Cost-effectiveness of a chronic pain intervention for people living with HIV (PLWH)

Background: Chronic pain is a common, disabling, and costly comorbidity, particularly in people living with HIV (PLWH). This study developed and pilot tested a pain self-management intervention for chronic pain tailored to PLWH called Skills TO Manage Pain (STOMP). Objectives: Given the additional resources needed to deliver STOMP in HIV clinical settings, an important objective of the pilot study was to assess not only STOMP’s preliminary efficacy, but also its cost-effectiveness. Research design and subjects: The present study draws from a 44-participant, 2-arm randomized pilot trial of the STOMP intervention vs usual care among PLWH and at least moderate chronic pain (Clinicaltrials.gov: NCT02824562). Cost-effectiveness is presented as the incremental cost-effectiveness ratio (ICER). Costs were considered from the clinic perspective over a 1-year time horizon using real costs from the pilot trial. It was conservatively assumed there would be no costs savings. The Standard Gamble (SG) method was used to directly measure utilities. Results: Thirty-six participants met inclusion criteria for the present analyses. Mean age was 52 years; 61% were female and 86% were black. The total cost of STOMP was $483.83 per person. Using the SG method, the change in QALYs was 0.15, corresponding to an ICER of$3,225. Conclusions: STOMP’s cost/QALY is substantially lower than the $50,000 to$100,000/QALY benchmark often used to indicate cost-effectiveness. Although based on a pilot trial and, therefore, preliminary, these findings are promising, and suggest the importance of cost analyses in future STOMP trials

Trimming Down the Willman 1 dSph

Willman 1 is a small low surface-brightness object identified in the Sloan Digital Sky Survey and tentatively classified as a very low luminosity dSph galaxy. Further study has supported this classification while hinting that it may be undergoing disruption by the Milky Way potential. In an effort to better constrain the nature of Willman 1, we present a comprehensive analysis of the brightest stars in a 0.6 square degree field centered on the overdensity. High-resolution HET spectra of two previously identified Willman 1 RGB stars show that one is a metal-rich foreground dwarf while the other is a metal-poor giant. The one RGB star that we confirm as a member of Willman 1 has a low metallicity ([Fe/H]=-2.2) and a surprisingly low alpha-element abundance ([alpha/Fe]=-0.11). Washington+DDO51 photometry indicates that 2-5 of the seven brightest Willman 1 stars identified in previous studies are actually dwarf stars, including some of the more metal-rich stars that have been used to argue both for an abundance spread and a more metal-rich stellar population than galaxies of similar luminosity. The remaining stars are too blue or too faint for photometric classification. The Washington+DDO51 photometry identifies three potential RGB stars in the field but HET spectra show that they are background halo stars. Time series photometry identifies one apparent variable star in the field, but it is unlikely to be associated with Willman 1. Our wide-field survey indicates that over 0.6 square degrees, Willman 1 does not have a single RR Lyrae star, a single BHB star or a single RGB star beyond its tidal radius. While our results confirm that Willman 1 is most likely a low-luminosity metal-poor dSph galaxy, the possibility remains that it is a tidally disrupted metal-poor globular cluster.Comment: 10 figures, accepted to Astronomical Journa

4th Biennial Employment Law Institute

Materials from the 4th Biennial Employment Law Institute held by UK/CLE in June 1994

SDSS-IV MaNGA IFS Galaxy Survey—Survey Design, Execution, and Initial Data Quality

The MaNGA Survey (Mapping Nearby Galaxies at Apache Point Observatory) is one of three core programs in the Sloan Digital Sky Survey IV. It is obtaining integral field spectroscopy for 10,000 nearby galaxies at a spectral resolution of R ~ 2000 from 3622 to 10354 Å. The design of the survey is driven by a set of science requirements on the precision of estimates of the following properties: star formation rate surface density, gas metallicity, stellar population age, metallicity, and abundance ratio, and their gradients; stellar and gas kinematics; and enclosed gravitational mass as a function of radius. We describe how these science requirements set the depth of the observations and dictate sample selection. The majority of targeted galaxies are selected to ensure uniform spatial coverage in units of effective radius (Re) while maximizing spatial resolution. About two-thirds of the sample is covered out to 1.5Re (Primary sample), and one-third of the sample is covered to 2.5Re (Secondary sample). We describe the survey execution with details that would be useful in the design of similar future surveys. We also present statistics on the achieved data quality, specifically the point-spread function, sampling uniformity, spectral resolution, sky subtraction, and flux calibration. For our Primary sample, the median r-band signal-to-noise ratio is ~70 per 1.4 Å pixel for spectra stacked between 1R e and 1.5Re. Measurements of various galaxy properties from the first-year data show that we are meeting or exceeding the defined requirements for the majority of our science goals

