External excitation of a short-wavelength fluctuation in the Alcator C-Mod edge plasma and its relationship to the quasi-coherent mode

A novel “Shoelace” antenna has been used to inductively excite a short-wavelength edge fluctuation in a tokamak boundary layer for the first time. The principal design parameters, k[subscript ⊥] = 1.5 ± 0.1 cm[superscript −1] and 45 < f < 300 kHz, match the Quasi-Coherent Mode (QCM, k[subscript ⊥] ∼ 1.5 cm[superscript −1], f ∼ 50−150 kHz) in Alcator C-Mod, responsible for exhausting impurities in the steady-state, ELM-free Enhanced D[subscript α] H-mode. In H-mode, whether or not there is a QCM, the antenna drives coherent, field-aligned perturbations in density, [˜ over n][subscript e], and field, [˜ over B][subscript θ], which are guided by field lines, propagate in the electron diamagnetic drift direction, and exhibit a weakly damped (γ/ω[subscript 0] ∼ 5%−10%) resonance near the natural QCM frequency. This result is significant, offering the possibility that externally driven modes may be used to enhance particle transport. In L-mode, the antenna drives only a non-resonant [˜ over B][subscript θ] response. The facts that the driven mode has the same wave number and propagation direction as the QCM, and is resonant at the QCM frequency, suggest the antenna may couple to this mode, which we have shown elsewhere to be predominantly drift-mode-like [B. LaBombard et al., Phys. Plasmas 21, 056108 (2014)].United States. Dept. of Energy (Cooperative Agreement DE-FC02-99ER54512

Phase II Study of Radiotherapy and Temsirolimus versus Radiochemotherapy with Temozolomide in Patients with Newly Diagnosed Glioblastoma without MGMT Promoter Hypermethylation (EORTC 26082).

EORTC 26082 assessed the activity of temsirolimus in patients with newly diagnosed glioblastoma harboring an unmethylated O6 methylguanine-DNA-methyltransferase (MGMT) promoter. Patients (n = 257) fulfilling eligibility criteria underwent central MGMT testing. Patients with MGMT unmethylated glioblastoma (n = 111) were randomized 1:1 between standard chemo-radiotherapy with temozolomide or radiotherapy plus weekly temsirolimus (25 mg). Primary endpoint was overall survival at 12 months (OS12). A positive signal was considered &gt;38 patients alive at 12 months in the per protocol population. A noncomparative reference arm of 54 patients evaluated the assumptions on OS12 in a standard-treated cohort of patients. Prespecified post hoc analyses of markers reflecting target activation were performed. Both therapies were administered per protocol with a median of 13 cycles of maintenance temsirolimus. Median age was 55 and 58 years in the temsirolimus and standard arms, the WHO performance status 0 or 1 for most patients (95.5%). In the per protocol population, 38 of 54 patients treated with temsirolimus reached OS12. The actuarial 1-year survival was 72.2% [95% confidence interval (CI), 58.2-82.2] in the temozolomide arm and 69.6% (95% CI, 55.8-79.9) in the temsirolimus arm [hazard ratio (HR) 1.16; 95% CI, 0.77-1.76; P = 0.47]. In multivariable prognostic analyses of clinical and molecular factors, phosphorylation of mTORSer2448 in tumor tissue (HR 0.13; 95% CI, 0.04-0.47; P = 0.002), detected in 37.6%, was associated with benefit from temsirolimus. Temsirolimus was not superior to temozolomide in patients with an unmethylated MGMT promoter. Phosphorylation of mTORSer2448 in the pretreatment tumor tissue may define a subgroup benefitting from mTOR inhibition. Clin Cancer Res; 22(19); 4797-806. ©2016 AACR

Radial localization of edge modes in Alcator C-Mod pedestals using optical diagnostics

