Off-equatorial current-driven instabilities ahead of approaching dipolarization fronts

NASA Astrophysics Data System (ADS)

Zhang, Xu; Angelopoulos, V.; Pritchett, P. L.; Liu, Jiang

2017-05-01

Recent kinetic simulations have revealed that electromagnetic instabilities near the ion gyrofrequency and slightly away from the equatorial plane can be driven by a current parallel to the magnetic field prior to the arrival of dipolarization fronts. Such instabilities are important because of their potential contribution to global electromagnetic energy conversion near dipolarization fronts. Of the several instabilities that may be consistent with such waves, the most notable are the current-driven electromagnetic ion cyclotron instability and the current-driven kink-like instability. To confirm the existence and characteristics of these instabilities, we used observations by two Time History of Events and Macroscale Interactions during Substorms satellites, one near the neutral sheet observing dipolarization fronts and the other at the boundary layer observing precursor waves and currents. We found that such instabilities with monochromatic signatures are rare, but one of the few cases was selected for further study. Two different instabilities, one at about 0.3 Hz and the other at a much lower frequency, 0.02 Hz, were seen in the data from the off-equatorial spacecraft. A parallel current attributed to an electron beam coexisted with the waves. Our instability analysis attributes the higher-frequency instability to a current-driven ion cyclotron instability and the lower frequency instability to a kink-like instability. The current-driven kink-like instability we observed is consistent with the instabilities observed in the simulation. We suggest that the currents needed to excite these low-frequency instabilities are so intense that the associated electron beams are easily thermalized and hence difficult to observe.

Pion and kaon valence-quark parton quasidistributions

NASA Astrophysics Data System (ADS)

Xu, Shu-Sheng; Chang, Lei; Roberts, Craig D.; Zong, Hong-Shi

2018-05-01

Algebraic Ansätze for the Poincaré-covariant Bethe-Salpeter wave functions of the pion and kaon are used to calculate their light-front wave functions, parton distribution amplitudes, parton quasidistribution amplitudes, valence parton distribution functions, and parton quasidistribution functions (PqDFs). The light-front wave functions are broad, concave functions, and the scale of flavor-symmetry violation in the kaon is roughly 15%, being set by the ratio of emergent masses in the s - and u -quark sectors. Parton quasidistribution amplitudes computed with longitudinal momentum Pz=1.75 GeV provide a semiquantitatively accurate representation of the objective parton distribution amplitude, but even with Pz=3 GeV , they cannot provide information about this amplitude's end point behavior. On the valence-quark domain, similar outcomes characterize PqDFs. In this connection, however, the ratio of kaon-to-pion u -quark PqDFs is found to provide a good approximation to the true parton distribution function ratio on 0.4 ≲x ≲0.8 , suggesting that with existing resources computations of ratios of parton quasidistributions can yield results that support empirical comparison.

Characterizing Ion Flows Across a Dipolarization Front

NASA Astrophysics Data System (ADS)

Arnold, H.; Drake, J. F.; Swisdak, M.

2017-12-01

In light of the Magnetospheric Multiscale Mission (MMS) moving to study predominately symmetric magnetic reconnection in the Earth's magnetotail, it is of interest to investigate various methods for determining the relative location of the satellites with respect to the x line or a dipolarization front. We use a 2.5 dimensional PIC simulation to explore the dependence of various characteristics of a front, or flux bundle, on the width of the front in the dawn-dusk direction. In particular, we characterize the ion flow in the x-GSM direction across the front. We find a linear relationship between the width of a front, w, and the maximum velocity of the ion flow in the x-GSM direction, Vxi, for small widths: Vxi/VA=w/di*1/2*(mVA2)/Ti*Bz/Bxwhere m, VA, di, Ti, Bz, and Bx are the ion mass, upstream Alfven speed, ion inertial length, ion temperature, and magnetic fields in the z-GSM and x-GSM directions respectively. However, once the width reaches around 5 di, the relationship gradually approaches the well-known theoretical limit for ion flows, the upstream Alfven speed. Furthermore, we note that there is a reversal in the Hall magnetic field near the current sheet on the positive y-GSM side of the front. This reversal is most likely due to conservation of momentum in the y-GSM direction as the ions accelerate towards the x-GSM direction. This indicates that while the ions are primarily energized in the x-GSM direction by the front, they transfer energy to the electromagnetic fields in the y-GSM direction. The former energy transfer is greater than the latter, but the reversal of the Hall magnetic field drags the frozen-in electrons along with it outside of the front. These simulations should better able researchers to determine the relative location of a satellite crossing a dipolarization front.

Supra Arcade Downflows with XRT Informed by Dipolarization Fronts with THEMIS

NASA Technical Reports Server (NTRS)

Kobelski, Adam; Savage, Sabrina Leah; Malaspina, David

2016-01-01

Magnetic reconnection can rapidly reconfigure the magnetic field of the corona, accelerating plasma through the site of reconnection. Ambiguities due to the nature of remote sensing have complicated the interpretation of observations of the inflowing and outflowing plasma in reconnecting regions. In particular, the interpretation of sunward moving density depletions above flare arcades (known as Supra Arcade Downflows - SADs) is still debated. Hinode/XRT has provided a wealth of observations for SADs and helped inform our current understanding of these structures. SADs have been interpreted as wakes behind newly reconnected and outflowing loops (Supra Arcade Downflowing Loops - SADLs). Models have shown the plausibility of this interpretation, though this interpretation has not yet been fully accepted. We present here observations of newly reconnected outflowing loops observed via in situ instruments in the magnetosphere. These observations, provided by five THEMIS spacecraft, show that around retracting loops (dipolarization fronts in this context) similar dynamic temperature and density structures are found as seen in SADs. We compare data from multiple SADs and dipolarization fronts to show that the observational signatures implied in the corona can be directly observed in similar plasma regimes in the magnetosphere, strongly favoring the interpretation of SADs as wakes behind retracting loops.

Energy conversion and dissipation at dipolarization fronts: Theory, modeling and MMS observations

NASA Astrophysics Data System (ADS)

Sitnov, M. I.; Motoba, T.; Merkin, V. G.; Ohtani, S.; Cohen, I. J.; Mauk, B.; Vines, S. K.; Anderson, B. J.; Moore, T. E.; Torbert, R. B.; Giles, B. L.; Burch, J. L.

2017-12-01

Magnetic reconnection is one of the most important energy conversion mechanisms in space plasmas. In the classical picture it converts the energy of antiparallel magnetic fields into the kinetic and thermal energy of accelerated plasma particles in reconnection exhausts. It also involves energy dissipation near the X-line. This classical picture may be substantially modified in real space plasma configurations, such as the dayside magnetopause and the magnetotail. In particular, in the magnetotail the flows of accelerated particles may be strongly asymmetric along the tail with the domination of earthward flows. At the same time, strong energy conversion and even dissipation may occur away from the X-line, in particular, at dipolarization fronts. Here we present a theoretical picture of spontaneous magnetotail reconnection based on 3-D PIC simulations with the focus on plasma bulk flows, energy conversion and dissipation. This picture is compared with some observations from the MMS tail season. An important finding from these observations is that dipolarizations fronts may not only be regions of the total energy conversion with jE>0, but they may also be the sites of energy dissipation, both positive (jE'>0, E' is the electric field E in the system moving with one of the plasma species) and negative (jE'<0). Observations are further compared with theory and modeling that predict the specific location and sign of the energy dissipation at fronts depending on their evolution phase (e.g., formation, propagation, braking).

Dipolarization Fronts from Reconnection Onset

NASA Astrophysics Data System (ADS)

Sitnov, M. I.; Swisdak, M. M.; Merkin, V. G.; Buzulukova, N.; Moore, T. E.

2012-12-01

Dipolarization fronts observed in the magnetotail are often viewed as signatures of bursty magnetic reconnection. However, until recently spontaneous reconnection was considered to be fully prohibited in the magnetotail geometry because of the linear stability of the ion tearing mode. Recent theoretical studies showed that spontaneous reconnection could be possible in the magnetotail geometries with the accumulation of magnetic flux at the tailward end of the thin current sheet, a distinctive feature of the magnetotail prior to substorm onset. That result was confirmed by open-boundary full-particle simulations of 2D current sheet equilibria, where two magnetotails were separated by an equilibrium X-line and weak external electric field was imposed to nudge the system toward the instability threshold. To investigate the roles of the equilibrium X-line, driving electric field and other parameters in the reconnection onset process we performed a set of 2D PIC runs with different initial settings. The investigated parameter space includes the critical current sheet thickness, flux tube volume per unit magnetic flux and the north-south component of the magnetic field. Such an investigation is critically important for the implementation of kinetic reconnection onset criteria into global MHD codes. The results are compared with Geotail visualization of the magnetotail during substorms, as well as Cluster and THEMIS observations of dipolarization fronts.

Rapid acceleration of protons upstream of earthward propagating dipolarization fronts

PubMed Central

Ukhorskiy, AY; Sitnov, MI; Merkin, VG; Artemyev, AV

2013-01-01

[1] Transport and acceleration of ions in the magnetotail largely occurs in the form of discrete impulsive events associated with a steep increase of the tail magnetic field normal to the neutral plane (Bz), which are referred to as dipolarization fronts. The goal of this paper is to investigate how protons initially located upstream of earthward moving fronts are accelerated at their encounter. According to our analytical analysis and simplified two-dimensional test-particle simulations of equatorially mirroring particles, there are two regimes of proton acceleration: trapping and quasi-trapping, which are realized depending on whether the front is preceded by a negative depletion in Bz. We then use three-dimensional test-particle simulations to investigate how these acceleration processes operate in a realistic magnetotail geometry. For this purpose we construct an analytical model of the front which is superimposed onto the ambient field of the magnetotail. According to our numerical simulations, both trapping and quasi-trapping can produce rapid acceleration of protons by more than an order of magnitude. In the case of trapping, the acceleration levels depend on the amount of time particles stay in phase with the front which is controlled by the magnetic field curvature ahead of the front and the front width. Quasi-trapping does not cause particle scattering out of the equatorial plane. Energization levels in this case are limited by the number of encounters particles have with the front before they get magnetized behind it. PMID:26167430

Supra Arcade Downflows in the Earth's Magnetotail

NASA Astrophysics Data System (ADS)

Kobelski, A.; Savage, S. L.; Malaspina, D.

2017-12-01

Pinpointing the location of a single reconnection event in the corona is difficult due to observational constraints, although features directly resulting from this rapid reconfiguration of the field lines can be observed beyond the reconnection site. One set of such features are outflows in the form of post-reconnection loops, which have been linked to observations of supra-arcade downflows (SADs). SADs appear as sunward-traveling, density-depleted regions above flare arcades that develop during long duration eruptions. The limitations of remote sensing methods inherently results in ambiguities regarding the interpretation of SAD formation. Of particular interest is how these features are related to post-reconnection retracting magnetic field lines. In planetary magnetospheres, similar events to solar flares occur in the form of substorms, where reconnection in the anti-sunward tail of the magnetosphere causes field lines to retract toward the planet. Using data from the Time History of Events and Macroscopic Interactions during Substorms (THEMIS), we compare one particular aspect of substorms, dipolarization fronts, to SADs. Dipolarization fronts are observed as rapid but temporary changes in the magnetic field of the magnetotail plasma sheet into a more potential-like dipolar shape. These dipolarization fronts are believed to be retracting post-reconnection field lines. We combine data sets to show that the while the densities and magnetic fields involved vary greatly between the regimes, the plasma βs and Alfvén speeds are similar. These similarities allow direct comparison between the retracting field lines and their accompanying wakes of rarified plasma observed with THEMIS around the Earth to the observed morphological density depletions visible with XRT and AIA on the Sun. These results are an important source of feedback for models of coronal current sheets.

Supra Arcade Downflows in the Earth's Magnetotail

NASA Technical Reports Server (NTRS)

Kobelski, Adam; Savage, Sabrina L.; Malaspina, David M.

2017-01-01

Pinpointing the location of a single reconnection event in the corona is difficult due to observational constraints, although features directly resulting from this rapid reconfiguration of the field lines can be observed beyond the reconnection site. One set of such features are outflows in the form of post-reconnection loops, which have been linked to observations of supra-arcade downflows (SADs). SADs appear as sunward-traveling, density-depleted regions above flare arcades that develop during long duration eruptions. The limitations of remote sensing methods inherently results in ambiguities regarding the interpretation of SAD formation. Of particular interest is how these features are related to post-reconnection retracting magnetic field lines. In planetary magnetospheres, similar events to solar flares occur in the form of substorms, where reconnection in the anti-sunward tail of the magnetosphere causes field lines to retract toward the planet. Using data from the Time History of Events and Macroscopic Interactions during Substorms (THEMIS), we compare one particular aspect of substorms, dipolarization fronts, to SADs. Dipolarization fronts are observed as rapid but temporary changes in the magnetic field of the magnetotail plasma sheet into a more potential-like dipolar shape. These dipolarization fronts are believed to be retracting post-reconnection field lines. We combine data sets to show that the while the densities and magnetic fields involved vary greatly between the regimes, the plasma betas and Alfvén speeds are similar. These similarities allow direct comparison between the retracting field lines and their accompanying wakes of rarified plasma observed with THEMIS around the Earth to the observed morphological density depletions visible with XRT and AIA on the Sun. These results are an important source of feedback for models of coronal current sheets.

Energetic electron injections and dipolarization events in Mercury's magnetotail: Substorm dynamics

NASA Astrophysics Data System (ADS)

Dewey, R. M.; Slavin, J. A.; Raines, J. M.; Imber, S.; Baker, D. N.; Lawrence, D. J.

2017-12-01

Despite its small size, Mercury's terrestrial-like magnetosphere experiences brief, yet intense, substorm intervals characterized by features similar to at Earth: loading/unloading of the tail lobes with open magnetic flux, dipolarization of the magnetic field at the inner edge of the plasma sheet, and, the focus of this presentation, energetic electron injection. We use the Gamma-Ray Spectrometer's high-time resolution (10 ms) energetic electron measurements to determine the relationship between substorm activity and energetic electron injections coincident with dipolarization fronts in the magnetotail. These dipolarizations were detected on the basis of their rapid ( 2 s) increase in the northward component of the tail magnetic field (ΔBz 30 nT), which typically persists for 10 s. We estimate the typical flow channel to be 0.15 RM, planetary convection speed of 750 km/s, cross-tail potential drop of 7 kV, and flux transport of 0.08 MWb for each dipolarization event, suggesting multiple simultaneous and sequential dipolarizations are required to unload the >1 MWb of magnetic flux typically returned to the dayside magnetosphere during a substorm interval. Indeed, while we observe most dipolarization-injections to be isolated or in small chains of events (i.e., 1-3 events), intervals of sawtooth-like injections with >20 sequential events are also present. The typical separation between dipolarization-injection events is 10 s. Magnetotail dipolarization, in addition to being a powerful source of electron acceleration, also plays a significant role in the substorm process at Mercury.

Broadband high-frequency waves and intermittent energy conversion at dipolarization fronts

NASA Astrophysics Data System (ADS)

Yang, J.; Cao, J.; Fu, H.; Wang, T.; Liu, W.; Yao, Z., Sr.

2017-12-01

Dipolarization front (DF) is a sharp boundary most probably separating the reconnection jet from the background plasma sheet. So far at this boundary, the observed waves are mainly in low-frequency range (e.g., magnetosonic waves and lower hybrid waves). Few high-frequency waves are observed in this region. In this paper, we report the broadband high-frequency wave emissions at the DF. These waves, having frequencies extending from the electron cyclotron frequency fce, up to the electron plasma frequency fpe, could contribute 10% to the in situ measurement of intermittent energy conversion at the DF layer. Their generation may be attributed to electron beams, which are simultaneously observed at the DF as well. Furthermore, we find intermittent energy conversion is primarily to the broadband fluctuations in the lower hybrid frequency range although the net energy conversion is small.

Energetic electron acceleration and injection during dipolarization events in Mercury's magnetotail

NASA Astrophysics Data System (ADS)

Dewey, R. M.; Slavin, J. A.; Raines, J. M.; Baker, D. N.; Lawrence, D. J.

2017-12-01

MESSENGER frequently observed bursts of energetic electrons (>10 keV to 300 keV) within Mercury's miniature terrestrial-like magnetosphere. These bursts are observed most often in the post-midnight sector near the magnetic equator, suggestive of the acceleration and injection of electrons from the magnetotail and their eastward drift about the planet. We use the Gamma-Ray Spectrometer's high-time resolution (10 ms) energetic electron measurements to examine the relationship between energetic electron injections and magnetospheric dynamics in Mercury's magnetotail. We find that these electron injections were observed most frequently in association with magnetic field dipolarization. Between March 2013 and April 2015, we identified 2976 magnetotail electron events of which 538 were coincident with the leading edge of a dipolarization event. These dipolarization fronts were detected on the basis of their rapid ( 2 s) increase in the northward component of the tail magnetic field (ΔBz 30 nT), which typically persists for 10 s. We find electrons experience brief, yet intense, betatron and Fermi acceleration during these dipolarization events, reaching energies 160 keV and contributing to nightside precipitation. Dipolarization events, and subsequently, the electron acceleration associated with them, display a strong dawn-dusk asymmetry, suggestive of a post-midnight maximum in magnetotail reconnection.

Magnetospheric Multiscale Observations of Field-Aligned Currents in the Magnetotail

NASA Astrophysics Data System (ADS)

Strangeway, R. J.; Russell, C. T.; Zhao, C.; Plaschke, F.; Fischer, D.; Anderson, B. J.; Weygand, J. M.; Le, G.; Kepko, L.; Nakamura, R.; Baumjohann, W.; Slavin, J. A.; Paterson, W. R.; Giles, B. L.; Shuster, J. R.; Torbert, R. B.; Burch, J. L.

2017-12-01

Field-aligned currents (FACs) are frequently observed by Magnetospheric Multiscale (MMS) within the Earth's magnetotail. However, unlike the FACs observed by MMS at the dayside magnetopause, which are of the order 100s of nA/m2, the magnetotail FACs are relatively weak, of the order 10s of nA/m2. There appear to be a variety of sources for the FACs. FACs are observed in association with dipolarization fronts that are propagating both earthward and tailward, at the boundary of the current sheet, and in flux-ropes. FACs are also observed to be embedded in regions of high speed flow, both earthward and tailward, and not just at the dipolarization front frequently associated with high speed flows. As is the case for FACs observed at the dayside magnetopause, these observations raise questions as to how or where the FACs close.

Electron Jet Detected by MMS at Dipolarization Front

NASA Astrophysics Data System (ADS)

Liu, C. M.; Fu, H. S.; Vaivads, A.; Khotyaintsev, Y. V.; Gershman, D. J.; Hwang, K.-J.; Chen, Z. Z.; Cao, D.; Xu, Y.; Yang, J.; Peng, F. Z.; Huang, S. Y.; Burch, J. L.; Giles, B. L.; Ergun, R. E.; Russell, C. T.; Lindqvist, P.-A.; Le Contel, O.

2018-01-01

Using MMS high-resolution measurements, we present the first observation of fast electron jet (Ve 2,000 km/s) at a dipolarization front (DF) in the magnetotail plasma sheet. This jet, with scale comparable to the DF thickness ( 0.9 di), is primarily in the tangential plane to the DF current sheet and mainly undergoes the E × B drift motion; it contributes significantly to the current system at the DF, including a localized ring-current that can modify the DF topology. Associated with this fast jet, we observed a persistent normal electric field, strong lower hybrid drift waves, and strong energy conversion at the DF. Such strong energy conversion is primarily attributed to the electron-jet-driven current (E ṡ je ≈ 2 E ṡ ji), rather than the ion current suggested in previous studies.

Electron acceleration behind a wavy dipolarization front

NASA Astrophysics Data System (ADS)

Wu, Mingyu; Lu, Quanming; Volwerk, Martin; Nakamura, Rumi; Zhang, Tielong

2018-02-01

In this paper, with the in-situ observations from the Time History of Events and Macroscale Interactions during Substorms (THEMIS) probes we report a wavy dipolarization front (DF) event, where the DF has different magnetic structures and electron distributions at different y positions in the Geocentric Solar Magnetospheric (GSM) coordinates. At y ˜2.1RE (RE is the radius of Earth), the DF has a relatively simple structure, which is similar to that of a conventional DF. At y ˜3.0RE, the DF is revealed to have a multiple DF structure, where the plasma exhibits a vortex flow. Such a wavy DF could be the results of the interchange instability. The different structure of such a wavy DF at different sites has a great effect on electron acceleration. Fermi acceleration can occur at the site of the DF with a simple or multiple DF structure, while betatron acceleration as a local process has the contribution to energetic electrons only at the site of the DF with a simple structure.

Energy conversion at dipolarization fronts

NASA Astrophysics Data System (ADS)

Khotyaintsev, Yu. V.; Divin, A.; Vaivads, A.; André, M.; Markidis, S.

2017-02-01

We use multispacecraft observations by Cluster in the Earth's magnetotail and 3-D particle-in-cell simulations to investigate conversion of electromagnetic energy at the front of a fast plasma jet. We find that the major energy conversion is happening in the Earth (laboratory) frame, where the electromagnetic energy is being transferred from the electromagnetic field to particles. This process operates in a region with size of the order several ion inertial lengths across the jet front, and the primary contribution to E·j is coming from the motional electric field and the ion current. In the frame of the front we find fluctuating energy conversion with localized loads and generators at sub-ion scales which are primarily related to the lower hybrid drift instability excited at the front; however, these provide relatively small net energy conversion.

Electron and Ion Acceleration Associated with Magnetotail Reconnection

NASA Astrophysics Data System (ADS)

Liang, Haoming

This dissertation is dedicated to understanding electron and ion acceleration associated with magnetotail reconnection during substorms by using numerical simulations. Electron dynamics were investigated by using the UCLA global magnetohydrodynamic (MHD) model and large scale kinetic (LSK) simulations. The neutral line configurations and magnetotail flows modify the amounts of the adiabatic and non-adiabatic acceleration that electrons undergo. This causes marked differences in the temperature anisotropy for different substorms. In particular, one substorm event analyzed shows T⊥ > T∥ (T⊥ / T ∥ ≈ 2.3)at -10RE while another shows T ∥ > T⊥ (T ⊥ / T∥ ≈ 0.8), where T⊥ and T∥ (second order moments of the distribution functions) are defined with respect to the magnetic field. These differences determine the subsequent acceleration of the energetic electrons in the inner magnetosphere. Whether the acceleration is mostly parallel or perpendicular is determined by the location of dayside reconnection. A 2.5D implicit Particle-in-Cell simulation was used to study the effects produced by oxygen ions on magnetotail reconnection, and the associated acceleration of protons and oxygen ions. The inertia of oxygen ions reduces the reconnection rate and slows down the earthward propagation of dipolarization fronts (DFs). An ambipolar electric field in the oxygen diffusion region contributes to the smaller reconnection rate. This change in the reconnection rate affects the ion acceleration. In particular 67% of protons and 58% of oxygen ions were accelerated in the exhaust (between the X-point and the DF) in a simulation corresponding to a magnetic storm in which there was a 50% concentration of oxygen ions. In addition, 42% of lobe oxygen-ions are accelerated locally by the Hall electric field, far away from the X-point without entering the exhaust. Protons at the same locations experience Ex B drift. This finding extends previous knowledge that oxygen and proton acceleration associated with reconnection mainly occurs in the exhaust and is consistent with Cluster observations. Oxygen ions and protons in the pre-existing current sheet are reflected by the DFs. The reflected oxygen beam forms a hook-shaped signature in phase space. In principle, this signature can be applied to deduce the DF speed history, and thus lead to remote-sensing of the reconnection dynamics.

Energy limits of electron acceleration in the plasma sheet during substorms: A case study with the Magnetospheric Multiscale (MMS) mission

NASA Astrophysics Data System (ADS)

Turner, D. L.; Fennell, J. F.; Blake, J. B.; Clemmons, J. H.; Mauk, B. H.; Cohen, I. J.; Jaynes, A. N.; Craft, J. V.; Wilder, F. D.; Baker, D. N.; Reeves, G. D.; Gershman, D. J.; Avanov, L. A.; Dorelli, J. C.; Giles, B. L.; Pollock, C. J.; Schmid, D.; Nakamura, R.; Strangeway, R. J.; Russell, C. T.; Artemyev, A. V.; Runov, A.; Angelopoulos, V.; Spence, H. E.; Torbert, R. B.; Burch, J. L.

2016-08-01

We present multipoint observations of earthward moving dipolarization fronts and energetic particle injections from NASA's Magnetospheric Multiscale mission with a focus on electron acceleration. From a case study during a substorm on 02 August 2015, we find that electrons are only accelerated over a finite energy range, from a lower energy threshold at 7-9 keV up to an upper energy cutoff in the hundreds of keV range. At energies lower than the threshold energy, electron fluxes decrease, potentially due to precipitation by strong parallel electrostatic wavefields or initial sources in the lobes. Electrons at energies higher than the threshold are accelerated cumulatively by a series of impulsive magnetic dipolarization events. This case demonstrates how the upper energy cutoff increases, in this case from 130 keV to >500 keV, with each dipolarization/injection during sustained activity. We also present a simple model accounting for these energy limits that reveals that electron energization is dominated by betatron acceleration.

A Tailward Moving Current Sheet Normal Magnetic Field Front Followed by an Earthward Moving Dipolarization Front

NASA Technical Reports Server (NTRS)

Hwang, K.-J.; Goldstein, M. L.; Moore, T. E.; Walsh, B. M.; Baishev, D. G.; Moiseyev, A. V.; Shevtsov, B. M.; Yumoto, K.

2014-01-01

A case study is presented using measurements from the Cluster spacecraft and ground-based magnetometers that show a substorm onset propagating from the inner to outer plasma sheet. On 3 October 2005, Cluster, traversing an ion-scale current sheet at the near-Earth plasma sheet, detected a sudden enhancement of Bz, which was immediately followed by a series of flux rope structures. Both the local Bz enhancement and flux ropes propagated tailward. Approximately 5 min later, another Bz enhancement, followed by a large density decrease, was observed to rapidly propagate earthward. Between the two Bz enhancements, a significant removal of magnetic flux occurred, possibly resulting from the tailward moving Bz enhancement and flux ropes. In our scenario, this flux removal caused the magnetotail to be globally stretched so that the thinnest sheet formed tailward of Cluster. The thinned current sheet facilitated magnetic reconnection that quickly evolved from plasma sheet to lobe and generated the later earthward moving dipolarization front (DF) followed by a reduction in density and entropy. Ground magnetograms located near the meridian of Cluster's magnetic foot points show two-step bay enhancements. The positive bay associated with the first Bz enhancement indicates that the substorm onset signatures propagated from the inner to the outer plasma sheet, consistent with the Cluster observation. The more intense bay features associated with the later DF are consistent with the earthward motion of the front. The event suggests that current disruption signatures that originated in the near-Earth current sheet propagated tailward, triggering or facilitating midtail reconnection, thereby preconditioning the magnetosphere for a later strong substorm enhancement.

Energy limits of electron acceleration in the plasma sheet during substorms: A case study with the Magnetospheric Multiscale (MMS) mission

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

Turner, Drew Lawson; Fennell, J. F.; Blake, J. B.

Here, we present multipoint observations of earthward moving dipolarization fronts and energetic particle injections from NASA's Magnetospheric Multiscale mission with a focus on electron acceleration. From a case study during a substorm on 02 August 2015, we find that electrons are only accelerated over a finite energy range, from a lower energy threshold at ~7–9 keV up to an upper energy cutoff in the hundreds of keV range. At energies lower than the threshold energy, electron fluxes decrease, potentially due to precipitation by strong parallel electrostatic wavefields or initial sources in the lobes. Electrons at energies higher than the thresholdmore » are accelerated cumulatively by a series of impulsive magnetic dipolarization events. This case demonstrates how the upper energy cutoff increases, in this case from ~130 keV to >500 keV, with each dipolarization/injection during sustained activity. We also present a simple model accounting for these energy limits that reveals that electron energization is dominated by betatron acceleration.« less

Electron Injections: A Study of Electron Acceleration by Multiple Dipolarizing Flux Bundles Using an Analytical Model

NASA Astrophysics Data System (ADS)

Gabrielse, C.; Angelopoulos, V.; Artemyev, A.; Runov, A.; Harris, C.

2016-12-01

We study energetic electron injections using an analytical model that self-consistently describes electric and magnetic field perturbations of transient, localized dipolarizing flux bundles (DFBs). Previous studies using THEMIS, Van Allen Probes, and the Magnetospheric Multiscale Mission have shown that injections can occur on short (minutes) or long (10s of minutes) timescales. These studies suggest that the short timescale injections correspond to a single DFB, whereas long timescale injections are likely caused by an aggregate of multiple DFBs, each incrementally heating the particle population. We therefore model the effects of multiple DFBs on the electron population using multi-spacecraft observations of the fields and particle fluxes to constrain the model parameters. The analytical model is the first of its kind to model multiple dipolarization fronts in order to better understand the transport and acceleration process throughout the plasma sheet. It can reproduce most injection signatures at multiple locations simultaneously, reaffirming earlier findings that multiple earthward-traveling DFBs can both transport and accelerate electrons to suprathermal energies, and can thus be considered the injections' primary driver.

Energy limits of electron acceleration in the plasma sheet during substorms: A case study with the Magnetospheric Multiscale (MMS) mission

DOE PAGES

Turner, Drew Lawson; Fennell, J. F.; Blake, J. B.; ...

2016-08-01

Here, we present multipoint observations of earthward moving dipolarization fronts and energetic particle injections from NASA's Magnetospheric Multiscale mission with a focus on electron acceleration. From a case study during a substorm on 02 August 2015, we find that electrons are only accelerated over a finite energy range, from a lower energy threshold at ~7–9 keV up to an upper energy cutoff in the hundreds of keV range. At energies lower than the threshold energy, electron fluxes decrease, potentially due to precipitation by strong parallel electrostatic wavefields or initial sources in the lobes. Electrons at energies higher than the thresholdmore » are accelerated cumulatively by a series of impulsive magnetic dipolarization events. This case demonstrates how the upper energy cutoff increases, in this case from ~130 keV to >500 keV, with each dipolarization/injection during sustained activity. We also present a simple model accounting for these energy limits that reveals that electron energization is dominated by betatron acceleration.« less

Near-earth injection of MeV electrons associated with intense dipolarization electric fields: Van Allen Probes observations

DOE PAGES

Dai, Lei; Wang, Chi; Duan, Suping; ...

2015-08-10

Substorms generally inject tens to hundreds of keV electrons, but intense substorm electric fields have been shown to inject MeV electrons as well. An intriguing question is whether such MeVelectron injections can populate the outer radiation belt. Here we present observations of a substorm injection of MeV electrons into the inner magnetosphere. In the premidnight sector at L ~ 5.5, Van Allen Probes (Radiation Belt Storm Probes)-A observed a large dipolarization electric field (50 mV/m) over ~40 s and a dispersionless injection of electrons up to ~3 MeV. Pitch angle observations indicated betatron acceleration of MeV electrons at the dipolarizationmore » front. Corresponding signals of MeV electron injection were observed at LANL-GEO, THEMIS-D, and GOES at geosynchronous altitude. Through a series of dipolarizations, the injections increased the MeV electron phase space density by 1 order of magnitude in less than 3 h in the outer radiation belt (L > 4.8). Our observations provide evidence that deep injections can supply significant MeV electrons.« less

MMS Observations of Protons and Heavy Ions Acceleration at Plasma Jet Fronts

NASA Astrophysics Data System (ADS)

Catapano, F.; Retino, A.; Zimbardo, G.; Cozzani, G.; Breuillard, H.; Le Contel, O.; Alexandrova, A.; Mirioni, L.; Cohen, I. J.; Turner, D. L.; Perri, S.; Greco, A.; Mauk, B.; Torbert, R. B.; Russell, C. T.; Khotyaintsev, Y. V.; Lindqvist, P. A.; Ergun, R.; Giles, B. L.; Fuselier, S. A.; Moore, T. E.; Burch, J.

2017-12-01

Plasma jet fronts in the Earth's magnetotail are kinetic-scale boundaries separating hot fast plasma jets, generally attributed to reconnection outflows, from colder ambient plasma. Jet fronts are typically associated with a sharp increase of the vertical component of the magnetic field Bz, an increase of the plasma temperature and a drop of plasma density. Spacecraft observations and numerical simulations indicate that jet fronts are sites of major ion acceleration. The exact acceleration mechanisms as well as the dependence of such mechanisms on ion composition are not fully understood, yet. Recent high-resolution measurements of ion distribution functions in the magnetotail allow for the first time to study the acceleration mechanisms in detail. Here, we show several examples of jet fronts and discuss ion acceleration therein. We show fronts that propagate in the mid-tail magnetotail both as isolated laminar boundaries and as multiple boundaries embedded in strong magnetic fluctuations and turbulence. We also show fronts in the near-Earth jet braking region, where they interact with the dipolar magnetic field and are significantly decelerated/diverted. Finally, we study the acceleration of different ion species (H+, He++, O+) at different types of fronts and we discuss possible different acceleration mechanisms and how they depend on the ion species.

Characteristics of DC electric fields at dipolarization fronts

NASA Astrophysics Data System (ADS)

Laakso, Harri; Escoubet, Philippe; Masson, Arnaud

2016-04-01

We investigate the characteristics of DC electric field at dipolarization fronts and BBF's using multi-point Cluster observations. There are plenty of important issues that are considered, such as what kind of DC electric fields exist in such events and what are their spatial scales. One can also recognize if electrons and ions perform ExB drift motions in these events. To investigate this, we take an advantage of five different DC electric field measurements in the plasma sheet available from the EFW double probe experiment, EDI electron drift instrument, CODIF and HIA ion spectrometers, and PEACE electron spectrometer. The calibrated observations of the three spectrometers are used to determine the proton and electron drift velocity and furthermore the DC electric field, assuming that the electron and proton velocity perpendicular to the magnetic field is dominated by the ExB drift motion. Naturally when ions and electrons do not perform a proper drift motion, which can happen in the plasma sheet, the estimated DC electric field from ion and electron motion is not correct. However, surprisingly often the DC electric fields estimated from electron and ion motions are identical suggesting that this field is a real DC electric field around the measurement point. This investigation also helps understand how well different measurements are calibrated.

Open Boundary Particle-in-Cell Simulation of Dipolarization Front Propagation

NASA Technical Reports Server (NTRS)

Klimas, Alex; Hwang, Kyoung-Joo; Vinas, Adolfo F.; Goldstein, Melvyn L.

2014-01-01

First results are presented from an ongoing open boundary 2-1/2D particle-in-cell simulation study of dipolarization front (DF) propagation in Earth's magnetotail. At this stage, this study is focused on the compression, or pileup, region preceding the DF current sheet. We find that the earthward acceleration of the plasma in this region is in general agreement with a recent DF force balance model. A gyrophase bunched reflected ion population at the leading edge of the pileup region is reflected by a normal electric field in the pileup region itself, rather than through an interaction with the current sheet. We discuss plasma wave activity at the leading edge of the pileup region that may be driven by gradients, or by reflected ions, or both; the mode has not been identified. The waves oscillate near but above the ion cyclotron frequency with wavelength several ion inertial lengths. We show that the waves oscillate primarily in the perpendicular magnetic field components, do not propagate along the background magnetic field, are right handed elliptically (close to circularly) polarized, exist in a region of high electron and ion beta, and are stationary in the plasma frame moving earthward. We discuss the possibility that the waves are present in plasma sheet data, but have not, thus far, been discovered.

Ion velocity distributions in dipolarization events: Distributions in the central plasma sheet

NASA Astrophysics Data System (ADS)

Birn, J.; Runov, A.; Zhou, X.-Z.

2017-08-01

Using combined MHD/test particle simulations, we further explore characteristic ion velocity distributions in the central plasma sheet (CPS) in relation to dipolarization events. Distributions in the CPS within the dipolarized flux bundle (DFB) that follows the passage of a dipolarization front typically show two opposing low subthermal-energy beams with a ring-like component perpendicular to the magnetic field at about twice the thermal energy. The dominance of the perpendicular anisotropy and a field-aligned peak at lower energy agree qualitatively with ion distribution functions derived from "Time History of Events and Macroscale Interactions during Substorms" observations. At locations somewhat off the equatorial plane the field-aligned peaks are shifted by a field-aligned component of the bulk flow, such that one peak becomes centered near zero net velocity, which makes it less likely to be observed. The origins of the field-aligned peaks are low-energy lobe (or near plasma sheet boundary layer) regions, while the ring distribution originates mostly from thermal plasma sheet particles on extended field lines. The acceleration mechanisms are also quite different: the beam ions are accelerated first by the E × B drift motion of the DFB and then by a slingshot effect of the earthward convecting DFB (akin to first-order Fermi, type B, acceleration), which causes an increase in field-aligned speed. In contrast, the ring particles are accelerated by successive, betatron-like acceleration after entering the high electric field region of an earthward propagating DFB.

Diagnostic value of inflammatory cell infiltrates, tumor stroma percentage and disease-free survival in patients with colorectal cancer

PubMed Central

Jakubowska, Katarzyna; Kisielewski, Wojciech; Kańczuga-Koda, Luiza; Koda, Mariusz; Famulski, Waldemar

2017-01-01

The anticancer immune defense mechanism involves humoral and cellular responses. The main effector mechanisms of antitumor responses involve the following: the activity of cytotoxic T cells; the activation of macrophages and neutrophils; the activity of cytokines secreted by T cells; and natural killer cell activity. Selected cell populations are responsible for the stimulation or suppression of the immune system against tumor cells. Therefore, the aim of the present study was to evaluate the location, extent and composition of the cellular inflammatory infiltration of tumors in patients with colorectal cancer (CRC). In addition, the correlation between cellular inflammatory infiltration, and anatomoclinical and histopathological features of patients was evaluated. The study involved 160 patients diagnosed with primary operable CRC. The local inflammatory infiltrate was assessed in the invasive front and center of the tumor using light microscopy with hematoxylin and eosin (H&E) staining, according to the Klintrup-Makinen criteria, tumor stroma percentage, and Glasgow microenvironment score. The inflammatory infiltrate in the invasive front of the tumor was correlated with gender (P=0.018), the invasion of blood vessels (P=0.020) and lymph vessels (P=0.038), the presence of tumor-infiltrating lymphocytes in the invasive front (P=0.033) and center (P<0.001) of the tumor, fibrosis (P<0.001), and the degree of desmoplasmic stroma (P=0.004). In contrast, inflammatory infiltration in the center of the tumor was associated with the tumor node metastasis stage (P=0.012), Dukes' stage (P=0.009), primary tumor stage (P=0.036), lymph node status (P=0.005), number of lymph nodes (P=0.006), invasion of lymph node pouches (P=0.021), size of lymph node metastasis (P=0.025) and the degree of desmoplasmic stroma (P=0.002). The low-group, who demonstrated an absent or weak inflammatory cell infiltrate in the invasive front of the tumor, had a statistically significant shorter disease-free survival (DFS) time (P=0.004). Inflammatory cell infiltrate in the invasive front was identified as an independent predictive factor in CRC (P=0.041). In conclusion, the degree of inflammatory cell infiltration in the invasive front of the primary tumor significantly affects various variables that determine disease progression and DFS rates of patients with CRC. Furthermore, the routine histopathological assessment of this parameter in tissue stained with H&E may have potential prognostic value. PMID:28927159

Intensified chemo-immunotherapy with or without stem cell transplantation in newly diagnosed patients with peripheral T-cell lymphoma.

PubMed

Corradini, P; Vitolo, U; Rambaldi, A; Miceli, R; Patriarca, F; Gallamini, A; Olivieri, A; Benedetti, F; Todeschini, G; Rossi, G; Salvi, F; Bruno, B; Baldini, L; Ferreri, A; Patti, C; Tarella, C; Pileri, S; Dodero, A

2014-09-01

Peripheral T-cell lymphomas (PTCLs) receiving conventional treatment have a poor clinical outcome. We conducted a phase II study to evaluate the feasibility and efficacy of chemo-immunotherapy in young (⩽60 years old, Clin A study) and elderly (>60 and < or =75 years old, Clin B study) patients with newly diagnosed PTCL. Clin A patients (n=61) received two courses of CHOP (cyclophosphamide, adriamycin, vincristine, prednisone)-21 with alemtuzumab (AL, 30 mg) followed by two courses of high-dose chemotherapy. On the basis of donor availability, patients in response received allogeneic (allo) or autologous (auto) stem cell transplantation (SCT). Clin B patients (n=25) received six courses of CHOP-21 and AL (10 mg). Clin A responding patients were 38 of 61 (62%) and received alloSCT (n=23) or autoSCT (n=14); one complete remission (CR) patient was not transplanted. At a median follow-up of 40 months, the 4-year overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) rates were 49, 44 and 65%, respectively. In Clin B study, the response rate was 72%. At a median follow-up of 48 months, the 4-year OS, PFS and DFS rates were 31, 26 and 44%, respectively. In conclusion, front-line alloSCT or autoSCT is effective in prolonging DFS in young patients; AL in elderly improved response with no survival benefit.

Ion Velocity Distributions in Dipolarization Events: Beams in the Vicinity of the Plasma Sheet Boundary

NASA Technical Reports Server (NTRS)

Birn, J.; Chandler, M.; Moore, T.; Runov, A.

2017-01-01

Using combined MHD/test particle simulations, we further explore characteristic ion velocity distributions in relation to magnetotail reconnection and dipolarization events, focusing on distributions at and near the plasma sheet boundary layer (PSBL). Simulated distributions right at the boundary are characterized by a single earthward beam, as discussed earlier. However, farther inside, the distributions consist of multiple beams parallel and antiparallel to the magnetic field, remarkably similar to recent Magnetospheric Multiscale observations. The simulations provide insight into the mechanisms: the lowest earthward beam results from direct acceleration at an earthward propagating dipolarization front (DF), with a return beam at somewhat higher energy. A higher-energy earthward beam results from dual acceleration, first near the reconnection site and then at the DF, again with a corresponding return beam resulting from mirroring closer to Earth. Multiple acceleration at the X line or the propagating DF with intermediate bounces may produce even higher-energy beams. Particles contributing to the lower energy beams are found to originate from the PSBL with thermal source energies, increasing with increasing beam energy. In contrast, the highest-energy beams consist mostly of particles that have entered the acceleration region via cross-tail drift with source energies in the suprathermal range.

Ion velocity distributions in dipolarization events: Beams in the vicinity of the plasma sheet boundary

NASA Astrophysics Data System (ADS)

Birn, J.; Chandler, M.; Moore, T.; Runov, A.

2017-08-01

Using combined MHD/test particle simulations, we further explore characteristic ion velocity distributions in relation to magnetotail reconnection and dipolarization events, focusing on distributions at and near the plasma sheet boundary layer (PSBL). Simulated distributions right at the boundary are characterized by a single earthward beam, as discussed earlier. However, farther inside, the distributions consist of multiple beams parallel and antiparallel to the magnetic field, remarkably similar to recent Magnetospheric Multiscale observations. The simulations provide insight into the mechanisms: the lowest earthward beam results from direct acceleration at an earthward propagating dipolarization front (DF), with a return beam at somewhat higher energy. A higher-energy earthward beam results from dual acceleration, first near the reconnection site and then at the DF, again with a corresponding return beam resulting from mirroring closer to Earth. Multiple acceleration at the X line or the propagating DF with intermediate bounces may produce even higher-energy beams. Particles contributing to the lower energy beams are found to originate from the PSBL with thermal source energies, increasing with increasing beam energy. In contrast, the highest-energy beams consist mostly of particles that have entered the acceleration region via cross-tail drift with source energies in the suprathermal range.

Design for Occupational Safety and Health of Workers in Construction in Developing Countries: A Study of Architects in Nigeria.

PubMed

Manu, Patrick; Poghosyan, Anush; Mshelia, Ibrahim Mark; Iwo, Samuel Tekena; Mahamadu, Abdul-Majeed; Dziekonski, Krzysztof

2018-06-14

Design for safety (DfS) of workers is amongst the prominent ways of tackling poor occupational safety and health (OSH) performance in construction. However, in developing countries there is an extremely limited research on DfS. This study thus makes an important contribution to the subject of DfS in developing countries by specifically examining the awareness and practice of DfS amongst architects within the construction sector of Nigeria. A survey of architects, yielding 161 valid responses, was conducted. While there is a high awareness of the concept of DfS, the actual practice is low. Additionally, although there is high interest in DfS training, the engagement in DfS training is low. Significantly, awareness of DfS, training and education related to DfS, and membership of a design professional body have very limited bearing on the practice of DfS by architects. The findings are thus symptomatic of the prevalence of influential DfS implementation barriers within the construction sector. Industry stakeholders should seek to raise the profile of DfS practice within the sector. Furthermore, similar empirical studies in the construction sector of other developing countries would be useful in shedding light on the status of DfS in these countries.

Diabetic foot syndrome (DFS) in patients with diabetes. A multicenter German/Austrian DPV analysis on 33,870 DFS patients among 358,986 adult subjects with diabetes.

PubMed

Bohn, Barbara; Grünerbel, Arthur; Altmeier, Marcus; Giesche, Carsten; Pfeifer, Martin; Wagner, Christian; Heise, Nikolai; Best, Frank; Fasching, Peter; Holl, Reinhard W

2018-05-03

The diabetic foot syndrome (DFS) is a serious complication in patients with diabetes increasing the risk for minor/major amputations. This analysis aimed to examine differences in diabetes patients with or without DFS stratified by type 1 (T1D) or type 2 diabetes (T2D). Adult patients (≥20y of age) with diabetes from the German/Austrian DPV-registry were included. The cross-sectional study comprised 45,722 subjects with T1D (n DFS =2,966) and 313,264 with T2D (n DFS =30,904). In DFS, minor/major amputations were analyzed. To compare HbA 1C , neuropathy, nephropathy, cardiovascular disease risk factors, and macrovascular complications between patients with our without DFS, regression models were conducted. Confounders: age, sex, diabetes duration. In patients with DFS, a minor amputation was documented in 27.2% (T1D) and 25.9% (T2D), a major amputation in 10.2% (T1D) and 11.3% (T2D). Regression models revealed that neuropathy was more frequent in subjects with DFS compared to patients without DFS (T1D: 70.7 vs. 29.8%; T2D: 59.4% vs. 36.9%; both p<0.0001). Hypertension, nephropathy, peripheral vascular disease, stroke, or myocardial infarction were more common compared to patients without DFS (all p<0.0001). In T1D with DFS, a slightly higher HbA 1C (8.11% vs. 7.95%; p<0.0001) and in T2D with DFS a lower HbA 1C (7.49% vs. 7.69%, p<0.0001) was observed. One third of the patients with DFS had an amputation of the lower extremity. Especially neuropathy or peripheral vascular disease were more prevalent in patients with DFS. New concepts to prevent DFS-induced amputations and to reduce cardiovascular risk factors before the occurrence of DFS are necessary. This article is protected by copyright. All rights reserved.

Prevalence of anti-DFS70 antibodies in patients with and without systemic autoimmune rheumatic diseases.

PubMed

Shovman, Ora; Gilburd, Boris; Chayat, Chen; Amital, Howard; Langevitz, Pnina; Watad, Abdulla; Guy, Adi; Perez, Dolores; Azoulay, Danielle; Blank, Miri; Segal, Yael; Bentow, Chelsea; Mahler, Michael; Shoenfeld, Yehuda

2018-01-01

Autoantibodies to the dense fine speckled 70 (DFS70) antigen are common among antinuclear antibodies (ANA) positive healthy individuals (HI). We assessed the prevalence of anti-DFS70 antibodies in patients with and without ANA-associated rheumatic diseases (AARDs) by two methods: chemiluminescent immunoassay (CIA) and an indirect immunofluorescence (IIF) assay based on immunoadsorption for DFS70. Fifty-one ANA-positive sera samples from patients with confirmed clinical diagnosis of AARD, 92 samples from HI and 85 samples submitted to a reference laboratory for routine ANA testing were evaluated for the presence of anti-DFS70 antibodies. The samples were evaluated by QUANTA Flash DFS70 CIA using BIO-FLASH instrument and by NOVA Lite selected HEp-2 kit on NOVA View - an automated IIF system. Sera with DFS positive pattern were pre-absorbed with highly purified human DFS70 antigen, and then tested again. Twenty-four samples (10.5%) tested by QUANTA Flash DFS70 CIA were positive for anti-DFS70 antibodies. The prevalence of monospecific anti-DFS70 antibodies was significantly higher in healthy subjects than in patients with AARDs (10.9% vs. 1.9%, p=0.02). The frequency of anti-DFS70 antibodies in samples submitted for routine ANA testing was 15.2%. A very good agreement was found between CIA and the DFS pattern identified by the automated HEp-2 IIF (kappa=0.97). In 80% of the samples obtained from patients without AARDs, immunoadsorption effectively inhibited the anti-DFS70 antibodies. The data confirm that mono-specific anti-DFS70 antibodies are a strong discriminator between ANA positive HI and AARD patients, and their evaluation should be included in ANA testing algorithms.

Energy Limits of Electron Acceleration in the Plasma Sheet During Substorms: A Case Study with the Magnetospheric Multiscale (MMS) Mission

NASA Technical Reports Server (NTRS)

Turner, D. L.; Fennell, J. F.; Blake, J. B.; Clemmons, J. H.; Mauk, B. H.; Cohen, I. J.; Jaynes, A. N.; Craft, J. V.; Wilder, F. D.; Baker, D. N.;

Chang'e-3 Extreme Ultraviolet Camera Observations of the Dynamics of the Earth's Plasmasphere

NASA Astrophysics Data System (ADS)

Fok, M. C. H.; Zhang, X.; He, F.; Chen, B.; Wang, H. N.; Shen, C.; Ping, J.; Nakano, S.

2015-12-01

The Moon-based Extreme Ultraviolet Camera (EUVC) aboard China's Chang'e-3 (CE-3) lunar lander has successfully imaged the global plasmasphere on the Moon for the first time through detecting the resonantly scattered sunlight by plasmaspheric He+ at 30.4 nm with a spatial resolution of 0.1 RE and a time resolution of 10 min. The characteristics and the analyzing methods of the EUVC images are introduced in detail in this report. The plasmapause locations on the magnetic equator are reconstructed with the Minimum L Algorithm and are quantitatively compared with those extracted from in-situ observations by DMSP, THEMIS, and RBSP satellites. Then the plasmapause evolutions during substorms on February 21 2014 and April 21 2014 are investigated. It is found that the evolutions of plasmapause correlate well in both universal time and magnetic local time with the equatorial boundaries of auroral oval during substorms. During these two cases, the solar-wind-driven convection and the geomagnetic activity are relatively weak and steady, and the plasmapause motions can reliably be attributed to the substorms. It is proposed that correlations between the auroral signatures and the plasmapause motions may be due to the generation and Earthward-propagation of dipolarization front and resultant pitch angle scattering. In future work, we will search more in-situ and remote sensing data in both the plasmasphere and the magnetotail regions to investigate the correlations between the plasmaspheric erosions, the dipolarization fronts, and the energetic ions injections.

Knowledge, attitude and practices for design for safety: A study on civil & structural engineers.

PubMed

Goh, Yang Miang; Chua, Sijie

2016-08-01

Design for safety (DfS) (also known as prevention through design, safe design and Construction (Design and Management)) promotes early consideration of safety and health hazards during the design phase of a construction project. With early intervention, hazards can be more effectively eliminated or controlled leading to safer worksites and construction processes. DfS is practiced in many countries, including Australia, the UK, and Singapore. In Singapore, the Manpower Ministry enacted the DfS Regulations in July 2015, which will be enforced from August 2016 onwards. Due to the critical role of civil and structural (C&S) engineers during design and construction, the DfS knowledge, attitude and practices (KAP) of C&S engineers have significant impact on the successful implementation of DfS. Thus, this study aims to explore the DfS KAP of C&S engineers so as to guide further research in measuring and improving DfS KAP of designers. During the study, it was found that there is a lack of KAP studies in construction management. Therefore, this study also aims to provide useful lessons for future applications of the KAP framework in construction management research. A questionnaire was developed to assess the DfS KAP of C&S engineers. The responses provided by 43 C&S engineers were analyzed. In addition, interviews with experienced construction professionals were carried out to further understand perceptions of DfS and related issues. The results suggest that C&S engineers are supportive of DfS, but the level of DfS knowledge and practices need to be improved. More DfS guidelines and training should be made available to the engineers. To ensure that DfS can be implemented successfully, there is a need to study the contractual arrangements between clients and designers and the effectiveness of different implementation approaches for the DfS process. The questionnaire and findings in this study provided the foundation for a baseline survey with larger sample size, which is currently being planned. In contrast to earlier studies, the study showed that the responding C&S engineers were supportive of the DfS. The study showed that the key to improving the DfS KAP of C&S engineers is by improving clients' motivation for DfS. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fluvial geomorphic elements in modern sedimentary basins and their potential preservation in the rock record: A review

NASA Astrophysics Data System (ADS)

Weissmann, G. S.; Hartley, A. J.; Scuderi, L. A.; Nichols, G. J.; Owen, A.; Wright, S.; Felicia, A. L.; Holland, F.; Anaya, F. M. L.

2015-12-01

Since tectonic subsidence in sedimentary basins provides the potential for long-term facies preservation into the sedimentary record, analysis of geomorphic elements in modern continental sedimentary basins is required to understand facies relationships in sedimentary rocks. We use a database of over 700 modern sedimentary basins to characterize the fluvial geomorphology of sedimentary basins. Geomorphic elements were delineated in 10 representative sedimentary basins, focusing primarily on fluvial environments. Elements identified include distributive fluvial systems (DFS), tributive fluvial systems that occur between large DFS or in an axial position in the basin, lacustrine/playa, and eolian environments. The DFS elements include large DFS (> 30 km in length), small DFS (< 30 km in length), coalesced DFS in bajada or piedmont plains, and incised DFS. Our results indicate that over 88% of fluvial deposits in the evaluated sedimentary basins are present as DFS, with tributary systems covering a small portion (1-12%) of the basin. These geomorphic elements are commonly arranged hierarchically, with the largest transverse rivers forming large DFS and smaller transverse streams depositing smaller DFS in the areas between the larger DFS. These smaller streams commonly converge between the large DFS, forming a tributary system. Ultimately, most transverse rivers become tributary to the axial system in the sedimentary basin, with the axial system being confined between transverse DFS entering the basin from opposite sides of the basin, or a transverse DFS and the edge of the sedimentary basin. If axial systems are not confined by transverse DFS, they will form a DFS. Many of the world's largest rivers are located in the axial position of some sedimentary basins. Assuming uniformitarianism, sedimentary basins from the past most likely had a similar configuration of geomorphic elements. Facies distributions in tributary positions and those on DFS appear to display specific morphologic patterns. Tributary rivers tend to increase in size in the downstream direction. Because axial tributary rivers are present in confined settings in the sedimentary basin, they migrate back and forth within a relatively narrow belt (relative to the overall size of the sedimentary basin). Thus, axial tributary rivers tend to display amalgamated channel belt form with minimal preservation potential of floodplain deposits. Chute and neck cutoff avulsions are also common on meandering rivers in these settings. Where rivers on DFS exit their confining valley on the basin margin, sediment transport capacity is reduced and sediment deposition occurs resulting in development of a 'valley exit' nodal avulsion point that defines the DFS apex. Rivers may incise downstream of the basin margin valley because of changes in sediment supply and discharge through climatic variability or tectonic processes. We demonstrate that rivers on DFS commonly decrease in width down-DFS caused by infiltration, bifurcation, and evaporation. In proximal areas, channel sands are amalgamated through repeated avulsion, reoccupation of previous channel belts, and limited accumulation space. When rivers flood on the medial to distal portions of a DFS, the floodwaters spread across a large area on the DFS surface and typically do not re-enter the main channel. In these distal areas, rivers on DFS commonly avulse, leaving a discrete sand body and providing high preservation potential for floodplain deposits. Additional work is needed to evaluate the geomorphic character of modern sedimentary basins in order to construct improved facies models for the continental sedimentary rock record. Specifically, models for avulsion, bifurcation, infiltration, and geomorphic form on DFS are required to better define and subsequently predict facies geometries. Studies of fluvial systems in sedimentary basins are also important for evaluating flood patterns and groundwater distributions for populations in these regions.

Ion Acceleration at Earth, Saturn and Jupiter and its Global Impact on Magnetospheric Structure

NASA Astrophysics Data System (ADS)

Brandt, Pontus

2016-07-01

The ion plasma pressures at Earth, Saturn and Jupiter are significant players in the electrodynamic force-balance that governs the structure and dynamics of these magnetospheres. There are many similarities between the physical mechanisms that are thought to heat the ion plasma to temperatures that even exceed those of the solar corona. In this presentation we compare the ion acceleration mechanisms at the three planetary magnetospheres and discuss their global impacts on magnetopsheric structure. At Earth, bursty-bulk flows, or "bubbles", have been shown to accelerate protons and O+ to high energies by the earthward moving magnetic dipolarization fronts. O+ ions display a more non-adiabatic energization in response to these fronts than protons do as they are energized and transported in to the ring-current region where they reach energies of several 100's keV. We present both in-situ measurements from the NASA Van Allen Probes Mission and global Energetic Neutral (ENA) images from the High-Energy Neutral Atom (HENA) Camera on board the IMAGE Mission, that illustrate these processes. The global impact on the magnetospheric structure is explored by comparing the empirical magnetic field model TS07d for given driving conditions with global plasma pressure distributions derived from the HENA images. At Saturn, quasi-periodic energization events, or large-scale injections, occur beyond about 9 RS around the post-midnight sector, clearly shown by the Ion and Neutral Atom Camera (INCA) on board the Cassini mission. In contrast to Earth, the corotational drift dominates even the energetic ion distributions. The large-scale injections display similar dipolarization front features can be found and there are indications that like at Earth the O+ responds more non-adiabatically than protons do. However, at Saturn there are also differences in that there appears to be energization events deep in the inner magnetosphere (6-9 RS) preferentially occurring in the pre-midnight sector that seem to be related to centrifugal interchange. We will show how the plasma pressure resulting from the large-scale injections perturb the magnetic field and give rise the periodic oscillations as measured by Cassini. At Jupiter, quasi-periodic, large-scale injections also occur in the post-midnight sector, but at much larger distances. Analysis of Galileo measurements have shown that there are also features with similarities to the effects of planetward moving dipolarization fronts, and that the protons, O+ and S+ have different spectral signatures. Although the magnetodisc structure is partly a result of centrifugal forces exerted by the cold plasma, the anisotropies of the hot plasma have been found to account for a very significant part of the force-balance responsible for the disc structure. We will briefly also discuss our science planning and development of the plasma, energetic particle and ENA instrumentation on board the ESA Jupiter Icy moon Explorer and how we plan to address these intriguing science topics.

Lycopene Attenuates Tulathromycin and Diclofenac Sodium-Induced Cardiotoxicity in Mice.

PubMed

Abdel-Daim, Mohamed M; Eltaysh, Rasha; Hassan, Azza; Mousa, Shaker A

2018-01-24

Recent experiments showed a potential cardiotoxic effect of the macrolide antibiotic (tulathromycin). This study was performed to investigate whether diclofenac sodium (DFS) potentiates the cardiotoxicity of tulathromycin and increases the cardioprotective effects of lycopene against DFS and tulathromycin. Seven groups (eight per group) of adult Swiss albino mice received saline (control), tulathromycin (a single subcutaneous dose of 28 mg/kg/bw on day 14), DFS (a single oral dose of 100 mg/kg/bw on day 14), tulathromycin plus DFS, or lycopene (oral, 10 mg/kg/bw daily for 15 d) combined with tulathromycin, DFS, or both. Compared to the control group, the administration of tulathromycin or DFS (individually or in combination) caused significantly elevated ( p < 0.05) serum levels of Creatine kinase-myocardial B fraction (CK-MB), lactate dehydrogenase, and cardiac-specific troponin-T and tissue levels of nitric oxide and malondialdehyde that were accompanied by significantly decreased tissue reduced glutathione content and glutathione peroxidase, superoxide dismutase, and catalase antioxidant enzyme activity. Upon histopathological and immunohistochemical examination, the mean pathology scores and the percentages of caspase-3-, Bax-, and CK-positive regions were significantly higher in the tulathromycin- and/or DFS-treated groups than in control mice. For all these parameters, the pathological changes were more significant in the tulathromycin-DFS combination group than in mice treated with either drug individually. Interestingly, co-administration of lycopene with tulathromycin and/or DFS significantly ameliorated the changes described above. In conclusion, DFS could potentiate the cardiotoxic effects of tulathromycin, whereas lycopene can serve as a cardioprotective agent against DFS and tulathromycin.

Global simulation study for the time sequence of events leading to the substorm onset

NASA Astrophysics Data System (ADS)

Tanaka, T.; Ebihara, Y.; Watanabe, M.; Den, M.; Fujita, S.; Kikuchi, T.; Hashimoto, K. K.; Kataoka, R.

2017-06-01

We have developed a global simulation code which gives numerical solutions having an extremely high resolution. The substorm solution obtained from this simulation code reproduces the precise features of the substorm onset in the ionosphere. It can reproduce the onset that starts from the equatorward side of the quiet arc, two step development of the onset, and the westward traveling surge (WTS) that starts 2 min after the initial brightening. Then, we investigated the counter structures in the magnetosphere that correspond to each event in the ionosphere. The structure in the magnetosphere promoting the onset is the near-Earth dynamo in the inner magnetospheric region away from the equatorial plane. The near-Earth dynamo is driven by the field-aligned pressure increase due to the parallel flow associated with the squeezing, combined with equatorward field-perpendicular flow induced by the near-Earth neutral line (NENL). The dipolarization front is launched from the NENL associated with the convection transient from the growth phase to the expansion phase, but neither the launch nor the arrival of the dipolarization front coincides with the onset timing. The arrival of flow to the equatorial plane of the inner magnetosphere occurs 2 min after the onset, when the WTS starts to develop toward the west. The expansion phase is further developed by this flow. Looking at the present result that the onset sequence induced by the near-Earth dynamo reproduces the details of observation quite well, we cannot avoid to conclude that the current wedge is a misleading concept.

Prognosis and Conditional Disease-Free Survival Among Patients With Ovarian Cancer

PubMed Central

Kurta, Michelle L.; Edwards, Robert P.; Moysich, Kirsten B.; McDonough, Kathleen; Bertolet, Marnie; Weissfeld, Joel L.; Catov, Janet M.; Modugno, Francesmary; Bunker, Clareann H.; Ness, Roberta B.; Diergaarde, Brenda

2014-01-01

Purpose Traditional disease-free survival (DFS) does not reflect changes in prognosis over time. Conditional DFS accounts for elapsed time since achieving remission and may provide more relevant prognostic information for patients and clinicians. This study aimed to estimate conditional DFS among patients with ovarian cancer and to evaluate the impact of patient characteristics. Patients and Methods Patients were recruited as part of the Hormones and Ovarian Cancer Prediction case-control study and were included in the current study if they had achieved remission after a diagnosis of cancer of the ovary, fallopian tube, or peritoneum (N = 404). Demographic and lifestyle information was collected at enrollment; disease, treatment, and outcome information was abstracted from medical records. DFS was calculated using the Kaplan-Meier method. Conditional DFS estimates were computed using cumulative DFS estimates. Results Median DFS was 2.54 years (range, 0.03-9.96 years) and 3-year DFS was 48.2%. The probability of surviving an additional 3 years without recurrence, conditioned on having already survived 1, 2, 3, 4, and 5 years after remission, was 63.8%, 80.5%, 90.4%, 97.0%, and 97.7%, respectively. Initial differences in 3-year DFS at time of remission between age, stage, histology, and grade groups decreased over time. Conclusion DFS estimates for patients with ovarian cancer improved dramatically over time, in particular among those with poorer initial prognoses. Conditional DFS is a more relevant measure of prognosis for patients with ovarian cancer who have already achieved a period of remission, and time elapsed since remission should be taken into account when making follow-up care decisions. PMID:25403208

Analysis of trans-2,6-difluoro-4'-(N,N-dimethylamino)stilbene (DFS) in biological samples by liquid chromatography-tandem mass spectrometry: metabolite identification and pharmacokinetics.

PubMed

Yeo, Samuel Chao Ming; Sviripa, Vitaliy M; Huang, Meng; Kril, Liliia; Watt, David S; Liu, Chunming; Lin, Hai-Shu

2015-09-01

The metabolism of a promising antineoplastic agent, trans-2,6-difluoro-4'-(N,N-dimethylamino)stilbene (DFS), was studied in mouse, rat, and human liver microsomes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with the multiple reaction monitoring-information-dependent acquisition-enhanced product ion scan (MRM-IDA-EPI) method. Ten putative metabolites were identified and the structures of four metabolites were confirmed using authentic standards. Since trans-2,6-difluoro-4'-(N-methylamino)stilbene (DMDFS, M1) was present in all species as metabolite and displayed in vitro growth inhibition superior to DFS, its pharmacokinetic profiles were examined in Sprague-Dawley rats using DFS as a comparator. A reliable LC-MS/MS multiple reaction monitoring (MRM) method was subsequently developed and validated for the simultaneous quantification of both DFS and DMDFS in rat plasma for this purpose. Upon intravenous administration (4 mg/kg), DFS had a moderate clearance (Cl = 62.7 ± 23.2 mL/min/kg), terminal elimination half-life (t 1/2 λZ  = 299 ± 73 min), and mean transit time (MTT = 123 ± 14 min) with demethylation metabolism accounting for about 10 % of its total clearance. DMDFS possessed an intravenous pharmacokinetic profile similar to DFS. During oral dosing (10 mg/kg) where both DFS and DMDFS were absorbed rapidly, the oral bioavailability of DFS was approximately 2-fold greater than that of DMDFS (DFS: F = 42.1 ± 12.8 %; DMDFS: F = 18.7 ± 3.9 %). Interestingly, the DMDFS exposure after oral dosing of DFS (10 mg/kg) was comparable to that after oral administration of DMDFS (10 mg/kg) alone. As DFS displayed potent anticancer activities and excellent pharmacokinetic profiles, it appears to be a favorable candidate for further pharmaceutical development.

Daily Fantasy Sports Players: Gambling, Addiction, and Mental Health Problems.

PubMed

Nower, Lia; Caler, Kyle R; Pickering, Dylan; Blaszczynski, Alex

2018-01-19

Studies point to a relationship between fantasy sports/daily fantasy sports (DFS) play and gambling behavior. However, little is known about the nature of those relationships, particularly regarding the development of gambling problems. This study investigates the nature, frequency, and preferences of gambling behavior as well as problem gambling severity and comorbid conditions among DFS players. Data were collected from an epidemiologic survey of 3634 New Jersey residents on gambling and leisure activities. Participants were contacted by phone (land-line and cell) and online to obtain a representative, cross-sectional sample of non-institutionalized adults, aged 18 years or older. Excluding non-gamblers, the remaining 2146 participants, included in these analyses, indicated they had either played DFS (n = 299) or had gambled but not played DFS (1847) in the past year. Univariate comparisons and multiple logistic regression analyses were performed to identify the most significant characteristics and predictors of DFS players. Overall, a higher number of gambling activities, high frequency gambling, male gender, and reports of suicidal thoughts in the past year were most predictive of DFS players. Being Hispanic (vs. Caucasian) and/or single (vs. married or living with a partner) also doubled the odds of DFS play. Findings suggest that DFS players are characterized by high gambling frequency and problem severity and comorbid problems, notably suicidal ideation. Future research should examine the motivations and possible etiological sub-types of DFS players and the nature and course of DFS play, particularly in relation to gambling behavior and the development of gambling and other problems.

The Prognostic Role of Cancer Stem Cell Markers for Long-term Outcome After Resection of Colonic Liver Metastases.

PubMed

Spelt, Lidewij; Sasor, Agata; Ansari, Daniel; Hilmersson, Katarzyna Said; Andersson, Roland

2018-01-01

To assess the expression of cancer stem cell (CSC) markers CD44, CD133 and CD24 in colon cancer liver metastases and analyse their predictive value for overall survival (OS) and disease-free survival (DFS) after liver resection. Patients operated on for colon cancer liver metastases were included. CSC marker expression was determined through immunohistochemistry analysis. OS and DFS were compared between marker-positive and marker-negative patients. Multivariate analysis was performed to select predictive variables for OS and DFS. CD133-positive patients had a worse DFS than CD133-negative patients, with a median DFS of 12 and 25 months (p=0.051). Multivariate analysis selected CD133 expression as a significant predictor for DFS. CD44 and CD24 were not found to predict OS or DFS. CD133 expression in colonic liver metastases is a negative prognostic factor for DFS after liver resection. In the future, CD133 could be used as a biomarker for risk stratification, and possibly for developing novel targeted therapy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Avoiding irreversible dynamics in quantum systems

NASA Astrophysics Data System (ADS)

Karasik, Raisa Iosifovna

2009-10-01

Devices that exploit laws of quantum physics offer revolutionary advances in computation and communication. However, building such devices presents an enormous challenge, since it would require technologies that go far beyond current capabilities. One of the main obstacles to building a quantum computer and devices needed for quantum communication is decoherence or noise that originates from the interaction between a quantum system and its environment, and which leads to the destruction of the fragile quantum information. Encoding into decoherence-free subspaces (DFS) provides an important strategy for combating decoherence effects in quantum systems and constitutes the focus of my dissertation. The theory of DFS relies on the existence of certain symmetries in the decoherence process, which allow some states of a quantum system to be completely decoupled from the environment and thus to experience no decoherence. In this thesis I describe various approaches to DFS that are developed in the current literature. Although the general idea behind various approaches to DFS is the same, I show that different mathematical definitions of DFS actually have different physical meaning. I provide a rigorous definition of DFS for every approach, explaining its physical meaning and relation to other definitions. I also examine the theory of DFS for Markovian systems. These are systems for which the environment has no memory, i.e., any change in the environment affects the quantum system instantaneously. Examples of such systems include many systems in quantum optics that have been proposed for implementation of a quantum computer, such as atomic and molecular gases, trapped ions, and quantum dots. Here I develop a rigorous theory that provides necessary and sufficient conditions for the existence of DFS. This theory allows us to identify a special new class of DFS that was not known before. Under particular circumstances, dynamics of a quantum system can connive together with the interactions between the system and its environment in a special way to reduce decoherence. This property is used to discover new DFS that rely on rather counterintuitive phenomenon, which I call an "incoherent generation of coherences." I also provide examples of physical systems that support such states. These DFS can be used to suppress & coherence, but may not be sufficient for performing full quantum computation. I also explore the possibility of physically generating the DFS that are useful for quantum computation. For quantum computation we need to preserve at least two quantum states to encode the quantum analogue of classical bits. Here I aim to generate DFS in a system composed from a large collection of atoms or molecules and I need to determine how one should position atoms or molecules in 3D space so that the overall system possesses a DFS with at least two states (i.e., non-trivial DFS). I show that for many Markovian systems, non-trivial DFS can exist only when particles are located in exactly the same position in space. This, of course, is not possible in the real world. For these systems, I also show that states in DFS are states with infinite lifetime. However, for all practical applications we just need long-lived states. Thus in reality, we do just need to bring quantum particles close together to generate an imperfect DFS, i.e. a collection of long-lived states. This can be achieved, for example, for atoms within a single molecule.

Do river channels decrease in width downstream on Distributive Fluvial Systems? An evaluation of modern mega-fans

NASA Astrophysics Data System (ADS)

Espinoza, T. N.; Scuderi, L. A.; Weissmann, G. S.; Hartley, A. J.

2014-12-01

Recent studies on aggradational continental sedimentary basins globally show that fluvial deposits in most modern sedimentary basins are dominated Distributive Fluvial Systems (DFS). DFS's are identified by: (1) pattern of channels and floodplain deposits that radiate outward from an apex located where the river enters the sedimentary basin, (2) deposition where an alluvial system becomes unconfined upon entering the sedimentary basin, (3) broadly fan shaped deposit that is convex upward across the DFS and concave upward down-fan, and (4) if the DFS is incised, an intersection point above which the alluvial system is held in an incised valley and below which it distributes sediment across an active depositional lobe. Several papers about DFS hypothesized that rivers on DFS decrease in size down-fan. We are testing this hypothesis through evaluation of LANDSAT and STRM data from large DFS described by Hartley et al (2010). We use ArcGIS to: (1) open the images and merge them together if there are more than one image corresponding to the DFS being studied, (2) use a Maximum Likelihood Analysis in six classes to segment different features on the DFS (e.g. exposed sands, water, vegetation, and other fan environments), (3) isolate the classes that correspond to the active channel belt (e.g., exposed sand bars and water), (4) divide the active channel belt into 1000 m long sections, (5) determine the area of active channel belt in each section, and (6) calculate the average width of the river in each section (e.g., W = area/1000m). We present our result for each DFS river on a graph that shows the change in width downstream. Our final product will be a dataset that contains width versus distance down-fan from the apex for as many of the large DFS from Hartley et al (2010) as possible. If the hypothesis is supported, the decrease in width could have a substantial predictive significance on sandstone geometry in fluvial successions.

Comparison of Quantitative Wall Motion Analysis and Strain For Detection Of Coronary Stenosis With Three-Dimensional Dobutamine Stress Echocardiography

PubMed Central

Parker, Katherine M.; Clark, Alexander P.; Goodman, Norman C.; Glover, David K.; Holmes, Jeffrey W.

2015-01-01

Background Quantitative analysis of wall motion from three-dimensional (3D) dobutamine stress echocardiography (DSE) could provide additional diagnostic information not available from qualitative analysis. In this study we compare the effectiveness of 3D fractional shortening (3DFS), a measure of wall motion computed from 3D echocardiography (3DE), to strain and strain rate measured with sonomicrometry for detecting critical stenoses during DSE. Methods Eleven open-chest dogs underwent DSE both with and without a critical stenosis. 3DFS was measured from 3DE images acquired at peak stress. 3DFS was normalized by subtracting average 3DFS during control peak stress (Δ3DFS). Strains in the perfusion defect (PD) were measured from sonomicrometry, and PD size and location were measured with microspheres. Results A Δ3DFS abnormality indicated the presence of a critical stenosis with high sensitivity and specificity (88% and 100%, respectively), and Δ3DFS abnormality size correlated with PD size (R2=0.54). The sensitivity and specificity for Δ3DFS was similar to that for area strain (88%, 100%) and circumferential strain and strain rate (88%, 92% and 88%, 86%, respectively), while longitudinal strain and strain rate were less specific. Δ3DFS correlated significantly with both coronary flow reserve (R2=0.71) and PD size (R2=0.97), while area strain correlated with PD size only (R2=0.67), and other measures were not significantly correlated with flow reserve or PD size. Conclusion Quantitative wall motion analysis using Δ3DFS is effective for detecting critical stenoses during DSE, performing similarly to 3D strain, and provides potentially useful information on the size and location of a perfusion defect. PMID:24815588

The clinical impact of Anti-DFS70 antibodies in undifferentiated connective tissue disease: case reports and a review of the literature.

PubMed

Infantino, M; Meacci, F; Grossi, V; Manfredi, M; Li Gobbi, F; Sarzi-Puttini, P; Atzeni, F; Benucci, M

2017-02-01

Anti-nuclear antibody (ANA) positivity suggests CTD but can also lead to a diagnosis of UCTD when a patient does not fulfill the CTD diagnostic criteria. An anti-dense fine speckled (DFS) immunofluorescence (IIF) pattern can be observed when using an ANA test on HEp-2 cells and is due to the presence of antibodies to the nuclear DFS70 antigen that has rarely found in CTD. Serological testing for anti-DFS70 antibodies could therefore play a very interesting negative predictive role in stratifying patients on the basis of the evolution of UCTD to CTD. We described two patients ANA and anti-DFS70 positive in which the use of new method allowing the immunoadsorption of anti-DFS70 antibodies has permitted to exclude the incorrect diagnosis of CTD.

Comparison between Magnetopause and Magnetotail Reconnection Processes

NASA Astrophysics Data System (ADS)

Walker, R. J.; Lapenta, G.; Berchem, J.; El-Alaoui, M.

2017-12-01

For the past two years the Magnetosphere Multiscale (MMS) mission has returned detailed observations of reconnection at Earth's dayside magnetopause and now apogee has moved into the magnetotail to enable investigations of reconnection in the plasma sheet. We have been using a combination of global magnetohydrodynamic (MHD) simulation and particle-in-cell (PIC) simulation to model the physics of the reconnection process in both regions. In these calculations, we first use the MHD simulation to model the overall magnetospheric configuration and then carry out a large implicit PIC simulation by using the resulting MHD state to set the initial and boundary conditions. In this presentation, we review the similarities and differences found between the physical processes involved in reconnection occurring in the two different regions. For instance, similar crescent shaped distribution functions have been both observed and found in simulations of reconnection at the magnetopause and in the tail current sheet. Likewise, kinetic simulations have shown that the agyrotropy (non-gyrotropy) of the electron distribution function is the cleanest indicator of the location of the electron diffusion region (EDR) of both regions. There are also significant differences between the two regions. These are mostly related to the fact that separatrices are different because the plasma density is asymmetric across the dayside magnetopause and that smaller electric and guide fields are present in the night side. For instance, the jetting plasmas from reconnection in the tail form dipolarization fronts where energy exchange occurs while flux transfer events (flux ropes) form on the magnetopause and then move away from the reconnection site without forming dipolarization fronts. However, many uncertainties remain. For example, strong waves associated with the reconnection are found in the EDR at both places but it is not understood whether the kinetic mechanisms leading to the waves are the same or different.

Performance of Dispersed Fringe Sensor in the Presence of Segmented Mirror Aberrations: Modeling and Simulation

NASA Technical Reports Server (NTRS)

Shi, Fang; Basinger, Scott A.; Redding, David C.

2006-01-01

Dispersed Fringe Sensing (DFS) is an efficient and robust method for coarse phasing of a segmented primary mirror such as the James Webb Space Telescope (JWST). In this paper, modeling and simulations are used to study the effect of segmented mirror aberrations on the fringe image, DFS signals and DFS detection accuracy. The study has shown due to the pixilation spatial filter effect from DFS signal extraction the effect of wavefront error is reduced and DFS algorithm will be more robust against wavefront aberration by using multi-trace DFS approach. We also studied the JWST Dispersed Hartmann Sensor (DHS) performance in presence of wavefront aberrations caused by the gravity sag and we use the scaled gravity sag to explore the JWST DHS performance relationship with the level of the wavefront aberration. This also includes the effect from line-of-sight jitter.

Comparison of Glasgow prognostic score and prognostic index in patients with advanced non-small cell lung cancer.

PubMed

Jiang, Ai-Gui; Chen, Hong-Lin; Lu, Hui-Yu

2015-03-01

Previous studies have shown that Glasgow prognostic score (GPS) and prognostic index (PI) are also powerful prognostic tool for patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to compare the prognostic value between GPS and PI. We enrolled consecutive patients with advanced NSCLC in this prospective cohort. GPS and PI were calculated before the onset of chemotherapy. The prognosis outcomes included 1-, 3-, and 5-year progression-free survival and overall survival (OS). The performance of two scores in predicting prognosis was analyzed regarding discrimination and calibration. 138 patients were included in the study. The area under the receiver operating characteristic curve for GPS predicting 1-year DFS was 0.62 (95 % confidence interval (CI) 0.56-0.68, P < 0.05), and the area under curve for PI predicting 1-year DFS was 0.57 (95 % CI 0.52-0.63). Delong's test showed that GPS was more accurate than PI in predicting 1-year DFS (P < 0.05). Similar results of discriminatory power were found for predicting 3-year DFS, 1-year OS, and 3-year OS. The predicted 1-year DFS by GPS 0, GPS 1, and GPS 2 were 62.5, 42.1, and 23.1 %, respectively, while actual 1-year DFS by GPS 0, GPS 1, and GPS 2 were 61.1, 43.8, and 27.2 %, respectively. Calibration of the Hosmer and Lemeshow statistic showed good fit of the predicted 1-year DFS to the actual 1-year DFS by GPS (χ(2) = 4.326, P = 0.462), while no fit was found between the predicted 1-year DFS and the actual 1-year DFS by PI (χ(2) = 15.234, P = 0.091). Similar results of calibration power were found for predicting 3-year DFS, 5-year DFS, 1-year OS, 3-year OS, and 5-year OS by GPS and PI. GPS is more accurate than PI in predicting prognosis for patients with advanced NSCLC. GPS can be used as a useful and simple tool for predicting prognosis in patients with NSCLC. However, GPS only can be used for preliminary assessment because of low predicting accuracy.

Extent of tooth decay in the mouth and increased need for replacement of dental restorations: the New England Children's Amalgam Trial.

PubMed

Trachtenberg, Felicia; Maserejian, Nancy Nairi; Tavares, Mary; Soncini, Jennifer Ann; Hayes, Catherine

2008-01-01

The purpose of this study was to assess the relationship between baseline caries experience and the restoration replacement rate in children. The 5-year New England Children's Amalgam Trial recruited 534 6- to 10-year-old children with 2 or more carious posterior teeth. The association between decoy and longevity of restorations was assessed. Restorations with no follow-up (N = 391) were excluded from analysis. The average follow-up was 3.0 +/- 1.6 years in 489 children. Restorations with follow-up (N = 3,604) were placed in mouths with a median of 15 dfs/DFS and 8 dft/DFT. The need for replacement increased significantly (P < or = .001) with increasing numbers of dfs/DFS and dft/DFT. After 5 years of follow-up, at least 15% of restorations in a mouth with > or = 14 dfs/DFS needed replacement, compared to 9% for 2 to 5 dfs/DFS. Comparing dft/DFT after 5 years of follow-up, there was a 23% replacement rate for > or = 12 dft/DFT compared to 10% for 2 to 3 dft/DFT. Decoy in the mouth had a greater association with the need for replacement due to new caries compared to replacement due to recurrent caries. Children with more decoy at the time of restoration placement were at higher risk for replacement of restorations.

Pattern of tumour growth of the primary colon cancer predicts long-term outcome after resection of liver metastases.

PubMed

Spelt, Lidewij; Sasor, Agata; Ansari, Daniel; Andersson, Roland

2016-10-01

To identify significant predictive factors for overall survival (OS) and disease-free survival (DFS) after liver resection for colon cancer metastases, with special focus on features of the primary colon cancer, such as lymph node ratio (LNR), vascular invasion, and perineural invasion. Patients operated for colonic cancer liver metastases between 2006 and 2014 were included. Details on patient characteristics, the primary colon cancer operation and metastatic disease were collected. Multivariate analysis was performed to select predictive variables for OS and DFS. Median OS and DFS were 67 and 20 months, respectively. 1-, 3- and 5-year OS were 97, 76, and 52%. 1-, 3- and 5-year DFS were 65, 42, and 37%. Multivariate analysis showed LNR to be an independent predictive factor for DFS but not for OS. Other identified predictive factors were vascular and perineural invasion of the primary colon cancer, size of the largest metastasis and severe complications after liver surgery for OS, and perineural invasion, number of liver metastases and preoperative CEA-level for DFS. Traditional N-stage was also considered to be an independent predictive factor for DFS in a separate multivariate analysis. LNR and perineural invasion of the primary colon cancer can be used as a prognostic variable for DFS after a concomitant liver resection for colon cancer metastases. Vascular and perineural invasion of the primary colon cancer are predictive for OS.

The health benefits of dietary fiber: beyond the usual suspects of type 2 diabetes mellitus, cardiovascular disease and colon cancer.

PubMed

Kaczmarczyk, Melissa M; Miller, Michael J; Freund, Gregory G

2012-08-01

Dietary fiber (DF) is deemed to be a key component in healthy eating. DF is not a static collection of undigestible plant materials that pass untouched or unencumbered through the gastrointestinal (GI) tract; instead, DFs are a vast array of complex saccharide-based molecules that can bind potential nutrients and nutrient precursors to prevent their absorption. Some DFs are fermentable, and the GI tract catabolism leads to the generation of various bioactive materials, such as short-chain fatty acids (SCFAs), that can markedly augment the GI tract biomass and change the composition of the GI tract flora. The health benefits of DFs include the prevention and mitigation of type 2 diabetes mellitus, cardiovascular disease and colon cancer. By modulating food ingestion, digestion, absorption and metabolism, DFs reduce the risk of hyperlipidemia, hypercholesterolemia and hyperglycemia. Emerging research has begun to investigate the role of DFs in immunomodulation. If substantiated, DFs could facilitate many biologic processes, including infection prevention and the improvement of mood and memory. This review describes the accepted physiologic functions of DFs and explores their new potential immune-based actions. Copyright © 2012 Elsevier Inc. All rights reserved.

The health benefits of dietary fiber: beyond the usual suspects of type 2 diabetes, cardiovascular disease and colon cancer

PubMed Central

Kaczmarczyk, Melissa M.; Miller, Michael J.; Freund, Gregory G.

2012-01-01

Dietary fiber (DF) is deemed to be a key component in healthy eating. DF is not a static collection of undigestible plant materials that pass untouched or unencumbered through the gastrointestinal (GI) tract; instead, DFs are a vast array of complex saccharide-based molecules that can bind potential nutrients and nutrient precursors to prevent their absorption. Some DFs are fermentable, and the GI tract catabolism leads to the generation of various bioactive materials, such as short-chain fatty acids (SCFAs), that can markedly augment the GI tract biomass and change the composition of the GI tract flora. The health benefits of DFs include the prevention and mitigation of type 2 diabetes, cardiovascular disease and colon cancer. By modulating food ingestion, digestion, absorption and metabolism, DFs reduce the risk of hyperlipidemia, hypercholesterolemia and hyperglycemia. Emerging research has begun to investigate the role of DFs in immunomodulation. If substantiated, DFs could facilitate many biologic processes, including infection prevention and the improvement of mood and memory. This review describes the accepted physiologic functions of DFs and explores their new potential immune-based actions. PMID:22401879

Autoantibodies to Dense Fine Speckles in Pediatric Diseases and Controls.

PubMed

Schmeling, Heinrike; Mahler, Michael; Levy, Deborah M; Moore, Katharine; Stevens, Anne M; Wick, James; McMillan, Jacob D; Horneff, Gerd; Assassi, Shervin; Charles, Julio; Salazar, Gloria; Mayes, Maureen D; Silverman, Earl D; Klien-Gitelman, Marissa; Lee, Tzelan; Brunner, Hermine I; Reed, Ann M; Fritzler, Marvin J

2015-12-01

Autoantibodies to the dense fine speckled 70 kDa antigen (DFS70) are reported to be more common in individuals who do not have an antinuclear antibody (ANA)-associated rheumatic disease (AARD) than in patients with AARD. The frequency of anti-DFS70 antibodies has been thoroughly studied in adult but not in pediatric populations. The primary objective of this observational study was to determine the frequency of anti-DFS70 in pediatric AARD and reference cohorts. Sera from 743 children with AARD and related conditions, and 345 samples from reference cohorts (healthy children and those being investigated for AARD) were studied for anti-DFS70 autoantibodies as measured by a chemiluminescence immunoassay. A de-identified administrative database was used to retrieve demographic, serologic, and clinical data. Anti-DFS70 antibodies were seen in 2.1% of healthy children and in 4.5% of sera from pediatric individuals referred for ANA testing. The frequency of anti-DFS70 was highest in juvenile localized scleroderma (LS; 4/29, 13.8%), juvenile dermatomyositis (JDM; 2/11, 18.2%), childhood systemic lupus erythematosus (cSLE; 19/331, 5.7%), diffuse cutaneous systemic sclerosis (1/22, 4.5%), celiac disease (2/49, 4.1%), and juvenile idiopathic arthritis (JIA; 5/202, 2.5%). Of note, anti-DFS70 antibodies were observed in 3/26 children (11.5%) with uveitis and JIA-associated uveitis. The frequency of anti-DFS70 autoantibodies in healthy pediatric subjects is within the lower range of that reported in adults. Anti-DFS70 antibodies can be found in childhood SSc and cSLE, but has a remarkably high frequency in children with LS, JDM, and uveitis.

Digital frequency synthesizer for radar astronomy

NASA Technical Reports Server (NTRS)

Sadr, R.; Satorius, E.; Robinett, L.; Olson, E.

1990-01-01

The digital frequency synthesizer (DFS) is an integral part of the programmable local oscillator (PLO) which is being developed for the NASA's Deep Space Network (DSN) and radar astronomy. Here, the theory of operation and the design of the DFS are discussed, and the design parameters in application for the Goldstone Solar System Radar (GSSR) are specified. The spectral purity of the DFS is evaluated by analytically evaluating the output spectrum of the DFS. A novel architecture is proposed for the design of the DFS with a frequency resolution of 1/2(exp 48) of the clock frequency (0.35 mu Hz at 100 MHz), a phase resolution of 0.0056 degrees (16 bits), and a frequency spur attenuation of -96 dBc.

Blind quantum computation over a collective-noise channel

NASA Astrophysics Data System (ADS)

Takeuchi, Yuki; Fujii, Keisuke; Ikuta, Rikizo; Yamamoto, Takashi; Imoto, Nobuyuki

2016-05-01

Blind quantum computation (BQC) allows a client (Alice), who only possesses relatively poor quantum devices, to delegate universal quantum computation to a server (Bob) in such a way that Bob cannot know Alice's inputs, algorithm, and outputs. The quantum channel between Alice and Bob is noisy, and the loss over the long-distance quantum communication should also be taken into account. Here we propose to use decoherence-free subspace (DFS) to overcome the collective noise in the quantum channel for BQC, which we call DFS-BQC. We propose three variations of DFS-BQC protocols. One of them, a coherent-light-assisted DFS-BQC protocol, allows Alice to faithfully send the signal photons with a probability proportional to a transmission rate of the quantum channel. In all cases, we combine the ideas based on DFS and the Broadbent-Fitzsimons-Kashefi protocol, which is one of the BQC protocols, without degrading unconditional security. The proposed DFS-based schemes are generic and hence can be applied to other BQC protocols where Alice sends quantum states to Bob.

Ultrasonographic characterization of follicle deviation in follicular waves with single dominant and codominant follicles in dromedary camels (Camelus dromedarius).

PubMed

Manjunatha, B M; Al-Bulushi, S; Pratap, N

2014-04-01

Follicular wave emergence was synchronized by treating camels with GnRH when a dominant follicle (DF) was present in the ovaries. Animals were scanned twice a day from day 0 (day of GnRH treatment) to day 10, to characterize emergence and deviation of follicles during the development of the follicular wave. Follicle deviation in individual animals was determined by graphical method. Single DFs were found in 16, double DFs in 9 and triple DFs in two camels. The incidence of codominant (double and triple DFs) follicles was 41%. The interval from GnRH treatment to wave emergence, wave emergence to deviation, diameter and growth rate of F1 follicle before or after deviation did not differ between the animals with single and double DFs. The size difference between future DF(s) and the largest subordinate follicle (SF) was apparent from the day of wave emergence in single and double DFs. Overall, interval from GnRH treatment to wave emergence and wave emergence to the beginning of follicle deviation was 70.6 ± 1.4 and 58.6 ± 2.7 h, respectively. Mean size of the DF and largest SF at the beginning of deviation was 7.4 ± 0.2 and 6.3 ± 0.1 mm, respectively. In conclusion, the characteristics of follicle deviation are similar between the animals that developed single or double DFs. © 2013 Blackwell Verlag GmbH.

Dynamic Foot Stimulation Attenuates Soleus Muscle Atrophy Induced by Hindlimb Unloading in Rats

NASA Technical Reports Server (NTRS)

Kyparos, Antonios; Feeback, Daniel L.; Layne, Charles S.; Martinez, Daniel A.; Clarke, Mark S. F.

2004-01-01

Unloading-induced myofiber atrophy is a phenomenon that occurs in the aging population, bed-ridden patients and astronauts. The objective of this study was to determine whether or not dynamic foot stimulation (DFS) applied to the plantar surface of the rat foot can serve as a countermeasure to the soleus muscle atrophy normally observed in hindlimb unloaded (HU) rats. Thirty mature adult (6-month-old) male Wistar rats were randomly assigned into ambulatory control (AMB), hindlimb unloaded alone (HU), or hindlimb unloaded with the application of DFS (HU+DFS) groups. A dynamic pattern of pressure was applied to the right foot of each HU animal using a specially fabricated boot containing an inflatable air bladder connected to a solenoid air pump controlled by a laptop computer. The anti-atrophic effects of DFS were quantified morphometrically in frozen cross-sections of soleus muscle stained using the metachromatic-ATPase fiber typing technique. Application of DFS during HU significantly counteracted the atrophic response observed in the soleus by preventing approximately 85% of the reduction in Type I myofiber cross-sectional area (CSA) observed during HU. However, DFS did not protect type II fibers of the soleus from HU-induced atrophy or any fiber type in the soleus muscle of the contralateral control leg of the DFS-treated HU animals. These results illustrate that the application of DFS to the rat foot is an effective countermeasure to soleus muscle atrophy induced by HU.

Missing the Benefit of Metformin in Acute Myeloid Leukemia: A Problem of Contrast?

