Purpose Patients with hippocampal sclerosis associated with focal cortical dysplasia can have a higher risk of seizure recurrence if both of these pathologies are not removed. The aim of our study ...was to determine the role of intraoperative electrocorticography in detection of this dual pathology. Methods Intraoperative electrocorticography recordings were obtained in patients who underwent anteromedial temporal lobe resection. Patients with histopathologically proven hippocampal sclerosis and temporal pole available for analysis were included and were divided into two groups according to histopathology: isolated hippocampal sclerosis ( n = 23) and hippocampal sclerosis associated with focal cortical dysplasia – FCD IIIa ( n = 23).Cortical activity was measured prior to the resection using two six-contact strips (sampling from latero-basal and temporo-polar regions respectively) and one four contact strip sampling from mesio-basal temporal cortex. Occurrence of isolated mesial and independent neocortical (basal or lateral) spike activity was evaluated. Data analysis was performed by raters blinded to histopathology. Results Independent neocortical spikes were identified more frequently in patients with dual pathology (sixteen patients with FCD IIIa vs. four patients with isolated hippocampal sclerosis; p = 0.01). On the contrary, isolated mesial spikes occurred more often in patients with isolated hippocampal sclerosis (19 patients vs. six patients with FCD IIIa). In one patient with FCD IIIa no spikes were recorded. Conclusion Independent latero-basal temporal spikes recorded during intraoperative electrocorticography in patients with hippocampal sclerosis suggest associated dysplastic tissue in neocortex, i.e. dual pathology. Support: IGA MZ ČR NT14489–3.
The nature of human error processing and the underlying cerebral mechanisms are of great interest in neuroscience, and error-related brain responses may provide information useful to improve the ...accuracy of brain-machine interfaces (BMIs). So far, many studies focused on error-related responses below 30Hz. We were interested in error-related effects in the high-gamma band (HGB, 50–150Hz), as this frequency range is thought to reflect local cortical information processing more directly than lower frequencies.
30 healthy subjects performed a flanker task as classically used to study error processing (Gehring et al., 1993). Under time pressure, the subjects had to use the left or right index finger to respond to the respective flanker. Recordings of 128-channel EEG were acquired within an optimized setting for non-invasive EEG high-gamma mapping in an electromagnetically shielded cabin with full optical decoupling of all devices and high-resolution binocular eye tracking. Additionally, 9 patients with pharmacoresistant epilepsy and implanted stereo-EEG (SEEG) electrodes performed the identical task.
As our main result, we show for the first time error-related HGB spectral power modulations up to 120Hz in non-invasive EEG (Fig. 1A), which could also be used for decoding on a single-trial basis. Additional SEEG data (Fig. 1B) revealed possible sources of these effects, including the premotor cortex. Additional responses were seen in areas not reflected in the non-invasive EEG, such as hippocampus and insula. Importantly, based on the eye-tracking data, we show that the error-related effects in the gamma range cannot be explained by differences in eye movements including micro-saccades, which had a different spatial distribution compared to the error-related effects.
Our findings open a new window for investigation of the complex neuronal processes related to error perception and ensuing behavioral adaptation. The similarity of intracranial and non-invasive measurements further show that data of healthy subjects and epilepsy patients is comparable and physiological high-gamma activity can be found in both cases.
COMET Phase-I technical design report Abramishvili, R; Adamov, G; Allin, A ...
Progress of theoretical and experimental physics,
03/2020, Volume:
2020, Issue:
3
Journal Article
Peer reviewed
Open access
Abstract
The Technical Design for the COMET Phase-I experiment is presented in this paper. COMET is an experiment at J-PARC, Japan, which will search for neutrinoless conversion of muons into ...electrons in the field of an aluminum nucleus ($\mu$–$e$ conversion, $\mu^{-}N \rightarrow e^{-}N$); a lepton flavor-violating process. The experimental sensitivity goal for this process in the Phase-I experiment is $3.1\times10^{-15}$, or 90% upper limit of a branching ratio of $7\times 10^{-15}$, which is a factor of 100 improvement over the existing limit. The expected number of background events is 0.032. To achieve the target sensitivity and background level, the 3.2 kW 8 GeV proton beam from J-PARC will be used. Two types of detectors, CyDet and StrECAL, will be used for detecting the $\mu$–$e$ conversion events, and for measuring the beam-related background events in view of the Phase-II experiment, respectively. Results from simulation on signal and background estimations are also described.
Superconductor MgB2 thin films with thickness 200nm were prepared on sapphire substrates by co-deposition of boron and magnesium. Precursor MgB thin films were deposited from two independent ...magnetron sources—boron by rf magnetron sputtering and magnesium by dc magnetron sputtering. MgB precursor thin films annealed ex situ in argon atmosphere at temperature range from 500°C to 700°C exhibit smooth superconducting transition with onset critical temperature Tcon⩽35K and zero resistance Tc0⩽32 K. Preparation of microstructures and measurement of critical current density are also discussed.
In the Piedmont region of North Carolina, USA, a rich herptofauna lives largely unnoticed by the general populace. Many youth are unaware of the rich diversity of life that our local woodlands and ...wetlands harbor as well as the specific habitat needs of these various reptiles and amphibians (herptofauna, or “herps”). For the past four years we have conducted a herpetology program for high school students to introduce them to these elusive organisms, their specific habitats and connections to the global environment. Our students have constructed rich science content and science process understandings but, most importantly, we claim that students have developed a sense of place.
