The Protean Challenge of Game Collections at Academic Libraries

The rise of game development and game studies on university campuses prompts academic libraries to consider how to support teaching and research in this area. This article examines current issues and challenges in the development of game collections at academic libraries. The gaming ecosystem has become more complex and libraries may need to move beyond collections largely based on console video games. This article will advance the discussion by considering emerging issues to support access to the full range of games. The article will use examples from Carleton University Library, Ottawa, which has been developing a game collection since 2008

A Randomized Study Evaluating Oral Fusidic Acid (CEM-102) in Combination With Oral Rifampin Compared With Standard-of-Care Antibiotics for Treatment of Prosthetic Joint Infections: A Newly Identified Drug–Drug Interaction

BACKGROUND: Fusidic acid (FA) has been used for decades for bone infection, including prosthetic joint infection (PJI), often in combination with rifampin (RIF). An FA/RIF pharmacokinetic interaction has not previously been described. METHODS: In a phase 2 open-label randomized study, we evaluated oral FA/RIF vs standard-of-care (SOC) intravenous antibiotics for treatment of hip or knee PJI. Outcome assessment occurred at reimplantation (week 12) for subjects with 2-stage exchange, and after 3 or 6 months of treatment for subjects with hip or knee debride and retain strategies, respectively. RESULTS: Fourteen subjects were randomized 1:1 to FA/RIF or SOC. Pharmacokinetic profiles were obtained for 6 subjects randomized to FA/RIF. FA concentrations were lower than anticipated in all subjects during the first week of therapy, and at weeks 4 and 6, blood levels continued to decline. By week 6, FA exposures were 40%-45% lower than expected. CONCLUSIONS: The sponsor elected to terminate this study due to a clearly illustrated drug-drug interaction between FA and RIF, which lowered FA levels to a degree that could influence subject outcomes. Optimization of FA exposure if used in combination with RIF should be a topic of future research. CLINICAL TRIALS REGISTRATION: NCT01756924

Detection of weak gravitational lensing distortions of distant galaxies by cosmic dark matter at large scales

Most of the matter in the universe is not luminous and can be observed directly only through its gravitational effect. An emerging technique called weak gravitational lensing uses background galaxies to reveal the foreground dark matter distribution on large scales. Light from very distant galaxies travels to us through many intervening overdensities which gravitationally distort their apparent shapes. The observed ellipticity pattern of these distant galaxies thus encodes information about the large-scale structure of the universe, but attempts to measure this effect have been inconclusive due to systematic errors. We report the first detection of this ``cosmic shear'' using 145,000 background galaxies to reveal the dark matter distribution on angular scales up to half a degree in three separate lines of sight. The observed angular dependence of this effect is consistent with that predicted by two leading cosmological models, providing new and independent support for these models.Comment: 18 pages, 5 figures: To appear in Nature. (This replacement fixes tex errors and typos.

Hubble Space Telescope Observations of the Draco Dwarf Spheroidal

We present an F606W-F814W color-magnitude diagram for the Draco dwarf spheroidal galaxy based on Hubble Space Telescope WFPC2 images. The luminosity function is well-sampled to 3 magnitudes below the turn-off. We see no evidence for multiple turnoffs and conclude that, at least over the field of the view of the WFPC2, star formation was primarily single-epoch. If the observed number of blue stragglers is due to extended star formation, then roughly 6% (upper limit) of the stars could be half as old as the bulk of the galaxy. The color difference between the red giant branch and the turnoff is consistent with an old population and is very similar to that observed in the old, metal-poor Galactic globular clusters M68 and M92. Despite its red horizontal branch, Draco appears to be older than M68 and M92 by 1.6 +/- 2.5 Gyrs, lending support to the argument that the ``second parameter'' which governs horizontal branch morphology must be something other than age. Draco's observed luminosity function is very similar to that of M68, and the derived initial mass function is consistent with that of the solar neighborhood.Comment: 16 pages, AASTeX, 9 postscript figures, figures 1 and 2 available at ftp://bb3.jpl.nasa.gov/pub/draco/. Accepted for publication in the Astronomical Journa

