“Trying, But Failing” : The Role of Inhaler Technique and Mode of Delivery in Respiratory Medication Adherence

Recognition of Commercial Support: The Expert Adherence Panel Meeting from which the concepts presented in this article were first discussed and the manuscript submission costs were supported by the Respiratory Effectiveness Group.Peer reviewedPublisher PD

Near-infrared transit photometry of the exoplanet HD 149026b

The transiting exoplanet HD 149026b is an important case for theories of planet formation and planetary structure, because the planet's relatively small size has been interpreted as evidence for a highly metal-enriched composition. We present observations of 4 transits with the Near Infrared Camera and Multi-Object Spectrometer on the Hubble Space Telescope, within a wavelength range of 1.1--2.0 $\mu$m. Analysis of the light curve gives the most precise estimate yet of the stellar mean density, $\rho_\star = 0.497^{+0.042}_{-0.057}$ g cm$^{-3}$. By requiring agreement between the observed stellar properties (including $\rho_\star$) and stellar evolutionary models, we refine the estimate of the stellar radius: $R_\star = 1.541^{+0.046}_{-0.042}$ R_\sun. We also find a deeper transit than has been measured at optical and mid-infrared wavelengths. Taken together, these findings imply a planetary radius of $R_p = 0.813^{+0.027}_{-0.025}$ $R_{\rm Jup}$, which is larger than earlier estimates. Models of the planetary interior still require a metal-enriched composition, although the required degree of metal enrichment is reduced. It is also possible that the deeper NICMOS transit is caused by wavelength-dependent absorption by constituents in the planet's atmosphere, although simple model atmospheres do not predict this effect to be strong enough to account for the discrepancy. We use the 4 newly-measured transit times to compute a refined transit ephemeris.Comment: 18 pages, 13 figures, accepted for publication in Ap

Knowledge-based patient screening for rare and emerging infectious/parasitic diseases: a case study of brucellosis and murine typhus.

Many infectious and parasitic diseases, especially those newly emerging or reemerging, present a difficult diagnostic challenge because of their obscurity and low incidence. Important clues that could lead to an initial diagnosis are often overlooked, misinterpreted, not linked to a disease, or disregarded. We constructed a computer-based decision support system containing 223 infectious and parasitic diseases and used it to conduct a historical intervention study based on field investigation records of 200 cases of human brucellosis and 96 cases of murine typhus that occurred in Texas from 1980 through 1989. Knowledge-based screening showed that the average number of days from the initial patient visit to the time of correct diagnosis was significantly reduced (brucellosis-from 17.9 to 4.5 days, p = 0.0001, murine typhus-from 11.5 to 8.6 days, p = 0.001). This study demonstrates the potential value of knowledge-based patient screening for rare infectious and parasitic diseases

Gram-Negative Bacterial Infection in Thigh Abscess Can Migrate to Distant Burn Depending on Burn Depth

Sepsis remains the major cause of death in patients with major burn injuries. In the present investigation we evaluated the interaction between burn injuries of varying severity and preexisting distant infection. We used Gram-negative bacteria (Pseudomonas aeruginosa and Proteus mirabilis) that were genetically engineered to be bioluminescent, which allowed for noninvasive, sequential optical imaging of the extent and severity of the infection. The bioluminescent bacteria migrated from subcutaneous abscesses in the leg to distant burn wounds on the back depending on the severity of the burn injury, and this migration led to increased mortality of the mice. Treatment with ciprofloxacin, injected either in the leg with the bacterial infection or into the burn eschar, prevented this colonization of the wound and decreased mortality. The present data suggest that burn wounds can readily become colonized by infections distant from the wound itself

NICMOS Observations of the Transiting Hot Jupiter XO-1b

We refine the physical parameters of the transiting hot Jupiter planet XO-1b and its stellar host XO-1 using HST NICMOS observations. XO-1b has a radius Rp=1.21+/-0.03 RJup, and XO-1 has a radius Rs=0.94+/-0.02 RSun, where the uncertainty in the mass of XO-1 dominates the uncertainty of Rp and Rs. There are no significant differences in the XO-1 system properties between these broad-band NIR observations and previous determinations based upon ground-based optical observations. We measure two transit timings from these observations with 9 s and 15 s precision. As a residual to a linear ephemeris model, there is a 2.0 sigma timing difference between the two HST visits that are separated by 3 transit events (11.8 days). These two transit timings and additional timings from the literature are sufficient to rule out the presence of an Earth mass planet orbiting in 2:1 mean motion resonance coplanar with XO-1b. We identify and correct for poorly understood gain-like variations present in NICMOS time series data. This correction reduces the effective noise in time series photometry by a factor of two, for the case of XO-1.Comment: 13 pages, 8 figures, submitted to Ap

Precise Estimates of the Physical Parameters for the Exoplanet System HD-17156 Enabled by HST FGS Transit and Asteroseismic Observations

