Sample records for harang discontinuity

  1. The Harang discontinuity in auroral belt ionospheric currents.

    NASA Technical Reports Server (NTRS)

    Heppner, J. P.

    1972-01-01

    Discussion of the nature of a discontinuity in the ionospheric current of the auroral belt whose existence was suggested by Harang in 1946. Convection characteristics, time variability, and current continuity in the auroral belt are considered in a context of observations and arguments supporting the reality of Harang's discontinuity.

  2. Electric field measurements across the harang discontinuity. [of the auroral zone

    NASA Technical Reports Server (NTRS)

    Maynard, N. C.

    1974-01-01

    The Harang discontinuity, the area separating the positive and negative bay regions in the midnight sector of the auroral zone, is a focal point for changes in behavior of many phenomena. Through this region the electric field rotates through the west from a basically northward field in the positive bay region to a basically southward field in the negative bay region, appearing as a reversal in a single axis measurement; 32 of these reversals have been identified in the OGO-6 data from November and December, 1969. The discontinuity is dynamic in nature, moving southward and steepening its latitudinal profile as magnetic activity is increased. As activity decreases it relaxes poleward and spreads out in latitudinal width. It occurs over several hours of magnetic local time. The boundary in the electric field data is consistent with the reversal of ground magnetic disturbances from a positive to negative bay condition. The discontinuity is present in the electric field data both during substorms and during quiet times and appears to define a pattern on which other effects can occur.

  3. Mesoscale thermospheric wind in response to nightside auroral brightening

    NASA Astrophysics Data System (ADS)

    Nishimura, T.; Zou, Y.; Gabrielse, C.; Lyons, L. R.; Varney, R. H.; Conde, M.; Hampton, D. L.; Mende, S. B.

    2017-12-01

    Although high-latitude ionospheric flows and thermospheric winds in the F-region are overall characterized by two-cell patterns over a global scale ( 1000 km), intense energy input from the magnetosphere often occurs in a mesoscale ( 100 km) and transient manner ( 10 min). Intense mesoscale energy input would drive enhanced mesoscale winds, whose properties are closely associated with auroral arcs and associated ionospheric flows. However, how thermospheric winds respond to and distribute around mesoscale magnetospheric input has not been characterized systematically. This presentation addresses how mesoscale winds distribute around quasi-steady arcs, evolve and distribute around transient arcs, and vary with geomagnetic and solar activity. We use Scanning Doppler Imagers (SDIs), all-sky imagers and PFISR over Alaska. A channel of azimuthal neutral wind is often found associated with localized flow channels adjacent to quasi-steady discrete aurora. The wind speed dynamically changes after a short time lag (a few tens of minutes) from auroral brightenings, including auroral streamers and intensifications on preexisting auroral arcs. This is in contrast to a much longer time lag ( 1 hour) reported previously. During a storm main phase, a coherent equatorward motion of the Harang discontinuity was seen in plasma flow, aurora and neutral wind, with a few degrees of equatorward displacement of the neutral wind Harang, which is probably due to the inertia. These results suggest that a tight M-I-T connection exists under the energy input of assorted auroral arcs and that mesoscale coupling processes are important in M-I-T energy transfer.

  4. Auroral research at the Tromsø Northern Lights Observatory: the Harang directorship, 1928-1946

    NASA Astrophysics Data System (ADS)

    Egeland, Alv; Burke, William J.

    2016-03-01

    The Northern Lights Observatory in Tromsø began as Professor Lars Vegard's dream for a permanent facility in northern Norway, dedicated to the continuous study of auroral phenomenology and dynamics. Fortunately, not only was Vegard an internationally recognized spectroscopist, he was a great salesman and persuaded the Rockefeller Foundation that such an observatory represented an important long-term investment. A shrewd judge of talent, Vegard recognized the scientific and managerial skills of Leiv Harang, a recent graduate from the University of Oslo, and recommended that he become the observatory's first director. In 1929, subsequent to receiving the Rockefeller Foundation grant, the University of Oslo established a low temperature laboratory to support Vegard's spectroscopic investigations. This paper follows the scientific accomplishments of observatory personnel during the 18 years of Harang's directorship. These include: identifying the chemical sources of auroral emissions, discovering the Vegard-Kaplan bands, quantifying height distributions of different auroral forms, interpreting patterns of magnetic field variations, remotely probing auroral electron distribution profiles in the polar ionosphere, and monitoring the evolving states of the ozone layer. The Rockefeller Foundation judges got it right: the Tromsø Nordlysobservatoriet was, and for decades remained, an outstanding scientific investment.

  5. A High-resolution Model of Field-aligned Currents Through Empirical Orthogonal Functions Analysis (MFACE)

    NASA Technical Reports Server (NTRS)

    He, Maosheng; Vogt, Joachim; Luehr, Hermann; Sorbalo, Eugen; Blagau, Adrian; Le, Guan; Lu, Gang

    2012-01-01

    Ten years of CHAMP magnetic field measurements are integrated into MFACE, a model of field-aligned currents (FACs) using empirical orthogonal functions (EOFs). EOF1 gives the basic Region-1/Region-2 pattern varying mainly with the interplanetary magnetic field Bz component. EOF2 captures separately the cusp current signature and By-related variability. Compared to existing models, MFACE yields significantly better spatial resolution, reproduces typically observed FAC thickness and intensity, improves on the magnetic local time (MLT) distribution, and gives the seasonal dependence of FAC latitudes and the NBZ current signature. MFACE further reveals systematic dependences on By, including 1) Region-1/Region-2 topology modifications around noon; 2) imbalance between upward and downward maximum current density; 3) MLT location of the Harang discontinuity. Furthermore, our procedure allows quantifying response times of FACs to solar wind driving at the bow shock nose: we obtain 20 minutes and 35-40 minutes lags for the FAC density and latitude, respectively.

  6. A mechanism for magnetospheric substorms

    NASA Technical Reports Server (NTRS)

    Erickson, G. M.; Heinemann, M.

    1994-01-01

    Energy-principle analysis performed on two-dimensional, self-consistent solutions for magnetospheric convection indicates that the magnetosphere is unstable to isobaric (yet still frozen-in) fluctuations of plasma-sheet flux tubes. Normally, pdV work associated with compression maintains stability of the inward/outward oscillating normal mode. However, if Earth's ionosphere can provide sufficient mass flux, isobaric expansion of flux tubes can occur. The growth of a field-aligned potential drop in the near-Earth, midnight portion of the plasma sheet, associated with upward field-aligned currents responsible for the Harang discontinuity, redistributes plasma along field lines in a manner that destabilizes the normal mode. The growth of this unstable mode results in an out-of-equilibrium situation near the inner edge. When this occurs over a downtail extent comparable to the half-thickness of the plasma sheet, collapse ensues and forces thinning of the plasma sheet whereby conditions favorable to reconnection occur. This scenario for substorm onset is consistent with observed upward fluxes of ions, parallel potential drops, and observations of substorm onset. These observations include near Earth onset, pseudobreakups, the substorm current wedge, and local variations of plasma-sheet thickness.

  7. The Harang reversal and the interchange stability of the magnetotail

    NASA Astrophysics Data System (ADS)

    Ohtani, Shinichi; Gkioulidou, Matina; Wang, Chih-Ping; Wolf, Richard A.

    2016-04-01

    The present study addresses steady convection in the plasma sheet in terms of the interchange stability with special attention to the Harang reversal. The closure of the tail current with a field-aligned current (FAC) results from the divergence/convergence of the pressure gradient current. If the magnetotail is in a steady state, the associated change of local plasma pressure p has to balance with its advective change. Accordingly, for adiabatic transport, the flux tube entropy parameter pVγ increases and decreases along the convection path in regions corresponding to downward and upward FACs, respectively. This requirement, along with the condition for the interchange stability imposes an important constraint on the direction of convection especially in the regions of downward FACs. It is deduced that for the dusk cell, the convection in the downward R2 current has to be directed azimuthally duskward, which follows the sunward, possibly dawnward deflected, convection in the region of the premidnight upward R1 current. This duskward turn of convection takes place in the vicinity of the R1-R2 demarcation, and it presumably corresponds to the Harang reversal. For the dawn cell the convection in the postmidnight downward R1 current has to deflect dawnward, and then it proceeds sunward in the upward R2 current. The continuity of the associated ionospheric currents consistently reproduces the assumed FAC distribution. The proposed interrelationships between the convection and FACs are also verified with a quasi-steady plasma sheet configuration and convection reproduced by a modified Rice Convection Model with force balance.

  8. Effect of self-consistent magnetic field on plasma sheet penetration to the inner magnetosphere: Rice convection model simulations combined with modified Dungey force-balanced magnetic field solver

    NASA Astrophysics Data System (ADS)

    Gkioulidou, Matina; Wang, Chih-Ping; Lyons, Larry R.

    2011-12-01

    Transport of plasma sheet particles into the inner magnetosphere is crucial to the development of the region 2 (R2) field-aligned current system (FAC), which results in the shielding of the penetration electric field and the formation of subauroral polarization streams (SAPS) and the Harang reversal, phenomena closely associated with storms and substorms. In addition to the electric field, this transport is also strongly affected by the magnetic field, which changes with plasma pressure and is distinctly different from the dipole field in the inner plasma sheet. To determine the feedback of force-balanced magnetic field to the transport, we have integrated the Rice convection model (RCM) with a modified Dungey magnetic field solver to obtain the required force balance in the equatorial plane. Comparing our results with those from a RCM run using a T96 magnetic field, we find that transport under a force-balanced magnetic field results in weaker pressure gradients and thus weaker R2 FAC in the near-Earth region and weaker shielding of the penetration electric field. As a result, plasma sheet protons and electrons penetrate farther earthward, and their inner edges become closer together and more azimuthally symmetric than in the T96 case. The Harang reversal extends farther dawnward, and the SAPS become more confined in radial and latitudinal extents. The magnitudes of azimuthal pressure gradient, the inner edges of thermal protons and electrons, the latitudinal range of the Harang reversal, and the radial and latitudinal widths of the SAPS from the force-balanced run are found to be more consistent with observations.

  9. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Inhester, B.; Untiedt, J.; Segatz, M.

    From two-dimensional ground magnetic and ionospheric electric field observations it should in principle be possible to estimate the two-dimensional distribution of the ionospheric conductance. The authors have developed a method to directly deduce the Hall conductance distribution {Sigma}{sub H} from ground magnetic and ionospheric electric field observations based upon some assumption for the ratio of the Hall to the Pedersen conductivity. In general, the solutions are shown not to be unique because for a specific solution the value of {Sigma}{sub H} on certain parts of the boundary of the two-dimensional domain has to be specified. However, in many situations, especiallymore » in the presence of strong and isolated field-aligned currents, these boundary values become less influential, and the solution can be shown to be practically unique over a large area of the domain. In some cases, a rather restrictive relation between the electric field and the equivalent height-integrated current density is shown to hold that could be used to cross-check the quality of the observations. As a specific example, they apply their formalism to the observation of a Harang discontinuity obtained in northern Scandinavia simultaneously by the STARE coherent radar system and the IMS Scandinavian Magnetometer Array.« less

  10. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sandahl, I.; Eliasson, L.; Pellinen-Wannberg, A.

    On the night of November 4, 1986, a very complex precipitation pattern was observed by Viking in the magnetic midnight sector over Scandinavia and Svalbard. The pass took place during a magnetic storm, and during substorm recovery phase. Going from north to south, the satellite first encountered a plasma region of BPS-type (name derived from boundary plasma sheet) and then a region of CPS type (derived from central plasma sheet). Then, however, a new region of BPS-type was traversed. The quite intense, most equatorward aurora corresponded to a plasma region which was not of ordinary CPS type but contained sharpmore » quasi-monoenergetic peaks. The high-latitude midnight sector was totally dominated by eastward convection. The Harang discontinuity had passed northern Scandinavia the first time as early as 17 to 20 MLT, more than three house before the Viking pass. It is suggested that the particle precipitation pattern and the general shape of the aurora as observed by the Viking imager can be explained in a natural way by the convection pattern. The northernmost BPS- and CPS-type regions originated in the morningside convection cell, while the more equatorward population of BPS type had drifted in from the eveningside. The interpretation is supported by ground-based measurements by EISCAT and magnetometers.« less

  11. Studies of Polar Current Systems Using the IMS Scandinavian Magnetometer Array

    NASA Astrophysics Data System (ADS)

    Untiedt, J.; Baumjohann, W.

    1993-09-01

    As a contribution to the International Magnetospheric Study (IMS, 1976 1979) a two-dimensional array of 42 temporary magnetometer stations was run in Scandinavia, supplementary to the permanent observatories and concentrated in the northern part of the region. This effort aimed at the time-dependent (periods above about 100 s) determination of the two-dimensional structure of substorm-related magnetic fields at the Earth's surface with highest reasonable spatial resolution (about 100 km, corresponding to the height of the ionosphere) near the footpoints of field-aligned electric currents that couple the disturbed magnetosphere to the ionosphere at auroral latitudes. It has been of particular advantage for cooperative studies that not only simultaneous data were available from all-sky cameras, riometers, balloons, rockets, and satellites, but also from the STARE radar facility yielding colocated two-dimensional ionospheric electric field distributions. In many cases it therefore was possible to infer the three-dimensional regional structure of substorm-related ionospheric current systems. The first part of this review outlines the basic relationships and methods that have been used or have been developed for such studies. The second short part presents typical equivalent current patterns observed by the magnetometer array in the course of substorms. Finally we review main results of studies that have been based on the magnetometer array observations and on additional data, omitting studies on geomagnetic pulsations. These studies contributed to a clarification of the nature of auroral electrojets including the Harang discontinuity and of ionospheric current systems related to auroral features such as the break-up at midnight, the westward traveling surge, eastward drifting omega bands, and spirals.

  12. Electrical changes of the polar ionosphere during magnetospheric substorms

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ahn, B.H.; Kamide, Y.; Akasofu, S.H.

    1986-05-01

    Changes of the distribution of the potential, electric fields, ionospheric currents, field-aligned currents, the Joule heat production rate, the particle energy injection rate and the total energy dissipation rate are examined in detail by comparing them at a presubstorm epoch and the maximum epoch for several substorms on March 17, 18, and 19, 1978. The data sets are obtained on the basis of the magnetic records from the six International Magnetospheric Study meridian chains of observatories by using the computer code developed by Kamide e-italict-italic a-italicl-italic. (1981) and the conductivity model developed by Ahn et al. (1983b). A number ofmore » global features that are found to be common to most of the substorms examined in this study include the following: (1) The positive potential cell in the morning sector extends into the evening sector during substorms. (2) When it is intensified, the westward electrojet on the nightside tends to flow equatorward of the positive potential ridge. (3) The so-called ''Harang discontinuity'' may be identified as the ridge of the negative potential cell. (4) The distribution of field- aligned currents determined by our method is more complicated than the statistical pattern obtained by polar orbiting satellites. (5) The basic ionospheric current pattern is fundamentally the same during a fairly quiet period, a slightly disturbed period and a substorm period. (6) The highest Joule heat production occurs along the westward extension of the westward electrojet, while the particle energy injection rate is high along the westward electrojet in the morning sector.« less

  13. Magnetosphere-Ionosphere Coupling During a Geomagnetic Substorm on March 1, 2017

    NASA Astrophysics Data System (ADS)

    Coster, A. J.; Hampton, D. L.; Sazykin, S. Y.; Wolf, R.; Huba, J.; Varney, R. H.; Reimer, A.; Lynch, K. A.; Samara, M.; Michell, R.

    2017-12-01

    On March 1, 2017, at approximately 10 UT, magnetometers at Ft Yukon and Poker Flat in Alaska measured the classic signature of an auroral substorm: a rapid decrease in the northward component of the magnetic field. Nearby, a camera at Venetie Alaska captured intensive visual brightening of multiple auroral arcs at approximately the same time. Our data and model analysis focuses on this time period. We are taking advantage of the extensive instrumentation that was in place in Northern Alaska on this date due to the ISINGLASS rocket campaign. Although no rockets were flown on March 1, 2017, this substorm was monitored at Poker by the three-filter all-sky survey and at Venetie by three all-sky cameras running simultaneously with each filtered for a different wavelength. Our analysis includes co-incidental high precision GNSS receiver data providing total electron content (TEC) measurements during the overhead auroral arcs. The receiver at Venetie also monitored L-band scintillation. In addition, the Poker Flat Incoherent Scatter radar captured the rapid ionization enhancement in the 100-200 km region across multiple beams looking to the north of Poker. The timing of these events between the multiple sites is closely monitored, and inferences of the propagation of this event are described. The available SuperDARN data from this time period indicates this substorm happened at about the same time within the Harang discontinuity. This event presented an unprecedented opportunity to observe occurrence and development of a substorm with a combination of ground-based remote sensing instruments. To support our interpretation of the data, we present first simulations of the magnetosphere-ionosphere coupled system during a substorm with the self-consistently coupled SAMI/RCM code.

  14. Electric currents and voltage drops along auroral field lines

    NASA Technical Reports Server (NTRS)

    Stern, D. P.

    1983-01-01

    An assessment is presented of the current state of knowledge concerning Birkeland currents and the parallel electric field, with discussions focusing on the Birkeland primary region 1 sheets, the region 2 sheets which parallel them and appear to close in the partial ring current, the cusp currents (which may be correlated with the interplanetary B(y) component), and the Harang filament. The energy required by the parallel electric field and the associated particle acceleration processes appears to be derived from the Birkeland currents, for which evidence is adduced from particles, inverted V spectra, rising ion beams and expanded loss cones. Conics may on the other hand signify acceleration by electrostatic ion cyclotron waves associated with beams accelerated by the parallel electric field.

  15. Stormtime substorm onsets: occurrence and flow channel triggering

    NASA Astrophysics Data System (ADS)

    Lyons, Larry R.; Zou, Ying; Nishimura, Yukitoshi; Gallardo-Lacourt, Bea; Angelopulos, Vassilis; Donovan, Eric F.

    2018-05-01

    Bright auroral emissions during geomagnetic storms provide a good opportunity for testing the proposal that substorm onset is frequently triggered by plasma sheet flow bursts that are manifested in the ionosphere as auroral streamers. We have used the broad coverage of the ionospheric mapping of the plasma sheet offered by the high-resolution THEMIS all-sky-imagers (ASIs) and chose the main phases of 9 coronal mass ejection (CME) related and 9 high-speed stream (HSS)-related geomagnetic storms, and identified substorm auroral onsets defined as brightening followed by poleward expansion. We found a detectable streamer heading to near the substorm onset location for all 60 onsets that we identified and were observed well by the ASIs. This indicates that substorm onsets are very often triggered by the intrusion of plasma with lower entropy than the surrounding plasma to the onset region, with the caveat that the ASIs do not give a direct measure of the intruding plasma. The majority of the triggering streamers are "tilted streamers," which extend eastward as their eastern tip tilts equatorward to near the substorm onset location. Fourteen of the 60 cases were identified as "Harang streamers," where the streamer discernibly turns toward the west poleward of reaching to near the onset latitude, indicating flow around the Harang reversal. Using the ASI observations, we observed substantially less substorm onsets for CME storms than for HSS storms, a result in disagreement with a recent finding of approximately equal substorm occurrences. We suggest that this difference is a result of strong non-substorm streamers that give substorm-like signatures in ground magnetic field observations but are not substorms based on their auroral signature. Our results from CME storms with steady, strong southward IMF are not consistent with the 2-4 h repetition of substorms that has been suggested for moderate to strong southward IMF conditions. Instead, our results indicate substantially lower substorm occurrence during such steady driving conditions. Our results also show the much more frequent occurrence of substorms during HSS period, which is likely due to the highly fluctuating IMF. [Figure not available: see fulltext.

  16. Possibility of Ionospheric Cause of FACs and Convection Field in the Magnetosphere-Ionosphere System: The Harang Reversal, Premidnight Upward-FAC, and the Ionospheric Hall Polarization Field

    NASA Astrophysics Data System (ADS)

    Nakamizo, A.; Yoshikawa, A.

    2016-12-01

    Whereas it is generally thought that Birkeland Currents (FACs) are generated in the magnetosphere and that the ionospheric convection reflects the magnetospheric convection, we present a possibility that the ionosphere drives FACs and the convection field in the M-I system. We apply this idea to the Harang Reversal (HR) for demonstration. By using an ionospheric potential solver we calculate the electrostatic field for given distributions of FACs and conductance. The result shows that a conspicuous structure resembling HR is generated even for a symmetric distribution of the R1-type FACs and that the Hall polarization field is produced at the equatorward boundary of the auroral region as the primary currents diverge/converge at the conductance gradient there, which causes the potential deformation (HR). Conventionally HR has been considered to be of the magnetospheric origin, and a ring current model actually produces the corresponding structure in the magnetosphere [e.g., Erickson et al., 1991]. Observationally the divE equivalent to HR is consistent with the premidnight upward-FAC seen in Iijima and Potemra's diagram. A recent theoretical study [Ohtani et al., 2016] proposes that HR is a required structure for the interchange stability of the magnetotail in the presence of the R1 and R2-FAC systems including a premidnight upward-FAC. Returning to our result, the important point is that HR is reproduced at the conductance edge by the ionospheric polarization field, for which the primary field originates from the R1-FACs distributed far from that region. We also suggest: (i) In a more realistic finite ΣA, the total ionospheric polarization is partly released by a FAC, which may be a part of the premidnight upward-FAC. (ii) However, existing simulation models do not allow this type of current closure, and accordingly they may enhance the HR structure in the magnetosphere. This discussion should hold generally and would promote the global M-I coupling studies to the next step.

  17. Effects of Ionospheric Hall Polarization on Magnetospheric Configurations and Dynamics in Global MHD Simulation

    NASA Astrophysics Data System (ADS)

    Nakamizo, A.; Yoshikawa, A.; Tanaka, T.

    2017-12-01

    We investigate how the M-I coupling and boundary conditions affects the results of global simulations of the magnetosphere. More specifically, we examine the effects of ionospheric Hall polarization on magnetospheric convection and dynamics by using an MHD code developed by Tanaka et al. [2010]. This study is motivated by the recently proposed idea that the ionospheric convection is modified by the ionospheric polarization [Yoshikawa et al., 2013]. We perform simulations for the following pairs of Hall conductance and IMF-By; Hall conductance set by αH = 2, 3.5, 5, and uniform distribution (1.0 [S] everywhere), where RH is the ratio of Hall to Pedersen conductance, and IMF-By of positive, negative, and zero. The results are summarized as follows. (a) Large-scale structure: In the cases of uniform Hall conductance, the magnetosphere is completely symmetric under the zero IMF-By. In the cases of non-uniform Hall conductance, the magnetosphere shows asymmetries globally even under the zero IMF-By. Asymmetries become severe for larger αH. The results indicate that ionospheric Hall polarization is one of the important factors to determine the global structure. (b) Formation of NENL: The location becomes closer to the earth and timing becomes earlier for larger RH. The difference is considered to be related to the combined effects of field lines twisting due to ionospheric Hall polarization and M-I energy/current closures. (c) Near-earth convection: In the cases of non-uniform Hall conductance, an inflection structure is formed around premidnight sector on equatorial plane inside 10 RE. Considering that the region 2 FAC is not sufficiently generated in MHD models, the structure corresponds to a convection reversal often shown in the RCM. Previous studies regard the structure as the Harang Reversal in the magnetosphere. In the cases of uniform Hall conductance, by contrast, such structure is not formed, indicating that the Harang Reversal may not be formed without the effect of ionospheric Hall polarization. The above initial research strongly suggests that the ionospheric Hall polarization plays a significant role in the M-I system.

  18. General practitioners' decisions about discontinuation of medication: an explorative study.

    PubMed

    Nixon, Michael Simon; Vendelø, Morten Thanning

    2016-06-20

    Purpose - The purpose of this paper is to investigate how general practitioners' (GPs) decisions about discontinuation of medication are influenced by their institutional context. Design/methodology/approach - In total, 24 GPs were interviewed, three practices were observed and documents were collected. The Gioia methodology was used to analyse data, drawing on a theoretical framework that integrate the sensemaking perspective and institutional theory. Findings - Most GPs, who actively consider discontinuation, are reluctant to discontinue medication, because the safest course of action for GPs is to continue prescriptions, rather than discontinue them. The authors conclude that this is in part due to the ambiguity about the appropriateness of discontinuing medication, experienced by the GPs, and in part because the clinical guidelines do not encourage discontinuation of medication, as they offer GPs a weak frame for discontinuation. Three reasons for this are identified: the guidelines provide dominating triggers for prescribing, they provide weak priming for discontinuation as an option, and they underscore a cognitive constraint against discontinuation. Originality/value - The analysis offers new insights about decision making when discontinuing medication. It also offers one of the first examinations of how the institutional context embedding GPs influences their decisions about discontinuation. For policymakers interested in the discontinuation of medication, the findings suggest that de-stigmatising discontinuation on an institutional level may be beneficial, allowing GPs to better justify discontinuation in light of the ambiguity they experience.

  19. Influence of pacer continuity on continuous and discontinuous visuo-motor synchronisation.

    PubMed

    Zelic, Gregory; Varlet, Manuel; Kim, Jeesun; Davis, Chris

    2016-09-01

    Previous research has reported that synchronising movements with an external pacer, known as sensorimotor synchronisation (SMS), is more stable when the movements are discrete/discontinuous rather than continuous. A standard explanation considers that more efficient mechanisms are involved for regulating synchronisation when producing discontinuous movements. To date, however, only discontinuous pacers (e.g., metronomes) have been investigated to compare discontinuous and continuous SMS. We propose an alternative explanation whereby the discontinuous SMS has benefited from the matching between the (dis)continuous nature of the pacer and the (dis)continuous nature of the movements of synchronisation. The present experiment tested this explanation by examining the relative stability of discontinuous and continuous SMS when synchronising with a continuous pacer. Twelve participants finger tapped (discontinuous SMS) or continuously oscillated their forearm (continuous SMS) in synchrony with an oscillatory visual target. The continuity of the pacer was manipulated by varying the kinematic (harmonic to Rayleigh-like oscillations) and the frequency (0.5 and 1Hz) of the target oscillations. Overall, the results showed a more stable continuous than discontinuous SMS. Furthermore, the stability of the discontinuous SMS improved when increasing the discontinuity of the target displacements (high nonlinear kinematic and low frequency), showing an interaction between movement type and pacer continuity in SMS. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Physics-based process model approach for detecting discontinuity during friction stir welding

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shrivastava, Amber; Pfefferkorn, Frank E.; Duffie, Neil A.

    2015-02-12

    The goal of this work is to develop a method for detecting the creation of discontinuities during friction stir welding. This in situ weld monitoring method could significantly reduce the need for post-process inspection. A process force model and a discontinuity force model were created based on the state-of-the-art understanding of flow around an friction stir welding (FSW) tool. These models are used to predict the FSW forces and size of discontinuities formed in the weld. Friction stir welds with discontinuities and welds without discontinuities were created, and the differences in force dynamics were observed. In this paper, discontinuities weremore » generated by reducing the tool rotation frequency and increasing the tool traverse speed in order to create "cold" welds. Experimental force data for welds with discontinuities and welds without discontinuities compared favorably with the predicted forces. The model currently overpredicts the discontinuity size.« less

  1. Reasons and correlates of contraceptive discontinuation in Kuwait.

    PubMed

    Shah, N M; Shah, M A; Chowdhury, R I; Menon, I

    2007-09-01

    (1) To examine the probability of discontinuation of various methods within 1, 2, and three years of use and the reasons for discontinuation; 2) to analyse the socio-demographic correlates of discontinuation. Data from a survey of Kuwaiti women in reproductive ages conducted in 1999 were used. Information on duration of use of modern and traditional methods, and reasons for discontinuation during the 72 months before the survey were analysed. Probabilities of discontinuation were estimated through multiple decrement life table analysis. After 1 year, 30% of modern and 40% of traditional method users had discontinued; after 3 years, discontinuation increased to 66 and 70%, respectively. After 36 months, only 40% of IUD users discontinued compared with 74% of oral contraceptive users. The desire to become pregnant was the leading reason for discontinuation of most modern methods, while method failure was an equally important reason for traditional methods. Discontinuation was significantly more frequent among higher parity, non-working and Bedouin women, and among those who said Islam disapproves of contraception. Contraception is used largely for spacing. More than two-thirds of the women studied had discontinued most methods after three years, except the IUD, which was used only by about 10% of them. Traditional methods are often discontinued due to method failure and may result in an unintended pregnancy. Better counselling is warranted for traditional methods. Health care for managing side effects of modern methods also needs improvement.

  2. 27 CFR 17.187 - Discontinuance of business.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Discontinuance of business... PRODUCTS Miscellaneous Provisions § 17.187 Discontinuance of business. The manufacturer shall notify TTB when business is to be discontinued. Upon discontinuance of business, a manufacturer's entire stock of...

  3. 27 CFR 555.128 - Discontinuance of business.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Discontinuance of business... Discontinuance of business. Where an explosive materials business or operations is discontinued and succeeded by... such facts and shall be delivered to the successor. Where discontinuance of the business or operations...

  4. 27 CFR 555.128 - Discontinuance of business.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2013-04-01 2013-04-01 false Discontinuance of business... Discontinuance of business. Where an explosive materials business or operations is discontinued and succeeded by... such facts and shall be delivered to the successor. Where discontinuance of the business or operations...

  5. 27 CFR 555.128 - Discontinuance of business.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2014-04-01 2014-04-01 false Discontinuance of business... Discontinuance of business. Where an explosive materials business or operations is discontinued and succeeded by... such facts and shall be delivered to the successor. Where discontinuance of the business or operations...

  6. 21 CFR 1301.52 - Termination of registration; transfer of registration; distribution upon discontinuance of business.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... discontinues business or professional practice. Any registrant who ceases legal existence or discontinues... registration; distribution upon discontinuance of business. 1301.52 Section 1301.52 Food and Drugs DRUG... of registration; transfer of registration; distribution upon discontinuance of business. (a) Except...

  7. 27 CFR 478.57 - Discontinuance of business.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Discontinuance of business... Licenses § 478.57 Discontinuance of business. (a) Where a firearm or ammunition business is either discontinued or succeeded by a new owner, the owner of the business discontinued or succeeded shall within 30...

  8. 27 CFR 478.127 - Discontinuance of business.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2014-04-01 2014-04-01 false Discontinuance of business... Records § 478.127 Discontinuance of business. Where a licensed business is discontinued and succeeded by a... be delivered to the successor. Where discontinuance of the business is absolute, the records shall be...

  9. 27 CFR 478.57 - Discontinuance of business.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2014-04-01 2014-04-01 false Discontinuance of business... Licenses § 478.57 Discontinuance of business. (a) Where a firearm or ammunition business is either discontinued or succeeded by a new owner, the owner of the business discontinued or succeeded shall within 30...

  10. 27 CFR 478.127 - Discontinuance of business.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2013-04-01 2013-04-01 false Discontinuance of business... Records § 478.127 Discontinuance of business. Where a licensed business is discontinued and succeeded by a... be delivered to the successor. Where discontinuance of the business is absolute, the records shall be...

  11. 27 CFR 478.57 - Discontinuance of business.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2013-04-01 2013-04-01 false Discontinuance of business... Licenses § 478.57 Discontinuance of business. (a) Where a firearm or ammunition business is either discontinued or succeeded by a new owner, the owner of the business discontinued or succeeded shall within 30...

  12. 39 CFR 241.3 - Discontinuance of USPS-operated retail facilities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 39 Postal Service 1 2013-07-01 2013-07-01 false Discontinuance of USPS-operated retail facilities... ESTABLISHMENT CLASSIFICATION, AND DISCONTINUANCE § 241.3 Discontinuance of USPS-operated retail facilities. (a... of whether an existing retail Post Office, station, or branch should be discontinued. The rules cover...

  13. 39 CFR 241.3 - Discontinuance of USPS-operated retail facilities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 39 Postal Service 1 2014-07-01 2014-07-01 false Discontinuance of USPS-operated retail facilities... ESTABLISHMENT CLASSIFICATION, AND DISCONTINUANCE § 241.3 Discontinuance of USPS-operated retail facilities. (a... of whether an existing retail Post Office, station, or branch should be discontinued. The rules cover...

  14. 39 CFR 241.3 - Discontinuance of USPS-operated retail facilities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 39 Postal Service 1 2012-07-01 2012-07-01 false Discontinuance of USPS-operated retail facilities... ESTABLISHMENT CLASSIFICATION, AND DISCONTINUANCE § 241.3 Discontinuance of USPS-operated retail facilities. (a... of whether an existing retail Post Office, station, or branch should be discontinued. The rules cover...

  15. Predictors of discontinuation of antipsychotic medication and subsequent outcomes in the European First Episode Schizophrenia Trial (EUFEST).

    PubMed

    Landolt, Karin; Rössler, Wulf; Ajdacic-Gross, Vladeta; Derks, Eske M; Libiger, Jan; Kahn, René S; Fleischhacker, W Wolfgang

    2016-04-01

    This study had two aims: to describe patients suffering from first-episode schizophrenia who had stopped taking any antipsychotic medication, and to gain information on the predictors of successful discontinuation. We investigated data from the European First Episode Schizophrenia Trial (EUFEST). From the 325 patients included, 15.7% discontinued all antipsychotic medication. In a first analysis, clinical and sociodemographical predictors of discontinuing any antipsychotic medication were identified, using Cox regression. In the second analysis, logistic regression was used to determine variables associated with those patients who had stopped taking antipsychotic medication and had a favourable outcome, i.e., successful discontinuation. A good outcome was defined as a) having had no relapse within the whole observation period (80.6%), and b) having had no relapse and symptomatic remission at 12-month-follow-up (37.2%). Cox regression revealed that a higher proportion of patients from Western European countries and Israel stopped antipsychotic medication than from Central and Eastern European countries, that relapse was associated with discontinuation, and that discontinuers had lower compliance and higher quality of life. Predictors of successful discontinuation differed with the outcome definition used. Using definition b), successful discontinuers had a better baseline prognosis and better baseline social integration. Using definition a), successful discontinuers more often were from Western European countries. Region and clinical factors were associated with discontinuation. Prognosis and social integration played an important role in predicting successful discontinuation. As this study had several limitations, for example the observational design regarding discontinuation, further studies are needed to identify predictors of successful discontinuation. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. High-order dynamic modeling and parameter identification of structural discontinuities in Timoshenko beams by using reflection coefficients

    NASA Astrophysics Data System (ADS)

    Fan, Qiang; Huang, Zhenyu; Zhang, Bing; Chen, Dayue

    2013-02-01

    Properties of discontinuities, such as bolt joints and cracks in the waveguide structures, are difficult to evaluate by either analytical or numerical methods due to the complexity and uncertainty of the discontinuities. In this paper, the discontinuity in a Timoshenko beam is modeled with high-order parameters and then these parameters are identified by using reflection coefficients at the discontinuity. The high-order model is composed of several one-order sub-models in series and each sub-model consists of inertia, stiffness and damping components in parallel. The order of the discontinuity model is determined based on the characteristics of the reflection coefficient curve and the accuracy requirement of the dynamic modeling. The model parameters are identified through the least-square fitting iteration method, of which the undetermined model parameters are updated in iteration to fit the dynamic reflection coefficient curve with the wave-based one. By using the spectral super-element method (SSEM), simulation cases, including one-order discontinuities on infinite- and finite-beams and a two-order discontinuity on an infinite beam, were employed to evaluate both the accuracy of the discontinuity model and the effectiveness of the identification method. For practical considerations, effects of measurement noise on the discontinuity parameter identification are investigated by adding different levels of noise to the simulated data. The simulation results were then validated by the corresponding experiments. Both the simulation and experimental results show that (1) the one-order discontinuities can be identified accurately with the maximum errors of 6.8% and 8.7%, respectively; (2) and the high-order discontinuities can be identified with the maximum errors of 15.8% and 16.2%, respectively; and (3) the high-order model can predict the complex discontinuity much more accurately than the one-order discontinuity model.

  17. Branch point reconstructors for discontinuous light phase functions

    NASA Astrophysics Data System (ADS)

    Le Bigot, Eric O.; Wild, Walter J.; Kibblewhite, Edward J.

    1998-09-01

    The study of phase discontinuities caused by atmospheric turbulence is a recent research topic; their study might yield significant improvements in high-quality adaptive optics systems, laser weapons and laser communication. We present in this paper an introduction to discontinuities in the light phase. We also provide a geometrical description of phase discontinuities, a study of their effect on Hartmann-Shack sensor measurements, as well as algorithms for measuring discontinuous light phases and the position of phase discontinuities.

  18. The 520 km Discontinuity: No Longer Just the Middle Child of the Transition Zone

    NASA Astrophysics Data System (ADS)

    Houser, C.; Williams, Q.

    2008-12-01

    The 520 km discontinuity is more difficult to image and changes character laterally more relative to its siblings the 410 km and 660 km discontinuities. The 520 km discontinuity is thought to result from the phase change of β-spinel to γ-spinel, a transition which has a smaller impedance contrast than the olivine to β-spinel or the γ-spinel to perovskite and periclase transitions that are associated with the 410 km and 660 km discontinuities, respectively. In addition, there are gradual phase changes occurring in the pyroxene component of the mantle between the 410 km and 660 km discontinuity which complicate imaging and interpretation of the 520 km discontinuity. The best global coverage of discontinuity depth comes from the stacking of SS precursors, seismic phases that bounce off the discontinuities and arrive as precursors to the main SS phase. A recent study by Houser et al. (2008) contains the largest compilation of SS precursor measurements. However, since the 520 km discontinuity is not ubiquitously observed, its characteristics were not addressed. Here, we examine the geographic distribution (which is global, but not even) of high quality 520 km discontinuity measurements derived from precursors. The principal result is that the depth of the 520 km discontinuity has a higher correlation with tomographically-imaged high and low seismic velocities than either the 410 km or 660 km discontinuities. This stronger temperature sensitivity is in accord with determinations of the Clapeyron slopes of the differing transitions. Furthermore, this correlation is observed in a wide range of tectonic environments, and the prospect thus exists that the 520 km discontinuity will, where it is observed, provide a tighter bound on temperature within the transition zone than either of the other major discontinuities. Furthermore, improved constraints on the temperature distribution at depth may produce improved insight into the relative roles of thermal and compositional effects on the 660 km disctoninuity.

  19. Strategies for discontinuation of proton pump inhibitors: a systematic review.

    PubMed

    Haastrup, Peter; Paulsen, Maja S; Begtrup, Luise M; Hansen, Jane M; Jarbøl, Dorte E

    2014-12-01

    Proton pump inhibitors (PPIs) are considered to be overprescribed. Consensus on how to attempt discontinuation is, however, lacking. We therefore conducted a systematic review of clinical studies on discontinuation of PPIs. Systematic review based on clinical studies investigating discontinuation strategies and discontinuation rates for users of antisecretory medication judged eligible for withdrawal. The databases Medline, Embase and Cochrane Library were searched to December 2013 using the terms antisecretory, anti-ulcer, PPI, acid suppressant, discontinuation, step-down, step down, cessation, tapering, withdrawal and withhold. Search terms were used either singularly or in combination. Papers written in English or Scandinavian were included. Concurrent hand searching was undertaken to pursue references of references. The website ClinicalTrials.gov was searched for unpublished results and ongoing studies. A total of 371 abstracts were scrutinized to determine relevancy. The thorough search resulted in six clinical studies on strategies for discontinuation of PPIs. All discontinuation regimens used in the studies differed, and several interventions have been tested in order to decrease use of PPIs. Discontinuations were reported across all studies ranging from 14% to 64% without deteriorating symptom control. Tapering seems to be a more effective discontinuation strategy than abrupt discontinuation. Discontinuation of PPIs is feasible in a clinical setting, and a substantial number of the patients treated without a clear indication can safely reduce or discontinue treatment. Tapering seems to be the most effective way of doing this. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Reasons for discontinuation of reversible contraceptive methods by women with epilepsy.

    PubMed

    Mandle, Hannah B; Cahill, Kaitlyn E; Fowler, Kristen M; Hauser, W Allen; Davis, Anne R; Herzog, Andrew G

    2017-05-01

    To report the reasons for discontinuation of contraceptive methods by women with epilepsy (WWE). These retrospective data come from a web-based survey regarding the contraceptive practices of 1,144 WWE in the community, ages 18-47 years. We determined the frequencies of contraceptive discontinuations and the reasons for discontinuation. We compared risk ratios for rates of discontinuation among contraceptive methods and categories. We used chi-square analysis to test the independence of discontinuation reasons among the various contraceptive methods and categories and when stratified by antiepileptic drug (AED) categories. Nine hundred fifty-nine of 2,393 (40.6%) individual, reversible contraceptive methods were discontinued. One-half (51.8%) of the WWE who discontinued a method discontinued at least two methods. Hormonal contraception was discontinued most often (553/1,091, 50.7%) with a risk ratio of 1.94 (1.54-2.45, p < 0.0001) compared to intrauterine devices (IUDs), the category that was discontinued the least (57/227, 25.1%). Among all individual methods, the contraceptive patch was stopped most often (79.7%) and the progestin-IUD was stopped the least (20.1%). The top three reasons for discontinuation among all methods were reliability concerns (13.9%), menstrual problems (13.5%), and increased seizures (8.6%). There were significant differences among discontinuation rates and reasons when stratified by AED category for hormonal contraception but not for any other contraceptive category. Contraception counseling for WWE should consider the special experience profiles that are unique to this special population on systemic hormonal contraception. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  1. 78 FR 60375 - Norfolk Southern Railway Company-Discontinuance of Service Exemption-in Claiborne County, TN, and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-01

    ...); Docket No. AB 55 (Sub-No. 732X)] Norfolk Southern Railway Company--Discontinuance of Service Exemption... exemption under 49 CFR part 1152 Subpart F--Exempt Abandonments and Discontinuances of Service and Trackage Rights for NSR to discontinue service over, and for CSXT to discontinue trackage rights operations over...

  2. Changes Ii Pain Intensity Following Discontinuation of Long-Term Opioid Therapy for Chronic Non-Cancer Pain.

    PubMed

    McPherson, Sterling; Smith, Crystal Lederhos; Dobscha, Steven K; Morasco, Benjamin J; Demidenko, Michael I; Meath, Thomas H A; Lovejoy, Travis I

    2018-06-13

    Little is known about changes in pain intensity that may occur following discontinuation of long-term opioid therapy (LTOT). The objective of this study was to characterize pain intensity following opioid discontinuation over 12 months. This retrospective VA administrative data study identified N=551 patients nationally who discontinued LTOT. Data over 24 months (12 months prior to and following discontinuation) were abstracted from VA administrative records. Random effects regression analyses examined changes in 0-10 pain numeric rating scale scores over time, while growth mixture models delineated pain trajectory sub-groups. Mean estimated pain at the time of opioid discontinuation was 4.9. Changes in pain following discontinuation were characterized by slight but statistically non-significant declines in pain intensity over 12 months post-discontinuation (B=-0.20, p=0.14). Follow-up growth mixture models identified four pain trajectory classes characterized by the following post-discontinuation pain levels: no pain (average pain at discontinuation=0.37), mild clinically-significant pain (average pain=3.90), moderate clinically-significant pain (average pain=6.33), and severe clinically-significant pain (average pain=8.23). Similar to the overall sample, pain trajectories in each of the four classes were characterized by slight reductions in pain over time, with patients in the mild and moderate pain trajectory categories experiencing the greatest pain reductions post-discontinuation (B=-0.11, p=0.05 and B=-0.11, p=0.04, respectively). Pain intensity following discontinuation of LTOT does not, on average, worsen for patients and may slightly improve, particularly for patients with mild-to-moderate pain at the time of discontinuation. Clinicians should consider these findings when discussing risks of opioid therapy and potential benefits of opioid taper with patients.

  3. Wave field features of shallow vertical discontinuity and their application in non-destructive detection

    USGS Publications Warehouse

    Liu, J.; Xia, J.; Luo, Y.; Chen, C.; Li, X.; Huang, Y.

    2007-01-01

    The geotechnical integrity of critical infrastructure can be seriously compromised by the presence of fractures or crevices. Non-destructive techniques to accurately detect fractures in critical infrastructure such as dams and highways could be of significant benefit to the geotechnical industry. This paper investigates the application of shallow seismic and georadar methods to the detection of a vertical discontinuity using numerical simulations. The objective is to address the kinematical analysis of a vertical discontinuity, determine the resulting wave field characteristics, and provide the basis for determining the existence of vertical discontinuities based on the recorded signals. Simulation results demonstrate that: (1) A reflection from a vertical discontinuity produces a hyperbolic feature on a seismic or georadar profile; (2) In order for a reflection from a vertical discontinuity to be produced, a reflecting horizon below the discontinuity must exist, the offset between source and receiver (x0) must be non-zero, on the same side of the vertical discontinuity; (3) The range of distances from the vertical discontinuity where a reflection event is observed is proportional to its length and to x0; (4) Should the vertical crevice (or fracture) pass through a reflecting horizon, dual hyperbolic features can be observed on the records, and this can be used as a determining factor that the vertical crevice passes through the interface; and (5) diffractions from the edges of the discontinuity can be recorded with relatively smaller amplitude than reflections and their ranges are not constrained by the length of discontinuity. If the length of discontinuity is short enough, diffractions are the dominant feature. Real-world examples show that the shallow seismic reflection method and the georadar method are capable of recording the hyperbolic feature, which can be interpreted as vertical discontinuity. Thus, these methods show some promise as effective non-destructive detection methods for locating vertical discontinuities (e.g., fractures or crevices) in infrastructure such as dams and highway pavement. ?? 2007 Elsevier B.V. All rights reserved.

  4. Learning from failure - rationale and design for a study about discontinuation of randomized trials (DISCO study)

    PubMed Central

    2012-01-01

    Background Randomized controlled trials (RCTs) may be discontinued because of apparent harm, benefit, or futility. Other RCTs are discontinued early because of insufficient recruitment. Trial discontinuation has ethical implications, because participants consent on the premise of contributing to new medical knowledge, Research Ethics Committees (RECs) spend considerable effort reviewing study protocols, and limited resources for conducting research are wasted. Currently, little is known regarding the frequency and characteristics of discontinued RCTs. Methods/Design Our aims are, first, to determine the prevalence of RCT discontinuation for specific reasons; second, to determine whether the risk of RCT discontinuation for specific reasons differs between investigator- and industry-initiated RCTs; third, to identify risk factors for RCT discontinuation due to insufficient recruitment; fourth, to determine at what stage RCTs are discontinued; and fifth, to examine the publication history of discontinued RCTs. We are currently assembling a multicenter cohort of RCTs based on protocols approved between 2000 and 2002/3 by 6 RECs in Switzerland, Germany, and Canada. We are extracting data on RCT characteristics and planned recruitment for all included protocols. Completion and publication status is determined using information from correspondence between investigators and RECs, publications identified through literature searches, or by contacting the investigators. We will use multivariable regression models to identify risk factors for trial discontinuation due to insufficient recruitment. We aim to include over 1000 RCTs of which an anticipated 150 will have been discontinued due to insufficient recruitment. Discussion Our study will provide insights into the prevalence and characteristics of RCTs that were discontinued. Effective recruitment strategies and the anticipation of problems are key issues in the planning and evaluation of trials by investigators, Clinical Trial Units, RECs and funding agencies. Identification and modification of barriers to successful study completion at an early stage could help to reduce the risk of trial discontinuation, save limited resources, and enable RCTs to better meet their ethical requirements. PMID:22928744

  5. Efficacy and Safety Outcomes in Patients With Advanced Melanoma Who Discontinued Treatment With Nivolumab and Ipilimumab Because of Adverse Events: A Pooled Analysis of Randomized Phase II and III Trials.

    PubMed

    Schadendorf, Dirk; Wolchok, Jedd D; Hodi, F Stephen; Chiarion-Sileni, Vanna; Gonzalez, Rene; Rutkowski, Piotr; Grob, Jean-Jacques; Cowey, C Lance; Lao, Christopher D; Chesney, Jason; Robert, Caroline; Grossmann, Kenneth; McDermott, David; Walker, Dana; Bhore, Rafia; Larkin, James; Postow, Michael A

    2017-12-01

    Purpose Approximately 40% of patients with advanced melanoma who received nivolumab combined with ipilimumab in clinical trials discontinued treatment because of adverse events (AEs). We conducted a retrospective analysis to assess the efficacy and safety of nivolumab plus ipilimumab in patients who discontinued treatment because of AEs. Methods Data were pooled from phase II and III trials of patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, every 3 weeks for four doses, followed by nivolumab monotherapy 3 mg/kg every 2 weeks (N = 409). Efficacy was assessed in all randomly assigned patients who discontinued because of AEs during the induction phase (n = 96) and in those who did not discontinue because of AEs (n = 233). Safety was assessed in treated patients who discontinued because of AEs (n = 176) at any time and in those who did not discontinue because of AEs (n = 231). Results At a minimum follow-up of 18 months, median progression-free survival was 8.4 months for patients who discontinued treatment because of AEs during the induction phase and 10.8 months for patients who did not discontinue because of AEs ( P = .97). Median overall survival had not been reached in either group ( P = .23). The objective response rate was 58.3% for patients who discontinued because of AEs during the induction phase and 50.2% for patients who did not discontinue. The vast majority of grade 3 or 4 AEs occurred during the induction phase, with most resolving after appropriate management. Conclusion Efficacy outcomes seemed similar between patients who discontinued nivolumab plus ipilimumab treatment because of AEs during the induction phase and those who did not discontinue because of AEs. Therefore, even after discontinuation, many patients may continue to derive benefit from combination therapy.

  6. Efficacy and Safety Outcomes in Patients With Advanced Melanoma Who Discontinued Treatment With Nivolumab and Ipilimumab Because of Adverse Events: A Pooled Analysis of Randomized Phase II and III Trials

    PubMed Central

    Schadendorf, Dirk; Wolchok, Jedd D.; Hodi, F. Stephen; Chiarion-Sileni, Vanna; Gonzalez, Rene; Rutkowski, Piotr; Grob, Jean-Jacques; Cowey, C. Lance; Lao, Christopher D.; Chesney, Jason; Robert, Caroline; Grossmann, Kenneth; McDermott, David; Walker, Dana; Bhore, Rafia; Larkin, James

    2017-01-01

    Purpose Approximately 40% of patients with advanced melanoma who received nivolumab combined with ipilimumab in clinical trials discontinued treatment because of adverse events (AEs). We conducted a retrospective analysis to assess the efficacy and safety of nivolumab plus ipilimumab in patients who discontinued treatment because of AEs. Methods Data were pooled from phase II and III trials of patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, every 3 weeks for four doses, followed by nivolumab monotherapy 3 mg/kg every 2 weeks (N = 409). Efficacy was assessed in all randomly assigned patients who discontinued because of AEs during the induction phase (n = 96) and in those who did not discontinue because of AEs (n = 233). Safety was assessed in treated patients who discontinued because of AEs (n = 176) at any time and in those who did not discontinue because of AEs (n = 231). Results At a minimum follow-up of 18 months, median progression-free survival was 8.4 months for patients who discontinued treatment because of AEs during the induction phase and 10.8 months for patients who did not discontinue because of AEs (P = .97). Median overall survival had not been reached in either group (P = .23). The objective response rate was 58.3% for patients who discontinued because of AEs during the induction phase and 50.2% for patients who did not discontinue. The vast majority of grade 3 or 4 AEs occurred during the induction phase, with most resolving after appropriate management. Conclusion Efficacy outcomes seemed similar between patients who discontinued nivolumab plus ipilimumab treatment because of AEs during the induction phase and those who did not discontinue because of AEs. Therefore, even after discontinuation, many patients may continue to derive benefit from combination therapy. PMID:28841387

  7. Automatic extraction of discontinuity orientation from rock mass surface 3D point cloud

    NASA Astrophysics Data System (ADS)

    Chen, Jianqin; Zhu, Hehua; Li, Xiaojun

    2016-10-01

    This paper presents a new method for extracting discontinuity orientation automatically from rock mass surface 3D point cloud. The proposed method consists of four steps: (1) automatic grouping of discontinuity sets using an improved K-means clustering method, (2) discontinuity segmentation and optimization, (3) discontinuity plane fitting using Random Sample Consensus (RANSAC) method, and (4) coordinate transformation of discontinuity plane. The method is first validated by the point cloud of a small piece of a rock slope acquired by photogrammetry. The extracted discontinuity orientations are compared with measured ones in the field. Then it is applied to a publicly available LiDAR data of a road cut rock slope at Rockbench repository. The extracted discontinuity orientations are compared with the method proposed by Riquelme et al. (2014). The results show that the presented method is reliable and of high accuracy, and can meet the engineering needs.

  8. Hidden dynamics in models of discontinuity and switching

    NASA Astrophysics Data System (ADS)

    Jeffrey, Mike R.

    2014-04-01

    Sharp switches in behaviour, like impacts, stick-slip motion, or electrical relays, can be modelled by differential equations with discontinuities. A discontinuity approximates fine details of a switching process that lie beyond a bulk empirical model. The theory of piecewise-smooth dynamics describes what happens assuming we can solve the system of equations across its discontinuity. What this typically neglects is that effects which are vanishingly small outside the discontinuity can have an arbitrarily large effect at the discontinuity itself. Here we show that such behaviour can be incorporated within the standard theory through nonlinear terms, and these introduce multiple sliding modes. We show that the nonlinear terms persist in more precise models, for example when the discontinuity is smoothed out. The nonlinear sliding can be eliminated, however, if the model contains an irremovable level of unknown error, which provides a criterion for systems to obey the standard Filippov laws for sliding dynamics at a discontinuity.

  9. Discontinuation of Buprenorphine Maintenance Therapy: Perspectives and Outcomes

    PubMed Central

    Bentzley, Brandon S.; Barth, Kelly S.; Back, Sudie E.; Book, Sarah W.

    2015-01-01

    Buprenorphine maintenance therapy (BMT) is increasingly the preferred opioid maintenance agent due to its reduced toxicity and availability in an office-based setting in the United States. Although BMT has been shown to be highly efficacious, it is often discontinued soon after initiation. No current systematic review has yet investigated providers’ or patients’ reasons for BMT discontinuation or the outcomes that follow. Hence, provider and patient perspectives associated with BMT discontinuation after a period of stable buprenorphine maintenance and the resultant outcomes were systematically reviewed with specific emphasis on pre-buprenorphine-taper parameters predictive of relapse following BMT discontinuation. Few identified studies address provider or patient perspectives associated with buprenorphine discontinuation. Within the studies reviewed providers with residency training in BMT were more likely to favor long term BMT instead of detoxification, and providers were likely to consider BMT discontinuation in the face of medication misuse. Patients often desired to remain on BMT because of fear of relapse to illicit opioid use if they were to discontinue BMT. The majority of patients who discontinued BMT did so involuntarily, often due to failure to follow strict program requirements, and 1 month following discontinuation, rates of relapse to illicit opioid use exceeded 50% in every study reviewed. Only lower buprenorphine maintenance dose, which may be a marker for attenuated addiction severity, predicted better outcomes across studies. Relaxed BMT program requirements and frequent counsel on the high probability of relapse if BMT is discontinued may improve retention in treatment and prevent the relapse to illicit opioid use that is likely to follow BMT discontinuation. PMID:25601365

  10. Premature trial discontinuation often not accurately reflected in registries: comparison of registry records with publications.

    PubMed

    Alturki, Reem; Schandelmaier, Stefan; Olu, Kelechi Kalu; von Niederhäusern, Belinda; Agarwal, Arnav; Frei, Roy; Bhatnagar, Neera; Hooft, Lotty; von Elm, Erik; Briel, Matthias

    2017-01-01

    One quarter of randomized clinical trials (RCTs) are prematurely discontinued and frequently remain unpublished. Trial registries can document whether a trial is ongoing, suspended, discontinued, or completed and therefore represent an important source for trial status information. The accuracy of this information is unclear. To examine the accuracy of completion status and reasons for discontinuation documented in trial registries as compared to corresponding publications of discontinued RCTs and to investigate potential predictors for accurate trial status information in registries. We conducted a cross-sectional study comparing information provided in publications (reference standard) to corresponding registry entries. First, we reviewed publications of RCTs providing information on both discontinuation and registration. We identified eligible publications through systematic searches of MEDLINE and EMBASE (2010-2014) and an international cohort of 1,017 RCTs initiated between 2000 and 2003. Second, pairs of investigators independently and in duplicate extracted data from publications and corresponding registry records. Third, for each discontinued RCT, we compared publication information to registry information. We used multivariable regression to examine whether accurate labeling of trials as discontinued (vs. other status) in the registry was associated with recent initiation of RCT, industry sponsorship, multicenter design, or larger sample size. We identified 173 publications of RCTs that were discontinued due to slow recruitment (55%), harm (16%), futility (11%), benefit (5%), other reasons (3%), or multiple reasons (9%). Trials were registered with clinicaltrials.gov (77%), isrctn.com (14%), or other registries (8%). Of the 173 corresponding registry records, 77 (45%) trials were labeled as discontinued and 57 (33%) provided a reason for discontinuation (of which 53, 93%, provided the same reason as in the publication). Labeling of discontinued trials as discontinued (vs. other label) in corresponding trial registry records improved over time (adjusted odds ratio 1.16 per year, confidence interval 1.04-1.30) and was possibly associated with industry sponsorship (2.01, 0.99-4.07) but unlikely with multicenter status (0.81, 0.32-2.04) or sample size (1.07, 0.89-1.29). Less than half of published discontinued RCTs were accurately labelled as discontinued in corresponding registry records. One-third of registry records provided a reason for discontinuation. Current trial status information in registries should be viewed with caution. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Factors Affecting Regression-Discontinuity.

    ERIC Educational Resources Information Center

    Schumacker, Randall E.

    The regression-discontinuity approach to evaluating educational programs is reviewed, and regression-discontinuity post-program mean differences under various conditions are discussed. The regression-discontinuity design is used to determine whether post-program differences exist between an experimental program and a control group. The difference…

  12. Risk of Vascular Thrombotic Events Following Discontinuation of Antithrombotics After Peptic Ulcer Bleeding.

    PubMed

    Kim, Seung Young; Hyun, Jong Jin; Suh, Sang Jun; Jung, Sung Woo; Jung, Young Kul; Koo, Ja Seol; Yim, Hyung Joon; Park, Jong Jae; Chun, Hoon Jai; Lee, Sang Woo

    2016-04-01

    To evaluate whether the risk of cardiovascular events increases when antithrombotics are discontinued after ulcer bleeding. Peptic ulcer bleeding associated with antithrombotics has increased due to the increase in the proportion of elderly population. Little is known about the long-term effects of discontinuing antithrombotics after peptic ulcer bleeding. The aim of this study was to evaluate whether the risk of cardiovascular events increases when antithrombotics are discontinued after ulcer bleeding. We reviewed the medical records of patients with ulcer bleeding who were taking antiplatelet agents or anticoagulants at the time of ulcer bleeding. Cox-regression model was used to adjust for potential confounders, and analyzed association between discontinuation of antithrombotic drugs after ulcer bleeding and thrombotic events such as ischemic heart disease or stroke. Of the 544 patients with ulcer bleeding, 72 patients who were taking antithrombotics and followed up for >2 months were analyzed. Forty patients discontinued antithrombotics after ulcer bleeding (discontinuation group) and 32 patients continued antithrombotics with or without transient interruption (continuation group). Thrombotic events developed more often in discontinuation group than in the continuation group [7/32 (21.9%) vs. 1/40 (2.5%), P=0.019]. Hazard ratio for thrombotic event when antithrombotics were continuously discontinued was 10.9 (95% confidence interval, 1.3-89.7). There were no significant differences in recurrent bleeding events between the 2 groups. Discontinuation of antithrombotics after peptic ulcer bleeding increases the risk of cardiovascular events. Therefore, caution should be taken when discontinuing antithrombotics after ulcer bleeding.

  13. Antipsychotic discontinuation syndromes: a narrative review of the evidence and its integration into Australian mental health nursing textbooks.

    PubMed

    Salomon, Carmela; Hamilton, Bridget

    2014-02-01

    In light of the high number of people discontinuing antipsychotics each year, it is essential that nurses develop a robust understanding of all aspects of the discontinuation experience. While there is a large body of published work documenting post-discontinuation relapse rates, less is known about other aspects of the discontinuation experience. This paper presents the results of a narrative review of international studies of antipsychotic discontinuation syndromes and their relevance to nursing practice. Four key mental health nursing textbooks used in student nurse education in Australia are examined to assess how this evidence has been incorporated into clinical recommendations. This review finds that the evidence for discontinuation syndromes could be more widely disseminated and applied than it is at present. Strikingly, this evidence has not been incorporated into key mental health nursing textbooks in Australia at all. Slow integration into nursing published work may be influenced by a number of clinical and research uncertainties. We consider the impact of this silence on key nursing roles of psycho-education and adverse event monitoring during antipsychotic discontinuation periods. Further robust research should be conducted into discontinuation syndromes as a matter of urgency. Given the high number of consumers potentially impacted upon by discontinuation syndromes, nurse authors and educators should consider revising key nursing textbooks to include the currently available information about discontinuation syndromes. © 2012 The Authors; International Journal of Mental Health Nursing © 2012 Australian College of Mental Health Nurses Inc.

  14. 38 CFR 21.5835 - Specific discontinuance dates.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... individual. If an individual dies— (1) VA will discontinue educational assistance effective the last day of... educational assistance. (2) VA will discontinue subsistence allowance effective the individual's last date of... in lieu of educational assistance, VA will discontinue educational assistance effective the date on...

  15. 38 CFR 21.5835 - Specific discontinuance dates.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... individual. If an individual dies— (1) VA will discontinue educational assistance effective the last day of... educational assistance. (2) VA will discontinue subsistence allowance effective the individual's last date of... in lieu of educational assistance, VA will discontinue educational assistance effective the date on...

  16. 38 CFR 21.5835 - Specific discontinuance dates.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... individual. If an individual dies— (1) VA will discontinue educational assistance effective the last day of... educational assistance. (2) VA will discontinue subsistence allowance effective the individual's last date of... in lieu of educational assistance, VA will discontinue educational assistance effective the date on...

  17. Hales discontinuity beneath India: selective appearance and a case for systematic modeling

    NASA Astrophysics Data System (ADS)

    Mitra, S.; Chaudhury, J.

    2016-12-01

    Hales discontinuity was first reported in Lake Superior at depth of 80-90 km, characterized by an increase in P-wave velocity from 8.05 to 8.45 km/s. Subsequent, worldwide studies have observed this discontinuity beneath selected continental regions and Pacific Ocean, with depth varying from 40 to 115 km. The cause for the absence of observable signal corresponding to the Hales discontinuity beneath a number of seismic stations and the large depth variation of the discontinuity are poorly understood. In the Indian subcontinent, the Hales discontinuity has been selectively imaged beneath the Southern Granulite Terrain, Eastern Dharwar, Bastar and Aravalli Cratons. These studies used low frequency P-wave receiver functions (P-RFs) to show that the Hales discontinuity corresponds to a PHs phase arriving between 7.5 and 11 s. A few studies have forwarded modeled this phase to demonstrate that this arrival is distinct from Moho reverberations and corresponds to a depth range of 75-90 km. However, these studies have ignored the effect of mid-crustal discontinuity, which had been observed in P-RF inverted crustal models beneath these stations, and its first reverberation coincide with the reported PHs. We demonstrate through forward modeling that the observed Hales discontinuity PHs can be matched by the PpPs from mid-crustal discontinuity beneath the cratons, with the exception of Hyderabad (HYB), where this discontinuity was reported to be deepest at 90 km. We perform joint inversion of the HYB P-RFs with Rayleigh wave dispersion to obtain a 32 km thick two layer crust, and Hales discontinuity at a depth of 108±2 km, with 4% increase in S-wave velocity from 4.6 to 4.8 km/s. Several mechanisms have been proposed to explain this velocity discontinuity, which include transition from spinel to garnet peridotite or changes in cation partitioning in olivine. We intend to evaluate the velocity increase based on thermoelasticity data of minerals constituting peridotite.

  18. Outpatient CPOE orders discontinued due to 'erroneous entry': prospective survey of prescribers' explanations for errors.

    PubMed

    Hickman, Thu-Trang T; Quist, Arbor Jessica Lauren; Salazar, Alejandra; Amato, Mary G; Wright, Adam; Volk, Lynn A; Bates, David W; Schiff, Gordon

    2018-04-01

    Computerised prescriber order entry (CPOE) systems users often discontinue medications because the initial order was erroneous. To elucidate error types by querying prescribers about their reasons for discontinuing outpatient medication orders that they had self-identified as erroneous. During a nearly 3 year retrospective data collection period, we identified 57 972 drugs discontinued with the reason 'Error (erroneous entry)." Because chart reviews revealed limited information about these errors, we prospectively studied consecutive, discontinued erroneous orders by querying prescribers in near-real-time to learn more about the erroneous orders. From January 2014 to April 2014, we prospectively emailed prescribers about outpatient drug orders that they had discontinued due to erroneous initial order entry. Of 2 50 806 medication orders in these 4 months, 1133 (0.45%) of these were discontinued due to error. From these 1133, we emailed 542 unique prescribers to ask about their reason(s) for discontinuing these mediation orders in error. We received 312 responses (58% response rate). We categorised these responses using a previously published taxonomy. The top reasons for these discontinued erroneous orders included: medication ordered for wrong patient (27.8%, n=60); wrong drug ordered (18.5%, n=40); and duplicate order placed (14.4%, n=31). Other common discontinued erroneous orders related to drug dosage and formulation (eg, extended release versus not). Oxycodone (3%) was the most frequent drug discontinued error. Drugs are not infrequently discontinued 'in error.' Wrong patient and wrong drug errors constitute the leading types of erroneous prescriptions recognised and discontinued by prescribers. Data regarding erroneous medication entries represent an important source of intelligence about how CPOE systems are functioning and malfunctioning, providing important insights regarding areas for designing CPOE more safely in the future. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. 27 CFR 40.331 - Discontinuance of operations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... operations. 40.331 Section 40.331 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... AND TUBES, AND PROCESSED TOBACCO Suspension and Discontinuance of Operations by Manufacturers § 40.331 Discontinuance of operations. Every manufacturer of tobacco products who desires to discontinue operations under...

  20. 41 CFR 109-39.105 - Discontinuance or curtailment of service.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... AVIATION, TRANSPORTATION, AND MOTOR VEHICLES 39-INTERAGENCY FLEET MANAGEMENT SYSTEMS 39.1-Establishment, Modification, and Discontinuance of Interagency Fleet Management Systems § 109-39.105 Discontinuance or... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Discontinuance or...

  1. Factors associated with discontinuation of aripiprazole treatment after switching from other antipsychotics in patients with chronic schizophrenia: A prospective observational study.

    PubMed

    Takaesu, Yoshikazu; Kishimoto, Taishiro; Murakoshi, Akiko; Takahashi, Nobutada; Inoue, Yuichi

    2016-02-28

    The purpose of the study was to identify factors associated with discontinuation of aripiprazole after switching from other antipsychotics in patients with schizophrenia in real world clinical settings. From January 2011 to December 2012, a prospective, 48-week open-label study was undertaken. Thirty-eight subjects on antipsychotic monotherapy were switched to aripiprazole. Patients who discontinued aripiprazole were compared to those who continued with regards to demographic characteristics as well as treatment factors. Multiple regression analysis was conducted to identify predictors for aripiprazole discontinuation. Thirteen out of 38 patients (34.2%) discontinued aripiprazole during the follow up period. Nine patients (23.7%) discontinued aripiprazole due to worsening of psychotic symptoms. Multiple logistic regression analysis revealed that only the duration of previous antipsychotic treatment was associated with aripiprazole discontinuation after switching to aripiprazole. The receiver operating curve (ROC) analysis identified that the cut-off length for duration of illness to predict aripiprazole discontinuation was 10.5 years. Longer duration of illness was associated with aripiprazole discontinuation. Greater caution may be required when treating such patients with aripiprazole. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Premature Discontinuation of Prospective Clinical Studies Approved by a Research Ethics Committee - A Comparison of Randomised and Non-Randomised Studies.

    PubMed

    Blümle, Anette; Schandelmaier, Stefan; Oeller, Patrick; Kasenda, Benjamin; Briel, Matthias; von Elm, Erik

    2016-01-01

    Premature discontinuation of clinical studies affects about 25% of randomised controlled trials (RCTs) which raises concerns about waste of scarce resources for research. The risk of discontinuation of non-randomised prospective studies (NPSs) is yet unclear. To compare the proportion of discontinued studies between NPSs and RCTs that received ethical approval. We systematically surveyed prospective longitudinal clinical studies that were approved by a single REC in Freiburg, Germany between 2000 and 2002. We collected study characteristics, identified subsequent publications, and surveyed investigators to elucidate whether a study was discontinued and, if so, why. Of 917 approved studies, 547 were prospective longitudinal studies (306 RCTs and 241 NPSs). NPSs were on average smaller than RCTs, more frequently single centre and pilot studies, and less frequently funded by industry. NPSs were less frequently discontinued than RCTs: 32/221 (14%) versus 78/288 (27%, p<0.001, missing data excluded). Poor recruitment was the most frequent reason for discontinuation in both NPSs (36%) and RCTs (37%). Compared to RCTs, NPSs were at lower risk for discontinuation. Measures to reliably predict, sustain, and stimulate recruitment could prevent discontinuation of many RCTs but also of some NPSs.

  3. Program Discontinuance: A Faculty Perspective Revisited. Adopted Fall 2012

    ERIC Educational Resources Information Center

    Academic Senate for California Community Colleges, 2012

    2012-01-01

    The 1998 Academic Senate for California Community Colleges paper Program Discontinuance: A Faculty Perspective presented issues of program discontinuance and addressed principles and key factors for effective faculty participation in the development of fair and equitable program discontinuance processes. In 2009, an Academic Senate resolution…

  4. An optimization-based approach for high-order accurate discretization of conservation laws with discontinuous solutions

    NASA Astrophysics Data System (ADS)

    Zahr, M. J.; Persson, P.-O.

    2018-07-01

    This work introduces a novel discontinuity-tracking framework for resolving discontinuous solutions of conservation laws with high-order numerical discretizations that support inter-element solution discontinuities, such as discontinuous Galerkin or finite volume methods. The proposed method aims to align inter-element boundaries with discontinuities in the solution by deforming the computational mesh. A discontinuity-aligned mesh ensures the discontinuity is represented through inter-element jumps while smooth basis functions interior to elements are only used to approximate smooth regions of the solution, thereby avoiding Gibbs' phenomena that create well-known stability issues. Therefore, very coarse high-order discretizations accurately resolve the piecewise smooth solution throughout the domain, provided the discontinuity is tracked. Central to the proposed discontinuity-tracking framework is a discrete PDE-constrained optimization formulation that simultaneously aligns the computational mesh with discontinuities in the solution and solves the discretized conservation law on this mesh. The optimization objective is taken as a combination of the deviation of the finite-dimensional solution from its element-wise average and a mesh distortion metric to simultaneously penalize Gibbs' phenomena and distorted meshes. It will be shown that our objective function satisfies two critical properties that are required for this discontinuity-tracking framework to be practical: (1) possesses a local minima at a discontinuity-aligned mesh and (2) decreases monotonically to this minimum in a neighborhood of radius approximately h / 2, whereas other popular discontinuity indicators fail to satisfy the latter. Another important contribution of this work is the observation that traditional reduced space PDE-constrained optimization solvers that repeatedly solve the conservation law at various mesh configurations are not viable in this context since severe overshoot and undershoot in the solution, i.e., Gibbs' phenomena, may make it impossible to solve the discrete conservation law on non-aligned meshes. Therefore, we advocate a gradient-based, full space solver where the mesh and conservation law solution converge to their optimal values simultaneously and therefore never require the solution of the discrete conservation law on a non-aligned mesh. The merit of the proposed method is demonstrated on a number of one- and two-dimensional model problems including the L2 projection of discontinuous functions, Burgers' equation with a discontinuous source term, transonic flow through a nozzle, and supersonic flow around a bluff body. We demonstrate optimal O (h p + 1) convergence rates in the L1 norm for up to polynomial order p = 6 and show that accurate solutions can be obtained on extremely coarse meshes.

