Historical cohort study examining comparative effectiveness of albuterol inhalers with and without integrated dose counter for patients with asthma or chronic obstructive pulmonary disease

This study was supported financially by an unrestricted grant from Teva Pharmaceuticals, Frazer, PA, USA. The authors thank Jenny Fanstone of Fanstone Medical Communications Ltd., UK, and Elizabeth V Hillyer for medical writing support, funded by Research in Real-Life. We acknowledge with gratitude Dr Ruchir Parikh for his review of and contributions to the manuscript.Peer reviewedPublisher PD

Cosmological Luminosity Evolution of QSO/AGN Population

We apply the observed optical/X-ray spectral states of the Galactic black hole candidates (GBHCs) to the cosmological QSO luminosity evolution under the assumptions that QSOs and GBHCs are powered by similar accretion processes and that their emission mechanisms are also similar. The QSO luminosity function (LF) evolution in various energy bands is strongly affected by the spectral evolution which is tightly correlated with the luminosity evolution. We generate a random sample of QSOs born nearly synchronously by allowing the QSOs to have redshifts in a narrow range around an initial high redshift, black hole masses according to a power-law, and mass accretion rates near Eddington rates. The QSOs evolve as a single long-lived population on the cosmological time scale. The pure luminosity evolution results in distinct luminosity evolution features due to the strong spectral evolution. Most notably, different energy bands (optical/UV, soft X-ray, and hard X-ray) show different evolutionary trends and the hard X-ray LF in particular shows an apparent reversal of the luminosity evolution (from decreasing to increasing luminosity) at low redshifts, which is not seen in the conventional pure luminosity evolution scenario without spectral evolution. The resulting mass function of black holes (BHs), which is qualitatively consistent with the observed QSO LF evolution, shows that QSO remnants are likely to be found as BHs with masses in the range 10**8-5x10**10 solar masses. The long-lived single population of QSOs are expected to leave their remnants as supermassive BHs residing in rare, giant elliptical galaxies.Comment: 9 pages, 2 figures, ApJ

QSO's from Galaxy Collisions with Naked Black Holes

In the now well established conventional view (see Rees [1] and references therein), quasi-stellar objects (QSOs) and related active galactic nuclei (AGN) phenomena are explained as the result of accretion of plasma onto giant black holes which are postulated to form via gravitational collapse of the high density regions in the centers of massive host galaxies. This model is supported by a wide variety of indirect evidence and seems quite likely to apply at least to some observed AGN phenomena. However, one surprising set of new Hubble Space Telescope (HST) observations [2-4] directly challenges the conventional model, and the well known evolution of the QSO population raises some additional, though not widely recognized, difficulties. We propose here an alternative possibility: the Universe contains a substantial independent population of super-massive black holes, and QSO's are a phenomenon that occurs due to their collisions with galaxies or gas clouds in the intergalactic medium (IGM). This hypothesis would naturally explain why the QSO population declines very rapidly towards low redshift, as well as the new HST data.Comment: plain TeX file, no figures, submitted to Natur

The Fall of the Quasar Population

We derive quantitative predictions of the optical and X-ray luminosity functions (LF) for QSs in the redshift range $z<3$. Based on BH paradigm, we investigate how the accretion is controlled by the surrounding structures, as these grow hierarchically. We argue that for $z < 3$ efficient black hole fueling is triggered by the encounters of a gas-rich host with its companions in a group. The dispersion of the dynamical parameters in the encounters produces a double power-law LF. Strong luminosity evolution (LE) is produced as these encounters deplete the gas supply in the host; an additional, milder density evolution obtains since the interactions become progressively rarer as the groups grow richer but less dense. From the agreement with the optical and the X-ray data, we conclude that the evolution of the bright quasars is articulated in two ways. Earlier than $z~3$ the gas-rich protogalaxies grow by merging, which also induces parallel growth of central holes accreting at Eddington rates. In the later era of group assemblage the host encounters with companions drive onto already existing holes further but meager accretion; these consume the gas in the hosts, and cause supply-limited emissions which are intermittent, go progressively sub-Eddington and peter out. Then other fueling processes come to the foreground; we discuss the faint emissions, especially noticeable in X-rays, which are expected when hosts in the field cannibalize satellite galaxies with their meager gas contents.Comment: 12 pages Latex + 3 EPS figures, ApJ in press, we have corrected the previous printing problems with the style \ca

