Comparison of osteoporosis pharmacotherapy fracture rates: Analysis of a marketScan® claims database cohort

Background: Several different classes of medications have been shown to be efficacious at preventing fractures in patients with osteoporosis. No study has compared real world efficacy at preventing fractures between all currently approved medications. Objectives: To directly compare the efficacy of all currently available osteoporosis medications by using a large population claims database. Methods: The Truven Health Analytics MarketScan® database from 2008 - 2012 was used to identify all patients who started a new osteoporosis medication. Patients who experienced a fracture after at least 12 months of treatment were identified and risk factors for fracture for all patients were recorded. Logistic regression was used to account for and quantify the contribution of risk factors, and to make direct comparisons between different osteoporosis medications. Results: A total of 51649 patients were included in the cohort, with an average age of 56 years. The overall incidence rate of fracture was 1.55 per 100 person - years of treatment. Orally administered medications had the lowest fracture rates, led by raloxifene and alendronate (1.24 and 1.54 respectively), while parenterally administered medications including teriparatide and zolerdonic acid had the highest rates (3.90 and 1.98 respectively). No statistically significant differences found between oral or parenterally administered bisphosphonate medications. Conclusions: While patients taking orally administered drugs including bisphosphonates had less frequent incident fracture no statistically significant differences were found between most drugs in head - to - head comparisons, even considering the route of administration of bisphosphonates. These findings support previous evidence that minimal differences in efficacy exist between different osteoporosis medications. This is the first study using a large database to compare all currently available osteoporosis treatments and will hopefully be augmented by further study to provide more evidence to make clinical decisions on osteoporosis medication use. © 2017 American Association of Neuropathologists, Inc

Improved gene delivery to human saphenous vein cells and tissue using a peptide-modified adenoviral vector

The establishment of efficient gene delivery to target human tissue is a major obstacle for transition of gene therapy from the pre-clinical phases to the clinic. The poor long-term patency rates for coronary artery bypass grafting (CABG) is a major clinical problem that lacks an effective and proven pharmacological intervention. Late vein graft failure occurs due to neointima formation and accelerated atherosclerosis. Since CABG allows a clinical window of opportunity to genetically modify vein ex vivo prior to grafting it represents an ideal opportunity to develop gene-based therapies. Adenoviral vectors have been frequently used for gene delivery to vein ex vivo and pre-clinical studies have shown effective blockade in neointima development by overexpression of candidate therapeutic genes. However, high titers of adenovirus are required to achieve sufficient gene delivery to provide therapeutic benefit. Improvement in the uptake of adenovirus into the vessel wall would therefore be of benefit. Here we determined the ability of an adenovirus serotype 5 vector genetically-engineered with the RGD-4C integrin targeting peptide inserted into the HI loop (Ad-RGD) to improve the transduction of human saphenous vein smooth muscle cells (HSVSMC), endothelial cells (HSVEC) and intact saphenous vein compared to a non-modified virus (Ad-CTL). We exposed each cell type to virus for 10, 30 or 60 mins and measured transgene at 24 h post infection. For both HSVSMC and HSVEC Ad-RGD mediated increased transduction, with the largest increases observed in HSVSMC. When the experiments were repeated with intact human saphenous vein (the ultimate clinical target for gene therapy), again Ad-RGD mediated higher levels of transduction, at all clinically relevant exposures times (10, 30 and 60 mins tissue:virus exposure). Our study demonstrates the ability of peptide-modified Ad vectors to improve transduction to human vein graft cells and tissue and has important implications for gene therapy for CABG