  5. Delirium Associated With Fluoxetine Discontinuation: A Case Report.

    PubMed

    Fan, Kuang-Yuan; Liu, Hsing-Cheng

    Withdrawal symptoms on selective serotonin reuptake inhibitor (SSRI) discontinuation have raised clinical attention increasingly. However, delirium is rarely reported in the SSRI discontinuation syndrome. We report a case of delirium developing after fluoxetine discontinuation in a 65-year-old female patient with major depressive disorder. She experienced psychotic depression with limited response to treatment of fluoxetine 40 mg/d and quetiapine 100 mg/d for 3 months. After admission, we tapered fluoxetine gradually in 5 days because of its limited effect. However, delirious pictures developed 2 days after we stopped fluoxetine. Three days later, we added back fluoxetine 10 mg/d. Her delirious features gradually improved, and the clinical presentation turned into previous psychotic depression state. We gradually increased the medication to fluoxetine 60 mg/d and olanzapine 20 mg/d in the following 3 weeks. Her psychotic symptoms decreased, and there has been no delirious picture noted thereafter. Delirium associated with fluoxetine discontinuation is a much rarer complication in SSRI discontinuation syndrome. The symptoms of SSRI discontinuation syndrome may be attributable to a rapid decrease in serotonin availability. In general, the shorter the half-life of any medication, the greater the likelihood patients will experience discontinuation symptoms. Genetic vulnerability might be a potential factor to explain that SSRI discontinuation syndrome also occurred rapidly in people taking long-half-life fluoxetine. The genetic polymorphisms of both pharmacokinetic and pharmacodynamic pathways might be potentially associated with SSRI discontinuation syndrome.

  6. 40 CFR 159.167 - Discontinued studies.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Discontinued studies. 159.167 Section... Discontinued studies. The fact that a study has been discontinued before the planned termination must be reported to EPA, with the reason for termination, if submission of information concerning the study is, or...

  7. 40 CFR 159.167 - Discontinued studies.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Discontinued studies. 159.167 Section... Discontinued studies. The fact that a study has been discontinued before the planned termination must be reported to EPA, with the reason for termination, if submission of information concerning the study is, or...

  8. 47 CFR 1.764 - Discontinuance, reduction, or impairment of service.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Discontinuance, reduction, or impairment of... Applications Under Title II of Communications Act § 1.764 Discontinuance, reduction, or impairment of service... discontinuance, reduction, or impairment of service shall be made in the form and manner, with the number of...

  9. On one-sided filters for spectral Fourier approximations of discontinuous functions

    NASA Technical Reports Server (NTRS)

    Wei, Cai; Gottlieb, David; Shu, Chi-Wang

    1991-01-01

    The existence of one-sided filters, for spectral Fourier approximations of discontinuous functions, which can recover spectral accuracy up to discontinuity from one side, was proved. A least square procedure was also used to construct such a filter and test it on several discontinuous functions numerically.

  10. 27 CFR 478.127 - Discontinuance of business.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... business was located: Provided, however, Where State law or local ordinance requires the delivery of... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Discontinuance of business... Records § 478.127 Discontinuance of business. Where a licensed business is discontinued and succeeded by a...

  11. 27 CFR 46.138 - Discontinuance of business.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2012-04-01 2011-04-01 true Discontinuance of business. 46.138 Section 46.138 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU....138 Discontinuance of business. A dealer who for any reason discontinues business is not entitled to a...

  12. 27 CFR 46.138 - Discontinuance of business.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2014-04-01 2014-04-01 false Discontinuance of business. 46.138 Section 46.138 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU....138 Discontinuance of business. A dealer who for any reason discontinues business is not entitled to a...

  13. 27 CFR 31.162 - Discontinuance of business.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Discontinuance of business... and Reports § 31.162 Discontinuance of business. When a wholesale dealer in liquors who is required, under § 31.160, to file a monthly summary report discontinues business, a monthly summary report marked...

  14. Numerical Simulations of Shock Wave Refraction at Inclined Gas Contact Discontinuity

    ERIC Educational Resources Information Center

    Bulat, Pavel V.; Volkov, Konstantin N.

    2016-01-01

    When a shock wave interacts with a contact discontinuity, there may appear a reflected rarefaction wave, a deflected contact discontinuity and a refracted supersonic shock. The numerical simulation of shock wave refraction at a plane contact discontinuity separating gases with different densities is performed. Euler equations describing inviscid…

  15. 27 CFR 555.61 - Discontinuance of business or operations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Discontinuance of business... Permits § 555.61 Discontinuance of business or operations. Where an explosive materials business or operations is either discontinued or succeeded by a new owner, the owner of the business or operations...

  16. 21 CFR 314.91 - Obtaining a reduction in the discontinuance notification period.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG... manufacturer of certain products notifies FDA that it will discontinue manufacturing the product. The discontinuance notification period ends when manufacturing ceases. (b) When can FDA reduce the discontinuance...

  17. 21 CFR 314.91 - Obtaining a reduction in the discontinuance notification period.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG... manufacturer of certain products notifies FDA that it will discontinue manufacturing the product. The discontinuance notification period ends when manufacturing ceases. (b) When can FDA reduce the discontinuance...

  18. 21 CFR 314.91 - Obtaining a reduction in the discontinuance notification period.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG... manufacturer of certain products notifies FDA that it will discontinue manufacturing the product. The discontinuance notification period ends when manufacturing ceases. (b) When can FDA reduce the discontinuance...

  19. 21 CFR 314.91 - Obtaining a reduction in the discontinuance notification period.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG... manufacturer of certain products notifies FDA that it will discontinue manufacturing the product. The discontinuance notification period ends when manufacturing ceases. (b) When can FDA reduce the discontinuance...

  20. Contribution of strong discontinuities to the power spectrum of the solar wind.

    PubMed

    Borovsky, Joseph E

    2010-09-10

    Eight and a half years of magnetic field measurements (2(22) samples) from the ACE spacecraft in the solar wind at 1 A.U. are analyzed. Strong (large-rotation-angle) discontinuities in the solar wind are collected and measured. An artificial time series is created that preserves the timing and amplitudes of the discontinuities. The power spectral density of the discontinuity series is calculated and compared with the power spectral density of the solar-wind magnetic field. The strong discontinuities produce a power-law spectrum in the "inertial subrange" with a spectral index near the Kolmogorov -5/3 index. The discontinuity spectrum contains about half of the power of the full solar-wind magnetic field over this "inertial subrange." Warnings are issued about the significant contribution of discontinuities to the spectrum of the solar wind, complicating interpretation of spectral power and spectral indices.

  1. 77 FR 74736 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-17

    ... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... discontinuance or modification of a signal system. FRA assigned the petition docket number FRA-2012-0087... Street NE., Atlanta, Georgia 30309. NS seeks approval of the proposed discontinuance of automatic signals...

  2. 78 FR 11733 - Georgia Southwestern Railroad, Inc.-Discontinuance of Service Exemption-in Chattahoochee, Marion...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-19

    ... discontinue service, not to abandon the line, trail use/rail banking and public use conditions are not... No. AB 290 (Sub-No. 344X)] Georgia Southwestern Railroad, Inc.--Discontinuance of Service Exemption...--Discontinuance of Service Exemption--in Chattahoochee, Marion, and Schley Counties, GA Central of Georgia...

  3. 14 CFR 221.300 - Discontinuation of electronic tariff system.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Discontinuation of electronic tariff system... of electronic tariff system. In the event that the electronic tariff system is discontinued, or the source of the data is changed, or a filer discontinues its business, all electronic data records prior to...

  4. 14 CFR 221.300 - Discontinuation of electronic tariff system.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Discontinuation of electronic tariff system... of electronic tariff system. In the event that the electronic tariff system is discontinued, or the source of the data is changed, or a filer discontinues its business, all electronic data records prior to...

  5. 14 CFR 221.300 - Discontinuation of electronic tariff system.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Discontinuation of electronic tariff system... of electronic tariff system. In the event that the electronic tariff system is discontinued, or the source of the data is changed, or a filer discontinues its business, all electronic data records prior to...

  6. 14 CFR 221.300 - Discontinuation of electronic tariff system.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Discontinuation of electronic tariff system... of electronic tariff system. In the event that the electronic tariff system is discontinued, or the source of the data is changed, or a filer discontinues its business, all electronic data records prior to...

  7. Enhanced local tomography

    DOEpatents

    Katsevich, Alexander J.; Ramm, Alexander G.

    1996-01-01

    Local tomography is enhanced to determine the location and value of a discontinuity between a first internal density of an object and a second density of a region within the object. A beam of radiation is directed in a predetermined pattern through the region of the object containing the discontinuity. Relative attenuation data of the beam is determined within the predetermined pattern having a first data component that includes attenuation data through the region. In a first method for evaluating the value of the discontinuity, the relative attenuation data is inputted to a local tomography function .function..sub..LAMBDA. to define the location S of the density discontinuity. The asymptotic behavior of .function..sub..LAMBDA. is determined in a neighborhood of S, and the value for the discontinuity is estimated from the asymptotic behavior of .function..sub..LAMBDA.. In a second method for evaluating the value of the discontinuity, a gradient value for a mollified local tomography function .gradient..function..sub..LAMBDA..epsilon. (x.sub.ij) is determined along the discontinuity; and the value of the jump of the density across the discontinuity curve (or surface) S is estimated from the gradient values.

  8. Dynamics of Intense Currents in the Solar Wind

    NASA Astrophysics Data System (ADS)

    Artemyev, Anton V.; Angelopoulos, Vassilis; Halekas, Jasper S.; Vinogradov, Alexander A.; Vasko, Ivan Y.; Zelenyi, Lev M.

    2018-06-01

    Transient currents in the solar wind are carried by various magnetic field discontinuities that contribute significantly to the magnetic field fluctuation spectrum. Internal instabilities and dynamics of these discontinuities are believed to be responsible for magnetic field energy dissipation and corresponding charged particle acceleration and heating. Accurate modeling of these phenomena requires detailed investigation of transient current formation and evolution. By examining such evolution using a unique data set compiled from observations of the same solar wind flow by two spacecraft at Earth’s and Mars’s orbits, we show that it consists of several processes: discontinuity thinning (decrease in thickness normalized by the ion inertial length), intensification of currents normalized to the proton thermal current (i.e., the product of proton charge, density, and thermal velocity), and increase in the compressional component of magnetic field variations across discontinuities. The significant proton temperature variation around most observed discontinuities indicates possible proton heating. Plasma velocity jumps across the discontinuities are well correlated with Alfvén velocity changes. We discuss possible explanations of the observed discontinuity evolution. We also compare the observed evolution with predictions of models describing discontinuity formation due to Alfvén wave steepening. Our results show that discontinuity modeling likely requires taking into account both the effects of nonlinear Alfvén wave dynamics and solar wind expansion.

  9. Discontinuities in the shallow Martian crust at Lunae, Syria, and Sinai Plana

    USGS Publications Warehouse

    Davis, P.A.; Golombek, M.P.

    1990-01-01

    Detailed photoclinometric profiles across 125 erosional features and 141 grabens in the western equatorial region of Mars indicate the presence of three discontinuities within the shallow crust, at depths of 0.3, 0.6 km, 1 km, and 2-3 km. The shallowest discontinuity corresponds to thickness estimates for the ridged plains unit in this region, and thus the discontinuity probably is the contact between a sequence of layered rock making up this unit and the underlying megaregolith. The 1-km discontinuity is reflected in the base levels of erosion of all the features studied, and it may correspond to the base of the proposed layer of ground ice. Model calculations show that graben-bounding faults consistently intersect at the mechanical discontinuity at about 1 km depth. This discontinuity may represent an interface between ice-laden and dry regolith, ice-laden and water-laden regolith, or pristine and cemented regolith. A correlation between wall valley head depth and local thickness of the faulted layer suggests that the 1-km discontinuity also controlled the depth of the heads of sapping canyons. The third discontinuity, at a depth of 2-3 km, corresponds to the proposed base of the Martian megaregolith and is probably the interface between overlying, ejected breccia and in situ, fractured basement rocks. -from Authors

  10. Premature Discontinuation of Prospective Clinical Studies Approved by a Research Ethics Committee – A Comparison of Randomised and Non-Randomised Studies

    PubMed Central

    Oeller, Patrick; Kasenda, Benjamin; Briel, Matthias; von Elm, Erik

    2016-01-01

    Background Premature discontinuation of clinical studies affects about 25% of randomised controlled trials (RCTs) which raises concerns about waste of scarce resources for research. The risk of discontinuation of non-randomised prospective studies (NPSs) is yet unclear. Objectives To compare the proportion of discontinued studies between NPSs and RCTs that received ethical approval. Methods We systematically surveyed prospective longitudinal clinical studies that were approved by a single REC in Freiburg, Germany between 2000 and 2002. We collected study characteristics, identified subsequent publications, and surveyed investigators to elucidate whether a study was discontinued and, if so, why. Results Of 917 approved studies, 547 were prospective longitudinal studies (306 RCTs and 241 NPSs). NPSs were on average smaller than RCTs, more frequently single centre and pilot studies, and less frequently funded by industry. NPSs were less frequently discontinued than RCTs: 32/221 (14%) versus 78/288 (27%, p<0.001, missing data excluded). Poor recruitment was the most frequent reason for discontinuation in both NPSs (36%) and RCTs (37%). Conclusions Compared to RCTs, NPSs were at lower risk for discontinuation. Measures to reliably predict, sustain, and stimulate recruitment could prevent discontinuation of many RCTs but also of some NPSs. PMID:27792749

  11. Evaluation of Pump Discontinuation and Associated Factors in the T1D Exchange Clinic Registry

    PubMed Central

    Wong, Jenise C.; Boyle, Claire; DiMeglio, Linda A.; Mastrandrea, Lucy D.; Abel, Kimber-Lee; Cengiz, Eda; Cemeroglu, Pinar A.; Aleppo, Grazia; Largay, Joseph F.; Foster, Nicole C.; Beck, Roy W.; Adi, Saleh

    2017-01-01

    Background: The objectives of this study were to examine factors associated with insulin pump discontinuation among children and adults followed longitudinally for 1 year in the multicenter T1D Exchange clinic registry, and to provide participant-reported reasons for stopping pump therapy. Methods: We longitudinally followed 8935 participants of all ages using an insulin pump at the time of registry enrollment. Logistic regressions were used to identify demographic and clinical factors associated with pump discontinuation. Pump discontinuation was self-reported by participants on a first annual follow-up survey. Results: The overall frequency of pump discontinuation was 3%. Discontinuation was higher in adolescents (4%) and young adults (4%) than in younger children (3%) or older adults (1%). In multivariate analysis of children between 6 and <13 and 13 and <18 years, participants who discontinued pump use were more likely to have higher HbA1c levels at baseline (adjusted P < .001 for both). The top participant-reported reasons for discontinuing the pump included problems with wearability (57%), disliking the pump or feeling anxious (44%), and problems with glycemic control (30%). Conclusions: In T1D Exchange registry participants, insulin pump discontinuation is uncommon, but more prevalent among adolescents and young adults, and youth with poor glycemic control. Given the known benefits of pump therapy, these populations should be targeted for support and education on troubleshooting pump use. Common reasons for discontinuation should also be considered in future device design and technological improvement. PMID:27595711

  12. Evaluation of Pump Discontinuation and Associated Factors in the T1D Exchange Clinic Registry.

    PubMed

    Wong, Jenise C; Boyle, Claire; DiMeglio, Linda A; Mastrandrea, Lucy D; Abel, Kimber-Lee; Cengiz, Eda; Cemeroglu, Pinar A; Aleppo, Grazia; Largay, Joseph F; Foster, Nicole C; Beck, Roy W; Adi, Saleh

    2017-03-01

    The objectives of this study were to examine factors associated with insulin pump discontinuation among children and adults followed longitudinally for 1 year in the multicenter T1D Exchange clinic registry, and to provide participant-reported reasons for stopping pump therapy. We longitudinally followed 8935 participants of all ages using an insulin pump at the time of registry enrollment. Logistic regressions were used to identify demographic and clinical factors associated with pump discontinuation. Pump discontinuation was self-reported by participants on a first annual follow-up survey. The overall frequency of pump discontinuation was 3%. Discontinuation was higher in adolescents (4%) and young adults (4%) than in younger children (3%) or older adults (1%). In multivariate analysis of children between 6 and <13 and 13 and <18 years, participants who discontinued pump use were more likely to have higher HbA1c levels at baseline (adjusted P < .001 for both). The top participant-reported reasons for discontinuing the pump included problems with wearability (57%), disliking the pump or feeling anxious (44%), and problems with glycemic control (30%). In T1D Exchange registry participants, insulin pump discontinuation is uncommon, but more prevalent among adolescents and young adults, and youth with poor glycemic control. Given the known benefits of pump therapy, these populations should be targeted for support and education on troubleshooting pump use. Common reasons for discontinuation should also be considered in future device design and technological improvement.

  13. Longitudinal studies of botulinum toxin in cervical dystonia: Why do patients discontinue therapy?

    PubMed

    Jinnah, H A; Comella, Cynthia L; Perlmutter, Joel; Lungu, Codrin; Hallett, Mark

    2018-06-01

    Numerous studies have established botulinum toxin (BoNT) to be safe and effective for the treatment of cervical dystonia (CD). Despite its well-documented efficacy, there has been growing awareness that a significant proportion of CD patients discontinue therapy. The reasons for discontinuation are only partly understood. This summary describes longitudinal studies that provided information regarding the proportions of patients discontinuing BoNT therapy, and the reasons for discontinuing therapy. The data come predominantly from un-blinded long-term follow-up studies, registry studies, and patient-based surveys. All types of longitudinal studies provide strong evidence that BoNT is both safe and effective in the treatment of CD for many years. Overall, approximately one third of CD patients discontinue BoNT. The most common reason for discontinuing therapy is lack of benefit, often described as primary or secondary non-response. The apparent lack of response is only rarely related to true immune-mediated resistance to BoNT. Other reasons for discontinuing include side effects, inconvenience, cost, or other reasons. Although BoNT is safe and effective in the treatment of the majority of patients with CD, approximately one third discontinue. The increasing awareness of a significant proportion of patients who discontinue should encourage further efforts to optimize administration of BoNT, to improve BoNT preparations to extend duration or reduce side effects, to develop add-on therapies that may mitigate swings in symptom severity, or develop entirely novel treatment approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Mammographic density changes following discontinuation of tamoxifen in premenopausal women with oestrogen receptor-positive breast cancer.

    PubMed

    Kim, Won Hwa; Cho, Nariya; Kim, Young-Seon; Yi, Ann

    2018-04-06

    To evaluate the changes in mammographic density after tamoxifen discontinuation in premenopausal women with oestrogen receptor-positive breast cancers and the underlying factors METHODS: A total of 213 consecutive premenopausal women with breast cancer who received tamoxifen treatment after curative surgery and underwent three mammograms (baseline, after tamoxifen treatment, after tamoxifen discontinuation) were included. Changes in mammographic density after tamoxifen discontinuation were assessed qualitatively (decrease, no change, or increase) by two readers and measured quantitatively by semi-automated software. The association between % density change and clinicopathological factors was evaluated using univariate and multivariate regression analyses. After tamoxifen discontinuation, a mammographic density increase was observed in 31.9% (68/213, reader 1) to 22.1% (47/213, reader 2) by qualitative assessment, with a mean density increase of 1.8% by quantitative assessment compared to density before tamoxifen discontinuation. In multivariate analysis, younger age (≤ 39 years) and greater % density decline after tamoxifen treatment (≥ 17.0%) were independent factors associated with density change after tamoxifen discontinuation (p < .001 and p = .003, respectively). Tamoxifen discontinuation was associated with mammographic density change with a mean density increase of 1.8%, which was associated with younger age and greater density change after tamoxifen treatment. • Increased mammographic density after tamoxifen discontinuation can occur in premenopausal women. • Mean density increase after tamoxifen discontinuation was 1.8%. • Density increase is associated with age and density decrease after tamoxifen.

  15. Reasons for continuing or discontinuing olanzapine in the treatment of schizophrenia from the perspectives of patients and clinicians

    PubMed Central

    Chen, Jian; Ascher-Svanum, Haya; Nyhuis, Allen W; Case, Michael G; Phillips, Glenn A; Schuh, Kory J; Hoffmann, Vicki Poole

    2011-01-01

    Background The aim of this study was to assess the reasons for discontinuing or continuing olanzapine in patients with schizophrenia, from the perspectives of the patients and their clinicians. Methods The Reasons for Antipsychotic Discontinuation/Continuation (RAD) is a pair of questionnaires assessing these reasons from the perspectives of patients and their clinicians. Outpatients with schizophrenia (n = 199) who were not acutely ill participated in a 22-week open-label study of olanzapine from November 2006 to September 2008. Reasons for continuing or discontinuing olanzapine (on a five-point scale), along with the single most important reason and the top primary reasons, were identified. Concordance between reasons given by patients and clinicians was assessed. Results The top primary reasons for continuing olanzapine were patients’ perceptions of improvement, improvement of positive symptoms, and improved functioning. The study discontinuation rate was low (30.2%), and only a subset of patients who discontinued reported reasons for medication discontinuation. The top primary reasons for discontinuing olanzapine were insufficient improvement or worsening of positive symptoms, adverse events, and insufficient improvement or worsening of negative symptoms. Ratings given by patients and clinicians were highly concordant. Conclusion The main reason for continuing or discontinuing olanzapine appears to be medication efficacy, especially for positive symptoms. Reasons for medication discontinuation differ somewhat from reasons for continuation, with a high level of concordance between patient and clinician responses. PMID:22114469

  16. Discontinuation of tofacitinib after achieving low disease activity in patients with rheumatoid arthritis: a multicentre, observational study.

    PubMed

    Kubo, Satoshi; Yamaoka, Kunihiro; Amano, Koichi; Nagano, Shuji; Tohma, Shigeto; Suematsu, Eiichi; Nagasawa, Hayato; Iwata, Kanako; Tanaka, Yoshiya

    2017-08-01

    To determine whether tofacitinib can be discontinued in patients with RA who achieve low disease activity (LDA). RA patients with LDA after tofacitinib treatment in a phase III and long-term extension study were enrolled in this multicentre, non-randomized, open, prospective, observational study. The decision of discontinuation or continuation of tofacitinib was determined based on patient-physician decision making with informed consent. The primary endpoint was the proportion of patients who remained tofacitinib-free at post-treatment week 52. Clinical outcome was compared between those who continued and those who discontinued tofacitinib. The last observation carried forward method was used for patients who could not discontinue tofacitinib before week 52. Of 64 patients, 54 discontinued and 10 continued tofacitinib therapy. At post-treatment week 52, 20 of the 54 patients (37%) of the discontinuation group remained tofacitinib-free without disease flare. Disease activity at post-treatment week 52 was higher in the discontinuation group than the continuation group. Among the discontinuation group, the RF titre at baseline was significantly lower in patients who remained tofacitinib-free than those who did not (40 vs 113 U/ml). In fact, a higher proportion of patients with lower RF remained tofacitinib-free at week 52 compared with those with higher RF at baseline. In patients who could not achieve tofacitinib-free status, re-initiation of tofacitinib or other biologics improved disease activity. It is possible to discontinue tofacitinib without flare in about a third of patients with RA. A low RF predicts maintenance of LDA after discontinuation of tofacitinib. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  17. Cognitive function and discontinuation of adjuvant hormonal therapy in older breast cancer survivors: CALGB 369901 (Alliance).

    PubMed

    Bluethmann, Shirley M; Alfano, Catherine M; Clapp, Jonathan D; Luta, George; Small, Brent J; Hurria, Arti; Cohen, Harvey J; Sugarman, Steven; B Muss, Hyman; Isaacs, Claudine; Mandelblatt, Jeanne S

    2017-10-01

    To investigate the effects of cognitive function on discontinuation of hormonal therapy in breast cancer survivors ages 65+ ("older"). Older breast cancer survivors with invasive, non-metastatic disease, and no reported cognitive difficulties were recruited from 78 Alliance sites between 2004 and 2011. Eligible survivors (n = 1280) completed baseline interviews; follow-up was conducted annually for up to 7 years. Survivors with estrogen-receptor-positive (ER+) cancers who initiated hormonal therapy (n = 990) were included. Self-reported cognitive function was measured using the EORTC-QLQ30 scale; a difference of eight points on the 0-100 scale was considered clinically significant. Based on varying rates of discontinuation over time, discontinuation was evaluated separately for three time periods: early (<1 year); midpoint (1-3 years); and late discontinuation (>3-5 years). Cox models for each time period were used to evaluate the effects of cognition immediately preceding discontinuation, controlling for age, chemotherapy, and other covariates. Survivors were 65-91 years old (mean 72.6 years), and 79% had stages 1 or 2A disease. Overall, 43% discontinued hormonal therapy before 5 years. Survivors who reported lower cognitive function in the period before discontinuation had greater hazards of discontinuing therapy at the treatment midpoint (HR 1.22 per 8-point difference, CI 1.09-1.40, p < 0.001), considering covariates, but cognition was not related to discontinuation in the other periods. Self-reported cognitive problems were a significant risk factor for discontinuation of hormonal therapy 1-3 years post-initiation. Additional research is needed on the temporality of cognitive effects and hormonal therapy to support survivorship care needs of older survivors.

  18. Why do patients discontinue fertility treatment? A systematic review of reasons and predictors of discontinuation in fertility treatment.

    PubMed

    Gameiro, S; Boivin, J; Peronace, L; Verhaak, C M

    2012-01-01

    BACKGROUND Chances of achieving parenthood are high for couples who undergo fertility treatment. However, many choose to discontinue before conceiving. A systematic review was conducted to investigate patients' stated reasons for and predictors of discontinuation at five fertility treatment stages. METHODS Six databases were systematically searched. Search-terms referred to fertility treatment and discontinuation. Studies reporting on patients' stated reasons for or predictors of treatment discontinuation were included. A list of all reasons for discontinuation presented in each study was made, different categories of reasons were defined and the percentage of selections of each category was calculated. For each predictor, it was noted how many studies investigated it and how many found a positive and/or negative association with discontinuation. RESULTS The review included 22 studies that sampled 21 453 patients from eight countries. The most selected reasons for discontinuation were: postponement of treatment (39.18%, postponement of treatment or unknown 19.17%), physical and psychological burden (19.07%, psychological burden 14%, physical burden 6.32%), relational and personal problems (16.67%, personal reasons 9.27%, relational problems 8.83%), treatment rejection (13.23%) and organizational (11.68%) and clinic (7.71%) problems. Some reasons were common across stages (e.g. psychological burden). Others were stage-specific (e.g. treatment rejection during workup). None of the predictors reported were consistently associated with discontinuation. CONCLUSIONS Much longitudinal and theory led research is required to explain discontinuation. Meanwhile, treatment burden should be addressed by better care organization and support for patients. Patients should be well informed, have the opportunity to discuss values and worries about treatment and receive advice to decide about continuing treatment.

  19. Why do patients discontinue fertility treatment? A systematic review of reasons and predictors of discontinuation in fertility treatment

    PubMed Central

    Gameiro, S.; Boivin, J.; Peronace, L.; Verhaak, C.M.

    2012-01-01

    BACKGROUND Chances of achieving parenthood are high for couples who undergo fertility treatment. However, many choose to discontinue before conceiving. A systematic review was conducted to investigate patients' stated reasons for and predictors of discontinuation at five fertility treatment stages. METHODS Six databases were systematically searched. Search-terms referred to fertility treatment and discontinuation. Studies reporting on patients' stated reasons for or predictors of treatment discontinuation were included. A list of all reasons for discontinuation presented in each study was made, different categories of reasons were defined and the percentage of selections of each category was calculated. For each predictor, it was noted how many studies investigated it and how many found a positive and/or negative association with discontinuation. RESULTS The review included 22 studies that sampled 21 453 patients from eight countries. The most selected reasons for discontinuation were: postponement of treatment (39.18%, postponement of treatment or unknown 19.17%), physical and psychological burden (19.07%, psychological burden 14%, physical burden 6.32%), relational and personal problems (16.67%, personal reasons 9.27%, relational problems 8.83%), treatment rejection (13.23%) and organizational (11.68%) and clinic (7.71%) problems. Some reasons were common across stages (e.g. psychological burden). Others were stage-specific (e.g. treatment rejection during workup). None of the predictors reported were consistently associated with discontinuation. CONCLUSIONS Much longitudinal and theory led research is required to explain discontinuation. Meanwhile, treatment burden should be addressed by better care organization and support for patients. Patients should be well informed, have the opportunity to discuss values and worries about treatment and receive advice to decide about continuing treatment. PMID:22869759

  20. 77 FR 31429 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-25

    ... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... discontinuance or modification of a signal system. FRA assigned the petition Docket Number FRA-2012-0046... discontinuance of an automatic block signal (ABS) system and a traffic control signal (TCS) system on the...

  1. 47 CFR 63.505 - Contents of applications for any type of discontinuance, reduction, or impairment of telephone...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... discontinuance, reduction, or impairment of telephone service not specifically provided for in this part. 63.505... (CONTINUED) EXTENSION OF LINES, NEW LINES, AND DISCONTINUANCE, REDUCTION, OUTAGE AND IMPAIRMENT OF SERVICE BY...; Examples § 63.505 Contents of applications for any type of discontinuance, reduction, or impairment of...

  2. Effects of polyurethane matrices on fungal tannase and gallic acid production under solid state culture*

    PubMed Central

    Treviňo, Lucia; Contreras-Esquivel, Juan C.; Rodríguez-Herrera, Raul; Aguilar, Cristóbal Noé

    2007-01-01

    The influence of the physical structure of polyurethane matrix as a support in a solid state culture in tannase production and gallic acid accumulation by Aspergillus niger Aa-20 was evaluated. Three different polyurethane matrices were used as the support: continuous, semi-discontinuous and discontinuous. The highest tannase production at 2479.59 U/L during the first 12 h of culture was obtained using the discontinuous matrix. The gallic acid was accumulated at 7.64 g/L at the discontinuous matrix. The results show that the discontinuous matrix of polyurethane is better for tannase production and gallic acid accumulation in a solid state culture bioprocess than the continuous and semi-discontinuous matrices. PMID:17910122

  3. High Rate of Discontinuation May Diminish PrEP Coverage Among Young Men Who Have Sex with Men.

    PubMed

    Morgan, Ethan; Ryan, Daniel T; Newcomb, Michael E; Mustanski, Brian

    2018-05-04

    Understanding pre-exposure prophylaxis (PrEP) discontinuation is key to maximizing its effectiveness at the individual and population levels. Data came from the RADAR cohort study of MSM aged 16-29 years, 2015-2017. Participants included those who reported past 6-month PrEP use and discontinued its use by the interview date. Of the 197 participants who had used PrEP in the past 6 months, 65 discontinued use. Primary reasons for PrEP discontinuation included trouble getting to doctor's appointments (14, 21.5%) and issues related to insurance coverage or loss (13, 20.0%). Few (21%) who discontinued spoke to their doctor first, which has important implications for future long acting formulations.

  4. A comparison of discontinuation rates of tofacitinib and biologic disease-modifying anti-rheumatic drugs in rheumatoid arthritis: a systematic review and Bayesian network meta-analysis.

    PubMed

    Park, Sun-Kyeong; Lee, Min-Young; Jang, Eun-Jin; Kim, Hye-Lin; Ha, Dong-Mun; Lee, Eui-Kyung

    2017-01-01

    The purpose of this study was to compare the discontinuation rates of tofacitinib and biologics (tumour necrosis factor inhibitors (TNFi), abatacept, rituximab, and tocilizumab) in rheumatoid arthritis (RA) patients considering inadequate responses (IRs) to previous treatment(s). Randomised controlled trials of tofacitinib and biologics - reporting at least one total discontinuation, discontinuation due to lack of efficacy (LOE), and discontinuation due to adverse events (AEs) - were identified through systematic review. The analyses were conducted for patients with IRs to conventional synthetic disease-modifying anti-rheumatic drugs (cDMARDs) and for patients with biologics-IR, separately. Bayesian network meta-analysis was used to estimate rate ratio (RR) of a biologic relative to tofacitinib with 95% credible interval (CrI), and probability of RR being <1 (P[RR<1]). The analyses of 34 studies showed no significant differences in discontinuation rates between tofacitinib and biologics in the cDMARDs-IR group. In the biologics-IR group, however, TNFi (RR 0.17, 95% CrI 0.01-3.61, P[RR<1] 92.0%) and rituximab (RR 0.20, 95% CrI 0.01-2.91, P[RR<1] 92.3%) showed significantly lower total discontinuation rates than tofacitinib did. Despite the difference, discontinuation cases owing to LOE and AEs revealed that tofacitinib was comparable to the biologics. The comparability of discontinuation rate between tofacitinib and biologics was different based on previous treatments and discontinuation reasons: LOE, AEs, and total (due to other reasons). Therefore, those factors need to be considered to decide the optimal treatment strategy.

  5. Selective serotonin reuptake inhibitor discontinuation: side effects and other factors that influence medication adherence.

    PubMed

    Goethe, John W; Woolley, Stephen B; Cardoni, Alex A; Woznicki, Brenda A; Piez, Deborah A

    2007-10-01

    Patients with major depression discontinue taking their antidepressants for many reasons. Although side effects are often cited as the reason for discontinuation, few prospective studies have addressed this question, and none has specifically examined discontinuation in patients with severe depression. Inpatients and outpatients treated with a selective serotonin reuptake inhibitor for major depressive disorder were identified after admission. Three months later, patients were contacted and interviewed to determine antidepressant usage and the side effects experienced, including when these were experienced and their severity. Between October 2001 and April 2003, 406 English- or Spanish-speaking patients aged 18 to 75 years were followed up. One in 4 patients discontinued the index antidepressant. Among specific side effects noted, only "change in weight" and "anxiety" were significant predictors of discontinuation after controlling for confounders. Experiencing 1 or more "extremely" bothersome side effects was associated with more than a doubling of the risk of discontinuation, but the presence of side effects and side effects less severe than "extremely" bothersome were not significant predictors. There were no differences among selective serotonin reuptake inhibitor antidepressants in either the presence/absence of side effects or in the discontinuation rates. The results suggest that the contribution of side effects to antidepressant discontinuation is more complex than previously suggested. Disparate findings from earlier studies may reflect aspects of study design, such as examining populations whose severity of depression varied widely or not controlling for important confounding factors. Future research should separately examine high-risk groups (or control for severity of depression) and carefully rule out other potential contributors to discontinuation.

  6. Discontinuing Pneumocystis jirovecii Pneumonia Prophylaxis in HIV-Infected Patients With a CD4 Cell Count <200 cells/mm3.

    PubMed

    Sidhu, Vaninder K; Foisy, Michelle M; Hughes, Christine A

    2015-12-01

    To review the evidence for discontinuing primary and secondary Pneumocystis jirovecii pneumonia (PJP) prophylaxis in HIV-infected patients with a CD4 count <200 cells/mm(3). We conducted a literature search in MEDLINE, EMBASE, Cochrane Library, Google Scholar, and the International Aids Society Library (up to August 2015) using the following key search terms: Pneumocystis jirovecii, pneumonia, human immunodeficiency virus, primary prophylaxis, secondary prophylaxis, and discontinuation. All English-language studies that evaluated discontinuation of primary and/or secondary PJP prophylaxis in HIV-infected patients with CD4 count <200 cells/mm(3) were included. Five studies were identified, which varied in design, sample size, outcomes, and duration of follow-up. Three studies examined discontinuation of primary and secondary PJP prophylaxis; 1 study evaluated discontinuing primary PJP prophylaxis; and 1 study evaluated stopping secondary PJP prophylaxis. Two out of the 5 studies pooled data for all opportunistic infections. Overall, there was a low incidence of PJP among HIV-infected patients who discontinued primary PJP prophylaxis and were well controlled on antiretroviral therapy (ART). Discontinuation of primary PJP prophylaxis appears to be safe in patients on combination ART with a suppressed HIV viral load and a CD4 count >100 cells/mm(3). Additional data are needed to support the safety of discontinuing secondary PJP prophylaxis. Decisions to discontinue PJP prophylaxis in patients with a CD4 count <200 cells/mm(3) should be done on an individual patient basis, taking into consideration clinical factors, including ongoing adherence to ART. © The Author(s) 2015.

  7. Global Discontinuity Structure of the Mantle Transition Zone from Finite-Frequency Tomography of SS Precursors

    NASA Astrophysics Data System (ADS)

    Guo, Z.; Zhou, Y.

    2017-12-01

    We report global structure of the 410-km and 660-km discontinuities from finite-frequency tomography using frequency-dependent traveltime measurements of SS precursors recorded at the Global Seismological Network (GSN). Finite-frequency sensitivity kernels for discontinuity depth perturbations are calculated in the framework of traveling-wave mode coupling. We parametrize the global discontinuities using a set of spherical triangular grid points and solve the tomographic inverse problem based on singular value decomposition. Our global 410-km and 660-km discontinuity models reveal distinctly different characteristics beneath the oceans and subduction zones. In general, oceanic regions are associated with a thinner mantle transition zone and depth perturbations of the 410-km and 660-km discontinuities are anti-correlated, in agreement with a thermal origin and an overall warm and dry mantle beneath the oceans. The perturbations are not uniform throughout the oceans but show strong small-scale variations, indicating complex processes in the mantle transition zone. In major subduction zones (except for South America where data coverage is sparse), depth perturbations of the 410-km and 660-km discontinuities are correlated, with both the 410-km and the 660-km discontinuities occurring at greater depths. The distributions of the anomalies are consistent with cold stagnant slabs just above the 660-km discontinuity and ascending return flows in a superadiabatic upper mantle.

  8. Persistence of Antipsychotic Treatment in Elderly Dementia Patients: A Retrospective, Population-Based Cohort Study.

    PubMed

    Mast, Gavin; Fernandes, Kimberly; Tadrous, Mina; Martins, Diana; Herrmann, Nathan; Gomes, Tara

    2016-06-01

    Antipsychotics are commonly used to manage behavioral and psychological symptoms of dementia. Concerns over their safety and efficacy in this role have resulted in antipsychotics typically being recommended for short-term usage only when used among dementia patients. However, there is little work examining the duration of antipsychotic treatment in the elderly dementia patient population. To determine the persistence of use of antipsychotics in elderly dementia patients and the role of dose on therapy duration. A retrospective, population-based cohort study using administrative data, including dispensing records from a provincial public drug program, from Ontario, Canada between 2009 and 2012. Elderly dementia patients newly initiated onto antipsychotics were followed until drug discontinuation, death, 2-year follow-up, or end of study. Competing risk analysis was performed to determine time to discontinuation, stratified by categories of initial dose. After 2 years 49.1 % of the cohort ( N  = 22,927 of 46,695) had discontinued treatment. When stratified by dose, the high-dose group (51.1 % discontinued) discontinued more frequently than the medium- (48.7 % discontinued) and low- (47.5 % discontinued) dose groups ( p  < 0.0001). Approximately half of elderly dementia patients treated with antipsychotics discontinue within 2 years, with those on higher doses more likely to discontinue. However, the number of patients remaining on therapy represents a serious public health concern.

  9. FEMALE SEX AND DISCONTINUATION OF ISONIAZID DUE TO ADVERSE EFFECTS DURING THE TREATMENT OF LATENT TUBERCULOSIS

    PubMed Central

    Pettit, April C.; Bethel, James; Hirsch-Moverman, Yael; Colson, Paul W.; Sterling, Timothy R.

    2013-01-01

    SUMMARY Objectives To determine the rate of and risk factors for discontinuation of isoniazid due to adverse effects during the treatment of latent tuberculosis infection in a large, multi-site study. Methods The Tuberculosis Epidemiologic Studies Consortium (TBESC) conducted a prospective study from March 2007–September 2008 among adults initiating isoniazid for treatment of LTBI at 12 sites in the US and Canada. The relative risk for isoniazid discontinuation due to adverse effects was determined using negative binomial regression. Adjusted models were constructed using forward stepwise regression. Results Of 1,306 persons initiating isoniazid, 617 (47.2%, 95% CI 44.5–50.0%) completed treatment and 196 (15.0%, 95% CI 13.1–17.1%) discontinued due to adverse effects. In multivariable analysis, female sex (RR 1.67, 95% CI 1.32–2.10, p<0.001) and current alcohol use (RR 1.41, 95% CI 1.13–1.77, p=0.003) were independently associated with isoniazid discontinuation due to adverse effects. Conclusions The rate of discontinuation of isoniazid due to adverse effects was substantially higher than reported earlier. Women were at increased risk of discontinuing isoniazid due to adverse effects; close monitoring of women for adverse effects may be warranted. Current alcohol use was also associated with isoniazid discontinuation; counseling patients to abstain from alcohol could decrease discontinuation due to adverse effects. PMID:23845828

  10. Local Existence of MHD Contact Discontinuities

    NASA Astrophysics Data System (ADS)

    Morando, Alessandro; Trakhinin, Yuri; Trebeschi, Paola

    2018-05-01

    We prove the local-in-time existence of solutions with a contact discontinuity of the equations of ideal compressible magnetohydrodynamics (MHD) for two dimensional planar flows provided that the Rayleigh-Taylor sign condition {[partial p/partial N] <0 } on the jump of the normal derivative of the pressure is satisfied at each point of the initial discontinuity. MHD contact discontinuities are characteristic discontinuities with no flow across the discontinuity for which the pressure, the magnetic field and the velocity are continuous whereas the density and the entropy may have a jump. This paper is a natural completion of our previous analysis (Morando et al. in J Differ Equ 258:2531-2571, 2015) where the well-posedness in Sobolev spaces of the linearized problem was proved under the Rayleigh-Taylor sign condition satisfied at each point of the unperturbed discontinuity. The proof of the resolution of the nonlinear problem given in the present paper follows from a suitable tame a priori estimate in Sobolev spaces for the linearized equations and a Nash-Moser iteration.

  11. Generalized local emission tomography

    DOEpatents

    Katsevich, Alexander J.

    1998-01-01

    Emission tomography enables locations and values of internal isotope density distributions to be determined from radiation emitted from the whole object. In the method for locating the values of discontinuities, the intensities of radiation emitted from either the whole object or a region of the object containing the discontinuities are inputted to a local tomography function .function..sub..LAMBDA..sup.(.PHI.) to define the location S of the isotope density discontinuity. The asymptotic behavior of .function..sub..LAMBDA..sup.(.PHI.) is determined in a neighborhood of S, and the value for the discontinuity is estimated from the asymptotic behavior of .function..sub..LAMBDA..sup.(.PHI.) knowing pointwise values of the attenuation coefficient within the object. In the method for determining the location of the discontinuity, the intensities of radiation emitted from an object are inputted to a local tomography function .function..sub..LAMBDA..sup.(.PHI.) to define the location S of the density discontinuity and the location .GAMMA. of the attenuation coefficient discontinuity. Pointwise values of the attenuation coefficient within the object need not be known in this case.

  12. A Hyperspherical Adaptive Sparse-Grid Method for High-Dimensional Discontinuity Detection

    DOE PAGES

    Zhang, Guannan; Webster, Clayton G.; Gunzburger, Max D.; ...

    2015-06-24

    This study proposes and analyzes a hyperspherical adaptive hierarchical sparse-grid method for detecting jump discontinuities of functions in high-dimensional spaces. The method is motivated by the theoretical and computational inefficiencies of well-known adaptive sparse-grid methods for discontinuity detection. Our novel approach constructs a function representation of the discontinuity hypersurface of an N-dimensional discontinuous quantity of interest, by virtue of a hyperspherical transformation. Then, a sparse-grid approximation of the transformed function is built in the hyperspherical coordinate system, whose value at each point is estimated by solving a one-dimensional discontinuity detection problem. Due to the smoothness of the hypersurface, the newmore » technique can identify jump discontinuities with significantly reduced computational cost, compared to existing methods. In addition, hierarchical acceleration techniques are also incorporated to further reduce the overall complexity. Rigorous complexity analyses of the new method are provided as are several numerical examples that illustrate the effectiveness of the approach.« less

  13. Special discontinuities in nonlinearly elastic media

    NASA Astrophysics Data System (ADS)

    Chugainova, A. P.

    2017-06-01

    Solutions of a nonlinear hyperbolic system of equations describing weakly nonlinear quasitransverse waves in a weakly anisotropic elastic medium are studied. The influence of small-scale processes of dissipation and dispersion is investigated. The small-scale processes determine the structure of discontinuities (shocks) and a set of discontinuities with a stationary structure. Among the discontinuities with a stationary structure, there are special ones that, in addition to relations following from conservation laws, satisfy additional relations required for the existence of their structure. In the phase plane, the structure of such discontinuities is represented by an integral curve joining two saddles. Special discontinuities lead to nonunique self-similar solutions of the Riemann problem. Asymptotics of non-self-similar problems for equations with dissipation and dispersion are found numerically. These asymptotics correspond to self-similar solutions of the problems.

  14. Increments in plasma homovanillic acid concentrations after neuroleptic discontinuation are associated with worsening of schizophrenic symptoms.

    PubMed

    Khan, R S; Amin, F; Powchik, P; Knott, P; Goldstein, M; Apter, S; Kerman, B; Jaff, S; Davidson, M

    1990-01-01

    1. Thirty-two male schizophrenic patients participated in this study. 2. Plasma concentrations of the dopamine metabolite, homovanillic acid (pHVA) were assessed once on neuroleptic medication and twice a week for a maximum of six weeks after its discontinuation. 3. Psychiatric symptomatology was assessed once on neuroleptic medication and once a week for a maximum of six weeks after its discontinuation, using the brief psychiatric rating scale (BPRS). 4. pHVA and total BPRS score increased significantly after discontinuation of neuroleptic as compared to baseline. 5. The magnitude of pHVA and BPRS increments after discontinuation of neuroleptic correlated significantly. 6. Results of this study suggest that worsening of schizophrenic symptoms after discontinuation of neuroleptic treatment is associated with increased pHVA concentrations.

  15. An analysis of the personal reasons for discontinuing IUD use.

    PubMed

    Petta, C A; Amatya, R; Farr, G; Chi, I

    1994-10-01

    The objective of this study was to evaluate possible factors associated with discontinuing use of TCu 380A IUDs due to personal reasons among 2748 users. Overall, a total of 88 subjects discontinued using the TCu 380A IUD within 12 months postinsertion for personal reasons. The most common reasons were planned pregnancy (32%) and husband or family opinion against IUD use (26%). The gross cumulative 12-month life table discontinuation rate for all personal reasons was 4.0 per 100 women. Having no education and/or living in a rural area were the sociodemographic characteristics associated with an increased risk of discontinuation for personal reasons. Effective and regular counseling about IUD use, especially among illiterate women, may help prevent IUD discontinuations related to personal reasons.

  16. Hybridized Multiscale Discontinuous Galerkin Methods for Multiphysics

    DTIC Science & Technology

    2015-09-14

    discontinuous Galerkin method for the numerical solution of the Helmholtz equation , J. Comp. Phys., 290, 318–335, 2015. [14] N.C. NGUYEN, J. PERAIRE...approximations of the Helmholtz equation for a very wide range of wave frequencies. Our approach combines the hybridizable discontinuous Galerkin methodology...local approximation spaces of the hybridizable discontinuous Galerkin methods with precomputed phases which are solutions of the eikonal equation in

  17. What happens when people discontinue taking medications? Lessons from COMBINE.

    PubMed

    Stout, Robert L; Braciszewski, Jordan M; Subbaraman, Meenakshi Sabina; Kranzler, Henry R; O'Malley, Stephanie S; Falk, Daniel

    2014-12-01

    We use intensive longitudinal data methods to illuminate processes affecting patients' drinking in relation to the discontinuation of medications within an alcohol treatment study. Although previous work has focused on broad measures of medication adherence, we focus on dynamic changes in drinking both before and after patients discontinue. We conducted secondary data analyses using the COMBINE (Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence) study, focused on participants who discontinued medications prior to the planned end of treatment. Using an interrupted time-series analysis, we analysed drinking in the weeks before and after discontinuation and also studied outcomes at the end of the COMBINE follow-up. Unites States of America. We describe the subsample of COMBINE participants who discontinued medications (n = 450), and compare them with those who were medication-adherent (n = 559) and with those who discontinued but had substantial missing data (n = 217). The primary outcomes were percentage of days abstinent (PDA) and percentage of heavy drinking days (PHDD). Medication adherence data were used to approximate the date of discontinuation. For many patients, an increase in drinking began weeks before discontinuation (PDA: F(1,4803) = 19.07, P < 0.001; PHDD: F(1,4804) = 8.58, P = 0.003) then escalated at discontinuation (PDA: F(1,446) = 5.05, P = 0.025; PHDD: F(1,446) = 4.52, P = 0.034). Among other effects, the amount of change was moderated by the reason for discontinuation (e.g. adverse event; PDA: F(2,4803) = 3.85, P = 0.021; PHDD: F(2,4804) = 5.36, P = 0.005) and also whether it occurred in the first or second half of treatment (PDA: F(1,4803) = 5.23, P = 0.022; PHDD: F(1,4804) = 8.79, P = 0.003). A patient's decision to stop taking medications during alcohol treatment appears to take place during a weeks-long process of disengagement from treatment. Patients who discontinue medications early in treatment or without medical consultation appear to drink more frequently and more heavily. © 2014 Society for the Study of Addiction.

  18. Treatment, overall survival, and costs in patients with ALK-positive non-small-cell lung cancer after crizotinib monotherapy.

    PubMed

    Guérin, A; Sasane, M; Wakelee, H; Zhang, J; Culver, K; Dea, K; Nitulescu, R; Galebach, P; Macalalad, A R

    2015-08-01

    Limited post-crizotinib treatment options for ALK-positive non-small cell lung cancer (NSCLC) might lead to poor survival and high economic burden. To evaluate real-world treatment patterns, overall survival (OS), and costs following crizotinib discontinuation. This study used chart review and claims data. First, 27 participating US oncologists reviewed medical records of ALK-positive NSCLC patients who discontinued crizotinib monotherapy and reported patient demographic and clinical information, including post-crizotinib treatment and mortality. OS was estimated using Kaplan-Meier analyses. Second, three large administrative US claims databases were pooled. NSCLC patients were selected if they discontinued crizotinib monotherapy. Post-crizotinib costs were analyzed separately for patients who did or did not discontinue antineoplastic treatment after crizotinib monotherapy. All data were collected prior to ceritinib approval for this patient population. A total of 119 ALK-positive NSCLC patients discontinued crizotinib monotherapy. Upon discontinuation, 42% had no additional antineoplastic treatment and 13% received radiation therapy only. The median OS post-crizotinib was 61 days; patients with brain metastases had shorter OS than those who did not (44 vs. 69 days, P = 0.018), and patients without further antineoplastic treatment had shorter OS than those who did (17 vs. 180 days, P < 0.001). From claims data, 305 ALK-positive NSCLC patients discontinued crizotinib monotherapy. After discontinuation, 72% had no additional antineoplastic treatment. Among patients who continued antineoplastic treatment, monthly healthcare costs averaged $22,160, driven by pharmacy ($9202), inpatient ($6419), and outpatient radiotherapy ($2888) and imaging ($1179) costs. Among patients who discontinued any antineoplastic treatment, monthly healthcare costs averaged $3423, mostly driven by inpatient costs ($2074). After crizotinib monotherapy, most patients either received radiotherapy only or discontinued antineoplastic treatment altogether. OS after discontinuing crizotinib was poor and shorter among those with brain metastases than without, and among those without subsequent antineoplastic treatment than with. Patients who continued antineoplastic treatment incurred substantial healthcare costs.

  19. 27 CFR 25.277 - Discontinuance of operations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... BUREAU, DEPARTMENT OF THE TREASURY LIQUORS BEER Pilot Brewing Plants § 25.277 Discontinuance of operations. When operations of a pilot brewing plant are to be discontinued, the operator shall notify the...

  20. 27 CFR 25.277 - Discontinuance of operations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... BUREAU, DEPARTMENT OF THE TREASURY LIQUORS BEER Pilot Brewing Plants § 25.277 Discontinuance of operations. When operations of a pilot brewing plant are to be discontinued, the operator shall notify the...

  1. Discontinuation risk comparison among 'real-world' newly anticoagulated atrial fibrillation patients: Apixaban, warfarin, dabigatran, or rivaroxaban.

    PubMed

    Lip, Gregory Y H; Pan, Xianying; Kamble, Shital; Kawabata, Hugh; Mardekian, Jack; Masseria, Cristina; Phatak, Hemant

    2018-01-01

    Discontinuation of oral anticoagulants may expose non-valvular atrial fibrillation (NVAF) patients to an increased risk of stroke. This study describes the real-world discontinuation rates and compared the risk of drug discontinuation among NVAF patients initiating apixaban, warfarin, dabigatran, or rivaroxaban. This retrospective cohort study evaluated newly-anticoagulated NVAF patients in the MarketScan® data population from 01/01/2012 through 12/31/2014. Discontinuation was defined as a lack of subsequent prescription of the index drug within 30 days after the last supply day of the last prescription. A Cox model was used to estimate the hazard ratio (HR) of discontinuation, adjusted for age, sex, and comorbidities. Among 45,361 eligible NVAF patients, 15,461 (34.1%) initiated warfarin; 7,438 (16.4%) apixaban; 4,661 (10.3%) dabigatran; and 17,801 (39.2%) initiated rivaroxaban treatment. Compared to warfarin, patients who initiated dabigatran (adjusted HR [aHR]: 0.84, 95% confidence interval [CI]: 0.80-0.87, P<0.001), rivaroxaban (aHR: 0.70, 95% CI: 0.68-0.73, P<0.001), or apixaban (aHR: 0.57, 95% CI: 0.55-0.60, P<0.001) were 16%, 30%, and 43% less likely to discontinue treatment, respectively. When compared to apixaban, patients who initiated dabigatran (aHR: 1.46, 95% CI: 1.38-1.54, P<0.001) or rivaroxaban (aHR: 1.23, 95% CI: 1.17-1.28, P<0.001) were more likely to discontinue treatment. Among newly-anticoagulated NVAF patients in the real-world setting, initiation on rivaroxaban, dabigatran, or apixaban was associated with a significantly lower risk of discontinuation compared to warfarin. When compared to apixaban, patients who initiated treatment with warfarin, dabigatran, or rivaroxaban were more likely to discontinue treatment.

  2. Predictors of Discontinuation of Tumor Necrosis Factor Inhibitors in Patients with Rheumatoid Arthritis

    PubMed Central

    AGARWAL, SANDEEP K.; GLASS, ROBERTA J.; SHADICK, NANCY A.; COBLYN, JONATHAN S.; ANDERSON, RONALD J.; MAHER, NANCY E.; WEINBLATT, MICHAEL E.; SOLOMON, DANIEL H.

    2009-01-01

    Objective Tumor necrosis factor-α (TNF) inhibitors have transformed management of rheumatoid arthritis (RA); however, many patients discontinue TNF inhibitors. Our goal was to determine the discontinuation rate of TNF inhibitors and identify predictors associated with discontinuation. Methods Enrollees in the Brigham RA Sequential Study (BRASS) formed the eligible cohort. Patients reporting use of a TNF inhibitor with at least 6 months of followup were followed until reporting TNF inhibitor discontinuation or their last study visit if they continued therapy. Potential predictor variables, including demographic and clinical data assessed at baseline and 6 months prior to study endpoint, were identified using a Cox proportional regression. Results Among 961 patients in BRASS, 503 were using a TNF inhibitor with at least 6 months of followup in BRASS (mean length of followup 39 mo, SD 13). Two hundred ten patients (42%) reported discontinuation of TNF inhibitor. Higher physician global scores (hazard ratio 1.27, 95% CI 1.18–1.38) and RA Disease Activity Index scores (HR 1.13, 95% CI 1.05–1.22) 6 months prior to stopping the TNF inhibitor and higher number of TNF inhibitors used previously (HR 1.30, 95% CI 1.03–1.66) were associated with discontinuation of TNF inhibitor. Prior use of synthetic disease modifying antirheumatic drugs (HR 0.50, 95% CI 0.34–0.72) and more years of cumulative methotrexate use (HR 0.24, 95% CI 0.12–0.47) were inversely associated with discontinuation of TNF inhibitor. Conclusion These data demonstrate that a significant number of patients with RA discontinue TNF inhibitors. Several easily characterized clinical variables have a modest predictive association with reduced probability of TNF inhibitor discontinuation. PMID:18634159

  3. Impact of hypoglycemic events and HbA1c level on sulfonylurea discontinuation and down-titration.

    PubMed

    Laires, Pedro A; Tang, Jackson; Fan, Chun Po Steve; Li, Zhiyi; Qiu, Ying; Iglay, Kristy

    2017-04-01

    A retrospective cohort study using GE Centricity electronic medical records assessed the association between post-index hypoglycemia and HbA1c with discontinuation and down-titration of sulfonylureas among patients with Type 2 diabetes mellitus. Adult patients with an index prescription for a sulfonylurea and ≥12 months' continuous records pre- and post-index were eligible. Sulfonylurea discontinuation and down-titration was assessed 1-year post-index. Discontinuation occurred if the date of a prescription was >90 days from the preceding prescription plus days of supply. Down-titration occurred when a subsequent prescription was lower than the index dose. Cox regression assessed the association between post-index hypoglycemia and HbA1c with time to sulfonylurea discontinuation and down-titration, as well as other factors. 28,371 participants were included in the study; 13,459 (47.4%) were discontinuers, 717 (2.5%) were down-titraters, and 14,195 (50.0%) were continuers. 0.6% of continuers experienced hypoglycemia 1-year post-index, compared with 3.1% of down-titraters and 0.8% of discontinuers (p < 0.0001). Patients with post-index hypoglycemia had a significantly higher rate of discontinuation (hazard ratio [HR] = 1.82, 95% CI: 1.47-2.23) and down-titration (HR = 4.25, 95% CI: 1.92-8.03). Patients with higher post-index HbA1c and use of 2 nd generation sulfonylureas had an increased rate of discontinuation (HR = 1.05, 95% CI: 1.04-1.06; HR = 1.19, 95% CI: 1.14-1.24, respectively). Approximately half of participants who initiated sulfonylureas discontinued or down-titrated therapy within one year. Both post-index hypoglycemia and higher HbA1c were significant risk factors for sulfonylurea treatment change.

  4. Reasons and predictors of discontinuation of running after a running program for novice runners.

    PubMed

    Fokkema, Tryntsje; Hartgens, Fred; Kluitenberg, Bas; Verhagen, Evert; Backx, Frank J G; van der Worp, Henk; Bierma-Zeinstra, Sita M A; Koes, Bart W; van Middelkoop, Marienke

    2018-06-18

    To determine the proportion of participants of a running program for novice runners that discontinued running and investigate the main reasons to discontinue and characteristics associated with discontinuation. Prospective cohort study. The study included 774 participants of Start to Run, a 6-week running program for novice runners. Before the start of the program, participants filled-in a baseline questionnaire to collect information on demographics, physical activity and perceived health. The 26-weeks follow-up questionnaire was used to obtain information on the continuation of running (yes/no) and main reasons for discontinuation. To determine predictors for discontinuation of running, multivariable logistic regression was performed. Within 26 weeks after the start of the 6-week running program, 29.5% of the novice runners (n=225) had stopped running. The main reason for discontinuation was a running-related injury (n=108, 48%). Being female (OR 1.74; 95% CI 1.13-2.68), being unsure about the continuation of running after the program (OR 2.06; 95% CI 1.31-3.24) and (almost) no alcohol use (OR 1.62; 95%CI 1.11-2.37) were associated with a higher chance of discontinuation of running. Previous running experience less than one year previously (OR 0.46; 95% CI 0.26-0.83) and a higher score on the RAND-36 subscale physical functioning (OR 0.98; 95% CI 0.96-0.99) were associated with a lower chance of discontinuation. In this group of novice runners, almost one-third stopped running within six months. A running-related injury was the main reason to stop running. Women with a low perceived physical functioning and without running experience were prone to discontinue running. Copyright © 2018. Published by Elsevier Ltd.

  5. Resistive dissipation and magnetic field topology in the stellar corona

    NASA Technical Reports Server (NTRS)

    Parker, E. N.

    1993-01-01

    Tangential discontinuities, or current sheets, in a magnetic field embedded in a fluid with vanishing resistivity are created by discontinuous fluid motion. Tangential discontinuities are also created when a magnetic field is allowed to relax to magnetostatic equilibrium after mixing by fluid motions (either continuous or discontinuous) into any but the simplest topologies. This paper shows by formal examples that the current sheets arising solely from discontinuous fluid motions do not contribute significantly to the dissipation of magnetic free energy when a small resistivity is introduced. Dissipation that is significant under coronal conditions occurs only by rapid reconnection, which arises when, and only when, the current sheets are required by the field topology. Hence it is topological dissipation that is primarily responsible for heating tenuous coronal gases in astronomical settings, whether the fluid displacements of the field are continuous or discontinuous.

  6. Substructures of the mantle transition-zone discontinuities and compositional heterogeneities in the mid-mantle

    NASA Astrophysics Data System (ADS)

    Wei, S. S.; Shearer, P. M.

    2017-12-01

    The mantle transition-zone discontinuities are usually attributed to isochemical phase transformations of olivine and its high-pressure polymorphs. However, recent seismic observations have shown complexities in these discontinuities that cannot be explained by conventional models of thermal variations. Here we analyse SS precursor stacking results to investigate global mantle transition-zone properties. The precursor waveforms provide information on the seismic velocity and density profiles across and near the major mantle discontinuities. A sporadic low-velocity layer immediately above the 410-km discontinuity is observed worldwide, including East Asia, western North America, eastern South America, and 33-50% of the resolved Pacific Ocean. The 520-km discontinuity exhibits significant variations in its sharpness and depth, and occasionally appears to be split. Structures underlying the 660-km discontinuity show even larger complexities: a sub-discontinuity at 700-800 km depth is detected in some regions, of which some require a positive velocity gradient whereas others have a negative gradient. All of these lateral variations show no geographical correlation with discontinuity topography or tomographic models of seismic velocity, suggesting that they are not caused by regional thermal anomalies. Alternatively, our observations can be explained by compositional heterogeneities in the mid-mantle, including major minerals and volatile content, which may result in additional phase transformations and partial melting. These compositional heterogeneities should be taken into account in future geodynamic models of mantle convection and the deep water cycle.

  7. Identifying the factors underlying discontinuation of triptans.

    PubMed

    Wells, Rebecca E; Markowitz, Shira Y; Baron, Eric P; Hentz, Joseph G; Kalidas, Kavita; Mathew, Paul G; Halker, Rashmi; Dodick, David W; Schwedt, Todd J

    2014-02-01

    To identify factors associated with triptan discontinuation among migraine patients. It is unclear why many migraine patients who are prescribed triptans discontinue this treatment. This study investigated correlates of triptan discontinuation with a focus on potentially modifiable factors to improve compliance. This multicenter cross-sectional survey (n = 276) was performed at US tertiary care headache clinics. Headache fellows who were members of the American Headache Society Headache Fellows Research Consortium recruited episodic and chronic migraine patients who were current triptan users (use within prior 3 months and for ≥1 year) or past triptan users (no use within 6 months; prior use within 2 years). Univariate analyses were first completed to compare current triptan users to past users for: migraine characteristics, other migraine treatments, triptan education, triptan efficacy, triptan side effects, type of prescribing provider, Migraine Disability Assessment (MIDAS) scores and Beck Depression Inventory (BDI) scores. Then, a multivariable logistic regression model was selected from all possible combinations of predictor variables to determine the factors that best correlated with triptan discontinuation. Compared with those still using triptans (n = 207), those who had discontinued use (n = 69) had higher rates of medication overuse (30 vs. 18%, P = .04) and were more likely to have ever used opioids for migraine treatment (57 vs. 38%, P = .006) as well as higher MIDAS (mean 63 vs. 37, P = .001) and BDI scores (mean 10.4 vs. 7.4, P = .009). Compared with discontinued users, current triptan users were more likely to have had their triptan prescribed by a specialist (neurologist, headache specialist, or pain specialist) (74 vs. 54%, P = .002) and were more likely to report headache resolution (53 vs. 14%, P < .001) or a reduction in pain intensity (71 vs. 28%, P < .001) most of the time from their triptan. On a 1-5 scale (1 = disagree, 5 = agree), triptan users felt they had more: control over their migraine attacks (2.9 vs. 2.1), confidence in their prescribing provider (4.5 vs. 4.0), and were more educated about triptan use (4.2 vs. 3.7) compared with triptan discontinuers (P < .001 for all comparisons). Although both current and prior users reported similar rates of side effects (48 vs. 43%, P = .44), of those who discontinued use, the main reasons were for lack of effect (44%) and side effects (29%). Our multivariable modeling revealed that the strongest correlate of triptan discontinuation was lack of efficacy (odds ratio = 17, 95% confidence interval [8.8, 33.0]). Other factors associated with discontinuation included MIDAS > 24 (2.6, [1.5, 4.6]), BDI >4 (2.5, [1.4, 4.5]), and a history of ever using opioids for migraine therapy (2.2, [1.3, 3.8]). Having a triptan prescribed by a specialist and using at least 1 other abortive medication with the triptan were associated with a decreased likelihood of triptan discontinuation (0.41, [0.2-0.7] and 0.44 [0.3, 0.8], respectively). As expected, discontinuation was most correlated with lack of efficacy, but other important factors associated with those who had discontinued use included greater migraine-related disability, depression, and the use of opioids for migraine attacks. Compared with patients who had discontinued triptans, current triptan users felt more: educated about their triptan, control over their migraine attacks, and confidence in their prescribing provider. Current triptan users had their triptan prescribed by a specialist and used other abortive medications with their triptan more often compared with patients who had discontinued triptans. Given the cross-sectional nature of this study, we cannot determine if these factors contributed to triptan discontinuation or reflect the impact of such discontinuation. Interventions that address modifiable risk factors for triptan discontinuation may decrease the likelihood of triptan discontinuation and thus improve overall migraine control. Because lack of efficacy was most strongly associated with triptan discontinuation, future research should determine why triptans are effective for some patients but not others. © 2013 American Headache Society.

  8. Waiting-time distributions of magnetic discontinuities: clustering or Poisson process?

    PubMed

    Greco, A; Matthaeus, W H; Servidio, S; Dmitruk, P

    2009-10-01

    Using solar wind data from the Advanced Composition Explorer spacecraft, with the support of Hall magnetohydrodynamic simulations, the waiting-time distributions of magnetic discontinuities have been analyzed. A possible phenomenon of clusterization of these discontinuities is studied in detail. We perform a local Poisson's analysis in order to establish if these intermittent events are randomly distributed or not. Possible implications about the nature of solar wind discontinuities are discussed.

  9. 78 FR 68146 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-13

    ..., GA 30309. NS seeks approval of the proposed discontinuance of Control Point (CP) Oak and the discontinuance of the traffic control system (TCS) between CP Maumee, Milepost (MP) DY 1.2/CD 287.65, and Stanley... discontinued on the Oakdale Connection Track between CP 286, MP XA 286.90/CD 286.75, and CP Oak, MP XA 287.80...

  10. Waiting-time distributions of magnetic discontinuities: Clustering or Poisson process?

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Greco, A.; Matthaeus, W. H.; Servidio, S.

    2009-10-15

    Using solar wind data from the Advanced Composition Explorer spacecraft, with the support of Hall magnetohydrodynamic simulations, the waiting-time distributions of magnetic discontinuities have been analyzed. A possible phenomenon of clusterization of these discontinuities is studied in detail. We perform a local Poisson's analysis in order to establish if these intermittent events are randomly distributed or not. Possible implications about the nature of solar wind discontinuities are discussed.

  11. Severe disease exacerbations in patients with multiple sclerosis after discontinuing fingolimod.

    PubMed

    Członkowska, Anna; Smoliński, Łukasz; Litwin, Tomasz

    Discontinuation of fingolimod in patients with multiple sclerosis (MS) can lead to disease reactivation. In this review, we describe cases of severe exacerbations in patients with MS following discontinuation of fingolimod, including three cases from our center. We consider potential mechanisms of disease reactivation after cessation of fingolimod, and the evidence supporting this rebound effect. We conclude that discontinuation of fingolimod results in the return of disease activity, which then leads to severe exacerbations (i.e., rebounds) in a clinically significant proportion of patients. Lastly, we consider disease-modifying treatment options for patients who discontinue fingolimod. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

  12. On a direct connection of the transition metal impurity levels to the band edge discontinuities in semiconductor heterojunctions

    NASA Astrophysics Data System (ADS)

    Langer, Jerzy M.; Heinrich, Helmut

    1985-11-01

    Our recent proposal of using the transition metal impurity levels to predict the isovalent heterojunction (HJ) band-edge discontinuities is further discussed. It is shown that for Ga 1-xAl xAs/GaAs heterojunctions most of the recent discontinuity data follow within experimental error the prediction of the ΔE cb: ΔE vb= 0.64:0.36 discontinuity ratio derived from the Fe 2+ level position in Ga 1-xAl xAs compound. Predictions of valence-band discontinuities for the other III-V and II-VI HJ systems are also given.

  13. Hyperspherical Sparse Approximation Techniques for High-Dimensional Discontinuity Detection

    DOE PAGES

    Zhang, Guannan; Webster, Clayton G.; Gunzburger, Max; ...

    2016-08-04

    This work proposes a hyperspherical sparse approximation framework for detecting jump discontinuities in functions in high-dimensional spaces. The need for a novel approach results from the theoretical and computational inefficiencies of well-known approaches, such as adaptive sparse grids, for discontinuity detection. Our approach constructs the hyperspherical coordinate representation of the discontinuity surface of a function. Then sparse approximations of the transformed function are built in the hyperspherical coordinate system, with values at each point estimated by solving a one-dimensional discontinuity detection problem. Due to the smoothness of the hypersurface, the new technique can identify jump discontinuities with significantly reduced computationalmore » cost, compared to existing methods. Several approaches are used to approximate the transformed discontinuity surface in the hyperspherical system, including adaptive sparse grid and radial basis function interpolation, discrete least squares projection, and compressed sensing approximation. Moreover, hierarchical acceleration techniques are also incorporated to further reduce the overall complexity. In conclusion, rigorous complexity analyses of the new methods are provided, as are several numerical examples that illustrate the effectiveness of our approach.« less

  14. Contraceptive discontinuation and switching among Ghanaian women: evidence from the Ghana Demographic and Health Survey, 2008.

    PubMed

    Modey, Emefa J; Aryeetey, Richmond; Adanu, Richard

    2014-03-01

    This study identifies factors associated with contraceptive discontinuation and switching among Ghanaian women of reproductive age, using data from 1,378 female respondents of the 2008 Ghana Demographic and Health Survey. Logistic regression models were used to determine relationships between key socio-demographic factors and user status. Discontinued use occurred among 56% of ever users and switching among 55% of current users. The IUD was most abandoned (70%) and its use was associated with almost twice the odds of discontinuation (OR = 1.97; 95% CI (1.04, 3.75)). Having a history of terminated pregnancy significantly predicted both discontinuation (OR = 1.36; 95% CI (1.03, 1.79) and switching (OR = 1.78; 95% CI (1.16, 2.73)) and intention to limit births significantly predicted lower discontinuation (OR = 0.71; 95% CI (0.52, 0.96)). Counseling services emphasizing contraceptive options and reinforcing switching are critically needed to reduce unwanted pregnancies that may result from poor method use and discontinuation especially among post-abortion clients and IUD users.

  15. Physicians' reasons not to discontinue long-term used off-label antipsychotic drugs in people with intellectual disability.

