Hosing of a Long Relativistic Particle Bunch in Plasma.

Experimental results show that hosing of a long particle bunch in plasma can be induced by wakefields driven by a short, misaligned preceding bunch. Hosing develops in the plane of misalignment, self-modulation in the perpendicular plane, at frequencies close to the plasma electron frequency, and are reproducible. Development of hosing depends on misalignment direction, its growth on misalignment extent and on proton bunch charge. Results have the main characteristics of a theoretical model, are relevant to other plasma-based accelerators and represent the first characterization of hosing.

Controlled Growth of the Self-Modulation of a Relativistic Proton Bunch in Plasma.

A long, narrow, relativistic charged particle bunch propagating in plasma is subject to the self-modulation (SM) instability. We show that SM of a proton bunch can be seeded by the wakefields driven by a preceding electron bunch. SM timing reproducibility and control are at the level of a small fraction of the modulation period. With this seeding method, we independently control the amplitude of the seed wakefields with the charge of the electron bunch and the growth rate of SM with the charge of the proton bunch. Seeding leads to larger growth of the wakefields than in the instability case.

Transition between Instability and Seeded Self-Modulation of a Relativistic Particle Bunch in Plasma.

We use a relativistic ionization front to provide various initial transverse wakefield amplitudes for the self-modulation of a long proton bunch in plasma. We show experimentally that, with sufficient initial amplitude [≥(4.1±0.4) MV/m], the phase of the modulation along the bunch is reproducible from event to event, with 3%-7% (of 2π) rms variations all along the bunch. The phase is not reproducible for lower initial amplitudes. We observe the transition between these two regimes. Phase reproducibility is essential for deterministic external injection of particles to be accelerated.

Proton Bunch Self-Modulation in Plasma with Density Gradient.

We study experimentally the effect of linear plasma density gradients on the self-modulation of a 400 GeV proton bunch. Results show that a positive or negative gradient increases or decreases the number of microbunches and the relative charge per microbunch observed after 10 m of plasma. The measured modulation frequency also increases or decreases. With the largest positive gradient we observe two frequencies in the modulation power spectrum. Results are consistent with changes in wakefields' phase velocity due to plasma density gradients adding to the slow wakefields' phase velocity during self-modulation growth predicted by linear theory.

Advanced neutral alkali beam diagnostics for applications in fusion research (invited).

Diagnosing the density profile at the edge of high temperature fusion plasmas by an accelerated lithium beam is a known technique since decades. By knowledge of the relevant atomic physics rate coefficients, the plasma electron density profile can be calculated from the relatively calibrated light profile along the beam. Several additional possibilities have already been demonstrated: Charge Exchange Resonance Spectroscopy (CXRS) for ion temperature/flow and Zeeman polarimetry for edge plasma current; therefore the Li-beam diagnostic offers a wealth of information at the plasma edge. The weaknesses of the method are the relatively faint light signal, background light, and technical difficulties of the beam injector which usually seriously limit the applicability. In this talk, we present systematic developments in alkali-beam diagnostics (Li, Na) for the injector and the observation system and detectors which resulted in strongly increased capabilities. Advanced systems have been built, and microsecond scale density profile, turbulence, and zonal flow measurement have been demonstrated. A novel edge current measurement technique has also been designed, and components have been tested with potential microsecond-scale time resolution. Additional possibilities of these advanced systems for spectral measurements (CXRS and various Zeeman schemes) are also discussed.

Sorafenib with or without everolimus in patients with advanced hepatocellular carcinoma (HCC): a randomized multicenter, multinational phase II trial (SAKK 77/08 and SASL 29).