Differences Between The Optical/Uv Spectra Of X-Ray Bright And X-Ray Faint QSOs

We contrast measurements of composite optical and ultraviolet (UV) spectra constructed from samples of QSOs defined by their soft X-ray brightness. X-ray bright (XB) composites show stronger emission lines in general, but particularly from the narrow line region. The difference in the [OIII]/Hbeta ratio is particularly striking, and even more so when blended FeII emission is properly subtracted. The correlation of this ratio with X-ray brightness were principal components of QSO spectral diversity found by Boroson & Green (1992). We find here that other, much weaker narrow optical forbidden lines ([OII] and NeV) are enhanced by factors of 2 to 3 in our XB composites, and that narrow line emission is also strongly enhanced in the XB UV composite. Broad permitted line fluxes are slightly larger for all XB spectra, but the narrow/broad line ratio stays similar or increases strongly with X-ray brightness for all strong permitted lines except Hbeta. Spectral differences between samples divided by their relative X-ray brightness (as measured by alpha_{ox}) exceed those seen between complementary samples divided by luminosity or radio loudness. We propose that the Baldwin effect may be a secondary correlation to the primary relationship between alpha_{ox} and emission line equivalent width. We conclude that either 1) equivalent width depends strongly on the SHAPE of the ionizing continuum, as crudely characterized here by alpha_{ox} or 2) both equivalent width and alpha_{ox} are related to some third parameter characterizing the QSO physics. One such possibility is intrinsic warm absorption; a soft X-ray absorber situated between the broad and narrow line regions can successfully account for many of the properties observed.Comment: 16 pages including 3 figures, AAS latex, plus 4 tables totaling 5 pages, to appear in ApJ Vol. 498, May 1, 199

Differences in night-time and daytime ambulatory blood pressure when diurnal periods are defined by self-report, fixed-times, and actigraphy: Improving the Detection of Hypertension study

To determine whether defining diurnal periods by self-report, fixed-time or actigraphy produce different estimates of nighttime and daytime ambulatory blood pressure (ABP)

Label-free segmentation of co-cultured cells on a nanotopographical gradient

The function and fate of cells is influenced by many different factors, one of which is surface topography of the support culture substrate. Systematic studies of nanotopography and cell response have typically been limited to single cell types and a small set of topographical variations. Here, we show a radical expansion of experimental throughput using automated detection, measurement, and classification of co-cultured cells on a nanopillar array where feature height changes continuously from planar to 250 nm over 9 mm. Individual cells are identified and characterized by more than 200 descriptors, which are used to construct a set of rules for label-free segmentation into individual cell types. Using this approach we can achieve label-free segmentation with 84% confidence across large image data sets and suggest optimized surface parameters for nanostructuring of implant devices such as vascular stents

Oral Delivery of Nisin in Resistant Starch Based Matrices Alters the Gut Microbiota in Mice

peer-reviewedThere is a growing recognition of the role the gastrointestinal microbiota plays in health and disease. Ingested antimicrobial proteins and peptides have the potential to alter the gastrointestinal microbiota; particularly if protected from digestion. Nisin is an antimicrobial peptide that is used as a food preservative. This study examined the ability of nisin to affect the murine microbiota when fed to mice in two different starch based matrices; a starch dough comprising raw starch granules and a starch gel comprising starch that was gelatinized and retrograded. The effects of the two starch matrices by themselves on the microbiota were also examined. Following 16S rRNA compositional sequencing, beta diversity analysis highlighted a significant difference (p = 0.001, n = 10) in the murine microbiota between the four diet groups. The differences between the two nisin containing diets were mainly attributable to differences in the nisin release from the starch matrices while the differences between the carriers were mainly attributable to the type of resistant starch they possessed. Indeed, the differences in the relative abundance of several genera in the mice consuming the starch dough and starch gel diets, in particular Akkermansia, the relative abundance of which was 0.5 and 11.9%, respectively (p = 0.0002, n = 10), points to the potential value of resistance starch as a modulator of beneficial gut microbes. Intact nisin and nisin digestion products (in particular nisin fragment 22–31) were detected in the feces and the nisin was biologically active. However, despite a three-fold greater consumption of nisin in the group fed the nisin in starch dough diet, twice as much nisin was detected in the feces of the group which consumed the nisin in starch gel diet. In addition, the relative abundance of three times as many genera from the lower gastrointestinal tract (GIT) were significantly different (p < 0.001, n = 10) to the control for the group fed the nisin in starch gel diet, implying that the starch gel afforded a degree of protection from digestion to the nisin entrapped within it

