Improving question formulation for use in evidence appraisal in a tertiary care setting: a randomised controlled trial [ISRCTN66375463]

BACKGROUND: The specificity of clinical questions is gauged by explicit descriptions of four dimensions: subjects, interventions, comparators and outcomes of interest. This study determined whether adding simple instructions and examples on clinical question formulation would increase the specificity of the submitted question compared to using a standard form without instructions and examples. METHODS: A randomised controlled trial was conducted in an evidence-search and appraisal service. New participants were invited to reformulate clinical queries. The Control Group was given no instructions. The Intervention Group was given a brief explanation of proper formulation, written instructions, and diagrammatic examples. The primary outcome was the change in the proportion of reformulated questions that described each the dimensions of specificity. RESULTS: Fifty-two subjects agreed to participate in the trial of which 13 were lost to follow-up. The remaining 17 Intervention Group and 22 Control Group participants were analysed. Baseline characteristics were comparable. Overall, 20% of initially submitted questions from both groups were properly specified (defined as an explicit statement describing all dimensions of specificity). On follow-up, 7/14 questions previously rated as mis-specified in the Intervention Group had all dimensions described at follow-up (p = 0.008) while the Control Group did not show any changes from baseline. Participants in the Intervention Group were also more likely to explicitly describe patients (p = 0.028), comparisons (p = 0.014), and outcomes (p = 0.008). CONCLUSIONS: This trial demonstrated the positive impact of specific instructions on the proportion of properly-specified clinical queries. The evaluation of the long-term impact of such changes is an area of continued research

Science with the Second Wide Field and Planetary Camera

With the commencement of Cycle 4 observations, the General Observer community will have access to the second Wide Field and Planetary Camera (WFPC-2), a replacement for the original WFPC instrument. WFPC-2, a wide-field photometric camera which covers the spectrum from 1200 to 10000 Angstroms, will be installed in the Hubble radial bay during the currently manifested December 1992 Shuttle servicing mission. Besides optical correction for the aberrated Hubble primary mirror, the WFPC-2 incorporates evolutionary improvements in photometric imaging capabilities. The CCD sensors, signal chain electronics, filter set, FUV performance, internal calibrations, and operational efficiency have all been improved through new technologies and lessons learned from WFPC operations and Hubble experience since launch. Here we provide an overview of the new instrument, beginning with the assumption that the reader is already familiar with the original WFPC now in service

Arylmethylamino steroids as antiparasitic agents

In search of antiparasitic agents, we here identify arylmethylamino steroids as potent compounds and characterize more than 60 derivatives. The lead compound 1o is fast acting and highly active against intraerythrocytic stages of chloroquine-sensitive and resistant Plasmodium falciparum parasites (IC50 1–5?nM) as well as against gametocytes. In P. berghei-infected mice, oral administration of 1o drastically reduces parasitaemia and cures the animals. Furthermore, 1o efficiently blocks parasite transmission from mice to mosquitoes. The steroid compounds show low cytotoxicity in mammalian cells and do not induce acute toxicity symptoms in mice. Moreover, 1o has a remarkable activity against the blood-feeding trematode parasite Schistosoma mansoni. The steroid and the hydroxyarylmethylamino moieties are essential for antimalarial activity supporting a chelate-based quinone methide mechanism involving metal or haem bioactivation. This study identifies chemical scaffolds that are rapidly internalized into blood-feeding parasites

Antimalarial drug discovery - the path towards eradication

Malaria is a disease that still affects a significant proportion of the global human population. Whilst advances have been made in lowering the numbers of cases and deaths, it is clear that a strategy based solely on disease control year on year, without reducing transmission and ultimately eradicating the parasite, is unsustainable. This article highlights the current mainstay treatments alongside a selection of emerging new clinical molecules from the portfolio of Medicines for Malaria Venture (MMV) and our partners. In each case, the key highlights from each research phase are described to demonstrate how these new potential medicines were discovered. Given the increased focus of the community on eradicating the disease, the strategy for next generation combination medicines that will provide such potential is explaine

Hubble Space Telescope Imaging of the Circumstellar Nebulosity of T Tauri

Short-exposure Planetary Camera images of T Tauri have been obtained using broadband filters spanning the wavelength range 0.55-0.80 μm. The optically visible star lies very close to an arc of reflection nebulosity. The arc's northern arm extends approximately 5" from the star, while its southwestern arm appears brighter and extends only 2". The arc shows an approximate symmetry along an axis toward the west-northwest, the direction of Hind's Nebula and the blueshifted molecular outflow. The morphology of the reflected light is similar to models of scattered light within an illuminated, axisymmetric outflow cavity in a circumbinary envelope, viewed ≈ 45° from the outflow axis. However, our model images do not successfully account for the amount of limb brightening that is seen. No optical counterpart to the infrared companion is seen to a limiting magnitude of V = 19.6, which suggests A_V > 7 mag toward this source. There is no evidence for an optical tertiary, to a limiting ΔV = 5.1 mag fainter than the primary, at the position where such an object has been previously reported

