Efficacy and safety of perampanel in patients with drug-resistant partial seizures after conversion from double-blind placebo to open-label perampanel

SummaryObjectiveTo evaluate the efficacy and safety of perampanel in patients with drug-resistant partial seizures after the conversion from double-blind placebo in three phase III studies to open-label perampanel, and to assess the impact of perampanel titration rates through a comparison of weekly vs biweekly dose increases.MethodsPatients who completed the three multinational, double-blind, placebo-controlled, phase III core studies (studies 304, 305, or 306) were eligible to enroll in the extension study (study 307). Patients completing the double-blind treatment (6-week titration, 13-week maintenance) with placebo (DB-PBO) or perampanel (DB-PER) began the extension study with a 16-week blinded conversion period, during which DB-PBO patients were switched to perampanel. Doses were titrated in 2-mg increments (biweekly) to an individualized maximum tolerated dose of perampanel (up to 12mg/day). Patients then entered a planned, open-label treatment period.ResultsPerampanel treatment during the extension study reduced total seizure frequency/28 days relative to the double-blind prerandomization baseline regardless of prior perampanel or placebo treatment in the core studies. In the DB-PBO patients, median percent reductions in seizure frequency at the end of the double-blind period, at the end of the conversion period, and at Weeks 40–52 in the open-label maintenance period were 18.6%, 44.3%, and 55.0%, respectively. Seizure control was also improved in the DB-PER patients during the extension period compared to the end of the double-blind period. Responder rates were similar between the 2 patient groups at the end of the conversion period. Perampanel was well tolerated, with the most common treatment-emergent adverse events being dizziness, somnolence, weight increase, irritability, fatigue, and headache. For those patients randomized to the 12mg group (DB-PER 12mg), 78.4% reached the daily dose of 10 or 12mg by the end of the 6-week titration period of the double-blind phase. By the end of the 16-week conversion period of the extension study, 64.0% of DB-PBO patients reached the daily dose of 10 or 12mg. Seizure frequency reduction was greater after the first 13-week maintenance period of the extension study in the DB-PBO group compared to patients assigned to DB-PER 12mg during the 13-week maintenance period of the double-blind study.ConclusionPatients who received placebo in the phase III core DB studies and transitioned to perampanel in the open-label extension study (DB-PBO) achieved seizure control at the end of the conversion period similar to that of patients who had been previously exposed to perampanel (DB-PER) as well as comparable safety outcomes. Patients who received perampanel during the core studies and continued with treatment during the extension study (DB-PER) also showed sustained improvements in seizure control with long-term exposure to perampanel

Enhancing methane sensors by sensing without detection

We propose a novel methane sensor based on sensing without detection. First used in quantum imaging, this technique relies on the interference effects seen in three wave mixing when pump signal and idler modes make a double pass through a nonlinear crystal. The method allows sensing at wavelengths where detectors are poor and detecting at wavelengths where photon counting sensitivity can be achieved. This compact interferometer, potentially set in a portable device for field operations, could allow the detection of low concentrations of methane at up to 100m range. Signal-to-noise ratio calculations point out that the method's sensitivity can overcome the integrated path differential absorption direct sensing at high non-linear gain regimes.Comment: 9 pages 4 figure

Progress in the seasonal variations of blood lipids: a mini-review.

The seasonal variations of blood lipids have recently gained increasing interest in this field of lipid metabolism. Elucidating the seasonal patterns of blood lipids is particularly helpful for the prevention and treatment of cardiovascular and cerebrovascular diseases. However, the previous results remain controversial and the underlying mechanisms are still unclear. This mini-review is focused on summarizing the literature relevant to the seasonal variability of blood lipid parameters, as well as on discussing its significance in clinical diagnoses and management decisions

Affective Affordance of Message Balloon Animations: An Early Exploration of AniBalloons

We introduce the preliminary exploration of AniBalloons, a novel form of chat balloon animations aimed at enriching nonverbal affective expression in text-based communications. AniBalloons were designed using extracted motion patterns from affective animations and mapped to six commonly communicated emotions. An evaluation study with 40 participants assessed their effectiveness in conveying intended emotions and their perceived emotional properties. The results showed that 80% of the animations effectively conveyed the intended emotions. AniBalloons covered a broad range of emotional parameters, comparable to frequently used emojis, offering potential for a wide array of affective expressions in daily communication. The findings suggest AniBalloons' promise for enhancing emotional expressiveness in text-based communication and provide early insights for future affective design.Comment: Accepted by CSCW 2023 poste

Time-course adaptive changes in hippocampal transcriptome and synaptic function induced by simulated microgravity associated with cognition

IntroductionThe investigation of cognitive function in microgravity, both short-term and long-term, remains largely descriptive. And the underlying mechanisms of the changes over time remain unclear.MethodsBehavioral tests, electrophysiological recording, and RNA sequencing were used to observe differences in behavior, synaptic plasticity, and gene expression.ResultsInitially, we measured the performance of spatial cognition exposed to long-term simulated microgravity (SM). Both working memory and advanced cognitive abilities were enhanced. Somewhat surprisingly, the synaptic plasticity of the hippocampal CA3-CA1 synapse was impaired. To gain insight into the mechanism of changing regularity over time, transcriptome sequencing in the hippocampus was performed. The analysis identified 20 differentially expressed genes (DEGs) in the hippocampus after short-term modeling, 19 of which were up-regulated. Gene Ontology (GO) analysis showed that these up-regulated genes were mainly enriched in synaptic-related processes, such as Stxbp5l and Epha6. This might be related to the enhancement of working memory performance under short-term SM exposure. Under exposure to long-term SM, 7 DEGs were identified in the hippocampus, all of which were up-regulated and related to oxidative stress and metabolism, such as Depp1 and Lrg1. Compensatory effects occurred with increased modeling time.DiscussionTo sum up, our current research indicates that the cognitive function under SM exposure is consistently maintained or potentially even being enhanced over both short and long durations. The underlying mechanisms are intricate and potentially linked to the differential expression of hippocampal-associated genes and alterations in synaptic function, with these effects being time-dependent. The present study will lay the experimental and theoretical foundation of the multi-level mechanism of cognitive function under space flight

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Space advanced technology demonstration satellite

The Space Advanced Technology demonstration satellite (SATech-01), a mission for low-cost space science and new technology experiments, organized by Chinese Academy of Sciences (CAS), was successfully launched into a Sun-synchronous orbit at an altitude of similar to 500 km on July 27, 2022, from the Jiuquan Satellite Launch Centre. Serving as an experimental platform for space science exploration and the demonstration of advanced common technologies in orbit, SATech-01 is equipped with 16 experimental payloads, including the solar upper transition region imager (SUTRI), the lobster eye imager for astronomy (LEIA), the high energy burst searcher (HEBS), and a High Precision Magnetic Field Measurement System based on a CPT Magnetometer (CPT). It also incorporates an imager with freeform optics, an integrated thermal imaging sensor, and a multi-functional integrated imager, etc. This paper provides an overview of SATech-01, including a technical description of the satellite and its scientific payloads, along with their on-orbit performance