    PubMed

    de Kuijper, G M; Hoekstra, P J

    2017-10-01

    People with intellectual disability (ID) frequently use antipsychotic drugs on an off-label base, often for many years. Physicians' decisions to discontinue these drugs not only depend on patient characteristics, like the presence of mental or behavioural disorders, but also on environmental factors, such as inappropriate living circumstances, and on attitudes, knowledge and beliefs of staff, clients and their representatives towards the effects of antipsychotic drug use. In this study, we therefore investigated the influence of participant and setting-related factors on decisions of physicians not to discontinue off-label prescribed antipsychotics. The study took place in living facilities of six service providers for people with ID spread over the Netherlands and staffed with support professionals, nurses, behavioural scientist and physicians and was part of an antipsychotics discontinuation trial. ID physicians had to decide whether the off-label use of antipsychotics could be discontinued. Medical and pharmaceutical records were used to establish the prevalence of antipsychotic drug use in the study population, along with duration of use and whether the use was off-label. Reasons of physicians not to discontinue the prescription of antipsychotics in those participants who used off-label antipsychotics for more than a year were collected and categorised as related to participant or setting characteristics, including lack of consent to discontinue, and staff members, participants or their legal representatives. Of the 3299 clients of the service providers, 977 used one or more antipsychotic drugs. The prevalence of antipsychotic drug use was 30%. Reasons for use were in 5% of cases, a chronic psychotic disorder classified according to Diagnostic System Mental Disorders, Fourth Edition, criteria, in 25%, present or past (suspected) non-schizophrenia-related psychotic symptoms and in 69%, challenging behaviours. Overall, physicians were willing to discontinue their prescriptions in 51% of cases, varying from 22% to 87% per service provider. The odds for decisions of physicians to discontinue off-label prescriptions varied from 0.19 to 13.95 per service provider. The variables 'a living situation with care and support' and 'challenging behaviour' were associated with a higher chance of discontinuation. The main reasons for decisions not to discontinue were concerns for symptoms of restlessness, the presence of an autism spectrum disorder, previously unsuccessful attempts to discontinue and objections against discontinuation of legal representatives. Reasons for physicians' decisions not to discontinue the off-label use of antipsychotics varied largely between the service providers. The prevalence of antipsychotic drug use for off-label indications in people with ID remains high. The results of this study indicate that there is a large variation in clinical practice of physicians regarding discontinuation of long-term antipsychotic drug prescriptions, which may be partially related to environmental factors as setting culture and attitudes of staff towards off-label antipsychotic drug use in persons with ID. © 2017 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

  16. A Fourier spectral-discontinuous Galerkin method for time-dependent 3-D Schrödinger-Poisson equations with discontinuous potentials

    NASA Astrophysics Data System (ADS)

    Lu, Tiao; Cai, Wei

    2008-10-01

    In this paper, we propose a high order Fourier spectral-discontinuous Galerkin method for time-dependent Schrödinger-Poisson equations in 3-D spaces. The Fourier spectral Galerkin method is used for the two periodic transverse directions and a high order discontinuous Galerkin method for the longitudinal propagation direction. Such a combination results in a diagonal form for the differential operators along the transverse directions and a flexible method to handle the discontinuous potentials present in quantum heterojunction and supperlattice structures. As the derivative matrices are required for various time integration schemes such as the exponential time differencing and Crank Nicholson methods, explicit derivative matrices of the discontinuous Galerkin method of various orders are derived. Numerical results, using the proposed method with various time integration schemes, are provided to validate the method.

  17. A Floating Node Method for the Modelling of Discontinuities Within a Finite Element

    NASA Technical Reports Server (NTRS)

    Pinho, Silvestre T.; Chen, B. Y.; DeCarvalho, Nelson V.; Baiz, P. M.; Tay, T. E.

    2013-01-01

    This paper focuses on the accurate numerical representation of complex networks of evolving discontinuities in solids, with particular emphasis on cracks. The limitation of the standard finite element method (FEM) in approximating discontinuous solutions has motivated the development of re-meshing, smeared crack models, the eXtended Finite Element Method (XFEM) and the Phantom Node Method (PNM). We propose a new method which has some similarities to the PNM, but crucially: (i) does not introduce an error on the crack geometry when mapping to natural coordinates; (ii) does not require numerical integration over only part of a domain; (iii) can incorporate weak discontinuities and cohesive cracks more readily; (iv) is ideally suited for the representation of multiple and complex networks of (weak, strong and cohesive) discontinuities; (v) leads to the same solution as a finite element mesh where the discontinuity is represented explicitly; and (vi) is conceptually simpler than the PNM.

  18. Reasons for discontinuation of subcutaneous interferon β-1a three times a week among patients with multiple sclerosis: a real-world cohort study.

    PubMed

    Sabidó-Espin, Meritxell; Munschauer, Rick

    2017-03-23

    Continuation of interferon (IFN) β-based therapies is important for maximum treatment effectiveness in patients with multiple sclerosis (MS); however, few real-world data are available on discontinuation from IFN β. The aim of this cohort analysis was to estimate real-world discontinuation rates up to 3 years among MS patients in the United States taking subcutaneous (sc) IFN β-1a three times a week (tiw) and to identify whether the factors associated with discontinuation change over time. Patient data were pooled from the MarketScan © Commercial and Medicare Supplemental healthcare claims databases. Patients with ≥1 multiple sclerosis diagnosis who were sc IFN β-1a tiw naïve, had ≥1 year of continuous eligibility before treatment, and ≥1 prescription were followed from first prescription (index date) until date of discontinuation, switch, or end of observation. Treatment status was analysed at exactly 1, 2 or 3 years after index. Multivariable models were used to identify drivers of discontinuation. Data from 5956 patients were included; 2862 patients (48.1%) discontinued therapy. Discontinuation rates were 36.9% (1 year), 49.5% (2 years) and 55.8% (3 years). A greater proportion of discontinuing patients had poor adherence (<80% [94.0%] versus ≥80% [51.7%]) or were taking additional medication at follow-up versus the overall population. Factors independently associated with discontinuation irrespective of time on therapy were increasing number of magnetic resonance imaging scans (1 year adjusted odds ratio 1.45, 95% confidence interval 1.26-1.67; 2 years 1.18, 1.06-1.32; 3 years 1.20, 1.07-1.34) and adherence <80% versus ≥80% (1 year 180.95, 135.84-241.03; 2 years 135.80, 100.10-184.23; 3 years 174.89, 115.27-265.38). Factors associated only with early discontinuation (at 1 year) were ≥3 sets of laboratory investigations versus none (2.54, 1.20-5.38), and anxiolytic use at follow-up (1.40, 1.06-1.82). Factors associated only with later discontinuation (at 2 years and/or at 3 years) were antidepressant use at follow-up (2 years 1.46, 1.10-1.94) and greater number of relapses (2 years 1.60, 1.11-2.30; 3 years 2.31, 1.27-4.22). Potential drivers of discontinuation change over time. Improved awareness of the drivers of discontinuation could lead to targeted interventions to improve adherence.

  19. Healthcare resource utilization following switch or discontinuation in multiple sclerosis patients on disease modifying drugs.

    PubMed

    Reynolds, Matthew W; Stephen, Reejis; Seaman, Chris; Rajagopalan, Kitty

    2010-03-01

    The objective of this study was to explore the cost and utilization in the period following discontinuations or switches of disease modifying drugs (DMDs) for patients with multiple sclerosis (MS). Secondary objectives included an assessment of the time to switch or discontinuation from index DMD treatment. Cases were defined as a billed MS diagnosis in continuously enrolled patients initiated with interferon-beta1a IM, interferon-beta1b SC, glatiramer acetate, and interferon-beta1a SC found in the PharMetrics Patient-Centric Database. Information on patient demographics, diagnoses, procedures, pharmacy-dispensed drugs, and costs was extracted; reasons for discontinuation and expenses outside of the healthcare system were not available. Treatment discontinuations and switches between study drugs were defined using pharmacy prescription patterns and analyzed by descriptive and regression methods. The non-pharmacy medical costs in the 18 months following switching or discontinuation were compared to the costs in a randomly selected similar period for those patients who did not switch or discontinue these agents. A total of 5,772 MS patients were continuously enrolled and were treated with one or more of the four drugs of interest, and about half of these patients switched drugs or discontinued treatment for at least 90 days. Patients initiated with interferon-beta1b SC were more likely to discontinue treatment compared to interferon-beta1a IM users. Non-pharmaceutical medical costs were highest for those switching treatments followed by those discontinuing DMDs in the 18 months following a switch or discontinuation, compared to persistent users of these drugs. Interferon beta1b SC initiators had higher costs following changes or discontinuations, while glatiramer acetate and interferon-beta1a SC users had lower subsequent costs compared to interferon-beta1a IM users. Unfortunately, the reasons for stopping the initial treatment cannot be determined from analysis of an administrative claims database. Also, the MS cases followed in this analysis are billing diagnostic events unconfirmed through a review of medical records or other data sources. The results are unstratified in terms of severity and thus while treatment patterns may vary for patients with different types of MS (e.g., progressive vs. relapsing-remitting), this cannot be examined in this analysis. Changing or discontinuing DMDs is common among MS patients and is associated with higher non-pharmaceutical medical costs that vary based on the initiating drug and other demographics characteristics.

  20. Self-reported reasons for breastfeeding cessation among low-income women enrolled in a peer counseling breastfeeding support program.

    PubMed

    Rozga, Mary R; Kerver, Jean M; Olson, Beth H

    2015-02-01

    Peer counseling programs have demonstrated efficacy in improving breastfeeding rates in the low-income population, but there is little research concerning why women enrolled in these programs ultimately discontinue breastfeeding. This study aimed to describe the self-reported reasons for discontinuing breastfeeding among women who are receiving peer counseling support by participant characteristics and timing of discontinuation. This study is a secondary analysis of data collected from 7942 participants who discontinued breastfeeding while enrolled in a peer counseling breastfeeding support program from 2005 to 2011. Reasons for discontinuing breastfeeding were assessed in relation to participant characteristics and weaning age using chi-square analyses and Kruskall-Wallis analyses of variance. The most common reasons reported for discontinuing breastfeeding were mother's preference (39%) and low milk supply (21%), although reasons differed by age of infant weaning (P < .001). Among participants who discontinued the earliest, the most commonly cited reasons were breastfeeding challenges [median duration (interquartile range), 4.7 (2.0, 13.4) weeks], followed by low milk supply [8.9 (4.6, 19.1) weeks] and mother's preference [12.9 (5.0, 25.7) weeks]. Women who were younger, were less educated, were non-Hispanic black, were unmarried, and had no prior breastfeeding experience were the most likely to discontinue breastfeeding due to mother's preference. Peer counselors are in a unique position to offer breastfeeding education and encouragement and may be able to use evidence presented here to anticipate specified concerns either prenatally or postpartum, to prevent early breastfeeding discontinuation. © The Author(s) 2014.

  1. Investigation of Efavirenz Discontinuation in Multi-ethnic Populations of HIV-positive Individuals by Genetic Analysis.

    PubMed

    Cummins, Nathan W; Neuhaus, Jacqueline; Chu, Haitao; Neaton, James; Wyen, Christoph; Rockstroh, Jürgen K; Skiest, Daniel J; Boyd, Mark A; Khoo, Saye; Rotger, Margalida; Telenti, Amalio; Weinshilboum, Richard; Badley, Andrew D

    2015-07-01

    Efavirenz (EFV) based antiretroviral therapy is expanding worldwide. However discontinuation of EFV containing regimens is common in some patients, particularly black patients, due most often to neuropsychiatric side effects. These adverse drug effects often result in premature drug discontinuation, as well as considerable morbidity. We genotyped CYP2A6, CYP2B6 and CYP3A4, which encode enzymes principally involved in EFV metabolism, from patients enrolled in the multinational SMART, FIRST and ESPRIT studies, for whom outcome data of treatment adherence was available. Patients with loss or decrease of function single nucleotide polymorphisms (SNPs) in the above genes were assigned a risk score based upon the number of SNPs present weighted relative to whether CYP2B6 (main metabolism pathway) and/or CYP2A6 and CYP3A4 (accessory pathways) were involved. Cox regression models were used to study the association between high genetic risk and time from initiation to EFV discontinuation. Failure was defined as discontinuation of an antiretroviral regimen other than for virologic failure or protocol determined discontinuation. Patients with highest pharmacogenetic risk, as defined by cumulative SNPs in CYP2A6, CYP2B6 and CYP3A4, have an increased risk of discontinuation of EFV containing therapy compared to patients with lower genetic risk scores (adjusted HR 1.9, 95% CI 1.2, 3.1, P = 0.009). High genetic risk score was not associated with an increased risk of discontinuing atazanavir or nevirapine. High genetic risk was present more often in blacks compared to non-blacks (Adjusted OR 4.5, 95% CI: 1.9,10.5), and treatment discontinuation was also increased in blacks overall (Adjusted HR 1.4, 95% CI 1.0, 1.9). However, high genetic risk was more associated with treatment discontinuation than race alone for both blacks (Adjusted OR 1.9, 95% CI 0.8, 4.8) and non-blacks (Adjusted OR 5.3, 95% CI 1.5, 18.0). Premature discontinuation of ART delays the time to effective long term viral suppression, and is associated with significant morbidity. Pharmacogenetic testing may predict those with a high risk of EFV discontinuation, and therefore should be considered in patients in whom initiation of EFV based ART is being considered. Funded by NIH.

  2. Etiology of Ibrutinib Discontinuation and Outcomes in Chronic Lymphocytic Leukemia Patients

    PubMed Central

    Maddocks, Kami J.; Ruppert, Amy S.; Lozanski, Gerard; Heerema, Nyla A.; Zhao, Weiqiang; Abruzzo, Lynne; Lozanski, Arletta; Davis, Melanie; Gordon, Amber; Smith, Lisa L.; Mantel, Rose; Jones, Jeffrey A.; Flynn, Joseph M.; Jaglowski, Samantha M.; Andritsos, Leslie A.; Awan, Farrukh; Blum, Kristie A.; Grever, Michael R.; Johnson, Amy J.; Byrd, John C.; Woyach, Jennifer A.

    2015-01-01

    Importance The Bruton’s Tyrosine Kinase inhibitor ibrutinib is effective in patients with chronic lymphocytic leukemia (CLL). Reasons for discontinuation from this drug and outcomes following discontinuation have not been evaluated outside of clinical trials with relatively short follow-up. Objective To determine features associated with discontinuation of ibrutinib and outcomes. Design 308 patients participating in four sequential trials of ibrutinib were included. These trials accrued patients included in this analysis from May 2010 until April 2014, and data were locked in June 2014. Setting The Ohio State University Comprehensive Cancer Center Participants Patients with CLL enrolled on 4 sequential clinical trials. Main Outcome Measure Patients were evaluated for time to discontinuation, reasons for discontinuation, and survival following discontinuation. For patients who discontinued due to progression, targeted deep sequencing was performed in samples at baseline and relapse. Results With a median follow-up of 20 months, 232 patients remain on therapy, 31 have discontinued because of progression, and 45 have discontinued for other reasons. Disease progression includes Richter’s transformation or progressive CLL. Richter’s appeared to occur early and CLL progressions later (cumulative incidence at 12 months: 4.5% (95% CI: 2.0% to 7.0%) and 0.3% (95% CI: 0% to 1.0%), respectively). Median survival following Richter’s transformation was 3.5 months (95% CI: 0.3–6.0), and 17.6 months (95% CI: 4.7-not reached) following CLL progression. Sequencing on peripheral blood from 8 patients with Richter’s transformation revealed 2 with mutations in BTK, and a lymph node sample showed no mutations in BTK or PLCγ2. Deep sequencing on 11 patients with CLL progression revealed BTK or PLCγ2 mutations in all. These mutations were not identified pre-treatment in any patient. Conclusions and Relevance This single institution experience with ibrutinib confirms it to be an effective therapy and identifies, for the first time, baseline factors associated with ibrutinib discontinuation. Outcomes data show poor prognosis after discontinuation, especially for those patients with Richter’s transformation. Finally, sequencing data confirm initial reports associating mutations in BTK and PLCγ2 with progression and clearly show that CLL progressions are associated with these mutations, while Richter’s transformation is likely not. PMID:26182309

  3. Discontinuity stresses in metallic pressure vessels

    NASA Technical Reports Server (NTRS)

    1971-01-01

    The state of the art, criteria, and recommended practices for the theoretical and experimental analyses of discontinuity stresses and their distribution in metallic pressure vessels for space vehicles are outlined. The applicable types of pressure vessels include propellant tanks ranging from main load-carrying integral tank structure to small auxiliary tanks, storage tanks, solid propellant motor cases, high pressure gas bottles, and pressurized cabins. The major sources of discontinuity stresses are discussed, including deviations in geometry, material properties, loads, and temperature. The advantages, limitations, and disadvantages of various theoretical and experimental discontinuity analysis methods are summarized. Guides are presented for evaluating discontinuity stresses so that pressure vessel performance will not fall below acceptable levels.

  4. Reasons and predictive factors for discontinuation of PDE-5 inhibitors despite successful intercourse in erectile dysfunction patients

    PubMed Central

    Kim, S-C; Lee, Y-S; Seo, K-K; Jung, G-W; Kim, T-H

    2014-01-01

    This study was aimed to identify characteristics of ED patients who discontinued PDE5i despite successful intercourse. Data were collected using a questionnaire from 34 urologic clinics regardless of the effect (success or failure) of PDE5i treatment by visiting the clinics (717), e-mail (64) or post (101) for 882 ED patients who had previously taken any kind of PDE5i on demand four or more times. Discontinuation of PDE5i was defined if the patient had never taken PDE5i for the previous 1 year despite successful intercourse. Of the 882 patients, 485 were included in the final analysis. Difference in the socio-demographic, ED- and partner-related data between the continuation and discontinuation group and factors influencing discontinuation of the PDE5i were analyzed. Among 485 respondents (mean age, 53.6), 116 (23.9%) had discontinued PDE5i use despite successful intercourse. Most common reasons for the discontinuation were ‘reluctant medication-dependent intercourse' (31.0%), ‘spontaneous recovery of erectile function without further treatment' (30.2%), and ‘high cost' (26.7%). In multiple logistic regression analysis, independent factors influencing discontinuation of the drug were cause of ED (psychogenic), short duration of ED, low education (⩽ middle school), and religion (Catholic). In partner-related compliance, only partner's religion (Catholic) was a significant factor. PMID:24305610

  5. OPG-Fc but Not Zoledronic Acid Discontinuation Reverses Osteonecrosis of the Jaws (ONJ) in Mice

    PubMed Central

    de Molon, Rafael Scaf; Shimamoto, Hiroaki; Bezouglaia, Olga; Pirih, Flavia Q; Dry, Sarah M; Kostenuik, Paul; Boyce, Rogely W; Dwyer, Denise; Aghaloo, Tara L; Tetradis, Sotirios

    2016-01-01

    Osteonecrosis of the jaws (ONJ) is a significant complication of antiresorptive medications, such as bisphosphonates and denosumab. Antiresorptive discontinuation to promote healing of ONJ lesions remains highly controversial and understudied. Here, we investigated whether antiresorptive discontinuation alters ONJ features in mice, employing the potent bisphosphonate zoledronic acid (ZA) or the receptor activator of NF-κB ligand (RANKL) inhibitor OPG-Fc, utilizing previously published ONJ animal models. Mice were treated with vehicle (veh), ZA, or OPG-Fc for 11 weeks to induce ONJ, and antiresorptives were discontinued for 6 or 10 weeks. Maxillae and mandibles were examined by µCT imaging and histologically. ONJ features in ZA and OPG-Fc groups included periosteal bone deposition, empty osteocyte lacunae, osteonecrotic areas, and bone exposure, each of which substantially resolved 10 weeks after discontinuing OPG-Fc but not ZA. Full recovery of tartrate-resistant acid phosphatase-positive (TRAP+) osteoclast numbers occurred after discontinuing OPG-Fc but not ZA. Our data provide the first experimental evidence demonstrating that discontinuation of a RANKL inhibitor, but not a bisphosphonate, reverses features of osteonecrosis in mice. It remains unclear whether antiresorptive discontinuation increases the risk of skeletal-related events in patients with bone metastases or fracture risk in osteoporosis patients, but these preclinical data may nonetheless help to inform discussions on the rationale for a “drug holiday” in managing the ONJ patient. PMID:25727550

  6. Magnetic discontinuities in magnetohydrodynamic turbulence and in the solar wind.

    PubMed

    Zhdankin, Vladimir; Boldyrev, Stanislav; Mason, Joanne; Perez, Jean Carlos

    2012-04-27

    Recent measurements of solar wind turbulence report the presence of intermittent, exponentially distributed angular discontinuities in the magnetic field. In this Letter, we study whether such discontinuities can be produced by magnetohydrodynamic (MHD) turbulence. We detect the discontinuities by measuring the fluctuations of the magnetic field direction, Δθ, across fixed spatial increments Δx in direct numerical simulations of MHD turbulence with an imposed uniform guide field B(0). A large region of the probability density function (pdf) for Δθ is found to follow an exponential decay, proportional to exp(-Δθ/θ(*)), with characteristic angle θ(*)≈(14°)(b(rms)/B(0))(0.65) for a broad range of guide-field strengths. We find that discontinuities observed in the solar wind can be reproduced by MHD turbulence with reasonable ratios of b(rms)/B(0). We also observe an excess of small angular discontinuities when Δx becomes small, possibly indicating an increasing statistical significance of dissipation-scale structures. The structure of the pdf in this case closely resembles the two-population pdf seen in the solar wind. We thus propose that strong discontinuities are associated with inertial-range MHD turbulence, while weak discontinuities emerge from dissipation-range turbulence. In addition, we find that the structure functions of the magnetic field direction exhibit anomalous scaling exponents, which indicates the existence of intermittent structures.

  7. Decreased responsiveness following lithium discontinuation in bipolar disorder: A naturalistic observation study.

    PubMed

    Cakir, Sibel; Yazıcı, Olcay; Post, Robert M

    2017-01-01

    Lithium is a cornerstone in treatment of bipolar disorder. Findings are conflicting as to whether acquired unresponsiveness occurs following the discontinuation. Retrospective life chart data were evaluated to investigate the incidence of loss of response. Sixty-five patients chosen from a larger cohort, followed with prospective life charts, who discontinued lithium and had a second lithium treatment. Patients who had at least 2 mood episodes when they were drug naïve to describe the natural frequency of illness and 3 mood episodes before the discontinuation were included. The type of response was defined as excellent, partial, or poor according to mirror design method. Eighteen of 65 patients (27.6%) had a decreased response to lithium following its discontinuation. Nine of these patients (13.8%) were unresponsive and nine patients (13.8%) had attenuated response to second lithium treatment. The mean time of discontinuation was longer in the patients who show decreased response (245.8+268.2 vs. 117.9+149.8 days, p=.01). Those who had episode recurrences during the discontinuation were more likely to show reduced responsiveness upon re-treatment. After discontinuation of lithium treatment, more than a quarter of the patients showed an attenuated response or unresponsiveness, and initial partial responders more likely to show unresponsiveness than excellent responders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. On the equivalence between traction- and stress-based approaches for the modeling of localized failure in solids

    NASA Astrophysics Data System (ADS)

    Wu, Jian-Ying; Cervera, Miguel

    2015-09-01

    This work investigates systematically traction- and stress-based approaches for the modeling of strong and regularized discontinuities induced by localized failure in solids. Two complementary methodologies, i.e., discontinuities localized in an elastic solid and strain localization of an inelastic softening solid, are addressed. In the former it is assumed a priori that the discontinuity forms with a continuous stress field and along the known orientation. A traction-based failure criterion is introduced to characterize the discontinuity and the orientation is determined from Mohr's maximization postulate. If the displacement jumps are retained as independent variables, the strong/regularized discontinuity approaches follow, requiring constitutive models for both the bulk and discontinuity. Elimination of the displacement jumps at the material point level results in the embedded/smeared discontinuity approaches in which an overall inelastic constitutive model fulfilling the static constraint suffices. The second methodology is then adopted to check whether the assumed strain localization can occur and identify its consequences on the resulting approaches. The kinematic constraint guaranteeing stress boundedness and continuity upon strain localization is established for general inelastic softening solids. Application to a unified stress-based elastoplastic damage model naturally yields all the ingredients of a localized model for the discontinuity (band), justifying the first methodology. Two dual but not necessarily equivalent approaches, i.e., the traction-based elastoplastic damage model and the stress-based projected discontinuity model, are identified. The former is equivalent to the embedded and smeared discontinuity approaches, whereas in the later the discontinuity orientation and associated failure criterion are determined consistently from the kinematic constraint rather than given a priori. The bi-directional connections and equivalence conditions between the traction- and stress-based approaches are classified. Closed-form results under plane stress condition are also given. A generic failure criterion of either elliptic, parabolic or hyperbolic type is analyzed in a unified manner, with the classical von Mises (J2), Drucker-Prager, Mohr-Coulomb and many other frequently employed criteria recovered as its particular cases.

  9. Spurious Behavior of Shock-Capturing Methods: Problems Containing Stiff Source Terms and Discontinuities

    NASA Technical Reports Server (NTRS)

    Yee, Helen M. C.; Kotov, D. V.; Wang, Wei; Shu, Chi-Wang

    2013-01-01

    The goal of this paper is to relate numerical dissipations that are inherited in high order shock-capturing schemes with the onset of wrong propagation speed of discontinuities. For pointwise evaluation of the source term, previous studies indicated that the phenomenon of wrong propagation speed of discontinuities is connected with the smearing of the discontinuity caused by the discretization of the advection term. The smearing introduces a nonequilibrium state into the calculation. Thus as soon as a nonequilibrium value is introduced in this manner, the source term turns on and immediately restores equilibrium, while at the same time shifting the discontinuity to a cell boundary. The present study is to show that the degree of wrong propagation speed of discontinuities is highly dependent on the accuracy of the numerical method. The manner in which the smearing of discontinuities is contained by the numerical method and the overall amount of numerical dissipation being employed play major roles. Moreover, employing finite time steps and grid spacings that are below the standard Courant-Friedrich-Levy (CFL) limit on shockcapturing methods for compressible Euler and Navier-Stokes equations containing stiff reacting source terms and discontinuities reveals surprising counter-intuitive results. Unlike non-reacting flows, for stiff reactions with discontinuities, employing a time step and grid spacing that are below the CFL limit (based on the homogeneous part or non-reacting part of the governing equations) does not guarantee a correct solution of the chosen governing equations. Instead, depending on the numerical method, time step and grid spacing, the numerical simulation may lead to (a) the correct solution (within the truncation error of the scheme), (b) a divergent solution, (c) a wrong propagation speed of discontinuities solution or (d) other spurious solutions that are solutions of the discretized counterparts but are not solutions of the governing equations. The present investigation for three very different stiff system cases confirms some of the findings of Lafon & Yee (1996) and LeVeque & Yee (1990) for a model scalar PDE. The findings might shed some light on the reported difficulties in numerical combustion and problems with stiff nonlinear (homogeneous) source terms and discontinuities in general.

  10. Forensic Excavation of Rock Masses: A Technique to Investigate Discontinuity Persistence

    NASA Astrophysics Data System (ADS)

    Shang, J.; Hencher, S. R.; West, L. J.; Handley, K.

    2017-11-01

    True persistence of rock discontinuities (areas with insignificant tensile strength) is an important factor controlling the engineering behaviour of fractured rock masses, but is extremely difficult to quantify using current geological survey methodologies, even where there is good rock exposure. Trace length as measured in the field or using remote measurement devices is actually only broadly indicative of persistence for rock engineering practice and numerical modelling. Visible traces of discontinuities are treated as if they were open fractures within rock mass classifications, despite many such traces being non-persistent and actually retaining considerable strength. The common assumption of 100% persistence, based on trace length, is generally extremely conservative in terms of strength and stiffness, but not always so and may lead to a wrong prediction of failure mechanism or of excavatability. Assuming full persistence would give hopelessly incorrect predictions of hydraulic conductivity. A new technique termed forensic excavation of rock masses is introduced, as a procedure for directly investigating discontinuity persistence. This technique involves non-explosive excavation of rock masses by injecting an expansive chemical splitter along incipient discontinuities. On expansion, the splitter causes the incipient traces to open as true joints. Experiments are described in which near-planar rock discontinuities, through siltstone and sandstone, were opened up by injecting the splitter into holes drilled along the lines of visible traces of the discontinuities in the laboratory and in the field. Once exposed the surfaces were examined to investigate the pre-existing persistence characteristics of the incipient discontinuities. One conclusion from this study is that visible trace length of a discontinuity can be a poor indicator of true persistence (defined for a fracture area with negligible tensile strength). An observation from this series of experiments was that freshly failed surfaces through pre-existing rock bridges were relatively rough compared to sections of pre-existing weaker areas of geologically developed (though still incipient) discontinuities. Fractographic features such as hackle and rib marks were typical of the freshly broken rock bridges, whereas opened-up areas of incipient discontinuity were smoother. Schmidt hammer rebound values were generally higher for the rock bridge areas, probably reflecting their lower degree of chemical and physical weathering.

  11. Reasons for lithium discontinuation in men and women with bipolar disorder: a retrospective cohort study.

    PubMed

    Öhlund, Louise; Ott, Michael; Oja, Sofia; Bergqvist, Malin; Lundqvist, Robert; Sandlund, Mikael; Salander Renberg, Ellinor; Werneke, Ursula

    2018-02-07

    Lithium remains first choice as maintenance treatment for bipolar affective disorder. Yet, about half of all individuals may stop their treatment at some point, despite lithium's proven benefits concerning the prevention of severe affective episodes and suicide. Retrospective cohort study in the Swedish region of Norrbotten into the causes of lithium discontinuation. The study was set up to (1) test whether patients with bipolar affective disorder or schizoaffective disorder, treated with lithium maintenance therapy, were more likely to discontinue lithium because of adverse effects than lack of therapeutic effectiveness, (2) explore gender differences, (3) understand the role of diagnosis and (4) identify who, patient or doctor, took the initiative to stop lithium. Review of medical records for all episodes of lithium discontinuation that had occurred between 1997 and 2013 with the intent to stop lithium for good. Of 873 patients treated with lithium, 54% discontinued lithium, corresponding to 561 episodes of lithium discontinuation. In 62% of episodes, lithium was discontinued due to adverse effects, in 44% due to psychiatric reasons, and in 12% due to physical reasons interfering with lithium treatment. The five single most common adverse effects leading to lithium discontinuation were diarrhoea (13%), tremor (11%), polyuria/polydipsia/diabetes insipidus (9%), creatinine increase (9%) and weight gain (7%). Women were as likely as men to take the initiative to stop lithium, but twice as likely to consult a doctor before taking action (p < 0.01). Patients with type 1 BPAD or SZD were more likely to discontinue lithium than patients with type 2 or unspecified BPAD (p < 0.01). Patients with type 1 BPAD or SZD were more likely to refuse medication (p < 0.01). Conversely, patients with type 2 or unspecified BPAD were three times as likely to discontinue lithium for lack or perceived lack of effectiveness (p < 0.001). Stopping lithium treatment is common and occurs mostly due to adverse effects. It is important to discuss potential adverse effects with patients before initiation and continuously during lithium treatment, to reduce the frequency of potentially unnecessary discontinuations.

  12. 14 CFR Section 16 - Objective Classification-Discontinued Operations

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Objective Classification-Discontinued Operations Section 16 Section 16 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION... AIR CARRIERS Profit and Loss Classification Section 16 Objective Classification—Discontinued...

  13. 38 CFR 21.4135 - Discontinuance dates.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) VOCATIONAL REHABILITATION AND EDUCATION Administration of Educational Assistance Programs Payments; Educational Assistance Allowance § 21.4135 Discontinuance dates. The effective date of reduction or discontinuance of educational assistance allowance will be as specified in this section. If more than one type of...

  14. 38 CFR 21.4135 - Discontinuance dates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) VOCATIONAL REHABILITATION AND EDUCATION Administration of Educational Assistance Programs Payments; Educational Assistance Allowance § 21.4135 Discontinuance dates. The effective date of reduction or discontinuance of educational assistance allowance will be as specified in this section. If more than one type of...

  15. Adherence, persistence, and medication discontinuation in patients with attention-deficit/hyperactivity disorder – a systematic literature review

    PubMed Central

    Gajria, Kavita; Lu, Mei; Sikirica, Vanja; Greven, Peter; Zhong, Yichen; Qin, Paige; Xie, Jipan

    2014-01-01

    Untreated attention-deficit/hyperactivity disorder (ADHD) can lead to substantial adverse social, economic, and emotional outcomes for patients. The effectiveness of current pharmacologic treatments is often reduced, due to low treatment adherence and medication discontinuation. This current systematic literature review analyzes the current state of knowledge surrounding ADHD medication discontinuation, focusing on: 1) the extent of patient persistence; 2) adherence; and 3) the underlying reasons for patients’ treatment discontinuation and how discontinuation rates and reasons vary across patient subgroups. We selected 91 original studies (67 with persistence/discontinuation results, 26 with adherence results, and 41 with reasons for discontinuation, switching, or nonadherence) and 36 expert opinion reviews on ADHD medication discontinuation, published from 1990 to 2013. Treatment persistence on stimulants, measured by treatment duration during the 12-month follow-up periods, averaged 136 days for children and adolescents and 230 days for adults. Owing to substantial study heterogeneity, comparisons across age or medication type subgroups were generally inconclusive; however, long-acting formulations and amphetamines were associated with longer treatment duration than short-acting formulations and methylphenidates. The medication possession ratio, used to measure adherence, was <0.7 for all age groups and medication classes during a 12-month period. Adverse effects were the most commonly cited reason for discontinuation in all studies. Original research studies reported the lack of symptom control as a common discontinuation reason, followed by dosing inconvenience, social stigma associated with ADHD medication, and the patient’s attitude. In summary, although there was a lack of consistency in the measurement of adherence and persistence, these findings indicate that drug adherence and persistence are generally poor among patients with ADHD. Clinicians may be able to help improve adherence and persistence to ADHD treatment by educating caregivers and patients on treatment goals, administering long-acting medications, and following-up with patients to verify if medication is still effective and well-tolerated. PMID:25187718

  16. Temporal trends of copper-bearing intrauterine device discontinuation: a population-based birth-cohort study of contraceptive use among rural married women in China.

    PubMed

    Zhou, Jie; Tan, Xiaodong; Song, Xiangjing; Zhang, Kaining; Fang, Jing; Peng, Lin; Qi, Wencai; Nie, Zonghui; Li, Ming; Deng, Rui; Yan, Chaofang

    2015-03-01

    Copper-bearing intrauterine device (IUD) insertion for long-term contraceptive use is high in China, but there has been evidence that first-year discontinuation rate of copper-bearing IUD has also increased rapidly in recent years especially among rural married women. To investigate long-term use of copper-bearing IUD, the authors examined the 7-year temporal trends of copper-bearing IUD discontinuation in a population-based birth-cohort study among 720 rural married women in China, from 2004 to 2012. Women requesting contraception were followed-up twice per year after the insertion of IUD. The gross cumulative life table discontinuation rates were calculated for each of the main reasons for discontinuation as well as for all reasons combined. By the end of 7 years, 384 discontinuations were observed. With a stepped-up trend, the gross cumulative life table rate for discontinuation increased from 10.06 (95% confidence interval = 7.86-12.27) per 100 women by the first year to 52.69 (95% confidence interval = 48.94-56.44) per 100 women by the end of 7 years, which increased rapidly in the first 2 years after copper-bearing IUD insertion, flattened out gradually in the following 2 years, then increased again in the last 3 years. Among reported method failure, expulsion and side effects were the main reasons for discontinuation of the copper-bearing IUD but not pregnancy. Personal reasons, such as renewal by personal will had influenced copper-bearing IUD use since the second year and should not be neglected. Based on this study, the temporal trends of copper-bearing IUD discontinuation was in a stepped-up trend in 7 years after insertion. Both reported method failure (expulsion and side effect) and personal reason had effect on the discontinuation of copper-bearing IUD, but pregnancy was no more the most important reason affecting the use of copper-bearing IUD. © 2014 APJPH.

  17. Regression Discontinuity Designs in Epidemiology

    PubMed Central

    Moscoe, Ellen; Mutevedzi, Portia; Newell, Marie-Louise; Bärnighausen, Till

    2014-01-01

    When patients receive an intervention based on whether they score below or above some threshold value on a continuously measured random variable, the intervention will be randomly assigned for patients close to the threshold. The regression discontinuity design exploits this fact to estimate causal treatment effects. In spite of its recent proliferation in economics, the regression discontinuity design has not been widely adopted in epidemiology. We describe regression discontinuity, its implementation, and the assumptions required for causal inference. We show that regression discontinuity is generalizable to the survival and nonlinear models that are mainstays of epidemiologic analysis. We then present an application of regression discontinuity to the much-debated epidemiologic question of when to start HIV patients on antiretroviral therapy. Using data from a large South African cohort (2007–2011), we estimate the causal effect of early versus deferred treatment eligibility on mortality. Patients whose first CD4 count was just below the 200 cells/μL CD4 count threshold had a 35% lower hazard of death (hazard ratio = 0.65 [95% confidence interval = 0.45–0.94]) than patients presenting with CD4 counts just above the threshold. We close by discussing the strengths and limitations of regression discontinuity designs for epidemiology. PMID:25061922

  18. Management applications of discontinuity theory | Science ...

    EPA Pesticide Factsheets

    1.Human impacts on the environment are multifaceted and can occur across distinct spatiotemporal scales. Ecological responses to environmental change are therefore difficult to predict, and entail large degrees of uncertainty. Such uncertainty requires robust tools for management to sustain ecosystem goods and services and maintain resilient ecosystems. 2.We propose an approach based on discontinuity theory that accounts for patterns and processes at distinct spatial and temporal scales, an inherent property of ecological systems. Discontinuity theory has not been applied in natural resource management and could therefore improve ecosystem management because it explicitly accounts for ecological complexity. 3.Synthesis and applications. We highlight the application of discontinuity approaches for meeting management goals. Specifically, discontinuity approaches have significant potential to measure and thus understand the resilience of ecosystems, to objectively identify critical scales of space and time in ecological systems at which human impact might be most severe, to provide warning indicators of regime change, to help predict and understand biological invasions and extinctions and to focus monitoring efforts. Discontinuity theory can complement current approaches, providing a broader paradigm for ecological management and conservation This manuscript provides insight on using discontinuity approaches to aid in managing complex ecological systems. In part

  19. EVALUATING DISCONTINUITIES IN COMPLEX SYSTEMS: TOWARD QUANTITATIVE MEASURE OF RESILIENCE

    EPA Science Inventory

    The textural discontinuity hypothesis (TDH) is based on the observation that animal body mass distributions exhibit discontinuities that may reflect the texture of the landscape available for exploitation. This idea has been extended to other complex systems, hinting that the ide...

  20. 47 CFR 90.157 - Discontinuance of station operation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Discontinuance of station operation. 90.157 Section 90.157 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Applications and Authorizations § 90.157 Discontinuance of...

  1. Nature of Fluctuations on Directional Discontinuities Inside a Solar Ejection: Wind and IMP 8 Observations

    NASA Technical Reports Server (NTRS)

    Vasquez, Bernard J.; Farrugia, Charles J.; Markovskii, Sergei A.; Hollweg, Joseph V.; Richardson, Ian G.; Ogilvie, Keith W.; Lepping, Ronald P.; Lin, Robert P.; Larson, Davin; White, Nicholas E. (Technical Monitor)

    2001-01-01

    A solar ejection passed the Wind spacecraft between December 23 and 26, 1996. On closer examination, we find a sequence of ejecta material, as identified by abnormally low proton temperatures, separated by plasmas with typical solar wind temperatures at 1 AU. Large and abrupt changes in field and plasma properties occurred near the separation boundaries of these regions. At the one boundary we examine here, a series of directional discontinuities was observed. We argue that Alfvenic fluctuations in the immediate vicinity of these discontinuities distort minimum variance normals, introducing uncertainty into the identification of the discontinuities as either rotational or tangential. Carrying out a series of tests on plasma and field data including minimum variance, velocity and magnetic field correlations, and jump conditions, we conclude that the discontinuities are tangential. Furthermore, we find waves superposed on these tangential discontinuities (TDs). The presence of discontinuities allows the existence of both surface waves and ducted body waves. Both probably form in the solar atmosphere where many transverse nonuniformities exist and where theoretically they have been expected. We add to prior speculation that waves on discontinuities may in fact be a common occurrence. In the solar wind, these waves can attain large amplitudes and low frequencies. We argue that such waves can generate dynamical changes at TDs through advection or forced reconnection. The dynamics might so extensively alter the internal structure that the discontinuity would no longer be identified as tangential. Such processes could help explain why the occurrence frequency of TDs observed throughout the solar wind falls off with increasing heliocentric distance. The presence of waves may also alter the nature of the interactions of TDs with the Earth's bow shock in so-called hot flow anomalies.

  2. Recruitment failure and futility were the most common reasons for discontinuation of clinical drug trials. Results of a nationwide inception cohort study in the Netherlands.

    PubMed

    van den Bogert, Cornelis A; Souverein, Patrick C; Brekelmans, Cecile T M; Janssen, Susan W J; Koëter, Gerard H; Leufkens, Hubert G M; Bouter, Lex M

    2017-08-01

    The objective of the study was to identify the reasons for discontinuation of clinical drug trials and to evaluate whether efficacy-related discontinuations were adequately planned in the trial protocol. All clinical drug trials in the Netherlands, reviewed by institutional review boards in 2007, were followed until December 2015. Data were obtained through the database of the Dutch competent authority (Central Committee on Research Involving Human Subjects [CCMO]) and a questionnaire to the principal investigators. Reasons for trial discontinuation were the primary outcome of the study. Three reasons for discontinuation were analyzed separately: all cause, recruitment failure, and efficacy related (when an interim analysis had demonstrated futility or superiority). Among the efficacy-related discontinuations, we examined whether the data monitoring committee, the stopping rule, and the moment of the interim analysis in the trial progress were specified in the trial protocol. Of the 574 trials, 102 (17.8%) were discontinued. The most common reasons were recruitment failure (33 of 574; 5.7%) and solely efficacy related (30 of 574; 5.2%). Of the efficacy-related discontinuations, 10 of 30 (33.3%) of the trial protocols reported all three aspects in the trial protocol, and 20 of 30 (66.7%) reported at least one aspect in the trial protocol. One out of five clinical drug trials is discontinued before the planned trial end, with recruitment failure and futility as the most common reasons. The target sample size of trials should be feasible, and interim analyses should be adequately described in trial protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Search for seismic discontinuities in the lower mantle

    NASA Astrophysics Data System (ADS)

    Vinnik, Lev; Kato, Mamoru; Kawakatsu, Hitoshi

    2001-09-01

    Indications of lower mantle discontinuities have been debated for decades, but still little is known about their properties, and their origins are enigmatic. In our study broad-band recordings of deep events are examined for the presence of signals from the lower-mantle discontinuities with a novel technique. We deconvolve vertical component of the P-wave coda in the period range around 10s by the S waveform and stack many deconvolved traces with moveout time corrections. In synthetic seismograms for an earth model without lower mantle discontinuities, the strongest signal thus detected in the time window of interest is often s`410'P phase (generated as S and reflected as P from the `410km' discontinuity above the source). In actual seismograms there are other phases that can be interpreted as converted from S to P at discontinuities in the lower mantle beneath the seismic source. We summarize the results of processing the seismograms (1) of deep events in Sunda arc at seismograph stations in east Asia, (2) deep Kermadec-Fiji-Tonga events at the J-array and FREESIA networks in Japan and stations in east Asia, and (3) deep events in the northwest Pacific region (Mariana, Izu-Bonin and the Japan arc) recorded at stations in north America. In our data there are indications of discontinuities near 860-880, 1010-1120, 1170-1250 and 1670-1800km depths. The clearest signals are obtained from the discontinuity at a depth of 1200km. We argue that the `900', `1200' and `1700km' discontinuities are global, but laterally variable in both depth and strength. Seismic stratification of the lower mantle may have bearings on the patterns of subduction, as revealed by tomographic models.

  4. Long-term outcomes for patients with chronic lymphocytic leukemia who discontinue ibrutinib.

    PubMed

    Jain, Preetesh; Thompson, Philip A; Keating, Michael; Estrov, Zeev; Ferrajoli, Alessandra; Jain, Nitin; Kantarjian, Hagop; Burger, Jan A; O'Brien, Susan; Wierda, William G

    2017-06-15

    Ibrutinib is a Bruton tyrosine kinase inhibitor and is approved for the treatment of patients with chronic lymphocytic leukemia (CLL) in frontline and relapsed/refractory settings. The authors previously reported poor outcomes for patients who discontinued ibrutinib; however, long-term outcomes were not reported. Data from 320 patients who received ibrutinib on clinical studies between 2010 and 2015 at The University of Texas MD Anderson Cancer Center were retrospectively analyzed. Long-term outcomes among patients with CLL after they discontinued ibrutinib were analyzed. Ninety of 320 patients (28%) who were treated on ibrutinib-based regimens discontinued ibrutinib. Of these, 80 had relapsed/refractory disease, and 10 were treatment-naive. The median time to discontinuation was 15 months (range, 1.2-54 months). After a median follow-up of 38 months after starting ibrutinib, 40 patients (44%) remained alive. Major reasons for ibrutinib discontinuation were intolerance (n = 29; 32%), miscellaneous (n = 28; 31%), progression (n = 19; 21%), and Richter transformation (RT) (n = 9; 10%). The median survival according to the reason for discontinuation was 33 months for ibrutinib intolerance, 11 months for miscellaneous causes, 16 months for progressive CLL, and 2 months for RT. Among the 19 patients who had progressive CLL, 42% responded to subsequent therapy. Ibrutinib discontinuation was observed during therapy. Patients with CLL who had disease transformation had especially poor outcomes, whereas those who developed progressive disease during ibrutinib therapy had a median survival of <1.5 years. Survival was associated with the reason for discontinuation; patients who had progressive CLL had better survival compared with those who had disease transformation. Effective salvage strategies for patients with CLL who progress on ibrutinib therapy is of critical importance. Cancer 2017;123:2268-2273. © 2017 American Cancer Society. © 2017 American Cancer Society.

  5. Fatigue behavior of 5Ni-Cr-Mo-V steel weldments containing fabrication discontinuities

    NASA Technical Reports Server (NTRS)

    Gill, Steven J.; Hauser, Joseph A., II; Crooker, Thomas W.; Kruse, Brian J.; Menon, Ravi

    1988-01-01

    The applicability of linear elastic fracture mechanics to characterize the fatigue behavior of high-strength steel weldments containing lack-of-penetration (LOP) and slag/lack-of-fusion (S/LOF) discontinuities is explored. Full penetration, double-V butt welds with reinforcements removed were tested under zero-to-tension axial loading. Various filler metals and welding techniques were used. Both sound welds and welds containing discontinuities were cycled to failure. Where possible, cycles to crack initiation were estimated by strain gage measurements. The fracture mechanics approach was successful in correlating the fatigue lifetimes of specimens containing single LOP discontinuities of varying size. However, the fatigue behavior of specimens containing multiple S/LOF discontinuities proved to be much more complex and difficult to analyze.

  6. Discontinuous precipitation at the deformation band in copper alloy

    NASA Astrophysics Data System (ADS)

    Han, Seung Zeon; Ahn, Jee Hyuk; You, Young Soo; Lee, Jehyun; Goto, Masahiro; Kim, Kwangho; Kim, Sangshik

    2018-01-01

    The Cu-Ni-Si alloy is known as a precipitation hardening alloy, where the Ni2Si intermetallic compound is precipitated in the matrix during aging. There are two types of precipitation of Ni2Si: continuous and discontinuous cellular. The discontinuous cellular precipitation is generally initiated at interfaces especially grain boundaries in the matrix. To observe the grain boundary effect on the discontinuous precipitation, a large-grained Cu-Ni-Si-Ti alloy was intentionally fabricated by unidirectional solidification and plastically deformed by groove rolling. While discontinuous cellular precipitation has been generally known to occur only at the high angled grain boundaries in the alloys, we found that it was also generated inside the grains, at the deformation bands formed by plastic deformation.

  7. PML-IRIS during Fingolimod Diagnosed after Natalizumab Discontinuation.

    PubMed

    Killestein, J; Vennegoor, A; van Golde, A E L; Bourez, R L J H; Wijlens, M L B; Wattjes, M P

    2014-01-01

    Background. Natalizumab treatment is frequently discontinued and replaced by alternative medication in multiple sclerosis (MS) patients having a high risk of progressive multifocal leukoencephalopathy (PML). Case Presentation. We report a PML case that was missed on magnetic resonance imaging (MRI) at the time Natalizumab treatment was discontinued. The patient subsequently developed a PML-immune reconstitution inflammatory syndrome after the initiation of Fingolimod treatment, suggesting that immune reconstitution may occur even during Fingolimod induced lymphopenia. Conclusion. This report highlights the need for strict drug surveillance using MRI of Natalizumab-associated MS patients at the time of drug discontinuation and beyond. This is important with respect to pharmacovigilance purposes not only for Natalizumab, but also for alternative drugs used after Natalizumab discontinuation.

  8. Analysis of shielded CPW discontinuities with air-bridges

    NASA Technical Reports Server (NTRS)

    Dib, N. I.; Katehi, P. B.; Ponchak, George E.

    1992-01-01

    The effect of air-bridges on the performance of various coplanar waveguides (CPW) discontinuities is studied. Specifically, the coupled open-end CPW's and the short-end shunt CPW stub discontinuities are considered. The high frequency effect of the air-bridge is evaluated using a hybrid technique. At first, the frequency dependent equivalent circuit of the planar discontinuity without the air-bridge is derived using the Space Domain Integral Equation (SDIE) method. Then, the circuit is modified by incorporating the air-bridge's parasitic inductance and capacitance which are evaluated using a simple quasi-static model. The frequency response of each discontinuity with and without the air-bridge is studied and the scattering parameters are plotted in the frequency range 30-50 GHz for typical CPW dimensions.

  9. Drug Discontinuation Effects Are Part of the Pharmacology of a Drug

    PubMed Central

    2011-01-01

    Most reviews of drug withdrawal effects focus on drugs of potential abuse such as opioids, benzodiazepines, etc. Abrupt discontinuation of many other drugs used in medicine cause withdrawal syndromes, some of which can be fatal. Discontinuation of a number of cardiovascular drugs can increase risk of cardiovascular events above that of people not taking these drugs. These include β-adrenergic receptor antagonists, aspirin, HMG-CoA reductase inhibitors (statins), and heparin. Rebound hypertension occurs after abrupt cessation of many antihypertensive drugs. The possibility of discontinuation syndromes has usually been neglected until adverse clinical events force them to be noticed. Attention to the possibility of drug discontinuation effects is an important part of drug safety evaluation. PMID:21849624

  10. 78 FR 8407 - Authorization To Manufacture and Distribute Postage Evidencing Systems; Discontinued Indicia

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-06

    ... discontinuing the non-IBI or non-IMI indicia over such a short period of time it would put them at risk in the... has discussed with the industry the need to discontinue these indicia. Since the introduction of the...

  11. 27 CFR 44.161 - Discontinuance of operations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... operations. 44.161 Section 44.161 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... Operations § 44.161 Discontinuance of operations. Every export warehouse proprietor who desires to discontinue operations and close out his warehouse shall dispose of all cigars, cigarettes, and cigarette...

  12. 47 CFR 63.63 - Emergency discontinuance, reduction, or impairment of service.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... impairment of service. 63.63 Section 63.63 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... AND IMPAIRMENT OF SERVICE BY COMMON CARRIERS; AND GRANTS OF RECOGNIZED PRIVATE OPERATING AGENCY STATUS Discontinuance, Reduction, Outage and Impairment § 63.63 Emergency discontinuance, reduction, or impairment of...

  13. 38 CFR 21.9635 - Discontinuance dates.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... effective the last date of attendance; and (ii) Independent study or distance learning effective on the... learning, VA will terminate educational assistance effective the date the last lesson was serviced... Discontinuance dates. The effective date of a reduction or discontinuance of educational assistance will be as...

  14. An Analysis of Contraceptive Discontinuation among Female, Reversible Method Users in Urban Honduras

    PubMed Central

    Barden-O’Fallon, Janine; Speizer, Ilene S.; Cálix, Javier; Rodriguez, Francisco

    2013-01-01

    A panel study examining the effects of individual characteristics, side effects experienced, and service quality on contraceptive discontinuation was undertaken in four urban areas of Honduras. Data were collected from October 2006 to December 2007. The baseline population included 800 women aged 15–44 who were new or continuing users of the injectable, IUD, or oral contraceptive pill. A total of 671 women (84%) were re-interviewed after one year. Life tables and Cox proportional hazards models are used to present discontinuation rates and factors associated with contraceptive discontinuation. Among new users, discontinuation of the baseline method at 12 months was high (45%); especially for users of the injectable (50%). In the hazards model, service quality had little effect on discontinuation, while individual characteristics and the experience of specific side effects showed significant effects. The results suggest that programs should emphasize continuous contraceptive coverage rather than continuous use of a particular method. PMID:21500697

  15. Observations of an Interplanetary Intermediate Shock Associated with a Magnetic Reconnection Exhaust

    NASA Astrophysics Data System (ADS)

    Feng, H. Q.; Li, Q. H.; Wang, J. M.; Zhao, G. Q.

    2016-07-01

    Two intermediate shocks (ISs) in interplanetary space have been identified via one spacecraft observation. However, Feng et al. suggested that the analysis using a single spacecraft observation based only on the Rankine-Hugoniot (R-H) relations could misinterpret a tangential discontinuity (TD) as an IS. The misinterpretation can be fixed if two spacecraft observations are available. In this paper, we report an IS-like discontinuity associated with a magnetic reconnection exhaust, which was observed by Wind on 2000 August 9 at 1 au. We investigated this discontinuity by fitting the R-H relations and referring to the Advanced Composition Explorer (ACE) observations. As a result, we found that the observed magnetic field and plasma data satisfy the R-H relations well, and the discontinuity satisfies all the requirements of the 2\\to 3 type IS. Although the discontinuity cannot be identified strictly by using two spacecraft observations, in light of the ACE observations we consider that the discontinuity should be an IS rather than a TD.

  16. Discontinuous dual-primal mixed finite elements for elliptic problems

    NASA Technical Reports Server (NTRS)

    Bottasso, Carlo L.; Micheletti, Stefano; Sacco, Riccardo

    2000-01-01

    We propose a novel discontinuous mixed finite element formulation for the solution of second-order elliptic problems. Fully discontinuous piecewise polynomial finite element spaces are used for the trial and test functions. The discontinuous nature of the test functions at the element interfaces allows to introduce new boundary unknowns that, on the one hand enforce the weak continuity of the trial functions, and on the other avoid the need to define a priori algorithmic fluxes as in standard discontinuous Galerkin methods. Static condensation is performed at the element level, leading to a solution procedure based on the sole interface unknowns. The resulting family of discontinuous dual-primal mixed finite element methods is presented in the one and two-dimensional cases. In the one-dimensional case, we show the equivalence of the method with implicit Runge-Kutta schemes of the collocation type exhibiting optimal behavior. Numerical experiments in one and two dimensions demonstrate the order accuracy of the new method, confirming the results of the analysis.

  17. Scaffold optimization in discontinuous epitope containing protein mimics of gp120 using smart libraries.

    PubMed

    Mulder, Gwenn E; Quarles van Ufford, H Linda C; van Ameijde, Jeroen; Brouwer, Arwin J; Kruijtzer, John A W; Liskamp, Rob M J

    2013-04-28

    A diversity of protein surface discontinuous epitope mimics is now rapidly and efficiently accessible. Despite the important role of protein-protein interactions involving discontinuous epitopes in a wide range of diseases, mimicry of discontinuous epitopes using peptide-based molecules remains a major challenge. Using copper(I) catalyzed azide-alkyne cycloaddition (CuAAC), we have developed a general and efficient method for the synthesis of collections of discontinuous epitope mimics. Up to three different cyclic peptides, representing discontinuous epitopes in HIV-gp120, were conjugated to a selection of scaffold molecules. Variation of the scaffold molecule, optimization of the ring size of the cyclic peptides and screening of the resulting libraries for successful protein mimics led to an HIV gp120 mimic with an IC50 value of 1.7 μM. The approach described here provides rapid and highly reproducible access to clean, smart libraries of very complex bio-molecular constructs representing protein mimics for use as synthetic vaccines and beyond.

  18. A hyper-spherical adaptive sparse-grid method for high-dimensional discontinuity detection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Guannan; Webster, Clayton G.; Gunzburger, Max D.

    This work proposes and analyzes a hyper-spherical adaptive hierarchical sparse-grid method for detecting jump discontinuities of functions in high-dimensional spaces is proposed. The method is motivated by the theoretical and computational inefficiencies of well-known adaptive sparse-grid methods for discontinuity detection. Our novel approach constructs a function representation of the discontinuity hyper-surface of an N-dimensional dis- continuous quantity of interest, by virtue of a hyper-spherical transformation. Then, a sparse-grid approximation of the transformed function is built in the hyper-spherical coordinate system, whose value at each point is estimated by solving a one-dimensional discontinuity detection problem. Due to the smoothness of themore » hyper-surface, the new technique can identify jump discontinuities with significantly reduced computational cost, compared to existing methods. Moreover, hierarchical acceleration techniques are also incorporated to further reduce the overall complexity. Rigorous error estimates and complexity analyses of the new method are provided as are several numerical examples that illustrate the effectiveness of the approach.« less

  19. Discontinuation of nicotine replacement therapy among smoking-cessation attempters.

    PubMed

    Burns, Emily K; Levinson, Arnold H

    2008-03-01

    Nicotine replacement therapy (NRT) doubles successful quitting, but more than half of NRT users do not comply with optimal treatment regimens. From the 2005 Colorado state tobacco survey, quit attempters who utilized NRT (N=366) were analyzed in spring 2007. Descriptive and regression analyses were used to examine reasons for discontinuing NRT, length of time on NRT, and quit intentions. The reasons for discontinuing NRT were resuming smoking (34%), side effects (17%), NRT not helping with quitting (14%), quitting smoking (10%), and cost (5%). Poverty, age, and non-Latino minority status were associated with reasons for discontinuation other than quitting smoking. Having side effects was associated with a short duration of NRT use and 95% lower odds of intending to quit in the next month. In the first population-level study examining reasons for discontinuing NRT, general-population smokers who initiate NRT use when attempting to quit are highly likely to discontinue NRT prematurely. Age and culturally-appropriate medication management interventions may increase NRT compliance and improve cessation outcomes.

  20. Effects of controlled discontinuation of long-term used antipsychotics on weight and metabolic parameters in individuals with intellectual disability.

    PubMed

    de Kuijper, Gerda; Mulder, Hans; Evenhuis, Heleen; Visser, Frank; Hoekstra, Pieter J

    2013-08-01

    Antipsychotics are frequently prescribed agents in individuals with intellectual disability, often for behavioral symptoms. Efficacy of antipsychotics for this is ambiguous, so discontinuation should be considered. Weight gain and metabolic dysregulation are well-known adverse effects of antipsychotics which increase the risk of the metabolic syndrome. We performed a discontinuation study in 99 adults with intellectual disability, living in residential facilities who used antipsychotics for behavioral symptoms for more than 1 year. The aim of the present study was to investigate the effects of discontinuation of long-term used antipsychotics on weight, body mass index (BMI), and parameters of the metabolic syndrome and to investigate the influence of genetic polymorphisms and medication factors on these outcomes. Discontinuation of antipsychotics led to a mean decrease of 4 cm waist circumference, of 3.5 kg weight, 1.4 kg/m2 BMI, and 7.1 mm Hg systolic blood pressure. In those participants who had not completely discontinued use of antipsychotics we found a decrease in weight and BMI and an increase in fasting glucose. The presence of the C-allele of serotonin 5-hydroxytryptamine receptor polymorphism rs141334 was associated with higher waist circumference and higher plasma levels of triglycerides and lower levels of high-density lipoprotein. Achievement of complete discontinuation predicted a larger decrease in waist circumference and BMI. In conclusion, results of the study show the beneficial effects of discontinuation of long-term used antipsychotics on metabolic outcomes.

  1. Experimental and Numerical Analysis of Performance Discontinuity of a Pump-Turbine under Pumping Mode

    NASA Astrophysics Data System (ADS)

    Zhang, X.; Burgstaller, R.; Lai, X.; Gehrer, A.; Kefalas, A.; Pang, Y.

    2016-11-01

    The performance discontinuity of a pump-turbine under pumping mode is harmful to stable operation of units in hydropower station. In this paper, the performance discontinuity phenomenon of the pump-turbine was studied by means of experiment and numerical simulation. In the experiment, characteristics of the pump-turbine with different diffuser vane openings were tested in order to investigate the effect of pumping casing to the performance discontinuity. While other effects such as flow separation and rotating stall are known to have an effect on the discontinuity, the present studied test cases show that prerotation is the dominating effect for the instability, positions of the positive slope of characteristics are almost the same in different diffuser vane opening conditions. The impeller has principal effect to the performance discontinuity. In the numerical simulation, CFD analysis of tested pump-turbine has been done with k-ω and SST turbulence model. It is found that the position of performance curve discontinuity corresponds to flow recirculation at impeller inlet. Flow recirculation at impeller inlet is the cause of the discontinuity of characteristics curve. It is also found that the operating condition of occurrence of flow recirculation at impeller inlet is misestimated with k-ω and SST turbulence model. Furthermore, the original SST model has been modified. We predict the occurrence position of flow recirculation at impeller inlet correctly with the modified SST turbulence model, and it also can improve the prediction accuracy of the pump- turbine performance at the same time.

  2. Age at treatment predicts reason for discontinuation of TNF antagonists: data from the BIOBADASER 2.0 registry.

    PubMed

    Busquets, Noemí; Tomero, Eva; Descalzo, Miguel Ángel; Ponce, Andrés; Ortiz-Santamaría, Vera; Surís, Xavier; Carmona, Loreto; Gómez-Reino, Juan J

    2011-11-01

    To assess the retention rate of TNF antagonists in elderly patients suffering from chronic arthropathies and to identify predictive variables of discontinuation by inefficacy or by adverse events (AEs). All patients treated with TNF antagonists in BIOBADASER 2.0, with a diagnosis of either RA or spondyloarthritis (SpA: AS and PsA) were included and classified as <65 (younger) or ≥65 years of age (older) at start of the treatment. Cumulative incidence function for discontinuation (inefficacy or AE) was estimated as being the alternative reason for a competing risk. Competing-risks regression models were used to measure the association between study groups, covariates and reason for discontinuation. A total of 4851 patients were studied; 2957 RA (2291 in the younger group and 666 in the older group) and 1894 SpA (1795 in the younger group and 99 in the older group). Retention curves were statistically differently stratified by age groups, with the SpA younger group having the largest retention rate. Competing-risks regression models showed that in the older group, AEs were the most common reason for discontinuation regardless of the diagnosis of the patient and TNF antagonist molecule, whereas in the younger group, the most common cause of discontinuation was inefficacy. In conclusion, factors predicting discontinuation of TNF antagonists due to AEs are older age and diagnosis of RA. On the other hand, younger age predicts discontinuation due to lack of efficacy.

  3. Primary care providers’ perspectives on discontinuing prostate cancer screening

    PubMed Central

    Pollack, Craig E.; Platz, Elizabeth A.; Bhavsar, Nrupen A.; Noronha, Gary; Green, Gene E.; Chen, Sean; Carter, H. Ballentine

    2012-01-01

    Background Clinical guidelines recommend against routine prostate specific antigen (PSA) screening in older men and those with lower life expectancies. We examined providers’ decision-making regarding discontinuing PSA screening. Methods We administered a survey of primary providers from a large, university-affiliated primary care practice. Providers were asked about their current screening practices, factors that influence their decision to discontinue screening, and barriers to discontinuing screening. Bivariate and multivariable logistic regression analyses were used to examine whether taking age and/or life expectancy into account and barriers to discontinuing were associated with clinician characteristics and practice styles. Results 88.7% of providers participated in the survey (125 out of 141). Over half (59.3%) took both age and life expectancy into account whereas 12.2% did not consider either in their decisions to discontinue PSA screening. Providers varied with the age they typically stop screening and majority (66.4%) report difficulty in assessing life expectancy. Taking patient age and life expectancy into account was not associated with provider characteristics or practice styles. The most frequently cited barriers to discontinuing PSA screening were patient expectation (74.4%) and time constraints (66.4%). Black providers were significantly less likely than non-black providers to endorse barriers related to time constraints and clinical uncertainty, though these results are limited by the small sample size of black providers. Conclusion Though age and life expectancy often figure prominently in decisions to employ screening, providers face multiple barriers to discontinue PSA routine screening, PMID:22517310

  4. Continuity and Discontinuity in Education: Example of Transition from Preschool to School

    ERIC Educational Resources Information Center

    Babic, Nada

    2017-01-01

    This article reconsiders multiple perspectives about continuity and discontinuity of early childhood education. Theoretical starting points, childhood policies and research of continuity and discontinuity exemplified through transition to school, are promising in rethinking and creating productive practices of childhood in different sociocultural…

  5. Reasons for Discontinuing Hashish Use in a Group of Central European Athletes.

    ERIC Educational Resources Information Center

    Duncan, David F.

    1988-01-01

    Examined self-reported reasons for discontinuing marijuana use among 61 former marijuana using students at central European sports training facility. Most common reasons given for discontinuing marijuana use were dislike of effects, athletic training regimen, health reasons, and mental/emotional problems. (Author/NB)

  6. Excursions in fluvial (dis)continuity

    Treesearch

    Gordon E. Grant; Jim E. O' Connor; Elizabeth Safran

    2017-01-01

    Lurking below the twin concepts of connectivity and disconnectivity are their first, and in someways, richer cousins: continuity and discontinuity. In this paper we explore how continuity and discontinuity represent fundamental and complementary perspectives in fluvial geomorphology, and how these perspectives inform and underlie our conceptions of connectivity in...

  7. 41 CFR 101-39.105 - Discontinuance or curtailment of service.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., AND MOTOR VEHICLES 39-INTERAGENCY FLEET MANAGEMENT SYSTEMS 39.1-Establishment, Modification, and Discontinuance of Interagency Fleet Management Systems § 101-39.105 Discontinuance or curtailment of service. (a... efficiencies are realized from the operation of any fleet management system, the Administrator, GSA, will...

  8. Fatigue Behavior of HY-130 Steel Weldments Containing Fabrication Discontinuities.

    DTIC Science & Technology

    1985-04-18

    discontinuities to solutions for elliptical discontinuities. One such approach has been formalized in the ASME Section XI Boiler and Pressure Vessel Code [1... Boiler and Pressure Vessel Code , Section XI, "Rules for Inservice Inspection of Nuclear Reactor Coolant Systems," American Society of Mechanical

  9. 7 CFR 247.17 - Notification of discontinuance of participant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Section 247.17 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.17... effective date of discontinuance. (b) What must a local agency do if it has to discontinue a participant...

  10. 7 CFR 247.17 - Notification of discontinuance of participant.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Section 247.17 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.17... effective date of discontinuance. (b) What must a local agency do if it has to discontinue a participant...

  11. 38 CFR 21.4210 - Suspension and discontinuance of educational assistance payments, and of enrollments or...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) VOCATIONAL REHABILITATION AND EDUCATION Administration of Educational Assistance Programs Schools § 21.4210 Suspension and discontinuance of educational assistance payments, and of enrollments or... discontinuance of educational assistance payments, and of enrollments or reenrollments for pursuit of approved...

  12. 38 CFR 21.4210 - Suspension and discontinuance of educational assistance payments, and of enrollments or...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) VOCATIONAL REHABILITATION AND EDUCATION Administration of Educational Assistance Programs Schools § 21.4210 Suspension and discontinuance of educational assistance payments, and of enrollments or... discontinuance of educational assistance payments, and of enrollments or reenrollments for pursuit of approved...

  13. 27 CFR 11.38 - Discontinued products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Discontinued products. 11.38 Section 11.38 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... products. When a producer or importer discontinues the production or importation of a product, a trade...

  14. Regression Discontinuity in Prospective Evaluations: The Case of the FFVP Evaluation

    ERIC Educational Resources Information Center

    Klerman, Jacob Alex; Olsho, Lauren E. W.; Bartlett, Susan

    2015-01-01

    While regression discontinuity has usually been applied retrospectively to secondary data, it is even more attractive when applied prospectively. In a prospective design, data collection can be focused on cases near the discontinuity, thereby improving internal validity and substantially increasing precision. Furthermore, such prospective…

  15. Effects of electric field methods on modeling the midlatitude ionospheric electrodynamics and inner magnetosphere dynamics

    DOE PAGES

    Yu, Yiqun; Jordanova, Vania Koleva; Ridley, Aaron J.; ...

    2017-05-10

    Here, we report a self-consistent electric field coupling between the midlatitude ionospheric electrodynamics and inner magnetosphere dynamics represented in a kinetic ring current model. This implementation in the model features another self-consistency in addition to its already existing self-consistent magnetic field coupling with plasma. The model is therefore named as Ring current-Atmosphere interaction Model with Self-Consistent magnetic (B) and electric (E) fields, or RAM-SCB-E. With this new model, we explore, by comparing with previously employed empirical Weimer potential, the impact of using self-consistent electric fields on the modeling of storm time global electric potential distribution, plasma sheet particle injection, andmore » the subauroral polarization streams (SAPS) which heavily rely on the coupled interplay between the inner magnetosphere and midlatitude ionosphere. We find the following phenomena in the self-consistent model: (1) The spatially localized enhancement of electric field is produced within 2.5 < L < 4 during geomagnetic active time in the dusk-premidnight sector, with a similar dynamic penetration as found in statistical observations. (2) The electric potential contours show more substantial skewing toward the postmidnight than the Weimer potential, suggesting the resistance on the particles from directly injecting toward the low-L region. (3) The proton flux indeed indicates that the plasma sheet inner boundary at the dusk-premidnight sector is located further away from the Earth than in the Weimer potential, and a “tongue” of low-energy protons extends eastward toward the dawn, leading to the Harang reversal. (4) SAPS are reproduced in the subauroral region, and their magnitude and latitudinal width are in reasonable agreement with data.« less

  16. Effects of electric field methods on modeling the midlatitude ionospheric electrodynamics and inner magnetosphere dynamics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yu, Yiqun; Jordanova, Vania Koleva; Ridley, Aaron J.

    Here, we report a self-consistent electric field coupling between the midlatitude ionospheric electrodynamics and inner magnetosphere dynamics represented in a kinetic ring current model. This implementation in the model features another self-consistency in addition to its already existing self-consistent magnetic field coupling with plasma. The model is therefore named as Ring current-Atmosphere interaction Model with Self-Consistent magnetic (B) and electric (E) fields, or RAM-SCB-E. With this new model, we explore, by comparing with previously employed empirical Weimer potential, the impact of using self-consistent electric fields on the modeling of storm time global electric potential distribution, plasma sheet particle injection, andmore » the subauroral polarization streams (SAPS) which heavily rely on the coupled interplay between the inner magnetosphere and midlatitude ionosphere. We find the following phenomena in the self-consistent model: (1) The spatially localized enhancement of electric field is produced within 2.5 < L < 4 during geomagnetic active time in the dusk-premidnight sector, with a similar dynamic penetration as found in statistical observations. (2) The electric potential contours show more substantial skewing toward the postmidnight than the Weimer potential, suggesting the resistance on the particles from directly injecting toward the low-L region. (3) The proton flux indeed indicates that the plasma sheet inner boundary at the dusk-premidnight sector is located further away from the Earth than in the Weimer potential, and a “tongue” of low-energy protons extends eastward toward the dawn, leading to the Harang reversal. (4) SAPS are reproduced in the subauroral region, and their magnitude and latitudinal width are in reasonable agreement with data.« less

  17. Statistical Patterns of Ionospheric Convection Derived From Mid-latitude, High-Latitude, and Polar SuperDARN HF Radar Observations

    NASA Astrophysics Data System (ADS)

    Thomas, E. G.; Shepherd, S. G.