Summary Background Effective systemic therapies for patients with advanced, progressive neuroendocrine tumours of the lung or gastrointestinal tract are scarce. We aimed to assess the efficacy and ...safety of everolimus compared with placebo in this patient population. Methods In the randomised, double-blind, placebo-controlled, phase 3 RADIANT-4 trial, adult patients (aged ≥18 years) with advanced, progressive, well-differentiated, non-functional neuroendocrine tumours of lung or gastrointestinal origin were enrolled from 97 centres in 25 countries worldwide. Eligible patients were randomly assigned in a 2:1 ratio by an interactive voice response system to receive everolimus 10 mg per day orally or identical placebo, both with supportive care. Patients were stratified by tumour origin, performance status, and previous somatostatin analogue treatment. Patients, investigators, and the study sponsor were masked to treatment assignment. The primary endpoint was progression-free survival assessed by central radiology review, analysed by intention to treat. Overall survival was a key secondary endpoint. This trial is registered with ClinicalTrials.gov , number NCT01524783. Findings Between April 3, 2012, and Aug 23, 2013, a total of 302 patients were enrolled, of whom 205 were allocated to everolimus 10 mg per day and 97 to placebo. Median progression-free survival was 11·0 months (95% CI 9·2–13·3) in the everolimus group and 3·9 months (3·6–7·4) in the placebo group. Everolimus was associated with a 52% reduction in the estimated risk of progression or death (hazard ratio HR 0·48 95% CI 0·35–0·67, p<0·00001). Although not statistically significant, the results of the first pre-planned interim overall survival analysis indicated that everolimus might be associated with a reduction in the risk of death (HR 0·64 95% CI 0·40–1·05, one-sided p=0·037, whereas the boundary for statistical significance was 0·0002). Grade 3 or 4 drug-related adverse events were infrequent and included stomatitis (in 18 9% of 202 patients in the everolimus group vs 0 of 98 in the placebo group), diarrhoea (15 7% vs 2 2%), infections (14 7% vs 0), anaemia (8 4% vs 1 1%), fatigue (7 3% vs 1 1%), and hyperglycaemia (7 3% vs 0). Interpretation Treatment with everolimus was associated with significant improvement in progression-free survival in patients with progressive lung or gastrointestinal neuroendocrine tumours. The safety findings were consistent with the known side-effect profile of everolimus. Everolimus is the first targeted agent to show robust anti-tumour activity with acceptable tolerability across a broad range of neuroendocrine tumours, including those arising from the pancreas, lung, and gastrointestinal tract. Funding Novartis Pharmaceuticals Corporation.
Summary Background Currently, metastatic renal cell carcinoma is treated with sequential single agents targeting VEGF or mTOR. Here, we aimed to assess lenvatinib, everolimus, or their combination as ...second-line treatment in patients with metastatic renal cell carcinoma. Methods We did a randomised, phase 2, open-label, multicentre trial at 37 centres in five countries and enrolled patients with advanced or metastatic, clear-cell, renal cell carcinoma. We included patients who had received treatment with a VEGF-targeted therapy and progressed on or within 9 months of stopping that agent. Patients were randomised via an interactive voice response system in a 1:1:1 ratio to either lenvatinib (24 mg/day), everolimus (10 mg/day), or lenvatinib plus everolimus (18 mg/day and 5 mg/day, respectively) administered orally in continuous 28-day cycles until disease progression or unacceptable toxic effects. The randomisation procedure dynamically minimised imbalances between treatment groups for the stratification factors haemoglobin and corrected serum calcium. The primary objective was progression-free survival in the intention-to-treat population. This study is closed to enrolment but patients' treatment and follow-up is ongoing. This study is registered with ClinicalTrials.gov , number NCT01136733. Findings Between March 16, 2012, and June 19, 2013, 153 patients were randomly allocated to receive either the combination of lenvatinib plus everolimus (n=51), single-agent lenvatinib (n=52), or single-agent everolimus (n=50). Lenvatinib plus everolimus significantly prolonged progression-free survival compared with everolimus alone (median 14·6 months 95% CI 5·9–20·1 vs 5·5 months 3·5–7·1; hazard ratio HR 0·40, 95% CI 0·24–0·68; p=0·0005), but not compared with lenvatinib alone (7·4 months 95% CI 5·6–10·2; HR 0·66, 95% CI 0·30–1·10; p=0·12). Single-agent lenvatinib significantly prolonged progression-free survival compared with everolimus alone (HR 0·61, 95% CI 0·38–0·98; p=0·048). Grade 3 and 4 events occurred in fewer patients allocated single-agent everolimus (25 50%) compared with those assigned lenvatinib alone (41 79%) or lenvatinib plus everolimus (36 71%). The most common grade 3 or 4 treatment-emergent adverse event in patients allocated lenvatinib plus everolimus was diarrhoea (ten 20%), in those assigned single-agent lenvatinib it was proteinuria (ten 19%), and in those assigned single-agent everolimus it was anaemia (six 12%). Two deaths were deemed related to study drug, one cerebral haemorrhage in the lenvatinib plus everolimus group and one myocardial infarction with single-agent lenvatinib. Interpretation Lenvatinib plus everolimus and lenvatinib alone resulted in a progression-free survival benefit for patients with metastatic renal cell carcinoma who have progressed after one previous VEGF-targeted therapy. Further study of lenvatinib is warranted in patients with metastatic renal cell carcinoma. Funding Eisai Inc.
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