographically distinct ecosystems when jellyfish are abundant and when fish harvest rates are reduced using ecosystem modeling. We propose that ecosystem-based fishery management approaches to forage fish stocks include the use of jellyfish as an independent, empirical “ecosystem health” indicator.Fil: Robinson, Kelly L. State University of Oregon; Estados UnidosFil: Ruzicka, James J.. State University of Oregon; Estados UnidosFil: Decker, Mary Beth. University of Yale; Estados UnidosFil: Brodeur, RIchard. NOAA Northwest Fisheries Science Center; Estados UnidosFil: Hernandez, Frank. University Of Mississippi; Estados UnidosFil: Quiñones Dávila, Javier. Instituto del Mar del Perú; PerúFil: Acha, Eduardo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Universidad Nacional de Mar del Plata; ArgentinaFil: Uye, Shin-ichi. Graduate School of Biosphere Science; JapónFil: Mianzan, Hermes Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Universidad Nacional de Mar del Plata; ArgentinaFil: Graham, William M.. The University of Southern Mississippi; Estados Unido

Evaluation of azlocillin in-vitro and in discriminative animal models of infection

Azlocillin was more active in vitro than ticarcillin or carbenicillin against 561 aminoglycoside-resistant strains of Pseudomonas aeruginosa collected from 74 hospitals distributed over a wide geographic area in the eastern United States. Azlocillin was compared with various other antimicrobial agents in discriminative animal models of Ps. aeruginosa pyelonephritis, osteomyelitis, endocarditis, and meningitis in a variety of mammalian species. Cefsulodin was more effective than azlocillin in reducing Ps. aeruginosa kidney concentrations in rat pyelonephritis induced by intrarenal inoculation. The mean±s.d. logl0 cfu/g kidney after three days of therapy were as follows: controls = 5.4±1.5, azlocillin = 4.4±1.8, cefsulodin = 2.6±0.9 (P < 0.01) but the MBC for the test strain was eight-fold higher for azlocillin (8 vs. 1 mg/l) and effective concentrations were maintained longer in rat serum for cefsulodin as against azlocillin. In addition, ticarcillin reduced kidney bacterial concentrations faster than azlocillin in a mouse pyelonephritis model induced by intravenous Ps. aeruginosa inoculation with subsequent iron loading. Azlocillin was less effective than tobramycin in experimental chronic Ps. aeruginosa osteomyelitis induced in rabbits by direct injection into the tibia. An azlocillin-tobramycin regimen was not more effective than tobramycin alone. After 28 days of therapy, the percentages of positive bone cultures after death were as follows: no antibiotic (controls) = 92%, azlocillin = 95%, tobramycin = 76%, azlocillin plus tobramycin = 60%. Both ticarcillin and azlocillin were less active than tobramycin in experimental Ps. aeruginosa endocarditis induced in rabbits by intravenous inoculation of 108 cfu following 1 h of catheter induced aortic valve trauma. The best results were noted with an azlocillin-tobramycin regimen. The mean±s.d. log10 cfu Ps. aeruginosa/g vegetation after five days of therapy were as follows: no antibiotic controls = 8.1 ± 1.1, tobramycin = 4.5 ±0.8, ticarcillin = 6.9 ± 0.8, azlocillin = 5.7 ± 1.5, ticarcillin phis tobramycin = 4.9 ± 1.0, azlocillin plus tobramycin = 3.3 ± 1.6. Sterile vegetations were rarely attained with any regimen. The mean percentage penetration into purulent cerebrospinal fluid (CSF) in experimental Ps. aeruginosa meningitis for azlocillin was 13.3%, comparable to many other β-lactam antibiotics. Azlocillin was the single most active (P < 0.01) agent evaluated after 8 h intravenous infusions in this model. An azlocillin-amikacin regimen was more rapidly bactericidal (P < 0.01) than either agent alone in vivo. None of the agents evaluated alone or in combination, however, produced a sterile CSF after 8 h of therapy in any anima

Patients' Attitudes and Experiences of Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis and Spondyloarthritis: A Qualitative Synthesis

Objective.Nonadherence to disease-modifying antirheumatic drugs (DMARDS) in rheumatoid arthritis (RA) and spondy-loarthritis (SpA) results in increased disease activity and symptoms and poorer quality of life. We aimed to describepatients’ attitudes and experiences of DMARDs in RA and SpA to inform strategies to improve medication adherence.Methods.Databases (MEDLINE, Embase, PsycINFO, and CINAHL) were searched to January 2016. Thematic synthesiswas used to analyze the findings.Results.From 56 studies involving 1,383 adult patients (RA [n=1,149], SpA [n=191], not specified [n=43]), we identified 6themes (with subthemes): intensifying disease identity (severity of sudden pharmacotherapy, signifying deteriorating health,daunting lifelong therapy), distressing uncertainties and consequences (poisoning the body, doubting efficacy, conflictingand confusing advice, prognostic uncertainty with changingtreatment regimens), powerful social influences (swayed byothers’ experiences, partnering with physicians, maintaining roles, confidence in comprehensive and ongoing care, valuingpeer support), privilege and right of access to biologic agents (expensive medications must be better, right to receive a biologicagent, fearing dispossession), maintaining control (complete ownership of decision, taking extreme risks, minimizing life-style intrusion), and negotiating treatment expectations (miraculous recovery, mediocre benefit, reaching the end of the line).Conclusion.Patients perceive DMARDs as strong medications with alarming side effects that intensify their disease iden-tity. Trust and confidence in medical care, positive experiences with DMARDS among other patients, and an expectationthat medications will help maintain participation in life can motivate patients to use DMARDs. Creating a supportive envi-ronment for patients to voice their concerns may improve treatment satisfaction, adherence, and health outcomes