    2018-04-01

    Over the last decade, the Super Dual Auroral Radar Network (SuperDARN) has undergone a dramatic expansion in the Northern Hemisphere with the addition of more than a dozen radars offering improved coverage at mid-latitudes (50°-60° magnetic latitude) and in the polar cap (80°-90° magnetic latitude). In this study, we derive a statistical model of ionospheric convection (TS18) using line-of-sight velocity measurements from the complete network of mid-latitude, high-latitude, and polar radars for the years 2010-2016. These climatological patterns are organized by solar wind, interplanetary magnetic field (IMF), and dipole tilt angle conditions. We find that for weak solar wind driving conditions the TS18 model patterns are largely similar to the average patterns obtained using high-latitude radar data only. For stronger solar wind driving the inclusion of mid-latitude radar data at the equatorward extent of the ionospheric convection can increase the measured cross-polar cap potential (ΦPC) by as much as 40%. We also derive an alternative model organized by the Kp index to better characterize the statistical convection under a range of magnetic activity conditions. These Kp patterns exhibit similar IMF By dependencies as the TS18 model results and demonstrate a linear increase in ΦPC with increasing Kp for a given IMF orientation. Overall, the mid-latitude radars provide a better specification of the flows within the nightside Harang reversal region for moderate to strong solar wind driving or geomagnetic activity, while the polar radars improve the quality of velocity measurements in the deep polar cap under all conditions.

  18. Effects of electric field methods on modeling the midlatitude ionospheric electrodynamics and inner magnetosphere dynamics

    NASA Astrophysics Data System (ADS)

    Yu, Yiqun; Jordanova, Vania K.; Ridley, Aaron J.; Toth, Gabor; Heelis, Roderick

    2017-05-01

    We report a self-consistent electric field coupling between the midlatitude ionospheric electrodynamics and inner magnetosphere dynamics represented in a kinetic ring current model. This implementation in the model features another self-consistency in addition to its already existing self-consistent magnetic field coupling with plasma. The model is therefore named as Ring current-Atmosphere interaction Model with Self-Consistent magnetic (B) and electric (E) fields, or RAM-SCB-E. With this new model, we explore, by comparing with previously employed empirical Weimer potential, the impact of using self-consistent electric fields on the modeling of storm time global electric potential distribution, plasma sheet particle injection, and the subauroral polarization streams (SAPS) which heavily rely on the coupled interplay between the inner magnetosphere and midlatitude ionosphere. We find the following phenomena in the self-consistent model: (1) The spatially localized enhancement of electric field is produced within 2.5 < L < 4 during geomagnetic active time in the dusk-premidnight sector, with a similar dynamic penetration as found in statistical observations. (2) The electric potential contours show more substantial skewing toward the postmidnight than the Weimer potential, suggesting the resistance on the particles from directly injecting toward the low-L region. (3) The proton flux indeed indicates that the plasma sheet inner boundary at the dusk-premidnight sector is located further away from the Earth than in the Weimer potential, and a "tongue" of low-energy protons extends eastward toward the dawn, leading to the Harang reversal. (4) SAPS are reproduced in the subauroral region, and their magnitude and latitudinal width are in reasonable agreement with data.

  19. 39 CFR 241.3 - Discontinuance of post offices.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    .... These rules are designed to ensure that the reasons leading a district manager, Customer Service and... originally assigned to the discontinued post office may be changed if the responsible district manager... to the discontinued post office. (ii) If the ZIP Code is changed and the parent post office covers...

  20. A Practical Guide to Regression Discontinuity

    ERIC Educational Resources Information Center

    Jacob, Robin; Zhu, Pei; Somers, Marie-Andrée; Bloom, Howard

    2012-01-01

    Regression discontinuity (RD) analysis is a rigorous nonexperimental approach that can be used to estimate program impacts in situations in which candidates are selected for treatment based on whether their value for a numeric rating exceeds a designated threshold or cut-point. Over the last two decades, the regression discontinuity approach has…

  1. 47 CFR 63.62 - Type of discontinuance, reduction, or impairment of telephone or telegraph service requiring...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... impairment of telephone or telegraph service requiring formal application. 63.62 Section 63.62... LINES, NEW LINES, AND DISCONTINUANCE, REDUCTION, OUTAGE AND IMPAIRMENT OF SERVICE BY COMMON CARRIERS... Impairment § 63.62 Type of discontinuance, reduction, or impairment of telephone or telegraph service...

  2. 47 CFR 63.71 - Procedures for discontinuance, reduction or impairment of service by domestic carriers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... impairment of service by domestic carriers. 63.71 Section 63.71 Telecommunication FEDERAL COMMUNICATIONS..., REDUCTION, OUTAGE AND IMPAIRMENT OF SERVICE BY COMMON CARRIERS; AND GRANTS OF RECOGNIZED PRIVATE OPERATING AGENCY STATUS Discontinuance, Reduction, Outage and Impairment § 63.71 Procedures for discontinuance...

  3. 47 CFR 27.66 - Discontinuance, reduction, or impairment of service.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Discontinuance, reduction, or impairment of..., reduction, or impairment of service. (a) Involuntary act. If the service provided by a fixed common carrier... notify the Commission, in writing, as to the reasons for discontinuance, reduction, or impairment of...

  4. Simplified Discontinuous Galerkin Methods for Systems of Conservation Laws with Convex Extension

    NASA Technical Reports Server (NTRS)

    Barth, Timothy J.

    1999-01-01

    Simplified forms of the space-time discontinuous Galerkin (DG) and discontinuous Galerkin least-squares (DGLS) finite element method are developed and analyzed. The new formulations exploit simplifying properties of entropy endowed conservation law systems while retaining the favorable energy properties associated with symmetric variable formulations.

  5. 38 CFR 21.7635 - Discontinuance dates.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-Educational Assistance § 21.7635 Discontinuance dates. The effective date of reduction or discontinuance of... mitigating circumstances VA will terminate or reduce educational assistance effective the first date of the... practices of the institution of higher learning. (Authority: 10 U.S.C. 16136(b), 38 U.S.C. 3680(a); Pub. L...

  6. 38 CFR 21.7635 - Discontinuance dates.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-Educational Assistance § 21.7635 Discontinuance dates. The effective date of reduction or discontinuance of... mitigating circumstances VA will terminate or reduce educational assistance effective the first date of the... practices of the institution of higher learning. (Authority: 10 U.S.C. 16136(b), 38 U.S.C. 3680(a); Pub. L...

  7. 38 CFR 21.7635 - Discontinuance dates.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-Educational Assistance § 21.7635 Discontinuance dates. The effective date of reduction or discontinuance of... mitigating circumstances VA will terminate or reduce educational assistance effective the first date of the... practices of the institution of higher learning. (Authority: 10 U.S.C. 16136(b), 38 U.S.C. 3680(a); Pub. L...

  8. 38 CFR 21.7635 - Discontinuance dates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-Educational Assistance § 21.7635 Discontinuance dates. The effective date of reduction or discontinuance of... mitigating circumstances VA will terminate or reduce educational assistance effective the first date of the... practices of the institution of higher learning. (Authority: 10 U.S.C. 16136(b), 38 U.S.C. 3680(a); Pub. L...

  9. 38 CFR 21.7635 - Discontinuance dates.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-Educational Assistance § 21.7635 Discontinuance dates. The effective date of reduction or discontinuance of... mitigating circumstances VA will terminate or reduce educational assistance effective the first date of the... practices of the institution of higher learning. (Authority: 10 U.S.C. 16136(b), 38 U.S.C. 3680(a); Pub. L...

  10. 46 CFR 550.507 - Postponement, discontinuance, or suspension of action.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... action. The Commission may, on its own motion or upon petition, postpone, discontinue, or suspend any and... 46 Shipping 9 2010-10-01 2010-10-01 false Postponement, discontinuance, or suspension of action. 550.507 Section 550.507 Shipping FEDERAL MARITIME COMMISSION REGULATIONS AND ACTIONS TO ADDRESS...

  11. 46 CFR 550.507 - Postponement, discontinuance, or suspension of action.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... action. The Commission may, on its own motion or upon petition, postpone, discontinue, or suspend any and... 46 Shipping 9 2011-10-01 2011-10-01 false Postponement, discontinuance, or suspension of action. 550.507 Section 550.507 Shipping FEDERAL MARITIME COMMISSION REGULATIONS AND ACTIONS TO ADDRESS...

  12. 27 CFR 31.138 - Discontinuance of business.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Discontinuance of business. 31.138 Section 31.138 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... § 31.138 Discontinuance of business. A dealer going out of business must register that event within 30...

  13. 27 CFR 19.19 - Discontinuance of storage facilities.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Discontinuance of storage... Provisions § 19.19 Discontinuance of storage facilities. If TTB determines that a proprietor's bonded storage... spirits stored in the facility to another storage facility. The transfer will take place at such time and...

  14. 27 CFR 19.79 - Discontinuance of storage facilities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Discontinuance of storage... Provisions Activities Not Subject to This Part § 19.79 Discontinuance of storage facilities. When the appropriate TTB officer finds that any facilities for the storage of spirits on bonded premises are unsafe or...

  15. 27 CFR 19.19 - Discontinuance of storage facilities.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Discontinuance of storage... Provisions § 19.19 Discontinuance of storage facilities. If TTB determines that a proprietor's bonded storage... spirits stored in the facility to another storage facility. The transfer will take place at such time and...

  16. 50 CFR 13.26 - Discontinuance of permit activity.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 1 2010-10-01 2010-10-01 false Discontinuance of permit activity. 13.26 Section 13.26 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR... PLANTS GENERAL PERMIT PROCEDURES Permit Administration § 13.26 Discontinuance of permit activity. When a...

  17. Method for thinning specimen

    DOEpatents

    Follstaedt, David M.; Moran, Michael P.

    2005-03-15

    A method for thinning (such as in grinding and polishing) a material surface using an instrument means for moving an article with a discontinuous surface with an abrasive material dispersed between the material surface and the discontinuous surface where the discontinuous surface of the moving article provides an efficient means for maintaining contact of the abrasive with the material surface. When used to dimple specimens for microscopy analysis, a wheel with a surface that has been modified to produce a uniform or random discontinuous surface significantly improves the speed of the dimpling process without loss of quality of finish.

  18. Accountability Accentuates Interindividual-Intergroup Discontinuity by Enforcing Parochialism.

    PubMed

    Wildschut, Tim; van Horen, Femke; Hart, Claire

    2015-01-01

    Interindividual-intergroup discontinuity is the tendency for relations between groups to be more competitive than relations between individuals. We examined whether the discontinuity effect arises in part because group members experience normative pressure to favor the ingroup (parochialism). Building on the notion that accountability enhances normative pressure, we hypothesized that the discontinuity effect would be larger when accountability is present (compared to absent). A prisoner's dilemma game experiment supported this prediction. Specifically, intergroup (compared to interindividual) interaction activated an injunctive ingroup-favoring norm, and accountability enhanced the influence of this norm on competitive behavior.

  19. Schrödinger propagation of initial discontinuities leads to divergence of moments

    NASA Astrophysics Data System (ADS)

    Marchewka, A.; Schuss, Z.

    2009-09-01

    We show that the large phase expansion of the Schrödinger propagation of an initially discontinuous wave function leads to the divergence of average energy, momentum, and displacement, rendering them unphysical states. If initially discontinuous wave functions are considered to be approximations to continuous ones, the determinant of the spreading rate of these averages is the maximal gradient of the initial wave function. Therefore a dilemma arises between the inclusion of discontinuous wave functions in quantum mechanics and the requirement of finite moments.

  20. Interferon alpha 2 maintenance therapy may enable high rates of treatment discontinuation in chronic myeloid leukemia.

    PubMed

    Burchert, A; Saussele, S; Eigendorff, E; Müller, M C; Sohlbach, K; Inselmann, S; Schütz, C; Metzelder, S K; Ziermann, J; Kostrewa, P; Hoffmann, J; Hehlmann, R; Neubauer, A; Hochhaus, A

    2015-06-01

    A minority of chronic myeloid leukemia (CML) patients is capable of successfully discontinuing imatinib. Treatment modalities to increase this proportion are currently unknown. Here, we assessed the role of interferon alpha 2a (IFN) on therapy discontinuation in a previously reported cohort of 20 chronic phase CML patients who were treated upfront with IFN alpha plus imatinib followed by IFN monotherapy to maintain cytogenetic or molecular remission (MR) after imatinib discontinuation. After a median follow-up of 7.9 years (range, 5.2-12.2), relapse-free survival was 73% (8/11 patients) and 84% (5/6 patients) for patients who discontinued imatinib in major MR (MMR) and MR4/MR4.5, respectively. Ten patients discontinued IFN after a median of 4.5 years (range, 0.24-9.3). After a median of 2.8 years (range, 0.7-5.1), nine of them remain in ongoing treatment-free remission with MR5 (n=6) and MR4.5 (n=3). The four patients who still administer IFN are in stable MR5, MR4.5, MR4, and MMR, respectively. In conclusion, an IFN/imatinib induction treatment followed by a temporary IFN maintenance therapy may enable a high rate of treatment discontinuation in CML patients in at least MMR when stopping imatinib.

  1. Blood, men and tears: keeping IUDs in place in Bangladesh.

    PubMed

    Bradley, Janet E; Alam, Mahboob-E-; Shabnam, Fatema; Beattie, Tara S H

    2009-06-01

    The Intra-Uterine Device (IUD) is an effective method of contraception, but in Bangladesh is associated with high levels of discontinuation within the first year. This study involved data collection from a retrospective cohort of women who had an IUD inserted 12 months earlier. In the cohort, 330 women were interviewed to identify factors associated with discontinuation. Later, 20 women, of the 103 who reported discontinuing because of excessive menstrual bleeding, were interviewed again and in depth about these issues. Of 330 women who had an IUD inserted, 47.3% had discontinued use one year post-insertion. In univariate and multivariate analyses, IUD discontinuation was strongly associated with side-effects (heavier periods; abdominal pain) and spousal factors (not discussing IUD with husband pre-insertion), but not with service delivery factors. In-depth interviews with women who reported excessive blood loss as the main reason for discontinuation found a doubling of both menstrual days and blood loss after IUD insertion. In Bangladesh, women cannot pray, have sexual intercourse, perform household tasks or participate in community activities during menstruation. Thus, women with menstrual side-effects faced serious physical, social and psychological challenges that made continuation difficult. Among those who discontinued, spouses were generally unsupportive and sometimes abusive, particularly when not involved in the decision to use the IUD.

  2. Fitness in animals correlates with proximity to discontinuities in body mass distributions.

    USGS Publications Warehouse

    Angeler, David G.; Allen, Craig R.; Vila-Gispert, Anna; Almeida, David

    2014-01-01

    Discontinuous structure in landscapes may cause discontinuous, aggregated species body-mass patterns, reflecting the scales of structure available to animal communities within a landscape. Empirical analyses have shown that the location of species within body mass aggregations, which reflect this scale-specific organization, is non-random with regard to several ecological phenomena, including species extinctions. The propensity of declining species to have body masses proximate to discontinuities suggests that transition zones between scaling regimes ultimately decreases the ecological fitness for some species. We test this proposition using vulnerable and unthreatened fish species in Mediterranean streams with differing levels of human impact. We show that the proximity to discontinuities in body mass aggregations (“distance-to-edge”) of more vs. less fit individuals within vulnerable and unthreatened populations differs. Specifically, regression analysis between the scaled mass index, a proxy of animal fitness, and distance-to-edge reveals negative and positive relationships for vulnerable and unthreatened species, respectively. That is, fitness is higher close to discontinuities in vulnerable populations and toward the center of body mass aggregation groups in unthreatened populations. Our results demonstrate the suitability of the discontinuity framework for scrutinizing non-random patterns of environmental impact in populations. Further exploration of the usefulness of this method across other ecosystems and organism groups is warranted.

  3. Changes in elderly women's health-related quality of life following discontinuation of hormone replacement therapy

    PubMed Central

    Heller, Debra A; Gold, Carol H; Ahern, Frank M; Pringle, Kristine E; Brown, Theresa V; Glessner, Margaret R

    2005-01-01

    Background Many women have discontinued hormone replacement therapy (HRT) in view of recent findings. The goal of this study was to determine if HRT discontinuation is associated with changes in health-related quality of life (HRQOL) in elderly women. Methods We studied women enrolled in Pennsylvania's Pharmaceutical Assistance Contract for the Elderly (PACE) program, linking prescription claims with data from a longitudinal mail survey. HRQOL measures included the number of days out of the last 30 that physical health was not good and analogous measures for mental health, pain, and interference with activities, as well as a composite "healthy days" measure developed by CDC. Longitudinal analyses focused on 2,357 women who completed surveys in both 2002 and 2003, and who used HRT at baseline (mean age = 75.5, range = 65–102). Propensity scores were used to match HRT continuers and discontinuers according to HRT type, demographics, and baseline HRQOL. Analysis of covariance was used to compare HRQOL change in continuers and discontinuers. Results Between 2002 and 2003, 43% of HRT users discontinued therapy. Analysis of covariance to examine HRQOL change revealed complex interactions with age. Discontinuers aged 65–74 reported greater increases in days in which mental health was not good (p < .05), fewer "healthy days" (p < .05), more days in which health interfered with activities (p < .01), and more days with pain (p < .01). Among women aged 75–84, HRT discontinuers reported more days in which physical health was not good (p < .01); no other significant effects were observed in this group. Relative to HRT continuers, discontinuers aged 85 and older experienced apparent HRQOL improvements following cessation, with fewer days in which physical health was not good (p < .01), fewer days of poor mental health (p < .05), and more "healthy days" (p < .01). Conclusions These results suggest that there are substantial age differences in response to HRT discontinuation. While women aged 65–74 experienced apparent declines in HRQOL following HRT cessation, women aged 85 and older experienced relative improvements. The HRQOL declines observed among younger women underscore the importance of communication between clinicians and patients throughout the discontinuation process. These results also demonstrate the value of HRQOL surveillance as a component of health program administration. PMID:15904516

  4. Local Variations in the Upper-Mantle Transition Zone Structure From a Novel Approach Using High-Frequency Triplication Data

    NASA Astrophysics Data System (ADS)

    Park, S.; Ishii, M.

    2017-12-01

    Constraining elastic properties of the 410- and 660-km discontinuities is vital for understanding the mantle composition and dynamics. One approach to study the transition zone is to use the "triplicated" arrivals of seismic data. These arrivals consist of three seismic phases that are sensitive to seismic structure slightly above, at, and below the discontinuity. Therefore, these data provide powerful constraints on the depth, width, and magnitude of velocity jump of the discontinuities with consequences for the studies of mantle composition, relevant phase transitions, and dynamics. Nevertheless, one of the most challenging aspects of using the triplication data is to identify the three individual phases that arrive close in time. In order to separate the three phases, we apply Radon transform to short-period seismograms recorded by a dense array of stations. This approach unwraps the triplication pattern, and brings out the high-frequency information that is not easily accessible in the original form of data. This method is applied to study the transition zone around the Kuril subduction zone, a region northeast of Japan. We take advantage of the High-Sensitivity Seismograph Network in Japan comprised of more than 700 stations whose dense sampling in distance allows us to capture the triplication pattern. The data are processed to obtain the variations in wave speeds around the discontinuities, i.e., at 410±100 and 660±100 km, resulting in models of topography and sharpness of discontinuities at various sampling locations. Both discontinuities exhibit local topography undulations consistent with the temperature effect; the 410- and 660-km discontinuities become shallower and deeper, respectively, nearer to the slab. Additional discontinuities around 660 km are also detected, which may be attributed to the garnet transitions occurring at similar depths as the post-spinel transition. The 410-km discontinuity is observed to be more diffuse than 660-km discontinuity. The wide transition cannot be explained solely by the presence of water or melt, suggesting the importance of other effects such as high Fe content of olivine or olivine-poor composition.

  5. A New Stochastic Approach to Predict Peak and Residual Shear Strength of Natural Rock Discontinuities

    NASA Astrophysics Data System (ADS)

    Casagrande, D.; Buzzi, O.; Giacomini, A.; Lambert, C.; Fenton, G.

    2018-01-01

    Natural discontinuities are known to play a key role in the stability of rock masses. However, it is a non-trivial task to estimate the shear strength of large discontinuities. Because of the inherent complexity to access to the full surface of the large in situ discontinuities, researchers or engineers tend to work on small-scale specimens. As a consequence, the results are often plagued by the well-known scale effect. A new approach is here proposed to predict shear strength of discontinuities. This approach has the potential to avoid the scale effect. The rationale of the approach is as follows: a major parameter that governs the shear strength of a discontinuity within a rock mass is roughness, which can be accounted for by surveying the discontinuity surface. However, this is typically not possible for discontinuities contained within the rock mass where only traces are visible. For natural surfaces, it can be assumed that traces are, to some extent, representative of the surface. It is here proposed to use the available 2D information (from a visible trace, referred to as a seed trace) and a random field model to create a large number of synthetic surfaces (3D data sets). The shear strength of each synthetic surface can then be estimated using a semi-analytical model. By using a large number of synthetic surfaces and a Monte Carlo strategy, a meaningful shear strength distribution can be obtained. This paper presents the validation of the semi-analytical mechanistic model required to support the new approach for prediction of discontinuity shear strength. The model can predict both peak and residual shear strength. The second part of the paper lays the foundation of a random field model to support the creation of synthetic surfaces having statistical properties in line with those of the data of the seed trace. The paper concludes that it is possible to obtain a reasonable estimate of peak and residual shear strength of the discontinuities tested from the information from a single trace, without having access to the whole surface.

  6. Upper Mantle Discontinuity Structure Beneath the Western Atlantic Ocean and Eastern North America from SS Precursors

    NASA Astrophysics Data System (ADS)

    Schmerr, N. C.; Beghein, C.; Kostic, D.; Baldridge, A. M.; West, J. D.; Nittler, L. R.; Bull, A. L.; Montesi, L.; Byrne, P. K.; Hummer, D. R.; Plescia, J. B.; Elkins-Tanton, L. T.; Lekic, V.; Schmidt, B. E.; Elkins, L. J.; Cooper, C. M.; ten Kate, I. L.; Van Hinsbergen, D. J. J.; Parai, R.; Glass, J. B.; Ni, J.; Fuji, N.; McCubbin, F. M.; Michalski, J. R.; Zhao, C.; Arevalo, R. D., Jr.; Koelemeijer, P.; Courtier, A. M.; Dalton, H.; Waszek, L.; Bahamonde, J.; Schmerr, B.; Gilpin, N.; Rosenshein, E.; Mach, K.; Ostrach, L. R.; Caracas, R.; Craddock, R. A.; Moore-Driskell, M. M.; Du Frane, W. L.; Kellogg, L. H.

    2015-12-01

    Seismic discontinuities within the mantle arise from a wide range of mechanisms, including changes in mineralogy, major element composition, melt content, volatile abundance, anisotropy, or a combination of the above. In particular, the depth and sharpness of upper mantle discontinuities at 410 and 660 km depth are attributed to solid-state phase changes sensitive to both mantle temperature and composition, where regions of thermal heterogeneity produce topography and chemical heterogeneity changes the impedance contrast across the discontinuity. Seismic mapping of this topography and sharpness thus provides constraint on the thermal and compositional state of the mantle. The EarthScope USArray is providing unprecedented access to a wide variety of new regions previously undersampled by the SS precursors. This includes the boundary between the oceanic plate in the western Atlantic Ocean and continental margin of eastern North America. Here we use a seismic array approach to image the depth, sharpness, and topography of the upper mantle discontinuities, as well as other possible upper mantle reflectors beneath this region. This array approach utilizes seismic waves that reflect off the underside of a mantle discontinuity and arrive several hundred seconds prior to the SS seismic phase as precursory energy. In this study, we collected high-quality broadband data SS precursors data from shallow focus (< 30 km deep), mid-Atlantic ridge earthquakes recorded by USArray seismometers in Alaska. We generated 4th root vespagrams to enhance the SS precursors and determine how they sample the mantle. Our data show detection of localized structure on the discontinuity boundaries as well as additional horizons, such as the X-discontinuity and a potential reflection from a discontinuity near the depth of the lithosphere-asthenosphere boundary. These structures are related to the transition from predominantly old ocean lithosphere to underlying continental lithosphere, as while deeper reflectors are associated with the subduction of the ancient Farallon slab. A comparison of the depth of upper mantle discontinuities to changes in seismic velocity and anisotropy will further quantify the relationship to mantle flow, compositional layering, and phases changes.

  7. How to achieve long-term breast-feeding: factors associated with early discontinuation.

    PubMed

    Camurdan, Aysu Duyan; Ilhan, Mustafa N; Beyazova, Ufuk; Sahin, Figen; Vatandas, Nilgun; Eminoglu, Sancar

    2008-11-01

    To evaluate the factors associated with discontinuation of breast-feeding before 12 months in order to make suggestions for achieving long-term breast-feeding. A descriptive cross-sectional study. Gazi University Medical School, Ankara, Turkey. Mothers of 1230 children who discontinued breast-feeding at least 15 d before the last visit were asked to fill out a questionnaire about the discontinuation process. Logistic regression analysis was performed to assess the independent effects of factors that might influence breast-feeding discontinuation. Mean breast-feeding duration of the study group was 11.04 (SD 7.45) months. Introduction of bottle-feeding correlated with discontinuation of breast-feeding (r=0.507, P = 0.001). Important risk factors for discontinuation of breast-feeding before the first 12 months were not exclusively breast-feeding at 3 and 6 months, prematurity, not having a plan about breast-feeding duration and maternity leave duration of

  8. Velocity structure around the 410 km discontinuity beneath the East China Sea based on the waveform modeling method

    NASA Astrophysics Data System (ADS)

    Li, W.; Cui, Q.; Gao, Y.; Wei, R.; Zhou, Y.; Yu, J.

    2017-12-01

    The 410 km discontinuity is the upper boundary of the mantle transition zone. Seismic detections on the structure and morphology of the 410 km discontinuity are helpful to understand the compositions of the Earth's interior and the relevant geodynamics. In this paper, we select the broadband P waveforms of an intermediate earthquake that occurred in the Ryukyu subduction zone and retrieved from the China Digital Seismograph Network, and study the fine velocity structure around the 410 km discontinuity by matching the observed triplicated waveforms with the theoretical ones. Our results reveal that (1) the 410 km discontinuity beneath the East China Sea is mostly a sharp boundary with a small-scale uplift of 8-15 km and a gradient boundary up to 20 km in the most southern part, and (2) there exist a low velocity layer atop the 410 km discontinuity with the thickness of 50-62 km and P-wave velocity decrease of 0.5%-1.5%, and (3) a high velocity anomaly with P-wave decrease of 1.0%-3.0% below 440 km. Combining with the previous topographic results in this area, we speculate that the high velocity anomaly is relevant to the stagnancy of the western Pacific slab in the mantle transition zone, the decomposition of phase E in the slab results in the increase of water content, which would cause the uplift of the 410 km discontinuity, and the low velocity layer atop the discontinuity should be related to the partial melting of the mantle peridotite induced by the dehydration of the hydrous minerals.

  9. Discontinuation among University Students in Southern Thailand

    ERIC Educational Resources Information Center

    Sittichai, Ruthaychonnee; Tongkumchum, Phattrawan; McNeil, Nittaya

    2009-01-01

    This study uses a statistical model to account for the pattern of discontinuation of university study at Pattani campus of Prince of Songkla University (PSU) in southern Thailand. University records for 11,408 bachelor degree students enrolled between 1999 and 2006 were used. Discontinuation rates were analyzed by using a logistic regression model…

  10. 78 FR 46679 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-01

    ... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... of a signal system. FRA assigned the petition Docket Number FRA-2013-0073. Applicant: Norfolk..., Georgia 30309. NS seeks approval of the proposed discontinuance of automatic signals within traffic...

  11. 78 FR 59754 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-27

    ... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... of a signal system. FRA assigned the petition Docket Number FRA-2013-0095. Applicant: Grenada Railway... seeks approval of the proposed discontinuance and removal of the automatic block signal (ABS) system...

  12. 78 FR 14874 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-07

    ... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... of a signal system. FRA assigned the petition Docket Number FRA-2013-0017. Applicant: Norfolk..., Georgia 30309. NS seeks approval of the proposed temporary discontinuance of the signal system at the...

  13. 78 FR 77785 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-24

    ... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... discontinuance or modification of a signal system. FRA assigned the petition Docket Number FRA-2013-0125. Applicants: Union Pacific Railroad, Mr. Phillip A. Danner, AVP Engineering-Signal, 1400 Douglas Street, MS...

  14. 78 FR 77786 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-24

    ... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... Federal Railroad Administration (FRA) seeking approval for the discontinuance or modification of a signal..., Inc., Mr. Timothy P. Purcell, Acting Chief Engineer--Signals, One Penn Plaza East, Newark, NJ 07105...

  15. 77 FR 9296 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-16

    ... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... or modification of a signal system. FRA assigned the petition Docket Number FRA-2012-0012. UP seeks approval of the proposed discontinuance of the automatic block signal (ABS) system between Control Point...

  16. 77 FR 40700 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-10

    ... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... discontinuance or modification of a signal system. FRA assigned the petition Docket Number FRA-2012-0053. Applicant: Alabama and Tennessee River Railway LLC, Mr. Jason Scott, Vice President Signals & Communications...

  17. 78 FR 12823 - Notice of Joint Application for Approval of Discontinuance or Modification of a Railroad Signal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-25

    ... of Joint Application for Approval of Discontinuance or Modification of a Railroad Signal System In... Administration (FRA) seeking approval for the discontinuance or modification of a signal system. FRA assigned the.... David B. Olson, Chief Engineer Communication and Signals, 500 Water Street, Speed Code J-350...

  18. 41 CFR 101-39.105-1 - Transfers from discontinued or curtailed fleet management systems.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... discontinued or curtailed fleet management systems. 101-39.105-1 Section 101-39.105-1 Public Contracts and... AVIATION, TRANSPORTATION, AND MOTOR VEHICLES 39-INTERAGENCY FLEET MANAGEMENT SYSTEMS 39.1-Establishment, Modification, and Discontinuance of Interagency Fleet Management Systems § 101-39.105-1 Transfers from...

  19. Cultural Discontinuity: Toward a Quantitative Investigation of a Major Hypothesis in Education

    ERIC Educational Resources Information Center

    Tyler, Kenneth M.; Uqdah, Aesha L.; Dillihunt, Monica L.; Beatty-Hazelbaker, ReShanta; Conner, Timothy; Gadson, Nadia; Henchy, Alexandra; Hughes, Travonia; Mulder, Shambra; Owens, Elizabeth; Roan-Belle, Clarissa; Smith, LaToya; Stevens, Ruby

    2008-01-01

    Education researchers have suggested that the academic challenges faced by many ethnic minority students are linked to perceived cultural discontinuity between students' home- and school-based experiences. However, there has been very little empirical inquiry into the existence and effects of cultural discontinuity for these students. The purpose…

  20. The Cultural Discontinuity Hypothesis: An Appalachian American Perspective in Eastern Kentucky

    ERIC Educational Resources Information Center

    Conner, Timothy W., II

    2017-01-01

    K.M. Tyler et al. (2008) propose a quantitative method to measure differences between school and home experiences had by students of ethnic minority status and how such differences (cultural discontinuity) may affect psychological factors related to student achievement. Although study of cultural discontinuity has been applied to understanding…

  1. Discontinuities in Early Development of the Understanding of Physical Causality

    ERIC Educational Resources Information Center

    Aschersleben, Gisa; Henning, Anne; Daum, Moritz M.

    2013-01-01

    Research on early physical reasoning has shown surprising discontinuities in developmental trajectories. Infants possess some skills that seem to disappear and then re-emerge in childhood. It has been suggested that prediction skills required in search tasks might cause these discontinuities (Keen, 2003). We tested 3.5- to 5-year-olds'…

  2. 76 FR 41413 - Post Office Organization and Administration: Establishment, Classification, and Discontinuance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-14

    ...) to improve the process for discontinuing Post Offices and other Postal Service-operated retail... appears below. The Postal Service is currently in the process of consultation under 39 U.S.C. 1004(b)-(d... or branches, the Postal Service is making that same process applicable to the discontinuance of all...

  3. 21 CFR 801.57 - Discontinuation of legacy FDA identification numbers assigned to devices.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Discontinuation of legacy FDA identification... Device Identification § 801.57 Discontinuation of legacy FDA identification numbers assigned to devices... been assigned an FDA labeler code to facilitate use of NHRIC or NDC numbers may continue to use that...

  4. Locating the Discontinuities of a Bounded Function by the Partial Sums of its Fourier Series I: Periodical Case

    NASA Technical Reports Server (NTRS)

    Kvernadze, George; Hagstrom,Thomas; Shapiro, Henry

    1997-01-01

    A key step for some methods dealing with the reconstruction of a function with jump discontinuities is the accurate approximation of the jumps and their locations. Various methods have been suggested in the literature to obtain this valuable information. In the present paper, we develop an algorithm based on identities which determine the jumps of a 2(pi)-periodic bounded not-too-highly oscillating function by the partial sums of its differentiated Fourier series. The algorithm enables one to approximate the locations of discontinuities and the magnitudes of jumps of a bounded function. We study the accuracy of approximation and establish asymptotic expansions for the approximations of a 27(pi)-periodic piecewise smooth function with one discontinuity. By an appropriate linear combination, obtained via derivatives of different order, we significantly improve the accuracy. Next, we use Richardson's extrapolation method to enhance the accuracy even more. For a function with multiple discontinuities we establish simple formulae which "eliminate" all discontinuities of the function but one. Then we treat the function as if it had one singularity following the method described above.

  5. Multistability of neural networks with discontinuous non-monotonic piecewise linear activation functions and time-varying delays.

    PubMed

    Nie, Xiaobing; Zheng, Wei Xing

    2015-05-01

    This paper is concerned with the problem of coexistence and dynamical behaviors of multiple equilibrium points for neural networks with discontinuous non-monotonic piecewise linear activation functions and time-varying delays. The fixed point theorem and other analytical tools are used to develop certain sufficient conditions that ensure that the n-dimensional discontinuous neural networks with time-varying delays can have at least 5(n) equilibrium points, 3(n) of which are locally stable and the others are unstable. The importance of the derived results is that it reveals that the discontinuous neural networks can have greater storage capacity than the continuous ones. Moreover, different from the existing results on multistability of neural networks with discontinuous activation functions, the 3(n) locally stable equilibrium points obtained in this paper are located in not only saturated regions, but also unsaturated regions, due to the non-monotonic structure of discontinuous activation functions. A numerical simulation study is conducted to illustrate and support the derived theoretical results. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Management applications of discontinuity theory

    USGS Publications Warehouse

    Angeler, David G.; Allen, Craig R.; Barichievy, Chris; Eason, Tarsha; Garmestani, Ahjond S.; Graham, Nicholas A.J.; Granholm, Dean; Gunderson, Lance H.; Knutson, Melinda; Nash, Kirsty L.; Nelson, R. John; Nystrom, Magnus; Spanbauer, Trisha; Stow, Craig A.; Sundstrom, Shana M.

    2015-01-01

    Human impacts on the environment are multifaceted and can occur across distinct spatiotemporal scales. Ecological responses to environmental change are therefore difficult to predict, and entail large degrees of uncertainty. Such uncertainty requires robust tools for management to sustain ecosystem goods and services and maintain resilient ecosystems.We propose an approach based on discontinuity theory that accounts for patterns and processes at distinct spatial and temporal scales, an inherent property of ecological systems. Discontinuity theory has not been applied in natural resource management and could therefore improve ecosystem management because it explicitly accounts for ecological complexity.Synthesis and applications. We highlight the application of discontinuity approaches for meeting management goals. Specifically, discontinuity approaches have significant potential to measure and thus understand the resilience of ecosystems, to objectively identify critical scales of space and time in ecological systems at which human impact might be most severe, to provide warning indicators of regime change, to help predict and understand biological invasions and extinctions and to focus monitoring efforts. Discontinuity theory can complement current approaches, providing a broader paradigm for ecological management and conservation.

  7. Interplanetary boundary layers at 1 AU. [magnetic field measurements from Explorer 34

    NASA Technical Reports Server (NTRS)

    Burlaga, L. F.; Lemaire, J. F.; Turner, J. M.

    1976-01-01

    The structure and nature of discontinuities in the interplanetary magnetic field at 1 AU in the period March 18, 1971 to April 9, 1971, is determined by using high-resolution magnetic field measurements from Explorer 34. The discontinuities that were selected for this analysis occurred under a variety of interplanetary conditions at an average rate of 0.5/hr. This set does not include all discontinuities that were present, but the sample is large and it is probably representative. Both tangential and rotational discontinuities were identified, the ratio of TD's to RD's being approximately 3 to 1. Tangential discontinuities were observed every day, even among Alfvenic fluctuations. The structure of most of the boundary layers was simple and ordered, i.e., the magnetic field usually changed smoothly and monotonically from one side of the boundary layer to the other.

  8. High Resolution Seismic Images of Transition Zone Discontinuities beneath the Hawaii-Emperor Seamount Chain

    NASA Astrophysics Data System (ADS)

    Cao, Q.; Wang, P.; van der Hilst, R. D.; Shim, S.

    2009-12-01

    Taking advantage of the abundance of natural sources (earthquakes) in western Pacific subduction zones and the many seismograph stations in the Americas, we use inverse scattering - a generalized Radon transform - of SS precursors to image the transition zone discontinuities underneath Hawaii and the Hawaii-Emperor seamount chain. The GRT makes use of scattering theory and extracts structural information from broad band data windows that include precursors to SS (which are the specular reflections at the discontinuities that form the main arrivals) as well as non-specular scattered energy (which is often discarded as noise). More than 150,000 seismograms (from the IRIS Data Management Center) are used to form a 3-D image of the transition zone discontinuities beneath the central Pacific. In addition to clear signals near 410, 520, and 660 km depth, the data also reveal scatter interfaces near 370 km dept and between 800-1000 km depth, which may be regional, laterally intermittent scatter horizons. Our images reveal a conspicuous uplift of the 660 discontinuity in a region of 800km in diameter to the west of the active volcanoes of Hawaii. No correspondent localized depression of the 410 discontinuity is found. Instead, we find a smaller scale anomaly suggesting that the 410 discontinuity is locally elevated in the same region. This may indicate the presence of melt or minor chemical constitutes. The lack of correlation between and differences in lateral length scale of the topographies of the 410 and 660 km discontinuities are also consistent with a deep-mantle plume impinging on the transition zone, creating a pond of hot material underneath 660 discontinuity, and with secondary plumes connecting to the present-day hotspot at Earth’s surface. Our observations suggest that more complicated plume morphology and plume dynamics within the Earth's mantle should be taken into account to describe the plumes and, in particular, mass transport across the transition zone (and, by implication, the relationships between Hawaiian basalt geochemistry and deep mantle domains).

  9. Effects of pill burden on discontinuation of the initial HAART regimen in minority female patients prescribed 1 pill/day versus any other pill burden.

    PubMed

    Hill, Seth; Kavookjian, Jan; Qian, Jingjing; Chung, Allison; Vandewaa, John

    2014-01-01

    Highly active antiretroviral therapy (HAART) is a mainstay of treatment for patients with Human Immunodeficiency Virus (HIV). Since second line HAART therapies can be costlier and less effective, it is essential to understand the duration of initial HAART therapies. The overall aim of this study was to estimate the effects of daily pill burden on the time to discontinuation of the initial HAART regimen. Patients were initially identified through the clinic's CAREWARE database. A chart review was conducted for data collection, where only adult, female, HIV-positive patients initiating therapy at the study clinic between 1 January 2001 and 31 December 2011 were included. All study subjects were followed up from the initiation of HAART to treatment discontinuation. A Kaplan-Meier curve was generated to describe time to discontinuation by regimens, and a Cox proportional hazards model was developed to assess the impact of different regimen and patient demographic characteristics on the hazard of discontinuation of the initial regimen. A total of 498 charts were initially reviewed. After assessment of these patients for inclusion criteria, a cohort of 115 adult female patients who initiated HAART at the study clinic was included. Patients treated with 1 pill/day regimen had a significantly longer time to discontinuation than regimens of >1 pills/day (mean duration of initial therapy was 1062.56 days vs. 631.70 days, respectively, p = 0.003). Compared to 1 pill/day regimens, >1 pills/day regimens were associated with a higher hazard of discontinuation (hazard ratio (HR) =3.44 with 95% confidence interval (CI) = 1.25, 9.48). A higher viral load and patients without insurance were also found to be significantly associated with increased hazards of discontinuation. Overall, female HIV patients initiating therapy with the 1 pill/day HAART regimen were less likely to discontinue their treatment compared to patients initiating with >1 pills/day HAART regimen.

  10. Risk factors associated with treatment discontinuation and down-titration in type 2 diabetes patients treated with sulfonylureas.

    PubMed

    Iglay, Kristy; Qiu, Ying; Steve Fan, Chun-Po; Li, Zhiyi; Tang, Jackson; Laires, Pedro

    2016-09-01

    Sulfonylurea therapy among patients with type 2 diabetes mellitus (T2DM) can be disrupted due to adverse events, including hypoglycemia. A retrospective study using the MarketScan claims database quantified the frequency of sulfonylurea discontinuation or down-titration and identified associated risk factors. Adult patients with an index sulfonylurea prescription between 2008 and 2012 and 1 year continuous enrollment pre- and post-index were included. Therapy changes assessed over 1 year post-index included discontinuation and down-titration. Discontinuation occurred if the date of a fill was >90 days from the end date of the preceding fill. Down-titration occurred when a fill had a lower equivalent dose than the fill on the index date. Kaplan-Meier methods estimated the probability of either discontinuation or down-titration over 12 months, and Cox regression models identified associated risk factors. A total of 104,082 sulfonylurea users were included in the study and the probability of either discontinuation or down-titration at 3, 6 and 12 months was 23.2%, 38.9%, and 52.3%, respectively. Major risk factors associated with therapy changes included post-index hypoglycemia (discontinuation hazard ratio [HR] = 1.78 [1.68, 1.89]; down-titration HR =2.79 [2.40, 3.23]) and concomitant use of insulin (discontinuation HR =1.48 [1.40, 1.57]; down-titration HR =1.82 [1.56, 2.11]). Other risk factors included younger age, female gender, use of second generation sulfonylureas, prior cardiovascular comorbidity and liver disease. The study was not able to assess unreported, potentially mild cases of hypoglycemia, nor was it able to evaluate the association between changes in therapy and HbA1c levels or body weight. More than half of T2DM patients who initiated sulfonylurea therapy discontinued or down-titrated within 1 year. Insulin use and hypoglycemia were associated with sulfonylurea therapy change.

  11. Ultrasound-detected bone erosion is a relapse risk factor after discontinuation of biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis whose ultrasound power Doppler synovitis activity and clinical disease activity are well controlled.

    PubMed

    Kawashiri, Shin-Ya; Fujikawa, Keita; Nishino, Ayako; Okada, Akitomo; Aramaki, Toshiyuki; Shimizu, Toshimasa; Umeda, Masataka; Fukui, Shoichi; Suzuki, Takahisa; Koga, Tomohiro; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Mizokami, Akinari; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Aoyagi, Kiyoshi; Maeda, Takahiro; Kawakami, Atsushi

    2017-05-25

    In the present study, we explored the risk factors for relapse after discontinuation of biologic disease-modifying antirheumatic drug (bDMARD) therapy in patients with rheumatoid arthritis (RA) whose ultrasound power Doppler (PD) synovitis activity and clinical disease activity were well controlled. In this observational study in clinical practice, the inclusion criteria were based on ultrasound disease activity and clinical disease activity, set as low or remission (Disease Activity Score in 28 joints based on erythrocyte sedimentation rate <3.2). Ultrasound was performed in 22 joints of bilateral hands at discontinuation for evaluating synovitis severity and presence of bone erosion. Patients with a maximum PD score ≤1 in each joint were enrolled. Forty patients with RA were consecutively recruited (November 2010-March 2015) and discontinued bDMARD therapy. Variables at the initiation and discontinuation of bDMARD therapy that were predictive of relapse during the 12 months after discontinuation were assessed. The median patient age was 54.5 years, and the median disease duration was 3.5 years. Nineteen (47.5%) patients relapsed during the 12 months after the discontinuation of bDMARD therapy. Logistic regression analysis revealed that only the presence of bone erosion detected by ultrasound at discontinuation was predictive of relapse (OR 8.35, 95% CI 1.78-53.2, p = 0.006). No clinical characteristics or serologic biomarkers were significantly different between the relapse and nonrelapse patients. The ultrasound synovitis scores did not differ significantly between the groups. Our findings are the first evidence that ultrasound bone erosion may be a relapse risk factor after the discontinuation of bDMARD therapy in patients with RA whose PD synovitis activity and clinical disease activity are well controlled.

  12. The effect of manufacturing conditions on discontinuity population and fatigue fracture behavior in carbon/epoxy composites

    NASA Astrophysics Data System (ADS)

    Hakim, Issa; Laquai, Rene; Walter, David; Mueller, Bernd; Graja, Paul; Meyendorf, Norbert; Donaldson, Steven

    2017-02-01

    Carbon fiber composites have been increasingly used in aerospace, military, sports, automotive and other fields due to their excellent properties, including high specific strength, high specific modulus, corrosion resistance, fatigue resistance, and low thermal expansion coefficient. Interlaminar fracture is a serious failure mode leading to a loss in composite stiffness and strength. Discontinuities formed during manufacturing process degrade the fatigue life and interlaminar fracture resistance of the composite. In his study, three approaches were implemented and their results were correlated to quantify discontinuities effecting static and fatigue interlaminar fracture behavior of carbon fiber composites. Samples were fabricated by hand layup vacuum bagging manufacturing process under three different vacuum levels, indicated High (-686 mmHg), Moderate (-330 mmHg) and Poor (0 mmHg). Discontinuity content was quantified through-thickness by destructive and nondestructive techniques. Eight different NDE methods were conducted including imaging NDE methods: X-Ray laminography, ultrasonic, high frequency eddy current, pulse thermography, pulse phase thermography and lock-in-thermography, and averaging NDE techniques: X-Ray refraction and thermal conductivity measurements. Samples were subsequently destructively serial sectioned through-thickness into several layers. Both static and fatigue interlaminar fracture behavior under Mode I were conducted. The results of several imaging NDE methods revealed the trend in percentages of discontinuity. However, the results of averaging NDE methods showed a clear correlation since they gave specific values of discontinuity through-thickness. Serial sectioning exposed the composite's internal structure and provided a very clear idea about the type, shape, size, distribution and location of most discontinuities included. The results of mechanical testing showed that discontinuities lead to a decrease in Mode I static interlaminar fracture toughness and a decrease in Mode I cyclic strain energy release rates fatigue life. Finally, all approaches were correlated: the resulted NDE percentages and parameters were correlated with the features revealed by the destructive test of serial sectioning and static and fatigue values in order to quantify discontinuities such as delamination and voids.

  13. Discontinuous Spectral Difference Method for Conservation Laws on Unstructured Grids

    NASA Technical Reports Server (NTRS)

    Liu, Yen; Vinokur, Marcel; Wang, Z. J.

    2004-01-01

    A new, high-order, conservative, and efficient method for conservation laws on unstructured grids is developed. The concept of discontinuous and high-order local representations to achieve conservation and high accuracy is utilized in a manner similar to the Discontinuous Galerkin (DG) and the Spectral Volume (SV) methods, but while these methods are based on the integrated forms of the equations, the new method is based on the differential form to attain a simpler formulation and higher efficiency. A discussion on the Discontinuous Spectral Difference (SD) Method, locations of the unknowns and flux points and numerical results are also presented.

  14. Method For Identifying Sedimentary Bodies From Images And Its Application To Mineral Exploration

    NASA Technical Reports Server (NTRS)

    Wilkinson, Murray Justin (Inventor)

    2006-01-01

    A method is disclosed for identifying a sediment accumulation from an image of a part of the earth's surface. The method includes identifying a topographic discontinuity from the image. A river which crosses the discontinuity is identified from the image. From the image, paleocourses of the river are identified which diverge from a point where the river crosses the discontinuity. The paleocourses are disposed on a topographically low side of the discontinuity. A smooth surface which emanates from the point is identified. The smooth surface is also disposed on the topographically low side of the point.

  15. Accountability Accentuates Interindividual-Intergroup Discontinuity by Enforcing Parochialism

    PubMed Central

    Wildschut, Tim; van Horen, Femke; Hart, Claire

    2015-01-01

    Interindividual-intergroup discontinuity is the tendency for relations between groups to be more competitive than relations between individuals. We examined whether the discontinuity effect arises in part because group members experience normative pressure to favor the ingroup (parochialism). Building on the notion that accountability enhances normative pressure, we hypothesized that the discontinuity effect would be larger when accountability is present (compared to absent). A prisoner’s dilemma game experiment supported this prediction. Specifically, intergroup (compared to interindividual) interaction activated an injunctive ingroup-favoring norm, and accountability enhanced the influence of this norm on competitive behavior. PMID:26635691

  16. Fundamental gaps with approximate density functionals: The derivative discontinuity revealed from ensemble considerations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kraisler, Eli; Kronik, Leeor

    2014-05-14

    The fundamental gap is a central quantity in the electronic structure of matter. Unfortunately, the fundamental gap is not generally equal to the Kohn-Sham gap of density functional theory (DFT), even in principle. The two gaps differ precisely by the derivative discontinuity, namely, an abrupt change in slope of the exchange-correlation energy as a function of electron number, expected across an integer-electron point. Popular approximate functionals are thought to be devoid of a derivative discontinuity, strongly compromising their performance for prediction of spectroscopic properties. Here we show that, in fact, all exchange-correlation functionals possess a derivative discontinuity, which arises naturallymore » from the application of ensemble considerations within DFT, without any empiricism. This derivative discontinuity can be expressed in closed form using only quantities obtained in the course of a standard DFT calculation of the neutral system. For small, finite systems, addition of this derivative discontinuity indeed results in a greatly improved prediction for the fundamental gap, even when based on the most simple approximate exchange-correlation density functional – the local density approximation (LDA). For solids, the same scheme is exact in principle, but when applied to LDA it results in a vanishing derivative discontinuity correction. This failure is shown to be directly related to the failure of LDA in predicting fundamental gaps from total energy differences in extended systems.« less

  17. Outcomes Following Discontinuation of E. coli l-Asparaginase Upon Severe Allergic Reactions in Children With Acute Lymphoblastic Leukemia.

    PubMed

    Yen, Hsiu-Ju; Chang, Wan-Hui; Liu, Hsi-Che; Yeh, Ting-Chi; Hung, Giun-Yi; Wu, Kang-Hsi; Peng, Ching-Tien; Chang, Yu-Hsiang; Chang, Te-Kao; Hsiao, Chih-Cheng; Sheen, Jiunn-Ming; Chao, Yu-Hua; Chang, Tai-Tsung; Chiou, Shyh-Shin; Lin, Pei-Chin; Wang, Shih-Chung; Lin, Ming-Tsan; Ho, Wan-Ling; Chen, Yu-Chieh; Liang, Der-Cherng

    2016-04-01

    Discontinuation of E. coli l-asparaginase in patients with acute lymphoblastic leukemia (ALL) is unavoidable upon severe allergic reaction. We sought to examine outcomes following E. coli l-asparaginase discontinuation due to severe allergic reactions. We evaluated the outcome of children enrolled in Taiwan Pediatric Oncology Group-2002-ALL protocol between 2002 and 2012, who had E. coli l-asparaginase discontinued due to severe allergic reactions, and compared the outcomes of those who continued with Erwinia l-asparaginase (Erwinase) with those who did not. Among 700 patients enrolled in this study, 33 patients had E. coli l-asparaginase treatment discontinued due to severe allergic reactions. Five-year overall survival did not differ significantly among the 648 patients without discontinuation (81 ± 1.6%, mean ± SE), compared to 17 patients with allergic reactions and treated with Erwinase (88 ± 7.8%) and 16 patients with allergic reactions but not treated with Erwinase (87 ± 8.6%). Among 16 patients who did not receive Erwinase, all 10 who received ≥50% of the scheduled doses of E. coli l-asparaginase before discontinuation survived without events. Erwinase treatment may not be needed for some ALL patients with severe allergy to E. coli l-asparaginase if ≥50% of prescribed doses were received and/or therapy is augmented with other agents. © 2015 Wiley Periodicals, Inc.

  18. Pregnancy Outcomes Related to Mycophenolate Exposure in Female Kidney Transplant Recipients.

    PubMed

    King, R W; Baca, M J; Armenti, V T; Kaplan, B

    2017-01-01

    In 2012, the U.S. Food and Drug Administration issued guidelines advising kidney transplant recipients (KTRs) to discontinue mycophenolate (MPA) in preparation for pregnancy. Little is known about how this guidance has affected pregnancy and graft outcomes. The purpose of this retrospective cohort study was to investigate any association between the discontinuation of MPA and KTR pregnancy and graft outcomes. Data from the National Transplantation Pregnancy Registry included 382 cases in which KTRs managed on MPA became pregnant. Overall, 22 variables, including the time in which a KTR discontinued MPA, were assessed across four end points: miscarriages, birth defects, and 2- and 5-year postpartum graft loss. Birth defects and miscarriages were similar among KTRs who discontinued MPA >6 and <6 weeks prior to pregnancy and during the first trimester. In contrast, discontinuing MPA during the second trimester or later significantly increased the risk of miscarriages (odds ratio [OR] 9.35, 95% confidence interval [CI] 4.31-20.00, p < 0.001) and birth defects (OR 6.06, 95% CI 1.96-18.87, p = 0.002). Discontinuing MPA <6 weeks prior to pregnancy was associated with an increased risk of 5-year graft loss. For the fetus, there is value to discontinuing MPA anytime prior to the second trimester. Adhering to current guidelines does not negatively affect graft survival. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  19. A CLASS OF RECONSTRUCTED DISCONTINUOUS GALERKIN METHODS IN COMPUTATIONAL FLUID DYNAMICS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hong Luo; Yidong Xia; Robert Nourgaliev

    2011-05-01

    A class of reconstructed discontinuous Galerkin (DG) methods is presented to solve compressible flow problems on arbitrary grids. The idea is to combine the efficiency of the reconstruction methods in finite volume methods and the accuracy of the DG methods to obtain a better numerical algorithm in computational fluid dynamics. The beauty of the resulting reconstructed discontinuous Galerkin (RDG) methods is that they provide a unified formulation for both finite volume and DG methods, and contain both classical finite volume and standard DG methods as two special cases of the RDG methods, and thus allow for a direct efficiency comparison.more » Both Green-Gauss and least-squares reconstruction methods and a least-squares recovery method are presented to obtain a quadratic polynomial representation of the underlying linear discontinuous Galerkin solution on each cell via a so-called in-cell reconstruction process. The devised in-cell reconstruction is aimed to augment the accuracy of the discontinuous Galerkin method by increasing the order of the underlying polynomial solution. These three reconstructed discontinuous Galerkin methods are used to compute a variety of compressible flow problems on arbitrary meshes to assess their accuracy. The numerical experiments demonstrate that all three reconstructed discontinuous Galerkin methods can significantly improve the accuracy of the underlying second-order DG method, although the least-squares reconstructed DG method provides the best performance in terms of both accuracy, efficiency, and robustness.« less

  20. Speedup of minimum discontinuity phase unwrapping algorithm with a reference phase distribution

    NASA Astrophysics Data System (ADS)

    Liu, Yihang; Han, Yu; Li, Fengjiao; Zhang, Qican

    2018-06-01

    In three-dimensional (3D) shape measurement based on phase analysis, the phase analysis process usually produces a wrapped phase map ranging from - π to π with some 2 π discontinuities, and thus a phase unwrapping algorithm is necessary to recover the continuous and nature phase map from which 3D height distribution can be restored. Usually, the minimum discontinuity phase unwrapping algorithm can be used to solve many different kinds of phase unwrapping problems, but its main drawback is that it requires a large amount of computations and has low efficiency in searching for the improving loop within the phase's discontinuity area. To overcome this drawback, an improvement to speedup of the minimum discontinuity phase unwrapping algorithm by using the phase distribution on reference plane is proposed. In this improved algorithm, before the minimum discontinuity phase unwrapping algorithm is carried out to unwrap phase, an integer number K was calculated from the ratio of the wrapped phase to the nature phase on a reference plane. And then the jump counts of the unwrapped phase can be reduced by adding 2K π, so the efficiency of the minimum discontinuity phase unwrapping algorithm is significantly improved. Both simulated and experimental data results verify the feasibility of the proposed improved algorithm, and both of them clearly show that the algorithm works very well and has high efficiency.

  1. 75 FR 71487 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-23

    ... Discontinuance or Modification of a Railroad Signal System Pursuant to Title 49 Code of Federal Regulations (CFR... Administration (FRA) seeking approval for the discontinuance or modification of a signal system, as detailed below. Docket Number FRA-2010-0159 Applicant: BNSF Railway, Mr. James LeVere, AVP Signals, BNSF Railway...

  2. 76 FR 4416 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-25

    ... Discontinuance or Modification of a Railroad Signal System Pursuant to Title 49 Code of Federal Regulations (CFR... Administration (FRA) seeking approval for the discontinuance or modification of the signal system. [Docket Number...--Signal/Comm./TCO, 1400 Douglas Street, Mail Stop 0910, Omaha, Nebraska 68179. The Union Pacific Railroad...

  3. 75 FR 29805 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-27

    ... Discontinuance or Modification of a Railroad Signal System or Relief Pursuant to title 49 Code of Federal... Administration (FRA) seeking approval for the discontinuance or modification of the signal system, or relief as... Trump, AVP Engineering--Signal/Comm/TCO, 1400 Douglas Street, STOP 0910, Omaha, Nebraska 68179. The...

  4. 75 FR 6252 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-08

    ... Discontinuance or Modification of a Railroad Signal System or Relief From the Requirements of Title 49 Code of... approval for the discontinuance or modification of the signal system or relief from the requirements of 49... Transportation, Inc. seeks approval of the proposed modification of the bridge tender controlled signals to...

  5. 78 FR 17282 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-20

    ... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... approval from the Federal Railroad Administration (FRA) for the discontinuance or modification of a signal... modifications that it will make to the signal system at the A&R crossing in preparation for the installation of...

  6. 75 FR 47880 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-09

    ... Discontinuance or Modification of a Railroad Signal System or Relief Pursuant to Title 49 Code of Federal... Administration (FRA) seeking approval for the discontinuance or modification of the signal system or relief from... & Louisville Railway, Inc., Mr. C. D. Edwards, General Supervisor of Signals & Structures, 1500 Kentucky Avenue...

  7. 75 FR 43610 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-26

    ... Discontinuance or Modification of a Railroad Signal System Pursuant to Title 49 Code of Federal Regulations (CFR... Administration (FRA), seeking approval for the discontinuance or modification of the signal system or relief from... Transportation, Inc., Mr. Joseph S. Ivanyo, Chief Engineer, Communications and Signals, 500 Water Street, SC J...

  8. 76 FR 34801 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-14

    ... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... the discontinuance or modification of a signal system. FRA assigned the petition Docket Number FRA... decrease of limits consists of moving the 2S signal on the siding south to the clearance point of the No...

  9. 76 FR 21943 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-19

    ... Discontinuance or Modification of a Railroad Signal System Pursuant to Title 49 Code of Federal Regulations (CFR... Administration (FRA) seeking approval for the discontinuance or modification of the signal system, as detailed... block signal system (ABS) on three sections of the Roseburg Subdivision and on one section of the...

  10. 75 FR 21717 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... Discontinuance or Modification of a Railroad Signal System or Relief From the Requirements of Title 49 Code of... approval for the discontinuance or modification of the signal system or relief from the requirements of 49... signals shall be provided, relative to CN's EJ&E Griffith Connection project involving the Matteson...

  11. Mandated Program Review and Program Discontinuance: Qualitative vs. Quantitative Standards. ASHE 1987 Annual Meeting Paper.

    ERIC Educational Resources Information Center

    Hammond, Martine F.; And Others

    Internal and external pressures that affect college program discontinuance schemes were investigated, based on minutes of the Kansas State Board of Regents and three other government-related groups/subgroups. During 1972-1986, a total of 206 programs were merged or discontinued. In 1972 a policy was enacted whereby masters programs that had…

  12. The Role of Cultural Discontinuity in the Academic Outcomes of Latina/o High School Students

    ERIC Educational Resources Information Center

    Taggart, Amanda

    2017-01-01

    This study examined the impact of cultural discontinuity on the academic outcomes of Latina/o high school students. Hierarchical multiple regression was utilized to (a) investigate the significant differences between the characteristics and academic outcomes of high school students who do and do not experience cultural discontinuity between their…

  13. 78 FR 67215 - Norfolk Southern Railway Company-Abandonment Exemption-in Fayette and Wayne Counties, Ind.; C&NC...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-08

    ... Wayne Counties, Ind.; C&NC Railroad Corporation-- Discontinuance of Service Exemption--in Fayette and...-Exempt Abandonments and Discontinuances of Service for NSR to abandon, and for CNUR to discontinue service over, approximately 0.61 miles of rail line between milepost CB 4.80 (near East County Road 450N...

  14. Transition density of one-dimensional diffusion with discontinuous drift

    NASA Technical Reports Server (NTRS)

    Zhang, Weijian

    1990-01-01

    The transition density of a one-dimensional diffusion process with a discontinuous drift coefficient is studied. A probabilistic representation of the transition density is given, illustrating the close connections between discontinuities of the drift and Brownian local times. In addition, some explicit results are obtained based on the trivariate density of Brownian motion, its occupation, and local times.

  15. 78 FR 47822 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-06

    ..., San Pedro, CA 90731. POLA seeks approval of the proposed discontinuance of Control Point (CP) Transfer Junction at Milepost 1.2 on the Pacific Harbor Line, San Pedro Subdivision. CP Transfer Junction will... discontinuance of CP Transfer Junction. A copy of the petition, as well as any written communications concerning...

  16. 78 FR 1292 - Self-Regulatory Organizations; National Securities Clearing Corporation; Notice of Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-08

    ... Retirement Processing Services and To Remove Reference to and the Fees Related to FundSPEED, a Discontinued... reference to FundSPEED, a discontinued service. II. Clearing Agency's Statement of the Purpose of, and... to and the fees related to FundSPEED, as this service was discontinued. The above changes took effect...

  17. Does research into contraceptive method discontinuation address women's own reasons? A critical review.

    PubMed

    Inoue, Kumiyo; Barratt, Alexandra; Richters, Juliet

    2015-10-01

    To examine the clinical and epidemiological literature addressing contraceptive method change or discontinuation and to assess whether the documented reasons reflected women's experiences. Major databases including Medline and PsycINFO were searched using keywords related to contraception and discontinuation, adherence and satisfaction, for articles published between January 2003 and February 2013. Studies in developed countries that focused on women of reproductive age and reasons for method change or discontinuation were included. Reasons reported were categorised and examined. A total of 123 papers were reviewed in detail. Medical terminology was generally used to describe reasons for method discontinuation. The top two reported reasons were bleeding and pregnancy, but there was a lack of consensus about the categorisation of reasons. Broad categories that were not self-explanatory were included in more than half of the papers, often without further explanation. Only 12 studies expanded on categories containing 'other', 'non-medical' or 'personal' reasons. Eight papers included categories that attributed discontinuation to the participant, such as 'dissatisfied with method'. Studies of reasons for discontinuation of contraceptives do not well describe women's specific reasons. Studies rely heavily on medical terms and often fail to document women's subjective experiences. Future studies should create an opportunity for women to articulate their non-medical reasons in their own words, including those related to their sexual lives. Furthermore, researchers should distinguish, if possible, between reasons for discontinuation of a method and reasons for ceasing participation in a research study. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. Incidence and predictors of single drug discontinuation according to the presence of HCV coinfection in HIV patients from the ICONA Foundation Cohort Study.

    PubMed

    Leone, Sebastiano; Shanyinde, Milensu; Cozzi Lepri, Alessandro; Lampe, Fiona C; Caramello, Pietro; Costantini, Andrea; Giacometti, Andrea; De Luca, Andrea; Cingolani, Antonella; Ceccherini Silberstein, Francesca; Puoti, Massimo; Gori, Andrea; d'Arminio Monforte, Antonella

    2018-05-01

    To evaluate incidence rates of and predictors for any antiretroviral (ART) drug discontinuation by HCV infection status in a large Italian cohort of HIV infected patients. All patients enrolled in ICONA who started combination antiretroviral therapy (cART) containing abacavir or tenofovir or emtricitabine or lamivudine plus efavirenz or rilpivirine or atazanavir/r or darunavir/r (DRV/r) or lopinavir/r or dolutegravir or elvitegravir or raltegravir were included. Multivariate Poisson regression models were used to determine factors independently associated with single ART drug discontinuation. Inverse probability weighting method to control for potential informative censoring was applied. Data from 10,637 patients were analyzed and 1,030 (9.7%) were HCV-Ab positive. Overall, there were 15,464 ART discontinuations due to any reason in 82,415.9 person-years of follow-up (PYFU) for an incidence rate (IR) of 18.8 (95% confidence interval [95%CI] 18.5-19.1) per 100 PYFU. No difference in IR of ART discontinuation due to any reason between HCV-infected and -uninfected patients was found. In a multivariable Poisson regression model, HCV-infected participants were at higher risk of darunavir/r discontinuation due to any reason (adjusted incidence rate ratio = 1.5, 95%CI 1.01-2.22, p value = 0.045) independently of demographics, HIV-related, ART and life-style factors. Among DRV/r treated patients, we found that HCV-viremic patients had twice the risk of ART discontinuation due to any reason than HCV-aviremic patients. In conclusion, HIV/HCV coinfected patients had a marginal risk increase of DRV/r discontinuation due to any reason compared with those without coinfection.

  19. Predictors of statin adherence, switching, and discontinuation in the USAGE survey: understanding the use of statins in America and gaps in patient education.

    PubMed

    Wei, Melissa Y; Ito, Matthew K; Cohen, Jerome D; Brinton, Eliot A; Jacobson, Terry A

    2013-01-01

    Although statins have been shown to reduce cardiovascular disease mortality, less than half of U.S. adults achieve their low-density lipoprotein cholesterol goal. In many patients initiated on a statin, adherence rates decrease over time. To characterize current and former statin users, identify reasons for the discontinuation or switching of statins, and identify factors associated with adherence. The USAGE survey is a cross-sectional, self-administered Internet-based survey of 10,138 U.S. adults fielded September to October 2011. The following statin users were identified and compared: adherent nonswitchers, adherent switchers, non-adherent switchers, and discontinuers. Univariate and multivariate models using a priori covariates for adherence and discontinuation were examined. Most participants were current statin users who adhered with their prescribed statin (82.5%, n = 8371). Former statin users or discontinuers (12%, n = 1220) cited muscle pain, a side effect, as the primary reason for discontinuation (60%), followed by cost (16%), and then perceived lack of efficacy (13%). Discontinuers were less satisfied with their physicians' explanation of cholesterol treatment, more likely to use the Internet to research statins, and less likely to undergo frequent cholesterol monitoring. Among adherent statin users, the primary reasons for switching were muscle side effects (33%) and cost (32%). Individuals at risk for non-adherence included those with low household income, those who experienced muscle pain as a side effect while on statin therapy, and those taking medication for cardiovascular disease. Statin-related muscle side effects are common and contribute significantly to rates of discontinuation, switching, and non-adherence. Improved physician patient communication about side effects and benefits of statins are necessary to improve both adherence and outcomes. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  20. The synergistic effect of breastfeeding discontinuation and cesarean section delivery on postpartum depression: A nationwide population-based cohort study in Korea.

    PubMed

    Nam, Jin Young; Choi, Young; Kim, Juyeong; Cho, Kyoung Hee; Park, Eun-Cheol

    2017-08-15

    The relationships between breastfeeding discontinuation and cesarean section delivery, and the occurrence of postpartum depression (PPD) remain unclear. Therefore, we aimed to investigate the association of breastfeeding discontinuation and cesarean section delivery with PPD during the first 6 months after delivery. Data were extracted from the Korean National Health Insurance Service-National Sample Cohort for 81,447 women who delivered during 2004-2013. PPD status was determined using the diagnosis code at outpatient or inpatient visit during the 6-month postpartum period. Breastfeeding discontinuation and cesarean section delivery were identified from prescription of lactation suppression drugs and diagnosis, respectively. Cox proportional hazards models were used to calculate adjusted hazard ratios. Of the 81,447 women, 666 (0.82%) had PPD. PPD risk was higher in women who discontinued breastfeeding than in those who continued breastfeeding (hazard ratio=3.23, P<0.0001), in women with cesarean section delivery than in those with vaginal delivery (hazard ratio=1.26, P=0.0040), and in women with cesarean section delivery who discontinued breastfeeding than in those with vaginal delivery who continued breastfeeding (hazard ratio=4.92, P<0.0001). Study limitations include low PPD incidence; use of indirect indicators for PPD, breastfeeding discontinuation, and working status, which could introduce selection bias and errors due to miscoding; and potential lack of adjustment for important confounders. Breastfeeding discontinuation and cesarean section delivery were associated with PPD during the 6-month postpartum period. Our results support the implementation of breastfeeding promoting policies, and PPD screening and treatment programs during the early postpartum period. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Effect of Discontinuation or Initiation of Methotrexate or Glucocorticoids on Tofacitinib Efficacy in Patients with Rheumatoid Arthritis: A Post Hoc Analysis.

    PubMed

    Fleischmann, Roy; Wollenhaupt, Jürgen; Cohen, Stanley; Wang, Lisy; Fan, Haiyun; Bandi, Vara; Andrews, John; Takiya, Liza; Bananis, Eustratios; Weinblatt, Michael E

    2018-06-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We evaluated the effect of concomitant methotrexate (MTX) or glucocorticoid (GC) use on tofacitinib clinical efficacy. Data were pooled from two open-label, long-term extension studies of tofacitinib 5 or 10 mg twice daily in patients with RA. Response according to Clinical Disease Activity Index (CDAI) was assessed separately in patients who discontinued (no MTX/GC use within 30 days prior to year-3 visit; assessment at month 3/year 3) or initiated (on/before year 3; assessment at initiation and year 3) MTX/GC. By year 3, among patients receiving background MTX at baseline, 186/1608 (11.6%) discontinued MTX, and 319/1434 (22.2%) patients receiving GC at baseline discontinued GC. Overall, 70.4/69.1% of patients who discontinued/continued MTX and 72.7/65.9% who discontinued/continued GC achieved CDAI remission or low disease activity (LDA) at year 3. Month 3 remission/LDA rates were maintained at year 3 in the majority of patients, irrespective of MTX/GC discontinuation/continuation. By year 3, 6.2% of patients receiving tofacitinib without MTX at baseline had initiated concomitant MTX, and 25.1% receiving tofacitinib without GC initiated GC; 69.0% and 45.4% initiating MTX or GC, respectively, had a CDAI-defined incomplete response prior to initiation. RA signs/symptoms improved following MTX initiation; only modest improvement was observed with GC initiation. Patients achieving remission/LDA with tofacitinib may discontinue MTX or GC and maintain treatment response. Patients with an incomplete response may benefit from adding concomitant MTX. Pfizer Inc. Study A3921024 [NCT00413699] and Study A3921041 [NCT00661661].

  2. Contrasting Reasons for Discontinuation of Antiretroviral Therapy in Workplace and Public-Sector HIV Programs in South Africa

    PubMed Central

    Kielmann, Karina; Charalambous, Salome; Karstaedt, Alan S.; Hamilton, Robin; La Grange, Lettie; Fielding, Katherine L.; Churchyard, Gavin J.; Grant, Alison D.

    2011-01-01

    Abstract We investigated reasons for clinical follow-up and treatment discontinuation among HIV-infected individuals receiving antiretroviral therapy (ART) in a public-sector clinic and in a workplace clinic in South Africa. Participants in a larger cohort study who had discontinued clinical care by the seventh month of treatment were traced using previously provided locator information. Those located were administered a semistructured questionnaire regarding reasons for discontinuing clinical follow-up. Participants who had discontinued antiretroviral therapy were invited to participate in further in-depth qualitative interviews. Fifty-one of 144 (35.4%) in the workplace cohort had discontinued clinical follow-up by the seventh month of treatment. The median age of those who discontinued follow-up was 46 years and median educational level was five years. By contrast, only 16.5% (44/267) of the public-sector cohort had discontinued follow-up. Among them the median age was 37.5 years and median education was 11 years. Qualitative interviews were conducted with 17 workplace participants and 10 public-sector participants. The main reasons for attrition in the workplace were uncertainty about own HIV status and above the value of ART, poor patient–provider relationships and workplace discrimination. In the public sector, these were moving away and having no money for clinic transport. In the workplace, efforts to minimize the time between testing and treatment initiation should be balanced with the need to provide adequate baseline counseling taking into account existing concepts about HIV and ART. In the public sector, earlier diagnosis and ART initiation may help to reduce early mortality, while links to government grants may reduce attrition. PMID:21214378

  3. First-line disease-modifying drugs in relapsing-remitting multiple sclerosis: an Italian real-life multicenter study on persistence.