BACKGROUND: Sorafenib (S), a multitargeted tyrosine kinase inhibitor, is the standard of care for first-line systemic treatment of advanced hepatocellular carcinoma (HCC). Everolimus (E) is a potent inhibitor of mTOR, a pathway frequently activated in HCC. Preclinical data suggest that the combination S + E has additive effects compared with single-agent S. PATIENTS AND METHODS: Patients with unresectable or metastatic HCC and Child-Pugh ≤7 liver dysfunction were randomized to receive daily S 800 mg alone or with E 5 mg until progression or unacceptable toxicity. The primary end point was progression-free survival at 12 weeks (PFS12). The secondary end points included response rate, PFS, time to progression (TTP), overall survival (OS), duration of disease stabilization (DDS), safety, and quality-of-life (QoL) assessments. RESULTS: A total of 106 patients were randomized: 46 patients received S and 60 patients received S + E. Ninety-three patients were assessable for the primary end point and 105 patients for the safety analysis. The PFS12 rate was 70% [95% confidence interval (CI) 54-83] and 68% (95% CI 53-81) in patients randomized to S and S + E, respectively. The RECIST (mRECIST) response rate was 0% (23%) in the S arm and 10% (35%) in the S + E arm. Median PFS (6.6 versus 5.7 months), TTP (7.6 versus 6.3 months), DDS (6.7 versus 6.7 months), and OS (10 versus 12 months) were similar in the S and S + E arms, respectively. Grade 3/4 adverse events occurred in 72% and 86% of patients in arm S and arm S + E, respectively. Patients had similar QoL scores over time, except for a greater worsening in physical well-being and mood in the arm S + E. CONCLUSIONS: No evidence was found that S + E improves the efficacy compared with S alone. Combining 5 mg E with full-dose S is feasible, but more toxic than S alone. Further testing of this drug combination in molecularly unselected HCCs appears unwarranted. CLINICALTRIALSGOV: NCT01005199.

Central venous oxygen saturation and carbon dioxide gap as resuscitation targets in a hemorrhagic shock.

BACKGROUND: Fluid resuscitation is still a major challenge. We aimed to describe changes in central venous oxygen saturation (ScvO2 ) and venous-to-arterial carbon dioxide gap (dCO2 ) during an experimental stroke volume (SV) index (SVI)-guided hemorrhage and fluid resuscitation model in pigs. METHODS: Twelve anesthetized, mechanically ventilated pigs were bled till baseline SVI (Tbsl ) dropped by 50% (T0 ), thereafter fluid resuscitation was performed with balanced crystalloid in four steps until initial SVI was reached (T4 ). Statistical analysis was performed with Statistical Program for Social Sciences version 18.0; data are expressed as mean ± standard deviation. RESULTS: After bleeding, ScvO2 dropped (Tbsl = 78 ± 7 vs. T0 = 61 ± 5% P < 0.05) and oxygen extraction ratio increased (Tbsl = 0.20 ± 0.07 vs. T0 = 0.36 ± 0.05, P < 0.05). By T4 the ScvO2 normalized, but on average it remained 5% lower than at Tbsl (T4 = 73 ± 9% P < 0.05) and oxygen extraction also remained higher as compared with Tbsl (T4 = 0.24 ± 0.09 P = 0.001). ScvO2 showed significant correlation with SVI (r = 0.564, P < 0.001). dCO2 increased during hypovolemia (Tbsl :5.3 ± 2.0 vs. T0 :9.6 ± 2.3 mmHg, P = 0.001), then returned to normal by T4 = 5.1 ± 2.6 mmHg, and it also showed significant correlation with SVI (R = -0.591, P < 0.001) and oxygen extraction (R = 0.735, P < 0.001). CONCLUSIONS: In this SV-guided bleeding and fluid resuscitation model, both ScvO2 and dCO2 correlated well with changes in SV, but only the dCO2 returned to its baseline, normal value, while ScvO2 remained significantly lower than at baseline. These results suggest that dCO2 may be a good hemodynamic endpoint of resuscitation, while ScvO2 is not strictly a hemodynamic parameter, but rather an indicator of the balance between oxygen delivery and consumption.

Central venous oxygen saturation is a good indicator of altered oxygen balance in isovolemic anemia.