Radio source calibration for the VSA and other CMB instruments at around 30 GHz

Accurate calibration of data is essential for the current generation of CMB experiments. Using data from the Very Small Array (VSA), we describe procedures which will lead to an accuracy of 1 percent or better for experiments such as the VSA and CBI. Particular attention is paid to the stability of the receiver systems, the quality of the site and frequent observations of reference sources. At 30 GHz the careful correction for atmospheric emission and absorption is shown to be essential for achieving 1 percent precision. The sources for which a 1 percent relative flux density calibration was achieved included Cas A, Cyg A, Tau A and NGC7027 and the planets Venus, Jupiter and Saturn. A flux density, or brightness temperature in the case of the planets, was derived at 33 GHz relative to Jupiter which was adopted as the fundamental calibrator. A spectral index at ~30 GHz is given for each. Cas A,Tau A, NGC7027 and Venus were examined for variability. Cas A was found to be decreasing at $0.394 \pm 0.019$ percent per year over the period March 2001 to August 2004. In the same period Tau A was decreasing at $0.22\pm 0.07$ percent per year. A survey of the published data showed that the planetary nebula NGC7027 decreased at $0.16\pm 0.04$ percent per year over the period 1967 to 2003. Venus showed an insignificant ($1.5 \pm 1.3$ percent) variation with Venusian illumination. The integrated polarization of Tau A at 33 GHz was found to be $7.8\pm 0.6$ percent at pa $= 148^\circ \pm 3^\circ$.}Comment: 13 pages, 15 figures, submitted to MNRA

The Lifetime of FRIIs in Groups and Clusters: Implications for Radio-Mode Feedback

We determine the maximum lifetime t_max of 52 FRII radio sources found in 26 central group galaxies from cross correlation of the Berlind SDSS group catalog with the VLA FIRST survey. Mock catalogs of FRII sources were produced to match the selection criteria of FIRST and the redshift distribution of our parent sample, while an analytical model was used to calculate source sizes and luminosities. The maximum lifetime of FRII sources was then determined via a comparison of the observed and model projected length distributions. We estimate the average FRII lifetime is 1.5x10^7 years and the duty cycle is ~8x10^8 years. Degeneracies between t_max and the model parameters: jet power distribution, axial ratio, energy injection index, and ambient density introduce at most a factor of two uncertainty in our lifetime estimate. In addition, we calculate the radio active galactic nuclei (AGN) fraction in central group galaxies as a function of several group and host galaxy properties. The lifetime of radio sources recorded here is consistent with the quasar lifetime, even though these FRIIs have substantially sub-Eddington accretion. These results suggest a fiducial time frame for energy injection from AGN in feedback models. If the morphology of a given extended radio source is set by large-scale environment, while the lifetime is determined by the details of the accretion physics, this FRII lifetime is relevant for all extended radio sources.Comment: 18 pages, 7 figures. Accepted for publication in ApJ. High resolution paper available at http://www.astronomy.ohio-state.edu/~bird/BMK07.pd

Flaring Behavior of the Quasar 3C~454.3 across the Electromagnetic Spectrum

We analyze the behavior of the parsec-scale jet of the quasar 3C~454.3 during pronounced flaring activity in 2005-2008. Three major disturbances propagated down the jet along different trajectories with Lorentz factors $\Gamma>$10. The disturbances show a clear connection with millimeter-wave outbursts, in 2005 May/June, 2007 July, and 2007 December. High-amplitude optical events in the $R$-band light curve precede peaks of the millimeter-wave outbursts by 15-50 days. Each optical outburst is accompanied by an increase in X-ray activity. We associate the optical outbursts with propagation of the superluminal knots and derive the location of sites of energy dissipation in the form of radiation. The most prominent and long-lasting of these, in 2005 May, occurred closer to the black hole, while the outbursts with a shorter duration in 2005 Autumn and in 2007 might be connected with the passage of a disturbance through the millimeter-wave core of the jet. The optical outbursts, which coincide with the passage of superluminal radio knots through the core, are accompanied by systematic rotation of the position angle of optical linear polarization. Such rotation appears to be a common feature during the early stages of flares in blazars. We find correlations between optical variations and those at X-ray and $\gamma$-ray energies. We conclude that the emergence of a superluminal knot from the core yields a series of optical and high-energy outbursts, and that the mm-wave core lies at the end of the jet's acceleration and collimation zone.Comment: 57 pages, 23 figures, 8 tables (submitted to ApJ