    PubMed

    Ferraro, Diana; Camera, Valentina; Baldi, Eleonora; Vacchiano, Veria; Curti, Erica; Guareschi, Angelica; Malagù, Susanna; Montepietra, Sara; Strumia, Silvia; Santangelo, Mario; Caniatti, Luisa; Foschi, Matteo; Lugaresi, Alessandra; Granella, Franco; Pesci, Ilaria; Motti, Luisa; Neri, Walter; Immovilli, Paolo; Montanari, Enrico; Vitetta, Francesca; Simone, Anna Maria; Sola, Patrizia

    2018-04-12

    The introduction of oral disease-modifying drugs (DMDs) in addition to the available, injectable, ones for relapsing-remitting multiple sclerosis (RRMS) could be expected to improve medication persistence due to a greater acceptability of the route of administration. The aim of the study was to compare the proportion of patients discontinuing injectable DMDs (interferon beta 1a/1b, pegylated interferon, glatiramer acetate) with those discontinuing oral DMDs (dimethylfumarate and teriflunomide) during an observation period of at least 12 months. Secondary aims were to compare the time to discontinuation and the reasons for discontinuation between the two groups and to explore the demographic and clinical factors associated with DMD discontinuation. In this prospective, multi-center, real-life observational study, patients commencing any first-line DMD between 1 January 2015 and 31 July 2016 were enrolled and followed up for at least 12 months or until the drug was discontinued. Of the 520 included patients, 262 (49.6%) started an injectable and 258 (50.4%) an oral DMD. There was no difference in the proportion of patients on oral (n = 62, 24%) or on injectable (n = 60, 23%) DMDs discontinuing treatment, the most frequent reason being adverse events/side-effects. Higher baseline Expanded Disability Status Scale (EDSS) scores and younger age increased the odds of treatment withdrawal. Time to treatment discontinuation was not different between the two groups and was not influenced by the initiated DMD (oral versus injectable), even after adjustment for baseline differences. The route of administration alone (i.e. oral versus injectable) was not a significant predictor of persistence with first-line DMDs in RRMS.

  4. Patients with Crohn's Disease Are More Likely to Remain on Biologics than Immunomodulators: A Meta-Analysis of Treatment Durability.

    PubMed

    Shah, Eric D; Siegel, Corey A; Chong, Kelly; Melmed, Gil Y

    2015-08-01

    The comparative effectiveness of treatments for moderate-to-severe Crohn's disease can be influenced by the likelihood of remaining on medication. We aimed to clarify this treatment durability by assessing subject discontinuations from clinical trials in the context of treatment efficacy. We conducted a literature search for double-blind RCT of Crohn's disease therapies recommended in international guidelines or with recent positive phase III trial results. Durability was defined through study discontinuation due to adverse events or disease exacerbation represented by number needed to discontinue (NND). Efficacy was defined as clinical remission represented by number needed to treat (NNT). The primary endpoint was NND/NNT, with a higher value representing more durable and effective treatment. Treatment with azathioprine/6-mercaptopurine (AZA/6MP) was associated with more discontinuations than with clinical remission (NND/NNT = 0.92) in maintenance trials. For induction, methotrexate was associated with similar rates of discontinuations and remission (NND/NNT = 1.4). In one maintenance trial, the remission rate for methotrexate was greater than the study discontinuation rate (NND/NNT = 23.3). In contrast, anti-TNF trials revealed greater durability among induction (no excess discontinuation) and maintenance (NND/NNT = 37.9) trials. Trials of anti-trafficking agents had fewer discontinuations in the drug treatment arms than placebo resulting in most favorable NND/NNT ratios. For patients with Crohn's disease, biologic therapies had higher durability than immunomodulators for induction and maintenance therapy. We also report the results of a novel NND/NNT ratio that should be validated in a prospective head-to-head placebo-controlled trial.

  5. Relationships Among Adverse Events, Disease Characteristics, and Demographics in Treatment of Postherpetic Neuralgia With Gastroretentive Gabapentin

    PubMed Central

    Slattum, Patricia W.; Bucior, Iwona; Nalamachu, Srinivas

    2015-01-01

    Objectives: To characterize risk factors for occurrence of adverse events (AEs) and treatment discontinuations due to AEs for improving safety and tolerability of treatment of postherpetic neuralgia (PHN). Methods: Patients with PHN (n=556) received 1800 mg once-daily gastroretentive gabapentin (G-GR) in 2 phase 3 and 1 phase 4 study. Safety assessments included the incidence and severity of AEs and analysis of discontinuations due to AEs. Multivariable, logistic regression analyses examined predictors of AE reporting and discontinuations due to AEs. Results: In total, 53.2% of patients reported any AE, and 12.9% discontinued because of AEs. Both AE incidence and treatment discontinuations decreased rapidly during the 2-week titration to sustained, low levels. The probability to report any AE was 0.6 for females versus 0.4 for males, whereas there were no differences in probabilities for age (less than 75 vs. 75 y and older) and race (nonwhite vs. white). Consistent with this, only female sex was a significant (P=0.0006) predictor of AE reporting. Experiencing moderate (P≤0.0001) or severe (P=0.0006) AEs, but not patient demographics, was predictive of treatment discontinuations. The probability of discontinuation due to moderate AEs was 0.4 and 0.5 for severe AEs. Discussion: The tolerability of G-GR was not affected by patient age, but was affected by AE severity. Although being female was predictive of reporting AEs, it did not influence treatment discontinuation. Given that PHN is a disease for which the risk and duration of PHN increases with age and with being female, G-GR appears to be a well-suited treatment option for PHN. PMID:25811794

  6. Sativex in resistant multiple sclerosis spasticity: Discontinuation study in a large population of Italian patients (SA.FE. study)

    PubMed Central

    Solaro, Claudio; Righini, Isabella; Bergamaschi, Roberto; Bonavita, Simona; Bossio, Roberto Bruno; Brescia Morra, Vincenzo; Costantino, Gianfranco; Cavalla, Paola; Centonze, Diego; Comi, Giancarlo; Cottone, Salvatore; Danni, Maura Chiara; Francia, Ada; Gajofatto, Alberto; Gasperini, Claudio; Zaffaroni, Mauro; Petrucci, Loredana; Signoriello, Elisabetta; Maniscalco, Giorgia Teresa; Spinicci, Gabriella; Matta, Manuela; Mirabella, Massimiliano; Pedà, Graziella; Castelli, Letizia; Rovaris, Marco; Sessa, Edoardo; Spitaleri, Daniele; Paolicelli, Damiano; Granata, Alfredo; Zappia, Mario

    2017-01-01

    Background The approval of Sativex for the management of multiple sclerosis (MS) spasticity opened a new opportunity to many patients. In Italy, the healthcare payer can be fully reimbursed by the involved pharma company with the cost of treatment for patients not responding after a 4 week (28 days) trial period (Payment by Results, PbR), and 50% reimbursed with the cost of 6 weeks (42 days) treatment for other patients discontinuing (Cost Sharing, CS). The aim of our study was to describe the Sativex discontinuation profile from a large population of spasticity treated Italian MS patients. Methods We collected data of patients from 30 MS centres across the country starting Sativex between January 2014 and February 2015. Data were collected from the mandatory Italian Medicines Agency (AIFA) web-registry. Predictors of treatment discontinuation were assessed using a multivariate Cox proportional regression analysis. Results During the observation period 631 out of 1597 (39.5%) patients discontinued Sativex. The Kaplan-Meier estimates curve showed that 333 patients (20.8%) discontinued treatment at 4 weeks while 422 patients (26.4%) discontinued at 6 weeks. We found after adjusted modeling that a higher NRS score at T1 (adjHR 2.23, 95% 2.07–2.41, p<0.001) and a lower baseline NRS score (adjHR 0.51 95% CI 0.46–0.56, p<0.001) were predictive of treatment discontinuation. Conclusion These data show that the first 6 weeks are useful in identifying those patients in which Sativex could be effective, thus avoiding the cost of longer term evaluation. PMID:28763462

  7. Unplanned medication discontinuation as a potential pharmacovigilance signal: a nested young person cohort study

    PubMed Central

    2014-01-01

    Background Because of relatively small treatment numbers together with low adverse drug reaction (ADR) reporting rates the timely identification of ADRs affecting children and young people is problematic. The primary objective of this study was to assess the utility of unplanned medication discontinuation as a signal for possible ADRs in children and young people. Methods Using orlistat as an exemplar, all orlistat prescriptions issued to patients up to 18 years of age together with patient characteristics, prescription duration, co-prescribed medicines and recorded clinical (Read) codes were identified from the Primary Care Informatics Unit database between 1st Jan 2006-30th Nov 2009. Binary logistic regression was used to assess association between characteristics and discontinuation. Results During the study period, 79 patients were prescribed orlistat (81% female, median age 17 years). Unplanned medication discontinuation rates for orlistat were 52% and 77% at 1 and 3-months. Almost 20% of patients were co-prescribed an anti-depressant. One month unplanned medication discontinuation was significantly lower in the least deprived group (SIMD 1–2 compared to SIMD 9–10 OR 0.09 (95% CI0.01 – 0.83)) and those co-prescribed at least one other medication. At 3 months, discontinuation was higher in young people (≥17 yr versus, OR 3.07 (95% CI1.03 – 9.14)). Read codes were recorded for digestive, respiratory and urinary symptoms around the time of discontinuation for 24% of patients. Urinary retention was reported for 7.6% of patients. Conclusions Identification of unplanned medication discontinuation using large primary care datasets may be a useful tool for pharmacovigilance signal generation and detection of potential ADRs in children and young people. PMID:24594374

  8. Final 3-year Results of the Dasatinib Discontinuation Trial in Patients With Chronic Myeloid Leukemia Who Received Dasatinib as a Second-line Treatment.

    PubMed

    Okada, Masaya; Imagawa, Jun; Tanaka, Hideo; Nakamae, Hirohisa; Hino, Masayuki; Murai, Kazunori; Ishida, Yoji; Kumagai, Takashi; Sato, Seiichi; Ohashi, Kazuteru; Sakamaki, Hisashi; Wakita, Hisashi; Uoshima, Nobuhiko; Nakagawa, Yasunori; Minami, Yosuke; Ogasawara, Masahiro; Takeoka, Tomoharu; Akasaka, Hiroshi; Utsumi, Takahiko; Uike, Naokuni; Sato, Tsutomu; Ando, Sachiko; Usuki, Kensuke; Mizuta, Syuichi; Hashino, Satoshi; Nomura, Tetsuhiko; Shikami, Masato; Fukutani, Hisashi; Ohe, Yokiko; Kosugi, Hiroshi; Shibayama, Hirohiko; Maeda, Yasuhiro; Fukushima, Toshihiro; Yamazaki, Hirohito; Tsubaki, Kazuo; Kukita, Toshimasa; Adachi, Yoko; Nataduka, Toshiki; Sakoda, Hiroto; Yokoyama, Hisayuki; Okamoto, Takahiro; Shirasugi, Yukari; Onishi, Yasushi; Nohgawa, Masaharu; Yoshihara, Satoshi; Morita, Satoshi; Sakamoto, Junichi; Kimura, Shinya

    2018-05-01

    We previously reported an interim analysis of the DADI (dasatinib discontinuation) trial. The results showed that 48% of patients with chronic myeloid leukemia in the chronic phase who maintained a deep molecular response (DMR) for ≥ 1 year could discontinue second- or subsequent-line dasatinib treatment safely at a median follow-up of 20 months. However, the results from longer follow-up periods would be much more useful from a clinical perspective. The DADI trial was a prospective, multicenter trial conducted in Japan. After confirming a stable DMR for ≥ 1 year, dasatinib treatment subsequent to imatinib or nilotinib was discontinued. After discontinuation, the loss of DMR (even of 1 point) was defined as stringent molecular relapse, thereby triggering therapy resumption. The predictive factors of treatment-free remission (TFR) were analyzed. The median follow-up period was 44.0 months (interquartile range, 40.5-48.0 months). The estimated overall TFR rate at 36 months was 44.4% (95% confidence interval, 32.0%-56.2%). Only 2 patients developed a molecular relapse after the 1-year cutoff point. The presence of imatinib resistance was a significant risk factor for molecular relapse. Moreover, high natural killer cell and low γδ + T-cell and CD4 + regulatory T-cell (CD25 + CD127 low ) counts before discontinuation correlated significantly with successful therapy discontinuation. These findings suggest that discontinuation of second- or subsequent-line dasatinib after a sustained DMR of ≥ 1 year is feasible, especially for patients with no history of imatinib resistance. In addition, the natural killer cell count was associated with the TFR. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Risk factors for discontinuation of insulin pump therapy in pediatric and young adult patients.

    PubMed

    Kostev, Karel; Rockel, Timo; Rosenbauer, Joachim; Rathmann, Wolfgang

    2014-12-01

    Previous studies have shown that only a small number of pediatric and young adult patients discontinue pump therapy, but risk factors for discontinuation are unclear. To identify characteristics of pediatric and young adult patients with pump therapy which are associated with discontinuation of treatment. Retrospective cohort study using a representative nationwide database (LRx; IMS Health) in Germany covering >80% of all prescriptions to members of statutory health insurances in 2008-2011. All patients (age group <25 years) with new prescriptions of insulin pumps were identified (2009-2010) and were followed for 12 months. Overall, 2452 new pump users were identified, of whom 177 (7.2%) switched to other forms of insulin therapy within 12 months. In multivariate logistic regression, younger age (<6 years; reference 18 to <25 years: Odds ratio, OR, 95% CI: 0.36; 0.17-0.74) and use of teflon needles (reference steel needles: OR, 95% CI: 0.59; 0.41-0.83) were related to a lower odds of pump discontinuation. A non-significant trend was found for male sex (OR, 95% CI: 0.75; 0.52-1.08). Prescriptions of thyroid therapeutics (ATC H03A: OR, 95% CI: 1.79; 1.23-2.61) and antiepileptics (N03: OR, 95% CI: 3.14; 1.49-6.59) were significantly associated with discontinuation of pump therapy. About 93% of pediatric and young adult patients maintained insulin pump therapy within 12 months. Age <6 years, male sex and teflon needle use were associated with a lower risk of discontinuation. Thyroid therapy (indicating autoimmunity) and antiepileptic drug prescriptions were associated with a higher likelihood for discontinuation of insulin pump treatment. Copyright © 2014 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  10. The Risk of Relapse after Anti-TNF Discontinuation in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis.

    PubMed

    Gisbert, Javier P; Marín, Alicia C; Chaparro, María

    2016-05-01

    To perform a meta-analysis of the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC), to evaluate risk factors for relapse, and to assess the response to retreatment with the same anti-TNF. Studies evaluating the incidence of relapse after anti-TNF discontinuation in patients with CD or UC who reached clinical remission with anti-TNFs were included. Bibliographies up to January 2015 were searched. Frequency of relapse after discontinuation of anti-TNF agents was determined; meta-analyses were performed using the inverse-variance method. We included 27 studies (21 infliximab and 6 infliximab/adalimumab). The overall risk of relapse after discontinuation of anti-TNF therapy was 44% for CD (95% confidence interval (CI) 36-51%; I(2)=79%; 912 patients) and 38% for UC (23-52%; I(2)=82%; 266 patients). In CD, the relapse rate was 38% at 6 months after discontinuation (short term), 40% at 12 months (medium term), and 49% at >25 months (long term). In UC, 28% of patients relapsed at 12 months. In CD, when clinical remission was the only criterion for stopping anti-TNF therapy, the relapse rate after 1 year was 42%, which decreased to 26% when endoscopic remission was also required. Retreatment with the same anti-TNF induced remission again in 80% of cases (68-91%). Approximately one-third of patients with inflammatory bowel disease in remission under anti-TNF treatment relapsed 1 year after discontinuation. This proportion increased to half in the long term. In CD patients, the risk of relapse was lower when the criterion for discontinuation was endoscopic remission and not only clinical remission. Response to retreatment with the same anti-TNF agent was favorable.

  11. Rates of IUCD discontinuation and its associated factors among the clients of a social franchising network in Pakistan.

    PubMed

    Azmat, Syed Khurram; Shaikh, Babar Tasneem; Hameed, Waqas; Bilgrami, Mohsina; Mustafa, Ghulam; Ali, Muhammad; Ishaque, Muhammad; Hussain, Wajahat; Ahmed, Aftab

    2012-03-29

    Modern Intrauterine contraceptive device (IUCD) is very safe, highly effective reversible and inexpensive family planning method which offers 5-10 years of protection against pregnancy. The contraceptive use in Pakistan has been merely 30% for over a decade with IUCD being the least used method. Higher discontinuation rates are documented in developing countries; however no such data is available for Pakistan. Marie Stopes Society (MSS) established a social franchise outlets network branded as 'SURAJ' (Sun) in Pakistan to provide quality family planning services. This study attempts to determine IUCD discontinuation rates and its associated risk factors. Using a semi-structured questionnaire, a cross-sectional study was conducted with 3000 clients who availed IUCD services from Suraj provider 6, 12 and 24 month back,. Data were analyzed in SPSS 17.0; adjusted prevalence ratios were calculated to see associations between discontinuation and its risk factors. We found that 22.7% of the IUCD acceptors experienced some health problem; while the overall discontinuation rate was 18.9% with average time of usage of 7.4 (SD ± 5.8) months before discontinuation. Half of them showed health concerns (49.8%); of which a majority (70.2%) returned to Suraj provider for IUCD removal. Women living in Punjab, residing at a travelling time of 30-60 minutes and no previous use of contraceptive are more likely to discontinue IUCD. However, among total women 81.7% still expressed willingness to avail IUCD services from Suraj provider in future, if needed. The findings suggest a need for training the providers and field workers to prevent early discontinuation of IUCD among the Suraj clients and by addressing the health concerns through proper counseling, continued follow-up and immediate medical aid/referral in case of complications.

  12. Nondestructive, epi-illumination surface microscopic characterization of surface discontinuity in bone: a new approach offers a descriptive vocabulary and new insights.

    PubMed

    Rothschild, Bruce M

    2013-04-01

    Perspectives are in the eye of the beholder and are expanded with increased scrutiny (e.g., magnification). The term "porosity' for macroscopically or radiologically identifiable discontinuity in bone is so variably applied as to be incomprehensible in its meanings. A closer examination of surface discontinuity seems appropriate. Histological and atomic level analysis of bone alterations misses the forest for the trees and the former destroys the very subject it attempts to characterize. Surface discontinuity was therefore evaluated at the three-dimensional submacroscopic level. An epifluorescent/illumination microscope was used to characterize surface discontinuity in intact specimens of known pathophysiology and/or derivation. The derived perspectives were then utilized to characterize other surface discontinuity. The smooth boundaries of vascular foramen and internal bifurcation, continuity of the expanded base of nerve structures and surrounding elevated rings of Sharpey fibers are all clearly distinguishable from fronts of resorption in erosive arthritis, serpentine discontinuity associated with infectious processes, specific zones of resorption noted in tuberculosis, and structural bone exposure by taphonomic abrasion. These perspectives allow the bone pathology associated with hematoma to be characterized as accentuated Sharpey fiber insertions; maxillary and sphenoid surface discontinuity, as vascular in origin; and periosteal reaction, as manifest by superficial bifurcating channels and in-growth, similar to healing trephanation. Epi-illumination microscopy bridges macroscopic and histological examination, providing greater understanding of the pathology, at no cost to the integrity of the material studied. It explains a number of observed results, while providing discriminatory descriptions of phenomena for which pathophysiology has not yet been clarified. Copyright © 2013 Wiley Periodicals, Inc.

  13. NATURAL COURSE OF PATIENTS DISCONTINUING TREATMENT FOR AGE-RELATED MACULAR DEGENERATION AND FACTORS ASSOCIATED WITH VISUAL PROGNOSIS.

    PubMed

    Kim, Jae Hui; Chang, Young Suk; Kim, Jong Woo

    2017-12-01

    To evaluate the 24-month natural course of visual changes in patients discontinuing treatment despite persistent or recurrent fluid and factors predictive of visual prognosis. This retrospective, observational study included 35 patients (35 eyes) who initially received anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration (AMD), but discontinued treatment despite persistent or recurrent fluid. The best-corrected visual acuity (BCVA) at treatment discontinuation was determined and compared with the 24-month BCVA, which was then compared between polypoidal choroidal vasculopathy and other neovascular age-related macular degeneration subtypes. Baseline characteristics predictive of visual outcome and the degree of visual change were also analyzed. The mean number of anti-vascular endothelial growth factor injections before treatment discontinuation was 4.0 ± 1.6. The mean logarithm of minimal angle of resolution of BCVA at treatment discontinuation and that at 24 months were 1.02 ± 0.20 (Snellen equivalents = 20/209) and 1.60 ± 0.56 (20/796), respectively (P < 0.001). The 24-month BCVA was not different between polypoidal choroidal vasculopathy and other neovascular age-related macular degeneration subtypes (P = 0.803). The type of fluid (intraretinal fluid vs. no intraretinal fluid) was predictive of 24-month BCVA (P = 0.004) and the degree of changes in BCVA (P = 0.043). Marked deterioration in visual acuity was noted in patients discontinuing treatment, regardless of neovascular age-related macular degeneration subtypes. The presence of intraretinal fluid was associated with worse visual prognosis, suggesting that patients with intraretinal fluid should be strongly warned about their poor prognosis before they decide to discontinue treatment.

  14. Father's Labour Migration and Children's School Discontinuation in Rural Mozambique.

    PubMed

    Yabiku, Scott T; Agadjanian, Victor

    2017-08-01

    We examine how the discontinuation of schooling among left-behind children is related to multiple dimensions of male labor migration: the accumulation of migration experience, the timing of these migration experiences in the child's life course, and the economic success of the migration. Our setting is rural southern Mozambique, an impoverished area with massive male labor out-migration. Results show that fathers' economically successful labor migration is more beneficial for children's schooling than unsuccessful migration or non-migration. There are large differences, however, by gender: compared to sons of non-migrants, sons of migrant fathers (regardless of migration success) have lower rates of school discontinuation, while daughters of migrant fathers have rates of school discontinuation no different than daughters of non-migrants. Furthermore, accumulated labor migration across the child's life course is beneficial for boys' schooling, but not girls'. Remittances sent in the past year reduce the rate of discontinuation for sons, but not daughters.

  15. New exponential synchronization criteria for time-varying delayed neural networks with discontinuous activations.

    PubMed

    Cai, Zuowei; Huang, Lihong; Zhang, Lingling

    2015-05-01

    This paper investigates the problem of exponential synchronization of time-varying delayed neural networks with discontinuous neuron activations. Under the extended Filippov differential inclusion framework, by designing discontinuous state-feedback controller and using some analytic techniques, new testable algebraic criteria are obtained to realize two different kinds of global exponential synchronization of the drive-response system. Moreover, we give the estimated rate of exponential synchronization which depends on the delays and system parameters. The obtained results extend some previous works on synchronization of delayed neural networks not only with continuous activations but also with discontinuous activations. Finally, numerical examples are provided to show the correctness of our analysis via computer simulations. Our method and theoretical results have a leading significance in the design of synchronized neural network circuits involving discontinuous factors and time-varying delays. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. O(t-α)-synchronization and Mittag-Leffler synchronization for the fractional-order memristive neural networks with delays and discontinuous neuron activations.

    PubMed

    Chen, Jiejie; Chen, Boshan; Zeng, Zhigang

    2018-04-01

    This paper investigates O(t -α )-synchronization and adaptive Mittag-Leffler synchronization for the fractional-order memristive neural networks with delays and discontinuous neuron activations. Firstly, based on the framework of Filippov solution and differential inclusion theory, using a Razumikhin-type method, some sufficient conditions ensuring the global O(t -α )-synchronization of considered networks are established via a linear-type discontinuous control. Next, a new fractional differential inequality is established and two new discontinuous adaptive controller is designed to achieve Mittag-Leffler synchronization between the drive system and the response systems using this inequality. Finally, two numerical simulations are given to show the effectiveness of the theoretical results. Our approach and theoretical results have a leading significance in the design of synchronized fractional-order memristive neural networks circuits involving discontinuous activations and time-varying delays. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Discontinuities, cross-scale patterns, and the organization of ecosystems

    USGS Publications Warehouse

    Nash, Kirsty L.; Allen, Craig R.; Angeler, David G.; Barichievy, Chris; Eason, Tarsha; Garmestani, Ahjond S.; Graham, Nicholas A.J.; Granholm, Dean; Knutson, Melinda; Nelson, R. John; Nystrom, Magnus; Stow, Craig A.; Sandstrom, Shana M.

    2014-01-01

    Ecological structures and processes occur at specific spatiotemporal scales, and interactions that occur across multiple scales mediate scale-specific (e.g., individual, community, local, or regional) responses to disturbance. Despite the importance of scale, explicitly incorporating a multi-scale perspective into research and management actions remains a challenge. The discontinuity hypothesis provides a fertile avenue for addressing this problem by linking measureable proxies to inherent scales of structure within ecosystems. Here we outline the conceptual framework underlying discontinuities and review the evidence supporting the discontinuity hypothesis in ecological systems. Next we explore the utility of this approach for understanding cross-scale patterns and the organization of ecosystems by describing recent advances for examining nonlinear responses to disturbance and phenomena such as extinctions, invasions, and resilience. To stimulate new research, we present methods for performing discontinuity analysis, detail outstanding knowledge gaps, and discuss potential approaches for addressing these gaps.

  18. Beyond the group mind: a quantitative review of the interindividual-intergroup discontinuity effect.

    PubMed

    Wildschut, Tim; Pinter, Brad; Vevea, Jack L; Insko, Chester A; Schopler, John

    2003-09-01

    This quantitative review of 130 comparisons of interindividual and intergroup interactions in the context of mixed-motive situations reveals that intergroup interactions are generally more competitive than interindividual interactions. The authors identify 4 moderators of this interindividual-intergroup discontinuity effect, each based on the theoretical perspective that the discontinuity effect flows from greater fear and greed in intergroup relative to interindividual interactions. Results reveal that each moderator shares a unique association with the magnitude of the discontinuity effect. The discontinuity effect is larger when (a) participants interact with an opponent whose behavior is unconstrained by the experimenter or constrained by the experimenter to be cooperative rather than constrained by the experimenter to be reciprocal, (b) group members make a group decision rather than individual decisions, (c) unconstrained communication between participants is present rather than absent, and (d) conflict of interest is severe rather than mild.

  19. A new method for automatic discontinuity traces sampling on rock mass 3D model

    NASA Astrophysics Data System (ADS)

    Umili, G.; Ferrero, A.; Einstein, H. H.

    2013-02-01

    A new automatic method for discontinuity traces mapping and sampling on a rock mass digital model is described in this work. The implemented procedure allows one to automatically identify discontinuity traces on a Digital Surface Model: traces are detected directly as surface breaklines, by means of maximum and minimum principal curvature values of the vertices that constitute the model surface. Color influence and user errors, that usually characterize the trace mapping on images, are eliminated. Also trace sampling procedures based on circular windows and circular scanlines have been implemented: they are used to infer trace data and to calculate values of mean trace length, expected discontinuity diameter and intensity of rock discontinuities. The method is tested on a case study: results obtained applying the automatic procedure on the DSM of a rock face are compared to those obtained performing a manual sampling on the orthophotograph of the same rock face.

  20. Effect of adhesive interleaving and discontinuous plies on failure of composite laminates subject to transverse normal loads

    NASA Technical Reports Server (NTRS)

    Jegley, Dawn C.

    1989-01-01

    Results of a series of tests to determine the effects of adhesive interleaving and discontinuous plies (plies with end-to-end gaps) on the displacements, failure loads and failure modes of graphite-epoxy laminates subjected to transverse normal loads are presented. Adhesive interleaving can be used to contain local damage within a group of plies, i.e., to arrest crack propagation on the interlaminate level, and it can increase the amount of normal displacement the laminate can withstand before failure. However, the addition of adhesive interleaving to a laminate does not significantly increase its load carrying capability. A few discontinuous plies in a laminate can reduce the normal displacement and load at failure by 10 to 40 percent compared to a laminate with no discontinuous plies, but the presence of the ply discontinuities does not generally change the failure location or the failure mode of the laminate.

  1. Magnetic field dissipation in D-sheets

    NASA Technical Reports Server (NTRS)

    Burlaga, L. F.; Scudder, J. D.

    1973-01-01

    The effects of magnetic field annihilation at a tangential or rotational discontinuity in a resistive plasma are examined. The magnetic field intensity profile depends on (1) the field intensities far from the current sheet (+ and - infinity), (2) the angle between the two intensities, and (3) the electrical resistivity. For a tangential discontinuity, the theory predicts a depression in B, centered at the discontinuity, and it predicts a monotonic transition. The theory provides satisfactory fits to the magnetic field intensity and proton temperature profiles observed for two extremely broad D-sheets in the solar wind. Assuming a diffusion time 10 days, one obtains effective resistivities or approximately = 3 x 10 to the 12th power and 2 x 10 to the 13th power emu for the D-sheets. Either resistivity at directional discontinuities is much lower than 10 to the 12th power emu or annihilation does not always occur at discontinuities.

  2. 75 FR 54220 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-03

    ... Discontinuance or Modification of a Railroad Signal System or Relief From the Requirements of Title 49 Code of... approval for the discontinuance or modification of the signal system or relief from the requirements of 49... Engineer Signals, New Jersey Transit, One Penn Plaza East, Newark, New Jersey 07105-2246. The New Jersey...

  3. 75 FR 26838 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-12

    ... Discontinuance or Modification of a Railroad Signal System or Relief From the Requirements of Title 49 Code of... approval for the discontinuance or modification of the signal system or relief from the requirements of 49..., Mr. William E. Van Trump, AVP Engineering -- Signal/Comm/TCO, 1400 Douglas Street, STOP 0910, Omaha...

  4. 75 FR 5638 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-03

    ... Discontinuance or Modification of a Railroad Signal System or Relief From the Requirements of Title 49 Code of... approval for the discontinuance or modification of the signal system or relief from the requirements of 49... Signal System (ABS) on the entire railroad line between, but not including, the point of ownership at the...

  5. 75 FR 6251 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-08

    ... Discontinuance or Modification of a Railroad Signal System or Relief From the Requirements of Title 49 Code of... approval for the discontinuance or modification of the signal system or relief from the requirements of 49... Company (BNSF) seeks approval of the proposed modification to the traffic control signal system over the...

  6. 78 FR 47822 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-06

    ... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... approval for the discontinuance or modification of a signal system. FRA assigned the petition Docket Number... block signal (ABS) system on Main Line 1 and 2, from Milepost (MP) 1.2 Bliss to MP 7.3 Jay Interlocking...

  7. 75 FR 6252 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-08

    ... Discontinuance or Modification of a Railroad Signal System or Relief From the Requirements of Title 49 Code of... approval for the discontinuance or modification of the signal system or relief from the requirements of 49... the conversion of dispatcher controlled holdout signals, 96L and 96R, to automatic signals, 8221 and...

  8. Estimation of discontinuous coefficients in parabolic systems: Applications to reservoir simulation

    NASA Technical Reports Server (NTRS)

    Lamm, P. D.

    1984-01-01

    Spline based techniques for estimating spatially varying parameters that appear in parabolic distributed systems (typical of those found in reservoir simulation problems) are presented. The problem of determining discontinuous coefficients, estimating both the functional shape and points of discontinuity for such parameters is discussed. Convergence results and a summary of numerical performance of the resulting algorithms are given.

  9. 47 CFR 27.17 - Discontinuance of service in the 2000-2020 MHz and 2180-2200 MHz bands.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Discontinuance of service in the 2000-2020 MHz... § 27.17 Discontinuance of service in the 2000-2020 MHz and 2180-2200 MHz bands. (a) Termination of authorization. A licensee's AWS authorization in the 2000-2020 MHz and 2180-2200 MHz bands will automatically...

  10. Adaptive Discontinuous Evolution Galerkin Method for Dry Atmospheric Flow

    DTIC Science & Technology

    2013-04-02

    standard one-dimensional approximate Riemann solver used for the flux integration demonstrate better stability, accuracy as well as reliability of the...discontinuous evolution Galerkin method for dry atmospheric convection. Comparisons with the standard one-dimensional approximate Riemann solver used...instead of a standard one- dimensional approximate Riemann solver , the flux integration within the discontinuous Galerkin method is now realized by

  11. A detailed map of the 660-kilometer discontinuity beneath the izu-bonin subduction zone.

    PubMed

    Wicks, C W; Richards, M A

    1993-09-10

    Dynamical processes in the Earth's mantle, such as cold downwelling at subduction zones, cause deformations of the solid-state phase change that produces a seismic discontinuity near a depth of 660 kilometers. Observations of short-period, shear-to-compressional wave conversions produced at the discontinuity yield a detailed map of deformation beneath the Izu-Bonin subduction zone. The discontinuity is depressed by about 60 kilometers beneath the coldest part of the subducted slab, with a deformation profile consistent with the expected thermal signature of the slab, the experimentally determined Clapeyron slope of the phase transition, and the regional tectonic history.

  12. Discontinuities of Plastic Deformation in Metallic Glasses with Different Glass Forming Ability

    NASA Astrophysics Data System (ADS)

    Hurakova, Maria; Csach, Kornel; Miskuf, Jozef; Jurikova, Alena; Demcak, Stefan; Ocelik, Vaclav; Hosson, Jeff Th. M. De

    The metallic ribbons Fe40Ni40B20, Cu47Ti35Zr11Ni6Si1 and Zr65Cu17.5Ni10Al7.5 with different microhardness and glass forming ability were studied at different loading rates from 0.05 to 100 mN/s. We describe in details the differences in elemental discontinuities on the loading curves for the studied alloys. It was found that the discontinuities began at a certain local deformation independently on the macroscopic mechanical properties of a ribbon. More developed discontinuities at higher deformations are created for the materials with lower microhardness and so lower strength.

  13. A method for modeling discontinuities in a microwave coaxial transmission line

    NASA Technical Reports Server (NTRS)

    Otoshi, T. Y.

    1992-01-01

    A method for modeling discontinuities in a coaxial transmission line is presented. The methodology involves the use of a nonlinear least-squares fit program to optimize the fit between theoretical data (from the model) and experimental data. When this method was applied to modeling discontinuities in a slightly damaged Galileo spacecraft S-band (2.295-GHz) antenna cable, excellent agreement between theory and experiment was obtained over a frequency range of 1.70-2.85 GHz. The same technique can be applied for diagnostics and locating unknown discontinuities in other types of microwave transmission lines, such as rectangular, circular, and beam waveguides.

  14. A method for modeling discontinuities in a microwave coaxial transmission line

    NASA Astrophysics Data System (ADS)

    Otoshi, T. Y.

    1992-08-01

    A method for modeling discontinuities in a coaxial transmission line is presented. The methodology involves the use of a nonlinear least-squares fit program to optimize the fit between theoretical data (from the model) and experimental data. When this method was applied to modeling discontinuities in a slightly damaged Galileo spacecraft S-band (2.295-GHz) antenna cable, excellent agreement between theory and experiment was obtained over a frequency range of 1.70-2.85 GHz. The same technique can be applied for diagnostics and locating unknown discontinuities in other types of microwave transmission lines, such as rectangular, circular, and beam waveguides.

  15. Diabetes insipidus after discontinuation of vasopressin infusion for septic shock.

    PubMed

    Rana, H; Ferguson, N; Dicpinigaitis, P V

    2018-04-01

    Despite widespread use of vasopressin for the treatment of septic shock, few cases of diabetes insipidus (DI) following its discontinuation have been reported. A 54-year-old man presented with pneumonia progressing to septic shock, requiring norepinephrine and vasopressin for refractory hypotension. After clinical improvement, the patient on 3 separate occasions developed polyuria and severe hypernatremia upon discontinuation of vasopressin, with prompt recovery upon its resumption. Occurrence of DI upon discontinuation of vasopressin infusion appears to be rare, but incidence may be underestimated due to a paucity of published reports. Actual incidence and underlying mechanism of this phenomenon remain to be elucidated. © 2017 John Wiley & Sons Ltd.

  16. Trapped particles at a magnetic discontinuity

    NASA Technical Reports Server (NTRS)

    Stern, D. P.

    1972-01-01

    At a tangential discontinuity between two constant magnetic fields a layer of trapped particles can exist, this work examines the conditions under which the current carried by such particles tends to maintain the discontinuity. Three cases are examined. If the discontinuity separates aligned vacuum fields, the only requirement is that they be antiparallel. With arbitrary relative orientations, the field must have equal intensities on both sides. Finally, with a guiding center plasma on both sides, the condition reduces to a relation which is also derivable from hydromagnetic theory. Arguments are presented for the occurrence of such trapped modes in the magnetopause and for the non-existence of specular particle reflection.

  17. Simulating Flaring Events via an Intelligent Cellular Automata Mechanism

    NASA Astrophysics Data System (ADS)

    Dimitropoulou, M.; Vlahos, L.; Isliker, H.; Georgoulis, M.

    2010-07-01

    We simulate flaring events through a Cellular Automaton (CA) model, in which, for the first time, we use observed vector magnetograms as initial conditions. After non-linear force free extrapolation of the magnetic field from the vector magnetograms, we identify magnetic discontinuities, using two alternative criteria: (1) the average magnetic field gradient, or (2) the normalized magnetic field curl (i.e. the current). Magnetic discontinuities are identified at the grid-sites where the magnetic field gradient or curl exceeds a specified threshold. We then relax the magnetic discontinuities according to the rules of Lu and Hamilton (1991) or Lu et al. (1993), i.e. we redistribute the magnetic field locally so that the discontinuities disappear. In order to simulate the flaring events, we consider several alternative scenarios with regard to: (1) The threshold above which magnetic discontinuities are identified (applying low, high, and height-dependent threshold values); (2) The driving process that occasionally causes new discontinuities (at randomly chosen grid sites, magnetic field increments are added that are perpendicular (or may-be also parallel) to the existing magnetic field). We address the question whether the coronal active region magnetic fields can indeed be considered to be in the state of self-organized criticality (SOC).

  18. Feature Detection and Curve Fitting Using Fast Walsh Transforms for Shock Tracking: Applications

    NASA Technical Reports Server (NTRS)

    Gnoffo, Peter A.

    2017-01-01

    Walsh functions form an orthonormal basis set consisting of square waves. Square waves make the system well suited for detecting and representing functions with discontinuities. Given a uniform distribution of 2p cells on a one-dimensional element, it has been proven that the inner product of the Walsh Root function for group p with every polynomial of degree < or = (p - 1) across the element is identically zero. It has also been proven that the magnitude and location of a discontinuous jump, as represented by a Heaviside function, are explicitly identified by its Fast Walsh Transform (FWT) coefficients. These two proofs enable an algorithm that quickly provides a Weighted Least Squares fit to distributions across the element that include a discontinuity. The detection of a discontinuity enables analytic relations to locally describe its evolution and provide increased accuracy. Time accurate examples are provided for advection, Burgers equation, and Riemann problems (diaphragm burst) in closed tubes and de Laval nozzles. New algorithms to detect up to two C0 and/or C1 discontinuities within a single element are developed for application to the Riemann problem, in which a contact discontinuity and shock wave form after the diaphragm bursts.

  19. Continuing weight-loss effect after topiramate discontinuation in obese persons with schizophrenia: a pilot open-label study.

    PubMed

    Liang, C-S; Yang, F-W; Huang, S-Y; Ho, P-S

    2014-07-01

    Few studies have investigated the likelihood of weight maintenance in obese persons with schizophrenia after their initial successful weight loss. This pilot open-label study examined the efficacy of topiramate in weight loss and the trajectory of weight changes after topiramate discontinuation. This study enrolled 10 obese persons with schizophrenia. A 4-month treatment phase was started, followed by a 12-month discontinuation phase. Body weight was measured as the primary outcome every month. Secondary outcomes included leptin levels, fasting glucose, lipid profiles, and insulin resistance index. After the 4-month addition of topiramate, participants lost 1.79 kg of their body weight (95% CI=-3.03 to -0.56, p=0.005). The maximum weight reduction was 4.32 kg, occurring when topiramate had been discontinued for 12 months (95% CI=-6.41 to -2.24, p<0.001). The continuing weight-loss effect after topiramate discontinuation might have resulted from topiramate's potential to improve leptin functioning. These findings demonstrate that topiramate's weight-loss effect could not only persist during its administration, but also continue to improve after its discontinuation. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Magnetic field directional discontinuities. 2: Characteristics between 0.46 and 1.0 AU. [interplanetary magnetic fields

    NASA Technical Reports Server (NTRS)

    Lepping, R. P.; Benhannon, K. W.

    1980-01-01

    The characteristics of directional discontinuities (DD's) in the interplanetary magnetic field are studied using data from the Mariner 10 primary mission between 1.0 and 0.46 AU. Statistical and visual survey methods for DD identification resulted in a total of 644 events. Two methods were used to estimate the ratio of the number of tangential discontinuities (TD's) to the number of rotational discontinuities (RD's). Both methods show that the ratio of TD's to RD's varied with time and decreased with decreasing radial distance. A decrease in average discontinuity thickness of approx. 40 percent was found between 1.0 and 0.72 AU and approx. 54 percent between 1.0 and 0.46 AU, independent of type (TD or RD). This decrease in thickness for decreasing r is in qualitative agreement with Pioneer 10 observations between 1 and 5 AU. When the individual DD thickness are normalized with respect to the estimated local proton gyroradius (RA sub L), the average thickness at the three locations is nearly constant, 43 + or - 6 R sub L. This also holds true for both RD's and TD's separately. Statistical distributions of other properties, such as normal components and discontinuity plane angles, are presented.

  1. Anticholinergics in the era of atypical antipsychotics: short-term or long-term treatment?

    PubMed

    Desmarais, Julie Eve; Beauclair, Linda; Margolese, Howard C

    2012-09-01

    Anticholinergic agents are usually prescribed to prevent or treat antipsychotic-induced extrapyramidal symptoms. Their long-term benefits are questionable and they carry diverse adverse effects, including cognitive impairment and worsening of tardive dyskinesia. This literature review explores the impact of anticholinergic medication discontinuation on movement disorders, cognition and psychopathology in patients receiving antipsychotics. Medline, Embase and PsycInfo were searched from 1950 to July 2011 using "cessation /withdrawal /discontinuation /stopping" with "anticholinergic*" or "antiparkinson*" and "neuroleptic*" or "antipsychotic*". Additional articles were obtained by searching the bibliographies of relevant references. Earlier studies of anticholinergic agent discontinuation in patients receiving first-generation antipsychotics reported relapse rates of extrapyramidal symptoms between 4% and 80%, reflecting the heterogeneity of the studies. Two recent studies of patients prescribed second-generation antipsychotics obtained relapse rates of 4% and 33%. Some studies suggest improvement in tardive dyskinesia with cessation of anticholinergics. Four studies examined the effects of anticholinergic agent discontinuation on cognition and all observed an improvement post-discontinuation. Changes in symptoms of schizophrenia with anticholinergic discontinuation are conflicting, with more recent studies suggesting an improvement. Given their questionable benefit with continued use, clinicians should consider a gradual withdrawal of anticholinergic agents in stable patients receiving antipsychotics.

  2. A new method for automated discontinuity trace mapping on rock mass 3D surface model

    NASA Astrophysics Data System (ADS)

    Li, Xiaojun; Chen, Jianqin; Zhu, Hehua

    2016-04-01

    This paper presents an automated discontinuity trace mapping method on a 3D surface model of rock mass. Feature points of discontinuity traces are first detected using the Normal Tensor Voting Theory, which is robust to noisy point cloud data. Discontinuity traces are then extracted from feature points in four steps: (1) trace feature point grouping, (2) trace segment growth, (3) trace segment connection, and (4) redundant trace segment removal. A sensitivity analysis is conducted to identify optimal values for the parameters used in the proposed method. The optimal triangular mesh element size is between 5 cm and 6 cm; the angle threshold in the trace segment growth step is between 70° and 90°; the angle threshold in the trace segment connection step is between 50° and 70°, and the distance threshold should be at least 15 times the mean triangular mesh element size. The method is applied to the excavation face trace mapping of a drill-and-blast tunnel. The results show that the proposed discontinuity trace mapping method is fast and effective and could be used as a supplement to traditional direct measurement of discontinuity traces.

  3. Behaviour of mantle transition zone discontinuities beneath the Indian Ocean from PP and SS precursors

    NASA Astrophysics Data System (ADS)

    Reiss, Anne-Sophie; Thomas, Christine

    2015-04-01

    As part of the RHUM-RUM project we investigate the upwelling plume beneath the island La Réunion, located in the Indian Ocean 200 km east of Madagascar. This plume belongs to one of the most active hotspot regions in the world and is still active today. Understanding the depth origin and dimensions of such a plume helps to better understand mantle processes and the heat flux of the Earth. If the plume originates at the core-mantle boundary the Earth is cooled down differently compared with an indirect cooling of plumes originating in the upper mantle. Here we use underside reflections of PP and SS waves off the seismic discontinuities at 410 km and 660 km depth that arrive as precursors to the main phase in order to investigate the topography of these discontinuities that mark the top and bottom of the mantle transition zone. If hotter or colder material intersects the mantle transition zone, the discontinuities at 410 km and 660 km depth are deflected, hence the topography of the mantle transition zone can be an indicator for an upwelling plume. The 410 km discontinuity, which exists due to the phase change of olivine to spinel, should be depressed significantly in the presence of hot upwelling material. Because of the opposite Clapeyron slope of the phase change of spinel to magnesiowuestite and perovskite at 660 km depth, the topography of this discontinuity should be elevated. For this study we analyse over 200 events with Mw ≥ 5.8 and bounce points distributed over the entire Indian Ocean. Array seismology methods, such as vespagrams and slowness-backazimuth analysis, are used to enhance the signal-to-noise-ratio and detect and identify precursors. Using different source-receiver combinations enables us to get a dense coverage of bounce points of PP and SS waves in the Indian Ocean and especially around La Réunion, also with crossing ray paths. The differential travel times of PP and SS arrivals and their precursors of robust stacks are converted into depth values of the seismic discontinuities. In our data, we can detect clear underside reflections off the 410 km discontinuity and also some off the 660 km discontinuity. The preliminary topography of the two discontinuities indicates a thinned mantle transition zone, which we interpret as a large upwelling beneath La Réunion.

  4. Discontinuing Oxytocin Infusion in the Active Phase of Labor: A Systematic Review and Meta-analysis.

    PubMed

    Saccone, Gabriele; Ciardulli, Andrea; Baxter, Jason K; Quiñones, Joanne N; Diven, Liany C; Pinar, Bor; Maruotti, Giuseppe Maria; Martinelli, Pasquale; Berghella, Vincenzo

    2017-11-01

    To evaluate the benefits and harms of discontinuation of oxytocin after the active phase of labor is reached. Electronic databases (ie, MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, ScienceDirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) were searched from their inception until April 2017. We included all randomized controlled trials comparing discontinuation (ie, intervention group) and continuation (ie, control group) of oxytocin infusion after the active phase of labor is reached, either after induction or augmentation of labor. Discontinuation of oxytocin infusion was defined as discontinuing oxytocin infusion when the active phase of labor was achieved. Continuation of oxytocin infusion was defined as continuing oxytocin infusion until delivery. Only trials in singleton gestations with vertex presentation at term were included. The primary outcome was the incidence of cesarean delivery. Nine randomized controlled trials, including 1,538 singleton gestations, were identified as relevant and included in the meta-analysis. All nine trials included only women undergoing induction of labor. In the discontinuation group, if arrest of labor occurred, usually defined as no cervical dilation in 2 hours or inadequate uterine contractions for 2 hours or more, oxytocin infusion was restarted. Women in the control group had oxytocin continued until delivery usually at the same dose used at the time the active phase was reached. Women who were randomized to have discontinuation of oxytocin infusion after the active phase of labor was reached had a significantly lower risk of cesarean delivery (9.3% compared with 14.7%; relative risk 0.64, 95% CI 0.48-0.87) and of uterine tachysystole (6.2% compared with 13.1%; relative risk 0.53, 95% CI 0.33-0.84) compared with those who were randomized to have continuation of oxytocin infusion until delivery. Discontinuation of oxytocin infusion was associated with an increase in the duration of the active phase of labor (mean difference 27.65 minutes, 95% CI 3.94-51.36). In singleton gestations with cephalic presentation at term undergoing induction, discontinuation of oxytocin infusion after the active phase of labor at approximately 5 cm is reached reduces the risk of cesarean delivery and of uterine tachysystole compared with continuous oxytocin infusion. Given this evidence, discontinuation of oxytocin infusion once the active stage of labor is established in women being induced should be considered as an alternative management plan.

  5. A Numerical Method for the Simulation of Skew Brownian Motion and its Application to Diffusive Shock Acceleration of Charged Particles

    NASA Astrophysics Data System (ADS)

    McEvoy, Erica L.

    Stochastic differential equations are becoming a popular tool for modeling the transport and acceleration of cosmic rays in the heliosphere. In diffusive shock acceleration, cosmic rays diffuse across a region of discontinuity where the up- stream diffusion coefficient abruptly changes to the downstream value. Because the method of stochastic integration has not yet been developed to handle these types of discontinuities, I utilize methods and ideas from probability theory to develop a conceptual framework for the treatment of such discontinuities. Using this framework, I then produce some simple numerical algorithms that allow one to incorporate and simulate a variety of discontinuities (or boundary conditions) using stochastic integration. These algorithms were then modified to create a new algorithm which incorporates the discontinuous change in diffusion coefficient found in shock acceleration (known as Skew Brownian Motion). The originality of this algorithm lies in the fact that it is the first of its kind to be statistically exact, so that one obtains accuracy without the use of approximations (other than the machine precision error). I then apply this algorithm to model the problem of diffusive shock acceleration, modifying it to incorporate the additional effect of the discontinuous flow speed profile found at the shock. A steady-state solution is obtained that accurately simulates this phenomenon. This result represents a significant improvement over previous approximation algorithms, and will be useful for the simulation of discontinuous diffusion processes in other fields, such as biology and finance.

  6. Seismic imaging of a mid-lithospheric discontinuity beneath Ontong Java Plateau

    NASA Astrophysics Data System (ADS)

    Tharimena, Saikiran; Rychert, Catherine A.; Harmon, Nicholas

    2016-09-01

    Ontong Java Plateau (OJP) is a huge, completely submerged volcanic edifice that is hypothesized to have formed during large plume melting events ∼90 and 120 My ago. It is currently resisting subduction into the North Solomon trench. The size and buoyancy of the plateau along with its history of plume melting and current interaction with a subduction zone are all similar to the characteristics and hypothesized mechanisms of continent formation. However, the plateau is remote, and enigmatic, and its proto-continent potential is debated. We use SS precursors to image seismic discontinuity structure beneath Ontong Java Plateau. We image a velocity increase with depth at 28 ± 4 km consistent with the Moho. In addition, we image velocity decreases at 80 ± 5 km and 282 ± 7 km depth. Discontinuities at 60-100 km depth are frequently observed both beneath the oceans and the continents. However, the discontinuity at 282 km is anomalous in comparison to surrounding oceanic regions; in the context of previous results it may suggest a thick viscous root beneath OJP. If such a root exists, then the discontinuity at 80 km bears some similarity to the mid-lithospheric discontinuities (MLDs) observed beneath continents. One possibility is that plume melting events, similar to that which formed OJP, may cause discontinuities in the MLD depth range. Plume-plate interaction could be a mechanism for MLD formation in some continents in the Archean prior to the onset of subduction.

  7. Biomarkers From Late Pregnancy to 6 Weeks Postpartum in HIV-Infected Women Who Continue Versus Discontinue Antiretroviral Therapy After Delivery

    PubMed Central

    Hoffman, Risa M.; Leister, Erin; Kacanek, Deborah; Shapiro, David E.; Read, Jennifer S.; Bryson, Yvonne; Currier, Judith S.

    2013-01-01

    Background Women who use antiretroviral therapy (ART) solely for the prevention of mother-to-child transmission of HIV discontinue postpartum. We hypothesized that women discontinuing ART by 6 weeks postpartum (“discontinuers”) would have elevated postpartum inflammatory biomarker levels relative to women remaining on ART postpartum (“continuers”). Methods Data from HIV-infected pregnant women enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group P1025 with CD4 counts >350 cells per cubic millimeter before initiating ART or first pregnancy CD4 counts >400 cells per cubic millimeter after starting ART and with available stored plasma samples at >20 weeks of gestation, delivery, and 6 weeks postpartum were analyzed. Plasma samples were tested for highly sensitive C-reactive protein, D-dimer, and interleukin-6. We used longitudinal linear spline regression to model biomarkers over time. Results Data from 128 women (65 continuers and 63 discontinuers) were analyzed. All biomarkers increased from late pregnancy to delivery, then decreased postpartum (slopes different from 0, P < 0.001). Continuers had a steeper decrease in log D-dimer between delivery and 6 weeks postpartum than discontinuers (P = 0.002). Conclusions In contrast to results from treatment interruption studies in adults, both ART continuers and ART discontinuers had significant decreases in the levels of D-dimer, highly sensitive C-reactive protein, or interleukin-6 postpartum. Continuation was associated with a more rapid decline in D-dimer levels compared with discontinuation. PMID:23714738

  8. Is being resolute better than being pragmatic when it comes to breastfeeding? Longitudinal qualitative study investigating experiences of women intending to breastfeed using the Theoretical Domains Framework.

    PubMed

    Jardine, E E; McLellan, J; Dombrowski, S U

    2017-09-01

    In the UK, initiating then discontinuing breastfeeding before two weeks post-partum is common. The aim of this longitudinal qualitative study was to explore which psychosocial factors may influence discontinuation. A sample of 10 pregnant women intending to breastfeed were recruited. A longitudinal qualitative design was used to capture views prior to and two weeks following birth. Semi-structured interviews were conducted underpinned by the Theoretical Domains Framework to explore a comprehensive list of psychosocial factors. Four women discontinued breastfeeding at the time of the second interview. Pre-partum differences were identified between maintainers and discontinuers; discontinuers appeared to have stronger intentions to breastfeed based on their self-determination, self-confidence and perception of fewer barriers to breastfeeding. Post-partum, discontinuers highlighted how they felt physically unable to carry on; their feeding experiences elicited negative emotions and pain. Negative emotions appeared to be exacerbated by original breastfeeding beliefs and advice given by healthcare professionals. The women in this study who discontinued breastfeeding showed less cognitive flexibility, which appeared to exacerbate post-partum emotional distress, when they encountered difficulties. Women with strong intentions and self-determination might benefit from support in anticipating potential barriers and identifying ways of overcoming them. © The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Low-Dose Aspirin Discontinuation and Risk of Cardiovascular Events: A Swedish Nationwide, Population-Based Cohort Study.

    PubMed

    Sundström, Johan; Hedberg, Jakob; Thuresson, Marcus; Aarskog, Pernilla; Johannesen, Kasper Munk; Oldgren, Jonas

    2017-09-26

    There are increasing concerns about risks associated with aspirin discontinuation in the absence of major surgery or bleeding. We investigated whether long-term low-dose aspirin discontinuation and treatment gaps increase the risk of cardiovascular events. We performed a cohort study of 601 527 users of low-dose aspirin for primary or secondary prevention in the Swedish prescription register between 2005 and 2009 who were >40 years of age, were free from previous cancer, and had ≥80% adherence during the first observed year of treatment. Cardiovascular events were identified with the Swedish inpatient and cause-of-death registers. The first 3 months after a major bleeding or surgical procedure were excluded from the time at risk. During a median of 3.0 years of follow-up, 62 690 cardiovascular events occurred. Patients who discontinued aspirin had a higher rate of cardiovascular events than those who continued (multivariable-adjusted hazard ratio, 1.37; 95% confidence interval, 1.34-1.41), corresponding to an additional cardiovascular event observed per year in 1 of every 74 patients who discontinue aspirin. The risk increased shortly after discontinuation and did not appear to diminish over time. In long-term users, discontinuation of low-dose aspirin in the absence of major surgery or bleeding was associated with a >30% increased risk of cardiovascular events. Adherence to low-dose aspirin treatment in the absence of major surgery or bleeding is likely an important treatment goal. © 2017 American Heart Association, Inc.

  10. Coplanar waveguide discontinuities for P-I-N diode switches and filter applications

    NASA Technical Reports Server (NTRS)

    Dib, N. I.; Katehi, P. B.; Ponchak, George E.; Simons, Rainee N.

    1990-01-01

    A full wave space domain integral equation (SDIE) analysis of coplanar waveguide (CPW) two port discontinuities is presented. An experimental setup to measure the S-parameters of such discontinuities is described. Experimental and theoretical results for CPW realizations of pass-band and stop-band filters are presented. The S-parameters of such structures are plotted in the frequency range 5 to 25 GHz.

  11. 3D modelling of squeeze flow of unidirectional and fabric composite inserts

    NASA Astrophysics Data System (ADS)

    Ghnatios, Chady; Abisset-Chavanne, Emmanuelle; Chinesta, Francisco; Keunings, Roland

    2016-10-01

    The enhanced design flexibility provided to the thermo-forming of thermoplastic materials arises from the use of both continuous and discontinuous thermoplastic prepregs. Discontinuous prepregs are patches used to locally strengthen the part. In this paper, we propose a new modelling approach for suspensions involving composite patches that uses theoretical concepts related to discontinuous fibres suspensions, transversally isotropic fluids and extended dumbbell models.

  12. Continuity or Discontinuity? Scientific Governance in the Pre-History of the 1977 Law of Higher Education and Research in Sweden

    ERIC Educational Resources Information Center

    Bragesjo, Fredrik; Elzinga, Aant; Kasperowski, Dick

    2012-01-01

    The objective of this paper is to balance two major conceptual tendencies in science policy studies, continuity and discontinuity theory. While the latter argue for fundamental and distinct changes in science policy in the late 20th century, continuity theorists show how changes do occur but not as abrupt and fundamental as discontinuity theorists…

  13. Uncertainty Quantification given Discontinuous Climate Model Response and a Limited Number of Model Runs

    NASA Astrophysics Data System (ADS)

    Sargsyan, K.; Safta, C.; Debusschere, B.; Najm, H.

    2010-12-01

    Uncertainty quantification in complex climate models is challenged by the sparsity of available climate model predictions due to the high computational cost of model runs. Another feature that prevents classical uncertainty analysis from being readily applicable is bifurcative behavior in climate model response with respect to certain input parameters. A typical example is the Atlantic Meridional Overturning Circulation. The predicted maximum overturning stream function exhibits discontinuity across a curve in the space of two uncertain parameters, namely climate sensitivity and CO2 forcing. We outline a methodology for uncertainty quantification given discontinuous model response and a limited number of model runs. Our approach is two-fold. First we detect the discontinuity with Bayesian inference, thus obtaining a probabilistic representation of the discontinuity curve shape and location for arbitrarily distributed input parameter values. Then, we construct spectral representations of uncertainty, using Polynomial Chaos (PC) expansions on either side of the discontinuity curve, leading to an averaged-PC representation of the forward model that allows efficient uncertainty quantification. The approach is enabled by a Rosenblatt transformation that maps each side of the discontinuity to regular domains where desirable orthogonality properties for the spectral bases hold. We obtain PC modes by either orthogonal projection or Bayesian inference, and argue for a hybrid approach that targets a balance between the accuracy provided by the orthogonal projection and the flexibility provided by the Bayesian inference - where the latter allows obtaining reasonable expansions without extra forward model runs. The model output, and its associated uncertainty at specific design points, are then computed by taking an ensemble average over PC expansions corresponding to possible realizations of the discontinuity curve. The methodology is tested on synthetic examples of discontinuous model data with adjustable sharpness and structure. This work was supported by the Sandia National Laboratories Seniors’ Council LDRD (Laboratory Directed Research and Development) program. Sandia National Laboratories is a multi-program laboratory operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Company, for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-AC04-94AL85000.

  14. Tuberculosis treatment discontinuation and symptom persistence: an observational study of Bihar, India’s public care system covering >100,000,000 inhabitants

    PubMed Central

    2014-01-01

    Background The effectiveness of India’s TB control programs depend critically on patients completing appropriate treatment. Discontinuing treatment prior to completion can leave patients infectious and symptomatic. Developing strategies to reduce early discontinuation requires characterizing its patterns and their link to symptom persistence. Methods The 2011 BEST-TB survey (360 clusters, 11 districts) sampled patients (n = 1007) from Bihar’s public healthcare system who had initiated treatment >6 months prior to being interviewed, administering questionnaires to patients about TB treatment duration and symptoms, prior treatment, and sociodemographic characteristics. Multivariate logistic regression models estimated the risk of treatment discontinuation for these characteristics. Similar models estimated probabilities of symptom persistence to 25 weeks post-treatment initiation adjusting for the same predictors and treatment duration. All models included district fixed effects, robust standard errors, and adjustments for the survey sampling design. Treatment default timing and symptom persistence relied solely on self-report. Results 24% of patients discontinued treatment prior to 25 weeks. Higher likelihood of discontinuation occurred in those who had failed to complete previous TB treatment episodes (aOR: 4.77 [95% CI: 1.98 – 11.53]) and those seeing multiple providers (3.67 per provider [1.94 – 6.95]). Symptoms persisted in 42% of patients discontinuing treatment within 5 weeks versus 28% for completing 25 weeks of treatment. Symptom persistence was more likely for those with prior TB treatment (aOR: 5.05 [1.90 – 13.38]); poorer patients (2.94 [1.51 – 5.72]); and women (1.79 [1.07 – 2.99]). Predictors for treatment discontinuation prior to 16 weeks were similar. Conclusions Premature TB treatment discontinuation and symptom persistence is particularly high among individuals who have failed to complete treatment for a prior episode. Strategies to identify and promote treatment completion in this group appear promising. Likewise, effective TB regimens of shortened duration currently in trials may eventually help to achieve higher treatment completion rates. PMID:24886314

  15. Real-world data to assess changes in low-density lipoprotein cholesterol and predicted cardiovascular risk after ezetimibe discontinuation post reporting of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression trial.

    PubMed

    Bays, Harold E; Patel, Mehul D; Mavros, Panagiotis; Ramey, Dena R; Tomassini, Joanne E; Tershakovec, Andrew M; Baxter, Carl A

    The 2008 Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) study demonstrated ezetimibe + simvastatin vs simvastatin alone had a neutral effect on the surrogate endpoint of carotid intima-media thickness. Subsequent media portrayal of the study prompted ezetimibe discontinuation in many patients. The objective of the study was to assess the impact of ENHANCE reporting on ezetimibe discontinuation, low-density lipoprotein cholesterol (LDL-C) changes, and potential cardiovascular disease (CVD) risk. This analysis used claims data in a retrospective, observational study of patients receiving ezetimibe + statin and compared LDL-C for patients who discontinued ezetimibe (n = 970) vs those who continued ezetimibe + statins (n = 3706) after ENHANCE results disclosure. Change in relative CVD risk was estimated from the absolute LDL-C difference between groups per the Cholesterol Treatment Trialists' meta-analysis of statin trials. The rate of ezetimibe discontinuation was 2% in the 6 months before and 21% in the 6 months after reporting of ENHANCE results. Among patients who ultimately discontinued vs continued ezetimibe, respective mean LDL-C levels were 79.8 and 78.3 mg/dL 6 months before reporting of the ENHANCE results and 93.5 and 78.1 mg/dL 6 months after reporting of ENHANCE. Predictive application of the Cholesterol Treatment Trialists' meta-analysis suggested the 13.9 mg/dL increase in mean LDL-C translated to a 9.4% increase in relative CVD risk for those who discontinued ezetimibe. After reporting of the neutral ENHANCE results, ezetimibe discontinuation rate increased, LDL-C levels increased, and predicted CVD risk increased among those who discontinued ezetimibe. Characterization of clinical outcomes regarding lipid-altering agents based on surrogate biomarker studies not designed to assess CVD outcomes may be misleading, potentially placing patients at increased CVD risk. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  16. Automated extraction and analysis of rock discontinuity characteristics from 3D point clouds

    NASA Astrophysics Data System (ADS)

    Bianchetti, Matteo; Villa, Alberto; Agliardi, Federico; Crosta, Giovanni B.

    2016-04-01

    A reliable characterization of fractured rock masses requires an exhaustive geometrical description of discontinuities, including orientation, spacing, and size. These are required to describe discontinuum rock mass structure, perform Discrete Fracture Network and DEM modelling, or provide input for rock mass classification or equivalent continuum estimate of rock mass properties. Although several advanced methodologies have been developed in the last decades, a complete characterization of discontinuity geometry in practice is still challenging, due to scale-dependent variability of fracture patterns and difficult accessibility to large outcrops. Recent advances in remote survey techniques, such as terrestrial laser scanning and digital photogrammetry, allow a fast and accurate acquisition of dense 3D point clouds, which promoted the development of several semi-automatic approaches to extract discontinuity features. Nevertheless, these often need user supervision on algorithm parameters which can be difficult to assess. To overcome this problem, we developed an original Matlab tool, allowing fast, fully automatic extraction and analysis of discontinuity features with no requirements on point cloud accuracy, density and homogeneity. The tool consists of a set of algorithms which: (i) process raw 3D point clouds, (ii) automatically characterize discontinuity sets, (iii) identify individual discontinuity surfaces, and (iv) analyse their spacing and persistence. The tool operates in either a supervised or unsupervised mode, starting from an automatic preliminary exploration data analysis. The identification and geometrical characterization of discontinuity features is divided in steps. First, coplanar surfaces are identified in the whole point cloud using K-Nearest Neighbor and Principal Component Analysis algorithms optimized on point cloud accuracy and specified typical facet size. Then, discontinuity set orientation is calculated using Kernel Density Estimation and principal vector similarity criteria. Poles to points are assigned to individual discontinuity objects using easy custom vector clustering and Jaccard distance approaches, and each object is segmented into planar clusters using an improved version of the DBSCAN algorithm. Modal set orientations are then recomputed by cluster-based orientation statistics to avoid the effects of biases related to cluster size and density heterogeneity of the point cloud. Finally, spacing values are measured between individual discontinuity clusters along scanlines parallel to modal pole vectors, whereas individual feature size (persistence) is measured using 3D convex hull bounding boxes. Spacing and size are provided both as raw population data and as summary statistics. The tool is optimized for parallel computing on 64bit systems, and a Graphic User Interface (GUI) has been developed to manage data processing, provide several outputs, including reclassified point clouds, tables, plots, derived fracture intensity parameters, and export to modelling software tools. We present test applications performed both on synthetic 3D data (simple 3D solids) and real case studies, validating the results with existing geomechanical datasets.

  17. Small subsidence of the 660-km discontinuity beneath Japan probed by ScS reverberations

    NASA Astrophysics Data System (ADS)

    Kato, Mamoru; Misawa, Mika; Kawakatsu, Hitoshi

    We investigate layering structure in the mantle beneath Japan using ScS reverberation waveforms of two recent large deep events in the northwest Pacific. We estimate regional variation of the elastic and anelastic structure of the mantle as well as properties of the major velocity discontinuities by modeling broadband seismograms recorded at two dense networks, J-Array and FREESIA. The 660-km discontinuity is the deepest in the region where the stagnant subducting slab in the transition zone is tomographically imaged, but the subsidence is of ∼10 km, much smaller than previous estimates with SS precursors. No significant elevation is detected for the 410-km discontinuity.

  18. Linear array optical edge sensor

    NASA Technical Reports Server (NTRS)

    Bejczy, Antal K. (Inventor); Primus, Howard C. (Inventor)

    1987-01-01

    A series of independent parallel pairs of light emitting and detecting diodes for a linear pixel array, which is laterally positioned over an edge-like discontinuity in a workpiece to be scanned, is disclosed. These independent pairs of light emitters and detectors sense along intersecting pairs of separate optical axes. A discontinuity, such as an edge in the sensed workpiece, reflects a detectable difference in the amount of light from that discontinuity in comparison to the amount of light that is reflected on either side of the discontinuity. A sequentially sychronized clamping and sampling circuit detects that difference as an electrical signal which is recovered by circuitry that exhibits an improved signal-to-noise capability for the system.

  19. Method and apparatus of spectro-acoustically enhanced ultrasonic detection for diagnostics

    DOEpatents

    Vo-Dinh, Tuan; Norton, Stephen J.

    2001-01-01

    An apparatus for detecting a discontinuity in a material includes a source of electromagnetic radiation has a wavelength and an intensity sufficient to induce an enhancement in contrast between a manifestation of an acoustic property in the material and of the acoustic property in the discontinuity, as compared to when the material is not irradiated by the electromagnetic radiation. An acoustic emitter directs acoustic waves to the discontinuity in the material. The acoustic waves have a sensitivity to the acoustic property. An acoustic receiver receives the acoustic waves generated by the acoustic emitter after the acoustic waves have interacted with the material and the discontinuity. The acoustic receiver also generates a signal representative of the acoustic waves received by the acoustic receiver. A processor, in communication with the acoustic receiver and responsive to the signal generated by the acoustic receiver, is programmed to generate informational output about the discontinuity based on the signal generated by the acoustic receiver.

  20. Seismic Observations Indicating That the 2015 Ogasawara (Bonin) Earthquake Ruptured Beneath the 660 km Discontinuity

    NASA Astrophysics Data System (ADS)

    Kuge, Keiko

    2017-11-01

    The termination of deep earthquakes at a depth of 700 km is a key feature for understanding the physical mechanism of deep earthquakes. The 680 km deep 30 May 2015, Ogasawara (Bonin) earthquake (Mw 7.9) and its aftershocks were recorded by seismic stations at distances from 7° to 19°. Synthetic seismograms indicate that the P waveforms depend on whether the earthquake is located above or below the 660 km discontinuity. In this study, I show that broadband recordings indicate that the 2015 earthquake may have occurred below the 660 km velocity discontinuity. Recordings of the P wave from the strongest aftershock lack evidence for wave triplication expected when a subhorizontal discontinuity underlies the hypocenter. Theoretical waveforms computed with a 660 km discontinuity above the aftershock and mainshock match the observed waveforms more accurately. These observations may indicate earthquake ruptures due to mantle minerals other than olivine or strong deformation of the 660 km phase transition.

  1. Magnetic field directional discontinuities - Characteristics between 0.46 and 1.0 AU

    NASA Technical Reports Server (NTRS)

    Lepping, R. P.; Behannon, K. W.

    1986-01-01

    Based on Mariner 10 data, a statistical survey and an application of the Sonnerup-Cahill variance procedure to a visual identification with 1.2-s averages for time intervals corresponding to the equally spaced heliocentric distances of 1.0, 0.72 and 0.46 AU, are employed to study the characteristics of directional discontinuities (DDs) in the interplanetary magnetic field. Analysis using two methods demonstrated that the ratio of tangential discontinuities (TDs) to rotational discontinuities (RDs) decreased with decreasing radial distance. Decreases in average discontinuity thickness of 41 percent between 1.0 and 0.72 AU, and 56 percent between 1.0 and 0.46 AU, were found for both TDs and RDs, in agreement with Pioneer 10 data between 1 and 5 AU. Normalization of the individual DD thicknesses with respect to the estimated local proton gyroradius (R sub L) gave a nearly constant average thickness at the three locations, 36 + or - 5 R sub L, for both RDs and TDs.

