BOUT++ turbulence simulations were performed to investigate the impact of turbulence spreading on the edge localized mode (ELM) size and divertor heat flux width $({\lambda _q})$ broadening in small ELM regimes. This study is motivated by EAST experiments. BOUT++ linear simulations of a pedestal radial electric field (Er) scan show that the dominant toroidal number mode (n) shifts from high-n to low-n, with a narrow mode spectrum, and the maximum linear growth rate increases as the pedestal Er well deepens. The nonlinear simulations show that as the net E × B pedestal flow increases, the pressure fluctuation level and its inward penetration beyond the top of the pedestal both increase. This leads to a transition from small ELMs to large ELMs. Both inward and outward turbulence spreading are sensitive to the scrape-off-layer (SOL) plasma profiles. The inward turbulence spreading increases for the steep SOL profiles, leading to increasing pedestal energy loss in the small ELM regime. The SOL width $({\lambda _q})$ is significantly broadened progressing from the ELM-free to small ELM regime, due to the onset of strong radial turbulent transport. The extent of the SOL width $({\lambda _q})$ broadening depends strongly on outward turbulence spreading. The fluctuation energy intensity flux ${\varGamma _\varepsilon }$ at the separatrix can be enhanced by increasing either pedestal Er flow shear or local SOL pressure gradient. The ${\lambda _q}$ is broadened as the fluctuation energy intensity flux ${\varGamma _\varepsilon }$ at the last close flux surface (LCFS) increases. Local SOL E × B flow shear will restrain outward turbulence spreading and the associated heat flux width broadening. Operating in H-mode with small ELMs has the potential to solve two critical problems: reducing the ELM size and broadening the SOL width.

A useful application of the hydrocarbon measurements collected during the Pacific Exploratory Mission (PEM-West A) is as markers or indices of atmospheric processing. Traditionally, ratios of particular hydrocarbons have been interpreted as photochemical indices, since much of the effect due to atmospheric transport is assumed to cancel by using ratios. However, an ever increasing body of observatonial and theoretical evidence suggests that turbulent mixing associated with atmospheric transport influences certain hydrocarbon ratios significantly. In this study a three-dimensional mesoscale photochemical model is used to study the interaction of photochemistry and atmospheric mixing on select hydrocarbons. In terms of correlations and functional relationships between various alkanes the model results and PEM-West A hydrocarbon observations share many similar characteristics as well as explainable differences. When the three-dimensional model is applied to inert tracers, hydrocarbon ratios and other relationships exactly follow those expected by simple dilution with model-imposed "background air," and the three-dimensional results for reactive hydrocarbons are quite consistent with a combined influence of photochemistry and simple dilution. Analogous to these model results, relationships between various hydrocarbons collected during the PEM-West A experiment appear to be consistent with this simplified picture of photochemistry and dilution affecting individual air masses. When hydrocarbons are chosen that have negligeble contributions to clean background air, unambiguous determinations of the relative contributions to photochemistry and dilution can be estimated from the hydrocarbon samples. Both the three-dimensional model results and the observations imply an average characteristic lifetime for dilution with background air roughly equivalent to the photochemical lifetime of butane for the western Pacific lower troposphere. Moreover, the dominance of OH as the primary photochemical oxidant downwind of anthropogenic source regions can be inferred from correlations between the highly reactive alkane ratios. By incorporating back-trajectory information within the three-dimensional model analysis, a correspondence between time and a particular hydrocarbon or hydrocarbon ratio can be determined, and the influence of atmospheric mixing or photochemistry can be quantified. Results of the three-dimensional model study are compared and applied to the PEM-West A hydrocarbon dataset, yielding a practical methodology for determining average OH concentrations and atmospheric mixing rates from the hydrocarbon measurements. Aircraft data taken below 2 km during wall flights east of Japan imply a diurnal average OH concentration of ∼3 × 106 cm-3. The characteristic time for dilution with background air is estimated to be ∼2.5 days for the two study areas examined in this work. Copyright 1996 by the American Geophysical Union.

Disrupted sleep has a profound adverse impact on lives of Parkinsons disease (PD) patients and their caregivers. Sleep disturbances are exceedingly common in PD, with substantial heterogeneity in type, timing, and severity. Among the most common sleep-related symptoms reported by PD patients are insomnia, excessive daytime sleepiness, and sleep fragmentation, characterized by interruptions and decreased continuity of sleep. Alterations in brain wave activity, as measured on the electroencephalogram (EEG), also occur in PD, with changes in the pattern and relative contributions of different frequency bands of the EEG spectrum to overall EEG activity in different vigilance states consistently observed. The mechanisms underlying these PD-associated sleep-wake abnormalities are poorly understood, and they are ineffectively treated by conventional PD therapies. To help fill this gap in knowledge, a new progressive model of PD - the MCI-Park mouse - was studied. Near the transition to the parkinsonian state, these mice exhibited significantly altered sleep-wake regulation, including increased wakefulness, decreased non-rapid eye movement (NREM) sleep, increased sleep fragmentation, reduced rapid eye movement (REM) sleep, and altered EEG activity patterns. These sleep-wake abnormalities resemble those identified in PD patients. Thus, this model may help elucidate the circuit mechanisms underlying sleep disruption in PD and identify targets for novel therapeutic approaches.