The LSST DESC data challenge 1: Generation and analysis of synthetic images for next-generation surveys

Data Challenge 1 (DC1) is the first synthetic data set produced by the Rubin Observatory Legacy Survey of Space and Time (LSST) Dark Energy Science Collaboration (DESC). DC1 is designed to develop and validate data reduction and analysis and to study the impact of systematic effects that will affect the LSST data set. DC1 is comprised of r-band observations of 40 deg2 to 10 yr LSST depth. We present each stage of the simulation and analysis process: (a) generation, by synthesizing sources from cosmological N-body simulations in individual sensor-visit images with different observing conditions; (b) reduction using a development version of the LSST Science Pipelines; and (c) matching to the input cosmological catalogue for validation and testing. We verify that testable LSST requirements pass within the fidelity of DC1. We establish a selection procedure that produces a sufficiently clean extragalactic sample for clustering analyses and we discuss residual sample contamination, including contributions from inefficiency in star-galaxy separation and imperfect deblending. We compute the galaxy power spectrum on the simulated field and conclude that: (i) survey properties have an impact of 50 per cent of the statistical uncertainty for the scales and models used in DC1; (ii) a selection to eliminate artefacts in the catalogues is necessary to avoid biases in the measured clustering; and (iii) the presence of bright objects has a significant impact (2-6) in the estimated power spectra at small scales (&gt; 1200), highlighting the impact of blending in studies at small angular scales in LSST

The effect of prior androgen synthesis inhibition on outcomes of subsequent therapy with docetaxel in patients with metastatic castrate-resistant prostate cancer: results from a retrospective analysis of a randomized phase 3 clinical trial (CALGB 90401) (Alliance).

BACKGROUND: Preliminary data suggest a potential decreased benefit of docetaxel in patients with metastatic, castration-resistant prostate cancer (mCRPC) who previously received abiraterone acetate, a novel androgen synthesis inhibitor (ASI). Cancer and Leukemia Group B (CALGB) trial 90401 (Alliance), a phase 3 trial in patients with mCRPC who received docetaxel-based chemotherapy, offered the opportunity to evaluate effect of prior ketoconazole, an earlier generation ASI, on clinical outcomes after docetaxel. METHODS: In CALGB trial 90401, 1050 men with chemotherapy-naive mCRPC were randomized to receive treatment with docetaxel and prednisone that included either bevacizumab or placebo. In total, 1005 men (96%) had data available regarding prior ketoconazole therapy. The observed effects of prior ketoconazole on overall survival (OS), progression-free survival (PFS), prostate-specific antigen (PSA) decline, and the objective response rate (ORR) were assessed using proportional hazards and Poisson regression methods adjusted for validated prognostic factors and treatment arm. RESULTS: Baseline characteristics between patients who did (N=277) and did not (N=728) receive prior ketoconazole therapy were similar. There were no statistically significant differences between patients who did and those who did not receive prior ketoconazole therapy with respect to OS (median OS, 21.1 months vs 22.3 months, respectively; stratified log-rank P=.635), PFS (median PFS, 8.1 months vs 8.6 months, respectively; stratified log-rank P=.342), the proportion achieving a decline ≥ 50% in PSA (61% vs 66%, respectively; relative risk, 1.09; adjusted P=.129), or ORR (39% vs 43%, respectively; relative risk, 1.11; adjusted P=.366). CONCLUSIONS: As measured by OS, PFS, PSA, and the ORR, there was no evidence that prior treatment with ketoconazole had an impact on the clinical outcomes of patients with mCRPC who received subsequent docetaxel-based therapy. The current results highlight the need for prospective studies to assess for potential cross-resistance with novel ASIs and to define the optimal sequence of therapy in mCRPC

Stimulation of sphingosine 1-phosphate signaling as an alveolar cell survival strategy in emphysema

RATIONALE: Vascular endothelial growth factor receptor (VEGFR) inhibition increases ceramides in lung structural cells of the alveolus, initiating apoptosis and alveolar destruction morphologically resembling emphysema. The effects of increased endogenous ceramides could be offset by sphingosine 1-phosphate (S1P), a prosurvival by-product of ceramide metabolism. OBJECTIVES: The aims of our work were to investigate the sphingosine-S1P-S1P receptor axis in the VEGFR inhibition model of emphysema and to determine whether stimulation of S1P signaling is sufficient to functionally antagonize alveolar space enlargement. METHODS: Concurrent to VEGFR blockade in mice, S1P signaling augmentation was achieved via treatment with the S1P precursor sphingosine, S1P agonist FTY720, or S1P receptor-1 (S1PR1) agonist SEW2871. Outcomes included sphingosine kinase-1 RNA expression and activity, sphingolipid measurements by combined liquid chromatography-tandem mass spectrometry, immunoblotting for prosurvival signaling pathways, caspase-3 activity and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assays, and airspace morphometry. MEASUREMENTS AND MAIN RESULTS: Consistent with previously reported de novo activation of ceramide synthesis, VEGFR inhibition triggered increases in lung ceramides, dihydroceramides, and dihydrosphingosine, but did not alter sphingosine kinase activity or S1P levels. Administration of sphingosine decreased the ceramide-to-S1P ratio in the lung and inhibited alveolar space enlargement, along with activation of prosurvival signaling pathways and decreased lung parenchyma cell apoptosis. Sphingosine significantly opposed ceramide-induced apoptosis in cultured lung endothelial cells, but not epithelial cells. FTY720 or SEW2871 recapitulated the protective effects of sphingosine on airspace enlargement concomitant with attenuation of VEGFR inhibitor-induced lung apoptosis. CONCLUSIONS: Strategies aimed at augmenting the S1P-S1PR1 signaling may be effective in ameliorating the apoptotic mechanisms of emphysema development