PubMed

Ceacareanu, Alice C; Nimako, George K; Wintrob, Zachary A P

2017-01-01

To evaluate whether metformin's cancer-related benefits reported in patients with solid tumors (ST) are also present in acute myeloid leukemia (AML) patients. Baseline demographic and clinical history for all diabetes mellitus patients newly diagnosed with AML or cancer of the breast, ovary, prostate, gastrointestinal tract, lung, or kidney at Roswell Park Cancer Institute in Buffalo, NY (January 2003-December 2010, n = 924) was collected. Overall survival (OS) and disease-free survival (DFS) were assessed by Kaplan-Meier (KM) analysis and Cox proportional hazards regression (hazard ratio [HR]). Baseline metformin use provided significant OS and DFS benefit in ST but not in AML (KM: P ST-OS = 0.003; P ST-DFS = 0.002; P AML-OS = 0.961; P AML-DFS = 0.943). AML median survival was slightly better with metformin use, but users derived no relapse benefit. In ST, metformin nonusers had shorter median survival, 57.7 versus 86 months, and poorer outcomes (HR ST-OS = 1.33; P ST-OS = 0.002; HR ST-DFS = 1.32; P ST-DFS = 0.002). These findings remained significant in age-adjusted models (HR ST-OS = 1.21; P ST-OS = 0.039; HR ST-DFS = 1.23; P ST-DFS = 0.02) but not fully adjusted models (HR ST-OS = 0.96; P ST-OS = 0.688; HR ST-DFS = 1.0; P ST-DFS = 0.94). Higher mortality was noted in AML patients taking insulin versus oral diabetes pharmacotherapy at baseline (HR AML-OS = 2.03; P AML-OS = 0.04). Lack of metformin benefit in AML could be due to advanced age at cancer diagnosis. Metformin substitution with insulin before computed tomography scans with contrast - a frequent AML assessment practice - may also explain the lack of subsequent benefit despite taking metformin at baseline. A temporary metformin substitution is recommended by the package insert due to a possible drug interaction with the contrast dye. Our data suggest that metformin substitution was permanent in many patients. Nonetheless, the observed benefit in other malignancies warrants further investigation of metformin use in AML.

Missing the Benefit of Metformin in Acute Myeloid Leukemia: A Problem of Contrast?

PubMed Central

Ceacareanu, Alice C.; Nimako, George K.; Wintrob, Zachary A. P.

2017-01-01

Objective: To evaluate whether metformin's cancer-related benefits reported in patients with solid tumors (ST) are also present in acute myeloid leukemia (AML) patients. Methods: Baseline demographic and clinical history for all diabetes mellitus patients newly diagnosed with AML or cancer of the breast, ovary, prostate, gastrointestinal tract, lung, or kidney at Roswell Park Cancer Institute in Buffalo, NY (January 2003–December 2010, n = 924) was collected. Overall survival (OS) and disease-free survival (DFS) were assessed by Kaplan–Meier (KM) analysis and Cox proportional hazards regression (hazard ratio [HR]). Findings: Baseline metformin use provided significant OS and DFS benefit in ST but not in AML (KM: PST-OS= 0.003; PST-DFS= 0.002; PAML-OS= 0.961; PAML-DFS= 0.943). AML median survival was slightly better with metformin use, but users derived no relapse benefit. In ST, metformin nonusers had shorter median survival, 57.7 versus 86 months, and poorer outcomes (HRST-OS= 1.33; PST-OS= 0.002; HRST-DFS= 1.32; PST-DFS= 0.002). These findings remained significant in age-adjusted models (HRST-OS= 1.21; PST-OS= 0.039; HRST-DFS= 1.23; PST-DFS= 0.02) but not fully adjusted models (HRST-OS= 0.96; PST-OS= 0.688; HRST-DFS= 1.0; PST-DFS= 0.94). Higher mortality was noted in AML patients taking insulin versus oral diabetes pharmacotherapy at baseline (HRAML-OS= 2.03; PAML-OS= 0.04). Conclusion: Lack of metformin benefit in AML could be due to advanced age at cancer diagnosis. Metformin substitution with insulin before computed tomography scans with contrast – a frequent AML assessment practice – may also explain the lack of subsequent benefit despite taking metformin at baseline. A temporary metformin substitution is recommended by the package insert due to a possible drug interaction with the contrast dye. Our data suggest that metformin substitution was permanent in many patients. Nonetheless, the observed benefit in other malignancies warrants further investigation of metformin use in AML. PMID:29026839

Iron-chelating agent, deferasirox, inhibits neutrophil activation and extracellular trap formation.

PubMed

Kono, Mari; Saigo, Katsuyasu; Yamamoto, Shiori; Shirai, Kohei; Iwamoto, Shuta; Uematsu, Tomoko; Takahashi, Takayuki; Imoto, Shion; Hashimoto, Makoto; Minami, Yosuke; Wada, Atsushi; Takenokuchi, Mariko; Kawano, Seiji

2016-10-01

Iron-chelating agents, which are frequently prescribed to transfusion-dependent patients, have various useful biological effects in addition to chelation. Reactive oxygen species (ROS) produced by neutrophils can cause pulmonary endothelial cell damage, which can lead to acute lung injury (ALI). We previously reported that deferasirox (DFS), an iron-chelating agent, inhibits phorbol myristate acetate (PMA) or formyl-methionyl-leucyl-phenylalanine (fMLP)-induced ROS production in neutrophils, in vitro. Here, we investigate whether DFS inhibits vacuolization in neutrophils and neutrophil extracellular trap (NET) formation. Human neutrophils were incubated with DFS and stimulated with PMA or fMLP. Human neutrophils were separated from heparinized peripheral blood using density gradient centrifugation, and subsequently incubated with DFS. After 10 minutes, neutrophils were stimulated by PMA or fMLP. Vacuole formation was observed by electron microscopy. For observing NET formations using microscopes, immunohistological analyses using citrullinated histone H3 and myeloperoxidase antibodies, and SYTOX Green (an impermeable DNA detection dye) staining, were conducted. NET formation was measured as the quantity of double-stranded DNA (dsDNA), using the AccuBlue Broad Range dsDNA Quantitation Kit. DFS (50 μmol/L) inhibited vacuole formation in the cytoplasm and NET formation. Additionally, 5-100 μmol/L concentration of DFS inhibited the release of dsDNA in a dose-independent manner. We demonstrate that DFS inhibits not only ROS production but also vacuolization and NET formation in neutrophils. These results suggest the possibility of protective effects of DFS against NET-related adverse effects, including ALI and thrombosis. © 2016 John Wiley & Sons Australia, Ltd.

German telecommunications satellite (Deutscher fernmelde satellit) (DFS-1 and -2)

NASA Technical Reports Server (NTRS)

Hiendlmeier, G.; Schmeller, H.

1991-01-01

The German Telecommunications Satellite (DFS) Program is to provide telecommunications service for high data rate transmission of text and video data to the Federal Republic of Germany within the 11-14 GHz and 20-30 GHz bands. The space segment of this program is composed of three satellites, DFS-1, DFS-2, and DFS-3, which will be located at 23.5 degrees E longitude of the geostationary orbit. The DFS will be launched from the Center Spatial Guyanis in French Giana on an Ariane launch vehicle. The mission follows the typical injection sequence: parking orbit, transfer orbit, and earth orbit. Attitude maneuvers will be performed to orient the spacecraft prior to Apogee Kick Motor (AKM) firing. After AKM firing, drift phase orbital and attitude maneuvers will be performed to place the spacecraft in its final geostationary position. The Deep Space Network (DSN) will support the transfer and drift orbit mission phases. Information is presented in tabular form for the following areas: DSN support, compatibility testing, frequency assignments, telemetry, command, and tracking support responsibilities.

Caries risk profiles in orthodontic patients at follow-up using Cariogram.

PubMed

Al Mulla, Anas H; Kharsa, Saad Al; Kjellberg, Heidrun; Birkhed, Dowen

2009-03-01

To analyze caries-related factors shortly after orthodontic treatment and to use the Cariogram computer program to describe caries risk profiles at follow-up in these patients. One hundred orthodontic patients age 12-29 years, with a mean age of 17.5 years, were included in the study. They were divided into two groups (50 in each) based on their prebonding decayed, filled surfaces index (DFS). High (5 > or = DFS) and low (2 < or = DFS) groups were created. All patients were examined after debonding in the following order: interview, plaque score, caries examination, saliva samples, bitewing radiographs, panoramic radiographs, and intra-oral digital photos. All types of carious lesions in both the enamel and dentine were diagnosed clinically and radiographically and included in the DFS index. A paraffin-stimulated whole saliva sample was collected for estimations of secretion rate, buffer capacity, and number of mutans streptococci and lactobacilli. The low caries group (2 < or = DFS) displayed a statistically significant difference and low values for the following factors, DFS (P < .001), lactobacilli (P < .001), mutans streptococci (P < .001), and high Cariogram percent (P < .001). The plaque index displayed very close significance (P = .051). Patients with high (5 > or = DFS) numbers before orthodontic treatment ran a higher risk of developing caries. They had significantly higher numbers of mutans streptococci and lactobacilli and had less chance of avoiding new cavities according to the Cariogram.

Genetic variants in the vitamin D pathway and breast cancer disease-free survival

PubMed Central

Brewster, Abenaa M.

2013-01-01

Epidemiological studies have investigated the association between vitamin D pathway genes and breast cancer risk; however, little is known about the association between vitamin D pathway genes and breast cancer prognosis. In a retrospective cohort of 1029 patients with early-stage breast cancer, we analyzed the association between 106 tagging single nucleotide polymorphisms (SNPs) in eight vitamin D pathway genes and breast cancer disease-free survival (DFS) using Cox regression analysis adjusted for known prognostic variables. Using a false discovery rate of 10%, six intronic SNPs were significantly associated with poorer DFS: retinoid-X receptor alpha (RXRA) SNPs (rs881658, rs11185659, rs10881583, rs881657 and rs7864987) and plasminogen activator and urokinase receptor (PLAUR) SNP (rs4251864). Treatment received (no systemic therapy, hormone therapy alone or chemotherapy) was an effect modifier of the RXRA SNPs association with DFS (P < 0.05); therefore, we stratified further analysis by treatment group. Among patients who did not receive systemic therapy, RXRA SNP [rs10881583 (P = 0.02)] was associated with poorer DFS, and among patients who received chemotherapy, RXRA SNPs (rs881658, rs11185659, rs10881583, rs881657 and rs7864987) were associated with poorer DFS (P < 0.001 for all SNPs). However, RXRA SNPs: rs10881583 (P < 0.001) and rs881657 (P = 0.02) were associated with improved DFS in patients treated with hormone therapy alone. Our results suggest that SNPs in the RXRA and PLAUR genes in the vitamin D pathway may contribute to breast cancer DFS. In particular, SNPs in RXRA may predict for poorer or improved DFS in patients, according to type of systemic treatment received. If validated, these markers could be used for risk stratification of breast cancer patients. PMID:23180655

Simultaneous Distinction of Monospecific and Mixed DFS70 Patterns During ANA Screening with a Novel HEp-2 ELITE/DFS70 Knockout Substrate

PubMed Central

Malyavantham, Kishore S.; Suresh, Lakshmanan

2018-01-01

Systemic autoimmune connective tissue disorders are characterized by circulating antinuclear antibodies (ANA). Although there are several technologies available for ANA screening, indirect immunofluorescence (IIF) using Human epithelial cells-2 (HEp-2) substrate remains the primary and recommended method because of its superior sensitivity. HEp-2 substrates can detect a multitude of patterns resulting from autoantibody binding to various protein and nucleic acid autoantigens distributed throughout the nucleus and cytoplasm of the cells. The great diversity of monospecific and mixed patterns resulting from positive reactions on HEp-2 substrate also complicate the interpretation and accuracy of reporting. One specific example which received utmost attention recently is the dense fine speckled 70 (DFS70) pattern resulting from autoantibodies that specifically bind to a protein called lens epithelium derived growth factor (LEDGF). Lack of clear association with a specific systemic autoimmune disease and high prevalence in healthy populations have made accurate interpretation of DFS70 pattern important. Accurate distinction of DFS70 pattern from disease-associated patterns using conventional HEp-2 substrate is challenging. Moreover, frequent co-occurrence of DFS70 pattern along with disease-associated patterns such as homogeneous, speckled, and mixed homogeneous-speckled patterns complicate the IIF interpretation. The goal of this paper is to demonstrate the utility of a novel engineered HEp-2 IIF substrate that retains all advantages of conventional HEp-2 substrate while simultaneously providing the ability to distinguish DFS70 pattern with high confidence in both monospecific and mixed ANA positive examples. The new substrate is further able to unmask disease-associated ANA patterns previously concealed by DFS70 pattern. PMID:29364249

Amputations and mortality in in-hospital treated patients with peripheral artery disease and diabetic foot syndrome.

PubMed

Malyar, Nasser M; Freisinger, Eva; Meyborg, Matthias; Lüders, Florian; Gebauer, Katrin; Reinecke, Holger; Lawall, Holger

2016-08-01

The prevalence of diabetes mellitus (DM) and its associated complications such as peripheral artery disease (PAD) and diabetic foot syndrome (DFS) are increasing worldwide. We aimed to determine the contemporary acute and long-term outcome of patients with PAD and DFS in Germany. Nationwide, anonymized data of 40,335 patients hospitalized for PAD and/or DFS from the years 2009-2011 were analyzed and followed up until 2013. Patients were classified into 3 groups: DFS, PAD+DM and PAD without DM. In-hospital and long-term outcome (1156days, 95% CI 1.151-1.161) regarding major and minor amputation and mortality was assessed. Cumulative amputation-free survival and overall survival rates were calculated using Kaplan-Meier analysis. The proportion of DFS, PAD+DM and PAD only was 17.3%, 21.5% and 61.2%, respectively. At index-hospitalization, DFS patients had the highest amputation (31.9% vs. 11.1% vs. 6.0%), yet the lowest revascularization rate (18.2% vs. 67.8% vs. 71.6%) compared to patients with PAD only and PAD+DM (P<0.001). Cumulative 4-year survival (57.4%, 60.8% and 70.0%) and amputation-free-survival (45.4%, 74.4% and 86.5%) were lowest for DFS followed by PAD+DM and PAD only (P<0.001). Patients with diabetes, particularly those with DFS, have persistent high rates of limb amputation and of mortality in a real-world setting. Our data emphasize the need for further dedicated research to identify and target the underlying causes of the extraordinary poor outcome in this high risk population. Copyright © 2016 Elsevier Inc. All rights reserved.

Daily Fantasy Football and Self-Reported Problem Behavior in the United States.

PubMed

Dwyer, Brendan; Shapiro, Stephen L; Drayer, Joris

2017-09-26

Traditional, season-long fantasy sport participation has grown considerably since the late 1990s, and in an attempt to capitalize on this growing demand, daily fantasy sports (DFS) providers have created a new game where money changes hands instantly. This change has led some legal commentators and state agencies to believe the game is a form of Internet gambling similar to online poker, blackjack, and sports wagering, and thus, it requires increased regulation or even prohibition. Little is known, however, about the gambling behavior associated with DFS participation. Thus, the purpose of the current study was to examine problem gambling severity in conjunction with DFS participant motives, perceptions, and consumption behavior. Over 500 DFS participants were surveyed, and the results suggest DFS participants behave similarly with participants in other forms of gambling activities. In addition, the findings suggest additional consumer protections may be needed to prevent further problem behavior such as chasing.

Prognostic Factors in Adult Soft Tissue Sarcoma Treated with Surgery Combined with Radiotherapy: A Retrospective Single-Center Study on 164 Patients

PubMed Central

Cai, Ling; Mirimanoff, René-Olivier; Mouhsine, Elyazid; Guillou, Louis; Leyvraz, Pierre-Francois; Leyvraz, Serge; Gay, Beatrice; Matzinger, Oscar; Ozsahin, Mahmut; Zouhair, Abderrahim

2013-01-01

The aim of the present study is to assess the disease profile, outcome and prognostic factors in patients treated with surgery combined with radiotherapy (RT), with or without chemotherapy (CXT), for soft-tissue sarcoma (STS) in a multidisciplinary setting. One hundred and sixty-four patients with STS treated between 1980 and 2010 at the Centre Hospitalier Universitaire Vaudois were enrolled in this retrospective study. Seventy-six percent of patients underwent postoperative RT with (24%), or without (52%) CXT, 15% preoperative RT with (5%), or without (10%) CXT, surgery alone (7%), or RT alone (2%) with or without CXT. The median follow-up was 60 months (range 6-292). Local failure was observed in 18%, and distant failure in 21% of the patients. Overall survival (OS), diseasefree survival (DFS), local control (LC) and distant metastases-free survival (DMFS) were 88%, 68%, 83%, and 79% at 5 years, and 80%, 56%, 76%, and 69% at 10 years, respectively. In univariate analyses, favorable prognostic factors for OS, DFS, and DMFS were tumor size 6 cm or less, World Health Organization (WHO)/Zubrod score 0, and stage 2 or less. Age and superficial tumors were favorable only for OS and DMFS respectively. STS involving the extremities had a better outcome regarding DFS and LC. Histological grade 2 or less was favorable for DFS, DMFS, and LC. Radical surgery was associated with better LC and DMFS. RT dose more than 60 Gy was favorable for OS, DFS, and LC. In multivariate analyses, independent factors were age for OS; tumor size for OS, DFS and DMFS; WHO/Zubrod score for OS, DFS and LC; hemoglobin level for DFS; site for DFS and LC; tumor depth for DMFS; histological grade for DFS and LC; surgical procedure for LC and DMFS; and RT dose for OS. This study confirms that in a multidisciplinary setting, STS have a fairly good prognosis. A number of prognostic and predictive factors, including the role of surgery combined with RT, were identified. Regarding RT, a dose of more than 60 Gy was associated with a better outcome, at the price of a higher toxicity. We could not demonstrate a superiority of preoperative RT over postoperative RT. PMID:24416489

Impact of tumor deposits on the prognosis and chemotherapy efficacy in stage III colorectal cancer patients with different lymph node status: a retrospective cohort study in China.

PubMed

Li, Xiao; An, Bang; Zhao, Qi; Qi, Jianni; Wang, Wenwen; Zhang, Di; Li, Zhen; Qin, Chengyong

2018-06-21

The goal was to determine whether tumor deposits (TDs) had effects on the overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS) and responses to chemotherapy in advanced colorectal cancer (CRC) patients with different lymph node (N) stages. The retrospective cohort study recruited 1,455 stage III CRC patients diagnosed at a single institution between January 2010 and July 2016. Patients were divided into TDs negative and positive groups. Based on whether they accepted chemotherapy, patients were further divided into chemotherapy and non-chemotherapy groups. Kaplan-Meier methods, univariate and multivariate analyses, and subset analyses based on the N stage were performed to compare the OS, CSS and DFS between different groups. Multivariate Cox analyses showed that TDs were independent prognostic markers for the OS (adjusted HR=1.929, 95% CI: 1.339-2.777), CSS (adjusted HR=1.789, 95% CI: 1.165-2.748) and DFS (adjusted HR=2.179, 95% CI: 1.612-2.944) in all N stages combined. In addition, subset analyses based on the N stage further demonstrated that TDs were independent risk factors for the OS (P=0.012), CSS (P=0.010) and DFS (P<0.001) in patients with the N1a, 1 b stages, and for the OS (P=0.023) and DFS (P<0.001) in patients with the N2a, 2 b stages. Furthermore, the OS, CSS and DFS in the TDs negative group could be extended significantly after the administration of chemotherapy, whereas patients with positive TDs lost the DFS benefit from chemotherapy. Stage III CRC patients with positive TDs had a poor prognosis, and they did not display a DFS benefit from chemotherapy. TDs had adverse effects on the OS and DFS in patients with the N1a, 1 b and N2a, 2 b stages, providing evidence for the feasibility of the new TNM category method. Copyright © 2018. Published by Elsevier Ltd.

High amplification of FGFR1 gene is a delayed poor prognostic factor in early stage ESCC patients

PubMed Central

Song, Qi; Liu, Yalan; Jiang, Dongxian; Wang, Haixing; Huang, Jie; Xu, Yifan; Sujie, Akesu; Zeng, Haiying; Xu, Chen; Hou, Yingyong

2017-01-01

Amplification of the fibroblast growth factor receptor 1 (FGFR1) is believed to predict response to FGFR inhibitors. The aim of this study was to investigate the frequency and the prognostic impact of FGFR1 amplification in patients with resected esophageal squamous cell carcinoma (ESCC) by using fluorescent in situ hybridization. Microarrayed paraffin embedded blocks were constructed, and the cohort of tissues came from 506 patients with ESCC. FGFR1 high amplification (FGFR1high) was defined by an FGFR1/centromere 8 ratio of ≥ 2.0, or average number of FGFR1 signals/tumor cell nucleus ≥ 6.0, or percentage of tumor cells containing ≥ 15 FGFR1 signals, or large cluster in ≥ 10% of cancer cells. FGFR1 low amplification was defined by ≥ 5 FGFR1 signals in ≥ 50% of cancer cells. Kaplan-Meier curves with log-rank tests and Cox proportional hazards model were used to analyze patients’ survival. Among 506 patients, high amplification, low amplification, and disomy were detected in 8.7%, 3.6% and 87.7%, respectively. In general, the FGFR1high group trended towards worse disease-free survival (DFS) and overall survival (OS) compared to the FGFR1 low amplification/disomy (FGFR1low/disomy) group (DFS, P=0.108; OS, P=0.112), but this trend was amplified for patients with DFS ≥ 30 months (DFS, P=0.009; OS, P=0.007). Furthermore, when patients were stratified into stage I-II and stage III-IV, the FGFR1high group directly presented with adverse DFS and OS than the FGFR1low/disomy group in stage I-II patients (DFS, P=0.019; OS, P=0.034), especially with DFS ≥ 30 months (DFS, P=0.002; OS, P=0.001). However, for patients in stage III-IV, FGFR1high had no effect on prognosis regardless of DFS time. FGFR1high occurs in a minority of ESCC, and it predicts delayed poor prognosis in stage I and II ESCC patients. PMID:29088806

Brominated, chlorinated and mixed brominated/chlorinated persistent organic pollutants in European eels (Anquilla anquilla) from Latvian lakes.

PubMed

Zacs, Dzintars; Rjabova, Jekaterina; Fernandes, Alwyn; Bartkevics, Vadims

2016-01-01

Fifty-eight European eel (Anquilla anquilla) specimens collected from five Latvian lakes were investigated for six groups of persistent organic pollutants (POPs), including polychlorinated, polybrominated and mixed bromo-chloro dibenzo-p-dioxins and dibenzofurans (PCDD/DFs, PBDD/DFs and PXDD/DFs), polychlorinated and mixed bromo-chloro biphenyls (PCBs and PXBs) and polybrominated diphenyl ethers (PBDEs). PCDD/DFs and PCBs were found to occur in the range 0.85-15.8 pg Total-WHO2005-TEQ g(-1) f.w., and concentrations in most of the samples were below the maximum levels specified in European Commission Regulation (EU) No. 1259/2011. The summed concentrations of 27 PBDEs (∑PBDE) and 16 non-dioxin-like PCBs (∑NDL-PCB) were in the ranges of 0.28-26.7 and 6.37-320 ng g(-1) f.w., respectively. PBDD/DFs, PXDD/DFs and PXBs show average upper-bound concentrations of 0.05, 0.06 and 0.01 pg TEQ f.w. and collectively contributed 3.4% to the sum TEQ of dioxin-like compounds. The highest contaminant concentrations were measured in samples from lakes near the Baltic Sea and the industrialised area near Riga (Liepajas and Kisezers lakes). A correlation of POP concentration with the length of collected specimens was observed.

Isolation of a buprofezin co-metabolizing strain of Pseudomonas sp. DFS35-4 and identification of the buprofezin transformation pathway.

PubMed

Chen, Kai; Liu, Xiao-Mei; Li, Rong; Liu, Yuan; Hu, Hai; Li, Shun-Peng; Jiang, Jian-Dong

2011-11-01

Buprofezin is a widely used insecticide that has caused environmental pollution in many areas. However, biodegradation of buprofezin by pure cultures has not been extensively studied, and the transformation pathway of buprofezin remains unclear. In this paper, a buprofezin co-metabolizing strain of DFS35-4 was isolated from a buprofezin-polluted soil in China. Strain DFS35-4 was preliminarily identified as Pseudomonas sp. based on its morphological, physiological, and biochemical properties, as well as 16S rRNA gene analysis. In the presence of 2.0 g l(-1) sodium citrate, strain DFS35-4 degraded over 70% of 50 mg l(-1) buprofezin in 3 days. Strain DFS35-4 efficiently degraded buprofezin in the pH range of 5.0-10.0 and at temperatures between 20 and 30°C. Three metabolites, 2-imino-5-phenyl-3-(propan-2-yl)-1,3,5-thiadiazinan-4-one, 2-imino-5-phenyl-1,3,5-thiadiazinan-4-one, and methyl(phenyl) carbamic acid, were identified during the degradation of buprofezin using gas chromatography-mass spectrometry (GC-MS) and tandem mass spectrometry (MS/MS). A partial transformation pathway of buprofezin in Pseudomonas sp. DFS35-4 was proposed based on these metabolites.

Randomized phase II trial evaluating two paclitaxel and cisplatin-containing chemoradiation regimens as adjuvant therapy in resected gastric cancer (RTOG-0114).

PubMed

Schwartz, Gary K; Winter, Kathryn; Minsky, Bruce D; Crane, Christopher; Thomson, P John; Anne, Pramila; Gross, Howard; Willett, Christopher; Kelsen, David

2009-04-20

The investigational arm of INT0116, a fluorouracil (FU) and leucovorin-containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed. We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin-containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116. From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%). Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials.

Randomized Phase II Trial Evaluating Two Paclitaxel and Cisplatin–Containing Chemoradiation Regimens As Adjuvant Therapy in Resected Gastric Cancer (RTOG-0114)

PubMed Central

Schwartz, Gary K.; Winter, Kathryn; Minsky, Bruce D.; Crane, Christopher; Thomson, P. John; Anne, Pramila; Gross, Howard; Willett, Christopher; Kelsen, David

2009-01-01

Purpose The investigational arm of INT0116, a fluorouracil (FU) and leucovorin–containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed. Patients and Methods We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin–containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116. Results From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%). Conclusion Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials. PMID:19273696

Protocol for a qualitative study exploring the roles of 'Diffusion Fellows' in bridging the research to practice gap in the Nottinghamshire, Derbyshire and Lincolnshire Collaboration for Leadership in Applied Health Research and Care (CLAHRC-NDL).

PubMed

Rowley, Emma

2012-01-01

Introduction Evidence produced by researchers is not comprehensibly used in practice. National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Nottinghamshire, Derbyshire and Lincolnshire's strategy for closing the research to practice gap relies on the use of 'Diffusion Fellows' (DFs). DFs are seconded from the local healthcare economy to act as champions for change, translating and disseminating knowledge from practice into the research studies and vice versa, taking the knowledge developed by academics back into their own practice environments. This paper outlines the rationale and design of a qualitative evaluation study of the DF role. Methods and analysis The evaluation responds to the research question: what are the barriers and facilitators to DFs acting as knowledge brokers and boundary spanners? Interviews will be carried out annually with DFs, the research team they work with and their line managers in the employing organisations. Interviews with DFs will be supplemented with a creative mapping component, offering them the opportunity to construct a 3D model to creatively illustrate some of the barriers precluding them from successfully carrying out their role. This method is popular for problem solving and is valuable for both introducing an issue that might be difficult to initially verbalise and to reflect upon experiences. Ethics and dissemination DFs have an important role within the CLAHRC and are central to our implementation and knowledge mobilisation strategies. It is important to understand as much about their activities as possible in order for the CLAHRC to support the DFs in the most appropriate way. Dissemination will occur through presentations and publications in order that learning from the use of DFs can be shared as widely as possible. The study has received ethical approval from Nottingham 2 Research Ethics Committee and has all appropriate NHS governance clearances.

Design and methods for a cluster-controlled trial conducted at sixty-eight daycare facilities evaluating the impact of "JolinchenKids - Fit and Healthy in Daycare", a program for health promotion in 3- to 6-year-old children.

PubMed

Steenbock, Berit; Zeeb, Hajo; Rach, Stefan; Pohlabeln, Hermann; Pischke, Claudia R

2017-07-11

The prevention of overweight and obesity during infancy is a highly relevant public health topic given the significant impact of childhood obesity on acute and chronic diseases, general health, and well-being in later stages of life. Apart from the family setting, daycare facilities (DFs) represent a key setting for health promotion among children under the age of six years. "JolinchenKids - Fit and Healthy in Daycare" is a multi-component program promoting physical activity (PA), healthy eating, and mental well-being in 3- to 6-year-old preschoolers at DFs, originally designed by the German health insurance AOK. To evaluate program effectiveness, a cluster-controlled trial involving 68 DFs is currently conducted. The objective of this article is to describe the background, study design, and aims of this trial. Sixty-eight DFs across Germany will be recruited to take part in the study, half of them serving as intervention DFs and half of them as delayed intervention control DFs (which receive the program upon completion of the study). At each DF, height, weight, and body composition, as well as motor skills, will be assessed in twenty 3- to 6-year-old children. Children's eating and PA habits, and mental well-being will be assessed via parental questionnaires. A subsample of children (i.e., at 24 DFs which are randomly selected within a geographic region) will be asked to wear accelerometers at their wrists to objectively measure PA over the course of seven days. To compare changes in body composition, motor skills, eating and PA habits, and mental well-being of children at intervention DFs with those observed among children at delayed intervention control DFs over one year, all measurements will take place at baseline and twelve months after the launch of the program at all DFs. This study investigates the influence of a health promotion program in the daycare setting on various outcomes, including body composition and objectively measured PA, in a nationwide sample of 3- to 6-year-old preschoolers. This study will provide evidence regarding the effectiveness of a multi-component program for health promotion in this setting and may provide insights into new strategies for preventing obesity in early life. German Clinical Trials Register DRKS00011065 (Date of registration 16-09-2016).

Association between obesity with disease-free survival and overall survival in triple-negative breast cancer: A meta-analysis.

PubMed

Mei, Lin; He, Lin; Song, Yuhua; Lv, Yang; Zhang, Lijiu; Hao, Fengxi; Xu, Mengmeng

2018-05-01

To investigate the relationship between obesity and disease-free survival (DFS) and overall survival (OS) of triple-negative breast cancer. Citations were searched in PubMed, Cochrane Library, and Web of Science. Random effect model meta-analysis was conducted by using Revman software version 5.0, and publication bias was evaluated by creating Egger regression with STATA software version 12. Nine studies (4412 patients) were included for DFS meta-analysis, 8 studies (4392 patients) include for OS meta-analysis. There were no statistical significances between obesity with DFS (P = .60) and OS (P = .71) in triple-negative breast cancer (TNBC) patients. Obesity has no impact on DFS and OS in patients with TNBC.

Association between ERCC1 and TS mRNA levels and disease free survival in colorectal cancer patients receiving oxaliplatin and fluorouracil (5-FU) adjuvant chemotherapy.

PubMed

Li, Sheng; Zhu, Liangjun; Yao, Li; Xia, Lei; Pan, Liangxi

2014-08-29

Aim was to explore the association of ERCC1 and TS mRNA levels with the disease free survival (DFS) in Chinese colorectal cancer (CRC) patients receiving oxaliplatin and 5-FU based adjuvant chemotherapy. Total 112 Chinese stage II-III CRC patients were respectively treated by four different chemotherapy regimens after curative operation. The TS and ERCC1 mRNA levels in primary tumor were measured by real-time RT-PCR. Kaplan-Meier curves and log-rank tests were used for DFS analysis. The Cox proportional hazards model was used for prognostic analysis. In univariate analysis, the hazard ratio (HR) for the mRNA expression levels of TS and ERCC1 (logTS: HR = 0.820, 95% CI = 0.600 - 1.117, P = 0.210; logERCC1: HR = 1.054, 95% CI = 0.852 - 1.304, P = 0.638) indicated no significant association of DFS with the TS and ERCC1 mRNA levels. In multivariate analyses, tumor stage (IIIc: reference, P = 0.083; IIb: HR = 0.240, 95% CI = 0.080 - 0.724, P = 0.011; IIc: HR < 0.0001, P = 0.977; IIIa: HR = 0.179, 95% CI = 0.012 - 2.593, P = 0.207) was confirmed to be the independent prognostic factor for DFS. Moreover, the Kaplan-Meier DFS curves showed that TS and ERCC1 mRNA levels were not significantly associated with the DFS (TS: P = 0.264; ERCC1: P = 0.484). The mRNA expression of ERCC1 and TS were not applicable to predict the DFS of Chinese stage II-III CRC patients receiving 5-FU and oxaliplatin based adjuvant chemotherapy.

The Influence of Total Nodes Examined, Number of Positive Nodes, and Lymph Node Ratio on Survival After Surgical Resection and Adjuvant Chemoradiation for Pancreatic Cancer: A Secondary Analysis of RTOG 9704

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

Showalter, Timothy N.; Winter, Kathryn A.; Berger, Adam C., E-mail: adam.berger@jefferson.edu

2011-12-01

Purpose: Lymph node status is an important predictor of survival in pancreatic cancer. We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 9704, an adjuvant chemotherapy and chemoradiation trial, to determine the influence of lymph node factors-number of positive nodes (NPN), total nodes examined (TNE), and lymph node ratio (LNR ratio of NPN to TNE)-on OS and disease-free survival (DFS). Patient and Methods: Eligible patients from RTOG 9704 form the basis of this secondary analysis of lymph node parameters. Actuarial estimates for OS and DFS were calculated using Kaplan-Meier methods. Cox proportional hazards models were performed to evaluatemore » associations of NPN, TNE, and LNR with OS and DFS. Multivariate Cox proportional hazards models were also performed. Results: There were 538 patients enrolled in the RTOG 9704 trial. Of these, 445 patients were eligible with lymph nodes removed. Overall median NPN was 1 (min-max, 0-18). Increased NPN was associated with worse OS (HR = 1.06, p = 0.001) and DFS (HR = 1.05, p = 0.01). In multivariate analyses, both NPN and TNE were associated with OS and DFS. TNE > 12, and >15 were associated with increased OS for all patients, but not for node-negative patients (n = 142). Increased LNR was associated with worse OS (HR = 1.01, p < 0.0001) and DFS (HR = 1.006, p = 0.002). Conclusion: In patients who undergo surgical resection followed by adjuvant chemoradiation, TNE, NPN, and LNR are associated with OS and DFS. This secondary analysis of a prospective, cooperative group trial supports the influence of these lymph node parameters on outcomes after surgery and adjuvant therapy using contemporary techniques.« less

Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of Ki67 assay according to histology: prognostic relevance for resected early stage 'pure' and 'mixed' lobular breast cancer.

PubMed

Carbognin, Luisa; Sperduti, Isabella; Brunelli, Matteo; Marcolini, Lisa; Nortilli, Rolando; Pilotto, Sara; Zampiva, Ilaria; Merler, Sara; Fiorio, Elena; Filippi, Elisa; Manfrin, Erminia; Pellini, Francesca; Bonetti, Franco; Pollini, Giovanni Paolo; Tortora, Giampaolo; Bria, Emilio

2016-03-22

The aim of this analysis was to investigate the potential impact of Ki67 assay in a series of patients affected by early stage invasive lobular carcinoma (ILC) undergone surgery. Clinical-pathological data were correlated with disease-free and overall survival (DFS/OS). The maximally selected Log-Rank statistics analysis was applied to the Ki67 continuous variable to estimate appropriate cut-offs. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed to assess the interaction between 'pure' or 'mixed' histology ILC and Ki67. At a median follow-up of 67 months, 10-years DFS and OS of 405 patients were 67.8 and 79.8%, respectively. Standardized Log-Rank statistics identified 2 optimal cut-offs (6 and 21%); 10-years DFS and OS were 75.1, 66.5, and 30.2% (p = 0.01) and 84.3, 76.4 and 59% (p = 0.003), for patients with a Ki67 < 6%, between 6 and 21%, and >21%, respectively. Ki67 and lymph-node status were independent predictor for longer DFS and OS at the multivariate analysis, with radiotherapy (for DFS) and age (for OS). Ki67 highly replicated at the internal cross-validation analysis (DFS 85%, OS 100%). The STEPP analysis showed that DFS rate decreases as Ki67 increases and those patients with 'pure' ILC performed worse than 'mixed' histology. Despite the retrospective and exploratory nature of the study, Ki67 was able to significantly discriminate the prognosis of patients with ILC, and the effect was more pronounced for patients with 'pure' ILC.

Randomized Phase III Trial of Adjuvant Pazopanib Versus Placebo After Nephrectomy in Patients With Localized or Locally Advanced Renal Cell Carcinoma.

PubMed

Motzer, Robert J; Haas, Naomi B; Donskov, Frede; Gross-Goupil, Marine; Varlamov, Sergei; Kopyltsov, Evgeny; Lee, Jae Lyun; Melichar, Bohuslav; Rini, Brian I; Choueiri, Toni K; Zemanova, Milada; Wood, Lori A; Reaume, M Neil; Stenzl, Arnulf; Chowdhury, Simon; Lim, Ho Yeong; McDermott, Ray; Michael, Agnieszka; Bao, Weichao; Carrasco-Alfonso, Marlene J; Aimone, Paola; Voi, Maurizio; Doehn, Christian; Russo, Paul; Sternberg, Cora N

2017-12-10

Purpose This phase III trial evaluated the efficacy and safety of pazopanib versus placebo in patients with locally advanced renal cell carcinoma (RCC) at high risk for relapse after nephrectomy. Patients and Methods A total of 1,538 patients with resected pT2 (high grade) or ≥ pT3, including N1, clear cell RCC were randomly assigned to pazopanib or placebo for 1 year; 403 patients received a starting dose of 800 mg or placebo. To address toxicity attrition, the 800-mg starting dose was lowered to 600 mg, and the primary end point analysis was changed to disease-free survival (DFS) for pazopanib 600 mg versus placebo (n = 1,135). Primary analysis was performed after 350 DFS events in the intent-to-treat (ITT) pazopanib 600 mg group (ITT 600mg ), and DFS follow-up analysis was performed 12 months later. Secondary end point analyses included DFS with ITT pazopanib 800 mg (ITT 800mg ) and safety. Results The primary analysis results of DFS ITT 600mg favored pazopanib but did not show a significant improvement over placebo (hazard ratio [HR], 0.86; 95% CI, 0.70 to 1.06; P = .165). The secondary analysis of DFS in ITT 800mg (n = 403) yielded an HR of 0.69 (95% CI, 0.51 to 0.94). Follow-up analysis in ITT 600mg yielded an HR of 0.94 (95% CI, 0.77 to 1.14). Increased ALT and AST were common adverse events leading to treatment discontinuation in the pazopanib 600 mg (ALT, 16%; AST, 5%) and 800 mg (ALT, 18%; AST, 7%) groups. Conclusion The results of the primary DFS analysis of pazopanib 600 mg showed no benefit over placebo in the adjuvant setting.

Acute lymphoblastic leukemia relapsing after first-line pediatric-inspired therapy: a retrospective GRAALL study.

PubMed

Desjonquères, A; Chevallier, P; Thomas, X; Huguet, F; Leguay, T; Bernard, M; Bay, J-O; Tavernier, E; Charbonnier, A; Isnard, F; Hunault, M; Turlure, P; Renaud, M; Bastié, J-N; Himberlin, C; Lepretre, S; Lioure, B; Lhéritier, V; Asnafi, V; Beldjord, K; Lafage-Pochitaloff, M; Béné, M C; Ifrah, N; Dombret, H

2016-12-09

The outcome of adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL) relapsing after pediatric-inspired front-line therapy is ill known. Here 229 relapsing Ph- ALL younger adults (18-63 years) treated within the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/-2005 trials were considered. Salvage regimens consisted of potentially curative therapies in 194 cases, low-intensity therapies in 21, allogeneic stem cell transplant (allo-SCT) in 6 and best supportive care in 8. Overall, 77 patients received allo-SCT after relapse. The median follow-up was 3.1 years. A second complete remission (CR2) was achieved in 121 patients (53%). In multivariate analysis, only younger age <45 years (P=0.008) and CR1 duration ⩾18 months (P=0.009) predicted CR2. Overall survival (OS) at 2 and 5 years was 19.3% (14-24%) and 13.3% (8-18%), respectively. In CR2 patients, disease-free survival (DFS) at 2 and 5 years was 29.0% (21-38%) and 25% (17-33%). In multivariate analysis, CR1 duration ⩾18 months and allo-SCT after relapse were associated with longer DFS (P<0.009 and P=0.004, respectively) and longer OS (P=0.004 and P<0.0001, respectively). In conclusion, although younger adults relapsing after pediatric-inspired ALL therapies retain a poor outcome, some of them may be cured if CR1 duration ⩾18 months and if allo-SCT can be performed in CR2. New therapies are definitely needed for these patients.

Stability of iodine in salt fortified with iodine and iron.

PubMed

Ranganathan, Srinivasaiyengar; Karmarkar, Madhu G; Krupadanam, Muddepaka; Brahmam, Ginnela N V; Rao, Mendhu Vishnuvardhana; Vijayaraghavan, Kamasamudram; Sivakumar, Bhattriprolu

2007-03-01

Determining the stability of iodine in fortified salt can be difficult under certain conditions. Current methods are sometimes unreliable in the presence of iron. To test the new method to more accurately estimate iodine content in double-fortified salt (DFS) fortified with iodine and iron by using orthophosphoric acid instead of sulfuric acid in the titration procedure. A double-blind, placebo-controlled study was carried out on DFS and iodized salt produced by the dry-mixing method. DFS and iodized salt were packed and sealed in color-coded, 0.5-kg, low-density polyethylene pouches, and 25 of these pouches were further packed and sealed in color-coded, double-lined, high-density polyethylene bags and transported by road in closed, light-protected containers to the International Council for the Control of Iodine Deficiency Disorders (ICCIDD), Delhi; the National Institute of Nutrition (NIN), Hyderabad; and the Orissa Unit of the National Nutrition Monitoring Bureau (NNMB), Bhubaneswar. The iodine content of DFS and iodized salt stored under normal room conditions in these places was measured by the modified method every month on the same prescribed dates during the first 6 months and also after 15 months. The iodine content of DFS and iodized salt stored under simulated household conditions was also measured in the first 3 months. After the color code was broken at the end of the study, it was found that the DFS and iodized salt stored at Bhubaneswar, Delhi, and Hyderabad retained more or less the same initial iodine content (30-40 ppm) during the first 6 months, and the stability was not affected after 15 months. The proportion of salt samples having more than 30 ppm iodine was 100% in DFS and iodized salt throughout the study period. Daily opening and closing of salt pouches under simulated household conditions did not result in any iodine loss. The DFS and iodized salt prepared by the dry-mixing method and stored at normal room conditions had excellent iodine stability for more than 1 year.

Propagation of Dipolarization Signatures Observed by the Van Allen Probes in the Inner Magnetosphere

NASA Astrophysics Data System (ADS)

Ohtani, S.; Motoba, T.; Gkioulidou, M.; Takahashi, K.; Kletzing, C.

2017-12-01

Dipolarization, the change of the local magnetic field from a stretched to a more dipolar configuration, is one of the most fundamental processes of magnetospheric physics. It is especially critical for the dynamics of the inner magnetosphere. The associated electric field accelerates ions and electrons and transports them closer to Earth. Such injected ions intensify the ring current, and electrons constitute the seed population of the radiation belt. Those ions and electrons may also excite various waves that play important roles in the enhancement and loss of the radiation belt electrons. Despite such critical consequences, the general characteristics of dipolarization in the inner magnetosphere still remain to be understood. The Van Allen Probes mission, which consists of two probes that orbit through the equatorial region of the inner magnetosphere, provides an ideal opportunity to examine dipolarization signatures in the core of the ring current. In the present study we investigate the spatial expansion of the dipolarization region by examining the correlation and time delay of dipolarization signatures observed by the two probes. Whereas in general it requires three-point measurements to deduce the propagation of a signal on a certain plane, we statically examined the observed time delays and found that dipolarization signatures tend to propagate radially inward as well as away from midnight. In this paper we address the propagation of dipolarization signatures quantitatively and compare with the propagation velocities reported previously based on observations made farther away from Earth. We also discuss how often and under what conditions the dipolarization region expands.

Energetic Electron Acceleration and Injection During Dipolarization Events in Mercury's Magnetotail

NASA Astrophysics Data System (ADS)

Dewey, Ryan M.; Slavin, James A.; Raines, Jim M.; Baker, Daniel N.; Lawrence, David J.

2017-12-01

Energetic particle bursts associated with dipolarization events within Mercury's magnetosphere were first observed by Mariner 10. The events appear analogous to particle injections accompanying dipolarization events at Earth. The Energetic Particle Spectrometer (3 s resolution) aboard MESSENGER determined the particle bursts are composed entirely of electrons with energies ≳ 300 keV. Here we use the Gamma-Ray Spectrometer high-time-resolution (10 ms) energetic electron measurements to examine the relationship between energetic electron injections and magnetic field dipolarization in Mercury's magnetotail. Between March 2013 and April 2015, we identify 2,976 electron burst events within Mercury's magnetotail, 538 of which are closely associated with dipolarization events. These dipolarizations are detected on the basis of their rapid ( 2 s) increase in the northward component of the tail magnetic field (ΔBz 30 nT), which typically persists for 10 s. Similar to those at Earth, we find that these dipolarizations appear to be low-entropy, depleted flux tubes convecting planetward following the collapse of the inner magnetotail. We find that electrons experience brief, yet intense, betatron and Fermi acceleration during these dipolarizations, reaching energies 130 keV and contributing to nightside precipitation. Thermal protons experience only modest betatron acceleration. While only 25% of energetic electron events in Mercury's magnetotail are directly associated with dipolarization, the remaining events are consistent with the Near-Mercury Neutral Line model of magnetotail injection and eastward drift about Mercury, finding that electrons may participate in Shabansky-like closed drifts about the planet. Magnetotail dipolarization may be the dominant source of energetic electron acceleration in Mercury's magnetosphere.

In vitro engineering of fibrocartilage using CDMP1 induced dermal fibroblasts and polyglycolide.

PubMed

Zhao, Guiqing; Yin, Shuo; Liu, Guangpeng; Cen, Lian; Sun, Jian; Zhou, Heng; Liu, Wei; Cui, Lei; Cao, Yilin

2009-07-01

This study was designed to explore the feasibility of using cartilage-derived morphogenetic protein-1 (CDMP1) induced dermal fibroblasts (DFs) as seed cells and polyglycolide (PGA) as scaffold for fibrocartilage engineering. DFs isolated from canine were expanded and seeded on PGA scaffold to fabricate cell/scaffold constructs which were cultured with or without CDMP1. Proliferation and differentiation of DFs in different constructs were determined by DNA assay and glycosaminoglycan (GAG) production. Histological and immunohistochemical staining of the constructs after being in vitro cultured for 4 and 6 weeks were carried out to observe the fibrocartilage formation condition. The fibrocartilage-specific gene expression by cells in the constructs was analyzed by real-time PCR. It was shown that in the presence of CDMP1 the proliferation and GAG synthesis of DFs were significantly enhanced compared to those without CDMP1. Fibrocartilage-like tissue was formed in the CDMP1 induced construct after being cultured for 4 weeks, and it became more matured at 6 weeks as stronger staining for GAG and higher gene expression of collagen type II was observed. Since only weak staining for GAG and collagen type II was observed for the construct engineered without CDMP1, the induction effect on the fibrocartilage engineering can be ascertained when using DFs as seed cells. Furthermore, the potential of using DFs as seed cells to engineer fibrocartilage is substantiated and further study on using the engineered tissue to repair fibrocartilage defects is currently ongoing in our group.

Collective excitation frequencies and stationary states of trapped dipolar Bose-Einstein condensates in the Thomas-Fermi regime

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

Bijnen, R. M. W. van; Department of Physics and Astronomy, McMaster University, Hamilton, Ontario L8S 4M1; Parker, N. G.

We present a general method for obtaining the exact static solutions and collective excitation frequencies of a trapped Bose-Einstein condensate (BEC) with dipolar atomic interactions in the Thomas-Fermi regime. The method incorporates analytic expressions for the dipolar potential of an arbitrary polynomial density profile, thereby reducing the problem of handling nonlocal dipolar interactions to the solution of algebraic equations. We comprehensively map out the static solutions and excitation modes, including non-cylindrically-symmetric traps, and also the case of negative scattering length where dipolar interactions stabilize an otherwise unstable condensate. The dynamical stability of the excitation modes gives insight into the onsetmore » of collapse of a dipolar BEC. We find that global collapse is consistently mediated by an anisotropic quadrupolar collective mode, although there are two trapping regimes in which the BEC is stable against quadrupole fluctuations even as the ratio of the dipolar to s-wave interactions becomes infinite. Motivated by the possibility of a fragmented condensate in a dipolar Bose gas due to the partially attractive interactions, we pay special attention to the scissors modes, which can provide a signature of superfluidity, and identify a long-range restoring force which is peculiar to dipolar systems. As part of the supporting material for this paper we provide the computer program used to make the calculations, including a graphical user interface.« less

Heat Transfer Through Dipolar Coupling: Sympathetic cooling without contact

NASA Astrophysics Data System (ADS)

Oktel, Mehmet; Renklioglu, Basak; Tanatar, Bilal

We consider two parallel layers of dipolar ultracold gases at different temperatures and calculate the heat transfer through dipolar coupling. As the simplest model we consider a system in which both of the layers contain two-dimensional spin-polarized Fermi gases. The effective interactions describing the correlation effects and screening between the dipoles are obtained by the Euler-Lagrange Fermi-hypernetted-chain approximation in a single layer. We use the random-phase approximation (RPA) for the interactions across the layers. We find that heat transfer through dipolar coupling becomes efficient when the layer separation is comparable to dipolar interaction length scale. We characterize the heat transfer by calculating the time constant for temperature equilibration between the layers and find that for the typical experimental parameter regime of dipolar molecules this is on the order of milliseconds. We generalize the initial model to Boson-Boson and Fermion-Boson layers and suggest that contactless sympathetic cooling may be used for ultracold dipolar molecules. Supported by TUBITAK 1002-116F030.

Risk factors contributing to a poor prognosis of papillary thyroid carcinoma: validity of UICC/AJCC TNM classification and stage grouping.

PubMed

Ito, Yasuhiro; Miyauchi, Akira; Jikuzono, Tomoo; Higashiyama, Takuya; Takamura, Yuuki; Miya, Akihiro; Kobayashi, Kaoru; Matsuzuka, Fumio; Ichihara, Kiyoshi; Kuma, Kanji

2007-04-01

In 2002, the UICC/AJCC TNM classification for papillary thyroid carcinoma was revised. In this study, we examined the validity of this classification system by investigating the predictors of disease-free survival (DFS) and cause-specific survival (CSS) in patients. We examined various clinicopathological features, including the component of the TNM classification, for 1,740 patients who underwent initial and curative surgery for papillary carcinoma between 1987 and 1995. Clinical and pathological T4a, clinical N1b in the TNM classification, and patient age were recognized as independent predictors of not only DFS, but also CSS of patients. Tumor size, male gender, and central node metastasis independently affected DFS only. There were 1,005 pathological N1b patients, but pathological N1b did not independently affect either DFS or CSS. Regarding the stage grouping, clinical stage IVA including clinical N1b more clearly affected DFS and CSS than pathological stage IVA including pathological N1b. Clinical stage grouping was more useful than pathological stage grouping for predicting the prognosis of papillary carcinoma patients possibly because pathological stage overestimates the biological characteristics of many pathological N1b tumors.

Divergence-free smoothing for MRV data on stenosed carotid artery phantom flows

NASA Astrophysics Data System (ADS)

Im, Chaehyuk; Ko, Seungbin; Song, Simon

2017-11-01

Magnetic Resonance Velocimetry (MRV) is a versatile technique for measuring flow velocity using an MRI machine. It is frequently used for visualization and analysis of blood flows. However, it is difficult to accurately estimate hemodynamics parameters like wall shear stress (WSS) and oscillatory shear index (OSI) due to its low spatial resolution and low signal-to-noise ratio. We suggest a divergence-free smoothing (DFS) method to correct the erroneous velocity vectors obtained with MRV and improve the estimation accuracy of those parameters. Unlike previous studies on DFS for a wall-free flow, we developed a house code to apply a DFS method to a wall-bounded flow. A Hagen-Poiseuille flow and stenosed carotid artery phantom flows were measured with MRV. Each of them was analyzed for validation of the DFS code and confirmation on the accuracy improvement of hemodynamic parameters. We will discuss the effects of DFS on the improvement of the estimation accuracy of velocity vectors, WSS, OSI and etc in detail This work was supported by the National Research Foundation of Korea(NRF) Grant funded by the Korea government(MSIP) (No. 2016R1A2B3009541).

NMR dipolar constants of motion in liquid crystals: Jeener-Broekaert, double quantum coherence experiments and numerical calculation on a 10-spin cluster.

PubMed

Segnorile, H H; Bonin, C J; González, C E; Acosta, R H; Zamar, R C

2009-10-01

Two proton quasi-equilibrium states were previously observed in nematic liquid crystals, namely the S and W quasi-invariants. Even though the experimental evidence suggested that they originate in a partition of the spin dipolar energy into a strong and a weak part, respectively, from a theoretical viewpoint, the existence of an appropriate energy scale which allows such energy separation remains to be confirmed and a representation of the quasi-invariants is still to be given. We compare the dipolar NMR signals yielded both by the Jeener-Broekaert (JB) experiment as a function of the preparation time and the free evolution of the double quantum coherence (DQC) spectra excited from the S state, with numerical calculations carried out from first principles under different models for the dipolar quasi-invariants, in a 10-spin cluster which represents the 5CB (4(')-pentyl-4-biphenyl-carbonitrile) molecule. The calculated signals qualitatively agree with the experiments and the DQC spectra as a function of the single-quantum detection time are sensible enough to the different models to allow both to probe the physical nature of the initial dipolar-ordered state and to assign a subset of dipolar interactions to each constant of motion, which are compatible with the experiments. As a criterion for selecting a suitable quasi-equilibrium model of the 5CB molecule, we impose on the time evolution operator consistency with the occurrence of two dipolar quasi-invariants, that is, the calculated spectra must be unaffected by truncation of non-secular terms of the weaker dipolar energy. We find that defining the S quasi-invariant as the subset of the dipolar interactions of each proton with its two nearest neighbours yields a realistic characterization of the dipolar constants of motion in 5CB. We conclude that the proton-spin system of the 5CB molecule admits a partition of the dipolar energy into a bilinear strong and a multiple-spin weak contributions therefore providing two orthogonal constants of motion, which can be prepared and observed by means of the JB experiment. This feature, which implies the existence of two timescales of very different nature in the proton-spin dynamics, is ultimately dictated by the topology of the spin distribution in the dipole network and can be expected in other liquid crystals. Knowledge of the nature of the dipolar quasi-invariants will be useful in studies of dipolar-order relaxation, decoherence and multiple quantum NMR experiments where the initial state is a dipolar-ordered one.

Connectivity algorithm with depth first search (DFS) on simple graphs

NASA Astrophysics Data System (ADS)

Riansanti, O.; Ihsan, M.; Suhaimi, D.

2018-01-01

This paper discusses an algorithm to detect connectivity of a simple graph using Depth First Search (DFS). The DFS implementation in this paper differs than other research, that is, on counting the number of visited vertices. The algorithm obtains s from the number of vertices and visits source vertex, following by its adjacent vertices until the last vertex adjacent to the previous source vertex. Any simple graph is connected if s equals 0 and disconnected if s is greater than 0. The complexity of the algorithm is O(n2).

Prognostic Significance of Nodal Location and Ratio in Stage IIIC Endometrial Carcinoma Among a Multi-Institutional Academic Collaboration.

PubMed

Mayadev, Jyoti; Elshaikh, Mohamed A; Christie, Alana; Nagel, Christa; Kennedy, Vanessa; Khan, Nadia; Lea, Jayanthi; Ghanem, Ahmad; Miller, David; Xie, Xian-Jin; Folkert, Michael; Albuquerque, Kevin

2018-04-20

Stage IIIC endometrial carcinoma (EC) represents pathologically heterogenous patients with single/multiple pelvic (stage IIIC1) or paraaortic (stage IIIC2) lymph nodes (LNs). There is an increasing trend to offer adjuvant chemotherapy (CT) +/- radiation (RT) uniformly to these patients, regardless of substage. We investigate the prognostic significance of positive LN (pLN) number, ratio (%pLN), location (IIC1 vs. IIC2), and adjuvant treatment on patterns of failure and survival in a large collaborative multi-institutional series. Clinical data for stage III EC patients such as patient characteristics, surgery/pathologic details, adjuvant therapies (including CT, RT, and chemotherapy and radiation), and outcomes (including pelvic control [PC], disease-free survival [DFS], distant DFS, and overall survival [OS]) were collected from 3 academic institutions. Log-rank analyses, Cox regression univariate and multivariate analyses were performed. Of the 264 patients queried for stage III disease, 237 (73%) had pLN, and complete LN sampling for analysis. The mean number of pLN in the combined data were 3.9, with 26.1% of all LN sampled positive; 121 patients (51%) staged IIIC1, and 116 patients (49%) staged IIIC2. There was a significant difference in number of pLN (P=0.0006) and total LN sampled by institution (range, 13 to 35; P=0.0004), without a difference in %pLN (P=0.35). Ninety-seven of 220 (44.1%) have ≥20% pLN. While controlling for substage and institution, a decrease in DFS (hazard ratio [HR], 1.1; P=0.007), and OS (HR, 1.1; P=0.01) was observed with every increase of 10% in the pLN ratio. There was a significant difference in DFS (HR, 1.8; P=0.003), PC (HR, 1.9; P=0.004), and distant DFS (HR, 1.6; P=0.03), as well as a trend for decreased OS (HR, 1.6; P=0.08) for substage IIIC2 versus IIIC1 disease; 5 years DFS 40% versus 45%, OS 50% versus 57%. Patients received no adjuvant therapy (10%), CT alone (27%), RT alone (16%), or chemotherapy and radiation (47%). There was no significant difference in PC, DFS, or OS between the various treatment regimens. On univariate analysis, while pLN was significant, treatment type did not impact DFS or OS. On multivariate analysis for DFS, patient age, race, and IIIC1 versus IIIC2 substage retained significance (HR, 0.56; P=0.01). Stage III EC patients with substage IIIC2 disease have a significantly increased risk of local and distant disease recurrence and death from EC. A decrease in DFS and OS was observed with every increase of 10% in the pLN ratio. Stage IIIC2 patients represent a high-risk subpopulation for whom clinical trials, or targeted regimens should be explored to achieve improved oncologic outcomes.

Mapping and Monitoring Delmarva Fox Squirrel Habitat Using an Airborne LiDAR Profiler

NASA Technical Reports Server (NTRS)

Nelson, Ross; Ratnaswamy, Mary; Keller, Cherry

2004-01-01

Twenty five hundred thirty nine kilometers of airborne laser profiling and videography data were acquired over the state of Delaware during the summer of 2000. The laser ranging measurements and video from approximately one-half of that data set (1304 km) were analyzed to identify and locate forested sites that might potentially support populations of Delmarva fox squirrel (DFS, Sciurus niger cinereus). The DFS is an endangered species previously endemic to tall, dense, mature forests with open understories on the Eastern Shore of the Chesapeake Bay. The airborne LiDAR employed in this study can measure forest canopy height and canopy closure, but cannot measure or infer understory canopy conditions. Hence the LiDAR must be viewed as a tool to map potential, not actual, habitat. Fifty-three potentially suitable DFS sites were identified in the 1304 km of flight transect data. Each of the 53 sites met the following criteria according to the LiDAR and video record: (1 ) at least 120m of contiguous forest; (2) an average canopy height greater than 20m; (3) an average canopy closure of >80%; and (4) no roofs, impervious surface (e.g., asphalt, concrete), and/or open water anywhere along the 120m length of the laser segment. Thirty-two of the 53 sites were visited on the ground and measurements taken for a DFS habitat suitability model. Seventy eight percent of the sites (25 of 32) were judged by the model to be suited to supporting a DFS population. Twenty-eight of the 32 sites visited in the field were in forest cover types (hardwood, mixed wood, conifer, wetlands) according to a land cover GIS map. Of these, 23 (82%) were suited to support DFS. The remaining 4 sites were located in nonforest cover types - agricultural or residential areas. Two of the four, or 50% were suited to the DFS. All of the LiDAR flight data, 2539 km, were analyzed to

The prognostic impact of tumor volume on stage I non-small cell lung cancer.

PubMed

Su, Xiao-Dong; Xie, Hao-Jun; Liu, Qian-Wen; Mo, Yun-Xian; Long, Hao; Rong, Tie-Hua

2017-02-01

The purpose of this study was to investigate the prognostic impact of tumor volume (TV) on patients with stage I non-small cell lung cancer (NSCLC) after complete resection. We retrospectively reviewed the clinicopathological characteristics of 274 patients with stage I NSCLC who had received preoperative chest computed tomography (CT) scans and complete resection. TV was semi-automatically measured from chest CT scans by using an imaging software program. The optimal cutoff values of TV were determined by X-tile software. Disease-free survival (DFS) and overall survival (OS) were compared using Kaplan-Meier analysis. Univariate and multivariate analyses were performed to identify risk factors for DFS and OS. By using 3.046cm 3 and 8.078cm 3 as two optimal cutoff values of TV, the patients were separated into three groups. The 5-year DFS and OS for patients with TV≤3.046cm 3 , 3.046-8.078cm 3 , and>8.078cm 3 were 88.0%, 73.6%, and 62.1%, respectively (P<0.001), and 91.4%, 84.5%, and 73.3%, respectively (p<0.001). Multivariate analysis showed that age and TV were independent factors associated with DFS. Sex, age, histology, visceral pleural invasion, and TV were independent factors associated with OS. Stage Ia patients might be separated into three groups on the basis of TV with significantly different DFS and OS. Patients with tumor diameter≤2cm and 2-3cm were also stratified into two groups with significantly different DFS and OS on the basis of TV, respectively. TV is an independent risk factor for DFS and OS for stage I NSCLC after complete resection. TV might provide additional prognostic information over tumor diameter in patients with stage I NSCLC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pathologic complete response and disease-free survival are not surrogate endpoints for 5-year survival in rectal cancer: an analysis of 22 randomized trials.

PubMed

Petrelli, Fausto; Borgonovo, Karen; Cabiddu, Mary; Ghilardi, Mara; Lonati, Veronica; Barni, Sandro

2017-02-01

We performed a literature-based analysis of randomized clinical trials to assess the pathologic complete response (pCR) (ypT0N0 after neoadjuvant therapy) and 3-year disease-free survival (DFS) as potential surrogate endpoints for 5-year overall survival (OS) in rectal cancer treated with neoadjuvant (chemo)radiotherapy (CT)RT. A systematic literature search of PubMed, EMBASE, the Web of Science, SCOPUS, CINAHL, and the Cochrane Library was performed. Treatment effects on 3-year DFS and 5-year OS were expressed as rates of patients alive (%), and those on pCR as differences in pCR rates (∆ pCR% ). A weighted regression analysis was performed at individual- and trial-level to test the association between treatment effects on surrogate (∆ pCR% and ∆ 3yDFS ) and the main clinical outcome (∆ 5yOS ). Twenty-two trials involving 10,050 patients, were included in the analysis. The individual level surrogacy showed that the pCR% and 3-year DFS were poorly correlated with 5-year OS (R=0.52; 95% CI, 0.31-0.91; P=0.002; and R=0.60; 95% CI, 0.36-1; P=0.002). The trial-level surrogacy analysis confirmed that the two treatment effects on surrogates (∆ pCR% and ∆ 3yDFS ) are not strong surrogates for treatment effects on 5-year OS % (R=0.2; 95% CI, -0.29-0.78; P=0.5 and R=0.64; 95% CI, 0.29-1; P=0.06). These findings were confirmed in neoadjuvant CTRT studies but not in phase III trials were 3-year DFS could still represent a valid surrogate. This analysis does not support the use of pCR and 3-year DFS% as appropriate surrogate endpoints for 5-year OS% in patients with rectal cancer treated with neoadjuvant therapy.

Immune Biomarkers Predictive for Disease-Free Survival with Adjuvant Sunitinib in High-Risk Locoregional Renal Cell Carcinoma: From Randomized Phase III S-TRAC Study.

PubMed

George, Daniel J; Martini, Jean-François; Staehler, Michael; Motzer, Robert J; Magheli, Ahmed; Escudier, Bernard; Gerletti, Paola; Li, Sherry; Casey, Michelle; Laguerre, Brigitte; Pandha, Hardev S; Pantuck, Allan J; Patel, Anup; Lechuga, Maria J; Ravaud, Alain

2018-04-01

Purpose: Adjuvant sunitinib therapy compared with placebo prolonged disease-free survival (DFS) in patients with locoregional high-risk renal cell carcinoma (RCC) in the S-TRAC trial (ClinicalTrials.gov number NCT00375674). A prospectively designed exploratory analysis of tissue biomarkers was conducted to identify predictors of treatment benefit. Experimental Design: Tissue blocks were used for immunohistochemistry (IHC) staining of programmed cell death ligand 1 (PD-L1), CD4, CD8, and CD68. DFS was compared between < versus ≥ median IHC parameter using the Kaplan-Meier method. For biomarkers with predictive potential, receiver operating characteristics curves were generated. Results: Baseline characteristics were similar in patients with ( n = 191) and without ( n = 419) IHC analysis. Among patients with IHC, longer DFS was observed in patients with tumor CD8 + T-cell density ≥ versus < median [median (95% CI), not reached (6.83-not reached) versus 3.47 years (1.73-not reached); hazard ratio (HR) 0.40 (95% CI, 0.20-0.81); P = 0.009] treated with sunitinib ( n = 101), but not with placebo ( n = 90). The sensitivity and specificity for CD8 + T-cell density in predicting DFS were 0.604 and 0.658, respectively. Shorter DFS was observed in placebo-treated patients with PD-L1 + versus PD-L1 - tumors (HR 1.75; P = 0.103). Among all patients with PD-L1 + tumors, DFS was numerically longer with sunitinib versus placebo (HR 0.58; P = 0.175). Conclusions: Greater CD8 + T-cell density in tumor tissue was associated with longer DFS with sunitinib but not placebo, suggesting predictive treatment effect utility. Further independent cohort validation studies are warranted. The prognostic value of PD-L1 expression in primary tumors from patients with high-risk nonmetastatic RCC should also be further explored. Clin Cancer Res; 24(7); 1554-61. ©2018 AACR . ©2018 American Association for Cancer Research.

Quantum Fluctuations in Quasi-One-Dimensional Dipolar Bose-Einstein Condensates

NASA Astrophysics Data System (ADS)

Edler, D.; Mishra, C.; Wächtler, F.; Nath, R.; Sinha, S.; Santos, L.

2017-08-01

Recent experiments have revealed that beyond-mean-field corrections are much more relevant in weakly interacting dipolar condensates than in their nondipolar counterparts. We show that in quasi-one-dimensional geometries quantum corrections in dipolar and nondipolar condensates are strikingly different due to the peculiar momentum dependence of the dipolar interactions. The energy correction of the condensate presents not only a modified density dependence, but it may even change from attractive to repulsive at a critical density due to the surprising role played by the transversal directions. The anomalous quantum correction translates into a strongly modified physics for quantum-stabilized droplets and dipolar solitons. Moreover, and for similar reasons, quantum corrections of three-body correlations, and hence of three-body losses, are strongly modified by the dipolar interactions. This intriguing physics can be readily probed in current experiments with magnetic atoms.

Quantum Fluctuations in Quasi-One-Dimensional Dipolar Bose-Einstein Condensates.

PubMed

Edler, D; Mishra, C; Wächtler, F; Nath, R; Sinha, S; Santos, L

2017-08-04

Recent experiments have revealed that beyond-mean-field corrections are much more relevant in weakly interacting dipolar condensates than in their nondipolar counterparts. We show that in quasi-one-dimensional geometries quantum corrections in dipolar and nondipolar condensates are strikingly different due to the peculiar momentum dependence of the dipolar interactions. The energy correction of the condensate presents not only a modified density dependence, but it may even change from attractive to repulsive at a critical density due to the surprising role played by the transversal directions. The anomalous quantum correction translates into a strongly modified physics for quantum-stabilized droplets and dipolar solitons. Moreover, and for similar reasons, quantum corrections of three-body correlations, and hence of three-body losses, are strongly modified by the dipolar interactions. This intriguing physics can be readily probed in current experiments with magnetic atoms.

Adjuvant Treatment after Surgery in Stage IIIA Endometrial Adenocarcinoma

PubMed Central

Yoon, Mee Sun; Huh, Seung Jae; Kim, Hak Jae; Kim, Young Seok; Kim, Yong Bae; Kim, Joo-Young; Lee, Jong-Hoon; Kim, Hun Jung; Cha, Jihye; Kim, Jin Hee; Kim, Juree; Yoon, Won Sup; Choi, Jin Hwa; Chun, Mison; Choi, Youngmin; Lee, Kang Kyoo; Kim, Myungsoo; Jeong, Jae-Uk; Chang, Sei Kyung; Park, Won

2016-01-01

Purpose We evaluated the role of adjuvant therapy in stage IIIA endometrioid adenocarcinoma patients who underwent surgery followed by radiotherapy (RT) alone or chemoradiotherapy (CTRT) according to risk group. Materials and Methods A multicenter retrospective study was conducted including patients with surgical stage IIIA endometrial cancertreated by radical surgery and adjuvant RT or CTRT. Disease-free survival (DFS) and overall survival (OS) were analyzed. Results Ninety-three patients with stage IIIA disease were identified. Nineteen patients (20.4%) experienced recurrence, mostly distant metastasis (17.2%). Combined CTRT did not affect DFS (74.1% vs. 82.4%, p=0.130) or OS (96.3% vs. 91.9%, p=0.262) in stage IIIA disease compared with RT alone. Patients with age ≥ 60 years, grade G2/3, and lymphovascular space involvement had a significantly worse DFS and those variables were defined as risk factors. The high-risk group showed a significant reduction in 5-year DFS (≥ 2 risk factors) (49.0% vs. 88.0%, p < 0.001) compared with the low-risk group (< 2). Multivariate analysis confirmed that more than one risk factor was the only predictor of worse DFS (hazard ratio, 5.45; 95% confidence interval, 2.12 to 13.98; p < 0.001). Of patients with no risk factors, a subset treated with RT alone showed an excellent 5-year DFS and OS (93.8% and 100%, respectively). Conclusion We identified a low-risk subset of stage IIIA endometrioid adenocarcinoma patients who might be reasonable candidates for adjuvant RT alone. Further randomized studies are needed to determine which subset might benefit from combined CTRT. PMID:26511800

The frequency and significance of WT-1 expression in serous endometrial carcinoma.

PubMed

Hedley, Catherine; Sriraksa, Ruethairat; Showeil, Rania; Van Noorden, Susan; El-Bahrawy, Mona

2014-09-01

Serous endometrial carcinoma is an aggressive type of endometrial carcinoma. Wilms tumor gene 1 (WT-1) is commonly expressed in ovarian serous carcinomas and considered a diagnostic marker of these tumors. However, it is generally believed that WT-1 is rarely expressed by endometrial serous carcinoma. The aim of this study was to evaluate the frequency and significance of WT-1 expression in endometrial serous carcinoma. We studied the expression of WT-1 in formalin-fixed, paraffin-embedded tumor sections from 77 cases of endometrial serous carcinoma. Thirty-four tumors showed positive expression for WT-1 (44%). There was a statistically significant association between the presence of WT-1 expression and disease-free survival (DFS), where patients with tumors expressing WT-1 had a shorter DFS compared with those with no WT-1 expression (P = .031; median DFS, 15 and 38 months, respectively). By multivariate Cox regression analysis, DFS was independent from other clinicopathological data (tumor stage, presence of lymphovascular space invasion, cervical involvement, and extrauterine spread), indicating that WT-1 expression is independently associated with DFS. Our study shows that WT-1 is expressed in a considerable percentage of endometrial serous carcinomas, suggesting a role for WT-1 in the pathology of these tumors. This has therapeutic significance, as WT-1 is an emerging target for immunotherapy. Moreover, our results show that WT-1 has prognostic value, being predictive of DFS. As a potential prognostic marker and therapeutic target, we recommend that WT-1 expression should be included in histopathologic reports of endometrial serous carcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.

Bose-Einstein condensation and superfluidity of dipolar excitons in a phosphorene double layer

NASA Astrophysics Data System (ADS)

Berman, Oleg L.; Gumbs, Godfrey; Kezerashvili, Roman Ya.

2017-07-01

We study the formation of dipolar excitons and their superfluidity in a phosphorene double layer. The analytical expressions for the single dipolar exciton energy spectrum and wave function are obtained. It is predicted that a weakly interacting gas of dipolar excitons in a double layer of black phosphorus exhibits superfluidity due to the dipole-dipole repulsion between the dipolar excitons. In calculations are employed the Keldysh and Coulomb potentials for the interaction between the charge carriers to analyze the influence of the screening effects on the studied phenomena. It is shown that the critical velocity of superfluidity, the spectrum of collective excitations, concentrations of the superfluid and normal component, and mean-field critical temperature for superfluidity are anisotropic and demonstrate the dependence on the direction of motion of dipolar excitons. The critical temperature for superfluidity increases if the exciton concentration and the interlayer separation increase. It is shown that the dipolar exciton binding energy and mean-field critical temperature for superfluidity are sensitive to the electron and hole effective masses. The proposed experiment to observe a directional superfluidity of excitons is addressed.

Asymmetric dipolar ring

DOEpatents

Prosandeev, Sergey A.; Ponomareva, Inna V.; Kornev, Igor A.; Bellaiche, Laurent M.

2010-11-16

A device having a dipolar ring surrounding an interior region that is disposed asymmetrically on the ring. The dipolar ring generates a toroidal moment switchable between at least two stable states by a homogeneous field applied to the dipolar ring in the plane of the ring. The ring may be made of ferroelectric or magnetic material. In the former case, the homogeneous field is an electric field and in the latter case, the homogeneous field is a magnetic field.

Accurate measurement of heteronuclear dipolar couplings by phase-alternating R-symmetry (PARS) sequences in magic angle spinning NMR spectroscopy

NASA Astrophysics Data System (ADS)

Hou, Guangjin; Lu, Xingyu; Vega, Alexander J.; Polenova, Tatyana

2014-09-01

We report a Phase-Alternating R-Symmetry (PARS) dipolar recoupling scheme for accurate measurement of heteronuclear 1H-X (X = 13C, 15N, 31P, etc.) dipolar couplings in MAS NMR experiments. It is an improvement of conventional C- and R-symmetry type DIPSHIFT experiments where, in addition to the dipolar interaction, the 1H CSA interaction persists and thereby introduces considerable errors in the dipolar measurements. In PARS, phase-shifted RN symmetry pulse blocks applied on the 1H spins combined with π pulses applied on the X spins at the end of each RN block efficiently suppress the effect from 1H chemical shift anisotropy, while keeping the 1H-X dipolar couplings intact. Another advantage over conventional DIPSHIFT experiments, which require the signal to be detected in the form of a reduced-intensity Hahn echo, is that the series of π pulses refocuses the X chemical shift and avoids the necessity of echo formation. PARS permits determination of accurate dipolar couplings in a single experiment; it is suitable for a wide range of MAS conditions including both slow and fast MAS frequencies; and it assures dipolar truncation from the remote protons. The performance of PARS is tested on two model systems, [15N]-N-acetyl-valine and [U-13C,15N]-N-formyl-Met-Leu-Phe tripeptide. The application of PARS for site-resolved measurement of accurate 1H-15N dipolar couplings in the context of 3D experiments is presented on U-13C,15N-enriched dynein light chain protein LC8.

Dynamic-force spectroscopy measurement with precise force control using atomic-force microscopy probe

NASA Astrophysics Data System (ADS)

Takeuchi, Osamu; Miyakoshi, Takaaki; Taninaka, Atsushi; Tanaka, Katsunori; Cho, Daichi; Fujita, Machiko; Yasuda, Satoshi; Jarvis, Suzanne P.; Shigekawa, Hidemi

2006-10-01

The accuracy of dynamic-force spectroscopy (DFS), a promising technique of analyzing the energy landscape of noncovalent molecular bonds, was reconsidered in order to justify the use of an atomic-force microscopy (AFM) cantilever as a DFS force probe. The advantages and disadvantages caused, for example, by the force-probe hardness were clarified, revealing the pivotal role of the molecular linkage between the force probe and the molecular bonds. It was shown that the feedback control of the loading rate of tensile force enables us a precise DFS measurement using an AFM cantilever as the force probe.

Tectonic reversal of the western Doruneh Fault System: Implications for Central Asian tectonics

NASA Astrophysics Data System (ADS)

Javadi, Hamid Reza; Esterabi Ashtiani, Marzieh; Guest, Bernard; Yassaghi, Ali; Ghassemi, Mohammad Reza; Shahpasandzadeh, Majid; Naeimi, Amir

2015-10-01

The left-lateral Doruneh Fault System (DFS) bounds the north margin of the Central Iranian microplate and has played an important role in the structural evolution of the Turkish-Iranian plateau. The western termination of the DFS is a sinistral synthetic branch fault array that shows clear kinematic evidence of having undergone recent slip sense inversion from a dextral array to a sinistral array in the latest Neogene or earliest Quaternary. Similarly, kinematic evidence from the Anarak Metamorphic complex suggests that this complex initially developed at a transpressive left-stepping termination of the DFS and that it was inverted in the latest Neogene to a transtensional fault termination. The recognition that the DFS and other faults in NE Iran were inverted from dextral to sinistral strike slip in the latest Neogene and the likely connection between the DFS and the Herat Fault of Afghanistan suggests that prior to the latest Miocene, all of the north Iranian and northern Afghan ranges were part of a distributed dextral fault network that extended from the west Himalayan syntaxes to the western Alborz. Also, the recognition that regional slip sense inversion occurred across northern and northeastern Iran after the latest Miocene invalidates tectonic models that extrapolate Pleistocene to recent fault slip kinematics and rates back beyond this time.

Asymptotic, multigroup flux reconstruction and consistent discontinuity factors

DOE PAGES

Trahan, Travis J.; Larsen, Edward W.

2015-05-12

Recent theoretical work has led to an asymptotically derived expression for reconstructing the neutron flux from lattice functions and multigroup diffusion solutions. The leading-order asymptotic term is the standard expression for flux reconstruction, i.e., it is the product of a shape function, obtained through a lattice calculation, and the multigroup diffusion solution. The first-order asymptotic correction term is significant only where the gradient of the diffusion solution is not small. Inclusion of this first-order correction term can significantly improve the accuracy of the reconstructed flux. One may define discontinuity factors (DFs) to make certain angular moments of the reconstructed fluxmore » continuous across interfaces between assemblies in 1-D. Indeed, the standard assembly discontinuity factors make the zeroth moment (scalar flux) of the reconstructed flux continuous. The inclusion of the correction term in the flux reconstruction provides an additional degree of freedom that can be used to make two angular moments of the reconstructed flux continuous across interfaces by using current DFs in addition to flux DFs. Thus, numerical results demonstrate that using flux and current DFs together can be more accurate than using only flux DFs, and that making the second angular moment continuous can be more accurate than making the zeroth moment continuous.« less

Principles of control for decoherence-free subsystems.

PubMed

Cappellaro, P; Hodges, J S; Havel, T F; Cory, D G

2006-07-28

Decoherence-free subsystems (DFSs) are a powerful means of protecting quantum information against noise with known symmetry properties. Although Hamiltonians that can implement a universal set of logic gates on DFS encoded qubits without ever leaving the protected subsystem theoretically exist, the natural Hamiltonians that are available in specific implementations do not necessarily have this property. Here we describe some of the principles that can be used in such cases to operate on encoded qubits without losing the protection offered by the DFSs. In particular, we show how dynamical decoupling can be used to control decoherence during the unavoidable excursions outside of the DFS. By means of cumulant expansions, we show how the fidelity of quantum gates implemented by this method on a simple two physical qubit DFS depends on the correlation time of the noise responsible for decoherence. We further show by means of numerical simulations how our previously introduced "strongly modulating pulses" for NMR quantum information processing can permit high-fidelity operations on multiple DFS encoded qubits in practice, provided that the rate at which the system can be modulated is fast compared to the correlation time of the noise. The principles thereby illustrated are expected to be broadly applicable to many implementations of quantum information processors based on DFS encoded qubits.

Correlation of treatment-emergent adverse events and clinical response to endocrine therapy in early breast cancer: a retrospective analysis of the German cohort of TEAM.

PubMed

Hadji, P; Kieback, D G; Tams, J; Hasenburg, A; Ziller, M

2012-10-01

Previous studies have suggested a correlation between the occurrence of vasomotor or joint symptoms during tamoxifen or aromatase inhibitor treatment and improved clinical response. A retrospective analysis of the German cohort of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial was carried out to assess disease-free survival (DFS) and overall survival (OS) in patients with and without arthralgia/myalgia and/or menopausal symptoms during adjuvant endocrine treatment. A total of 1502 patients were included; 739 patients received tamoxifen followed by exemestane and 763 received exemestane. Patients reporting arthralgia/myalgia and patients reporting menopausal symptoms during endocrine treatment had significantly longer OS and DFS than those not reporting these events. The effect on OS was irrespective of treatment. DFS was significantly improved in exemestane-treated patients reporting arthralgia/myalgia or those reporting menopausal symptoms versus those not reporting these events. This effect on DFS was not observed in patients receiving sequential treatment. A combined analysis of patients reporting either menopausal symptoms or arthralgia/myalgia showed that OS and DFS were significantly improved in patients reporting one of these symptoms versus those not reporting either symptom. The occurrence of arthralgia/myalgia or menopausal symptoms during endocrine treatment is associated with significantly improved OS.

Decomposed fuzzy systems and their application in direct adaptive fuzzy control.

PubMed

Hsueh, Yao-Chu; Su, Shun-Feng; Chen, Ming-Chang

2014-10-01

In this paper, a novel fuzzy structure termed as the decomposed fuzzy system (DFS) is proposed to act as the fuzzy approximator for adaptive fuzzy control systems. The proposed structure is to decompose each fuzzy variable into layers of fuzzy systems, and each layer is to characterize one traditional fuzzy set. Similar to forming fuzzy rules in traditional fuzzy systems, layers from different variables form the so-called component fuzzy systems. DFS is proposed to provide more adjustable parameters to facilitate possible adaptation in fuzzy rules, but without introducing a learning burden. It is because those component fuzzy systems are independent so that it can facilitate minimum distribution learning effects among component fuzzy systems. It can be seen from our experiments that even when the rule number increases, the learning time in terms of cycles is still almost constant. It can also be found that the function approximation capability and learning efficiency of the DFS are much better than that of the traditional fuzzy systems when employed in adaptive fuzzy control systems. Besides, in order to further reduce the computational burden, a simplified DFS is proposed in this paper to satisfy possible real time constraints required in many applications. From our simulation results, it can be seen that the simplified DFS can perform fairly with a more concise decomposition structure.

Van Allen Probe measurements of intense Poynting Flux, magnetic dipolarization, and particle energization and auroral arcs.

NASA Astrophysics Data System (ADS)

Wygant, J. R.; Tian, S.; Thaller, S. A.; Breneman, A. W.; Cattell, C. A.; Engel, A.; Mozer, F.; Bonnell, J. W.; Chaston, C. C.; Donovan, E.; Spanswick, E.; Reeves, G.; Kistler, L. M.; Mouikis, C.; Hudson, M.; Smith, C. W.; Fennell, J. F.; Blake, J. B.; Turner, D. L.; Baker, D. N.; Kletzing, C.

2017-12-01

In recent years, there has been a focus on measurements in the near Earth plasmasheet of intervals of intense parallel Poynting flux, magnetic dipolarizations, and energetic particle injection/ and acceleration, as well as, ion ouflow from low altitudes (Ergun et al., 2015; Wygant et al., 2015 and Tian et. al. this meeting). We describe observations from an event on 5/1/2013 and related events on 6/01/2013 and 4/14/2013. Measurements from Van Allen Probes demonstrate that intrinsic to the structure of these dipolarization events are intense pulses (>100 mW/m2) of Poynting flux lasting 1 minute at the leading edge of the dipolarization front. The electric field associated with the Poynting flux burst is primarily in the poloidal direction (70 mV/m) but does also have a significant azimuthal (dawn-dusk) component of 20 mV/m capable of injecting electrons earthward and energizing them via conservation of the first adiabatic invariant. The THEMIS auroral array is used to show that these intervals of Poynting flux are nearly exactly coincident with thin (30 km wide) intense auroral arcs, which also have durations comparable to the Poynting flux. The correspondence between the arc and the Poynting flux allows us to infer the spatial dimensions of the electric fields, which might accelerate particles. Based on the dimensions of the arc, we estimate that at the spacecraft, the region of strong electric field is 1- 1.5 Re in azimuthal extent and 600- 900 km in poloidal direction. The associated EMF along the longitudinal direction is 150-200 kilovolts while the EMF in the poloidal direction is 30-60 kilovolts.Van Allen Probe measurements show that there are abrupt peaks in energetic electrons between 30 keV to 2 MeV coincident with these fields.The enhancements are dispersion-less locally but show energy-time dispersion as seen by LANL spacecraft displaced in MLT. Subsequent to the initial pulse of Poynting flux, there is a longer term (5-30 minutes) second phase of the electric field structure with smaller earthward ExB convection on the order of 10 km/s likely over larger spatial scales. This phase can play an important role in controlling an ExB drift of lower energy particles (0.1-40 keV) especially up-flowing ions. There is evidence is ExB velocity filter for upflowing ions since the convection velocity tracks the energy of the ions.

When Ethyl Isocyanoacetate Meets Isatins: A 1,3-Dipolar/Inverse 1,3-Dipolar/Olefination Reaction for Access to 3-Ylideneoxindoles.

PubMed

Yuan, Wen-Kui; Cui, Tao; Liu, Wei; Wen, Li-Rong; Li, Ming

2018-03-16

A new CuI/1,10-phen-catalyzed reaction for the synthesis of 3-ylideneoxindoles from readily available isatins and ethyl isocyanoacetate, in which ethyl isocyanoacetate acts as a latent two-carbon donor like the Wittig reagent, is reported. A tandem procedure including 1,3-dipolar cycloaddition/inverse 1,3-dipolar ring opening/olefination allows the preparation of 3-ylideneoxindoles with broad functional group tolerance.

Equilibrium phases of dipolar lattice bosons in the presence of random diagonal disorder

NASA Astrophysics Data System (ADS)

Zhang, C.; Safavi-Naini, A.; Capogrosso-Sansone, B.

2018-01-01

Ultracold gases offer an unprecedented opportunity to engineer disorder and interactions in a controlled manner. In an effort to understand the interplay between disorder, dipolar interactions, and quantum degeneracy, we study two-dimensional hard-core dipolar lattice bosons in the presence of on-site bound disorder. Our results are based on large-scale path-integral quantum Monte Carlo simulations by the worm algorithm. We study the ground-state phase diagram at a fixed half-integer filling factor for which the clean system is either a superfluid at a lower dipolar interaction strength or a checkerboard solid at a larger dipolar interaction strength. We find that, even for weak dipolar interactions, superfluidity is destroyed in favor of a Bose glass at a relatively low disorder strength. Interestingly, in the presence of disorder, superfluidity persists for values of the dipolar interaction strength for which the clean system is a checkerboard solid. At a fixed disorder strength, as the dipolar interaction is increased, superfluidity is destroyed in favor of a Bose glass. As the interaction is further increased, the system eventually develops extended checkerboard patterns in the density distribution. Due to the presence of disorder, though, grain boundaries and defects, responsible for a finite residual compressibility, are present in the density distribution. Finally, we study the robustness of the superfluid phase against thermal fluctuations.

Reduction of verotoxigenic Escherichia coli by process and recipe optimisation in dry-fermented sausages.

PubMed

Heir, E; Holck, A L; Omer, M K; Alvseike, O; Høy, M; Måge, I; Axelsson, L

2010-07-15

Outbreaks of verotoxigenic Escherichia coli (VTEC) linked to dry-fermented sausages (DFSs) have emphasized the need for DFS manufacturers to introduce measures to obtain enhanced safety and still maintain the sensory qualities of their products. To our knowledge no data have yet been reported on non-O157:H7 VTEC survival in DFS. Here, the importance of recipe and process variables on VTEC (O157:H7 and O103:H25) reductions in two types of DFS, morr and salami, was determined through three statistically designed experiments. Linear regression and ANOVA analyses showed that no single variable had a dominant effect on VTEC reductions. High levels of NaCl, NaNO(2), glucose (low pH) and fermentation temperature gave enhanced VTEC reduction, while high fat and large casing diameter (a(w)) gave the opposite effect. Interaction effects were small. The process and recipe variables showed similar effects in morr and salami. In general, recipes combining high batter levels of salt (NaCl and NaNO(2)) and glucose along with high fermentation temperature that gave DFS with low final pH and a(w), provided approximately 3 log(10) reductions compared to approximately 1.5 log(10) reductions obtained for standard recipe DFS. Storage at 4 degrees C for 2 months provided log(10) 0.33-0.95 additional VTEC reductions and were only marginally affected by recipe type. Sensory tests revealed only small differences between the various recipes of morr and salami. By optimisation of recipe and process parameters, it is possible to obtain increased microbial safety of DFS while maintaining the sensory qualities of the sausages. 2010 Elsevier B.V. All rights reserved.

Dermal Fibroblasts from Different Layers of Pig Skin Exhibit Different Profibrotic and Morphological Characteristics.

PubMed

Zuo, Yanhai; Yu, Xiaoping; Lu, Shuliang

2016-11-01

In vitro studies of human dermal fibroblast (DF) heterogeneity have long been reported, yet in vivo studies and related research on animals are rare. The objectives of the study were to determine whether the DFs of pigs exhibit heterogeneity and to identify an animal model for the in vivo study of DF heterogeneity. The skin of three female red Duroc pigs (FRDPs) was separated into six layers, and the second and fifth layers (i.e., the superficial and deep dermis) were used in the establishment of wound models and cell cultures. To create the wound models, 54 tongue-shaped flaps were created on one side of the dorsum, and the underlying dermis was then fully replaced with the superficial or deep dermis (the superficial and deep groups, respectively). Skin samples were harvested at postoperative weeks 1, 2, and 3 for measurements of the normal and wounded skin thicknesses. Cells cultured from the superficial and deep dermis (i.e., superficial and deep DFs) were subjected to quantitative estimation of collagen and electron microscopy. The wounded skin thickness in the deep group was significantly greater than that in the superficial group. In contrast with the long deep DFs, the superficial DFs were short and exhibited microvilli-like cell surface projections. Compared with the superficial DFs, the deep DFs exhibited a greater density of rough endoplasmic reticulum and produced significantly more collagen. Similar to humans, FRDPs exhibit DF heterogeneity and should thus be a good animal model for in vivo studies of DF heterogeneity. Anat Rec, 299:1585-1599, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Primary cutaneous marginal zone B-cell lymphoma: response to treatment and disease-free survival in a series of 137 patients.

PubMed

Servitje, Octavio; Muniesa, Cristina; Benavente, Yolanda; Monsálvez, Verónica; Garcia-Muret, M Pilar; Gallardo, Fernando; Domingo-Domenech, Eva; Lucas, Anna; Climent, Fina; Rodriguez-Peralto, Jose L; Ortiz-Romero, Pablo L; Sandoval, Juan; Pujol, Ramon M; Estrach, M Teresa

2013-09-01

Primary cutaneous marginal zone B-cell lymphomas are low-grade lymphomas running an indolent course. Skin relapses have been frequently reported but little information about disease-free survival (DFS) is available. We sought to evaluate relapse rate and DFS in patients with primary cutaneous marginal zone B-cell lymphomas. Clinical features, European Organization for Research and Treatment of Cancer/International Society for Cutaneous Lymphomas stage, light chain restriction, clonality, treatments, skin relapses, DFS, stage progression, extracutaneous disease, and outcome are analyzed in a series of 137 patients. Patients were classified as solitary lesion (T1) (n = 70; 51%), regional skin involvement (T2) (n = 40; 29%), and generalized skin lesions (T3) (n = 27; 20%). Surgical excision, local radiotherapy, or a combination were the initial treatment in 118 patients (86%). In 121 of 137 patients (88%) a complete remission was observed after initial treatment, including 99 of 106 patients (93%) with solitary or localized disease and 22 of 31 patients (71%) with multifocal lesions. Cutaneous relapses were observed in 53 patients (44%). Median DFS was 47 months. Patients with multifocal lesions or T3 disease showed higher relapse rate and shorter DFS. No significant differences were observed between surgery and radiotherapy, but surgery alone was associated with more recurrences at initial site. Overall survival at 5 and 10 years was 93%. Six patients (4%) developed extracutaneous disease during follow-up. This was a case series retrospective study. Our results support long-term follow-up in patients with primary cutaneous marginal zone B-cell lymphomas. Disseminated skin lesions have higher relapse rate and shorter DFS suggesting further investigation on systemic therapies in such a group of patients. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Occurrence of brominated persistent organic pollutants (PBDD/DFs, PXDD/DFs, and PBDEs) in Baltic wild salmon ( Salmo salar ) and correlation with PCDD/DFs and PCBs.

