Patients' perspectives on how idiopathic pulmonary fibrosis affects the quality of their lives

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a debilitating lung disease with a survival of only three to five years from the time of diagnosis. Due to a paucity of studies, large gaps remain in our understanding of how IPF affects the quality of patients' lives. In only one other study did investigators ask patients directly for their perspectives on this topic. Further, currently there is no disease-specific instrument to measure health-related quality of life (HRQL) in patients with IPF. A carefully constructed measurement instrument, sensitive to underlying change, is needed for use in clinical trials and longitudinal studies of patients with IPF. Before developing such an instrument, researchers must improve their understanding of the relevant effects of IPF on patients' lives. On a broader scale, to provide the best care for people with IPF, clinicians must appreciate – from patients' perspectives – how this disease affects various aspects of their lives. METHODS: We used focus groups and individual in-depth interviews with 20 IPF patients to collect their perspectives on how IPF affects their lives (with a focus on the quality of their lives). We then analyzed these perspectives and organized them into a conceptual framework for describing HRQL in patients with IPF. Next, we examined how well certain existing measurement instruments – which have been administered to IPF patients in prior studies – covered the domains and topics our patients identified. RESULTS: In our framework, we identified 12 primary domains: symptoms, IPF therapy, sleep, exhaustion, forethought, employment and finances, dependence, family, sexual relations, social participation, mental and spiritual well-being, mortality. Each domain is composed of several topics, which describe how IPF affects patients' lives. When we compared the content of our conceptual framework with the existing instruments, we found the coverage of the existing instruments to be inadequate for several reasons, including they may tap general areas of QOL or HRQL but not some areas that appear to be most directly affected by IPF, and they include items that are relevant to symptoms and effects of other respiratory diseases but not IPF. CONCLUSION: Collecting patients' perspectives and developing an organized inventory of the relevant effects of IPF on patients' lives provides valuable information for improving our understanding of the impact of this disease on patients and their loved ones. We believe our findings will help alert clinicians and researchers to IPF patients' experiences and concerns. Based on the comparison or our conceptual framework with the content of four existing instruments, it would appear that developing an IPF-specific measurement instrument is justified. Our conceptual framework for describing health-related quality of life in patients with IPF lays a solid foundation for constructing such an instrument

Does probiotic consumption reduce antibiotic utilization for common acute infections? A systematic review and meta-analysis.

BackgroundOverall reduction of antibiotic use is a widely adopted public health goal. Given evidence that consuming probiotics reduce the incidence, duration and/or severity of certain types of common acute infections, we hypothesized that probiotics are associated with reduced antibiotic use. This systematic review of randomized controlled trials (RCTs) assessed the impact of probiotic supplementation (any strain, dose or duration), compared to placebo, on antibiotic utilization for common, acute infections in otherwise healthy people of all ages.MethodsWe searched 13 electronic databases including MEDLINE, Embase and CENTRAL from inception to 17th January 2017. Backward and forward citation searches were also conducted. Two reviewers independently selected studies for inclusion and extracted study data. We assessed risk of bias for individual studies using criteria adapted from the Centre for Reviews and Dissemination, and the quality of evidence for each outcome was assessed using the GRADE system. Studies that evaluated similar outcomes were pooled statistically in meta-analyses using a random-effects model.ResultsWe screened 1533 citations, and of these, 17 RCTs met our predefined inclusion criteria. All 17 were conducted in infants and/or children with a primary aim of preventing acute respiratory tract infections, acute lower digestive tract infections or acute otitis media. Included studies used 13 probiotic formulations, all comprising single or combination Lactobacillus and Bifidobacterium delivered in a range of food or supplement products. Mean duration of probiotic supplementation ranged from 4 days to 9 months. Trial quality was variable. Meta-analysis demonstrated that infants and children who received probiotics to prevent acute illnesses had a lower risk of being prescribed antibiotics, relative to those who received placebo (Pooled Relative Risk = 0.71, 95% CI: 0.54-0.94). When restricted to five studies with a low risk of bias, the pooled relative risk was 0.46 (95% CI: 0.23-0.97). Significant statistical heterogeneity was present in effect size estimates, which appeared to be due to one trial which could partly be considered as an outlier.ConclusionsProbiotics, provided to reduce the risk for common acute infections, may be associated with reduced antibiotic use in infants and children. Additional well-designed studies are needed to substantiate these findings in children and explore similar findings in other population groups