BACKGROUND: Red blood cell transfusion is done primarily as a means to improve oxygen delivery (DO2). Current transfusion guidelines are based solely on hemoglobin levels, regardless of actual DO2 need. As central venous oxygen saturation (ScvO2) may reflect imbalances in DO2 and consumption (VO2) the aim of this study was to investigate the value of ScvO2 as an indicator of oxygen balance in isovolemic anemia. METHODS: After splenectomy, anesthetized Vietnamese mini pigs (n = 13, weight range: 18-30 kg) underwent controlled bleeding in five stages (T0-T5). During each stage approximately 10% of the estimated starting total blood volume was removed and immediately replaced with an equal volume of colloid. Hemodynamic measurements and blood gas analysis were then performed. RESULTS: Each stage of bleeding resulted in a significant fall in hemoglobin, T0 : 125 (113-134) to T(5) : 49 (43-55) g/l [T0 : 7.7 (6.9-8.2) to T5 : 3.0 (2.6-3.4) mmol/l]. The O2-extraction (VO2/DO2) increased significantly only from T3 : 35 (21-40) %, P < 0.05. The change of ScvO2 showed a similar pattern and dropped below the physiological threshold of 70% at T4 : 68 (61-76) %. At this point, hemoglobin was below the recommended transfusion trigger value, 59 (53-67) g/l [3.6 (3.3-4.1) mmol/l]. There was a strong significant association between ScvO2< 70%) and VO2/DO2 > 30%): r = -0.71, r² = 0.50, P < 0.001. CONCLUSION: The results of this study show that ScvO2 reflects changes of VO2/DO2 in isovolemic anemia better than Hb alone, therefore it may be used as an additional indicator of blood transfusion in clinical practice.

Numerical study of optically induced director oscillations in nematic liquid crystals: transition to chaos via homoclinic gluings and the role of backflow.

We investigate the director oscillations of a homeotropically aligned nematic liquid crystal that are generated by cw laser radiation incident at a slightly oblique angle. The full nematodynamic equations are solved numerically, and it is shown that the inclusion of backflow leads to a qualitative change of the theoretical bifurcation scenario at moderate to high intensities. Very good correspondence is achieved with recent observations. The route to chaos via a sequence of homoclinic gluing bifurcations, whose existence was suggested by simple models, but doubted by recent calculations and experiments, is shown to exist in a parameter region unexplored by experiments.

Influence of the backflow effect on the orientational dynamics induced by light in nematics.

We investigate the dynamical phenomena induced by a circularly polarized plane wave incident perpendicularly on a homeotropically aligned nematic layer. We study theoretically the influence of the velocity field (backflow effect) on the bifurcation scenario. Whereas backflow leads to substantial quantitative changes of secondary bifurcation thresholds, the overall bifurcation scenario remains unchanged. In the regime of uniform precession of the director with large reorientation, an unanticipated spatial oscillation of the flow field across the layer is found. Quantitative comparison with experimental large-aspect ratio systems is now possible.

Pattern-forming instability induced by light in pure and dye-doped nematic liquid crystals.

We study theoretically the instabilities induced by a linearly polarized ordinary light wave incident at a small oblique angle on a thin layer of homeotropically oriented nematic liquid crystal with special emphasis on the dye-doped case. The spatially periodic Hopf bifurcation that occurs as the secondary instability after the stationary Freedericksz transition is analyzed.

Numerical investigation of optically induced director oscillations in nematic liquid crystals.

We present a theoretical study of the effects induced by the passage of a linearly polarized light beam through a thin cell of homeotropic nematic liquid crystal. The light is incident at a slightly oblique angle and is polarized perpendicular to the plane of incidence. Experiments in this geometry have revealed a rich variety of complex, time dependent director motion. We solve numerically the director equations for the nematic and compare the results with existing experimental findings.

Complex nonlinear behavior in optically excited nematic liquid crystals.

We present a study of the passage of a monochromatic, linearly polarized cw laser beam through a cell of homeotropically aligned nematic liquid crystal at a slightly oblique angle. The light is polarized perpendicular to the plane of incidence. Experiments in this geometry have revealed the existence of complex, time-dependent dynamics of the director motion. We present a model for the director dynamics derived from the basic equations that shows both periodic and chaotic behavior at different light intensities as observed in the experiments. The model we derive exhibits a variety of complex behaviors, among them an uncommon route to chaos via gluing bifurcations that has not yet been observed in any real physical system.