  2. THE FORMATION OF ROTATIONAL DISCONTINUITIES IN COMPRESSIVE THREE-DIMENSIONAL MHD TURBULENCE

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yang, Liping; Feng, Xueshang; Zhang, Lei

    Measurements of solar wind turbulence reveal the ubiquity of discontinuities. In this study we investigate how the discontinuities, especially rotational discontinuities (RDs), are formed in MHD turbulence. In a simulation of the decaying compressive three-dimensional (3D) MHD turbulence with an imposed uniform background magnetic field, we detect RDs with sharp field rotations and little variations of magnetic field intensity, as well as mass density. At the same time, in the de Hoffman–Teller frame, the plasma velocity is nearly in agreement with the Alfvén speed, and is field-aligned on both sides of the discontinuity. We take one of the identified RDsmore » to analyze its 3D structure and temporal evolution in detail. By checking the magnetic field and plasma parameters, we find that the identified RD evolves from the steepening of the Alfvén wave with moderate amplitude, and that steepening is caused by the nonuniformity of the Alfvén speed in the ambient turbulence.« less

  3. The 1D Richards' equation in two layered soils: a Filippov approach to treat discontinuities

    NASA Astrophysics Data System (ADS)

    Berardi, Marco; Difonzo, Fabio; Vurro, Michele; Lopez, Luciano

    2018-05-01

    The infiltration process into the soil is generally modeled by the Richards' partial differential equation (PDE). In this paper a new approach for modeling the infiltration process through the interface of two different soils is proposed, where the interface is seen as a discontinuity surface defined by suitable state variables. Thus, the original 1D Richards' PDE, enriched by a particular choice of the boundary conditions, is first approximated by means of a time semidiscretization, that is by means of the transversal method of lines (TMOL). In such a way a sequence of discontinuous initial value problems, described by a sequence of second order differential systems in the space variable, is derived. Then, Filippov theory on discontinuous dynamical systems may be applied in order to study the relevant dynamics of the problem. The numerical integration of the semidiscretized differential system will be performed by using a one-step method, which employs an event driven procedure to locate the discontinuity surface and to adequately change the vector field.

  4. Hippocampal agenesis in an individual who engaged in violent criminal behaviors after discontinuing carbamazepine and paroxetine treatment.

    PubMed

    Hanada, Hiroaki; Akiyoshi, Jotaro; Kanehisa, Masayuki; Ishitobi, Yoshinobu; Tsuru, Jusen; Tanaka, Yoshihiro; Shimomura, Tsuyoshi; Kawano, Yoshihisa

    2013-01-01

    Antidepressant discontinuation syndrome (ADS) occurs after abrupt discontinuation of an antidepressant medication. A 23-year-old man with right hippocampal agenesis demonstrated sexual crime (hypersexuality) since the age of eight and had been successfully treated with carbamazepine since the age of 13. He had required increased doses of paroxetine and carbamazepine owing to the development of an unstable affect after quitting his job. He abruptly stopped taking his medication for 3 days and his criminal behaviors re-emerged. We examined changes in brain structure and activity before and after medication cessation, using MRI and functional MRI (fMRI). The image of a girl in a swimsuit increased activity in the thalamus only after medication discontinuation. The alteration in thalamic activity might induce hypersexuality. We conclude that a primary hypersexuality had been suppressed with carbamazepine and paroxetine treatment, and the discontinuation of the medication caused the hypersexuality. © 2012 American Academy of Forensic Sciences.

  5. Acute renal failure induced by markedly decreased appetite secondary to a depressive episode after discontinuation of long-term lithium therapy in an elderly patient with bipolar disorder.

    PubMed

    Okada, Akira

    2014-05-16

    Some elderly patients on chronic lithium therapy for bipolar disorder and their doctors may be faced with a therapeutic dilemma over whether or not to continue prescribing/taking lithium given their increased risk of reduced renal function. We present the case of a 78-year-old woman with bipolar disorder who discontinued lithium therapy due to increased risk factors for renal injury. After discontinuation, she experienced markedly decreased appetite secondary to a depressive episode, and developed acute renal failure, which subsequently progressed to a more advanced stage of chronic kidney disease. This case suggests that extreme care must be taken to prevent the recurrence of depression in elderly patients with bipolar disorder who discontinue lithium therapy, even when they had been emotionally stable for a long time while receiving lithium. Medications other than lithium for bipolar disorder may be needed at the time lithium therapy is discontinued. 2014 BMJ Publishing Group Ltd.

  6. Discontinuous Galerkin finite element methods for radiative transfer in spherical symmetry

    NASA Astrophysics Data System (ADS)

    Kitzmann, D.; Bolte, J.; Patzer, A. B. C.

    2016-11-01

    The discontinuous Galerkin finite element method (DG-FEM) is successfully applied to treat a broad variety of transport problems numerically. In this work, we use the full capacity of the DG-FEM to solve the radiative transfer equation in spherical symmetry. We present a discontinuous Galerkin method to directly solve the spherically symmetric radiative transfer equation as a two-dimensional problem. The transport equation in spherical atmospheres is more complicated than in the plane-parallel case owing to the appearance of an additional derivative with respect to the polar angle. The DG-FEM formalism allows for the exact integration of arbitrarily complex scattering phase functions, independent of the angular mesh resolution. We show that the discontinuous Galerkin method is able to describe accurately the radiative transfer in extended atmospheres and to capture discontinuities or complex scattering behaviour which might be present in the solution of certain radiative transfer tasks and can, therefore, cause severe numerical problems for other radiative transfer solution methods.

  7. Predictors of premature discontinuation of outpatient treatment after discharge of patients with posttraumatic stress disorder.

    PubMed

    Wang, Hee Ryung; Woo, Young Sup; Jun, Tae-Youn; Bahk, Won-Myong

    2015-01-01

    This study aimed to examine the sociodemographic and disease-related variables associated with the premature discontinuation of psychiatric outpatient treatment after discharge among patients with noncombat-related posttraumatic stress disorder. We retrospectively reviewed the medical records of patients who were discharged with a diagnosis of posttraumatic stress disorder. Fifty-five percent of subjects (57/104) prematurely discontinued outpatient treatment within 6 months of discharge. Comparing sociodemographic variables between the 6-month non-follow-up group and 6-month follow-up group, there were no variables that differed between the two groups. However, comparing disease-related variables, the 6-month follow-up group showed a longer hospitalization duration and higher Global Assessment of Function score at discharge. The logistic regression analysis showed that a shorter duration of hospitalization predicted premature discontinuation of outpatient treatment within 6 months of discharge. The duration of psychiatric hospitalization for posttraumatic stress disorder appeared to influence the premature discontinuation of outpatient treatment after discharge.

  8. Discontinuous categories affect information-integration but not rule-based category learning.

    PubMed

    Maddox, W Todd; Filoteo, J Vincent; Lauritzen, J Scott; Connally, Emily; Hejl, Kelli D

    2005-07-01

    Three experiments were conducted that provide a direct examination of within-category discontinuity manipulations on the implicit, procedural-based learning and the explicit, hypothesis-testing systems proposed in F. G. Ashby, L. A. Alfonso-Reese, A. U. Turken, and E. M. Waldron's (1998) competition between verbal and implicit systems model. Discontinuous categories adversely affected information-integration but not rule-based category learning. Increasing the magnitude of the discontinuity did not lead to a significant decline in performance. The distance to the bound provides a reasonable description of the generalization profile associated with the hypothesis-testing system, whereas the distance to the bound plus the distance to the trained response region provides a reasonable description of the generalization profile associated with the procedural-based learning system. These results suggest that within-category discontinuity differentially impacts information-integration but not rule-based category learning and provides information regarding the detailed processing characteristics of each category learning system. ((c) 2005 APA, all rights reserved).

  9. A Moving Discontinuous Galerkin Finite Element Method for Flows with Interfaces

    DTIC Science & Technology

    2017-12-07

    Naval Research Laboratory Washington, DC 20375-5320 NRL/MR/6040--17-9765 A Moving Discontinuous Galerkin Finite Element Method for Flows with...guidance to revise the method to ensure such properties. Acknowledgements This work was sponsored by the Office of Naval Research through the Naval...18. NUMBER OF PAGES 17. LIMITATION OF ABSTRACT A Moving Discontinuous Galerkin Finite Element Method for Flows with Interfaces Andrew Corrigan, Andrew

  10. Bringing a Perspective from Outside the Field: A Commentary on Davis et al.'s (2010) Use of a Modified Regression Discontinuity Design to Evaluate a Gifted Program

    ERIC Educational Resources Information Center

    Adelson, Jill L.; Kelcey, Benjamin

    2016-01-01

    In this commentary of "Evaluating the Gifted Program of an Urban School District Using a Modified Regression Discontinuity Design" by Davis, Engberg, Epple, Sieg, and Zimmer, we examine the background of the study, critique the methods used, and discuss the results and implications. The study used a fuzzy regression discontinuity design…

  11. Egyptian ever-married women's attitude toward discontinuation of female genital cutting.

    PubMed

    Afifi, M

    2010-01-01

    This study aimed to examine Egyptian ever-married women's beliefs and attitude toward the discontinuation of female genital cutting (FGC). We also examined the significant sources of information which the women with positive attitude were exposed to the year prior to the survey. In a national representative community-based sample of 15,573 ever-married Egyptian women, the intention to continue the practice of FGC and other sociodemographical variables were collected from the 2000 Egypt Demographic and Health Survey data. A secondary in-depth analysis was conducted on the data in order to investigate the women's attitude and its associated factors. Only 12.4 percent of the sample intended to discontinue the practice. The logistic regression models showed that women with a positive attitude to discontinue the practice believed that FGC was not an important part of religious traditions, that husbands did not prefer a cut wife, and that FGC reduced sexual desire. The most significant sources of information related to a positive attitude to discontinue the practice were community discussions, the mosques or churches and the newspapers. The aforementioned sources of information are related to the social and religious aspects of women in the Egyptian community. In order to change women's attitude toward the discontinuation of this unhealthy practice, communication rather than passive learning is needed.

  12. Antileukemic Efficacy of Continuous vs Discontinuous Dexamethasone in Murine Models of Acute Lymphoblastic Leukemia

    PubMed Central

    Ramsey, Laura B.; Janke, Laura J.; Payton, Monique A.; Cai, Xiangjun; Paugh, Steven W.; Karol, Seth E.; Kamdem, Landry Kamdem; Cheng, Cheng; Williams, Richard T.; Jeha, Sima; Pui, Ching-Hon; Evans, William E.; Relling, Mary V.

    2015-01-01

    Osteonecrosis is one of the most common, serious, toxicities resulting from the treatment of acute lymphoblastic leukemia. In recent years, pediatric acute lymphoblastic leukemia clinical trials have used discontinuous rather than continuous dosing of dexamethasone in an effort to reduce the incidence of osteonecrosis. However, it is not known whether discontinuous dosing would compromise antileukemic efficacy of glucocorticoids. Therefore, we tested the efficacy of discontinuous dexamethasone against continuous dexamethasone in murine models bearing human acute lymphoblastic leukemia xenografts (n = 8 patient samples) or murine BCR-ABL+ acute lymphoblastic leukemia. Plasma dexamethasone concentrations (7.9 to 212 nM) were similar to those achieved in children with acute lymphoblastic leukemia using conventional dosages. The median leukemia-free survival ranged from 16 to 59 days; dexamethasone prolonged survival from a median of 4 to 129 days in all seven dexamethasone-sensitive acute lymphoblastic leukemias. In the majority of cases (7 of 8 xenografts and the murine BCR-ABL model) we demonstrated equal efficacy of the two dexamethasone dosing regimens; whereas for one acute lymphoblastic leukemia sample, the discontinuous regimen yielded inferior antileukemic efficacy (log-rank p = 0.002). Our results support the clinical practice of using discontinuous rather than continuous dexamethasone dosing in patients with acute lymphoblastic leukemia. PMID:26252865

  13. How do horizontal, frictional discontinuities affect reverse fault-propagation folding?

    NASA Astrophysics Data System (ADS)

    Bonanno, Emanuele; Bonini, Lorenzo; Basili, Roberto; Toscani, Giovanni; Seno, Silvio

    2017-09-01

    The development of new reverse faults and related folds is strongly controlled by the mechanical characteristics of the host rocks. In this study we analyze the impact of a specific kind of anisotropy, i.e. thin mechanical and frictional discontinuities, in affecting the development of reverse faults and of the associated folds using physical scaled models. We perform analog modeling introducing one or two initially horizontal, thin discontinuities above an initially blind fault dipping at 30° in one case, and 45° in another, and then compare the results with those obtained from a fully isotropic model. The experimental results show that the occurrence of thin discontinuities affects both the development and the propagation of new faults and the shape of the associated folds. New faults 1) accelerate or decelerate their propagation depending on the location of the tips with respect to the discontinuities, 2) cross the discontinuities at a characteristic angle (∼90°), and 3) produce folds with different shapes, resulting not only from the dip of the new faults but also from their non-linear propagation history. Our results may have direct impact on future kinematic models, especially those aimed to reconstruct the tectonic history of faults that developed in layered rocks or in regions affected by pre-existing faults.

  14. Segmentation of images for gingival growth measurement

    NASA Astrophysics Data System (ADS)

    Kim, Dong-Il; Wilson, Joseph N.

    1992-12-01

    The ability to measure gingival volume growth from dental casts would provide a valuable resource for periodontists. This problem is attractive from a computer vision standpoint due to the complexities of data acquisition, segmentation of gingival and tooth surfaces and boundaries, and extraction of features (such as tooth axes) to help solve the correspondence problem for multiple casts. In this paper, a structured light 3-D range finder is used to collect raw data. The most complicated subtask is that of detecting discontinuities such as the gingival margin. Discontinuity detection is hindered both by cast anomalies (such as bubbles and holes generated during the process of dental impression) and by the subtle nature of the discontinuities themselves. First, we discuss an approach to segmenting a dental cast into tooth and gingival units using depth and orientation discontinuities. The visible cast surface is reconstructed by obtaining the minimum of a parameterized functional. The first derivative of the energy functional (which corresponds to the Euler-Lagrange equation) is solved using the multigrid methods. both orientation and depth discontinuities are detected by adding a discrete discontinuity functional to the energy functional. The principal axes and boundaries of the teeth provide the information necessary to determine the region to be measured in estimating gingival growth. Finally, voxels corresponding to growth regions are counted to measure the target volume.

  15. Block Volume Estimation from the Discontinuity Spacing Measurements of Mesozoic Limestone Quarries, Karaburun Peninsula, Turkey

    PubMed Central

    Elci, Hakan; Turk, Necdet

    2014-01-01

    Block volumes are generally estimated by analyzing the discontinuity spacing measurements obtained either from the scan lines placed over the rock exposures or the borehole cores. Discontinuity spacing measurements made at the Mesozoic limestone quarries in Karaburun Peninsula were used to estimate the average block volumes that could be produced from them using the suggested methods in the literature. The Block Quality Designation (BQD) ratio method proposed by the authors has been found to have given in the same order of the rock block volume to the volumetric joint count (J v) method. Moreover, dimensions of the 2378 blocks produced between the years of 2009 and 2011 in the working quarries have been recorded. Assuming, that each block surfaces is a discontinuity, the mean block volume (V b), the mean volumetric joint count (J vb) and the mean block shape factor of the blocks are determined and compared with the estimated mean in situ block volumes (V in) and volumetric joint count (J vi) values estimated from the in situ discontinuity measurements. The established relations are presented as a chart to be used in practice for estimating the mean volume of blocks that can be obtained from a quarry site by analyzing the rock mass discontinuity spacing measurements. PMID:24696642

  16. Seismic imaging of mantle transition zone discontinuities beneath the northern Red Sea and adjacent areas

    NASA Astrophysics Data System (ADS)

    Mohamed, A. A.; Gao, S. S.; Elsheikh, A. A.; Liu, K. H.; Yu, Y.; Fat-Helbary, R. E.

    2014-11-01

    The dramatic asymmetry in terms of surface elevation, Cenozoic volcanisms and earthquake activity across the Red Sea is an enigmatic issue in global tectonics, partially due to the unavailability of broad-band seismic data on the African Plate adjacent to the Red Sea. Here, we report the first comprehensive image of the mantle transition zone (MTZ) discontinuities using data from the Egyptian National Seismic Network, and compare the resulting depths of the 410 and 660-km discontinuities with those observed on the Arabian side. Our results show that when a standard earth model is used for time-to-depth conversion, the resulting depth of the discontinuities increases systematically towards the axis of the Afro-Arabian Dome (AAD) from both the west and east. Relative to the westernmost area, the maximum depression of the 410-km discontinuity is about 30 km, and that of the 660-km discontinuity is about 45 km. The observed systematic variations can best be explained by a model involving a hydrated MTZ and an upper-mantle low-velocity zone beneath the AAD. Models invoking one or more mantle plumes originated from the MTZ or the lower-mantle beneath the study area are not consistent with the observations.

  17. Tolerability to beta-blocker therapy among heart failure patients in clinical practice.

    PubMed

    Butler, Javed; Khadim, Ghazanfar; Belue, Rhonda; Chomsky, Don; Dittus, Robert S; Griffin, Marie; Wilson, John R

    2003-06-01

    Although beta-blockers were well-tolerated by heart failure (HF) patients in clinical trials, tolerability of these drugs in a general population of HF patients is not well-described. We studied a total of 308 encounters with beta-blockers therapy in 268 ambulatory HF patients. Side effects and frequency and predictors of discontinuation of therapy were studied. Independent predictors of discontinuation were assessed. Weight gain (59%), fatigue (56%), dizziness (41%), and dyspnea (29%) were the most common side effects. Fifty-one patients (19%) were discontinued on therapy with any 1 particular beta-blocker. Fatigue (30%) and hypotension (28%) were the most common reasons for discontinuation. Forty (78%) of these were given a trial with a different beta-blocker. Of these, 22 (55%) attempts with a different beta-blocker were tolerated. Thus the overall absolute discontinuation rate was only 7% for patients who were given a trial with different beta-blockers or 11% for the entire study population. Independent predictors of discontinuation of therapy included advanced symptoms, nonischemic etiology, history of pulmonary disease, and higher diuretic doses. Side effects with beta-blockers in a general population of HF patients are common; however, with changes in medical management, most patients can tolerate them eventually. In case of intolerance to one kind, a trial with a different beta-blocker is indicated.

  18. Block volume estimation from the discontinuity spacing measurements of mesozoic limestone quarries, Karaburun Peninsula, Turkey.

    PubMed

    Elci, Hakan; Turk, Necdet

    2014-01-01

    Block volumes are generally estimated by analyzing the discontinuity spacing measurements obtained either from the scan lines placed over the rock exposures or the borehole cores. Discontinuity spacing measurements made at the Mesozoic limestone quarries in Karaburun Peninsula were used to estimate the average block volumes that could be produced from them using the suggested methods in the literature. The Block Quality Designation (BQD) ratio method proposed by the authors has been found to have given in the same order of the rock block volume to the volumetric joint count (J(v)) method. Moreover, dimensions of the 2378 blocks produced between the years of 2009 and 2011 in the working quarries have been recorded. Assuming, that each block surfaces is a discontinuity, the mean block volume (V(b)), the mean volumetric joint count (J(vb)) and the mean block shape factor of the blocks are determined and compared with the estimated mean in situ block volumes (V(in)) and volumetric joint count (J(vi)) values estimated from the in situ discontinuity measurements. The established relations are presented as a chart to be used in practice for estimating the mean volume of blocks that can be obtained from a quarry site by analyzing the rock mass discontinuity spacing measurements.

  19. Analysis and development of adjoint-based h-adaptive direct discontinuous Galerkin method for the compressible Navier-Stokes equations

    NASA Astrophysics Data System (ADS)

    Cheng, Jian; Yue, Huiqiang; Yu, Shengjiao; Liu, Tiegang

    2018-06-01

    In this paper, an adjoint-based high-order h-adaptive direct discontinuous Galerkin method is developed and analyzed for the two dimensional steady state compressible Navier-Stokes equations. Particular emphasis is devoted to the analysis of the adjoint consistency for three different direct discontinuous Galerkin discretizations: including the original direct discontinuous Galerkin method (DDG), the direct discontinuous Galerkin method with interface correction (DDG(IC)) and the symmetric direct discontinuous Galerkin method (SDDG). Theoretical analysis shows the extra interface correction term adopted in the DDG(IC) method and the SDDG method plays a key role in preserving the adjoint consistency. To be specific, for the model problem considered in this work, we prove that the original DDG method is not adjoint consistent, while the DDG(IC) method and the SDDG method can be adjoint consistent with appropriate treatment of boundary conditions and correct modifications towards the underlying output functionals. The performance of those three DDG methods is carefully investigated and evaluated through typical test cases. Based on the theoretical analysis, an adjoint-based h-adaptive DDG(IC) method is further developed and evaluated, numerical experiment shows its potential in the applications of adjoint-based adaptation for simulating compressible flows.

  20. Traveling waves in Hall-magnetohydrodynamics and the ion-acoustic shock structure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hagstrom, George I.; Hameiri, Eliezer

    Hall-magnetohydrodynamics (HMHD) is a mixed hyperbolic-parabolic partial differential equation that describes the dynamics of an ideal two fluid plasma with massless electrons. We study the only shock wave family that exists in this system (the other discontinuities being contact discontinuities and not shocks). We study planar traveling wave solutions and we find solutions with discontinuities in the hydrodynamic variables, which arise due to the presence of real characteristics in Hall-MHD. We introduce a small viscosity into the equations and use the method of matched asymptotic expansions to show that solutions with a discontinuity satisfying the Rankine-Hugoniot conditions and also anmore » entropy condition have continuous shock structures. The lowest order inner equations reduce to the compressible Navier-Stokes equations, plus an equation which implies the constancy of the magnetic field inside the shock structure. We are able to show that the current is discontinuous across the shock, even as the magnetic field is continuous, and that the lowest order outer equations, which are the equations for traveling waves in inviscid Hall-MHD, are exactly integrable. We show that the inner and outer solutions match, which allows us to construct a family of uniformly valid continuous composite solutions that become discontinuous when the diffusivity vanishes.« less

  1. The effect of topography of upper-mantle discontinuities on SS precursors

    NASA Astrophysics Data System (ADS)

    Koroni, Maria; Trampert, Jeannot

    2016-01-01

    Using the spectral-element method, we explored the effect of topography of upper-mantle discontinuities on the traveltimes of SS precursors recorded on transverse component seismograms. The latter are routinely used to infer the topography of mantle transition zone discontinuities. The step from precursory traveltimes to topographic changes is mainly done using linearised ray theory, or sometimes using finite-frequency kernels. We simulated exact seismograms in 1-D and 3-D elastic models of the mantle. In a second simulation, we added topography to the discontinuities. We compared the waveforms obtained with and without topography by cross correlation of the SS precursors. Since we did not add noise, the precursors are visible in individual seismograms without the need of stacking. The resulting time anomalies were then converted into topographic variations and compared to the original topographic models. Based on the correlation between initial and inferred models, and provided that ray coverage is good, we found that linearised ray theory gives a relatively good idea on the location of the uplifts and depressions of the discontinuities. It seriously underestimates the amplitude of the topographic variations by a factor ranging between 2 and 7. Real data depend on the 3-D elastic structure and the topography. All studies to date correct for the 3-D elastic effects assuming that the traveltimes can be linearly decomposed into a structure and a discontinuity part. We found a strong non-linearity in this decomposition which cannot be modelled without a fully non-linear inversion for elastic structure and discontinuities simultaneously.

  2. Topography of Upper Mantle Seismic Discontinuities Beneath the North Atlantic: The Azores, Canary and Cape Verde Plumes

    NASA Astrophysics Data System (ADS)

    Thomas, C.; Saki, M.; Nippress, S. E. J.; Lessing, S.

    2014-12-01

    We are mapping the topography of upper mantle seismic discontinuities beneath the North Atlantic and surrounding regions by using precursor arrivals to PP and SS seismic waves that reflect off the seismic discontinuities. Numerous source-receiver combinations have been used in order to collect a large dataset of reflection points beneath our investigation area. We analysed over 1700 seismograms from MW>5.8 events using array seismic methods to enhance the signal to noise ratio. The measured time lag between PP (SS) arrivals and their corresponding precursors on robust stacks are used to measure the depth of the transition zone boundaries. The reflectors' depths show a correlation between the location of known hotspots and a significantly depressed 410 km discontinuity indicating a temperature increase of 50-300 K compared to the surrounding mantle. For the 660 km discontinuity three distinct behaviours are visible: i) normal depths beneath Greenland and at a distance of a few hundred kilometres away from known hotspots, ii) shallower 660 km discontinuity compared with the global average value near hotspots closer to the Mid-Atlantic Ridge and iii) very few observations of a 660 km discontinuity at the hotspot locations. We interpret our observations as a large upwelling beneath the southern parts of our study region, possibly due to the South Atlantic convection cell. The thermal anomaly may be blocked by endothermic phase transformation and likely does not extend through the top of the transition zone except for those branches which appear as the Azores, Canaries and Cape Verde hotspots at the surface.

  3. Topography of upper mantle seismic discontinuities beneath the North Atlantic: the Azores, Canary and Cape Verde plumes

    NASA Astrophysics Data System (ADS)

    Saki, Morvarid; Thomas, Christine; Nippress, Stuart E. J.; Lessing, Stephan

    2015-04-01

    We are mapping the topography of upper mantle seismic discontinuities beneath the North Atlantic and surrounding regions by using precursor arrivals to PP and SS seismic waves that reflect off the seismic discontinuities. Many source-receiver combinations have been used in order to collect a large dataset of reflection points beneath our investigating area. We analyzed over 1700 seismograms from MW>5.8 events using array seismic methods to enhance the signal to noise ratio. The measured time lag between PP (SS) arrivals and their corresponding precursors on robust stacks are used to measure the depth of the transition zone boundaries. The reflectors' depths show a correlation between the location of hotspots and a significantly depressed 410 km discontinuity indicating a temperature increase of 200-300 K compared to the surrounding mantle. For the 660 km discontinuity three distinct behaviours are visible: i) normal depths beneath Greenland and at a distance of a few hundred kilometres away from the hotspots and ii) shallower 660 km discontinuity compared with the global average value near hotspots closer to the Mid-Atlantic Ridge and iii) very few observations of a 660 km discontinuity at the hotspot locations. We interpret our observations as a large upwelling beneath the southern parts of our study region, possibly due to the South Atlantic convection cell. The thermal anomaly may be blocked by endothermic phase transformation and likely does not extend through the top of the transition zone as whole except for those branches which appear as the Azores, Canaries and Cape Verde hotspots at the surface.

  4. The effect of topography of upper mantle discontinuities on SS precursors

    NASA Astrophysics Data System (ADS)

    Koroni, M.; Trampert, J.

    2015-12-01

    We assessed the reliability of methods used to infer the topography of the mantle transition zone discontinuities. In particular, using the spectral-element method,we explored the effect of topography of the '410' and '660' mantle discontinuities on the travel times of SS precursors recorded on transverse component seismograms.The latter are routinely used to infer the topography of mantle transition zone discontinuities. The step from precursorytravel times to topographic changes is mainly done using linearised ray theory, or sometimes using finite frequency kernels.We simulated exact seismograms in 1-D and 3-D elastic models of the mantle. In a second simulation, we added topography to the discontinuities. We compared the waveforms obtained with and without topography by cross-correlation of the SS precursors. Since we did not add noise, the precursors are visible in individual seismograms without the need of stacking. The resultingtime anomalies were then converted into topographic variations and compared to the original models of topography. We found that linearised ray theory gives a relatively good idea on the location of the uplifts and depressions of the discontinuities, provided that the ray coverage is good, although it seriously underestimates the amplitude of the topography. The amplitude of the topographic variation is underestimated in average by a factor of 2.8 for the '660' and of 4.5 for the '410'. Additionally, we found a strong non-linearity in the measured data which cannot be modelled without a fully non-linear inversion for elastic structure and discontinuities simultaneously.

  5. Oral Effects and Early Implant Survival Results After Imatinib Discontinuation Therapy for Chronic Myelogenous Leukemia: A Case Report.

    PubMed

    Dixon, Douglas R; Yassin, Alaa

    2017-08-01

    Little is known regarding the success, failure, or complication rates of advanced implant procedures in patients after discontinuation therapy of long-term medications for the treatment of chronic myelogenous leukemia (CML). This case report presents initial results of a case involving implant placement in the mandible and maxilla as well as reduction of palatal oral pigmentation in a patient discontinuing long-term tyrosine kinase inhibitor (TKI) therapy for CML. A 57-year-old male was referred to the Department of Periodontics, University of Washington, Seattle, Washington, for an assessment of edentulous areas (tooth sites #3 and #14) and failing tooth #19. Previous medical treatment included oral administration (>10 years) of TKI for the treatment of CML. Systemic complications arising from long-term TKI therapy were treated with discontinuation of this medication. Concurrently, after multispecialty dental and medical consultation, extraction of tooth #19 with immediate implant placement and bilateral sinus augmentation with simultaneous implant placement were successfully performed during three separate surgical appointments. Additionally, marked reduction of oral palatal pigmentation was observed during the surgical and restorative phases after TKI discontinuation. Patients with a history of long-term TKIs for CML are at risk for developing complications that result in discontinuation of therapy. Long-term benefits of therapy may allow these patients to enjoy remission with an extended and improved quality of life. Patients undergoing discontinuation therapy may seek dental care. Therefore, dental providers need to understand these systemic interactions and, with multispecialty consultation, may help effectively treat these individuals.

  6. Prospective evaluation of a bivalirudin to warfarin transition nomogram.

    PubMed

    Hohlfelder, Benjamin; Sylvester, Katelyn W; Rimsans, Jessica; DeiCicchi, David; Connors, Jean M

    2017-05-01

    Bivalirudin may cause a falsely prolonged international normalized ratio (INR) that complicates the discontinuation of bivalirudin when used as a bridge to warfarin. To prospectively validate our novel bivalirudin to warfarin transition nomogram, adult patients who received bivalirudin as a bridge to warfarin between July 2015 and June 2016 were prospectively evaluated, utilizing our predictive nomogram. The major outcome of our analysis was the correlation between the predicted change in INR upon bivalirudin discontinuation based on the nomogram, and the actual change in INR upon bivalirudin discontinuation. The major outcome was analyzed using the Pearson's correlation test. A Pearson's correlation coefficient >0.6 was considered to be a strong correlation. Bivalirudin was used as a bridge to warfarin in 29 patients. The majority of patients (86%) included in the analysis had a ventricular assist device. The median initial bivalirudin rate was 0.07 mg/kg/h and the mean increase in INR when starting bivalirudin was 0.6. The mean final weight-based bivalirudin rate was 0.08 mg/kg/h and the mean change in INR after stopping bivalirudin was 0.7. The Pearson correlation coefficient between the predicted change in INR upon bivalirudin discontinuation and the actual change in INR upon bivalirudin discontinuation was 0.86 (p < 0.001). After bivalirudin discontinuation, 68% of patients had a therapeutic INR. The results of this prospective analysis successfully validated our novel bivalirudin to warfarin transition nomogram. There was a very strong correlation between the predicted change and actual change in INR upon bivalirudin discontinuation.

  7. Safety of Temporary Discontinuation of Antihypertensive Medication in Patients With Difficult-to-Control Hypertension.

    PubMed

    Beeftink, Martine M A; van der Sande, Nicolette G C; Bots, Michiel L; Doevendans, Pieter A; Blankestijn, Peter J; Visseren, Frank L J; Voskuil, Michiel; Spiering, Wilko

    2017-05-01

    Successful control of blood pressure relies on identification of secondary causes and contributing factors of hypertension. As antihypertensive medication can interfere with diagnostic investigations, temporary discontinuation of medication is advised. However, there are concerns about the safety of temporary discontinuation of antihypertensive medication in patients with difficult-to-control hypertension. We assessed the occurrence of adverse cardiovascular and cerebrovascular events potentially attributable to temporary discontinuation of antihypertensive medication between February 2010 and March 2016 (n=604) in our Analysis of Complicated Hypertension screening program. A reference group (n=604) was extracted from the SMART study (Second Manifestations of Arterial Disease) cohort (comprising a similar cohort at our hospital in whom medication was not stopped) and individually matched for blood pressure, age, sex, and history of cardiovascular disease. Discontinuation of medication was well tolerated; 62% reported no complaints, 24% had mild discomfort that could be left untreated, and 14% experienced complaints that required prescription of antihypertensive escape medication. Three major adverse events were observed in the Analysis of Complicated Hypertension group between discontinuation of medication and 30 days after restart of medication (event rate=31.2 events per 1000 patient-year). In the reference cohort, 5 cardiovascular events were observed during a similar follow-up period (event rate=51.2 events per 1000 patient-year). In conclusion, discontinuation of antihypertensive medication for the diagnostic evaluation of hypertension does not increase the acute risk of cardiovascular events when performed in a well-controlled setting in specialized hospitals with appropriate protocols for monitoring safety. © 2017 American Heart Association, Inc.

  8. Healthcare Resource Waste Associated with Patient Nonadherence and Early Discontinuation of Traditional Continuous Glucose Monitoring in Real-World Settings: A Multicountry Analysis.

    PubMed

    Yu, Shengsheng; Varughese, Biju; Li, Zhiyi; Kushner, Pam R

    2018-06-01

    Traditional continuous glucose monitoring (CGM) provides detailed information on glucose patterns and trends to inform daily diabetes management decisions, which is particularly beneficial for patients with a history of hypoglycemia unawareness. However, a high level of patient adherence (≥70%) is required to achieve clinical benefits. The aim of this study was to assess the impact of real-world patient nonadherence and early discontinuation on healthcare resource use. A cost calculator was designed to evaluate monthly healthcare resource waste within the first year of traditional CGM initiation by combining estimates of real-world nonadherence and early discontinuation from the literature with the wholesale acquisition costs of the current technology in the United States (for a commercial payer and for Medicare), or its equivalent in Sweden, Germany, or the Netherlands. Based on an early discontinuation rate of 27% and nonadherence rates of 13.9%-31.1% over the 12 months following initiation, the healthcare resource waste associated with nonadherence and early discontinuation was $220,289 and $21,775, respectively, for every 100 patients initiating CGM in the U.S. commercial payer scenario. In the Medicare scenario, the corresponding figures were $72,648 and $5,675, respectively. In both scenarios, nonadherence and early discontinuation accounted for ∼24% of resources being wasted within the first year of CGM initiation. Similar results were observed using the local costs in the other countries analyzed. The healthcare resource waste associated with traditional CGM nonadherence and early discontinuation warrants deliberate consideration when selecting suitable patients for this technology.

  9. Quantity and economic value of unused oral anti-cancer and biological disease-modifying anti-rheumatic drugs among outpatient pharmacy patients who discontinue therapy.

    PubMed

    Bekker, C L; Melis, E J; Egberts, A C G; Bouvy, M L; Gardarsdottir, H; van den Bemt, B J F

    2018-03-24

    Patients sometimes discontinue the use of expensive oral anti-cancer drug (OACD) or biological disease-modifying anti-rheumatic drug (bDMARD) therapies early, leading to medication waste if the patient has not used all dispensed medication. To determine the proportion of patients who have unused OACDs or bDMARDs after therapy discontinuation, and the quantity and economic value of these unused medications. Furthermore, patients' reasons for therapy discontinuation and their disposal method for unused medications were determined. In a retrospective follow-up study using a Dutch outpatient pharmacy database, patients (≥18 years) who did not refill an OACD or bDMARD prescription, dispensed between November 2015 and February 2016, within two weeks of the prescription end date were contacted by phone and asked about their unused medication and reasons thereof. The economic value was calculated using Dutch medication prices. Data were descriptively analyzed in STATA13. The database included 1173 patients, of whom 159 likely had discontinued therapy and were contacted. Of these, 88 patients were excluded (39 refilled, 47 missing, and 2 other). Of the 71 patients who had discontinued therapy, 39 (54.9%) had unused medications, comprising 22 OACD users (mean age 63.0 (SD ± 15.9) years, 50.0% female) and 17 bDMARD users (mean age 50.7 (SD ± 13.5) years, 47.1% female). A total of 59 packages were unused, with a total value of €60,341. Unused OACD packages and bDMARD packages had median values of €179 (IQR €24-2487) and €992 (IQR €681-1093), respectively. Patients primarily discontinued therapy due to adverse or insufficient effects. This study illustrates that more than half of patients discontinuing OACD or bDMARD therapies have unused medication. This emphasizes the need for waste-reducing interventions. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Incomplete reversibility of estimated glomerular filtration rate decline following tenofovir disoproxil fumarate exposure.

    PubMed

    Jose, Sophie; Hamzah, Lisa; Campbell, Lucy J; Hill, Teresa; Fisher, Martin; Leen, Clifford; Gilson, Richard; Walsh, John; Nelson, Mark; Hay, Phillip; Johnson, Margaret; Chadwick, David; Nitsch, Dorothea; Jones, Rachael; Sabin, Caroline A; Post, Frank A

    2014-08-01

    Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. We observed declines in the eGFR during TDF exposure (mean slopes, -15.7 mL/minute/1.73 m(2)/year [95% confidence interval {CI}, -20.5 to -10.9] during the first 3 months and -3.1 mL/minute/1.73 m(2)/year [95% CI, -4.6 to -1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m(2)/year [95% CI, 8.9-16.1] during the first 3 months and 0.8 mL/minute/1.73 m(2)/year [95% CI, .1-1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  11. Incomplete Reversibility of Estimated Glomerular Filtration Rate Decline Following Tenofovir Disoproxil Fumarate Exposure

    PubMed Central

    Jose, Sophie; Hamzah, Lisa; Campbell, Lucy J.; Hill, Teresa; Fisher, Martin; Leen, Clifford; Gilson, Richard; Walsh, John; Nelson, Mark; Hay, Phillip; Johnson, Margaret; Chadwick, David; Nitsch, Dorothea; Jones, Rachael; Sabin, Caroline A.; Post, Frank A.; Ainsworth, Jonathan; Anderson, Jane; Babiker, Abdel; Chadwick, David; Delpech, Valerie; Dunn, David; Fisher, Martin; Gazzard, Brian; Gilson, Richard; Gompels, Mark; Hay, Phillip; Hill, Teresa; Johnson, Margaret; Kegg, Stephen; Leen, Clifford; Nelson, Mark; Orkin, Chloe; Palfreeman, Adrian; Phillips, Andrew; Pillay, Deenan; Post, Frank; Sabin, Caroline; Sachikonye, Memory; Schwenk, Achim; Walsh, John; Hill, Teresa; Huntington, Susie; Josie, Sophie; Phillips, Andrew; Sabin, Caroline; Thornton, Alicia; Dunn, David; Glabay, Adam; Orkin, C.; Garrett, N.; Lynch, J.; Hand, J.; de Souza, C.; Fisher, M.; Perry, N.; Tilbury, S.; Churchill, D.; Gazzard, B.; Nelson, M.; Waxman, M.; Asboe, D.; Mandalia, S.; Delpech, V.; Anderson, J.; Munshi, S.; Korat, H.; Poulton, M.; Taylor, C.; Gleisner, Z.; Campbell, L.; Babiker, Abdel; Dunn, David; Glabay, Adam; Gilson, R.; Brima, N.; Williams, I.; Schwenk, A.; Ainsworth, J.; Wood, C.; Miller, S.; Johnson, M.; Youle, M.; Lampe, F.; Smith, C.; Grabowska, H.; Chaloner, C.; Puradiredja, D.; Walsh, J.; Weber, J.; Ramzan, F.; Mackie, N.; Winston, A.; Leen, C.; Wilson, A.; Gompels, M.; Allan, S.; Palfreeman, A.; Moore, A.; Chadwick, D.; Wakeman, K.; Kegg, Stephen; Main, Paul; Mitchell; Hunter; Sachikonye, Memory; Hay, Phillip; Dhillon, Mandip

    2014-01-01

    Background. Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. Methods. Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. Results. We observed declines in the eGFR during TDF exposure (mean slopes, −15.7 mL/minute/1.73 m2/year [95% confidence interval {CI}, −20.5 to −10.9] during the first 3 months and −3.1 mL/minute/1.73 m2/year [95% CI, −4.6 to −1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m2/year [95% CI, 8.9–16.1] during the first 3 months and 0.8 mL/minute/1.73 m2/year [95% CI, .1–1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. Conclusions. This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided. PMID:24585896

  12. Second tyrosine kinase inhibitor discontinuation attempt in patients with chronic myeloid leukemia.

    PubMed

    Legros, Laurence; Nicolini, Franck E; Etienne, Gabriel; Rousselot, Philippe; Rea, Delphine; Giraudier, Stéphane; Guerci-Bresler, Agnès; Huguet, Françoise; Gardembas, Martine; Escoffre, Martine; Ianotto, Jean-Christophe; Noël, Marie-Pierre; Varet, Bruno R; Pagliardini, Thomas; Touitou, Irit; Morisset, Stéphane; Mahon, Francois-Xavier

    2017-11-15

    Several studies have demonstrated that approximately one-half of patients with chronic myeloid leukemia (CML) who receive treatment with tyrosine kinase inhibitors (TKIs) and achieve and maintain a deep molecular response (DMR) are able to successfully discontinue therapy. In patients who have a molecular relapse, a DMR is rapidly regained upon treatment re-initiation. The authors report the results from RE-STIM, a French observational, multicenter study that evaluated treatment-free remission (TFR) in 70 patients who re-attempted TKI discontinuation after a first unsuccessful attempt. After the second TKI discontinuation attempt, the trigger for treatment re-introduction was the loss of a major molecular response in all patients. The median follow-up was 38.3 months (range, 4.7-117 months), and 45 patients (64.3%) lost a major molecular response after a median time off therapy of 5.3 months (range, 2-42 months). TFR rates at 12, 24, and 36 months were 48% (95% confidence interval [CI], 37.6%-61.5%), 42% (95% CI, 31.5%-55.4%), and 35% (95% CI, 24.4%-49.4%), respectively. No progression toward advanced-phase CML occurred, and no efficacy issue was observed upon TKI re-introduction. In univariate analysis, the speed of molecular relapse after the first TKI discontinuation attempt was the only factor significantly associated with outcome. The TFR rate at 24 months was 72% (95% CI, 48.8%-100%) in patients who remained in DMR within the first 3 months after the first TKI discontinuation and 36% (95% CI, 25.8%-51.3%) for others. This study is the first to demonstrate that a second TKI discontinuation attempt is safe and that a first failed attempt at discontinuing TKI does not preclude a second successful attempt. Cancer 2017;123:4403-10. © 2017 American Cancer Society. © 2017 American Cancer Society.

  13. Rates of IUCD discontinuation and its associated factors among the clients of a social franchising network in Pakistan

    PubMed Central

    2012-01-01

    Background Modern Intrauterine contraceptive device (IUCD) is very safe, highly effective reversible and inexpensive family planning method which offers 5-10 years of protection against pregnancy. The contraceptive use in Pakistan has been merely 30% for over a decade with IUCD being the least used method. Higher discontinuation rates are documented in developing countries; however no such data is available for Pakistan. Marie Stopes Society (MSS) established a social franchise outlets network branded as 'SURAJ' (Sun) in Pakistan to provide quality family planning services. This study attempts to determine IUCD discontinuation rates and its associated risk factors. Using a semi-structured questionnaire, a cross-sectional study was conducted with 3000 clients who availed IUCD services from Suraj provider 6, 12 and 24 month back,. Data were analyzed in SPSS 17.0; adjusted prevalence ratios were calculated to see associations between discontinuation and its risk factors. Case presentation We found that 22.7% of the IUCD acceptors experienced some health problem; while the overall discontinuation rate was 18.9% with average time of usage of 7.4 (SD ± 5.8) months before discontinuation. Half of them showed health concerns (49.8%); of which a majority (70.2%) returned to Suraj provider for IUCD removal. Women living in Punjab, residing at a travelling time of 30-60 minutes and no previous use of contraceptive are more likely to discontinue IUCD. However, among total women 81.7% still expressed willingness to avail IUCD services from Suraj provider in future, if needed. Conclusion The findings suggest a need for training the providers and field workers to prevent early discontinuation of IUCD among the Suraj clients and by addressing the health concerns through proper counseling, continued follow-up and immediate medical aid/referral in case of complications. PMID:22458444

  14. Hypoglycemia After Initiation of Basal Insulin in Patients with Type 2 Diabetes in the United States: Implications for Treatment Discontinuation and Healthcare Costs and Utilization.

    PubMed

    Dalal, Mehul R; Kazemi, Mahmood; Ye, Fen; Xie, Lin

    2017-09-01

    Hypoglycemia and fear of hypoglycemia may contribute to basal insulin discontinuation, poor glycemic control, and increased healthcare burden in patients with type 2 diabetes (T2D). This study aimed to determine the impact of hypoglycemia soon after basal insulin initiation on treatment discontinuation and economic outcomes in patients with T2D. Hypoglycemic events within 6 months of basal insulin initiation were identified using retrospective cohort data from patients with T2D, at least 18 years of age, initiated on basal insulin therapy in the Clinformatics™ Data Mart for Multiplan claims database from January 1, 2008, through August 31, 2012. Data were adjusted for baseline characteristics. Discontinuation was established for patients with 12-month follow-up data, while discontinuation risk was assessed in the extended analysis (6- to 24-month follow-up) by Cox regression analysis. Healthcare use and costs were determined. Of 55,608 patients, 4.5% experienced hypoglycemia within 6 months of basal insulin initiation. Patients with hypoglycemia were more likely to discontinue basal insulin within 12 months of initiation (79.0% vs. 74.2%; P < 0.001). Data, adjusted for baseline characteristics such as age, any baseline hypoglycemia, and use of oral antidiabetes drugs, showed that patients with hypoglycemia had a greater risk of discontinuation (hazard ratio 1.16; 95% confidence interval 1.03, 1.32; P = 0.0164), were more likely to have a hospitalization (41.0% vs. 24.3%; P < 0.001) or an ED visit (55.8% vs. 35.1%; P < 0.001), and had higher diabetes-related ($13,662 vs. $7506; P < 0.001) and all-cause ($30,719 vs. $19,079; P < 0.001) healthcare costs. US patients with T2D who experienced hypoglycemia within 6 months of basal insulin initiation were more likely to discontinue treatment, accompanied by a greater healthcare burden. Sanofi US, Inc.

  15. Lack of cooperation between physicians and dentists during osteoporosis treatment may increase fractures and osteonecrosis of the jaw.

    PubMed

    Taguchi, Akira; Shiraki, Masataka; Sugimoto, Toshitsugu; Ohta, Hiroaki; Soen, Satoshi

    2016-07-01

    Our previous questionnaire-based survey suggested that discontinuation of antiresorptive agents before tooth extraction may increase adverse events and disturb osteoporosis treatment without completely preventing osteonecrosis of the jaw (O.N.J.). We also found little cooperation between physicians and dentists in Japan. However, limitations of our previous study included a survey of doctors belonging to small clinics and a small sample size. Our current study aimed to confirm the results of our previous survey in doctors mainly belonging to academia. A structured questionnaire including 14 key clinical queries was sent to 1812 physicians of the Japan Osteoporosis Society, and 629 responses were received. Dentists requested discontinuation of many medications that were not associated with the incidence of O.N.J. A total of 523 respondents had received discontinuation requests from dentists. Of these, 97 respondents experienced 119 adverse events including 25 fractures and seven incidences of O.N.J. The ratios of valid responses for fractures were 3.6% and 5.3% in patients with a discontinuation of <3 and ≥3 months, respectively. Those for O.N.J. were 0.7% and 1.6%, respectively. Respondents who refused discontinuation requests reported no cases of O.N.J. Approximately 17% of respondents had patients who discontinued osteoporosis treatment following a requested drug discontinuation after tooth extraction. Approximately 62% of respondents did not request oral health care by a dentist before antiresorptive therapy, and 72% reported no cooperation between physicians and dentists in their region. This study reconfirms the results of our previous survey. Discontinuation of antiresorptive treatment may increase both fractures and O.N.J. Immediate development of a strategy for sharing information about O.N.J. among physicians, dentists, and patients is required to reduce the incidence of both O.N.J. and skeletal events in osteoporosis treatment. Study limitations were selection bias due to low response rate and possible inaccurate responses to the questionnaire.

  16. Hospital Factors Associated With Care Discontinuity Following Emergency General Surgery.

    PubMed

    Havens, Joaquim M; Olufajo, Olubode A; Tsai, Thomas C; Jiang, Wei; Columbus, Alexandra B; Nitzschke, Stephanie L; Cooper, Zara; Salim, Ali

    2017-03-01

    Although there is evidence that changes in clinicians during the continuum of care (care discontinuity) are associated with higher mortality and complications among surgical patients, little is known regarding the drivers of care discontinuity among emergency general surgery (EGS) patients. To identify hospital factors associated with care discontinuity among EGS patients. We performed a retrospective analysis of the 100% Medicare inpatient claims file, from January 1, 2008, to November 30, 2011, and matched patient details to hospital information in the 2011 American Hospital Association Annual Survey database. We selected patients aged 65 years and older who had the most common procedures associated with the previously defined American Association for the Surgery of Trauma EGS diagnosis categories and survived to hospital discharge across the United States. The current analysis was conducted from February 1, 2016, to March 24, 2016. Care discontinuity defined as readmission within 30 days to nonindex hospitals. There were 109 443 EGS patients readmitted within 30 days of discharge and 20 396 (18.6%) were readmitted to nonindex hospitals. Of the readmitted patients, 61 340 (56%) were female. Care discontinuity was higher among patients who were male (19.5% vs 18.0%), those younger than 85 years old (19.0% vs 16.6%), and those who lived 12.8 km (8 miles) or more away from the index hospitals (23.7% vs 14.8%) (all P < .001). Care discontinuity was independently associated with mortality (adjusted odds ratio [aOR], 1.16; 95% CI, 1.08-1.25). Hospital factors associated with care discontinuity included bed size of 200 or more (aOR, 1.45; 95% CI, 1.36-1.54), safety-net status (aOR, 1.35; 95% CI, 1.27-1.43), and teaching status (aOR, 1.18; 95% CI, 1.09-1.28). Care discontinuity was significantly lower among designated trauma centers (aOR, 0.89; 95% CI, 0.83-0.94) and highest among hospitals in the Midwest (aOR, 1.15; 95% CI, 1.05-1.26). Nearly 1 in 5 older EGS patients is readmitted to a hospital other than where their original procedure was performed. This care discontinuity is independently associated with mortality and is highest among EGS patients who are treated at large, teaching, safety-net hospitals. These data underscore the need for sustained efforts in increasing continuity of care among these hospitals and highlight the importance of accounting for these factors in risk-adjusted hospital comparisons.

  17. Risk of unsafe abortion associated with long-term contraception behaviour: a case control study from Sri Lanka.

    PubMed

    Arambepola, Carukshi; Rajapaksa, Lalini C

    2017-06-29

    When faced with an unintended pregnancy, some women choose to undergo an unsafe abortion, while others do not. This choice may depend on long-term contraception that shapes the fertility goals of women, along with many other risk factors. We assessed the risk for unsafe abortion associated with contraceptive practices based on women's long-term behaviour, and its likely modification by the use of different types of contraceptives among women in Sri Lanka. An unmatched case-control study was conducted in nine hospitals among 171 women admitted for care following an unsafe abortion (Cases) and 600 women admitted to same hospitals for delivery of an unintended term pregnancy (Controls). Interviewer-administered-questionnaires assessed their socio-economic, reproductive and fertility (decisions on family size, family completion) characteristics, contraceptive method last used (traditional, modern), reasons for discontinuation/never-use, and contraceptive practices assessed at different time points. Using several regression models, the risk of abortion was assessed for 'non-use' of contraception against 'ineffective use' at conception; for non-use further categorised as 'never-use', 'early-discontinuation' (discontinued before last birth interval) and 'late-discontinuation' (discontinued during last birth interval); and for any interaction between the contraceptive practice and contraceptive method last used among the ever-users of contraception. At conception, 'non-use' of contraception imparted a two-fold risk for abortion against ineffective use (adjusted-OR = 2.0; 95% CI: 1.2-3.2). The abortion risk on 'non-use' varied further according to 'early' (adjusted-OR = 1.7; 95% CI: 1.1-3.1) and 'late' (adjusted-OR = 2.3; 95% CI: 1.5-3.6) discontinuation of contraception, but not with 'never-use' (crude-OR = 1.1; 95% CI: 0.6-2.3). Among the ever-users, the risk of abortion varied within each contraceptive practice by their last used contraceptive method and reasons for discontinuation. A significant interaction between modern contraceptives and early discontinuation (adjusted-OR = 1.4; 95% CI = 1.1-3.1) demonstrated a seven-fold abortion risk for early discontinuation of modern methods against its ineffective use. In particular, hormonal methods seemed to be responsible for this risk (51.1% cases versus 42.5% controls). Long-term contraceptive practices showed varying risk for abortion, and was further modified by early discontinuation of modern contraceptives. This knowledge should be applied during postnatal visits by public-health staff.

  18. Cauchy problem with general discontinuous initial data along a smooth curve for 2-d Euler system

    NASA Astrophysics Data System (ADS)

    Chen, Shuxing; Li, Dening

    2014-09-01

    We study the Cauchy problems for the isentropic 2-d Euler system with discontinuous initial data along a smooth curve. All three singularities are present in the solution: shock wave, rarefaction wave and contact discontinuity. We show that the usual restrictive high order compatibility conditions for the initial data are automatically satisfied. The local existence of piecewise smooth solution containing all three waves is established.

  19. Local Discontinuous Galerkin Methods for the Cahn-Hilliard Type Equations

    DTIC Science & Technology

    2007-01-01

    Kuramoto-Sivashinsky equations , the Ito-type coupled KdV equa- tions, the Kadomtsev - Petviashvili equation , and the Zakharov-Kuznetsov equation . A common...Local discontinuous Galerkin methods for the Cahn-Hilliard type equations Yinhua Xia∗, Yan Xu† and Chi-Wang Shu ‡ Abstract In this paper we develop...local discontinuous Galerkin (LDG) methods for the fourth-order nonlinear Cahn-Hilliard equation and system. The energy stability of the LDG methods is

  20. Heat exchanger containing a component capable of discontinuous movement

    DOEpatents

    Wilson, D.G.

    1993-11-09

    Regenerative heat exchangers are described for transferring heat between hot and cold fluids. The heat exchangers have seal-leakage rates significantly less than those of conventional regenerative heat exchangers because the matrix is discontinuously moved and is releasably sealed while in a stationary position. Both rotary and modular heat exchangers are described. Also described are methods for transferring heat between a hot and cold fluid using the discontinuous movement of matrices. 11 figures.

  1. Heat exchanger containing a component capable of discontinuous movement

    DOEpatents

    Wilson, David Gordon

    2001-04-17

    Regenerative heat exchangers are described for transferring heat between hot and cold fluids. The heat exchangers have seal-leakage rates significantly less than those of conventional regenerative heat exchangers because the matrix is discontinuously moved and is releasably sealed while in a stationary position. Both rotary and modular heat exchangers are described. Also described are methods for transferring heat between a hot and cold fluid using the discontinuous movement of matrices.

  2. Heat exchanger containing a component capable of discontinuous movement

    DOEpatents

    Wilson, David G.

    1993-01-01

    Regenerative heat exchangers are described for transferring heat between hot and cold fluids. The heat exchangers have seal-leakage rates significantly less than those of conventional regenerative heat exchangers because the matrix is discontinuously moved and is releasably sealed while in a stationary position. Both rotary and modular heat exchangers are described. Also described are methods for transferring heat between a hot and cold fluid using the discontinuous movement of matrices.

  3. Heat exchanger containing a component capable of discontinuous movement

    DOEpatents

    Wilson, David Gordon

    2002-01-01

    Regenerative heat exchangers are described for transferring heat between hot and cold fluids. The heat exchangers have seal-leakage rates significantly less than those of conventional regenerative heat exchangers because the matrix is discontinuously moved and is releasably sealed while in a stationary position. Both rotary and modular heat exchangers are described. Also described are methods for transferring heat between a hot and cold fluid using the discontinuous movement of matrices.

  4. High-order Discontinuous Element-based Schemes for the Inviscid Shallow Water Equations: Spectral Multidomain Penalty and Discontinuous Galerkin Methods

    DTIC Science & Technology

    2011-07-19

    multidomain methods, Discontinuous Galerkin methods, interfacial treatment ∗ Jorge A. Escobar-Vargas, School of Civil and Environmental Engineering, Cornell...Click here to view linked References 1. Introduction Geophysical flows exhibit a complex structure and dynamics over a broad range of scales that...hyperbolic problems, where the interfacial patching was implemented with an upwind scheme based on a modified method of characteristics. This approach

  5. Full wave characterization of microstrip open end discontinuities patterned on anisotropic substrates using potential theory

    NASA Technical Reports Server (NTRS)

    Toncich, S. S.; Collin, R. E.; Bhasin, K. B.

    1993-01-01

    A technique for a full wave characterization of microstrip open end discontinuities fabricated on uniaxial anisotropic substrates using potential theory is presented. The substrate to be analyzed is enclosed in a cutoff waveguide, with the anisotropic axis aligned perpendicular to the air-dielectric interface. A full description of the sources on the microstrip line is included with edge conditions built in. Extention to other discontinuities is discussed.

  6. Pseudolocal tomography

    DOEpatents

    Katsevich, Alexander J.; Ramm, Alexander G.

    1996-01-01

    Local tomographic data is used to determine the location and value of a discontinuity between a first internal density of an object and a second density of a region within the object. A beam of radiation is directed in a predetermined pattern through the region of the object containing the discontinuity. Relative attenuation data of the beam is determined within the predetermined pattern having a first data component that includes attenuation data through the region. The relative attenuation data is input to a pseudo-local tomography function, where the difference between the internal density and the pseudo-local tomography function is computed across the discontinuity. The pseudo-local tomography function outputs the location of the discontinuity and the difference in density between the first density and the second density.

  7. A non-conventional discontinuous Lagrangian for viscous flow

    PubMed Central

    Marner, F.

    2017-01-01

    Drawing an analogy with quantum mechanics, a new Lagrangian is proposed for a variational formulation of the Navier–Stokes equations which to-date has remained elusive. A key feature is that the resulting Lagrangian is discontinuous in nature, posing additional challenges apropos the mathematical treatment of the related variational problem, all of which are resolvable. In addition to extending Lagrange's formalism to problems involving discontinuous behaviour, it is demonstrated that the associated equations of motion can self-consistently be interpreted within the framework of thermodynamics beyond local equilibrium, with the limiting case recovering the classical Navier–Stokes equations. Perspectives for applying the new formalism to discontinuous physical phenomena such as phase and grain boundaries, shock waves and flame fronts are provided. PMID:28386415

  8. The structure of rotational discontinuities. [in solar wind

    NASA Technical Reports Server (NTRS)

    Neugebauer, M.

    1989-01-01

    This study examines the structures of a set of rotational discontinuities detected in the solar wind by the ISEE-3 spacecraft. It is found that the complexity of the structure increases as the angle theta between the propagation vector k and the magnetic field decreases. For rotational discontinuities that propagate at a large angle to the field with an ion (left-hand) sense of rotation, the magnetic hodograms tend to be flattened, in agreement with prior numerical simulations. When theta is large, angular 'overshoots' are often observed at one or both ends of the discontinuity. When the propagation is nearly parallel to the field (when theta is small), many different types of structure are seen, ranging from straight lines, to S-shaped curves, to complex, disorganized shapes.

  9. A High Order Discontinuous Galerkin Method for 2D Incompressible Flows

    NASA Technical Reports Server (NTRS)

    Liu, Jia-Guo; Shu, Chi-Wang

    1999-01-01

    In this paper we introduce a high order discontinuous Galerkin method for two dimensional incompressible flow in vorticity streamfunction formulation. The momentum equation is treated explicitly, utilizing the efficiency of the discontinuous Galerkin method The streamfunction is obtained by a standard Poisson solver using continuous finite elements. There is a natural matching between these two finite element spaces, since the normal component of the velocity field is continuous across element boundaries. This allows for a correct upwinding gluing in the discontinuous Galerkin framework, while still maintaining total energy conservation with no numerical dissipation and total enstrophy stability The method is suitable for inviscid or high Reynolds number flows. Optimal error estimates are proven and verified by numerical experiments.

  10. Super-convergence of Discontinuous Galerkin Method Applied to the Navier-Stokes Equations

    NASA Technical Reports Server (NTRS)

    Atkins, Harold L.

    2009-01-01

    The practical benefits of the hyper-accuracy properties of the discontinuous Galerkin method are examined. In particular, we demonstrate that some flow attributes exhibit super-convergence even in the absence of any post-processing technique. Theoretical analysis suggest that flow features that are dominated by global propagation speeds and decay or growth rates should be super-convergent. Several discrete forms of the discontinuous Galerkin method are applied to the simulation of unsteady viscous flow over a two-dimensional cylinder. Convergence of the period of the naturally occurring oscillation is examined and shown to converge at 2p+1, where p is the polynomial degree of the discontinuous Galerkin basis. Comparisons are made between the different discretizations and with theoretical analysis.

  11. Method for simulating discontinuous physical systems

    DOEpatents

    Baty, Roy S.; Vaughn, Mark R.

    2001-01-01

    The mathematical foundations of conventional numerical simulation of physical systems provide no consistent description of the behavior of such systems when subjected to discontinuous physical influences. As a result, the numerical simulation of such problems requires ad hoc encoding of specific experimental results in order to address the behavior of such discontinuous physical systems. In the present invention, these foundations are replaced by a new combination of generalized function theory and nonstandard analysis. The result is a class of new approaches to the numerical simulation of physical systems which allows the accurate and well-behaved simulation of discontinuous and other difficult physical systems, as well as simpler physical systems. Applications of this new class of numerical simulation techniques to process control, robotics, and apparatus design are outlined.

  12. A non-conventional discontinuous Lagrangian for viscous flow.

    PubMed

    Scholle, M; Marner, F

    2017-02-01

    Drawing an analogy with quantum mechanics, a new Lagrangian is proposed for a variational formulation of the Navier-Stokes equations which to-date has remained elusive. A key feature is that the resulting Lagrangian is discontinuous in nature, posing additional challenges apropos the mathematical treatment of the related variational problem, all of which are resolvable. In addition to extending Lagrange's formalism to problems involving discontinuous behaviour, it is demonstrated that the associated equations of motion can self-consistently be interpreted within the framework of thermodynamics beyond local equilibrium, with the limiting case recovering the classical Navier-Stokes equations. Perspectives for applying the new formalism to discontinuous physical phenomena such as phase and grain boundaries, shock waves and flame fronts are provided.

  13. Strain tolerant microfilamentary superconducting wire

    DOEpatents

    Finnemore, D.K.; Miller, T.A.; Ostenson, J.E.; Schwartzkopf, L.A.; Sanders, S.C.

    1993-02-23

    A strain tolerant microfilamentary wire capable of carrying superconducting currents is provided comprising a plurality of discontinuous filaments formed from a high temperature superconducting material. The discontinuous filaments have a length at least several orders of magnitude greater than the filament diameter and are sufficiently strong while in an amorphous state to withstand compaction. A normal metal is interposed between and binds the discontinuous filaments to form a normal metal matrix capable of withstanding heat treatment for converting the filaments to a superconducting state. The geometry of the filaments within the normal metal matrix provides substantial filament-to-filament overlap, and the normal metal is sufficiently thin to allow supercurrent transfer between the overlapped discontinuous filaments but is also sufficiently thick to provide strain relief to the filaments.

  14. Pseudolocal tomography

    DOEpatents

    Katsevich, A.J.; Ramm, A.G.

    1996-07-23

    Local tomographic data is used to determine the location and value of a discontinuity between a first internal density of an object and a second density of a region within the object. A beam of radiation is directed in a predetermined pattern through the region of the object containing the discontinuity. Relative attenuation data of the beam is determined within the predetermined pattern having a first data component that includes attenuation data through the region. The relative attenuation data is input to a pseudo-local tomography function, where the difference between the internal density and the pseudo-local tomography function is computed across the discontinuity. The pseudo-local tomography function outputs the location of the discontinuity and the difference in density between the first density and the second density. 7 figs.

  15. Mantle transition zone structure beneath India and Western China from migration of PP and SS precursors

    NASA Astrophysics Data System (ADS)

    Lessing, Stephan; Thomas, Christine; Rost, Sebastian; Cobden, Laura; Dobson, David P.

    2014-04-01

    We investigate the seismic structure of the upper-mantle and mantle transition zone beneath India and Western China using PP and SS underside reflections off seismic discontinuities, which arrive as precursors to the PP and SS arrival. We use high-resolution array seismic techniques to identify precursory energy and to map lateral variations of discontinuity depths. We find deep reflections off the 410 km discontinuity (P410P and S410S) beneath Tibet, Western China and India at depths of 410-440 km and elevated underside reflections of the 410 km discontinuity at 370-390 km depth beneath the Tien Shan region and Eastern Himalayas. These reflections likely correspond to the olivine to wadsleyite phase transition. The 410 km discontinuity appears to deepen in Central and Northern Tibet. We also find reflections off the 660 km discontinuity beneath Northern China at depths between 660 and 700 km (P660P and S660S) which could be attributed to the mineral transformation of ringwoodite to magnesiowuestite and perovskite. These observations could be consistent with the presence of cold material in the middle and lower part of the mantle transition zone in this region. We also find a deeper reflector between 700 and 740 km depth beneath Tibet which cannot be explained by a depressed 660 km discontinuity. This structure could, however, be explained by the segregation of oceanic crust and the formation of a neutrally buoyant garnet-rich layer beneath the mantle transition zone, due to subduction of oceanic crust of the Tethys Ocean. For several combinations of sources and receivers we do not detect arrivals of P660P and S660S although similar combinations of sources and receivers give well-developed P660P and S660S arrivals. Our thermodynamic modelling of seismic structure for a range of compositions and mantle geotherms shows that non-observations of P660P and S660S arrivals could be caused by the dependence of underside reflection coefficients on the incidence angle of the incoming seismic waves. Apart from reflections off the 410 and 660 km discontinuities, we observe intermittent reflectors at 300 and 520 km depth. The discontinuity structure of the study region likely reflects lateral thermal and chemical variations in the upper-mantle and mantle transition zone connected to past and present subduction and mantle convection processes.

  16. Levels and determinants of switching following intrauterine device discontinuation in 14 developing countries.

    PubMed

    Ali, Mohamed M; Park, Min Hae; Ngo, Thoai D

    2014-07-01

    To examine the levels and determinants of switching to any reversible modern contraceptive method following intrauterine device (IUD) discontinuation due to method-related reasons among women in developing countries. We analysed 5-year contraceptive calendar data from 14 Demographic and Health Surveys, conducted in 1993-2008 (n=218,092 women; 17,151 women contributed a total of 18,485 IUD episodes). Life-table methods were used to determine overall and cause-specific probabilities of IUD discontinuation at 12 months of use. For IUD episodes discontinued due to method-related reasons, the probability of switching to another reversible modern method within 3 months was estimated, overall and by place of residence, education level, motivation for use, age category and wealth tertiles. Country-specific rate ratios (RR) were estimated using generalized linear models, and pooled RRs using meta-analyses. The median duration of uninterrupted IUD use was 37 months. At 12 months, median probability of discontinuation was 13.2% and median probability of discontinuation due to method-related reasons was 8.9%. Within 3 months of discontinuation due to method-related reasons, half of the women had switched to another reversible modern method, 12% switched to traditional methods, 12% became pregnant, and 25% remained at risk for pregnancy. More educated women were more likely to switch to another reversible modern method than women with primary education or less (pooled RR 1.47; 95% CI 1.10-1.96), as were women in the highest wealth tertile (pooled RR 1.38; 95% CI 1.04-1.83) and women who were limiting births (pooled RR 1.35; 95% CI 1.08-1.68). Delays to switching and switching to less reliable methods following IUD discontinuation remain a problem, exposing women to the risk of unwanted pregnancy. Family planning programmes should aim to improve quality of services through strengthening of counselling and follow-up services to support women's continuation of effective methods. The risk of unintended pregnancy following IUD discontinuation remains high in developing countries. The quality of family planning services may be an important factor in switching to alternative modern contraceptive methods. Service providers should focus on counselling services and follow-up of women to support the continued use of effective methods. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Topography of upper mantle seismic discontinuities beneath the North Atlantic: The Azores, Canary and Cape Verde plumes

    NASA Astrophysics Data System (ADS)

    Saki, Morvarid; Thomas, Christine; Nippress, Stuart E. J.; Lessing, Stephan

    2015-01-01

    We are mapping the topography of upper mantle seismic discontinuities beneath the North Atlantic and surrounding regions by using precursor arrivals to PP and SS seismic waves that reflect off the seismic discontinuities. Numerous source-receiver combinations have been used in order to collect a large dataset of reflection points beneath our investigation area. We analysed over 1700 seismograms from MW > 5.8 events using array seismic methods to enhance the signal to noise ratio. The measured time lag between PP (SS) arrivals and their corresponding precursors on robust stacks are used to measure the depth of the transition zone boundaries. The reflectors' depths show a correlation between the location of known hotspots and a significantly depressed 410 km discontinuity indicating a temperature increase of 50-300 K compared to the surrounding mantle. For the 660 km discontinuity three distinct behaviours are visible: (i) normal depths beneath Greenland and at a distance of a few hundred kilometres away from known hotspots, (ii) shallower 660 km discontinuity compared with the global average value near hotspots closer to the Mid-Atlantic Ridge, and (iii) very few observations of a 660 km discontinuity at the hotspot locations. We interpret our observations as a large upwelling beneath the southern parts of our study region, possibly due to the South Atlantic convection cell. The thermal anomaly may be ponding beneath the endothermic 660 km phase transformation and likely does not extend through the top of the transition zone as a whole, except for those branches which appear as the thinner upwellings of Azores, Canaries and Cape Verde hotspots at the surface.

  18. Constraining Seismic Structure of Upper-Mantle Discontinuities: A New Approach Using High-Frequency Triplication Data

    NASA Astrophysics Data System (ADS)

    Ishii, M.; Park, S.

    2016-12-01

    Constraining elastic properties of the 410- and 660-km discontinuities is crucial for understanding the mantle composition and dynamics. One approach to study the transition zone is to use the "triplicated" arrivals of seismic data. These arrivals consist of three seismic phases that are sensitive to seismic structure slightly above, at, and below the discontinuity. Thus, these data are powerful tools in providing constraints on the depth and velocity jump of the discontinuities with consequences for the studies of mantle composition and relevant phase transitions. One of the most challenging aspects of using the triplication data, however, is to identify the three individual phases that arrive close in time. In order to separate the three phases, we apply Radon transform to short-period seismograms recorded by a dense array of stations. This approach unwraps the triplication pattern, and brings out the high-frequency information that is not easily accessible in the original form of data. Subsequent modeling of the unwrapped data allows velocity jump, depth, and width of the discontinuities to be obtained. This method is applied to study the transition zone around the Kuril subduction zone, a region northeast of Japan. We take advantage of the High-Sensitivity Seismograph Network in Japan that consists of more than 700 stations. These stations provide dense sampling in distance that allows us to capture the triplication pattern. The wave speeds immediately above and below the 410- and 660-km discontinuities as well as their depths and widths are constrained. In general, both discontinuities are depressed compared to the global average, and exhibit finite widths. The width estimates have implications on effects such as the existence of water or melt, and garnet transformations occurring at similar depths as the post-spinel transition.