The Absolute Magnitude of RRc Variables From Statistical Parallax

We present the first definitive measurement of the absolute magnitude of RR Lyrae c-type variable stars (RRc) determined purely from statistical parallax. We use a sample of 247 RRc selected from the All Sky Automated Survey (ASAS) for which high-quality light curves, photometry and proper motions are available. We obtain high-resolution echelle spectra for these objects to determine radial velocities and abundances as part of the Carnegie RR Lyrae Survey (CARRS). We find that M_(V,RRc) = 0.52 +/- 0.11 at a mean metallicity of [Fe/H] = -1.59. This is to be compared with previous estimates for RRab stars (M_(V,RRab) = 0.75 +/- 0.13 and the only direct measurement of an RRc absolute magnitude (RZ Cephei, M_(V, RRc) = 0.27 +/- 0.17). We find the bulk velocity of the halo to be (W_pi, W_theta, W_z) = (10.9,34.9,7.2) km/s in the radial, rotational and vertical directions with dispersions (sigma_(W_pi), sigma_(W_theta), sigma_(W_z)) = (154.7, 103.6, 93.8) km/s. For the disk, we find (W_pi, W_theta, W_z) = (8.5, 213.2, -22.1) km/s with dispersions (sigma_(W_pi), sigma_(W_theta), sigma_(W_z)) = (63.5, 49.6, 51.3) km/s. Finally, we suggest that UCAC2 proper motion errors may be overestimated by about 25%Comment: Submitted to ApJ. 11 pages including 6 figure

Transcript Profiling of Elf5+/− Mammary Glands during Pregnancy Identifies Novel Targets of Elf5

Background: Elf5, an epithelial specific Ets transcription factor, plays a crucial role in the pregnancy-associated development of the mouse mammary gland. Elf5 2/2 embryos do not survive, however the Elf5 +/2 mammary gland displays a severe pregnancy-associated developmental defect. While it is known that Elf5 is crucial for correct mammary development and lactation, the molecular mechanisms employed by Elf5 to exert its effects on the mammary gland are largely unknown. Principal Findings: Transcript profiling was used to investigate the transcriptional changes that occur as a result of Elf5 haploinsufficiency in the Elf5 +/2 mouse model. We show that the development of the mouse Elf5 +/2 mammary gland is delayed at a transcriptional and morphological level, due to the delayed increase in Elf5 protein in these glands. We also identify a number of potential Elf5 target genes, including Mucin 4, whose expression, is directly regulated by the binding of Elf5 to an Ets binding site within its promoter. Conclusion: We identify novel transcriptional targets of Elf5 and show that Muc4 is a direct target of Elf5, further elucidatin

Kepler Mission Stellar and Instrument Noise Properties

Kepler Mission results are rapidly contributing to fundamentally new discoveries in both the exoplanet and asteroseismology fields. The data returned from Kepler are unique in terms of the number of stars observed, precision of photometry for time series observations, and the temporal extent of high duty cycle observations. As the first mission to provide extensive time series measurements on thousands of stars over months to years at a level hitherto possible only for the Sun, the results from Kepler will vastly increase our knowledge of stellar variability for quiet solar-type stars. Here we report on the stellar noise inferred on the timescale of a few hours of most interest for detection of exoplanets via transits. By design the data from moderately bright Kepler stars are expected to have roughly comparable levels of noise intrinsic to the stars and arising from a combination of fundamental limitations such as Poisson statistics and any instrument noise. The noise levels attained by Kepler on-orbit exceed by some 50% the target levels for solar-type, quiet stars. We provide a decomposition of observed noise for an ensemble of 12th magnitude stars arising from fundamental terms (Poisson and readout noise), added noise due to the instrument and that intrinsic to the stars. The largest factor in the modestly higher than anticipated noise follows from intrinsic stellar noise. We show that using stellar parameters from galactic stellar synthesis models, and projections to stellar rotation, activity and hence noise levels reproduces the primary intrinsic stellar noise features.Comment: Accepted by ApJ; 26 pages, 20 figure

