Epilepsy is characterized by recurrent, unprovoked seizures. Accurate prediction of seizure occurrence has long been a clinical goal since this would allow to optimize patient treatment, prevent injuries due to seizures, and alleviate the patient burden of unpredictability. Advances in implantable electroencephalographic (EEG) devices, allowing for long-term interictal EEG recordings, have facilitated major progress in this field. Recently, it has been discovered that interictal brain activity demonstrates circadian and multi-dien cycles that are strongly aligned, or phase locked, with seizure risk. Thus, cyclical brain activity patterns have been used to forecast seizures. However, in the effort to develop a clinically useful EEG based seizure forecasting system, challenges remain. Firstly, multiple EEG features demonstrate cyclical patterns, but it remains unclear which feature is best suited for predicting seizures. Secondly, the technology for long-term EEG recording is currently limited in both spatial and temporal sampling resolution. In this study, we compare five established EEG metrics:synchrony, spatial correlation, temporal correlation, signal variance which have been motivated from critical dynamics theory, and interictal epileptiform discharge (IED) which are a traditional marker of seizure propensity. We assess their effectiveness in detecting 24-h and seizure cycles as well as their robustness under spatial and temporal subsampling. Analyzing intracranial EEG data from 23 patients, we report that all examined features exhibit 24-h cycles. Spatial correlation, signal variance, and synchrony showed the highest phase locking with seizures, while IED rates were the lowest. Notably, spatial and temporal correlation were also found to be highly correlated to each other, as were signal variance and IED-suggesting some features may reflect similar aspects of cortical dynamics, whereas others provide complementary information. All features proved robust under subsampling, indicating that the dynamic properties of interictal activity evolve slowly and are not confined to specific brain regions. Our results may aid future translational research by assisting in design and testing of EEG based seizure forecasting systems.

UNASSIGNED: Neurologic circadian influences, including sleep/wake transitions, processes (e.g., hormonal variation), and behavioral patterns (e.g., consumption of food and oral medications), may affect seizure patterns. Specific circadian patterns of seizures have been reported depending on type, onset location, and severity; however, data on patterns for patients with seizure clusters and effectiveness of rescue therapy by time of day are limited.
UNASSIGNED: We conducted post hoc analyses using patient diary data from the phase 3 safety study of diazepam nasal spray, which is indicated for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. Patients were administered age- and weight-based doses; second doses could be administered if needed to control a seizure cluster. We assessed clock timing of seizure-cluster onset along with second-dose use as a proxy for effectiveness. Treatment-emergent adverse events were recorded.
UNASSIGNED: Seizure-cluster onset was observed to be generally highest during mornings and late evenings and lowest in the early evening and middle of the night. Second-dose use was not consistently associated with a specific time of day. The safety profile was consistent with that expected from previous studies of diazepam nasal spray.
UNASSIGNED: These results suggest that diazepam nasal spray can be effectively administered at any time of day.

BACKGROUND: No definite conclusion has yet to be reached for immunotherapy beyond progression(IBP) of first-line immunotherapy as the second-line treatment for advanced NSCLC patients with negative driver genes. Therefore a retrospective study was conducted to evaluate the efficacy of IBP in this population and investigated whether the cycles best response and progressive mode of first-line immunotherapy could affect the results.
METHODS: The clinical data of patients with advanced NSCLC whose response was evaluated as progressive disease (PD) after receiving a PD-1/PD-L1 inhibitors as first-line therapy were retrospectively collected and the patients were assigned to the IBP and non-IBP groups. The overall survival (OS), progression-free survival (PFS) were evaluated between the two groups. The survival effects of cycles best response and progressive mode of first-line immunotherapy were also evaluated.
RESULTS: Between January 2019 and January 2022, a total of 121 patients was evaluated as PD after first-line immunotherapy in our institution; 53 (43.8%) patients were included in the IBP group and 68 (56.2%) patients were included in the non-IBP group. The OS and PFS were no significantly different between the two groups in whole population. Further analysis revealed the OS was prolonged with the prolongation of first-line medication cycle. The median OS was 15.4m (15.4 vs 10.8 p=0.047) 16.1m (16.1 vs 10.8 p=0.039), 16.3m (16.3 vs 10.9 p=0.029) for patients with ≥4, ≥6, ≥8 cycles in first-line immunotherapy, respectively. The advantages of OS and PFS were also seen in the subgroup of PR (best response) and oligo progression of first-line immunotherapy.
CONCLUSIONS: The clinical outcomes of IBP were similar to those of non-IBP in patients with PD after first-line immnuotherapy in advanced NSCLC. But more cycles, PR as best response and oligo progression in first-line was benefit.

Coffee silverskin is a byproduct of the coffee industry, appearing in large quantities during the roasting step. In this work, a sober and simple water process is proposed, using extractions cycles, to produce valuable products including (a) an extract rich in caffeine, (b) possibly pure caffeine, and (c) insoluble fibers. The hypothetical number of necessary cycles was calculated and compared to the number of cycles used experimentally. Two types of cycles, with and without water compensation, were compared for their water consumption and the amount of caffeine extracted. The use of cycles, with the resulting product from a previous extraction as a solvent for fresh biomass, drove a significant rise in the content of caffeine determined by a UV-visible detector with a spectrophotometer and ultra-performance liquid chromatography (UPLC). After 11 extraction cycles with water compensation, we obtained an extract 4.5 times more concentrated in caffeine (4.25 mg/mL) than after a single extraction (1.03 mg/mL).

