Plasma discharges with a negative triangularity (δ=-0.4) shape have been created in the DIII-D tokamak with a significant normalized beta (β_{N}=2.7) and confinement characteristic of the high ...confinement mode (H_{98y2}=1.2) despite the absence of an edge pressure pedestal and no edge localized modes (ELMs). These inner-wall-limited plasmas have a similar global performance as a positive triangularity (δ=+0.4) ELMing H-mode discharge with the same plasma current, elongation and cross sectional area. For cases both of dominant electron cyclotron heating with T_{e}/T_{i}>1 and dominant neutral beam injection heating with T_{e}/T_{i}=1, turbulent fluctuations over radii 0.5<ρ<0.9 were reduced by 10-50% in the negative triangularity shape compared to the matching positive triangularity shape, depending on the radius and conditions.
Summary Background Present mechanical devices are unable to achieve recanalisation in up to 20–40% of large vessel occlusion strokes. We compared efficacy and safety of the Trevo Retriever, a new ...stent-like device, with its US Food and Drug Administration-cleared predecessor, the Merci Retriever. Methods In this open-label randomised controlled trial, we recruited patients at 26 sites in the USA and one in Spain. We included adults aged 18–85 years with angiographically confirmed large vessel occlusion strokes and US National Institutes of Health Stroke Scale (NIHSS) scores of 8–29 within 8 h of symptom onset. We randomly assigned patients (1:1) with sequentially numbered sealed envelopes to thrombectomy with Trevo or Merci devices. Randomisation was stratified by age (≤68 years vs 69–85 years) and NIHSS scores (≤18 vs 19–29) with alternating blocks of various sizes. The primary efficacy endpoint, assessed by an unmasked core laboratory, was thrombolysis in cerebral infarction (TICI) scores of 2 or greater reperfusion with the assigned device alone. The primary safety endpoint was a composite of procedure-related adverse events. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov , number NCT01270867. Findings Between Feb 3, 2011, and Dec 1, 2011, we randomly assigned 88 patients to the Trevo Retriever group and 90 patients to Merci Retriever group. 76 (86%) patients in the Trevo group and 54 (60%) in the Merci group met the primary endpoint after the assigned device was used (odds ratio 4·22, 95% CI 1·92–9·69; psuperiority <0·0001). Incidence of the primary safety endpoint did not differ between groups (13 15% patients in the Trevo group vs 21 23% in the Merci group; p=0·1826). Interpretation Patients who have had large vessel occlusion strokes but are ineligible for (or refractory to) intravenous tissue plasminogen activator should be treated with the Trevo Retriever in preference to the Merci Retriever. Funding Stryker Neurovascular.
Accurately predicting an outcome requires that animals learn supporting and conflicting evidence from sequential experience. In mammals and invertebrates, learned fear responses can be suppressed by ...experiencing predictive cues without punishment, a process called memory extinction. Here, we show that extinction of aversive memories in Drosophila requires specific dopaminergic neurons, which indicate that omission of punishment is remembered as a positive experience. Functional imaging revealed co-existence of intracellular calcium traces in different places in the mushroom body output neuron network for both the original aversive memory and a new appetitive extinction memory. Light and ultrastructural anatomy are consistent with parallel competing memories being combined within mushroom body output neurons that direct avoidance. Indeed, extinction-evoked plasticity in a pair of these neurons neutralizes the potentiated odor response imposed in the network by aversive learning. Therefore, flies track the accuracy of learned expectations by accumulating and integrating memories of conflicting events.
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•Omission of expected punishment extinguishes learned avoidance behavior•Lack of punishment is learned as a positive experience•The original aversive and the new appetitive memory co-exist in different places•Opposing memories are integrated within specific output neurons to steer behavior
The omission of punishment is remembered as a rewarding experience, and this positive memory then competes against prior aversive memory to mediate the extinction of avoidance behavior.
