Loss of treatment benefit due to low compliance with bisphosphonate therapy

Among 8,822 new female bisphosphonate users, non-compliant bisphosphonate use was associated with a 45% increased risk of osteoporotic fracture compared to compliant use (MPR ≥80%). Classifying compliance into five categories, fracture risk gradually increased with poorer compliance. These results emphasize the importance of treatment compliance in obtaining maximal treatment benefit. Introduction: Bisphosphonates are widely used to treat osteoporosis and reduce fracture risk. Low compliance is frequent and will limit treatment benefit. Methods: New female users of alendronate or risedronate between 1999-2004, aged ≥45 years were identified from PHARMO-RLS, including drug-dispensing and hospitalization data of ≥2 million residents of the Netherlands. Patients were followed until first hospitalisation for an osteoporotic fracture, death, or end of study period. Compliance with bisphosphonates during follow-up was measured over 90-day intervals using Medication Possession Ratio (MPR). The association between compliance and fracture risk was analyzed using time-dependent Cox-regression. Results: The study cohort included 8,822 new female bisphosphonate users, contributing in total 22,484 person-years of follow-up. During follow-up, 176 osteoporotic fractures occurred (excluding the first six months). Non-compliant bisphosphonate use was associated with a 45% increased fracture risk compared to compliant use (MPR ≥80%). Classifying compliance into five categories, fracture risk gradually increased with poorer compliance (p-value <0.05 for trend). A MPR <20% was associated with an 80% increased fracture risk compared to a MPR ≥90%. Conclusions: These results show a statistically significant association between level of compliance with bisphosphonates and level of fracture risk, emphasizing the importance of treatment compliance in obtaining maximal treatment benefit

Analytic frameworks for assessing dialogic argumentation in online learning environments

Over the last decade, researchers have developed sophisticated online learning environments to support students engaging in argumentation. This review first considers the range of functionalities incorporated within these online environments. The review then presents five categories of analytic frameworks focusing on (1) formal argumentation structure, (2) normative quality, (3) nature and function of contributions within the dialog, (4) epistemic nature of reasoning, and (5) patterns and trajectories of participant interaction. Example analytic frameworks from each category are presented in detail rich enough to illustrate their nature and structure. This rich detail is intended to facilitate researchers’ identification of possible frameworks to draw upon in developing or adopting analytic methods for their own work. Each framework is applied to a shared segment of student dialog to facilitate this illustration and comparison process. Synthetic discussions of each category consider the frameworks in light of the underlying theoretical perspectives on argumentation, pedagogical goals, and online environmental structures. Ultimately the review underscores the diversity of perspectives represented in this research, the importance of clearly specifying theoretical and environmental commitments throughout the process of developing or adopting an analytic framework, and the role of analytic frameworks in the future development of online learning environments for argumentation

Behavioural and physiological consequences of acute social defeat in growing gilts: effects of the social environment

Endocrine, behavioural and immunologic processes, together with body growth, were evaluated in gilts that were defeated at 10 weeks of age in resident-intruder tests. Immediately after defeat, gilts were either separated from or reunited with a familiar conspecific (litter-mate; always a barrow). Gilts were assigned to one of four treatments: (a) DI: defeat, followed by isolation (separation from original litter-mate; n=8); (b) I: no defeat, isolation (control group; n=9); (c) DP; defeat, followed by pair-housing (reunion with original litter-mate; n=8); and (d) P: no defeat, pair-housing (control group; n=8). The following general conclusions were derived: (1) social defeat caused pronounced short-term elevations in hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal medullary activities, and of prolactin levels. Moreover, as soon as 1 h after defeat, percentages of blood lymphocytes and neutrophilic granulocytes were, respectively, decreased and increased; (2) social defeat had some long-lasting influence on behaviour and physiology, but isolation predominantly determined responses in the longer term. Defeat, as well as isolation, resulted in increased cardiovascular activities compared to P controls, as observed in a novel object test (NOT: +7 days) and an aversion test (AVT: +14 days). Moreover, defeated as well as isolated gilts did not habituate to a repeated novel environment test (NET: -7, +2 and +7 days) in terms of frequencies of vocalising, whereas P controls did. Isolation, through the separation from any other pig, was responsible for the other observed long-term characteristics, which developed progressively. Isolated gilts showed high mobilities and high cortisol responses in the repeated NET (+7 days), not being habituated. This contrasted the reactions of pair-housed gilts, which were much reduced. In addition to their high cardiovascular activities in the NOT and the AVT, isolated gilts also displayed higher heart rates in the repeated NET and during human presence following the NOT, compared to pair-housed gilts. Finally, isolated gilts were more inhibited to approach a novel object (in the NOT) than pair-housed pigs; and (3) stress responses of defeated gilts were modulated by the subsequent social environment. Stimulation of the HPA-axis (plasma- and salivary cortisol) was prolonged in those defeated gilts which were isolated (observed in the first hour). Changes in leucocyte subsets were still observed after 3 days in DI, but were `normalised' within 1 day in DP gilts. Two days after defeat, habituation to the repeated NET in terms of mobility and salivary cortisol responses occurred in control and DP gilts, but not in DI gilts. We argue that these effects of the social environment shortly after defeat were related to a stress-reducing effect of a stable social relationship, i.e. social support.