Iron doping of nickel oxide films results in enhanced activity for promoting the oxygen evolution reaction (OER). Whereas this enhanced activity has been ascribed to a unique iron site within the nickel oxide matrix, we show here that Fe doping influences the Ni valency. The percent of Fe³⁺ doping promotes the formation of formal Ni⁴⁺, which in turn directly correlates with an enhanced activity of the catalyst in promoting OER. The role of Fe³⁺ is consistent with its behavior as a superior Lewis acid.

A three-dimensional mesoscale transport/photochemical model is used to study the transport and photochemical transformation of trace species over eastern Asia and western Pacific for the period from September 20 to October 6, 1991, of the Pacific Exploratory Mission-West A experiment. The influence of emissions from the continental boundary layer that was evident in the observed trace species distributions in the lower troposphere over the ocean is well simulated by the model. In the upper troposphere, species such as O3, NOy (total reactive nitrogen species), and SO2 which have a significant source in the stratosphere are also simulated well in the model, suggesting that the upper tropospheric abundances of these species are strongly influenced by stratospheric fluxes and upper tropospheric sources. In the case of SO2 the stratospheric flux is identified to be mostly from the Mount Pinatubo eruption. Concentrations in the upper troposphere for species such as CO and hydrocarbons, which are emitted in the continental boundary layer and have a sink in the troposphere, are significantly underestimated by the model. Two factors have been identified to contribute significantly to the underestimate: one is emissions upwind of the model domain (eastern Asia and western Pacific); the other is that vertical transport is underestimated in the model. Model results are also grouped by back trajectories to study the contrast between compositions of marine and continental air masses. The model-calculated altitude profiles of trace species in continental and marine air masses are found to be qualitatively consistent with observations. However, the difference in the median values of trace species between continental air and marine air is about twice as large for the observed values as for model results. This suggests that the model underestimates the outflow fluxes of trace species from the Asian continent and the Pacific rim countries to the ocean. Observed altitude profiles for species like CO and hydrocarbons show a negative gradient in continental air and a positive gradient in marine air. A mechanism which may be responsible for the altitude gradients is proposed.

Background

Adjuvant sunitinib has significantly improved disease-free survival versus placebo in patients with renal cell carcinoma at high risk of recurrence post-nephrectomy (hazard ratio 0.76; 95% confidence interval, 0.59-0.98; two-sided P = 0.03). We report safety, therapy management, and patient-reported outcomes for patients receiving sunitinib and placebo in the S-TRAC trial.

Patients and methods

Patients were stratified by the University of California, Los Angeles Integrated Staging System and Eastern Cooperative Oncology Group performance status score, and randomized (1 : 1) to receive sunitinib (50 mg/day) or placebo. Single dose reductions to 37.5 mg, dose delays, and dose interruptions were used to manage adverse events (AEs). Patients' health-related quality of life, including key symptoms typically associated with sunitinib, were evaluated with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).

Results

Patients maintained treatment for 9.5 (mean, SD 4.4) and 10.3 (mean, SD 3.7) months in the sunitinib and placebo arms, respectively. In the sunitinib arm, key AEs occurred ∼1 month (median) after start of treatment and resolved within ∼3.5 weeks (median). Many (40.6%) AEs leading to permanent discontinuation were grade 1/2, and most (87.2%) resolved or were resolving by 28 days after last treatment. Patients taking sunitinib showed a significantly lower EORTC QLQ-C30 overall health status score versus placebo, although this reduction was not clinically meaningful. Patients reported symptoms typically related to sunitinib treatment with diarrhea and loss of appetite showing clinically meaningful increases.

Conclusions

In S-TRAC, AEs were predictable, manageable, and reversible via dose interruptions, dose reductions, and/or standard supportive medical therapy. Patients on sunitinib did report increased symptoms and reduced HRQoL, but these changes were generally not clinically meaningful, apart from appetite loss and diarrhea, and were expected in the context of known sunitinib effects.

Clinical trial registration

ClinicalTrials.gov, NCT00375674.

Coherence phenomena arise from interference, or the addition, of wave-like amplitudes with fixed phase differences. Although coherence has been shown to yield transformative ways for improving function, advances have been confined to pristine matter and coherence was considered fragile. However, recent evidence of coherence in chemical and biological systems suggests that the phenomena are robust and can survive in the face of disorder and noise. Here we survey the state of recent discoveries, present viewpoints that suggest that coherence can be used in complex chemical systems, and discuss the role of coherence as a design element in realizing function.