PubMed

Zacs, Dzintars; Rjabova, Jekaterina; Bartkevics, Vadims

2013-08-20

The contamination profiles of polybrominated dibenzo-p-dioxins (PBDDs), dibenzofurans (PBDFs), diphenyl ethers (PBDEs), and mixed monobromo/chloro dibenzo-p-dioxins (PXDDs) and dibenzofurans (PXDFs) were determined in the tissue of Baltic wild salmon and compared with those of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs). Out of the analyzed PXDD/DFs, only the 3-B-2,7,8-triCDF was detected (in the concentration range of 0.039-0.075 pg g(-1) fresh weight (f.w.)). The toxic equivalents (TEQs) for analyzed PBDD/DFs (0.074-0.142 pg TEQ g(-1) f.w.) were found to contribute on average 2.1% to the total PCDD/DF-PBDD/DF-TEQ. The total concentrations of 27 PBDE congeners were in the range of 1.3-5.6 ng g(-1) f.w., with an average of 3.3 ng g(-1) f.w. The levels of PCDD/DFs and PCBs were found to be in the range of 4.53-14.6 pg WHO(2005)-PCDD/DF-PCB-TEQ g(-1) f.w., and concentrations of these compounds in most of the analyzed samples were above the maximum levels specified in Commission Regulation (EU) No. 1259/2011. Good correlation was observed between WHO(2005)-PCDD/DF-TEQ and WHO(2005)-PCB-TEQ (r(2) = 0.98), and these parameters were well correlated with the total sum of PBDE concentrations (r(2) = 0.91 and r(2) = 0.94, respectively). The results suggest that the consumption of Baltic wild salmon has no crucial impact on the average POP intake for typical Latvians.

Sequential Versus Concurrent Trastuzumab in Adjuvant Chemotherapy for Breast Cancer

PubMed Central

Perez, Edith A.; Suman, Vera J.; Davidson, Nancy E.; Gralow, Julie R.; Kaufman, Peter A.; Visscher, Daniel W.; Chen, Beiyun; Ingle, James N.; Dakhil, Shaker R.; Zujewski, JoAnne; Moreno-Aspitia, Alvaro; Pisansky, Thomas M.; Jenkins, Robert B.

2011-01-01

Purpose NCCTG (North Central Cancer Treatment Group) N9831 is the only randomized phase III trial evaluating trastuzumab added sequentially or used concurrently with chemotherapy in resected stages I to III invasive human epidermal growth factor receptor 2–positive breast cancer. Patients and Methods Patients received doxorubicin and cyclophosphamide every 3 weeks for four cycles, followed by paclitaxel weekly for 12 weeks (arm A), paclitaxel plus sequential trastuzumab weekly for 52 weeks (arm B), or paclitaxel plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks (arm C). The primary end point was disease-free survival (DFS). Results Comparison of arm A (n = 1,087) and arm B (n = 1,097), with 6-year median follow-up and 390 events, revealed 5-year DFS rates of 71.8% and 80.1%, respectively. DFS was significantly increased with trastuzumab added sequentially to paclitaxel (log-rank P < .001; arm B/arm A hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.85). Comparison of arm B (n = 954) and arm C (n = 949), with 6-year median follow-up and 313 events, revealed 5-year DFS rates of 80.1% and 84.4%, respectively. There was an increase in DFS with concurrent trastuzumab and paclitaxel relative to sequential administration (arm C/arm B HR, 0.77; 99.9% CI, 0.53 to 1.11), but the P value (.02) did not cross the prespecified O'Brien-Fleming boundary (.00116) for the interim analysis. Conclusion DFS was significantly improved with 52 weeks of trastuzumab added to adjuvant chemotherapy. On the basis of a positive risk-benefit ratio, we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important standard-of-care treatment alternative to a sequential regimen. PMID:22042958

Accurate measurement of heteronuclear dipolar couplings by phase-alternating R-symmetry (PARS) sequences in magic angle spinning NMR spectroscopy

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

Hou, Guangjin, E-mail: hou@udel.edu, E-mail: tpolenov@udel.edu; Lu, Xingyu, E-mail: luxingyu@udel.edu, E-mail: lexvega@comcast.net; Vega, Alexander J., E-mail: luxingyu@udel.edu, E-mail: lexvega@comcast.net

2014-09-14

We report a Phase-Alternating R-Symmetry (PARS) dipolar recoupling scheme for accurate measurement of heteronuclear {sup 1}H-X (X = {sup 13}C, {sup 15}N, {sup 31}P, etc.) dipolar couplings in MAS NMR experiments. It is an improvement of conventional C- and R-symmetry type DIPSHIFT experiments where, in addition to the dipolar interaction, the {sup 1}H CSA interaction persists and thereby introduces considerable errors in the dipolar measurements. In PARS, phase-shifted RN symmetry pulse blocks applied on the {sup 1}H spins combined with π pulses applied on the X spins at the end of each RN block efficiently suppress the effect from {supmore » 1}H chemical shift anisotropy, while keeping the {sup 1}H-X dipolar couplings intact. Another advantage over conventional DIPSHIFT experiments, which require the signal to be detected in the form of a reduced-intensity Hahn echo, is that the series of π pulses refocuses the X chemical shift and avoids the necessity of echo formation. PARS permits determination of accurate dipolar couplings in a single experiment; it is suitable for a wide range of MAS conditions including both slow and fast MAS frequencies; and it assures dipolar truncation from the remote protons. The performance of PARS is tested on two model systems, [{sup 15}N]-N-acetyl-valine and [U-{sup 13}C,{sup 15}N]-N-formyl-Met-Leu-Phe tripeptide. The application of PARS for site-resolved measurement of accurate {sup 1}H-{sup 15}N dipolar couplings in the context of 3D experiments is presented on U-{sup 13}C,{sup 15}N-enriched dynein light chain protein LC8.« less

Suppression of quantum phase interference in the molecular magnet Fe8 with dipolar-dipolar interaction

NASA Astrophysics Data System (ADS)

Chen, Zhi-De; Liang, J.-Q.; Shen, Shun-Qing

2002-09-01

Renormalized tunnel splitting with a finite distribution in the biaxial spin model for molecular magnets is obtained by taking into account the dipolar interaction of enviromental spins. Oscillation of the resonant tunnel splitting with a transverse magnetic field along the hard axis is smeared by the finite distribution, which subsequently affects the quantum steps of the hysteresis curve evaluated in terms of the modified Landau-Zener model of spin flipping induced by the sweeping field. We conclude that the dipolar-dipolar interaction drives decoherence of quantum tunneling in the molecular magnet Fe8, which explains why the quenching points of tunnel splitting between odd and even resonant tunneling predicted theoretically were not observed experimentally.

Oil Palm Defensin: A Thermal Stable Peptide that Restricts the Mycelial Growth of Ganoderma boninense.

PubMed

Tan, Yung-Chie; Ang, Cheng-Liang; Wong, Mui-Yun; Ho, Chai-Ling

2016-01-01

Plant defensins are plant defence peptides that have many different biological activities, including antifungal, antimicrobial, and insecticidal activities. A cDNA (EgDFS) encoding defensin was isolated from Elaeis guineensis. The open reading frame of EgDFS contained 231 nucleotides encoding a 71-amino acid protein with a predicted molecular weight at 8.69 kDa, and a potential signal peptide. The eight highly conserved cysteine sites in plant defensins were also conserved in EgDFS. The EgDFS sequence lacking 30 amino acid residues at its N-terminus (EgDFSm) was cloned into Escherichia coli BL21 (DE3) pLysS and successfully expressed as a soluble recombinant protein. The recombinant EgDFSm was found to be a thermal stable peptide which demonstrated inhibitory activity against the growth of G. boninense possibly by inhibiting starch assimilation. The role of EgDFSm in oil palm defence system against the infection of pathogen G. boninense was discussed.

Browns Ferry Nuclear Plant Unit 2: Control rod drive scram discharge headers decontamination effort

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

Traynor, J.C.

1983-08-01

The control rod drive (CRD) scram discharge headers were decontaminated during the Browns Ferry unit 2, cycle 4 refueling outage (August 2-5, 1982). Hydrolasing (high-pressure water blasting) was used as the method of decontamination to remove fixed and loose radioactive contaminants from the headers. It was found that hydrolasing of the west scram discharge headers resulted in approximate maximum and average decontamination factors (DFs) on contact of 13 and 5, respectively. For the east scram discharge headers, hydrolasing resulted in a maximum and average DF on contact of approximately 3. The maximum and average DFs on contact for the individualmore » headers ranged from 1 to 33 and 1 to 10, respectively, while the walkway (head-level) DFs were in the range of 3 to 4. Higher DFs were impeded by inadequate drainage and backwashing of fluid. This led to increased radiation levels in some areas and recontamination of adjacent headers.« less

Simulations in site error estimation for direction finders

NASA Astrophysics Data System (ADS)

López, Raúl E.; Passi, Ranjit M.

1991-08-01

The performance of an algorithm for the recovery of site-specific errors of direction finder (DF) networks is tested under controlled simulated conditions. The simulations show that the algorithm has some inherent shortcomings for the recovery of site errors from the measured azimuth data. These limitations are fundamental to the problem of site error estimation using azimuth information. Several ways for resolving or ameliorating these basic complications are tested by means of simulations. From these it appears that for the effective implementation of the site error determination algorithm, one should design the networks with at least four DFs, improve the alignment of the antennas, and increase the gain of the DFs as much as it is compatible with other operational requirements. The use of a nonzero initial estimate of the site errors when working with data from networks of four or more DFs also improves the accuracy of the site error recovery. Even for networks of three DFs, reasonable site error corrections could be obtained if the antennas could be well aligned.

Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients

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

Pasquier, David, E-mail: d-pasquier@o-lambret.fr; Barney, Brandon; Sundar, Santhanam

2015-07-15

Purpose: Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. Methods and Materials: Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. Results: The study includedmore » 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). Conclusions: The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease suggests that conservative treatment is appropriate in this situation.« less

Neoadjuvant rectal score as individual-level surrogate for disease-free survival in rectal cancer in the CAO/ARO/AIO-04 randomized phase 3 trial.

PubMed

Fokas, E; Fietkau, R; Hartmann, A; Hohenberger, W; Grützmann, R; Ghadimi, M; Liersch, T; Ströbel, P; Grabenbauer, G G; Graeven, U; Hofheinz, R-D; Köhne, C-H; Wittekind, C; Sauer, R; Kaufmann, M; Hothorn, T; Rödel, C

2018-04-27

Surrogate endpoints in rectal cancer after preoperative chemoradiation are lacking as their statistical validation poses major challenges, including confirmation based on large phase 3 trials. We examined the prognostic role and individual-level surrogacy of neoadjuvant rectal (NAR) score that incorporates weighted cT, ypT and ypN categories for disease-free survival (DFS) in 1191 patients with rectal carcinoma treated within the CAO/ARO/AIO-04 phase 3 trial. Cox regression models adjusted for treatment arm, resection status, and NAR score were used in multivariable analysis. The four Prentice criteria (PC1-4) were used to assess individual-level surrogacy of NAR for DFS. After a median follow-up of 50 months, the addition of oxaliplatin to fluorouracil-based chemoradiotherapy (CRT) significantly improved 3-year DFS (75.9% [95% CI 72.30-79.50] vs 71.3% [95% CI 67.60-74.90]; P = 0.034; PC 1) and resulted in a shift towards lower NAR groups (P = 0.034, PC 2) compared to fluorouracil-only CRT. The 3-year DFS was 91.7% (95% CI, 88.2 95.2), 81.8% (95% CI, 78.4-85.1) and 58.1 (95% CI 52.4-63.9) for low, intermediate and high NAR score, respectively (P < 0.001; PC 3). NAR score remained an independent prognostic factor for DFS (low vs high NAR: HR 4.670; 95% CI 3.106-7.020; P < 0.001; low vs intermediate NAR: HR 1.971; 95% CI 1.303-2.98; P = 0.001) in multivariable analysis. Notwithstanding the inherent methodological difficulty in interpretation of PC 4 to establish surrogacy, the treatment effect on DFS was captured by NAR, supporting satisfaction of individual-level PC4. Our study validates the prognostic role and individual-level surrogacy of NAR score for DFS within a large randomized phase 3 trial. NAR score could help oncologists to speed up response-adapted therapeutic decision, and further large phase 3 trial datasets should aim to confirm trial-level surrogacy.

Independent prognostic impact of preoperative serum carcinoembryonic antigen and cancer antigen 15-3 levels for early breast cancer subtypes.

PubMed

Imamura, Michiko; Morimoto, Takashi; Nomura, Takashi; Michishita, Shintaro; Nishimukai, Arisa; Higuchi, Tomoko; Fujimoto, Yukie; Miyagawa, Yoshimasa; Kira, Ayako; Murase, Keiko; Araki, Kazuhiro; Takatsuka, Yuichi; Oh, Koshi; Masai, Yoshikazu; Akazawa, Kouhei; Miyoshi, Yasuo

2018-02-12

Although the prognosis for operable breast cancers is reportedly worse if serum carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) levels are above normal, the usefulness of this prognosis is limited due to the low sensitivity and specificity; in addition, the optimal cutoff levels remain unknown. A total of 1076 patients who were operated for breast cancers (test set = 608, validation set = 468) without evidence of metastasis were recruited, and their baseline and postoperative serum CEA and CA15-3 levels were analyzed. The optimal cutoff values of CEA and CA15-3 for disease-free survival (DFS) were 3.2 ng/mL and 13.3 U/mL, respectively, based on receiver operating characteristic curve and area under the curve analyses. The DFS of patients with high CEA levels (CEA-high: n = 191, 5-year DFS 70.6%) was significantly worse (p < 0.0001) than that of CEA-low patients (n = 885, 5-year DFS 87.2%). There was a significant difference in DFS (p < 0.0001) between CA15-3-high and CA15-3-low patients (n = 314 and n = 762, respectively; 5-year DFS 71.8 vs. 89.3%). Significant associations between DFS and CA15-3 levels were observed irrespective of the subtypes. Multivariable analysis indicated that tumor size, lymph node metastasis, tumor grade, and CEA (p = 0.0474) and CA15-3 (p < 0.0001) levels were independent prognostic factors (hazard ratio [HR] 1.520, 95% confidence interval [CI] 1.005-2.245 for CEA; HR 2.088, 95% CI 1.457-2.901 for CA15-3). These findings suggest that CEA and CA15-3 levels might be useful for predicting the prognosis of patients with operable early breast cancer irrespective of the subtype. Serum levels at baseline may reflect tumor characteristics for metastatic potential even when these levels are within the normal ranges.

Genetic variants of cell cycle pathway genes predict disease-free survival of hepatocellular carcinoma.

PubMed

Liu, Shun; Yang, Tian-Bo; Nan, Yue-Li; Li, An-Hua; Pan, Dong-Xiang; Xu, Yang; Li, Shu; Li, Ting; Zeng, Xiao-Yun; Qiu, Xiao-Qiang

2017-07-01

Disruption of the cell cycle pathway has previously been related to development of human cancers. However, associations between genetic variants of cell cycle pathway genes and prognosis of hepatocellular carcinoma (HCC) remain largely unknown. In this study, we evaluated the associations between 24 potential functional single nucleotide polymorphisms (SNPs) of 16 main cell cycle pathway genes and disease-free survival (DFS) of 271 HCC patients who had undergone radical surgery resection. We identified two SNPs, i.e., SMAD3 rs11556090 A>G and RBL2 rs3929G>C, that were independently predictive of DFS in an additive genetic model with false-positive report probability (FPRP) <0.2. The SMAD3 rs11556090G allele was associated with a poorer DFS, compared with the A allele [hazard ratio (HR) = 1.46, 95% confidential interval (95% CI) = 1.13-1.89, P = 0.004]; while the RBL2 rs3929 C allele was associated with a superior DFS, compared with the G allele (HR = 0.74, 95% CI = 0.57-0.96, P = 0.023). Additionally, patients with an increasing number of unfavorable genotypes (NUGs) of these loci had a significant shorter DFS (P trend  = 0.0001). Further analysis using receiver operating characteristic (ROC) curves showed that the model including the NUGs and known prognostic clinical variables demonstrated a significant improvement in predicting the 1-year DFS (P = 0.011). Moreover, the RBL2 rs3929 C allele was significantly associated with increased mRNA expression levels of RBL2 in liver tissue (P = 1.8 × 10 -7 ) and the whole blood (P = 3.9 × 10 -14 ). Our data demonstrated an independent or a joint effect of SMAD3 rs11556090 and RBL2 rs3929 in the cell cycle pathway on DFS of HCC, which need to be validated by large cohort and biological studies. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Determinants of survival after liver resection for metastatic colorectal carcinoma.

PubMed

Parau, Angela; Todor, Nicolae; Vlad, Liviu

2015-01-01

Prognostic factors for survival after liver resection for metastatic colorectal cancer identified up to date are quite inconsistent with a great inter-study variability. In this study we aimed to identify predictors of outcome in our patient population. A series of 70 consecutive patients from the oncological hepatobiliary database, who had undergone curative hepatic surgical resection for hepatic metastases of colorectal origin, operated between 2006 and 2011, were identified. At 44.6 months (range 13.7-73), 30 of 70 patients (42.85%) were alive. Patient demographics, primary tumor and liver tumor factors, operative factors, pathologic findings, recurrence patterns, disease-free survival (DFS), overall survival (OS) and cancer-specific survival (CSS) were analyzed. Clinicopathologic variables were tested using univariate and multivariate analyses. The 3-year CSS after first hepatic resection was 54%. Median CSS survival after first hepatic resection was 40.2 months. Median CSS after second hepatic resection was 24.2 months. The 3-year DFS after first hepatic resection was 14%. Median disease free survival after first hepatic resection was 18 months. The 3-year DFS after second hepatic resection was 27% and median DFS after second hepatic resection 12 months. The 30-day mortality and morbidity rate after first hepatic resection was 5.71% and 12.78%, respectively. In univariate analysis CSS was significantly reduced for the following factors: age >53 years, advanced T stage of primary tumor, moderately- poorly differentiated tumor, positive and narrow resection margin, preoperative CEA level >30 ng/ml, DFS <18 months. Perioperative chemotherapy related to metastasectomy showed a trend in improving CSS (p=0.07). Perioperative chemotherapy improved DFS in a statistically significant way (p=0.03). Perioperative chemotherapy and achievement of resection margins beyond 1 mm were the major determinants of both CSS and DFS after first liver resection in multivariate analysis. In our series predictors of outcome in multivariate analysis were resection margins beyond 1mm and perioperative chemotherapy. Studies on larger population and analyses of additional clinicopathologic factors like genetic markers could contribute to development of clinical scoring models to assess the risk of relapse and survival.

Preservation of distributive vs. tributive and other fluvial system deposits in the rock record (Invited)

NASA Astrophysics Data System (ADS)

Fielding, C. R.

2010-12-01

A recent paper (Weissmann et al., 2010, Geology 38, 39-42) has suggested that deposits of distributive fluvial systems (DFS) “may represent the norm in the continental rock record, with axial and incised river deposits composing a relatively minor proportion of the succession”. Herein, I examine this hypothesis by reference to a number of well-exposed fluvial successions from a variety of basinal settings. The cited paper suggests that DFS dominate modern fluvial landscapes in subsiding sedimentary basins, while acknowledging that many merge into a trunk stream in the basin depocenter. Most of the modern World’s largest rivers, however, are tributive, and many of them preserve significant thicknesses of alluvium beneath and lateral to the modern channel belt. Because DFS are abundant on modern landscapes does not necessarily mean that they will be proportionately well-represented in the ancient. Consideration must also be given to the location within a basin where fluvial systems are most likely to be preserved (the depocenter), and to other factors. DFS (or fluvial/alluvial fans) are commonly developed on the tilted margins of asymmetric basins (hangingwalls of half-grabens and supradetachment basins, transtensional and foreland basins), but not in the depocenters. Symmetrically subsiding basins and long wavelength passive margin basins, however, facilitate development of extensive, very low-gradient plains where trunk streams with tributive or anabranching planforms are typical. Such basins, and the depocenters of asymmetric basins, are most likely to facilitate long-term establishment of trunk systems that have the greatest preservation potential. Incised and/or trunk stream deposits have, furthermore, been interpreted from a large number of ancient examples, some long-lived on timescales of millions of years. In the latter cases it has been argued that tectonic stability of the drainage basin is a key characteristic. A survey of the modern landscape therefore represents only a snapshot of time and one minor component of any climatically- or tectonically-driven cycle. It seems unlikely that DFS dominate alluvial stratigraphy. Criteria for recognition of DFS in the ancient have not yet been fully formulated, but might include 1) a relatively tightly constrained width vs. thickness distribution of channel lithosomes, and 2) lack of outsized channel bodies, in association with 3) centrifugal palaeocurrent distributions, and 4) down-paleoslope decreases in channel body dimensions. Neither these criteria, nor those cited in Weissmann et al. (2010), are necessarily unique to DFS, however. Accordingly, I consider it unlikely that a dominance of DFS in the alluvial rock record could be persuasively demonstrated even it were true.

European Nationality Influence in the Management of Squamous Cell Vulvar Cancer.

PubMed

Iacoponi, Sara; Zapardiel, Ignacio

2017-01-01

Vulvar cancer is a rare disease. In western European countries, the incidence is 1.2 cases per 100,000 women/year. The aim of this study was to analyze the management and disease-free survival (DFS) of vulvar cancer among European countries. An international multicenter retrospective study including patients diagnosed of squamous cell vulvar cancer was performed. Countries analyzed included Austria, Germany, Greece, Italy, Latvia, Lithuania, Poland, Portugal, Spain and Turkey. One hundred different centers were enrolled including 1,505 squamous cell tumors treated from January 2001 until December 2005. The mean free surgical margin was 9.93 mm, which was different between countries (p = 0.076); it ranged from 5.79 mm (95% CI 4.44-7.13) in Germany to 33.39 mm (95% CI 22.21-44.58) in Lithuania. The global 5-year overall survival rate was 61.4%, and the global 5-year DFS rate was 32%. DFS times were different between countries as well as the treatments carried out. The country with the shortest DFS time had 15.9 ± 3.1 months compared to the one with the longest time with 66.0 ± 17.4 months. Wide differences in treatments and DFS times have been observed between countries. Homogeneous management for squamous cell vulvar cancer is needed to obtain the best survival rates for all patients. © 2016 S. Karger AG, Basel.

Advanced Dispersed Fringe Sensing Algorithm for Coarse Phasing Segmented Mirror Telescopes

NASA Technical Reports Server (NTRS)

Spechler, Joshua A.; Hoppe, Daniel J.; Sigrist, Norbert; Shi, Fang; Seo, Byoung-Joon; Bikkannavar, Siddarayappa A.

2013-01-01

Segment mirror phasing, a critical step of segment mirror alignment, requires the ability to sense and correct the relative pistons between segments from up to a few hundred microns to a fraction of wavelength in order to bring the mirror system to its full diffraction capability. When sampling the aperture of a telescope, using auto-collimating flats (ACFs) is more economical. The performance of a telescope with a segmented primary mirror strongly depends on how well those primary mirror segments can be phased. One such process to phase primary mirror segments in the axial piston direction is dispersed fringe sensing (DFS). DFS technology can be used to co-phase the ACFs. DFS is essentially a signal fitting and processing operation. It is an elegant method of coarse phasing segmented mirrors. DFS performance accuracy is dependent upon careful calibration of the system as well as other factors such as internal optical alignment, system wavefront errors, and detector quality. Novel improvements to the algorithm have led to substantial enhancements in DFS performance. The Advanced Dispersed Fringe Sensing (ADFS) Algorithm is designed to reduce the sensitivity to calibration errors by determining the optimal fringe extraction line. Applying an angular extraction line dithering procedure and combining this dithering process with an error function while minimizing the phase term of the fitted signal, defines in essence the ADFS algorithm.

Role of Adjuvant Radiotherapy in Granulosa Cell Tumors of the Ovary

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

Hauspy, Jan; Beiner, Mario E.; Harley, Ian

2011-03-01

Purpose: To review the role of adjuvant radiotherapy (RT) in the outcome and recurrence patterns of granulosa cell tumors (GCTs) of the ovary. Methods and Materials: The records of all patients with GCTs referred to the Princess Margaret Hospital University Health Network between 1961 and 2006 were retrospectively reviewed. The patient, tumor, and treatment factors were assessed by univariate and multivariate analyses using disease-free survival (DFS) as the endpoint. Results: A total of 103 patients with histologically confirmed GCTs were included in the present study. The mean duration of follow-up was 100 months (range, 1-399). Of the 103 patients, 31more » received adjuvant RT. A total of 39 patients developed tumor recurrence. The tumor size, incidence of intraoperative rupture, and presence of concurrent endometrial cancer were not significant risk factors for DFS. The median DFS was 251 months for patients who underwent adjuvant RT compared with 112 months for patients who did not (p = .02). On multivariate analysis, adjuvant RT remained a significant prognostic factor for DFS (p = .004). Of the 103 patients, 12 had died and 44 were lost to follow-up. Conclusion: Ovarian GCTs can be indolent, with patients achieving long-term survival. In our series, adjuvant RT resulted in a significantly longer DFS. Ideally, randomized trials with long-term follow-up are needed to define the role of adjuvant RT for ovarian GCTs.« less

Role of adjuvant radiotherapy in granulosa cell tumors of the ovary.

PubMed

Hauspy, Jan; Beiner, Mario E; Harley, Ian; Rosen, Barry; Murphy, Joan; Chapman, William; Le, Lisa W; Fyles, Anthony; Levin, Wilfred

2011-03-01

To review the role of adjuvant radiotherapy (RT) in the outcome and recurrence patterns of granulosa cell tumors (GCTs) of the ovary. The records of all patients with GCTs referred to the Princess Margaret Hospital University Health Network between 1961 and 2006 were retrospectively reviewed. The patient, tumor, and treatment factors were assessed by univariate and multivariate analyses using disease-free survival (DFS) as the endpoint. A total of 103 patients with histologically confirmed GCTs were included in the present study. The mean duration of follow-up was 100 months (range, 1-399). Of the 103 patients, 31 received adjuvant RT. A total of 39 patients developed tumor recurrence. The tumor size, incidence of intraoperative rupture, and presence of concurrent endometrial cancer were not significant risk factors for DFS. The median DFS was 251 months for patients who underwent adjuvant RT compared with 112 months for patients who did not (p=.02). On multivariate analysis, adjuvant RT remained a significant prognostic factor for DFS (p=.004). Of the 103 patients, 12 had died and 44 were lost to follow-up. Ovarian GCTs can be indolent, with patients achieving long-term survival. In our series, adjuvant RT resulted in a significantly longer DFS. Ideally, randomized trials with long-term follow-up are needed to define the role of adjuvant RT for ovarian GCTs. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

The Prognostic Nutritional Index Predicts Survival and Identifies Aggressiveness of Gastric Cancer.

PubMed

Eo, Wan Kyu; Chang, Hye Jung; Suh, Jungho; Ahn, Jin; Shin, Jeong; Hur, Joon-Young; Kim, Gou Young; Lee, Sookyung; Park, Sora; Lee, Sanghun

2015-01-01

Nutritional status has been associated with long-term outcomes in cancer patients. The prognostic nutritional index (PNI) is calculated by serum albumin concentration and absolute lymphocyte count, and it may be a surrogate biomarker for nutritional status and possibly predicts overall survival (OS) of gastric cancer. We evaluated the value of the PNI as a predictor for disease-free survival (DFS) in addition to OS in a cohort of 314 gastric cancer patients who underwent curative surgical resection. There were 77 patients in PNI-low group (PNI ≤ 47.3) and 237 patients in PNI-high group (PNI > 47.3). With a median follow-up of 36.5 mo, 5-yr DFS rates in PNI-low group and PNI-high group were 63.5% and 83.6% and 5-yr OS rates in PNI-low group and PNI-high group were 63.5% and 88.4%, respectively (DFS, P < 0.0001; OS, P < 0.0001). In the multivariate analysis, the only predictors for DFS were PNI, tumor-node-metastasis (TNM) stage, and perineural invasion, whereas the only predictors for OS were PNI, age, TNM stage, and perineural invasion. In addition, the PNI was independent of various inflammatory markers. In conclusion, the PNI is an independent prognostic factor for both DFS and OS, and provides additional prognostic information beyond pathologic parameters.

Disease-free survival in patients with non-metastatic breast cancer.

PubMed

Diniz, Roberta Wolp; Guerra, Maximiliano Ribeiro; Cintra, Jane Rocha Duarte; Fayer, Vívian Assis; Teixeira, Maria Teresa Bustamante

2016-01-01

Breast cancer is the second most common malignancy in the world and the one with highest incidence in the female population; it is also a major cause of death from cancer among women. To analyze the disease-free survival (DFS) at 5 years and prognostic factors in women with non-metastatic invasive breast cancer treated at a referral center for cancer care located in a medium-sized city in the Southeast of Brazil. Patients diagnosed with the disease between 2003 and 2005 and identified through the institution's cancer hospital records were analyzed. The follow-up of cases was carried out through hospital records, and complemented by search in the database of the Mortality Information System (SIM) as well as telephone contact. The variables analyzed were distributed in the following blocks: socio-demographic data, tumor-related characteristics, and treatment-related characteristics. Survival functions were calculated using the Kaplan-Meier method and the prognostic factors were analyzed based on Cox proportional hazard model. The study showed a DFS at 5 years of 72% (95CI 67.6-75.9). The main variables independently associated with DFS were lymph node involvement, use of hormone therapy, and education level. This study reinforces the importance of early diagnosis for DFS, pointing to the role of social aspects in this regard. The relevance of this research in the country is also highlighted, given the scarcity of studies on DFS in the Brazilian population.

Dipolar excitation in the third stability region.

PubMed

Konenkov, Nikolai V; Chernyak, Eugenii Ya; Stepanov, Vladimir A

Dipole resonant excitation of ions creates instability bands which follow iso-β lines where β is the characteristic exponent (stability parameter). Instability bands are exited most effectively on the fundamental frequency π= βΩ/2. Here π is the angle resonance frequency of the dipolar voltage applied to x or y pair rods of the analyzer, and Ω is the angle frequency of the main drive voltage. Our goal is to study the mass peak shape in the third stability region with dipolar resonance excitation of the instability band with respect to the resonance frequency π and the dipolar potential amplitude. Numerical integration of the ion motion equations with a given ion source emittance is used to investigate peak shapes and ion transmission. We show that it is possible to vary the resolution power at any part of the third stability region. A change of the dipolar potential phase leads to a periodical variation of the resolution with period π.The most effective dipolar excitation in the y direction is along βy near the stability boundary. The mass peak shape is calculated also for a quadrupole with round rods. The best peak shape (small tails and high resolution) takes place for the rod set with r/r0=1.130. Dipolar excitation increases the transmission by approximately 5-10% at a given resolution.

Participatory Research in an Arts Integration Professional Development Program

ERIC Educational Resources Information Center

Cawthon, Stephanie W.; Dawson, Kathryn M.; Judd-Glossy, Laura; Ihorn, Shasta

2012-01-01

Drama for Schools (DFS) is an arts integration professional development program rooted in critical pedagogy and constructivism that emphasizes partnerships between school districts and a major research university. As a part of the research initiative embedded in this professional development program, DFS began an Arts integration Research Teacher…

Type Ia Supernovae: Nature's Grandest Thermonuclear Explosions

NASA Astrophysics Data System (ADS)

Woosley, Stan

2003-10-01

When carbon fusion ignites near the center of an accreting white dwarf near the Chandrasekhar Mass, an irreversible series of events is initiated that ultimately leads to the complete disruption of the star and a bright display powered by radioactive decay. Though studied for over 40 years, the details of how this happens remain elusive. Three areas of uncertainty will be discussed: 1) the "ignition" of the bomb: one point or many, central or off-center; 2) the propagation of an unconfined Rayleigh-Taylor unstable burning front - does a robust transition to detonation occur as the front moves into a regime of ``distributed burning"? 3) the generation of the light curve and the Philipps relation. Studies of question 1), equally critical to the other two, suggest a dipolar flow at ignition time and off-center ignition. There may be an uncontrolable degree of chaos in the peak brightness resulting from the ignition process that will affect how SN Ia are used for cosmology. Question 2) is a frontier subject in the chemical combustion community. Results of new multi-dimensional studies will be presented. Question 3) involves atomic physics more than hydrodynamics, but current views suggest that SN Ia light curves should be characterized, at some level, by more than a single parameter.

Kinetic feature of dipolarization fronts produced by interchange instability in the magnetotail

NASA Astrophysics Data System (ADS)

Lyu, Haoyu

2017-04-01

A two-dimensional extended MHD simulation is performed to study the kinetic feature of depolarization fronts (DF) in the scale of the ion inertial length / ion Larmor radius. The interchange instability, arising due to the force imbalance between the tailward gradient of thermal pressure and Earthward magnetic curvature force, self-consistently produces the DF in the near-Earth region. Numerical investigations indicate that the DF is a tangential discontinuity, which means that the normal plasma velocity across the DF should be zero in the reference system that is static with the DF structure. The electric system, including electric field and current, is determined by Hall effect arising in the scale of ion inertial length. Hall effect not only mainly contributes on the electric field normal to the tangent plane of the DF, increases the current along the tangent plane of the DF, but also makes the DF structure asymmetric. The drifting motion of the large-scale DF structure is determined by the FLR effect arising in the scale of ion Larmor radius. The ion magnetization velocity induced by the FLR effect is towards to duskward at the subsolar point of the DF, but the y component of velocity in the region after the DF, which dominantly results in the drifting motion of the whole mushroom structure towards the dawn.

Structures and dynamics in a two-dimensional dipolar dust particle system

NASA Astrophysics Data System (ADS)

Hou, X. N.; Liu, Y. H.; Kravchenko, O. V.; Lapushkina, T. A.; Azarova, O. A.; Chen, Z. Y.; Huang, F.

2018-05-01

The effects of electric dipole moment, the number of dipolar particles, and system temperature on the structures and dynamics of a dipolar dust particle system are studied by molecular dynamics simulations. The results show that the larger electric dipole moment is favorable for the formation of a long-chain structure, the larger number of dipolar dust particles promotes the formation of the multi-chain structure, and the higher system temperature can cause higher rotation frequency. The trajectories, mean square displacement (MSD), and the corresponding spectrum functions of the MSDs are also calculated to illustrate the dynamics of the dipolar dust particle system, which is also closely related to the growth of dust particles. Some simulations are qualitatively in agreement with our experiments and can provide a guide for the study on dust growth, especially on the large-sized particles.

Magnetic Field Dipolarization and Its Associated Ion Flux Variations in the Inner Magnetosphere: Simultaneous Observations by Arase and Michibiki Satellites

NASA Astrophysics Data System (ADS)

Nose, M.; Matsuoka, A.; Kasahara, S.; Yokota, S.; Higashio, N.; Koshiishi, H.; Imajo, S.; Teramoto, M.; Nomura, R.; Fujimoto, A.; Keika, K.; Tanaka, Y.; Shinohara, M.; Shinohara, I.; Yoshizumi, M.

2017-12-01

Recent satellite observations by MDS-1 and Van Allen Probes statistically revealed that magnetic field dipolarization can be detected over a wide range of L in the deep inner magnetosphere (i.e., L = 3.5-6.5, which is far inside the geosynchronous altitude). It is accompanied by magnetic field fluctuations having a characteristic timescale of a few to 10 s, which is comparable to the local gyroperiod of O+ ions. These magnetic field fluctuations are considered to cause nonadiabatic local acceleration of ions. In this study, we intend to confirm the above-mentioned characteristics of magnetic field dipolarization in the inner magnetosphere, using the magnetic field data and the energetic ion flux data measured by the Exploration of energization and Radiation in Geospace (ERG) "Arase" satellite. The Arase satellite was launched on December 20, 2016 into an elliptical orbit having an apogee of 6.0 Re, a perigee of 440 km altitude, an orbital period of 9.5 h, and an orbital inclination of 32 degrees. During the first magnetic storm of March 27, 2017 after Arase started scientific operation, Arase observes clear dipolarization signatures around 1500 UT at L 4.6 and MLT 5.7 hr. Strong magnetic field fluctuations are embedded in the magnetic field dipolarization and their characteristic frequency is close to the local gyrofrequency of O+ ions. Both H+ and O+ flux enhancements are observed in accordance with the dipolarization. These results are consistent with the previous results. In this event, the Quasi-Zenith Satellite (QZS)-1 "Michibiki" satellite was located at L 7.0 and MLT 23.8 hr, and observes similar dipolarization signatures with a few minute time difference. Simultaneous observations by both Arase and Michibiki provides us a unique opportunity to investigate how fast and wide the dipolarization propagates in the inner magnetosphere. In the presentation, we will show detailed analysis results of the dipolarization event on March 27, 2017 as well as similar events.

Extended Bose-Hubbard model with dipolar and contact interactions

NASA Astrophysics Data System (ADS)

Biedroń, Krzysztof; Łącki, Mateusz; Zakrzewski, Jakub

2018-06-01

We study the phase diagram of the one-dimensional boson gas trapped inside an optical lattice with contact and dipolar interaction, taking into account next-nearest terms for both tunneling and interaction. Using the density-matrix renormalization group, we calculate how the locations of phase transitions change with increasing dipolar interaction strength for average density ρ =1 . Furthermore, we show the emergence of pair-correlated phases for a large dipolar interaction strength and ρ ≥2 , including a supersolid phase with an incommensurate density wave ordering manifesting the corresponding spontaneous breaking of the translational symmetry.

Probing the Dipolar Coupling in a Heterospin Endohedral Fullerene-Phthalocyanine Dyad.

PubMed

Zhou, Shen; Yamamoto, Masanori; Briggs, G Andrew D; Imahori, Hiroshi; Porfyrakis, Kyriakos

2016-02-03

Paramagnetic endohedral fullerenes and phthalocyanine (Pc) complexes are promising building blocks for molecular quantum information processing, for which tunable dipolar coupling is required. We have linked these two spin qubit candidates together and characterized the resulting electron paramagnetic resonance properties, including the spin dipolar coupling between the fullerene spin and the copper spin. Having interpreted the distance-dependent coupling strength quantitatively and further discussed the antiferromagnetic aggregation effect of the CuPc moieties, we demonstrate two ways of tuning the dipolar coupling in such dyad systems: changing the spacer group and adjusting the solution concentration.

Dietary fibers from mushroom sclerotia: 1. Preparation and physicochemical and functional properties.

PubMed

Wong, Ka-Hing; Cheung, Peter C K

2005-11-30

Preparation of three novel dietary fibers (DFs) from mushroom sclerotia, namely, Pleurotus tuberregium, Polyporous rhinocerus, and Wolfiporia cocos, by a scale-up modified AOAC procedure using industrial enzymes was investigated. A remarkably high level of total dietary fiber (TDF) ranging from 81.7 to 96.3% sample dry matter (DM), in which a content of nonstarch polysaccharide (NSP) ranging from 86.6 to 94.3% sclerotial TDF DM, was obtained from the three sclerotia. All sclerotial DFs were rich in beta-glucan (the glucose residue ranged from 89.7 to 94.5% NSP DM) with a very low level of resistant glycogen (ranged from 3.77 to 3.94% sclerotial TDF DM). All three novel sclerotial DFs also exhibited similar, if not better, physicochemical and functional properties (pH, color, water binding capacity, oil holding capacity, and emulsifying properties) as those of barely DF control and commercial DF-rich ingredients. The potential use of the three mushroom sclerotial DFs as a new beta-glucan type DF-rich ingredient in the food industry was discussed.

Ordinary and extraordinary dielectric functions of rutile SnO{sub 2} up to 20 eV

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

Feneberg, Martin, E-mail: martin.feneberg@ovgu.de; Lidig, Christian; Lange, Karsten

2014-06-09

Spectroscopic ellipsometry at room temperature is applied in order to determine the ordinary (ε{sub ⊥}) and extraordinary (ε{sub ∥}) dielectric functions (DFs) of rutile SnO{sub 2} corresponding to electric field (E) polarization perpendicular (E⊥c) and parallel (E∥c) to the optical axis (c), respectively. Strong anisotropic behavior is found for the full spectral range from 0.5 up to 20 eV. The onsets of strong absorption are found at 4.28 eV and 5.42 eV for E⊥c and E∥c, respectively. A dipole-forbidden band gap at (3.59 ± 0.2) eV at room temperature is found by line shape fits to the imaginary parts of the DFs. Further high-energy transitionsmore » are resolved. Their accurate energy values are obtained by fitting the second derivatives of the DFs. Comparison to published DFs calculated by ab-initio theory demonstrates that the electron-hole interaction in SnO{sub 2} is strong and has to be included for interpretation.« less

Resveratrol may be beneficial in treatment of diabetic foot syndrome.

PubMed

Bashmakov, Yuriy K; Assaad-Khalil, Samir; Petyaev, Ivan M

2011-09-01

Diabetic foot syndrome (DFS) is a late-stage complication of type 2 diabetes which originates from interplay among impaired tissue regeneration, vasculopathy, neuropathy and inflammation all on the background of insulin resistance. Despite astonishing mortality rate pharmacological approach in management of diabetic ulceration is almost non-existent. Foot pressure relief, wound debridement and infection control remain widely accepted options in the treatment of DFS. We hypothesize that resveratrol treatment and subsequent activation of SIRT1 pathway might be highly beneficial for patients with DFS. This prediction is based on multiple lines of evidence implicating resveratrol and sirtuins in restoration of insulin sensitivity, microcirculation, tissue regeneration, function of peripheral nerves and production of cytokines. Stabilized "nutraceutical" formulations of resveratrol with high absorption rate are essential to examine its potential medical benefits since dietary polyphenols are known to be rapidly metabolized by gut microflora and oxidized during absorption. Clinical trials with nutraceutical formulations and placebo are required to understand if resveratrol indeed holds the promise for treatment of DFS. Copyright © 2011 Elsevier Ltd. All rights reserved.

Clinical impact of sentinel lymph node biopsy in patients with thick (>4 mm) melanomas.

PubMed

White, Ian; Fortino, Jeanine; Curti, Brendan; Vetto, John

2014-05-01

The role of sentinel lymph node status (SLNS) in thick melanoma is evolving. The purpose of this study was to determine the prognostic value of SLNS in thick melanoma. A retrospective analysis of 120 prospectively collected clinically node-negative thick melanomas over 5 years was performed. Patient (age/sex) and tumor (thickness, ulceration, SLNS, mitoses, metastases, and recurrence) features were collected. Multivariate analysis was performed using Cox proportional hazard model. Factors predictive of positive SLN included male sex, ulceration, and high mitoses. Factors associated with positive SLN had higher local-regional recurrence and metastases than negative SLN. SLNS and tumor thickness impacted 5-year disease-free survival (DFS) and overall survival (OS). Positive SLN, ulceration, age, and mitoses were independent predictors of DFS/OS. Nonulcerated/lower mitoses thick melanomas had lower positive SLN rates. Positive SLN develop recurrence and metastases and have worse OS/DFS. SLNS is an important prognosticator for OS/DFS. Sentinel lymph node biopsy delineates prognostic groups in thick melanomas and can impact management. Copyright © 2014 Elsevier Inc. All rights reserved.

Layer-oriented total pelvic exenteration for locally advanced primary colorectal cancer.

PubMed

Koda, Keiji; Shuto, Kiyohiko; Matsuo, Kenichi; Kosugi, Chihiro; Mori, Mikito; Hirano, Atsushi; Hiroshima, Yukihiko; Tanaka, Kuniya

2016-01-01

The clinical outcomes of patients who have undergone total pelvic exenteration (TPE) for locally advanced primary colorectal cancer have not been satisfactory. For the last 13 years, we have performed layer-oriented, en bloc resection of tumor for which TPE is indicated, in the hope of improving postoperative outcomes. The clinical outcomes of these cases were retrospectively analyzed. A total of 54 patients who underwent TPE from 1986 to 2013 were retrospectively analyzed. Since 2002, a layer-oriented removal for clinical T4 colorectal cancer, as in T3 or less invasive tumors removed by total mesorectal excision, was applied to 23 cases for which TPE was indicated. Postoperative mortality, morbidity, overall survival (OS), and disease-free survival (DFS) were evaluated. On univariate analysis, good postoperative OS and DFS were associated with the layer-oriented operative maneuver, blood loss less than 2000 mL, negative nodal metastasis, and no preoperative radiation therapy. Male sex was the marginal determinant correlated with good OS and DFS. Depth of invasion to T3 was the marginal determinant correlated with good DFS. On multivariate analysis using the 4 factors identified on univariate analyses, the layer-oriented operative procedure was a significant determinant for both good OS and DFS, together with negative nodal metastases. Postoperative mortality and morbidity in the layer-oriented excision were acceptable. For primary colorectal cancers for which TPE is indicated, layer-oriented excision was a safe and effective procedure, and it may be recommended as one of the standard surgical approaches in TPE.

Evaluation of the impact of observations on blended sea surface winds in a two-dimensional variational scheme using degrees of freedom

NASA Astrophysics Data System (ADS)

Wang, Ting; Xiang, Jie; Fei, Jianfang; Wang, Yi; Liu, Chunxia; Li, Yuanxiang

2017-12-01

This paper presents an evaluation of the observational impacts on blended sea surface winds from a two-dimensional variational data assimilation (2D-Var) scheme. We begin by briefly introducing the analysis sensitivity with respect to observations in variational data assimilation systems and its relationship with the degrees of freedom for signal (DFS), and then the DFS concept is applied to the 2D-Var sea surface wind blending scheme. Two methods, a priori and a posteriori, are used to estimate the DFS of the zonal ( u) and meridional ( v) components of winds in the 2D-Var blending scheme. The a posteriori method can obtain almost the same results as the a priori method. Because only by-products of the blending scheme are used for the a posteriori method, the computation time is reduced significantly. The magnitude of the DFS is critically related to the observational and background error statistics. Changing the observational and background error variances can affect the DFS value. Because the observation error variances are assumed to be uniform, the observational influence at each observational location is related to the background error variance, and the observations located at the place where there are larger background error variances have larger influences. The average observational influence of u and v with respect to the analysis is about 40%, implying that the background influence with respect to the analysis is about 60%.

A decision tree-based combination of ezrin-interacting proteins to estimate the prognostic risk of patients with esophageal squamous cell carcinoma.

PubMed

He, Jian-Zhong; Wu, Zhi-Yong; Wang, Shao-Hong; Ji, Xia; Yang, Cui-Xia; Xu, Xiu-E; Liao, Lian-Di; Wu, Jian-Yi; Li, En-Min; Zhang, Kai; Xu, Li-Yan

2017-08-01

Our previous studies have highlighted the importance of ezrin in esophageal squamous cell carcinoma (ESCC). Here our objective was to explore the clinical significance of ezrin-interacting proteins, which would provide a theoretical basis for understanding the function of ezrin and potential therapeutic targets for ESCC. We used affinity purification and mass spectrometry to identify PDIA3, CNPY2, and STMN1 as potential ezrin-interacting proteins. Confocal microscopy and coimmunoprecipitation analysis further confirmed the colocalization and interaction of ezrin with PDIA3, CNPY2, and STMN1. Tissue microarray data of ESCC samples (n=263) showed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower for the CNPY2 (OS, P=.003; DFS, P=.011) and STMN1 (OS, P=.010; DFS, P=.002) high-expression groups compared with the low-expression groups. By contrast, overexpression of PDIA3 was significantly correlated with favorable survival (OS, P<.001; DFS, P=.001). Cox regression demonstrated the prognostic value of PDIA3, CNPY2, and STMN1 in ESCC. Furthermore, decision tree analysis revealed that the resulting classifier of both ezrin and its interacting proteins could be used to better predict OS and DFS of patients with ESCC. In conclusion, a signature of ezrin-interacting proteins accurately predicts ESCC patient survival or tumor recurrence. Copyright © 2017 Elsevier Inc. All rights reserved.

Prognostic and Predictive Value of CpG Island Methylator Phenotype in Patients with Locally Advanced Nonmetastatic Sporadic Colorectal Cancer

PubMed Central

Long, Yadong; Xu, Ye; Guan, Zuqing; Lian, Peng; Peng, Junjie

2014-01-01

Purpose. In the present study, the prognostic significance of CpG island methylator phenotype (CIMP) in stage II/III sporadic colorectal cancer was evaluated using a five-gene panel. Methods. Fifty stage II/III colorectal cancer patients who received radical resection were included in this study. Promoter methylation of p14ARF, hMLH1, p16INK4a, MGMT, and MINT1 was determined by methylation specific polymerase chain reaction (MSP). CIMP positive was defined as hypermethylation of three or more of the five genes. Impact factors on disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier method (log-rank test) and adjusted Cox proportional hazards model. Results. Twenty-four percent (12/50) of patients were characterized as CIMP positive. Univariate analysis showed stage III (P = 0.049) and CIMP positive (P = 0.014) patients who had significantly inferior DFS. In Cox regression analysis, CIMP positive epigenotype was independently related with poor DFS with HR = 2.935 and 95% CI: 1.193–7.220 (P = 0.019). In patients with CIMP positive tumor, those receiving adjuvant chemotherapy had a poor DFS than those without adjuvant chemotherapy (P = 0.023). Conclusions. CIMP positive was significantly correlated with decreased DFS in stage II/III colorectal cancer. Patients with CIMP positive locally advanced sporadic colorectal cancers may not benefit from 5-fluorouracil based adjuvant chemotherapy. PMID:24822060

Stepwise π-extension of meso-alkylidenyl porphyrins through sequential 1,3-dipolar cycloaddition and redox reactions.

PubMed

Park, Dowoo; Jeong, Seung Doo; Ishida, Masatoshi; Lee, Chang-Hee

2014-08-25

Several regioselectively π-extended, pyrrole fused porphyrinoids have been synthesized by the 1,3-dipolar cycloaddition of meso-alkylidene-(benzi)porphyrins. Pd(II) complexes gave oxidation resistant, bis-pyrrole fused adducts. The repeated 1,3-dipolar cycloaddition followed by oxidation-reduction of pentaphyrin analogs afforded π-extended porphyrin analogs.

Open versus closed reduction: diacapitular fractures of the mandibular condyle.

PubMed

Chrcanovic, Bruno Ramos

2012-09-01

The purpose of the study was to review the literature regarding the evolution of current thoughts on management of diacapitular fractures (DFs) of the mandibular condyle. An electronic search in PubMed was undertaken in March 2012. The titles and abstracts from these results were read to identify studies within the selection criteria. Eligibility criteria included studies reporting clinical series of DFs, including both animal and human studies, without date or language restrictions. The search strategy initially yielded 108 references. Twenty-eight studies were identified without repetition within the selection criteria. Additional hand-searching of the reference lists of selected studies yielded three additional papers. The current indications for open reduction and internal fixation (ORIF) of DFs described in the literature are: (a) fractures affecting the lateral condyle with reduction of mandibular height; (b) fractures in which the proximal fragment dislocates laterally out of the glenoid fossa, which cannot be reduced by closed or open treatment of another part of the mandibular fracture. The indications for conservative treatment are: (a) fractures that do not shorten the condylar height (a fracture with displacement of the medial parts of the condyle); (b) undisplaced fractures; (c) comminution of the condylar head, when the bony fragments are too small for stable fixation; and (d) fractures in children. As the temporomandibular joint disk plays an important role as a barrier preventing ankylosis, it is important to reposition the disk (if displaced/dislocated) during the surgical treatment of DFs. The lateral pterygoid muscle should never be stripped from the medially displaced fragment because its desinsertion disrupts circulation to the medial bony fragment, and also because this muscle helps to restore the muscle function after surgery. ORIF of selected DFs improves prognosis by anatomical bone and soft tissue recovery when combined with physical therapy. If conducted properly, surgical treatment of DFs is a safe and predictable procedure and yields good results.

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

Gunderson, Leonard L., E-mail: gunderson.leonard@mayo.edu; Moughan, Jennifer; Ajani, Jaffer A.

Purpose: The long-term update of US GI Intergroup RTOG 98-11 anal cancer trial found that concurrent chemoradiation (CCRT) with fluorouracil (5-FU) plus mitomycin had a significant impact on disease-free survival (DFS) and overall survival (OS) compared with induction plus concurrent 5-FU plus cisplatin. The intent of the current analysis was to determine the impact of tumor node (TN) category of disease on survival (DFS and OS), colostomy failure (CF), and relapse (local-regional failure [LRF] and distant metastases [DM]) in this patient group. Methods and Materials: DFS and OS were estimated univariately by using the Kaplan-Meier method, and 6 TN categoriesmore » were compared by the log–rank test (T2N0, T3N0, T4N0, T2N1-3, T3N1-3, and T4N1-3). Time to relapse and colostomy were estimated by the cumulative incidence method, and TN categories were compared using Gray's test. Results: Of 682 patients, 620 were analyzable for outcomes by TN category. All endpoints showed statistically significant differences among the TN categories of disease (OS, P<.0001; DFS, P<.0001; LRF, P<.0001; DM, P=.0011; CF, P=.01). Patients with the poorest OS, DFS, and LRF outcomes were those with T3-4N-positive (+) disease. CF was lowest for T2N0 and T2N+ (11%, 11%, respectively) and worst for the T4N0, T3N+, and T4N+ categories (26%, 27%, 24%, respectively). Conclusions: TN category of disease has a statistically significant impact on OS, DFS, LRF, DM, and CF in patients treated with CCRT and provides excellent prognostic information for outcomes in patients with anal carcinoma. Significant challenges remain for patients with T4N0 and T3-4N+ categories of disease with regard to survival, relapse, and CF and lesser challenges for T2-3N0/T2N+ categories.« less

The association of polymorphisms in folate-metabolizing genes with response to adjuvant chemotherapy of colorectal cancer.

PubMed

Yousef, Al-Motassem; Zawiah, Mohammed; Al-Yacoub, Shorouq; Kadi, Taha; Tantawi, Dua' A; Al-Ramadhani, Hanguin

2018-05-29

Colorectal cancer (CRC) is one of the major health issues worldwide. 5-Fluorouracil (5-FU) is a cornerstone of chemotherapy for CRC and the major targets of 5-FU are folate-metabolizing enzymes. A total of 103 CRC patients with complete clinical data were included in this prospective cohort study. Genotyping was performed using polymerase chain reaction (PCR) followed by sequencing. Using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models, we evaluated associations between functional polymorphisms in four genes MTHFR (1298A>C and 677C>T), DPYD (496A>G and 85T>C), DHFR 19 bp del, and MTR (2756 A>G) with disease-free survival (DFS). The minor allele frequencies of MTHFR 1298A>C, MTHFR 677C>T, DPYD 496A>G, DPYD 85T>C, DHFR 19 bp del, and MTR 2756 A>G were 0.364, 0.214, 0.116, 0.209, 0.383, and 0.097, respectively. CRC patients carrying the homozygous GG genotype in DPYD 496A>G had 4.36 times shorter DFS than wild-type AA carriers, (DFS GG vs AA : 8.0 ± 4 vs 69.0 ± 10 months; HR 4.36, 95% CI 1.04-18; p = 0.04). Moreover, female carriers of homozygous CC genotype of DPYD 85T>C had shorter DFS compared to either heterozygous or wild-type genotypes, and were 12.7 times shorter than wild-type TT carriers (DFS CC vs TT : 5.0 ± 1.5 vs 42.0 ± 7.6 months; HR 12.7, 95% CI 2.2-71.4; p = 0.004). However, there were no significant associations with the other studied polymorphisms. Genetic polymorphism in DPYD seems to be associated with DFS in CRC patients receiving an adjuvant regimen of 5-FU/capecitabine-based chemotherapy. Further studies are needed to verify these findings.

The outcome of allogeneic hematopoietic cell transplantation for children with FMS-like tyrosine kinase 3 internal tandem duplication-positive acute myelogenous leukemia.

PubMed

Schechter, Tal; Gassas, Adam; Chen, Heidi; Pollard, Jessica; Meshinchi, Soheil; Zaidman, Irina; Hitzler, Johann; Abdelhaleem, Mohamed; Ho, Richard; Domm, Jennifer; Woolfrey, Ann; Frangoul, Haydar

2015-01-01

FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) is a somatic mutation associated with poor outcome when treated with chemotherapy alone. In children, hematopoietic stem cell transplantation (HSCT) is recommended, but very limited data on outcome are reported. We determined the outcome of 29 children with FLT3/ITD-positive acute myelogenous leukemia (AML) who underwent allogeneic HSCT in 4 pediatric centers. Eleven patients (38%) received matched related donor hematopoietic stem cells and 18 (62%) received alternative donors. Eighteen patients (62%) received total body irradiation (TBI)-based regimens. No patients experienced transplantation-related mortality. Eleven patients (38%) experienced relapsed disease. The cumulative incidence of relapse at 2 years was 34.7% (95% confidence interval [CI], 20.4% to 54.9%). Two-year disease-free survival (DFS) and overall survival (OS) were 65.3% (95% CI, 45.1% to 79.6%) and 82.2% (95% CI, 58.5% to 91.3%), respectively. There was no difference in the DFS of patients who received transplants from related donors versus the DFS of those who received transplants from alternative donors (hazard ratio [HR], 2.64; 95% CI, .79 to 8.76; P = .10), using univariate analysis. Patients with higher FLT3/ITD ratio at diagnosis had significantly worse DFS (HR, 1.42; 95% CI, 1.04 to 1.93; P = .03). The use of TBI in the preparative regimen was associated with superior DFS (HR, .29; 95% CI, .08 to .99; P = .04) and OS (HR, .07; 95% CI, .01 to .62; P = .002). We conclude that allogeneic HSCT improves DFS and OS in children with FLT3/ITD-positive AML compared with what has been reported in those treated with chemotherapy alone. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis.

PubMed

Mocellin, Simone; Pasquali, Sandro; Rossi, Carlo R; Nitti, Donato

2010-04-07

Based on previous meta-analyses of randomized controlled trials (RCTs), the use of interferon alpha (IFN-alpha) in the adjuvant setting improves disease-free survival (DFS) in patients with high-risk cutaneous melanoma. However, RCTs have yielded conflicting data on the effect of IFN-alpha on overall survival (OS). We conducted a systematic review and meta-analysis to examine the effect of IFN-alpha on DFS and OS in patients with high-risk cutaneous melanoma. The systematic review was performed by searching MEDLINE, EMBASE, Cancerlit, Cochrane, ISI Web of Science, and ASCO databases. The meta-analysis was performed using time-to-event data from which hazard ratios (HRs) and 95% confidence intervals (CIs) of DFS and OS were estimated. Subgroup and meta-regression analyses to investigate the effect of dose and treatment duration were also performed. Statistical tests were two-sided. The meta-analysis included 14 RCTs, published between 1990 and 2008, and involved 8122 patients, of which 4362 patients were allocated to the IFN-alpha arm. IFN-alpha alone was compared with observation in 12 of the 14 trials, and 17 comparisons (IFN-alpha vs comparator) were generated in total. IFN-alpha treatment was associated with a statistically significant improvement in DFS in 10 of the 17 comparisons (HR for disease recurrence = 0.82, 95% CI = 0.77 to 0.87; P < .001) and improved OS in four of the 14 comparisons (HR for death = 0.89, 95% CI = 0.83 to 0.96; P = .002). No between-study heterogeneity in either DFS or OS was observed. No optimal IFN-alpha dose and/or treatment duration or a subset of patients more responsive to adjuvant therapy was identified using subgroup analysis and meta-regression. In patients with high-risk cutaneous melanoma, IFN-alpha adjuvant treatment showed statistically significant improvement in both DFS and OS.

Impact of margin status and lymphadenectomy on clinical outcomes in resected pancreatic adenocarcinoma: implications for adjuvant radiotherapy.

PubMed

Osipov, Arsen; Naziri, Jason; Hendifar, Andrew; Dhall, Deepti; Rutgers, Joanne K; Chopra, Shefali; Li, Quanlin; Tighiouart, Mourad; Annamalai, Alagappan; Nissen, Nicholas N; Tuli, Richard

2016-04-01

Adjuvant chemoradiotherapy (CRT) in the treatment of pancreatic ductal adenocarcinoma (PDA) is controversial. Minimal data exists regarding the clinical significance of margin clearance distance and lymph node (LN) parameters, such as extent of dissection and LN ratio. We assessed the impact of these variables on clinical outcomes to more clearly define the subset of patients who may benefit from adjuvant radiotherapy (RT). We identified 106 patients with resected stage 1-3 PDA from 2007-2013. Resection margins were categorized as positive (tumor at ink), ≤1, or >1 mm. LN evaluation included total number examined (NE), number of positive nodes (NP), ratio of NP to NE (NR), extent of dissection, and positive periportal LNs. The impact of these variables was assessed on disease-free survival (DFS) and overall survival (OS) using multivariate cox proportional hazards modeling. In patients receiving adjuvant chemotherapy (CT) alone, greater margin clearance led to improved DFS (P=0.0412, HR =0.51). Range of NE was 4-37, with a mean of 19. NE was not associated with DFS or OS, yet absolute NP of 5 or more was associated with a significantly worse DFS (P=0.005). Whereas periportal lymphadenectomy did not result in improved DFS or OS, patients with positive periportal LN had worse clinical outcomes (DFS, P=0.0052; OS, P=0.023). The use of adjuvant CRT was associated with improved OS (P=0.049; HR=0.29). In patients receiving adjuvant CT alone, there was a clinically significant benefit to clearing the surgical margin beyond tumor at ink. Having ≥5 NP and positive periportal LN led to significantly worse clinical outcomes. The addition of adjuvant RT to CT in resected PDA improved OS. A comprehensive evaluation of resection margin distance and LN parameters may identify more patients at risk for locoregional failure who may benefit from adjuvant CRT.

Impact of margin status and lymphadenectomy on clinical outcomes in resected pancreatic adenocarcinoma: implications for adjuvant radiotherapy

PubMed Central

Osipov, Arsen; Naziri, Jason; Hendifar, Andrew; Dhall, Deepti; Rutgers, Joanne K.; Chopra, Shefali; Li, Quanlin; Tighiouart, Mourad; Annamalai, Alagappan; Nissen, Nicholas N.

2016-01-01

Background Adjuvant chemoradiotherapy (CRT) in the treatment of pancreatic ductal adenocarcinoma (PDA) is controversial. Minimal data exists regarding the clinical significance of margin clearance distance and lymph node (LN) parameters, such as extent of dissection and LN ratio. We assessed the impact of these variables on clinical outcomes to more clearly define the subset of patients who may benefit from adjuvant radiotherapy (RT). Methods We identified 106 patients with resected stage 1-3 PDA from 2007-2013. Resection margins were categorized as positive (tumor at ink), ≤1, or >1 mm. LN evaluation included total number examined (NE), number of positive nodes (NP), ratio of NP to NE (NR), extent of dissection, and positive periportal LNs. The impact of these variables was assessed on disease-free survival (DFS) and overall survival (OS) using multivariate cox proportional hazards modeling. Results In patients receiving adjuvant chemotherapy (CT) alone, greater margin clearance led to improved DFS (P=0.0412, HR =0.51). Range of NE was 4-37, with a mean of 19. NE was not associated with DFS or OS, yet absolute NP of 5 or more was associated with a significantly worse DFS (P=0.005). Whereas periportal lymphadenectomy did not result in improved DFS or OS, patients with positive periportal LN had worse clinical outcomes (DFS, P=0.0052; OS, P=0.023). The use of adjuvant CRT was associated with improved OS (P=0.049; HR=0.29). Conclusions In patients receiving adjuvant CT alone, there was a clinically significant benefit to clearing the surgical margin beyond tumor at ink. Having ≥5 NP and positive periportal LN led to significantly worse clinical outcomes. The addition of adjuvant RT to CT in resected PDA improved OS. A comprehensive evaluation of resection margin distance and LN parameters may identify more patients at risk for locoregional failure who may benefit from adjuvant CRT. PMID:27034792

Divergent effects of insulin-like growth factor-1 receptor expression on prognosis of estrogen receptor positive versus triple negative invasive ductal breast carcinoma.

PubMed

Hartog, Hermien; Horlings, Hugo M; van der Vegt, Bert; Kreike, Bas; Ajouaou, Abderrahim; van de Vijver, Marc J; Marike Boezen, H; de Bock, Geertruida H; van der Graaf, Winette T A; Wesseling, Jelle

2011-10-01

The insulin-like growth factor type 1 receptor (IGF1R) is involved in progression of breast cancer and resistance to systemic treatment. Targeting IGF1R signaling may, therefore, be beneficial in systemic treatment. We report the effect of IGF1R expression on prognosis in invasive ductal breast carcinoma (IDC), the most common type of breast cancer. Immunohistochemistry was performed on tumor tissue of a consecutive cohort of 429 female patients treated for operable primary IDC. Associations between IGF1R expression with clinicopathological parameters, disease free survival (DFS) and breast cancer specific survival (BCSS) were evaluated by multivariate analyses focusing on ER-positive and triple negative IDC (TN-IDC). To enlarge the TN-IDCs cohort, we analyzed a combined dataset of 51 TN-IDC tumors from our series with 64 TN-IDCs with similar clinicopathological parameters. Patients with tumors expressing cytoplasmic IGF1R have a longer DFS and BCSS (DFS: HR 0.46, 95% CI 0.27-0.49, P = 0.005, BCSS: HR 0.38, 95% CI 0.19-0.74, P = 0.005). This effect was most prominent in ER-positive tumors. However, in a combined series of 105 TN-IDCs cytoplasmic IGF1R expression was associated with a shorter DFS (HR = 2.29, 95% CI 1.08-4.84, P = 0.03), also when combined in a multivariate model, including well-known prognostic factors (HR 2.06; 95% CI 0.95-4.47; P = 0.07). IGF1R expression in ER-positive IDC is strongly related to a favorable DFS and BCSS, but to a shorter DFS in TN-IDC tumors. This divergent effect of IGF1R expression in subgroups of IDC may affect selection of patients for IGF1R targeted therapy.

Percutaneous Lung Thermal Ablation of Non-surgical Clinical N0 Non-small Cell Lung Cancer: Results of Eight Years’ Experience in 87 Patients from Two Centers

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

Palussiere, Jean, E-mail: J.Palussiere@bordeaux.unicancer.fr; Lagarde, Philippe, E-mail: P.Lagarde@bordeaux.unicancer.fr; Aupérin, Anne, E-mail: auperin@igr.fr

2015-02-15

PurposeTo evaluate the survival outcomes of percutaneous thermal ablation (RFA + microwaves) for patients presenting N0 non-small-cell lung cancer (NSCLC) ineligible for surgery.Materials and MethodsEighty-seven patients from two comprehensive cancer centers were included. Eighty-two patients were treated with RFA electrodes and five with microwave antenna. Overall survival (OS) and disease-free survival (DFS) were estimated and predictive factors of local tumor progression, OS and DFS identified and compared by univariate and multivariate analysesResultsMedian follow-up was 30.5 months (interquartile range 16.7–51) and tumor size was 21 mm (range 10–54 mm). Treatment was incomplete for 14 patients with a local tumor progression of 11.5, 18.3, and 21.1 % atmore » 1, 2, and 3 years, respectively. Two patients presented with neurological (grade III or IV) complications, and one died of respiratory and multivisceral failure as a result of the procedure at 29 days. In univariate analysis, increasing tumor size (P = 0.003) was the only predictive factor related to risk of local tumor progression. 5-year OS and DFS were 58.1 and 27.9 %, respectively. Sex (P = 0.044), pathology (P = 0.032), and tumor size >2 cm (P = 0.046) were prognostic factors for DFS. In multivariate analysis, pathology (P = 0.033) and tumor size >2 cm (P = 0.032) were independent prognostic factors for DFS.ConclusionsOversized and overlapping ablation of N0 NSCLC was well tolerated, effective, with few local tumor progressions, even over long-term follow-up. Increasing tumor size was the main prognostic factor linked to OS, DFS, and local tumor progression.« less

Conditional Disease-Free Survival After Surgical Resection of Gastrointestinal Stromal Tumors

PubMed Central

Bischof, Danielle A.; Kim, Yuhree; Dodson, Rebecca; Jimenez, M. Carolina; Behman, Ramy; Cocieru, Andrei; Fisher, Sarah B.; Groeschl, Ryan T.; Squires, Malcolm H.; Maithel, Shishir K.; Blazer, Dan G.; Kooby, David A.; Gamblin, T. Clark; Bauer, Todd W.; Quereshy, Fayez A.; Karanicolas, Paul J.; Law, Calvin H. L.; Pawlik, Timothy M.

2015-01-01

IMPORTANCE Gastrointestinal stromal tumors (GISTs) are the most commonly diagnosed mesenchymal tumors of the gastrointestinal tract. The risk of recurrence following surgical resection of GISTs is typically reported from the date of surgery. However, disease-free survival (DFS) over time is dynamic and changes based on disease-free time already accumulated following surgery. OBJECTIVES To assess the comparative performance of established GIST recurrence risk prognostic scoring systems and to characterize conditional DFS following surgical resection of GISTs. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study of 502 patients who underwent surgery for a primary, nonmetastatic GIST between January 1, 1998, and December 31, 2012, at 7 major academic cancer centers in the United States and Canada. MAIN OUTCOMES AND MEASURES Disease-free survival of the patients was classified according to 5 prognostic scoring systems, including the National Institutes of Health criteria, modified National Institutes of Health criteria, Memorial Sloan Kettering Cancer Center GIST nomogram, and American Joint Committee on Cancer gastric and nongastric categories. The concordance index (also known as the C statistic or the area under the receiver operating curve) of established GIST recurrence risk prognostic scoring systems. Conditional DFS estimates were calculated. RESULTS Overall 1-year, 3-year, and 5-year DFS following resection of GISTs was 95%, 83%, and 74%, respectively. All the prognostic scoring systems had fair prognostic ability. For all tumor sites, the American Joint Committee on Cancer gastric category demonstrated the best discrimination (C = 0.79). Using conditional DFS, the probability of remaining disease free for an additional 3 years given that a patient was disease free at 1 year, 3 years, and 5 years was 82%, 89%, and 92%, respectively. Patients with the highest initial recurrence risk demonstrated the greatest increase in conditional survival as time elapsed. CONCLUSIONS AND RELEVANCE Conditional DFS improves over time following resection of GISTs. This is valuable information about long-term prognosis to communicate to patients who are disease free after a period following surgery. PMID:25671681

Chronicle: results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control.

PubMed

Glynne-Jones, R; Counsell, N; Quirke, P; Mortensen, N; Maraveyas, A; Meadows, H M; Ledermann, J; Sebag-Montefiore, D

2014-07-01

In stage III colon cancer, oxaliplatin/5-fluorouracil (5-FU)-based adjuvant chemotherapy (FOLFOX) improves disease-free survival (DFS) and overall survival (OS). In rectal adenocarcinoma following neoadjuvant chemoradiation (CRT), we examined the benefit of postoperative adjuvant capecitabine and oxaliplatin (XELOX) chemotherapy. Eligible patients were randomly assigned following fluoropyrimidine-based CRT and curative resection to observation or six cycles of XELOX. The primary end point was DFS; secondary end points were acute toxicity and OS. 390 patients were required in each arm, to detect an improvement in 3-year DFS from 40% to 50.5%, with 85% power and two-sided 5% significance level. The study closed prematurely in 2008 because of poor accrual. Only 113 patients were randomly assigned to either observation (n = 59) or XELOX (n = 54). Compliance was poor, 93% allocated chemotherapy started and 48% completed six cycles. Protocolised dose reductions in XELOX were 39%, and levels of G3/G4 toxicity 40%. After a median follow-up of 44.8 months, 16 patients (27%) in the observation arm had relapsed or died compared with 12 patients (22%) in XELOX. The 3-year DFS rate was 78% with XELOX and 71% with observation [hazard ratio (HR) for DFS = 0.80; 95% confidence interval (CI) 0.38-1.69; P = 0.56]. The 3-year OS for XELOX and observation were 89% and 88%, respectively (HR for OS = 1.18; 95% CI 0.43-3.26; P = 0.75). The observed improvement in DFS for adjuvant XELOX and similar OS were not statistically significant, as expected given the small number of patients and consequent low power. Our findings support the need for trials that test the role of neoadjuvant chemotherapy. NCT00427713. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

c-Met Expression Is a Marker of Poor Prognosis in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Treated With Chemoradiation

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

Baschnagel, Andrew M.; Williams, Lindsay; Hanna, Alaa

2014-03-01

Purpose: To examine the prognostic significance of c-Met expression in relation to p16 and epidermal growth factor receptor (EGFR) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with definitive concurrent chemoradiation. Methods and Materials: Archival tissue from 107 HNSCC patients treated with chemoradiation was retrieved, and a tissue microarray was assembled. Immunohistochemical staining of c-Met, p16, and EGFR was performed. c-Met expression was correlated with p16, EGFR, clinical characteristics, and clinical endpoints including locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS). Results: Fifty-one percent of patients were positive for p16,more » and 53% were positive for EGFR. Both p16-negative (P≤.001) and EGFR-positive (P=.019) status predicted for worse DFS. Ninety-three percent of patients stained positive for c-Met. Patients were divided into low (0, 1, or 2+ intensity) or high (3+ intensity) c-Met expression. On univariate analysis, high c-Met expression predicted for worse LRC (hazard ratio [HR] 2.27; 95% CI, 1.08-4.77; P=.031), DM (HR 4.41; 95% CI, 1.56-12.45; P=.005), DFS (HR 3.00; 95% CI, 1.68-5.38; P<.001), and OS (HR 4.35; 95% CI, 2.13-8.88; P<.001). On multivariate analysis, after adjustment for site, T stage, smoking history, and EGFR status, only high c-Met expression (P=.011) and negative p16 status (P=.003) predicted for worse DFS. High c-Met expression was predictive of worse DFS in both EGFR-positive (P=.032) and -negative (P=.008) patients. In the p16-negative patients, those with high c-Met expression had worse DFS (P=.036) than did those with low c-Met expression. c-Met expression was not associated with any outcome in the p16-positive patients. Conclusions: c-Met is expressed in the majority of locally advanced HNSCC cases, and high c-Met expression predicts for worse clinical outcomes. High c-Met expression predicted for worse DFS in p16-negative patients but not in p16-positive patients. c-Met predicted for worse outcome regardless of EGFR status.« less

Post-hepatectomy survival in advanced hepatocellular carcinoma with portal vein tumor thrombosis.

PubMed

Yamamoto, Yusuke; Ikoma, Hisashi; Morimura, Ryo; Shoda, Katsutoshi; Konishi, Hirotaka; Murayama, Yasutoshi; Komatsu, Shuhei; Shiozaki, Atsushi; Kuriu, Yoshiaki; Kubota, Takeshi; Nakanishi, Masayoshi; Ichikawa, Daisuke; Fujiwara, Hitoshi; Okamoto, Kazuma; Sakakura, Chouhei; Ochiai, Toshiya; Otsuji, Eigo

2015-01-07

To analyze hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) using the tumor-node-metastasis (TNM) staging system. We retrospectively analyzed 372 patients with HCC who underwent hepatectomy between 1980 and 2009. We studied the outcomes of HCC patients with PVTT to evaluate the American Joint Committee on Cancer TNM staging system (7(th) edition) for stratifying and predicting the prognosis of a large cohort of HCC patients after hepatectomy in a single-center. Portal vein invasion (vp) 1 was defined as an invasion or tumor thrombus distal to the second branch of the portal vein, vp2 as an invasion or tumor thrombus in the second branch of the portal vein, vp3 as an invasion or tumor thrombus in the first branch of the portal vein, and vp4 as an invasion or tumor thrombus in the portal trunk or extending to a branch on the contralateral side. The cumulative 5-year overall survival (5yrOS) and 5-year disease-free survival (5yrDFS) rates of the 372 patients were 58.3% and 31.3%, respectively. The 5yrDFS and 5yrOS of vp3-4 patients (n = 10) were 20.0%, and 30.0%, respectively, which was comparable with the corresponding survival rates of vp1-2 patients (P = 0.466 and 0.586, respectively). In the subgroup analysis of patients with macroscopic PVTT (vp2-4), the OS of the patients who underwent preoperative transarterial chemoembolization was comparable to that of patients who did not (P = 0.747). There was a significant difference in the DFS between patients with stage I HCC and those with stage II HCC (5yrDFS 39.2% vs 23.1%, P < 0.001); however, the DFS for stage II was similar to that for stage III (5yrDFS 23.1% vs 13.8%, P = 0.330). In the subgroup analysis of stage II-III HCC (n = 148), only alpha-fetoprotein (AFP) > 100 mg/dL was independently associated with DFS. Hepatectomy for vp3-4 HCC results in a survival rate similar to hepatectomy for vp1-2. AFP stratified the stage II-III HCC patients according to prognosis.

NMR polarization echoes in a nematic liquid crystal

NASA Astrophysics Data System (ADS)

Levstein, Patricia R.; Chattah, Ana K.; Pastawski, Horacio M.; Raya, Jésus; Hirschinger, Jérôme

2004-10-01

We have modified the polarization echo (PE) sequence through the incorporation of Lee-Goldburg cross polarization steps to quench the 1H-1H dipolar dynamics. In this way, the 13C becomes an ideal local probe to inject and detect polarization in the proton system. This improvement made possible the observation of the local polarization P00(t) and polarization echoes in the interphenyl proton of the liquid crystal N-(4-methoxybenzylidene)-4-butylaniline. The decay of P00(t) was well fitted to an exponential law with a characteristic time τC≈310 μs. The hierarchy of the intramolecular dipolar couplings determines a dynamical bottleneck that justifies the use of the Fermi Golden Rule to obtain a spectral density consistent with the structural parameters. The time evolution of P00(t) was reversed by the PE sequence generating echoes at the time expected by the scaling of the dipolar Hamiltonian. This indicates that the reversible 1H-1H dipolar interaction is the main contribution to the local polarization decrease and that the exponential decay for P00(t) does not imply irreversibility. The attenuation of the echoes follows a Gaussian law with a characteristic time τφ≈527 μs. The shape and magnitude of the characteristic time of the PE decay suggest that it is dominated by the unperturbed homonuclear dipolar Hamiltonian. This means that τφ is an intrinsic property of the dipolar coupled network and not of other degrees of freedom. In this case, one cannot unambiguously identify the mechanism that produces the decoherence of the dipolar order. This is because even weak interactions are able to break the fragile multiple coherences originated on the dipolar evolution, hindering its reversal. Other schemes to investigate these underlying mechanisms are proposed.

Involvement of apoptosis in the atresia of nonovulatory dominant follicle during the bovine estrous cycle.

PubMed

Yang, M Y; Rajamahendran, R

2000-11-01

The present study was designed to 1) investigate whether apoptosis is responsible for the atresia of nonovulatory dominant follicle (DF), 2) to determine if atresia of a nonovulatory DF is associated with alterations in Bcl-2 and Bax expression, 3) to test whether progesterone P(4) has a direct effect on apoptosis in bovine follicles, and 4) to study the pattern of expression of Bcl-2 and Bax in follicles at different developmental stages (small, medium, and large). In experiment 1, 16 cycling cows received a norgestomet ear implant at proestrus (Day 1) for 9 days to mimic the subluteal phase. The cows were assigned either to a control (n = 4) or P(4)-treated groups (n = 12). Injections of P(4) (150 mg, i.m.) were given on Day 3 (n = 4); on Days 3 and 4 (n = 4), and on Days 3, 4, and 5 (n = 4) of the implant period. Controls received injections of corn oil on Days 3, 4, and 5. Unilateral ovariectomy was performed on Days 4, 5, and 6 to recover DFs from cows that had been treated with P(4) for 24, 48, and 72 h, respectively. DFs in the control group were collected on Day 6. The onset of atresia of DFs was assessed morphologically by ultrasound to determine DF diameters, histologically by light microscopic inspection of tissue sections, and functionally by quantification of follicular fluid steroid hormone levels. Apoptosis was detected by DNA analysis and in situ TUNEL labeling. Expression of Bcl-2 and Bax proteins was examined by Western blot analysis. The earliest signs of atresia were detected 24 h after P(4) injection as evidenced by decreased diameter, degeneration and detachment of granulosa cells (GCs) from the basal lamina, and a dramatically reduced ratio of estrogen to P(4). Electrophoretic analysis of DNA extracted from DFs of cows treated with P(4) for 24 h revealed a distinct ladder pattern of DNA fragments. In contrast, this pattern was not obvious in DFs from control cows. Similar results were also obtained from TUNEL analysis of DFs. Furthermore, both Bcl-2 and Bax were found to be present in all DFs; however, the ratio of Bcl-2 and Bax protein levels was significantly reduced by 24 h of P(4) treatment compared with DFs from the control group (P < 0.05). Experiment 2 investigated the direct effect of P(4) (4 ng/ml) on apoptosis of cultured GCs using ovaries obtained from a local slaughterhouse. In addition, the pattern of expressions of Bcl-2 and Bax in follicles at different developmental stages (small, medium, and large) was studied. No increase in apoptotic DNA fragments was detected in GCs treated with P(4). The ratio of Bcl-2 and Bax protein levels was variable in small follicles; however, Bax protein level was always relatively higher than that of Bcl-2 in medium and large follicles. In conclusion, our study suggests that apoptosis is the mechanism that underlies the atresia of nonovulatory DFs that develops during the luteal phase of bovine estrous cycle.

Tumor-Associated Macrophages and Regulatory T Cells Infiltration and the Clinical Outcome in Colorectal Cancer.

PubMed

Waniczek, Dariusz; Lorenc, Zbigniew; Śnietura, Mirosław; Wesecki, Mariusz; Kopec, Agnieszka; Muc-Wierzgoń, Małgorzata

2017-10-01

The aim of the study is the assessment of the intensity of the infiltration of tumor-associated macrophages (TAMs) CD68 + /iNOS - and Tregs CD8 + /FoxP3 + in colorectal cancer (CRC) patients as prognostic factors with respect to disease-free survival (DFS) and overall survival (OS). In this retrospective study, tissue samples were obtained from 89 patients undergoing resection for CRC (stage IIA, pT3N0M0 and stages IIIB and IIIC, pT3N1-2M0). Recurrence was observed in 45 patients at the time of the follow-up (10 local recurrences, 35 distant metastases). In patients with recurrence the following were present: a tendency to an older average age at the time of diagnosis (p = 0.07), higher nodal involvement (p = 0.002) and more advanced clinical disease (p = 0.01). The analysis of the clinical data and immunohistochemical studies were performed with the methodology of identification of TAM and Treg subsets in histological sections, with the aim to use it in routine clinical management. Both DSF and OS were the clinical parameters assessed in the study. The presence of intense infiltration of TAMs in the tumor stroma was related to shorter DFS (p = 0.005) and OS (p = 0.006). The opposite tendency was observed in the tumor front (p = 0.061). The relative risks of recurrence and cancer-related death were more than twice higher in the group of patients with intense infiltration of TAMs in the tumor stroma (RR 2.05, 95% CI 1.33-3.14; p = 0.001 and RR 2.08, 95% CI 1.28-3.39; p = 0.003, respectively). Intense infiltration of Tregs in the tumor stroma was related to shorter DFS and OS (p < 0.0001). The relative risks of recurrence and death in a group of patients with intense infiltration of Tregs in the tumor stroma were more than 12 times higher than in patients with less intense infiltration (RR 12.3, 95% CI 5.44-27.9; p < 0.0001 and RR 12.5, 95% CI 4.9-32.4; p < 0.0001, respectively). Infiltration of TAMs CD68 + /iNOS - and Tregs CD8 + /FoxP3 + in the tumor stroma are negative prognostic factors with a positive correlation between them. Tregs may constitute an independent prognostic factor in patients with CRC.

Comparing the Efficacy of Digital Flashcards versus Paper Flashcards to Improve Receptive and Productive L2 Vocabulary

ERIC Educational Resources Information Center

Dizon, Gilbert; Tang, Daniel

2017-01-01

Several researchers have compared the efficacy of digital flashcards (DFs) versus paper flashcards (PFs) to improve L2 vocabulary and have concluded that using DFs is more effective (Azabdaftari & Mozaheb, 2012; Basoglu & Akdemir, 2010; Kiliçkaya & Krajka, 2010). However, these studies did not utilize vocabulary learning strategies…

The extreme dipolarization during the Galaxy 15 spacecraft anomaly

NASA Astrophysics Data System (ADS)

Loto'aniu, P. T. M.; Redmon, R. J.; Welling, D. T.; Rodriguez, J. V.; Haiducek, J. D.

2016-12-01

The substorm just prior to the Galaxy 15 spacecraft anomaly on 5 April 2010 was intriguing for a number of reasons, including that multiple spacecraft were well located near-midnight to observe the event. Another reason is that the associated dipolarization was one of the most severe ever observed by GOES satellites, even though the solar wind conditions were moderate. In this study, we compare the Galaxy 15 event to other substorms in order to understand why the dipolarization was so extreme. Presented will be simulations from the Space Weather Modeling Framework (SWMF) of different storms and comparisons made to model results for the Galaxy 15 anomaly event. The SWMF does well in predicting some storms, particularly when heavier O+ ions outflowing from the ionosphere are included. However, the SWMF significantly under-predicts the magnitude of the Galaxy 15 event, regardless of the inclusion of a heavy ion outflow model. The model dipolarization occurs around 30 minutes later than the observed event, while the strength of the dipolarization in terms of the magnetic field was not predicted by the model, although, the model does well overall predicting Dst and Kp. We will also present statistical results representing a survey of dipolarizations observed by the GOES spacecraft over a solar cycle when the satellites were located in the near-midnight local time region. The statistical results are used to determine the occurrence rate and characteristics of similar events to the Galaxy 15 dipolarization event.

Vertical Phase Segregation Induced by Dipolar Interactions in Planar Polymer Brushes

DOE PAGES

Mahalik, Jyoti P.; Sumpter, Bobby G.; Kumar, Rajeev

2016-09-13

In this paper, we present a generalized theory for studying structural properties of a planar dipolar polymer brush immersed in a polar solvent. We show that an explicit treatment of the dipolar interactions yields a macroscopic concentration dependent effective “chi” (the Flory–Huggins-like interaction) parameter. Furthermore, it is shown that the concentration dependent chi parameter promotes phase segregation in polymer solutions and brushes so that the polymer-poor phase consists of a finite/nonzero polymer concentration. Such a destabilization of the homogeneous phase by the dipolar interactions appears as vertical phase segregation in a planar polymer brush. In a vertically phase segregated polymermore » brush, the polymer-rich phase near the grafting surface coexists with the polymer-poor phase at the other end. Predictions of the theory are directly compared with prior reported experimental results for dipolar polymers in polar solvents. Excellent agreements with the experimental results are found, hinting that the dipolar interactions play a significant role in vertical phase segregation of planar polymer brushes. We also compare our field theoretical approach with the two-state and other models invoking ad hoc concentration dependence of the chi parameter. Interplay between the short-ranged excluded volume interactions and long-ranged dipolar interactions is shown to play an important role in affecting the vertical phase separation. Finally, effects of mismatch between the dipole moments of the polymer segments and the solvent molecules are investigated in detail.« less

Observation of Dipolar Spin-Exchange Interactions with Polar Molecules in a Lattice

DTIC Science & Technology

2013-01-01

extend beyond nearest neighbours. This allows coherent spin dynamics to persist even for gases with relatively high entropy and low lattice filling...dynamics to persist even for gases with relatively high entropy and low lat- tice filling. While measured effects of dipolar interactions in ultracold...limits superexchange to nearest-neighbor interactions and requires extremely low temperature and entropy . In contrast, long-range dipolar

Lorentz microscopy sheds light on the role of dipolar interactions in magnetic hyperthermia

NASA Astrophysics Data System (ADS)

Campanini, M.; Ciprian, R.; Bedogni, E.; Mega, A.; Chiesi, V.; Casoli, F.; de Julián Fernández, C.; Rotunno, E.; Rossi, F.; Secchi, A.; Bigi, F.; Salviati, G.; Magén, C.; Grillo, V.; Albertini, F.

2015-04-01

Monodispersed Fe3O4 nanoparticles with comparable size distributions have been synthesized by two different synthesis routes, co-precipitation and thermal decomposition. Thanks to the different steric stabilizations, the described samples can be considered as a model system to investigate the effects of magnetic dipolar interactions on the aggregation states of the nanoparticles. Moreover, the presence of magnetic dipolar interactions can strongly affect the nanoparticle efficiency as a hyperthermic mediator. In this paper, we present a novel way to visualize and map the magnetic dipolar interactions in different kinds of nanoparticle aggregates by the use of Lorentz microscopy, an easy and reliable in-line electron holographic technique. By exploiting Lorentz microscopy, which is complementary to the magnetic measurements, it is possible to correlate the interaction degrees of magnetic nanoparticles with their magnetic behaviors. In particular, we demonstrate that Lorentz microscopy is successful in visualizing the magnetic configurations stabilized by dipolar interactions, thus paving the way to the comprehension of the power loss mechanisms for different nanoparticle aggregates.Monodispersed Fe3O4 nanoparticles with comparable size distributions have been synthesized by two different synthesis routes, co-precipitation and thermal decomposition. Thanks to the different steric stabilizations, the described samples can be considered as a model system to investigate the effects of magnetic dipolar interactions on the aggregation states of the nanoparticles. Moreover, the presence of magnetic dipolar interactions can strongly affect the nanoparticle efficiency as a hyperthermic mediator. In this paper, we present a novel way to visualize and map the magnetic dipolar interactions in different kinds of nanoparticle aggregates by the use of Lorentz microscopy, an easy and reliable in-line electron holographic technique. By exploiting Lorentz microscopy, which is complementary to the magnetic measurements, it is possible to correlate the interaction degrees of magnetic nanoparticles with their magnetic behaviors. In particular, we demonstrate that Lorentz microscopy is successful in visualizing the magnetic configurations stabilized by dipolar interactions, thus paving the way to the comprehension of the power loss mechanisms for different nanoparticle aggregates. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr00273g

The effect of difference frequency on electrocommunication: chirp production and encoding in a species of weakly electric fish, Apteronotus leptorhynchus.

PubMed

Hupé, Ginette J; Lewis, John E; Benda, Jan

2008-01-01

The brown ghost knifefish, Apteronotus leptorhynchus, is a model wave-type gymnotiform used extensively in neuroethological studies. As all weakly electric fish, they produce an electric field (electric organ discharge, EOD) and can detect electric signals in their environments using electroreceptors. During social interactions, A. leptorhynchus produce communication signals by modulating the frequency and amplitude of their EOD. The Type 2 chirp, a transient increase in EOD frequency, is the most common modulation type. We will first present a description of A. leptorhynchus chirp production from a behavioural perspective, followed by a discussion of the mechanisms by which chirps are encoded by electroreceptor afferents (P-units). Both the production and encoding of chirps are influenced by the difference in EOD frequency between interacting fish, the so-called beat or difference frequency (Df). Chirps are produced most often when the Df is small, whereas attacks are more common when Dfs are large. Correlation analysis has shown that chirp production induces an echo response in interacting conspecifics and that chirps are produced when attack rates are low. Here we show that both of these relationships are strongest when Dfs are large. Electrophysiological recordings from electroreceptor afferents (P-units) have suggested that small, Type 2 chirps are encoded by increases in electroreceptor synchrony at low Dfs only. How Type 2 chirps are encoded at higher Dfs, where the signals seem to exert the greatest behavioural influence, was unknown. Here, we provide evidence that at higher Dfs, chirps could be encoded by a desynchronization of the P-unit population activity.

Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy.

PubMed

Parissenti, Amadeo M; Guo, Baoqing; Pritzker, Laura B; Pritzker, Kenneth P H; Wang, Xiaohui; Zhu, Mu; Shepherd, Lois E; Trudeau, Maureen E

2015-08-01

In a prior substudy of the CAN-NCIC-MA.22 clinical trial (ClinicalTrials.gov identifier NCT00066443), we observed that neoadjuvant chemotherapy reduced tumor RNA integrity in breast cancer patients, a phenomenon we term "RNA disruption." The purpose of the current study was to assess in the full patient cohort the relationship between mid-treatment tumor RNA disruption and both pCR post-treatment and, subsequently, disease-free survival (DFS) up to 108 months post-treatment. To meet these objectives, we developed the RNA disruption assay (RDA) to quantify RNA disruption and stratify it into 3 response zones of clinical importance. Zone 1 is a level of RNA disruption inadequate for pathologic complete response (pCR); Zone 2 is an intermediate level, while Zone 3 has high RNA disruption. The same RNA disruption cut points developed for pCR response were then utilized for DFS. Tumor RDA identified >fourfold more chemotherapy non-responders than did clinical response by calipers. pCR responders were clustered in RDA Zone 3, irrespective of tumor subtype. DFS was about 2-fold greater for patients with tumors in Zone 3 compared to Zone 1 patients. Kaplan-Meier survival curves corroborated these findings that high tumor RNA disruption was associated with increased DFS. DFS values for patients in zone 3 that did not achieve a pCR were similar to that of pCR recipients across tumor subtypes, including patients with hormone receptor positive tumors that seldom achieve a pCR. RDA appears superior to pCR as a chemotherapy response biomarker, supporting the prospect of its use in response-guided chemotherapy.

The modified glasgow prognostic score is an independent prognostic indicator in neoadjuvantly treated adenocarcinoma of the esophagogastric junction

PubMed Central

Jomrich, Gerd; Hollenstein, Marlene; John, Maximilian; Baierl, Andreas; Paireder, Matthias; Kristo, Ivan; Ilhan-Mutlu, Aysegül; Asari, Reza; Preusser, Matthias; Schoppmann, Sebastian F.