Comparative chromosome band mapping in primates byin situ suppression hybridization of band specific DNA microlibraries

A DNA-library established from microdissected bands 8q23 to 8q24.1 of normal human chromosomes 8 (Lüdecke et al., 1989) was used as a probe for chromosomal in situ suppression (CISS-) hybridization to metaphase chromosomes of man and primates including Hylobates lar and Macaca fuscata. Comparative band mapping as first applied in this study shows the specific visualization of a single subchromosomal region in all three species and thus demonstrates that synteny of the bulk sequences of a specific human chromosome subregion has been conserved for more than 20 million years

Rhythmic dynamics and synchronization via dimensionality reduction : application to human gait

Reliable characterization of locomotor dynamics of human walking is vital to understanding the neuromuscular control of human locomotion and disease diagnosis. However, the inherent oscillation and ubiquity of noise in such non-strictly periodic signals pose great challenges to current methodologies. To this end, we exploit the state-of-the-art technology in pattern recognition and, specifically, dimensionality reduction techniques, and propose to reconstruct and characterize the dynamics accurately on the cycle scale of the signal. This is achieved by deriving a low-dimensional representation of the cycles through global optimization, which effectively preserves the topology of the cycles that are embedded in a high-dimensional Euclidian space. Our approach demonstrates a clear advantage in capturing the intrinsic dynamics and probing the subtle synchronization patterns from uni/bivariate oscillatory signals over traditional methods. Application to human gait data for healthy subjects and diabetics reveals a significant difference in the dynamics of ankle movements and ankle-knee coordination, but not in knee movements. These results indicate that the impaired sensory feedback from the feet due to diabetes does not influence the knee movement in general, and that normal human walking is not critically dependent on the feedback from the peripheral nervous system

Hyperpolarized 13C-pyruvate MRI detects real-time metabolic flux in prostate cancer metastases to bone and liver: a clinical feasibility study.

BackgroundHyperpolarized (HP) 13C-pyruvate MRI is a stable-isotope molecular imaging modality that provides real-time assessment of the rate of metabolism through glycolytic pathways in human prostate cancer. Heretofore this imaging modality has been successfully utilized in prostate cancer only in localized disease. This pilot clinical study investigated the feasibility and imaging performance of HP 13C-pyruvate MR metabolic imaging in prostate cancer patients with metastases to the bone and/or viscera.MethodsSix patients who had metastatic castration-resistant prostate cancer were recruited. Carbon-13 MR examination were conducted on a clinical 3T MRI following injection of 250 mM hyperpolarized 13C-pyruvate, where pyruvate-to-lactate conversion rate (kPL) was calculated. Paired metastatic tumor biopsy was performed with histopathological and RNA-seq analyses.ResultsWe observed a high rate of glycolytic metabolism in prostate cancer metastases, with a mean kPL value of 0.020 ± 0.006 (s-1) and 0.026 ± 0.000 (s-1) in bone (N = 4) and liver (N = 2) metastases, respectively. Overall, high kPL showed concordance with biopsy-confirmed high-grade prostate cancer including neuroendocrine differentiation in one case. Interval decrease of kPL from 0.026 at baseline to 0.015 (s-1) was observed in a liver metastasis 2 months after the initiation of taxane plus platinum chemotherapy. RNA-seq found higher levels of the lactate dehydrogenase isoform A (Ldha,15.7 ± 0.7) expression relative to the dominant isoform of pyruvate dehydrogenase (Pdha1, 12.8 ± 0.9).ConclusionsHP 13C-pyruvate MRI can detect real-time glycolytic metabolism within prostate cancer metastases, and can measure changes in quantitative kPL values following treatment response at early time points. This first feasibility study supports future clinical studies of HP 13C-pyruvate MRI in the setting of advanced prostate cancer