  19. Discontinuation and Nonpublication of Randomized Clinical Trials Conducted in Children

    PubMed Central

    Pica, Natalie

    2016-01-01

    BACKGROUND: Trial discontinuation and nonpublication represent potential waste in research resources and lead to compromises in medical evidence. Pediatric trials may be particularly vulnerable to these outcomes given the challenges encountered in conducting trials in children. We aimed to determine the prevalence of discontinuation and nonpublication of randomized clinical trials (RCTs) conducted in pediatric populations. METHODS: Retrospective, cross-sectional study of pediatric RCTs registered in ClinicalTrials.gov from 2008 to 2010. Data were collected from the registry and associated publications identified (final search on September 1, 2015). RESULTS: Of 559 trials, 104 (19%) were discontinued early, accounting for an estimated 8369 pediatric participants. Difficulty with patient accrual (37%) was the most commonly cited reason for discontinuation. Trials were less likely to be discontinued if they were funded by industry compared with academic institutions (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.27–0.77). Of the 455 completed trials, 136 (30%) were not published, representing 69 165 pediatric participants. Forty-two unpublished trials posted results on ClinicalTrials.gov. Trials funded by industry were more than twice as likely to result in nonpublication at 24 and 36 months (OR 2.21, 95% CI 1.35–3.64; OR 3.12, 95% CI 1.6–6.08, respectively) and had a longer mean time to publication compared with trials sponsored by academia (33 vs 24 months, P < .001). CONCLUSIONS: In this sample of pediatric RCTs, discontinuation and nonpublication were common, with thousands of children exposed to interventions that did not lead to informative or published findings. Trial funding source was an important determinant of these outcomes, with both academic and industry sponsors contributing to inefficiencies. PMID:27492817

  20. Discontinuation and Nonpublication of Randomized Clinical Trials Conducted in Children.

    PubMed

    Pica, Natalie; Bourgeois, Florence

    2016-09-01

    Trial discontinuation and nonpublication represent potential waste in research resources and lead to compromises in medical evidence. Pediatric trials may be particularly vulnerable to these outcomes given the challenges encountered in conducting trials in children. We aimed to determine the prevalence of discontinuation and nonpublication of randomized clinical trials (RCTs) conducted in pediatric populations. Retrospective, cross-sectional study of pediatric RCTs registered in ClinicalTrials.gov from 2008 to 2010. Data were collected from the registry and associated publications identified (final search on September 1, 2015). Of 559 trials, 104 (19%) were discontinued early, accounting for an estimated 8369 pediatric participants. Difficulty with patient accrual (37%) was the most commonly cited reason for discontinuation. Trials were less likely to be discontinued if they were funded by industry compared with academic institutions (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.27-0.77). Of the 455 completed trials, 136 (30%) were not published, representing 69 165 pediatric participants. Forty-two unpublished trials posted results on ClinicalTrials.gov. Trials funded by industry were more than twice as likely to result in nonpublication at 24 and 36 months (OR 2.21, 95% CI 1.35-3.64; OR 3.12, 95% CI 1.6-6.08, respectively) and had a longer mean time to publication compared with trials sponsored by academia (33 vs 24 months, P < .001). In this sample of pediatric RCTs, discontinuation and nonpublication were common, with thousands of children exposed to interventions that did not lead to informative or published findings. Trial funding source was an important determinant of these outcomes, with both academic and industry sponsors contributing to inefficiencies. Copyright © 2016 by the American Academy of Pediatrics.

  1. Medication persistence and discontinuation of rivaroxaban and dabigatran etexilate among patients with non-valvular atrial fibrillation.

    PubMed

    Nelson, Winnie W; Song, Xue; Thomson, Erin; Smith, David M; Coleman, Craig I; Damaraju, C V; Schein, Jeffrey R

    2015-01-01

    To compare real-world persistence and discontinuation among non-valvular atrial fibrillation (NVAF) patients on rivaroxaban and dabigatran in the US. A large nationally representative US claims database was used to conduct a retrospective cohort analysis of patients with NVAF on rivaroxaban or dabigatran between October 2010 and March 2013. The index date was the date of the first prescription of rivaroxaban or dabigatran. All patients had ≥6 months of data prior to the index date and were followed until the earliest of inpatient death, end of continuous enrollment, or end of the study period. Rivaroxaban patients were matched 1:1 with dabigatran patients using the propensity score matching technique. Cox proportional hazards models were employed to estimate the adjusted hazard ratios (aHRs) of non-persistence and discontinuation. Persistence was defined as absence of a refill gap of ≥60 days. Discontinuation was defined as no additional refill for at least 90 days and until the end of follow-up. A total of 30,337 NVAF patients on rivaroxaban or dabigatran met the study criteria. All 7259 rivaroxaban patients were matched 1:1 to dabigatran patients. Compared with dabigatran users, rivaroxaban patients were 11% less likely to become non-persistent with therapy (aHR: 0.89, 95% CI 0.84-0.95) and 29% less likely to discontinue therapy (aHR: 0.71, 95% CI 0.66-0.77). Claims data are subject to miscoding and inaccuracies. Refill data may not fully reflect actual medication taken. Confounding may remain even after propensity score matching and additional adjustments in model. Longer follow-up may produce more precise estimates of persistence and discontinuation. This matched cohort analysis indicated that, compared to dabigatran, rivaroxaban was associated with better persistence and lower rates of discontinuation.

  2. Medication persistence and discontinuation of rivaroxaban versus warfarin among patients with non-valvular atrial fibrillation.

    PubMed

    Nelson, Winnie W; Song, Xue; Coleman, Craig I; Thomson, Erin; Smith, David M; Damaraju, C V; Schein, Jeffrey R

    2014-12-01

    To compare real-world persistence and discontinuation among non-valvular atrial fibrillation (NVAF) patients on rivaroxaban and warfarin in the US. A large nationally representative US claims database was used to conduct a retrospective cohort analysis of patients with NVAF treated with rivaroxaban or warfarin from 1 July 2010 through 31 March 2013. Index date was the date of the first prescription of rivaroxaban or warfarin. All patients were followed until the earliest of inpatient death, end of continuous enrollment, or end of study period. Rivaroxaban patients were matched 1:1 by propensity scores. Medication persistence was defined as absence of refill gap of ≥ 60 days. Discontinuation was defined as no additional refill for at least 90 days and until the end of follow-up. Cox proportional hazards models were estimated to examine the adjusted hazard ratios (aHRs) of rivaroxaban vs. warfarin on non-persistence and discontinuation. A total of 32,886 NVAF patients on rivaroxaban or warfarin met the study inclusion criteria. Each of the 7259 rivaroxaban patients identified were matched 1:1 to warfarin patients. Patients on rivaroxaban had a significantly better rate of persistence (aHR: 0.63, 95% CI 0.59-0.68) and lower rate of discontinuation (aHR: 0.54, 95% CI 0.49-0.58) compared to warfarin recipients. Claims data may have contained inaccuracies and miscoding. Confounding may remain even after propensity score matching and additional adjustments in model. Refill data may not fully reflect actual medication use. Longer follow-up may produce more precise estimates of persistence and discontinuation. This matched cohort analysis indicated that rivaroxaban was associated with significantly higher medication persistence and lower discontinuation rates compared to warfarin.

  3. Measuring persistence to hormonal therapy in patients with breast cancer: accounting for temporary treatment discontinuation.

    PubMed

    Huiart, Laetitia; Ferdynus, Cyril; Dell'Aniello, Sophie; Bakiri, Naciba; Giorgi, Roch; Suissa, Samy

    2014-08-01

    Several studies have been conducted to estimate persistence to hormonal therapy among women with breast cancer (BC). Most studies focus on first treatment discontinuation. Patients, however, can have numerous periods of treatment discontinuation or treatment exposure. Our objective is to estimate persistence to tamoxifen in patients with BC while accounting for temporary treatment discontinuations and this by using multi-state (MS) models. A cohort of 10,806 women with BC having received at least one prescription of tamoxifen between 1998 and 2008 was constituted from the UK General Practice Research Database. We fitted a semi-Markov model with three states to estimate the probability of being off treatment over a 5-year period while accounting for temporary treatment discontinuations (transition between on treatment and off treatment) and competing risks (recurrence of BC or death). Non-persistence, as estimated from the MS model, ranged from 12.1% (95% confidence interval [95%CI]: 9.2-15.1) at 1 year to 14.9% (95%CI: 11.7-18.1) at 5 years. Estimations of non-persistence based on the Kaplan-Meier model were higher, i.e., 29.3% (95%CI: 28.1-30.6) at 5 years, as well as those obtained from a competing risk model, i.e., 24.0% (95%CI: 22.9-25.1). Most temporary discontinuations (94.7%) lasted less than 6 months. Temporary treatment discontinuations are frequent and should be accounted for when measuring adherence to treatment. MS models can provide a useful framework for this sort of analysis insofar as they help describe patients' complex behavior. This may help tailor interventions that improve persistence to hormonal therapy among women with BC. Copyright © 2014 John Wiley & Sons, Ltd.

  4. Medication persistence and the use of generic and brand-name blood pressure-lowering agents.

    PubMed

    Corrao, Giovanni; Soranna, Davide; La Vecchia, Carlo; Catapano, Alberico; Agabiti-Rosei, Enrico; Gensini, Gianfranco; Merlino, Luca; Mancia, Giuseppe

    2014-05-01

    Because of their lower cost, healthcare systems recommend physicians to prefer generic products, rather than brand-name medicaments. There is then considerable interest and debate concerning safety and effectiveness of generic products. Few studies have compared patients treated with brand-name and generic drugs for adherence to treatment, with somewhat inconsistent results. The primary objective of this study was to compare the risk of discontinuing antihypertensive drug therapy in patients treated with generic or brand-name agents. The 101,618 beneficiaries of the Healthcare system of Lombardy, Italy, aged 18 years or older who were newly treated on monotherapy with antihypertensive generic or brand-name drugs during 2008, were followed until the earliest date among those of the occurrence of treatment discontinuation to whatever antihypertensive drug therapy (outcome), or censoring (death, emigration, 12 months after treatment initiation). Hazard ratios of discontinuation associated with starting on generic or brand-name products (intention-to-treat analysis), and incidence rate ratio of discontinuation during periods on generic and brand-name products (as-treated analysis) were respectively estimated from a cohort and self-controlled case series analyses. Patients who started on generics did not experience a different risk of discontinuation compared with those starting on brand-name agents (hazard ratio: 1.00; 95% confidence interval 0.98-1.02). Discontinuation did not occur with different rates during periods covered by generics or brand-name agents (incidence rate ratio: 1.01; 95% confidence interval 0.96-1.11) within the same individuals. A number of sensitivity and subgroup analyses confirmed the robustness of these findings. Generic products are not responsible for the high rate of discontinuation from antihypertensive drug therapy. Assuming therapeutic equivalence, clinical implication is of prescribing generic drug therapies.

  5. Tolerability of buprenorphine transdermal system in nursing home patients with advanced dementia: a randomized, placebo-controlled trial (DEP.PAIN.DEM).

    PubMed

    Erdal, Ane; Flo, Elisabeth; Aarsland, Dag; Selbaek, Geir; Ballard, Clive; Slettebo, Dagrun D; Husebo, Bettina S

    2018-01-01

    Buprenorphine transdermal system is increasingly prescribed in people with advanced dementia, but no clinical trial has investigated the safety and factors associated with discontinuation due to adverse events in this population. One hundred sixty-two people with advanced dementia and significant depression from 47 nursing homes were included and randomized to active analgesic treatment (acetaminophen/buprenorphine) or identical placebo for 13 weeks. In this secondary analysis, the main outcomes were time to and reasons for discontinuation of buprenorphine due to adverse events. Change in daytime activity as measured by actigraphy was a secondary outcome. Of the 44 patients who received active buprenorphine 5 µg/hour, 52.3% (n=23) discontinued treatment due to adverse events compared to 13.3% (6 of 45) in the placebo group ( p <0.001). Psychiatric and neurological adverse events were the most frequently reported causes of discontinuation (69.6%, n=16). Concomitant use of antidepressants significantly increased the risk of discontinuation (HR 23.2, 95% CI: 2.95-182, p =0.003). Adjusted for age, sex, cognitive function, pain and depression at baseline, active buprenorphine was associated with 24.0 times increased risk of discontinuation (Cox model, 95% CI: 2.45-235, p =0.006). Daytime activity dropped significantly during the second day of active treatment (-21.4%, p =0.005) and decreased by 12.9% during the first week ( p =0.053). Active buprenorphine had significantly higher risk of discontinuation compared with placebo in people with advanced dementia and depression, mainly due to psychiatric and neurological adverse events. Daytime activity dropped significantly during the first week of treatment. Concomitant use of antidepressants further reduced the tolerability of buprenorphine.

  6. Predictors for Permanent Discontinuation of Systemic Immunosuppression in Severely Affected Chronic Graft-Versus-Host Disease Patients.

    PubMed

    Curtis, Lauren M; Pirsl, Filip; Steinberg, Seth M; Mitchell, Sandra A; Baird, Kristin; Cowen, Edward W; Mays, Jacqueline; Buxbaum, Nataliya P; Pichard, Dominique C; Im, Annie; Avila, Daniele; Taylor, Tiffani; Fowler, Daniel H; Gress, Ronald E; Pavletic, Steven Z

    2017-11-01

    Predicting the duration of systemic therapy in patients with chronic graft-versus-host disease (cGVHD) is of critical clinical importance when counseling patients and for treatment planning. cGVHD characteristics associated with this outcome have not been studied in severely affected patients. The National Institutes of Health (NIH) cGVHD scoring provides a standardized set of organ severity measures that could represent clinically useful and reproducible predictive characteristics. We analyzed 227 previously treated patients most with moderate (n = 54) or severe (n = 170) cGVHD defined by NIH criteria who were prospectively enrolled in a natural history protocol (NCT00092235). Patients received a median of 4 prior systemic therapy regimens and were seen at the NIH for a single time-point visit and were then monitored for survival and ability to discontinue cGVHD systemic therapy. With a median follow-up of 71.1 months, the cumulative incidence of systemic therapy discontinuation was 9.5% (95% confidence interval, 6.0% to 13.9%) at 2 years and 27.7% (95% confidence interval, 20.9% to 34.8%) by 5 years after the initial visit. Factors associated with a higher incidence of immunosuppression discontinuation included lower NIH global severity (P = .019) and lung (P = .030) scores and less extensive deep sclerosis (<37% body surface area, P = .024). Lower patient- and clinician-reported 0 to 10 severity NIH scores and noncyclosporine prophylaxis regimens were also associated with higher incidence of immunosuppression discontinuation (P <.05). In conclusion, we found low success rates for immune suppression discontinuation in previously treated patients who were severely affected with cGVHD. NIH scoring and clinical measures provide new standardized disease-specific tools to predict discontinuation of systemic therapy. Published by Elsevier Inc.

  7. Alternative stable states and phase shifts in coral reefs under anthropogenic stress.

    PubMed

    Fung, Tak; Seymour, Robert M; Johnson, Craig R

    2011-04-01

    Ecosystems with alternative stable states (ASS) may shift discontinuously from one stable state to another as environmental parameters cross a threshold. Reversal can then be difficult due to hysteresis effects. This contrasts with continuous state changes in response to changing environmental parameters, which are less difficult to reverse. Worldwide degradation of coral reefs, involving "phase shifts" from coral to algal dominance, highlights the pressing need to determine the likelihood of discontinuous phase shifts in coral reefs, in contrast to continuous shifts with no ASS. However, there is little evidence either for or against the existence of ASS for coral reefs. We use dynamic models to investigate the likelihood of continuous and discontinuous phase shifts in coral reefs subject to sustained environmental perturbation by fishing, nutrification, and sedimentation. Our modeling results suggest that coral reefs with or without anthropogenic stress can exhibit ASS, such that discontinuous phase shifts can occur. We also find evidence to support the view that high macroalgal growth rates and low grazing rates on macroalgae favor ASS in coral reefs. Further, our results suggest that the three stressors studied, either alone or in combination, can increase the likelihood of both continuous and discontinuous phase shifts by altering the competitive balance between corals and algae. However, in contrast to continuous phase shifts, we find that discontinuous shifts occur only in model coral reefs with parameter values near the extremes of their empirically determined ranges. This suggests that continuous shifts are more likely than discontinuous shifts in coral reefs. Our results also suggest that, for ecosystems in general, tackling multiple human stressors simultaneously maximizes resilience to phase shifts, ASS, and hysteresis, leading to improvements in ecosystem health and functioning.

  8. Long-interval Cytapheresis as a Novel Therapeutic Strategy Leading to Dosage Reduction and Discontinuation of Steroids in Steroid-dependent Ulcerative Colitis

    PubMed Central

    Iizuka, Masahiro; Etou, Takeshi; Kumagai, Makoto; Matsuoka, Atsushi; Numata, Yuka; Sagara, Shiho

    2017-01-01

    Objective This study was performed to confirm the efficacy of long-interval cytapheresis on steroid-dependent ulcerative colitis (UC). Methods To discontinue steroids in patients with steroid-dependent UC, we previously designed a novel regimen of cytapheresis (CAP), which we termed “long-interval cytapheresis (LI-CAP)”, in which CAP was performed as one session every two or three weeks and continued during the whole period of tapering steroid dosage. In this study, we performed LI-CAP therapy 20 times (11 male and 9 female; mean age 41.8 years) between April 2010 and April 2015 for 14 patients with steroid-dependent UC. We evaluated the effectiveness of LI-CAP by examining the improvement in Lichtiger's clinical activity index (CAI), the rate of clinical remission, and the rate of steroid discontinuation. We further examined the rate of sustained steroid-free clinical remission at 6 and 12 months after LI-CAP in patients who successfully discontinued steroid-use after LI-CAP. The primary endpoint was the rate of discontinuation of steroids after LI-CAP. Results The mean CAI score before LI-CAP (7.550) significantly decreased to 1.65 after LI-CAP (p<0.0001). The rate of clinical remission after LI-CAP was 80%. The rate of steroid discontinuation after LI-CAP was 60.0%. The mean dose of daily prednisolone was significantly decreased after LI-CAP (2.30 mg) compared with that before therapy (17.30 mg) (p=0.0003). The rate of sustained steroid-free clinical remission after LI-CAP was 66.7% at 6 months and 66.7% at 12 months. Conclusion We confirmed that LI-CAP has therapeutic effects on reducing the dosage and discontinuing steroids in patients with steroid-dependent UC. PMID:28924114

  9. Long-interval Cytapheresis as a Novel Therapeutic Strategy Leading to Dosage Reduction and Discontinuation of Steroids in Steroid-dependent Ulcerative Colitis.

    PubMed

    Iizuka, Masahiro; Etou, Takeshi; Kumagai, Makoto; Matsuoka, Atsushi; Numata, Yuka; Sagara, Shiho

    2017-10-15

    Objective This study was performed to confirm the efficacy of long-interval cytapheresis on steroid-dependent ulcerative colitis (UC). Methods To discontinue steroids in patients with steroid-dependent UC, we previously designed a novel regimen of cytapheresis (CAP), which we termed "long-interval cytapheresis (LI-CAP)", in which CAP was performed as one session every two or three weeks and continued during the whole period of tapering steroid dosage. In this study, we performed LI-CAP therapy 20 times (11 male and 9 female; mean age 41.8 years) between April 2010 and April 2015 for 14 patients with steroid-dependent UC. We evaluated the effectiveness of LI-CAP by examining the improvement in Lichtiger's clinical activity index (CAI), the rate of clinical remission, and the rate of steroid discontinuation. We further examined the rate of sustained steroid-free clinical remission at 6 and 12 months after LI-CAP in patients who successfully discontinued steroid-use after LI-CAP. The primary endpoint was the rate of discontinuation of steroids after LI-CAP. Results The mean CAI score before LI-CAP (7.550) significantly decreased to 1.65 after LI-CAP (p<0.0001). The rate of clinical remission after LI-CAP was 80%. The rate of steroid discontinuation after LI-CAP was 60.0%. The mean dose of daily prednisolone was significantly decreased after LI-CAP (2.30 mg) compared with that before therapy (17.30 mg) (p=0.0003). The rate of sustained steroid-free clinical remission after LI-CAP was 66.7% at 6 months and 66.7% at 12 months. Conclusion We confirmed that LI-CAP has therapeutic effects on reducing the dosage and discontinuing steroids in patients with steroid-dependent UC.

  10. Healthcare resource use and costs of privately insured patients who switch, discontinue, or persist on anti-muscarinic therapy for overactive bladder.

    PubMed

    Ivanova, Jasmina I; Hayes-Larson, Eleanor; Sorg, Rachael A; Birnbaum, Howard G; Berner, Todd

    2014-10-01

    To compare the healthcare costs of patients with overactive bladder (OAB) who switch vs persist on anti-muscarinic agents (AMs), describe resource use and costs among OAB patients who discontinue AMs, and assess factors associated with persisting vs switching or discontinuing. OAB patients initiating an AM between January 1, 2007 and March 31, 2012 were identified from a claims database of US privately insured beneficiaries (n ≈ 16 million) and required to have no AM claims in the 12 months before AM initiation (baseline period). Patients were classified as persisters, switchers, or discontinuers, and assigned a study index date based on their AM use in the 6 months following initiation. Baseline characteristics, resource use, and costs were compared between persisters and the other groups. Resource use and costs in the 1 month before and 6 months after the study index date (for switchers, the date of index AM switching; for persisters, a randomly assigned date to reflect the distribution of the time from AM initiation to switching among switchers) were also compared between persisters and switchers in unadjusted and adjusted analyses. Factors associated with persisting vs switching or discontinuing were assessed. After controlling for baseline characteristics and costs, persisters vs switchers had significantly lower all-cause and OAB-related costs in both the month before (all-cause $1222 vs $1759, OAB-related $142 vs $170) and 6 months after the study index date (all-cause $7017 vs $8806, OAB-related $642 vs $797). Factors associated with switching or discontinuing vs persisting included index AM, younger age, and history of UTI. A large proportion of OAB patients discontinue or switch AMs shortly after initiation, and switching is associated with higher costs.

  11. Algorithms to Identify Statin Intolerance in Medicare Administrative Claim Data.

    PubMed

    Colantonio, Lisandro D; Kent, Shia T; Huang, Lei; Chen, Ligong; Monda, Keri L; Serban, Maria-Corina; Manthripragada, Angelika; Kilgore, Meredith L; Rosenson, Robert S; Muntner, Paul

    2016-10-01

    To compare characteristics of patients with possible statin intolerance identified using different claims-based algorithms versus patients with high adherence to statins. We analyzed 134,863 Medicare beneficiaries initiating statins between 2007 and 2011. Statin intolerance and discontinuation, and high adherence to statins, defined by proportion of days covered ≥80 %, were assessed during the 365 days following statin initiation. Definition 1 of statin intolerance included statin down-titration or discontinuation with ezetimibe initiation, having a claim for a rhabdomyolysis or antihyperlipidemic event followed by statin down-titration or discontinuation, or switching between ≥3 types of statins. Definition 2 included beneficiaries who met Definition 1 and those who down-titrated statin intensity. We also analyzed beneficiaries who met Definition 2 of statin intolerance or discontinued statins. The prevalence of statin intolerance was 1.0 % (n = 1320) and 5.2 % (n = 6985) using Definitions 1 and 2, respectively. Overall, 45,266 (33.6 %) beneficiaries had statin intolerance by Definition 2 or discontinued statins and 55,990 (41.5 %) beneficiaries had high adherence to statins. Compared with beneficiaries with high adherence to statins, those with statin intolerance and who had statin intolerance or discontinued statins were more likely to be female versus male, and black, Hispanic or Asian versus white. The multivariable adjusted odds ratio for statin intolerance by Definitions 1 and 2 comparing patients initiating high versus low/moderate intensity statins were 2.82 (95%CI: 2.42-3.29), and 8.58 (8.07-9.12), respectively, and for statin intolerance or statin discontinuation was 2.35 (2.25-2.45). Definitions of statin intolerance presented herein can be applied to analyses using administrative claims data.

  12. Persistence to disease-modifying therapies for multiple sclerosis in a Canadian cohort

    PubMed Central

    Melesse, Dessalegn Y; Marrie, Ruth Ann; Blanchard, James F; Yu, Bo Nancy; Evans, Charity

    2017-01-01

    Purpose To examine the long-term persistence to the first-line injectable disease-modifying therapies (DMTs) for multiple sclerosis (MS) and to identify the factors associated with nonpersistence. Patients and methods We used population-based administrative data from Manitoba, Canada. All adult subjects who were diagnosed with MS and dispensed a first-line injectable DMT (beta-interferon-1b, beta-interferon-1a, and glatiramer acetate) between 1996 and 2011 and had a minimum of 1 year of follow-up were included. The primary outcome was the median time to discontinuation of any DMT. The associations between potential predictors and persistence were estimated using multivariable Cox-proportional hazard models. Results Overall, 721 subjects were followed for a median of 7.8 years (interquartile range 6.1). The median time to discontinuation of all first-line DMTs was 4.2 years (25th and 75th percentile: 1.7, 10.6 years). Of the 451 (62.6%) subjects who discontinued their DMT during the study period, 259 (57.4%) eventually resumed or restarted a DMT. Subjects who were younger when starting a DMT, had prior MS-related hospitalizations, were more recently diagnosed with MS, or had a greater lag time between their MS diagnosis and DMT initiation were more likely to discontinue therapy. Conclusion Over half of the individuals receiving a DMT for MS in Manitoba remained on therapy for at least 4 years. DMT discontinuation occurred in 60% of the cohort, but most restarted a DMT within 1 year. While not all of the factors identified with discontinuing DMT are modifiable, they may help practitioners enhance MS care by identifying individuals who may be at particular risk for DMT discontinuation. PMID:28721023

  13. Determinants for drug survival of methotrexate in patients with psoriasis, split according to different reasons for discontinuation: results of the prospective MTX-CAPTURE.

    PubMed

    Otero, M E; van den Reek, J M; Seyger, M M; van de Kerkhof, P C; Kievit, W; de Jong, E M

    2017-08-01

    As methotrexate (MTX) is a widely used treatment for psoriasis, it is important to gain insight into the reasons for the discontinuation of MTX and to understand the determinants for drug survival. To describe 5-year drug survival for MTX in patients with psoriasis, split according to different reasons for discontinuation, and to identify the determinants for drug survival. Data were extracted from a prospective psoriasis registry of patients treated with MTX (MTX-CAPTURE). Drug survival was analysed using Kaplan-Meier estimates and the determinants for discontinuation were analysed using Cox regression analysis. Analyses were split according to the reason for discontinuation: side-effects or ineffectiveness. We included 85 patients treated with MTX, with a maximum treatment duration of 5·2 years. The overall drug survival rates were 63%, 30% and 15% after 1, 3 and 5 years, respectively. The median survival was 1·8 years. Overall, 55 patients (65%) discontinued MTX for the following reasons: side-effects (35%), ineffectiveness (26%), combination of side-effects and ineffectiveness (13%), other reasons (16%) and 11% were lost to follow-up. The most reported side-effects were gastrointestinal symptoms, despite the use of folic acid in 99% of patients. Based on univariate analysis, a high Psoriasis Area and Severity Index score and a high score on the visual analogue scale for disease severity at baseline were possible determinants for a short drug survival. Drug survival of MTX was low with 15% of patients 'on drug' after 5 years. Side-effects alone or in combination with inadequate disease control were more important in the context of treatment discontinuation than inadequate disease control alone. © 2017 British Association of Dermatologists.

  14. Clinical outcomes associated with per-operative discontinuation of aspirin in patients with coronary artery disease: A systematic review and meta-analysis.

    PubMed

    Luni, Faraz Khan; Riaz, Haris; Khan, Abdur Rahman; Riaz, Talha; Husnain, Muhammad; Riaz, Irbaz Bin; Khan, Muhammad Shahzeb; Taleb, Mohammed; Kanjwal, Yusuf; Cooper, Christopher J; Khuder, Sadik A

    2017-06-01

    Postoperative state is characterized by increased thrombotic risk by virtue of platelet activation. Whether aspirin ameliorates this risk in patients with established coronary artery disease undergoing cardiac or noncardiac surgery is unknown. We conducted a systematic review and meta-analysis to compare the risk of major adverse cardiac events (MACE) and the risk of bleeding in patients with early (3-5 or more days before surgery) vs. late discontinuation(<3-5 days)/no discontinuation of aspirin. Multiple databases were searched from inception of these databases until March 2015 to identify studies that reported discontinuation of aspirin in patients undergoing surgery. The outcomes measured were all cause mortality, nonfatal myocardial infarction and other relevant thrombotic events (MACE) which also may include, fatal and nonfatal MI, stent thrombosis and restenosis, stroke, perioperative cardiovascular complications (heart failure, MI, VTE, acute stroke) and perioperative bleeding during the perioperative period to up to 30 days after surgery. A total of 1,018 titles were screened, after which six observational studies met the inclusion criteria. Our analysis suggests that there is no difference in MACE with planned discontinuation of aspirin (OR = 1.17, 95% CI = 0.76-1.81; P = 0.05; I 2  = 55%). Early discontinuation of aspirin showed a decreased risk of peri-operative bleeding (OR 0.82, 95% CI = 0.67-0.99; P = 0.04; I 2  = 42%). Our analysis suggests that planned short-term discontinuation in the appropriate clinical setting appears to be safe in the correct clinical setting with no increased risk of thrombotic events and with a decreased risk of bleeding. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Mass Conservation of the Unified Continuous and Discontinuous Element-Based Galerkin Methods on Dynamically Adaptive Grids with Application to Atmospheric Simulations

    DTIC Science & Technology

    2015-09-01

    Discontinuous Element-Based Galerkin Methods on Dynamically Adaptive Grids with Application to Atmospheric Simulations 5a. CONTRACT NUMBER 5b. GRANT NUMBER...Discontinuous Element-Based Galerkin Methods on Dynamically Adaptive Grids with Application to Atmospheric Simulations. Michal A. Koperaa,∗, Francis X...mass conservation, as it is an important feature for many atmospheric applications . We believe this is a good metric because, for smooth solutions

  16. The Application of Deterministic Spectral Domain Method to the Analysis of Planar Circuit Discontinuities on Open Substrates

    DTIC Science & Technology

    1990-08-01

    the spectral domain is extended to include the effects of two-dimensional, two-component current flow in planar transmission line discontinuities 6n...PROFESSOR: Tatsuo Itoh A deterministic formulation of the method of moments carried out in the spectral domain is extended to include the effects of...two-dimensional, two- component current flow in planar transmission line discontinuities on open substrates. The method includes the effects of space

  17. Improved method for detecting local discontinuities in CMB data by finite differencing

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bowyer, Jude; Jaffe, Andrew H.

    2011-01-15

    An unexpected distribution of temperatures in the CMB could be a sign of new physics. In particular, the existence of cosmic defects could be indicated by temperature discontinuities via the Kaiser-Stebbins effect. In this paper, we show how performing finite differences on a CMB map, with the noise regularized in harmonic space, may expose such discontinuities, and we report the results of this process on the 7-year Wilkinson Microwave Anisotropy Probe data.

  18. The Influence of Antithyroid Drug Discontinuation to the Therapeutic Efficacy of (131)I in Hyperthyroidism.

    PubMed

    Kartamihardja, A Hussein Sundawa; Massora, Stepanus

    2016-01-01

    The influence of antithyroid drugs (ATDs) on the therapeutic efficacy of radioactive iodine in hyperthyroidism is still controversial. The aim of this study was to evaluate the effect of ATD discontinuation to the therapeutic efficacy of I-131 in hyperthyroidism patients with long-term ATD treatment. Retrospective study was done to 39 subjects with hyperthyroidism who had been treated with doses of 300 MBq radioactive iodine. The subjects were divided into three groups: Group I (n = 14) had been using ATDs for more than one year and discontinued more than three days; group II (n = 14) had been using ATDs for more than one year but discontinued only for three days or less, and group III (n = 11) has never been used any ATD before radioactive iodine treatment. There was a significant difference in the therapeutic efficacy after three months of radioactive iodine treatment between group I and group II (P = 0.018), group II and group III (P = 0.017), but not between group I and group III (P = 1.0). There was no observed difference on the therapeutic efficacy between the three groups at 6 months after radioactive iodine therapy (P = 0.143). Administration of ATDs more than 1 year without discontinuation decreased response of radioactive iodine treatment in 3 months follow-up. Discontinuation of ATDs for more than 3 days before radioactive iodine treatment is recommended.

  19. The Influence of Antithyroid Drug Discontinuation to the Therapeutic Efficacy of 131I in Hyperthyroidism

    PubMed Central

    Kartamihardja, A. Hussein Sundawa; Massora, Stepanus

    2016-01-01

    The influence of antithyroid drugs (ATDs) on the therapeutic efficacy of radioactive iodine in hyperthyroidism is still controversial. The aim of this study was to evaluate the effect of ATD discontinuation to the therapeutic efficacy of I-131 in hyperthyroidism patients with long-term ATD treatment. Retrospective study was done to 39 subjects with hyperthyroidism who had been treated with doses of 300 MBq radioactive iodine. The subjects were divided into three groups: Group I (n = 14) had been using ATDs for more than one year and discontinued more than three days; group II (n = 14) had been using ATDs for more than one year but discontinued only for three days or less, and group III (n = 11) has never been used any ATD before radioactive iodine treatment. There was a significant difference in the therapeutic efficacy after three months of radioactive iodine treatment between group I and group II (P = 0.018), group II and group III (P = 0.017), but not between group I and group III (P = 1.0). There was no observed difference on the therapeutic efficacy between the three groups at 6 months after radioactive iodine therapy (P = 0.143). Administration of ATDs more than 1 year without discontinuation decreased response of radioactive iodine treatment in 3 months follow-up. Discontinuation of ATDs for more than 3 days before radioactive iodine treatment is recommended. PMID:27134556

  20. The Impact of Continuity Editing in Narrative Film on Event Segmentation

    PubMed Central

    Magliano, Joseph P.; Zacks, Jeffrey M.

    2011-01-01

    Filmmakers use continuity editing to engender a sense of situational continuity or discontinuity at editing boundaries. The goal of this study was to assess the impact of continuity editing on how people perceive the structure of events in a narrative film and to identify brain networks that are associated with the processing of different types of continuity editing boundaries. Participants viewed a commercially produced film and segmented it into meaningful events while brain activity was recorded with functional MRI. We identified three degrees of continuity that can occur at editing locations: edits that are continuous in space, time, and action; edits that are discontinuous in space or time but continuous in action; and edits that are discontinuous in action as well as space or time. Discontinuities in action had the biggest impact on behavioral event segmentation and discontinuities in space and time had minor effects. Edits were associated with large transient increases in early visual areas. Spatial-temporal changes and action changes produced strikingly different patterns of transient change, and provided evidence that specialized mechanisms in higher-order perceptual processing regions are engaged to maintain continuity of action in the face of spatiotemporal discontinuities. These results suggest that commercial film editing is shaped to support the comprehension of meaningful events that bridge breaks in low-level visual continuity, and even breaks in continuity of spatial and temporal location. PMID:21972849

  1. Consciousness across Sleep and Wake: Discontinuity and Continuity of Memory Experiences As a Reflection of Consolidation Processes

    PubMed Central

    Horton, Caroline L.

    2017-01-01

    The continuity hypothesis (1) posits that there is continuity, of some form, between waking and dreaming mentation. A recent body of work has provided convincing evidence for different aspects of continuity, for instance that some salient experiences from waking life seem to feature in dreams over others, with a particular role for emotional arousal as accompanying these experiences, both during waking and while asleep. However, discontinuities have been somewhat dismissed as being either a product of activation-synthesis, an error within the consciousness binding process during sleep, a methodological anomaly, or simply as yet unexplained. This paper presents an overview of discontinuity within dreaming and waking cognition, arguing that disruptions of consciousness are as common a feature of waking cognition as of dreaming cognition, and that processes of sleep-dependent memory consolidation of autobiographical experiences can in part account for some of the discontinuities of sleeping cognition in a functional way. By drawing upon evidence of the incorporation, fragmentation, and reorganization of memories within dreams, this paper proposes a model of discontinuity whereby the fragmentation of autobiographical and episodic memories during sleep, as part of the consolidation process, render salient aspects of those memories subsequently available for retrieval in isolation from their contextual features. As such discontinuity of consciousness in sleep is functional and normal. PMID:28936183

  2. The effect of fluoridation and its discontinuation on fluoride profiles in the alveolar bone of rat.

    PubMed

    Ohmi, Kyohei; Nakagaki, Haruo; Tsuboi, Shinji; Okumura, Akihiro; Sugiyama, Tomoko; Thuy, Tran Thu; Robinson, Colin

    2005-10-01

    We investigated the effect of fluoridation and its discontinuation on fluoride content in the alveolar portion of the mandible in rats. Drinking water with three different fluoride contents (0, 50, 100 ppmF) was given to rats for three different periods (4, 13 and 25 weeks). Fluoride concentrations were measured in the crest, the middle, and the apical parts of the alveolar bone and in the body of the mandible. Furthermore, after fluoridated drinking water was given to rats for 4 or 13 weeks, distilled water was given to them for 21 or 12 weeks respectively; and the effect of the discontinuation on fluoride profiles was investigated. Layer samples were analyzed by abrasive microsampling. Fluoride and phosphorus concentrations were determined by ion-specific electrode and colorimetric procedures, respectively. There was an increase in fluoride concentrations in the mandible in proportion to the fluoride content in the drinking water and the duration of fluoridation. After fluoridation was discontinued, fluoride concentrations in the surface layers of the mandible presented a decrease. Among the four different parts of the mandible, the upper part of the alveolar bone and the alveolar crest part presented the highest rates of reduction. The relative reduction rate of fluoride concentration was closely related to the duration of discontinuation. The alveolar crest was affected most by the discontinuation of fluoridation, presenting the greatest reduction.

  3. Change in the discontinuation pattern of tumour necrosis factor antagonists in rheumatoid arthritis over 10 years: data from the Spanish registry BIOBADASER 2.0.

    PubMed

    Gómez-Reino, Juan J; Rodríguez-Lozano, Carlos; Campos-Fernández, Cristina; Montoro, María; Descalzo, Miguel Ángel; Carmona, Loreto

    2012-03-01

    To investigate in rheumatoid arthritis (RA) the rate and reason of discontinuation of tumour necrosis factor (TNF) antagonists over the past decade. RA patients in BIOBADASER 2.0 were stratified according to the start date of their first TNF antagonist into 2000-3, 2004-6 and 2007-9 interval years. Cumulative incidence function of discontinuation for inefficacy or toxicity was estimated with the alternative reason as competing risk. Competing risks regression models were used to measure the association of study groups with covariates and reasons for discontinuation. Association is expressed as subhazard ratios (SHR). 2907 RA patients were included in the study. Competing risk regression for inefficacy shows larger SHR for patients starting treatment in 2004-6 (SHR 2.57; 95% CI 1.55 to 4.25) and 2007-9 (SHR 3.4; 95% CI 2.08 to 5.55) than for those starting in 2000-3, after adjusting for TNF antagonists, clinical activity and concomitant treatment. Competing risk regression analysis for adverse events revealed no differences across the three time intervals. In RA, the discontinuation rate of TNF antagonists in the first year of treatment is higher more recently than a decade ago, inefficacy being the main reason for the increased rate. The rate of discontinuation for adverse events has remained stable.

  4. Discontinuous and continuous hardening processes in calcium and calcium—tin micro-alloyed lead: influence of 'secondary-lead' impurities

    NASA Astrophysics Data System (ADS)

    Bouirden, L.; Hilger, J. P.; Hertz, J.

    Different transformations in leadcalcium and leadcaciumtin alloys are observed with various complementary techniques such as anisothermal microcalorimetry, optical and electronic microscopy, hardness measurements. Three alloy states are studied: as-cast, rehomogenised/water-quenched, rehomogenised/air-cooled. With binary leadcalcium alloys, three successive discontinuous transformations are observed, namely: an initial and complete discontinuous transformation with regular moving of the front of reaction; a second and incomplete discontinuous transformation (puzzle-shaped); a third and incomplete discontinuous transformation with precipitation of Pb 3Ca. The role of secondary-lead impurities is complex: Ag reduces and Bi accelerates the rate of the discontinuous reaction, while Al refines the grain size. Leadcalciumtin are characterized by the Sn/Ca ratio. For very small values of this ratio, the hardening is similar to that of leadcalcium alloys. For high ratio values, the hardening takes place after an incubation period and proceeds via a continuous micro-precipitation of the (PbSn) 3Ca Compound. For intermediate ratios, the different processes are able to operate separately in sequence. Ag increases the rate of the continuous precipitation and reduces the incubation time. No significant effects are observed with Bi or Al. The kinetic laws of the different transformations are presented and values for the energy of activation are determined.

  5. Effective homogeneity of the exchange-correlation and non-interacting kinetic energy functionals under density scaling.

    PubMed

    Borgoo, Alex; Teale, Andrew M; Tozer, David J

    2012-01-21

    Correlated electron densities, experimental ionisation potentials, and experimental electron affinities are used to investigate the homogeneity of the exchange-correlation and non-interacting kinetic energy functionals of Kohn-Sham density functional theory under density scaling. Results are presented for atoms and small molecules, paying attention to the influence of the integer discontinuity and the choice of the electron affinity. For the exchange-correlation functional, effective homogeneities are highly system-dependent on either side of the integer discontinuity. By contrast, the average homogeneity-associated with the potential that averages over the discontinuity-is generally close to 4/3 when the discontinuity is computed using positive affinities for systems that do bind an excess electron and negative affinities for those that do not. The proximity to 4/3 becomes increasingly pronounced with increasing atomic number. Evaluating the discontinuity using a zero affinity in systems that do not bind an excess electron instead leads to effective homogeneities on the electron abundant side that are close to 4/3. For the non-interacting kinetic energy functional, the effective homogeneities are less system-dependent and the effect of the integer discontinuity is less pronounced. Average values are uniformly below 5/3. The study provides information that may aid the development of improved exchange-correlation and non-interacting kinetic energy functionals. © 2012 American Institute of Physics

  6. Discontinuity of the exchange-correlation potential and the functional derivative of the noninteracting kinetic energy as the number of electrons crosses integer boundaries in Li, Be, and B.

    PubMed

    Morrison, Robert C

    2015-01-07

    Accurate densities were determined from configuration interaction wave functions for atoms and ions of Li, Be, and B with up to four electrons. Exchange-correlation potentials, Vxc(r), and functional derivatives of the noninteracting kinetic energy, δK[ρ]/δρ(r), obtained from these densities were used to examine their discontinuities as the number of electrons N increases across integer boundaries for N = 1, N = 2, and N = 3. These numerical results are consistent with conclusions that the discontinuities are characterized by a jump in the chemical potential while the shape of Vxc(r) varies continuously as an integer boundary is crossed. The discontinuity of the Vxc(r) is positive, depends on the ionization potential, electron affinity, and orbital energy differences, and the discontinuity in δK[ρ]/δρ(r) depends on the difference between the energies of the highest occupied and lowest unoccupied orbitals. The noninteracting kinetic energy and the exchange correlation energy have been computed for integer and noninteger values of N between 1 and 4.

  7. The excitation of long period seismic waves by a source spanning a structural discontinuity

    NASA Astrophysics Data System (ADS)

    Woodhouse, J. H.

    Simple theoretical results are obtained for the excitation of seismic waves by an indigenous seismic source in the case that the source volume is intersected by a structural discontinuity. In the long wavelength approximation the seismic radiation is identical to that of a point source placed on one side of the discontinuity or of a different point source placed on the other side. The moment tensors of these two equivalent sources are related by a specific linear transformation and may differ appreciably both in magnitude and geometry. Either of these sources could be obtained by linear inversion of seismic data but the physical interpretation is more complicated than in the usual case. A source which involved no volume change would, for example, yield an isotropic component if, during inversion, it were assumed to lie on the wrong side of the discontinuity. The problem of determining the true moment tensor of the source is indeterminate unless further assumptions are made about the stress glut distribution; one way to resolve this indeterminancy is to assume proportionality between the integrated stress glut on each side of the discontinuity.

  8. Reciprocity principle for scattered fields from discontinuities in waveguides.

    PubMed

    Pau, Annamaria; Capecchi, Danilo; Vestroni, Fabrizio

    2015-01-01

    This study investigates the scattering of guided waves from a discontinuity exploiting the principle of reciprocity in elastodynamics, written in a form that applies to waveguides. The coefficients of reflection and transmission for an arbitrary mode can be derived as long as the principle of reciprocity is satisfied at the discontinuity. Two elastodynamic states are related by the reciprocity. One is the response of the waveguide in the presence of the discontinuity, with the scattered fields expressed as a superposition of wave modes. The other state is the response of the waveguide in the absence of the discontinuity oscillating according to an arbitrary mode. The semi-analytical finite element method is applied to derive the needed dispersion relation and wave mode shapes. An application to a solid cylinder with a symmetric double change of cross-section is presented. This model is assumed to be representative of a damaged rod. The coefficients of reflection and transmission of longitudinal waves are investigated for selected values of notch length and varying depth. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Applicability of radon emanometry in lithologically discontinuous sites contaminated by organic chemicals.

    PubMed

    De Miguel, Eduardo; Barrio-Parra, Fernando; Elío, Javier; Izquierdo-Díaz, Miguel; García-González, Jerónimo Emilio; Mazadiego, Luis Felipe; Medina, Rafael

    2018-06-02

    The applicability of radon ( 222 Rn) measurements to delineate non-aqueous phase liquids (NAPL) contamination in subsoil is discussed at a site with lithological discontinuities through a blind test. Three alpha spectroscopy monitors were used to measure radon in soil air in a 25,000-m 2 area, following a regular sampling design with a 20-m 2 grid. Repeatability and reproducibility of the results were assessed by means of duplicate measurements in six sampling positions. Furthermore, three points not affected by oil spills were sampled to estimate radon background concentration in soil air. Data histograms, Q-Q plots, variograms, and cluster analysis allowed to recognize two data populations, associated with the possible path of a fault and a lithological discontinuity. Even though the concentration of radon in soil air was dominated by this discontinuity, the characterization of the background emanation in each lithological unit allowed to distinguish areas potentially affected by NAPL, thus justifying the application of radon emanometry as a screening technique for the delineation of NAPL plumes in sites with lithological discontinuities.

  10. A full vectorial generalized discontinuous Galerkin beam propagation method (GDG-BPM) for nonsmooth electromagnetic fields in waveguides

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fan Kai; Cai Wei; Ji Xia

    2008-07-20

    In this paper, we propose a new full vectorial generalized discontinuous Galerkin beam propagation method (GDG-BPM) to accurately handle the discontinuities in electromagnetic fields associated with wave propagations in inhomogeneous optical waveguides. The numerical method is a combination of the traditional beam propagation method (BPM) with a newly developed generalized discontinuous Galerkin (GDG) method [K. Fan, W. Cai, X. Ji, A generalized discontinuous Galerkin method (GDG) for Schroedinger equations with nonsmooth solutions, J. Comput. Phys. 227 (2008) 2387-2410]. The GDG method is based on a reformulation, using distributional variables to account for solution jumps across material interfaces, of Schroedinger equationsmore » resulting from paraxial approximations of vector Helmholtz equations. Four versions of the GDG-BPM are obtained for either the electric or magnetic field components. Modeling of wave propagations in various optical fibers using the full vectorial GDG-BPM is included. Numerical results validate the high order accuracy and the flexibility of the method for various types of interface jump conditions.« less

  11. The elusive character of discontinuous deep-water channels: New insights from Lucia Chica channel system, offshore California

    USGS Publications Warehouse

    Maier, K.L.; Fildani, A.; Paull, C.K.; Graham, S.A.; McHargue, T.R.; Caress, D.W.; McGann, M.

    2011-01-01

    New high-resolution autonomous underwater vehicle (AUV) seafloor images, with 1 m lateral resolution and 0.3 m vertical resolution, reveal unexpected seafloor rugosity and low-relief (<10 m), discontinuous conduits over ~70 km2. Continuous channel thalwegs were interpreted originally from lower-resolution images, but newly acquired AUV data indicate that a single sinuous channel fed a series of discontinuous lower-relief channels. These discontinuous channels were created by at least four avulsion events. Channel relief, defined as the height from the thalweg to the levee crest, controls avulsions and overall stratigraphic architecture of the depositional area. Flowstripped turbidity currents separated into and reactivated multiple channels to create a distributary pattern and developed discontinuous trains of cyclic scours and megaflutes, which may be erosional precursors to continuous channels. The diverse features now imaged in the Lucia Chica channel system (offshore California) are likely common in modern and ancient systems with similar overall morphologies, but have not been previously mapped with lower-resolution detection methods in any of these systems. ?? 2011 Geological Society of America.

  12. Discontinuous functional for linear-response time-dependent density-functional theory: The exact-exchange kernel and approximate forms

    NASA Astrophysics Data System (ADS)

    Hellgren, Maria; Gross, E. K. U.

    2013-11-01

    We present a detailed study of the exact-exchange (EXX) kernel of time-dependent density-functional theory with an emphasis on its discontinuity at integer particle numbers. It was recently found that this exact property leads to sharp peaks and step features in the kernel that diverge in the dissociation limit of diatomic systems [Hellgren and Gross, Phys. Rev. APLRAAN1050-294710.1103/PhysRevA.85.022514 85, 022514 (2012)]. To further analyze the discontinuity of the kernel, we here make use of two different approximations to the EXX kernel: the Petersilka Gossmann Gross (PGG) approximation and a common energy denominator approximation (CEDA). It is demonstrated that whereas the PGG approximation neglects the discontinuity, the CEDA includes it explicitly. By studying model molecular systems it is shown that the so-called field-counteracting effect in the density-functional description of molecular chains can be viewed in terms of the discontinuity of the static kernel. The role of the frequency dependence is also investigated, highlighting its importance for long-range charge-transfer excitations as well as inner-shell excitations.

  13. Charge renormalization and inversion of a highly charged lipid bilayer: effects of dielectric discontinuities and charge correlations.

    PubMed

    Taheri-Araghi, Sattar; Ha, Bae-Yeun

    2005-08-01

    We reexamine the problem of charge renormalization and inversion of a highly charged surface of a low dielectric constant immersed in ionic solutions. To be specific, we consider an asymmetrically charged lipid bilayer, in which only one layer is negatively charged. In particular, we study how dielectric discontinuities and charge correlations (among lipid charges and condensed counterions) influence the effective charge of the surface. When counterions are monovalent (e.g., Na+), our mean-field approach implies that dielectric discontinuities can enhance counterion condensation. A simple scaling picture shows how the effects of dielectric discontinuities and surface-charge distributions are intertwined: Dielectric discontinuities diminish condensation if the backbone charge is uniformly smeared out while counterions are localized in space; they can, however, enhance condensation when the backbone charge is discrete. In the presence of asymmetric salts such as CaCl2 , we find that the correlation effect, treated at the Gaussian level, is more pronounced when the surface has a lower dielectric constant, inverting the sign of the charge at a smaller value of Ca2+ concentration.

  14. A test of the cross-scale resilience model: Functional richness in Mediterranean-climate ecosystems

    USGS Publications Warehouse

    Wardwell, D.A.; Allen, Craig R.; Peterson, G.D.; Tyre, A.J.

    2008-01-01

    Ecological resilience has been proposed to be generated, in part, in the discontinuous structure of complex systems. Environmental discontinuities are reflected in discontinuous, aggregated animal body mass distributions. Diversity of functional groups within body mass aggregations (scales) and redundancy of functional groups across body mass aggregations (scales) has been proposed to increase resilience. We evaluate that proposition by analyzing mammalian and avian communities of Mediterranean-climate ecosystems. We first determined that body mass distributions for each animal community were discontinuous. We then calculated the variance in richness of function across aggregations in each community, and compared observed values with distributions created by 1000 simulations using a null of random distribution of function, with the same n, number of discontinuities and number of functional groups as the observed data. Variance in the richness of functional groups across scales was significantly lower in real communities than in simulations in eight of nine sites. The distribution of function across body mass aggregations in the animal communities we analyzed was non-random, and supports the contentions of the cross-scale resilience model. ?? 2007 Elsevier B.V. All rights reserved.

  15. Discontinuous Observers Design for Finite-Time Consensus of Multiagent Systems With External Disturbances.

    PubMed

    Liu, Xiaoyang; Ho, Daniel W C; Cao, Jinde; Xu, Wenying

    This brief investigates the problem of finite-time robust consensus (FTRC) for second-order nonlinear multiagent systems with external disturbances. Based on the global finite-time stability theory of discontinuous homogeneous systems, a novel finite-time convergent discontinuous disturbed observer (DDO) is proposed for the leader-following multiagent systems. The states of the designed DDO are then used to design the control inputs to achieve the FTRC of nonlinear multiagent systems in the presence of bounded disturbances. The simulation results are provided to validate the effectiveness of these theoretical results.This brief investigates the problem of finite-time robust consensus (FTRC) for second-order nonlinear multiagent systems with external disturbances. Based on the global finite-time stability theory of discontinuous homogeneous systems, a novel finite-time convergent discontinuous disturbed observer (DDO) is proposed for the leader-following multiagent systems. The states of the designed DDO are then used to design the control inputs to achieve the FTRC of nonlinear multiagent systems in the presence of bounded disturbances. The simulation results are provided to validate the effectiveness of these theoretical results.

  16. 21 CFR 1309.62 - Termination of registration.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... terminate if and when such person dies, ceases legal existence, or discontinues business or professional practice. Any registrant who cases legal existence or discontinues business or professional practice shall...

  17. Continuous and discontinuous transitions to synchronization.

    PubMed

    Wang, Chaoqing; Garnier, Nicolas B

    2016-11-01

    We describe how the transition to synchronization in a system of globally coupled Stuart-Landau oscillators changes from continuous to discontinuous when the nature of the coupling is moved from diffusive to reactive. We explain this drastic qualitative change as resulting from the co-existence of a particular synchronized macrostate together with the trivial incoherent macrostate, in a range of parameter values for which the latter is linearly stable. In contrast to the paradigmatic Kuramoto model, this particular state observed at the synchronization transition contains a finite, non-vanishing number of synchronized oscillators, which results in a discontinuous transition. We consider successively two situations where either a fully synchronized state or a partially synchronized state exists at the transition. Thermodynamic limit and finite size effects are briefly discussed, as well as connections with recently observed discontinuous transitions.

  18. Effects of discontinuous drooped wing leading-edge modifications on the spinning characteristics of a low-wing general aviation airplane

    NASA Technical Reports Server (NTRS)

    Dicarlo, D. J.; Stough, H. P., III; Patton, J. M., Jr.

    1980-01-01

    Wind tunnel and flight tests were conducted to determine the effects of several discontinuous drooped wing leading-edge configurations on the spinning characteristics of a light, single-engine, low-wing research airplane. Particular emphasis was placed on the identification of modifications which would improve the spinning characteristics. The spanwise length of a discontinuous outboard droop was varied and several additional inboard segments were added to determine the influence of such leading-edge configurations on the spin behavior. Results of the study indicated that the use of only the discontinuous outboard droop, over a specific spanwise area, was most effective towards improving spin and spin recovery characteristics, whereas the segmented configurations having both inboard and outboard droop exhibited a tendency to enter a flat spin.

  19. [Social representations of TB patients on treatment discontinuation].

    PubMed

    Chirinos, Narda Estela Calsin; Meirelles, Betina Hörner Schlindwein; Bousfield, Andréa Barbará Silva

    2015-01-01

    To understand the social representations of people with TB who discontinued treatment in a Program of Tuberculosis Control. a descriptive study of qualitative approach conducted in the city of Lima, Peru. Data were collected from October to November 2012, through semi-structured interviews with eight individuals and the method used was thematic content analysis. The categories led to the construction of the social representation that the disease and the treatment bring suffering. This representation influences non-adherence to treatment and may increase the rates of treatment discontinuation. Educational strategies linked to social interaction processes, to subjectivity and to the patient context are needed to reduce the rates of discontinuation of tuberculosis treatment, relapses and multi-drug resistance. The evaluations point to new challenges that must be faced to achieve the Millennium Development Goals.

  20. Method for producing strain tolerant multifilamentary oxide superconducting wire

    DOEpatents

    Finnemore, D.K.; Miller, T.A.; Ostenson, J.E.; Schwartzkopf, L.A.; Sanders, S.C.

    1994-07-19

    A strain tolerant multifilamentary wire capable of carrying superconducting currents is provided comprising a plurality of discontinuous filaments formed from a high temperature superconducting material. The discontinuous filaments have a length at least several orders of magnitude greater than the filament diameter and are sufficiently strong while in an amorphous state to withstand compaction. A normal metal is interposed between and binds the discontinuous filaments to form a normal metal matrix capable of withstanding heat treatment for converting the filaments to a superconducting state. The geometry of the filaments within the normal metal matrix provides substantial filament-to-filament overlap, and the normal metal is sufficiently thin to allow supercurrent transfer between the overlapped discontinuous filaments but is also sufficiently thick to provide strain relief to the filaments. 6 figs.

  1. Method for producing strain tolerant multifilamentary oxide superconducting wire

    DOEpatents

    Finnemore, Douglas K.; Miller, Theodore A.; Ostenson, Jerome E.; Schwartzkopf, Louis A.; Sanders, Steven C.

    1994-07-19

    A strain tolerant multifilamentary wire capable of carrying superconducting currents is provided comprising a plurality of discontinuous filaments formed from a high temperature superconducting material. The discontinuous filaments have a length at least several orders of magnitude greater than the filament diameter and are sufficiently strong while in an amorphous state to withstand compaction. A normal metal is interposed between and binds the discontinuous filaments to form a normal metal matrix capable of withstanding heat treatment for converting the filaments to a superconducting state. The geometry of the filaments within the normal metal matrix provides substantial filament-to-filament overlap, and the normal metal is sufficiently thin to allow supercurrent transfer between the overlapped discontinuous filaments but is also sufficiently thick to provide strain relief to the filaments.

  2. Upwind methods for the Baer–Nunziato equations and higher-order reconstruction using artificial viscosity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fraysse, F., E-mail: francois.fraysse@rs2n.eu; E. T. S. de Ingeniería Aeronáutica y del Espacio, Universidad Politécnica de Madrid, Madrid; Redondo, C.

    This article is devoted to the numerical discretisation of the hyperbolic two-phase flow model of Baer and Nunziato. A special attention is paid on the discretisation of intercell flux functions in the framework of Finite Volume and Discontinuous Galerkin approaches, where care has to be taken to efficiently approximate the non-conservative products inherent to the model equations. Various upwind approximate Riemann solvers have been tested on a bench of discontinuous test cases. New discretisation schemes are proposed in a Discontinuous Galerkin framework following the criterion of Abgrall and the path-conservative formalism. A stabilisation technique based on artificial viscosity is appliedmore » to the high-order Discontinuous Galerkin method and compared against classical TVD-MUSCL Finite Volume flux reconstruction.« less

  3. Continuous versus discontinuous albedo representations in a simple diffusive climate model

    NASA Astrophysics Data System (ADS)

    Simmons, P. A.; Griffel, D. H.

    1988-07-01

    A one-dimensional annually and zonally averaged energy-balance model, with diffusive meridional heat transport and including icealbedo feedback, is considered. This type of model is found to be very sensitive to the form of albedo used. The solutions for a discontinuous step-function albedo are compared to those for a more realistic smoothly varying albedo. The smooth albedo gives a closer fit to present conditions, but the discontinuous form gives a better representation of climates in earlier epochs.

  4. A discontinuous Poisson-Boltzmann equation with interfacial jump: homogenisation and residual error estimate.

    PubMed

    Fellner, Klemens; Kovtunenko, Victor A

    2016-01-01

    A nonlinear Poisson-Boltzmann equation with inhomogeneous Robin type boundary conditions at the interface between two materials is investigated. The model describes the electrostatic potential generated by a vector of ion concentrations in a periodic multiphase medium with dilute solid particles. The key issue stems from interfacial jumps, which necessitate discontinuous solutions to the problem. Based on variational techniques, we derive the homogenisation of the discontinuous problem and establish a rigorous residual error estimate up to the first-order correction.

  5. Annual peak discharges from small drainage areas in Montana for stations discontinued before 1978

    USGS Publications Warehouse

    Omang, R.J.; Hull, J.A.; Parrett, Charles

    1979-01-01

    Annual peak stage and discharge data have been tabulated for crest-stage gage sites in Montana. The crest-stage program was begun in July 1955 to investigate the magnitude and frequency of floods from samll drainage areas. The program has expanded from 45 crest-stage gaging stations initially to 172 stations maintained in 1978. From 1955 to 1978, 156 stations have been discontinued. This report is a tabulation of the stage and discharge data for the discontinued stations. (Woodard-USGS)

  6. A Discontinuous Galerkin Finite Element Method for Hamilton-Jacobi Equations

    NASA Technical Reports Server (NTRS)

    Hu, Changqing; Shu, Chi-Wang

    1998-01-01

    In this paper, we present a discontinuous Galerkin finite element method for solving the nonlinear Hamilton-Jacobi equations. This method is based on the Runge-Kutta discontinuous Galerkin finite element method for solving conservation laws. The method has the flexibility of treating complicated geometry by using arbitrary triangulation, can achieve high order accuracy with a local, compact stencil, and are suited for efficient parallel implementation. One and two dimensional numerical examples are given to illustrate the capability of the method.

  7. News and views in discontinuous phase transitions

    NASA Astrophysics Data System (ADS)

    Nagler, Jan

    2014-03-01

    Recent progress in the theory of discontinuous percolation allow us to better understand the the sudden emergence of large-scale connectedness both in networked systems and on the lattice. We analytically study mechanisms for the amplification of critical fluctuations at the phase transition point, non-self-averaging and power law fluctuations. A single event analysis allow to establish criteria for discontinuous percolation transitions, even on the high-dimensional lattice. Some applications such as salad bowl percolation, and inverse fragmentation are discussed.

  8. On cell entropy inequality for discontinuous Galerkin methods

    NASA Technical Reports Server (NTRS)

    Jiang, Guangshan; Shu, Chi-Wang

    1993-01-01

    We prove a cell entropy inequality for a class of high order discontinuous Galerkin finite element methods approximating conservation laws, which implies convergence for the one dimensional scalar convex case.

  9. Investigation of upper mantle seismic discontinuities beneath the Indian Ocean using array seismology methods

    NASA Astrophysics Data System (ADS)

    van Driel, J.; Reiss, A. S.; Thomas, C.

    2016-12-01

    The topography of upper mantle seismic discontinuities can be used to constrain regional variations in composition and temperature of the Earths mantle. The 410 km discontinuity is caused by the solid-solid phase transition from olivine to wadsleyite. Due to its positive Clapeyron slope, the discontinuity is depressed in hot regimes. The phase transition from ringwoodite to bridgemanite and magnesiowüstite in contrast has a negative Clapeyron slope and therefore is elevated when hot material is present. Cold material is expected to yield an opposing topographic signature, culminating in an elevated 410 km and a depressed 660 km discontinuity. As part of the RHUM-RUM project (Réunion Hotspot and Upper Mantle - Réunions Unterer Mantel) we extract relevant geophysical parameters, by investigating the properties of upper mantle seismic discontinuities beneath the Indian Ocean. The topography of the 410 and 660 km discontinuities, which define the upper and lower bounds of the mantle transition zone, have been mapped using PP and SS underside reflections. This study has utilised over 8500 events with Mw ≥ 5.8, distributed over the entire Indian Ocean. Our robust data set yields a dense coverage of points, which are defined by consistently crossing ray paths. Array seismology methods, such as vespagrams and slowness-backazimuth analysis, are used to enhance the signal-to-noise-ratio and detect and identify weak precursor signals. The differential travel times are corrected for crustal features and converted into depth values of the discontinuities by comparing the measured travel times with theoretical ones derived from ray tracing through the 1D reference Earth model ak135. A `travel-time' stacking method has also been applied for 4° radius bins around each of the bounce points. The addition of a secondary method derives greater stability of our results and allows an enhanced error analysis procedure. In order to better constrain the mineralogical processes taking place within the mantle transition zone, amplitude ratios, polarities and velocity gradients have also been investigated.

  10. A Combined Remote Sensing-Numerical Modelling Approach to the Stability Analysis of Delabole Slate Quarry, Cornwall, UK

    NASA Astrophysics Data System (ADS)

    Havaej, Mohsen; Coggan, John; Stead, Doug; Elmo, Davide

    2016-04-01

    Rock slope geometry and discontinuity properties are among the most important factors in realistic rock slope analysis yet they are often oversimplified in numerical simulations. This is primarily due to the difficulties in obtaining accurate structural and geometrical data as well as the stochastic representation of discontinuities. Recent improvements in both digital data acquisition and incorporation of discrete fracture network data into numerical modelling software have provided better tools to capture rock mass characteristics, slope geometries and digital terrain models allowing more effective modelling of rock slopes. Advantages of using improved data acquisition technology include safer and faster data collection, greater areal coverage, and accurate data geo-referencing far exceed limitations due to orientation bias and occlusion. A key benefit of a detailed point cloud dataset is the ability to measure and evaluate discontinuity characteristics such as orientation, spacing/intensity and persistence. This data can be used to develop a discrete fracture network which can be imported into the numerical simulations to study the influence of the stochastic nature of the discontinuities on the failure mechanism. We demonstrate the application of digital terrestrial photogrammetry in discontinuity characterization and distinct element simulations within a slate quarry. An accurately geo-referenced photogrammetry model is used to derive the slope geometry and to characterize geological structures. We first show how a discontinuity dataset, obtained from a photogrammetry model can be used to characterize discontinuities and to develop discrete fracture networks. A deterministic three-dimensional distinct element model is then used to investigate the effect of some key input parameters (friction angle, spacing and persistence) on the stability of the quarry slope model. Finally, adopting a stochastic approach, discrete fracture networks are used as input for 3D distinct element simulations to better understand the stochastic nature of the geological structure and its effect on the quarry slope failure mechanism. The numerical modelling results highlight the influence of discontinuity characteristics and kinematics on the slope failure mechanism and the variability in the size and shape of the failed blocks.

  11. Contraceptive discontinuation and pregnancy postabortion in Nepal: a longitudinal cohort study.

    PubMed

    Puri, Mahesh; Henderson, Jillian T; Harper, Cynthia C; Blum, Maya; Joshi, Deepak; Rocca, Corinne H

    2015-04-01

    To examine postabortion contraceptive discontinuation and pregnancy in Nepal, where abortion was decriminalized in 2002. We conducted an observational cohort study of 654 women obtaining abortions from four public and nongovernmental facilities in 2011. Patients completed questionnaires at their abortion visit and 6 and 12 months later. We used Cox proportional hazards models to assess contraceptive discontinuation and pregnancy by method initiated postabortion and other sociodemographic and reproductive factors. Among the 78% (508/654) of women who initiated a modern contraceptive method within 3 months postabortion, the 1-year contraceptive discontinuation rate was 62 per 100 person-years. Discontinuation was far lower among the 5% of women using long-acting reversible methods (21/100 person-years) than among those using condoms (74/100 person-years), pills (61/100 person-years) and the injectable [64/100 person-years; adjusted hazard ratio (aHR)=0.32 (0.15-0.68)]. Unmarried women and those not living with their husband experienced higher contraceptive discontinuation [aHR=2.16 (1.47-3.17)]. The 1-year pregnancy rate for all women was 9/100 person-years. Pregnancy was highest among those who initiated no modern method postabortion (13/100 person-years) and condoms (12/100 person-years), and pregnancy was lowest among users of long-acting reversible methods (3/100 person-years). The poorest women were at increased pregnancy risk [aHR=2.31 (1.32-4.10)]. Women using intrauterine devices and implants experienced greatly reduced contraceptive discontinuation and pregnancy within a year postabortion, although initiation of these long-acting methods was low. Increased availability of long-acting methods in Nepal and similar settings may help to prevent unwanted pregnancy and attendant maternal mortality and morbidities. Initiation of modern contraception was high postabortion; however, 1-year discontinuation was high for the condom, pill and injectable, the methods most commonly used. Rates for intrauterine devices and implants were low. Results support efforts to facilitate patient knowledge and access to the full range of contraceptives, including long-acting reversible methods. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Long-term outcome of patients with Crohn's disease who discontinued infliximab therapy upon clinical remission.

    PubMed

    Papamichael, Konstantinos; Vande Casteele, Niels; Gils, Ann; Tops, Sophie; Hauenstein, Scott; Singh, Sharat; Princen, Fred; Van Assche, Gert; Rutgeerts, Paul; Vermeire, Severine; Ferrante, Marc

    2015-06-01

    There are limited data on the effects of discontinuing infliximab therapy for Crohn's disease (CD). We investigated the long-term outcome of patients with CD who discontinued infliximab while in clinical remission, and searched for prognostic markers of continued remission after infliximab cessation. We performed a retrospective, single-center study of 100 patients with CD who discontinued infliximab upon achieving clinical remission; 84 patients continued immunomodulator therapy. Clinical and endoscopic data were retrieved from a medical database in Belgium, and patients were followed up through April 2013 (median, 9.7 y; interquartile range, 8-11.5 y). Sustained clinical remission (SCR) was defined as maintenance of disease remission, without escalation in medical therapy or CD-related surgeries, until the end of the follow-up period. We measured trough concentrations of infliximab, antibodies to microbial antigens, and circulating inflammatory markers in serum samples collected before treatment and at the time of infliximab discontinuation. At the end of the follow-up period, 52 patients had SCR. Univariate (log-rank) analysis associated SCR with patient age at diagnosis (≥25 y; P = .012) and disease duration (<1 y; P = .017). Among factors evaluated at the time of infliximab discontinuation, infliximab trough concentrations (<6 μg/mL; P = .031), complete mucosal healing (P = .046), and serum positivity for vascular cell adhesion molecule-1 (>0.67 μg/mL; P = .024) were associated with SCR. In multiple Cox proportional hazards regression analysis, only age at diagnosis of 25 years and older was associated independently with SCR (hazard ratio, 1.83; 95% confidence interval, 1.03-3.25; P = .04). In a large, real-life study, 52% of patients with CD who discontinued infliximab upon achieving clinical remission remained in SCR after a median period of approximately 10 years; Most patients remained on immunomodulator therapy. Although patients with CD have variable responses to infliximab, a subgroup achieved long-term remission after infliximab discontinuation. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  13. Etanercept and adalimumab treatment patterns in psoriatic arthritis patients enrolled in a commercial health plan.

    PubMed

    Chastek, Benjamin; Fox, Kathleen M; Watson, Crystal; Gandra, Shravanthi R

    2012-08-01

    Treatment patterns, including persistence, gaps in therapy, switching, and discontinuation, were examined in patients with psoriatic arthritis (PsA) who received the tumor necrosis factor (TNF)-blockers etanercept or adalimumab. This retrospective study utilized administrative claims data from a United States commercial health plan. Adults (age 18-64 years) with PsA who started therapy with etanercept or adalimumab as index therapy between January 1, 2006 and December 31, 2008 were included in the analysis. Patients were continuously enrolled in the health plan for at least 6 months before and at least 12 months after the start of index therapy. Initial TNF-blocker dose and rates of therapy persistence (continuous use of index medication without a gap of at least 60 days), therapy gaps, and discontinuation (gap in therapy of at least 60 days) were estimated. Those who discontinued were further classified as: (1) discontinued all biologic therapy, (2) restarted index medication, (3) switched to another biologic therapy, or (4) other. A total of 346 patients with PsA (202 etanercept, 144 adalimumab) were eligible. Most (90.6% etanercept; 88.9% adalimumab) started index therapy at the labeled dose. Persistence with index therapy for 12 months was observed in 50% of patients on etanercept and 45% of patients on adalimumab (P = 0.37). Patients on etanercept had a longer duration of persistence (434 vs. 353 days; P = 0.02), more pauses of at least 7 days (4.7 vs. 3.5; P = 0.004), and a longer mean pause length (48.6 vs. 29.3 days; P = 0.01) than patients on adalimumab. Of patients who discontinued (24.8% etanercept; 35.1% adalimumab), 46.4% and 41.5% restarted etanercept and adalimumab, respectively; 24.8% and 35.1% discontinued all TNF-blockers; 20.0% and 19.2% switched to another biologic; and 8.8% and 4.3% had other therapy changes. Approximately half of PsA patients were persistent on their index TNF-blocker for 12 months. Pauses in therapy and therapy discontinuation were common, but more than 40% of patients restarted their index TNF-blocker after discontinuation.

