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Larkin J.,Royal Marsden Hospital | Chiarion-Sileni V.,Veneto Region Oncology Research Institute | Gonzalez R.,University of Colorado at Denver | Grob J.J.,Aix - Marseille University | And 31 more authors.
New England Journal of Medicine | Year: 2015

BACKGROUND Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, double-blind, phase 3 study, nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma. METHODS We assigned, in a 1:1:1 ratio, 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone. Progression-free survival and overall survival were coprimary end points. Results regarding progression-free survival are presented here. RESULTS The median progression-free survival was 11.5 months (95% confidence interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 99.5% CI, 0.43 to 0.76; P<0.001). In patients with tumors positive for the PD-1 ligand (PD-L1), the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group, but in patients with PD-L1-negative tumors, progression-free survival was longer with the combination therapy than with nivolumab alone (11.2 months [95% CI, 8.0 to not reached] vs. 5.3 months [95% CI, 2.8 to 7.1]). Treatment-related adverse events of grade 3 or 4 occurred in 16.3% of the patients in the nivolumab group, 55.0% of those in the nivolumab-plus-ipilimumab group, and 27.3% of those in the ipilimumab group. CONCLUSIONS Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone. (Funded by Bristol-Myers Squibb; CheckMate 067 ClinicalTrials.gov number, NCT01844505.). Copyright © 2015 Massachusetts Medical Society.


Lerner E.J.,Lawrenceville Plasma Physics Inc. | Falomo R.,National institute for astrophysics | Scarpa R.,Institute of Astrophysics of Canarias
International Journal of Modern Physics D | Year: 2014

The Tolman test for surface brightness (SB) dimming was originally proposed as a test for the expansion of the universe. The test, which is independent of the details of the assumed cosmology, is based on comparisons of the SB of identical objects at different cosmological distances. Claims have been made that the Tolman test provides compelling evidence against a static model for the universe. In this paper we reconsider this subject by adopting a static Euclidean universe (SEU) with a linear Hubble relation at all z (which is not the standard Einstein-de Sitter model), resulting in a relation between flux and luminosity that is virtually indistinguishable from the one used for ΛCDM models. Based on the analysis of the UV SB of luminous disk galaxies from HUDF and GALEX datasets, reaching from the local universe to z ∼ 5, we show that the SB remains constant as expected in a static universe. A re-analysis of previously published data used for the Tolman test at lower redshift, when treated within the same framework, confirms the results of the present analysis by extending our claim to elliptical galaxies. We conclude that available observations of galactic SB are consistent with a SEU model. We do not claim that the consistency of the adopted model with SB data is sufficient by itself to confirm what would be a radical transformation in our understanding of the cosmos. However, we believe this result is more than sufficient reason to examine this combination of hypotheses further. © 2014 World Scientific Publishing Company.


Ivanov V.V.,University of Nevada, Reno | Altemara S.D.,University of Nevada, Reno | Astanovitskiy A.A.,University of Nevada, Reno | Sarkisov G.S.,Ktech Corporation | And 3 more authors.
IEEE Transactions on Plasma Science | Year: 2010

Laser probing diagnostics at the wavelength of 266 nm were developed for investigation of the 1-MA z-pinch plasmas. The absorption and refraction in plasma are significantly smaller at 266 nm than at the regular wavelength of 532 nm. These features allow observation of fine details in the z-pinch plasma at the ablation, implosion, and stagnation phases. Two-color shadowgraphy at 532/266 nm presents a structure of ablating wires and implosion bubbles in wire arrays. Plasma distribution and dynamics in compact cylindrical, star, and planar wire arrays can be studied at the wavelength of 266 nm. An electron density Ne > 5 • 1019 cm-3 was reconstructed with interferometry at 266 nm in the stagnated z-pinch. Further development of laser probing diagnostics of the z-pinch plasmas is discussed. © 2010 IEEE.


Krupakar Murali S.,Lawrenceville Plasma Physics Inc. | Blake A.M.,Lawrenceville Plasma Physics Inc. | Haboub A.,Lawrenceville Plasma Physics Inc.
Journal of Fusion Energy | Year: 2011

To gain insight into the synchronization, simultaneity, and switching behavior of the individual switch, two TIA-525 Optical/Electrical converters have been recently introduced to DPF experiments at Lawrenceville Plasma Physics (LPP). These electronic devices, attached to two spark gap switches through optical fibers, detect light sampled from the switch firing and convert it to amplified voltage signals. We observed that in terms of simultaneity and synchronization, the firing behavior and quality of the pair of switches monitored are not the same. Some switches, among the twelve that are being used, fired at the trigger voltage within few tens of ns while the others fired much later (after ~1-2 μs) and are triggered at or after the pinch voltage rise. The results from the present work show evidence of pinch voltage triggering the switches. Since the pinch voltage is over three times the voltage of the capacitors, this voltage triggers those capacitors that do not fire during the regular high voltage trigger pulse. This, we suggest, could affect the efficiency of the device as it simply drains the reserved energy in the system. We present results of an empirical study of spark gap switch firing as well as the total current that is followed using the Rogowski coil. © 2011 Springer Science+Business Media, LLC.