Dedicated experiments in ion cyclotron range heated enhanced D-alpha (EDA) H-mode and I-mode plasmas have been performed on Alcator C-Mod to identify the location of edge fluctuations inside the pedestal and to determine their plasma frame phase velocity. For this purpose, measurements from gas puff imaging (GPI) and gas puff charge exchange recombination spectroscopy (GP-CXRS) have been collected using the same optical views. The data suggest that the EDA H-mode-specific quasi-coherent mode (QCM) is centered near the radial electric field (E r) well minimum and propagates along the ion diamagnetic drift direction in the plasma frame. The weakly coherent mode (WCM) and the geodesic acoustic mode observed in I-mode, on the other hand, are found to be located around the outer shear layer of the E r well. This results in a weak plasma frame phase velocity mostly along the electron diamagnetic drift direction for the WCM. The findings in these EDA H-mode plasmas differ from probe measurements in ohmic EDA H-mode (LaBombard et al 2014 Phys. Plasmas 21 056108), where the QCM was identified as an electron drift-wave located several mm outside the E r well minimum in a region of positive E r. To explore if instrumental effects of the optical diagnostics could be the cause of the difference, a synthetic diagnostic for GPI is introduced. This diagnostic reproduces amplitude ratios and relative radial shifts of the mode profiles determined from poloidally and toroidally oriented optics and, if instrumental effects related to GP-CXRS are also included, indicates that the measured location of the QCM and WCM relative to the E r well reported here is only weakly affected by instrumental effects

Phase II Study of Radiotherapy and Temsirolimus versus Radiochemotherapy with Temozolomide in Patients with Newly Diagnosed Glioblastoma without MGMT Promoter Hypermethylation (EORTC 26082).

EORTC 26082 assessed the activity of temsirolimus in patients with newly diagnosed glioblastoma harboring an unmethylated O6 methylguanine-DNA-methyltransferase (MGMT) promoter. Patients (n = 257) fulfilling eligibility criteria underwent central MGMT testing. Patients with MGMT unmethylated glioblastoma (n = 111) were randomized 1:1 between standard chemo-radiotherapy with temozolomide or radiotherapy plus weekly temsirolimus (25 mg). Primary endpoint was overall survival at 12 months (OS12). A positive signal was considered &gt;38 patients alive at 12 months in the per protocol population. A noncomparative reference arm of 54 patients evaluated the assumptions on OS12 in a standard-treated cohort of patients. Prespecified post hoc analyses of markers reflecting target activation were performed. Both therapies were administered per protocol with a median of 13 cycles of maintenance temsirolimus. Median age was 55 and 58 years in the temsirolimus and standard arms, the WHO performance status 0 or 1 for most patients (95.5%). In the per protocol population, 38 of 54 patients treated with temsirolimus reached OS12. The actuarial 1-year survival was 72.2% [95% confidence interval (CI), 58.2-82.2] in the temozolomide arm and 69.6% (95% CI, 55.8-79.9) in the temsirolimus arm [hazard ratio (HR) 1.16; 95% CI, 0.77-1.76; P = 0.47]. In multivariable prognostic analyses of clinical and molecular factors, phosphorylation of mTORSer2448 in tumor tissue (HR 0.13; 95% CI, 0.04-0.47; P = 0.002), detected in 37.6%, was associated with benefit from temsirolimus. Temsirolimus was not superior to temozolomide in patients with an unmethylated MGMT promoter. Phosphorylation of mTORSer2448 in the pretreatment tumor tissue may define a subgroup benefitting from mTOR inhibition. Clin Cancer Res; 22(19); 4797-806. ©2016 AACR

Efficient generation of energetic ions in multi-ion plasmas by radio-frequency heating

We describe a new technique for the efficient generation of high-energy ions with electromagnetic ion cyclotron waves in multi-ion plasmas. The discussed ‘three-ion’ scenarios are especially suited for strong wave absorption by a very low number of resonant ions. To observe this effect, the plasma composition has to be properly adjusted, as prescribed by theory. We demonstrate the potential of the method on the world-largest plasma magnetic confinement device, JET (Joint European Torus, Culham, UK), and the high-magnetic-field tokamak Alcator C-Mod (Cambridge, USA). The obtained results demonstrate efficient acceleration of 3He ions to high energies in dedicated hydrogen–deuterium mixtures. Simultaneously, effective plasma heating is observed, as a result of the slowing-down of the fast 3He ions. The developed technique is not only limited to laboratory plasmas, but can also be applied to explain observations of energetic ions in space-plasma environments, in particular, 3He-rich solar flares.This paper is dedicated to the late P. E. M. Vandenplas, founder and first director of LPP-ERM/KMS, in recognition of his lifelong outstanding commitment to fusion research, in particular to ICRH. The support from the JET and Alcator C-Mod Teams is warmly acknowledged. We are grateful to A. Cardinali, C. Castaldo, R. Dumont, J. Eriksson, T. Fülöp, C. Giroud, C. Hellesen, S. Menmuir and M. Schneider for fruitful discussions. This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014–2018 under grant agreement no. 633053. The views and opinions expressed herein do not necessarily reflect those of the European Commission. This work was also supported by the US DoE, Office of Science, Office of Fusion Energy Sciences, SciDAC Center for Simulation of Wave Plasma Interactions under DE-FC02-01ER54648 and the User Facility Alcator C-Mod under DE-FC02-99ER54512. The Alcator C-Mod Team author list is reproduced from ref. 12. The JET Contributors author list is reproduced from ref. 33.Peer ReviewedPostprint (author's final draft