2018-01-01

The modified Glasgow Prognostic Score (mGPS) combines the indicators of decreased plasma albumin and elevated CRP. In a number of malignancies, elevated mGPS is associated with poor survival. Aim of this study was to investigate the prognostic role of mGPS in patients with neoadjuvantly treated adenocarcinomas of the esophagogastric junction 256 patients from a prospective database undergoing surgical resection after neoadjuvant treatment between 2003 and 2014 were evaluated. mGPS was scored as 0, 1, or 2 based on CRP (>1.0 mg/dl) and albumin (<35 g/L) from blood samples taken prior (preNT-mGPS) and after (postNT-mGPS) neoadjuvant therapy. Scores were correlated with clinicopathological patients’ characteristics. From 155 Patients, sufficient data was available. Median follow-up was 63.8 months (33.3–89.5 months). In univariate analysis, Cox proportional hazard model shows significant shorter patients OS (p = 0.04) and DFS (p = 0.02) for increased postNT-mGPS, preNT-hypoalbuminemia (OS: p = 0.003; DFS: p = 0.002) and post-NT-CRP (OS: p = 0.03; DFS: p = 0.04). Elevated postNT-mGPS and preNT-hypoalbuminemia remained significant prognostic factors in multivariate analysis for OS (p = 0.02; p = 0.005,) and DFS (p = 0.02, p = 0.004) with tumor differentiation and tumor staging as significant covariates. PostNT-mGPS and preNT-hypoalbuminemia are independent prognostic indicators in patients with neoadjuvantly treated adenocarcinomas of the esophagogastric junction and significantly associated with diminished OS and DFS. PMID:29467943

Treatment and Prognosis of Squamous Cell Carcinoma of the External Auditory Canal and Middle Ear: A Multi-Institutional Retrospective Review of 87 Patients

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

Ogawa, Kazuhiko; Nakamura, Katsumasa; Hatano, Kazuo

Purpose: To examine the relative roles of surgery, radiotherapy, and chemotherapy in the management of patients with squamous cell carcinomas of the external auditory canal and middle ear. Methods and Materials: The records of 87 patients with histologically confirmed squamous cell carcinoma who were treated between 1984 and 2005 were reviewed. Fifty-three patients (61%) were treated with surgery and radiotherapy (S + RT group) and the remaining 34 patients with radiotherapy alone (RT group). Chemotherapy was administered in 34 patients (39%). Results: The 5-year actuarial overall and disease-free survival (DFS) rates for all patients were 55% and 54%, respectively. Onmore » univariate analysis, T stage (Stell's classification), treatment modality, and Karnofsky performance status had significant impact on DFS. On multivariate analysis, T stage and treatment modality were significant prognostic factors. Chemotherapy did not influence DFS. The 5-year DFS rate in T1, T2, and T3 patients was 83%, 45%, and 0 in the RT group (p < 0.0001) and 75%, 75%, and 46% in the S + RT group (p = 0.13), respectively. The 5-year DFS rate in patients with negative surgical margins, those with positive margins, and those with macroscopic residual disease was 83%, 55%, and 38%, respectively (p = 0.007). Conclusions: Radical radiotherapy is the treatment of choice for early-stage (T1) diseases, whereas surgery (negative surgical margins if possible) with radiotherapy is recommended as the standard care for advanced (T2-3) disease. Further clarification on the role of chemotherapy is necessary.« less

High levels of serum CA15-3 and residual invasive tumor size are associated with poor prognosis for breast cancer patients with non-pathological complete response after neoadjuvant chemotherapy.

PubMed

Fujimoto, Yukie; Higuchi, Tomoko; Nishimukai, Arisa; Miyagawa, Yoshimasa; Kira, Ayako; Ozawa, Hiromi; Bun, Ayako; Imamura, Michiko; Miyoshi, Yasuo

2018-06-24

To identify surrogate markers for prognosis of breast cancer patients with non-pathological complete response (non-pCR) to neoadjuvant chemotherapy (NAC), our investigation focused on serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA15-3) as well as clinicopathological factors both pre- and post-NAC. A total of 185 breast cancer patients treated with NAC were recruited. Serum CEA and CA15-3 were measured at baseline and at completion of NAC. Among the non-pCR cancers (n = 142), disease-free survival (DFS) of patients with CA15-3-low at baseline (3-year DFS: 0.908, n = 73) was significantly better than of those with CA15-3-high (3-year DFS: 0.681, n = 69, P = 0.0134). Multivariable analysis demonstrated that baseline CA15-3 levels (hazard ratio (HR): 3.31, 95% confidence interval (CI): 1.28-10.23; P = 0.0122) and residual invasive size (HR: 4.47, 1.26-28.39; P = 0.0171) were significant independent factors for DFS. The combination of these factors proved to be accurate predictor for DFS regardless of breast cancer subtypes. The combination of residual invasive size and serum CA15-3 levels at baseline seems to be a significant and independent surrogate marker of poor outcome for patients with non-pCR. These findings suggest that these markers may be useful for identifying patients with inferior prognosis and candidates for additional adjuvant treatments. © 2018 Wiley Periodicals, Inc.

Both the intratumoral immune and microbial microenvironment are linked to recurrence in human colon cancer: results from a prospective, multicenter nodal ultrastaging trial

PubMed Central

Noguti, Juliana; Chan, Alfred A.; Bandera, Bradley; Brislawn, Colin J.; Protic, Mladjan; Sim, Myung S.; Jansson, Janet K.; Bilchik, Anton J.; Lee, Delphine J.

2018-01-01

Colon cancer (CC) is the third most common cancer diagnosed in the United States and the incidence has been rising among young adults. We and others have shown a relationship between the immune infiltrate and prognosis, with improved disease-free survival (DFS) being associated with a higher expression of CD8+ T cells. We hypothesized that a microbial signature might be associated with intratumoral immune cells as well as DFS. We found that the relative abundance of one Operational Taxonomic Unit (OTU), OTU_104, was significantly associated with recurrence even after applying false discovery correction (HR 1.21, CI 1.08 to 1.36). The final multivariable model showed that DFS was influenced by three parameters: N-stage, CD8+ labeling, as well as this OTU_104 belonging to the order Clostridiales. Not only were CD8+ labeling and OTU_104 significant contributors in the final DFS model, but they were also inversely correlated to each other (p=0.022). Interestingly, CD8+ was also significantly associated with the microbiota composition in the tumor: CD8+ T cells was inversely correlated with alpha diversity (p=0.027) and significantly associated with the beta diversity. This study is the first to demonstrate an association among the intratumoral microbiome, CD8+ T cells, and recurrence in CC. An increased relative abundance of a specific OTU_104 was inversely associated with CD8+ T cells and directly associated with CC recurrence. The link between this microbe, CD8+ T cells, and DFS has not been previously shown.

Synergistic Benefit of Statin and Metformin in Gastrointestinal Malignancies.

PubMed

Nimako, George K; Wintrob, Zachary A P; Sulik, Dmitriy A; Donato, Jennifer L; Ceacareanu, Alice C

2017-04-01

To evaluate whether statin use influences gastrointestinal cancer prognosis in patients with diabetes mellitus (DM). We reviewed all DM patients diagnosed at Roswell Park Cancer Institute with emergent gastrointestinal malignancy (January 2003 to December 2010) (N = 222). Baseline demographic, clinical history, and cancer outcomes were documented. Overall survival (OS) and disease-free survival (DFS) comparisons across various treatment groups were assessed by Kaplan-Meier and Cox proportional hazards. Use of statin, alone or in combination, was associated with improved OS and DFS (hazard ratio [HR] = 0.65, P = .06; HR = 0.60, P < .02). We report similar OS and DFS advantage among users of mono- or combined metformin therapy (HR = 0.55, P < .01; HR = 0.63, P < .02). Concomitant use of metformin and statin provided a synergistic OS and DFS benefit (HR = 0.42, P < .01; HR = 0.44, P < .01). Despite significant tobacco and alcohol use history, patients with upper gastrointestinal cancers derived enhanced cancer outcomes from this combination (HR = 0.34, P < .01; HR = 0.43, P < .02), while receiving a statin without metformin or metformin without a statin did not provide significant cancer-related benefits. Use of statin and metformin provides a synergistic improvement in gastrointestinal malignancies outcomes.

Retrospective Comparison of Fludarabine in Combination With Intermediate-Dose Cytarabine Versus High-Dose Cytarabine As Consolidation Therapies for Acute Myeloid Leukemia

PubMed Central

Zhang, Wenjun; Ding, Yi; Wu, Hao; Chen, Yuhua; Lu, Huina; Chen, Chunying; Fu, Jianfei; Wang, Weiguang; Liang, Aibin; Zou, Shanhua

2014-01-01

Abstract This retrospective study compared efficacy and safety of fludarabine combined with intermediate-dose cytarabine (FA regimen) versus high-dose cytarabine (HiDAC regimen) as consolidation therapy in acute myeloid leukemia (AML) patients who achieved complete remission. Disease-free survival (DFS) and overall survival (OS) based on age (≥60, <60 years) and cytogenetics were evaluated from data between January 2005 and March 2013. Total 82 patients (FA, n = 45; HiDAC, n = 37; 14–65 years) were evaluated. Five-year DFS was 32.0% and 36.2% for FA and HiDAC groups, respectively (P = 0.729), and 5-year OS was 39.5% and 47.8% (P = 0.568), respectively. Among older patients (≥60 years), 3-year DFS was 26.0% for FA group and 12.5% for HiDAC group (P = 0.032), and 3-year OS was 34.6% and 12.5%, respectively (P = 0.026). In FA group, hematological toxicities were significantly lower. FA regimen was as effective as HiDAC regimen in patients with good/intermediate cytogenetics and significantly improved DFS and OS in older patients. PMID:25501050

Expression of extracellular matrix metalloproteinase inducer in odontogenic cysts.

PubMed

Ali, Mohammad Abdulhadi Abbas

2008-08-01

Extracellular matrix metalloproteinase inducer (EMMPRIN) is known to induce matrix metalloproteinase (MMP) production. The expression of EMMPRIN in odontogenic cysts has not been previously studied. This study was done to determine the presence and the variability of EMMPRIN expression in various types of odontogenic cysts. An immunohistochemical study using a polyclonal anti-EMMPRIN antibody was done using 48 odontogenic cyst cases: 13 odontogenic keratocysts (OKCs), 18 dentigerous cysts (DCs), and 17 periapical cysts (PAs). Twelve cases of normal dental follicles (DFs) were also included in this study for comparison. EMMPRIN immunoreactivity was detected in all of the cysts and DFs studied. In odontogenic cysts, EMMPRIN immunoreactivity was generally higher in basal cells than in suprabasal cells. The overall EMMPRIN expression in the epithelial lining of the 3 different types of odontogenic cyst was significantly higher than in the DFs. Overall EMMPRIN expression was also found to be significantly higher in the epithelial lining of OKCs than in the other types of cysts. This study confirmed that EMMPRIN is present in odontogenic cysts and DFs. The higher EMMPRIN expression in OKCs suggests that it may be involved in the aggressive behavior of this type of cyst.

Acoustic feedback margin improvements in hearing instruments using a prototype DFS (digital feedback suppression) system.

PubMed

Dyrlund, O; Bisgaard, N

1991-01-01

The properties of a prototype DFS (digital feedback suppression) system have been investigated. 21 ears fitted with behind-the-ear (BTE) hearing instruments and hard acrylic ear-moulds and 4 ears fitted with vented in-the-ear (ITE) hearing instruments were selected for the investigation. Two ITE instruments with different venting were employed to one of the ears. Complex loop gain has been measured in an anechoic room, and from these measurements the improvements in acoustic feedback margin due to the DFS system have been determined. For the BTE group, median values of 13.1 and 10.0 dB of improvement were established for two sets of measurements introducing a 180 degrees phase shift in connection with the last set of measurements. For the ITE group, values from 9.8 to 16.1 dB and from 13.7 to 16.3 dB of improvement were observed for the normal and the 180 degrees phase shift conditions respectively. Beyond this the DFS system may improve the sound quality to some extent, because the amplitude distortion, caused by the external feedback signal, is almost completely eliminated.

Risk Factors Associated with Disease Recurrence in Patients with Stage III/IV Squamous Cell Carcinoma of the Oral Cavity Treated with Surgery and Postoperative Radiotherapy.

PubMed

Noble, Anisha R; Greskovich, John F; Han, Jaehong; Reddy, Chandana A; Nwizu, Tobenna I; Khan, Mumtaz F; Scharpf, Joseph; Adelstein, David J; Burkey, Brian B; Koyfman, Shlomo A

2016-02-01

The purpose of the present study was to identify variables associated with high risk of failure in patients with locally advanced squamous cell carcinoma of the oral cavity (SCC-OC). This retrospective study included 191 patients with stage III-IVb SCC-OC treated with post-operative radiotherapy (RT) or chemoradiotherapy (CRT) between 1995 and 2013. Disease-free (DFS) and overall survival (OS) were analyzed; variables associated with inferior DFS were identified. Seventy-five patients (39%) recurred. DFS and five-year OS were 52% and 54%, respectively. Poorly differentiated tumors (p=0.03), recurrent tumors (p=0.02) and high nodal ratio (p=0.02) were associated with an increased risk of recurrence. CRT was associated with improved DFS in patients with positive margins and/or extracapsular extension (p=0.021). Tumors that are recurrent, high grade, or have high nodal ratio are at risk of recurrence. Presence of these disease features should be taken into consideration for better risk stratification. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

[Hematopoietic stem cell transplantation in the myelodisplastic syndromes].

PubMed

León-Rodríguez, Eucario

2005-01-01

Myelodisplastic syndromes (MDS) are clonal hematopoietic disorders, characterized by ineffective hemopoiesis resulting in single or multiple lineages and a high risk of conversion to acute leukemia. Currently, the only established therapy with curative potential for MDS is a hemopoietic stem cell transplant (HSCT). Their results are determined by the type of MDS, age at the BMT and the score according to the international index. In the main studies the disease-free survival (DFS) were 35-43%, relapse 20 to 39% and transplantation-related mortality (TRM) 36-45%. HSCT offers best results in goods prognosis MDS (refractory anemia, refractory anemia with ring sideroblasts) with DFS of 53-72% and 13% of relapse, in contrast with the advanced MDS (refractory anemia with blast in excess (AREB), AREB in transformation and secondary acute leukemia) where the DFS is about approximately 33%, the relapse 23-34% and MRT 37-60%. The HSCT from unrelated donor is an option for patients that do not an HLA-matched related donor, with a approximately 30% of DFS, but with a MRT up to 58%. The HSCT with regimens of low intensity (minitransplants) for aged patients are feasible but their efficacy has not yet been determined.

Electrostatic contribution to the persistence length of a semiflexible dipolar chain.

PubMed

Podgornik, Rudi

2004-09-01

We investigate the electrostatic contribution to the persistence length of a semiflexible polymer chain whose segments interact via a screened Debye-Hückel dipolar interaction potential. We derive the expressions for the renormalized persistence length on the level of a 1/D-expansion method already successfully used in other contexts of polyelectrolye physics. We investigate different limiting forms of the renormalized persistence length of the dipolar chain and show that, in, general, it depends less strongly on the screening length than in the context of a monopolar chain. We show that for a dipolar chain the electrostatic persistence length in the same regime of the parameter phase space as the original Odijk-Skolnick-Fixman (OSF) form for a monopolar chain depends logarithmically on the screening length rather than quadratically. This can be understood solely on the basis of a swifter decay of the dipolar interactions with separation compared to the monopolar electrostatic interactions. We comment also on the general contribution of higher multipoles to the electrostatic renormalization of the bending rigidity.

Internal structure of vortices in a dipolar spinor Bose-Einstein condensate

NASA Astrophysics Data System (ADS)

Borgh, Magnus O.; Lovegrove, Justin; Ruostekoski, Janne

2017-04-01

We demonstrate how dipolar interactions (DI) can have pronounced effects on the structure of vortices in atomic spinor Bose-Einstein condensates and illustrate generic physical principles that apply across dipolar spinor systems. We then find and analyze the cores of singular non-Abelian vortices in a spin-3 52Cr condensate. Using a simpler spin-1 model system, we analyze the underlying dipolar physics and show how a dipolar healing length interacts with the hierarchy of healing lengths of the contact interaction and leads to simple criteria for the core structure: vortex core size is restricted to the shorter spin-dependent healing length when the interactions both favor the ground-state spin condition, but can conversely be enlarged by DI when interactions compete. We further demonstrate manifestations of spin-ordering induced by the DI anisotropy, including DI-dependent angular momentum of nonsingular vortices, as a result of competition with adaptation to rotation, and potentially observable internal vortex-core spin textures. We acknowledge financial support from the EPSRC.

DFS Dive-control Brakes for Gliders and Airplanes ; And, Analytical Study of the Drag of the DFS Dive-control Brake

NASA Technical Reports Server (NTRS)

Jacobs, Hans; Wanner, Adolf

1940-01-01

These two reports are surveys on the progress and present state of development of dive-control flaps for gliders and airplanes. The second article describes how on the basis of wind tunnel and free-flight tests, the drag increase on brake flaps of the type DFS, can be predicted. Pressure records confirm a two-dimensional load distribution along the brake-flap surface Aerodynamically, the location of the brake flaps along the span is of importance for reasons of avoidance of vibration and oscillation phenomena on control and tail surfaces; statically, because of the magnitude of the frontal drag in diving with respect to the bending moments, which may become decisive for the dimensions of the wing attachment and for the wing covering.

Dipolar response of hydrated proteins

NASA Astrophysics Data System (ADS)

Matyushov, Dmitry V.

2012-02-01

The paper presents an analytical theory and numerical simulations of the dipolar response of hydrated proteins in solution. We calculate the effective dielectric constant representing the average dipole moment induced at the protein by a uniform external field. The dielectric constant shows a remarkable variation among the proteins, changing from 0.5 for ubiquitin to 640 for cytochrome c. The former value implies a negative dipolar susceptibility, that is a dia-electric dipolar response and negative dielectrophoresis. It means that ubiquitin, carrying an average dipole of ≃240 D, is expected to repel from the region of a stronger electric field. This outcome is the result of a negative cross-correlation between the protein and water dipoles, compensating for the positive variance of the intrinsic protein dipole in the overall dipolar susceptibility. In contrast to the neutral ubiquitin, charged proteins studied here show para-electric dipolar response and positive dielectrophoresis. The study suggests that the dipolar response of proteins in solution is strongly affected by the coupling of the protein surface charge to the hydration water. The protein-water dipolar cross-correlations are long-ranged, extending ˜2 nm from the protein surface into the bulk. A similar correlation length of about 1 nm is seen for the electrostatic potential produced by the hydration water inside the protein. The analysis of numerical simulations suggests that the polarization of the protein-water interface is highly heterogeneous and does not follow the standard dielectric results for cavities carved in dielectrics. The polarization of the water shell gains in importance, relative to the intrinsic protein dipole, at high frequencies, above the protein Debye peak. The induced interfacial dipole can be either parallel or antiparallel to the protein dipole, depending on the distribution of the protein surface charge. As a result, the high-frequency absorption of the protein solution can be either higher or lower than the absorption of water. Both scenarios have been experimentally observed in the THz window of radiation.

Dipolar response of hydrated proteins.

PubMed

Matyushov, Dmitry V

2012-02-28

The paper presents an analytical theory and numerical simulations of the dipolar response of hydrated proteins in solution. We calculate the effective dielectric constant representing the average dipole moment induced at the protein by a uniform external field. The dielectric constant shows a remarkable variation among the proteins, changing from 0.5 for ubiquitin to 640 for cytochrome c. The former value implies a negative dipolar susceptibility, that is a dia-electric dipolar response and negative dielectrophoresis. It means that ubiquitin, carrying an average dipole of ≃240 D, is expected to repel from the region of a stronger electric field. This outcome is the result of a negative cross-correlation between the protein and water dipoles, compensating for the positive variance of the intrinsic protein dipole in the overall dipolar susceptibility. In contrast to the neutral ubiquitin, charged proteins studied here show para-electric dipolar response and positive dielectrophoresis. The study suggests that the dipolar response of proteins in solution is strongly affected by the coupling of the protein surface charge to the hydration water. The protein-water dipolar cross-correlations are long-ranged, extending ~2 nm from the protein surface into the bulk. A similar correlation length of about 1 nm is seen for the electrostatic potential produced by the hydration water inside the protein. The analysis of numerical simulations suggests that the polarization of the protein-water interface is highly heterogeneous and does not follow the standard dielectric results for cavities carved in dielectrics. The polarization of the water shell gains in importance, relative to the intrinsic protein dipole, at high frequencies, above the protein Debye peak. The induced interfacial dipole can be either parallel or antiparallel to the protein dipole, depending on the distribution of the protein surface charge. As a result, the high-frequency absorption of the protein solution can be either higher or lower than the absorption of water. Both scenarios have been experimentally observed in the THz window of radiation.

Writing user selectable data on the extended header of seismic recordings made on the Texas Instruments DFS-V

USGS Publications Warehouse

Robinson, W.C.

1996-01-01

A circuit has been developed to allow the writing of up to 192 digits of user-selectable data on a portion of tape called extended header, which is always available for use before each DFS-V seismic record is written. Such data could include navigation information, air gun and streamer depth and shot times.

Psychometric properties of the Arabic version of the 12-item diabetes fatalism scale

PubMed Central

Abi Kharma, Joelle

2018-01-01

Background There are widespread fatalistic beliefs in Arab countries, especially among individuals with diabetes. However, there is no tool to assess diabetes fatalism in this population. This study describes the processes used to create an Arabic version of the Diabetes Fatalism Scale (DFS) and examine its psychometric properties. Methods A descriptive correlational design was used with a convenience sample of Lebanese adults (N = 274) with type 2 diabetes recruited from a major hospital in Beirut, Lebanon and by snowball sampling. The 12- item Diabetes Fatalism Scale- Arabic (12-item DFS-Ar) was back-translated from the original version, pilot tested on 22 adults with type 2 diabetes and then administered to 274 patients to assess the validity and reliability of the scale. Confirmatory factor analysis (CFA) was used to test the hypothesized factor structure. Cronbach’s alpha was used to test for reliability. Results CFA supported the existence of the three factor hypothesis of the original DFS scale. The five items measuring “emotional distress” loaded under Factor 1, the four items measuring “spiritual coping” loaded under factor 2 and the last three items measuring “perceived self-efficacy” of the original scale loaded under Factor 3 (p <0.001 for all three subscales). Goodness of fit indices confirmed adequateness of the CFA model (CFI = 0.97, TLI = 0.96, RMSEA = 0.067 and pclose = 0.05). The 12-item DFS-Ar showed good reliability (Cronbach’s alpha of 0.86) and significantly predicted HbA1c (β = 0.20, p < 0.01). After adjusting for the demographic characteristics and the number of diabetes comorbid conditions, the 12-item DFS-Ar score was independently associated with HbA1c in a multivariable model (β = 0.16, p < 0.05). Conclusions The 12-item DFS-Ar demonstrated good psychometric properties that are comparable to the original scale. It is a valid and reliable measure of diabetes fatalism. Further testing with larger and non-Lebanese Arabic population is needed. PMID:29324827

[Prognostic value of sequencing of radiotherapy and chemotherapy following breast-conserving surgery for patients with breast cancer].

PubMed

Zhong, Q Z; Wang, Z; Tang, Y; Rong, Q L; Wang, S L; Jin, J; Wang, W H; Liu, Y P; Song, Y W; Fang, H; Chen, B; Qi, S N; Li, N; Tang, Y; Zhang, J H; Li, Y X

2017-04-23

Objective: To evaluate the prognostic value of sequencing of adjuvant radiotherapy and chemotherapy following breast-conserving surgery for patients with breast cancer. Methods: A total of 1 154 patients withT1-2N0-3M0 breast cancer retrospectively reviewed. All patients received sequential radiotherapy and chemotherapy following breast-conserving surgery. Among them, 603 patients received radiotherapy first and 551 patients received chemotherapy first. Log-rank tests were used to determine significance of disease-free survival (DFS) and overall survival (OS) rates in the Kaplan-Meier curve. Results: The 5-year DFS and OS rates for all patients were 93.0% and 97.8%. The 5-year OS rate was 98.6% in the radiotherapy first group and 96.4% in the chemotherapy first group ( P =0.191), and the corresponding DFS rate was 92.7% and 93.2% ( P =0.430), respectively. Among the patients with Luminal A subtype, the 5-year OS rate was 99.6% in the radiotherapy first group and 97.8% in the chemotherapy first group ( P =0.789). Among the patients with Luminal B subtype, the 5-year OS rate was 94.2% and 96.0%, respectively ( P =0.680). Among the patients with triple negative breast cancer, the 5-year OS rate was 100% and 90.9%, respectively, with statistically significant differences ( P =0.019). Among the patients with HER-2 positive breast cancer, The 5-year DFS rate was 80.1% and 100%, respectively ( P =0.045). Conclusions: The OS and DFS rates in the chemotherapy first group are not significantly different from those of radiotherapy first group after breast-conserving surgery. Patients with HER-2 positive breast cancer in chemotherapy first group have a much higher DFS rate than that of radiotherapy first group, whereas patients with triple negative breast cancer in radiotherapy first group have a better OS rate than that of chemotherapy first group. Further research is warranted to investigate the benefit of different molecular types in different sequencing of radiotherapy and chemotherapy after breast-conserving surgery.

Anal Carcinoma: Impact of TN Category of Disease on Survival, Disease Relapse, and Colostomy Failure in US Gastrointestinal Intergroup RTOG 98-11 Phase 3 Trial

PubMed Central

Gunderson, Leonard L.; Moughan, Jennifer; Ajani, Jaffer A.; Pedersen, John E.; Winter, Kathryn A.; Benson, Al B.; Thomas, Charles R.; Mayer, Robert J.; Haddock, Michael G.; Rich, Tyvin A.; Willett, Christopher G.

2013-01-01

Purpose The long-term update of US GI Intergroup RTOG 98-11 anal cancer trial found that concurrent chemoradiation (CCRT) with fluorouracil (5-FU) plus mitomycin had a significant impact on disease-free survival (DFS) and overall survival (OS) compared with induction plus concurrent 5-FU plus cisplatin. The intent of the current analysis was to determine the impact of tumor node (TN) category of disease on survival (DFS and OS), colostomy failure (CF), and relapse (local-regional failure [LRF] and distant metastases [DM]) in this patient group. Methods and Materials DFS and OS were estimated univariately by using the Kaplan-Meier method, and 6 TN categories were compared by the log–rank test (T2N0, T3N0, T4N0, T2N1-3, T3N1-3, and T4N1-3). Time to relapse and colostomy were estimated by the cumulative incidence method, and TN categories were compared using Gray’s test. Results Of 682 patients, 620 were analyzable for outcomes by TN category. All endpoints showed statistically significant differences among the TN categories of disease (OS, P<.0001; DFS, P<.0001; LRF, P<.0001; DM, P=.0011; CF, P=.01). Patients with the poorest OS, DFS, and LRF outcomes were those with T3-4N-positive (+) disease. CF was lowest for T2N0 and T2N+ (11%, 11%, respectively) and worst for the T4N0, T3N+, and T4N+ categories (26%, 27%, 24%, respectively). Conclusions TN category of disease has a statistically significant impact on OS, DFS, LRF, DM, and CF in patients treated with CCRT and provides excellent prognostic information for outcomes in patients with anal carcinoma. Significant challenges remain for patients with T4N0 and T3-4N+ categories of disease with regard to survival, relapse, and CF and lesser challenges for T2-3N0/T2N+ categories. PMID:24035327

United States Military Cancer Institute Clinical Trials Group (USMCI GI-01) randomized controlled trial comparing targeted nodal assessment and ultrastaging with standard pathological evaluation for colon cancer.

PubMed

Nissan, Aviram; Protic, Mladjan; Bilchik, Anton J; Howard, Robin S; Peoples, George E; Stojadinovic, Alexander

2012-09-01

Our randomized controlled trial previously demonstrated improved staging accuracy with targeted nodal assessment and ultrastaging (TNA-us) in colon cancer (CC). Our objective was to test the hypothesis that TNA-us improves disease-free survival (DFS) in CC. In this randomized trial, targeted nodal assessment and ultrastaging resulted in enhanced lymph node diagnostic yield associated with improved staging accuracy, which was further associated with improved disease-free survival in early colon cancer. Clinical parameters of the control (n = 94) and TNA-us (n = 98) groups were comparable. Median (interquartile range) lymph node yield was higher in the TNA-us arm: 16 (12-22) versus 13 (10-18); P = 0.002. Median follow-up was 46 (29-70) months. Overall 5-year DFS was 61% in the control arm and 71% in the TNA-us arm (P = 0.11). Clinical parameters of node-negative patients in the control (n = 51) and TNA-us (n = 55) groups were comparable. Lymph node yield was higher in the TNA-us arm: 15 (12-21) versus 13 (8-18); P = 0.03. Five-year DFS differed significantly between groups with node-negative CC (control 71% vs TNA-us 86%; P = 0.04). Survival among stage II CC alone was higher in the TNA-us group, 83% versus 65%; P = 0.03. Adjuvant chemotherapy use was nearly identical between groups. TNA-us stratified CC prognosis; DFS differed significantly between ultrastaged and conventionally staged node-negative patients [control pN0 72% vs TNA-us pN0(i-) 87%; P = 0.03]. Survival varied according to lymph node yield in patients with node-negative CC [5-year DFS: <12 lymph nodes = 57% vs 12+ lymph nodes = 85%; P = 0.011] but not in stage III CC. TNA-us is associated with improved nodal diagnostic yield and enhanced staging accuracy (stage migration), which is further associated with improved DFS in early CC. This study is registered at clinicaltrials.gov under the registration number: NCT01623258.

The prognostic significance of minimal residual disease in adult Egyptian patients with precursor acute lymphoblastic leukemia.

PubMed

Samra, Mohamed A; Mahmoud, Hossam K; Abdelhamid, Thoraya M; El Sharkawy, Nahla M; Elnahass, Yasser H; Elgammal, Mossaad; Abdelfattah, Rafaat M; Eid, Salem; Ghaleb, Fayek M; Kamel, Azza M

2013-09-01

Minimal residual disease (MRD) studies in adult acute lymphoblastic leukemia (ALL) give highly significant prognostic information superior to other standard criteria as age, gender and total leucocytic count (TLC) in distinguishing patients at high and low risk of relapse. We aimed to determine the value of MRD monitoring by flowcytometry (FCM) in predicting outcome in adult Precursor ALL patients. Bone marrow (BM) samples were analyzed by 4-color FCM collected at diagnosis and after induction therapy (MRD1) to correlate MRD positivity with disease free survival (DFS) and overall survival (OS). Study included 57 adult ALL patients (44 males and 13 females) with a median age of 22 years (18-49). DFS showed no significant difference with age, gender and initial TLC (p=0.838, 0.888 and 0.743, respectively). Cumulative DFS at 2 years was 34% for B-lineage ALL (n: 35) and 57% for T-lineage ALL (n: 18) (p = 0.057). Cumulative DFS at 2 years was 7% for MRD1 positive (high risk, HR) versus 57% for MRD1 negative patients (Low risk, LR) (p < 0.001). Cumulative DFS at 2 years was 29% for HR patients (n: 26) versus 55% for LR (n: 27) according to GMALL classification (p = 0.064). Cumulative OS did not differ according to age, gender and TLC (p = 0.526, 0.594 and 0.513, respectively). Cumulative OS at 2 years was 36% for B ALL (n: 39) versus 77% for TALL (n: 18) (p = 0.016) and was 49% for Philadelphia chromosome (Ph) negative patients versus 0% for Ph-positive patients (p < 0.001). Regarding MRD1, OS at 2 years was 18% for MRD1 HR (n: 17) versus 65% for MRD1 LR (n: 38) (p < 0.001). OS was 35% for high-risk patients (n: 30) and 62% for low-risk patients (n: 27) classified according to GMALL risk stratification (p = 0.017). MRD by FCM is a strong independent predictor of outcome in terms of DFS and OS and is a powerful informative parameter in guiding individual treatment in ALL patients. Copyright © 2013. Production and hosting by Elsevier B.V.

Randomized Adjuvant Chemotherapy of EGFR-Mutated Non-Small Cell Lung Cancer Patients with or without Icotinib Consolidation Therapy

PubMed Central

Cai, Kaican; Wu, Hua; Xiong, Gang; Wang, Haofei; Zhang, Ziliang

2015-01-01

Background Epidermal growth factor receptor (EGFR) mutations occur in up to 50% of Asian patients with non-small cell lung cancer (NSCLC). Treatment of advanced NSCLC patients with EGFR-tyrosine kinase inhibitor (EGFR-TKI) confers a significant survival benefit. This study assessed the efficacy and safety of chemotherapy with or without icotinib in patients undergoing resection of stage IB to ⅢA EGFR-mutated NSCLC. Methods Patients with surgically resected stage IB (with high risk factors) to ⅢA EGFR-mutated NSCLC were randomly assigned (1:1) to one of two treatment plans. One group received four cycles of platinum-based doublet chemotherapy every three weeks, and the other group received platinum-based chemotherapy supplemented with consolidation therapy of orally administered icotinib (125 mg thrice daily) two weeks after chemotherapy. The icotinib treatment continued for four to eight months, or until the occurrence of disease relapse, metastasis or unacceptable icotinib or chemotherapy toxicity. The primary endpoint was disease-free survival (DFS). Results 41 patients were enrolled between Feb 9, 2011 and Dec 17, 2012. 21 patients were assigned to the combined chemotherapy plus icotinib treatment group, while 20 patients received chemotherapy only. DFS at 12 months was 100% for icotinib-treated patients and 88.9% for chemotherapy-only patients (p = 0. 122). At 18 months DFS for icotinib-treated vs. chemotherapy-only patients was 95.2% vs. 83.3% (p = 0. 225), respectively, and at 24 months DFS was 90.5% vs. 66.7% (p = 0. 066). The adverse chemotherapy effects predominantly presented as gastrointestinal reactions and marrow suppression, and there was no significant difference between the two treatment groups. Patients in the chemotherapy plus icotinib treatment group showed favorable tolerance to oral icotinib. Conclusions The results suggest that chemotherapy plus orally icotinib displayed better DFS compared with chemotherapy only, yet the difference in DFS was not significant. We would think the preliminary result here was promising, and further trials with larger sample sizes might confirm the efficiency of adjuvant TKI in selected patients. Trial Registration ClinicalTrials.gov NCT02430974 PMID:26474174

Randomized Adjuvant Chemotherapy of EGFR-Mutated Non-Small Cell Lung Cancer Patients with or without Icotinib Consolidation Therapy.

PubMed

Feng, Siyang; Wang, Yuanyuan; Cai, Kaican; Wu, Hua; Xiong, Gang; Wang, Haofei; Zhang, Ziliang

2015-01-01

Epidermal growth factor receptor (EGFR) mutations occur in up to 50% of Asian patients with non-small cell lung cancer (NSCLC). Treatment of advanced NSCLC patients with EGFR-tyrosine kinase inhibitor (EGFR-TKI) confers a significant survival benefit. This study assessed the efficacy and safety of chemotherapy with or without icotinib in patients undergoing resection of stage IB to ⅢA EGFR-mutated NSCLC. Patients with surgically resected stage IB (with high risk factors) to ⅢA EGFR-mutated NSCLC were randomly assigned (1:1) to one of two treatment plans. One group received four cycles of platinum-based doublet chemotherapy every three weeks, and the other group received platinum-based chemotherapy supplemented with consolidation therapy of orally administered icotinib (125 mg thrice daily) two weeks after chemotherapy. The icotinib treatment continued for four to eight months, or until the occurrence of disease relapse, metastasis or unacceptable icotinib or chemotherapy toxicity. The primary endpoint was disease-free survival (DFS). 41 patients were enrolled between Feb 9, 2011 and Dec 17, 2012. 21 patients were assigned to the combined chemotherapy plus icotinib treatment group, while 20 patients received chemotherapy only. DFS at 12 months was 100% for icotinib-treated patients and 88.9% for chemotherapy-only patients (p = 0. 122). At 18 months DFS for icotinib-treated vs. chemotherapy-only patients was 95.2% vs. 83.3% (p = 0. 225), respectively, and at 24 months DFS was 90.5% vs. 66.7% (p = 0. 066). The adverse chemotherapy effects predominantly presented as gastrointestinal reactions and marrow suppression, and there was no significant difference between the two treatment groups. Patients in the chemotherapy plus icotinib treatment group showed favorable tolerance to oral icotinib. The results suggest that chemotherapy plus orally icotinib displayed better DFS compared with chemotherapy only, yet the difference in DFS was not significant. We would think the preliminary result here was promising, and further trials with larger sample sizes might confirm the efficiency of adjuvant TKI in selected patients. ClinicalTrials.gov NCT02430974.

Prognostic factors in clinical T1N0M0 thoracic esophageal squamous cell carcinoma invading the muscularis mucosa or submucosa.

PubMed

Uchinami, Yusuke; Myojin, Miyako; Takahashi, Hiroaki; Harada, Keiichi; Shimizu, Shinichi; Hosokawa, Masao

2016-06-21

Multimodality treatment is widely performed for clinical T1N0M0 (UICC-TNM classification, 7th edition) thoracic esophageal squamous cell carcinoma (ESCC), but available articles regarding treatment results are limited. This study assessed the outcomes of clinical T1N0M0 thoracic ESCC invading the muscularis mucosa (MM) or submucosa (SM) treated with radiotherapy (RT) or chemoradiotherapy (CRT). We retrospectively reviewed the medical charts of 90 patients with clinical T1N0M0 thoracic ESCC treated with RT or CRT in our hospital in 2004-2011. Of these 90 patients, we analyzed the cases of 71 patients who met our inclusion criteria. All 71 patients had MM or SM cancer. In the 47 patients treated with CRT, the chemotherapy regimen of 5-fluorouracil (5-FU) plus cisplatin (CDDP) was used for 46 patients and 5-FU and nedaplatin was used for one patient. Forty-five patients underwent endoscopic resection (ER) followed by RT or CRT as an additional treatment. Elective nodal irradiation (ENI) was used in 39 patients. For all analyses, statistical significance was defined as 0.05, and the Bonferroni correction was used for the multivariate analysis. The median age was 70 years (range 47-84). With a median follow-up of 43.6 months (range 1.5-124.2), the 5-year overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) rates were 64.0, 72.8 and 50.0 %, respectively. The multivariate analysis showed that performance status (PS) was an independent prognostic factors for DSS and DFS (DSS, p < 0.001; DFS, p < 0.001). Chemotherapy in addition to RT showed a trend for better DSS (p = 0.032) but was not significant following Bonferroni correction. ER and ENI were not significant predictive factors for DSS and DFS. PS was an independent prognostic factor for DSS and DFS. ER and ENI had no significant relationship with DSS or DFS. The present results may be helpful in treatment decisions for clinical T1N0M0 thoracic ESCC.

Dental caries clusters among adolescents.

PubMed

Warren, John J; Van Buren, John M; Levy, Steven M; Marshall, Teresa A; Cavanaugh, Joseph E; Curtis, Alexandra M; Kolker, Justine L; Weber-Gasparoni, Karin

2017-12-01

There have been very few longitudinal studies of dental caries in adolescents, and little study of the caries risk factors in this age group. The purpose of this study was to describe different caries trajectories and associated risk factors among members of the Iowa Fluoride Study (IFS) cohort. The IFS recruited a birth cohort from 1992 to 1995, and has gathered dietary, fluoride and behavioural data at least twice yearly since recruitment. Examinations for dental caries were completed when participants were ages 5, 9, 13 and 17 years. For this study, only participants with decayed and filled surface (DFS) caries data at ages 9, 13 and 17 were included (N=396). The individual DFS counts at age 13 and the DFS increment from 13 to 17 were used to identify distinct caries trajectories using Ward's hierarchical clustering algorithm. A number of multinomial logistic regression models were developed to predict trajectory membership, using longitudinal dietary, fluoride and demographic/behavioural data from 9 to 17 years. Model selection was based on the akaike information criterion (AIC). Several different trajectory schemes were considered, and a three-trajectory scheme-no DFS at age 17 (n=142), low DFS (n=145) and high DFS (n=109)-was chosen to balance sample sizes and interpretability. The model selection process resulted in use of an arithmetic average for dietary variables across the period from 9 to 17 years. The multinomial logistic regression model with the best fit included the variables maternal education level, 100% juice consumption, brushing frequency and sex. Other favoured models also included water and milk consumption and home water fluoride concentration. The high caries cluster was most consistently associated with lower maternal education level, lower 100% juice consumption, lower brushing frequency and being female. The use of a clustering algorithm and use of Akaike's Information Criterion (AIC) to determine the best representation of the data were useful means in presenting longitudinal caries data. Findings suggest that high caries incidence in adolescence is associated with lower maternal educational level, less frequent tooth brushing, lower 100% juice consumption and being female. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Vaccination With Patient-Specific Tumor-Derived Antigen in First Remission Improves Disease-Free Survival in Follicular Lymphoma

PubMed Central

Schuster, Stephen J.; Neelapu, Sattva S.; Gause, Barry L.; Janik, John E.; Muggia, Franco M.; Gockerman, Jon P.; Winter, Jane N.; Flowers, Christopher R.; Nikcevich, Daniel A.; Sotomayor, Eduardo M.; McGaughey, Dean S.; Jaffe, Elaine S.; Chong, Elise A.; Reynolds, Craig W.; Berry, Donald A.; Santos, Carlos F.; Popa, Mihaela A.; McCord, Amy M.; Kwak, Larry W.

2011-01-01

Purpose Vaccination with hybridoma-derived autologous tumor immunoglobulin (Ig) idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) and administered with granulocyte-monocyte colony-stimulating factor (GM-CSF) induces follicular lymphoma (FL) –specific immune responses. To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial. Patients and Methods Treatment-naive patients with advanced stage FL achieving complete response (CR) or CR unconfirmed (CRu) after chemotherapy were randomly assigned two to one to receive either Id vaccine (Id-KLH + GM-CSF) or control (KLH + GM-CSF). Primary efficacy end points were disease-free survival (DFS) for all randomly assigned patients and DFS for randomly assigned patients receiving at least one dose of Id vaccine or control. Results Of 234 patients enrolled, 177 (81%) achieved CR/CRu after chemotherapy and were randomly assigned. For 177 randomly assigned patients, including 60 patients not vaccinated because of relapse (n = 55) or other reasons (n = 5), median DFS between Id-vaccine and control arms was 23.0 versus 20.6 months, respectively (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.16; P = .256). For 117 patients who received Id vaccine (n = 76) or control (n = 41), median DFS after randomization was 44.2 months for Id-vaccine arm versus 30.6 months for control arm (HR, 0.62; 95% CI, 0.39 to 0.99; P = .047) at median follow-up of 56.6 months (range, 12.6 to 89.3 months). In an unplanned subgroup analysis, median DFS was significantly prolonged for patients receiving IgM-Id (52.9 v 28.7 months; P = .001) but not IgG-Id vaccine (35.1 v 32.4 months; P = .807) compared with isotype-matched control-treated patients. Conclusion Vaccination with patient-specific hybridoma-derived Id vaccine after chemotherapy-induced CR/CRu may prolong DFS in patients with FL. Vaccine isotype may affect clinical outcome and explain differing results between this and other controlled Id-vaccine trials. PMID:21632504

Isospin equilibration processes and dipolar signals: Coherent cluster production

NASA Astrophysics Data System (ADS)

Papa, M.; Berceanu, I.; Acosta, L.; Agodi, C.; Auditore, L.; Cardella, G.; Chatterjee, M. B.; Dell'Aquila, D.; De Filippo, E.; Francalanza, L.; Lanzalone, G.; Lombardo, I.; Maiolino, C.; Martorana, N.; Pagano, A.; Pagano, E. V.; Pirrone, S.; Politi, G.; Quattrocchi, L.; Rizzo, F.; Russotto, P.; Trifiró, A.; Trimarchi, M.; Verde, G.; Vigilante, M.

2017-11-01

The total dipolar signal related to multi-break-up processes induced on the system ^{48}Ca +{^{27}Al} at 40MeV/nucleon has been investigated with the CHIMERA multi-detector. Experimental data related to semi-peripheral collisions are shown and compared with CoMD-III calculations. The strong connection between the dipolar signal as obtained from the detected fragments and the dynamics of the isospin equilibration processes is also shortly discussed.

Third-harmonic generation from Mie-type resonances of isolated all-dielectric nanoparticles

NASA Astrophysics Data System (ADS)

Melik-Gaykazyan, Elizaveta V.; Shcherbakov, Maxim R.; Shorokhov, Alexander S.; Staude, Isabelle; Brener, Igal; Neshev, Dragomir N.; Kivshar, Yuri S.; Fedyanin, Andrey A.

2017-03-01

Subwavelength silicon nanoparticles are known to support strongly localized Mie-type modes, including those with resonant electric and magnetic dipolar polarizabilities. Here we compare experimentally the efficiency of the third-harmonic generation from isolated silicon nanodiscs for resonant excitation at the two types of dipolar resonances. Using nonlinear spectroscopy, we observe that the magnetic dipolar mode yields more efficient third-harmonic radiation in contrast to the electric dipolar (ED) mode. This is further supported by full-wave numerical simulations, where the volume-integrated local fields and the directly simulated nonlinear response are shown to be negligible at the ED resonance compared with the magnetic one. This article is part of the themed issue 'New horizons for nanophotonics'.

Altered expression of HER-2 and the mismatch repair genes MLH1 and MSH2 predicts the outcome of T1 high-grade bladder cancer.

PubMed

Sanguedolce, Francesca; Cormio, Antonella; Massenio, Paolo; Pedicillo, Maria C; Cagiano, Simona; Fortunato, Francesca; Calò, Beppe; Di Fino, Giuseppe; Carrieri, Giuseppe; Bufo, Pantaleo; Cormio, Luigi

2018-04-01

The identification of factors predicting the outcome of stage T1 high-grade bladder cancer (BC) is a major clinical issue. We performed immunohistochemistry to assess the role of human epidermal growth factor receptor-2 (HER-2) and microsatellite instability (MSI) factors MutL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in predicting recurrence and progression of T1 high-grade BCs having undergone transurethral resection of bladder tumor (TURBT) alone or TURBT + intravesical instillations of bacillus Calmette-Guerin (BCG). HER-2 overexpression was a significant predictor of disease-free survival (DFS) in the overall as well as in the two patients' population; as for progression-free survival (PFS), it was significant in the overall but not in the two patients' population. MLH1 was an independent predictor of PFS only in patients treated with BCG and MSH2 failed to predict DFS and PFS in all populations. Most importantly, the higher the number of altered markers the lowers the DFS and PFS. In multivariate Cox proportional-hazards regression analysis, the number of altered molecular markers and BCG treatment were significant predictors (p = 0.0004 and 0.0283, respectively) of DFS, whereas the number of altered molecular markers was the only significant predictor (p = 0.0054) of PFS. Altered expression of the proto-oncogene HER-2 and the two molecular markers of genetic instability MLH1 and MSH2 predicted T1 high-grade BC outcome with the higher the number of altered markers the lower the DFS and PFS. These findings provide grounds for further testing them in predicting the outcome of this challenging disease.

A Novel Optoelectronic Device Based on Correlated Two-Dimensional Fermions

NASA Astrophysics Data System (ADS)

Dianat, Pouya

Conventional metallic contacts can be replicated by quantum two dimensional charge (of Fermion) systems (2DFS). Unlike metals, the particle concentration of these "unconventional" systems can be accurately controlled in an extensive range and by means of external electronic or optical stimuli. A 2DFS can, hence, transition from a high-density kinetic liquid into a dilute-but highly correlated-gas state, in which inter-particle Coulombic interactions are significant. Such interactions contribute negatively, by so-called exchange-correlation energies, to the overall energetics of the system, and are manifested as a series negative quantum capacitance. This dissertation investigates the capacitive performance of a class of unconventional devices based on a planar metal-semiconductor-metal structure with an embedded 2DFS. They constitute an opto-electronically controlled variable capacitor, with record breaking figures-of-merit in capacitance tuning ranges of up to 7000 and voltage sensitivities as large as 400. Internal eld manipulations by localized depletion of a dense 2DFS account for the enlarged maximum and reduced minimum capacitances. The capacitance-voltage characteristics of these devices incur an anomalous "Batman" shape capacitance enhancement (CE) of up to 200% that may be triggered optically. The CE is attributed to the release and storage of exchange-correlation energies; from the "unconventional" plate and in the dielectric, respectively. This process is enforced by density manipulation of the 2DFS by a hybrid of an external eld and light-generated carriers. Under moderate optical powers, the capacitance becomes 43 times greater than the dark value; thus a new capacitance-based photodetection method is offered. This new capacitance based photodetection method has a range of applications in optoelectronics, particularly in the next generation of photonic integrated systems.

Adjuvant Radioactive iodine 131 ablation in papillary microcarcinoma of thyroid: Saudi Arabian experience [corrected].

PubMed

Al-Qahtani, Khalid Hussain; Al Asiri, Mushabbab; Tunio, Mutahir A; Aljohani, Naji J; Bayoumi, Yasser; Fatani, Hanadi; AlHadab, Abdulrehman

2015-12-01

Papillary Microcarcinoma (PMC) of thyroid is a rare type of differentiated thyroid cancer (DTC), which according to the World Health Organization measures 1.0 cm or less. The gold standard of treatment of PMC is still controversy. Our aim was to contribute in resolving the debate on the therapeutic choices of the surgical and adjuvant I-131 (RAI) treatment in PMC. From 2000 to 2012, 326 patients were found to have PMC and were retrospectively reviewed for clinicopathological characteristics, treatment outcomes and prognostic factors. Mean age of cohort was 42.6 years (range: 18-76) and the mean tumor size was 0.61 cm ± 0.24; lymph node involvement was seen in 12.9 % of cases. Median follow up period was 8.05 years (1.62-11.4). Total 23 all site recurrences (7.13 %) were observed; more observed in patients without I-131 ablation (p <0.0001). Ten year DFS rates were 89.6 %. Cox regression Model analysis revealed size, histopathologic variants, multifocality, extrathyroidal extension, lymphovascular space invasion, nodal status, and adjuvant RAI ablation the important prognostic factors affecting DFS. Despite excellent DFS rates, a small proportion of patients with PMC develop recurrences after treatment. Adjuvant RAI therapy improves DFS in PMC patients with aggressive histopathologic variants, multifocality, ETE, LVSI, tumor size (> 0.5 cm) and lymph node involvement. Failure of RAI ablation to decrease risk in N1a/b supports prophylactic central neck dissection during thyroidectomy, however more trials are warranted. Adjuvant I-131 ablation following thyroidectomy in PMC patients, particularly with poor prognostic factors improves DFS rates.

Symptoms of endocrine treatment and outcome in the BIG 1-98 study.

PubMed

Huober, J; Cole, B F; Rabaglio, M; Giobbie-Hurder, A; Wu, J; Ejlertsen, B; Bonnefoi, H; Forbes, J F; Neven, P; Láng, I; Smith, I; Wardley, A; Price, K N; Goldhirsch, A; Coates, A S; Colleoni, M; Gelber, R D; Thürlimann, B

2014-01-01

There may be a relationship between the incidence of vasomotor and arthralgia/myalgia symptoms and treatment outcomes for postmenopausal breast cancer patients with endocrine-responsive disease who received adjuvant letrozole or tamoxifen. Data on patients randomized into the monotherapy arms of the BIG 1-98 clinical trial who did not have either vasomotor or arthralgia/myalgia/carpal tunnel (AMC) symptoms reported at baseline, started protocol treatment and were alive and disease-free at the 3-month landmark (n = 4,798) and at the 12-month landmark (n = 4,682) were used for this report. Cohorts of patients with vasomotor symptoms, AMC symptoms, neither, or both were defined at both 3 and 12 months from randomization. Landmark analyses were performed for disease-free survival (DFS) and for breast cancer free interval (BCFI), using regression analysis to estimate hazard ratios (HR) and 95 % confidence intervals (CI). Median follow-up was 7.0 years. Reporting of AMC symptoms was associated with better outcome for both the 3- and 12-month landmark analyses [e.g., 12-month landmark, HR (95 % CI) for DFS = 0.65 (0.49-0.87), and for BCFI = 0.70 (0.49-0.99)]. By contrast, reporting of vasomotor symptoms was less clearly associated with DFS [12-month DFS HR (95 % CI) = 0.82 (0.70-0.96)] and BCFI (12-month DFS HR (95 % CI) = 0.97 (0.80-1.18). Interaction tests indicated no effect of treatment group on associations between symptoms and outcomes. While reporting of AMC symptoms was clearly associated with better DFS and BCFI, the association between vasomotor symptoms and outcome was less clear, especially with respect to breast cancer-related events.

Results of third-generation epirubicin/cisplatin/xeloda adjuvant chemotherapy in patients with radically resected gastric cancer.

PubMed

Cainap, Calin; Nagy, Viorica; Seicean, Andrada; Gherman, Alexandra; Laszlo, Istvan; Lisencu, Cosmin; Nadim, Al Hajar; Constantin, Anne-Marie; Cainap, Simona

2016-01-01

The purpose of this study was to evaluate the efficacy and toxicity of a third-generation chemotherapy regimen in the adjuvant setting to radically operated patients with gastric cancer. This proposed new adjuvant regimen was also compared with a consecutive retrospective cohort of patients treated with the classic McDonald regimen. Starting in 2006, a non-randomized prospective phase II study was conducted at the Institute of Oncology of Cluj-Napoca on 40 patients with stage IB-IV radically resected gastric adenocarcinoma. These patients were administered a chemotherapy regimen already considered to be standard treatment in the metastatic setting: ECX (epirubicin, cisplatin, xeloda) and were compared to a retrospective control group consisting of 54 patients, treated between 2001 and 2006 according to McDonald's trial. In a previous paper, we reported toxicities and the possible predictive factors for these toxicities; in the present article, we report on the results concerning predictive factors on overall survival (OS) and disease free survival (DFS). The proposed ECX treatment was not less effective than the standard suggested by McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage was an independent prognostic factor for OS and DFS. N ratio >70% was an independent predictive factor for OS and locoregional disease control. The resection margins were independent prognostic factors for OS and DFS. The proposed treatment is not less effective compared with the McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage represented an independent prognostic factor and N ratio >70% was a predictive factor for OS and DFS. The resection margins were proven to be independent prognostic factors for OS and DFS.

Definitive chemoradiotherapy versus neoadjuvant chemoradiotherapy followed by surgery for stage II to III esophageal squamous cell carcinoma.

PubMed

Barbetta, Arianna; Hsu, Meier; Tan, Kay See; Stefanova, Dessislava; Herman, Koby; Adusumilli, Prasad S; Bains, Manjit S; Bott, Matthew J; Isbell, James M; Janjigian, Yelena Y; Ku, Geoffrey Y; Park, Bernard J; Wu, Abraham J; Jones, David R; Molena, Daniela

2018-06-01

Definitive chemoradiotherapy (CRT) remains the most commonly used treatment for locally advanced esophageal squamous cell carcinoma (SCC), because of perceptions that esophagectomy offers an unclear survival advantage. We compare recurrence, overall survival (OS), and disease-free survival (DFS) in patients treated with definitive CRT or neoadjuvant CRT followed by surgery (trimodality). This was a retrospective cohort study of patients with stage II and III SCC of the middle and distal esophagus in patients who completed CRT. Treatment groups were matched (1:1) on covariates using a propensity score-matching approach. The effect of trimodality treatment, compared with definitive CRT, on OS, DFS, and site-specific recurrence was evaluated as a time-dependent variable and analyzed using Cox regression with a gamma frailty term for matched units. We included 232 patients treated between 2000 and 2016: 124 (53%) with definitive CRT and 108 (47%) with trimodality. Trimodality was used less frequently over time (61% before 2009 and 29% after 2009; P < .0001). After matching, each group contained 56 patients. Median OS and DFS were 3.1 and 1.8 years for trimodality versus 2.3 and 1.0 years for CRT. Surgery was independently associated with improved OS (hazard ratio, 0.57; 95% confidence interval, 0.34-0.97; P = .039) and DFS (hazard ratio, 0.51; 95% confidence interval, 0.32-0.83; P = .007). CRT followed by surgery might decrease local recurrence and increase DFS and OS in patients with esophageal SCC. Until better tools to select patients with pathological complete response are available, surgery should remain an integral component of the treatment of locally advanced esophageal SCC. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

KRAS-G12C mutation is associated with poor outcome in surgically resected lung adenocarcinoma.

PubMed

Nadal, Ernest; Chen, Guoan; Prensner, John R; Shiratsuchi, Hiroe; Sam, Christine; Zhao, Lili; Kalemkerian, Gregory P; Brenner, Dean; Lin, Jules; Reddy, Rishindra M; Chang, Andrew C; Capellà, Gabriel; Cardenal, Felipe; Beer, David G; Ramnath, Nithya

2014-10-01

The aim of this study was to examine the effects of KRAS mutant subtypes on the outcome of patients with resected lung adenocarcinoma (AC). Using clinical and sequencing data, we identified 179 patients with resected lung AC for whom KRAS mutational status was determined. A multivariate Cox model was used to identify factors associated with disease-free survival (DFS) and overall survival (OS). Publicly available mutation and gene-expression data from lung cancer cell lines and lung AC were used to assess whether distinct KRAS mutant variants have a different profile. Patients with KRAS mutation had a significantly shorter DFS compared with those with KRAS wild-type (p = 0.009). Patients with KRAS-G12C mutant tumors had significantly shorter DFS compared with other KRAS mutants and KRAS wild-type tumors (p < 0.001). In the multivariate Cox model, KRAS-G12C remained as an independent prognostic marker for DFS (Hazard ratio = 2.46, 95% confidence interval 1.51-4.00, p < 0.001) and for OS (Hazard ratio = 2.35, 95% confidence interval 1.35-4.10, p = 0.003). No genes were statistically significant when comparing the mutational or transcriptional profile of lung cancer cell lines and lung AC harboring KRAS-G12C with other KRAS mutant subtypes. Gene set enrichment analysis revealed that KRAS-G12C mutants overexpressed epithelial to mesenchymal transition genes and expressed lower levels of genes predicting KRAS dependency. KRAS-G12C mutation is associated with worse DFS and OS in resected lung AC. Gene-expression profiles in lung cancer cell lines and surgically resected lung AC revealed that KRAS-G12C mutants had an epithelial to mesenchymal transition and a KRAS-independent phenotype.

[Outcome of laparoscopic radical right hemicolectomy with complete mesocolic resection and D3 lymphadenectomy].

PubMed

Xiao, Yi; Qiu, Huizhong; Wu, Bin; Lin, Guole; Xiong, Guangbing; Niu, Beizhan; Sun, Xiyu

2014-04-01

To investigate the feasibility of laparoscopic approach for totally mesocolic resection and D3 lymphadenectomy in right colectomy. A retrospective study was conducted to analyze the operating time, blood loss, lymph node retrieval, postoperative complications and converting rate. The relationships of 3-year disease-free survival (DFS), 3-year overall survival (OS) to gender, age, American Society of Anesthesiologists (ASA) score, body mass index (BMI), T-staging, N-staging and TNM classification were also analyzed by Kaplan-Meier surviving curve and Log-rank test. A total of 111 patients were enrolled in present study. There were 50 male and 61 female patients. The average operating time was (168 ± 42) minutes, blood loss was (81 ± 63) ml, lymph node retrieval was (30 ± 12). The converting rate to open surgery was 1.8%. There was no death within 30 days after operation. The 3-year DFS and 3-year OS was 86.5% and 93.7% respectively. The short-term complications occurred in 17.1% of the patients, including diarrhea (7 cases), ileus (3 cases), urinary infection (3 cases), wound dehiscence (2 cases) and so on. With the T staging progress, DFS and OS in patients showed a gradual decline, but the difference did not reach statistical significance (P > 0.05). TNM classification had relation to DFS (χ(2) = 6.985, P = 0.030), while N-staging showed significant relations both to DFS and OS (χ(2) = 14.397, P = 0.001; χ(2) = 16.699, P = 0.000). Laparascopic approach to right hemicolectomy with complete mesocolic resection and D3 lymphadenectomy is safe and has satisfied oncological outcome.

Epidermal growth factor receptor pathway polymorphisms and the prognosis of hepatocellular carcinoma

PubMed Central

Wang, Wenjia; Ma, Xiao-Pin; Shi, Zhuqing; Zhang, Pengyin; Ding, Dong-Lin; Huang, Hui-Xing; Saiyin, Hexi Ge; Chen, Tao-Yang; Lu, Pei-Xin; Wang, Neng-Jin; Yu, Hongjie; Sun, Jielin; Zheng, S Lilly; Yu, Long; Xu, Jianfeng; Jiang, De-Ke

2015-01-01

The EGFR signaling pathway is important in the control of vital processes in the carcinogenesis of hepatocellular carcinoma (HCC), including cell survival, cell cycle progression, tumor invasion and angiogenesis. In the current study, we aim to assess if genetic variants in the genes of the EGFR signaling pathway are associated with the prognosis of HCC. We genotyped 36 single nucleotide polymorphisms (SNP) in four core genes (EGF, EGFR, VEGF, and VEGFR2) by using DNA from blood samples of 363 HCC patients with surgical resection. The associations between genotypes and overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Hazard ratios (HRs) and 95% confident intervals (CIs) were estimated for the multivariate survival analyses by Cox proportional hazards regression models, adjusting for age, gender, family history, HBsAg and AFP. We found that five SNPs in the VEGFR2 gene were significantly associated with clinical outcomes of HCC patients. Among them, four SNPs (rs7692791, rs2305948, rs13109660, rs6838752) were associated with OS (p=0.035, 0.038, 0.029 and 0.028, respectively), and two SNPs (rs7692791 and rs2034965) were associated with DFS (p=0.039 and 0.017, respectively). Particularly, rs7692791 TT genotype was associated with both reduced OS (p=0.037) and DFS (p=0.043). However, only one SNP rs2034965 with the AA genotype was shown to be an independent effect on DFS (p=0.009) in the multivariate analysis. None of the other 31 polymorphisms or 9 haplotypes attained from the four genes was significantly associated with OS or DFS. Our results illustrated the potential use of VEGFR2 polymorphisms as prognostic markers for HCC patients. PMID:25628948

Characterization of A Three-Dimensional Organotypic Co-Culture Skin Model for Epidermal Differentiation of Rat Adipose-Derived Stem Cells.

PubMed

Ghanavati, Zeinab; Orazizadeh, Mahmoud; Bayati, Vahid; Abbaspour, Mohammad Reza; Khorsandi, Layasadat; Mansouri, Esrafil; Neisi, Niloofar

2016-01-01

The organotypic co-culture is a well-known technique to examine cellular interactions and their roles in stem cell proliferation and differentiation. This study aims to evaluate the effects of dermal fibroblasts (DFs) on epidermal differentiation of adipose-derived stem cells (ASCs) using a three-dimensional (3D) organotypic co- culture technique. In this experimental research study, rat DFs and ASCs were isolated and cultured separately on electrospun polycaprolactone (PCL) matrices. The PCL matrices seeded by ASCs were superimposed on to the matrices seeded by DFs in order to create a 3D organotypic co-culture. In the control groups, PCL matrices seeded by ASCs were placed on matrices devoid of DFs. After 10 days, we assessed the expressions of keratinocyte-related genes by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and expression of pan-cytokeratin protein by immunofluorescence in the differentiated keratinocyte-like cells from co- culture and control groups. Keratinocyte-like cell morphologies were also observed by scanning electron microscopy (SEM). The early, intermediate, and terminal differentiation keratinocyte markers-Cytokeratin14, Filaggrin, and Involucrin significantly expressed in the co-culture groups com- pared to the control ones (P<0.05). We observed pan-cytokeratin in keratinocyte-like cells of both groups by immunofluorescence. SEM observation of the co-culture groups showed that the differentiated keratinocyte-like cells developed a polygonal cobblestone shape, considered characteristic of keratinocytes. The 3D organotypic co-culture bilayered construct that consisted of DFs and ASCs was an effective technique for epidermal differentiation of ASCs. This co-culture might be useful for epidermal differentiation of stem cells for future applications in skin regeneration.

Characterization of A Three-Dimensional Organotypic Co-Culture Skin Model for Epidermal Differentiation of Rat Adipose-Derived Stem Cells

PubMed Central

Ghanavati, Zeinab; Orazizadeh, Mahmoud; Bayati, Vahid; Abbaspour, Mohammad Reza; Khorsandi, Layasadat; Mansouri, Esrafil; Neisi, Niloofar

2016-01-01

Objective The organotypic co-culture is a well-known technique to examine cellular interactions and their roles in stem cell proliferation and differentiation. This study aims to evaluate the effects of dermal fibroblasts (DFs) on epidermal differentiation of adipose-derived stem cells (ASCs) using a three-dimensional (3D) organotypic co- culture technique. Materials and Methods In this experimental research study, rat DFs and ASCs were isolated and cultured separately on electrospun polycaprolactone (PCL) matrices. The PCL matrices seeded by ASCs were superimposed on to the matrices seeded by DFs in order to create a 3D organotypic co-culture. In the control groups, PCL matrices seeded by ASCs were placed on matrices devoid of DFs. After 10 days, we assessed the expressions of keratinocyte-related genes by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and expression of pan-cytokeratin protein by immunofluorescence in the differentiated keratinocyte-like cells from co- culture and control groups. Keratinocyte-like cell morphologies were also observed by scanning electron microscopy (SEM). Results The early, intermediate, and terminal differentiation keratinocyte markers-Cytokeratin14, Filaggrin, and Involucrin significantly expressed in the co-culture groups com- pared to the control ones (P<0.05). We observed pan-cytokeratin in keratinocyte-like cells of both groups by immunofluorescence. SEM observation of the co-culture groups showed that the differentiated keratinocyte-like cells developed a polygonal cobblestone shape, considered characteristic of keratinocytes. Conclusion The 3D organotypic co-culture bilayered construct that consisted of DFs and ASCs was an effective technique for epidermal differentiation of ASCs. This co-culture might be useful for epidermal differentiation of stem cells for future applications in skin regeneration. PMID:27602310

Number of negative lymph nodes should be considered for incorporation into staging for breast cancer

PubMed Central

Wu, San-Gang; Wang, Yan; Zhou, Juan; Sun, Jia-Yuan; Li, Feng-Yan; Lin, Huan-Xin; He, Zhen-Yu

2015-01-01

This study aimed to investigate the prognostic value of the number of involved lymph nodes (pN), number of removed lymph nodes (RLNs), lymph node ratio (LNR), number of negative lymph nodes (NLNs), and log odds of positive lymph nodes (LODDS) in breast cancer patients. The records of 2,515 breast cancer patients who received a mastectomy or breast-conserving surgery were retrospectively reviewed. The log-rank test was used to compare survival curves, and Cox regression analysis was performed to identify prognostic factors. The median follow-up time was 64.2 months, and the 8-year disease-free survival (DFS) and overall survival (OS) were 74.6% and 82.3%, respectively. Univariate analysis showed that pN stage, LNR, number of RLNs, and number of NLNs were significant prognostic factors for DFS and OS (all, P < 0.05). LODDS was a significant prognostic factor for OS (P = 0.021). Multivariate analysis indicated that pN stage and the number of NLNs were independent prognostic factors for DFS and OS. A higher number of NLNs was associated with higher DFS and OS, and a higher number of involved lymph nodes were associated with poorer DFS and OS. Patients with a NLNs count > 9 had better survival (P < 0.001). Subgroup analysis showed that the NLNs count had a prognostic value in patients with different pT stages and different lymph node status (log-rank P < 0.05). For breast cancer, pN stage and NLNs count have a better prognostic value compared to the RLNs count, LNR, and LODDS. Number of negative lymph nodes should be considered for incorporation into staging for breast cancer. PMID:25973321

Prognostic value of PAX9 in patients with esophageal squamous cell carcinoma and its prediction value to radiation sensitivity.

PubMed

Tan, Bingxu; Wang, Jianbo; Song, Qingxu; Wang, Nana; Jia, Yibin; Wang, Cong; Yao, Bin; Liu, Zhulong; Zhang, Xiaomei; Cheng, Yufeng

2017-07-01

Abnormal paired box 9 (PAX9) expression is associated with tumorigenesis, cancer development, invasion and metastasis. The present study investigated the prognostic significance of PAX9 in esophageal squamous cell carcinoma (ESCC) and its role in predicting radiation sensitivity. A total of 52.8% (121/229) ESCC tissues were positive for PAX9. The 1‑, 3‑ and 5‑year disease‑free survival (DFS) rates were 72.2, 35.2 and 5.6%, respectively, and the overall survival (OS) rates were and 86.1, 44.4, and 23.1%, respectively, in PAX9‑positive tumors. In PAX9‑negative tumors, the one‑, three‑ and five‑year DFS rates were 76.9, 47.9 and 24.0%, and the OS rates were 90.9, 57.9 and 38.8%, respectively. Univariate analysis revealed that PAX9, differentiation, T stage, lymph node metastasis, and tumor‑node‑metastasis stage were associated with OS. Multivariate analysis of DFS and OS revealed that the hazard ratios for PAX9 were 0.624 (95% CI: 0.472‑0.869, P=0.004) and 0.673 (95% CI: 0.491‑0.922, P=0.014), respectively. Patients that received adjuvant therapy exhibited significant differences in the 5‑year DFS (P<0.001) and OS (P<0.001). PAX9‑positive ESCC patients who received post‑surgery radiotherapy had a significantly greater 5‑year DFS (P=0.011) and OS (P=0.009) than patients who received surgery only. Thus, PAX9 may be an independent prognostic factor for the surgical treatment of ESCC and a possible predictor of radiation sensitivity.

GPR30 and estrogen receptor expression: new insights into hormone dependence of inflammatory breast cancer.

PubMed

Arias-Pulido, Hugo; Royce, Melanie; Gong, Yun; Joste, Nancy; Lomo, Lesley; Lee, Sang-Joon; Chaher, Nabila; Verschraegen, Claire; Lara, Juanita; Prossnitz, Eric R; Cristofanilli, Massimo

2010-08-01

GPR30 is a novel G protein-coupled estrogen receptor (ER) associated with metastases in breast cancer (BC) and poor survival in endometrial and ovarian tumors. The association of GPR30 expression with inflammatory breast cancer (IBC), an aggressive and commonly hormone-independent form of BC, has not been studied. GPR30, ER, progesterone receptor (PR), epidermal growth factor receptor (EGFR), and HER-2 expression were assessed by immunohistochemistry (and FISH for HER-2) in 88 primary IBCs. GPR30 expression was correlated with patient overall survival (OS), disease-free survival (DFS), pathologic variables, and other biomarkers. GPR30 expression was found in 69% of IBC cases. ER, PR, HER-2, and EGFR were found in 43, 35, 39, and 34% of IBC cases, respectively. GPR30 expression correlated inversely with ER expression (P = 0.02). Co-expression of ER and GPR30 was found in 24% of IBC samples; 19% expressed only ER and 46% expressed only GPR30. Univariate analysis showed no association between GPR30 expression and OS or DFS. However, co-expression of ER and GPR30 was associated with improved OS (P < 0.03) and marginally with DFS (P < 0.06); the absence of both ER and GPR30 was associated with worse OS and DFS (P = 0.03 for both). Multivariate analysis identified ER as an independent prognostic factor of OS (P = 0.008) and DFS (P = 0.02). The majority of IBC tumors are GPR30-positive, suggesting that estrogen signaling may be active in ER-negative IBC patients. These findings suggest potential new therapeutic targets for IBC such as novel endocrine agents or direct modulation of GPR30.

Response of energetic particles to local magnetic dipolarization inside geosynchronous orbit

NASA Astrophysics Data System (ADS)

Motoba, T.; Ohtani, S.; Gkioulidou, M.; Takahashi, K.

2017-12-01

Magnetic field dipolarization and energetic particle injections are the most distinct phenomena observed in the inner magnetosphere during the substorm expansion phase. Compared to a wealth of knowledge about the phenomenology of magnetic dipolarizations and particle injections at/outside geosynchronous orbit (GEO), our understanding of them inside GEO remains incomplete because of a very limited number of previous studies. In the present study, we statistically examine the response of 1-1000 keV energetic particles to local magnetic dipolarization by performing a superposed epoch analysis of energetic particle fluxes with the zero epoch defined as the dipolarization onset times. Based on data from the Van Allen Probes tail seasons in 2012-2016, we identified a total of 97 magnetic dipolarization events which occurred closer to the magnetic equator (i.e., BH, which is antiparallel to the Earth's dipole axis, is the dominant component of the local magnetic field at least for 5 min before the onset). For major ion species (hydrogen, helium, and oxygen ions), the relative flux intensity to the pre-onset level increases at > 50 keV and decreases at < 30 keV. The hydrogen and helium ion fluxes in the hundreds of keV range sharply increase within a minute after the onset and then decay. Compared to the short-lived nature of hydrogen and helium ion flux enhancements, oxygen ion fluxes are enhanced more gradually (on the order of several minutes). The relative ion flux intensity and peak energy generally tend to increase for stronger dipolarization-related impulsive westward electric field. This suggests that the impulsive electric field is responsible for the energization and/or transport of energetic ions inside GEO. On the other hand, the electron flux enhancement first appears from several tens of keV to a few hundreds of keV, and then exhibits an inverse energy dispersion. For dipolarizations with strong impulsive westward electric fields, the relative electron flux intensity increases up to 5-10 times, in particular most significant at several tens of keV. This result suggests that the impulsive electric field acts as an efficient factor in the rapid energization of the tens-of-keV electrons. We also discuss how the response of energetic particles to dipolarization depends on MLT, radial distance, and pitch angle.

Bio-artificial pleura using an autologous dermal fibroblast sheet

NASA Astrophysics Data System (ADS)

Kanzaki, Masato; Takagi, Ryo; Washio, Kaoru; Kokubo, Mami; Yamato, Masayuki

2017-10-01

Air leaks (ALs) are observed after pulmonary resections, and without proper treatment, can produce severe complications. AL prevention is a critical objective for managing patients after pulmonary resection. This study applied autologous dermal fibroblast sheets (DFS) to close ALs. For sealing ALs in a 44-year-old male human patient with multiple bullae, a 5 × 15-mm section of skin was surgically excised. From this skin specimen, primary dermal fibroblasts were isolated and cultured for 4 weeks to produce DFSs that were harvested after a 10-day culture. ALs were completely sealed using surgical placement of these autologous DFSs. DFS were found to be a durable long-term AL sealant, exhibiting requisite flexibility, elasticity, durability, biocompatibility, and usability, resulting reliable AL closure. DFS should prove to be an extremely useful tissue-engineered pleura substitute.

Analytical models for coupling reliability in identical two-magnet systems during slow reversals

NASA Astrophysics Data System (ADS)

Kani, Nickvash; Naeemi, Azad

2017-12-01

This paper follows previous works which investigated the strength of dipolar coupling in two-magnet systems. While those works focused on qualitative analyses, this manuscript elucidates reversal through dipolar coupling culminating in analytical expressions for reversal reliability in identical two-magnet systems. The dipolar field generated by a mono-domain magnetic body can be represented by a tensor containing both longitudinal and perpendicular field components; this field changes orientation and magnitude based on the magnetization of neighboring nanomagnets. While the dipolar field does reduce to its longitudinal component at short time-scales, for slow magnetization reversals, the simple longitudinal field representation greatly underestimates the scope of parameters that ensure reliable coupling. For the first time, analytical models that map the geometric and material parameters required for reliable coupling in two-magnet systems are developed. It is shown that in biaxial nanomagnets, the x ̂ and y ̂ components of the dipolar field contribute to the coupling, while all three dimensions contribute to the coupling between a pair of uniaxial magnets. Additionally, the ratio of the longitudinal and perpendicular components of the dipolar field is also very important. If the perpendicular components in the dipolar tensor are too large, the nanomagnet pair may come to rest in an undesirable meta-stable state away from the free axis. The analytical models formulated in this manuscript map the minimum and maximum parameters for reliable coupling. Using these models, it is shown that there is a very small range of material parameters which can facilitate reliable coupling between perpendicular-magnetic-anisotropy nanomagnets; hence, in-plane nanomagnets are more suitable for coupled systems.

Pitch angle distributions of electrons at dipolarization sites during geomagnetic activity: THEMIS observations

NASA Astrophysics Data System (ADS)

Wang, Kaiti; Lin, Ching-Huei; Wang, Lu-Yin; Hada, Tohru; Nishimura, Yukitoshi; Turner, Drew L.; Angelopoulos, Vassilis

2014-12-01

Changes in pitch angle distributions of electrons with energies from a few eV to 1 MeV at dipolarization sites in Earth's magnetotail are investigated statistically to determine the extent to which adiabatic acceleration may contribute to these changes. Forty-two dipolarization events from 2008 and 2009 observed by Time History of Events and Macroscale Interactions during Substorms probes covering the inner plasma sheet from 8 RE to 12 RE during geomagnetic activity identified by the AL index are analyzed. The number of observed events with cigar-type distributions (peaks at 0° and 180°) decreases sharply below 1 keV after dipolarization because in many of these events, electron distributions became more isotropized. From above 1 keV to a few tens of keV, however, the observed number of cigar-type events increases after dipolarization and the number of isotropic events decreases. These changes can be related to the ineffectiveness of Fermi acceleration below 1 keV (at those energies, dipolarization time becomes comparable to electron bounce time). Model-calculated pitch angle distributions after dipolarization with the effect of betatron and Fermi acceleration tested indicate that these adiabatic acceleration mechanisms can explain the observed patterns of event number changes over a large range of energies for cigar events and isotropic events. Other factors still need to be considered to assess the observed increase in cigar events around 2 keV. Indeed, preferential directional increase/loss of electron fluxes, which may contribute to the formation of cigar events, was observed. Nonadiabatic processes to accelerate electrons in a parallel direction may also be important for future study.

Noninvasive Subharmonic Pressure Estimation for Monitoring Breast Cancer Response to Neoadjuvant Therapy

DTIC Science & Technology

2011-09-01

predict disease free survival for cervix cancer (34% disease free survival (DFS) if IFP > 19 mmHg, 68% DFS if IFP < 19 mmHg (p = 0.002)) [11]. Thus, the...pressure predicts survival in patients with cervix cancer independent of clinical prognostic factors and tumor oxygen measurements. Cancer Res...Estimation for Monitoring Breast Cancer Response to Neoadjuvant Therapy PRINCIPAL INVESTIGATOR: Flemming Forsberg, Ph.D

Prognostic significance of serum lactate dehydrogenase levels in Ewing's sarcoma: A meta-analysis.

PubMed

Li, Suoyuan; Yang, Qing; Wang, Hongsheng; Wang, Zhuoying; Zuo, Dongqing; Cai, Zhengdong; Hua, Yingqi

2016-12-01

A number of studies have investigated the role of serum lactate dehydrogenase (LDH) levels in patients with Ewing's sarcoma, although these have yielded inconsistent and inconclusive results. Therefore, the present study aimed to systematically review the published studies and conduct a meta-analysis to assess its prognostic value more precisely. Cohort studies assessing the prognostic role of LDH levels in patients with Ewing's sarcoma were included. A pooled hazard ratio (HR) with 95% confidence intervals (CIs) of overall survival (OS) or 5-year disease-free survival (DFS) was used to assess the prognostic role of the levels of serum LDH. Nine studies published between 1980 and 2014, with a total of 1,412 patients with Ewing's sarcoma, were included. Six studies, with a total of 644 patients, used OS as the primary endpoint and four studies, with 795 patients, used 5-year DFS. Overall, the pooled HR evaluating high LDH levels was 2.90 (95% CI: 2.09-4.04) for OS and 2.40 (95% CI: 1.93-2.98) for 5-year DFS. This meta-analysis demonstrates that high levels of serum LDH are associated with lower OS and 5-year DFS rates in patients with Ewing's sarcoma. Therefore, serum LDH levels are an effective biomarker of Ewing's sarcoma prognosis.

Surrogate endpoints for overall survival in lung cancer trials: a review.

PubMed

Fiteni, Frédéric; Westeel, Virginie; Bonnetain, Franck

2017-05-01

Intermediate endpoints are often used as primary endpoints instead of overall survival (OS) in lung cancer trials but they are not systematically validated as surrogate endpoints for OS. Areas covered: The aim of the study was to review the studies which assessed potential surrogate endpoints for OS in lung cancer trials. Expert commentary: Twenty studies were identified. In operable non-small cell lung cancer (NSCLC) (adjuvant trials) and locally advanced NSCLC (radiotherapy trials), one individual-patient data meta-analysis found a high correlation of disease-free survival (DFS) and progression-free survival (PFS) with OS at patient and trial level. In trials of adjuvant chemotherapy, correlation between disease-free survival DFS and OS were 0.83 at the individual level (95% CI 0.83-0.83) and 0.92 at trial level (95% CI 0.88-0.95). In locally advanced disease, correlation between PFS and OS was 0.77 to 0.85 at the individual level, and 0.89 to 0.97 at trial level. This study provides a 'proof' of the surrogacy of PFS and DFS on OS according to the IQWiG framework and the surrogacy of PFS and DFS on OS was classified level 2 according to Fleming hierarchy. In all the other setting, no endpoint was judged to be valid surrogate for OS.

Adaptation of a 3-D Quadrupole Ion Trap for Dipolar DC Collisional Activation

PubMed Central

Prentice, Boone M.; Santini, Robert E.; McLuckey, Scott A.

2011-01-01

Means to allow for the application of a dipolar DC pulse to the end-cap electrodes of a three-dimensional (3-D) quadrupole ion trap for as short as a millisecond to as long as hundreds of milliseconds are described. The implementation of dipolar DC does not compromise the ability to apply AC waveforms to the end-cap electrodes at other times in the experiment. Dipolar DC provides a nonresonant means for ion acceleration by displacing ions from the center of the ion trap where they experience stronger rf electric fields, which increases the extent of micro-motion. The evolution of the product ion spectrum to higher generation products with time, as shown using protonated leucine enkephalin as a model protonated peptide, illustrates the broad-band nature of the activation. Dipolar DC activation is also shown to be effective as an ion heating approach in mimicking high amplitude short time excitation (HASTE)/pulsed Q dissociation (PQD) resonance excitation experiments that are intended to enhance the likelihood for observing low m/z products in ion trap tandem mass spectrometry. PMID:21953251

Pressure and compressibility factor of bidisperse magnetic fluids

NASA Astrophysics Data System (ADS)

Minina, Elena S.; Blaak, Ronald; Kantorovich, Sofia S.

2018-04-01

In this work, we investigate the pressure and compressibility factors of bidisperse magnetic fluids with relatively weak dipolar interactions and different granulometric compositions. In order to study these properties, we employ the method of diagram expansion, taking into account two possible scenarios: (1) dipolar particles repel each other as hard spheres; (2) the polymer shell on the surface of the particles is modelled through a soft-sphere approximation. The theoretical predictions of the pressure and compressibility factors of bidisperse ferrofluids at different granulometric compositions are supported by data obtained by means of molecular dynamics computer simulations, which we also carried out for these systems. Both theory and simulations reveal that the pressure and compressibility factors decrease with growing dipolar correlations in the system, namely with an increasing fraction of large particles. We also demonstrate that even if dipolar interactions are too weak for any self-assembly to take place, the interparticle correlations lead to a qualitative change in the behaviour of the compressibility factors when compared to that of non-dipolar spheres, making the dependence monotonic.

Scissors Mode of Dipolar Quantum Droplets of Dysprosium Atoms

NASA Astrophysics Data System (ADS)

Ferrier-Barbut, Igor; Wenzel, Matthias; Böttcher, Fabian; Langen, Tim; Isoard, Mathieu; Stringari, Sandro; Pfau, Tilman

2018-04-01

We report on the observation of the scissors mode of a single dipolar quantum droplet. The existence of this mode is due to the breaking of the rotational symmetry by the dipole-dipole interaction, which is fixed along an external homogeneous magnetic field. By modulating the orientation of this magnetic field, we introduce a new spectroscopic technique for studying dipolar quantum droplets. This provides a precise probe for interactions in the system, allowing us to extract a background scattering length for 164Dy of 69 (4 )a0 . Our results establish an analogy between quantum droplets and atomic nuclei, where the existence of the scissors mode is also only due to internal interactions. They further open the possibility to explore physics beyond the available theoretical models for strongly dipolar quantum gases.

Quantum Hall signatures of dipolar Mahan excitons

NASA Astrophysics Data System (ADS)

Schinner, G. J.; Repp, J.; Kowalik-Seidl, K.; Schubert, E.; Stallhofer, M. P.; Rai, A. K.; Reuter, D.; Wieck, A. D.; Govorov, A. O.; Holleitner, A. W.; Kotthaus, J. P.

2013-01-01

We explore the photoluminescence of spatially indirect, dipolar Mahan excitons in a gated double quantum well diode containing a mesoscopic electrostatic trap for neutral dipolar excitons at low temperatures down to 250 mK and in quantizing magnetic fields. Mahan excitons in the surrounding of the trap, consisting of individual holes interacting with a degenerate two-dimensional electron system confined in one of the quantum wells, exhibit strong quantum Hall signatures at integer filling factors and related anomalies around filling factor ν=(2)/(3),(3)/(5), and (1)/(2), reflecting the formation of composite fermions. Interactions across the trap perimeter are found to influence the energy of the confined neutral dipolar excitons by the presence of the quantum Hall effects in the two-dimensional electron system surrounding the trap.

Tight coupling of metabolic oscillations and intracellular water dynamics in Saccharomyces cerevisiae.

PubMed

Thoke, Henrik Seir; Tobiesen, Asger; Brewer, Jonathan; Hansen, Per Lyngs; Stock, Roberto P; Olsen, Lars F; Bagatolli, Luis A

2015-01-01

We detected very strong coupling between the oscillating concentration of ATP and the dynamics of intracellular water during glycolysis in Saccharomyces cerevisiae. Our results indicate that: i) dipolar relaxation of intracellular water is heterogeneous within the cell and different from dilute conditions, ii) water dipolar relaxation oscillates with glycolysis and in phase with ATP concentration, iii) this phenomenon is scale-invariant from the subcellular to the ensemble of synchronized cells and, iv) the periodicity of both glycolytic oscillations and dipolar relaxation are equally affected by D2O in a dose-dependent manner. These results offer a new insight into the coupling of an emergent intensive physicochemical property of the cell, i.e. cell-wide water dipolar relaxation, and a central metabolite (ATP) produced by a robustly oscillating metabolic process.

Tight Coupling of Metabolic Oscillations and Intracellular Water Dynamics in Saccharomyces cerevisiae

PubMed Central

Thoke, Henrik Seir; Tobiesen, Asger; Brewer, Jonathan; Hansen, Per Lyngs; Stock, Roberto P.; Olsen, Lars F.; Bagatolli, Luis A.

2015-01-01

We detected very strong coupling between the oscillating concentration of ATP and the dynamics of intracellular water during glycolysis in Saccharomyces cerevisiae. Our results indicate that: i) dipolar relaxation of intracellular water is heterogeneous within the cell and different from dilute conditions, ii) water dipolar relaxation oscillates with glycolysis and in phase with ATP concentration, iii) this phenomenon is scale-invariant from the subcellular to the ensemble of synchronized cells and, iv) the periodicity of both glycolytic oscillations and dipolar relaxation are equally affected by D2O in a dose-dependent manner. These results offer a new insight into the coupling of an emergent intensive physicochemical property of the cell, i.e. cell-wide water dipolar relaxation, and a central metabolite (ATP) produced by a robustly oscillating metabolic process. PMID:25705902

Demixing in simple dipolar mixtures: Integral equation versus density functional results

NASA Astrophysics Data System (ADS)

Range, Gabriel M.; Klapp, Sabine H. L.

2004-09-01

Using reference hypernetted chain (RHNC) integral equations and density functional theory in the modified mean-field (MMF) approximation we investigate the phase behavior of binary mixtures of dipolar hard spheres. The two species ( A and B ) differ only in their dipole moments mA and mB , and the central question investigated is under which conditions these asymmetric mixtures can exhibit demixing phase transitions in the fluid phase regime. Results from our two theoretical approaches turn out to strongly differ. Within the RHNC (which we apply to the isotropic high-temperature phase) demixing does indeed occur for dense systems with small interaction parameters Γ=mB2/mA2 . This result generalizes previously reported observations on demixing in mixtures of dipolar and neutral hard spheres (Γ=0) to the case of true dipolar hard sphere mixtures. The RHNC approach also indicates that these demixed fluid phases are isotropic at temperatures accessible by the theory, whereas isotropic-to-ferroelectric transitions occur only at larger Γ . The MMF theory, on the other hand, yields a different picture in which demixing occurs in combination with spontaneous ferroelectricity at all Γ considered. This discrepancy underlines the relevance of correlational effects for the existence of demixing transitions in dipolar systems without dispersive interactions. Indeed, supplementing the dipolar interactions by small, asymmetric amounts of van der Waals-like interactions (and thereby supporting the systems tendency to demix) one finally reaches good agreement between MMF and RHNC results.

Both the intratumoral immune and microbial microenvironment are linked to recurrence in human colon cancer: results from a prospective, multicenter nodal ultrastaging trial

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

Noguti, Juliana; Chan, Alfred A.; Bandera, Bradley

Background: Colon cancer (CC) is the third most common cancer diagnosed in the United States and the incidence has been rising among young adults. We and others have shown a relationship between the immune infiltrate and prognosis, with improved disease-free survival (DFS) associated with a higher expression of CD8+ T cells. Additionally, numerous studies indicate the gut microbiota is linked to colon cancer and clinical outcomes. Therefore, we hypothesized a microbial signature might be associated with both the intratumoral immune cells as well as DFS. Results: Ninety-one patients were randomly selected from a prospective NCI-sponsored multicenter trial evaluating ultrastaging inmore » CC to investigate the intratumoral microbiota by 16S rRNA gene amplicon sequencing. Operational taxonomic units (OTUs) were grouped by 97% sequence similarity. A series of clinical, immunohistochemical, and microbiota-related data were first evaluated by univariable cox regression to determine candidate variables associated with DFS. DFS was influenced by three parameters: N-stage, CD8+ labeling, and one microbiota principal component by multivariate analysis (MVA). Not only were the microbiota and CD8 significant contributors to the DFS model, but they were also significantly associated with each other. Alpha diversity showed an inverse correlation to CD8+ T cells (p=0.010, R=-0.278) and beta diversity showed an association with the CD8+ T cells (u-UniFrac p=0.026, w-UniFrac p=0.034). Further analysis at the OTU level with false discovery correction revealed one OTU, OTU_104, belonging to the order Clostridiales to be associated with increased recurrence (HR 1.21, CI 1.08 to 1.36). This OTU_104 was then found to be inversely correlated to CD8+ T cells (p=0.031, R=-0.35). Conclusions: This study is the first to demonstrate an association between the intratumoral microbiota, CD8+ T cells, and recurrence in CC. An increased relative abundance of a specific OTU_104 was inversely associated with CD8+ T cells and increased CC recurrence. The link between this microbe, CD8+ T cells and DFS has not been previously shown. Further studies are warranted to examine the role of infiltrating immune cells and the microbiota on colon cancer.« less

Web-based tool for dynamic functional outcome after acute ischemic stroke and comparison with existing models.

PubMed

Ji, Ruijun; Du, Wanliang; Shen, Haipeng; Pan, Yuesong; Wang, Penglian; Liu, Gaifen; Wang, Yilong; Li, Hao; Zhao, Xingquan; Wang, Yongjun

2014-11-25

Acute ischemic stroke (AIS) is one of the leading causes of death and adult disability worldwide. In the present study, we aimed to develop a web-based risk model for predicting dynamic functional status at discharge, 3-month, 6-month, and 1-year after acute ischemic stroke (Dynamic Functional Status after Acute Ischemic Stroke, DFS-AIS). The DFS-AIS was developed based on the China National Stroke Registry (CNSR), in which eligible patients were randomly divided into derivation (60%) and validation (40%) cohorts. Good functional outcome was defined as modified Rankin Scale (mRS) score ≤ 2 at discharge, 3-month, 6-month, and 1-year after AIS, respectively. Independent predictors of each outcome measure were obtained using multivariable logistic regression. The area under the receiver operating characteristic curve (AUROC) and plot of observed and predicted risk were used to assess model discrimination and calibration. A total of 12,026 patients were included and the median age was 67 (interquartile range: 57-75). The proportion of patients with good functional outcome at discharge, 3-month, 6-month, and 1-year after AIS was 67.9%, 66.5%, 66.9% and 66.9%, respectively. Age, gender, medical history of diabetes mellitus, stroke or transient ischemic attack, current smoking and atrial fibrillation, pre-stroke dependence, pre-stroke statins using, admission National Institutes of Health Stroke Scale score, admission blood glucose were identified as independent predictors of functional outcome at different time points after AIS. The DFS-AIS was developed from sets of predictors of mRS ≤ 2 at different time points following AIS. The DFS-AIS demonstrated good discrimination in the derivation and validation cohorts (AUROC range: 0.837-0.845). Plots of observed versus predicted likelihood showed excellent calibration in the derivation and validation cohorts (all r = 0.99, P < 0.001). When compared to 8 existing models, the DFS-AIS showed significantly better discrimination for good functional outcome and mortality at discharge, 3-month, 6-month, and 1-year after AIS (all P < 0.0001). The DFS-AIS is a valid risk model to predict functional outcome at discharge, 3-month, 6-month, and 1-year after AIS.

Triple negative breast tumors in African-American and Hispanic/Latina women are high in CD44+, low in CD24+, and have loss of PTEN.