WFPC2 Observations of Compact Star Cluster Nuclei in Low Luminosity Spiral Galaxies

We have used the Wide Field Planetary Camera 2 aboard the Hubble Space Telescope to image the compact star cluster nuclei of the nearby, late-type, low-luminosity spiral galaxies NGC 4395, NGC 4242, and ESO 359-029. We also analyze archival WFPC2 observations of the compact star cluster nucleus of M33. A comparative analysis of the structural and photometric properties of these four nuclei is presented. All of the nuclei are very compact, with luminosity densities increasing at small radii to the resolution limit of our data. NGC 4395 contains a Seyfert 1 nucleus with a distinct bipolar structure and bright associated filaments which are likely due to [OIII] emission. The M33 nucleus has a complex structure, with elongated isophotes and possible signatures of weak activity, including a jet-like component. The other two nuclei are not known to be active, but share similar physical size scales and luminosities to the M33 and NGC 4395 nuclei. The circumnuclear environments of all four of our program galaxies are extremely diffuse, have only low-to-moderate star formation, and appear to be devoid of large quantities of dust. The central gravitational potentials of the galaxies are also quite shallow, making the origin of these types of `naked' nuclei problematic.Comment: to appear in the July 1999 Astronomical Journal; 38 pages (Latex), 5 tables (postscript), 21 figures (gif); postscript versions of the figures may be obtained via anonymous ftp at ftp://ftp.cv.nrao.edu/NRAO-staff/lmatthew/lanl-nucle

Visible and Far-Ultraviolet WFPC2 Imaging of the Nucleus of the Galaxy NGC 205

We have imaged the nucleus of NGC 205 through the F555W and F160BW filters of WFPC2 on the high-resolution planetary camera (PC). The nucleus consists of a resolved cluster of stars extending 7" X 6". The projected radial distribution of surface brightness can be fitted by a Hubble law with a small core of FWHM 214 x 190 mas (0.74 x 0.66 pc). We find that the nucleus of NGC 205 shares a number of characteristics with globular clusters. Absolute photometry is also presented in a half-arcsec aperture and is found to verify the amount of UV upturn observed in the spectral energy distribution of the nucleus by others (e.g., Bertola et al. 1995). Of the hypotheses available to explain the origin of the nucleus, the observations are most consistent with its being an intermediate age cluster. The most likely scenarios are that it is a either a star cluster whose orbit has decayed-therefore drawing it to rest at the galaxy center-or a cluster that has formed as the repository of the gas from generations of star formation. Together with the ground-based measurement of a low-velocity dispersion, the small core radius implies a 107 yr relaxation time, suggesting the cluster core may have collapsed. An upper limit of 9 x 10^4 M_☉ can be put on the mass of any central black hole

Role of DNA methylation and epigenetic silencing of HAND2 in endometrial cancer development