On the nature of Seyfert galaxies with high [OIII]5007 blueshifts

We have studied the properties of Seyfert galaxies with high [OIII]5007 blueshifts (`blue outliers'), originally identified because of their strong deviation from the M_BH - sigma relation of normal, narrow-line Seyfert 1 (NLS1) and broad-line Seyfert 1 (BLS1) galaxies. These blue outliers turn out to be important test-beds for models of the narrow-line region (NLR), for mechanisms of driving large-scale outflows, for links between NLS1 galaxies and radio galaxies, and for orientation-dependent NLS1 models. We report the detection of a strong correlation of line blueshift with ionization potential in each galaxy, including the measurement of coronal lines with radial velocities up to 500--1000 km/s. All [OIII] blue outliers have narrow widths of their broad Balmer lines and high Eddington ratios. While the presence of non-shifted low-ionization lines signifies the presence of a classical outer quiescent NLR in blue outliers, we also report the absence of any second, non-blueshifted [OIII] component from a classical inner NLR. These results place tight constraints on NLR models. We favor a scenario in which the NLR clouds are entrained in a decelerating wind which explains the strong stratification and the absence of a zero-blueshift inner NLR of blue outliers. The origin of the wind remains speculative at this time (collimated radio plasma, thermal winds, radiatively accelerated clouds). It is perhaps linked to the high Eddington ratios of blue outliers. Similar, less powerful winds could be present in all Seyfert galaxies, but would generally only affect the coronal line region (CLR), or level off even before reaching the CLR. Similarities between blue outliers in NLS1 galaxies and (compact) radio sources are briefly discussed.Comment: ApJ in press (scheduled for June 20 issue); incl. 4 colour figures. This, and related paper showing that NLS1 galaxies follow the M-sigma relation based on [SII], is also available at http://www.xray.mpe.mpg.de/~skomossa

Разработка технологии и проектирование участка сборки-сварки траверсы задней механизированной крепи МКЮ4У.56

Актуальность работы: в данной выпускной квалификационной работе производится проектирование участка сборки-сварки траверсы задней крепи механизированной МКЮ 4У.56. Объектом исследования является процесс изготовления траверсы. В результате данной работы следует получить производство с наибольшей степенью механизации и автоматизации повышающей производительность труда.Relevance of the work: in the final qualifying work is done tooling design and site assembly welding traverses back lining mechanized MKY 4U.56 As a result of this work should be obtained from producing the greatest degree of mechanization and automation increases productivity

Extended High-Ionization Nuclear Emission-Line Region in the Seyfert Galaxy NGC 4051

We present an optical spectroscopic analysis of the well-known Seyfert galaxy NGC 4051. The high-ionization nuclear emission-line region (HINER) traced by [Fe X]6374 is found to be spatially extended to a radius of 3a rcseconds (150 pc) west and southwest from the nucleus; NGC 4051 is the third example which has an extended HINER. The nuclear spectrum shows that the flux of [Fe X]6374 is stronger than that of [Fe VII] 6087 in our observation. This property cannot be interpreted in terms of a simple one-zone photoionization model. In order to understand what happens in the nuclear region in NGC 4051, we investigate the physical condition of the nuclear emission-line region in detail using new photoionization models in which the following three emission-line components are taken into account; (1) optically thick, ionization-bounded clouds; (2) optically thin, matter-bounded clouds; and (3) a contamination component which emits H$\alpha$ and H$\beta$ lines. Here the observed extended HINER is considered to be associated with the low-density, matter-bounded clouds. Candidates of the contamination component are either the broad-line region (BLR) or nuclear star forming regions or both. The complexity of the excitation condition found in NGC 4051 can be consistently understood if we take account of these contamination components.Comment: 16 pages, including figures. To Appear in the Astronomical Journal February 2000 Issu

Variability of Moderate Luminosity Active Galactic Nuclei at z=0.36

We monitored 13 moderate luminosity active galactic nuclei at z=0.36 to measure flux variability, explore feasibility of reverberation mapping, and determine uncertainties on estimating black hole mass from single-epoch data. Spectra and images were obtained with approximately weekly cadence for up to 4 months, using the KAST spectrograph on the 3-m Shane Telescope. In broad band we detect peak-to-peak variations of 9-37% and rms variations of 2-10%. The observed flux variability in the g' band (rest-frame 2800-4000\AA) is consistent with that in the r' band (rest-frame 4000-5200\AA), but with larger amplitude. However, after correcting for stellar light dilution, using Hubble Space Telescope images, we find nuclear variability of 3-24% (rms variation) with similar amplitudes in the g' and r' bands within the errors. Intrinsic flux variability of the H$\beta$ line is also detected at the 3-13% level, after accounting for systematic errors on the spectrophotometry. This demonstrates that a reverberation mapping campaign beyond the local universe can be carried out with a 3-m class telescope, provided that sufficiently long light curves are obtained. Finally, we compare the H$\beta$ FWHM measured from mean spectra with that measured from single-epoch data, and find no bias but an rms scatter of 14%, mostly accounted for by the uncertainty on FWHM measurements. The propagated uncertainty on black hole mass estimates, due to the FWHM measurement errors using low S/N (10--15 per pixel) single-epoch spectra, is 30%.Comment: 12 pages, 7 figures, accepted by Ap