OBJECTIVE: Seizure clusters require prompt medical treatment to minimize possible progression to status epilepticus, increased health care use, and disruptions to daily life. Isolated seizures may exhibit cyclical patterns, including circadian and longer rhythms. However, little is known about the cyclical patterns in seizure clusters. This post hoc analysis of data from a long-term, phase 3, open-label, repeat-dose safety study of diazepam nasal spray modeled the periodicity of treated seizure clusters.
METHODS: Mixed-effects cosinor analysis evaluated circadian rhythmicity, and single component cosinors using 12 and 24 h were used to calculate cosinor parameters (e.g., midline statistic of rhythm, wave ampitude, and acrophase [peak]). Analysis was completed for the full cohort and a consistent cohort of participants with two or more seizure clusters in each of four, 3-month periods. The influence of epilepsy type on cosinor parameters was also analyzed.
RESULTS: Seizure-cluster events plotted across 24 h showed a bimodal distribution with acrophases (peaks) at ~06:30 and ~18:30. A 12-h plot showed a single peak at ~06:30. Cosinor analyses of the full and consistent cohort aligned, with acrophases for both models predicting peak seizure activity at ~23:30 on a 24-h scale and ~07:30 on a 12-h scale. The consistent cohort was associated with increases in baseline and peak seizure-cluster activity. Analysis by epilepsy type identified distinct trends. Seizure clusters in the focal epilepsy group peaked in the evening (acrophase 19:19), whereas events in the generalized epilepsy group peaked in the morning (acrophase 04:46). Together they compose the bimodal clustering observed over 24 h.
CONCLUSIONS: This analysis of seizure clusters treated with diazepam nasal spray demonstrated that seizure clusters occur cyclically in 12- and 24-h time frames similar to that reported with isolated seizures. Further elucidation of these patterns may provide important information for patient care, ranging from improved patient-centered outcomes to seizure-cluster prediction.

The purpose of this paper is twofold: analyzing stationarity of energy consumption by source in the United States and studying their cycles and pairwise synchronization. We study a panel of nine time series of monthly energy consumption for the period 1973-2022. Four of the series (namely coal, natural gas, petroleum, and nuclear electric power consumption) are non-renewables, whereas the remaining ones (hydroelectric power, geothermal, biomass, solar, and wind energy consumption) are renewable energy sources. We employ a nonparametric, panel stationarity testing approach. The results indicate that most of the series may be trend-stationarity, with nuclear and geothermal energy consumption being the only exceptions. Additionally, a study on potential cycles in the series of energy consumption by source is carried out, and subsequently we analyze pairwise concordance between states of different energy sources and between states of energy sources and the business cycle. Significant correlations are detected in the latter analysis, which are positive in the case of fossil fuel sources and negative for two renewable sources, namely geothermal and biomass energy consumption.

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Explaining the complex structure and dynamics of sleep, which consist of alternating and physiologically distinct nonREM and REM sleep episodes, has posed a significant challenge. In this study, we demonstrate that a single-wave model concept captures the distinctly different overnight dynamics of the four primary sleep measures-the duration and intensity of nonREM and REM sleep episodes-with high quantitative precision for both regular and extended sleep. The model also accurately predicts how these polysomnographic measures respond to sleep deprivation or abundance. Furthermore, the model passes the ultimate test, as its prediction leads to a novel experimental finding-an invariant relationship between the duration of nonREM episodes and the intensity of REM episodes, the product of which remains constant over consecutive sleep cycles. These results suggest a functional unity between nonREM and REM sleep, establishing a comprehensive and quantitative framework for understanding normal sleep and sleep disorders.

In this article, we find an α-valuation for disjoint union of some bipartite graphs and the tensor product of paths and even cycles.

What propelled the human \'revolutions\' that started the Anthropocene? and what could speed humanity out of trouble? Here, we focus on the role of reinforcing feedback cycles, often comprised of diverse, unrelated elements (e.g. fire, grass, humans), in propelling abrupt and/or irreversible, revolutionary changes. We suggest that differential \'spread of the cycles\' has been critical to the past human revolutions of fire use, agriculture, rise of complex states and industrialization. For each revolution, we review and map out proposed reinforcing feedback cycles, and describe how new systems built on previous ones, propelling us into the Anthropocene. We argue that to escape a bleak Anthropocene will require abruptly shifting from existing unsustainable \'vicious cycles\', to alternative sustainable \'virtuous cycles\' that can outspread and outpersist them. This will need to be complemented by a revolutionary cultural shift from maximizing growth to maximizing persistence (sustainability). To achieve that we suggest that non-human elements need to be brought back into the feedback cycles underlying human cultures and associated measures of progress. This article is part of the theme issue \'Evolution and sustainability: gathering the strands for an Anthropocene synthesis\'.