Background: Endometrial cancer incidence is continuing to rise in the wake of the current ageing and obesity epidemics. Much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Accumulating evidence suggests that the epigenome serves as the interface between the genome and the environment and that hypermethylation of stem cell polycomb group target genes is an epigenetic hallmark of cancer. The objective of this study was to determine the functional role of epigenetic factors in endometrial cancer development. Methods and Findings: Epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancer tissue samples (n = 64) and control samples (n = 23) revealed that HAND2 (a gene encoding a transcription factor expressed in the endometrial stroma) is one of the most commonly hypermethylated and silenced genes in endometrial cancer. A novel integrative epigenome-transcriptome-interactome analysis further revealed that HAND2 is the hub of the most highly ranked differential methylation hotspot in endometrial cancer. These findings were validated using candidate gene methylation analysis in multiple clinical sample sets of tissue samples from a total of 272 additional women. Increased HAND2 methylation was a feature of premalignant endometrial lesions and was seen to parallel a decrease in RNA and protein levels. Furthermore, women with high endometrial HAND2 methylation in their premalignant lesions were less likely to respond to progesterone treatment. HAND2 methylation analysis of endometrial secretions collected using high vaginal swabs taken from women with postmenopausal bleeding specifically identified those patients with early stage endometrial cancer with both high sensitivity and high specificity (receiver operating characteristics area under the curve = 0.91 for stage 1A and 0.97 for higher than stage 1A). Finally, mice harbouring a Hand2 knock-out specifically in their endometrium were shown to develop precancerous endometrial lesions with increasing age, and these lesions also demonstrated a lack of PTEN expression. Conclusions: HAND2 methylation is a common and crucial molecular alteration in endometrial cancer that could potentially be employed as a biomarker for early detection of endometrial cancer and as a predictor of treatment response. The true clinical utility of HAND2 DNA methylation, however, requires further validation in prospective studies.publishedVersio

Deep HST Observations of Star Clusters in NGC 1275

We present an analysis of compact star clusters in deep HST/WFPC2 images of NGC 1275. B and R band photometry of roughly 3000 clusters shows a bimodality in the B-R colors, suggesting that distinct old and young cluster populations are present. The small spread in the colors of the blue clusters is consistent with the hypothesis that they are a single age population, with an inferred age of 0.1 to 1 Gyr. The luminosity function shows increasing numbers of blue clusters to the limit of our photometry, which reaches several magnitudes past the turnover predicted if the cluster population were identical to current Galactic globulars seen at a younger age. The blue clusters have a spatial distribution which is more centrally peaked than that of the red clusters. The individual clusters are slightly resolved, with core radii <~ 0.75 pc if they have modified Hubble profiles. We estimate the specific frequencies of the old and young populations and discuss the uncertainties in these estimates. We find that the specific frequency of the young population in NGC 1275 is currently larger than that of the old population and will remain so as the young population evolves, even if the majority of the low mass clusters are eventually destroyed. If the young population formed during a previous merger, this suggests that mergers can increase the specific frequency of globulars in a galaxy. However, the presently observed young population likely contains too few clusters to have a significant impact on the overall specific frequency as it will be observed in the future.Comment: 26 pages, 9 figures, to be published in the Astronomical Journa

PKQuest: a general physiologically based pharmacokinetic model. Introduction and application to propranolol

BACKGROUND: A "physiologically based pharmacokinetic" (PBPK) approach uses a realistic model of the animal to describe the pharmacokinetics. Previous PBPKs have been designed for specific solutes, required specification of a large number of parameters and have not been designed for general use. METHODS: This new PBPK program (PKQuest) includes a "Standardhuman" and "Standardrat" data set so that the user input is minimized. It has a simple user interface, graphical output and many new features: 1) An option that uses the measured plasma concentrations to solve for the time course of the gastrointestinal, intramuscular, intraperotineal or skin absorption and systemic availability of a drug – for a general non-linear system. 2) Capillary permeability limitation defined in terms of the permeability-surface area products. 4) Saturable plasma and tissue protein binding. 5) A lung model that includes perfusion-ventilation mismatch. 6) A general optimization routine using either a global (simulated annealing) or local (Powell) minimization applicable to all model parameters. RESULTS: PKQuest was applied to measurements of human propranolol pharmacokinetics and intestinal absorption. A meal has two effects: 1) increases portal blood flow by 50%; and 2) decreases liver metabolism by 20%. There is a significant delay in the oval propranolol absorption in fasting subjects that is absent in fed subjects. The oral absorption of the long acting form of propranolol continues for a period of more than 24 hours. CONCLUSIONS: PKQuest provides a new general purpose, easy to use, freely distributed and physiologically rigorous PBPK software routine

Role of DNA Methylation and Epigenetic Silencing of HAND2 in Endometrial Cancer Development

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