Subaru High-Dispersion Spectroscopy of Narrow-Line Region in the Seyfert Galaxy NGC 4151

We report on a study of forbidden emission-line spectrum of nearby Seyfert 1.5 galaxy NGC 4151 based on the high-resolution (R ~ 45,000) optical spectrum obtained by using the High Dispersion Spectrograph boarded on the Subaru Telescope. The profile parameters such as the emission-line widths, the velocity shifts from the recession velocity of the host galaxy, and the asymmetry indices, for emission lines including very faint ones such as [Ar IV]4712,4740 and [Fe VI]5631,5677 are investigated. Statistically significant correlations between the measured profile parameters and the critical densities of transitions are found while there are no meaningful correlations between the profile parameters and the ionization potentials of ions. By comparing the results with photoionization model calculations, we remark that a simple power-law distribution of the gas density which is independent of the radius from the nucleus cannot explain the observed correlation between the emission-line widths and the critical densities of the transitions. Taking the additional dense gas component expected to exist at the innermost of the narrow-line region into account, the observed correlations between the emission-line width and the critical density of the transitions can be understood since high-critical-density emission lines can arise at such relatively inner regions even if their ionization potentials are low. The observed correlation between the blueshift amounts of emission lines and the critical densities of the ions is also explained if such dense gas clouds located closer to the nucleus have larger outflowing velocities.Comment: 19 pages and 1 separate jpeg figure. Accepted for publication in A

XMM-Newton observations of the Narrow-Line Seyfert 1 galaxy Mrk 335 in an historical low X-ray flux state

We report the discovery of strong soft X-ray emission lines and a hard continuum above 2 keV in the Narrow-Line Seyfert 1 galaxy Mrk 335 during an extremely low X-ray flux state. Mrk 335 was observed for 22 ks by XMM-Newton in July 2007 as a Target of Opportunity to examine it in its X-ray low-flux state, which was discovered with Swift. Long-term light curves suggest that this is the lowest flux state this AGN has ever been seen in. However, Mrk 335 is still sufficiently bright that its X-ray properties can be studied in detail. The X-ray continuum spectrum is very complex and requires several components to model. Statistically, partial covering and blurred reflection models work well. We confirm the presence of a strong narrow Fe line at 6.4 keV. High-resolution spectroscopy with the XMM-RGS reveals strong, soft X-ray emission lines not detected in previous, higher signal-to-noise, XMM-Newton observations, such as: highly ionized Fe lines, O VII, Ne IX and Mg XI lines. The optical/UV fluxes are similar to those previously measured with Swift. Optical spectroscopy taken in 2007 September do not show any changes to optical spectra obtained 8 years earlier.Comment: Accepted for publication in ApJ; 26 pages, 10 figues, in press, ApJ 681 (July 01, 2008); Updated version with corrections made by the edito

Probing the Ionizing Continuum of Narrow-Line Seyfert 1 Galaxies. I.Observational Results

We present optical spectra and emission-line ratios of 12 Narrow-Line Seyfert 1 (NLS1) galaxies that we observed to study the ionizing EUV continuum. A common feature in the EUV continuum of active galactic nuclei is the big blue bump (BBB), generally associated with thermal accretion disk emission. While Galactic absorption prevents direct access to the EUV range, it can be mapped by measuring the strength of a variety of forbidden optical emission lines that respond to different EUV continuum regions. We find that narrow emission-line ratios involving [OII]3727, Hbeta, [OIII]5007, [OI]6300, Halpha,[NII]6583, and [SII]6716,6731 indicate no significant difference between NLS1s and Broad-Line Seyfert 1 (BLS1) galaxies, which suggests that the spectral energy distributions of their ionizing EUV - soft X-ray continua are similar. The relative strength of important forbidden high ionization lines like [NeV]3426 compared to HeII4686 and the relative strength of [FeX]6374 appear to show the same range as in BLS1 galaxies. However, a trend of weaker F([OI]6300)/F(Halpha) emission-line ratios is indicated for NLS1s compared to BLS1s. To recover the broad emission-line profiles we used Gaussian components. This approach indicates that the broad Hbeta profile can be well described with a broad component (FWHM = 3275 +- 800 km/s) and an intermediate broad component (FWHM = 1200 +- 300 km/s). The width of the broad component is in the typical range of normal BLS1s. The emission-line flux that is associated with the broad component in these NLS1s amounts to at least 60% of the total flux. Thus it dominates the total line flux, similar to BLS1 galaxies.Comment: 34 pages, 9 figures. accepted for publication in the Astrophys.Journa