PubMed

Wu, Yanyuan; Sarkissyan, Marianna; Elshimali, Yahya; Vadgama, Jaydutt V

2013-01-01

African-American women have higher mortality from breast cancer than other ethnic groups. The association between poor survival and differences with tumor phenotypes is not well understood. The purpose of this study is to assess the clinical significance of (1) Stem cell-like markers CD44 and CD24; (2) PI3K/Akt pathway associated targets PTEN, activation of Akt, and FOXO1; and (3) the Insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP3) in different breast cancer subtypes, and compare the differences between African-American and Hispanic/Latina women who have similar social-economic-status. A total of N=318 African-American and Hispanic/Latina women, with clinically-annotated information within the inclusion criteria were included. Formalin fixed paraffin embedded tissues from these patients were tested for the different markers using immunohistochemistry techniques. Kaplan-Meier survival-curves and Cox-regression analyses were used to assess Relative Risk and Disease-Free-Survival (DFS). The triple-negative-breast-cancer (TNBC) receptor-subtype was more prevalent among premenopausal women, and the Hormonal Receptor (HR) positive subtype was most common overall. TNBC tumors were more likely to have loss of PTEN, express high Ki67, and have increased CD44+/CD24- expression. TNBC was also associated with higher plasma-IGF-I levels. HR-/HER2+ tumors showed high pAkt, decreased FOXO1, and high CD24+ expression. The loss of PTEN impacted DFS significantly in African Americans, but not in Hispanics/Latinas after adjusted for treatment and other tumor pathological factors. The CD44+/CD24- and CD24+/CD44- phenotypes decreased DFS, but were not independent predictors for DFS. HER2-positive and TNBC type of cancers continued to exhibit significant decrease in DFS after adjusting for the selected biomarkers and treatment. TNBC incidence is high among African-American and Hispanic/Latino women residing in South Los Angeles. Our study also shows for the first time that TNBC was significantly associated with PTEN loss, high Ki67 and the CD44+/CD24- phenotype. The loss of PTEN impacts DFS significantly in African Americans.

Intense Current Structures Observed at Electron Kinetic Scales in the Near-Earth Magnetotail During Dipolarization and Substorm Current Wedge Formation

NASA Astrophysics Data System (ADS)

Grigorenko, E. E.; Dubyagin, S.; Malykhin, A. Yu.; Khotyaintsev, Yu V.; Kronberg, E. A.; Lavraud, B.; Ganushkina, N. Yu

2018-01-01

We use data from the 2013-2014 Cluster Inner Magnetosphere Campaign, with its uniquely small spacecraft separations (less than or equal to electron inertia length, λe), to study multiscale magnetic structures in 14 substorm-related prolonged dipolarizations in the near-Earth magnetotail. Three time scales of dipolarization are identified: (i) a prolonged growth of the BZ component with duration ≤20 min; (ii) BZ pulses with durations ≤1 min during the BZ growth; and (iii) strong magnetic field gradients with durations ≤2 s during the dipolarization growth. The values of these gradients observed at electron scales are several dozen times larger than the corresponding values of magnetic gradients simultaneously detected at ion scales. These nonlinear features in magnetic field gradients denote the formation of intense and localized (approximately a few λe) current structures during the dipolarization and substorm current wedge formation. These observations highlight the importance of electron scale processes in the formation of a 3-D substorm current system.

Examining Energetic Particle Injections and the Effects on the Inner Magnetosphere with Multiple Spacecraft/Missions

NASA Astrophysics Data System (ADS)

Leonard, T. W.; Baker, D. N.; Blake, J. B.; Burch, J. L.; Cohen, I. J.; Ergun, R.; Fennell, J. F.; Gershman, D. J.; Giles, B. L.; Jaynes, A. N.; Le Contel, O.; Mauk, B.; Russell, C. T.; Strangeway, R. J.; Torbert, R. B.; Turner, D. L.; Wilder, F. D.

2017-12-01

The Magnetospheric Multiscale (MMS) Fly's Eye Energetic Particle Spectrometer (FEEPS) instrument has observed a multitude of particle injection events since its launch in 2014. These injections often lead to enhancements observed by the Van Allen Probes MagEIS instrument, as well as other elements of the modern-day Heliophysics System Observatory. The high spatial resolution and unprecedented time scales of the MMS observations provide a microscope view of the plasma physical properties in Earth's neighborhood while the combination with other missions in the Heliophysics System Observatory provides a telescope view of the larger Sun-Earth system. Past studies have found a relationship between substorm activity, which can be more powerful during high speed solar wind stream events, and enhancements of the outer radiation belt electrons. In this study, we examine several distinct particle injection events with dipolarization front characteristics observed by MMS and multiple complementary missions. In particular, cases involving multiple injection events are compared to singular injection events for their effectiveness of creating radiation belt enhancements.

A Telescopic and Microscopic Examination of Acceleration in the June 2015 Geomagnetic Storm: Magnetospheric Multiscale and Van Allen Probes Study of Substorm Particle Injection

NASA Technical Reports Server (NTRS)

Baker, D. N.; Jaynes, A. N.; Turner, D. L.; Nakamura, R.; Schmid, D.; Mauk, B. H.; Cohen, I. J.; Fennell, J. F.; Blake, J. B.; Strangeway, R. J.;

Long-term outcome of 6-month maintenance chemotherapy for acute lymphoblastic leukemia in children.

PubMed

Kato, M; Ishimaru, S; Seki, M; Yoshida, K; Shiraishi, Y; Chiba, K; Kakiuchi, N; Sato, Y; Ueno, H; Tanaka, H; Inukai, T; Tomizawa, D; Hasegawa, D; Osumi, T; Arakawa, Y; Aoki, T; Okuya, M; Kaizu, K; Kato, K; Taneyama, Y; Goto, H; Taki, T; Takagi, M; Sanada, M; Koh, K; Takita, J; Miyano, S; Ogawa, S; Ohara, A; Tsuchida, M; Manabe, A

2017-03-01

In the treatment of childhood acute lymphoblastic leukemia (ALL), excess shortening of maintenance therapy resulted in high relapse rate, as shown by our previous trial, TCCSG L92-13, in which maintenance therapy was terminated at 1 year from initiation of treatment. In this study, we aimed to confirm the long-term outcome of L92-13, and to identify who can or cannot be cured by shorter duration of maintenance therapy. To obtain sentinel cytogenetics information that had been missed before, we performed genetic analysis with genomic microarray and target intron-capture sequencing from diagnostic bone marrow smear. Disease-free survival (DFS) at 10 years from the end of therapy was 66.0±2.8%. Females (n=138) had better DFS (74.6±3.7%) than males (n=142, 57.5±4.2%, P=0.002). Patients with TCF3-PBX1 (n=11) and ETV6-RUNX1 (n=16) had excellent DFS (90.9±8.7% and 93.8±6.1%, respectively), whereas high hyperdiploidy (n=23) was the most unfavorable subgroup, with 56.6±10.3% of DFS. Short duration of therapy can cure more than half of pediatric ALL, especially females, TCF3-PBX1 and ETV6-RUNX1. Our retrospective observations suggest a gender/karyotype inhomogeneity on the impact of brief therapy.

A critical prognostic analysis of neutrophil-lymphocyte ratio for patients undergoing nephroureterectomy due to upper urinary tract urothelial carcinoma.

PubMed

Altan, Mesut; Haberal, Hakan Bahadır; Akdoğan, Bülent; Özen, Haluk

2017-10-01

To determine preoperative serum complete blood count parameters that affects survival of patients who underwent surgery for upper urinary tract urothelial cancer (UUT-UC). Since 1990, 150 patients underwent nephroureterectomy with bladder cuff excision for UUT-UC at Hacettepe University. Patients with a history of muscle-invasive bladder cancer, adjuvant chemotherapy or metastasis at the time of diagnosis were excluded. One hundred and thirteen patients without infective symptoms and with a full set of serum data were evaluated retrospectively. Effects of the neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), and leukocyte count on disease-free survival (DFS) and progression-free survival (PFS) were investigated. Threshold values for each parameter to predict PFS were calculated. The mean age and median follow-up were 63.7 ± 11.1 years and 34 (3-186) months, respectively. Male to female ratio was 86/27. The 5-years PFS (bladder recurrence was excluded) and DFS were 59.6 and 38.4%, respectively. In multivariate analysis, NLR was independent prognostic factor for PFS and DFS (p = 0.006 and p = 0.021, respectively) while LMR was prognostic only for PFS (p = 0.037). For UUT-UC, NLR is a prognostic factor for PFS and DFS, while LMR is a prognostic indicator for PFS in present series.

Luminal-like HER2-negative stage IA breast cancer: a multicenter retrospective study on long-term outcome with propensity score analysis

PubMed Central

De Angelis, Carmine; Di Maio, Massimo; Crispo, Anna; Giuliano, Mario; Schettini, Francesco; Bonotto, Marta; Gerratana, Lorenzo; Iacono, Donatella; Cinausero, Marika; Riccardi, Ferdinando; Ciancia, Giuseppe; De Laurentiis, Michelino; Puglisi, Fabio; De Placido, Sabino; Arpino, Grazia

2017-01-01

The benefit of adding chemotherapy (CT) to adjuvant hormone therapy (HT) in stage IA luminal-like HER2-negative breast cancer (BC) is unclear. We retrospectively evaluated predictive factors and clinical outcome of 1,222 patients from 4 oncologic centers. Three hundred and eighty patients received CT and HT (CT-cohort) and 842 received HT alone (HT-cohort). Disease-free survival (DFS) and overall survival (OS) were evaluated with univariate and multivariate analyses. We also applied the propensity score methodology. Compared with the HT-cohort, patients in the CT-cohort were more likely to be younger, have larger tumors of a higher histological grade that were Ki67-positive, and lower estrogen and progesterone receptor expression. At univariate analysis, a higher histological grade and Ki67 were significantly associated to a lower DFS. At multivariable analysis, only histological grade was predictive of DFS. The CT-cohort had a worse outcome than the HT-cohort in terms of DFS and OS, but differences disappeared when matched according to propensity score. In summary, patients with stage IA luminal-like BC had an excellent prognosis, however relapse and mortality were higher in the CT-cohort than in the HT-cohort. Longer use of adjuvant HT or other therapeutic strategies may be needed to improve outcome. PMID:29348868

Surgical Management and Prognostic Factors of Vulvovaginal Melanoma.

PubMed

Ditto, Antonino; Bogani, Giorgio; Martinelli, Fabio; Di Donato, Violante; Laufer, Joel; Scasso, Santiago; Chiappa, Valentina; Signorelli, Mauro; Indini, Alice; Lorusso, Domenica; Raspagliesi, Francesco

2016-07-01

The aim of the study was to evaluate the surgical management and the role of different prognostic factors on survival outcomes of women affected by genital (i.e., vulvar and vaginal) melanoma. Data of patients undergoing primary surgical treatment for genital melanoma were evaluated in this retrospective study. Baseline, pathological, and postoperative variables were tested to identify prognostic factors. Five-year disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox proportional hazards models. Overall, 98 patients met the inclusion criteria. Sixty-seven (68%) and 31 (32%) patients in this study population were diagnosed with vulvar and vaginal melanoma, respectively. Median (range) DFS and OS were 12 (1-70) and 22 (1-70) months, respectively. Considering factors influencing DFS, we observed that at multivariate analysis, only vaginal localization (hazard ratio [HR] = 3.72; 95% CI = 1.05-13.2) and number of mitoses (HR = 1.24; 95% CI = 1.11-1.39) proved to be associated with worse DFS. Nodal status was the only independent factor influencing 5-year OS in patients with vulvar (HR = 1.76; 95% CI = 1.22-2.54; p = .002) and vaginal (HR = 3.65; 95% CI = 1.08-12.3; p = .03) melanoma. Genital melanomas are characterized by a poor prognosis. Number of mitoses and lymph node status are the main factors influencing survival. Surgery is the mainstay of treatment. A correct and prompt diagnosis is paramount.

Significance of prophylactic modified radical neck dissection for patients with low-risk papillary thyroid carcinoma measuring 1.1-3.0 cm: first report of a trial at Kuma Hospital.

PubMed

Ito, Yasuhiro; Tsushima, Yukiko; Masuoka, Hiroo; Yabuta, Tomonori; Fukushima, Mitsuhiro; Inoue, Hiroyuki; Tomoda, Chisato; Kihara, Minoru; Higashiyama, Takuya; Takamura, Yuuki; Kobayashi, Kaoru; Miya, Akihiro; Miyauchi, Akira

2011-11-01

Papillary thyroid carcinoma (PTC) frequently metastasizes to and recurs in regional lymph nodes. Of the two compartments, the central compartment can be dissected through the same wound as the thyroidectomy, and the central node dissection (CND) is routinely performed in most Japanese surgical departments. However, the indications for prophylactic lateral compartment dissection (modified radical neck dissection [MND]) for low-risk PTC remain unclear. In this study, we investigated the indications for prophylactic MND for PTC patients with tumor measuring 1.1-3.0 cm without significant extrathyroid extension or distant metastasis. We investigated the lymph node disease-free survival (LN-DFS) rates of 829 patients who underwent CND and of 414 patients who underwent MND and CND between 2005 and 2007 at Kuma Hospital. The LN-DFS of these two groups was not significantly different. In the subset of patients with CND only, clinical central node metastasis (N1a) significantly predicted a worse LN-DFS. All N1a patients recognized as showing recurrence developed such recurrence in the lateral compartment. Other conventional prognostic factors, such as sex and age, were not related to LN-DFS. Taken together, N1a patients with low-risk PTC measuring 1.1-3.0 cm can be considered as candidates for prophylactic MND.

Berry Curvature in Magnon-Phonon Hybrid Systems.

PubMed

Takahashi, Ryuji; Nagaosa, Naoto

2016-11-18

We study theoretically the Berry curvature of the magnon induced by the hybridization with the acoustic phonons via the spin-orbit and dipolar interactions. We first discuss the magnon-phonon hybridization via the dipolar interaction, and show that the dispersions have gapless points in momentum space, some of which form a loop. Next, when both spin-orbit and dipolar interactions are considered, we show anisotropic texture of the Berry curvature and its divergence with and without gap closing. Realistic evaluation of the consequent anomalous velocity is given for yttrium iron garnet.

Nonlocal and nonlinear electrostatics of a dipolar Coulomb fluid.

PubMed

Sahin, Buyukdagli; Ralf, Blossey

2014-07-16

We study a model Coulomb fluid consisting of dipolar solvent molecules of finite extent which generalizes the point-like dipolar Poisson-Boltzmann model (DPB) previously introduced by Coalson and Duncan (1996 J. Phys. Chem. 100 2612) and Abrashkin et al (2007 Phys. Rev. Lett. 99 077801). We formulate a nonlocal Poisson-Boltzmann equation (NLPB) and study both linear and nonlinear dielectric response in this model for the case of a single plane geometry. Our results shed light on the relevance of nonlocal versus nonlinear effects in continuum models of material electrostatics.

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

Băloi, Mihaela-Andreea, E-mail: mihaela.baloi88@e-uvt.ro; Crucean, Cosmin

The production of fermions in dipolar electric fields on de Sitter universe is studied. The amplitude and probability of pair production are computed using the exact solution of the Dirac equation in de Sitter spacetime. The form of the dipolar fields is established using the conformal invariance of the Maxwell equations. We obtain that the momentum conservation law is broken in the process of pair production in dipolar electric fields. Also we establish that there are nonvanishing probabilities for processes in which the helicity is conserved/nonconserved. The Minkowski limit is recovered when the expansion factor becomes zero.

1,3-Dipolar Cycloadditions of Diazo Compounds in the Presence of Azides.

PubMed

Aronoff, Matthew R; Gold, Brian; Raines, Ronald T

2016-04-01

The diazo group has untapped utility in chemical biology. The tolerance of stabilized diazo groups to cellular metabolism is comparable to that of azido groups. However, chemoselectivity has been elusive, as both groups undergo 1,3-dipolar cycloadditions with strained alkynes. Removing strain and tuning dipolarophile electronics yields diazo group selective 1,3-dipolar cycloadditions that can be performed in the presence of an azido group. For example, diazoacetamide but not its azido congener react with dehydroalanine residues, as in the natural product nisin.

Synthesis of Trifluoromethylated Isoxazolidines: 1,3-Dipolar Cycloaddition of Nitrosoarenes, (Trifluoromethyl)diazomethane, and Alkenes

PubMed Central

Molander, Gary A.; Cavalcanti, Livia N.

2013-01-01

Isoxazolidines have proven to be important substrates in synthetic organic chemistry. Limited examples in the literature that provide trifluoromethylated versions of these compounds have prompted us to investigate a 1,3-dipolar cycloaddition route providing access to N-functionalized isoxazolidines containing a trifluoromethyl group. Thus, a 1,3-dipolar cycloaddition of nitrosoarenes, (trifluoromethyl)diazomethane, and alkenes was developed. The starting materials can be synthesized from easy to handle and accessible reagents. The reaction proved to be tolerant of a variety of electron-deficient alkenes and nitrosoarenes. PMID:24490778

The structure of ions and zwitterionic lipids regulates the charge of dipolar membranes.

PubMed

Szekely, Or; Steiner, Ariel; Szekely, Pablo; Amit, Einav; Asor, Roi; Tamburu, Carmen; Raviv, Uri

2011-06-21

In pure water, zwitterionic lipids form lamellar phases with an equilibrium water gap on the order of 2 to 3 nm as a result of the dominating van der Waals attraction between dipolar bilayers. Monovalent ions can swell those neutral lamellae by a small amount. Divalent ions can adsorb onto dipolar membranes and charge them. Using solution X-ray scattering, we studied how the structure of ions and zwitterionic lipids regulates the charge of dipolar membranes. We found that unlike monovalent ions that weakly interact with all of the examined dipolar membranes, divalent and trivalent ions adsorb onto membranes containing lipids with saturated tails, with an association constant on the order of ∼10 M(-1). One double bond in the lipid tail is sufficient to prevent divalent ion adsorption. We suggest that this behavior is due to the relatively loose packing of lipids with unsaturated tails that increases the area per lipid headgroup, enabling their free rotation. Divalent ion adsorption links two lipids and limits their free rotation. The ion-dipole interaction gained by the adsorption of the ions onto unsaturated membranes is insufficient to compensate for the loss of headgroup free-rotational entropy. The ion-dipole interaction is stronger for cations with a higher valence. Nevertheless, polyamines behave as monovalent ions near dipolar interfaces in the sense that they interact weakly with the membrane surface, whereas in the bulk their behavior is similar to that of multivalent cations. Advanced data analysis and comparison with theory provide insight into the structure and interactions between ion-induced regulated charged interfaces. This study models biologically relevant interactions between cell membranes and various ions and the manner in which the lipid structure governs those interactions. The ability to monitor these interactions creates a tool for probing systems that are more complex and forms the basis for controlling the interactions between dipolar membranes and charged proteins or biopolymers for encapsulation and delivery applications. © 2011 American Chemical Society

Quantum Theory of Atoms in Molecules Charge-Charge Transfer-Dipolar Polarization Classification of Infrared Intensities.

PubMed

Duarte, Leonardo J; Richter, Wagner E; Silva, Arnaldo F; Bruns, Roy E

2017-10-26

Fundamental infrared vibrational transition intensities of gas-phase molecules are sensitive probes of changes in electronic structure accompanying small molecular distortions. Models containing charge, charge transfer, and dipolar polarization effects are necessary for a successful classification of the C-H, C-F, and C-Cl stretching and bending intensities. C-H stretching and in-plane bending vibrations involving sp 3 carbon atoms have small equilibrium charge contributions and are accurately modeled by the charge transfer-counterpolarization contribution and its interaction with equilibrium charge movement. Large C-F and C═O stretching intensities have dominant equilibrium charge movement contributions compared to their charge transfer-dipolar polarization ones and are accurately estimated by equilibrium charge and the interaction contribution. The C-F and C-Cl bending modes have charge and charge transfer-dipolar polarization contribution sums that are of similar size but opposite sign to their interaction values resulting in small intensities. Experimental in-plane C-H bends have small average intensities of 12.6 ± 10.4 km mol -1 owing to negligible charge contributions and charge transfer-counterpolarization cancellations, whereas their average out-of-plane experimental intensities are much larger, 65.7 ± 20.0 km mol -1 , as charge transfer is zero and only dipolar polarization takes place. The C-F bending intensities have large charge contributions but very small intensities. Their average experimental out-of-plane intensity of 9.9 ± 12.6 km mol -1 arises from the cancellation of large charge contributions by dipolar polarization contributions. The experimental average in-plane C-F bending intensity, 5.8 ± 7.3 km mol -1 , is also small owing to charge and charge transfer-counterpolarization sums being canceled by their interaction contributions. Models containing only atomic charges and their fluxes are incapable of describing electronic structure changes for simple molecular distortions that are of interest in classifying infrared intensities. One can expect dipolar polarization effects to also be important for larger distortions of chemical interest.

Dipolar eddies in a decaying stratified turbulent flow

NASA Astrophysics Data System (ADS)

Voropayev, S. I.; Fernando, H. J. S.; Morrison, R.

2008-02-01

Laboratory experiments on the evolution of dipolar (momentum) eddies in a stratified fluid in the presence of random background motions are described. A turbulent jet puff was used to generate the momentum eddies, and a decaying field of ambient random vortical motions was generated by a towed grid. Data on vorticity/velocity fields of momentum eddies, those of background motions, and their interactions were collected in the presence and absence of the other, and the main characteristics thereof were parametrized. Similarity arguments predict that dipolar eddies in stratified fluids may preserve their identity in decaying grid-generated stratified turbulence, which was verified experimentally. Possible applications of the results include mushroomlike currents and other naturally/artificially generated large dipolar eddies in strongly stratified layers of the ocean, the longevity of which is expected to be determined by the characteristics of the eddies and random background motions.

Quantum phases of dipolar soft-core bosons

NASA Astrophysics Data System (ADS)

Grimmer, D.; Safavi-Naini, A.; Capogrosso-Sansone, B.; Söyler, Ş. G.

2014-10-01

We study the phase diagram of a system of soft-core dipolar bosons confined to a two-dimensional optical lattice layer. We assume that dipoles are aligned perpendicular to the layer such that the dipolar interactions are purely repulsive and isotropic. We consider the full dipolar interaction and perform path-integral quantum Monte Carlo simulations using the worm algorithm. Besides a superfluid phase, we find various solid and supersolid phases. We show that, unlike what was found previously for the case of nearest-neighbor interaction, supersolid phases are stabilized by doping the solids not only with particles but with holes as well. We further study the stability of these quantum phases against thermal fluctuations. Finally, we discuss pair formation and the stability of the pair checkerboard phase formed in a bilayer geometry, and we suggest experimental conditions under which the pair checkerboard phase can be observed.

Improved heteronuclear dipolar decoupling sequences for liquid-crystal NMR

NASA Astrophysics Data System (ADS)

Thakur, Rajendra Singh; Kurur, Narayanan D.; Madhu, P. K.

2007-04-01

Recently we introduced a radiofrequency pulse scheme for heteronuclear dipolar decoupling in solid-state nuclear magnetic resonance under magic-angle spinning [R.S. Thakur, N.D. Kurur, P.K. Madhu, Swept-frequency two-pulse phase modulation for heteronuclear dipolar decoupling in solid-state NMR, Chem. Phys. Lett. 426 (2006) 459-463]. Variants of this sequence, swept-frequency TPPM, employing frequency modulation of different types have been further tested to improve the efficiency of heteronuclear dipolar decoupling. Among these, certain sequences that were found to perform well at lower spinning speeds are demonstrated here on a liquid-crystal sample of MBBA for application in static samples. The new sequences are compared with the standard TPPM and SPINAL schemes and are shown to perform better than them. These modulated schemes perform well at low decoupler radiofrequency power levels and are easy to implement on standard spectrometers.

German adjuvant intergroup node-positive study: a phase III trial to compare oral ibandronate versus observation in patients with high-risk early breast cancer.

PubMed

von Minckwitz, Gunter; Möbus, Volker; Schneeweiss, Andreas; Huober, Jens; Thomssen, Christoph; Untch, Michael; Jackisch, Christian; Diel, Ingo J; Elling, Dirk; Conrad, Bettina; Kreienberg, Rolf; Müller, Volkmar; Lück, Hans-Joachim; Bauerfeind, Ingo; Clemens, Michael; Schmidt, Marcus; Noeding, Stefanie; Forstbauer, Helmut; Barinoff, Jana; Belau, Antje; Nekljudova, Valentina; Harbeck, Nadia; Loibl, Sibylle

2013-10-01

Bisphosphonates prevent skeletal-related events in patients with metastatic breast cancer. Their effect in early breast cancer is controversial. Ibandronate is an orally and intravenously available amino-bisphosphonate with a favorable toxicity profile. It therefore qualifies as potential agent for adjuvant use. The GAIN (German Adjuvant Intergroup Node-Positive) study was an open-label, randomized, controlled phase III trial with a 2 × 2 factorial design. Patients with node-positive early breast cancer were randomly assigned 1:1 to two different dose-dense chemotherapy regimens and 2:1 to ibandronate 50 mg per day orally for 2 years or observation. In all, 2,640 patients and 728 events were estimated to be required to demonstrate an increase in disease-free survival (DFS) by ibandronate from 75% to 79.5% by using a two-sided α = .05 and 1-β of 80%. We report here the efficacy analysis for ibandronate, which was released by the independent data monitoring committee because the futility boundary was not crossed after 50% of the required DFS events were observed. Between June 2004 and August 2008, 2,015 patients were randomly assigned to ibandronate and 1,008 to observation. Patients randomly assigned to ibandronate showed no superior DFS or overall survival (OS) compared with patients randomly assigned to observation (DFS: hazard ratio, 0.945; 95% CI, 0.768 to 1.161; P = .589; OS: HR, 1.040; 95% CI, 0.763 to 1.419; P = .803). DFS was numerically longer if ibandronate was used in patients younger than 40 years or older than 60 years compared with patients age 40 to 59 years (test for interaction P = .093). Adjuvant treatment with oral ibandronate did not improve outcome of patients with high-risk early breast cancer who received dose-dense chemotherapy.

Rectal cancer delivery of radiotherapy in adequate time and with adequate dose is influenced by treatment center, treatment schedule, and gender and is prognostic parameter for local control: Results of study CAO/ARO/AIO-94

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

Fietkau, Rainer; Roedel, Claus; Hohenberger, Werner

2007-03-15

Purpose: The impact of the delivery of radiotherapy (RT) on treatment results in rectal cancer patients is unknown. Methods and Materials: The data from 788 patients with rectal cancer treated within the German CAO/AIO/ARO-94 phase III trial were analyzed concerning the impact of the delivery of RT (adequate RT: minimal radiation RT dose delivered, 4300 cGy for neoadjuvant RT or 4700 cGy for adjuvant RT; completion of RT in <44 days for neoadjuvant RT or <49 days for adjuvant RT) in different centers on the locoregional recurrence rate (LRR) and disease-free survival (DFS) at 5 years. The LRR, DFS, andmore » delivery of RT were analyzed as endpoints in multivariate analysis. Results: A significant difference was found between the centers and the delivery of RT. The overall delivery of RT was a prognostic factor for the LRR (no RT, 29.6% {+-} 7.8%; inadequate RT, 21.2% {+-} 5.6%; adequate RT, 6.8% {+-} 1.4%; p = 0.0001) and DFS (no RT, 55.1% {+-} 9.1%; inadequate RT, 57.4% {+-} 6.3%; adequate RT, 69.1% {+-} 2.3%; p = 0.02). Postoperatively, delivery of RT was a prognostic factor for LRR on multivariate analysis (together with pathologic stage) but not for DFS (independent parameters, pathologic stage and age). Preoperatively, on multivariate analysis, pathologic stage, but not delivery of RT, was an independent prognostic parameter for LRR and DFS (together with adequate chemotherapy). On multivariate analysis, the treatment center, treatment schedule (neoadjuvant vs. adjuvant RT), and gender were prognostic parameters for adequate RT. Conclusion: Delivery of RT should be regarded as a prognostic factor for LRR in rectal cancer and is influenced by the treatment center, treatment schedule, and patient gender.« less

Immunohistochemical analysis of PTEN, HER2/neu, and ki67 expression in patients with gastric cancer and their association with survival.

PubMed

Badary, Dalia M; Abdel-Wanis, Mostafa E; Hafez, Mohamed Z; Aboulhagag, Noha A

2017-06-01

Considering the poor prognosis of patients with gastric cancer, molecular diagnostic and prognostic markers for this cancer should be established. The aims of our study were to assess the correlations between PTEN, HER2/neu, and Ki67 expressions and clinicopathological factors of gastric cancer patients in upper Egypt, as well as their influence on OS and DFS. In this descriptive-analytic study, 42 patients with gastric carcinoma treated by postioerative chemoradiation between 2004 and 2014. Pathological review was done. Immunohistochemical staining and evaluation were performed. All the studied markers were significantly correlated with increased TNM stage. Her2/neu overexpression and positive Ki67 expression were significantly associated with histological grade. High percentage of positive Her2/neu and Ki67expression was found in gastric carcinoma tissue samples which lack PTEN expression. The one-year OS rate for the entire group (n=42) was 77.4%, whereas the DFS rate was 45%. Pathological T stage PTEN status significantly affected both OS (p=0.029 and 0.027 respectively) and DFS (p=0.006 and 0.012 respectively) rates. Multivariate Cox analyses showed that only pathological T stage was an independent prognostic factor affecting OS (P=0. 007, HR: 2.02; 95% CI: 1.2-3.38)and DFS(P<0.0001, HR: 2.69; 95% CI: 1.54-4.69). All the studied molecular markers, was significantly correlated with pathological T stage that significantly affected both OS and DFS rates. These findings indicate that these markers have an important role in gastric cancer growth and dissemination so these markers can be used as a prognostic biomarker. In addition, therapies targeting Her2 and PTEN may help develop novel therapeutics for gastric cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Suitability of human Tenon's fibroblasts as feeder cells for culturing human limbal epithelial stem cells.

PubMed

Scafetta, Gaia; Tricoli, Eleonora; Siciliano, Camilla; Napoletano, Chiara; Puca, Rosa; Vingolo, Enzo Maria; Cavallaro, Giuseppe; Polistena, Andrea; Frati, Giacomo; De Falco, Elena

2013-12-01

Corneal epithelial regeneration through ex vivo expansion of limbal stem cells (LSCs) on 3T3-J2 fibroblasts has revealed some limitations mainly due to the corneal microenvironment not being properly replicated, thus affecting long term results. Insights into the feeder cells that are used to expand LSCs and the mechanisms underlying the effects of human feeder cells have yet to be fully elucidated. We recently developed a standardized methodology to expand human Tenon's fibroblasts (TFs). Here we aimed to investigate whether TFs can be employed as feeder cells for LSCs, characterizing the phenotype of the co-cultures and assessing what human soluble factors are secreted. The hypothesis that TFs could be employed as alternative human feeder layer has not been explored yet. LSCs were isolated from superior limbus biopsies, co-cultured on TFs, 3T3-J2 or dermal fibroblasts (DFs), then analyzed by immunofluorescence (p63α), colony-forming efficiency (CFE) assay and qPCR for a panel of putative stem cell and epithelial corneal differentiation markers (KRT3). Co-cultures supernatants were screened for a set of soluble factors. Results showed that the percentage of p63α(+)LSCs co-cultured onto TFs was significantly higher than those on DFs (p = 0.032) and 3T3-J2 (p = 0.047). Interestingly, LSCs co-cultures on TFs exhibited both significantly higher CFE and mRNA expression levels of ΔNp63α than on 3T3-J2 and DFs (p < 0.0001), showing also significantly greater levels of soluble factors (IL-6, HGF, b-FGF, G-CSF, TGF-β3) than LSCs on DFs. Therefore, TFs could represent an alternative feeder layer to both 3T3-J2 and DFs, potentially providing a suitable microenvironment for LSCs culture.

[Disease-free survival related factors in breast cancer].

PubMed

Dávila-Arias, Cristina; Ocón, Olga; Fernández, Mariana F; Arrebola, Juan Pedro; Sánchez, María José; Aneiros, José; Torné, Pablo; Olea, Nicolás

2014-10-07

To evaluate the relationship between the clinical and pathological parameters of the primary tumor and disease-free survival (DFS) in a sample of hospital cases of invasive breast cancer. We performed a retrospective cohort study in 635 patients recruited at San Cecilio University Hospital in Granada (Spain) between 1994 and 2006. Information on the primary tumor and the outcomes of patients was collected by reviewing the medical records. Predictors of recurrence and/or metastasis and DFS (follow up of 3, 5 and 10 years) were analyzed by using Cox regression analysis. Multivariate models adjusted for age, tumor size, lymph nodal status, histological grade and estrogen and progesterone receptor expression showed a higher risk of recurrence and/or metastasis and lower DFS (adjusted relative risk, 95% confidence intervals) with tumor size (3 yrs: 3.00, 1.79-5.03; 5 yrs: 2.56, 1.65-3.98; 10 yrs: 2.16, 1.44-3.24), lymph nodal status (3 yrs: 4.58, 2.42-8.65; 5 yrs: 3.84, 2.35-6.30; 10 yrs: 3.08, 2.05-4.61), lymphovascular invasion (5 yrs: 1.88, 1.16-3.04; 10 yrs: 2.19, 1.43-3.35), multifocal and/or multicenter tumors (3 yrs: 2.69, 1.46-4.96; 5 yrs: 1.90, 1.08-3.35) and p53 protein expression (3 yrs: 2.03, 1.00-4.09). DFS was positively associated with an increased expression of progesterone receptor (3 yr: 0.48, 0.26-0.89; 5 yrs: 0.58, 0.35-0.97; 10 yrs: 0.59, 0.38-0.90). The biological characteristics of the primary tumor can be used to identify patients with distinctive prognoses and DFS, and could be helpful in making individual follow up strategies. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Lymphovascular invasion in clear cell renal cell carcinoma--association with disease-free and cancer-specific survival.

PubMed

Belsante, Michael; Darwish, Oussama; Youssef, Ramy; Bagrodia, Aditya; Kapur, Payal; Sagalowsky, Arthur I; Lotan, Yair; Margulis, Vitaly

2014-01-01

The objective is to evaluate the effect of lymphovascular invasion (LVI) on disease-free survival (DFS) and cancer-specific survival (CSS) in patients with clinically localized clear cell renal cell carcinoma (ccRCC). Patients with ccRCC who were treated surgically in 1997 to 2010 were identified. Retrospective chart review was performed to identify clinical outcomes. Independent pathologic re-review was performed by a single pathologist to confirm LVI status. Pathologic features were correlated with clinical outcomes using Kaplan-Meier and Cox regression analyses. Four hundred and nineteen patients with nonmetastatic ccRCC comprised the study cohort. Three hundred and thirty-three of these patients had an organ-confined (pT1-2, N any, and M0) disease. LVI was present in 14.3% of all nonmetastatic patients. In all patients with nonmetastatic ccRCC, presence of LVI was correlated with significantly shorter DFS (P <0.001) and CSS (P = 0.001) on Kaplan-Meier analysis. In cases of organ-confined, nonmetastatic ccRCC, presence of LVI was a significant predictor of DFS (hazard ratio = 4.0, P = 0.026) and CSS (hazard ratio = 12.7, P = 0.01) on multivariate analysis. Patients with organ-confined RCC who were LVI positive had similar DFS (P = 0.957) and CSS (P = 0.799) to patients with locally advanced tumors (pT3-pT4, N any, and M0) on Kaplan-Meier analysis. The presence of LVI is an independent predictor of both DFS and CSS in organ-confined, nonmetastatic ccRCC. LVI positivity in patients with otherwise pathologically organ-confined ccRCC confers oncologic outcomes similar to those of patients with locally advanced disease. If confirmed by others, future revisions to the tumor-node-metastasis staging system may incorporate LVI status into the prognostic algorithm of patients with RCC. Copyright © 2014 Elsevier Inc. All rights reserved.

Metabolic tumour volume and total lesion glycolysis, measured using preoperative 18F-FDG PET/CT, predict the recurrence of endometrial cancer.

PubMed

Shim, S-H; Kim, D-Y; Lee, D-Y; Lee, S-W; Park, J-Y; Lee, J J; Kim, J-H; Kim, Y-M; Kim, Y-T; Nam, J-H

2014-08-01

To investigate the prognostic value of metabolic tumour volume (MTV) and total lesion glycolysis (TLG), measured by preoperative positron emission tomography and computerised tomography (PET/CT), in women with endometrial cancer. Retrospective cohort study. A tertiary referral centre. Women with endometrial cancer who underwent preoperative (18)F-FDG PET/CT in the period 2004-2009. Clinicopathological data for 84 women with endometrial cancer were reviewed from medical records. Cox proportional hazards modelling identified recurrence predictors. The receiver operating characteristic (ROC) curve was used to determine the cut-off value for predicting recurrence. Disease-free survival (DFS). The number of patients with International Federation of Gynecology and Obstetrics (FIGO) stages were: I (58); II (11); III (13); and IV (2). The median DFS was 48 (1-85) months. By univariate analysis, DFS was significantly associated with FIGO stage, histology, peritoneal cytology, myometrial invasion, nodal metastasis, serum CA-125, MTV, and TLG. Using multivariate analysis, the MTV (P = 0.010; hazard ratio, HR = 1.010; 95% confidence interval, 95% CI = 1.002-1.018) and TLG (P = 0.024; HR = 1.001; 95% CI = 1.000-1.002) were associated with DFS. The area under the ROC curve was 0.679 (95% CI = 0.505-0.836) after discriminating for recurrence using an MTV cut-off value of 17.15 ml. Regarding TLG, the cut-off value was 56.43 g and the area under the ROC plot was 0.661 (95% CI = 0.501-0.827). Kaplan-Meier survival graphs demonstrated a significant difference in DFS between groups categorised using the cut-off values for MTV and TLG (P < 0.022 for MTV and P < 0.047 for TLG, by log-rank test). Preoperative MTV and TLG could be independent prognostic factors predicting the recurrence of endometrial cancer. © 2014 Royal College of Obstetricians and Gynaecologists.

PD-1 and PD-L1 expression in HNSCC primary cancer and related lymph node metastasis - impact on clinical outcome.

PubMed

Schneider, Sven; Kadletz, Lorenz; Wiebringhaus, Robert; Kenner, Lukas; Selzer, Edgar; Füreder, Thorsten; Rajky, Orsolya; Berghoff, Anna S; Preusser, Matthias; Heiduschka, Gregor

2018-05-09

Expression profiles and clinical impact of programmed cell death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) expressing tumour infiltrating lymphocytes (TILs) in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. This study evaluates expression patterns in primary HNSCC and related lymph node metastasis and impact on patients' clinical outcome. Immunohistochemical staining patterns of PD-L1 and PD-1 were evaluated in 129 specimens of primary HNSCC and 77 lymph node metastases. Results were correlated to patients' clinical data. PD-L1 expression was observed in 36% of primary carcinoma and 33% of lymph node metastasis and significantly correlates with decreased overall survival (OS) (p=0.01) and disease free survival (DFS) (p=0.001) in oral cavity squamous cell carcinoma patients. PD-L1 expression was associated with presence of lymph node metastasis (p=0.0223). Infiltration of PD-1 expressing lymphocytes significantly correlates with favorable OS (p=0.001) and DFS (p=0.001) in oropharyngeal cancer and hypopharyngeal cancer patients OS (p=0.007) and DFS (p=0.001). Presence of PD-1 TILs significantly correlates with better OS (p=0.005) and DFS (p=0) also in the HPV negative cohort. Cox regression multivariate analysis revealed PD-1 TIL expression as an independent prognostic marker for OS (p=0.004) and DFS (p=0.001) and T stage was validated as negative prognostic marker for OS (p=0.011). PD-1 expressing lymphocytes (p=0.0412) and PD-L1 expression (p=0.0022) patterns correlate significantly in primary cancers and matched lymph node metastases. Our results characterize the expression profiles of PD-1 axis proteins in HNSCC which might serve as possible clinical prognostic markers. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Is modern external beam radiotherapy with androgen deprivation therapy still a viable alternative for prostate cancer in an era of robotic surgery and brachytherapy: a comparison of Australian series.

PubMed

Wilcox, Shea William; Aherne, Noel J; McLachlan, Craig Steven; McKay, Michael J; Last, Andrew J; Shakespeare, Thomas P

2015-02-01

We compare the results of modern external-beam radiotherapy (EBRT), using combined androgen deprivation and dose-escalated intensity-modulated radiotherapy with MRI-CT fusion and daily image guidance with fiducial markers (DE-IG-IMRT), with recently published Australian series of brachytherapy and surgery. Five-year actuarial biochemical disease-free survival (bDFS), metastasis-free survival (MFS) and prostate cancer-specific survival (PCaSS) were calculated for 675 patients treated with DE-IG-IMRT and androgen deprivation therapy (ADT). Patients had intermediate-risk (IR) and high-risk (HR) disease. A search was conducted identifying Australian reports from 2005 onwards of IR and HR patients treated with surgery or brachytherapy, reporting actuarial outcomes at 3 years or later. With a median follow-up of 59 months, our 5-year bDFS was 93.3% overall: 95.5% for IR and 91.3% for HR disease. MFS was 96.9% overall (99.0% IR, 94.9% HR), and PCaSS was 98.8% overall (100% IR, 97.7% HR). Prevalence of Grade 2 genitourinary and gastrointestinal toxicity at 5 years was 1.3% and 1.6%, with 0.3% Grade 3 genitourinary toxicity and no Grade 3 gastrointestinal toxicity. Eight reports of brachytherapy and surgery were identified. The HDR brachytherapy series' median 5-year bDFS was 82.5%, MFS 90.0% and PCaSS 97.9%. One surgical series reported 5-year bDFS of 65.5% for HR patients. One LDR series reported 5-year bDFS of 85% for IR patients. Modern EBRT is at least as effective as modern Australian surgical and brachytherapy techniques. All patients considering treatment for localised prostate cancer should be referred to a radiation oncologist to discuss EBRT as an equivalent option. © 2015 The Royal Australian and New Zealand College of Radiologists.

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

Dinshaw, Ketayun A.; Budrukkar, Ashwini N.; Chinoy, Roshan F.

Purpose: The outcome of breast cancer treatment can vary in different geographic and ethnic groups. A multivariate analysis was performed for various prognostic factors in 1022 Indian women with pathologic Stage I-II breast cancer treated between 1980 and 2000 with standard breast-conserving therapy with or without systemic adjuvant therapy. Methods and Materials: At a mean follow-up of 53 months, the outcomes studied were local failure, locoregional failure, and distant failure, overall survival (OS), and disease-free survival (DFS). Results: The median pathologic tumor size was 3 cm (range, 1-5 cm), and axillary lymph node metastasis was present in 39% of women.more » The actuarial 5- and 10-year OS and DFS rate was 87% and 77% and 76% and 68%, respectively. Lymphovascular emboli or invasion (LVI) was the strongest independent adverse factor for all failure and survival (local failure, hazard ratio 2.85; 95% confidence interval, 1.68-4.83; OS; hazard ratio, 2.01, 95% confidence interval, 1.35-2.99). Lymph node metastasis was also an independent adverse factor for local failure, locoregional failure, distant failure, DFS, and OS (hazard ratio, 1.55, 95% confidence interval, 1.04-2.30). Age {<=}40 years increased the incidence of local recurrence, and patients with inner quadrant tumors had inferior DFS. The incidence of LVI was significantly greater in women with lymph node metastases than in node-negative women (p < 0.001) and in women with Grade 3 tumors than in those with Grade 1 or 2 tumors (p = 0.001). Conclusion: In Indian women, LVI was the strongest independent prognostic factor for OS, DFS, and local recurrence, irrespective of nodal status and systemic adjuvant treatment. Although LVI may not be a contraindication for BCT, as has been proposed by certain groups, it is necessary to define its role in prospective studies in determining local and systemic treatment.« less

The benefit of a sentinel lymph node biopsy and adjuvant therapy in thick (>4 mm) melanoma: multicenter, retrospective study of 291 Japanese patients.

PubMed

Fujisawa, Yasuhiro; Otsuka, Fujio

2012-10-01

The benefit of a sentinel lymph node (SLN) biopsy and adjuvant therapy for patients with thick (>4 mm) melanoma has not been well studied in the Asian population. We examined the benefit of an SLN biopsy and adjuvant therapy on prognosis in Japanese patients with thick melanoma. A review of the melanoma database collected from 26 institutions in Japan identified 291 patients with thick melanoma between 2005 and 2010. Univariate and multivariate analyses were performed to evaluate the factors predictive of the overall survival (OS) and the disease-free survival (DFS). Of the 242 patients with thick melanoma who underwent an SLN biopsy, the results for 96 (40%) were positive. On multivariate analysis, increased Breslow thickness (relative risk, 1.11; 95% confidence interval, 1.05-1.17; P=0.0002) and SLN metastasis (2.14; 1.04-4.43; P=0.040) were associated with a poor OS. Increased Breslow thickness (1.11; 1.04-1.18; P =0.0018), ulceration (3.11; 1.25-7.72; P=0.014), satellitosis (3.89; 1.62-9.31; P=0.0023), and SLN metastasis (2.24; 1.16-4.36; P=0.017) were associated with DFS. Adjuvant chemotherapy had no impact on either OS or DFS. Adjuvant use of a monthly dermal injection of interferon-β (IFN-β) was associated with a improvement in both OS (0.34; 0.17-0.67; P=0.0022) and DFS (0.42; 0.20-0.86; P=0.018). An SLN biopsy provided useful prognostic information and the adjuvant use of IFN-β improved both OS and DFS in Japanese patients with thick melanoma. These results were consistent with those of previous studies carried out on a white population. Therefore, we suggest that an SLN biopsy and adjuvant IFN should be considered for patients with thick melanoma irrespective of the Breslow thickness or ethnicity.

Improving estimation of kinetic parameters in dynamic force spectroscopy using cluster analysis

NASA Astrophysics Data System (ADS)

Yen, Chi-Fu; Sivasankar, Sanjeevi

2018-03-01

Dynamic Force Spectroscopy (DFS) is a widely used technique to characterize the dissociation kinetics and interaction energy landscape of receptor-ligand complexes with single-molecule resolution. In an Atomic Force Microscope (AFM)-based DFS experiment, receptor-ligand complexes, sandwiched between an AFM tip and substrate, are ruptured at different stress rates by varying the speed at which the AFM-tip and substrate are pulled away from each other. The rupture events are grouped according to their pulling speeds, and the mean force and loading rate of each group are calculated. These data are subsequently fit to established models, and energy landscape parameters such as the intrinsic off-rate (koff) and the width of the potential energy barrier (xβ) are extracted. However, due to large uncertainties in determining mean forces and loading rates of the groups, errors in the estimated koff and xβ can be substantial. Here, we demonstrate that the accuracy of fitted parameters in a DFS experiment can be dramatically improved by sorting rupture events into groups using cluster analysis instead of sorting them according to their pulling speeds. We test different clustering algorithms including Gaussian mixture, logistic regression, and K-means clustering, under conditions that closely mimic DFS experiments. Using Monte Carlo simulations, we benchmark the performance of these clustering algorithms over a wide range of koff and xβ, under different levels of thermal noise, and as a function of both the number of unbinding events and the number of pulling speeds. Our results demonstrate that cluster analysis, particularly K-means clustering, is very effective in improving the accuracy of parameter estimation, particularly when the number of unbinding events are limited and not well separated into distinct groups. Cluster analysis is easy to implement, and our performance benchmarks serve as a guide in choosing an appropriate method for DFS data analysis.

Chain Dynamics in Magnetorheological Suspensions

NASA Technical Reports Server (NTRS)

Gast, A. P.; Furst, E. M.

1999-01-01

Magnetorheological (MR) suspensions are composed of colloidal particles which acquire dipole moments when subjected to an external magnetic field. At sufficient field strengths and concentrations, the dipolar particles rapidly aggregate to form long chains. Subsequent lateral cross-linking of the dipolar chains is responsible for a rapid liquid-to-solid-like rheological transition. The unique, magnetically-activated rheological properties of MR suspensions make them ideal for interfacing mechanical systems to electronic controls. Additionally, the ability to experimentally probe colloidal suspensions interacting through tunable anisotropic potentials is of fundamental interest. Our current experimental work has focused on understanding the fluctuations of dipolar chains. It has been proposed by Halsey and Toor (HT) that the strong Landau-Peierls thermal fluctuations of dipolar chains could be responsible for long-range attractions between chains. Such interactions will govern the long-time relaxation of MR suspensions. We have synthesized monodisperse neutrally buoyant MR suspensions by density matching stabilized ferrofluid emulsion droplets with D2O. This allows us to probe the dynamics of the dipolar chains using light scattering without gravitational, interfacial, and polydispersity effects to resolve the short-wavelength dynamics of the dipolar chains. We used diffusing wave spectroscopy to measure these dynamics. The particle displacements at short times that show an independence to the field strength, but at long times exhibit a constrained, sub-diffusive motion that slows as the dipole strength is increased. The experiments are in good qualitative agreement with Brownian dynamics simulations of dipolar chains. Although there have been several important and detailed studies of the structure and interactions in MR suspensions, there has not been conclusive evidence that supports or contradicts the HT model prediction that long-range interactions exist between fluctuating chains of dipolar particles. Resolving this issue would contribute greatly to the understanding of these interesting and important materials. We have begun to test the predictions of the HT model by both examining the dynamics of individual chains and by measuring the forces between dipolar chains directly to accurately and quantitatively assess the interactions that they experience. To do so, we employ optical trapping techniques and video-microscopy to manipulate and observe our samples on the microscopic level. With these techniques, it is possible to observe chains that are fluctuating freely in three-dimensions, independent of interfacial effects. More importantly, we are able to controllably observe the interactions of two chains at various separations to measure the force-distance profile. The techniques also allow us to study the mechanical properties of individual chains and chain clusters. Our work to this point has focused on reversibly-formed dipolar chains due to field induced dipoles where the combination of this chaining, the dipolar forces, and the hydrodynamic interactions that dictate the rheology of the suspensions. One can envision, however, many situations where optical, electronic, or rheological behavior may be optimized with magneto-responsive anisotropic particles. Chains of polarizable particles may have the best properties as they can coil and flex in the absence of a field and stiffen and orient when a field is applied. We have recently demonstrated a synthesis of stable, permanent paramagnetic chains by both covalently and physically linking paramagnetic colloidal particles. The method employed allows us to create monodisperse chains of controlled length. We observed the stability, field-alignment, and rigidity of this new class of materials. The chains may exhibit unique rheological properties in an applied magnetic field over isotropic suspensions of paramagnetic particles. They are also useful rheological models as bead-spring systems. These chains form the basis for our current experiments with optical traps.

Entanglement dynamics of coupled qubits and a semi-decoherence free subspace

NASA Astrophysics Data System (ADS)

Campagnano, Gabriele; Hamma, Alioscia; Weiss, Ulrich

2010-01-01

We study the entanglement dynamics and relaxation properties of a system of two interacting qubits in the cases of (I) two independent bosonic baths and (II) one common bath. We find that in the case (II) the existence of a decoherence-free subspace (DFS) makes entanglement dynamics very rich. We show that when the system is initially in a state with a component in the DFS the relaxation time is surprisingly long, showing the existence of semi-decoherence free subspaces.

The Role of eIF4E Activity in Breast Cancer

DTIC Science & Technology

2010-08-01

marker with some success. Furthermore, eIF4E is an established target for cancer therapy [3] and clinical trials of the efficacy and safety of cancer...individual group was small, for overall survival (OS), disease-free survival (DFS) and disease- specific survival ( DSS ) (Figure 2). High eIF4E scores were...indicative of poor prognosis. Prognosis seemed to worsen with each increasing eIF4E score for OS, whereas patterns for DFS and DSS sug- gested weaker

Clinical outcome in patients with hepatocellular carcinoma after living-donor liver transplantation

PubMed Central

Choi, Ho Joong; Kim, Dong Goo; Na, Gun Hyung; Han, Jae Hyun; Hong, Tae Ho; You, Young Kyoung

2013-01-01

AIM: To investigate risk factors for hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT) and efficacy of various criteria. METHODS: From October 2000 to November 2011, 233 adult patients underwent LDLT for HCC at our institution. After excluding nine postoperative mortality cases, we analyzed retrospectively 224 patients. To identify risk factors for recurrence, we evaluated recurrence, disease-free survival (DFS) rate, survival rate, and various other factors which are based on the characteristics of both the patient and tumor. Additionally, we developed our own criteria based on our data. Next, we compared our selection criteria with various tumor-grading scales, such as the Milan criteria, University of California, San Francisco (UCSF) criteria, TNM stage, Barcelona Clinic Liver Cancer (BCLC) stage and Cancer of the Liver Italian Program (CLIP) scoring system. The median follow up was 68 (6-139) mo. RESULTS: In 224 patients who received LDLT for HCC, 37 (16.5%) experienced tumor recurrence during the follow-up period. The 5-year DFS and overall survival rates after LDLT in all patients with HCC were 80.9% and 76.4%, respectively. On multivariate analysis, the tumor diameter {5 cm; P < 0.001; exponentiation of the B coefficient [Exp(B)], 11.89; 95%CI: 3.784-37.368} and alpha fetoprotein level [AFP, 100 ng/mL; P = 0.021; Exp(B), 2.892; 95%CI: 1.172-7.132] had significant influences on HCC recurrence after LDLT. Therefore, these two factors were included in our criteria. Based on these data, we set our selection criteria as a tumor diameter ≤ 5 cm and AFP ≤ 100 ng/mL. Within our new criteria (140/214, 65.4%), the 5-year DFS and overall survival rates were 88.6% and 81.8%, respectively. Our criteria (P = 0.001), Milan criteria (P = 0.009), and UCSF criteria (P = 0.001) showed a significant difference in DFS rate. And our criteria (P = 0.006) and UCSF criteria (P = 0.009) showed a significant difference in overall survival rate. But Milan criteria did not show significant difference in overall survival rate (P = 0.137). Among stages 0, A, B and C of BCLC, stage C had a significantly higher recurrence rate (P = 0.001), lower DFS (P = 0.001), and overall survival rate (P = 0.005) compared with the other stages. Using the CLIP scoring system, the group with a score of 4 to 5 showed a high recurrence rate (P = 0.023) and lower DFS (P = 0.011); however, the overall survival rate did not differ from that of the lower scoring group. The TNM system showed a trend of increased recurrence rate, decreased DFS, or survival rate according to T stage, albeit without statistical significance. CONCLUSION: LDLT is considered the preferred therapeutic option in patients with an AFP level less than 100 ng/mL and a tumor diameter of less than 5 cm. PMID:23922471

Dipolar ferromagnetic phase transition in Fe3O4 nanoparticle arrays observed by Lorentz microscopy and electron holography

NASA Astrophysics Data System (ADS)

Yamamoto, Kazuo; Hogg, Charles R.; Yamamuro, Saeki; Hirayama, Tsukasa; Majetich, Sara A.

2011-02-01

Dipolar ferromagnetism formed in Fe3O4 nanoparticle arrays is revealed by Fresnel Lorentz microscopy and electron holography. Dipolar domain walls do not lie preferentially along macrograin boundaries but depend on the overall shape of the assembly, meaning magnetostatic energy dominates. The domain structures are imaged at different temperatures for both monolayer and bilayer arrays. The domain wall contrast in the monolayer region is visible until 575 °C, and the magnetic order parameter steeply drops toward the temperature. In the bilayer region, finer and more complicated domains are formed.

Dipolar particles in a double-trap confinement: Response to tilting the dipolar orientation

NASA Astrophysics Data System (ADS)

Bjerlin, J.; Bengtsson, J.; Deuretzbacher, F.; Kristinsdóttir, L. H.; Reimann, S. M.

2018-02-01

We analyze the microscopic few-body properties of dipolar particles confined in two parallel quasi-one-dimensional harmonic traps. In particular, we show that an adiabatic rotation of the dipole orientation about the trap axes can drive an initially nonlocalized few-fermion state into a localized state with strong intertrap pairing. With an instant, nonadiabatic rotation, however, localization is inhibited and a highly excited state is reached. This state may be interpreted as the few-body analog of a super-Tonks-Girardeau state, known from one-dimensional systems with contact interactions.

Gas-liquid coexistence in a system of dipolar soft spheres.

PubMed

Jia, Ran; Braun, Heiko; Hentschke, Reinhard

2010-12-01

The existence of gas-liquid coexistence in dipolar fluids with no other contribution to attractive interaction than dipole-dipole interaction is a basic and open question in the theory of fluids. Here we compute the gas-liquid critical point in a system of dipolar soft spheres subject to an external electric field using molecular dynamics computer simulation. Tracking the critical point as the field strength is approaching zero we find the following limiting values: T(c)=0.063 and ρ(c)=0.0033 (dipole moment μ=1). These values are confirmed by independent simulation at zero field strength.

Ground-state candidate for the classical dipolar kagome Ising antiferromagnet

NASA Astrophysics Data System (ADS)

Chioar, I. A.; Rougemaille, N.; Canals, B.

2016-06-01

We have investigated the low-temperature thermodynamic properties of the classical dipolar kagome Ising antiferromagnet using Monte Carlo simulations, in the quest for the ground-state manifold. In spite of the limitations of a single-spin-flip approach, we managed to identify certain ordering patterns in the low-temperature regime and we propose a candidate for this unknown state. This configuration presents some intriguing features and is fully compatible with the extrapolations of the at-equilibrium thermodynamic behavior sampled so far, making it a very likely choice for the dipolar long-range ordered state of the classical kagome Ising antiferromagnet.

Spin coherence in a Mn3 single-molecule magnet

NASA Astrophysics Data System (ADS)

Abeywardana, Chathuranga; Mowson, Andrew M.; Christou, George; Takahashi, Susumu

2016-01-01

Spin coherence in single crystals of the spin S = 6 single-molecule magnet (SMM) [Mn3O(O2CEt)3(mpko)3]+ (abbreviated Mn3) has been investigated using 230 GHz electron paramagnetic resonance spectroscopy. Coherence in Mn3 was uncovered by significantly suppressing dipolar contribution to the decoherence with complete spin polarization of Mn3 SMMs. The temperature dependence of spin decoherence time (T2) revealed that the dipolar decoherence is the dominant source of decoherence in Mn3 and T2 can be extended up to 267 ns by quenching the dipolar decoherence.

STRUCTURAL ESTIMATES OF TREATMENT EFFECTS ON OUTCOMES USING RETROSPECTIVE DATA: AN APPLICATION TO DUCTAL CARCINOMA IN SITU

PubMed Central

Gold, Heather Taffet; Sorbero, Melony E. S.; Griggs, Jennifer J.; Do, Huong T.; Dick, Andrew W.

2013-01-01

Analysis of observational cohort data is subject to bias from unobservable risk selection. We compared econometric models and treatment effectiveness estimates using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare claims data for women diagnosed with ductal carcinoma in situ. Treatment effectiveness estimates for mastectomy and breast conserving surgery (BCS) with or without radiotherapy were compared using three different models: simultaneous-equations model, discrete-time survival model with unobserved heterogeneity (frailty), and proportional hazards model. Overall trends in disease-free survival (DFS), or time to first subsequent breast event, by treatment are similar regardless of the model, with mastectomy yielding the highest DFS over 8 years of follow-up, followed by BCS with radiotherapy, and then BCS alone. Absolute rates and direction of bias varied substantially by treatment strategy. DFS was underestimated by single-equation and frailty models compared to the simultaneous-equations model and RCT results for BCS with RT and overestimated for BCS alone. PMID:21602195

[EFFICACY OF CYTOFLAVIN IN COMPLEX TREATMENT OF DIABETIC FOOT SYNDROME].

PubMed

Skrypko, V; Kovalenko, A; Zaplutanov, V; Kharitonova, T; Myhaloyko, I

2017-04-01

The study involved 97 patients with severe diabetic foot syndrome (DFS) subcompensated type 2 diabetes. All patients were available mediacalcification foot and lower leg arteries of different severity. Depending on the treatment, all patients were divided into 2 groups by stratified randomization. The І group received standard therapy, which is indicated for the DFS. A ІІ group of patients additionally received basic therapy drug Cytoflavin 10 ml 0,9% NaCl 200 ml for 10 days, followed by transfer to tablet form Cytoflavin 2 tablets 2 times per day orally for one month. We noted a positive trend of treatment of patients who, in addition to standard therapy received the drug Cytoflavin. Thus, the use of complex surgical treatment of patients with mixed form of DFS Cytoflavin reduces the severity of distal polyneuropathy, improves oxygenation of tissues and restores the enzyme activity of antioxidant system, that manifested neuroprotective, antioxidant and anti-hypoxic effects of drugs, which substantiates the indications for its use in the this pathology.

Clinical value of Xenopus kinesin-like protein 2 as a prognostic marker in patients with digestive system cancers: a systematic review and meta-analysis.

PubMed

Wang, Gang; Wang, Qian; Li, Zhengyan; Liu, Chaoxu; He, Xianli

2018-01-01

Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein that plays an important role in spindle assembly and dynamics. However, the clinical and prognostic value of TPX2 in the digestive system cancers remains unclear. The objective of this review was to evaluate the association of TPX2 expression with disease-free survival (DFS), overall survival (OS), and clinicopathological features of digestive system cancers. The software Stata 12.0 was used to analyze the outcomes, including OS, disease-free survival (DFS), and clinicopathological characteristics. A total of 10 eligible studies with 906 patients were included. Elevated TPX2 expression was significantly associated with poor DFS (pooled hazard ratio [HR] =2.48, 95% confidence interval [CI]: 1.96-3.13) and OS (pooled HR =2.66, 95% CI: 2.04-3.48) of digestive system malignancies. Subgroup analyses showed that cancer type, sample size, study quality, and laboratory detection methods did not alter the significant prognostic value of TPX2. Additionally, TPX2 expression was found to be an independent predictive factor for DFS (HR =2.31, 95% CI: 1.78-3.01). TPX2 expression might be associated with TNM stage and pathological grade in digestive system cancer. In conclusion, TPX2 is an independent prognostic factor for survival of patients with digestive system cancer. Furthermore, its overexpression is associated with TNM stage and pathological grade in digestive system cancer.

Clinical value of Xenopus kinesin-like protein 2 as a prognostic marker in patients with digestive system cancers: a systematic review and meta-analysis

PubMed Central

Liu, Chaoxu; He, Xianli

2018-01-01

Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein that plays an important role in spindle assembly and dynamics. However, the clinical and prognostic value of TPX2 in the digestive system cancers remains unclear. The objective of this review was to evaluate the association of TPX2 expression with disease-free survival (DFS), overall survival (OS), and clinicopathological features of digestive system cancers. The software Stata 12.0 was used to analyze the outcomes, including OS, disease-free survival (DFS), and clinicopathological characteristics. A total of 10 eligible studies with 906 patients were included. Elevated TPX2 expression was significantly associated with poor DFS (pooled hazard ratio [HR] =2.48, 95% confidence interval [CI]: 1.96–3.13) and OS (pooled HR =2.66, 95% CI: 2.04–3.48) of digestive system malignancies. Subgroup analyses showed that cancer type, sample size, study quality, and laboratory detection methods did not alter the significant prognostic value of TPX2. Additionally, TPX2 expression was found to be an independent predictive factor for DFS (HR =2.31, 95% CI: 1.78–3.01). TPX2 expression might be associated with TNM stage and pathological grade in digestive system cancer. In conclusion, TPX2 is an independent prognostic factor for survival of patients with digestive system cancer. Furthermore, its overexpression is associated with TNM stage and pathological grade in digestive system cancer. PMID:29551902

Correlation of High-Risk Soft Tissue Sarcoma Biomarker Expression Patterns with Outcome following Neoadjuvant Chemoradiation

PubMed Central

Magliocco, Anthony; Zhang, Qiang; Wang, Dian; Klimowicz, Alex; Harris, Jonathan; Simko, Jeff; DeLaney, Thomas; Kraybill, William; Kirsch, David G.

2018-01-01

Background Sarcoma mortality remains high despite adjuvant chemotherapy. Biomarker predictors of treatment response and outcome could improve treatment selection. Methods Tissue microarrays (TMAs) were created using pre- and posttreatment tumor from two prospective trials (MGH pilot and RTOG 9514) of neoadjuvant/adjuvant MAID chemotherapy and preoperative radiation. Biomarkers were measured using automated computerized imaging (AQUA or ACIS). Expression was correlated with disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). Results Specimens from 60 patients included 23 pretreatment (PRE), 40 posttreatment (POST), and 12 matched pairs (MPs). In the MP set, CAIX, GLUT1, and PARP1 expression significantly decreased following neoadjuvant therapy, but p53 nuclear/cytoplasmic (N/C) ratio increased. In the PRE set, no biomarker expression was associated with DFS, DDFS, or OS. In the POST set, increased p53 N/C ratio was associated with a significantly decreased DFS and DDFS (HR 4.13, p=0.017; HR 4.16, p=0.016), while increased ERCC1 and XPF expression were associated with an improved DFS and DDFS. No POST biomarkers were associated with OS. Conclusions PRE biomarker expression did not predict survival outcomes. Expression pattern changes after neoadjuvant chemoradiation supports the concepts of tumor reoxygenation, altered HIF-1α signaling, and a p53 nuclear accumulation DNA damage response. Clinical Trial Registration NRG Oncology RTOG 9514 is registered with ClinicalTrials.gov. The ClinicalTrials.gov Identifier is NCT00002791. PMID:29681762

Adjuvant sequential chemo and radiotherapy improves the oncological outcome in high risk endometrial cancer

PubMed Central

Signorelli, Mauro; Lissoni, Andrea Alberto; De Ponti, Elena; Grassi, Tommaso; Ponti, Serena

2015-01-01

Objective Evaluation of the impact of sequential chemoradiotherapy in high risk endometrial cancer (EC). Methods Two hundred fifty-four women with stage IB grade 3, II and III EC (2009 FIGO staging), were included in this retrospective study. Results Stage I, II, and III was 24%, 28.7%, and 47.3%, respectively. Grade 3 tumor was 53.2% and 71.3% had deep myometrial invasion. One hundred sixty-five women (65%) underwent pelvic (+/- aortic) lymphadenectomy and 58 (22.8%) had nodal metastases. Ninety-eight women (38.6%) underwent radiotherapy, 59 (23.2%) chemotherapy, 42 (16.5%) sequential chemoradiotherapy, and 55 (21.7%) were only observed. After a median follow-up of 101 months, 78 women (30.7%) relapsed and 91 women (35.8%) died. Sequential chemoradiotherapy improved survival rates in women who did not undergo nodal evaluation (disease-free survival [DFS], p=0.040; overall survival [OS], p=0.024) or pelvic (+/- aortic) lymphadenectomy (DFS, p=0.008; OS, p=0.021). Sequential chemoradiotherapy improved both DFS (p=0.015) and OS (p=0.014) in stage III, while only a trend was found for DFS (p=0.210) and OS (p=0.102) in stage I-II EC. In the multivariate analysis, only age (≤65 years) and sequential chemoradiotherapy were statistically related to the prognosis. Conclusion Sequential chemoradiotherapy improves survival rates in high risk EC compared with chemotherapy or radiotherapy alone, in particular in stage III. PMID:26197768

Xp11.2 Translocation renal cell carcinomas have a poorer prognosis than non-Xp11.2 translocation carcinomas in children and young adults: a meta-analysis.

PubMed

Qiu Rao; Bing Guan; Zhou, Xiao-jun

2010-12-01

Renal cell carcinomas (RCCs) in children and adolescents are much rarer than in adults. In this age group, Xp11.2 translocation RCCs were the most common subtype of pediatric RCCs. Information regarding the clinical behavior of pediatric RCCs remains controversial because of their relatively rare incidence. The authors aimed to perform a systematic review and meta-analysis to better define the biological features of pediatric RCCs. Eligible studies were identified through multiple search strategies. Studies were assessed for quality using the Jadad Quality Scale. Data were collected comparing overall survival (OS), disease-free survival (DFS), and stage in patients with TFE3 + pediatric RCCs and TFE3 - RCCs. A total of 4 studies were included for meta-analysis, and pooled odds ratios (ORs) with 95% confidence interval (CI) were calculated. The meta-analysis outcomes showed that TFE3 + pediatric RCCs were significantly associated with poorer outcomes (OS and DFS) and a higher stage (III/IV) than TFE3 - RCCs (pooled ORs for each group: 4.59 [95% CI = 1.46-14.42] for OS; 5.79 [95% CI = 1.85-18.16] for DFS; and 5.89 [95% CI = 2.23-15.52] for stage). This result was also confirmed by OS and DFS curves (P = .005 and P = .001). Xp11.2 translocation carcinomas appear to have a poorer prognosis than non-Xp11.2 translocation carcinomas in children and young adults.

Hypoxic volume evaluated by 18F-fluoromisonidazole positron emission tomography (FMISO-PET) may be a prognostic factor in patients with oral squamous cell carcinoma: preliminary analyses.

PubMed

Sato, J; Kitagawa, Y; Watanabe, S; Asaka, T; Ohga, N; Hirata, K; Shiga, T; Satoh, A; Tamaki, N

2018-05-01

Tumour hypoxia can be detected by 18 F-fluoromisonidazole positron emission tomography (FMISO-PET). Few studies have assessed the relationships of new PET parameters, including hypoxic volume (HV), metabolic tumour volume (MTV), and total lesion glycolysis (TLG), with 5-year survival of patients treated surgically for oral squamous cell carcinoma (OSCC). This study evaluated the relationships between these PET parameters and 5-year survival in OSCC patients. Twenty-three patients (age 42-84 years; 15 male, eight female) with OSCC underwent FMISO- and 18 F-fluoro-2-deoxyglucose (FDG)-PET computed tomography before surgery. All of them underwent radical surgery and were followed up for more than 5 years. The FDG-PET maximum standardized uptake value (SUV max ), HV, MTV, and TLG were measured. The ability of PET parameters to predict disease-free survival (DFS) and loco-regional recurrence (LR) was evaluated using receiver operating characteristic curve analysis. During the follow-up period, five of the 23 patients (22%) died and six (26%) experienced LR. Although FDG-PET SUV max was not significantly associated with DFS or LR, HV correlated significantly with both DFS and LR. TLG, but not MTV, was significantly associated with DFS; however neither MTV nor TLG was related significantly to LR. In conclusion, tumour HV may predict outcomes in patients with OSCC. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

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

Barral, M., E-mail: matthias-barral@yahoo.fr; Auperin, A., E-mail: anne.auperin@gustaveroussy.fr; Hakime, A., E-mail: thakime@yahoo.com

ObjectiveTo evaluate prognostic factors associated with local control and disease-free-survival (DFS) of oligometastatic breast cancer patients treated by percutaneous thermal ablation (PTA).Materials and MethodsSeventy-nine consecutive patients (54.5 ± 11.2 years old) with 114 breast cancer metastases (28.9 ± 16.1 mm in diameter), involving the lungs, the liver, and/or the bone, were treated using PTA with a curative intent. The goal was to achieve a complete remission in association with systemic chemotherapy and hormonal therapy. We retrospectively evaluated the prognostic factors associated with 1- and 2-year local control and the 1- and 2-year DFS rates.ResultsThe 1- and 2-year local control rates were 83.0 and 76.1 %, respectively. Tumormore » burden was associated with a poorer outcome for local control after PTA (HR 1.027 by additional millimeter, p = 0.026; >4 cm HR 3.90). The 1- and 2-year DFS rates were 54.2 and 30.4 %, respectively. In multivariate analysis, triple-negative histological subtype and increased size of treated metastases were associated with a poorer DFS (HR 2.22; 95 % CI [1.13–4.36]; p = 0.02 and HR 2.43; 95 % CI [1.22–4.82]; p = 0.011, respectively).ConclusionPTA is effective for local control of breast cancer oligometastases. Tumor burden >4 cm and triple-negative histological subtype are associated with a poorer outcome.« less

Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy

PubMed Central

Wang, H. M.; Liao, Z. X.; Komaki, R.; Welsh, J. W.; O'Reilly, M. S.; Chang, J. Y.; Zhuang, Y.; Levy, L. B.; Lu, C.; Gomez, D. R.

2013-01-01

Background Preclinical studies have shown that norepinephrine can directly stimulate tumor cell migration and that this effect is mediated by the beta-adrenergic receptor. Patients and methods We retrospectively reviewed 722 patients with non-small-cell lung cancer (NSCLC) who received definitive radiotherapy (RT). A Cox proportional hazard model was utilized to determine the association between beta-blocker intake and locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). Results In univariate analysis, patients taking beta-blockers (n = 155) had improved DMFS (P < 0.01), DFS (P < 0.01), and OS (P = 0.01), but not LRPFS (P = 0.33) compared with patients not taking beta-blockers (n = 567). In multivariate analysis, beta-blocker intake was associated with a significantly better DMFS [hazard ratio (HR), 0.67; P = 0.01], DFS (HR, 0.74; P = 0.02), and OS (HR, 0.78; P = 0.02) with adjustment for age, Karnofsky performance score, stage, histology type, concurrent chemotherapy, radiation dose, gross tumor volume, hypertension, chronic obstructive pulmonary disease and the use of aspirin. There was no association of beta-blocker use with LRPFS (HR = 0.91, P = 0.63). Conclusion Beta-blocker use is associated with improved DMFS, DFS, and OS in this large cohort of NSCLC patients. Future prospective trials can validate these retrospective findings and determine whether the length and timing of beta-blocker use influence survival outcomes. PMID:23300016

Prognostic value of endoglin-assessed microvessel density in cancer patients: a systematic review and meta-analysis

PubMed Central

Zhang, Jinguo; Zhang, Lingyun; Lin, Qunbo; Ren, Weimin; Xu, Guoxiong

2018-01-01

Background Endoglin (ENG, CD105), an auxiliary receptor for several TGF-β superfamily ligands, is constitutively expressed in tumor microvessels. The prognostic value of ENG-assessed microvessel density (MVD) has not been systemically analyzed. This meta-analysis reviews and evaluates the association between ENG expression and prognosis in cancer patients. Materials and Methods Thirty published studies involving in 3613 patients were included after searching of PubMed, Web of Science, and EMBASE. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) were calculated using random-effects models. The publication bias was detected by a Begg’s test and Egger’s test. The outcome stability was verified by sensitivity analysis. Results The high ENG-assessed MVD was significantly associated with poor OS (HR = 2.14, 95% CI 1.62–2.81; P < 0.001), DFS (HR = 3.23, 95% CI 2.10–4.95; P < 0.001), CSS (HR = 3.33, 95% CI 1.32–8.37; P < 0.001). Furthermore, subgroup analysis revealed that the association between the overexpression of ENG in tumor microvessels and the outcome endpoints (OS or DFS) were also significant in the Asians and Caucasians patients with different cancer types. Conclusions ENG of tumor microvessels is a predictor of poor OS, DFS and CSS and may be a prognostic marker of patients with cancer. PMID:29484142

Adjuvant Gemcitabine and Gemcitabine-based Chemoradiotherapy Versus Gemcitabine Alone After Pancreatic Cancer Resection: The Indiana University Experience.

PubMed

Khawaja, Muhammad R; Kleyman, Svetlana; Yu, Zhangsheng; Howard, Thomas; Burns, Matthew; Nakeeb, Attila; Loehrer, Patrick J; Cardenes, Higinia R; Chiorean, Elena Gabriela

2017-02-01

Adjuvant therapy after surgical resection is the current standard for pancreatic adenocarcinoma; however, the role of chemoradiotherapy (CRT) remains unclear. This study was conducted to compare the efficacy outcomes with adjuvant gemcitabine and gemcitabine-based CRT (CT-CRT) versus gemcitabine chemotherapy (CT) alone after pancreaticoduodenectomy. Among 165 patients who underwent surgical resection for pancreatic cancer at Indiana University Medical Center between 2004 and 2008, we retrospectively identified 53 consecutive patients who received adjuvant therapy (CT-CRT=34 patients; CT=19 patients) and had adequate follow-up medical records. The median follow-up was 19.1 months. Median disease-free (DFS) and overall survival (OS) were determined using Kaplan-Meier method, and a Cox-regression model was used to compare survival outcomes after adjusting for age, status of resection margins, and lymph node involvement. The OS for the CT-CRT group was significantly higher compared with the CT group (median, 20.4 vs. 16.6 mo; hazard ratio, 2.42; 95% CI, 1.17-5.01). The median DFS for the CT-CRT group was 13.7 versus 11.1 months for the CT group (hazard ratio, 2.88; 95% CI, 1.37-6.06). On subgroup analyses, significantly superior OS and DFS were observed among patients younger than 65 years, T3/T4 tumor stage, negative resection margins, and positive lymph node involvement. Gemcitabine plus gemcitabine-based CRT compared with gemcitabine alone leads to superior DFS and OS for patients with resected pancreatic cancer.

Van Allen Probes observations of magnetic field dipolarization and its associated O + flux variations in the inner magnetosphere at L<6.6: Dipolarization in Inner Magnetosphere

DOE PAGES

Nosé, M.; Keika, K.; Kletzing, C. A.; ...

2016-07-20

Here we investigate the magnetic field dipolarization in the inner magnetosphere and its associated ion flux variations, using the magnetic field and energetic ion flux data acquired by the Van Allen Probes. From a study of 74 events that appeared at L=4.5–6.6 between 1 October 2012 and 31 October 2013, we reveal the following characteristics of the dipolarization in the inner magnetosphere: (1) its time scale is approximately 5 min; (2) it is accompanied by strong magnetic fluctuations that have a dominant frequency close to the O + gyrofrequency; (3) ion fluxes at 20–50 keV are simultaneously enhanced with largermore » magnitudes for O + than for H +; (4) after a few minutes of the dipolarization, the flux enhancement at 0.1–5keV appears with a clear energy-dispersion signature only for O +; and (5) the energy-dispersed O + flux enhancement appears in directions parallel or antiparallel to the magnetic field. From these characteristics, we discuss possible mechanisms that can provide selective acceleration to O + ions at >20keV. We conclude that O + ions at L = 5.4–6.6 undergo nonadiabatic local acceleration caused by oscillating electric field associated with the magnetic fluctuations and/or adiabatic convective transport from the plasma sheet to the inner magnetosphere by the impulsive electric field. At L = 4.5–5.4, however, only the former acceleration is plausible. Finally, we also conclude that the field-aligned energy-dispersed O + ions at 0.1–5 keV originate from the ionosphere and are extracted nearly simultaneously to the onset of the dipolarization.« less

Van Allen Probes observations of magnetic field dipolarization and its associated O + flux variations in the inner magnetosphere at L<6.6: Dipolarization in Inner Magnetosphere

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

Nosé, M.; Keika, K.; Kletzing, C. A.

Here we investigate the magnetic field dipolarization in the inner magnetosphere and its associated ion flux variations, using the magnetic field and energetic ion flux data acquired by the Van Allen Probes. From a study of 74 events that appeared at L=4.5–6.6 between 1 October 2012 and 31 October 2013, we reveal the following characteristics of the dipolarization in the inner magnetosphere: (1) its time scale is approximately 5 min; (2) it is accompanied by strong magnetic fluctuations that have a dominant frequency close to the O + gyrofrequency; (3) ion fluxes at 20–50 keV are simultaneously enhanced with largermore » magnitudes for O + than for H +; (4) after a few minutes of the dipolarization, the flux enhancement at 0.1–5keV appears with a clear energy-dispersion signature only for O +; and (5) the energy-dispersed O + flux enhancement appears in directions parallel or antiparallel to the magnetic field. From these characteristics, we discuss possible mechanisms that can provide selective acceleration to O + ions at >20keV. We conclude that O + ions at L = 5.4–6.6 undergo nonadiabatic local acceleration caused by oscillating electric field associated with the magnetic fluctuations and/or adiabatic convective transport from the plasma sheet to the inner magnetosphere by the impulsive electric field. At L = 4.5–5.4, however, only the former acceleration is plausible. Finally, we also conclude that the field-aligned energy-dispersed O + ions at 0.1–5 keV originate from the ionosphere and are extracted nearly simultaneously to the onset of the dipolarization.« less

Influence of anisotropic dipolar interaction on the spin dynamics of Ni80Fe20 nanodot arrays arranged in honeycomb and octagonal lattices

NASA Astrophysics Data System (ADS)

Mondal, Sucheta; Barman, Saswati; Choudhury, Samiran; Otani, Yoshichika; Barman, Anjan

2018-07-01

Ultrafast spin dynamics in ferromagnetic nanodot arrays with dot diameter 100 nm and thickness 20 nm arranged in honeycomb and octagonal lattice symmetries are studied to explore the tunability of the collective magnetization dynamics. By varying the inter-dot separation between 30 nm and 300 nm drastic variation in the precessional dynamics from strongly collective to completely isolated regime has been observed by using all-optical time-resolved magneto-optical Kerr microscope. Micromagnetic simulation is exploited to gain insights about the resonant mode profiles and magnetic coupling between the nanodots. A significant spectral and spatial variation in the resonant mode with increasing dipolar interaction is demonstrated with increasing inter-dot separation. The spins driven by effective field inside single nanodots are prone to precess independently, generating two self-standing centre and edge modes in the array that are influenced by the relative orientation between the inter-dot coupling direction and bias magnetic field. The anisotropic behavior of dipolar field is rigorously investigated here. Splitting of the centre mode in case of octagonal lattice is experimentally observed here as a consequence of the anisotropic dipolar field between the nanodot pairs coupled horizontally and vertically, which is not found in the honeycomb lattice. In addition, proper understanding of the modification of dynamic mode profile by neighboring dipolar interaction built up here, is imperative for further control of the dynamic dipolar interaction and the corresponding collective excitation in magnonic crystals. The usage of nanodot lattices with complex basis structures can be advantageous for the designing of high density magnetic recording media, spin-wave filter and logic devices.

Potential application of a triaxial three-dimensional fabric (3-DF) as an implant.

PubMed

Shikinami, Y; Kawarada, H

1998-01-01

Various three-dimensional fabrics (3-DFs) woven with a triaxial three-dimensional (3A-3D) structure in which the warps, wefts and vertical fibres are three-dimensionally orientated with orthogonal, off-angle, cylindrical or complex fibre alignments using a single long fibre, which may be one of several kinds of fibres, have been developed. The physical strengths and behaviour of these fabrics under different external forces were measured for such stress-strain relationships as compressive, tensile and cyclic bending, compressing torsional and compressive tensile systems to evaluate the effect of the continuous loading caused by living body movements over a long period of time. The 3-DFs led to downward convex 'J'-shaped curves in stress-strain profiles, because they were markedly flexible at low strain levels, but became rigid as strain increased. In this behaviour they reflected the behaviour of natural cartilage rather than that of conventional artificial biomaterials. There were also some 3-DFs that showed hysteresis loss curves with quite similar mechanical strengths and behaviour to natural intervertebral discs with regard to the compressive-tensile cyclic stress and showed little variation from the first 'J'-shaped hysteresis profile even after 100,000 deformation cycles. Accordingly, it has been shown that, without a doubt, 3-DFs can be effective implants possessing both design and mechanical biocompatibilities as well as the durability necessary for long-term implantation in the living body. The surface of bioinert linear low-density polyethylene coating on multifilaments of ultra-high molecular weight polyethylene, a constructional fibre of 3A-3D weaving, was modified by treatment with corona-discharge and spray-coating of unsintered hydroxyapatite powder to impart chemical (surface) compatibility and biological activity, respectively. Since the modified surface of the 3-DF was ascertained to have affinity and activity with simulated body fluid, an orthogonal 3-DF block was implanted in the tibia of a rabbit. Sufficient surrounding tissues entering into the textural space of the 3-DF could be observed at 4 weeks after implantation and the load necessary to break the block away from the bone reached a high value at 8 weeks. These results decisively showed that the 3-DFs could also acquire chemical (surface) and biological biocompatibilities and bonding capacity with bone and soft tissues through modification of the surface of the constructional fibre. The 3-DFs have definite potential in such applications as novel and effective artificial articular cartilages, intervertebral discs, menisci and materials for osteosynthesis and prosthesis, and the like.

Dipolarization in the inner magnetosphere during a geomagnetic storm on 7 October 2015

NASA Astrophysics Data System (ADS)

Matsui, H.; Erickson, P. J.; Foster, J. C.; Torbert, R. B.; Argall, M. R.; Anderson, B. J.; Blake, J. B.; Cohen, I. J.; Ergun, R.; Farrugia, C. J.; Khotyaintsev, Y. V.; Korth, H.; Lindqvist, P. A.; Magnes, W.; Marklund, G. T.; Mauk, B.; Paulson, K. W.; Russell, C.; Strangeway, R. J.; Turner, D. L.

2016-12-01

A dipolarization event was observed by the Magnetospheric Multiscale (MMS) spacecraft at L=3.8 and 19.8 magnetic local time (MLT) starting at 23:42:36 UT on 7 October 2015. The magnetic and electric fields showed initially coherent variations between the spacecraft. The sunward convection turned tailward after the dipolarization. The observation is interpreted in terms of the pressure balance or the momentum equation. This was followed by a region traversed where the fields were irregular. The scale length was of the order of the ion gyroradius, suggesting the kinetic nature of the fluctuations. Combination of the multi-instrument, multi-spacecraft data reveals a more detailed picture of the dipolarization event in the inner magnetosphere. Conjunction ionosphere-plasmasphere observations from DMSP, two-dimensional GPS TEC, the Millstone Hill mid-latitude incoherent scatter radar, and AMPERE measurements imply that MMS observations are located on the poleward edge of the ionospheric trough where Region 2 field aligned currents flow.

Dipolarization in the inner magnetosphere during a geomagnetic storm on 7 October 2015

NASA Astrophysics Data System (ADS)

Matsui, H.; Erickson, P. J.; Foster, J. C.; Torbert, R. B.; Argall, M. R.; Anderson, B. J.; Blake, J. B.; Cohen, I. J.; Ergun, R. E.; Farrugia, C. J.; Khotyaintsev, Yu. V.; Korth, H.; Lindqvist, P.-A.; Magnes, W.; Marklund, G. T.; Mauk, B. H.; Paulson, K. W.; Russell, C. T.; Strangeway, R. J.; Turner, D. L.

2016-09-01

A dipolarization event was observed by the Magnetospheric Multiscale (MMS) spacecraft at L = 3.8 and 19.8 magnetic local time starting at ˜23:42:36 UT on 7 October 2015. The magnetic and electric fields showed initially coherent variations between the spacecraft. The sunward convection turned tailward after the dipolarization. The observation is interpreted in terms of the pressure balance or the momentum equation. This was followed by a region traversed where the fields were irregular. The scale length was of the order of the ion gyroradius, suggesting the kinetic nature of the fluctuations. Combination of the multi-instrument, multispacecraft data reveals a more detailed picture of the dipolarization event in the inner magnetosphere. Conjunction ionosphere-plasmasphere observations from DMSP, two-dimensional GPS total electron content, the Millstone Hill midlatitude incoherent scatter radar, and AMPERE measurements imply that MMS observations are located on the poleward edge of the ionospheric trough where Region 2 field-aligned currents flow.

High-Temperature and High-Energy-Density Dipolar Glass Polymers Based on Sulfonylated Poly(2,6-dimethyl-1,4-phenylene oxide).

PubMed

Zhang, Zhongbo; Wang, David H; Litt, Morton H; Tan, Loon-Seng; Zhu, Lei

2018-02-05

A new class of high-temperature dipolar polymers based on sulfonylated poly(2,6-dimethyl-1,4-phenylene oxide) (SO 2 -PPO) was synthesized by post-polymer functionalization. Owing to the efficient rotation of highly polar methylsulfonyl side groups below the glass transition temperature (T g ≈220 °C), the dipolar polarization of these SO 2 -PPOs was enhanced, and thus the dielectric constant was high. Consequently, the discharge energy density reached up to 22 J cm -3 . Owing to its high T g  , the SO 2 -PPO 25 sample also exhibited a low dielectric loss. For example, the dissipation factor (tan δ) was 0.003, and the discharge efficiency at 800 MV m -1 was 92 %. Therefore, these dipolar glass polymers are promising for high-temperature, high-energy-density, and low-loss electrical energy storage applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dipolar collisions of ultracold 23Na87Rb molecules.

NASA Astrophysics Data System (ADS)

Guo, Mingyang; Ye, Xin; He, Junyu; Quéméner, Goulven; González-Martínez, Maykel; Dulieu, Olivier; Wang, Dajun

2017-04-01

Although ultracold polar molecules have long been proposed as a primary candidate for investigating dipolar many body physics, many of their basic properties, like their collisions in external electric fields, are still largely unknown. In fact, despite the successful production of several new ultracold molecular species in the last two years, so far the only available dipolar collision data is still from JILA's fermionic 40K87Rb experiment in 2010. In this talk, we will describe our investigation on dipolar collisions of ultracold bosonic and chemically stable 23Na87Rb molecules which possess a large permanent electric dipole moment. With a moderate electric field, an effective dipole moment large enough to strongly couple higher partial waves into the collisions can be achieved. We will report the influence of this effect on the molecular collisions observed in our experiment. Our theoretical model for understanding these observations will also be presented. This work is supported by the Hong Kong RGC CUHK404712 and the ANR/RGC Joint Research Scheme ACUHK403/13.

Quasi-molecular bosonic complexes-a pathway to SQUID with controlled sensitivity

NASA Astrophysics Data System (ADS)

Safavi-Naini, Arghavan; Capogrosso-Sansone, Barbara; Kuklov, Anatoly; Penna, Vittorio

2016-02-01

Recent experimental advances in realizing degenerate quantum dipolar gases in optical lattices and the flexibility of experimental setups in attaining various geometries offer the opportunity to explore exotic quantum many-body phases stabilized by anisotropic, long-range dipolar interaction. Moreover, the unprecedented control over the various physical properties of these systems, ranging from the quantum statistics of the particles, to the inter-particle interactions, allow one to engineer novel devices. In this paper, we consider dipolar bosons trapped in a stack of one-dimensional optical lattice layers, previously studied in (Safavi-Naini et al 2014 Phys. Rev. A 90 043604). Building on our prior results, we provide a description of the quantum phases stabilized in this system which include composite superfluids (CSFs), solids, and supercounterfluids, most of which are found to be threshold-less with respect to the dipolar interaction strength. We also demonstrate the effect of enhanced sensitivity to rotations of a SQUID-type device made of two CSF trapped in a ring-shaped optical lattice layer with weak links.

Colloidal Random Terpolymers: Controlling Reactivity Ratios of Colloidal Comonomers via Metal Tipping

DOE PAGES

Pavlopoulos, Nicholas G.; Dubose, Jeffrey T.; Hartnett, Erin D.; ...

2016-07-26

We report on a versatile synthetic m-shell nanoparticles (NPs) in the backbone, along with semiconductor CdSe@CdS nanorod (NR), or tetrapod (TP) side chain groups. A seven-step colloidal total synthesis enabled the synthesis of well-defined colloidal comonomers composed of a dipolar Au@CoNP attached to a single CdSe@CdS NR, or TP, where magnetic dipolar associations between Au@CoNP units promoted the formation of colloidal co- or terpolymers. The key step in this synthesis was the ability to photodeposit a single AuNP tip onto CdSe@CdS NR or TP that enables selective seeding of a dipolar CoNP onto the AuNP seed. In conclusion, we showmore » that the variation of the AuNP size directly controlled the size and dipolar character of the CoNP tip, where the size modulation of the Au and Au@CoNP tips is analogous to control of comonomer reactivity ratios in classical copolymerization processes.« less

Communication: molecular dynamics and (1)H NMR of n-hexane in liquid crystals.

PubMed

Weber, Adrian C J; Burnell, E Elliott; Meerts, W Leo; de Lange, Cornelis A; Dong, Ronald Y; Muccioli, Luca; Pizzirusso, Antonio; Zannoni, Claudio

2015-07-07

The NMR spectrum of n-hexane orientationally ordered in the nematic liquid crystal ZLI-1132 is analysed using covariance matrix adaptation evolution strategy (CMA-ES). The spectrum contains over 150 000 transitions, with many sharp features appearing above a broad, underlying background signal that results from the plethora of overlapping transitions from the n-hexane as well as from the liquid crystal. The CMA-ES requires initial search ranges for NMR spectral parameters, notably the direct dipolar couplings. Several sets of such ranges were utilized, including three from MD simulations and others from the modified chord model that is specifically designed to predict hydrocarbon-chain dipolar couplings. In the end, only inaccurate dipolar couplings from an earlier study utilizing proton-proton double quantum 2D-NMR techniques on partially deuterated n-hexane provided the necessary estimates. The precise set of dipolar couplings obtained can now be used to investigate conformational averaging of n-hexane in a nematic environment.

Communication: Molecular dynamics and {sup 1}H NMR of n-hexane in liquid crystals

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

Weber, Adrian C. J., E-mail: WeberA@BrandonU.CA; Burnell, E. Elliott, E-mail: elliott.burnell@ubc.ca; Meerts, W. Leo, E-mail: leo.meerts@science.ru.nl

The NMR spectrum of n-hexane orientationally ordered in the nematic liquid crystal ZLI-1132 is analysed using covariance matrix adaptation evolution strategy (CMA-ES). The spectrum contains over 150 000 transitions, with many sharp features appearing above a broad, underlying background signal that results from the plethora of overlapping transitions from the n-hexane as well as from the liquid crystal. The CMA-ES requires initial search ranges for NMR spectral parameters, notably the direct dipolar couplings. Several sets of such ranges were utilized, including three from MD simulations and others from the modified chord model that is specifically designed to predict hydrocarbon-chain dipolar couplings.more » In the end, only inaccurate dipolar couplings from an earlier study utilizing proton-proton double quantum 2D-NMR techniques on partially deuterated n-hexane provided the necessary estimates. The precise set of dipolar couplings obtained can now be used to investigate conformational averaging of n-hexane in a nematic environment.« less

Evanescent Wave Atomic Mirror

NASA Astrophysics Data System (ADS)

Ghezali, S.; Taleb, A.