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Design, Synthesis and Characterization of a Highly Effective Inhibitor for Analog-Sensitive (as) Kinases

Highly selective, cell-permeable and fast-acting inhibitors of individual kinases are sought-after as tools for studying the cellular function of kinases in real time. A combination of small molecule synthesis and protein mutagenesis, identified a highly potent inhibitor (1-Isopropyl-3-(phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine) of a rationally engineered Hog1 serine/threonine kinase (Hog1T100G). This inhibitor has been successfully used to study various aspects of Hog1 signaling, including a transient cell cycle arrest and gene expression changes mediated by Hog1 in response to stress. This study also underscores that the general applicability of this approach depends, in part, on the selectivity of the designed the inhibitor with respect to activity versus the engineered and wild type kinases. To explore this specificity in detail, we used a validated chemogenetic assay to assess the effect of this inhibitor on all gene products in yeast in parallel. The results from this screen emphasize the need for caution and for case-by-case assessment when using the Analog-Sensitive Kinase Allele technology to assess the physiological roles of kinases

Detecting Radio AGN Signatures in Red Geysers

A new class of quiescent galaxies harboring possible AGN-driven winds has been discovered using spatially resolved optical spectroscopy from the ongoing SDSS-IV MaNGA survey. These galaxies, termed "red geysers", constitute 5−10% of the local quiescent population and are characterized by narrow bisymmetric patterns in ionized gas emission features. Cheung et al. argued that these galaxies host large-scale AGN-driven winds that may play a role in suppressing star formation at late times. In this work, we test the hypothesis that AGN activity is ultimately responsible for the red geyser phenomenon. We compare the nuclear radio activity of the red geysers to a matched control sample with similar stellar mass, redshift, rest frame NUV−r color, axis ratio and presence of ionized gas. We have used the 1.4 GHz radio continuum data from VLA FIRST survey to stack the radio flux from the red geyser and control samples. In addition to a 3 times higher FIRST detection rate, we find that red geysers have a 5σ higher level of average radio flux than control galaxies. After restricting to rest-frame NUV−r color > 5 and checking mid-IR WISE photometry, we rule out star formation contamination and conclude that red geysers are associated with more active AGN. Red geysers and a possibly-related class with disturbed Hα emission account for 40\% of all radio-detected red galaxies with log (M⋆/M⊙)<11. Our results support a picture in which episodic AGN activity drives large-scale-relatively weak ionized winds that may provide a feedback mechanism for many early-type galaxies

Structural basis for native agonist and synthetic inhibitor recognition by the Pseudomonas aeruginosa quorum sensing regulator PqsR (MvfR)

Bacterial populations co-ordinate gene expression collectively through quorum sensing (QS), a cell-to-cell communication mechanism employing diffusible signal molecules. The LysR-type transcriptional regulator (LTTR) protein PqsR (MvfR) is a key component of alkyl-quinolone (AQ)-dependent QS in Pseudomonas aeruginosa. PqsR is activated by 2-alkyl-4-quinolones including the Pseudomonas quinolone signal (PQS; 2-heptyl-3-hydroxy-4(1H)-quinolone), its precursor 2-heptyl-4- hydroxyquinoline (HHQ) and their C9 congeners, 2-nonyl-3-hydroxy-4(1H)-quinolone (C9-PQS) and 2-nonyl-4-hydroxyquinoline (NHQ). These drive the autoinduction of AQ biosynthesis and the up-regulation of key virulence determinants as a function of bacterial population density. Consequently, PqsR constitutes a potential target for novel antibacterial agents which attenuate infection through the blockade of virulence. Here we present the crystal structures of the PqsR co-inducer binding domain (CBD) and a complex with the native agonist NHQ. We show that the structure of the PqsR CBD has an unusually large ligand-binding pocket in which a native AQ agonist is stabilized entirely by hydrophobic interactions. Through a ligand-based design strategy we synthesized and evaluated a series of 50 AQ and novel quinazolinone (QZN) analogues and measured the impact on AQ biosynthesis, virulence gene expression and biofilm development. The simple exchange of two isosteres (OH for NH2) switches a QZN agonist to an antagonist with a concomitant impact on the induction of bacterial virulence factor production. We also determined the complex crystal structure of a QZN antagonist bound to PqsR revealing a similar orientation in the ligand binding pocket to the native agonist NHQ. This structure represents the first description of an LTTR-antagonist complex. Overall these studies present novel insights into LTTR ligand binding and ligand-based drug design and provide a chemical scaffold for further anti-P. aeruginosa virulence drug development by targeting the AQ receptor PqsR