Weak Lensing with SDSS Commissioning Data: The Galaxy-Mass Correlation Function To 1/h Mpc

(abridged) We present measurements of galaxy-galaxy lensing from early commissioning imaging data from the Sloan Digital Sky Survey (SDSS). We measure a mean tangential shear around a stacked sample of foreground galaxies in three bandpasses out to angular radii of 600'', detecting the shear signal at very high statistical significance. The shear profile is well described by a power-law. A variety of rigorous tests demonstrate the reality of the gravitational lensing signal and confirm the uncertainty estimates. We interpret our results by modeling the mass distributions of the foreground galaxies as approximately isothermal spheres characterized by a velocity dispersion and a truncation radius. The velocity dispersion is constrained to be 150-190 km/s at 95% confidence (145-195 km/s including systematic uncertainties), consistent with previous determinations but with smaller error bars. Our detection of shear at large angular radii sets a 95% confidence lower limit $s>140^{\prime\prime}$, corresponding to a physical radius of $260h^{-1}$ kpc, implying that galaxy halos extend to very large radii. However, it is likely that this is being biased high by diffuse matter in the halos of groups and clusters. We also present a preliminary determination of the galaxy-mass correlation function finding a correlation length similar to the galaxy autocorrelation function and consistency with a low matter density universe with modest bias. The full SDSS will cover an area 44 times larger and provide spectroscopic redshifts for the foreground galaxies, making it possible to greatly improve the precision of these constraints, measure additional parameters such as halo shape, and measure the properties of dark matter halos separately for many different classes of galaxies.Comment: 28 pages, 11 figures, submitted to A

Fashionably Late? Building up the Milky Way's Inner Halo

Using a sample of 248 metal-poor stars (RR Lyraes, red giants and RHB stars) which is remarkable for the accuracy of its 6-D kinematical data, we find a new component for the local halo which has an axial ratio c/a ~ 0.2, a similar flattening to the thick disk. It has a small prograde rotation but is supported by velocity anisotropy, and contains more intermediate-metallicity stars (with -1.5 < [Fe/H] < -1.0) than the rest of our sample. We suggest that this component was formed quite late, during or after the formation of the disk. It formed either from the gas that was accreted by the last major mergers experienced by the Galaxy, or by dynamical friction of massive infalling satellite(s) with the halo and possibly the stellar disk or thick disk. The remainder of the stars in our sample exhibit a clumpy distribution in energy and angular momentum, suggesting that the early, chaotic conditions under which the inner halo formed were not violent enough to erase the record of their origins. The clumpy structure suggests that a relatively small number of progenitors were responsible for building up the inner halo, in line with theoretical expectations. We find a difference in mean binding energy between the RR Lyrae variables and the red giants in our sample, suggesting that more of the RR Lyraes in the sample belong to the outer halo, and that the outer halo may be somewhat younger, as first suggested by Searle and Zinn (1978). We also find that the RR Lyrae mean rotation is more negative than the red giants, which is consistent with the recent result of Carollo et al.(2007) that the outer halo has a retrograde rotation and with the difference in kinematics seen between RR Lyraes and BHB stars by Kinman et al.(2007).Comment: 16 pages, 10 figures, this version accepted by Ap

Advection-Dominated Accretion and the Spectral States of Black Hole X-Ray Binaries: Application to Nova Muscae 1991

We present a self-consistent model of accretion flows which unifies four distinct spectral states observed in black hole X-ray binaries: quiescent, low, intermediate and high states. In the quiescent, low and intermediate states, the flow consists of an inner hot advection-dominated part extending from the black hole horizon to a transition radius and an outer thin disk. In the high state the thin disk is present at all radii. The model is essentially parameter-free and treats consistently the dynamics of the accretion flow, the thermal balance of the ions and electrons, and the radiation processes in the accreting gas. With increasing mass accretion rate, the model goes through a sequence of stages for which the computed spectra resemble very well observations of the four spectral states; in particular, the low-to-high state transition observed in black hole binaries is naturally explained as resulting from a decrease in the transition radius. We also make a tentative proposal for the very high state, but this aspect of the model is less secure. We test the model against observations of the soft X-ray transient Nova Muscae during its 1991 outburst. The model reproduces the observed lightcurves and spectra surprisingly well, and makes a number of predictions which can be tested with future observations.Comment: 68 pages, LaTeX, includes 1 table (forgotten in the previous version) and 14 figures; submitted to The Astrophysical Journa