2008-09-01

A research project at the "Laboratoire d'électronique quantique" consists in a theoretical study of the reflection and diffraction phenomena via an atomic mirror. This poster presents the principle of an atomic mirror. Many groups in the world have constructed this type of atom optics experiments such as in Paris-Orsay-Villetaneuse (France), Stanford-Gaithersburg (USA), Munich-Heidelberg (Germany), etc. A laser beam goes into a prism with an incidence bigger than the critical incidence. It undergoes a total reflection on the plane face of the prism and then exits. The transmitted resulting wave out of the prism is evanescent and repulsive as the frequency detuning of the laser beam compared to the atomic transition δ = ωL-ω0 is positive. The cold atomic sample interacts with this evanescent wave and undergoes one or more elastic bounces by passing into backward points in its trajectory because the atoms' kinetic energy (of the order of the μeV) is less than the maximum of the dipolar potential barrier ℏΩ2/Δ where Ω is the Rabi frequency [1]. In fact, the atoms are cooled and captured in a magneto-optical trap placed at a distance of the order of the cm above the prism surface. The dipolar potential with which interact the slow atoms is obtained for a two level atom in a case of a dipolar electric transition (D2 Rubidium transition at a wavelength of 780nm delivered by a Titane-Saphir laser between a fundamental state Jf = l/2 and an excited state Je = 3/2). This potential is corrected by an attractive Van der Waals term which varies as 1/z3 in the Lennard-Jones approximation (typical atomic distance of the order of λ0/2π where λ0 is the laser wavelength) and in 1/z4 if the distance between the atom and its image in the dielectric is big in front of λ0/2π. This last case is obtained in a quantum electrodynamic calculation by taking into account an orthornormal base [2]. We'll examine the role of spontaneous emission for which the rate is inversely proportional to the detuning δ and is responsible of the non specular aspect of the atomic reflection (atomic diffusion). In the contrary, we note that the specularity of the reflection preserve the coherence of the atomic wave packet. The atoms will constitute a probe of the rugosity of the prism surface which can be imperfect or super-polished.

Diazo Compounds as Highly Tunable Reactants in 1,3-Dipolar Cycloaddition Reactions with Cycloalkynes†

PubMed Central

McGrath, Nicholas A.

2012-01-01

Diazo compounds, which can be accessed directly from azides by deimidogenation, are shown to be extremely versatile dipoles in 1,3-dipolar cycloaddition reactions with a cyclooctyne. The reactivity of a diazo compound can be much greater or much less than its azide analog, and is enhanced markedly in polar-protic solvents. These reactivities are predictable from frontier molecular orbital energies. The most reactive diazo compound exhibited the highest known second-order rate constant to date for a dipolar cycloaddition with a cycloalkyne. These data provide a new modality for effecting chemoselective reactions in a biological context. PMID:23227302

Refocused continuous-wave decoupling: a new approach to heteronuclear dipolar decoupling in solid-state NMR spectroscopy.

PubMed

Vinther, Joachim M; Nielsen, Anders B; Bjerring, Morten; van Eck, Ernst R H; Kentgens, Arno P M; Khaneja, Navin; Nielsen, Niels Chr

2012-12-07

A novel strategy for heteronuclear dipolar decoupling in magic-angle spinning solid-state nuclear magnetic resonance (NMR) spectroscopy is presented, which eliminates residual static high-order terms in the effective Hamiltonian originating from interactions between oscillating dipolar and anisotropic shielding tensors. The method, called refocused continuous-wave (rCW) decoupling, is systematically established by interleaving continuous wave decoupling with appropriately inserted rotor-synchronized high-power π refocusing pulses of alternating phases. The effect of the refocusing pulses in eliminating residual effects from dipolar coupling in heteronuclear spin systems is rationalized by effective Hamiltonian calculations to third order. In some variants the π pulse refocusing is supplemented by insertion of rotor-synchronized π/2 purging pulses to further reduce the residual dipolar coupling effects. Five different rCW decoupling sequences are presented and their performance is compared to state-of-the-art decoupling methods. The rCW decoupling sequences benefit from extreme broadbandedness, tolerance towards rf inhomogeneity, and improved potential for decoupling at relatively low average rf field strengths. In numerical simulations, the rCW schemes clearly reveal superior characteristics relative to the best decoupling schemes presented so far, which we to some extent also are capable of demonstrating experimentally. A major advantage of the rCW decoupling methods is that they are easy to set up and optimize experimentally.

Windowed R-PDLF recoupling: a flexible and reliable tool to characterize molecular dynamics.

PubMed

Gansmüller, Axel; Simorre, Jean-Pierre; Hediger, Sabine

2013-09-01

This work focuses on the improvement of the R-PDLF heteronuclear recoupling scheme, a method that allows quantification of molecular dynamics up to the microsecond timescale in heterogeneous materials. We show how the stability of the sequence towards rf-imperfections, one of the main sources of error of this technique, can be improved by the insertion of windows without irradiation into the basic elements of the symmetry-based recoupling sequence. The impact of this modification on the overall performance of the sequence in terms of scaling factor and homonuclear decoupling efficiency is evaluated. This study indicates the experimental conditions for which precise and reliable measurement of dipolar couplings can be obtained using the popular R18(1)(7) recoupling sequence, as well as alternative symmetry-based R sequences suited for fast MAS conditions. An analytical expression for the recoupled dipolar modulation has been derived that applies to a whole class of sequences with similar recoupling properties as R18(1)(7). This analytical expression provides an efficient and precise way to extract dipolar couplings from the experimental dipolar modulation curves. We hereby provide helpful tools and information for tailoring R-PDLF recoupling schemes to specific sample properties and hardware capabilities. This approach is particularly well suited for the study of materials with strong and heterogeneous molecular dynamics where a precise measurement of dipolar couplings is crucial. Copyright © 2013 Elsevier Inc. All rights reserved.

13C-13C rotational resonance in a transmembrane peptide: A comparison of the fluid and gel phases

NASA Astrophysics Data System (ADS)

Langlais, Denis B.; Hodges, Robert S.; Davis, James H.

1999-05-01

A comparative study of two doubly 13C labeled amphiphilic transmembrane peptides was undertaken to determine the potential of rotational resonance for measuring internuclear distances through the direct dipolar coupling in the presence of motion. The two peptides, having the sequence acetyl-K2-G-L16-K2-A-amide, differed only in the position of 13C labels. The first peptide, [1-13C]leu11:[α-13C]leu12, had labels on adjacent residues, at the carbonyl of leu11 and the α carbon of leu12. The second, [1-13C]leu8:[α-13\\|C]leu11, was labeled on consecutive turns of the α-helical peptide. The internuclear distance between labeled positions of the first peptide, which for an ideal α helix has a value of 2.48 Å, is relatively independent of internal flexibility or peptide conformational change. The dipolar coupling between these two nuclei is sensitive to motional averaging by molecular reorientation, however, making this peptide ideal for investigating these motions. The internuclear distance between labels on the second peptide has an expected static ideal α-helix value of 4.6 Å, but this is sensitive to internal flexibility. In addition, the dipolar coupling between these two nuclei is much weaker because of their larger separation, making this peptide a much more difficult test of the rotational resonance technique. The dipolar couplings between the labeled nuclei of these two peptides were measured by rotational resonance in the dry peptide powders and in multilamellar dispersions with dimyristoylphosphatidylcholine in the gel phase, at -10 °C, and in the fluid phase, at 40 °C. The results for the peptide having adjacent labels can be readily interpreted in terms of a simple model for the peptide motion. The results for the second peptide show that, in the fluid phase, the motionally averaged dipolar coupling is too small to be measured by rotational resonance. Rotational resonance, rotational echo double resonance, and related techniques can be used to obtain reliable and valuable dipolar couplings in static solid and membrane systems. The interpretation of these couplings in terms of internuclear distances is straightforward in the absence of molecular motion. These techniques hold considerable promise for membrane protein structural studies under conditions, such as at low temperatures, where molecular motion does not modulate the dipolar couplings. However, a typical membrane at physiological temperatures exhibits complex molecular motions. In the absence of an accurate and detailed description of both internal and whole body molecular motions, it is unlikely that techniques of this type, which are based on extracting distances from direct internuclear dipolar couplings, can be used to study molecular structure under these conditions. Furthermore, the reduction in the strengths of the dipolar couplings by these motions dramatically reduces the useful range of distances which can be measured.

Algorithm for optimal dialysis access timing.

PubMed

Heaf, J G

2007-02-01

Acute initiation of dialysis is associated with increased morbidity due to access and uremia complications. It is frequent despite early referral and regular out-patient control. We studied factors associated with end-stage renal disease (ESRD) progression in order to optimize the timing of dialysis access (DA). In a retrospective longitudinal study (Study 1), the biochemical and clinical course of 255 dialysis and 64 predialysis patients was registered to determine factors associated with dialysis-free survival (DFS). On the basis of these results an algorithm was developed to predict timely DA, defined as >6 weeks and <26 weeks before dialysis initiation, with too late placement weighted twice as harmful as too early. The algorithm was validated in a prospective study (Study 2) of 150 dialysis and 28 predialysis patients. Acute dialysis was associated with increased 90-day hospitalization (17.9 vs. 9.0 days) and mortality (14% vs. 6%). P-creatinine and p-urea were poor indicators of DFS. At any level of p-creatinine, DFS was shorter with lower creatinine clearance and vice versa. Patients with systemic renal disease had a significantly shorter DFS than primary renal disease, due to faster GFR loss and earlier dialysis initiation. Short DFS was seen with hypoalbuminemia and cachexia; these patients were recommended early DA. The following algorithm was used to time DA (units: 1iM and ml/min/1.73 m2): P-Creatinine - 50 x GFR + (100 if Systemic Renal Disease) >200. Use of the algorithm was associated with earlier dialysis placement and a fall in acute dialysis requirements from 50% to 23%. The incidence of too early DA was unchanged (7% vs. 9%), and was due to algorithm non-application. The algorithm failed to predict imminent dialysis in 10% of cases, primarily due to acute exacerbation of stable uremia. Dialysis initiation was advanced by approximately one month. A predialysis program based on early dialysis planning and GFR-based DA timing may reduce the requirement for acute dialysis initiation and patient morbidity and mortality, at the cost of slightly earlier dialysis initiation.

Survival and Neurocognitive Outcomes After Cranial or Craniospinal Irradiation Plus Total-Body Irradiation Before Stem Cell Transplantation in Pediatric Leukemia Patients With Central Nervous System Involvement

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

Hiniker, Susan M.; Agarwal, Rajni; Modlin, Leslie A.

Purpose: To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen. Methods and Materials: Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methodsmore » with outcomes. Results: All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college. Conclusion: The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy of further protocol investigation in children with CNS leukemia.« less

Surgical Management of Metastatic Colorectal Cancer: A Single-Centre Experience on Oncological Outcomes of Pulmonary Resection vs Cytoreductive Surgery and HIPEC.

PubMed

Wong, Evelyn Yi Ting; Tan, Grace Hwei Ching; Ng, Deanna Wan Jie; Koh, Tina Puay Theng; Kumar, Mrinal; Teo, Melissa Ching Ching

2017-12-01

Metastasectomy is accepted as standard of care for selected patients with colorectal pulmonary metastases (CLM); however, the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases (CPM) is not universally accepted. We aim to compare oncological outcomes of patients with CLM and CPM after pulmonary resection and CRS-HIPEC, respectively, by comparing overall survival (OS) and disease-free survival (DFS). A retrospective review of 49 CLM patients who underwent pulmonary resection, and 52 CPM patients who underwent CRS-HIPEC in a single institution from January 2003 to March 2015, was performed. The 5-year OS for CLM patients and CPM patients were 59.6 and 40.5%, respectively (p = 0.100), while the 5-year DFS were 24.0 and 14.2%, respectively (p = 0.173). CPM patients had longer median operative time (8.38 vs. 1.75 h, p < 0.001), median hospital stay (13 vs. 5 days, p < 0.001), a higher rate of intensive care unit (ICU) admissions (67.3 vs. 8.2%, p < 0.001), and a higher rate of high-grade complications (17.3 vs. 4.1%, p < 0.001). Multivariate analysis demonstrated that recurrent lung metastasis after metastasectomy was an independent prognostic factor for OS of CLM patients (OR = 0.045, 95%, CL 0.003-0.622, p = 0.021). There were no independent prognostic factors for OS in CPM patients by multivariate analysis. There were no independent prognostic factors for DFS in CLM patients by multivariate analysis, but peritoneal cancer index score, bladder involvement, and higher nodal stage at presentation of the initial malignancy were independent prognostic factors for DFS in CPM patients. OS and DFS for CPM patients after CRS and HIPEC are comparable to CLM patients after lung resection, although morbidity appears higher. The prognostic factors affecting survival after surgery are different between CPM and CLM patients and must be considered when selecting patients for metastasectomy.

Regional Nodal Irradiation After Breast Conserving Surgery for Early HER2-Positive Breast Cancer: Results of a Subanalysis From the ALTTO Trial.

PubMed

Gingras, Isabelle; Holmes, Eileen; De Azambuja, Evandro; Nguyen, David H A; Izquierdo, Miguel; Anne Zujewski, Jo; Inbar, Moshe; Naume, Bjorn; Tomasello, Gianluca; Gralow, Julie R; Wolff, Antonio C; Harris, Lyndsay; Gnant, Michael; Moreno-Aspitia, Alvaro; Piccart, Martine J; Azim, Hatem A

2017-08-01

Two randomized trials recently demonstrated that regional nodal irradiation (RNI) could reduce the risk of recurrence in early breast cancer; however, these trials were conducted in the pretrastuzumab era. Whether these results are applicable to human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with anti-HER2-targeted therapy is unknown. This retrospective analysis was performed on patients with node-positive breast cancer who were enrolled in the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization phase III adjuvant trial and subjected to BCS. The primary objective of the present study was to examine the effect of RNI on disease-free survival (DFS). A multivariable cox regression analysis adjusted for number of positive lymph nodes, tumor size, grade, age, hormone receptors status, presence of macrometastatis, treatment arm, and chemotherapy timing was carried out to investigate the relationship between RNI and DFS. One thousand six hundred sixty-four HER2-positive breast cancer patients were included, of whom 878 (52.8%) had received RNI to the axillary, supraclavicular, and/or internal mammary lymph nodes. Patients in the RNI group had higher nodal burden and more frequently had tumors larger than 2 cm. At a median follow-up of 4.5 years, DFS was 84.3% in the RNI group and 88.3% in the non-RNI group. No differences in regional recurrence (0.9 % vs 0.6 %) or in overall survival (93.6% vs 95.3%) were observed between the two groups. After adjustment in multivariable analysis, there was no statistically significant association between RNI and DFS (hazard ratio = 0.96, 95% confidence interval = 0.71 to 1.29). Our analysis did not demonstrate a DFS benefit of RNI in HER2-positive, node-positive patients treated with adjuvant HER2-targeted therapy. The benefit of RNI in HER2-positive breast cancer needs further testing within randomized clinical trials. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Why do pathological stage IA lung adenocarcinomas vary from prognosis?: a clinicopathologic study of 176 patients with pathological stage IA lung adenocarcinoma based on the IASLC/ATS/ERS classification.

PubMed

Zhang, Jie; Wu, Jie; Tan, Qiang; Zhu, Lei; Gao, Wen

2013-09-01

Patients with pathological stage IA adenocarcinoma (AC) have a variable prognosis, even if treated in the same way. The postoperative treatment of pathological stage IA patients is also controversial. We identified 176 patients with pathological stage IA AC who had undergone a lobectomy and mediastinal lymph node dissection at the Shanghai Chest Hospital, Shanghai, China, between 2000 and 2006. No patient had preoperative treatment. The histologic subtypes of all patients were classified according to the 2011 International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) international multidisciplinary lung AC classification. Patients' 5-year overall survival (OS) and 5-year disease-free survival (DFS) were calculated using Kaplan-Meier and Cox regression analyses. One hundred seventy-six patients with pathological stage IA AC had an 86.6% 5-year OS and 74.6% 5-year DFS. The 10 patients with micropapillary predominant subtype had the lowest 5-year DFS (40.0%).The 12 patients with solid predominant with mucin production subtype had the lowest 5-year OS (66.7%). Univariate and multivariate analysis showed that sex and prognositic groups of the IASLC/ATS/ERS histologic classification were significantly associated with 5-year DFS of pathological stage IA AC. Our study revealed that sex was an independent prognostic factor of pathological stage IA AC. The IASLC/ATS/ERS classification of lung AC identifies histologic categories with prognostic differences that could be helpful in clinical therapy.

The clinical value of circulating tumour cells (CTCs) in patients undergoing pulmonary metastasectomy for metastatic colorectal cancer.

PubMed

Hashimoto, Masaki; Tanaka, Fumihiro; Yoneda, Kazue; Takuwa, Teruhisa; Kuroda, Ayumi; Matsumoto, Seiji; Okumura, Yoshitomo; Kondo, Nobuyuki; Tsujimura, Tohru; Nakano, Takashi; Hasegawa, Seiki

2018-03-01

Circulating tumour cells (CTCs) are a potential surrogate for distant metastasis and are considered a useful clinical prognostic marker for metastatic colorectal cancer (mCRC). This prospective study evaluated the preoperative CTC count as a prognostic factor for pulmonary metastasectomy in mCRC patients. Seventy-nine mCRC patients who underwent curative-intent pulmonary metastasectomy were included. Preoperatively, 7.5 mL of peripheral blood from each patient was quantitatively evaluated for CTCs with the CellSearch ® system. The clinical significance of CTC count was evaluated according to Kaplan-Meier analyses and log-rank test. Multivariate analyses of the perioperative variables were performed. The distribution of CTC counts were as follows; 0 in 66 patients (83.5%), 1 in eight patients (10.1%), 2 in three patients (3.8%), and 3 and 6 in one patient (1.3%). The patients with multiple CTCs (CTC count ≥2) had significant shorter disease-free survival (DFS) (P=0.005, median DFS; 19.8 vs . 8.6 months) and overall survival (OS) (P=0.035, median DFS; not reached vs. 37.8 months), respectively. Multivariate analysis showed the patients with multiple CTCs had elevated risk of recurrence [hazard ratio (HR), 3.28; 95% confidence interval (CI), 1.24-8.67; P=0.017]. The detected rate of CTCs was quite low in mCRC patients who underwent pulmonary metastasectomy. The patient with multiple CTCs had shorter DFS in this study. The larger prospective clinical study is needed to establish the meaning of CTC in mCRC candidate for pulmonary metastasectomy.

Solitary Fibrous Tumor of Central Nervous System: Clinical and Prognostic Study of 24 Cases.

PubMed

Jiang, Nian; Xie, Yuan-Yang; Chen, Wen; Peng, Ze-Feng; Yuan, Xian-Rui; Li, Xue-Jun; Feng, Cheng-Yuan; Wang-Gou, Si-Yi

2017-03-01

Solitary fibrous tumors (SFTs) are rare mesenchymal tumors that occasionally occur in the central nervous system (CNS). It is difficult to fully understand their clinical characteristics, partly due to a limited number of reported cases. We reviewed 24 patients admitted to our institution between 2009 and 2016 with CNS solitary fibrous tumors. We reviewed and analyzed patient profiles, such as demographics, presentations, imaging studies, extent of resection, and adjuvant treatment. Differences between malignant and benign SFTs were assessed using the χ2 test or Student's t-test. Kaplan-Meier analysis was used to estimate the disease-free survival (DFS) rate. The multivariate Cox regression analysis was performed to evaluate the possible predictive value of the DFS rate of the previously mentioned covariates. A total of 13 men and 11 women were enrolled in the study (the average age was 43). The median follow-up time was 58 months. Twenty-one patients underwent gross total resection (GTR), and 3 patients received a subtotal resection (STR). The tumors in 15 patients (62.5%) were atypical or malignant. One patient (4.2%) suffered SFT-related death (multiple organ failure by tumor metastasis), and 3 patients (12.5%) experienced tumor recurrence. We found that a large tumor size (≥10 cm, P < 0.001) and STR (P < 0.001) were negatively associated with the DFS rate. CNS SFTs are rare, slow-growing, less aggressive, and recrudescent tumors. Complete resection is the most effective therapy. Large tumor size and STRs might shorten DFS time. Copyright © 2016 Elsevier Inc. All rights reserved.

Cytotoxic tumour-infiltrating T lymphocytes influence outcome in resected pancreatic ductal adenocarcinoma.

PubMed

Lohneis, Philipp; Sinn, Marianne; Bischoff, Sven; Jühling, Anja; Pelzer, Uwe; Wislocka, Lilianna; Bahra, Marcus; Sinn, Bruno V; Denkert, Carsten; Oettle, Helmut; Bläker, Hendrik; Riess, Hanno; Jöhrens, Korinna; Striefler, Jana K

2017-09-01

We studied the prognostic effect of CD3-, CD8- and CD103-positive T lymphocytes in a cohort of 165 patients with resected pancreatic ductal adenocarcinomas (PDACs) of the treatment group (adjuvant gemcitabine) and the untreated control group of the CONKO-001 study. Immunohistochemical stainings on tissue microarrays (TMAs) against CD3, CD8 and CD103 were performed according to standard procedures. A high number of CD8-positive lymphocytes were significantly and independently associated with longer disease-free survival (DFS) and overall survival (OS) in the overall study population. Median DFS/OS were 7.4/18.1 months for patients with a low number of CD8-positive intratumoural lymphocytes (≤42 per 1 mm tissue core) and 12.7/25.2 months for patients with high numbers (>42 per 1-mm tissue core; p = 0.008/0.020; HR 0.62/0.65). The ratio of intraepithelial to total CD103-positive lymphocytes, but not total numbers of CD103-positive lymphocytes or CD103-positive intraepithelial lymphocytes, was associated with significantly improved DFS and OS in the overall study population (p = 0.022/0.009). Median DFS/OS was 5.9/15.7 for patients with a ratio of intraepithelial to total CD103-positive intratumoural lymphocytes higher than 0.3 and 11.6/24.7 for patients with a lower ratio. T-lymphocyte subpopulations might be prognostic in resectable PDAC but need standardization and verification by further studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of Cervical Node Necrosis of Different Grades on the Prognosis of Nasopharyngeal Carcinoma Patients Treated with Intensity-Modulated Radiotherapy.

PubMed

Zhang, Lu-Lu; Li, Jia-Xiang; Zhou, Guan-Qun; Tang, Ling-Long; Ma, Jun; Lin, Ai-Hua; Qi, Zhen-Yu; Sun, Ying

2017-01-01

Background: To analyze the prognostic value of cervical node necrosis (CNN) observed on pretreatment magnetic resonance imaging (MRI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Patients and Methods: The medical records of 1423 NPC patients with cervical node metastasis who underwent IMRT were retrospectively reviewed. Lymph nodes in the axial plane of pretreatment MRI were classified as follows: grade 0 CNN, no hypodense zones; grade 1 CNN, ≤33% areas showing hypodense zones; and grade 2, >33% areas showing hypodense zones. Results: CNN was detectable in 470/1423 (33%) patients. Of these 470 patients, 213 (15%) and 257 (18%) exhibited grade 1 and grade 2 CNN. The grade 0 and grade 1 CNN groups showed significant differences with regard to distant metastasis-free survival (DMFS), but not overall survival (OS), regional relapse-free survival (RRFS), local relapse-free survival (LRFS), and disease-free survival (DFS). Significant differences were observed among the grade 0 and grade 2 CNN groups with regard to OS, RRFS, LRFS, DMFS, and DFS. Moreover, OS, LRFS, RRFS, and DFS were significantly different between the grade 1 and grade 2 CNN groups, whereas DMFS showed no significant differences. Univariate and multivariate analyses revealed CNN on MRI as a significant negative prognostic factor for OS, LRFS, RRFS, DMFS, and DFS in NPC patients. Conclusions: NPC patients with CNN of different grades show various prognosis and failure patterns after IMRT. CNN on MRI can be adopted as a predictive factor for formulating individualized treatment plans for NPC patients.

Minimal residual disease assessed by multi-parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukaemia

PubMed Central

Ravandi, Farhad; Jorgensen, Jeffrey L.; O'Brien, Susan M.; Jabbour, Elias; Thomas, Deborah A.; Borthakur, Gautam; Garris, Rebecca; Huang, Xuelin; Garcia-Manero, Guillermo; Burger, Jan A.; Ferrajoli, Alessandra; Wierda, William; Kadia, Tapan; Jain, Nitin; Wang, Sa A.; Konoplev, Sergei; Kebriaei, Partow; Champlin, Richard E.; McCue, Deborah; Estrov, Zeev; Cortes, Jorge E; Kantarjian, Hagop M.

2016-01-01

SUMMARY The prognostic value of minimal residual disease (MRD) assessed by multi-parameter flow cytometry (MFC) was investigated among 340 adult patients with B-cell acute lymphoblastic leukaemia (B-ALL) treated between 2004 and 2014 using regimens including the hyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine) backbone. Among them, 323 (95%) achieved complete remission (CR) and were included in this study. Median age was 52 years (range, 15-84). Median white blood cell count (WBC) was 9.35 × 109/l (range, 0.4-658.1 ×109/l). MRD by MFC was initially assessed with a sensitivity of 0.01%, using a 15-marker, 4-colour panel and subsequently a 6-colour panel on bone marrow specimens obtained at CR achievement and at approximately 3 month intervals thereafter. MRD negative status at CR was associated with improved disease-free survival (DFS) and overall survival (OS)(P=0.004 and P=0.04, respectively). Similarly, achieving MRD negative status at approximately 3 and 6 months was associated with improved DFS (P=0.002 and P<0.0001, respectively) and OS (P=0.003 and P<0.0001, respectively). Multivariate analysis including age, WBC at presentation, cytogenetics (standard vs. high risk) and MRD status at CR, 3 months and 6 months, indicated that MRD negative status at CR was an independent predictor of DFS (P<0.05). Achievement of an MRD negative state assessed by MFC is an important predictor of DFS and OS in adult patients with ALL PMID:26492205

Retrospective Analysis of 255 Papillary Thyroid Carcinomas ≤2 cm: Clinicohistological Features and Prognostic Factors.

PubMed

Marques, Pedro; Leite, Valeriano; Bugalho, Maria João

2014-12-01

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. The widespread use of neck ultrasound (US) and US-guided fine-needle aspiration cytology is triggering an overdiagnosis of PTC. To evaluate clinical behavior and outcomes of patients with PTCs ≤2 cm, seeking for possible prognostic factors. Clinical records of cases with histological diagnosis of PTC ≤2 cm followed at the Endocrine Department of Instituto Português de Oncologia, Lisbon between 2002 and 2006 were analyzed retrospectively. We identified 255 PTCs, 111 were microcarcinomas. Most patients underwent near-total thyroidectomy, with lymph node dissections in 55 cases (21.6%). Radioiodine therapy was administered in 184 patients. At the last evaluation, 38 (14.9%) had evidence of disease. Two deaths were attributed to PTC. Median (±SD) follow-up was 74 (±23) months. Multivariate analysis identified vascular invasion, lymph node and systemic metastases significantly associated with recurrence/persistence of disease. In addition, lymph node involvement was significantly associated with extrathyroidal extension and angioinvasion. Median (±SD) disease-free survival (DFS) was estimated as 106 (±3) months and the 5-year DFS rate was 87.5%. Univariate Cox analysis identified some relevant parameters for DFS, but multivariate regression only identified lymph node and systemic metastases as significant independent factors. The median DFS estimated for lymph node and systemic metastases was 75 and 0 months, respectively. In the setting of small PTCs, vascular invasion, extrathyroidal extension and lymph node and/or systemic metastases may confer worse prognosis, perhaps justifying more aggressive therapeutic and follow-up approaches in such cases.

Do aggressive variants of papillary thyroid carcinoma have worse clinical outcome than classical papillary thyroid carcinoma?

PubMed

Song, Eyun; Jeon, Min Ji; Oh, Hye-Seon; Han, Minkyu; Lee, Yu-Mi; Kim, Tae Yong; Chung, Ki-Wook; Kim, Won Bae; Shong, Young-Kee; Song, Dong Eun; Kim, Won Gu

2018-06-06

Evidence for unfavorable outcomes of each type of aggressive variant papillary thyroid carcinoma (AV-PTC) is not clear because most previous studies are focused on tall cell variant (TCV) and did not control for other major confounding factors contributing to clinical outcomes. Retrospective cohort study. This study included 763 patients with classical PTC (cPTC) and 144 with AV-PTC, including TCV, columnar cell variant (CCV), and hobnail variants. Disease-free survival (DFS) and dynamic risk stratification (DRS) were compared after two-to-one propensity score matching by age, sex, tumor size, lymph node metastasis, and extrathyroidal extension. The AV-PTC group had significantly lower DFS rates than its matched cPTC group (HR=2.16, 95% CI 1.12-4.16, p=0.018). When TCV and CCV were evaluated separately, there was no significant differences in DFS and DRS between patients with TCV (n=121) and matched cPTC. However, CCV group (n=18) had significantly poorer DFS than matched cPTC group (HR=12.19, 95% CI 2.11-70.33, p=0.005). In DRS, there were significantly more patients with structural incomplete responses in CCV group compared by matched cPTC group (p=0.047). CCV was an independent risk factor for structural persistent/recurrent disease in multivariate analysis (HR, 4.28; 95% CI, 1.66-11.00, p=0.001). When other clinicopathological factors were similar, patients with TCV did not exhibit unfavorable clinical outcome whereas those with CCV had significantly poorer clinical outcome. Individualized therapeutic approach might be necessary for each type of AV-PTCs.

Dose Intensification of Daunorubicin and Cytarabine during Treatment of Adult Acute Lymphoblastic Leukemia: Results of Cancer and Leukemia Group B Study 19802

PubMed Central

Stock, Wendy; Johnson, Jeffrey L.; Stone, Richard M.; Kolitz, Jonathan E.; Powell, Bayard L.; Wetzler, Meir; Westervelt, Peter; Marcucci, Guido; DeAngelo, Daniel J.; Vardiman, James W.; McDonnell, Diane; Mrózek, Krzysztof; Bloomfield, Clara D.; Larson, Richard A.

2014-01-01

Purpose CALGB 19802, a phase II study, evaluated whether dose intensification of daunorubicin and cytarabine could improve disease-free survival (DFS) of adults with acute lymphoblastic leukemia (ALL), and whether high-dose systemic and intrathecal methotrexate could replace cranial radiotherapy for central nervous system (CNS) prophylaxis. Patients and Methods One hundred sixty-one eligible, previously untreated patients age 16–82 years (median, 40 years) were enrolled; 33 (20%) were ≥60years old. Results One hundred twenty-eight patients (80%) achieved a complete remission (CR). Dose intensification of daunorubicin and cytarabine was feasible. With a median follow-up of 10.4 years for surviving patients, 5-year DFS was 25% (95% CI, 18–33%) and overall survival (OS) was 30% (95% CI, 23–37%). Patients <60 years who received the 80 mg/m2 dose of daunorubicin had a DFS of 33% (22–44%) and OS of 39% (29–49%) at 5 years. Eighty-four (52%) patients relapsed, including nine (6%) with isolated CNS relapses. Omission of cranial irradiation did not result in higher than historical CNS relapse rates. Conclusion Intensive systemic, oral, and intrathecal methotrexate dosing permitted omission of CNS irradiation. This intensive approach using higher doses of daunorubicin and cytarabine failed to result in an overall improvement in DFS or OS compared with historical CALGB studies. Future therapeutic strategies for adults with ALL should be tailored to specific age and molecular genetic subsets. PMID:22744771

Impact on acute myeloid leukemia relapse in granulocyte colony-stimulating factor application: a meta-analysis.

PubMed

Feng, Xiaoqin; Lan, He; Ruan, Yongsheng; Li, Chunfu

2018-03-08

This meta-analysis evaluated the impact of granulocyte colony-stimulating factor (G-CSF) added to chemotherapy on treatment outcomes including survival and disease recurrence in patients with acute myeloid leukemia (AML). Medline, Cochrane, EMBASE, and Google Scholar databases were searched until 19 September 2016 using search terms. Studies that investigated patients with AML who underwent stem-cell transplantation were included. The overall analysis revealed a significant improvement in overall survival (OS) (P = .019) and disease-free survival (DFS) (P = .002) for patients receiving G-CSF with chemotherapy. Among patients without prior AML treatment, there was a significant improvement in DFS (P = .014) and reduction in incidence of relapse (P = .015) for those who received G-CSF. However, subgroup analyses found no significant difference between G-CSF (+) and G-CSF (-) treatments in rates of OS (P = .104) and complete remission (CR) (P = .572) for patients without prior AML treatment. Among patients with relapsed/refractory AML, there was no significant difference found between G-CSF (+) and G-CSF (-) groups for OS (P = .225), DFS (P = .209), and CR (P = .208). Treatment with chemotherapy plus G-CSF appears to provide better survival and treatment responses compared with chemotherapy alone, particularly for patients with previously untreated AML. AML, acute myeloid leukemia; CI, confidence interval; CR, complete remission; DFS, disease-free survival; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte macrophage colony-stimulating factor; HR, hazard ratio; MDS, myelodysplastic syndrome; OR, odds ratio; OS, overall survival; RCTs, randomized control trials; RR, relative risk.

Nomograms Predicting Response to Therapy and Outcomes After Bladder-Preserving Trimodality Therapy for Muscle-Invasive Bladder Cancer

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

Coen, John J., E-mail: jcoen@harthosp.org; Paly, Jonathan J.; Niemierko, Andrzej

2013-06-01

Purpose: Selective bladder preservation by use of trimodality therapy is an established management strategy for muscle-invasive bladder cancer. Individual disease features have been associated with response to therapy, likelihood of bladder preservation, and disease-free survival. We developed prognostic nomograms to predict the complete response rate, disease-specific survival, and likelihood of remaining free of recurrent bladder cancer or cystectomy. Methods and Materials: From 1986 to 2009, 325 patients were managed with selective bladder preservation at Massachusetts General Hospital (MGH) and had complete data adequate for nomogram development. Treatment consisted of a transurethral resection of bladder tumor followed by split-course chemoradiation. Patientsmore » with a complete response at midtreatment cystoscopic assessment completed radiation, whereas those with a lesser response underwent a prompt cystectomy. Prognostic nomograms were constructed predicting complete response (CR), disease-specific survival (DSS), and bladder-intact disease-free survival (BI-DFS). BI-DFS was defined as the absence of local invasive or regional recurrence, distant metastasis, bladder cancer-related death, or radical cystectomy. Results: The final nomograms included information on clinical T stage, presence of hydronephrosis, whether a visibly complete transurethral resection of bladder tumor was performed, age, sex, and tumor grade. The predictive accuracy of these nomograms was assessed. For complete response, the area under the receiving operating characteristic curve was 0.69. The Harrell concordance index was 0.61 for both DSS and BI-DFS. Conclusions: Our nomograms allow individualized estimates of complete response, DSS, and BI-DFS. They may assist patients and clinicians making important treatment decisions.« less

Recurrence in Uterine Tumors with Ovarian Sex-Cord Tumor Resemblance: A Case Report and Systematic Review.

PubMed

Cömert, Günsu Kimyon; Kiliç, Çiğdem; Çavuşoğlu, Deniz; Türkmen, Osman; Karalok, Alper; Turan, Taner; Başaran, Derman; Boran, Nurettin

2018-05-10

The aim of this study was to evaluate the prognostic factors of recurrence in uterine tumors resembling ovarian sex-cord tumors (UTROSCT) and to determine clinical-pathological characteristics, treatment options and outcome. An electronic literature search was conducted from 1976 to 2018. After the comprehensive evaluation and conjunction with our case, the study included 79 cases. The median age at initial diagnosis was 49 years (range; 16-86 years). The age was under 40 years in 21 (26.6%) patients. Whereas 68 patients underwent at least hysterectomy, 9 patients had organ sparing surgery. There was necrosis in 4 (5.1%) patients, atypia in 16 (20.3%) patients, and infiltrative tumor border in 34 (43%) patients. At least one mitosis per 10 high power fields was determined in 36 (45.5%) patients. The tumor involved at least part of the myometrium in 54 (68.3%) patients. Median follow-up time was 30 months (range; 3-296 months). Recurrence was determined in 5 (6.3%) patients. The disease free survival (DFS) was significantly related only to surgery type. None of the pathologic features were associated with DFS. The 5-year DFS was 86% and 96% in patients who underwent organ sparing surgery or not, respectively (p=0.038). The accurate pathologic diagnosis of UTROSCT has great value in shaping surgical management and management during the follow-up period. Organ sparing surgery was related to poor DFS. Although recurrence is rare, it should be kept in mind for patients with UTROSCT.

Experimental Validation of Advanced Dispersed Fringe Sensing (ADFS) Algorithm Using Advanced Wavefront Sensing and Correction Testbed (AWCT)

NASA Technical Reports Server (NTRS)

Wang, Xu; Shi, Fang; Sigrist, Norbert; Seo, Byoung-Joon; Tang, Hong; Bikkannavar, Siddarayappa; Basinger, Scott; Lay, Oliver

2012-01-01

Large aperture telescope commonly features segment mirrors and a coarse phasing step is needed to bring these individual segments into the fine phasing capture range. Dispersed Fringe Sensing (DFS) is a powerful coarse phasing technique and its alteration is currently being used for JWST.An Advanced Dispersed Fringe Sensing (ADFS) algorithm is recently developed to improve the performance and robustness of previous DFS algorithms with better accuracy and unique solution. The first part of the paper introduces the basic ideas and the essential features of the ADFS algorithm and presents the some algorithm sensitivity study results. The second part of the paper describes the full details of algorithm validation process through the advanced wavefront sensing and correction testbed (AWCT): first, the optimization of the DFS hardware of AWCT to ensure the data accuracy and reliability is illustrated. Then, a few carefully designed algorithm validation experiments are implemented, and the corresponding data analysis results are shown. Finally the fiducial calibration using Range-Gate-Metrology technique is carried out and a <10nm or <1% algorithm accuracy is demonstrated.

Prognostic Significance of Solid and Micropapillary Components in Invasive Lung Adenocarcinomas Measuring ≤3 cm.

PubMed

Matsuoka, Yuki; Yurugi, Yohei; Takagi, Yuzo; Wakahara, Makoto; Kubouchi, Yasuaki; Sakabe, Tomohiko; Haruki, Tomohiro; Araki, Kunio; Taniguchi, Yuji; Nakamura, Hiroshige; Umekita, Yoshihisa

2016-09-01

We aimed to analyze the clinical impact of solid and micropapillary components in a series of Japanese patients resected for ≤3 cm lung adenocarcinoma. A total of 115 patients with ≤3 cm lung adenocarcinomas were reviewed and classified according to the American Thoracic Society and the European Respiratory Society classification. The presence of solid (S+) or micropapillary component (MP+) was defined when the component constituted ≥1% of the entire tumor. The impact of these components on disease-free (DFS) and disease-specific (DSS) survival was analyzed. Thirty (26.1%) cases with S+ and 27 (23.5%) with MP+ were identified, and multivariate analysis indicated that S+ status significantly reduced the duration of DFS and DSS. In 86 patients of acinar- and papillary-predominant subgroups, S+ and/or MP+ had the most significant effect on DFS and DSS by multivariate analysis. S+ and/or MP+ status predict worse prognosis in patients with acinar- and papillary-predominant lung adenocarcinoma. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Electric Dipolar Kondo Effect Emerging from a Vibrating Magnetic Ion

NASA Astrophysics Data System (ADS)

Hotta, Takashi; Ueda, Kazuo

2012-06-01

When a magnetic ion vibrates in a metal, it inevitably introduces a new channel of hybridization with conduction electrons, and in general, the vibrating ion induces an electric dipole moment. In such a situation, we find that magnetic and nonmagnetic Kondo effects alternatively occur due to the screening of the spin moment and electric dipole moment of the vibrating ion. In particular, the electric dipolar two-channel Kondo effect is found to occur for a weak Coulomb interaction. We also show that a magnetically robust heavy-electron state appears near the fixed point of the electric dipolar two-channel Kondo effect. We believe that the vibrating magnetic ion opens a new door in Kondo physics.

Atom-Pair Kinetics with Strong Electric-Dipole Interactions.

PubMed

Thaicharoen, N; Gonçalves, L F; Raithel, G

2016-05-27

Rydberg-atom ensembles are switched from a weakly to a strongly interacting regime via adiabatic transformation of the atoms from an approximately nonpolar into a highly dipolar quantum state. The resultant electric dipole-dipole forces are probed using a device akin to a field ion microscope. Ion imaging and pair-correlation analysis reveal the kinetics of the interacting atoms. Dumbbell-shaped pair-correlation images demonstrate the anisotropy of the binary dipolar force. The dipolar C_{3} coefficient, derived from the time dependence of the images, agrees with the value calculated from the permanent electric-dipole moment of the atoms. The results indicate many-body dynamics akin to disorder-induced heating in strongly coupled particle systems.

Ionic-liquid-induced ferroelectric polarization in poly(vinylidene fluoride) thin films

NASA Astrophysics Data System (ADS)

Wang, Feipeng; Lack, Alexander; Xie, Zailai; Frübing, Peter; Taubert, Andreas; Gerhard, Reimund

2012-02-01

Thin films of ferroelectric β-phase poly(vinylidene fluoride) (PVDF) were spin-coated from a solution that contained small amounts of the ionic liquid (IL) 1-ethyl-3-methylimidazolium nitrate. A remanent polarization of 60 mC/m2 and a quasi-static pyroelectric coefficient of 19 μC/m2K at 30 °C were observed in the films. It is suggested that the IL promotes the formation of the β phase through dipolar interactions between PVDF chain-molecules and the IL. The dipolar interactions are identified as Coulomb attraction between hydrogen atoms in PVDF chains and anions in IL. The strong crystallinity increase is probably caused by the same dipolar interaction as well.

Dipolar and spinor bosonic systems

NASA Astrophysics Data System (ADS)

Yukalov, V. I.

2018-05-01

The main properties and methods of describing dipolar and spinor atomic systems, composed of bosonic atoms or molecules, are reviewed. The general approach for the correct treatment of Bose-condensed atomic systems with nonlocal interaction potentials is explained. The approach is applied to Bose-condensed systems with dipolar interaction potentials. The properties of systems with spinor interaction potentials are described. Trapped atoms and atoms in optical lattices are considered. Effective spin Hamiltonians for atoms in optical lattices are derived. The possibility of spintronics with cold atom is emphasized. The present review differs from the previous review articles by concentrating on a thorough presentation of basic theoretical points, helping the reader to better follow mathematical details and to make clearer physical conclusions.

Complex Dipolar Matter

DTIC Science & Technology

2014-11-10

opportunities for advanced material development and quantum simulators. These molecules include (1) the already quantum degenerate bi- alkali singlet sigma...case potassium-rubidium (KRb) and related molecules; (2) opto-electrically trapped symmetric top molecules soon to reach quantum degeneracy and...rubidium; (C) a correction of phase diagrams for dipolar gases necessary to understand experimental measurements and build accurate quantum simulators

Intermediate couplings: NMR at the solids-liquids interface

NASA Astrophysics Data System (ADS)

Spence, Megan

2006-03-01

Anisotropic interactions like dipolar couplings and chemical shift anisotropy have long offered solid-state NMR spectroscopists valuable structural information. Recently, solution-state NMR structural studies have begun to exploit residual dipolar couplings of biological molecules in weakly anisotropic solutions. These residual couplings are about 0.1% of the coupling magnitudes observed in the solid state, allowing simple, high-resolution NMR spectra to be retained. In this work, we examine the membrane-associated opioid, leucine enkephalin (lenk), in which the ordering is ten times larger than that for residual dipolar coupling experiments, requiring a combination of solution-state and solid-state NMR techniques. We adapted conventional solid-state NMR techniques like adiabatic cross- polarization and REDOR for use with such a system, and measured small amide bond dipolar couplings in order to determine the orientation of the amide bonds (and therefore the peptide) with respect to the membrane surface. However, the couplings measured indicate large structural rearrangements on the surface and contradict the published structures obtained by NOESY constraints, a reminder that such methods are of limited use in the presence of large-scale dynamics.

Topological defect formation in rotating binary dipolar Bose–Einstein condensate

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

Zhang, Xiao-Fei, E-mail: xfzhang@ntsc.ac.cn; University of Chinese Academy of Sciences, Beijing 100049; Department of Engineering Science, University of Electro-Communications, Tokyo 182-8585

We investigate the topological defects and spin structures of a rotating binary Bose–Einstein condensate, which consists of both dipolar and scalar bosonic atoms confined in spin-dependent optical lattices, for an arbitrary orientation of the dipoles with respect to their plane of motion. Our results show that the tunable dipolar interaction, especially the orientation of the dipoles, can be used to control the direction of stripe phase and its related half-vortex sheets. In addition, it can also be used to obtain a regular arrangement of various topological spin textures, such as meron, circular and cross disgyration spin structures. We point outmore » that such topological defects and regular arrangement of spin structures arise primarily from the long-range and anisotropic nature of dipolar interaction and its competition with the spin-dependent optical lattices and rotation. - Highlights: • Effects of both strength and orientation of the dipoles are discussed. • Various topological defects can be formed in different parameter regions. • Present one possible way to obtain regular arrangements of spin textures.« less

Random acoustic metamaterial with a subwavelength dipolar resonance.

PubMed

Duranteau, Mickaël; Valier-Brasier, Tony; Conoir, Jean-Marc; Wunenburger, Régis

2016-06-01

The effective velocity and attenuation of longitudinal waves through random dispersions of rigid, tungsten-carbide beads in an elastic matrix made of epoxy resin in the range of beads volume fraction 2%-10% are determined experimentally. The multiple scattering model proposed by Luppé, Conoir, and Norris [J. Acoust. Soc. Am. 131(2), 1113-1120 (2012)], which fully takes into account the elastic nature of the matrix and the associated mode conversions, accurately describes the measurements. Theoretical calculations show that the rigid particles display a local, dipolar resonance which shares several features with Minnaert resonance of bubbly liquids and with the dipolar resonance of core-shell particles. Moreover, for the samples under study, the main cause of smoothing of the dipolar resonance of the scatterers and the associated variations of the effective mass density of the dispersions is elastic relaxation, i.e., the finite time required for the shear stresses associated to the translational motion of the scatterers to propagate through the matrix. It is shown that its influence is governed solely by the value of the particle to matrix mass density contrast.

The effect of bottom friction on tidal dipolar vortices and the associated transport

NASA Astrophysics Data System (ADS)

Duran-Matute, Matias; Kamp, Leon; van Heijst, Gertjan

2016-11-01

Tidal dipolar vortices can be formed in a semi-enclosed basin as the tides flow in and out through an inlet. If they are strong enough to overcome the opposing tidal currents, these vortices can travel away from the inlet due to their self-propelling mechanism, and hence, act as an efficient transport agent for suspended material. We present results of two-dimensional numerical simulations of the flow through an idealized tidal inlet, with either a linear or a nonlinear parameterization of the bottom friction. We then quantify the effect of the bottom friction on the propagation of the dipolar vortex and on its ability as a transport agent by computing the flushing and residence times of passive particles. Bottom friction is detrimental to the ability of tidal dipolar vortices to propagate and hinders transport away from the inlet. The magnitude of this effect is related to the relative duration of the tidal period as compared to the typical decay time scale of the vortex dipole. This research is funded by NWO (the Netherlands) through the VENI Grant 863.13.022.

Quantum Landau damping in dipolar Bose-Einstein condensates

NASA Astrophysics Data System (ADS)

Mendonça, J. T.; Terças, H.; Gammal, A.

2018-06-01

We consider Landau damping of elementary excitations in Bose-Einstein condensates (BECs) with dipolar interactions. We discuss quantum and quasiclassical regimes of Landau damping. We use a generalized wave-kinetic description of BECs which, apart from the long-range dipolar interactions, also takes into account the quantum fluctuations and the finite-energy corrections to short-range interactions. Such a description is therefore more general than the usual mean-field approximation. The present wave-kinetic approach is well suited for the study of kinetic effects in BECs, such as those associated with Landau damping, atom trapping, and turbulent diffusion. The inclusion of quantum fluctuations and energy corrections changes the dispersion relation and the damping rates, leading to possible experimental signatures of these effects. Quantum Landau damping is described with generality, and particular examples of dipolar condensates in two and three dimensions are studied. The occurrence of roton-maxon excitations, and their relevance to Landau damping, are also considered in detail. The present approach is mainly based on a linear perturbative procedure, but the nonlinear regime of Landau damping, which includes atom trapping and atom diffusion, is also briefly discussed.

Nuclear magnetic resonance signal dynamics of liquids in the presence of distant dipolar fields, revisited

PubMed Central

Barros, Wilson; Gochberg, Daniel F.; Gore, John C.

2009-01-01

The description of the nuclear magnetic resonance magnetization dynamics in the presence of long-range dipolar interactions, which is based upon approximate solutions of Bloch–Torrey equations including the effect of a distant dipolar field, has been revisited. New experiments show that approximate analytic solutions have a broader regime of validity as well as dependencies on pulse-sequence parameters that seem to have been overlooked. In order to explain these experimental results, we developed a new method consisting of calculating the magnetization via an iterative formalism where both diffusion and distant dipolar field contributions are treated as integral operators incorporated into the Bloch–Torrey equations. The solution can be organized as a perturbative series, whereby access to higher order terms allows one to set better boundaries on validity regimes for analytic first-order approximations. Finally, the method legitimizes the use of simple analytic first-order approximations under less demanding experimental conditions, it predicts new pulse-sequence parameter dependencies for the range of validity, and clarifies weak points in previous calculations. PMID:19425789

Quantum spin ices and magnetic states from dipolar-octupolar doublets on the pyrochlore lattice

NASA Astrophysics Data System (ADS)

Chen, Gang

We consider a class of electron systems in which dipolar-octupolar Kramers doublets arise on the pyrochlore lattice. In the localized limit, the Kramers doublets are described by the effective spin 1/2 pseudospins. The most general nearest-neighbor exchange model between these pseudospins is the XYZ model. In additional to dipolar ordered and octupolar ordered magnetic states, we show that this XYZ model exhibits two distinct quantum spin ice (QSI) phases, that we dub dipolar QSI and octupolar QSI. These two QSIs are distinct symmetry enriched U(1) quantum spin liquids, enriched by the lattice symmetry. Moreover, the XYZ model is absent from the notorious sign problem for a quantum Monte Carlo simulation in a large parameter space. We discuss the potential relevance to real material systems such as Dy2Ti2O7, Nd2Zr2O7, Nd2Hf2O7, Nd2Ir2O7, Nd2Sn2O7 and Ce2Sn2O7. chggst@gmail.com, Refs: Y-P Huang, G Chen, M Hermele, Phys. Rev. Lett. 112, 167203 (2014).

Electron heating and Tp/Te variations during magnetic dipolarizations

NASA Astrophysics Data System (ADS)

Grigorenko, Elena; Kronberg, Elena; Daly, Patrick; Ganushkina, Natalia; Lavraud, Benoit; Sauvaud, Jean-Andre; Zelenyi, Lev

2017-04-01

The proton-to-electron temperature ratio (Tp/Te) in the plasma sheet (PS) of the Earth's magnetotail is studied by using 5 years of Cluster observations (2001-2005). The PS intervals are searched within a region defined with -19

The 3D Kasteleyn transition in dipolar spin ice: a numerical study with the conserved monopoles algorithm

NASA Astrophysics Data System (ADS)

Baez, M. L.; Borzi, R. A.

2017-02-01

We study the three-dimensional Kasteleyn transition in both nearest neighbours and dipolar spin ice models using an algorithm that conserves the number of excitations. We first limit the interactions range to nearest neighbours to test the method in the presence of a field applied along ≤ft[1 0 0\\right] , and then focus on the dipolar spin ice model. The effect of dipolar interactions, which is known to be greatly self screened at zero field, is particularly strong near full polarization. It shifts the Kasteleyn transition to lower temperatures, which decreases  ≈0.4 K for the parameters corresponding to the best known spin ice materials, \\text{D}{{\\text{y}}2}\\text{T}{{\\text{i}}2}{{\\text{O}}7} and \\text{H}{{\\text{o}}2}\\text{T}{{\\text{i}}2}{{\\text{O}}7} . This shift implies effective dipolar fields as big as 0.05 T opposing the applied field, and thus favouring the creation of ‘strings’ of reversed spins. We compare the reduction in the transition temperature with results in previous experiments, and study the phenomenon quantitatively using a simple molecular field approach. Finally, we relate the presence of the effective residual field to the appearance of string-ordered phases at low fields and temperatures, and we check numerically that for fields applied along ≤ft[1 0 0\\right] there are only three different stable phases at zero temperature.

Theoretical and experimental analysis of a linear accelerator endowed with single feed coupler with movable short-circuit.

PubMed

Dal Forno, Massimo; Craievich, Paolo; Penco, Giuseppe; Vescovo, Roberto

2013-11-01

The front-end injection systems of the FERMI@Elettra linac produce high brightness electron beams that define the performance of the Free Electron Laser. The photoinjector mainly consists of the radiofrequency (rf) gun and of two S-band rf structures which accelerate the beam. Accelerating structures endowed with a single feed coupler cause deflection and degradation of the electron beam properties, due to the asymmetry of the electromagnetic field. In this paper, a new type of single feed structure with movable short-circuit is proposed. It has the advantage of having only one waveguide input, but we propose a novel design where the dipolar component is reduced. Moreover, the racetrack geometry allows to reduce the quadrupolar component. This paper presents the microwave design and the analysis of the particle motion inside the linac. A prototype has been machined at the Elettra facility to verify the new coupler design and the rf field has been measured by adopting the bead-pull method. The results are here presented, showing good agreement with the expectations.

Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus

PubMed Central

Noble, Fergus; Nolan, Luke; Bateman, Adrian C; Byrne, James P; Kelly, Jamie J; Bailey, Ian S; Sharland, Donna M; Rees, Charlotte N; Iveson, Timothy J; Underwood, Tim J; Bateman, Andrew R

2013-01-01

AIM: To assess tumour regression grade (TRG) and lymph node downstaging to help define patients who benefit from neoadjuvant chemotherapy. METHODS: Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005 and 2011 at a single institution were reviewed. Triplet neoadjuvant chemotherapy consisting of platinum, fluoropyrimidine and anthracycline was considered for operable patients (World Health Organization performance status ≤ 2) with clinical stage T2-4 N0-1. Response to neoadjuvant chemotherapy (NAC) was assessed using TRG, as described by Mandard et al. In addition lymph node downstaging was also assessed. Lymph node downstaging was defined by cN1 at diagnosis: assessed radiologically (computed tomography, positron emission tomography, endoscopic ultrasonography), then pathologically recorded as N0 after surgery; ypN0 if NAC given prior to surgery, or pN0 if surgery alone. Patients were followed up for 5 years post surgery. Recurrence was defined radiologically, with or without pathological confirmation. An association was examined between t TRG and lymph node downstaging with disease free survival (DFS) and a comprehensive range of clinicopathological characteristics. RESULTS: Two hundred and eighteen patients underwent esophageal resection during the study interval with a mean follow up of 3 years (median follow up: 2.552, 95%CI: 2.022-3.081). There was a 1.8% (n = 4) inpatient mortality rate. One hundred and thirty-six (62.4%) patients received NAC, with 74.3% (n = 101) of patients demonstrating some signs of pathological tumour regression (TRG 1-4) and 5.9% (n = 8) having a complete pathological response. Forty four point one percent (n = 60) had downstaging of their nodal disease (cN1 to ypN0), compared to only 15.9% (n = 13) that underwent surgery alone (pre-operatively overstaged: cN1 to pN0), (P < 0.0001). Response to NAC was associated with significantly increased DFS (mean DFS; TRG 1-2: 5.1 years, 95%CI: 4.6-5.6 vs TRG 3-5: 2.8 years, 95%CI: 2.2-3.3, P < 0.0001). Nodal down-staging conferred a significant DFS advantage for those patients with a poor primary tumour response to NAC (median DFS; TRG 3-5 and nodal down-staging: 5.533 years, 95%CI: 3.558-7.531 vs TRG 3-5 and no nodal down-staging: 1.114 years, 95%CI: 0.961-1.267, P < 0.0001). CONCLUSION: Response to NAC in the primary tumour and in the lymph nodes are both independently associated with improved DFS. PMID:24409055

Association of Prognostic Value of Primary Tumor Location in Stage III Colon Cancer With RAS and BRAF Mutational Status.

PubMed

Taieb, Julien; Kourie, Hampig Raphael; Emile, Jean-François; Le Malicot, Karine; Balogoun, Ralyath; Tabernero, Josep; Mini, Enrico; Folprecht, Gunnar; Van Laethem, Jean-Luc; Mulot, Claire; Bouché, Olivier; Aparicio, Thomas; Michel, Pierre; Thaler, Josef; Bridgewater, John; Van Cutsem, Eric; Perkins, Géraldine; Lepage, Come; Salazar, Ramon; Laurent-Puig, Pierre

2017-11-22

We know of no data on the prognostic value of primary tumor location (PTL) according to BRAF, RAS, and microsatellite instability (MSI) status in patients who have undergone resection for colon cancer (CC) and have been treated with current standard adjuvant chemotherapy. To determine the prognostic and predictive value of PTL according to BRAF, RAS, and MSI status in patients with stage III CC receiving adjuvant treatment with FOLFOX (folinic acid [leucovorin calcium], fluorouracil, and oxaliplatin) with or without cetuximab. This post hoc analysis included patients with available tumor blocks of resected stage III colon adenocarcinoma who participated in the Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 phase 3 randomized trial. Among the 2559 patients who underwent randomization, 1900 were screened by next-generation sequencing, which showed that 1869 had full information concerning PTL. We categorized primary tumor site as located proximal (right) or distal (left) to the splenic flexure. The associations between PTL (right- vs left-sided) and disease-free survival (DFS), survival after relapse (SAR), and overall survival (OS) were assessed by Cox models and adjusted for clinical and pathological features, treatment, and MSI, BRAF, and RAS status. Among the 1869 patients (1056 [57%] male; mean [SD] age, 59.4 [9.5] years) with full molecular data analyzed, 755 (40%) had a right-sided tumor, 164 (10%) had MSI, 942 (50%) had RAS mutations, and 212 (11%) had BRAF mutations. Right-sided tumor location was not prognostic for DFS in the whole population but was associated with a shorter SAR (hazard ratio [HR], 1.54; 95% CI, 1.23-1.93; P = .001) and OS (HR, 1.25; 95% CI, 1.02-1.54; P = .03). When looking at DFS in the different molecular subgroups, we found similar results for microsatellite-stable tumors and tumors with MSI; a better DFS in right-sided vs left-sided tumors in patients with RAS mutations (HR, 0.80; 95% CI, 0.64-1.00; P = .046); and a worse DFS in right-sided vs left-sided tumors in patients with RAS and BRAF double wild type (HR, 1.39; 95% CI, 1.01-1.92; P = .04). These results were found independently of the treatment received, and no beneficial effect of cetuximab on DFS or OS was observed in left-sided tumors. Although right-sided tumor location is associated with poor survival in patients with metastatic CC as previously reported, the association with disease recurrence appears to vary for patients with stage III CC and RAS or BRAF mutations vs those with double wild type.

The combined use of dynamic factor analysis and wavelet analysis to evaluate latent factors controlling complex groundwater level fluctuations in a riverside alluvial aquifer

NASA Astrophysics Data System (ADS)

Oh, Yun-Yeong; Yun, Seong-Taek; Yu, Soonyoung; Hamm, Se-Yeong

2017-12-01

To identify and quantitatively evaluate complex latent factors controlling groundwater level (GWL) fluctuations in a riverside alluvial aquifer influenced by barrage construction, we developed the combined use of dynamic factor analysis (DFA) and wavelet analysis (WA). Time series data of GWL, river water level and precipitation were collected for 3 years (July 2012 to June 2015) from an alluvial aquifer underneath an agricultural area of the Nakdong river basin, South Korea. Based on the wavelet coefficients of the final approximation, the GWL data was clustered into three groups (WCG1 to WCG3). Two dynamic factors (DFs) were then extracted using DFA for each group; thus, six major factors were extracted. Next, the time-frequency variability of the extracted DFs was examined using multiresolution cross-correlation analysis (MRCCA) with the following steps: 1) major driving forces and their scales in GWL fluctuations were identified by comparing maximum correlation coefficients (rmax) between DFs and the GWL time series and 2) the results were supplemented using the wavelet transformed coherence (WTC) analysis between DFs and the hydrological time series. Finally, relative contributions of six major DFs to the GWL fluctuations could be quantitatively assessed by calculating the effective dynamic efficiency (Def). The characteristics and relevant process of the identified six DFs are: 1) WCG1DF4,1 as an indicative of seasonal agricultural pumping (scales = 64-128 days; rmax = 0.68-0.89; Def ≤ 23.1%); 2) WCG1DF4,4 representing the cycle of regional groundwater recharge (scales = 64-128 days; rmax = 0.98-1.00; Def ≤ 11.1%); 3) WCG2DF4,1 indicating the complex interaction between the episodes of precipitation and direct runoff (scales = 2-8 days; rmax = 0.82-0.91; Def ≤ 35.3%) and seasonal GW-RW interaction (scales = 64-128 days; rmax = 0.76-0.91; Def ≤ 14.2%); 4) WCG2DF4,4 reflecting the complex effects of seasonal pervasive pumping and the local recharge cycle (scales = 64-128 days; rmax = 0.86-0.94; Def ≤ 16.4%); 5) WCG3DF4,2 as the result of temporal pumping (scales = 2-8 days; rmax = 0.98-0.99; Def ≤ 7.7%); and 6) WCG3DF4,4 indicating the local recharge cycle (scales = 64-128 days; rmax = 0.76-0.91; Def ≤ 34.2 %). This study shows that major driving forces controlling GWL time series data in a complex hydrological setting can be identified and quantitatively evaluated by the combined use of DFA and WA and applying MRCCA and WTC.

15N CSA tensors and 15N-1H dipolar couplings of protein hydrophobic core residues investigated by static solid-state NMR

NASA Astrophysics Data System (ADS)

Vugmeyster, Liliya; Ostrovsky, Dmitry; Fu, Riqiang

2015-10-01

In this work, we assess the usefulness of static 15N NMR techniques for the determination of the 15N chemical shift anisotropy (CSA) tensor parameters and 15N-1H dipolar splittings in powder protein samples. By using five single labeled samples of the villin headpiece subdomain protein in a hydrated lyophilized powder state, we determine the backbone 15N CSA tensors at two temperatures, 22 and -35 °C, in order to get a snapshot of the variability across the residues and as a function of temperature. All sites probed belonged to the hydrophobic core and most of them were part of α-helical regions. The values of the anisotropy (which include the effect of the dynamics) varied between 130 and 156 ppm at 22 °C, while the values of the asymmetry were in the 0.32-0.082 range. The Leu-75 and Leu-61 backbone sites exhibited high mobility based on the values of their temperature-dependent anisotropy parameters. Under the assumption that most differences stem from dynamics, we obtained the values of the motional order parameters for the 15N backbone sites. While a simple one-dimensional line shape experiment was used for the determination of the 15N CSA parameters, a more advanced approach based on the ;magic sandwich; SAMMY pulse sequence (Nevzorov and Opella, 2003) was employed for the determination of the 15N-1H dipolar patterns, which yielded estimates of the dipolar couplings. Accordingly, the motional order parameters for the dipolar interaction were obtained. It was found that the order parameters from the CSA and dipolar measurements are highly correlated, validating that the variability between the residues is governed by the differences in dynamics. The values of the parameters obtained in this work can serve as reference values for developing more advanced magic-angle spinning recoupling techniques for multiple labeled samples.

Unexpected Catalytic Reactions of Silyl-protected Enoldiazoacetates With Nitrile Oxides That Form 5- Arylaminofuran-2(3H)-one-4-carboxylates

PubMed Central

Xu, Xinfang; Shabashov, Dmitry; Zavalij, Peter Y.; Doyle, Michael P.

2012-01-01

Silyl-protected enoldiazoacetates undergo dirhodium(II) catalyzed reactions with nitrile oxides to form acid-labile ketenimines via dipolar cycloaddition of nitrile oxides to a donor/acceptor cyclopropene and Lossen rearrangement of the dipolar adduct; acid catalysis converts the ketenimine to the furan product. PMID:22272728

Detection of magnetic dipolar coupling of water molecules at the nanoscale using quantum magnetometry

NASA Astrophysics Data System (ADS)

Yang, Zhiping; Shi, Fazhan; Wang, Pengfei; Raatz, Nicole; Li, Rui; Qin, Xi; Meijer, Jan; Duan, Changkui; Ju, Chenyong; Kong, Xi; Du, Jiangfeng

2018-05-01

It is a crucial issue to study interactions among water molecules and hydrophobic interfacial water at the nanoscale. Here we succeed in measuring the nuclear magnetic resonance spectrum of a diamond-water interfacial ice with a detection volume of about 2.2 ×10-22 L. More importantly, the magnetic dipolar coupling between the two protons of a water molecule is resolved by measuring the signal contributed from about 7000 water molecules at the nanoscale. The resolved intramolecule magnetic dipolar interactions are about 15 and 33 kHz with spectral resolution of 5 kHz. This work provides a platform for hydrophobic interfacial water study under ambient conditions, with further applications in more general nanoscale structural analysis.

Overflow of a dipolar exciton trap at high magnetic fields

NASA Astrophysics Data System (ADS)

Dietl, Sebastian; Kowalik-Seidl, Katarzyna; Hammer, Lukas; Schuh, Dieter; Wegscheider, Werner; Holleitner, Alexander; Wurstbauer, Ursula

We study the photoluminescence of trapped dipolar excitons (IX) in coupled double GaAs quantum wells at low temperatures and high magnetic fields. A voltage-tunable electrode geometry controls the strength of the quantum confined Stark effect and defines the lateral trapping potential. Furthermore, it enhances the IX lifetime, enabling them to cool down to lattice temperature. We show that a magnetic field in Faraday configuration effectively prevents the escape of unbound photogenerated charge carriers from the trap area, thus increasing the density of dipolar excitons. For large magnetic fields, we observe an overflow of the IX trap and an effectively suppressed quantum confined Stark effect. We acknowledge financial support by the German Excellence Initiative via the Nanosystems Initiative Munich (NIM).

High Ki-67 Immunohistochemical Reactivity Correlates With Poor Prognosis in Bladder Carcinoma

PubMed Central

Luo, Yihuan; Zhang, Xin; Mo, Meile; Tan, Zhong; Huang, Lanshan; Zhou, Hong; Wang, Chunqin; Wei, Fanglin; Qiu, Xiaohui; He, Rongquan; Chen, Gang

2016-01-01

Abstract Ki-67 is considered as one of prime biomarkers to reflect cell proliferation and immunohistochemical Ki-67 staining has been widely applied in clinical pathology. To solve the widespread controversy whether Ki-67 reactivity significantly predicts clinical prognosis of bladder carcinoma (BC), we performed a comprehensive meta-analysis by combining results from different literature. A comprehensive search was conducted in the Chinese databases of WanFang, China National Knowledge Infrastructure and Chinese VIP as well as English databases of PubMed, ISI web of science, EMBASE, Science Direct, and Wiley online library. Independent studies linking Ki-67 to cancer-specific survival (CSS), disease-free survival (DFS), overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS) were included in our meta-analysis. With the cut-off values literature provided, hazard ratio (HR) values between the survival distributions were extracted and later combined with STATA 12.0. In total, 76 studies (n = 13,053 patients) were eligible for the meta-analysis. It was indicated in either univariate or multivariate analysis for survival that high Ki-67 reactivity significantly predicted poor prognosis. In the univariate analysis, the combined HR for CSS, DFS, OS, PFS, and RFS were 2.588 (95% confidence interval [CI]: 1.623–4.127, P < 0.001), 2.697 (95%CI: 1.874–3.883, P < 0.001), 2.649 (95%CI: 1.632–4.300, P < 0.001), 3.506 (95%CI: 2.231–5.508, P < 0.001), and 1.792 (95%CI: 1.409–2.279, P < 0.001), respectively. The pooled HR of multivariate analysis for CSS, DFS, OS, PFS, and RFS were 1.868 (95%CI: 1.343–2.597, P < 0.001), 2.626 (95%CI: 2.089–3.301, P < 0.001), 1.104 (95%CI: 1.008–1.209, P = 0.032), 1.518 (95%CI: 1.299–1.773, P < 0.001), and 1.294 (95%CI: 1.203–1.392, P < 0.001), respectively. Subgroup analysis of univariate analysis by origin showed that Ki-67 reactivity significantly correlated with all 5 clinical outcome in Asian and European-American patients (P < 0.05). For multivariate analysis, however, the pooled results were only significant for DFS, OS, and RFS in Asian patients, for CSS, DFS, PFS, and RFS in European-American patients (P < 0.05). In the subgroup with low cut-off value (<20%), our meta-analysis indicated that high Ki-67 reactivity was significantly correlated with worsened CSS, DFS, OS, PFS, and RFS on univariate analysis (P < 0.05). For multivariate analysis, the meta-analysis of literature with low cut-off value (<20%) demonstrated that high Ki-67 reactivity predicted shorter DFS, PFS, and RFS in BC patients (P < 0.05). In the subgroup analysis of high cut-off value (≥20%), our meta-analysis indicated that high Ki-67 reactivity, in either univariate or multivariate analysis, significantly correlated with all five clinical outcomes in BC patients (P < 0.05). The meta-analysis indicates that high Ki-67 reactivity significantly correlates with deteriorated clinical outcomes in BC patients and that Ki-67 can be considered as an independent indicator for the prognosis by the meta-analyses of multivariate analysis. PMID:27082587

Development and validation of a prognostic nomogram for colorectal cancer after radical resection based on individual patient data from three large-scale phase III trials

PubMed Central

Akiyoshi, Takashi; Maeda, Hiromichi; Kashiwabara, Kosuke; Kanda, Mitsuro; Mayanagi, Shuhei; Aoyama, Toru; Hamada, Chikuma; Sadahiro, Sotaro; Fukunaga, Yosuke; Ueno, Masashi; Sakamoto, Junichi; Saji, Shigetoyo; Yoshikawa, Takaki

2017-01-01

Background Few prediction models have so far been developed and assessed for the prognosis of patients who undergo curative resection for colorectal cancer (CRC). Materials and Methods We prepared a clinical dataset including 5,530 patients who participated in three major randomized controlled trials as a training dataset and 2,263 consecutive patients who were treated at a cancer-specialized hospital as a validation dataset. All subjects underwent radical resection for CRC which was histologically diagnosed to be adenocarcinoma. The main outcomes that were predicted were the overall survival (OS) and disease free survival (DFS). The identification of the variables in this nomogram was based on a Cox regression analysis and the model performance was evaluated by Harrell's c-index. The calibration plot and its slope were also studied. For the external validation assessment, risk group stratification was employed. Results The multivariate Cox model identified variables; sex, age, pathological T and N factor, tumor location, size, lymphnode dissection, postoperative complications and adjuvant chemotherapy. The c-index was 0.72 (95% confidence interval [CI] 0.66-0.77) for the OS and 0.74 (95% CI 0.69-0.78) for the DFS. The proposed stratification in the risk groups demonstrated a significant distinction between the Kaplan–Meier curves for OS and DFS in the external validation dataset. Conclusions We established a clinically reliable nomogram to predict the OS and DFS in patients with CRC using large scale and reliable independent patient data from phase III randomized controlled trials. The external validity was also confirmed on the practical dataset. PMID:29228760

KRAS and BRAF Mutations and PTEN Expression Do Not Predict Efficacy of Cetuximab-Based Chemoradiotherapy in Locally Advanced Rectal Cancer

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

Erben, Philipp, E-mail: philipp.erben@medma.uni-heidelberg.de; Stroebel, Philipp; Horisberger, Karoline

2011-11-15

Purpose: Mutations in KRAS and BRAF genes as well as the loss of expression of phosphatase and tensin homolog (PTEN) (deleted on chromosome 10) are associated with impaired activity of antibodies directed against epidermal growth factor receptor in patients with metastatic colorectal cancer. The predictive and prognostic value of the KRAS and BRAF point mutations as well as PTEN expression in patients with locally advanced rectal cancer (LARC) treated with cetuximab-based neoadjuvant chemoradiotherapy is unknown. Methods and Materials: We have conducted phase I and II trials of the combination of weekly administration of cetuximab and irinotecan and daily doses ofmore » capecitabine in conjunction with radiotherapy (45 Gy plus 5.4 Gy) in patients with LARC (stage uT3/4 or uN+). The status of KRAS and BRAF mutations was determined with direct sequencing, and PTEN expression status was determined with immunohistochemistry testing of diagnostic tumor biopsies. Tumor regression was evaluated by using standardized regression grading, and disease-free survival (DFS) was calculated according to the Kaplan-Meier method. Results: A total of 57 patients were available for analyses. A total of 31.6% of patients carried mutations in the KRAS genes. No BRAF mutations were found, while the loss of PTEN expression was observed in 9.6% of patients. Six patients achieved complete remission, and the 3-year DFS rate was 73%. No correlation was seen between tumor regression or DFS rate and a single marker or a combination of all markers. Conclusions: In the present series, no BRAF mutation was detected. The presence of KRAS mutations and loss of PTEN expression were not associated with impaired response to cetuximab-based chemoradiotherapy and 3-year DFS.« less

Gene expression in triple-negative breast cancer in relation to survival.

PubMed

Wang, Shuyang; Beeghly-Fadiel, Alicia; Cai, Qiuyin; Cai, Hui; Guo, Xingyi; Shi, Liang; Wu, Jie; Ye, Fei; Qiu, Qingchao; Zheng, Ying; Zheng, Wei; Bao, Ping-Ping; Shu, Xiao-Ou

2018-05-10

The identification of biomarkers related to the prognosis of triple-negative breast cancer (TNBC) is critically important for improved understanding of the biology that drives TNBC progression. We evaluated gene expression in total RNA isolated from formalin-fixed paraffin-embedded tumor samples using the NanoString nCounter assay for 469 TNBC cases from the Shanghai Breast Cancer Survival Study. We used Cox regression to quantify Hazard Ratios (HR) and corresponding confidence intervals (CI) for overall survival (OS) and disease-free survival (DFS) in models that included adjustment for breast cancer intrinsic subtype. Of 302 genes in our discovery analysis, 22 were further evaluated in relation to OS among 134 TNBC cases from the Nashville Breast Health Study and the Southern Community Cohort Study; 16 genes were further evaluated in relation to DFS in 335 TNBC cases from four gene expression omnibus datasets. Fixed-effect meta-analysis was used to combine results across data sources. Twofold higher expression of EOMES (HR 0.90, 95% CI 0.83-0.97), RASGRP1 (HR 0.89, 95% CI 0.82-0.97), and SOD2 (HR 0.80, 95% CI 0.66-0.96) was associated with better OS. Twofold higher expression of EOMES (HR 0.89, 95% CI 0.81-0.97) and RASGRP1 (HR 0.87, 95% CI 0.81-0.95) was also associated with better DFS. On the contrary, a doubling of FA2H (HR 1.14, 95% CI 1.06-1.22) and GSPT1 (HR 1.33, 95% CI 1.14-1.55) expression was associated with shorter DFS. We identified five genes (EOMES, FA2H, GSPT1, RASGRP1, and SOD2) that may serve as potential prognostic biomarkers and/or therapeutic targets for TNBC.

Treatment Adherence and Its Impact on Disease-Free Survival in the Breast International Group 1-98 Trial of Tamoxifen and Letrozole, Alone and in Sequence.

PubMed

Chirgwin, Jacquie H; Giobbie-Hurder, Anita; Coates, Alan S; Price, Karen N; Ejlertsen, Bent; Debled, Marc; Gelber, Richard D; Goldhirsch, Aron; Smith, Ian; Rabaglio, Manuela; Forbes, John F; Neven, Patrick; Láng, István; Colleoni, Marco; Thürlimann, Beat

2016-07-20

To investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial. The BIG 1-98 trial is a double-blind trial that randomly assigned 6,193 postmenopausal women with hormone receptor-positive early breast cancer in the four-arm option to 5 years of tamoxifen (Tam), letrozole (Let), or the agents in sequence (Let-Tam, Tam-Let). This analysis included 6,144 women who received at least one dose of study treatment. Conditional landmark analyses and marginal structural Cox proportional hazards models were used to evaluate the relationship between DFS and treatment adherence (persistence [duration] and compliance with dosage). Competing risks regression was used to assess demographic, disease, and treatment characteristics of the women who stopped treatment early because of adverse events. Both aspects of low adherence (early cessation of letrozole and a compliance score of < 90%) were associated with reduced DFS (multivariable model hazard ratio, 1.45; 95% CI, 1.09 to 1.93; P = .01; and multivariable model hazard ratio, 1.61; 95% CI, 1.08 to 2.38; P = .02, respectively). Sequential treatments were associated with higher rates of nonpersistence (Tam-Let, 20.8%; Let-Tam, 20.3%; Tam 16.9%; Let 17.6%). Adverse events were the reason for most trial treatment early discontinuations (82.7%). Apart from sequential treatment assignment, reduced adherence was associated with older age, smoking, node negativity, or prior thromboembolic event. Both persistence and compliance are associated with DFS. Toxicity management and, for sequential treatments, patient and physician awareness, may improve adherence. © 2016 by American Society of Clinical Oncology.

Digital, phase-sensitive detection for in situ diode-laser spectroscopy under rapidly changing transmission conditions

NASA Astrophysics Data System (ADS)

Fernholz, T.; Teichert, H.; Ebert, V.

A new harmonic detection scheme for fully digital, fast-scanning wavelength-modulation spectroscopy (DFS-WMS) is presented. DFS-WMS is specially suited for in situ absorption measurements in combustion environments under fast fluctuating transmission conditions and is demonstrated for the first time by open-path monitoring of ambient oxygen using a distributed-feedback diode laser, which is doubly modulated with a fast linear 1 kHz-scan and a sinusoidal 300 kHz-modulation. After an analog high-pass filter, the detector signal is digitized with a 5 megasample/s 12-bit AD-converter card plugged into a PC and subsequently - unlike standard lock-ins - filtered further by co-adding 100 scans, to generate a narrowband comb filter. All further filtering and the demodulation are performed completely digitally on a PC with the help of discrete Fourier transforms (DFT). Both 1f- and 2f-signals, are simultaneously extracted from the detector signal using one ADC input channel. For the 2f-signal, a linearity of 2% and a minimum detectable absorption of 10-4 could be verified experimentally, with the sensitivity to date being limited only by insufficient gain on the 2f-frequency channel. Using the offset in the 1f signal as a transmission `probe', we could show that the 2f-signal can be transmission-corrected by a simple division by the 1f-background, proving that DFS-WMS provides the possibility of compensating for transmission fluctuations. With the inherent suppression of additive noise, DFS-WMS seems well suited for quantitative in situ absorption spectroscopy in large combustion systems. This assumption is supported by the first measurements of oxygen in a high-pressure combustor at 12 bar.

Risk Factors of Anastomotic Leakage and Long-Term Survival After Colorectal Surgery

PubMed Central

Park, Jong Seob; Huh, Jung Wook; Park, Yoon Ah; Cho, Yong Beom; Yun, Seong Hyeon; Kim, Hee Cheol; Lee, Woo Yong

2016-01-01

Abstract Anastomotic leakage (AL) is one of the most serious complications of colorectal surgery. It can affect long-term oncologic outcomes, but the impact on long-term survival remains uncertain. The aim of this study is to evaluate the operative characteristics of leakage and no leakage groups and to analyze long-term oncologic outcomes. We prospectively enrolled 10,477 patients from 2000 to 2011 and retrospectively reviewed the data. Male sex (odds ratio [OR], 3.90; P < 0.001), intraoperative transfusion (OR, 2.31; P = 0.042), and operative time (OR, 1.73; P = 0.032) were independent risk factors of AL in the colon. In the rectum, male sex (OR, 2.37; P < 0.001), neoadjuvant chemoradiotherapy (OR, 2.26; P < 0.001), and regional lymph node metastasis (OR, 1.43; P = 0.012) were independent risk factors of AL, and diverting stoma (OR, 0.24; P < 0.001) was associated with a deceased risk of AL. AL in the rectum without a diverting stoma was associated with disease-free survival (DFS, OR, 1.47; P = 0.037). Colonic leakage was not associated with 5-year DFS (leakage group vs nonleakage group, 72.4% vs 80.9%, P = 0.084); however, in patients undergoing rectal resection, there was a significant difference in 5-year DFS (67.0% vs 76.6%, P = 0.005, respectively). AL in the rectum is associated with worse long-term DFS and overall survival. A diverting stoma was shown to protect against this effect and was associated with long-term survival in rectal surgery. Therefore, creating a diverting stoma should be considered in high-risk patients undergoing rectal surgery. PMID:26937928

Multicenter Analysis of Long-Term Oncologic Impact of Anastomotic Leakage After Laparoscopic Total Mesorectal Excision

PubMed Central

Kang, Jeonghyun; Choi, Gyu-Seog; Oh, Jae Hwan; Kim, Nam Kyu; Park, Jun Seok; Kim, Min Jung; Lee, Kang Young; Baik, Seung Hyuk

2015-01-01

Abstract This study aims to validate the oncologic outcomes of anastomotic leakage (AL) after laparoscopic total mesorectal excision (TME) in a large multicenter cohort. The impact of AL after laparoscopic TME for rectal cancer surgery has not yet been clearly described. This was a multicenter retrospective study of 1083 patients who underwent laparoscopic TME for nonmetastatic rectal cancer (stage 0–III). AL was defined as an anastomotic complication within 30 days of surgery irrespective of requiring a reoperation or interventional radiology. Estimated local recurrence (LR), disease-free survival (DFS), and overall survival (OS) were compared between the leakage group and the no leakage group using the log-rank method. Multivariate Cox-regression analysis was used to adjust confounding for survival. The incidence of AL was 6.4%. Mortality within 30 days of surgery occurred in 1 patient (1.4%) in the leakage group and 2 patients (0.2%) in the no leakage group. The leakage group showed a higher LR rate (6.4% vs 1.8%, P = 0.011). Five-year DFS and OS were significantly lower in the leakage group than the no leakage group (DFS 71.7% vs 82.1%, P = 0.016, OS 81.8% vs 93.5%, P = 0.007). Multivariate analysis showed that AL was an independent poor prognostic factor for DFS and OS (hazard ratio [HR] = 1.6; 95% confidence intervals [CI]: 1.0–2.6; P = 0.042, HR = 2.1; 95% CI: 1.0–4.2; P = 0.028, respectively). AL after laparoscopic TME was significantly associated with an increased rate of LR, systemic recurrence and poor OS. PMID:26200636

Early Stage olfactory neuroblastoma and the impact of resecting dura and olfactory bulb.

PubMed

Mays, Ashley C; Bell, Diana; Ferrarotto, Renata; Phan, Jack; Roberts, Dianna; Fuller, Clifton D; Frank, Steven J; Raza, Shaan M; Kupferman, Michael E; DeMonte, Franco; Hanna, Ehab Y; Su, Shirley Y

2018-06-01

Compare outcomes of patients with olfactory neuroblastoma (ONB) without skull base involvement treated with and without resection of the dura and olfactory bulb. Retrospective review of ONB patients treated from 1992 to 2013 at the MD Anderson Cancer Center (The University of Texas, Houston, Texas, U.S.A.). Primary outcomes were overall and disease-free survival. Thirty-five patients were identified. Most patients had Kadish A/B. tumors (97%), Hyams grade 2 (70%), with unilateral involvement (91%), and arising from the nasal cavity (68%). Tumor involved the mucosa abutting the skull base in 42% of patients. Twenty-five patients (71%) received surgery and radiation, whereas the remainder had surgery alone. Five patients (14%) had bony skull base resection, and eight patients (23%) had resection of bony skull base, dura, and olfactory bulb. Surgical margins were grossly positive in one patient (3%) and microscopically positive in four patients (12%). The 5- and 10-year overall survival were 93% and 81%, respectively. The 5- and 10-year disease-free survival (DFS) were 89% and 78%, respectively. Bony cribriform plate resection was associated with better DFS (P = 0.05), but dura and olfactory bulb resection was not (P = 0.11). There was a trend toward improved DFS in patients with negative resection margins (P = 0.19). Surgical modality (open vs. endoscopic) and postoperative radiotherapy did not impact DFS. Most Kadish A/B ONB tumors have low Hyams grade, unilateral involvement, and favorable survival outcomes. Resection of the dura and olfactory bulb is not oncologically advantageous in patients without skull base involvement who are surgically treated with negative resection margins and cribriform resection. 4. Laryngoscope, 128:1274-1280, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Validation of the CPS+EG and Neo-Bioscore staging systems after preoperative systemic therapy for breast cancer in a single center in China.

PubMed

Xu, Ling; Duan, Xuening; Zhou, Bin; Liu, Yinhua; Ye, Jingming; Liu, Zhaorui; Ma, Chao; Zhang, Hong; Zhang, Shuang; Zhang, Lanbo; Zhao, Jianxin; Cheng, Yuanjia

2018-04-17

Prognostic assessment after preoperative systemic therapy (PST) plays a vital role in determining treatment in breast cancer patients. Many researchers have sought to develop a system to quantitate residual tumor and its correlation with prognosis after PST. This retrospective study validated the CPS + EG staging system and Neo-Bioscore in a single center in China. Data from patients with non-metastatic primary breast cancer who were treated with PST and surgery from Jan. 2008 to Dec. 2014 at the Breast Disease Center of Peking University First Hospital, China, were reviewed. DFS, DSS and OS were calculated using the K-M curve and AUC. Multivariate analysis was used for a Cox proportional hazards model. All calculations were performed with SAS 9.4. A total of 403 patients were enrolled in this study. The median follow-up period was 45 (range 11-107) months. The five-year DFS, DSS and OS rates were 86.4%, 91.2% and 90.5%, respectively. The CS, PS, CPS + EG staging system and Neo-Bioscore stratified patients according to DFS, DSS, and OS after PST, with all P values < 0.0001. The CPS + EG staging system and Neo-Bioscore stratified prognosis after PST better than CS. HER2-positive patients without trastuzumab treatment had obviously worse DFS and OS than other subgroups with different HER2 statuses that scored a 3 in the Neo-Bioscore system. The CPS + EG staging system and Neo-Bioscore can improve prognostic prediction in non-pCR breast cancer patients after PST and, provided unfavorable prognostic factors such as insufficient treatment are incorporated, will have broader clinical applicability. Copyright © 2018 Elsevier Ltd. All rights reserved.

Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis.

PubMed

Bleyzac, N; Cuzzubbo, D; Rénard, C; Garnier, N; Dubois, V; Domenech, C; Goutagny, M-P; Plesa, A; Grardel, N; Goutelle, S; Janoly-Duménil, A; Bertrand, Y

2016-05-01

There is currently a major concern regarding the optimal immunosuppression therapy to be administered after hematopoietic stem cell transplantation (HSCT) to reduce both the toxicity of GvHD and the rate of relapse. We report the outcome of high-risk leukemia children transplanted with a new way of managing cyclosporine (CsA)-based GvHD prophylaxis. A total of 110 HSCT in 109 ALL or AML children who received CsA without mycophenolate or methotrexate in matched related as well as in matched or mismatched unrelated stem cell transplantation were included. CsA dosage regimens were individualized to obtain specific trough blood concentrations values. The incidences of grade I-II and III-IV acute GvHD were 69.1% and 1.8%, respectively, and 8.4% for chronic GvHD. GvHD was neither more frequent nor severe in unrelated than in related HSCT. GvHD occurred in 87% of patients with a mean CsA trough concentration ⩽120 ng/mL versus 43% with concentration >120 ng/mL (P<0.0001). Five-year disease-free survival (DFS) and overall survival were 78% and 83.6%, respectively. DFS was 76.9% for ALL and 80.4% for AML patients. There was no difference in DFS between matched siblings and matched unrelated or mismatched unrelated HSCT. DFS in patients with minimal residual disease (MRD) ⩾10(-3) and in those with MRD <10(-3) before SCT was comparable. Our results indicate that a GvHD prophylaxis regimen based on CsA without mycophenolate or methotrexate is safe and effective whatever the donor compatibility is. These results suggest that GvL effect may be enhanced by this strategy of GvHD prophylaxis.

Phenotype-dependent Ca(2+) dynamics in single boutons of various anatomically identified GABAergic interneurons in the rat hippocampus.

PubMed

Lőrincz, Tibor; Kisfali, Máté; Lendvai, Balázs; Sylvester Vizi, Elek

2016-02-01

Interneurons (INs) of the hippocampus exert versatile inhibition on pyramidal cells by silencing the network at different oscillation frequencies. Although IN discharge can phase-lock to various rhythms in the hippocampus, under high-frequency axon firing, the boutons may not be able to follow the fast activity. Here, we studied Ca(2+) responses to action potentials (APs) in single boutons using combined two-photon microscopy and patch clamp electrophysiology in three types of INs: non-fast-spiking (NFS) neurons showing cannabinoid 1 receptor labelling and dendrite targeting, fast-spiking partially parvalbumin-positive cells synapsing with dendrites (DFS), and parvalbumin-positive cells with perisomatic innervation (PFS). The increase in [Ca(2+) ]i from AP trains was substantially higher in NFS boutons than in DFS or PFS boutons. The decay of bouton Ca(2+) responses was markedly faster in DFS and PFS cells compared with NFS neurons. The bouton-to-bouton variability of AP-evoked Ca(2+) transients in the same axon was surprisingly low in each cell type. Importantly, local responses were saturated after shorter trains of APs in NFS cells than in PFS cells. This feature of fast-spiking neurons might allow them to follow higher-frequency gamma oscillations for a longer time than NFS cells. The function of NFS boutons may better support asynchronous GABA release. In conclusion, we demonstrate several neuron-specific Ca(2+) transients in boutons of NFS, PFS and DFS neurons, which may serve differential functions in hippocampal networks. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Watershed Hepatocellular Carcinomas: The Risk of Incomplete Response following Transhepatic Arterial Chemoembolization.

PubMed

Kothary, Nishita; Takehana, Chris; Mueller, Kerstin; Sullivan, Patrick; Tahvildari, Ali; Sidhar, Vishal; Rosenberg, Jarrett; Louie, John D; Sze, Daniel Y

2015-08-01

Hepatocellular carcinomas (HCCs) bridging two or more Couinaud-Bismuth segments of the liver ("watershed tumors") can recruit multiple segmental arteries. The primary hypothesis of this study was that fewer watershed tumors show complete response (CR) after chemoembolization, with shorter time to local recurrence. Secondary analysis on the impact on transplantation eligibility in the presence of progressive disease was also performed. A total of 155 transplantation-eligible patients whose HCC met Milan criteria (watershed, n = 83; nonwatershed, n = 72) and was treated with chemoembolization were included. Cone-beam computed tomography (CT) was used for guidance and for confirmation of circumferential uptake. Local response to chemoembolization per modified Response Evaluation Criteria In Solid Tumors and local disease-free survival (DFS) for the index tumor were calculated. Differences were assessed by univariate and multivariate analyses. CR after a single of chemoembolization was observed in 55.4% of watershed tumors and in 72.2% of nonwatershed tumors (P = .045). Estimated DFS intervals were 151 days (95% confidence interval [CI], 93-245 d) and 336 days (95% CI, 231-747 d; P = .040) in the watershed and nonwatershed groups, respectively. Worse DFS was observed with a Model for End-Stage Liver Disease score > 20 (P = .0001), higher Child-Pugh-Turcotte score (P = .049), and watershed location (P = .040). Waiting list drop-off rates were statistically similar between groups. Hepatocellular carcinomas located in the watershed region of the liver have a poorer response to chemoembolization than those located elsewhere. These tumors are associated with worse DFS and require additional treatments to maintain transplantation eligibility per Milan criteria. Cone-beam CT can identify crossover supply and confirm complete geographic drug uptake, possibly reducing (but not eliminating) the risk of incomplete response. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

Intratumoral gene expression of 5-fluorouracil pharmacokinetics-related enzymes in stage I and II non-small cell lung cancer patients treated with uracil-tegafur after surgery: a prospective multi-institutional study in Japan.