Functional (psychogenic or somatoform) symptoms are common in neurology clinics. Cognitive-behavioral therapy (CBT) can be an effective treatment, but there are major obstacles to its provision in ...practice. We tested the hypothesis that adding CBT-based guided self-help (GSH) to the usual care (UC) received by patients improves outcomes.
We conducted a randomized trial in 2 neurology services in the United Kingdom. Outpatients with functional symptoms (rated by the neurologist as "not at all" or only "somewhat" explained by organic disease) were randomly allocated to UC or UC plus GSH. GSH comprised a self-help manual and 4 half-hour guidance sessions. The primary outcome was self-rated health on a 5-point clinical global improvement scale (CGI) at 3 months. Secondary outcomes were measured at 3 and 6 months.
In this trial, 127 participants were enrolled, and primary outcome data were collected for 125. Participants allocated to GSH reported greater improvement on the primary outcome (adjusted common odds ratio on the CGI 2.36 95% confidence interval 1.17-4.74; p = 0.016). The absolute difference in proportion "better" or "much better" was 13% (number needed to treat was 8). At 6 months the treatment effect was no longer statistically significant on the CGI but was apparent in symptom improvement and in physical functioning.
CBT-based GSH is feasible to implement and efficacious. Further evaluation is indicated.
This study provides Class III evidence that CBT-based GSH therapy improves self-reported general health, as measured by the CGI, in patients with functional neurologic symptoms.
This study uses a multimodal analytical approach to evaluate the rates of (co)amorphization of milled drug and excipient and the effectiveness of different analytical methods in detecting these ...changes. Indomethacin and tryptophan were the model substances, and the analytical methods included low-frequency Raman spectroscopy (785 nm excitation and capable of measuring both low- (10 to 250 cm–1) and midfrequency (450 to 1800 cm–1) regimes, and a 830 nm system (5 to 250 cm–1)), conventional (200–3000 cm–1) Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR), and X-ray powder diffraction (XRPD). The kinetics of amorphization were found to be faster for the mixture, and indeed, for indomethacin, only partial amorphization occurred (after 360 min of milling). Each technique was capable of identifying the transformations, but some, such as low-frequency Raman spectroscopy and XRPD, provided less ambiguous signatures than the midvibrational frequency techniques (conventional Raman and FTIR). The low-frequency Raman spectra showed intense phonon mode bands for the crystalline and cocrystalline samples that could be used as a sensitive probe of order. Multivariate analysis has been used to further interpret the spectral changes. Overall, this study demonstrates the potential of low-frequency Raman spectroscopy, which has several practical advantages over XRPD, for probing (dis-)order during pharmaceutical processing, showcasing its potential for future development, and implementation as an in-line process monitoring method.
This randomized trial comparing labor induction between 39 weeks 0 days and 39 weeks 6 days of gestation with expectant management showed no significant between-group difference in the rate of ...cesarean section. The trial was not powered to assess effects on stillbirth.
The average age of women at childbirth in industrialized nations has been increasing steadily for approximately 30 years.
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Between 1996 and 2006, births to women 35 years of age or older in the United Kingdom increased from 12% to 20% of all births.
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In 2006, a total of 5.6% of live births in the United Kingdom were to nulliparous women 35 years of age or older.
The risks of perinatal death, hypertensive disease, gestational diabetes mellitus, placenta previa, and placental abruption are higher among women 35 years of age or older than among younger women.
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Older mothers are . . .