Weak Responses to Auditory Feedback Perturbation during Articulation in Persons Who Stutter: Evidence for Abnormal Auditory-Motor Transformation

Previous empirical observations have led researchers to propose that auditory feedback (the auditory perception of self-produced sounds when speaking) functions abnormally in the speech motor systems of persons who stutter (PWS). Researchers have theorized that an important neural basis of stuttering is the aberrant integration of auditory information into incipient speech motor commands. Because of the circumstantial support for these hypotheses and the differences and contradictions between them, there is a need for carefully designed experiments that directly examine auditory-motor integration during speech production in PWS. In the current study, we used real-time manipulation of auditory feedback to directly investigate whether the speech motor system of PWS utilizes auditory feedback abnormally during articulation and to characterize potential deficits of this auditory-motor integration. Twenty-one PWS and 18 fluent control participants were recruited. Using a short-latency formant-perturbation system, we examined participants’ compensatory responses to unanticipated perturbation of auditory feedback of the first formant frequency during the production of the monophthong [ε]. The PWS showed compensatory responses that were qualitatively similar to the controls’ and had close-to-normal latencies (~150 ms), but the magnitudes of their responses were substantially and significantly smaller than those of the control participants (by 47% on average, p<0.05). Measurements of auditory acuity indicate that the weaker-than-normal compensatory responses in PWS were not attributable to a deficit in low-level auditory processing. These findings are consistent with the hypothesis that stuttering is associated with functional defects in the inverse models responsible for the transformation from the domain of auditory targets and auditory error information into the domain of speech motor commands

The effects of stimulus complexity on the preattentive processing of self-generated and nonself voices: an ERP study

The ability to differentiate one's own voice from the voice of somebody else plays a critical role in successful verbal self-monitoring processes and in communication. However, most of the existing studies have only focused on the sensory correlates of self-generated voice processing, whereas the effects of attentional demands and stimulus complexity on self-generated voice processing remain largely unknown. In this study, we investigated the effects of stimulus complexity on the preattentive processing of self and nonself voice stimuli. Event-related potentials (ERPs) were recorded from 17 healthy males who watched a silent movie while ignoring prerecorded self-generated (SGV) and nonself (NSV) voice stimuli, consisting of a vocalization (vocalization category condition: VCC) or of a disyllabic word (word category condition: WCC). All voice stimuli were presented as standard and deviant events in four distinct oddball sequences. The mismatch negativity (MMN) ERP component peaked earlier for NSV than for SGV stimuli. Moreover, when compared with SGV stimuli, the P3a amplitude was increased for NSV stimuli in the VCC only, whereas in the WCC no significant differences were found between the two voice types. These findings suggest differences in the time course of automatic detection of a change in voice identity. In addition, they suggest that stimulus complexity modulates the magnitude of the orienting response to SGV and NSV stimuli, extending previous findings on self-voice processing.This work was supported by Grant Numbers IF/00334/2012, PTDC/PSI-PCL/116626/2010, and PTDC/MHN-PCN/3606/2012, funded by the Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) and the Fundo Europeu de Desenvolvimento Regional through the European programs Quadro de Referencia Estrategico Nacional and Programa Operacional Factores de Competitividade, awarded to A.P.P., and by FCT Doctoral Grant Number SFRH/BD/77681/2011, awarded to T.C.info:eu-repo/semantics/publishedVersio