We present observations of three distinct transits of HD 17156b obtained with the Fine Guidance Sensors (FGS) on board the Hubble Space Telescope} (HST). We analyzed both the transit photometry and previously published radial velocities to find the planet-star radius ratio R_p/R_s = 0.07454 +/- 0.00035, inclination i=86.49 +0.24/-0.20 deg, and scaled semi-major axis a/R = 23.19 +0.32/-0.27. This last value translates directly to a mean stellar density determination of 0.522 +0.021/-0.018 g cm^-3. Analysis of asteroseismology observations by the companion paper of Gilliland et al. (2009) provides a consistent but significantly refined measurement of the stellar mean density. We compare stellar isochrones to this density estimate and find M_s = 1.275 +/- 0.018 M_sun and a stellar age of $3.37 +0.20/-0.47 Gyr. Using this estimate of M_s and incorporating the density constraint from asteroseismology, we model both the photometry and published radial velocities to estimate the planet radius R_p= 1.0870 +/- 0.0066 Jupiter radii and the stellar radius R_s = 1.5007 +/- 0.0076 R_sun. The planet radius is larger than that found in previous studies and consistent with theoretical models of a solar-composition gas giant of the same mass and equilibrium temperature. For the three transits, we determine the times of mid-transit to a precision of 6.2 s, 7.6 s, and 6.9 s, and the transit times for HD 17156 do not show any significant departures from a constant period. The joint analysis of transit photometry and asteroseismology presages similar studies that will be enabled by the NASA Kepler Mission.Comment: Accepted for publication to Ap

The Transit Ingress and the Tilted Orbit of the Extraordinarily Eccentric Exoplanet HD 80606b

We present the results of a transcontinental campaign to observe the 2009 June 5 transit of the exoplanet HD 80606b. We report the first detection of the transit ingress, revealing the transit duration to be 11.64 +/- 0.25 hr and allowing more robust determinations of the system parameters. Keck spectra obtained at midtransit exhibit an anomalous blueshift, giving definitive evidence that the stellar spin axis and planetary orbital axis are misaligned. The Keck data show that the projected spin-orbit angle is between 32-87 deg with 68.3% confidence and between 14-142 deg with 99.73% confidence. Thus the orbit of this planet is not only highly eccentric (e=0.93), but is also tilted away from the equatorial plane of its parent star. A large tilt had been predicted, based on the idea that the planet's eccentric orbit was caused by the Kozai mechanism. Independently of the theory, it is noteworthy that all 3 exoplanetary systems with known spin-orbit misalignments have massive planets on eccentric orbits, suggesting that those systems migrate differently than lower-mass planets on circular orbits.Comment: ApJ, in press [13 pg

Validation of Kepler's Multiple Planet Candidates. III: Light Curve Analysis & Announcement of Hundreds of New Multi-planet Systems

The Kepler mission has discovered over 2500 exoplanet candidates in the first two years of spacecraft data, with approximately 40% of them in candidate multi-planet systems. The high rate of multiplicity combined with the low rate of identified false-positives indicates that the multiplanet systems contain very few false-positive signals due to other systems not gravitationally bound to the target star (Lissauer, J. J., et al., 2012, ApJ 750, 131). False positives in the multi- planet systems are identified and removed, leaving behind a residual population of candidate multi-planet transiting systems expected to have a false-positive rate less than 1%. We present a sample of 340 planetary systems that contain 851 planets that are validated to substantially better than the 99% confidence level; the vast majority of these have not been previously verified as planets. We expect ~2 unidentified false-positives making our sample of planet very reliable. We present fundamental planetary properties of our sample based on a comprehensive analysis of Kepler light curves and ground-based spectroscopy and high-resolution imaging. Since we do not require spectroscopy or high-resolution imaging for validation, some of our derived parameters for a planetary system may be systematically incorrect due to dilution from light due to additional stars in the photometric aperture. None the less, our result nearly doubles the number of verified exoplanets.Comment: 138 pages, 8 Figures, 5 Tables. Accepted for publications in the Astrophysical Journa

Glaucoma in primates: cytochrome oxidase reactivity in parvo- and magnocellular

PURPOSE. To evaluate the differential effects of ganglion cell depletion from experimental glaucoma on the relative metabolic activities of neurons in the parvo (P)-and magno (M)-cellular visual pathways of the macaque visual system. METHODS. Monocular experimental glaucoma was induced in monkeys (Macaca mulatta and M. fascicularis) by applying a laser to the trabecular meshwork to increase intraocular pressure (IOP). After other behavioral and electrophysiological studies, the lateral geniculate nuclei (LGNs) and the primary visual cortices were analyzed for functional afference from surviving ganglion cells, indicated by cytochrome oxidase (CO) histochemistry. RESULTS. CO reactivity (COR) indicated a general reduction in neural metabolism with increasing severity of glaucoma. COR in the LGNs was reduced to the same degree in both the P-and M-cellular layers. In layer 4C␤ of the V1 cortex, the reactivity was always reduced more than in the layer 4C␣ division. CONCLUSIONS. Experimental glaucoma in monkeys reduces visual afference to the central nervous system, thereby reducing the metabolic drive as indicated by COR. The detrimental effect of glaucoma did not appear to be any greater for the M-cell, rather than the P-cell pathway in the LGN or in the visual cortex. Both are affected by the duration and severity of the experimental glaucoma. Overall, the alterations in metabolism of neurons in the parallel visual pathways supplied by the P␣ and P␤ ganglion cells do not suggest that tests based on the functional properties of one or the other would provide optimal assessment of glaucoma. (Invest Ophthalmol Vis Sci. 2000;41: 1791-180