Murali S.K.,Lawrenceville Plasma Physics Inc. | Emmert G.A.,University of Wisconsin - Madison | Santarius J.F.,University of Wisconsin - Madison | Kulcinski G.L.,University of Wisconsin - Madison
Physics of Plasmas | Year: 2010

Inertial electrostatic confinement fusion devices are compact sources of neutrons, protons, electrons, and x rays. Such sources have many applications. Improving the efficiency of the device also increases the applications of this device. Hence a thorough understanding of the operation of this device is needed. In this paper, we study the effect of chamber pressure on the temperature of the cathode. Experimentally, the grid temperature decreases as the chamber pressure increases; numerical simulations suggest that this is caused by the reduction of the hot ion current to the cathode as the pressure increases for constant power supply current. Such an understanding further supports the conclusion that the asymmetric heating of the cathode can be decreased by homogenizing the ion flow around the cathode. © 2010 American Institute of Physics.


Lerner E.J.,Lawrenceville Plasma Physics Inc. | Krupakar Murali S.,Lawrenceville Plasma Physics Inc. | Haboub A.,Lawrenceville Plasma Physics Inc.
Journal of Fusion Energy | Year: 2011

Lawrenceville Plasma Physics Inc. has initiated a 2-year-long experimental project to test the scientific feasibility of achieving controlled fusion using the dense plasma focus (DPF) device with hydrogen-boron (p-B 11) fuel. The goals of the experiment are: first, to confirm the achievement of high ion and electron energies observed in previous experiments from 2001; second, to greatly increase the efficiency of energy transfer into the plasmoid where the fusion reactions take place; third, to achieve the high magnetic fields (>1 GG) needed for the quantum magnetic field effect, which will reduce cooling of the plasma by X-ray emission; and finally, to use p-B 11 fuel to demonstrate net energy gain. The experiments are being conducted with a newly constructed dense plasma focus in Middlesex, NJ which is expected to generate peak currents in excess of 2 MA. Some preliminary results are reported. © 2011 Springer Science+Business Media, LLC.


Lerner E.J.,Lawrenceville Plasma Physics Inc. | Murali S.K.,Lawrenceville Plasma Physics Inc. | Shannon D.,Lawrenceville Plasma Physics Inc. | Blake A.M.,Lawrenceville Plasma Physics Inc. | Roessel F.V.,Lawrenceville Plasma Physics Inc.
Physics of Plasmas | Year: 2012

Using a dense plasma focus device with a 50 kJ capacitor charge, we have observed fusion reactions from deuterium ions with record energies of 150 keV, which are confined for durations of 7-30 ns in the cores of plasmoids with typical radii of 300-500 m and densities ∼3 10 19 cm -3. We have for the first time simultaneously imaged the plasmoid at high (30 m) resolution and measured trapped ion energy and neutron anisotropy. The isotropy of the neutron emission as well as other observations confirms that the observed neutrons per pulse of up to 1.5 10 11 are produced mainly by confined ions, not an unconfined beam. The conditions achieved are of interest for aneutronic fusion, such as with pB11 fuel. © 2012 American Institute of Physics.


Murali S.K.,Lawrenceville Plasma Physics Inc. | Santarius J.F.,University of Wisconsin - Madison | Kulcinski G.L.,University of Wisconsin - Madison
IEEE Transactions on Plasma Science | Year: 2010

Recent work [S. Krupakar Murali, J. F. Santarius, and G. L. Kulcinski, Phys. Plasmas, 15, 122702, (2008)] indicates that fusion reactions in an inertial electrostatic confinement (IEC) device primarily occur in microchannels. Since microchannels form discretely all around the cathode, the proton calibration procedure necessitated the estimation of fusion reactivity within the microchannels. Unlike neutron detectors that see a point source, the proton detectors can follow the nonuniformities in the fusion source regime. Hence, the variation in microchannel distribution around the cathode has to be taken into account for independently calibrating a proton detector. Experiments were conducted to characterize the microchannels generated within an IEC device. A new calibration factor has been derived for specific grid geometry (5 latitudes and 12 longitudes) based on the experimental results. The new factor is 16% lower than the previously used values. Moreover, the wild variation in the proton data by as much as 50% between two measurements has been determined to be caused by the variation in grid orientation. It is suggested that for consistent proton measurements, the grid orientation with respect to the detector should be kept constant such that the least number of protons are detected by the proton detector. This not only prevents detector saturation, but also ensures that nonlinear effects in proton rate measurements are eliminated. © 2006 IEEE.


Murali S.K.,Lawrenceville Plasma Physics Inc. | Santarius J.F.,University of Wisconsin - Madison | Kulcinski G.L.,University of Wisconsin - Madison
IEEE Transactions on Plasma Science | Year: 2011

Gridded inertial-electrostatic confinement (IEC) devices interest fusion researchers owing to their ability to burn advanced fusion fuels and have many near-term applications. In these devices, a high voltage (10180 kV) accelerates ions radially between nearly transparent electrodes in spherical or cylindrical geometry. In this paper, we report experiments that study fusion reactions within the microchannels formed between the wires of the nearly transparent IEC cathode grid. Fusion proton counts were measured while sweeping the microchannels across a proton detector by rotating the central cathode grid with respect to the detector. The observed proton counts increased or decreased in correspondence with the grid wire orientation with respect to the proton detector. The fusion reactions were thus inferred to be nonuniform around the central grid and primarily occurring in channels formed by the grid wire gaps. We interpret this effect as an indication that most ions and charge-exchanged neutrals traverse radially along these microchannels. The grid wires will also shadow fusion reactions taking place at radii smaller than the cathode radius. Both the microchannels and the grid-wire shadowing causes the proton counts to vary, in measurements presented herein, by as much as 45%. We explore whether these effects could have played a role in previous research that reported potential-well structures. © 2010 IEEE.


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