Identification of carcinogenic activity is the primary goal of the 2-year bioassay. The expense of these studies limits the number of chemicals that can be studied and therefore chemicals need to be ...prioritized based on a variety of parameters. We have developed an ensemble of support vector machine classification models based on male F344 rat liver gene expression following 2, 14 or 90 days of exposure to a collection of hepatocarcinogens (aflatoxin B1, 1-amino-2,4-dibromoanthraquinone,
N-nitrosodimethylamine, methyleugenol) and non-hepatocarcinogens (acetaminophen, ascorbic acid, tryptophan). Seven models were generated based on individual exposure durations (2, 14 or 90 days) or a combination of exposures (2
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90 days). All sets of data, with the exception of one yielded models with 0% cross-validation error. Independent validation of the models was performed using expression data from the liver of rats exposed at 2 dose levels to a collection of alkenylbenzene flavoring agents. Depending on the model used and the exposure duration of the test data, independent validation error rates ranged from 47% to 10%. The variable with the most notable effect on independent validation accuracy was exposure duration of the alkenylbenzene test data. All models generally exhibited improved performance as the exposure duration of the alkenylbenzene data increased. The models differentiated between hepatocarcinogenic (estragole and safrole) and non-hepatocarcinogenic (anethole, eugenol and isoeugenol) alkenylbenzenes previously studied in a carcinogenicity bioassay. In the case of safrole the models correctly differentiated between carcinogenic and non-carcinogenic dose levels. The models predict that two alkenylbenzenes not previously assessed in a carcinogenicity bioassay, myristicin and isosafrole, would be weakly hepatocarcinogenic if studied at a dose level of 2 mmol/kg bw/day for 2 years in male F344 rats; therefore suggesting that these chemicals should be a higher priority relative to other untested alkenylbenzenes for evaluation in the carcinogenicity bioassay. The results of the study indicate that gene expression-based predictive models are an effective tool for identifying hepatocarcinogens. Furthermore, we find that exposure duration is a critical variable in the success or failure of such an approach, particularly when evaluating chemicals with unknown carcinogenic potency.
During the International Polar Year (IPY), comprehensive observational research programs were undertaken to increase our understanding of the Canadian polar cryosphere response to a changing climate. ...Cryospheric components considered were snow, permafrost, sea ice, freshwater ice, glaciers and ice shelves. Enhancement of conventional observing systems and retrieval algorithms for satellite measurements facilitated development of a snapshot of current cryospheric conditions, providing a baseline against which future change can be assessed. Key findings include: 1. surface air temperatures across the Canadian Arctic exhibit a warming trend in all seasons over the past 40 years. A consistent pan-cryospheric response to these warming temperatures is evident through the analysis of multi-decadal datasets; 2. in recent years (including the IPY period) a higher rate of change was observed compared to previous decades including warming permafrost, reduction in snow cover extent and duration, reduction in summer sea ice extent, increased mass loss from glaciers, and thinning and break-up of the remaining Canadian ice shelves. These changes illustrate both a reduction in the spatial extent and mass of the cryosphere and an increase in the temporal persistence of melt related parameters. The observed changes in the cryosphere have important implications for human activity including the close ties of northerners to the land, access to northern regions for natural resource development, and the integrity of northern infrastructure.
We present a comparison of Submillimetre Common User Bolometer Array-2 (SCUBA-2) 850-μm and Herschel 70–500-μm observations of the L1495 filament in the Taurus Molecular Cloud with the goal of ...characterizing the SCUBA-2 Gould Belt Survey (GBS) data set. We identify and characterize starless cores in three data sets: SCUBA-2 850-μm, Herschel 250-μm, and Herschel 250-μm spatially filtered to mimic the SCUBA-2 data. SCUBA-2 detects only the highest-surface-brightness sources, principally detecting protostellar sources and starless cores embedded in filaments, while Herschel is sensitive to most of the cloud structure, including extended low-surface-brightness emission. Herschel detects considerably more sources than SCUBA-2 even after spatial filtering. We investigate which properties of a starless core detected by Herschel determine its detectability by SCUBA-2, and find that they are the core's temperature and column density (for given dust properties). For similar-temperature cores, such as those seen in L1495, the surface brightnesses of the cores are determined by their column densities, with the highest-column-density cores being detected by SCUBA-2. For roughly spherical geometries, column density corresponds to volume density, and so SCUBA-2 selects the densest cores from a population at a given temperature. This selection effect, which we quantify as a function of distance, makes SCUBA-2 ideal for identifying those cores in Herschel catalogues that are closest to forming stars. Our results can now be used by anyone wishing to use the SCUBA-2 GBS data set.
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