Stellar Populations at the Center of IC 1613

We have observed the center of the Local Group dwarf irregular galaxy IC 1613 with WFPC2 aboard the Hubble Space Telescope in the F439W, F555W, and F814W filters. We find a dominant old stellar population (aged ~7 Gyr), identifiable by the strong red giant branch (RGB) and red clump populations. From the (V-I) color of the RGB, we estimate a mean metallicity of the intermediate-age stellar population [Fe/H] = -1.38 +/- 0.31. We confirm a distance of 715 +/- 40 kpc using the I-magnitude of the RGB tip. The main-sequence luminosity function down to I ~25 provides evidence for a roughly constant SFR of approximately 0.00035 solar masses per year across the WFPC2 field of view (0.22 square kpc) during the past 250-350 Myr. Structure in the blue loop luminosity function implies that the SFR was ~50% higher 400-900 Myr ago than today. The mean heavy element abundance of these young stars is 1/10th solar. The best explanation for a red spur on the main-sequence at I = 24.7 is the blue horizontal branch component of a very old stellar population at the center of IC 1613. We have also imaged a broader area of IC 1613 using the 3.5-meter WIYN telescope under excellent seeing conditions. The AGB-star luminosity function is consistent with a period of continuous star formation over at least the age range 2-10 Gyr. We present an approximate age-metallicity relation for IC 1613, which appears similar to that of the Small Magellanic Cloud. We compare the Hess diagram of IC 1613 to similar data for three other Local Group dwarf galaxies, and find that it most closely resembles the nearby, transition-type dwarf galaxy Pegasus (DDO 216).Comment: To appear in the September 1999 Astronomical Journal. LaTeX, uses AASTeX v4.0, emulateapj style file, 19 pages, 12 postscript figures, 2 tables. 5 of the figures available separately via the WW

HD 98800: A Unique Stellar System of Post-T Tauri Stars

HD 98800 is a system of four stars, and it has a large infrared excess that is thought to be due to a dust disk within the system. In this paper we present new astrometric observations made with Hipparcos, as well as photometry from Hubble Space Telescope WFPC2 images. Combining these observations and reanalyzing previous work allow us to estimate the age and masses of the stars in the system. Uncertainty in these ages and masses results from uncertainty in the temperatures of the stars and any reddening they may have. We find that HD 98800 is most probably about 10 Myr old, although it may be as young as 5 Myr or as old as 20 Myr. The stars in HD 98800 appear to have metallicities that are about solar. An age of 10 Myr means that HD 98800 is a member of the post-T Tauri class of objects, and we argue that the stars in HD 98800 can help us understand why post-T Tauris have been so elusive. HD 98800 may have formed in the Centaurus star-forming region, but it is extraordinary in being so young and yet so far from where it was born

CHARIS Science: Performance Simulations for the Subaru Telescope's Third-Generation of Exoplanet Imaging Instrumentation

We describe the expected scientific capabilities of CHARIS, a high-contrast integral-field spectrograph (IFS) currently under construction for the Subaru telescope. CHARIS is part of a new generation of instruments, enabled by extreme adaptive optics (AO) systems (including SCExAO at Subaru), that promise greatly improved contrasts at small angular separation thanks to their ability to use spectral information to distinguish planets from quasistatic speckles in the stellar point-spread function (PSF). CHARIS is similar in concept to GPI and SPHERE, on Gemini South and the Very Large Telescope, respectively, but will be unique in its ability to simultaneously cover the entire near-infrared $J$, $H$, and $K$ bands with a low-resolution mode. This extraordinarily broad wavelength coverage will enable spectral differential imaging down to angular separations of a few $\lambda/D$, corresponding to $\sim$0.\!\!''1. SCExAO will also offer contrast approaching $10^{-5}$ at similar separations, $\sim$0.\!\!''1--0.\!\!''2. The discovery yield of a CHARIS survey will depend on the exoplanet distribution function at around 10 AU. If the distribution of planets discovered by radial velocity surveys extends unchanged to $\sim$20 AU, observations of $\sim$200 mostly young, nearby stars targeted by existing high-contrast instruments might find $\sim$1--3 planets. Carefully optimizing the target sample could improve this yield by a factor of a few, while an upturn in frequency at a few AU could also increase the number of detections. CHARIS, with a higher spectral resolution mode of $R \sim 75$, will also be among the best instruments to characterize planets and brown dwarfs like HR 8799 cde and $\kappa$ And b.Comment: 13 pages, 7 figures, proceedings from SPIE Montrea

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