PubMed

Eguchi, Keisuke; Oyama, Takahiko; Tajima, Atsushi; Abiko, Tomohiro; Sawafuji, Makoto; Horio, Hirotoshi; Hashizume, Toshinori; Matsutani, Noriyuki; Kato, Ryoichi; Nakayama, Mitsuo; Kawamura, Masafumi; Kobayashi, Koichi

2015-01-01

This investigation was conducted to assess the use of the intratumoral mRNA expression levels of nucleic acid-metabolizing enzymes as biomarkers of adjuvant chemotherapy for non-small cell lung cancer (NSCLC) using uracil-tegafur in a multi-institutional prospective study. 236 patients with a completely resected NSCLC (adenocarcinoma and squamous cell carcinoma) of pathological stage IA (maximum tumor diameter of 2 cm or greater), IB, and II tumors were given a dose of 250 mg of uracil-tegafur per square meter of body surface area per day orally for two years after surgery. Intratumoral mRNA levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), and thymidine phosphorylase (TP) genes relative to an internal standard, β-actin, were determined using laser-capture microdissection and fluorescence-based real time PCR detection systems. Among 5-FU target enzymes, TS was the only one that showed a significant difference in the level of gene expression between the high and low gene expression groups, for both disease-free survival (DFS) and overall survival (OS), when patients were divided according to median values; 5-year DFS rates in high/low TS gene expression were 60.4% and 72.6%, respectively (p=0.050), 5-year OS rates were 78.1% and 88.6%, respectively (p=0.011). Cox's proportional hazard model indicated that the pathological stage and TS gene expression level were independent values for predicting DFS. The TS gene expression level was shown to be an independent predictive factor for DFS in stage I and II NSCLC patients who were treated with uracil-tegafur following surgery. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Peritoneal Carcinomatosis of Rare Ovarian Origin Treated by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Multi-Institutional Cohort from PSOGI and BIG-RENAPE.

PubMed

Mercier, Frédéric; Bakrin, Naoual; Bartlett, David L; Goere, Diane; Quenet, François; Dumont, Frédéric; Heyd, Bruno; Abboud, Karine; Marolho, Christelle; Villeneuve, Laurent; Glehen, Olivier

2018-06-01

Ovarian cancer is the most common deadly cancer of gynecologic origin. Patients often are diagnosed at advanced stage with peritoneal metastasis. There are many rare histologies of ovarian cancer; some have outcomes worse than serous ovarian cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can be considered for patients with recurrence. This study was designed to assess the impact of CRS and HIPEC on survival of patient with peritoneal metastasis from rare ovarian malignancy. A prospective, multicentric, international database was retrospectively searched to identify all patients with rare ovarian tumor (mucinous, clear cells, endometrioid, small cell hypercalcemic, and other) and peritoneal metastasis who underwent CRS and HIPEC through the Peritoneal Surface Oncology Group International (PSOGI) and BIG-RENAPE working group. The postoperative complications, long-term results, and principal prognostic factors were analyzed. The analysis included 210 patients with a median follow-up of 43.5 months. Median overall survival (OS) was 69.3 months, and the 5-year OS was 57.7%. For mucinous tumors, median OS and DFS were not reached at 5 years. For granulosa tumors, median overall survival was not reached at 5 years, and median DFS was 34.6 months. Teratoma or germinal tumor showed median overall survival and DFS that were not reached at 5 years. Differences in OS were not statistically significant between histologies (p = 0.383), whereas differences in DFS were (p < 0.001). CRS and HIPEC may increases long-term survival in selected patients with peritoneal metastasis from rare ovarian tumors especially in mucinous, granulosa, or teratoma histological subtypes.

Prognostic role of human equilibrative transporter 1 (hENT1) in patients with resected gastric cancer.

PubMed

Santini, Daniele; Vincenzi, Bruno; Fratto, Maria Elisabetta; Perrone, Giuseppe; Lai, Raymond; Catalano, Vincenzo; Cass, Carol; Ruffini, Pier Adelchi; Spoto, Chiara; Muretto, Pietro; Rizzo, Sergio; Muda, Andrea Onetti; Mackey, John R; Russo, Antonio; Tonini, Giuseppe; Graziano, Francesco

2010-05-01

Nucleoside transporter proteins are specialized proteins that mediate the transport of nucleosides and nucleoside analog drugs across the plasma membrane. The human equilibrative nucleoside transporter 1 (hENT1) is a member of these proteins and mediates cellular entry of gemcitabine, cytarabine, and fludarabine. The hENT1 expression has been demonstrated to be related with prognosis and activity of gemcitabine-based therapy in breast, ampullary, lung, and pancreatic cancer. We investigated the immunohistochemical expression of hENT in tumor samples from 111 patients with resected gastric adenocarcinoma, correlating these data with clinical parameters and disease outcomes. None of the patients received chemotherapy or radiation therapy before or after surgery as a part of an adjuvant or neoadjuvant program. On univariate survival analysis, the hENT1 expression was associated with overall survival (OS) and disease free survival (DFS). Specifically, those patients with overexpression of hENT1 showed a shorter OS (P = 0.021) and a shorter DFS (P = 0.033). Considering only the node positive patients, higher hENT levels were associated with significantly shorter median DFS (21.7 months; 95% CI 11.1-32.4) compared with patients with low expression of hENT1. The hENT1 expression was defined, in the lymph-node positive patients, as an independent prognostic factor (P = 0.019). Furthermore, considering only patients with diffuse or mixed tumors and lymph-node positive, the expression of hENT1 was strongly related with DFS and OS. Immunohistochemistry for the hENT1 protein carries prognostic information in patients with resected gastric cancer and holds promise as a predictive factor in chemotherapy decisions.

Survival benefit of patients with early-stage ovarian carcinoma treated with paclitaxel chemotherapeutic regimens

PubMed Central

2018-01-01

Objective Adjuvant chemotherapy was introduced in patients with early-stage ovarian cancer (OC). The benefit of standard chemotherapeutic regimens including taxane has not been established. Methods Patients with early-stage OC from the National Health Insurance Research database of Taiwan who received platinum plus cyclophosphamide (CP) or platinum plus paclitaxel (PT) for 3–6 cycles were recruited, and the disease-free survival (DFS) and overall survival (OS) were determined. Results A total of 1,510 early-stage OC patients, including 841 who received CP regimen and 699 who received PT regimen, were included. The 2 groups had a similar estimated probability of 5-year DFS (PT vs. CP, 79.0% vs. 77.6%; p=0.410) and OS (84.6% vs. 84.3%; p=0.691). Patients >50 years of age who received the CP regimen had a lower 5-year DFS than the patients ≤50 years of age who received the CP (p<0.001) or PT regimens (p=0.001). Additionally, patients >50 years of age who received the CP regimen had a worse 5-year OS compared with the other 3 groups (p=0.019) (p=0.179 for patients >50 years of age in the PT group; p=0.002 for patients ≤50 years of age in the CP group; and p=0.061 for patients ≤50 years of age in the PT group). Patients with the CP or PT regimen for 3–5 cycles had a similar 5-year DFS and OS compared to 6 cycles (p>0.050). Conclusion Chemotherapeutic regimens with taxane could be recommended for early-stage OC patients >50 years of age. PMID:29185274

Retrospective Analysis of 255 Papillary Thyroid Carcinomas ≤2 cm: Clinicohistological Features and Prognostic Factors

PubMed Central

Marques, Pedro; Leite, Valeriano; Bugalho, Maria João

2014-01-01

Background Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. The widespread use of neck ultrasound (US) and US-guided fine-needle aspiration cytology is triggering an overdiagnosis of PTC. Objective To evaluate clinical behavior and outcomes of patients with PTCs ≤2 cm, seeking for possible prognostic factors. Methods Clinical records of cases with histological diagnosis of PTC ≤2 cm followed at the Endocrine Department of Instituto Português de Oncologia, Lisbon between 2002 and 2006 were analyzed retrospectively. Results We identified 255 PTCs, 111 were microcarcinomas. Most patients underwent near-total thyroidectomy, with lymph node dissections in 55 cases (21.6%). Radioiodine therapy was administered in 184 patients. At the last evaluation, 38 (14.9%) had evidence of disease. Two deaths were attributed to PTC. Median (±SD) follow-up was 74 (±23) months. Multivariate analysis identified vascular invasion, lymph node and systemic metastases significantly associated with recurrence/persistence of disease. In addition, lymph node involvement was significantly associated with extrathyroidal extension and angioinvasion. Median (±SD) disease-free survival (DFS) was estimated as 106 (±3) months and the 5-year DFS rate was 87.5%. Univariate Cox analysis identified some relevant parameters for DFS, but multivariate regression only identified lymph node and systemic metastases as significant independent factors. The median DFS estimated for lymph node and systemic metastases was 75 and 0 months, respectively. Conclusions In the setting of small PTCs, vascular invasion, extrathyroidal extension and lymph node and/or systemic metastases may confer worse prognosis, perhaps justifying more aggressive therapeutic and follow-up approaches in such cases. PMID:25759803

High amplification levels of MDM2 and CDK4 correlate with poor outcome in patients with dedifferentiated liposarcoma: A cytogenomic microarray analysis of 47 cases.

PubMed

Ricciotti, Robert W; Baraff, Aaron J; Jour, George; Kyriss, McKenna; Wu, Yu; Liu, Yuhua; Li, Shao-Chun; Hoch, Benjamin; Liu, Yajuan J

2017-12-01

Dedifferentiated liposarcoma (DDLS) is characterized at the molecular level by amplification of genes within 12q13-15 including MDM2 and CDK4. However, other than FNCLCC grade, prognostic markers are limited. We aim to identify molecular prognostic markers for DDLS to help risk stratify patients. To this end, we studied 49 cases of DDLS in our institutional archives and performed cytogenomic microarray analysis on 47 cases. Gene copy numbers for 12 loci were evaluated and correlated with outcome data retrieved from our institutional electronic medical records. Using cut point analysis and comparison of Kaplan-Meier survival curves by log rank tests, high amplification levels of MDM2 (>38 copies) and CDK4 (>30 copies) correlated with decreased disease free survival (DFS) (P = .0168 and 0.0169 respectively) and disease specific survival (DSS) (P = .0082 and 0.0140 respectively). Additionally, MDM2 and CDK4 showed evidence of a synergistic effect so that each additional copy of one enhances the effect on prognosis of each additional copy of the other for decreased DFS (P = .0227, 0.1% hazard). High amplification of JUN (>16 copies) also correlated with decreased DFS (P = .0217), but not DSS. The presence of copy number alteration at 3q29 correlated with decreased DSS (P = .0192). The presence of >10 mitoses per 10 high power fields and FNCLCC grade 3 also correlated with decreased DFS (P = .0310 and 0.0254 respectively). MDM2 and CDK4 gene amplification levels, along with JUN amplification and copy alterations at 3q29, can be utilized for predicting outcome in patients with DDLS. Published by Elsevier Inc.

Estimation of salivary flow rate, pH, buffer capacity, calcium, total protein content and total antioxidant capacity in relation to dental caries severity, age and gender.

PubMed

Pandey, Pallavi; Reddy, N Venugopal; Rao, V Arun Prasad; Saxena, Aditya; Chaudhary, C P

2015-03-01

The aim of the study was to evaluate salivary flow rate, pH, buffering capacity, calcium, total protein content and total antioxidant capacity in relation to dental caries, age and gender. The study population consisted of 120 healthy children aged 7-15 years that was further divided into two groups: 7-10 years and 11-15 years. In this 60 children with DMFS/dfs = 0 and 60 children with DMFS/dfs ≥5 were included. The subjects were divided into two groups; Group A: Children with DMFS/dfs = 0 (caries-free) Group B: Children with DMFS/dfs ≥5 (caries active). Unstimulated saliva samples were collected from all groups. Flow rates were determined, and samples analyzed for pH, buffer capacity, calcium, total protein and total antioxidant status. Salivary antioxidant activity is measured with spectrophotometer by an adaptation of 2,2'-azino-di-(3-ethylbenzthiazoline-6-sulphonate) assays. The mean difference of the two groups; caries-free and caries active were proved to be statistically significant (P < 0.05) for salivary calcium, total protein and total antioxidant level for both the sexes in the age group 7-10 years and for the age 11-15 years the mean difference of the two groups were proved to be statistically significant (P < 0.05) for salivary calcium level for both the sexes. Salivary total protein and total antioxidant level were proved to be statistically significant for male children only. In general, total protein and total antioxidants in saliva were increased with caries activity. Calcium content of saliva was found to be more in caries-free group and increased with age.

Lymph node density as a prognostic predictor in patients with betel nut-related oral squamous cell carcinoma.

PubMed

Chang, Wei-Chin; Lin, Chun-Shu; Yang, Cheng-Yu; Lin, Chih-Kung; Chen, Yuan-Wu

2018-04-01

Lymph node metastasis in oral squamous cell carcinoma (OSCC) is a poor prognostic factor. The histopathologic stage (e.g., pN) is used to evaluate the severity of lymph node metastasis; however, the current staging system insufficiently predicts survival and recurrence. We investigated clinical outcomes and lymph node density (LND) in betel nut-chewing individuals. We retrospectively analyzed 389 betel nut-exposed patients with primary OSCC who underwent surgical resection in 2002-2015. The prognostic significance of LND was evaluated by overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method. Kaplan-Meier analyses showed that the 5-year OS and DFS rates in all patients were 60.9 and 48.9%, respectively. Multivariate analysis showed that variables independently prognostic for OS were aged population (hazard ratio [HR] = 1.6, 95% confidence interval [95% CI] = 1.1-2.5; P = .025), and cell differentiation classification (HR = 2.4, 95% CI = 1.4-4.2; P = .002). In pathologic N-positive patients, a receiver operating characteristic (ROC) curve for OS was used and indicated the best cutoff of 0.05, and the multivariate analysis showed that LND was an independent predictor of OS (HR = 2.2, 95% CI = 1.3-3.7; P = .004). Lymph node density, at a cutoff of 0.05, was an independent predictor of OS and DFS. OS and DFS underwent multiple analyses, and LND remained significant. The pathologic N stage had no influence in the OS analysis. LND is a more reliable predictor of survival in betel nut-chewing patients for further post operation adjuvant treatment, such as reoperation or adjuvant radiotherapy.

Presence of bone marrow micro-metastases in stage I-III colon cancer patients is associated with worse disease-free and overall survival.

PubMed

Viehl, Carsten T; Weixler, Benjamin; Guller, Ulrich; Dell-Kuster, Salome; Rosenthal, Rachel; Ramser, Michaela; Banz, Vanessa; Langer, Igor; Terracciano, Luigi; Sauter, Guido; Oertli, Daniel; Zuber, Markus

2017-05-01

The prognostic significance of bone marrow micro-metastases (BMM) in colon cancer patients remains unclear. We conducted a prospective cohort study with long-term follow-up to evaluate the relevance of BMM as a prognostic factor for disease free (DFS) and overall survival (OS) in stage I-III colon cancer patients. In this prospective multicenter cohort study 144 stage I-III colon cancer patients underwent bone marrow aspiration from both iliac crests prior to open oncologic resection. The bone marrow aspirates were stained with the pancytokeratin antibody A45-B/B3 and analyzed for the presence of epithelial tumor cells. DFS and OS were analyzed using a Cox proportional hazard model and robust standard errors to account for clustering in the multicenter setting. Median overall follow-up was 6.2 years with no losses to follow-up, and 7.3 years in patients who survived. BMM were found in 55 (38%) patients. In total, 30 (21%) patients had disease recurrence and 56 (39%) patients died. After adjusting for known prognostic factors, BMM positive patients had a significantly worse DFS (hazard ratio [HR] 1.33; 95% confidence interval [95% CI]: 1.02-1.73; P = 0.037) and OS (HR 1.30; 95% CI: 1.09-1.55; P = 0.003) compared to BMM negative patients. Bone marrow micro-metastases occur in over one third of stage I-III colon cancer patients and are a significant, independent negative prognostic factor for DFS and OS. Future trials should evaluate whether node-negative colon cancer patients with BMM benefit from adjuvant chemotherapy. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Nottingham Clinico-Pathological Response Index (NPRI) after neoadjuvant chemotherapy (Neo-ACT) accurately predicts clinical outcome in locally advanced breast cancer.

PubMed

Abdel-Fatah, Tarek M; Ball, Graham; Lee, Andrew H S; Pinder, Sarah; MacMilan, R Douglas; Cornford, Eleanor; Moseley, Paul M; Silverman, Rafael; Price, James; Latham, Bruce; Palmer, David; Chan, Arlene; Ellis, Ian O; Chan, Stephen Y T

2015-03-01

There is a need to identify more sensitive clinicopathologic criteria to assess the response to neoadjuvant chemotherapy (Neo-ACT) and guide subsequent adjuvant therapy. We performed a clinicopathologic assessment of 426 patients who had completed Neo-ACT for locally advanced breast cancer (LABC) with a median follow-up of 70 months. Patients were divided into a training set treated with anthracycline combination chemotherapy (n = 172); an internal validation set treated with anthracycline and taxane (n = 129); and an external validation set treated with anthracycline with or without taxane (n = 125). A multivariate Cox regression model demonstrated the absence of fibrosis, presence of lymphovascular invasion, increasing number of lymph node metastases, and administration of hormone therapy were significantly associated with short breast cancer-specific survival (BCSS) and disease-free survival (DFS); Ps < 0.01, while reduction of tumor size was associated with DFS (P = 0.022). Nottingham Clinico-Pathological Response Indexes (NPRI) were calculated, and four prognostic groups (NPRI-PG) were identified. Patients in prognostic group 2 (NPRI-PG2) for BCSS (66 of 172; 38.4%) have the same prognosis as those who achieved pathologic complete response (pCR; NPRI-PG1; 15%). Receiver-operating characteristic (ROC) curves indicated that the NPRI outperformed the currently used prognostic factors and adding the NPRI improved their performance as a predictor for both BCSS (area under the curve [AUC], 0.88) and DFS (AUC, 0.87). The NPRI predicts BCSS and DFS, with a higher sensitivity than pCR. The NPRI can also improve the sensitivity and specificity of clinicopathologic response as a study endpoint, for assessing response to Neo-ACT, and can serve as a valuable tool for the discovery of future predictive molecular markers. ©2014 American Association for Cancer Research.

FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene-expression signature among younger adults with de novo cytogenetically normal acute myeloid leukemia lacking FLT3 internal tandem duplications

PubMed Central

Ruppert, Amy S.; Radmacher, Michael D.; Mrózek, Krzysztof; Paschka, Peter; Langer, Christian; Baldus, Claudia D.; Wen, Jing; Racke, Frederick; Powell, Bayard L.; Kolitz, Jonathan E.; Larson, Richard A.; Caligiuri, Michael A.; Marcucci, Guido; Bloomfield, Clara D.

2008-01-01

The prognostic relevance of FLT3 D835/I836 mutations (FLT3-TKD) in cytogenetically normal acute myeloid leukemia (CN-AML) remains to be established. After excluding patients with FLT3 internal tandem duplications, we compared treatment outcome of 16 de novo CN-AML patients with FLT3-TKD with that of 123 patients with wild-type FLT3 (FLT3-WT), less than 60 years of age and similarly treated on Cancer and Leukemia Group B protocols. All FLT3-TKD+ patients and 85% of FLT3-WT patients achieved a complete remission (P = .13). Disease-free survival (DFS) of FLT3-TKD+ patients was worse than DFS of FLT3-WT patients (P = .01; estimated 3-year DFS rates, 31% vs 60%, respectively). In a multivariable analysis, FLT3-TKD was associated with worse DFS (P = .02) independent of NPM1 status and percentage of bone marrow blasts. To gain further biologic insights, a gene-expression signature differentiating FLT3-TKD+ from FLT3-WT patients was identified. The signature (333 probe sets) included overexpression of VNN1, C3AR1, PTPN6, and multiple other genes involved in monocarboxylate transport activity, and underexpression of genes involved in signal transduction regulation. These associations with outcome, other prognostic markers, and the elucidated expression signature enhance our understanding of FLT3-TKD–associated biology and may lead to development of novel therapies that improve clinical outcome of CN-AML patients with FLT3-TKD. PMID:17940205

Ten-year follow-up of pediatric patients with non-Hodgkin lymphoma treated with allogeneic or autologous stem cell transplantation.

PubMed

Giulino-Roth, Lisa; Ricafort, Rosanna; Kernan, Nancy A; Small, Trudy N; Trippett, Tanya M; Steinherz, Peter G; Prockop, Susan E; Scaradavou, Andromachi; Chiu, Michelle; O'Reilly, Richard J; Boulad, Farid

2013-12-01

Autologous or allogeneic hematopoietic stem cell transplant (SCT) is often considered in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) but there are limited data on the use of SCT for the treatment of NHL in the pediatric setting. To evaluate the role of SCT for children with NHL, we reviewed 36 consecutive pediatric patients with NHL who underwent an allogeneic (n = 21) or autologous (n = 15) SCT at our institution between 1982 and 2004. Pathologic classification included: lymphoblastic lymphoma (n = 12), Burkitt lymphoma (BL) (n = 5), diffuse large B-cell lymphoma (n = 4), anaplastic large cell lymphoma (ALCL) (n = 13), peripheral T cell lymphoma (n = 1), and undifferentiated NHL (n = 1). Donor source for allogeneic-SCT recipients was an HLA-matched related donor (n = 15), a matched unrelated donor (n = 4), or a mismatched donor (related n = 1; unrelated n = 1). Twenty-eight patients (78%) had chemotherapy responsive disease at the time of transplant (either CR or PR). Overall survival (OS) and disease-free survival (DFS) were 55% and 53% with a median follow-up of 9.75 years. Outcomes were similar in patients receiving autologous and allogeneic-SCT (DFS 53% in both groups). Patients with ALCL had a DFS of 76.9%. In contrast, of five patients transplanted for BL, none survived. DFS among patients with chemotherapy sensitive disease was 61%, compared with 25% among patients with relapsed/refractory disease (P = 0.019). Allogeneic and autologous SCT offer the prospect of durable, disease-free survival for a significant proportion of pediatric patients with relapsed or refractory NHL. Survival is superior among patients with chemotherapy sensitive disease. © 2013 Wiley Periodicals, Inc.

Treatment Adherence and Its Impact on Disease-Free Survival in the Breast International Group 1-98 Trial of Tamoxifen and Letrozole, Alone and in Sequence

PubMed Central

Giobbie-Hurder, Anita; Coates, Alan S.; Price, Karen N.; Ejlertsen, Bent; Debled, Marc; Gelber, Richard D.; Goldhirsch, Aron; Smith, Ian; Rabaglio, Manuela; Forbes, John F.; Neven, Patrick; Láng, István; Colleoni, Marco; Thürlimann, Beat

2016-01-01

Purpose To investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial. Methods The BIG 1-98 trial is a double-blind trial that randomly assigned 6,193 postmenopausal women with hormone receptor–positive early breast cancer in the four-arm option to 5 years of tamoxifen (Tam), letrozole (Let), or the agents in sequence (Let-Tam, Tam-Let). This analysis included 6,144 women who received at least one dose of study treatment. Conditional landmark analyses and marginal structural Cox proportional hazards models were used to evaluate the relationship between DFS and treatment adherence (persistence [duration] and compliance with dosage). Competing risks regression was used to assess demographic, disease, and treatment characteristics of the women who stopped treatment early because of adverse events. Results Both aspects of low adherence (early cessation of letrozole and a compliance score of < 90%) were associated with reduced DFS (multivariable model hazard ratio, 1.45; 95% CI, 1.09 to 1.93; P = .01; and multivariable model hazard ratio, 1.61; 95% CI, 1.08 to 2.38; P = .02, respectively). Sequential treatments were associated with higher rates of nonpersistence (Tam-Let, 20.8%; Let-Tam, 20.3%; Tam 16.9%; Let 17.6%). Adverse events were the reason for most trial treatment early discontinuations (82.7%). Apart from sequential treatment assignment, reduced adherence was associated with older age, smoking, node negativity, or prior thromboembolic event. Conclusion Both persistence and compliance are associated with DFS. Toxicity management and, for sequential treatments, patient and physician awareness, may improve adherence. PMID:27217455

The Prognostic Impact of Molecular Subtypes and Very Young Age on Breast Conserving Surgery in Early Stage Breast Cancer

PubMed Central

McGuire, Kandace; Alco, Gul; Nur Pilanci, Kezban; Koksal, Ulkuhan I; Elbüken, Filiz; Erdogan, Zeynep; Agacayak, Filiz; Ilgun, Serkan; Sarsenov, Dauren; Öztürk, Alper; İğdem, Şefik; Okkan, Sait; Eralp, Yeşim; Dincer, Maktav; Ozmen, Vahit

2016-01-01

Background Premenopausal breast cancer with a triple-negative phenotype (TNBC) has been associated with inferior locoregional recurrence free survival (LRFS) and overall survival (OS) after breast conserving surgery (BCS). The aim of this study is to analyze the association between age, subtype, and surgical treatment on survival in young women (≤40 years) with early breast cancer in a population with a high rate of breast cancer in young women. Methods Three hundred thirty-two patients ≤40 years old with stage I-II invasive breast cancer who underwent surgery at a single institution between 1998 and 2012 were identified retrospectively. Uni- and multivariate analysis evaluated predictors of LRFS, OS, and disease free survival (DFS). Results Most patients (64.2%) underwent BCS. Mean age and follow-up time were 35 (25 ± 3.61) years, and 72 months (range, 24–252), respectively. In multivariate analysis, multicentricity/multifocality and young age (<35 years) independently predicted for poorer DFS and OS. Those aged 35–40 years had higher LRFS and DFS than those <35 in the mastectomy group (p=0.007 and p=0.039, respectively). Patients with TNBC had lower OS compared with patients with luminal A subtype (p=0.042), and those who underwent BCS had higher OS than patients after mastectomy (p=0.015). Conclusion Young age (< 35 years) is an independent predictor of poorer OS and DFS as compared with ages 35–40, even in countries with a lower average age of breast cancer presentation. In addition, TNBC in the young predicts for poorer OS. BCS can be performed in young patients with TNBC, despite their poorer overall survival. PMID:27433412

Validation of a Proposed Tumor Regression Grading Scheme for Pancreatic Ductal Adenocarcinoma After Neoadjuvant Therapy as a Prognostic Indicator for Survival.

PubMed

Lee, Sun Mi; Katz, Matthew H G; Liu, Li; Sundar, Manonmani; Wang, Hua; Varadhachary, Gauri R; Wolff, Robert A; Lee, Jeffrey E; Maitra, Anirban; Fleming, Jason B; Rashid, Asif; Wang, Huamin

2016-12-01

Neoadjuvant therapy has been increasingly used to treat patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC). Although the College of American Pathologists (CAP) grading scheme for tumor response in posttherapy specimens has been used, its clinical significance has not been validated. Previously, we proposed a 3-tier histologic tumor regression grading (HTRG) scheme (HTRG 0, no viable tumor; HTRG 1, <5% viable tumor cells; HTRG 2, ≥5% viable tumor cells) and showed that the 3-tier HTRG scheme correlated with prognosis. In this study, we sought to validate our proposed HTRG scheme in a new cohort of 167 consecutive PDAC patients who completed neoadjuvant therapy and pancreaticoduodenectomy. We found that patients with HTRG 0 or 1 were associated with a lower frequency of lymph node metastasis (P=0.004) and recurrence (P=0.01), lower ypT (P<0.001) and AJCC stage (P<0.001), longer disease-free survival (DFS, P=0.004) and overall survival (OS, P=0.02) than those with HTRG 2. However, there was no difference in either DFS or OS between the groups with CAP grade 2 and those with CAP grade 3 (P>0.05). In multivariate analysis, HTRG grade 0 or 1 was an independent prognostic factor for better DFS (P=0.03), but not OS. Therefore we validated the proposed HTRG scheme from our previous study. The proposed HTRG scheme is simple and easy to apply in practice by pathologists and might be used as a successful surrogate for longer DFS in patients with potentially resectable PDAC who completed neoadjuvant therapy and surgery.

The impact of primary tumour location in patients undergoing hepatic resection for colorectal liver metastasis.

PubMed

Wang, Kun; Xu, Da; Yan, Xiao-Luan; Poston, Graeme; Xing, Bao-Cai

2018-06-01

Primary tumour location has long been debated as a prognostic factor in colorectal cancer patients with liver metastases (CRLM) undergoing liver resection. This retrospective study was conducted to clarify the prognostic value of tumour location after radical hepatectomy for CRLM and its underlying causes. We retrospectively analysed clinical data from 420 patients with CRLM whom underwent liver resection between January 2002 and December 2015. Right-sided (RS) tumours include tumours located in the cecum, ascending colon, and transverse colon, and left-sided (LS) tumours include those located in the splenic flexure, descending colon, sigmoid colon, and rectum. Both overall survival (OS) and disease-free survival (DFS) were similar between patients with RS and LS primary tumours (5-year OS: 46.5% vs 38.3%, P = 0.699; 5-year DFS: 29.1% vs 22.4%, P = 0.536). Specifically, RAS mutation rate was significantly higher in patients with RS tumours (P = 0.007). Subgroup analysis showed that the RAS mutation on the LS and RS tumours have different prognostic impact for CRLM patients on long-term survival after hepatic resection (RS, OS: P = 0.437, DFS: P = 0.471; LS, OS: P < 0.001, DFS: P = 0.002). The multivariable analysis showed that RAS mutant is an independent factor influencing OS in patients with LS primary tumour only. The site of the primary tumour has no significant impact on the long-term survival in patients with CRLM undergoing radical surgery. However, prognostic value of RAS status differs depending on the site of the primary tumour. Copyright © 2018. Published by Elsevier Ltd.

Endometriosis is the independent prognostic factor for survival in Chinese patients with epithelial ovarian carcinoma.

PubMed

Ren, Tong; Wang, Shu; Sun, Jian; Qu, Ji-Min; Xiang, Yang; Shen, Keng; Lang, Jing He

2017-10-03

Clinico-pathological characteristics and possible prognostic factors among women with epithelial ovarian carcinoma (EOC) with or without concurrent endometriosis were explored. We retrospectively identified 304 patients with EOC treated primarily at Peking Union Medical College Hospital with median follow-up time of 60 months. Of 304 patients with EOC, concurrent endometriosis was identified in 69 (22.7%). The patients with concurrent endometriosis were younger and more probably post-menopausal at onset, were less likely to have abdominal distension, with significantly lower level of pre-surgery serum Ca125 and less possibility of having the history of tubal ligation. The women with concurrent endometriosis group were more likely to have early stage tumors (88.41% versus 52.77%), receive optimal cytoreductive surgery (92.75% versus 71.06%), and less likely to have lymph node metastasis or to develop platinum resistance disease (7.25% versus 14.89%, and 7.35% versus 20%), when compared with women without coexisting endometriosis. The univariate analysis showed that concurrent endometriosis was a prognostic factor for overall survival (OS) and disease-free survival (DFS), but this association just remained in the DFS by multivariate analysis. Besides, multivariate analysis also showed that FIGO stage, residual disease, chemotherapy cycles, chemotherapy resistance and concomitant hypertension were the independent impact factors of OS for EOC patients; whereas FIGO stage, lymphadenectomy, residual disease, coexisting endometriosis and chemoresistance were independent impact factors of DFS for those patients. EOC patients with concurrent endometriosis showed distinct characteristics and had longer overall survival and disease-free survival when compared with those without endometriosis. Endometriosis was the independent prognostic factor for DFS for patients in this series.

Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors

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

Nakamura, Takatoshi; Yamashita, Keishi; Sato, Takeo

2014-07-01

Purpose: To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials: The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results: Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months,more » the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung. Conclusions: NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.« less

Unexpected catalytic reactions of silyl-protected enol diazoacetates with nitrile oxides that form 5-arylaminofuran-2(3H)-one-4-carboxylates.

PubMed

Xu, Xinfang; Shabashov, Dmitry; Zavalij, Peter Y; Doyle, Michael P

2012-02-03

Silyl-protected enol diazoacetates undergo dirhodium(II)-catalyzed reactions with nitrile oxides to form acid-labile ketenimines via dipolar cycloaddition of nitrile oxides to a donor/acceptor cyclopropene and Lossen rearrangement of the dipolar adduct; acid catalysis converts the ketenimine to the furan product. © 2012 American Chemical Society

Obtaining molecular and structural information from 13C-14N systems with 13C FIREMAT experiments.

PubMed

Strohmeier, Mark; Alderman, D W; Grant, David M

2002-04-01

The effect of dipolar coupling to 14N on 13C FIREMAT (five pi replicated magic angle turning) experiments is investigated. A method is developed for fitting the 13C FIREMAT FID employing the full theory to extract the 13C-14N dipolar and 13C chemical shift tensor information. The analysis requires prior knowledge of the electric field gradient (EFG) tensor at the 14N nucleus. In order to validate the method the analysis is done for the amino acids alpha-glycine, gamma-glycine, l-alanine, l-asparagine, and l-histidine on FIREMAT FIDs recorded at 13C frequencies of 50 and 100 MHz. The dipolar and chemical shift data obtained with this analysis are in very good agreement with the previous single-crystal 13C NMR results and neutron diffraction data on alpha-glycine, l-alanine, and l-asparagine. The values for gamma-glycine and l-histidine obtained with this new method are reported for the first time. The uncertainties in the EFG tensor on the resultant 13C chemical shift and dipolar tensor values are assessed. (c) 2002 Elsevier Science (USA).

Tuning dipolar magnetic interactions by controlling individual silica coating of iron oxide nanoparticles

NASA Astrophysics Data System (ADS)

Rivas Rojas, P. C.; Tancredi, P.; Moscoso Londoño, O.; Knobel, M.; Socolovsky, L. M.

2018-04-01

Single and fixed size core, core-shell nanoparticles of iron oxides coated with a silica layer of tunable thickness were prepared by chemical routes, aiming to generate a frame of study of magnetic nanoparticles with controlled dipolar interactions. The batch of iron oxides nanoparticles of 4.5 nm radii, were employed as cores for all the coated samples. The latter was obtained via thermal decomposition of organic precursors, resulting on nanoparticles covered with an organic layer that was subsequently used to promote the ligand exchange in the inverse microemulsion process, employed to coat each nanoparticle with silica. The amount of precursor and times of reaction was varied to obtain different silica shell thicknesses, ranging from 0.5 nm to 19 nm. The formation of the desired structures was corroborated by TEM and SAXS measurements, the core single-phase spinel structure was confirmed by XRD, and superparamagnetic features with gradual change related to dipolar interaction effects were obtained by the study of the applied field and temperature dependence of the magnetization. To illustrate that dipolar interactions are consistently controlled, the main magnetic properties are presented and analyzed as a function of center to center minimum distance between the magnetic cores.

Recoupling of Heteronuclear Dipolar Interactions with Rotational-Echo Double-Resonance at High Magic-Angle Spinning Frequencies

NASA Astrophysics Data System (ADS)

Jaroniec, Christopher P.; Tounge, Brett A.; Rienstra, Chad M.; Herzfeld, Judith; Griffin, Robert G.

2000-09-01

Heteronuclear dipolar recoupling with rotational-echo double-resonance (REDOR) is investigated in the rapid magic-angle spinning regime, where radiofrequency irradiation occupies a significant fraction of the rotor period (10-60%). We demonstrate, in two model 13C-15N spin systems, [1-13C, 15N] and [2-13C, 15N]glycine, that REDOR ΔS/S0 curves acquired at high MAS rates and relatively low recoupling fields are nearly identical to the ΔS/S0 curve expected for REDOR with ideal δ-function pulses. The only noticeable effect of the finite π pulse length on the recoupling is a minor scaling of the dipolar oscillation frequency. Experimental results are explained using both numerical calculations and average Hamiltonian theory, which is used to derive analytical expressions for evolution under REDOR recoupling sequences with different π pulse phasing schemes. For xy-4 and extensions thereof, finite pulses scale only the dipolar oscillation frequency by a well-defined factor. For other phasing schemes (e.g., xx-4 and xx¯-4) both the frequency and amplitude of the oscillation are expected to change.

Determination of the chirality of the saturated pyrrole in sulfmyoglobin using the nuclear Overhauser effect.

PubMed

Parker, W O; Chatfield, M J; La Mar, G N

1989-02-21

The interproton nuclear Overhauser effect (NOE) and paramagnetic dipolar relaxation rates for hyperfine-shifted resonances in the proton NMR spectra of sperm whale met-cyano sulfmyoglobin have led to the location and assignment of the proton signals of the heme pocket residue isoleucine 99 (FG5) in two sulfmyoglobin isomers. Dipolar relaxation rates of these protein signals indicate a highly conserved geometry of the heme pocket upon sulfmyoglobin formation, while the similar upfield direction of dipolar shifts for this residue to that observed in native sperm whale myoglobin reflects largely retained magnetic properties. Dipolar connectivity of this protein residue to the substituents of the reacted heme pyrrole ring B defines the stereochemistry of the puckered thiolene ring found in one isomer, with the 3-CH3 tilted out of the heme plane proximally. The chirality of the saturated carbons of pyrrole ring B in both the initial sulfmyoglobin product and the terminal alkaline product is consistent with a mechanism of formation in which an atom of sulfur is incorporated distally to form an episulfide across ring B, followed by reaction of the vinyl group to yield the thiolene ring that retains the C3 chirality.

Freezing point and solid-liquid interfacial free energy of Stockmayer dipolar fluids: a molecular dynamics simulation study.

PubMed

Wang, Jun; Apte, Pankaj A; Morris, James R; Zeng, Xiao Cheng

2013-09-21

Stockmayer fluids are a prototype model system for dipolar fluids. We have computed the freezing temperatures of Stockmayer fluids at zero pressure using three different molecular-dynamics simulation methods, namely, the superheating-undercooling method, the constant-pressure and constant-temperature two-phase coexistence method, and the constant-pressure and constant-enthalpy two-phase coexistence method. The best estimate of the freezing temperature (in reduced unit) for the Stockmayer (SM) fluid with the dimensionless dipole moment μ*=1, √2, √3 is 0.656 ± 0.001, 0.726 ± 0.002, and 0.835 ± 0.005, respectively. The freezing temperature increases with the dipolar strength. Moreover, for the first time, the solid-liquid interfacial free energies γ of the fcc (111), (110), and (100) interfaces are computed using two independent methods, namely, the cleaving-wall method and the interfacial fluctuation method. Both methods predict that the interfacial free energy increases with the dipole moment. Although the interfacial fluctuation method suggests a weaker interfacial anisotropy, particularly for strongly dipolar SM fluids, both methods predicted the same trend of interfacial anisotropy, i.e., γ100 > γ110 > γ111.

Modeling and simulation of magnetic resonance imaging based on intermolecular multiple quantum coherences

NASA Astrophysics Data System (ADS)

Cai, Congbo; Dong, Jiyang; Cai, Shuhui; Cheng, En; Chen, Zhong

2006-11-01

Intermolecular multiple quantum coherences (iMQCs) have many potential applications since they can provide interaction information between different molecules within the range of dipolar correlation distance, and can provide new contrast in magnetic resonance imaging (MRI). Because of the non-localized property of dipolar field, and the non-linear property of the Bloch equations incorporating the dipolar field term, the evolution behavior of iMQC is difficult to deduce strictly in many cases. In such cases, simulation studies are very important. Simulation results can not only give a guide to optimize experimental conditions, but also help analyze unexpected experimental results. Based on our product operator matrix and the K-space method for dipolar field calculation, the MRI simulation software was constructed, running on Windows operation system. The non-linear Bloch equations are calculated by a fifth-order Cash-Karp Runge-Kutta formulism. Computational time can be efficiently reduced by separating the effects of chemical shifts and strong gradient field. Using this software, simulation of different kinds of complex MRI sequences can be done conveniently and quickly on general personal computers. Some examples were given. The results were discussed.

Two-dimensional fluorescence spectroscopy of uranium isotopes in femtosecond laser ablation plumes

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

Phillips, Mark C.; Brumfield, Brian E.; LaHaye, Nicole

Here, we demonstrate measurement of uranium isotopes in femtosecond laser ablation plumes using two-dimensional fluorescence spectroscopy (2DFS). The high-resolution, tunable CW-laser spectroscopy technique clearly distinguishes atomic absorption from 235U and 238U in natural and highly enriched uranium metal samples. We present analysis of spectral resolution and analytical performance of 2DFS as a function of ambient pressure. Simultaneous measurement using time-resolved absorption spectroscopy provides information on temporal dynamics of the laser ablation plume and saturation behavior of fluorescence signals. The rapid, non-contact measurement is promising for in-field, standoff measurements of uranium enrichment for nuclear safety and security.

Two-dimensional fluorescence spectroscopy of uranium isotopes in femtosecond laser ablation plumes

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

Phillips, Mark C.; Brumfield, Brian E.; LaHaye, Nicole L.

We demonstrate measurement of uranium isotopes in femtosecond laser ablation plumes using two-dimensional fluorescence spectroscopy (2DFS). The high-resolution, tunable CW-laser spectroscopy technique clearly distinguishes atomic absorption from 235U and 238U in natural and highly enriched uranium metal samples. We present analysis of spectral resolution and analytical performance of 2DFS as a function of ambient pressure. Simultaneous measurement using time-resolved absorption spectroscopy provides information on temporal dynamics of the laser ablation plume and saturation behavior of fluorescence signals. The rapid, non-contact measurement is promising for in-field, standoff measurements of uranium enrichment for nuclear safety and security applications.

Two-dimensional fluorescence spectroscopy of uranium isotopes in femtosecond laser ablation plumes

DOE PAGES

Phillips, Mark C.; Brumfield, Brian E.; LaHaye, Nicole; ...

2017-06-19

Here, we demonstrate measurement of uranium isotopes in femtosecond laser ablation plumes using two-dimensional fluorescence spectroscopy (2DFS). The high-resolution, tunable CW-laser spectroscopy technique clearly distinguishes atomic absorption from 235U and 238U in natural and highly enriched uranium metal samples. We present analysis of spectral resolution and analytical performance of 2DFS as a function of ambient pressure. Simultaneous measurement using time-resolved absorption spectroscopy provides information on temporal dynamics of the laser ablation plume and saturation behavior of fluorescence signals. The rapid, non-contact measurement is promising for in-field, standoff measurements of uranium enrichment for nuclear safety and security.

Nonpolar Solvation Free Energy from Proximal Distribution Functions

PubMed Central

Ou, Shu-Ching; Drake, Justin A.; Pettitt, B. Montgomery

2017-01-01

Using precomputed near neighbor or proximal distribution functions (pDFs) that approximate solvent density about atoms in a chemically bonded context one can estimate the solvation structures around complex solutes and the corresponding solute–solvent energetics. In this contribution, we extend this technique to calculate the solvation free energies (ΔG) of a variety of solutes. In particular we use pDFs computed for small peptide molecules to estimate ΔG for larger peptide systems. We separately compute the non polar (ΔGvdW) and electrostatic (ΔGelec) components of the underlying potential model. Here we show how the former can be estimated by thermodynamic integration using pDF-reconstructed solute–solvent interaction energy. The electrostatic component can be approximated with Linear Response theory as half of the electrostatic solute–solvent interaction energy. We test the method by calculating the solvation free energies of butane, propanol, polyalanine, and polyglycine and by comparing with traditional free energy simulations. Results indicate that the pDF-reconstruction algorithm approximately reproduces ΔGvdW calculated by benchmark free energy simulations to within ~ kcal/mol accuracy. The use of transferable pDFs for each solute atom allows for a rapid estimation of ΔG for arbitrary molecular systems. PMID:27992228

Expression and clinical significance of connective tissue growth factor in advanced head and neck squamous cell cancer.

PubMed

Kikuchi, Ryoko; Kikuchi, Yoshihiro; Tsuda, Hitoshi; Maekawa, Hitoshi; Kozaki, Ken-Ichi; Imoto, Issei; Tamai, Seiichi; Shiotani, Akihiro; Iwaya, Keiichi; Sakamoto, Masaru; Sekiya, Takao; Matsubara, Osamu

2014-07-01

Connective tissue growth factor (CTGF) has been reported to play critical roles in the tumorigenesis of several human malignancies. This study was performed to evaluate CTGF protein expression in head and neck squamous cell carcinoma (HNSCC). Surgical specimens from 76 primary HNSCC were obtained with written informed consents and the expression level of CTGF was immunohistochemically evaluated. The cytoplasmic immunoreactivity of CTGF in cancer cells was semiquantitatively classified into low and high expression. Among all 76 cases with or without neoadjuvant therapy, low CTGF showed significantly longer (P = 0.0282) overall survival (OS), but not disease-free survival (DFS) than high CTGF. Although low CTGF in patients with stage I, II and III did not result in any significant difference of the OS and DFS, stage IV HNSCC patients with low CTGF showed significantly longer OS (P = 0.032) and DFS (P = 0.0107) than those with high CTGF. These differences in stage IV cases were also confirmed using multivariate analyses. These results suggest that low CTGF in stage IV HNSCC is an independent prognostic factor, despite with or without neoadjuvant therapy.

The role of anthropometry in designing for sustainability.

PubMed

Nadadur, Gopal; Parkinson, Matthew B

2013-01-01

An understanding of human factors and ergonomics facilitates the design of artefacts, tasks and environments that fulfil their users' physical and cognitive requirements. Research in these fields furthers the goal of efficiently accommodating the desired percentage of user populations through enhanced awareness and modelling of human variability. Design for sustainability (DfS) allows for these concepts to be leveraged in the broader context of designing to minimise negative impacts on the environment. This paper focuses on anthropometry and proposes three ways in which its consideration is relevant to DfS: reducing raw material consumption, increasing usage lifetimes and ethical human resource considerations. This is demonstrated through the application of anthropometry synthesis, virtual fitting, and sizing and adjustability allocation methods in the design of an industrial workstation seat for use in five distinct global populations. This work highlights the importance of and opportunities for using ergonomic design principles in DfS efforts. This research demonstrates the relevance of some anthropometry-based ergonomics concepts to the field of design for sustainability. A global design case study leverages human variability considerations in furthering three sustainable design goals: reducing raw material consumption, increasing usage lifetimes and incorporating ethical human resource considerations in design.

Interim analysis of postoperative chemoradiotherapy with capecitabine and oxaliplatin versus capecitabine alone for pathological stage II and III rectal cancer: a randomized multicenter phase III trial.

PubMed

Feng, Yan-Ru; Zhu, Yuan; Liu, Lu-Ying; Wang, Wei-Hu; Wang, Shu-Lian; Song, Yong-Wen; Wang, Xin; Tang, Yuan; Liu, Yue-Ping; Ren, Hua; Fang, Hui; Zhang, Shi-Ping; Liu, Xin-Fan; Yu, Zi-Hao; Li, Ye-Xiong; Jin, Jing

2016-05-03

The aim of this study is to present an interim analysis of a phase III trial (NCT00714077) of postoperative concurrent capecitabine and radiotherapy with or without oxaliplatin for pathological stage II and III rectal cancer. Patients with pathologically confirmed stage II and III rectal cancer were randomized to either radiotherapy with concurrent capecitabine (Cap-RT group) or with capecitabine and oxaliplatin (Capox-RT group). The primary endpoint was 3-year disease-free survival rate (DFS). The 3-year DFS rate was 73.9% in the Capox-RT group and 71.6% in the Cap-RT group (HR 0.92, p = 0.647), respectively. No significant difference was observed in overall survival, cumulative incidence of local recurrence and distant metastasis between the two groups (p > 0.05). More grade 3-4 acute toxicity was observed in the Capox-RT group than in the Cap-RT group (38.1% vs. 29.2%, p = 0.041). Inclusion of oxaliplatin in the capecitabine-based postoperative regimen did not improve DFS but increased toxicities for pathological stage II and III rectal cancer in this interim analysis.

Downstage migration after neoadjuvant chemoradiotherapy for rectal cancer: the reverse of the Will Rogers phenomenon?

PubMed

Fokas, Emmanouil; Liersch, Torsten; Fietkau, Rainer; Hohenberger, Werner; Hess, Clemens; Becker, Heinz; Sauer, Rolf; Wittekind, Christian; Rödel, Claus

2015-06-01

Downstaging after neoadjuvant treatment is increasingly used as a prognostic factor and surrogate endpoint in clinical trials. However, in recent trials of neoadjuvant 5-fluorouracil-based chemoradiotherapy for rectal cancer, downstaging did not translate into a benefit with regard to either disease-free survival (DFS) or overall survival. By analyzing the 10-year outcome data of the German CAO/ARO/AIO-94 phase 3 trial, the authors demonstrated that significantly fewer patients had poor prognostic features (eg, ypT3-4, ypN1-2) after preoperative 5-fluorouracil-based chemoradiotherapy. Nevertheless, these patients with International Union for Cancer Control stage II disease were found to be at a higher risk of developing distant metastases and had poorer DFS compared with patients with corresponding TNM tumor (sub)groups in the postoperative treatment arm, whereas patients with International Union for Cancer Control stage III disease demonstrated a nonsignificant trend toward a worse outcome after preoperative treatment. Overall, DFS remained identical in both treatment arms. Thus, "downstage migration" after neoadjuvant treatment resembles the reverse of the Will Rogers phenomenon and therefore may not be a reliable endpoint for long-term outcomes. © 2015 American Cancer Society.

Characterisation of male breast cancer: a descriptive biomarker study from a large patient series.

PubMed

Humphries, Matthew P; Sundara Rajan, Sreekumar; Honarpisheh, Hedieh; Cserni, Gabor; Dent, Jo; Fulford, Laura; Jordan, Lee B; Jones, J Louise; Kanthan, Rani; Litwiniuk, Maria; Di Benedetto, Anna; Mottolese, Marcella; Provenzano, Elena; Shousha, Sami; Stephens, Mark; Kulka, Janina; Ellis, Ian O; Titloye, Akinwale N; Hanby, Andrew M; Shaaban, Abeer M; Speirs, Valerie

2017-03-28

Male breast cancer (MBC) is rare. We assembled 446 MBCs on tissue microarrays and assessed clinicopathological information, together with data from 15 published studies, totalling 1984 cases. By immunohistochemistry we investigated 14 biomarkers (ERα, ERβ1, ERβ2, ERβ5, PR, AR, Bcl-2, HER2, p53, E-cadherin, Ki67, survivin, prolactin, FOXA1) for survival impact. The main histological subtype in our cohort and combined analyses was ductal (81%, 83%), grade 2; (40%, 44%), respectively. Cases were predominantly ERα (84%, 82%) and PR positive (74%, 71%), respectively, with HER2 expression being infrequent (2%, 10%), respectively. In our cohort, advanced age (>67) was the strongest predictor of overall (OS) and disease free survival (DFS) (p = 0.00001; p = 0.01, respectively). Node positivity negatively impacted DFS (p = 0.04). FOXA1 p = 0.005) and AR p = 0.009) were both positively prognostic for DFS, remaining upon multivariate analysis. Network analysis showed ERα, AR and FOXA1 significantly correlated. In summary, the principle phenotype of MBC was luminal A, ductal, grade 2. In ERα+ MBC, only AR had prognostic significance, suggesting AR blockade could be employed therapeutically.

Survival after neoadjuvant chemotherapy with or without bevacizumab or everolimus for HER2-negative primary breast cancer (GBG 44-GeparQuinto)†.

PubMed

von Minckwitz, G; Loibl, S; Untch, M; Eidtmann, H; Rezai, M; Fasching, P A; Tesch, H; Eggemann, H; Schrader, I; Kittel, K; Hanusch, C; Huober, J; Solbach, C; Jackisch, C; Kunz, G; Blohmer, J U; Hauschild, M; Fehm, T; Nekljudova, V; Gerber, B

2014-12-01

The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline-taxane-based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses. Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (α = 0.05, β = 0.8) 379 events had to be observed in the bevacizumab arms. With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1-3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups. Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline-taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients. NCT 00567554, www.clinicaltrials.gov. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Prognostic value of body mass index and change in body weight in postoperative outcomes of lung cancer surgery.

PubMed

Nakagawa, Tatsuo; Toyazaki, Toshiya; Chiba, Naohisa; Ueda, Yuichiro; Gotoh, Masashi

2016-10-01

Nutritional status is associated with an effect on oncological outcomes. However, the effect of nutritional status on postoperative survival in lung cancer has not been well studied. We retrospectively analysed and evaluated the effect of preoperative body mass index (BMI) and changes in body weight on postoperative outcomes of lung cancer surgery. A total of 1311 patients with non-small-cell lung cancer who underwent surgery between January 2001 and December 2011 were included in this study. Preoperative body weight at 4-12 weeks prior to surgery was obtained in 737 patients and the ratio of change in body weight was calculated. The patients were classified into four groups as follows: underweight (BMI < 18.5), normal weight (BMI from ≥18.5 to <25), overweight (BMI from ≥25 to <30) and obese (BMI ≥ 30). Postoperative survival curves of the BMI groups showed that the underweight group had a poorer prognosis than the other groups, especially for disease-free survival (DFS) (P = 0.03). Univariate and adjusted survival analyses using Cox's proportional hazards regression model showed that low BMI was a significantly poor prognostic factor in overall survival (OS) (P = 0.03 and P = 0.02, respectively) and DFS (P < 0.01 and P < 0.01, respectively). Among the BMI groups, the underweight group had a significant worse prognosis than the other groups for DFS in univariate and adjusted analyses (P = 0.04 and P < 0.01, respectively). With regard to changes in body weight, patients with a body weight loss of 3.7% or greater had a significantly poorer prognosis for OS and DFS in univariate analysis and for DFS in adjusted analyses compared with the other patients. Regarding short-term outcomes, the weight loss group had a significantly longer postoperative hospital stay than the non-weight loss group (P = 0.02) and postoperative 90-day mortality was significantly lower in the normal weight group than in the underweight group (P = 0.03). Low BMI and significant body weight loss before surgery have a negative effect on surgical outcomes for patients with non-small-cell lung cancer. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Screening molecular associations with lipid membranes using natural abundance 13C cross-polarization magic-angle spinning NMR and principal component analysis.

PubMed

Middleton, David A; Hughes, Eleri; Madine, Jillian

2004-08-11

We describe an NMR approach for detecting the interactions between phospholipid membranes and proteins, peptides, or small molecules. First, 1H-13C dipolar coupling profiles are obtained from hydrated lipid samples at natural isotope abundance using cross-polarization magic-angle spinning NMR methods. Principal component analysis of dipolar coupling profiles for synthetic lipid membranes in the presence of a range of biologically active additives reveals clusters that relate to different modes of interaction of the additives with the lipid bilayer. Finally, by representing profiles from multiple samples in the form of contour plots, it is possible to reveal statistically significant changes in dipolar couplings, which reflect perturbations in the lipid molecules at the membrane surface or within the hydrophobic interior.

A novel dipolar dephasing method for the slow magic angle turning experiment.

PubMed

Hu, J Z; Taylor, C M; Pugmire, R J; Grant, D M

2001-09-01

Complete suppression of the resonances from protonated carbons in a slow magic angle spinning experiment can be achieved using five dipolar dephasing (Five-DD) periods distributed in one rotor period. This produces a spectrum containing only the spinning sidebands (SSB) from the nonprotonated carbons. It is shown that the SSB patterns corresponding to the nonprotonated carbons are not distorted over a wide range of dipolar dephasing times. Hence, this method can be used to obtain reliable principal values of the chemical shift tensors for each nonprotonated carbon. The Five-DD method can be readily incorporated into isotropic-anisotropic 2D experiments such as FIREMAT and 2D-PASS to facilitate the measurement of the (13)C chemical shift tensors in complex systems. Copyright 2001 Academic Press.

Cascade oxime formation, cyclization to a nitrone, and intermolecular dipolar cycloaddition.

PubMed

Furnival, Rachel C; Saruengkhanphasit, Rungroj; Holberry, Heather E; Shewring, Jonathan R; Guerrand, Hélène D S; Adams, Harry; Coldham, Iain

2016-11-22

Simple haloaldehydes, including enolisable aldehydes, were found to be suitable for the formation of cyclic products by cascade (domino) condensation, cyclisation, dipolar cycloaddition chemistry. This multi-component reaction approach to heterocyclic compounds was explored by using hydroxylamine, a selection of aldehydes, and a selection of activated dipolarophiles. Initial condensation gives intermediate oximes that undergo cyclisation with displacement of halide to give intermediate nitrones; these nitrones undergo in situ intermolecular dipolar cycloaddition reactions to give isoxazolidines. The cycloadducts from using dimethyl fumarate were treated with zinc/acetic acid to give lactam products and this provides an easy way to prepare pyrrolizinones, indolizinones, and pyrrolo[2,1-a]isoquinolinones. The chemistry is illustrated with a very short synthesis of the pyrrolizidine alkaloid macronecine and a formal synthesis of petasinecine.

Geometric stability spectra of dipolar Bose gases in tunable optical lattices

NASA Astrophysics Data System (ADS)

Corson, John P.; Wilson, Ryan M.; Bohn, John L.

2013-07-01

We examine the stability of quasi-two-dimensional dipolar Bose-Einstein condensates in the presence of weak optical lattices of various geometries. We find that when the condensate possesses a roton-maxon quasiparticle dispersion, the conditions for stability exhibit a strong dependence both on the lattice geometry and the polarization tilt. This results in rich structures in the system's stability diagram akin to spectroscopic signatures. We show how these structures originate from the mode matching of rotons to the perturbing lattice. In the case of a one-dimensional lattice, some of the features emerge only when the polarization axis is tilted into the plane of the condensate. Our results suggest that the stability diagram may be used as a novel means to spectroscopically measure rotons in dipolar condensates.

Development and application of high-resolution solid- state NMR dipolar recovery techniques for spin-1/2 nuclei

NASA Astrophysics Data System (ADS)

Joers, James M.

The use of magic angle spinning to obtain high resolution solid state spectra has been well documented. This resolution occurs by coherently averaging the chemical shift anisotropy and dipolar interactions to zero over the period of a full rotation. While this allows for higher resolution, the structural information is seemingly lost to the spectrometer eye. Thus, high resolution spectra and structural information appear to be mutually exlusive. Recently, the push in solid state NMR is the development of recoupling techniques which afford both high resolution and structural information. The following dissertation demonstrates the feasibility of implementing such experiments in solving real world problems, and is centered on devising a method to recover homonuclear dipolar interactions in the high resolution regime.

Dielectric relaxation in ionic liquid/dipolar solvent binary mixtures: A semi-molecular theory.

PubMed

Daschakraborty, Snehasis; Biswas, Ranjit

2016-03-14

A semi-molecular theory is developed here for studying dielectric relaxation (DR) in binary mixtures of ionic liquids (ILs) with common dipolar solvents. Effects of ion translation on DR time scale, and those of ion rotation on conductivity relaxation time scale are explored. Two different models for the theoretical calculations have been considered: (i) separate medium approach, where molecularities of both the IL and dipolar solvent molecules are retained, and (ii) effective medium approach, where the added dipolar solvent molecules are assumed to combine with the dipolar ions of the IL, producing a fictitious effective medium characterized via effective dipole moment, density, and diameter. Semi-molecular expressions for the diffusive DR times have been derived which incorporates the effects of wavenumber dependent orientational static correlations, ion dynamic structure factors, and ion translation. Subsequently, the theory has been applied to the binary mixtures of 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim][BF4]) with water (H2O), and acetonitrile (CH3CN) for which experimental DR data are available. On comparison, predicted DR time scales show close agreement with the measured DR times at low IL mole fractions (x(IL)). At higher IL concentrations (x(IL) > 0.05), the theory over-estimates the relaxation times and increasingly deviates from the measurements with x(IL), deviation being the maximum for the neat IL by almost two orders of magnitude. The theory predicts negligible contributions to this deviation from the x(IL) dependent collective orientational static correlations. The drastic difference between DR time scales for IL/solvent mixtures from theory and experiments arises primarily due to the use of the actual molecular volume (V(mol)(dip)) for the rotating dipolar moiety in the present theory and suggests that only a fraction of V(mol)(dip) is involved at high x(IL). Expectedly, nice agreement between theory and experiments appears when experimental estimates for the effective rotational volume (V(eff)(dip)) are used as inputs. The fraction, V(eff)(dip)/V(mol)(dip), sharply decreases from ∼1 at pure dipolar solvent to ∼0.01 at neat IL, reflecting a dramatic crossover from viscosity-coupled hydrodynamic angular diffusion at low IL mole fractions to orientational relaxation predominantly via large angle jumps at high x(IL). Similar results are obtained on applying the present theory to the aqueous solution of an electrolyte guanidinium chloride (GdmCl) having a permanent dipole moment associated with the cation, Gdm(+).

'Extra-regional' strike-slip fault systems in Chile and Alaska: the North Pacific Rim orogenic Stream vs. Beck's Buttress

NASA Astrophysics Data System (ADS)

Redfield, T. F.; Scholl, D. W.; Fitzgerald, P. G.

2010-12-01

The ~2000 km long Denali Fault System (DFS) of Alaska is an example of an extra-regional strike-slip fault system that terminates in a zone of widely-distributed deformation. The ~1200 km long Liquiñe-Ofqui Fault Zone (LOFZ) of Patagonia (southern Chile) is another. Both systems are active, having undergone large-magnitude seismic rupture is 2002 (DFS) and 2007 (LOFZ). Both systems appear to be long-lived: the DFS juxtaposes terranes that docked in at least early Tertiary time, whilst the central LOFZ appears to also record early Tertiary or Mesozoic deformation. Both fault systems comprise a relatively well-defined central zone where individual fault traces can be identified from topographic features or zones of deformed rock. In both cases the proximal and distal traces are much more diffuse tributary and distributary systems of individual, branching fault traces. However, since their inception the DFS and LOFZ have followed very different evolutionary paths. Copious Alaskan paleomagnetic data are consistent with vertical axis small block rotation, long-distance latitudinal translation, and a recently-postulated tectonic extrusion towards a distributary of subordinate faults that branch outward towards the Aleution subduction zone (the North Pacific Rim orogenic Stream; see Redfield et al., 2007). Paleomagnetic data from the LOFZ region are consistent with small block rotation but preclude statistically-significant latitudinal transport. Limited field data from the southernmost LOFZ suggest that high-angle normal and reverse faults dominate over oblique to strike-slip structures. Rather than the high-angle oblique 'slivering regime' of the southeasternmost DFS, the initiation of the LOFZ appears to occur across a 50 to 100 km wide zone of brittly-deformed granitic and gneissic rock characterized by bulk compression and vertical pathways of exhumation. In both cases, relative plate motions are consistent with the hypothetical style, and degree, of offset, leading us to speculate towards the role of obliquity of plate tectonic convergence for the along-strike evolution of extra-regional strike-slip systems. Highly-oblique initiation of the DFS encourages detachment of fault-bounded terranes and provides a driver that encourages a westward-fanning pattern of extrusion towards the free face of the Beringian margin. Plausibly, its less-oblique central segment promotes vertical pathway exhumation observed at (for example) Denali itself. A more orthogonal regime drives the entire LOFZ, precluding slivering at its initiation and promoting upstream buttressing (Beck et al., 1993). The convergent plate boundary setting opens a window through time and space on the evolution of large-magnitude fault-systems. Escape, or not to escape ~ what best answers the question ? Citations Redfield, T. F., Scholl, D. W., Fitzgerald, P. G., and Beck, M. E., & 2007. Escape tectonics and the extrusion of Alaska: past, present, and future. Geology. 35, 11, 1039-1042 Beck, M.E., Rojas, C. and Cembrano, J. (1993). “On the nature of buttressing in margin-parallel strike-fault systems.” Geology, Vol. 21, pp. 755-758.

Interpretation of magnetization transfer from inhomogeneously broadened lines (ihMT) in tissues as a dipolar order effect within motion restricted molecules

NASA Astrophysics Data System (ADS)

Varma, G.; Girard, O. M.; Prevost, V. H.; Grant, A. K.; Duhamel, G.; Alsop, D. C.

2015-11-01

Comparison of off-resonance saturation with single and dual frequency irradiation indicates a contribution of inhomogeneously broadened lines to magnetization transfer in tissues. This inhomogeneous magnetization transfer (ihMT) phenomenon can be exploited to produce images that highlight tissues containing myelin, in vivo. Here, a model for ihMT is described that includes dipolar order effects from magnetization associated with motion-restricted macromolecules. In this model, equal irradiation at positive and negative frequency offsets eliminates dipolar order and achieves greater saturation than irradiation at a single offset frequency using the same power. Fitting of mouse and human volunteer brain data at different irradiation powers and offset frequencies was performed to assess the relevance of the model and approximate tissue parameters. A key parameter in determining ihMT signal was found to be the relaxation time T1D associated with the dipolar order reservoir and the fraction f of the semi-solid, bound magnetization that possessed a nonzero T1D. Indeed, better fits of myelinated tissue were achieved when assuming f ≠ 1. From such fits, estimated T1Ds of mice in the white matter, (34 ± 14)ms, were much longer than in muscle, T1D = (1 ± 1)ms and the average f from white matter volunteer data was 2.2 times greater than that in grey matter. The combination of f and longer T1Ds was primarily responsible for the much higher ihMT in myelinated tissues, and provided explanation for the species variation. This dipolar order ihMT model should help guide future research, pulse sequence optimization, and clinical applications.

Variations of High-Energy Ions during Fast Plasma Flows and Dipolarization in the Plasma Sheet: Comparison Among Different Ion Species

NASA Astrophysics Data System (ADS)

Ohtani, S.; Nose, M.; Miyashita, Y.; Lui, A.

2014-12-01

We investigate the responses of different ion species (H+, He+, He++, and O+) to fast plasma flows and local dipolarization in the plasma sheet in terms of energy density. We use energetic (9-210 keV) ion composition measurements made by the Geotail satellite at r = 10~31 RE. The results are summarized as follows: (1) whereas the O+-to-H+ ratio decreases with earthward flow velocity, it increases with tailward flow velocity with Vx dependence steeper for perpendicular flows than for parallel flows; (2) for fast earthward flows, the energy density of each ion species increases without any clear preference for heavy ions; (3) for fast tailward flows the ion energy density increases initially, then it decreases to below pre-flow levels except for O+; (4) the O+-to-H+ ratio does not increase through local dipolarization irrespective of dipolarization amplitude, background BZ, X distance, and VX; (5) in general, the H+ and He++ ions behave similarly. Result (1) can be attributed to radial transport along with the earthward increase of the background O+-to-H+ ratio. Results (2) and (4) indicate that ion energization associated with local dipolarization is not mass-dependent possibly because in the energy range of our interest the ions are not magnetized irrespective of species. In the tailward outflow region of reconnection, where the plasma sheet becomes thinner, the H+ ions escape along the field line more easily than the O+ ions, which possibly explains result (3). Result (5) suggests that the solar wind is the primary source of the high-energy H+ ions.

Quantum phases of dipolar rotors on two-dimensional lattices

NASA Astrophysics Data System (ADS)

Abolins, B. P.; Zillich, R. E.; Whaley, K. B.

2018-03-01

The quantum phase transitions of dipoles confined to the vertices of two-dimensional lattices of square and triangular geometry is studied using path integral ground state quantum Monte Carlo. We analyze the phase diagram as a function of the strength of both the dipolar interaction and a transverse electric field. The study reveals the existence of a class of orientational phases of quantum dipolar rotors whose properties are determined by the ratios between the strength of the anisotropic dipole-dipole interaction, the strength of the applied transverse field, and the rotational constant. For the triangular lattice, the generic orientationally disordered phase found at zero and weak values of both dipolar interaction strength and applied field is found to show a transition to a phase characterized by net polarization in the lattice plane as the strength of the dipole-dipole interaction is increased, independent of the strength of the applied transverse field, in addition to the expected transition to a transverse polarized phase as the electric field strength increases. The square lattice is also found to exhibit a transition from a disordered phase to an ordered phase as the dipole-dipole interaction strength is increased, as well as the expected transition to a transverse polarized phase as the electric field strength increases. In contrast to the situation with a triangular lattice, on square lattices, the ordered phase at high dipole-dipole interaction strength possesses a striped ordering. The properties of these quantum dipolar rotor phases are dominated by the anisotropy of the interaction and provide useful models for developing quantum phases beyond the well-known paradigms of spin Hamiltonian models, implementing in particular a novel physical realization of a quantum rotor-like Hamiltonian that possesses an anisotropic long range interaction.

Corresponding-states behavior of a dipolar model fluid with variable dispersion interactions and its relevance to the anomalies of hydrogen fluoride

NASA Astrophysics Data System (ADS)

Weiss, Volker C.; Leroy, Frédéric

2016-06-01

More than two decades ago, the elusiveness of a liquid-vapor equilibrium and a corresponding critical point in simulations of the supposedly simple model of dipolar hard spheres came as a surprise to many liquid matter theorists. van Leeuwen and Smit [Phys. Rev. Lett. 71, 3991 (1993)] showed that a minimum of attractive dispersion interactions among the dipolar particles may be needed to observe regular fluid behavior. Here, we adopt their approach and use an only slightly modified model, in which the original point dipole is replaced by a dipole moment produced by charges that are separated in space, to study the influence of dispersion interactions of variable strength on the coexistence and interfacial properties of a polar fluid. The thermophysical properties are discussed in terms of Guggenheim's corresponding-states approach. In this way, the coexistence curve, the critical compressibility factor, the surface tension, Guggenheim's ratio, and modifications of Guldberg's and Trouton's rules (related to the vapor pressure and the enthalpy of vaporization) are analyzed. As the importance of dispersion is decreased, a crossover from simple-fluid behavior to that characteristic of strongly dipolar systems takes place; for some properties, this transition is monotonic, but for others it occurs non-monotonically. For strongly dipolar systems, the reduced surface tension is very low, whereas Guggenheim's ratio and Guldberg's ratio are found to be high. The critical compressibility factor is smaller, and the coexistence curve is wider and more skewed than for simple fluids. For very weak dispersion, liquid-vapor equilibrium is still observable, but the interfacial tension is extremely low and may, eventually, vanish marking the end of the existence of a liquid phase. We discuss the implications of our findings for real fluids, in particular, for hydrogen fluoride.

Van Allen Probes Observations of Magnetic Field Dipolarization and Its Associated O+ Flux Variations in the Inner Magnetosphere at L 6.6

NASA Technical Reports Server (NTRS)

Nose, M.; Keika, K.; Kletzing, C. A.; Spence, H. E.; Smith, C. W.; MacDowall, R. J.; Reeves, G. D.; Larsen, B. A.; Mitchell, D. G.

2016-01-01

We investigate the magnetic field dipolarization in the inner magnetosphere and its associated ion flux variations, using the magnetic field and energetic ion flux data acquired by the Van Allen Probes. From a study of 74 events that appeared at L= 4.5-6.6 between 1 October 2012 and 31 October 2013, we reveal the following characteristics of the dipolarization in the inner magnetosphere: (1) its time scale is approximately 5 min; (2) it is accompanied by strong magnetic fluctuations that have a dominant frequency close to the O+ gyrofrequency; (3) ion fluxes at 20-50 keV are simultaneously enhanced with larger magnitudes for O+ than for H+; (4) after a few minutes of the dipolarization, the flux enhancement at 0.1-5 keV appears with a clear energy-dispersion signature only for O+; and (5) the energy-dispersed O+ flux enhancement appears in directions parallel or antiparallel to the magnetic field. From these characteristics, we discuss possible mechanisms that can provide selective acceleration to O+ ions at > 20 keV. We conclude that O+ ions at L= 5.4-6.6 undergo nonadiabatic local acceleration caused by oscillating electric field associated with the magnetic fluctuations and/or adiabatic convective transport from the plasma sheet to the inner magnetosphere by the impulsive electric field. At L= 4.5-5.4, however, only the former acceleration is plausible. We also conclude that the field-aligned energy-dispersed O+ ions at 0.1-5 keV originate from the ionosphere and are extracted nearly simultaneously to the onset of the dipolarization.

Effect of magnetic dipolar interactions on temperature dependent magnetic hyperthermia in ferrofluids

NASA Astrophysics Data System (ADS)

Palihawadana-Arachchige, Maheshika; Nemala, Humeshkar; Naik, Vaman M.; Naik, Ratna

2017-01-01

Magnetic hyperthermia (MHT), where localized heating is generated when magnetic nanoparticles (MNPs) are subjected to a radiofrequency magnetic field, has a great potential as a non-invasive cancer therapy treatment. The efficiency of heat generation depends on the magnetic properties of MNPs, such as saturation magnetization (Ms) and magnetic anisotropy (K), as well as the particle size distribution and magnetic dipolar interactions. We have investigated MHT in two Fe3O4 ferrofluids prepared by co-precipitation (CP) and hydrothermal (HT) synthesis methods showing similar physical particle size distribution (14 ± 4 nm) and saturation magnetization (70 ± 2 emu/g of Fe3O4) but very different specific absorption rates (SAR) of ˜110 W/g and ˜40 W/g at room temperature (measured with an ac magnetic field amplitude of 240 Oe and a frequency of 375 kHz). This observed reduction in SAR has been explained by taking into account the dipolar interactions and the distribution of the magnetic core size of MNPs in ferrofluids. The HT ferrofluid shows a higher effective dipolar interaction and a wider distribution of the magnetic core size of MNPs compared to those of the CP ferrofluid. We have fitted the temperature dependent SAR data using the linear response theory, incorporating an effective dipolar interaction, to determine the magnetic anisotropy constant of MNPs prepared by CP (22 ± 2 kJ/m3) and HT (26 ± 2 kJ/m3) synthesis methods. These values are in good agreement with the magnetic anisotropy constant determined using frequency and temperature dependent magnetic susceptibility data obtained on powder samples.

Long-range dipolar order and dispersion forces in polar liquids

NASA Astrophysics Data System (ADS)

Besford, Quinn Alexander; Christofferson, Andrew Joseph; Liu, Maoyuan; Yarovsky, Irene

2017-11-01

Complex solvation phenomena, such as specific ion effects, occur in polar liquids. Interpretation of these effects in terms of structure and dispersion forces will lead to a greater understanding of solvation. Herein, using molecular dynamics, we probe the structure of polar liquids through specific dipolar pair correlation functions that contribute to the potential of mean force that is "felt" between thermally rotating dipole moments. It is shown that unique dipolar order exists at separations at least up to 20 Å for all liquids studied. When the structural order is compared with a dipolar dispersion force that arises from local co-operative enhancement of dipole moments, a strong agreement is found. Lifshitz theory of dispersion forces was compared with the structural order, where the theory is validated for all liquids that do not have significant local dipole correlations. For liquids that do have significant local dipole correlations, specifically liquid water, Lifshitz theory underestimates the dispersion force by a factor of 5-10, demonstrating that the force that leads to the increased structure in liquid water is missed by Lifshitz theory of van der Waals forces. We apply similar correlation functions to an ionic aqueous system, where long-range order between water's dipole moment and a single chloride ion is found to exist at 20 Å of separation, revealing a long-range perturbation of water's structure by an ion. Furthermore, we found that waters within the 1st, 2nd, and 3rd solvation shells of a chloride ion exhibit significantly enhanced dipolar interactions, particularly with waters at larger distances of separation. Our results provide a link between structures, dispersion forces, and specific ion effects, which may lead to a more robust understanding of solvation.

A cross-polarization based rotating-frame separated-local-field NMR experiment under ultrafast MAS conditions

NASA Astrophysics Data System (ADS)

Zhang, Rongchun; Damron, Joshua; Vosegaard, Thomas; Ramamoorthy, Ayyalusamy

2015-01-01

Rotating-frame separated-local-field solid-state NMR experiments measure highly resolved heteronuclear dipolar couplings which, in turn, provide valuable interatomic distances for structural and dynamic studies of molecules in the solid-state. Though many different rotating-frame SLF sequences have been put forth, recent advances in ultrafast MAS technology have considerably simplified pulse sequence requirements due to the suppression of proton-proton dipolar interactions. In this study we revisit a simple two-dimensional 1H-13C dipolar coupling/chemical shift correlation experiment using 13C detected cross-polarization with a variable contact time (CPVC) and systematically study the conditions for its optimal performance at 60 kHz MAS. In addition, we demonstrate the feasibility of a proton-detected version of the CPVC experiment. The theoretical analysis of the CPVC pulse sequence under different Hartmann-Hahn matching conditions confirms that it performs optimally under the ZQ (w1H - w1C = ±wr) condition for polarization transfer. The limits of the cross polarization process are explored and precisely defined as a function of offset and Hartmann-Hahn mismatch via spin dynamics simulation and experiments on a powder sample of uniformly 13C-labeled L-isoleucine. Our results show that the performance of the CPVC sequence and subsequent determination of 1H-13C dipolar couplings are insensitive to 1H/13C frequency offset frequency when high RF fields are used on both RF channels. Conversely, the CPVC sequence is quite sensitive to the Hartmann-Hahn mismatch, particularly for systems with weak heteronuclear dipolar couplings. We demonstrate the use of the CPVC based SLF experiment as a tool to identify different carbon groups, and hope to motivate the exploration of more sophisticated 1H detected avenues for ultrafast MAS.

Carrier-envelope phase effects for a dipolar molecule interacting with two-color pump-probe laser pulses

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

Cheng Taiwang; Brown, Alex

2004-12-01

The interaction of a two-level dipolar molecule with two laser pulses, where one laser's frequency is tuned to the energy level separation (pump laser) while the second laser's frequency is extremely small (probe laser), is investigated. A dipolar molecule is one with a nonzero difference between the permanent dipole moments of the molecular states. As shown previously [A. Brown, Phys. Rev. A 66, 053404 (2002)], the final population transfer between the two levels exhibits a dependence on the carrier-envelope phase of the probe laser. Based on the rotating-wave approximation (RWA), an effective Hamiltonian is derived to account for the basicmore » characteristics of the carrier-envelope phase dependence effect. By analysis of the effective Hamiltonian, scaling properties of the system are found with regard to field strengths, pulse durations, and frequencies. According to these scaling properties, the final-state population transfer can be controlled by varying the carrier-envelope phase of the probe laser field using lasers with weak field strengths (low intensities) and relatively long pulse durations. In order to examine the possible roles of background states, the investigation is extended to a three-level model. It is demonstrated that the carrier-envelope phase effect still persists in a well-defined manner even when neighboring energy levels are present. These results illustrate the potential of utilizing excitation in dipolar molecules as a means of measuring the carrier-envelope phase of a laser pulse or if one can manipulate the carrier envelope phase, as a method of controlling population transfer in dipolar molecules. The results also suggest that the carrier-envelope phases must be taken into account properly when performing calculations involving pump-probe excitation schemes with laser frequencies which differ widely in magnitude.« less

Coherent manipulation of dipolar coupled spins in an anisotropic environment

NASA Astrophysics Data System (ADS)

Baibekov, E. I.; Gafurov, M. R.; Zverev, D. G.; Kurkin, I. N.; Malkin, B. Z.; Barbara, B.

2014-11-01

We study coherent dynamics in a system of dipolar coupled spin qubits diluted in a solid and subjected to a driving microwave field. In the case of rare earth ions, an anisotropic crystal background results in anisotropic g tensor and thus modifies the dipolar coupling. We develop a microscopic theory of spin relaxation in a transient regime for the frequently encountered case of axially symmetric crystal field. The calculated decoherence rate is nonlinear in the Rabi frequency. We show that the direction of a static magnetic field that corresponds to the highest spin g factor is preferable in order to obtain a higher number of coherent qubit operations. The results of calculations are in excellent agreement with our experimental data on Rabi oscillations recorded for a series of CaW O4 crystals with different concentrations of N d3 + ions.

Nanoscale control of competing interactions and geometrical frustration in a dipolar trident lattice

DOE PAGES

Farhan, Alan; Petersen, Charlotte F.; Dhuey, Scott; ...

2017-10-17

Geometrical frustration occurs when entities in a system, subject to given lattice constraints, are hindered to simultaneously minimize their local interactions. In magnetism, systems incorporating geometrical frustration are fascinating, as their behavior is not only hard to predict, but also leads to the emergence of exotic states of matter. Here, we provide a first look into an artificial frustrated system, the dipolar trident lattice, where the balance of competing interactions between nearest-neighbor magnetic moments can be directly controlled, thus allowing versatile tuning of geometrical frustration and manipulation of ground state configurations. Our findings not only provide the basis for futuremore » studies on the low-temperature physics of the dipolar trident lattice, but also demonstrate how this frustration-by-design concept can deliver magnetically frustrated metamaterials.« less

Fingering instabilities and pattern formation in a two-component dipolar Bose-Einstein condensate

NASA Astrophysics Data System (ADS)

Xi, Kui-Tian; Byrnes, Tim; Saito, Hiroki

2018-02-01

We study fingering instabilities and pattern formation at the interface of an oppositely polarized two-component Bose-Einstein condensate with strong dipole-dipole interactions in three dimensions. It is shown that the rotational symmetry is spontaneously broken by fingering instability when the dipole-dipole interactions are strengthened. Frog-shaped and mushroom-shaped patterns emerge during the dynamics due to the dipolar interactions. We also demonstrate the spontaneous density modulation and domain growth of a two-component dipolar BEC in the dynamics. Bogoliubov analyses in the two-dimensional approximation are performed, and the characteristic lengths of the domains are estimated analytically. Patterns resembling those in magnetic classical fluids are modulated when the number ratio of atoms, the trap ratio of the external potential, or tilted polarization with respect to the z direction is varied.

Towards novel multiferroic and magnetoelectric materials: dipole stability in tetragonal tungsten bronzes

PubMed Central

Rotaru, Andrei; Miller, Andrew J.; Arnold, Donna C.; Morrison, Finlay D.

2014-01-01

We discuss the strategy for development of novel functional materials with the tetragonal tungsten bronze structure. From the starting composition Ba6GaNb9O30, the effect of A- and B-site substitutions on the dielectric properties is used to develop an understanding of the origin and stability of the dipolar response in these compounds. Both tetragonal strain induced by large B-site cations and local strain variations created by isovalent A-site substitutions enhance dipole stability but result in a dilute, weakly correlated dipolar response and canonical relaxor behaviour. Decreasing cation size at the perovskite A2-site increases the dipolar displacements in the surrounding octahedra, but insufficiently to result in dipole ordering. Mechanisms introducing small A-site lanthanide cations and incorporation of A-site vacancies to induce ferroelectricity and magnetism are presented. PMID:24421377

Cooling without contact in bilayer dipolar Fermi gases

NASA Astrophysics Data System (ADS)

Tanatar, Bilal; Renklioglu, Basak; Oktel, M. Ozgur

2016-05-01

We consider two parallel layers of dipolar ultracold Fermi gases at different temperatures and calculate the heat transfer between them. The effective interactions describing screening and correlation effects between the dipoles in a single layer are modelled within the Euler-Lagrange Fermi-hypernetted chain approximation. The random-phase approximation is employed for the interactions across the layers. We investigate the amount of transferred power between the layers as a function of the temperature difference. Energy transfer proceeds via the long-range dipole-dipole interactions. A simple thermal model is developed to investigate the feasibility of using the contactless sympathetic cooling of the ultracold polar atoms/molecules. Our calculations indicate that dipolar heat transfer is effective for typical polar molecule experiments and may be utilized as a cooling process. Supported by TUBA and TUBITAK (112T974).

Synthesis of Functionalized Pyrazoles via 1,3-Dipolar Cycloaddition of α-Diazo-β-ketophosphonates, Sufones and Esters with Electron-Deficient Alkenes.

PubMed

Baiju, T V; Namboothiri, Irishi N N

2017-10-01

1,3-Dipolar cycloaddition of diazo compounds with olefinic substrates is a promising atom-economic strategy for the construction of functionalized pyrazoles. Over the last few years, our group has been engaged in the synthesis of phosphonyl/sulfonylpyrazoles and pyrazole esters by employing Bestmann-Ohira Reagent (BOR) and its sulfur and ester analogs as 1,3-dipole precursors with various dipolarophiles. This account describes the novel synthetic methods developed in our laboratory, in the perspective of closely related work by others, for the synthesis of phosphonyl/sulfonylpyrazoles, pyrazole esters and the total synthesis of Withasomnine, a natural product, by using 1,3-dipolar cycloaddition as the key step. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Weyl Superfluidity in a Three-dimensional Dipolar Fermi Gas

NASA Astrophysics Data System (ADS)

Liu, Bo; Li, Xiaopeng; Yin, Lan; Liu, W. Vincent

2015-03-01

Weyl superconductivity or superfluidity, a fascinating topological state of matter, features novel phenomena such as emergent Weyl fermionic excitations and anomalies. Here we report that an anisotropic Weyl superfluid state can arise as a low temperature stable phase in a 3D dipolar Fermi gas. A crucial ingredient of our model is a direction-dependent two-body effective attraction generated by a rotating external field. Experimental signatures are predicted for cold gases in radio-frequency spectroscopy. The finite temperature phase diagram of this system is studied and the transition temperature of the Weyl superfluidity is found to be within the experimental scope for atomic dipolar Fermi gases. Work supported in part by U.S. ARO, AFOSR, DARPA-OLE-ARO, Charles E. Kaufman Foundation and The Pittsburgh Foundation, JQI-NSF-PFC, ARO-Atomtronics-MURI, and NSF of China.

Magnetar-like emission in different neutron star classes

NASA Astrophysics Data System (ADS)

Rea, N.

2017-10-01

I will present new results on magnetar-like transient events in neutron stars having low dipolar fields or generally catalogued as normal radio pulsars or central compact objects. I will then present simulations of magnetic field evolution that might explain the apparently puzzling behaviour of these objects. Strong surface magnetic field might be an almost ubiquitous properties of pulsars, regardless their external dipolar magnetic field measured via their spin down properties.

Optical Switching Using Transition from Dipolar to Charge Transfer Plasmon Modes in Ge2Sb2Te5 Bridged Metallodielectric Dimers

PubMed Central

Ahmadivand, Arash; Gerislioglu, Burak; Sinha, Raju; Karabiyik, Mustafa; Pala, Nezih

2017-01-01

Capacitive coupling and direct shuttling of charges in nanoscale plasmonic components across a dielectric spacer and through a conductive junction lead to excitation of significantly different dipolar and charge transfer plasmon (CTP) resonances, respectively. Here, we demonstrate the excitation of dipolar and CTP resonant modes in metallic nanodimers bridged by phase-change material (PCM) sections, material and electrical characteristics of which can be controlled by external stimuli. Ultrafast switching (in the range of a few nanoseconds) between amorphous and crystalline phases of the PCM section (here Ge2Sb2Te5 (GST)) allows for designing a tunable plasmonic switch for optical communication applications with significant modulation depth (up to 88%). Judiciously selecting the geometrical parameters and taking advantage of the electrical properties of the amorphous phase of the GST section we adjusted the extinction peak of the dipolar mode at the telecommunication band (λ~1.55 μm), which is considered as the OFF state. Changing the GST phase to crystalline via optical heating allows for direct transfer of charges through the junction between nanodisks and formation of a distinct CTP peak at longer wavelengths (λ~1.85 μm) far from the telecommunication wavelength, which constitutes the ON state. PMID:28205643

Optical Switching Using Transition from Dipolar to Charge Transfer Plasmon Modes in Ge2Sb2Te5 Bridged Metallodielectric Dimers.

PubMed

Ahmadivand, Arash; Gerislioglu, Burak; Sinha, Raju; Karabiyik, Mustafa; Pala, Nezih

2017-02-16

Capacitive coupling and direct shuttling of charges in nanoscale plasmonic components across a dielectric spacer and through a conductive junction lead to excitation of significantly different dipolar and charge transfer plasmon (CTP) resonances, respectively. Here, we demonstrate the excitation of dipolar and CTP resonant modes in metallic nanodimers bridged by phase-change material (PCM) sections, material and electrical characteristics of which can be controlled by external stimuli. Ultrafast switching (in the range of a few nanoseconds) between amorphous and crystalline phases of the PCM section (here Ge 2 Sb 2 Te 5 (GST)) allows for designing a tunable plasmonic switch for optical communication applications with significant modulation depth (up to 88%). Judiciously selecting the geometrical parameters and taking advantage of the electrical properties of the amorphous phase of the GST section we adjusted the extinction peak of the dipolar mode at the telecommunication band (λ~1.55 μm), which is considered as the OFF state. Changing the GST phase to crystalline via optical heating allows for direct transfer of charges through the junction between nanodisks and formation of a distinct CTP peak at longer wavelengths (λ~1.85 μm) far from the telecommunication wavelength, which constitutes the ON state.

Fluid transport by dipolar vortices

NASA Astrophysics Data System (ADS)

I, Eames; J.-B, Flór

1998-08-01

The transport properties of dipolar vortices propagating on an f-plane are studied experimentally by examining the distortion of a series of material surfaces. The observations are compared with a model based on characterising the flow around the dipole as irrotational flow past a rigid cylinder of volume V. Measurements made of the volume of fluid permanently displaced forward by the vortices, agree to within 20% of that predicted by the proposition of Darwin [Darwin, C., 1953. A note on hydrodynamics. Proc. Cambridge Philos. Soc., 49, 342-354], namely that the vortex will displace a volume CMV forward, where CM=1 for a Lamb's dipole. The results are applied to examine fluid transport by dipolar vortices propagating on the β-plane, where the ambient potential vorticity field causes easterly propagating dipolar vortices to meander sinusoidally between the North and South. We demonstrate that as the vortex moves between the North and South, it exchanges a volume CMV sin α by the drift effect (where α is the angle between the velocity of the dipole and the material surface), which is generally larger than that attributed to other mechanisms such as lobe shedding. The results are applied to give new insight to the effect of vortices in enhancing diffusion, and the secondary flow generated by the transport of ambient potential vorticity.

Absence of Long-Range Order in a Triangular Spin System with Dipolar Interactions

NASA Astrophysics Data System (ADS)

Keleş, Ahmet; Zhao, Erhai

2018-05-01

The antiferromagnetic Heisenberg model on the triangular lattice is perhaps the best known example of frustrated magnets, but it orders at low temperatures. Recent density matrix renormalization group (DMRG) calculations find that the next nearest neighbor interaction J2 enhances the frustration, and it leads to a spin liquid for J2/J1∈(0.08 ,0.15 ). In addition, a DMRG study of a dipolar Heisenberg model with longer range interactions gives evidence for a spin liquid at a small dipole tilting angle θ ∈[0 ,1 0 ° ). In both cases, the putative spin liquid region appears to be small. Here, we show that for the triangular lattice dipolar Heisenberg model, a robust quantum paramagnetic phase exists in a surprisingly wide region, θ ∈[0 ,5 4 ° ) , for dipoles tilted along the lattice diagonal direction. We obtain the phase diagram of the model by functional renormalization group (RG), which treats all magnetic instabilities on equal footing. The quantum paramagnetic phase is characterized by a smooth continuous flow of vertex functions and spin susceptibility down to the lowest RG scale, in contrast to the apparent breakdown of RG flow in phases with stripe or spiral order. Our finding points to a promising direction to search for quantum spin liquids in ultracold dipolar molecules.

Dipolar DC Collisional Activation in a "Stretched" 3-D Ion Trap: The Effect of Higher Order Fields on rf-Heating

NASA Astrophysics Data System (ADS)

Prentice, Boone M.; McLuckey, Scott A.

2012-04-01

Applying dipolar DC (DDC) to the end-cap electrodes of a 3-D ion trap operated with a bath gas at roughly 1 mTorr gives rise to `rf-heating' and can result in collision-induced dissociation (CID). This approach to ion trap CID differs from the conventional single-frequency resonance excitation approach in that it does not rely on tuning a supplementary frequency to coincide with the fundamental secular frequeny of the precursor ion of interest. Simulations using the program ITSIM 5.0 indicate that application of DDC physically displaces ions solely in the axial (inter end-cap) dimension whereupon ion acceleration occurs via power absorption from the drive rf. Experimental data shows that the degree of rf-heating in a stretched 3-D ion trap is not dependent solely on the ratio of the dipolar DC voltage/radio frequency (rf) amplitude, as a model based on a pure quadrupole field suggests. Rather, ion temperatures are shown to increase as the absolute values of the dipolar DC and rf amplitude both decrease. Simulations indicate that the presence of higher order multi-pole fields underlies this unexpected behavior. These findings have important implications for the use of DDC as a broad-band activation approach in multi-pole traps.

Optical Switching Using Transition from Dipolar to Charge Transfer Plasmon Modes in Ge2Sb2Te5 Bridged Metallodielectric Dimers

NASA Astrophysics Data System (ADS)

Ahmadivand, Arash; Gerislioglu, Burak; Sinha, Raju; Karabiyik, Mustafa; Pala, Nezih

2017-02-01

Capacitive coupling and direct shuttling of charges in nanoscale plasmonic components across a dielectric spacer and through a conductive junction lead to excitation of significantly different dipolar and charge transfer plasmon (CTP) resonances, respectively. Here, we demonstrate the excitation of dipolar and CTP resonant modes in metallic nanodimers bridged by phase-change material (PCM) sections, material and electrical characteristics of which can be controlled by external stimuli. Ultrafast switching (in the range of a few nanoseconds) between amorphous and crystalline phases of the PCM section (here Ge2Sb2Te5 (GST)) allows for designing a tunable plasmonic switch for optical communication applications with significant modulation depth (up to 88%). Judiciously selecting the geometrical parameters and taking advantage of the electrical properties of the amorphous phase of the GST section we adjusted the extinction peak of the dipolar mode at the telecommunication band (λ~1.55 μm), which is considered as the OFF state. Changing the GST phase to crystalline via optical heating allows for direct transfer of charges through the junction between nanodisks and formation of a distinct CTP peak at longer wavelengths (λ~1.85 μm) far from the telecommunication wavelength, which constitutes the ON state.