  14. Excursions in fluvial (dis)continuity

    NASA Astrophysics Data System (ADS)

    Grant, Gordon E.; O'Connor, Jim; Safran, Elizabeth

    2017-01-01

    Lurking below the twin concepts of connectivity and disconnectivity are their first, and in some ways, richer cousins: continuity and discontinuity. In this paper we explore how continuity and discontinuity represent fundamental and complementary perspectives in fluvial geomorphology, and how these perspectives inform and underlie our conceptions of connectivity in landscapes and rivers. We examine the historical roots of continuum and discontinuum thinking, and how much of our understanding of geomorphology rests on contrasting views of continuity and discontinuity. By continuum thinking we refer to a conception of geomorphic processes as well as geomorphic features that are expressed along continuous gradients without abrupt changes, transitions, or thresholds. Balance of forces, graded streams, and hydraulic geometry are all examples of this perspective. The continuum view has played a prominent role in diverse disciplinary fields, including ecology, paleontology, and evolutionary biology, in large part because it allows us to treat complex phenomena as orderly progressions and invoke or assume equilibrium processes that introduce order and prediction into our sciences. In contrast the discontinuous view is a distinct though complementary conceptual framework that incorporates non-uniform, non-progressive, and non-equilibrium thinking into understanding geomorphic processes and landscapes. We distinguish and discuss examples of three different ways in which discontinuous thinking can be expressed: 1) discontinuous spatial arrangements or singular events; 2) specific process domains generally associated with thresholds, either intrinsic or extrinsic; and 3) physical dynamics or changes in state, again often threshold-linked. In moving beyond the continuous perspective, a fertile set of ideas comes into focus: thresholds, non-equilibrium states, heterogeneity, catastrophe. The range of phenomena that is thereby opened up to scientific exploration similarly expands: punctuated episodes of cutting and filling, discretization of landscapes into hierarchies of structure and control, the work of extreme events. Orderly and progressive evolution towards a steady or ideal state is replaced by chaotic episodes of disturbance and recovery. Recent developments in the field of geomorphology suggest that we may be on the cusp of a new paradigm that recognizes that both continuous and discontinuous processes and mechanisms play a role in fluvial processes and landscape evolution with neither holding sway over the other and both needed to see rivers as they are.

  15. IUD discontinuation rates, switching behavior, and user satisfaction: findings from a retrospective analysis of a mobile outreach service program in Pakistan

    PubMed Central

    Azmat, Syed Khurram; Hameed, Waqas; Mustafa, Ghulam; Hussain, Wajahat; Ahmed, Aftab; Bilgrami, Mohsina

    2013-01-01

    Background In Pakistan, the uptake rate for the intrauterine device (IUD) is very low at 2.5%. The most popular modern contraceptive methods in Pakistan are female sterilization and use of condoms. The Marie Stopes Society established its mobile outreach service delivery program with the aim of increasing use of modern quality contraceptive services, including the long-term reversible IUD, by women living in hard-to-reach areas. The present study attempts to assess IUD discontinuation rates and associated factors, including switching behavior and level of satisfaction with this type of service delivery. Methods Using a cross-sectional approach, we contacted 681 women who had received an IUD from the Marie Stopes Society mobile outreach program during July and August 2009. Successful interviews were conducted with 639 of these women using a structured questionnaire. The data were analyzed with Stata 11.2 using simple descriptive Chi-square and Cox proportional techniques. Results Analysis revealed that 19.4% (95% confidence interval 16.3–22.5) of the women discontinued use of their IUD at 10 months and, of these women, the majority (69.4%) cited side effects as the main reason for discontinuation. Other factors, such as geographical catchment province, age of the woman, history of contraceptive use before IUD insertion, and side effects following insertion of the device, were found to be significantly associated with IUD. Amongst the women who had their IUD removed, 56.5% did not switch to any other contraceptive method, while 36.3% switched to either short-term or traditional methods, such as withdrawal, rhythm, and folk methods. Degree of satisfaction with the device was also significantly associated with discontinuation. Conclusion Early discontinuation and not switching to another contraceptive method increases the risk of unplanned pregnancy. Health care workers should be trained in managing clients’ concerns about the IUD to prevent discontinuation and providing counseling services for clients to select an alternative contraceptive method if they decide to discontinue. PMID:23359788

  16. Discontinued Information and Communication Technology Usage among Older Adults in Continuing Care Retirement Communities in the United States.

    PubMed

    Rikard, R V; Berkowsky, Ronald W; Cotten, Shelia R

    2018-01-01

    Older adults are increasingly using information and communication technologies (ICTs). Recent studies show beneficial effects of using ICTs for older adults, particularly in terms of reducing loneliness and depression. However, little is known about the factors that may prevent discontinued ICT use in populations that may be at greater risk, such as those in continuing care retirement communities (CCRCs). The purpose of this study is to examine a range of factors that may influence discontinued (1) ICT use, (2) searching for health information, and (3) searching for general information over time among CCRC residents. We use longitudinal data from a randomized controlled trial conducted with residents of 19 CCRCs. We use flexible parametric models to estimate the hazard ratio or hazard rate over 5 waves of data to determine what factors significantly predict discontinued (1) ICT use, (2) health information searching, and (3) general information searching. The analysis reveals that independent living residents who took part in an 8-week ICT training intervention were less likely to stop using ICTs. Age and the number of instrumental activities of daily living (IADL) impairments significantly predicted an increased likelihood of stopping ICT use. When examining specific ICT-related activities, the analysis reveals that independent living residents who took part in the ICT training intervention were less likely to stop searching for health information and general information online. In addition, age and the number of IADL impairments were associated with increased likelihood of discontinued health information searches and discontinued general information searches. ICT training interventions may motivate residents of CCRCs to stay connected by increasing the ICT skill level and promoting confidence, thus decreasing the probability that they will discontinue using ICTs and searching for general information. However, the effects of ICT training on motivating continued ICT usage may be more pronounced among independent living residents. Limitations in the number of IADL impairments is a key factor leading to discontinued use of ICTs among CCRC residents, suggesting that designers of ICTs should be cognizant of the cognitive and physical limitations among this group. © 2017 S. Karger AG, Basel.

  17. Persistence in Therapy With Risperidone and Aripiprazole in Pediatric Outpatients: A 2-Year Naturalistic Comparison.

    PubMed

    Pozzi, Marco; Pisano, Simone; Bertella, Silvana; Capuano, Annalisa; Rizzo, Renata; Antoniazzi, Stefania; Auricchio, Fabiana; Carnovale, Carla; Cattaneo, Dario; Ferrajolo, Carmen; Gentili, Marta; Guastella, Giuseppe; Mani, Elisa; Rafaniello, Concetta; Riccio, Maria Pia; Scuderi, Maria Grazia; Sperandeo, Serena; Sportiello, Liberata; Villa, Laura; Radice, Sonia; Clementi, Emilio; Rossi, Francesco; Pascotto, Antonio; Bernardini, Renato; Molteni, Massimo; Bravaccio, Carmela

    2016-12-01

    The practical effectiveness of second-generation antipsychotics in children and adolescents is an understudied issue. It is a crucial area of study, though, because such patients are often treated for long-lasting disorders. We carried out a 24-month (March 2012-March 2014) observational study on an unselected population of pediatric outpatients treated with risperidone, aripiprazole, olanzapine, or quetiapine aiming to (1) describe drug use, (2) compare post hoc the discontinuation rates due to specific causes and dose adjustments by Kaplan-Meier analyses between drugs, and (3) analyze predictors influencing these outcomes by Cox multivariate models. Among 184 pediatric patients, 77% patients were prescribed risperidone, and 18% were prescribed aripiprazole. Olanzapine or quetiapine were scantly used; therefore, they were excluded from analyses. Risperidone was prevalent in younger, male patients with disruptive behavioral disorders; aripiprazole, in patients with tic disorders. Overall, discontinuations occurred mostly in the first 6 months, and, at 24 months, the discontinuation numbers were similar between users of risperidone and aripiprazole (41.5% vs 39.4%). In univariate analyses, dose reduction was higher for aripiprazole (P = .033). Multivariate analyses yielded the following predictors: for all-cause discontinuation, baseline severity (hazard ratio [HR] = 1.48, P = .001) and dose increase (HR = 3.55, P = .001); for patient-decided discontinuation, dose change (increase: HR = 6.43, P = .004; reduction: HR = 7.89, P = .049) and the presence of concomitant drugs (HR = 4.03, P = .034), while autistic patients discontinued less (HR = 0.23, P = .050); for clinician-decided discontinuation due to adverse drug reactions, baseline severity (HR = 1.96, P = .005) and dose increase (HR = 5.09, P = .016); for clinician-decided discontinuation due to inefficacy, baseline severity (HR = 2.88, P = .014) and the use of aripiprazole (HR = 5.55, P = .013); for dose increase, none; for dose reduction, the occurrence of adverse drug reactions (HR = 4.74, P = .046), while dose reduction was less probable in autistic patients (HR = 0.22, P = .042). The findings of this study show a similarity between the overall effectiveness of risperidone and aripiprazole in a real-life pediatric outpatient setting. © Copyright 2016 Physicians Postgraduate Press, Inc.

  18. Twelve-month discontinuation rates of levonorgestrel intrauterine system 13.5 mg and subdermal etonogestrel implant in women aged 18-44: A retrospective claims database analysis.

    PubMed

    Law, Amy; Liao, Laura; Lin, Jay; Yaldo, Avin; Lynen, Richard

    2018-04-21

    To investigate the 12-month discontinuation rates of levonorgestrel intrauterine system 13.5 mg (LNG-IUS 13.5) and subdermal etonogestrel (ENG) implant in the US. We identified women aged 18-44 who had an insertion of LNG-IUS 13.5 or ENG implant from the MarketScan Commercial claims database (7/1/2013-9/30/2014). Women were required to have 12 months of continuous insurance coverage prior to the insertion (baseline) and at least 12-months after (follow-up). Discontinuation was defined as presence of an insurance claim for pregnancy-related services, hysterectomy, female sterilization, a claim for another contraceptive method, or removal of the index contraceptive without re-insertion within 30 days. Using Cox regression we examined the potential impact of ENG implant vs. LNG-IUS 13.5 on the likelihood for discontinuation after controlling for patient characteristics. A total of 3680 (mean age: 25.4 years) LNG-IUS 13.5 and 23,770 (mean age: 24.6 years) ENG implant users met the selection criteria. Prior to insertion, 56.6% of LNG-IUS 13.5 and 42.1% of ENG implant users had used contraceptives, with oral contraceptives being most common (LNG-IUS 13.5: 42.1%; ENG implant: 28.5%). Among users of LNG-IUS 13.5 and ENG implant, rates of discontinuation were similar during the 12-month follow-up (LNG-IUS 13.5: 24.9%; ENG implant: 24.0%). Regression results showed that women using LNG-IUS 13.5 vs. ENG implant had similar likelihood for discontinuation (hazard ratio: 0.97, 95% confidence interval: 0.90-1.05, p=.41). In the real-world US setting, women aged 18-44 using LNG-IUS 13.5 and ENG implant have similar discontinuation rates after 12 months. In the United States, women aged 18-44 using levonorgestrel intrauterine system (13.5 mg) and subdermal etonogestrel implant have similar discontinuation rates after 12 months. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Number needed to treat to harm for discontinuation due to adverse events in the treatment of bipolar depression, major depressive disorder, and generalized anxiety disorder with atypical antipsychotics.

    PubMed

    Gao, Keming; Kemp, David E; Fein, Elizabeth; Wang, Zuowei; Fang, Yiru; Ganocy, Stephen J; Calabrese, Joseph R

    2011-08-01

    To estimate the number needed to treat to harm (NNTH) for discontinuation due to adverse events with atypical antipsychotics relative to placebo during the treatment of bipolar depression, major depressive disorder (MDD), and generalized anxiety disorder (GAD). English-language literature published and cited in MEDLINE from January 1966 to May 2009 was searched with the terms antipsychotic, atypical antipsychotic, generic and brand names of atypical antipsychotics, safety, tolerability, discontinuation due to adverse events, somnolence, sedation, weight gain, akathisia, or extrapyramidal side effect; and bipolar depression, major depressive disorder, or generalized anxiety disorder; and randomized, placebo-controlled clinical trial. This search was augmented with a manual search. Studies with a cumulative sample of ≥ 100 patients were included. The NNTHs for discontinuation due to adverse events, somnolence, sedation, ≥ 7% weight gain, and akathisia relative to placebo were estimated with 95% confidence intervals to reflect the magnitude of variance. Five studies in bipolar depression, 10 studies in MDD, and 4 studies in GAD were identified. Aripiprazole and olanzapine have been studied in bipolar depression and refractory MDD. Only quetiapine extended release (quetiapine-XR) has been studied in 3 psychiatric conditions with different fixed dosing schedules. For aripiprazole, the mean NNTH for discontinuation due to adverse events was 14 in bipolar depression, but was not significantly different from placebo in MDD. For olanzapine, the mean NNTHs were 24 in bipolar depression and 9 in MDD. The risk for discontinuation due to adverse events during quetiapine-XR treatment appeared to be associated with dose. For quetiapine-XR 300 mg/d, the NNTHs for discontinuation due to adverse events were 9 for bipolar depression, 8 for refractory MDD, 9 for MDD, and 5 for GAD. At the same dose of quetiapine-XR, patients with GAD appeared to have a lower tolerability than those with bipolar depression or MDD. Due to flexible dosing, the risk for discontinuation due to adverse events in the treatment of bipolar depression, MDD, or GAD with other atypical antipsychotics could not be compared. © Copyright 2011 Physicians Postgraduate Press, Inc.

  20. Excursions in fluvial (dis)continuity

    USGS Publications Warehouse

    Grant, Gordon E.; O'Connor, James E.; Safran, Elizabeth

    2017-01-01

    Lurking below the twin concepts of connectivity and disconnectivity are their first, and in some ways, richer cousins: continuity and discontinuity. In this paper we explore how continuity and discontinuity represent fundamental and complementary perspectives in fluvial geomorphology, and how these perspectives inform and underlie our conceptions of connectivity in landscapes and rivers. We examine the historical roots of continuum and discontinuum thinking, and how much of our understanding of geomorphology rests on contrasting views of continuity and discontinuity. By continuum thinking we refer to a conception of geomorphic processes as well as geomorphic features that are expressed along continuous gradients without abrupt changes, transitions, or thresholds. Balance of forces, graded streams, and hydraulic geometry are all examples of this perspective. The continuum view has played a prominent role in diverse disciplinary fields, including ecology, paleontology, and evolutionary biology, in large part because it allows us to treat complex phenomena as orderly progressions and invoke or assume equilibrium processes that introduce order and prediction into our sciences.In contrast the discontinuous view is a distinct though complementary conceptual framework that incorporates non-uniform, non-progressive, and non-equilibrium thinking into understanding geomorphic processes and landscapes. We distinguish and discuss examples of three different ways in which discontinuous thinking can be expressed: 1) discontinuous spatial arrangements or singular events; 2) specific process domains generally associated with thresholds, either intrinsic or extrinsic; and 3) physical dynamics or changes in state, again often threshold-linked. In moving beyond the continuous perspective, a fertile set of ideas comes into focus: thresholds, non-equilibrium states, heterogeneity, catastrophe. The range of phenomena that is thereby opened up to scientific exploration similarly expands: punctuated episodes of cutting and filling, discretization of landscapes into hierarchies of structure and control, the work of extreme events. Orderly and progressive evolution towards a steady or ideal state is replaced by chaotic episodes of disturbance and recovery. Recent developments in the field of geomorphology suggest that we may be on the cusp of a new paradigm that recognizes that both continuous and discontinuous processes and mechanisms play a role in fluvial processes and landscape evolution with neither holding sway over the other and both needed to see rivers as they are.

  1. 47 CFR 5.81 - Discontinuance of station operation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... THAN BROADCAST) Applications and Licenses § 5.81 Discontinuance of station operation. In case of... mobile station in the Experimental Radio Service, the licensee shall forward the station license to the...

  2. Stratigraphy -- The Fall of Continuity.

    ERIC Educational Resources Information Center

    Byers, Charles W.

    1982-01-01

    Reviews advances in stratigraphy as illustrated in the current geological literature, discussing discontinuity and how the recognition of discontinuity in the stratigraphic record is changing views of Superposition and Original Lateral Continuity. (Author/JN)

  3. Discontinuation and non-publication of randomised clinical trials supported by the main public funding body in Switzerland: a retrospective cohort study.

    PubMed

    Amstutz, Alain; Schandelmaier, Stefan; Frei, Roy; Surina, Jakub; Agarwal, Arnav; Olu, Kelechi Kalu; Alturki, Reem; Von Niederhäusern, Belinda; Von Elm, Erik; Briel, Matthias

    2017-08-01

    The Swiss National Science Foundation (SNSF) promotes academic excellence through competitive selection of study proposals and rigorous evaluation of feasibility, but completion status and publication history of SNSF-supported randomised clinical trials (RCTs) remain unclear. The main objectives were to review all healthcare RCTs supported by the SNSF for trial discontinuation and non-publication, to investigate potential risk factors for trial discontinuation due to poor recruitment and non-publication, and to compare findings to other Swiss RCTs not supported by the SNSF. We established a retrospective cohort of all SNSF-supported RCTs for which recruitment and funding had ended in 2015 or earlier. For each RCT, two investigators independently searched corresponding publications in electronic databases. In addition, we approached all principal investigators to ask for additional publications and information about trial discontinuation. Teams of two investigators independently extracted details about study design, recruitment of participants, outcomes, analysis and sample size from the original proposal and, if available, from trial registries and publications. We used multivariable regression analysis to explore potential risk factors associated with discontinuation due to poor recruitment and with non-publication, and to compare our results with data from a previous cohort of Swiss RCTs not supported by the SNSF. We included 101 RCTs supported by the SNSF between 1986 and 2015. Eighty-seven (86%) principal investigators responded to our survey. Overall, 69 (68%) RCTs were completed, 26 (26%) RCTs were prematurely discontinued (all due to slow recruitment) and the completion status remained unclear for 6 (6%) RCTs. For analysing publication status, we excluded 4 RCTs for which follow-up was still ongoing and 9 for which manuscripts were still in preparation. Of the remaining 88 RCTs, 53 (60%) were published as full articles in peer-reviewed journals. Multivariable regression models suggested that discontinued trials were at higher risk for non-publication than completed trials (adjusted OR 7.61; 95% CI 2.44 to 27.09). Compared with other Swiss RCTs, the risk of discontinuation for SNSF-supported RCTs was higher than in industry-initiated RCTs (adjusted OR 3.84; 95% CI 1.68 to 8.74), but not significantly different from investigator-initiated RCTs not supported by the SNSF (adjusted OR 1.05; 95% CI 0.51 to 2.11). We found no evidence that the proportion of discontinued or unpublished RCTs decreased over the last 20 years. One out of four SNSF-supported RCTs were prematurely discontinued due to slow recruitment, 40% of all included RCTs and 70% of all discontinued RCTs were not published in peer-reviewed journals. There is a case to reconsider how public funding bodies such as the SNSF could improve their feasibility assessment and promote publication of RCTs irrespective of completion status. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Environmental Discontinuity, Stress, and Sex Effects Upon Susceptibility to Social Influence

    ERIC Educational Resources Information Center

    Zohner, Dorin

    1970-01-01

    Social influence was influenced most by prestige suggestion, conformity, and baseline suggestion, in that order. Differential effects of suggestion depended on the effects of type of discontinuity and sex. (MH)

  5. Deep structure of the Afro-Arabian hotspot by S receiver functions

    NASA Astrophysics Data System (ADS)

    Vinnik, L. P.; Farra, V.; Kind, R.

    2004-06-01

    We investigated deep structure of the Afro-Arabian hotspot by using recordings from Geoscope seismograph station ATD. The records are processed with the S receiver function technique, which allows a detection of Sp converted phases from the upper mantle discontinuities. The seismic data reveal two unusual discontinuities. The discontinuity at a depth of 160 km beneath the Gulf of Aden corresponds to the onset of melting. If the water content in olivine is around 800 H/106Si, melting at this depth requires a temperature close to 1550°C, about 120°C higher than the average. Another remarkable discontinuity is found at a depth of 480 km, where S velocity drops with depth by about 0.2 km/s. This can be the head of another plume which is trapped in the mantle transition zone.

  6. A flux splitting scheme with high-resolution and robustness for discontinuities

    NASA Technical Reports Server (NTRS)

    Wada, Yasuhiro; Liou, Meng-Sing

    1994-01-01

    A flux splitting scheme is proposed for the general nonequilibrium flow equations with an aim at removing numerical dissipation of Van-Leer-type flux-vector splittings on a contact discontinuity. The scheme obtained is also recognized as an improved Advection Upwind Splitting Method (AUSM) where a slight numerical overshoot immediately behind the shock is eliminated. The proposed scheme has favorable properties: high-resolution for contact discontinuities; conservation of enthalpy for steady flows; numerical efficiency; applicability to chemically reacting flows. In fact, for a single contact discontinuity, even if it is moving, this scheme gives the numerical flux of the exact solution of the Riemann problem. Various numerical experiments including that of a thermo-chemical nonequilibrium flow were performed, which indicate no oscillation and robustness of the scheme for shock/expansion waves. A cure for carbuncle phenomenon is discussed as well.

  7. The Local Discontinuous Galerkin Method for Time-Dependent Convection-Diffusion Systems

    NASA Technical Reports Server (NTRS)

    Cockburn, Bernardo; Shu, Chi-Wang

    1997-01-01

    In this paper, we study the Local Discontinuous Galerkin methods for nonlinear, time-dependent convection-diffusion systems. These methods are an extension of the Runge-Kutta Discontinuous Galerkin methods for purely hyperbolic systems to convection-diffusion systems and share with those methods their high parallelizability, their high-order formal accuracy, and their easy handling of complicated geometries, for convection dominated problems. It is proven that for scalar equations, the Local Discontinuous Galerkin methods are L(sup 2)-stable in the nonlinear case. Moreover, in the linear case, it is shown that if polynomials of degree k are used, the methods are k-th order accurate for general triangulations; although this order of convergence is suboptimal, it is sharp for the LDG methods. Preliminary numerical examples displaying the performance of the method are shown.

  8. Numerical Homogenization of Jointed Rock Masses Using Wave Propagation Simulation

    NASA Astrophysics Data System (ADS)

    Gasmi, Hatem; Hamdi, Essaïeb; Bouden Romdhane, Nejla

    2014-07-01

    Homogenization in fractured rock analyses is essentially based on the calculation of equivalent elastic parameters. In this paper, a new numerical homogenization method that was programmed by means of a MATLAB code, called HLA-Dissim, is presented. The developed approach simulates a discontinuity network of real rock masses based on the International Society of Rock Mechanics (ISRM) scanline field mapping methodology. Then, it evaluates a series of classic joint parameters to characterize density (RQD, specific length of discontinuities). A pulse wave, characterized by its amplitude, central frequency, and duration, is propagated from a source point to a receiver point of the simulated jointed rock mass using a complex recursive method for evaluating the transmission and reflection coefficient for each simulated discontinuity. The seismic parameters, such as delay, velocity, and attenuation, are then calculated. Finally, the equivalent medium model parameters of the rock mass are computed numerically while taking into account the natural discontinuity distribution. This methodology was applied to 17 bench fronts from six aggregate quarries located in Tunisia, Spain, Austria, and Sweden. It allowed characterizing the rock mass discontinuity network, the resulting seismic performance, and the equivalent medium stiffness. The relationship between the equivalent Young's modulus and rock discontinuity parameters was also analyzed. For these different bench fronts, the proposed numerical approach was also compared to several empirical formulas, based on RQD and fracture density values, published in previous research studies, showing its usefulness and efficiency in estimating rapidly the Young's modulus of equivalent medium for wave propagation analysis.

  9. Regression Discontinuity for Causal Effect Estimation in Epidemiology.

    PubMed

    Oldenburg, Catherine E; Moscoe, Ellen; Bärnighausen, Till

    Regression discontinuity analyses can generate estimates of the causal effects of an exposure when a continuously measured variable is used to assign the exposure to individuals based on a threshold rule. Individuals just above the threshold are expected to be similar in their distribution of measured and unmeasured baseline covariates to individuals just below the threshold, resulting in exchangeability. At the threshold exchangeability is guaranteed if there is random variation in the continuous assignment variable, e.g., due to random measurement error. Under exchangeability, causal effects can be identified at the threshold. The regression discontinuity intention-to-treat (RD-ITT) effect on an outcome can be estimated as the difference in the outcome between individuals just above (or below) versus just below (or above) the threshold. This effect is analogous to the ITT effect in a randomized controlled trial. Instrumental variable methods can be used to estimate the effect of exposure itself utilizing the threshold as the instrument. We review the recent epidemiologic literature reporting regression discontinuity studies and find that while regression discontinuity designs are beginning to be utilized in a variety of applications in epidemiology, they are still relatively rare, and analytic and reporting practices vary. Regression discontinuity has the potential to greatly contribute to the evidence base in epidemiology, in particular on the real-life and long-term effects and side-effects of medical treatments that are provided based on threshold rules - such as treatments for low birth weight, hypertension or diabetes.

  10. Pasture succession in the Neotropics: extending the nucleation hypothesis into a matrix discontinuity hypothesis.

    PubMed

    Peterson, Chris J; Dosch, Jerald J; Carson, Walter P

    2014-08-01

    The nucleation hypothesis appears to explain widespread patterns of succession in tropical pastures, specifically the tendency for isolated trees to promote woody species recruitment. Still, the nucleation hypothesis has usually been tested explicitly for only short durations and in some cases isolated trees fail to promote woody recruitment. Moreover, at times, nucleation occurs in other key habitat patches. Thus, we propose an extension, the matrix discontinuity hypothesis: woody colonization will occur in focal patches that function to mitigate the herbaceous vegetation effects, thus providing safe sites or regeneration niches. We tested predictions of the classical nucleation hypothesis, the matrix discontinuity hypothesis, and a distance from forest edge hypothesis, in five abandoned pastures in Costa Rica, across the first 11 years of succession. Our findings confirmed the matrix discontinuity hypothesis: specifically, rotting logs and steep slopes significantly enhanced woody colonization. Surprisingly, isolated trees did not consistently significantly enhance recruitment; only larger trees did so. Finally, woody recruitment consistently decreased with distance from forest. Our results as well as results from others suggest that the nucleation hypothesis needs to be broadened beyond its historical focus on isolated trees or patches; the matrix discontinuity hypothesis focuses attention on a suite of key patch types or microsites that promote woody species recruitment. We argue that any habitat discontinuities that ameliorate the inhibition by dense graminoid layers will be foci for recruitment. Such patches could easily be manipulated to speed the transition of pastures to closed canopy forests.

  11. Estimating the effect of hospital closure on areawide inpatient hospital costs: a preliminary model and application.

    PubMed Central

    Shepard, D S

    1983-01-01

    A preliminary model is developed for estimating the extent of savings, if any, likely to result from discontinuing a specific inpatient service. By examining the sources of referral to the discontinued service, the model estimates potential demand and how cases will be redistributed among remaining hospitals. This redistribution determines average cost per day in hospitals that receive these cases, relative to average cost per day of the discontinued service. The outflow rate, which measures the proportion of cases not absorbed in other acute care hospitals, is estimated as 30 percent for the average discontinuation. The marginal cost ratio, which relates marginal costs of cases absorbed in surrounding hospitals to the average costs in those hospitals, is estimated as 87 percent in the base case. The model was applied to the discontinuation of all inpatient services in the 75-bed Chelsea Memorial Hospital, near Boston, Massachusetts, using 1976 data. As the precise value of key parameters is uncertain, sensitivity analysis was used to explore a range of values. The most likely result is a small increase ($120,000) in the area's annual inpatient hospital costs, because many patients are referred to more costly teaching hospitals. A similar situation may arise with other urban closures. For service discontinuations to generate savings, recipient hospitals must be low in costs, the outflow rate must be large, and the marginal cost ratio must be low. PMID:6668181

  12. Adverse mood effects of combined oral contraceptives in relation to personality traits.

    PubMed

    Borgström, Anna; Odlind, Viveca; Ekselius, Lisa; Sundström-Poromaa, Inger

    2008-12-01

    Mood symptoms, such as depressed mood, anxiety and increased irritability, remain one of the major reasons for discontinuation of combined oral contraceptive (COC) pills. The aim of this study was to compare personality traits in women with ongoing or previous use of COCs and different experiences from these compounds with respect to adverse mood symptoms. Thirty women currently on COCs with no reports of adverse mood symptoms, 28 women currently on COCs and experiencing mood-related side effects, 27 women who had discontinued COC use for reasons other than adverse mood symptoms and 33 women who had discontinued COC use due to adverse mood effects were included. All participants were asked to fill out the Swedish universities Scales of Personality (SSP) to assess different personality traits. The women who were experiencing mood-related side effects on their current COC use exhibited higher scores on the somatic anxiety and stress susceptibility traits as compared to the women who did not experience any mood-related side effects from their current COCs. Women who had discontinued COC treatment because of adverse mood effects had higher scores of detachment and mistrust compared to women who had discontinued COC for reasons unrelated to mood effects. Higher scores on specific personality traits such as somatic anxiety and stress susceptibility are found in women with ongoing experience of adverse mood symptoms from COC. Higher scores of mistrust and detachment are more common among women who have discontinued COC treatment due to adverse mood effects.

  13. Using EHR Data to Detect Prescribing Errors in Rapidly Discontinued Medication Orders.

    PubMed

    Burlison, Jonathan D; McDaniel, Robert B; Baker, Donald K; Hasan, Murad; Robertson, Jennifer J; Howard, Scott C; Hoffman, James M

    2018-01-01

    Previous research developed a new method for locating prescribing errors in rapidly discontinued electronic medication orders. Although effective, the prospective design of that research hinders its feasibility for regular use. Our objectives were to assess a method to retrospectively detect prescribing errors, to characterize the identified errors, and to identify potential improvement opportunities. Electronically submitted medication orders from 28 randomly selected days that were discontinued within 120 minutes of submission were reviewed and categorized as most likely errors, nonerrors, or not enough information to determine status. Identified errors were evaluated by amount of time elapsed from original submission to discontinuation, error type, staff position, and potential clinical significance. Pearson's chi-square test was used to compare rates of errors across prescriber types. In all, 147 errors were identified in 305 medication orders. The method was most effective for orders that were discontinued within 90 minutes. Duplicate orders were most common; physicians in training had the highest error rate ( p  < 0.001), and 24 errors were potentially clinically significant. None of the errors were voluntarily reported. It is possible to identify prescribing errors in rapidly discontinued medication orders by using retrospective methods that do not require interrupting prescribers to discuss order details. Future research could validate our methods in different clinical settings. Regular use of this measure could help determine the causes of prescribing errors, track performance, and identify and evaluate interventions to improve prescribing systems and processes. Schattauer GmbH Stuttgart.

  14. Matched Interface and Boundary Method for Elasticity Interface Problems

    PubMed Central

    Wang, Bao; Xia, Kelin; Wei, Guo-Wei

    2015-01-01

    Elasticity theory is an important component of continuum mechanics and has had widely spread applications in science and engineering. Material interfaces are ubiquity in nature and man-made devices, and often give rise to discontinuous coefficients in the governing elasticity equations. In this work, the matched interface and boundary (MIB) method is developed to address elasticity interface problems. Linear elasticity theory for both isotropic homogeneous and inhomogeneous media is employed. In our approach, Lamé’s parameters can have jumps across the interface and are allowed to be position dependent in modeling isotropic inhomogeneous material. Both strong discontinuity, i.e., discontinuous solution, and weak discontinuity, namely, discontinuous derivatives of the solution, are considered in the present study. In the proposed method, fictitious values are utilized so that the standard central finite different schemes can be employed regardless of the interface. Interface jump conditions are enforced on the interface, which in turn, accurately determines fictitious values. We design new MIB schemes to account for complex interface geometries. In particular, the cross derivatives in the elasticity equations are difficult to handle for complex interface geometries. We propose secondary fictitious values and construct geometry based interpolation schemes to overcome this difficulty. Numerous analytical examples are used to validate the accuracy, convergence and robustness of the present MIB method for elasticity interface problems with both small and large curvatures, strong and weak discontinuities, and constant and variable coefficients. Numerical tests indicate second order accuracy in both L∞ and L2 norms. PMID:25914439

  15. The use of discontinuities and functional groups to assess relative resilience in complex systems

    USGS Publications Warehouse

    Allen, Craig R.; Gunderson, Lance; Johnson, A.R.

    2005-01-01

    It is evident when the resilience of a system has been exceeded and the system qualitatively changed. However, it is not clear how to measure resilience in a system prior to the demonstration that the capacity for resilient response has been exceeded. We argue that self-organizing human and natural systems are structured by a relatively small set of processes operating across scales in time and space. These structuring processes should generate a discontinuous distribution of structures and frequencies, where discontinuities mark the transition from one scale to another. Resilience is not driven by the identity of elements of a system, but rather by the functions those elements provide, and their distribution within and across scales. A self-organizing system that is resilient should maintain patterns of function within and across scales despite the turnover of specific elements (for example, species, cities). However, the loss of functions, or a decrease in functional representation at certain scales will decrease system resilience. It follows that some distributions of function should be more resilient than others. We propose that the determination of discontinuities, and the quantification of function both within and across scales, produce relative measures of resilience in ecological and other systems. We describe a set of methods to assess the relative resilience of a system based upon the determination of discontinuities and the quantification of the distribution of functions in relation to those discontinuities. ?? 2005 Springer Science+Business Media, Inc.

  16. The impact of continuity editing in narrative film on event segmentation.

    PubMed

    Magliano, Joseph P; Zacks, Jeffrey M

    2011-01-01

    Filmmakers use continuity editing to engender a sense of situational continuity or discontinuity at editing boundaries. The goal of this study was to assess the impact of continuity editing on how people perceive the structure of events in a narrative film and to identify brain networks that are associated with the processing of different types of continuity editing boundaries. Participants viewed a commercially produced film and segmented it into meaningful events, while brain activity was recorded with functional magnetic resonance imaging (MRI). We identified three degrees of continuity that can occur at editing locations: edits that are continuous in space, time, and action; edits that are discontinuous in space or time but continuous in action; and edits that are discontinuous in action as well as space or time. Discontinuities in action had the biggest impact on behavioral event segmentation, and discontinuities in space and time had minor effects. Edits were associated with large transient increases in early visual areas. Spatial-temporal changes and action changes produced strikingly different patterns of transient change, and they provided evidence that specialized mechanisms in higher order perceptual processing regions are engaged to maintain continuity of action in the face of spatiotemporal discontinuities. These results suggest that commercial film editing is shaped to support the comprehension of meaningful events that bridge breaks in low-level visual continuity, and even breaks in continuity of spatial and temporal location. Copyright © 2011 Cognitive Science Society, Inc.

  17. Safety and Benefit of Discontinuing Statin Therapy in the Setting of Advanced, Life-Limiting Illness

    PubMed Central

    Kutner, Jean S.; Blatchford, Patrick J.; Taylor, Don H.; Ritchie, Christine S.; Bull, Janet H.; Fairclough, Diane L.; Hanson, Laura C.; LeBlanc, Thomas W.; Samsa, Greg P.; Wolf, Steven; Aziz, Noreen M.; Currow, David C.; Ferrell, Betty; Wagner-Johnston, Nina; Zafar, S. Yousuf; Cleary, James F.; Dev, Sandesh; Goode, Patricia S.; Kamal, Arif H.; Kassner, Cordt; Kvale, Elizabeth A.; McCallum, Janelle G.; Ogunseitan, Adeboye B.; Pantilat, Steven Z.; Portenoy, Russell K.; Prince-Paul, Maryjo; Sloan, Jeff A.; Swetz, Keith M.; Von Gunten, Charles F.; Abernethy, Amy P.

    2015-01-01

    IMPORTANCE For patients with limited prognosis, some medication risks may outweigh the benefits, particularly when benefits take years to accrue; statins are one example. Data are lacking regarding the risks and benefits of discontinuing statin therapy for patients with limited life expectancy. OBJECTIVE To evaluate the safety, clinical, and cost impact of discontinuing statin medications for patients in the palliative care setting. DESIGN, SETTING, AND PARTICIPANTS This was a multicenter, parallel-group, unblinded, pragmatic clinical trial. Eligibility included adults with an estimated life expectancy of between 1 month and 1 year, statin therapy for 3 months or more for primary or secondary prevention of cardiovascular disease, recent deterioration in functional status, and no recent active cardiovascular disease. Participants were randomized to either discontinue or continue statin therapy and were monitored monthly for up to 1 year. The study was conducted from June 3, 2011, to May 2, 2013. All analyses were performed using an intent-to-treat approach. INTERVENTIONS Statin therapy was withdrawn from eligible patients who were randomized to the discontinuation group. Patients in the continuation group continued to receive statins. MAIN OUTCOMES AND MEASURES Outcomes included death within 60 days (primary outcome), survival, cardiovascular events, performance status, quality of life (QOL), symptoms, number of nonstatin medications, and cost savings. RESULTS A total of 381 patients were enrolled; 189 of these were randomized to discontinue statins, and 192 were randomized to continue therapy. Mean (SD) age was 74.1 (11.6) years, 22.0% of the participants were cognitively impaired, and 48.8% had cancer. The proportion of participants in the discontinuation vs continuation groups who died within 60 days was not significantly different (23.8% vs 20.3%; 90% CI, −3.5% to 10.5%; P = .36) and did not meet the noninferiority end point. Total QOL was better for the group discontinuing statin therapy (mean McGill QOL score, 7.11 vs 6.85; P = .04). Few participants experienced cardiovascular events (13 in the discontinuation group vs 11 in the continuation group). Mean cost savings were $3.37 per day and $716 per patient. CONCLUSIONS AND RELEVANCE This pragmatic trial suggests that stopping statin medication therapy is safe and may be associated with benefits including improved QOL, use of fewer nonstatin medications, and a corresponding reduction in medication costs. Thoughtful patient-provider discussions regarding the uncertain benefit and potential decrement in QOL associated with statin continuation in this setting are warranted. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01415934 PMID:25798575

  18. Factors for drop-out psychiatric treatment in patients with substance-related disorders.

    PubMed

    Masaki, Naoko; Toyomasu, Koji

    2010-01-01

    We studied 199 inpatients and outpatients at a public psychiatric hospital to clarify the factors related to outcome following psychiatric care for substance-related disorder (SRD), and we discuss approaches for more effective community care in the future. The percentage of patients who discontinued treatment was 33.7%, suggesting that creation of a follow-up system for continuing outpatient care is an urgent task. Women were 35% more likely higher to discontinue treatment than men. Those with solvent dependence were 12% and 7.32 times more likely, respectively, to discontinue treatment than those with alcohol dependence. Those without complications were 2.24 times more likely than those with complications to discontinue treatment. Divorced patients were 18% and 6.35 times more likely, respectively, to discontinue treatment than married patients. There is insufficient support for patients with solvent dependence, and we observed that patients tended to have little motivation to stop using drugs or alcohol until physical complications occurred. Among the many divorced patients, desire for treatment was weak following breakdown of the family. The present findings suggest the importance of comprehensive efforts to treat substance use disorder at specialist medical institutions.

  19. Periodic synchronization control of discontinuous delayed networks by using extended Filippov-framework.

    PubMed

    Cai, Zuowei; Huang, Lihong; Guo, Zhenyuan; Zhang, Lingling; Wan, Xuting

    2015-08-01

    This paper is concerned with the periodic synchronization problem for a general class of delayed neural networks (DNNs) with discontinuous neuron activation. One of the purposes is to analyze the problem of periodic orbits. To do so, we introduce new tools including inequality techniques and Kakutani's fixed point theorem of set-valued maps to derive the existence of periodic solution. Another purpose is to design a switching state-feedback control for realizing global exponential synchronization of the drive-response network system with periodic coefficients. Unlike the previous works on periodic synchronization of neural network, both the neuron activations and controllers in this paper are allowed to be discontinuous. Moreover, owing to the occurrence of delays in neuron signal, the neural network model is described by the functional differential equation. So we introduce extended Filippov-framework to deal with the basic issues of solutions for discontinuous DNNs. Finally, two examples and simulation experiments are given to illustrate the proposed method and main results which have an important instructional significance in the design of periodic synchronized DNNs circuits involving discontinuous or switching factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Bilateral filter regularized accelerated Demons for improved discontinuity preserving registration.

    PubMed

    Demirović, D; Šerifović-Trbalić, A; Prljača, N; Cattin, Ph C

    2015-03-01

    The classical accelerated Demons algorithm uses Gaussian smoothing to penalize oscillatory motion in the displacement fields during registration. This well known method uses the L2 norm for regularization. Whereas the L2 norm is known for producing well behaving smooth deformation fields it cannot properly deal with discontinuities often seen in the deformation field as the regularizer cannot differentiate between discontinuities and smooth part of motion field. In this paper we propose replacement the Gaussian filter of the accelerated Demons with a bilateral filter. In contrast the bilateral filter not only uses information from displacement field but also from the image intensities. In this way we can smooth the motion field depending on image content as opposed to the classical Gaussian filtering. By proper adjustment of two tunable parameters one can obtain more realistic deformations in a case of discontinuity. The proposed approach was tested on 2D and 3D datasets and showed significant improvements in the Target Registration Error (TRE) for the well known POPI dataset. Despite the increased computational complexity, the improved registration result is justified in particular abdominal data sets where discontinuities often appear due to sliding organ motion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Effect of manufacturing defects on optical performance of discontinuous freeform lenses.

    PubMed

    Wang, Kai; Liu, Sheng; Chen, Fei; Liu, Zongyuan; Luo, Xiaobing

    2009-03-30

    Discontinuous freeform lens based secondary optics are essential to LED illumination systems. Surface roughness and smooth transition between two discrete sub-surfaces are two of the most common manufacturing defects existing in discontinuous freeform lenses. The effects of these two manufacturing defects on the optical performance of two discontinuous freeform lenses were investigated by comparing the experimental results with the numerical simulation results based on Monte Carlo ray trace method. The results demonstrated that manufacturing defects induced surface roughness had small effect on the light output efficiency and the shape of light pattern of the PMMA lens but significantly affected the uniformity of light pattern, which declined from 0.644 to 0.313. The smooth transition surfaces with deviation angle more than 60 degrees existing in the BK7 glass lens, not only reduced the uniformity of light pattern, but also reduced the light output efficiency from 96.9% to 91.0% and heavily deformed the shape of the light pattern. Comparing with the surface roughness, the smooth transition surface had a much more adverse effect on the optical performance of discontinuous freeform lenses. Three methods were suggested to improve the illumination performance according to the analysis and discussion.

  2. Severe multiple sclerosis reactivation during prolonged lymphopenia after dimethyl fumarate discontinuation.

    PubMed

    Zecca, C; Antozzi, C G; Torri Clerici, V; Ferrazzini, M; Mantegazza, R E; Rossi, S; Gobbi, C

    2018-06-01

    Delayed-release dimethyl fumarate (DMF) treatment can be associated with reduced lymphocyte and leucocyte counts, which might persist after DMF discontinuation. We report the case of a patient with severe disease reactivation despite prolonged lymphopenia after DMF discontinuation. We describe the frequency and impact of prolonged lymphopenia after DMF discontinuation at two tertiary MS centres. A 36-year-old female patient with multiple sclerosis was switched to DMF after 14 years of treatment with interferon beta-1a. DMF was suspended after 4 months because of persistent lymphopenia for 3 months. Six months later, the patient had a severe relapse with multiple enhancing brain lesions at MRI although lymphopenia was still persistent. Haematological assessment excluded other causes of lymphopenia, which was evaluated as a probable iatrogenic complication of DMF. The patient was treated with i.v. methylprednisolone 1 gr daily for 3 days with clinical recovery. Prolonged lymphopenia after DMT discontinuation does not protect against disease reactivation. Starting a new immune therapy should be balanced against the option of a "wait and see." A different immunotherapeutic strategy such as an anti-B therapeutic approach could be considered. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Parents’ Subjective Assessment of Effects of Antiepileptic Drug Discontinuation

    PubMed Central

    Kim, Gun-Ha; Byeon, Jung Hye; Eun, So-Hee; Eun, Baik-Lin

    2015-01-01

    Background and Purpose: Many parents express worries about potential negative side effects of antiepileptic drugs (AED) on cognition, behavior, mood, and academic achievement. We aimed to evaluate parents’ subjective feelings about cognitive or behavioral changes in their children and their quality of life after antiepileptic drug (AED) discontinuation. Methods: A modified questionnaire based on the Korean-Quality of Life in Childhood Epilepsy and the Korean-Child Behavior Checklist was answered by parents whose children were seizure-free over the course of 1 month after AED discontinuation. All children were seizure-free for at least 2 years before AED withdrawal. Results: Fifty-eight eligible patients (mean age, 14.1 ± 4.5 years) were examined. Except valproate in cognition (p = 0.03), parents did not feel significant change after discontinuation of different drugs. They felt improvement of behavior in generalized epilepsy (p = 0.04) and better quality of life in children less than 6 year of age at diagnosis of epilepsy (p = 0.02). Conclusions: We propose that factors such as earlier age at diagnosis of epilepsy or type of epilepsy might influence parents’ subjective feelings about their children’s well-being after drug discontinuation, rather than the drug itself. PMID:26157667

  4. AED discontinuation may be dangerous for seizure-free patients.

    PubMed

    Schmidt, Dieter

    2011-02-01

    Despite its benefits, stopping antiepileptic drugs (AEDs) in seizure-free patients is associated with several risks. AED discontinuation doubles the risk of seizure recurrence for up to 2 years compared with continued treatment. On average, one in three patients has a seizure recurrence, though the range can go up to 66% (34%, range 12-66%, 95% CI: 27-43). Furthermore, the outcome of treating a seizure recurrence in patients who have been seizure-free for years is surprisingly poor in some patients. Although the long-term prognosis is not worsened by drug discontinuation, one in five patients does not re-enter remission and for some patients, it may take several years to become seizure-free again. The risk of seizure recurrence is particularly high for those with juvenile myoclonic epilepsy and symptomatic focal epilepsy, the most frequent epilepsies in adults. Seizure-recurrence may have devastating, medical, psychological and social consequences for the individual, for example injury, loss of self-esteem, unemployment and losing a driver's license. Discontinuation should be avoided in patients with a high risk of seizure recurrence. Given these risks, patients will ultimately have to decide themselves whether they wish to discontinue drug treatment after full informed consent.

  5. Preferred flavors and reasons for e-cigarette use and discontinued use among never, current, and former smokers.

    PubMed

    Berg, Carla J

    2016-03-01

    To compare e-cigarette flavors preferred and reasons for use and discontinued use across never, current, and former e-cigarette users and cigarette smokers. We recruited 1567 participants aged 18-34 years through Facebook ads targeting tobacco users and nonusers in August 2014 to complete an online survey. We assessed tobacco use, preferred flavors, and reasons for e-cigarette use and discontinued use. Our sample was 49 % male, 87 % White; 56 % current cigarette smokers; and 53 % e-cigarette users. Current e-cigarette users used an average of 20.9 days in the past 30 (SD = 11.7) and 55.2 puffs/day (SD = 37.3). Compared to never and current smokers, former smokers used e-cigarettes more frequently (p's <0.001). Among users and nonusers, the most preferred was fruit flavors, and the most commonly reported reason for e-cigarette use was "they might be less harmful than cigarettes". The most endorsed reason for discontinued e-cigarette use was "using other tobacco products instead". Never, current, and former smokers had distinct reasons for e-cigarette use and discontinued use and differed in flavor preferences. Regulating marketing and flavors may impact e-cigarette uptake by young adults.

  6. A systematic review of discontinued trials suggested that most reasons for recruitment failure were preventable.

    PubMed

    Briel, Matthias; Olu, Kelechi Kalu; von Elm, Erik; Kasenda, Benjamin; Alturki, Reem; Agarwal, Arnav; Bhatnagar, Neera; Schandelmaier, Stefan

    2016-12-01

    To collect and classify reported reasons for recruitment failure in discontinued randomized controlled trials (RCTs) and to assess reporting quality. We systematically searched MEDLINE and EMBASE (2010-2014) and a previous cohort of RCTs for published RCTs reporting trial discontinuation due to poor recruitment. Teams of two investigators selected eligible RCTs working independently and extracted information using standardized forms. We used an iterative approach to classify reasons for poor recruitment. We included 172 RCTs discontinued due to poor recruitment (including 26 conference abstracts and 63 industry-funded RCTs). Of those, 131 (76%) reported one or more reasons for discontinuation due to poor recruitment. We identified 28 different reasons for recruitment failure; most frequently mentioned were overestimation of prevalence of eligible participants and prejudiced views of recruiters and participants on trial interventions. Few RCTs reported relevant details about the recruitment process such as how eligible participants were identified, the number of patients assessed for eligibility, and who actually recruited participants. Our classification could serve as a checklist to assist investigators in the planning of RCTs. Most reasons for recruitment failure seem preventable with a pilot study that applies the planned informed consent procedure. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Continuity Conditions on Schrodinger Wave Functions at Discontinuities of the Potential.

    ERIC Educational Resources Information Center

    Branson, David

    1979-01-01

    Several standard arguments which attempt to show that the wave function and its derivative must be continuous across jump discontinuities of the potential are reviewed and their defects discussed. (Author/HM)

  8. Regularization of discontinuous foliations: Blowing up and sliding conditions via Fenichel theory

    NASA Astrophysics Data System (ADS)

    Panazzolo, Daniel; da Silva, Paulo R.

    2017-12-01

    We study the regularization of an oriented 1-foliation F on M ∖ Σ where M is a smooth manifold and Σ ⊂ M is a closed subset, which can be interpreted as the discontinuity locus of F. In the spirit of Filippov's work, we define a sliding and sewing dynamics on the discontinuity locus Σ as some sort of limit of the dynamics of a nearby smooth 1-foliation and obtain conditions to identify whether a point belongs to the sliding or sewing regions.

  9. Finite-time robust stabilization of uncertain delayed neural networks with discontinuous activations via delayed feedback control.

    PubMed

    Wang, Leimin; Shen, Yi; Sheng, Yin

    2016-04-01

    This paper is concerned with the finite-time robust stabilization of delayed neural networks (DNNs) in the presence of discontinuous activations and parameter uncertainties. By using the nonsmooth analysis and control theory, a delayed controller is designed to realize the finite-time robust stabilization of DNNs with discontinuous activations and parameter uncertainties, and the upper bound of the settling time functional for stabilization is estimated. Finally, two examples are provided to demonstrate the effectiveness of the theoretical results. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Observations of seismic anisotropy above/below D" discontinuity and its mineral physics interpretation

    NASA Astrophysics Data System (ADS)

    Usui, Y.; Tsuchiya, T.

    2011-12-01

    Many studies have reported a VSV < VSH anisotropy in various places of the D" layer. However, the depth distribution of the anisotropy is still unclear because the anisotropy has not been investigated above the D" layer. Here, to get a large number of data sets, we used seismic data recorded by new five broad-band stations at East Antarctica. Then we carefully analyzed the shear wave splitting focusing above the D" layer beneath the Antarctic Ocean. Most of the data showed that SH waves arrive earlier than SV waves. We also found that shear wave splitting occurs even above the D" discontinuity. Although the lattice preferred orientation (LPO) of MgSiO3 post-perovskite (PPv) is now thought to be the major source of anisotropy below the discontinuity, this strongly suggests that the anisotropy is caused not only by the PPv phase. The root mean square minimization using seismic waveform modeling has been performed to construct a new transverse isotropic shear wave velocity model. The obtained velocity model has a 2.0 % velocity discontinuity at 2500 km for VSH and undetectable discontinuity for VSV. The anisotropy is estimated to be about 0.5% and 2.5% above and below the discontinuity, respectively. Since perovskite (Pv) and MgO are expected as the primary lower mantle phases and also anisotropic, they could be a source of the anisotropy. However deformation mechanisms of the minerals under high-P,T condition are still under debate. In order to clarify the origin of the anisotropy above/below the discontinuity, we examined the elastic anisotropy of two phase polycrystalline aggregates (Pv + MgO) and (PPv + MgO). We modeled the anisotropy in several different LPO directions with different degree. Results suggest that transversely isotropic aggregate (TIA) of MgO[100] in two phase aggregates (Pv + MgO) reproduces the anisotropy above the discontinuity. This is consistent with a (100) slip plane determined by experiments [Karato, 1998]. Since this system corresponds to TIA of MgO with [100] oriented vertically, the MgO LPO model could explain the anisotropy above the discontinuity. On the other hand, we found that TIA of PPv[001] in the aggregates (PPv + MgO) can explain the anisotropy below the discontinuity. Recent deformation experiment [Miyagi et al., 2010] and theoretical calculation [Metsue and Tsuchiya, 2011] suggest that the deformation texture of PPv is dominated by the (001) slip plane under the lowermost mantle condition. This slip system can make the TIA of PPv with [001] oriented vertically under the stressed condition. Therefore, the TIA of PPv[001] could be a main cause of the anisotropy in the D" layer. The LPO pattern is very limited to explain the observation. The VSV < VSH anisotropy could be caused by horizontal shear in the lowermost mantle. Thus, the shear stress may exist even above D" layer. Research supported by the Ehime Univ. G-COE program "Deep Earth Mineralogy".

  11. Effect of discontinuation of antihypertensive medication on orthostatic hypotension in older persons with mild cognitive impairment: the DANTE Study Leiden.

    PubMed

    Moonen, Justine E F; Foster-Dingley, Jessica C; de Ruijter, Wouter; van der Grond, Jeroen; de Craen, Anton J M; van der Mast, Roos C

    2016-03-01

    the relationship between antihypertensive medication and orthostatic hypotension in older persons remains ambiguous, due to conflicting observational evidence and lack of data of clinical trials. to assess the effect of discontinuation of antihypertensive medication on orthostatic hypotension in older persons with mild cognitive impairment. a total of 162 participants with orthostatic hypotension were selected from the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study. This randomised clinical trial included community-dwelling participants aged ≥75 years, with mild cognitive impairment, using antihypertensive medication and without serious cardiovascular disease. Participants were randomised to discontinuation or continuation of antihypertensive treatment (ratio 1:1). Orthostatic hypotension was defined as a drop of at least 20 mmHg in systolic blood pressure and/or 10 mmHg in diastolic blood pressure on standing from a seated position. Outcome was the absence of orthostatic hypotension at 4-month follow-up. Relative risks (RR) were calculated by intention-to-treat and per-protocol analyses. at follow-up, according to intention-to-treat analyses, of the 86 persons assigned to discontinuation of antihypertensive medication, 43 (50%) were free from orthostatic hypotension, compared with 29 (38%) of the 76 persons assigned to continuation of medication [RR 1.31 (95% confidence interval (CI) 0.92-1.87); P = 0.13]. Per-protocol analysis showed that recovery from orthostatic hypotension was significantly higher in persons who completely discontinued all antihypertensive medication (61%) compared with the continuation group (38%) [RR 1.60 (95% CI 1.10-2.31); P = 0.01]. in older persons with mild cognitive impairment and orthostatic hypotension receiving antihypertensive medication, discontinuation of antihypertensive medication may increase the probability of recovery from orthostatic hypotension. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Potentially disruptive life events: what are the immediate impacts on chronic disease management? A case-crossover analysis.

    PubMed

    Lauffenburger, Julie C; Gagne, Joshua J; Song, Zirui; Brill, Gregory; Choudhry, Niteesh K

    2016-08-04

    To explore the association between unexpected potentially disruptive life events in a patient or family member that may challenge an individual's ability to take medications as prescribed and the discontinuation of evidence-based medications for common, chronic conditions. Understanding the relationship between medication adherence and life stressors, especially those that can be identified using administrative data, may help identify patients at risk of non-adherence. Observational self-controlled case-crossover design. Individuals in a nationally representative US commercial health insurance database. Adult individuals who initiated an oral hypoglycaemic, antihypertensive and/or statin and subsequently stopped the medication for ≥90 days. Potentially disruptive life events among patients and their family members measured in the 30 days just before the medication was discontinued ('hazard period') compared with the 30 days before this period ('control period'). These events included personal injury, hospitalisation, emergency room visits, changes in insurance coverage, acute stress or acute anxiety. Among the 326 519 patients meeting study criteria who discontinued their chronic disease medications, 88 896 (27.2%) experienced at least one potentially disruptive life event. Newly experiencing an injury (OR: 1.26, 95% CI 1.12 to 1.42), an emergency room visit (OR: 1.19, 95% CI 1.13 to 1.26) and acute stress (OR: 1.19, 95% CI 1.08 to 1.31) were associated with discontinuation. Life events among patients' family members did not appear to be associated with medication discontinuation or occurred less frequently just prior to discontinuation. Potentially disruptive life events among individuals identified using routinely collected claims data are associated with discontinuation of chronic disease medications. Awareness of these events may help providers or payers identify patients at risk of non-adherence to maximise patient outcomes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  13. Global seismic data reveal little water in the mantle transition zone

    NASA Astrophysics Data System (ADS)

    Houser, C.

    2016-08-01

    Knowledge of the Earth's present water content is necessary to constrain the amount of water and other volatiles the Earth acquired during its formation and the amount that is cycled back into the interior from the surface. This study compares 410 and 660 km discontinuity depth with shear wave tomography within the mantle transition zone to identify regions with seismic signals consistent with water. The depth of the 410 and 660 km discontinuities is determined from a large updated dataset of SS-S410S and SS-S660S differential travel times, known as SS precursors. The discontinuity depths measured from binning and stacking the SS precursor data are then compared to the shear velocity model HMSL-S06 in the transition zone. Mapping all the possible combinations, very few locations match the predictions from mineral physics for the effects of water on discontinuity depth and shear velocity. The predictions, although not yet measured at actual transition zone temperatures and pressures, are a shallow 410 km discontinuity, a deep 660 km discontinuity, and a slow shear velocity. Only 8% of the bins with high-quality data are consistent with these predictions, and the calculated average water content within these bins is around 0.6 wt.%. A few isolated locations have patterns of velocity/topography that are consistent with water, while there are large regional-scale patterns consistent with cold/hot temperature anomalies. Combining this global analysis of long period seismic data and the current mineral physics predictions for water in transition zone minerals, I find that the mantle transition zone is generally dry, containing less than one Earth ocean of water. Although subduction zones could be locally hydrated, the combined discontinuity and velocity data show no evidence that wadsleyite or ringwoodite have been globally hydrated by subduction or initial Earth conditions.

  14. Imatinib discontinuation in chronic myeloid leukaemia patients with undetectable BCR-ABL transcript level: A systematic review and a meta-analysis.

    PubMed

    Campiotti, Leonardo; Suter, Matteo Basilio; Guasti, Luigina; Piazza, Rocco; Gambacorti-Passerini, Carlo; Grandi, Anna Maria; Squizzato, Alessandro

    2017-05-01

    Tyrosine kinase inhibitors (TKIs) are the cornerstones of treatment for patients with chronic myeloid leukaemia (CML). In recent years, several studies were conducted to evaluate the safety of TKIs discontinuation. We performed a systematic review of the literature to determine the incidence of CML relapse, to identify possible factors relapse rates and to evaluate the long-term safety in CML patients with stable undetectable BCR-ABL transcript level who discontinued TKIs. Studies evaluating TKIs discontinuation in CML patients with undetectable BCR-ABL transcript level were identified by electronic search of MEDLINE and EMBASE database until May 2015. Weighted mean proportion and 95% confidence intervals (CIs) of CML relapse was calculated using a fixed-effects and a random-effects model. Statistical heterogeneity was evaluated using the I 2 statistic. Fifteen cohort studies, for a total of 509 patients, were included. Nine studies were at low-risk of bias. All 15 studies included only patients on imatinib. Overall weighted mean molecular relapse rate of CML was 51% (95% CI 44-58%; I 2  = 55). Weighted mean molecular relapse rate at 6-month follow-up was 41% (95% CI 32-51%; I 2  = 78). Eighty percent of molecular relapses occurred in the first 6 months. All 509 patients were alive at 2-year follow-up and only one patient (0.8%, 95% CI 0.2-1.8%; I 2  = 0) has progressed to a blastic crisis. Our findings suggest that imatinib discontinuation is feasible for the majority of CML patients with stable undetectable BCR-ABL transcript level. Approximately 50% of patients remain therapy-free after imatinib discontinuation. Restarting TKIs therapy was followed by a very high rate of molecular response, with no deaths 2 years after discontinuation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Differential Drug Survival of Second-Line Biologic Therapies in Patients with Psoriasis: Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

    PubMed

    Iskandar, Ireny Y K; Warren, Richard B; Lunt, Mark; Mason, Kayleigh J; Evans, Ian; McElhone, Kathleen; Smith, Catherine H; Reynolds, Nick J; Ashcroft, Darren M; Griffiths, Christopher E M

    2018-04-01

    Little is known about the drug survival of second-line biologic therapies for psoriasis in routine clinical practice. We assessed drug survival of second-line biologic therapies and estimated the risk of recurrent discontinuation due to adverse events or ineffectiveness in patients with psoriasis who had failed a first biologic therapy and switched to a second in a large, multicenter pharmacovigilance registry (n = 1,239; adalimumab, n = 538; etanercept, n = 104; ustekinumab, n = 597). The overall drug survival rate in the first year after switching was 77% (95% confidence interval = 74-79%), falling to 58% (55-61%) in the third year. Female sex, multiple comorbidities, concomitant therapy with cyclosporine, and a high Psoriasis Area and Severity Index at switching to the second-line biologic therapy were predictors of overall discontinuation (multivariable Cox proportional hazard model). Compared to adalimumab, patients receiving etanercept were more likely to discontinue therapy (hazard ratio = 1.87, 95% confidence interval = 1.24-2.83), whereas patients receiving ustekinumab were more likely to persist (hazard ratio = 0.46; 95% confidence interval = 0.33-0.64). Discontinuation of the first biologic therapy because of adverse events was associated with an increased rate of second drug discontinuation because of adverse events (hazard ratio = 2.55; 95% confidence interval = 1.50-4.32). In conclusion, drug survival rates differed among biologic therapies and decreased over time; second-line discontinuation because of adverse events was more common among those who discontinued first-line treatment for this reason. The results of this study should support clinical decision making when choosing second-line biologic therapy for patients with psoriasis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. A Receiver Function Study of Mantle Transition Zone Discontinuities beneath Egypt and Saudi Arabia

    NASA Astrophysics Data System (ADS)

    Liu, K. H.; Mohamed, A. A.; Gao, S. S.; Elsheikh, A. A.; Yu, Y.; Fat-Helbary, R. E.

    2014-12-01

    The dramatic asymmetry in terms of surface elevation, Cenozoic volcanisms, and earthquake activity across the Red Sea is an enigmatic issue in global tectonics, partially due to the unavailability of broadband seismic data on the African plate adjacent to the Red Sea. Here we report the first results from a receiver function study of the mantle transition zone (MTZ) discontinuities using data from the Egyptian National Seismic Network, and compare the resulting depths of the 410 and 660 km discontinuities (d410 and d660) with those observed on the Arabian side. Results using more than 6000 P-to-S receiver functions recorded at 49 broadband seismic stations in Egypt, Saudi Arabia and adjacent areas show that when the IASP91 Earth model is used for time-to-depth conversion, the resulting depth of the discontinuities increases systematically toward the axis of the Afro-Arabian Dome (AAD) from both the west and east. Relative to the westernmost area, the maximum depression of the 410-km discontinuity is about 30 km, and that of the 660-km discontinuity is about 45 km. Highly correlated d410 and d660 depths suggest that the observed apparent depth variations are mostly caused by lateral velocity anomalies in the upper mantle, while the 15 km additional depression of the d660 relative to the d410 requires either a colder-than-normal MTZ or the presence of water in the MTZ. We tested several models involving upper mantle and MTZ velocity anomalies and undulations of the MTZ discontinuities due to temperature anomalies and water content, and found that the observed systematic variations can best be explained by a model involving a hydrated MTZ and an upper-mantle low-velocity zone beneath the AAD (Mohamed et al., 2014, doi: 10.1093/gji/ggu284). Models invoking one or more mantle plumes originated from the MTZ or the lower-mantle beneath the study area are not consistent with the observations.

  17. Biomarker-based strategy for early discontinuation of empirical antifungal treatment in critically ill patients: a randomized controlled trial.

    PubMed

    Rouzé, Anahita; Loridant, Séverine; Poissy, Julien; Dervaux, Benoit; Sendid, Boualem; Cornu, Marjorie; Nseir, Saad

    2017-11-01

    The aim of this study was to determine the impact of a biomarker-based strategy on early discontinuation of empirical antifungal treatment. Prospective randomized controlled single-center unblinded study, performed in a mixed ICU. A total of 110 patients were randomly assigned to a strategy in which empirical antifungal treatment duration was determined by (1,3)-β-D-glucan, mannan, and anti-mannan serum assays, performed on day 0 and day 4; or to a routine care strategy, based on international guidelines, which recommend 14 days of treatment. In the biomarker group, early stop recommendation was determined using an algorithm based on the results of biomarkers. The primary outcome was the percentage of survivors discontinuing empirical antifungal treatment early, defined as a discontinuation strictly before day 7. A total of 109 patients were analyzed (one patient withdraw consent). Empirical antifungal treatment was discontinued early in 29 out of 54 patients in the biomarker strategy group, compared with one patient out of 55 in the routine strategy group [54% vs 2%, p < 0.001, OR (95% CI) 62.6 (8.1-486)]. Total duration of antifungal treatment was significantly shorter in the biomarker strategy compared with routine strategy [median (IQR) 6 (4-13) vs 13 (12-14) days, p < 0.0001). No significant difference was found in the percentage of patients with subsequent proven invasive Candida infection, mechanical ventilation-free days, length of ICU stay, cost, and ICU mortality between the two study groups. The use of a biomarker-based strategy increased the percentage of early discontinuation of empirical antifungal treatment among critically ill patients with suspected invasive Candida infection. These results confirm previous findings suggesting that early discontinuation of empirical antifungal treatment had no negative impact on outcome. However, further studies are needed to confirm the safety of this strategy. This trial was registered at ClinicalTrials.gov, NCT02154178.

  18. The challenge of pelvic discontinuity: cup-cage reconstruction does better than conventional cages in mid-term.

    PubMed

    Abolghasemian, M; Tangsaraporn, S; Drexler, M; Barbuto, R; Backstein, D; Safir, O; Kuzyk, P; Gross, A

    2014-02-01

    The use of ilioischial cage reconstruction for pelvic discontinuity has been replaced by the Trabecular Metal (Zimmer, Warsaw, Indiana) cup-cage technique in our institution, due to the unsatisfactory outcome of using a cage alone in this situation. We report the outcome of 26 pelvic discontinuities in 24 patients (20 women and four men, mean age 65 years (44 to 84)) treated by the cup-cage technique at a mean follow-up of 82 months (12 to 113) and compared them with a series of 19 pelvic discontinuities in 19 patients (18 women and one man, mean age 70 years (42 to 86)) treated with a cage at a mean follow-up of 69 months (1 to 170). The clinical and radiological outcomes as well as the survivorship of the groups were compared. In all, four of the cup-cage group (15%) and 13 (68%) of the cage group failed due to septic or aseptic loosening. The seven-year survivorship was 87.2% (95% confidence interval (CI) 71 to 103) for the cup-cage group and 49.9% (95% CI 15 to 84) for the cage-alone group (p = 0.009). There were four major complications in the cup-cage group and nine in the cage group. Radiological union of the discontinuity was found in all successful cases in the cup-cage group and three of the successful cage cases. Three hips in the cup-cage group developed early radiological migration of the components, which stabilised with a successful outcome. Cup-cage reconstruction is a reliable technique for treating pelvic discontinuity in mid-term follow-up and is preferred to ilioischial cage reconstruction. If the continuity of the bone graft at the discontinuity site is not disrupted, early migration of the components does not necessarily result in failure.

  19. Durable Complete Response After Discontinuation of Pembrolizumab in Patients With Metastatic Melanoma.

    PubMed

    Robert, Caroline; Ribas, Antoni; Hamid, Omid; Daud, Adil; Wolchok, Jedd D; Joshua, Anthony M; Hwu, Wen-Jen; Weber, Jeffrey S; Gangadhar, Tara C; Joseph, Richard W; Dronca, Roxana; Patnaik, Amita; Zarour, Hassane; Kefford, Richard; Hersey, Peter; Zhang, Jin; Anderson, James; Diede, Scott J; Ebbinghaus, Scot; Hodi, F Stephen

    2017-12-28

    Purpose Pembrolizumab provides durable antitumor activity in metastatic melanoma, including complete response (CR) in about 15% of patients. Data are limited on potential predictors of CR and patient disposition after pembrolizumab discontinuation after CR. We describe baseline characteristics and long-term follow-up in patients who experienced CR with pembrolizumab in the KEYNOTE-001 study ( ClinicalTrials.gov identifier: NCT01295827). Patients and Methods Patients with ipilimumab-naive or -treated advanced/metastatic melanoma received one of three dose regimens of pembrolizumab. Eligible patients who received pembrolizumab for ≥ 6 months and at least two treatments beyond confirmed CR could discontinue therapy. Response was assessed every 12 weeks by central Response Evaluation Criteria in Solid Tumors version 1.1. For this analysis, CR was defined per investigator assessment, immune-related response criteria, and potential predictors of CR were evaluated using univariate and multivariate analyses. Results Of 655 treated patients, 105 (16.0%) achieved CR after median follow-up of 43 months. At data cutoff, 92 patients (87.6%) had CR, with median follow-up of 30 months from first CR. Fourteen (13.3%) patients continued to receive treatment for a median of ≥ 40 months. Pembrolizumab was discontinued by 91 patients (86.7%), including 67 (63.8%) who proceeded to observation without additional anticancer therapy. The 24-month disease-free survival rate from time of CR was 90.9% in all 105 patients with CR and 89.9% in the 67 patients who discontinued pembrolizumab after CR for observation. Tumor size and programmed death-ligand 1 status were among the baseline factors independently associated with CR by univariate analysis. Conclusion Patients with metastatic melanoma can have durable complete remission after discontinuation of pembrolizumab, and the low incidence of relapse after median follow-up of approximately 2 years from discontinuation provides hope for a cure for some patients. The mechanisms underlying durable CR require further investigation.

  20. Pathogenic Variants in Complement Genes and Risk of Atypical Hemolytic Uremic Syndrome Relapse after Eculizumab Discontinuation.

    PubMed

    Fakhouri, Fadi; Fila, Marc; Provôt, François; Delmas, Yahsou; Barbet, Christelle; Châtelet, Valérie; Rafat, Cédric; Cailliez, Mathilde; Hogan, Julien; Servais, Aude; Karras, Alexandre; Makdassi, Raifah; Louillet, Feriell; Coindre, Jean-Philippe; Rondeau, Eric; Loirat, Chantal; Frémeaux-Bacchi, Véronique

    2017-01-06

    The complement inhibitor eculizumab has dramatically improved the outcome of atypical hemolytic uremic syndrome. However, the optimal duration of eculizumab treatment in atypical hemolytic uremic syndrome remains debated. We report on the French atypical hemolytic uremic syndrome working group's first 2-year experience with eculizumab discontinuation in patients with atypical hemolytic uremic syndrome. Using the French atypical hemolytic uremic syndrome registry database, we retrospectively identified all dialysis-free patients with atypical hemolytic uremic syndrome who discontinued eculizumab between 2010 and 2014 and reviewed their relevant clinical and biologic data. The decision to discontinue eculizumab was made by the clinician in charge of the patient. All patients were closely monitored by regular urine dipsticks and blood tests. Eculizumab was rapidly (24-48 hours) restarted in case of relapse. Among 108 patients treated with eculizumab, 38 patients (nine children and 29 adults) discontinued eculizumab (median treatment duration of 17.5 months). Twenty-one patients (55%) carried novel or rare complement genes variants. Renal recovery under eculizumab was equally good in patients with and those without complement gene variants detected. After a median follow-up of 22 months, 12 patients (31%) experienced atypical hemolytic uremic syndrome relapse. Eight of 11 patients (72%) with complement factor H variants, four of eight patients (50%) with membrane cofactor protein variants, and zero of 16 patients with no rare variant detected relapsed. In relapsing patients, early reintroduction (≤48 hours) of eculizumab led to rapid (<7 days) hematologic remission and a return of serum creatinine to baseline level in a median time of 26 days. At last follow-up, renal function remained unchanged in nonrelapsing and relapsing patients compared with baseline values before eculizumab discontinuation. Pathogenic variants in complement genes were associated with higher risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation. Prospective studies are needed to identify biomarkers predictive of relapse and determine the best strategy of retreatment in relapsing patients. Copyright © 2016 by the American Society of Nephrology.

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