The Type Ia Supernova Rate in Redshift 0.5--0.9 Galaxy Clusters

Supernova (SN) rates are potentially powerful diagnostics of metal enrichment and SN physics, particularly in galaxy clusters with their deep, metal-retaining potentials and relatively simple star-formation histories. We have carried out a survey for supernovae (SNe) in galaxy clusters, at a redshift range 0.5<z<0.9, using the Advanced Camera for Surveys (ACS) on the Hubble Space Telescope. We reimaged a sample of 15 clusters that were previously imaged by ACS, thus obtaining two to three epochs per cluster, in which we discovered five likely cluster SNe, six possible cluster SNe Ia, two hostless SN candidates, and several background and foreground events. Keck spectra of the host galaxies were obtained to establish cluster membership. We conducted detailed efficiency simulations, and measured the stellar luminosities of the clusters using Subaru images. We derive a cluster SN rate of 0.35 SNuB +0.17/-0.12 (statistical) \pm0.13 (classification) \pm0.01 (systematic) [where SNuB = SNe (100 yr 10^10 L_B_sun)^-1] and 0.112 SNuM +0.055/-0.039 (statistical) \pm0.042 (classification) \pm0.005 (systematic) [where SNuM = SNe (100 yr 10^10 M_sun)^-1]. As in previous measurements of cluster SN rates, the uncertainties are dominated by small-number statistics. The SN rate in this redshift bin is consistent with the SN rate in clusters at lower redshifts (to within the uncertainties), and shows that there is, at most, only a slight increase of cluster SN rate with increasing redshift. The low and fairly constant SN Ia rate out to z~1 implies that the bulk of the iron mass in clusters was already in place by z~1. The recently observed doubling of iron abundances in the intracluster medium between z=1 and 0, if real, is likely the result of redistribution of existing iron, rather than new production of iron.Comment: Accepted to ApJ. Full resolution version available at http://kicp.uchicago.edu/~kerens/HSTclusterSNe

Planet Occurrence within 0.25 AU of Solar-type Stars from Kepler

We report the distribution of planets as a function of planet radius (R_p), orbital period (P), and stellar effective temperature (Teff) for P < 50 day orbits around GK stars. These results are based on the 1,235 planets (formally "planet candidates") from the Kepler mission that include a nearly complete set of detected planets as small as 2 Earth radii (Re). For each of the 156,000 target stars we assess the detectability of planets as a function of R_p and P. We also correct for the geometric probability of transit, R*/a. We consider first stars within the "solar subset" having Teff = 4100-6100 K, logg = 4.0-4.9, and Kepler magnitude Kp < 15 mag. We include only those stars having noise low enough to permit detection of planets down to 2 Re. We count planets in small domains of R_p and P and divide by the included target stars to calculate planet occurrence in each domain. Occurrence of planets varies by more than three orders of magnitude and increases substantially down to the smallest radius (2 Re) and out to the longest orbital period (50 days, ~0.25 AU) in our study. For P < 50 days, the radius distribution is given by a power law, df/dlogR= k R^\alpha. This rapid increase in planet occurrence with decreasing planet size agrees with core-accretion, but disagrees with population synthesis models. We fit occurrence as a function of P to a power law model with an exponential cutoff below a critical period P_0. For smaller planets, P_0 has larger values, suggesting that the "parking distance" for migrating planets moves outward with decreasing planet size. We also measured planet occurrence over Teff = 3600-7100 K, spanning M0 to F2 dwarfs. The occurrence of 2-4 Re planets in the Kepler field increases with decreasing Teff, making these small planets seven times more abundant around cool stars than the hottest stars in our sample. [abridged]Comment: Submitted to ApJ, 22 pages, 10 figure