Donor and recipient chemokine receptor CCR5 genotype is associated with survival after bone marrow transplantation

PubMed Central

McDermott, David H.; Conway, Susan E.; Wang, Tao; Ricklefs, Stacy M.; Agovi, Manza A.; Porcella, Stephen F.; Tran, Huong Thi Bich; Milford, Edgar; Spellman, Stephen

2010-01-01

Despite continual improvement, morbidity and mortality after hematopoietic stem cell transplantation (HSCT) remain high. The importance of chemokines in HSCT lies in their regulation of immune responses that determine transplantation outcomes. We investigated the role of recipient and donor chemokine system gene polymorphisms by using a candidate gene approach on the incidence of graft-versus-host disease and posttransplantation outcomes in 1370 extensively human leukocyte antigen–matched, unrelated donor-recipient pairs by using multivariate Cox regression models. Our analysis identified that recipients homozygous for a common CCR5 haplotype (H1/H1) had better disease-free survival (DFS; P = .005) and overall survival (P = .021). When the same genotype of both the donor and recipient were considered in the models, a highly significant association with DFS and overall survival was noted (P < .001 and P = .007, respectively) with absolute differences in survival of up to 20% seen between the groups at 3 years after transplantation (50% DFS for pairs with recipient CCR5 H1/H1 vs 30% for pairs with donor CCR5 H1/H1). This finding suggests that donor and/or recipient CCR5 genotypes may be associated with HSCT outcome and suggests new diagnostic and therapeutic strategies for optimizing therapy. PMID:20068218

Tumors with unmethylated MLH1 and the CpG island methylator phenotype are associated with a poor prognosis in stage II colorectal cancer patients

PubMed Central

Fu, Tao; Liu, Yanliang; Li, Kai; Wan, Weiwei; Pappou, Emmanouil P.; Iacobuzio-Donahue, Christine A.; Kerner, Zachary; Baylin, Stephen B.; Wolfgang, Christopher L.; Ahuja, Nita

2016-01-01

We previously developed a novel tumor subtype classification model for duodenal adenocarcinomas based on a combination of the CpG island methylator phenotype (CIMP) and MLH1 methylation status. Here, we tested the prognostic value of this model in stage II colorectal cancer (CRC) patients. Tumors were assigned to CIMP+/MLH1-unmethylated (MLH1-U), CIMP+/MLH1-methylated (MLH1-M), CIMP−/MLH1-U, or CIMP−/MLH1-M groups. Age, tumor location, lymphovascular invasion, and mucin production differed among the four patient subgroups, and CIMP+/MLH1-U tumors were more likely to have lymphovascular invasion and mucin production. Kaplan-Meier analyses revealed differences in both disease-free survival (DFS) and overall survival (OS) among the four groups. In a multivariate analysis, CIMP/MLH1 methylation status was predictive of both DFS and OS, and DFS and OS were shortest in CIMP+/MLH1-U stage II CRC patients. These results suggest that tumor subtype classification based on the combination of CIMP and MLH1 methylation status is informative in stage II CRC patients, and that CIMP+/MLH1-U tumors exhibit aggressive features and are associated with poor clinical outcomes. PMID:27880934

Tumors with unmethylated MLH1 and the CpG island methylator phenotype are associated with a poor prognosis in stage II colorectal cancer patients.

PubMed

Fu, Tao; Liu, Yanliang; Li, Kai; Wan, Weiwei; Pappou, Emmanouil P; Iacobuzio-Donahue, Christine A; Kerner, Zachary; Baylin, Stephen B; Wolfgang, Christopher L; Ahuja, Nita

2016-12-27

We previously developed a novel tumor subtype classification model for duodenal adenocarcinomas based on a combination of the CpG island methylator phenotype (CIMP) and MLH1 methylation status. Here, we tested the prognostic value of this model in stage II colorectal cancer (CRC) patients. Tumors were assigned to CIMP+/MLH1-unmethylated (MLH1-U), CIMP+/MLH1-methylated (MLH1-M), CIMP-/MLH1-U, or CIMP-/MLH1-M groups. Age, tumor location, lymphovascular invasion, and mucin production differed among the four patient subgroups, and CIMP+/MLH1-U tumors were more likely to have lymphovascular invasion and mucin production. Kaplan-Meier analyses revealed differences in both disease-free survival (DFS) and overall survival (OS) among the four groups. In a multivariate analysis, CIMP/MLH1 methylation status was predictive of both DFS and OS, and DFS and OS were shortest in CIMP+/MLH1-U stage II CRC patients. These results suggest that tumor subtype classification based on the combination of CIMP and MLH1 methylation status is informative in stage II CRC patients, and that CIMP+/MLH1-U tumors exhibit aggressive features and are associated with poor clinical outcomes.

Preoperative Platelet to Albumin Ratio Predicts Outcome of Patients with Cholangiocarcinoma.

PubMed

Saito, Nobuhiro; Shirai, Yoshihiro; Horiuchi, Takashi; Sugano, Hiroshi; Shiba, Hiroaki; Sakamoto, Taro; Uwagawa, Tadashi; Yanaga, Katsuhiko

2018-02-01

The purpose of this study was to evaluate the prognostic index of the preoperative platelet to albumin ratio (PAR) in patients who underwent primary resection for cholangiocarcinoma. A total of 59 patients were divided into two groups: those with PAR ≥72.6×10 3 or <72.6×10 3 according to the area under the receiver operating characteristics curve. PAR was significantly inversely associated with overall (OS) and disease-free (DFS) survival on univariate analysis. PAR showed significance on multivariate analysis for OS (hazard ratio=6.232, 95% confidence interval=1.283-30.279, p=0.023), along with tumor differentiation (p=0.009), nodal involvement (p=0.001), intraoperative blood loss (p=0.001), and serum carcinoembryonic antigen (CEA) (p=0.012). High PAR was also significantly associated poor DFS on multivariate analysis (hazard ratio(HR)=4.422, 95% confidence interval(CI)=1.168-16.732, p=0.029), along with tumor differentiation (p=0.009). PAR is a useful prognostic index for OS and DFS in patients with cholangiocarcinoma after primary resection. By accumulating cases prospectively, this new index may be a reference for use before neoadjuvant chemotherapy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Infant breast-feeding and childhood caries: a nine-year study.

PubMed

Hong, Liang; Levy, Steven M; Warren, John J; Broffitt, Barbara

2014-01-01

This study's purpose was to assess the association between infant breast-feeding and caries experience of primary second molars in a nine-year longitudinal cohort study. Study sample was 509 subjects recruited at birth. Information about breast-feeding duration and other factors was collected through parents' responses to periodic questionnaires. Primary teeth were examined for dental caries at five years old and nine years old by calibrated dentist examiners. Caries experience (yes/no) and number of decayed and/or filled surfaces (dfs) were determined for five- and nine-year-olds. For primary second molars at five years old, 18 percent of children who were breast-fed less than six months had caries (mean dfs=0.55) while only 9 percent of children who were breast-fed at least six months had caries (mean dfs=0.33). From five to nine years old, caries incidence was 32 percent and 31 percent, respectively, for children breast-fed less than six months and at least six months. In multivariable regression analyses, shorter breast-feeding duration was positively associated with caries experience of primary second molars at five years old (P=.005), both before and after controlling for other important factors. Shorter duration of breast-feeding is suggested to be associated with increased risk for early childhood caries, but its impact might diminish with age.

Additional Prognostic Value of SUVmax Measured by F-18 FDG PET/CT over Biological Marker Expressions in Surgically Resected Cervical Cancer Patients.

PubMed

Yun, Man Soo; Kim, Seong-Jang; Pak, Kyoungjune; Lee, Chang Hun

2015-01-01

We compared the prognostic ability of the maximum standardized uptake value (SUVmax) and various biological marker expressions to predict recurrence in patients with surgically resected cervical cancer. A retrospective review identified 60 patients with cervical cancer who received [18F]fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) at the time of the diagnosis of cancer. The SUVmax, expressions of carbonic anhydrase-IX (CA-IX), glucose transporter 1 (GLUT-1), and vascular endothelial growth factor (VEGF), and known prognostic factors were investigated. The median follow-up time was 22.2 months (range 3.4-43.1 months). Using univariate analyses, the stage (stage II, p = 0.0066), SUVmax (> 6, p = 0.027), parametrial involvement (p < 0.0001), and positivity for CA-IX (p = 0.0191) were associated with recurrences of cervical cancer. With the Cox proportional hazard regression model, the SUVmax was a potent predictor for disease-free survival (DFS). Although CA-IX expression was related to DFS in the current study, the potent predictor for DFS was SUVmax. Therefore, SUVmax is of greater prognostic value than biological marker expression in patients with surgically resected cervical cancer. © 2015 S. Karger GmbH, Freiburg.

Immunohistochemical detection of receptor activator nuclear κB ligand and osteoprotegerin in odontogenic cysts and tumors.

PubMed

de Matos, Felipe Rodrigues; de Moraes, Maiara; das Neves Silva, Emília Beatriz; Galvão, Hébel Cavalcanti; de Almeida Freitas, Roseana

2013-11-01

The aim of the present study was to compare the immunohistochemical detection of receptor activator nuclear κB ligand (RANKL) and osteoprotegerin (OPG) in radicular cysts (RCs), dentigerous cysts (DCs), solid ameloblastomas (SAs), and keratocystic odontogenic tumors (KOTs). A total of 20 RCs, 20 DCs, 20 KOTs, 14 dental follicles (DFs), and 18 SAs were evaluated by immunohistochemistry using anti-RANKL and anti-OPG antibodies. The analysis was quantitative, and the number of positive cells was counted in 10 microscopic high-power fields (400×). The DFs, KOTs, and SAs showed higher expression of RANKL than did the RCs and DCs in the epithelium (P < .05). The epithelial expression of OPG was higher in the DFs, KOTs, RCs, and DCs than in the SAs (P < .05). The ratio of OPG less than RANKL was more frequent in SAs and OPG greater than RANKL in DCs (P < .05). Our results have shown differences in RANKL and OPG detection in the odontogenic cysts and tumors studied. The higher RANKL and lower OPG detection in SA could play a role in bone resorption, compatible with the tumor's biologic behavior. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Prevalence of Strongyloides stercoralis infection and other soil-transmitted helminths by cross-sectional survey in a rural community in Gisagara District, Southern Province, Rwanda

PubMed Central

Tuyizere, Aloys; Ndayambaje, Alphonse; Bayingana, Claude; Ntirenganya, Cyprien; Dusabejambo, Vincent; Hale, DeVon C

2018-01-01

Abstract Background Strongyloides stercoralis is one of the most neglected tropical diseases. Sparse, dated central African and Rwandan data on seroprevalence are available to guide public health efforts and clinical care. Methods In February 2016 we conducted a community-based cross-sectional study among 539 asymptomatic participants in a rural area in the Gisagara District, Southern Province, Rwanda. Direct faecal smear (DFS) and modified Koga agar plate culture (APC) were used to detect S. stercoralis infection in a single stool sample. Data on other soil-transmitted helminths diagnosed by DFS were also recorded. Results Four intestinal helminth infections were diagnosed, with S. stercoralis (17.4%) and hookworms (8.2%) seen most often. APC, compared with DFS, increased the diagnosis rate for S. stercoralis from 1.9% to 17.4% (p<0.01). The prevalence was higher in farmers and those with lower socio-economic status. Females were less often infected than males (odds ratio 0.6 [95% confidence interval 0.3 to 0.9], p=0.02). Conclusions S. stercoralis is highly prevalent among the general population in a rural area of Gisagara District, Southern Province, Rwanda. Access to effective diagnosis and treatment is needed for this neglected disease. PMID:29726969

Fludarabine Melphalan reduced-intensity conditioning allotransplanation provides similar disease control in lymphoid and myeloid malignancies: analysis of 344 patients.

PubMed

Bryant, A; Nivison-Smith, I; Pillai, E S; Kennedy, G; Kalff, A; Ritchie, D; George, B; Hertzberg, M; Patil, S; Spencer, A; Fay, K; Cannell, P; Berkahn, L; Doocey, R; Spearing, R; Moore, J

2014-01-01

This was an Australasian Bone Marrow Transplant Recipient Registry (ABMTRR)-based retrospective study assessing the outcome of Fludarabine Melphalan (FluMel) reduced-intensity conditioning between 1998 and 2008. Median follow-up was 3.4 years. There were 344 patients with a median age of 54 years (18-68). In all, 234 patients had myeloid malignancies, with AML (n=166) being the commonest indication. There were 110 lymphoid patients with non-hodgkins lymphoma (NHL) (n=64) the main indication. TRM at day 100 was 14% with no significant difference between the groups. OS and disease-free survival (DFS) were similar between myeloid and lymphoid patients (57 and 50% at 3 years, respectively). There was no difference in cumulative incidence of relapse or GVHD between groups. Multivariate analysis revealed four significant adverse risk factors for DFS: donor other than HLA-identical sibling donor, not in remission at transplant, previous autologous transplant and recipient CMV positive. Chronic GVHD was associated with improved DFS in multivariate analysis predominantly due to a marked reduction in relapse (HR:0.44, P=0.003). This study confirms that FluMel provides durable and equivalent remissions in both myeloid and lymphoid malignancies. Disease stage and chronic GVHD remain important determinants of outcome for FluMel allografting.

[Therapeutic outcomes in patients with cervical cancer FIGO stage IB1].

PubMed

Kornovski, Y; Ismail, E; Kaneva, M

2012-01-01

To establish overall and disease-free survival (OS and DFS) for patients with FIGO IB1 stage cervical cancer for median period of follow-up of 41 months. Between 11.2002-11.2011 110 women with histologically confirmed cervical cancer IB1 stage were operated on by the author. Surgery was radical hysterectomy class III (Piver) and pelvic lymphonodulectomy (ovariectomy was optionally). 76 patients were submitted to adjuvant RT (TGT- 52 - 54 Gy). The period of follow-up ranges from 2 to 104 monts, median 41 monts. The acturial OS and DFS in patients with cervical cancer IB1 stage were estimated as 90% and 90.9%, respectively. Eleven patients had died for the period of follow-up and in 10 occurred local or distant recurrences. The time to develop recurrences was estimated as 16.81 months. Four patients developed local recurrences and six--distant metastases. Surgical and combined therapy of cervical cancer patients IB1 stage leads to high rate OS and DFS--90% and 90.9%, respectively. The incidence rate of distant metastases (5.5%)--in six patients in this stage makes pelvic lymph node dissection crucial and the presence of LM in gluteal and presacral lymph nodes requires paraaortic lymph node dissection.

Theoretical models of non-Maxwellian equilibria for one-dimensional collisionless plasmas

NASA Astrophysics Data System (ADS)

Allanson, O.; Neukirch, T.; Wilson, F.; Troscheit, S.

2016-12-01

It is ideal to use exact equilibrium solutions of the steady state Vlasov-Maxwell system to intialise collsionless simulations. However, exact equilibrium distribution functions (DFs) for a given macroscopic configuration are typically unknown, and it is common to resort to using `flow-shifted' Maxwellian DFs in their stead. These DFs may be consistent with a macrosopic system with the target number density and current density, but could well have inaccurate higher order moments. We present recent theoretical work on the `inverse problem in Vlasov-Maxwell equilibria', namely calculating an exact solution of the Vlasov equation for a specific given magnetic field. In particular, we focus on one-dimensional geometries in Cartesian (current sheets) coordinates.1. From 1D fields to Vlasov equilibria: Theory and application of Hermite Polynomials: (O. Allanson, T. Neukirch, S. Troscheit and F. Wilson, Journal of Plasma Physics, 82, 905820306 (2016) [28 pages, Open Access] )2. An exact collisionless equilibrium for the Force-Free Harris Sheet with low plasma beta: (O. Allanson, T. Neukirch, F. Wilson and S. Troscheit, Physics of Plasmas, 22, 102116 (2015) [11 pages, Open Access])3. Neutral and non-neutral collisionless plasma equilibria for twisted flux tubes: The Gold-Hoyle model in a background field (O. Allanson, F. Wilson and T. Neukirch, (2016)) (accepted, Physics of Plasmas)

Preoperative chemoradiotherapy creates an opportunity to perform sphincter preserving resection for low-lying locally advanced rectal cancer based on an oncologic outcome study

PubMed Central

Lu, Zhen-Hai; Wu, Xiao-Jun; Chen, Gong; Ding, Pei-Rong; Li, Li-Ren; Gao, Yuan-Hong; Zeng, Zhi-Fan; Wan, De-Sen; Pan, Zhi-Zhong

2016-01-01

Low-lying locally advanced rectal cancer (LARC) after preoperative chemoradiotherapy (CRT) can be surgically removed by either abdominperineal resection (APR) or sphincter preserving resection (SPR). This retrospective cohort study of 251 consecutive patients with low lying LARC who underwent CRT followed by radical surgery in a single institute, between March 2003 and November 2012, aimed to compare the oncological benefits between the two groups. 3-year disease free survival (DFS), overall survival (OS), cumulative incidence of recurrence and postoperative complications were compared between the two approaches. With median follow-up of 48.6 months, SPR group had higher 3-year DFS rate (86.4% vs 73.6%, P=0.023) and lower incidence of distant recurrence (12.0% vs 23.7%, P=0.026). The postoperative complications, incidence of local recurrence and the 3-year OS were comparable between the two groups. Pathologic T and N stage were the independent predictors for 3-year DFS (P=0.020 and P<0.001). In conclusion, our study suggest that low-lying LARC patients with a significant response to preoperative CRT can benefit from the advantage of SPR in preserving the anal sphincter function without compromising their oncologic outcome. PMID:27374175

Radiofrequency Ablation of Hepatocellular Carcinoma with a “Nodule-in-Nodule” Appearance: Long-Term Follow-up and Clinical Implications

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

Kang, Tae Wook; Rhim, Hyunchul, E-mail: rhimhc@skku.edu; Song, Kyoung Doo

PurposeHepatocellular carcinoma (HCC) with a “nodule-in-nodule” (NIN) appearance has unique histological characteristics as an early HCC. We assessed long-term therapeutic outcomes of radiofrequency ablation (RFA) in HCC patients considering this appearance.Materials and MethodsOur Institutional Review Board approved this retrospective study, and the requirement for written informed consent was waived. Between May 2006 and April 2012, a total of 572 patients underwent RFA for single HCC as a first-line treatment. Patients were divided into a NIN HCC group (n = 22) and a non-NIN HCC group (n = 550), according to the NIN feature on pretreatment imaging studies. Local tumor progression (LTP) and disease-free survivalmore » (DFS) were compared. Prognostic factors for LTP and DFS were assessed using a Cox proportional hazards model.ResultsThe cumulative LTP rates were 4.6 and 4.6% at 3 and 5 years, respectively, in the NIN HCC group, and 15.9 and 20.5% in the non-NIN HCC group, with borderline statistical significance (p = 0.085). The corresponding DFS rates were 53.8 and 37.7% in the NIN HCC group and 44.0 and 31.7% in the non-NIN HCC group, with no significant difference (p = 0.318). Although on multivariate analysis only tumor size was a significant prognostic factor for LTP, there was a trend bordering on the significance for the NIN feature [hazard ratio (HR) = 0.19; p = 0.099]. However, it was not a significant factor for DFS (HR = 0.18; p = 0.682).ConclusionsThe NIN appearance, a rare (4%, 22/550) but unique feature of early HCC, may be a favorable prognostic factor for RFA in terms of local tumor control.« less

Impact of Genetic Ancestry on Outcomes in ECOG-ACRIN-E5103

PubMed Central

Schneider, Bryan P.; Shen, Fei; Jiang, Guanglong; O'Neill, Anne; Radovich, Milan; Li, Lang; Gardner, Laura; Lai, Dongbing; Foroud, Tatiana; Sparano, Joseph A.; Sledge, George W.; Miller, Kathy D.

2017-01-01

Purpose Racial disparity in breast cancer outcomes exists between African American and Caucasian women in the United States. We have evaluated the impact of genetically determined ancestry on disparity in efficacy and therapy-induced toxicity for breast cancer patients in the context of a randomized, phase III adjuvant trial. Patients and Methods This study compared outcomes between 386 patients of African ancestry (AA) and 2473 patients of European ancestry (EA) in a randomized, phase III breast cancer trial; ECOG-ACRIN-E5103. The primary efficacy endpoint, invasive disease free survival (DFS) and clinically significant toxicities were compared including: anthracycline-induced congestive heart failure (CHF), taxane-induced peripheral neuropathy (TIPN), and bevacizumab-induced hypertension. Results Overall, AAs had significantly inferior DFS (p=0.002; HR=1.5) compared with EAs. This was significant in the estrogen receptor-positive subgroup (p=0.03); with a similar, non-significant trend for those who had triple negative breast cancer (TNBC; p=0.12). AAs also had significantly more grade 3-4 TIPN (OR=2.9; p=2.4 ×10-11) and grade 3-4 bevacizumab-induced hypertension (OR=1.6; p=0.02), with a trend for more CHF (OR=1.8; p=0.08). AAs had significantly more dose reductions for paclitaxel (p=6.6 ×10-6). In AAs, dose reductions in paclitaxel had a significant negative impact on DFS (p=0.03); whereas in EAs, dose reductions did not impact outcome (p=0.35). Conclusion AAs had inferior DFS with more clinically important toxicities in ECOG-ACRIN-E5103. The altered risk to benefit ratio for adjuvant breast cancer chemotherapy should lead to additional research with the focus centered on the impact of genetic ancestry on both efficacy and toxicity. Strategies to minimize dose reductions for paclitaxel, especially due to TIPN, are warranted for this population. PMID:29333527

Prognostic role of tumor necrosis in patients undergoing curative resection for gastric gastrointestinal stromal tumor: a multicenter analysis of 740 cases in China.

PubMed

Liu, Xuechao; Qiu, Haibo; Zhang, Peng; Feng, Xingyu; Chen, Tao; Li, Yong; Tao, Kaixiong; Li, Guoxin; Sun, Xiaowei; Zhou, Zhiwei

2017-12-01

Tumor necrosis is associated with poor clinical outcomes in many malignancies. We aimed to determine whether tumor necrosis was an independent predictor of outcomes in gastric gastrointestinal stromal tumors (GISTs). We retrospectively analyzed data from 740 patients undergoing curative resection for gastric GIST at four centers between 2001 and 2015. Disease-free survival (DFS) was estimated with the Kaplan-Meier method, and associations with prognosis were assessed with Cox regression models. Tumor necrosis was present in 122 cases (16.5%). The prevalence of tumor necrosis increased with higher risk-stratification, including 0.7%, 7.4%, 17.3%, and 39.3% for very low-, low-, intermediate- and high-risk tumors, respectively (P < 0.001). Tumor necrosis was associated with aggressive tumor biology, such as larger tumor size, higher mitotic index, tumor rupture, and presence of nuclear atypia (all P < 0.05). Multivariate analysis revealed that tumor necrosis was an independent predictor of unfavorable DFS (HR: 2.641; 95% CI: 1.359-5.131; P = 0.004). When stratified by the modified National Institutes of Health (NIH) classification, tumor necrosis still independently predicted DFS in high-risk patients (P = 0.001) but not in non-high-risk patients (P = 0.349). The 5-year DFS rate in high-risk patients with and without tumor necrosis was 56.5% and 82.9%, respectively (P = 0.004). Notably, the prognostic significance of tumor necrosis was maintained when the patients were stratified by age, sex, tumor location, tumor size, and mitotic index (All P < 0.05). Tumor necrosis is a useful predictor of outcomes in gastric GIST, especially in high-risk patients. Based on these results, we recommend that the current NIH classification should be further improved and expanded to include tumor necrosis as a valuable prognostic indicator. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Preoperative magnetic resonance imaging assessment of circumferential resection margin predicts disease-free survival and local recurrence: 5-year follow-up results of the MERCURY study.

PubMed

Taylor, Fiona G M; Quirke, Philip; Heald, Richard J; Moran, Brendan J; Blomqvist, Lennart; Swift, Ian R; Sebag-Montefiore, David; Tekkis, Paris; Brown, Gina

2014-01-01

The prognostic relevance of preoperative high-resolution magnetic resonance imaging (MRI) assessment of circumferential resection margin (CRM) involvement is unknown. This follow-up study of 374 patients with rectal cancer reports the relationship between preoperative MRI assessment of CRM staging, American Joint Committee on Cancer (AJCC) TNM stage, and clinical variables with overall survival (OS), disease-free survival (DFS), and time to local recurrence (LR). Patients underwent protocol high-resolution pelvic MRI. Tumor distance to the mesorectal fascia of ≤ 1 mm was recorded as an MRI-involved CRM. A Cox proportional hazards model was used in multivariate analysis to determine the relationship of MRI assessment of CRM to survivorship after adjusting for preoperative covariates. Surviving patients were followed for a median of 62 months. The 5-year OS was 62.2% in patients with MRI-clear CRM compared with 42.2% in patients with MRI-involved CRM with a hazard ratio (HR) of 1.97 (95% CI, 1.27 to 3.04; P < .01). The 5-year DFS was 67.2% (95% CI, 61.4% to 73%) for MRI-clear CRM compared with 47.3% (95% CI, 33.7% to 60.9%) for MRI-involved CRM with an HR of 1.65 (95% CI, 1.01 to 2.69; P < .05). Local recurrence HR for MRI-involved CRM was 3.50 (95% CI, 1.53 to 8.00; P < .05). MRI-involved CRM was the only preoperative staging parameter that remained significant for OS, DFS, and LR on multivariate analysis. High-resolution MRI preoperative assessment of CRM status is superior to AJCC TNM-based criteria for assessing risk of LR, DFS, and OS. Furthermore, MRI CRM involvement is significantly associated with distant metastatic disease; therefore, colorectal cancer teams could intensify treatment and follow-up accordingly to improve survival outcomes.

Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience.

PubMed

Patel, Uday B; Taylor, Fiona; Blomqvist, Lennart; George, Christopher; Evans, Hywel; Tekkis, Paris; Quirke, Philip; Sebag-Montefiore, David; Moran, Brendan; Heald, Richard; Guthrie, Ashley; Bees, Nicola; Swift, Ian; Pennert, Kjell; Brown, Gina

2011-10-01

To assess magnetic resonance imaging (MRI) and pathologic staging after neoadjuvant therapy for rectal cancer in a prospectively enrolled, multicenter study. In a prospective cohort study, 111 patients who had rectal cancer treated by neoadjuvant therapy were assessed for response by MRI and pathology staging by T, N and circumferential resection margin (CRM) status. Tumor regression grade (TRG) was also assessed by MRI. Overall survival (OS) was estimated by using the Kaplan-Meier product-limit method, and Cox proportional hazards models were used to determine associations between staging of good and poor responders on MRI or pathology and survival outcomes after controlling for patient characteristics. On multivariate analysis, the MRI-assessed TRG (mrTRG) hazard ratios (HRs) were independently significant for survival (HR, 4.40; 95% CI, 1.65 to 11.7) and disease-free survival (DFS; HR, 3.28; 95% CI, 1.22 to 8.80). Five-year survival for poor mrTRG was 27% versus 72% (P = .001), and DFS for poor mrTRG was 31% versus 64% (P = .007). Preoperative MRI-predicted CRM independently predicted local recurrence (LR; HR, 4.25; 95% CI, 1.45 to 12.51). Five-year survival for poor post-treatment pathologic T stage (ypT) was 39% versus 76% (P = .001); DFS for the same was 38% versus 84% (P = .001); and LR for the same was 27% versus 6% (P = .018). The 5-year survival for involved pCRM was 30% versus 59% (P = .001); DFS, 28 versus 62% (P = .02); and LR, 56% versus 10% (P = .001). Pathology node status did not predict outcomes. MRI assessment of TRG and CRM are imaging markers that predict survival outcomes for good and poor responders and provide an opportunity for the multidisciplinary team to offer additional treatment options before planning definitive surgery. Postoperative histopathology assessment of ypT and CRM but not post-treatment N status were important postsurgical predictors of outcome.

FGFR2 Point Mutations in 466 Endometrioid Endometrial Tumors: Relationship with MSI, KRAS, PIK3CA, CTNNB1 Mutations and Clinicopathological Features

PubMed Central

Powell, Matthew A.; Wellens, Candice L.; Gao, Feng; Mutch, David G.; Goodfellow, Paul J.; Pollock, Pamela M.

2012-01-01

Mutations in multiple oncogenes including KRAS, CTNNB1, PIK3CA and FGFR2 have been identified in endometrial cancer. The aim of this study was to provide insight into the clinicopathological features associated with patterns of mutation in these genes, a necessary step in planning targeted therapies for endometrial cancer. 466 endometrioid endometrial tumors were tested for mutations in FGFR2, KRAS, CTNNB1, and PIK3CA. The relationships between mutation status, tumor microsatellite instability (MSI) and clinicopathological features including overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier survival analysis and Cox proportional hazard models. Mutations were identified in FGFR2 (48/466); KRAS (87/464); CTNNB1 (88/454) and PIK3CA (104/464). KRAS and FGFR2 mutations were significantly more common, and CTNNB1 mutations less common, in MSI positive tumors. KRAS and FGFR2 occurred in a near mutually exclusive pattern (p = 0.05) and, surprisingly, mutations in KRAS and CTNNB1 also occurred in a near mutually exclusive pattern (p = 0.0002). Multivariate analysis revealed that mutation in KRAS and FGFR2 showed a trend (p = 0.06) towards longer and shorter DFS, respectively. In the 386 patients with early stage disease (stage I and II), FGFR2 mutation was significantly associated with shorter DFS (HR = 3.24; 95% confidence interval, CI, 1.35–7.77; p = 0.008) and OS (HR = 2.00; 95% CI 1.09–3.65; p = 0.025) and KRAS was associated with longer DFS (HR = 0.23; 95% CI 0.05–0.97; p = 0.045). In conclusion, although KRAS and FGFR2 mutations share similar activation of the MAPK pathway, our data suggest very different roles in tumor biology. This has implications for the implementation of anti-FGFR or anti-MEK biologic therapies. PMID:22383975

Effect of Whole Pelvic Radiotherapy for Patients With Locally Advanced Prostate Cancer Treated With Radiotherapy and Long-Term Androgen Deprivation Therapy

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

Mantini, Giovanna; Tagliaferri, Luca, E-mail: luca.tagliaferri@rm.unicatt.it; Mattiucci, Gian Carlo

2011-12-01

Purpose: To evaluate the effect of whole pelvic radiotherapy (WPRT) in prostate cancer patients treated with RT and long-term (>1 year) androgen deprivation therapy (ADT). Methods and materials: Prostate cancer patients with high-risk features (Stage T3-T4 and/or Gleason score {>=}7 and/or prostate-specific antigen level {>=}20 ng/mL) who had undergone RT and long-term ADT were included in the present analysis. Patients with bowel inflammatory disease, colon diverticula, and colon diverticulitis were excluded from WPRT and treated with prostate-only radiotherapy (PORT). Patients were grouped according to nodal risk involvement as assessed by the Roach formula using different cutoff levels (15%, 20%, 25%,more » and 30%). Biochemical disease-free survival (bDFS) was analyzed in each group according to the RT type (WPRT or PORT). Results: A total of 358 patients treated between 1994 and 2007 were included in the analysis (46.9% with WPRT and 53.1% with PORT). The median duration of ADT was 24 months (range, 12-38). With a median follow-up of 52 months (range, 20-150), the overall 4-year bDFS rate was 90.5%. The 4-year bDFS rate was similar between the patients who had undergone WPRT or PORT (90.4% vs. 90.5%; p = NS). However, in the group of patients with the greatest nodal risk (>30%), a significant bDFS improvement was recorded for the patients who had undergone WPRT (p = .03). No differences were seen in acute toxicity among the patients treated with WPRT or PORT. The late gastrointestinal toxicity was similar in patients treated with PORT or WPRT (p = NS). Conclusions: Our analysis has supported the use of WPRT in association with long-term ADT for patients with high-risk nodal involvement (>30%), although a definitive recommendation should be confirmed by a randomized trial.« less

AIC identifies optimal representation of longitudinal dietary variables.

PubMed

VanBuren, John; Cavanaugh, Joseph; Marshall, Teresa; Warren, John; Levy, Steven M

2017-09-01

The Akaike Information Criterion (AIC) is a well-known tool for variable selection in multivariable modeling as well as a tool to help identify the optimal representation of explanatory variables. However, it has been discussed infrequently in the dental literature. The purpose of this paper is to demonstrate the use of AIC in determining the optimal representation of dietary variables in a longitudinal dental study. The Iowa Fluoride Study enrolled children at birth and dental examinations were conducted at ages 5, 9, 13, and 17. Decayed or filled surfaces (DFS) trend clusters were created based on age 13 DFS counts and age 13-17 DFS increments. Dietary intake data (water, milk, 100 percent-juice, and sugar sweetened beverages) were collected semiannually using a food frequency questionnaire. Multinomial logistic regression models were fit to predict DFS cluster membership (n=344). Multiple approaches could be used to represent the dietary data including averaging across all collected surveys or over different shorter time periods to capture age-specific trends or using the individual time points of dietary data. AIC helped identify the optimal representation. Averaging data for all four dietary variables for the whole period from age 9.0 to 17.0 provided a better representation in the multivariable full model (AIC=745.0) compared to other methods assessed in full models (AICs=750.6 for age 9 and 9-13 increment dietary measurements and AIC=762.3 for age 9, 13, and 17 individual measurements). The results illustrate that AIC can help researchers identify the optimal way to summarize information for inclusion in a statistical model. The method presented here can be used by researchers performing statistical modeling in dental research. This method provides an alternative approach for assessing the propriety of variable representation to significance-based procedures, which could potentially lead to improved research in the dental community. © 2017 American Association of Public Health Dentistry.

Alternative Lengthening of Telomeres and Loss of DAXX/ATRX Expression Predicts Metastatic Disease and Poor Survival in Patients with Pancreatic Neuroendocrine Tumors.

PubMed

Singhi, Aatur D; Liu, Ta-Chiang; Roncaioli, Justin L; Cao, Dengfeng; Zeh, Herbert J; Zureikat, Amer H; Tsung, Allan; Marsh, J Wallis; Lee, Kenneth K; Hogg, Melissa E; Bahary, Nathan; Brand, Randall E; McGrath, Kevin M; Slivka, Adam; Cressman, Kristi L; Fuhrer, Kimberly; O'Sullivan, Roderick J

2017-01-15

Pancreatic neuroendocrine tumors (PanNET) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing has identified recurrent mutations in the genes DAXX and ATRX, which correlate with loss of protein expression and alternative lengthening of telomeres (ALT). Both ALT and DAXX/ATRX loss were initially reported to be associated with a favorable prognosis; however, recent studies suggest the contrary. Our aims were to assess the prevalence and prognostic significance of ALT and DAXX/ATRX in both primary and metastatic PanNETs. Telomere-specific FISH and DAXX/ATRX IHC was performed on a multi-institutional cohort of 321 patients with resected PanNET and 191 distant metastases from 52 patients. These results were correlated with clinicopathologic features, including disease-free survival (DFS) and disease-specific survival (DSS). The prevalence of ALT and DAXX/ATRX loss in resected PanNETs was 31% and 26%, respectively, and associated with larger tumor size, higher WHO grade, lymph node metastasis, and distant metastasis (P < 0.001). The 5-year DFS and 10-year DSS of patients with ALT-positive and DAXX/ATRX-negative PanNETs were 40% and 50%, respectively, as compared with 96% and 89%, respectively, for wild-type PanNETs. Among distant metastases, ALT and DAXX/ATRX loss was 67% and 52%, respectively, and only occurred in the setting of an ALT-positive and DAXX/ATRX-negative primary PanNET. By multivariate analysis, both ALT and DAXX/ATRX loss were negative, independent prognostic factors for DFS. ALT and DAXX/ATRX loss in PanNETs was associated with shorter DFS and DSS and likely plays a significant role in driving metastatic disease. Clin Cancer Res; 23(2); 600-9. ©2016 AACR. ©2016 American Association for Cancer Research.

Comparative Effectiveness Study to Assess Two Examination Modalities Used to Detect Dental Caries in Preschool Urban Children

PubMed Central

Billings, Ronald J.

2013-01-01

Abstract Background: Dental caries affecting the primary dentition of U.S. children continues to be the most prevalent chronic childhood disease. Preventive screening for dental caries in toddlers by dental professionals is labor-intensive and costly. Studies are warranted to examine innovative screening modalities that reduce cost, are less labor-intensive, and have the potential to identify caries in high-risk children. Subjects and Methods: Two hundred ninety-one children were randomized into two groups: Group 1 received a traditional, visual tactile examination initially and follow up-examinations at 6 and 12 months, and Group 2 received a teledentistry examination initially and follow-up examinations at 6 and 12 months. The mean primary tooth decayed and filled surfaces (dfs) scores were calculated for all children at baseline and 6 and 12 months. Results: At baseline, the mean dfs score for children examined by means of teledentistry was 2.19, and for the children examined by means of the traditional method, the mean was 1.27; the means were not significantly different. At the 12-month examination, the mean dfs score for the children examined by means of teledentistry was 3.02, and for the children examined by means of the clinical method, the mean dfs was 1.70; the means were not significantly different. At 12 months the mean fillings score for the children examined by means of teledentistry was 1.43 and for the children examined by means of the clinical method was 0.51; the means were statistically significantly different (p<0.001). Conclusions: These results suggest that the teledentistry examinations were comparable to clinical examinations when screening for early childhood caries in preschool children. The data further showed that color printouts of teeth with cavities provided to parents of children who received teledentistry screenings promoted oral healthcare utilization, as children from the teledentistry study group received more dental care than children from the clinical study group. PMID:24053114

Oral tetra-arsenic tetra-sulfide formula versus intravenous arsenic trioxide as first-line treatment of acute promyelocytic leukemia: a multicenter randomized controlled trial.

PubMed

Zhu, Hong-Hu; Wu, De-Pei; Jin, Jie; Li, Jian-Yong; Ma, Jun; Wang, Jian-Xiang; Jiang, Hao; Chen, Sai-Juan; Huang, Xiao-Jun

2013-11-20

This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of an oral tetra-arsenic tetra-sulfide (As4S4) -containing formula named the Realgar-Indigo naturalis formula (RIF) compared with intravenous arsenic trioxide (ATO) as both induction and maintenance therapies for newly diagnosed acute promyelocytic leukemia (APL). In all, 242 patients with APL were randomly assigned (1:1) to oral RIF (60 mg/kg) or ATO (0.16 mg/kg) combined with all-trans retinoic acid (ATRA; 25 mg/m(2)) during induction therapy. After achieving complete remission (CR), all patients received three courses of consolidation chemotherapy and maintenance treatment with sequential ATRA followed by either RIF or ATO for 2 years. The primary end point was the rate of disease-free survival (DFS) at 2 years, which was assessed for noninferiority with a 10% noninferiority margin. The median follow-up time was 39 months. DFS at 2 years was 98.1% (106 of 108) in the RIF group and 95.5% (107 of 112) in the ATO group. The DFS difference was 2.6% (95% CI, -3.0% to 8.0%). The lower limit of the 95% CI of DFS difference was greater than the -10% noninferiority margin, confirming noninferiority (P < .001). No significant differences were noted between the RIF and ATO groups with regard to the CR rate (99.1% v 97.2%; P = .62) or the overall survival at 3 years (99.1% v 96.6%; P = .18). The rates of adverse events were similar in the two groups. Oral RIF plus ATRA is not inferior to intravenous ATO plus ATRA as first-line treatment of APL and may be considered as a routine treatment option for appropriate patients.

E2F1/TS Immunophenotype and Survival of Patients with Colorectal Cancer Treated with 5FU-Based Adjuvant Therapy.

PubMed

Sulzyc-Bielicka, Violetta; Domagala, Pawel; Bielicki, Dariusz; Safranow, Krzysztof; Rogowski, Wojciech; Domagala, Wenancjusz

2016-07-01

The predictive value of thymidylate synthase (TS) expression alone for 5FU-based treatment of colorectal cancer (CRC) has not been clinically confirmed. Little is known on the association of expression of E2F1, which controls the transcription of genes encoding proteins engaged in DNA synthesis including TS, and survival of patients with CRC. The purpose of this study is to assess the correlation between expression of both E2F1 and TS in CRCs and survival of patients administered adjuvant 5FU-based chemotherapy, in order to find a better predictor of treatment outcome than expression of TS or E2F1 alone. Nuclear TS and E2F1 were detected by immunohistochemistry in tissue microarrays from 190 CRCs (Astler-Coller stage B2 or C). Multivariate analysis identified significant association of the combined E2F1+TS+ immunophenotype with worse OS (HR = 3,78, P = 0,009) and DFS (HR = 2,30, P = 0,03) of patients with colon cancer. There were significant differences between E2F1+TS+ and E2F1-TS- Kaplan-Meier survival curves in relation to DFS (P = 0.008) and OS (P = 0.01). About 37 and 31 % difference in 3-year DFS and OS respectively were seen between patients with E2F1+TS+ vs. E2F1-TS- colon cancer immunophenotype. The E2F1+TS+ immunophenotype may be a marker of poor prognosis (the worst DFS and OS) of patients with colon cancer treated with 5FU-based adjuvant therapy. A subgroup of patients with this immunophenotype may require different and perhaps more aggressive treatment than 5FU-based chemotherapy. Thus, the combined E2F1/TS immunophenotype could be a potential indicator of colon cancer sensitivity to 5FU.

[Planned neck dissection in the treatment of locally advanced head and neck squamous cell carcinoma].

PubMed

Jiang, L; Lou, J L; Wang, K J; Fang, M Y; Fu, Z F

2018-02-07

Objective: To investigate the value of planned neck dissection combined with induction chemotherapy and concurrent chemoradiotherapy in regional control and the outcome of locally advanced head and neck squamous cell carcinoma. Methods: A prospective randomized controlled study totally enrolled sixty-four patients of head and neck squamous cell carcinomas(include oropharynx, hypopharynx, and larynx) in stages Ⅳa-Ⅳb with lymph node metastase was were N2-N3. All patients firstly received 2-3 cycles of induction chemotherapy(ICT), then divided into two groups randomly, according to the efficacy of ICT. Group A(the study group) received planned neck dissection(PND) and concurrent chemoradiotherapy(CCRT). Group B(the control group) received concurrent chemoradiotherapy(CCRT). The differences in clinicopathologic features, local recurrence(LR), regional recurrence(RR), disease-free survival(DFS), and overall survival(OS) between the two groups were estimated. SPSS 19.0 software was used to analyze the data. Results: Group A enrolled twenty-one patients, and group B enrolled forty-three patients.The follow-up of all patients were 4-55 months, median follow-up time was 22 months. In study group, two-year OS and DFS were 80.9% and 68.3%, respectively. In control group, two-year OS and DFS were 90.7% and 67.1%, respectively. There was no significant difference in gender( P =0.215), age( P =0.828), primary tumor site( P =0.927), LR( P =0.126), DFS( P =0.710), and OS( P =0.402) between the two groups, while the RR(χ(2)=5.640, P <0.05) and distant metastasis(χ(2)=10.363, P <0.01) showed significant differences between the two groups. Conclusion: The ICT+ PND+ CCRT treatment model has benefit on regional control of locally advanced head and neck squamous cell carcinoma.

Ten-year Biochemical Disease-free Survival After High-intensity Focused Ultrasound (HIFU) for Localized Prostate Cancer: Comparison with Four Different Generation Devices

NASA Astrophysics Data System (ADS)

Uchida, T.; Nakano, M.; Shoji, S.; Omata, T.; Harano, Y.; Nagata, Y.; Usui, Y.; Terachi, T.

2010-03-01

HIFU has been recognized as a minimally invasive treatment option for localized prostate cancer. The purpose of the study was to assess with a long-term outcome of HIFU for prostate cancer. From January 1999, a total of 657 patients who had HIFU with at least 2 year follow-up were treated with four different types of Sonablate® (Focus Surgery, Indianapolis, USA) devices. Thirty-three patients were treated with Sonablate® 200 (S200) from 1999 to 2001, 406 patients with Sonablate® 500 (S500) from 2001 to 2005, 200 patients with Sonablate® 500 version 4 (V4) from 2005-2008 and 19 patients with Sonablate® 500 TCM (TCM) from 2007. Biochemical disease-free survival rate (bDFS) in all patients was 59% in 8 years. bDFS in 8 years in patients with S200 and S500 groups were 55% and 56%, and bDFS in 4 and 2 years in patients with V4 and TCM group were 72% and 84%, respectively. bDFS in low, intermediate, and high risk groups were 75%, 54%, and 43% in S200/S500 and 93%, 72%, and 58% in V4/TCM group. Negative prostate biopsy rate after HIFU was 97% in S200, 79% in S500, 94% in V4 and 100% in TCM group. HIFU as primary therapy for prostate cancer is indicated in patients with low- and intermediate-risk (T1-T2b N0M0 disease, a Gleason score of ⩽7, a PSA level of <20 ng/mL) and a prostate volume of less than 40 mL. The rate of clinical outcome has significantly improved over the years due to technical improvements in the device.

Clinical value of the preoperative neutrophil-to-lymphocyte ratio and red blood cell distribution width in patients with colorectal carcinoma.

PubMed

Han, Fuyan; Shang, Xuming; Wan, Furong; Liu, Zhanfeng; Tian, Wenjun; Wang, Dan; Liu, Yiqing; Wang, Yong; Zhang, Bingchang; Ju, Ying

2018-03-01

The aim of the present study was to investigate the clinical value of the preoperative neutrophil-to-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) in the peripheral blood of colorectal carcinoma (CRC) patients. Clinical data obtained from 240 patients with CRC undergoing radical surgical resection in Shandong Provincial Hospital Affiliated to Shandong University (Jinan, Shandong, China) between January 2011 and April 2015 were retrospectively analyzed. Data were also collected from 110 patients with colon polyps and 48 healthy volunteers to serve as controls for comparative analysis. The clinicopathological characteristics of the patients in the low and high NLR and RDW groups were compared. The NLR and RDW values were compared prior to and following surgery. Kaplan-Meier analyses and Cox regression modeling were performed to predict overall survival (OS) and disease-free survival (DFS). The NLR and RDW levels in the CRC patients were markedly higher than those in the colon polyp patients and the healthy controls. The optimum NLR and RDW cutoff points for CRC were 2.06 and 13.45%, respectively. Significant differences were detected in tumor location, diameter, degree of differentiation, tumor depth, carcinoembryonic antigen and carbohydrate antigen 199 when comparing the high and low NLR groups (P<0.05). A high RDW was significantly associated with distant metastasis and older age in CRC patients. No significant difference was detected in the NLR and RDW levels of CRC patients prior to and following surgery (P>0.05). CRC patients with an increased RDW had significantly worse OS and DFS rates, particularly those with metastatic CRC (P<0.05). Patients with a high NLR exhibited a reduced DFS time in CRC (P=0.053), although this difference was not significant, and a significantly worse DFS time in metastatic CRC (P=0.047). In conclusion, it is convenient to use preoperative NLR and RDW to predict prognosis following surgery for patients with CRC.

Prognostic Effect of Tumor Lymphocytic Infiltration in Resectable Non–Small-Cell Lung Cancer

PubMed Central

Le Teuff, Gwénaël; Marguet, Sophie; Lantuejoul, Sylvie; Dunant, Ariane; Graziano, Stephen; Pirker, Robert; Douillard, Jean-Yves; Le Chevalier, Thierry; Filipits, Martin; Rosell, Rafael; Kratzke, Robert; Popper, Helmut; Soria, Jean-Charles; Shepherd, Frances A.; Seymour, Lesley; Tsao, Ming Sound

2016-01-01

Purpose Tumor lymphocytic infiltration (TLI) has differing prognostic value among various cancers. The objective of this study was to assess the effect of TLI in lung cancer. Patients and Methods A discovery set (one trial, n = 824) and a validation set (three trials, n = 984) that evaluated the benefit of platinum-based adjuvant chemotherapy in non–small-cell lung cancer were used as part of the LACE-Bio (Lung Adjuvant Cisplatin Evaluation Biomarker) study. TLI was defined as intense versus nonintense. The main end point was overall survival (OS); secondary end points were disease-free survival (DFS) and specific DFS (SDFS). Hazard ratios (HRs) and 95% CIs associated with TLI were estimated through a multivariable Cox model in both sets. TLI-histology and TLI-treatment interactions were explored in the combined set. Results Discovery and validation sets with complete data included 783 (409 deaths) and 763 (344 deaths) patients, respectively. Median follow-up was 4.8 and 6 years, respectively. TLI was intense in 11% of patients in the discovery set compared with 6% in the validation set (P < .001). The prognostic value of TLI in the discovery set (OS: HR, 0.56; 95% CI, 0.38 to 0.81; P = .002; DFS: HR, 0.59; 95% CI, 0.42 to 0.83; P = .002; SDFS: HR, 0.56; 95% CI, 0.38 to 0.82; P = .003) was confirmed in the validation set (OS: HR, 0.45; 95% CI, 0.23 to 0.85; P = .01; DFS: HR, 0.44; 95% CI, 0.24 to 0.78; P = .005; SDFS: HR, 0.42; 95% CI, 0.22 to 0.80; P = .008) with no heterogeneity across trials (P ≥ .38 for all end points). No significant predictive effect was observed for TLI (P ≥ .78 for all end points). Conclusion Intense lymphocytic infiltration, found in a minority of tumors, was validated as a favorable prognostic marker for survival in resected non–small-cell lung cancer. PMID:26834066

The Prognostic Value of the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging System in HER2-Enriched Subtype Breast Cancer, a Retrospective Analysis.

PubMed

Zhou, Bin; Xu, Ling; Ye, Jingming; Xin, Ling; Duan, Xuening; Liu, Yinhua

2017-08-01

The American Joint Committee on Cancer (AJCC) released its 8th edition of tumor staging which is to be implemented in early 2018. The present study aimed to analyze the prognostic value of AJCC 8th edition Cancer Staging System in HER2-enriched breast cancer, on a retrospective cohort. This study was a retrospective single-center study of HER2-enriched breast cancer cases diagnosed from January 2008 to December 2014. Clinicopathological features and follow up data including disease-free survival (DFS) and overall survival (OS) were analyzed to explore prognostic factors for disease outcome. We restaged patients based on the 8th edition of the AJCC cancer staging system and analyzed prognostic value of the Anatomic Stage Group and the Prognostic Stage Group. The study enrolled 170 HER2-enriched subtype breast cancer patients with 5-year disease free survival (DFS) of 85.1% and 5-year overall survival (OS) of 86.8%. Prognostic stages of 117 cases (68.8%) changed compared with anatomic stages, with 116 upstaged cases and 1 downstaged case. The Anatomic Stage Groups had a significant prognostic impact on DFS (χ 2 =16.752, p<0.001) and OS (χ 2 =25.038, p<0.001). The Prognostic Staging Groups had a significant prognostic impact on DFS (χ 2 =6.577, p=0.037) and OS (χ 2 =21.762, p<0.001). In the multivariate analysis, both stage groups were independent predictors of OS. Both Anatomic and Prognostic Stage Groups in the 8th edition of the AJCC breast cancer staging system had prognostic value in HER2-enriched subtype breast cancer. The Prognostic Stage system was a breakthrough on the basis of anatomic staging system. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

[Possibilities of a software-based hybrid single photon emission computed tomography/magnetic resonance imaging in the diagnosis of complicated diabetic foot syndrome].

PubMed

Zavadovskaya, V D; Zorkal'tsev, M A; Udodov, V D; Zamyshevskaya, M A; Kilina, O Yu; Kurazhov, A P; Popov, K M

2015-01-01

To give the results of a software-based hybrid single photon emission computed tomography/magnetic resonance imaging (SPECT/MRI) in detecting osteomyelitis (OM) in patients with diabetic foot syndrome (DFS). Seventy-six patients (35 men and 41 women) (mean age, 59.4 +/- 7.1 years) with type 1 and 2 diabetes mellitus and suspected OM were examined. The investigation enrolled patients with neuropathic (n = 25), ischemic (n = 13), and mixed (n = 38) DFS. All the patients underwent (99m)Tc-HMPAO/ (99m)Tc-technefit labeled leukocyte scintigraphy; magnetic resonance imaging was performed in 30 patients. The results were combined using RView 9.06 software (Colin Studholme). Labeled leukocyte SPECT to Diagnose OM yielded 255 true positive (TP), 38 true negative (TN), 12 false negative (FP), and 1 false negative (FN) results. The accuracy of the technique was 82.9%. The FP results were due to the low resolution of the technique and to the small sizes of the object under study. One FN result was detected in a patient with ischemic DFS because of reduced blood flow. MRI to identify OM in patients with DFS provided 20 TP, 16 TN, 4 FP, and 2 FN results. Its diagnostic accuracy was 85.7%. The relative low specificity of MRI was associated with the presence of FP results due to the complexity of differential diagnosis of bone marrow edema and inflammatory infiltration. Assessing 42 hybrid SPECT/MR-images revealed 21 TP, 17 TN, 3 FP, and I FN results. The diagnostic accuracy was equal to 95.9%. Thus, comparing MRI (90.9% sensitivity and 80.0% specificity), labeled leukocyte scintigraphy (96.2% sensitivity and 76.0% specificity), and hybrid SPECT/MRI (95.5% sensitivity and 85.0% specificity) showed the high diagnostic efficiency of the latter.

Association of CYP2D6*10 (c.100C>T) polymorphisms with clinical outcome of breast cancer after tamoxifen adjuvant endocrine therapy in Chinese population.

PubMed

Lei, Lei; Wang, Xian; Wu, Xiao-Dan; Wang, Zeng; Chen, Zhan-Hong; Zheng, Ya-Bin; Wang, Xiao-Jia

2016-01-01

Tamoxifen is the most widely used adjuvant endocrine therapy for breast cancer. However, the pharmacogenetic effect of CYP2D6 on its efficacy remains unclear. Therefore, this study aimed to evaluate the association of CYP2D6*10 (c.100C>T) polymorphisms with clinical outcome in Chinese breast cancer patients. A total of 72 tamoxifen-treated early breast cancer patients were included in this study. CYP2D6*10 (c.100C>T) polymorphisms (C/C: wild type; T/T: homozygous mutant genotype T; C/T: heterozygote genotype C) were detected by pyrosequencing. The plasma concentrations of tamoxifen and its two major active metabolites were determined by liquid chromatography tandem mass spectrometry (LC-MS). Disease-free survival (DFS) and overall survival (OS) were assessed by Kaplan-Meier analysis, while the Cox proportional hazards model was used in multivariate tests for prognostic significance. We found that T/T carrier showed the lowest serum concentration of endoxifen as compared to C/C and C/T carriers (p<0.01). In the subgroup of patients below 40 years of age, T/T carriers appeared to have the shortest DFS and OS as compared to other genotype carriers (p<0.01). When genotypes (C/C, C/T and T/T carriers) and other clinical characteristics were adjusted, tumor size (>2 cm) and grades were independent prognostic factors for DFS but not OS (tumor size >2 cm: HR: 3.870, 95% CI: 1.045-14.330, P = 0.043; tumor grades: HR: 2.230, 95% CI: 1.090-4.562, P = 0.028). In conclusion, the T/T genotype is a negative prognostic factor in young breast cancer patients using tamoxifen. Tumor size (>2 cm) and grades are independent prognostic factors for DFS, when genotype of CYP2D6*10 (c.100C>T) is adjusted.

Human papilloma virus load and PD-1/PD-L1, CD8+ and FOXP3 in anal cancer patients treated with chemoradiotherapy: Rationale for immunotherapy

PubMed Central

Balermpas, Panagiotis; Martin, Daniel; Wieland, Ulrike; Rave-Fränk, Margret; Strebhardt, Klaus; Rödel, Claus; Fokas, Emmanouil; Rödel, Franz

2017-01-01

ABSTRACT We examined the prognostic role of immune markers programmed cell death protein-1 (PD-1) and its ligand (PD-L1), CD8+ tumor-infiltrating lymphocytes (TILs), FOXP3+ Tregs and phosphorylated Caspase-8 (T273) in patients with anal squamous cell cancer (ASCC) treated with standard chemoradiotherapy (CRT). The baseline immunohistochemical expression of immune markers was correlated with clinicopathologic characteristics, and cumulative incidence of local failure, disease-free survival (DFS) and overall survival (OS) in 150 patients, also in the context of human papilloma virus 16 (HPV16) DNA load and p16INK4a expression. After a median follow-up of 40 mo (1–205 mo), the 5-y cumulative incidence of local failure and DFS was 19.4% and 67.2%, respectively. Strong immune marker expression was significantly more common in tumors with high HPV16 viral load. In multivariant analysis, high CD8+ and PD-1+ TILs expression predicted for improved local control (p = 0.023 and p = 0.007, respectively) and DFS (p = 0.020 and p = 0.014, respectively). Also, high p16INK4a (p = 0.011) and PD-L1 (p = 0.033) expression predicted for better local control, whereas high FOXP3+ Tregs (p = 0.050) and phosphorylated Caspase-8 (p = 0.031) expression correlated with superior DFS. Female sex and high HPV16 viral load correlated with favorable outcome for all three clinical endpoints. The present data provide, for the first time, robust explanation for the favorable clinical outcome of HPV16-positive ASCC patients harboring strong immune cell infiltration. Our findings are relevant for treatment stratification with immune PD-1/PD-L1 checkpoint inhibitors to complement CRT and should be explored in a clinical trial. PMID:28405521

Once-Daily Radiation Therapy for Inflammatory Breast Cancer

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

Brown, Lindsay; Harmsen, William; Blanchard, Miran

2014-08-01

Purpose: Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer variant treated with multimodality therapy. A variety of approaches intended to escalate the intensity and efficacy of radiation therapy have been reported, including twice-daily radiation therapy, dose escalation, and aggressive use of bolus. Herein, we examine our outcomes for patients treated with once-daily radiation therapy with aggressive bolus utilization, focusing on treatment technique. Methods and Materials: A retrospective review of patients with nonmetastatic IBC treated from January 1, 2000, through December 31, 2010, was performed. Locoregional control (LRC), disease-free survival (DFS), overall survival (OS) and predictors thereof weremore » assessed. Results: Fifty-two women with IBC were identified, 49 (94%) of whom were treated with neoadjuvant chemotherapy. All underwent mastectomy followed by adjuvant radiation therapy. Radiation was delivered in once-daily fractions of 1.8 to 2.25 Gy (median, 2 Gy). Patients were typically treated with daily 1-cm bolus throughout treatment, and 33 (63%) received a subsequent boost to the mastectomy scar. Five-year Kaplan Meier survival estimates for LRC, DFS, and OS were 81%, 56%, and 64%, respectively. Locoregional recurrence was associated with poorer OS (P<.001; hazard ratio [HR], 4.1). Extracapsular extension was associated with worse LRC (P=.02), DFS (P=.007), and OS (P=.002). Age greater than 50 years was associated with better DFS (P=.03). Pathologic complete response was associated with a trend toward improved LRC (P=.06). Conclusions: Once-daily radiation therapy with aggressive use of bolus for IBC results in outcomes consistent with previous reports using various intensified radiation therapy regimens. LRC remains a challenge despite modern systemic therapy. Extracapsular extension, age ≤50 years, and lack of complete response to chemotherapy appear to be associated with worse outcomes. Novel strategies are needed in IBC, particularly among these subsets of patients.« less

Association of Aurora-A (STK15) Kinase Polymorphisms With Clinical Outcome of Esophageal Cancer Treated With Preoperative Chemoradiation

PubMed Central

Pan, Jennifer Y.; Ajani, Jaffer A.; Gu, Jian; Gong, Yubo; Quin, Angel; Hung, Maosheng; Wu, Xifeng; Izzo, Julie G.

2013-01-01

BACKGROUND: Aurora-A/STK15 is a serine/threonine kinase critical for regulated chromosome segregation and cytokinesis. We investigated the association between 2 nonsynonymous single nucleotide polymorphisms in the coding region of STK15, T91A (Phe31Ile) and G169A (Val57Ile), and clinical outcome of esophageal cancer treated with preoperative chemoradiation. METHODS: Genotypes at Phe31Ile and Val57Ile were assessed from peripheral blood lymphocytes of 190 esophageal cancer patients and were correlated to response to treatment, recurrence rate, risk of death, disease-free survival (DFS) and median survival time (MTS). RESULTS: All patients had resectable esophageal or gastroesophageal junction cancer and received preoperative chemoradiation followed by esophagectomy. The heterozygous variant Phe31/Ile variant was significantly associated with tumor recurrence (odds ratio [OR] = 4.39; 95% confidence interval [CI], 2.12-8.94; P < .001), shorter DFS (P = .0001), and shorter MTS (P = .012). For patients receiving cisplatin-based therapy, only the variant Phe31/Ile had an adverse effect on response (OR = 2.8; 95% CI, 1.01-5.17; P = .048) and MTS (P = .026). The variant 91A-169G haplotype carried a significant risk for lack of complete response (OR = 2.54; 95% CI, 1.15-5.54) and higher rate of recurrence (OR = 2.73; 95%CI, 1.00-7.29). The presence of at least 1 variant allele at each locus further increased the risk of recurrence (adjusted OR = 6.21; 95% CI, 2.28-17.11; P = <.001), and was associated significantly shorter DFS (P = .003). CONCLUSIONS: Our study shows that functional SNPs in the STK15 gene are associated with higher rate of recurrence, higher likelihood of chemoratiotherapy-resistance, shorter DFS, and shorter MTS. Confirmation of our data and understanding the mechanisms through which STK15 functional SNPs mediate resistance to chemoradiotherapy are warranted. PMID:22213102

Operative Method for Transverse Colon Carcinoma: Transverse Colectomy Versus Extended Colectomy.

PubMed

Chong, Choon Seng; Huh, Jung Wook; Oh, Bo Young; Park, Yoon Ah; Cho, Yong Beom; Yun, Seong Hyeon; Kim, Hee Cheol; Lee, Woo Yong

2016-07-01

The type of surgery performed for primary transverse colon cancer varies based on tumor characteristics and surgeon perspective. The optimal oncological outcome following different surgical options has not been clearly established, and transverse colectomy has shown oncological equivalence only in small cohort studies. Our aim was to compare long-term oncological outcomes after transverse colectomy versus extended resection for transverse colon cancer. This study is a retrospective review of prospectively collected data. This study was conducted at a tertiary care hospital. All patients treated for transverse colon cancer at the Samsung Medical Center between 1995 and 2013 were included. Oncological outcomes were compared between 2 groups of patients: a transverse colectomy group and an extended colectomy group (which included extended right hemicolectomy and left hemicolectomy). A total of 1066 patients were included, of whom 750 (70.4%) underwent extended right hemicolectomy, 127 (11.9%) underwent transverse colectomy, and 189 (17.7%) underwent left hemicolectomy. According to univariate analysis, surgical approach, histological type, tumor morphology, cancer T and N stage, cancer size, and lymphovascular invasion were significant factors contributing to disease-free survival (DFS). However, as seen in multivariate analysis, only node-positive disease (HR = 2.035 (1.188-3.484)), tumors with ulcerative morphology (HR = 3.643 (1.132-11.725)), and the presence of vascular invasion (HR = 2.569 (1.455-4.538)) were significant factors for DFS. Further analysis with a propensity-matched cohort between the transverse and extended colectomy groups demonstrated no significant differences in DFS and overall survival. This study was limited because it was performed at a single institution and it was retrospective in nature. In terms of perioperative and oncological outcomes, transverse colectomy and extended colectomy did not differ despite a shorter specimen length and fewer lymph nodes harvested in the transverse colectomy group. Independent prognostic factors for DFS were node-positive disease, the presence of vascular invasion, and ulcerative morphology.

SWOG S0221: A Phase III Trial Comparing Chemotherapy Schedules in High-Risk Early-Stage Breast Cancer

PubMed Central

Budd, George T.; Barlow, William E.; Moore, Halle C.F.; Hobday, Timothy J.; Stewart, James A.; Isaacs, Claudine; Salim, Muhammad; Cho, Jonathan K.; Rinn, Kristine J.; Albain, Kathy S.; Chew, Helen K.; Burton, Gary V.; Moore, Timothy D.; Srkalovic, Gordan; McGregor, Bradley A.; Flaherty, Lawrence E.; Livingston, Robert B.; Lew, Danika L.; Gralow, Julie R.; Hortobagyi, Gabriel N.

2015-01-01

Purpose To determine the optimal dose and schedule of anthracycline and taxane administration as adjuvant therapy for early-stage breast cancer. Patients and Methods A 2 × 2 factorial design was used to test two hypotheses: (1) that a novel continuous schedule of doxorubicin-cyclophosphamide was superior to six cycles of doxorubicin-cyclophosphamide once every 2 weeks and (2) that paclitaxel once per week was superior to six cycles of paclitaxel once every 2 weeks in patients with node-positive or high-risk node-negative early-stage breast cancer. With 3,250 patients, a disease-free survival (DFS) hazard ratio of 0.82 for each randomization could be detected with 90% power with two-sided α = .05. Overall survival (OS) was a secondary outcome. Results Interim analyses crossed the futility boundaries for demonstrating superiority of both once-per-week regimens and once-every-2-weeks regimens. After a median follow-up of 6 years, a significant interaction developed between the two randomization factors (DFS P = .024; OS P = .010) in the 2,716 patients randomly assigned in the original design, which precluded interpretation of the two factors separately. Comparing all four arms showed a significant difference in OS (P = .040) but not in DFS (P = .11), with all treatments given once every 2 weeks associated with the highest OS. This difference in OS seemed confined to patients with hormone receptor–negative/human epidermal growth factor receptor 2 (HER2) –negative tumors (P = .067), with no differences seen with hormone receptor–positive/HER2-negative (P = .90) or HER2-positive tumors (P = .40). Conclusion Patients achieved a similar DFS with any of these regimens. Subset analysis suggests the hypothesis that once-every-2-weeks dosing may be best for patients with hormone receptor–negative/HER2-negative tumors. PMID:25422488

SWOG S0221: a phase III trial comparing chemotherapy schedules in high-risk early-stage breast cancer.

PubMed

Budd, George T; Barlow, William E; Moore, Halle C F; Hobday, Timothy J; Stewart, James A; Isaacs, Claudine; Salim, Muhammad; Cho, Jonathan K; Rinn, Kristine J; Albain, Kathy S; Chew, Helen K; Burton, Gary V; Moore, Timothy D; Srkalovic, Gordan; McGregor, Bradley A; Flaherty, Lawrence E; Livingston, Robert B; Lew, Danika L; Gralow, Julie R; Hortobagyi, Gabriel N

2015-01-01

To determine the optimal dose and schedule of anthracycline and taxane administration as adjuvant therapy for early-stage breast cancer. A 2 × 2 factorial design was used to test two hypotheses: (1) that a novel continuous schedule of doxorubicin-cyclophosphamide was superior to six cycles of doxorubicin-cyclophosphamide once every 2 weeks and (2) that paclitaxel once per week was superior to six cycles of paclitaxel once every 2 weeks in patients with node-positive or high-risk node-negative early-stage breast cancer. With 3,250 patients, a disease-free survival (DFS) hazard ratio of 0.82 for each randomization could be detected with 90% power with two-sided α = .05. Overall survival (OS) was a secondary outcome. Interim analyses crossed the futility boundaries for demonstrating superiority of both once-per-week regimens and once-every-2-weeks regimens. After a median follow-up of 6 years, a significant interaction developed between the two randomization factors (DFS P = .024; OS P = .010) in the 2,716 patients randomly assigned in the original design, which precluded interpretation of the two factors separately. Comparing all four arms showed a significant difference in OS (P = .040) but not in DFS (P = .11), with all treatments given once every 2 weeks associated with the highest OS. This difference in OS seemed confined to patients with hormone receptor-negative/human epidermal growth factor receptor 2 (HER2) -negative tumors (P = .067), with no differences seen with hormone receptor-positive/HER2-negative (P = .90) or HER2-positive tumors (P = .40). Patients achieved a similar DFS with any of these regimens. Subset analysis suggests the hypothesis that once-every-2-weeks dosing may be best for patients with hormone receptor-negative/HER2-negative tumors. © 2014 by American Society of Clinical Oncology.

Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial

PubMed Central

Yothers, Greg; O’Connell, Michael J.; Beart, Robert W.; Wozniak, Timothy F.; Pitot, Henry C.; Shields, Anthony F.; Landry, Jerome C.; Ryan, David P.; Arora, Amit; Evans, Lisa S.; Bahary, Nathan; Soori, Gamini; Eakle, Janice F.; Robertson, John M.; Moore, Dennis F.; Mullane, Michael R.; Marchello, Benjamin T.; Ward, Patrick J.; Sharif, Saima; Roh, Mark S.; Wolmark, Norman

2015-01-01

Background: National Surgical Adjuvant Breast and Bowel Project R-04 was designed to determine whether the oral fluoropyrimidine capecitabine could be substituted for continuous infusion 5-FU in the curative setting of stage II/III rectal cancer during neoadjuvant radiation therapy and whether the addition of oxaliplatin could further enhance the activity of fluoropyrimidine-sensitized radiation. Methods: Patients with clinical stage II or III rectal cancer undergoing preoperative radiation were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU or oral capecitabine with or without oxaliplatin. The primary endpoint was local-regional tumor control. Time-to-event endpoint distributions were estimated using the Kaplan-Meier method. Hazard ratios were estimated from Cox proportional hazard models. All statistical tests were two-sided. Results: Among 1608 randomized patients there were no statistically significant differences between regimens using 5-FU vs capecitabine in three-year local-regional tumor event rates (11.2% vs 11.8%), 5-year DFS (66.4% vs 67.7%), or 5-year OS (79.9% vs 80.8%); or for oxaliplatin vs no oxaliplatin for the three endpoints of local-regional events, DFS, and OS (11.2% vs 12.1%, 69.2% vs 64.2%, and 81.3% vs 79.0%). The addition of oxaliplatin was associated with statistically significantly more overall and grade 3–4 diarrhea (P < .0001). Three-year rates of local-regional recurrence among patients who underwent R0 resection ranged from 3.1 to 5.1% depending on the study arm. Conclusions: Continuous infusion 5-FU produced outcomes for local-regional control, DFS, and OS similar to those obtained with oral capecitabine combined with radiation. This study establishes capecitabine as a standard of care in the pre-operative rectal setting. Oxaliplatin did not improve the local-regional failure rate, DFS, or OS for any patient risk group but did add considerable toxicity. PMID:26374429

Dispersed Fringe Sensing Analysis - DFSA

NASA Technical Reports Server (NTRS)

Sigrist, Norbert; Shi, Fang; Redding, David C.; Basinger, Scott A.; Ohara, Catherine M.; Seo, Byoung-Joon; Bikkannavar, Siddarayappa A.; Spechler, Joshua A.

2012-01-01

Dispersed Fringe Sensing (DFS) is a technique for measuring and phasing segmented telescope mirrors using a dispersed broadband light image. DFS is capable of breaking the monochromatic light ambiguity, measuring absolute piston errors between segments of large segmented primary mirrors to tens of nanometers accuracy over a range of 100 micrometers or more. The DFSA software tool analyzes DFS images to extract DFS encoded segment piston errors, which can be used to measure piston distances between primary mirror segments of ground and space telescopes. This information is necessary to control mirror segments to establish a smooth, continuous primary figure needed to achieve high optical quality. The DFSA tool is versatile, allowing precise piston measurements from a variety of different optical configurations. DFSA technology may be used for measuring wavefront pistons from sub-apertures defined by adjacent segments (such as Keck Telescope), or from separated sub-apertures used for testing large optical systems (such as sub-aperture wavefront testing for large primary mirrors using auto-collimating flats). An experimental demonstration of the coarse-phasing technology with verification of DFSA was performed at the Keck Telescope. DFSA includes image processing, wavelength and source spectral calibration, fringe extraction line determination, dispersed fringe analysis, and wavefront piston sign determination. The code is robust against internal optical system aberrations and against spectral variations of the source. In addition to the DFSA tool, the software package contains a simple but sophisticated MATLAB model to generate dispersed fringe images of optical system configurations in order to quickly estimate the coarse phasing performance given the optical and operational design requirements. Combining MATLAB (a high-level language and interactive environment developed by MathWorks), MACOS (JPL s software package for Modeling and Analysis for Controlled Optical Systems), and DFSA provides a unique optical development, modeling and analysis package to study current and future approaches to coarse phasing controlled segmented optical systems.

Dual Fan Separator within the Universal Waste Management System

NASA Technical Reports Server (NTRS)

Stapleton, Tom; Converse, Dave; Broyan, James Lee, Jr.

2014-01-01

Since NASA's new spacecraft in development for both LEO and Deep Space capability have considerable crew volume reduction in comparison to the Space Shuttle, the need became apparent for a smaller commode. In response the Universal Waste Management System (UWMS) was designed, resulting in an 80% volume reduction from the last US commode, while enhancing performance. The ISS WMS and previous shuttle commodes have a fan supplying air flow to capture feces and a separator to capture urine and separate air from the captured air/urine mixture. The UWMS combined both rotating equipment components into a single unit, referred to at the Dual Fan Separator (DFS). The combination of these components resulted in considerable packaging efficiency and weight reduction, removing inter-component plumbing, individual mounting configurations and required only a single motor and motor controller, in some of the intended UWMS platform applications the urine is pumped to the ISS Urine Processor Assembly (UPA) system. It requires the DFS to include less than 2.00% air inclusion, by volume, in the delivered urine. The rotational speed needs to be kept as low as possible in centrifugal urine separators to reduce air inclusion in the pumped fluid, while fans depend on rotational speed to develop delivered head. To satisfy these conflicting requirements, a gear reducer was included, allowing the fans to rotate at a much higher speed than the separator. This paper outlines the studies and analysis performed to develop the DFS configuration. The studies included a configuration trade study, dynamic stability analysis of the rotating bodies and a performance analysis of included labyrinth seals. NASA is considering a program to fly the UWMS aboard the ISS as a flight experiment. The goal of this activity is to advance the Technical Readiness Level (TRL) of the DFS and determine if the concept is ready to be included as part of the flight experiment deliverable.

Multicenter Validation Study of Pathologic Response and Tumor Thickness at the Tumor–Normal Liver Interface as Independent Predictors of Disease-Free Survival after Preoperative Chemotherapy and Surgery for Colorectal Liver Metastases

PubMed Central

Brouquet, Antoine; Zimmitti, Giuseppe; Kopetz, Scott; Stift, Judith; Julié, Catherine; Lemaistre, Anne-Isabelle; Agarwal, Atin; Patel, Viren; Benoist, Stephane; Nordlinger, Bernard; Gandini, Alessandro; Rivoire, Michel; Stremitzer, Stefan; Gruenberger, Thomas; Vauthey, Jean-Nicolas; Maru, Dipen M.

2014-01-01

Purpose To validate pathologic markers of response to preoperative chemotherapy as predictors of disease-free survival (DFS) after resection of colorectal liver metastases (CLM). Patients and Methods One hundred seventy one patients who underwent resection of CLM after preoperative chemotherapy at 4 centers were studied. Pathologic response defined as proportion of tumor cells remaining (categorized complete (0%), major (<50%) or minor (≥50%)) and tumor thickness at tumor–normal liver interface (TNI) (categorized <0.5 mm, 0.5 mm-<5 mm and ≥5 mm)—were assessed by a central pathology reviewer and local pathologists. Results Pathologic response was complete in 8%, major in 49% and minor in 43%. Tumor thickness at the TNI was <0.5 mm in 21%, 0.5 mm-<5 mm in 56% and ≥5 mm in 23%.In multivariate analyses, using either pathologic response or tumor thickness at TNI, pathologic response (P=.002,.009), tumor thickness at TNI (P=0.015, <.001), duration of preoperative chemotherapy(P=.028,.043), number of CLM (P=.038,.037) and margin (P=.011,.016) were associated with DFS. In a multivariate analysis using both parameters, tumor thickness at TNI (P=.004,.015), duration of preoperative chemotherapy(P=.025), number of nodules(P=.027) and margin(P=.014) were associated with DFS. Tumor size by pathology examination was the predictor of pathologic response. Predictors of tumor thickness at the TNI were tumor size and chemotherapy regimen. There was near perfect agreement for pathologic response (κ=.82) and substantial agreement (κ=.76) for tumor thickness between central reviewer and local pathologists. Conclusion Pathologic response and tumor thickness at the TNI are valid predictors of DFS after preoperative chemotherapy and surgery for CLM. PMID:23868456

Multicenter validation study of pathologic response and tumor thickness at the tumor-normal liver interface as independent predictors of disease-free survival after preoperative chemotherapy and surgery for colorectal liver metastases.

PubMed

Brouquet, Antoine; Zimmitti, Giuseppe; Kopetz, Scott; Stift, Judith; Julié, Catherine; Lemaistre, Anne-Isabelle; Agarwal, Atin; Patel, Viren; Benoist, Stephane; Nordlinger, Bernard; Gandini, Alessandro; Rivoire, Michel; Stremitzer, Stefan; Gruenberger, Thomas; Vauthey, Jean-Nicolas; Maru, Dipen M

2013-08-01

To validate pathologic markers of response to preoperative chemotherapy as predictors of disease-free survival (DFS) after resection of colorectal liver metastases (CLM). One hundred seventy-one patients who underwent resection of CLM after preoperative chemotherapy at 4 centers were studied. Pathologic response-defined as the proportion of tumor cells remaining (complete, 0%; major, <50%; minor, ≥50%) and tumor thickness at the tumor-normal liver interface (TNI) (<0.5 mm, 0.5 to <5 mm, ≥5 mm)-was assessed by a central pathology reviewer and local pathologists. Pathologic response was complete in 8% of patients, major in 49% of patients, and minor in 43% of patients. Tumor thickness at the TNI was <0.5 mm in 21% of patients, 0.5 to <5 mm in 56% of patients, and ≥5 mm in 23% of patients. On multivariate analyses, using either pathologic response or tumor thickness at TNI, pathologic response (P = .002, .009), tumor thickness at TNI (P = 0.015, <.001), duration of preoperative chemotherapy (P = .028, .043), number of CLM (P = .038, . 037), and margin (P = .011, .016) were associated with DFS. In a multivariate analysis using both parameters, tumor thickness at TNI (P = .004, .015), duration of preoperative chemotherapy (P = .025), number of nodules (P = .027), and margin (P = .014) were associated with DFS. Tumor size by pathology examination was the predictor of pathologic response. Predictors of tumor thickness at the TNI were tumor size and chemotherapy regimen. There was near perfect agreement for pathologic response (κ = .82) and substantial agreement (κ = .76) for tumor thickness between the central reviewer and local pathologists. Pathologic response and tumor thickness at the TNI are valid predictors of DFS after preoperative chemotherapy and surgery for CLM. Copyright © 2013 American Cancer Society.

Outcome of proximal esophageal cancer after definitive combined chemo-radiation: a Swiss multicenter retrospective study.

PubMed

Herrmann, Evelyn; Mertineit, Nando; De Bari, Berardino; Hoeng, Laura; Caparotti, Francesca; Leiser, Dominic; Jumeau, Raphael; Cihoric, Nikola; Jensen, Alexandra D; Aebersold, Daniel M; Ozsahin, Mahmut

2017-06-14

To report oncological outcomes and toxicity rates, of definitive platin-based chemoradiadiationtherapy (CRT) in the management of proximal esophageal cancer. We retrospectively reviewed the medical records of patients with cT1-4 cN0-3 cM0 cervical esophageal cancer (CEC) (defined as tumors located below the inferior border of the cricoid cartilage, down to 22 cm from the incisors) treated between 2004 and 2013 with platin-based definitive CRT in four Swiss institutions. Acute and chronic toxicities were retrospectively scored using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE-NCI v.4.0). Primary endpoint was loco-regional control (LRC). We also evaluated overall survival (OS) and disease-free survival (DFS) rates. The influence of patient- and treatment related features have been calculated using the Log-rank test and multivariate Cox proportional hazards model. We enrolled a total of 55 patients. Median time interval from diagnosis to CRT was 78 days (6-178 days). Median radiation dose was 56Gy (28-72Gy). Induction chemotherapy (ICHT) was delivered in 58% of patients. With a median follow up of 34 months (6-110months), actuarial 3-year LRC, DFS and OS were 52% (95% CI: 37-67%), 35% (95% CI: 22-50%) and 52% (95% CI: 37-67%), respectively. Acute toxicities (dysphagia, pain, skin-toxicity) ranged from grade 0 - 4 without significant dose-dependent differences. On univariable analyses, the only significant prognostic factor for LRC was the time interval > 78 days from diagnosis to CRT. On multivariable analysis, total radiation dose >56Gy (p <0.006) and ICHT (p < 0.004) were statistically significant positive predictive factors influencing DFS and OS. Definitive CRT is a reliable therapeutic option for proximal esophageal cancer, with acceptable treatment related toxicities. Higher doses and ICHT may improve OS and DFS and. These findings need to be confirmed in further prospective studies.

Adjuvant treatment for resected rectal cancer: impact of standard and intensified postoperative chemotherapy on disease-free survival in patients undergoing preoperative chemoradiation-a propensity score-matched analysis of an observational database.

PubMed

Garlipp, Benjamin; Ptok, Henry; Benedix, Frank; Otto, Ronny; Popp, Felix; Ridwelski, Karsten; Gastinger, Ingo; Benckert, Christoph; Lippert, Hans; Bruns, Christiane

2016-12-01

Adjuvant chemotherapy for resected rectal cancer is widely used. However, studies on adjuvant treatment following neoadjuvant chemoradiotherapy (CRT) and total mesorectal excision (TME) have yielded conflicting results. Recent studies have focused on adding oxaliplatin to both preoperative and postoperative therapy, making it difficult to assess the impact of adjuvant oxaliplatin alone. This study was aimed at determining the impact of (i) any adjuvant treatment and (ii) oxaliplatin-containing adjuvant treatment on disease-free survival in CRT-pretreated, R0-resected rectal cancer patients. Patients undergoing R0 TME following 5-fluorouracil (5FU)-only-based CRT between January 1, 2008, and December 31, 2010, were selected from a nationwide registry. After propensity score matching (PSM), comparison of disease-free survival (DFS) using Kaplan-Meier analysis and log-rank test was performed in (i) patients receiving no vs. any adjuvant treatment and (ii) patients treated with adjuvant 5FU/capecitabine without vs. with oxaliplatin. Out of 1497 patients, 520 matched pairs were generated for analysis of no vs. any adjuvant treatment. Mean DFS was significantly prolonged with adjuvant treatment (81.8 ± 2.06 vs. 70.1 ± 3.02 months, p < 0.001). One hundred forty-eight matched pairs were available for analysis of adjuvant therapy with or without oxaliplatin, showing no improvement in DFS in patients receiving oxaliplatin (76.9 ± 4.12 vs. 79.3 ± 4.44 months, p = 0.254). Local recurrence rate was not significantly different between groups in either analysis. In this cohort of rectal cancer patients treated with neoadjuvant CRT and TME surgery under routine conditions, adjuvant chemotherapy significantly improved DFS. No benefit was observed for the addition of oxaliplatin to adjuvant chemotherapy in this setting.

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial

PubMed Central

Holmes, Eileen; Baselga, José; de Azambuja, Evandro; Dueck, Amylou C.; Viale, Giuseppe; Zujewski, Jo Anne; Goldhirsch, Aron; Armour, Alison; Pritchard, Kathleen I.; McCullough, Ann E.; Dolci, Stella; McFadden, Eleanor; Holmes, Andrew P.; Tonghua, Liu; Eidtmann, Holger; Dinh, Phuong; Di Cosimo, Serena; Harbeck, Nadia; Tjulandin, Sergei; Im, Young-Hyuck; Huang, Chiun-Sheng; Diéras, Véronique; Hillman, David W.; Wolff, Antonio C.; Jackisch, Christian; Lang, Istvan; Untch, Michael; Smith, Ian; Boyle, Frances; Xu, Binghe; Gomez, Henry; Suter, Thomas; Gelber, Richard D.; Perez, Edith A.

2016-01-01

Background Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2–positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2–positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Results Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Conclusion Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care. PMID:26598744

Phase III Comparison of Prophylactic Cranial Irradiation Versus Observation in Patients With Locally Advanced Non–Small-Cell Lung Cancer: Primary Analysis of Radiation Therapy Oncology Group Study RTOG 0214

PubMed Central

Gore, Elizabeth M.; Bae, Kyounghwa; Wong, Stuart J.; Sun, Alexander; Bonner, James A.; Schild, Steven E.; Gaspar, Laurie E.; Bogart, Jeffery A.; Werner-Wasik, Maria; Choy, Hak

2011-01-01

Purpose This study was conducted to determine if prophylactic cranial irradiation (PCI) improves survival in locally advanced non–small-cell lung cancer (LA-NSCLC). Patients and Methods Patients with stage III NSCLC without disease progression after treatment with surgery and/or radiation therapy (RT) with or without chemotherapy were eligible. Participants were stratified by stage (IIIA v IIIB), histology (nonsquamous v squamous), and therapy (surgery v none) and were randomly assigned to PCI or observation. PCI was delivered to 30 Gy in 15 fractions. The primary end point of the study was overall survival (OS). Secondary end points were disease-free survival (DFS), neurocognitive function (NCF), and quality of life. Kaplan-Meier and log-rank analyses were used for OS and DFS. The incidence of brain metastasis (BM) was evaluated with the logistic regression model. Results Overall, 356 patients were accrued of the targeted 1,058. The study was closed early because of slow accrual; 340 of the 356 patients were eligible. The 1-year OS (P = .86; 75.6% v 76.9% for PCI v observation) and 1-year DFS (P = .11; 56.4% v 51.2% for PCI v observation) were not significantly different. The hazard ratio for observation versus PCI was 1.03 (95% CI, 0.77 to 1.36). The 1-year rates of BM were significantly different (P = .004; 7.7% v 18.0% for PCI v observation). Patients in the observation arm were 2.52 times more likely to develop BM than those in the PCI arm (unadjusted odds ratio, 2.52; 95% CI, 1.32 to 4.80). Conclusion In patients with stage III disease without progression of disease after therapy, PCI decreased the rate of BM but did not improve OS or DFS. PMID:21135270

Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

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

Ohri, Nitin, E-mail: ohri.nitin@gmail.com; Garg, Madhur K.; Aparo, Santiago

2013-06-01

Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated frommore » survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy.« less

Molecular orientation in a dielectric liquid-vapor interphase

NASA Astrophysics Data System (ADS)

Chacón, E.; Mederos, L.; Navascués, G.; Tarazona, P.

1985-04-01

The density functional theory of Chacón et al. is used to study the molecular orientation in an interphase of a weak dipolar fluid. Explicit expressions are obtained using standard perturbation techniques. Molecular orientation, local susceptibility, and the Gibbsean surface susceptibility are evaluated for a Stockmayer model of dipolar fluid. The effect of the surface structure on the bulk ferroelectric transition is discussed in the light of the present theory and the numerical results.

Observation of plasmonic dipolar anti-bonding mode in silver nanoring structures.

PubMed

Ye, Jian; Van Dorpe, Pol; Lagae, Liesbet; Maes, Guido; Borghs, Gustaaf

2009-11-18

We report on a clear experimental observation of the plasmonic dipolar anti-bonding resonance in silver nanorings. The data can be explained effectively by the plasmon hybridization model, which is confirmed by the numerical calculations of the electromagnetic field and surface charge distribution profiles. The experimental demonstration of the plasmon hybridization model indicates its usefulness as a valuable tool to understand, design and predict optical properties of metallic nanostructures.

Observation of plasmonic dipolar anti-bonding mode in silver nanoring structures

NASA Astrophysics Data System (ADS)

Ye, Jian; Van Dorpe, Pol; Lagae, Liesbet; Maes, Guido; Borghs, Gustaaf

2009-11-01

We report on a clear experimental observation of the plasmonic dipolar anti-bonding resonance in silver nanorings. The data can be explained effectively by the plasmon hybridization model, which is confirmed by the numerical calculations of the electromagnetic field and surface charge distribution profiles. The experimental demonstration of the plasmon hybridization model indicates its usefulness as a valuable tool to understand, design and predict optical properties of metallic nanostructures.

Arrays of dipolar molecular rotors in Tris(o-phenylenedioxy) cyclotriphosphazene.

PubMed

Zhao, Ke; Dron, Paul I; Kaleta, Jiří; Rogers, Charles T; Michl, Josef

2014-01-01

Regular two-dimensional or three-dimensional arrays of mutually interacting dipolar molecular rotors represent a worthy synthetic objective. Their dielectric properties, including possible collective behavior, will be a sensitive function of the location of the rotors, the orientation of their axes, and the size of their dipoles. Host-guest chemistry is one possible approach to gaining fine control over these factors. We describe the progress that has been achieved in recent years using tris (o-phenylenedioxy)cyclotriphosphazene as a host and a series of rod-shaped dipolar molecular rotors as guests. Structures of both surface and bulk inclusion compounds have been established primarily by solid-state nuclear magnetic resonance (NMR) and powder X-ray diffraction (XRD) techniques. Low-temperature dielectric spectroscopy revealed rotational barriers as low as 1.5 kcal/mol, but no definitive evidence for collective behavior has been obtained so far.

Classical and quantum filaments in the ground state of trapped dipolar Bose gases

NASA Astrophysics Data System (ADS)

Cinti, Fabio; Boninsegni, Massimo

2017-07-01

We study, by quantum Monte Carlo simulations, the ground state of a harmonically confined dipolar Bose gas with aligned dipole moments and with the inclusion of a repulsive two-body potential of varying range. Two different limits can clearly be identified, namely, a classical one in which the attractive part of the dipolar interaction dominates and the system forms an ordered array of parallel filaments and a quantum-mechanical one, wherein filaments are destabilized by zero-point motion, and eventually the ground state becomes a uniform cloud. The physical character of the system smoothly evolves from classical to quantum mechanical as the range of the repulsive two-body potential increases. An intermediate regime is observed in which ordered filaments are still present, albeit forming different structures from the ones predicted classically; quantum-mechanical exchanges of indistinguishable particles across different filaments allow phase coherence to be established, underlying a global superfluid response.

Critical Time Crystals in Dipolar Systems

NASA Astrophysics Data System (ADS)

Ho, Wen Wei; Choi, Soonwon; Lukin, Mikhail D.; Abanin, Dmitry A.

2017-07-01

We analyze the quantum dynamics of periodically driven, disordered systems in the presence of long-range interactions. Focusing on the stability of discrete time crystalline (DTC) order in such systems, we use a perturbative procedure to evaluate its lifetime. For 3D systems with dipolar interactions, we show that the corresponding decay is parametrically slow, implying that robust, long-lived DTC order can be obtained. We further predict a sharp crossover from the stable DTC regime into a regime where DTC order is lost, reminiscent of a phase transition. These results are in good agreement with the recent experiments utilizing a dense, dipolar spin ensemble in diamond [Nature (London) 543, 221 (2017), 10.1038/nature21426]. They demonstrate the existence of a novel, critical DTC regime that is stabilized not by many-body localization but rather by slow, critical dynamics. Our analysis shows that the DTC response can be used as a sensitive probe of nonequilibrium quantum matter.

Monte Carlo simulations of kagome lattices with magnetic dipolar interactions

NASA Astrophysics Data System (ADS)

Plumer, Martin; Holden, Mark; Way, Andrew; Saika-Voivod, Ivan; Southern, Byron

Monte Carlo simulations of classical spins on the two-dimensional kagome lattice with only dipolar interactions are presented. In addition to revealing the sixfold-degenerate ground state, the nature of the finite-temperature phase transition to long-range magnetic order is discussed. Low-temperature states consisting of mixtures of degenerate ground-state configurations separated by domain walls can be explained as a result of competing exchange-like and shape-anisotropy-like terms in the dipolar coupling. Fluctuations between pairs of degenerate spin configurations are found to persist well into the ordered state as the temperature is lowered until locking in to a low-energy state. Results suggest that the system undergoes a continuous phase transition at T ~ 0 . 43 in agreement with previous MC simulations but the nature of the ordering process differs. Preliminary results which extend this analysis to the 3D fcc ABC-stacked kagome systems will be presented.

New metal phthalocyanines/metal simple hydroxide multilayers: experimental evidence of dipolar field-driven magnetic behavior.

PubMed

Bourzami, Riadh; Eyele-Mezui, Séraphin; Delahaye, Emilie; Drillon, Marc; Rabu, Pierre; Parizel, Nathalie; Choua, Sylvie; Turek, Philippe; Rogez, Guillaume

2014-01-21

A series of new hybrid multilayers has been synthesized by insertion-grafting of transition metal (Cu(II), Co(II), Ni(II), and Zn(II)) tetrasulfonato phthalocyanines between layers of Cu(II) and Co(II) simple hydroxides. The structural and spectroscopic investigations confirm the formation of new layered hybrid materials in which the phthalocyanines act as pillars between the inorganic layers. The magnetic investigations show that all copper hydroxide-based compounds behave similarly, presenting an overall antiferromagnetic behavior with no ordering down to 1.8 K. On the contrary, the cobalt hydroxide-based compounds present a ferrimagnetic ordering around 6 K, regardless of the nature of the metal phthalocyanine between the inorganic layers. The latter observation points to strictly dipolar interactions between the inorganic layers. The amplitude of the dipolar field has been evaluated from X-band and Q-band EPR spectroscopy investigation (Bdipolar ≈ 30 mT).

Frustrated Magnetism of Dipolar Molecules on a Square Optical Lattice: Prediction of a Quantum Paramagnetic Ground State

NASA Astrophysics Data System (ADS)

Zou, Haiyuan; Zhao, Erhai; Liu, W. Vincent

2017-08-01

Motivated by the experimental realization of quantum spin models of polar molecule KRb in optical lattices, we analyze the spin 1 /2 dipolar Heisenberg model with competing anisotropic, long-range exchange interactions. We show that, by tilting the orientation of dipoles using an external electric field, the dipolar spin system on square lattice comes close to a maximally frustrated region similar, but not identical, to that of the J1-J2 model. This provides a simple yet powerful route to potentially realize a quantum spin liquid without the need for a triangular or kagome lattice. The ground state phase diagrams obtained from Schwinger-boson and spin-wave theories consistently show a spin disordered region between the Néel, stripe, and spiral phase. The existence of a finite quantum paramagnetic region is further confirmed by an unbiased variational ansatz based on tensor network states and a tensor renormalization group.