Suppressing star formation in quiescent galaxies with supermassive black hole winds.

This is the author accepted manuscript. The final version is available from the Nature Publishing Group via https://doi.org/10.1038/nature18006Quiescent galaxies with little or no ongoing star formation dominate the population of galaxies with masses above 2 × 10(10) times that of the Sun; the number of quiescent galaxies has increased by a factor of about 25 over the past ten billion years (refs 1-4). Once star formation has been shut down, perhaps during the quasar phase of rapid accretion onto a supermassive black hole, an unknown mechanism must remove or heat the gas that is subsequently accreted from either stellar mass loss or mergers and that would otherwise cool to form stars. Energy output from a black hole accreting at a low rate has been proposed, but observational evidence for this in the form of expanding hot gas shells is indirect and limited to radio galaxies at the centres of clusters, which are too rare to explain the vast majority of the quiescent population. Here we report bisymmetric emission features co-aligned with strong ionized-gas velocity gradients from which we infer the presence of centrally driven winds in typical quiescent galaxies that host low-luminosity active nuclei. These galaxies are surprisingly common, accounting for as much as ten per cent of the quiescent population with masses around 2 × 10(10) times that of the Sun. In a prototypical example, we calculate that the energy input from the galaxy's low-level active supermassive black hole is capable of driving the observed wind, which contains sufficient mechanical energy to heat ambient, cooler gas (also detected) and thereby suppress star formation.We are grateful to Yu-Yen Chang for checks on the SED fitting and implied SFR. We thank Stephanie Juneau, Jeffrey Newman, Hai Fu, and Kristina Nyland for discussions and comments. This work was supported by World Premier International Research Center Initiative (WPI Initia- tive), MEXT, Japan, and JSPS KAKENHI Grant Number 15K17603. AW acknowledges support of a Leverhulme Trust Early Career Fellowship. S.P. acknowledges support from the Japan Society for the Promotion of Science (JSPS long-term invitation fellowship). Funding for the Sloan Digital Sky Survey IV has been provided by the Alfred P. Sloan Foundation, the U.S. Department of Energy Office of Science, and the Participating Institutions. SDSS- IV acknowledges support and resources from the Center for High-Performance Computing at the University of Utah. The SDSS web site is www.sdss.org. SDSS-IV is managed by the Astrophysical Research Consortium for the Participating Institutions of the SDSS Collaboration including the Brazilian Participation Group, the Carnegie Institution for Science, Carnegie Mellon University, the Chilean Participation Group, the French Participation Group, Harvard-Smithsonian Center for Astrophysics, Instituto de Astrofísica de Canarias, The Johns Hopkins University, Kavli Institute for the Physics and Mathematics of the Universe (IPMU) / University of Tokyo, Lawrence Berkeley National Laboratory, Leibniz Institut für Astrophysik Potsdam (AIP), Max-Planck-Institut für Astronomie (MPIA Heidelberg), Max-Planck-Institut für Astrophysik (MPA Garching), Max-Planck-Institut für Extraterrestrische Physik (MPE), National Astronomical Observatory of China, New Mexico State University, New York University, Uni- versity of Notre Dame, Observatório Nacional / MCTI, The Ohio State University, Pennsylvania State University, Shanghai Astronomical Observatory, United Kingdom Participation Group, Uni- versidad Nacional Autónoma de México, University of Arizona, University of Colorado Boulder, University of Oxford, University of Portsmouth, University of Utah, University of Virginia, Uni- versity of Washington, University of Wisconsin, Vanderbilt University, and Yale University

Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July